Bactericidal

Indian J Exp Biol, 2003 Dec, 41(12), 1372 - 83
Male accessory gland proteins in Drosophila: a multifaceted field {corrected}; Ravi Ram K et al.; Male accessory gland in Drosophila is a secretory tissue of the reproductive system . The proteins synthesized in the accessory gland are tissue specific, stage specific-seen only during the adult stage and sex specific in the sense of male limited expression . These secretions that form a component of the seminal fluid are transferred to the female at the time of copulation and play an important role in reproduction . In conjunction with sperm, these secretory proteins assure reproductive success by reducing the female's receptivity to mating and escalating the rate of egg laying . Some of these proteins are antibacterial in nature with a likely function of protecting the female's genital tract against microbial infection during/after mating . Most of the genes involved in the synthesis of accessory gland proteins are autosomal but a few are still X-linked . Their male specific expression is achieved at the time of sex determination . The level of expression of these genes is dose dependent and they follow Mendelian pattern of segregation . Further, majority of these proteins are rapidly evolving with high rates of non-synonymous substitutions . In this review, by considering the work carried out in different fields, we have tried to generate a comprehensive picture about the male accessory gland and the role of its proteins in the reproduction of Drosophila.

Vestn Khir Im I I Grek, 2004, 163(3), 68 - 70
{Optimization of strategy of surgical treatment for acute destructive pancreatitis}; Vinokurov MM et al.; Results of surgical treatment of 142 patients with acute destructive pancreatitis were analyzed . The treatment of patients was divided into two periods . The first period included 59 (41.5%) patients when active surgical strategy was used . The second period of observations included 83 (53.5%) patients with the optimized strategy of treatment based on intensive therapy, prognosis of the course of the disease, new antibacterial medicines and new technologies of operative treatment . A comparison of the results of treatment has revealed the advantages of using the optimized strategy and allowed the postoperative lethality to be reduced from 59.3 to 32.5%.

Infez Med, 2004 Jun, 12(2), 90 - 100
{Management of severe bacterial infections and role of the infectious disease specialist: results of an interview-based survey}; Esposito S et al.; Ascertainment of SBIs plays a central role in their management, which can affect the prognosis, hopefully avoiding an inappropriate antibacterial therapy concerning choice, dosing, timing, duration and route of administration of antibiotics . Different aspects of SBI management were evaluated by interviewing doctors practising in ICU, Surgery and Haematology wards . In the period 16 June - 7 July 2003, 150 doctors, equally distributed by specialty and geographical location, experienced in the management of antibiotic therapy, were interviewed in order to acquire the following information: criteria adopted to define SBIs, presumed incidence, most frequent diagnosis, initial approach to antibiotic therapy (empirical or not, route of administration, mono- or combination therapy), ID consultation request . In most cases generic and empirical criteria are used to define SBI, generally associated to the presence of co-morbidities, the highest rates being reported in ICUs (35.1%) and Haematology (34.7%) wards . Pneumonia is the top reported SBI in all the wards, followed by sepsis in ICUs and Haematology, and by intrabdominal infections in Surgery . Antibiotic therapy is often empirical (~90%), often performed i.v . with antibiotics given in combination . Following treatment failure, which occurs on average in 35.5% of cases, ID consultation and microbiological investigation are required . ID consultation is required in 20.2%, 26.1% and 28.1% of cases by haematologists, surgeons and ICU specialists, respectively . SBIs frequently occur in all the wards where the interviews were conducted . Their management is generally empirical and either ID consultation or microbiological investigation is infrequently required especially as an initial approach . The use of appropriate guidelines and ID consultation, as proven in many controlled studies, could be efficacious in reducing the incidence of inappropriate therapies and increasing favourable outcome rates.

J Med Microbiol, 2004 Sep, 53(Pt 9), 911 - 4
Risk factors for primary Helicobacter pylori resistance in Bulgarian children; Boyanova L et al.; Risk factors for primary Helicobacter pylori resistance in 186 children with gastroduodenal diseases (44 from villages/small towns and 130 from large towns/cities) in 2000-2003 were tested . Susceptibility was tested by a limited agar dilution method . Overall resistance rates to metronidazole, clarithromycin, tetracycline and both metronidazole and clarithromycin were 14.5, 11.9, 3.3 and 4.3 %, respectively . No amoxycillin resistance was observed . Tetracycline resistance was found in six children aged 7-18 years . Clarithromycin resistance was more common in children from small towns/villages (22.7 %) than in those from large towns/cities (8.5 %, P < 0.05) . There were no significant differences (P > 0.05) in resistance rates between children from northern Bulgaria and those from southern regions . Resistance rates in duodenal ulcer patients and other children were, respectively, 10.5 and 15 % (P > 0.20) for metronidazole and 10.5 and 12 % (P > 0.20) for clarithromycin . No combined resistance to metronidazole and clarithromycin was found in 22 children aged 1-7 years and in 34 children living in northern Bulgaria . There were no significant associations of resistance with sex and age group (1-7- versus 8-18-year-old children) for all antibacterial agents tested . In conclusion, primary H . pylori resistance was absent (for metronidazole + clarithromycin) or low (4.5 % for clarithromycin) in children aged 1-7 years . Place of residence was associated with clarithromycin resistance rates.

J Med Microbiol, 2004 Sep, 53(Pt 9), 855 - 60
Sensitivity of Helicobacter pylori to an innate defence mechanism, the lactoperoxidase system, in buffer and in human whole saliva; Haukioja A et al.; Helicobacter pylori has frequently been isolated from human dental plaque, and oral spread via saliva is thought to be one of its principal modes of transmission . Among other innate defence systems human saliva contains peroxidase enzymes and lysozyme . The sensitivity of H . pylori to physiological concentrations of lactoperoxidase and its salivary substrate thiocyanate, and different amounts of hydrogen peroxide (H(2)O(2)) was investigated in buffer and in human whole saliva . The effect of lysozyme was also studied in saliva . All tested H . pylori strains, ATCC 43504(T) and five clinical isolates, were efficiently inhibited by the peroxidase system with high concentrations of H(2)O(2) in buffer . The inhibition was stronger at lower pH . However, in human saliva these high concentrations of H(2)O(2) generated less hypothiocyanite, the antibacterial product of the peroxidase system and the effects of the peroxidase system were weaker . Physiological concentration of lysozyme was not bacteriocidal against H . pylori, nor did it enhance the effect of the peroxidase system in saliva . Thus, further studies are needed to enhance the efficacy of peroxidase systems in human saliva to make it more beneficial not only against dental but also against gastric pathogens.

Clin Chim Acta, 2004 Sep, 347(1-2), 81 - 8
Protein composition of apical surface fluid from the human airway cell line Calu-3: effect of ion transport mediators; Babu PB et al.; BACKGROUND: Analysis of the protein components of airway secretions is a potential means of detecting and characterizing biochemical alterations associated with airway diseases . METHODS: We evaluated airway protein secretions using the airway epithelial cell line Calu-3 grown at an air-liquid interface . To observe changes in apically secreted proteins, we analyzed the protein content of apical surface fluid (ASF) washings of Calu-3 monolayers treated with ion transport mediators . RESULTS: Immunoassay screening for antibacterial and inflammatory proteins indicated the presence of measurable levels of lysozyme and IL-8 in Calu-3 ASF . RT-PCR and immunoassay studies indicated that Calu-3 cells do not produce clara cell 10 kDa protein (CC10) . The total protein secretion of Calu-3 was not altered by bradykinin, but amiloride and adenosine significantly increased Calu-3 protein secretion . Lysozyme secretion was not altered by bradykinin, but amiloride and adenosine significantly reduced lysozyme secretion . IL-8 secretion was not altered by bradykinin or adenosine, but amiloride significantly decreased IL-8 secretion . CONCLUSION: Our results demonstrate the presence of antibacterial protein lysozyme and the pro-inflammatory cytokine IL-8 in Calu-3 ASF and that ion transport mediators such as bradykinin, amiloride and adenosine influence the secretion of Calu-3 ASF proteins.

J Clin Periodontol, 2004 Sep, 31(9), 697 - 707
Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis . A review; Preshaw PM et al.; BACKGROUND: Subantimicrobial dose doxycycline (SDD--20 mg doxycycline twice daily) is indicated as an adjunctive treatment for periodontitis . Doxycycline downregulates the activity of matrix metalloproteinases (MMPs), key destructive enzymes in periodontal disease . Current understanding of periodontal pathogenesis suggests that MMPs play a major role in the destruction of periodontal tissues, leading to the clinical signs of periodontitis . Research supports that downregulation of MMPs by SDD confers benefit to patients with periodontitis . METHOD: We review the clinical, microbiological and safety data relating to the use of SDD in patients with periodontitis, and consider the historical events that led to the development of adjunctive SDD as a treatment for periodontitis . RESULTS: Studies have shown that SDD, when prescribed as an adjunct to scaling and root planing (SRP), results in statistically and clinically significant gains in clinical attachment levels and reductions in probing depths over and above those that are achieved by SRP alone . SRP must be thorough and performed to the highest standard to maximise the benefits of adjunctive SDD . SDD does not result in antibacterial effects, or lead to the development of resistant strains or the acquisition of multiantibiotic resistance . The frequency of adverse events is low, and does not differ significantly from placebo . CONCLUSIONS: Adjunctive SDD confers clinical benefit to patients with periodontitis . A comprehensive treatment strategy is suggested, involving patient education and motivation, reduction of the bacterial burden by SRP, host response modulation with SDD, and periodontal risk factor modification.

Drug Ther Bull, 2004 Aug, 42(8), 61 - 2
Moxifloxacin--a new fluoroquinolone antibacterial.
{Exchange amnioinfusion in conceptus with laparoschisis (first experience)}
Turkota L, Hinst J, Rusnak I, Cunderlik A, Slezak I, Feitscher P, Stencl J, Horn F, Babala J, Siman J.

Gynekologicko-porodnicka klinika SZU, FNsP akad . L . Derera, Bratislava, Slovenske RepublikeOBJECTIVE: During amnioinfusion exchange (AE) a certain amount of amniotic fluid is repeatedly extracted and the same amount of physiological solution is consequently instilled into the amniotic fetal cavity . The aim of this procedure is to dilute the amniotic fluid that surrounds the eviscerated organs of fetuses with laparoschisis so as to avoid the genesis of fibrous coating on these organs . DESIGN: Prospective study . SETTING: Gynekologicko-porodnicka klinika SZU, FNsP akad . L . Derera, Bratislava, Slovakia . METHODS: We have executed AE in five fetuses with laparoschisis since June 2002 . Two patients underwent the treatment 2 times during the 32nd and 36th weeks of gestation . Two other patients were treated once during the 32nd week and one patient once during the 36th week . Under ultrasound control we used a spinal needle to extract 120-180 ml of dense, cloudy amniotic fluid . Consequently, we instilled the same amount of physiological solution warmed up to the temperature of 37 degrees C into the amniotic cavity through antibacterial filter . The fetuses were monitored cardiotocographically and with the help of ultrasound flowmetry in umbilical vessels, before and after the treatment . RESULTS: The AE were successful and without complications in all five cases . All patients delivered via elective caesarean section during the 36th - 37th gestation week . One patient delivered 24 hours after second AE due to the danger of intrauterine fetal hypoxia that was verified cardiotocographically . The other patients delivered 1-4 weeks after AE . CONCLUSION: The significance of AE lies primarily in the reduction of the occurrence of fibrous coating on eviscerated organs . It enables postnatal primary surgical closure of the defect in the front abdominal wall, an earlier onset of intestine peristalsis, transition from parenteral to peroral nutrition and shorter hospitalization.

Infect Dis Clin North Am, 2004 Sep, 18(3), 717 - 33, x
Topical antibacterial agents; Lio PA et al.; Decreased systemic toxicity, ease of application, and increased concentration at the target site are some of the important advantages topical antibacterial agents offer . This article reviews the literature on selected indications of these agents and provides in-depth examination of specific agents for the prophylaxis and treatment of skin and wound infections.

Infect Dis Clin North Am, 2004 Sep, 18(3), 669 - 89, x
Current use for old antibacterial agents: polymyxins, rifampin, and aminoglycosides; Kaye D; This article discusses three classes of antibacterial agents that are uncommonly used in bacterial infections (other than mycobacterial infections) and can be thought of as special-use agents . These are the polymyxins, rifampin, and the aminoglycosides.

Infect Dis Clin North Am, 2004 Sep, 18(3), 551 - 79, viii-ix
Use of antibacterial agents in renal failure; Livornese LL Jr et al.; This article provides background information on the pharmacokinetics of antibacterial agents in patients with normal and impaired renal function . Tables are provided to allow quick determination of appropriate dosages for varying degrees of renal failure . The use of serum levels, newer strategies for cefazolin, vancomycin, and aminoglycoside dosing, methods of dialysis and associated antibiotics dosage adjustments, and antibiotic toxicity in renal failure are reviewed.

Infect Dis Clin North Am, 2004 Sep, 18(3), 513 - 31, viii
Antibacterial agents in pediatrics; Bowlware KL et al.; Antibiotics are among the most widely prescribed therapeutic agents in children . Several new trends in antibiotic usage for pediatric care have emerged . New mechanisms of antibacterial resistance have required a broader repertoire of antibiotic usage, including new agents directed at multidrug resistance . After promotion of judicious antibiotic use, there has been a decline in the number of pediatric prescriptions for antibiotics . Recent legislation addresses the necessity for pediatric clinical drug trials, ensuring development of further antibacterial agents for use in pediatric patients.

Infect Dis Clin North Am, 2004 Sep, 18(3), 401 - 34, vii
Antibacterial susceptibility testing in the clinical laboratory; Joyce M et al.; This article familiarizes the clinician with the principles of bacterial susceptibility testing and reporting to facilitate communication with the clinical microbiology laboratory . The emergence of resistance in nearly all commonly isolated bacterial organisms has highlighted the need for ongoing dialogue between the laboratory and those who use its services.

Pest Manag Sci, 2004 Aug, 60(8), 833 - 8
Fumigation toxicity of volatile natural and synthetic cyanohydrins to stored-product pests and activity as soil fumigants; Park DS et al.; Insecticidal fumigation toxicity of natural and synthetic cyanohydrins was evaluated with four stored-product pests: the lesser grain borer, Rhyzopertha dominica (F), the red flour beetle, Tribolium castaneum Herbst, the saw-toothed grain beetle Oryzaephilus surinamensis L, the maize weevil, Sitophilus zeamais (Motsch) and the house fly, Musca domestica L . The fumigation LC50 values were calculated by probit analysis . For house flies, all but one of the cyanohydrins tested were more potent than 1,3-dichloropropene (Telone) . Three were as efficacious as chloropicrin . For the lesser grain borer, all cyanohydrins tested were more insecticidal than dichloropropene, and all but one were more potent than chloropicrin . Four were as insecticidal as dichlorvos . The acetate of 1-cyano-1-hydroxy-2-propene (CHP-ace) was also tested in soil for antifungal and antibacterial activity, and inhibition of weed seed germination . CHP-ace reduced the total soil bacterial and fungal counts significantly, and was effective in inhibiting the germination of weed seeds in soil, indicating a broad spectrum of activity as a soil fumigant.

Nature, 2004 Aug 12, 430(7001), 764 - 8
Self-assembly of amphiphilic dendritic dipeptides into helical pores; Percec V et al.; Natural pore-forming proteins act as viral helical coats and transmembrane channels, exhibit antibacterial activity and are used in synthetic systems, such as for reversible encapsulation or stochastic sensing . These diverse functions are intimately linked to protein structure . The close link between protein structure and protein function makes the design of synthetic mimics a formidable challenge, given that structure formation needs to be carefully controlled on all hierarchy levels, in solution and in the bulk . In fact, with few exceptions, synthetic pore structures capable of assembling into periodically ordered assemblies that are stable in solution and in the solid state have not yet been realized . In the case of dendrimers, covalent and non-covalent coating and assembly of a range of different structures has only yielded closed columns . Here we describe a library of amphiphilic dendritic dipeptides that self-assemble in solution and in bulk through a complex recognition process into helical pores . We find that the molecular recognition and self-assembly process is sufficiently robust to tolerate a range of modifications to the amphiphile structure, while preliminary proton transport measurements establish that the pores are functional . We expect that this class of self-assembling dendrimers will allow the design of a variety of biologically inspired systems with functional properties arising from their porous structure.

Appl Biochem Biotechnol, 2004 Jul-Sep, 118(1-3), 283 - 92
Synthesis, characterization, and antifungal studies of transition metal complexes of omega-bromoacetoacetanilide isonicotinylhydrazone; Deepa KP et al.; Isonicotinic acid hydrazide or isonicotinylhydrazide, commonly known as isoniazid, is an antibacterial agent that has been used to treat tuberculosis . It interacts with microbial cell walls . Schiff's bases or anils are the compounds having >C=N-N< linkages, which have immense applications as catalysts, stabilizers, pigments, dyes, and drugs . They have good ability to form chelates with many metal ions . Isoniazid can form Schiff's bases with diketones such as acetoacetanilide . Acetoacetanilide isonicotinylhydrazone and its metal chelates exhibit anticancer activity . Our studies on N-methylacetoacetanilide isonicotinylhydrazone and its metal chelates revealed that they are active against pathogenic fungal strains . Hence, it is worthwhile to synthesize new complexes of ligands having different substituents on the acetoacetanilide moiety . We synthesized five new metal chelates of omega-bromoacetoacetanilide isonicotinylhydrazone . The ligand behaved as a tridentate monoanion or as a tridentate dianion in the complexes . These compounds were characterized mainly by elemental analysis; conductivity measurements; and electronic, infrared, and nuclear magnetic resonance spectral studies . We also carried out antifungal studies of these compounds against four selected pathogenic fungal strains using a cup-plate technique . Both the ligand and its metal chelates were active against all fungal strains investigated . However, the chelates were found to be more active than the ligand.

FEBS Lett, 2004 Aug 13, 572(1-3), 109 - 17
Isolation and characterization of Psalmopeotoxin I and II: two novel antimalarial peptides from the venom of the tarantula Psalmopoeus cambridgei; Choi SJ et al.; Two novel peptides that inhibit the intra-erythrocyte stage of Plasmodium falciparum in vitro were identified in the venom of the Trinidad chevron tarantula, Psalmopoeus cambridgei . Psalmopeotoxin I (PcFK1) is a 33-residue peptide and Psalmopeotoxin II (PcFK2) has 28-amino acid residues; both have three disulfide bridges and belong to the Inhibitor Cystine Knot superfamily . The cDNAs encoding both peptides were cloned, and nucleotide sequence analysis showed that the peptides are synthesized with typical signal peptides and pro-sequences that are cleaved at a basic doublet before secretion of the mature peptides . The IC(5O) of PcFK1 for inhibiting P . falciparum growth was 1.59+/-1.15 microM and that of PcFK2 was 1.15+/-0.95 microM . PcFK1 was adsorbed strongly to uninfected erythrocytes, but PcFK2 was not . Neither peptide has significant hemolytic activity at 10 microM . Electrophysiological recordings in isolated frog and mouse neuromuscular preparations revealed that the peptides (at up to 9.3 microM) do not affect neuromuscular transmission or quantal transmitter release . PcFK1 and PcFK2 do not affect the growth or viability of human epithelial cells, nor do they have any antifungal or antibacterial activity at 20 microM . Thus, PcFK1 and PcFK2 seem to interact specifically with infected erythrocytes . They could therefore be promising tools for antimalaria research and be the basis for the rational development of antimalarial drugs.

J Drugs Dermatol, 2004 Jul-Aug, 3(4), 427 - 31
The use of sulfur in dermatology; Gupta AK et al.; Sulfur has antifungal, antibacterial, and keratolytic activity . In the past, its use was widespread in dermatological disorders such as acne vulgaris, rosacea, seborrheic dermatitis, dandruff, pityriasis versicolor, scabies, and warts . Adverse events associated with topically applied sulfur are rare and mainly involve mild application site reactions . Sulfur, used alone or in combination with agents such as sodium sulfacetamide or salicylic acid, has demonstrated efficacy in the treatment of many dermatological conditions.

Yao Xue Xue Bao, 2004 Apr, 39(4), 263 - 5
{Synthesis and antibacterial activity of 2-(3-pyridyl)-5-({(5-aryl-1,3,4-oxadiazol-2-yl) methylene}thio)-1,3,4-oxadiazoles}; Hu GQ et al.; AIM: Studies on synthesis and antibacterial activity of new heterocycles . METHODS: The cyclocondensation of {(3-pyridyl)-1,3,4-oxadiazol-2-yl} thio acetic acid with various aroyl hydrazines in the presence of POCl3 and xylene gave the corresponding titled compounds, and the in vitro antibacterial activity was primarily evaluated by the method of cupplate diffusion solution . RESULTS: Sixteen novel titled compounds were synthesized, their structures were confirmed by IR, 1HNMR, MS and elemental analysis . Biological screening results demonstrated that most of the compounds prepared displayed potential antibacterial activity . CONCLUSION: Oxadiazoles incorporting pyridyl oxadiazole ring may be usefully antibacterial candidate drugs.

J Antibiot (Tokyo), 2004 May, 57(5), 311 - 5
Two new biologically active cyclopentenones from Dasyscyphus sp . A47-98; Mierau V et al.; Two new biological active cyclopentenones VM 4798-1a (1a) and VM 4798-1b (1b) were obtained as a 3:1 inseparable mixture from fermentations of Dasyscyphus sp . A47-98 . The mixture of the two isomers showed cytotoxic and weak antibacterial and antifungal properties . VM 4898-1 (2-hydroxy-3,4-dimethyl-2-cyclopenten-1-one, 4), produced by another Dasyscyphus sp . showed no significant biological activity . The structures were elucidated by NMR techniques.

Arch Ophthalmol, 2004 Aug, 122(8), 1166 - 9
Comparative efficacy of topical gatifloxacin with ciprofloxacin, amikacin, and clarithromycin in the treatment of experimental Mycobacterium chelonae keratitis; Hyon JY et al.; OBJECTIVE: To determine the comparative efficacy of topical gatifloxacin with ciprofloxacin, fortified amikacin, and clarithromycin against Mycobacterium chelonae keratitis in an animal model . METHODS: Experimental M chelonae keratitis was induced via intrastromal inoculation in a rabbit model . Thirty-five rabbits were randomly divided into 5 groups and each group was treated hourly for 12 hours with topical 0.9% balanced salt solution, 0.3% gatifloxacin, 0.3% ciprofloxacin hydrochloride, a combination of topical fortified amikacin sulfate (50 mg/mL) and clarithromycin (10 mg/mL), or a triple combination of topical 0.3% gatifloxacin, fortified amikacin sulfate (50 mg/mL), and clarithromycin (10 mg/mL) . Antibacterial efficacy of each regimen was determined by quantitative bacteriologic analysis . RESULTS: Treatment with 0.3% gatifloxacin or the triple combination of 0.3% gatifloxacin, topical fortified amikacin sulfate (50 mg/mL), and clarithromycin (10 mg/mL) reduced the number of mycobacterial organisms more significantly than the controls that were treated with a topical balanced salt solution (both P<.001) . Therapy with 0.3% gatifloxacin was more effective than 0.3% ciprofloxacin alone (P<.001) and demonstrated synergy by enhancing the efficacy of the combination of fortified amikacin (50 mg/mL) and clarithromycin (10 mg/mL) (P<.001) . Neither 0.3% ciprofloxacin nor the combination of fortified amikacin (50 mg/mL) and clarithromycin (10 mg/mL) demonstrated a significant difference in activity against mycobacteria compared with the topical balanced salt solution . CONCLUSION: These results suggest that topical 0.3% gatifloxacin ophthalmic solution can be a new initial treatment agent against M chelonae keratitis.Clinical Relevance Topical gatifloxacin 0.3% may provide an initial alternative in therapy of M chelonae keratitis.

Am J Clin Dermatol, 2004, 5(4), 211 - 6
Phototherapy in the treatment of acne vulgaris: what is its role?
Charakida A, Seaton ED, Charakida M, Mouser P, Avgerinos A, Chu AC.
Acne vulgaris is a common dermatosis affecting 80% of the population . To date, different treatments have been used to manage this condition . Antibacterials and retinoids are currently the mainstay of treatment for acne, but their success rate varies . Phototherapy is emerging as an alternative option to treat acne vulgaris.Studies examining the role of different wavelengths and methods of light treatment have shown that phototherapy with visible light, specifically blue light, has a marked effect on inflammatory acne lesions and seems sufficient for the treatment of acne . In addition, the combination of blue-red light radiation seems to be superior to blue light alone, with minimal adverse effects . Photodynamic therapy has also been used, even in nodular and cystic acne, and had excellent therapeutic outcomes, although with significant adverse effects . Recently, low energy pulsed dye laser therapy has been used, and seems to be a promising alternative that would allow the simultaneous treatment of active acne and acne scarring.Further studies are needed to clarify the role of phototherapy as a monotherapy or an adjuvant treatment in the current management of acne vulgaris.

Medicina (Kaunas), 2004, 40(8), 771 - 4
{Investigation of chemical composition of propolis extract}; Majiene D et al.; Propolis is a natural product, produced by bees and containing exudates from plants, mixed with bee wax . Propolis and its ethanolic extract are usually used for treatment and prevention of different diseases . Propolis has antibacterial, antiviral, antifungal, anti-inflammatory, anesthetic and immunomodulating properties . Till now there is no data about chemical composition of Lithuanian propolis . Thus, the aim of our work was to investigate the chemical composition of Lithuanian propolis and its ethanolic extract by using gas chromatography / mass spectrometry . We found, that the main structural types of compounds were terpenoids, aromatic and aliphatic acid esters . The most of terpenoids were mono- and sesquiterpens: azulene, alpha-bisabolol, citral, valerenol, etc . Thus, our data show, that the composition of propolis is various and depends on the origin of plants, from where propolis was collected.

Acta Crystallogr D Biol Crystallogr, 1996 Jan, 52(Pt 1), 115 - 23
Structure of a complex between bulgecin, a bacterial metabolite, and lysozyme from the rainbow trout; Karlsen S; Bulgecin, a sulfonated glycopeptide produced by Pseudomonas acidophila and Pseudomonas mesoacidophila, induces bulge formation and enhances lysis of bacterial cell walls when used in combination with beta-lactam antibiotics . The compound does not itself exhibit any antibacterial activity, but has been shown to inhibit a soluble lytic transglycosylase (SLT70) from Escherichia coli which has a lysozyme-like domain . Recently, the crystal structure of an SLT-bulgecin complex has been determined to 3.5 A resolution . We report here the crystal structure of a complex between lysozyme from the rainbow trout (RBTL) and bulgecin A at 2.0 A resolution . As for the SLT-bulgecin complex, bulgecin is bound with the glycosaminyl moiety in subsite C and the proline residue in site D of the active-site cleft of RBTL, where it makes hydrogen-bonding interactions with the catalytic residues . The taurine moiety is bound to the left side of subsites E and F in the lower part of the active-site cleft . From the observed position of the bulgecin molecule, it seems reasonable that it is an inhibitor of rainbow trout lysozyme . The lysozymes may, in general, be a target for the design of a novel type of antibiotics distinct from the beta-lactams which are insensitive to the muramidases.

Acta Crystallogr D Biol Crystallogr, 1996 Nov, 52(Pt 6), 1181 - 4
Crystallization of Escherichia coli enoyl reductase and its complex with diazaborine; Baldock C; Recent work has shown that the NADH-dependent enoyl acyl carrier protein reductase from Escherichia coli is the target for diazaborine, an antibacterial agent . This enzyme has been crystallized by the hanging-drop method of vapour diffusion complexed with NAD(+) and in the presence and absence of a thieno diazaborine . The crystals grown in the absence of diazaborine (form A) are in the space group P2(1) with unit-cell dimensions a = 74.0, b = 81.2, c = 79.0 A and beta = 92.9 degrees, and with a tetramer in the asymmetric unit, whilst those grown in the presence of diazaborine (form B) are in the space group P6(1)22 (or P6(5)22) with unit-cell dimensions a = b = 80.9 and c = 328.3 A, and with a dimer in the asymmetric unit . The structure determination of this enzyme in the presence of diazaborine will provide information on the nature of the drug binding site and contribute to a programme of rational drug design.

Acta Crystallogr D Biol Crystallogr, 1995 May, 51(Pt 3), 354 - 67
Refined crystal structure of lysozyme from the rainbow trout (Oncorhynchus mykiss); Karlsen S; Lysozymes (E.C . 3.2.1.17) are well characterized ubiquitous enzymes that have an antibacterial effect . The lysozymes from rainbow trout (RBTL) (Oncorhynchus mykiss) could be particularly interesting in aquaculture since they show higher activity than egg-white lysozyme and lysozymes from other fish species against a variety of pathogenic bacteria . Two lysozymes, I and II, differing only in a single amino acid, were purified from the kidney of rainbow trout and shown to belong to the c-type class of lysozymes . The type II form was shown to be much more potent against a variety of bacteria than the type I enzyme . We have grown crystals from a mixture containing about 80% type I and 20% type II lysozyme from rainbow trout, and solved the X-ray crystal structure . The crystals are trigonal with a = 76.68, c = 54.46 A and space group P3(1)21 . The phase problem was solved by the molecular-replacement method, and the structure was refined to an R-factor of 17.4% using data to 1.8 A resolution . The crystal structure shows that the three-dimensional structure of rainbow trout lysozyme is very similar to the previously solved structures of other c-type lysozymes . The single polypeptide of 129 amino acids is folded into two domains separated by a deep cleft which contains the active site . Secondary-structure elements, four alpha-helices and a three-stranded beta-sheet, are located in the same sequential positions as in the hen, turkey and human enzymes . The beta-sheet is found to be common for structures of both c- and g-type lysozymes . We suggest that differences in antibiotic activity of the two forms of RBTL are probably due to small differences in the hydophobicity of a small surface region.

J Med Food, 2004 Summer, 7(2), 256 - 9
Study on wound healing activity of Punica granatum peel; Murthy KN et al.; The methanolic extract of dried pomegranate (Punica granatum) peels showed the presence of a high content of phenolic compounds (44.0%) along with other constituents . This extract was formulated as a 10% (wt/wt) water-soluble gel and was studied for its wound healing property against an excision wound on the skin of Wistar rats . The activity was compared with that of a commercial topical antibacterial applicant . The wound healing activity was assessed by measuring the percent contraction in skin and estimation of collagen content in terms of hydroxyproline content . Healed skin was also subjected to histopathological studies to examine the microscopic changes . The animals treated with 2.5% gel showed moderate healing (55.8% and 40.8% healing compared with negative and positive controls, respectively), whereas the group treated with 5.0% gel showed good healing (59.5% and 44.5% healing compared with negative and positive controls, respectively) . The amount of hydroxyproline increased by twofold in the group treated with 5.0% gel . Histopathological studies also supported the wound healing on application of the gels . The group of rats that received 5.0% gel showed complete healing after 10 days, whereas in rats treated with 2.5% gel, healing was observed on day 12, in contrast to the positive control animals receiving the blank gel, which took 16-18 days for complete healing . The results of this study may be extended to different types of wounds so that the formulation could be exploited to develop it as a topical dermatological formulation . High-performance liquid chromatography analysis of the extract showed the presence of gallic acid and catechin as major components.

J Pept Sci, 2004 Jul, 10(7), 414 - 22
Structure-activity relationship of an antibacterial peptide, maculatin 1.1, from the skin glands of the tree frog, Litoria genimaculata; Niidome T et al.; Maculatin 1.1 (Mac) is a cationic antibacterial peptide isolated from the dorsal glands of the tree frog, Litoria genimaculata, and has a sequence of GLFGVLAKVAAHVVPAIAEHF-NH2 . A short peptide lacking the N-terminal two residues of Mac was reported to have no activity . To investigate the structure-activity relationship in detail, several analogs and related short peptides of Mac were synthesized . CD measurement showed that all the peptides took more or less an alpha-helical structure in the presence of anionic lipid vesicles . Analogs which are more basic than Mac had strong antibacterial and hemolytic activities, while short peptides lacking one or two terminal residues exhibited weak or no activity . Outer and inner membrane permeabilization activities of the peptides were also reduced with shortening of the peptide chain . These results indicate that the entire chain length of Mac is necessary for full activity, and the basicity of the peptides greatly affects the activity.

Berl Munch Tierarztl Wochenschr, 2004 Jul-Aug, 117(7-8), 304 - 9
Clinical efficacy of meloxicam (Metacam) and flunixin (Finadyne) as adjuncts to antibacterial treatment of respiratory disease in fattening cattle; Friton GM et al.; The clinical efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam (Metacam 20 mg/ml) and flunixin meglumine (Finadyne), as adjuncts to antibacterial therapy in the treatment of acute febrile respiratory disease in cattle was compared . The randomised blind, positive controlled study was conducted under feedlot conditions in Mexico . Overall, 201 female cattle (weighing 220-250 kg) diagnosed with bronchopneumonia at the feedlot were recruited into the study . On Day 0 all animals were treated with 20 mg oxytetracycline/kg body-weight (Bivatop 200) by subcutaneous injection, in conjunction with either meloxicam (0.5 mg/kg subcutaneously, Metacam 20 mg/ml, n = 100), or flunixin meglumine (2.2 mg/kg intravenously, Finadyne, n = 101) . According to label instructions, meloxicam was administered as a single dose, whereas flunixin meglumine could be administered daily for up to 3 consecutive days depending on the rectal temperature (with re-administration, if rectal temperature > or = 40.0 degrees C) . Rectal temperature, respiratory rate, appetite, dyspnoea, coughing, nasal discharge and general condition were recorded on Days 0 (prior to treatment), 1, 2, 3 and 7 using a weighted numerical score . Scores were summed to generate a 'Clinical Sum Score' (CSS, range 7 to 24 points) . Individual animal body weights were measured on Days 0 and 7 . Nasal swabs were collected from 10 animals per treatment group on Day 0 for microbiological culture . Clinical parameters and the mean CSS showed no significant differences between treatment groups with mean CSS on Days 0 and 7 of 16.18 and 10.55 in the meloxicam group and 16.41 and 10.88 in the flunixin meglumine group . However, a significantly lower mean rectal temperature was measured in the meloxicam group on Day 2 (p < or = 0.01) . No significant differences in mean body weights were found between groups . Repeated administration of flunixin meglumine was performed in 45% of the animals . No suspected adverse drug events related to treatments were reported . It is concluded that a single subcutaneous dose of meloxicam was as clinically effective as up to 3 consecutive daily intravenous doses of flunixin meglumine when used as an adjunctive therapy to antibacterial therapy in the treatment of acute febrile respiratory disease in feedlot cattle.

Oligonucleotides, 2004, 14(2), 80 - 9
Inhibition of ampicillin-resistant bacteria by novel mono-DNAzymes and di-DNAzyme targeted to beta-lactamase mRNA; Chen F et al.; In view of the weakness of antibiotics and the properties of antisense drugs, we applied DNAzymes to the field of drug resistance in bacteria . Two 10-23 mono-DNAzymes (Dz1, Dz2) and a di-DNAzyme (Dz1-2) targeted to beta-lactamase mRNA were designed to determine to what degree the growth of ampicillin-resistant bacteria (TEM-1, TEM-3) was inhibited . All three DNAzymes can play a role both in vitro and in vivo . In vitro, they exhibited high catalytic efficiency (kcat/KM) of 63.5, 91.1, and 30.8 pM(-1) min(-1), respectively, under multiple-turnover conditions . In vivo, after 9 hours' incubation, the degree of inhibition of Dz1, Dz2, and Dz1-2 for TEM-1 bacteria was 27.2%, 39.6%, and 57.7%, respectively, and that for TEM-3 bacteria was 39.1%, 44%, and 62.6%, respectively . Dz1-2 showed the greatest inhibiting effect, demonstrating in vivo activity may be increased by constructing multiple-target DNAzymes . The results indicated a potential possibility for DNAzymes to act as a new type of antibacterial or a tool of gene functional analysis for prokaryocytes.

Biochem J, 2004 Oct 15, 383(Pt 2), 201 - 8
Targeting the A site RNA of the Escherichia coli ribosomal 30 S subunit by 2'-O-methyl oligoribonucleotides: a quantitative equilibrium dialysis binding assay and differential effects of aminoglycoside antibiotics; Abelian A et al.; The bacterial ribosome comprises 30 S and 50 S ribonucleoprotein subunits, contains a number of binding sites for known antibiotics and is an attractive target for selection of novel antibacterial agents . On the 30 S subunit, for example, the A site (aminoacyl site) close to the 3'-end of 16 S rRNA is highly important in the decoding process . Binding by some aminoglycoside antibiotics to the A site leads to erroneous protein synthesis and is lethal for bacteria . We targeted the A site on purified 30 S ribosomal subunits from Escherichia coli with a set of overlapping, complementary OMe (2'-O-methyl) 10-mer oligoribonucleotides . An equilibrium dialysis technique was applied to measure dissociation constants of these oligonucleotides . We show that there is a single high-affinity region, spanning from A1493 to C1510 (Kd, 29-130 nM), flanked by two lower-affinity regions, within a span from U1485 to G1516 (Kd, 310-4300 nM) . Unexpectedly, addition of the aminoglycoside antibiotic paromomycin (but not hygromycin B) caused a dose-dependent increase of up to 7.5-fold in the binding of the highest affinity 10-mer 1493 to 30 S subunits . Oligonucleotides containing residues complementary to A1492 and/or A1493 showed particularly marked stimulation of binding by paromomycin . The results are consistent with high-resolution structures of antibiotic binding to the A site and with greater accessibility of residues of A1492 and A1493 upon paromomycin binding . 10-mer 1493 binding is thus a probe of the conformational switch to the 'closed' conformation triggered by paromomycin that is implicated in the discrimination by 30 S subunits of cognate from non-cognate tRNA and the translational misreading caused by paromomycin . Finally, we show that OMe oligonucleotides targeted to the A site are moderately good inhibitors of in vitro translation and that there is a limited correlation of inhibition activity with binding strength to the A site.

J Med Chem, 2004 Aug 12, 47(17), 4188 - 201
Validation of automated docking programs for docking and database screening against RNA drug targets; Detering C et al.; The increasing awareness of the essential role of RNA in controlling viral replication and in bacterial protein synthesis emphasizes the potential of ribonucleoproteins as targets for developing new antibacterial and antiviral drugs . RNA forms well defined three-dimensional structures with clefts and binding pockets reminiscent of the active sites of proteins . Furthermore, it precedes proteins in the translation pathway; inhibiting the function of a single RNA molecule would result in inhibition of multiple proteins . Thus, small molecules that bind RNA specifically would combine the advantages of antisense and RNAi strategies with the much more favorable medicinal chemistry of small-molecule therapeutics . The discovery of small-molecule inhibitors of RNA with attractive pharmacological potential would be facilitated if we had available effective computational tools of structure-based drug design . Here, we systematically test automated docking tools developed for proteins using existing three-dimensional structures of RNA-small molecule complexes . The results show that the native structures can generally be reproduced to within 2.5 angstroms more than 50-60% of the time . For more than half of the test complexes, the native ligand ranked among the top 10% compounds in a database-scoring test . Through this work, we provide parameters for the validated application of automated docking tools to the discovery of new inhibitors of RNA function .

J Med Chem, 2004 Aug 12, 47(17), 4159 - 62
Bulky nonproteinogenic amino acids permit the design of very small and effective cationic antibacterial peptides; Haug BE et al.; The rate of multidrug-resistant infections is rapidly rising . Cationic antibacterial peptides are active against resistant pathogens and have low propensity for resistance development, but because of their unfavorable medicinal properties, cationic antibacterial peptides have been a limited clinical success . We have found that introduction of nongenetically coded amino acids and other lipophilic modifications opens the opportunity for development of extremely short and highly active antibacterial peptides with improved medicinal properties .

Mikrobiyol Bul, 2004 Jan-Apr, 38(1-2), 137 - 43
{Comparison of antibacterial effects of different antiseptics after hand washing}; Bulus N et al.; The aim of this study was to compare 4% chlorhexidine gluconate, 7.5% povidone iodine and liquid soap, which are used as hand washing solutions for the immediate, cumulative and residual effects in bacterial growth . For this purpose, 18 volunteers washed their hands with 7.5% povidone iodine, 4% chlorhexidine gluconate and liquid soap by applying standard hygienic hand washing technique . In order to find out the bacterial amount in the hands of study group, glove liquid test was used . For the evaluation of immediate effects, samples were collected just after the washing procedure, for the residual effects samples were collected from gloved hands after 3 hours, and for the cumulative effects, samples were collected after 5 days with daily hand washings . It is found that the immediate effects of 4% chlorhexidine gluconate was superior than others, and 7.5% povidone iodine was superior to liquid soap . There was no difference between 4% chlorhexidine gluconate and 7.5% povidone iodine for residual effects . The cumulative effects were observed for 4% chlorhexidine gluconate and 7.5% povidone iodine, while there was no cumulative effect for liquid soap . According to these results, it can be suggested that 4% chlorhexidine gluconate can be used as a reliable antiseptic agent in the hospitals, especially for laboratories, intensive care units and operating rooms, owing to its favourable immediate, residual and cumulative effects.

Arch Pharm (Weinheim), 2004 Aug, 337(8), 427 - 33
Novel analogues of sydnone: synthesis, characterization and antibacterial evaluation; Moustafa MA et al.; New sydnone derivatives bearing a substituted phenyl ring at the 3-position have been synthesized . Two separate series of 3-(carboxyphenyl)sydnone derivatives have been prepared by cyclization of the corresponding N-nitroso-N-(carboxyphenyl)-glycine 3 . The obtained 3-(carboxyphenyl)sydnones 4 were subjected to a series of different chemical reactions on the carboxylic acid group . Compound 5, the potassium salt of 4a, was reacted with alpha-chloroacetanilide derivatives 6 to give the corresponding esters 7 . On the other hand, the acid hydrazide 9 was condensed with different aromatic aldehydes to give the corresponding arylidene derivatives 10 . The synthesized compounds were tested for their antibacterial activities against both gram-positive and gram-negative organisms . Some of the test compounds exhibited high activity; among them, 10d is considered to be a lead compound possessing high broad-spectrum antibacterial activity.

Ann Pharmacother, 2004 Oct, 38(10), 1651 - 4 Epub 2004 Aug 03.
Possible interaction between sevoflurane and Aloe vera; Lee A et al.; OBJECTIVE: To describe a patient with massive intraoperative bleeding after oral consumption of Aloe vera tablets . CASE SUMMARY: A 35-year-old woman lost 5 L of blood during surgery as a result of a possible herb-drug interaction between Aloe vera and sevoflurane . DISCUSSION: Aloe vera is a common herb used for antiinflammatory and antiarthritic activity, as well as antibacterial, hypoglycemic, and lipid-lowering effects . Compounds contained within Aloe vera can cause a reduction in prostaglandin synthesis, which may inhibit secondary aggregation of platelets . Sevoflurane inhibits thromboxane A(2) formation by suppression of cyclooxygenase activity, impairs platelet aggregation, and prolongs bleeding . Although the vascularity and size of the hemangioma were the most important factors for the massive intraoperative blood loss, concomitant use of sevoflurane and Aloe vera played a contributory role . An objective causality assessment revealed that this adverse event was possible as a result of the sevoflurane and Aloe vera interaction . CONCLUSIONS: There is a potential herb-drug interaction between Aloe vera and sevoflurane based on the antiplatelet effects of these 2 agents . Herbal medications with antiplatelet potential should be discontinued before anesthesia and surgery.

Am J Clin Oncol, 2004 Aug, 27(4), 328 - 32
Oral fluconazole for empiric treatment of prolonged Fever in neutropenic patients: prospective study in 250 consecutive patients after stem cell transplantation; Stemmer SM et al.; Neutropenic patients who continue to be febrile despite adequate broad-spectrum antibacterial treatment require empirical antifungal therapy . The aim of the present study was to evaluate the safety and efficacy of oral fluconazole for empirical antifungal therapy in neutropenic patients with persistent fever . A prospective cohort design was used . The study sample included 250 consecutive patients with high-risk stage II, III, or responding metastatic breast cancer who received high-dose chemotherapy (HDC) with autologous peripheral blood progenitor stem cell transplantation . Those with neutropenic fever lasting more than 72 hours despite broad-spectrum antibacterial coverage were treated with fluconazole . Treatment was continued until fever dropped and/or neutrophil count recovered with blood cultures remaining negative . Antifungal treatment was required in 173 patients (69%) . There were no cases of documented deep systemic fungal infection . Two patients (<1%) had positive blood cultures for fungi . None of the patients experienced toxicity related to fluconazole . There was one transplant-related death . Thirty-one patients (18%) were unable to complete the oral fluconazole protocol because of severe mucositis, and they received intravenous fluconazole at the same dose, with similar efficacy . Oral fluconazole is a safe and effective alternative to amphotericin B for empirical early antifungal treatment in persistent neutropenic fever in breast cancer patients undergoing HDC with autologous stem cell support . Further study of oral fluconazole and amphotericin B as empirical agents in other groups of patients with persistent neutropenic fever is warranted.

J Exp Med, 2004 Aug 2, 200(3), 367 - 76
Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases; Xanthoulea S et al.; Tumor necrosis factor (TNF) is a potent cytokine exerting critical functions in the activation and regulation of immune and inflammatory responses . Due to its pleiotropic activities, the amplitude and duration of TNF function must be tightly regulated . One of the mechanisms that may have evolved to modulate TNF function is the proteolytic cleavage of its cell surface receptors . In humans, mutations affecting shedding of the p55TNF receptor (R) have been linked with the development of the TNFR-associated periodic syndromes, disorders characterized by recurrent fever attacks and localized inflammation . Here we show that knock-in mice expressing a mutated nonsheddable p55TNFR develop Toll-like receptor-dependent innate immune hyperreactivity, which renders their immune system more efficient at controlling intracellular bacterial infections . Notably, gain of function for antibacterial host defenses ensues at the cost of disbalanced inflammatory reactions that lead to pathology . Mutant mice exhibit spontaneous hepatitis, enhanced susceptibility to endotoxic shock, exacerbated TNF-dependent arthritis, and experimental autoimmune encephalomyelitis . These results introduce a new concept for receptor shedding as a mechanism setting up thresholds of cytokine function to balance resistance and susceptibility to disease . Assessment of p55TNFR shedding may thus be of prognostic value in infectious, inflammatory, and autoimmune diseases.

J Exp Med, 2004 Aug 2, 200(3), 287 - 95
A contribution of mouse dendritic cell-derived IL-2 for NK cell activation; Granucci F et al.; Dendritic cells (DCs) play a predominant role in activation of natural killer (NK) cells that exert their functions against pathogen-infected and tumor cells . Here, we used a murine model to investigate the molecular mechanisms responsible for this process . Two soluble molecules produced by bacterially activated myeloid DCs are required for optimal priming of NK cells . Type I interferons (IFNs) promote the cytotoxic functions of NK cells . IL-2 is necessary both in vitro and in vivo for the efficient production of IFNgamma, which has an important antimetastatic and antibacterial function . These findings provide new information about the mechanisms that mediate DC-NK cell interactions and define a novel and fundamental role for IL-2 in innate immunity.

Bioresour Technol, 2004 Dec, 95(3), 309 - 17
Characterization of the radical scavenging activity of lignins--natural antioxidants; Dizhbite T et al.; The present work is devoted to studies of the radical scavenging properties of lignins, which are recognized as efficient antioxidants of natural origin . Radical scavenging efficiency of a series of lignins isolated from deciduous and coniferous wood species and 10 lignin related monomeric compounds were examined against 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical in homogeneous conditions using ESR and spectrophotometry methods . Some structure-activity relationships are proposed, pointing out the importance of the non-etherified OH phenolic groups, ortho-methoxy groups, hydroxyl groups and the double bond between the outermost carbon atoms in the side chain for increasing scavenger activity . Analysis of rate constants for the lignins-DPPH* interaction revealed the contribution of polymer molecular weight and pi-polyconjugation systems . The pi-conjugation systems of lignins operate as catalysts/activators of the interaction with DPPH* . Heterogeneity in terms of component composition (carbohydrate admixtures) and polydispersity is the factor which can decrease drastically the antioxidant efficiency of isolated lignins . The connection of the antibacterial effect of kraft lignin with radical scavenging activity of its soluble fraction was assumed.

J Comput Aided Mol Des, 2004 Feb, 18(2), 135 - 43
Quantitative structure-activity relationships from optimised ab initio bond lengths: steroid binding affinity and antibacterial activity of nitrofuran derivatives; Smith PJ et al.; The present day abundance of cheap computing power enables the use of quantum chemical ab initio data in Quantitative Structure-Activity Relationships (QSARs) . Optimised bond lengths are a new such class of descriptors, which we have successfully used previously in representing electronic effects in medicinal and ecological QSARs (enzyme inhibitory activity, hydrolysis rate constants and pKas) . Here we use AM1 and HF/3-21G* bond lengths in conjunction with Partial Least Squares (PLS) and a Genetic Algorithm (GA) to predict the Corticosteroid-Binding Globulin (CBG) binding activity of the classic steroid data set, and the antibacterial activity of nitrofuran derivatives . The current procedure, which does not require molecular alignment, produces good r2 and q2 values . Moreover, it highlights regions in the common steroid skeleton deemed relevant to the active regions of the steroids and nitrofuran derivatives.

J Dent Res, 2004, 83 Spec No C, C39 - 42
The continuum of dental caries--evidence for a dynamic disease process; Featherstone JD; The eventual outcome of dental caries is determined by the dynamic balance between pathological factors that lead to demineralization and protective factors that lead to remineralization . Pathological factors include acidogenic bacteria, inhibition of salivary function, and frequency of ingestion of fermentable carbohydrates . Protective factors include salivary flow, numerous salivary components, antibacterials (both natural and applied), fluoride from extrinsic sources, and selected dietary components . Intervention in the caries process can occur at any stage, either naturally or by the insertion of some procedure or treatment . Dental caries covers the continuum from the first atomic level of demineralization, through the initial enamel or root lesion, through dentinal involvement, to eventual cavitation . The dynamic balance between demineralization and remineralization determines the end result . The disease is reversible, if detected early enough . Since demineralization can be quantified at early stages, before frank cavitation, intervention methods can be tested by short-term clinical trials.

FASEB J, 2004 Aug, 18(11), 1185 - 91
Improved survival in experimental sepsis with an orally administered inhibitor of apoptosis; Weaver JG et al.; The pathophysiology of sepsis involves excessive lymphocyte apoptosis, which correlates with adverse outcomes, and disordered cytokine production, which may promote host injury . As the protease inhibitor (PI) class of antiretroviral agents is known to prevent apoptosis in vitro, we evaluated their effect on survival, lymphocyte apoptosis, and consequent cytokine production in mice with sepsis induced by cecal ligation and perforation . Mice pretreated with PIs have improved survival (67%; P<0.0005) compared with controls (17%) and a significant (P<0.05) reduction in lymphocyte apoptosis . Even mice receiving therapy beginning 4 h after perforation demonstrated improved survival (50%; P<0.05) compared with controls . PI therapy is also associated with an increase in the Th1 cytokine TNF-alpha (P<0.05) early in sepsis and a reduction in the Th2 cytokines IL-6 and IL-10 (P<0.05) late in sepsis; despite no intrinsic antibacterial effects, PI also reduced quantitative bacterial blood cultures . The beneficial effects of PI appear to be specific to lymphocyte apoptosis, as lymphocyte-deficient Rag1-/- mice did not experience benefit from treatment with PI . Thus, inhibition of lymphocyte apoptosis by PI is a candidate approach for the treatment of sepsis.

Arch Pharm Res, 2004 Jun, 27(6), 670 - 5
Preparation and characterization of enrofloxacin/carbopol complex in aqueous solution; Chun MK et al.; Since the bitter taste of enrofloxacin apparently limit the patient compliance in the oral formulations of the antibacterial agent, the masking of the taste is essential for the improvement of the therapeutic effectiveness . Therefore, this study was carried out to examine the feasibility of taste masking of enrofloxacin by the retardation of its dissolution rate using the formation of complex between the drug and Carbopol . The complexation between Carbopol and enrofloxacin was confirmed by turbidity, UV spectrophotometry, wide angle X-ray diffraction, and differential scanning calorimetry . The enrofloxacin content in the complexes was 34% (Carbo-enrofloxacin complex I) and 57% (Carbo-enrofloxacin complex II) depending on the preparation method . The dissolution rate of enrofloxacin from the complex increased as the pH was reduced . The dissolution rate of enrofloxacin from the Carbo-enrofloxacin complex I was significantly lower than that of the enrofloxacin powder . Therefore, these observations suggest that Carbo-enrofloxacin complex I can be used to mask the taste of enrofloxacin.

Mini Rev Med Chem, 2004 Aug, 4(6), 625 - 32
COX-2 selective inhibitors, carbonic anhydrase inhibition and anticancer properties of sulfonamides belonging to this class of pharmacological agents; Supuran CT et al.; The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycaemic, antithyroid, protease inhibitory and anticancer activity among others . A recently developed class of pharmacological agents incorporating primary sulfamoyl moieties in their molecule is constituted by the COX-2 selective inhibitors, with at least two clinically used drugs, celecoxib and valdecoxib . Another drug of this class, rofecoxib, does not contain sulfonamide moieties, but the isosteric and isoelectronic methylsulfone group . It was recently shown that the sulfonamide COX-2 selective inhibitors (but not the methylsulfone ones) also act as nanomolar inhibitors of several isozymes of the metallo-enzyme carbonic anhydrase (CA), some of which are strongly involved in tumourigenesis . In consequence, the potent anticancer effects of the sulfonamide COX-2 selective inhibitors and the much weaker such effects of rofecoxib, reported ultimately by many researchers, may be explained by the contribution of CA inhibition to such processes in addition to COX-2 inhibition.

Curr Med Chem, 2004 Jul, 11(14), 1921 - 49
Beta-lactams as versatile synthetic intermediates for the preparation of heterocycles of biological interest; Alcaide B et al.; Since the advent of penicillin, the beta-lactam antibiotics have been the subject of much discussion and investigation, within both the scientific and public sectors . The primary biological targets of the beta-lactam antibacterial drugs are the penicillin binding proteins, a group of transpeptidases anchored within the bacterial cellular membrane, which mediate the final step of cell wall biosynthesis . The extensive use of common beta-lactam antibiotics such as penicillins and cephalosporins in medicine has resulted in an increasing number of resistant strains of bacteria through mutation and beta-lactamase gene transfer . Thus, a handful of nonconventional fused polycyclic beta-lactams have been described in the literature in order to overcome the defence mechanisms of the bacteria . In fact, tricyclic beta-lactam antibiotics, generally referred to as trinems, are a new class of synthetic antibacterial agents featuring good resistance to beta-lactamases and dehydropeptidases . In addition, recent discoveries have shown other biological properties of these compounds apart from their antibacterial action . In this sense, beta-lactams can serve as inhibitors of serine proteases, such as human leukocyte elastase (HLE) or thrombin, acyl-CoA cholesterol acyltransferase inhibitors and inhibitors of human cytomegalovirus . Additional impetus for research efforts on beta-lactam chemistry has been provided by the introduction of the beta-lactam synthon method, a term coined by Ojima 20 years ago, according to which 2-azetidinones can be employed as useful intermediates in organic synthesis . The usefulness of beta-lactams in the stereocontrolled synthesis of heterocycles of biological significance is based on the impressive variety of transformations, which can be derived from this system, due inter alia to a high chirality content that can be transferred into a variety of products . The cyclic 2-azetidinone skeleton has been extensively used as a template on which to build the heterocyclic structure fused to the four-membered ring, using the chirality and functionalisation of the beta-lactam nucleus as a stereocontrolling element . Alternatively, the direct one-pot generation of fused nitrogen heterocyclic systems from the nitrogen framework of 2-azetidinone derivatives has been achieved by selective bond breakage and rearrangement . It is our aim in this Review to highlight the state of the art in this endeavour, consisting either of the stereocontrolled synthesis of fused polycyclic beta-lactams of antibacterial interest, or stereoselective synthesis of different sized heterocycles of biological significance . Representative examples of the latter include indolizidines, pyrrolizidines, pirrolidines, pyrroles, taxoids and macrolide natural products.

Curr Med Chem, 2004 Aug, 11(16), 2213 - 43
Advances in the discovery of novel antibacterial agents during the year 2002; Harris CR et al.; The development of bacterial resistance is a significant problem in the treatment of infection, and the importance of research directed toward the discovery of novel agents to treat infections cannot be underestimated . In the past, discovery programs have focused on modification of natural products or existing classes of marketed antibacterial agents . A significant period of time lapsed between the introduction of the nalidixic acid-based quinolones and the next novel antibacterial agent (Zyvox) . However, the advent of the "genomics era" has provided a wealth of new targets that afford the opportunity to discover novel antibacterial agents . This review reports on the state of antibacterial research directed toward the development of novel antibacterial agents with novel mechanisms of action for the calendar year, 2002 . While variations on existing drug classes continue to appear, we have chosen to limit our discussion to novel classes of antibacterial agents which have not yet been marketed.

Urol Res, 2004 Aug, 32(4), 278 - 82 Epub 2004 Jul 20.
Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats; Parlakpinar H et al.; Aminoglycoside antibiotics have long been used in antibacterial therapy . Despite their beneficial effects, aminoglycosides have considerable nephrotoxic and ototoxic side effects . It has been reported that reactive oxygen radical species (ROS) play role in the pathophysiology of aminoglycosides-induced nephrotoxicity . Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against nephrotoxicity . We investigated the effects of AG on amikacin (AK)-induced changes of renal malondialdehyde (MDA), glutathione (GSH), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) which are used to monitor the development of renal tubular damage . Morphological changes in the kidney were also examined using light microscopy . A total of 21 rats were equally divided into three groups which were: (1) injected with saline, (2) injected with AK, and (3) injected with AK + AG, respectively . AK administration to control rats increased renal MDA and decreased GSH levels . AG administration before AK injection caused significant decreases in MDA and increases in GSH levels in kidneys compared to rats treated with AK alone . The serum BUN level increased slightly, Cr and serum Alb did not change as a result of any treatment . AG tended to decrease the level of serum BUN and did not cause any change in Alb or Cr levels . Morphological changes, including glomerular, tubular epithelial alterations and interstitial edema, were clearly observed in AK-treated rats . In addition, AG reversed the morphological damage to the kidney induced by AK . The results show that AG has a protective effect on nephrotoxicity induced by AK and may therefore improve the therapeutic index of AK .

J Herb Pharmcother, 2003, 3(2), 31 - 7
Evaluation of the biological activities of crude extracts from patagonian prosopis seeds and some of their active principles; Mazzuca M et al.; Extracts of different polarities from three species and three varieties of the genera Prosopis: P . alpataco, P . denudans var . denudans, P . denudans var . patagonica, and P . denudans var . stenocarpa, were screened in order to evaluate their antibacterial, antifungal, antifeedant, antihelminthic, molluscicidal and toxic activities . The extractions of the plant materials were carried out successively with petroleum ether, dichloromethane, ethyl acetate, methanol and water . All petroleum ether extracts showed antibacterial activity . The dichloromethane extract of P . alpataco showed antibacterial and antifungal activities . Methanol and aqueous extracts of P . denudans var . denudans and P . denudans var . patagonica showed antifungal activities and a slight response to the toxicity test . Fatty acids and a group of pentacyclic triterpenes were identified as responsible for antibacterial activities in some of the active extracts.

Chem Biol Interact, 2004 Jul 20, 148(3), 101 - 13
Inhibition of proliferation and induction of apoptosis by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide in adult T-cell leukemia cells; Harakeh S et al.; Human T-cell lymphotrophic virus type-1 (HTLV-1) is a retrovirus which causes adult T-cell leukemia (ATL), an aggressive malignancy of activated T-cells . So far, there is no proven therapy for this disease . The compound 2-benzoyl-3-phenyl-6,7-dichloro quinoxaline 1,4-dioxide (DCQ) has been shown to exhibit a wide range of antibacterial activities and to induce antiproliferation and apoptosis of human colon cancer cell lines . In the present study, we investigated the in vitro effects of DCQ in HTLV-1 positive (C91-PL and HuT-102) and negative (CEM and Jurkat) malignant T-cells . The results indicate that DCQ induced growth inhibition in all four cell lines examined in a dose-dependent manner . The inhibitory effect was mainly due to the induction of apoptosis which was verified by flow cytometry analyses and ELISA-based apoptosis assays . The role of transforming growth factor (TGF) in mediating the antiproliferative and apoptotic effects of DCQ in ATL cells was investigated . Interestingly, in three of the four cell lines used, DCQ increased the TGF-beta1 transcript levels and decreased TGF-alpha mRNA, but did not induce changes in TGF-beta2 expression . DCQ treatment also induced an upregulation of p53 and p21 protein levels, key mediators of cell cycle arrest and apoptosis . The anti-apoptotic Bcl-2alpha protein level was found to be reduced . These findings indicate that DCQ inhibits the growth of ATL cell lines, at least in part, by inducing apoptosis mediated by the modulation of TGF expression, the upregulation in p53 and p21 proteins and downregulation in Bcl-2alpha expression . The present findings suggest that DCQ merits further investigation as a potential therapeutic agent for this incurable disease.

Ann Thorac Surg, 2004 Aug, 78(2), 608 - 12; discussion 608-12
Simplified treatment of postoperative mediastinitis; Merrill WH et al.; BACKGROUND: Wound infection after median sternotomy for cardiac or thoracic surgery is a serious complication . A variety of treatment plans have been advocated, and there is lack of agreement regarding the best treatment method . We present our results in patients with mediastinitis who have been treated in a simple, consistent manner . METHODS: We reviewed our experience with 40 consecutive patients with mediastinitis who were treated between January 1995 and May 2003 with a single-stage treatment consisting of sternal and soft tissue debridement and wound closure over mediastinal tubes with continuous irrigation and drainage . Tubes were placed posterior to the sternum in all patients and were irrigated continuously for at least 7 days with antibiotic or antibacterial solution . Systemic antibiotics were selected based on culture and sensitivity data and were administered for 2 to 6 weeks . RESULTS: All patients with mediastinitis treated in this manner survived . Of the 40 patients, 38 achieved complete healing of the wound without further operative intervention or major complication . One patient had recurrent infection and required sternal resection and advancement of muscle flaps . One patient had a residual localized focus of chondritis and underwent limited resection of cartilage . CONCLUSIONS: In this series of patients with postoperative mediastinitis, a simplified approach consisting of wound debridement, reclosure over drains, and anterior mediastinal irrigation has been an effective treatment . The results we have achieved suggest that this technique may be a suitable option for treating this condition.

Biomaterials, 2005 Feb, 26(5), 501 - 8
Antibacterial activity of polymeric substrate with surface grafted viologen moieties; Shi Z et al.; An asymmetric viologen, N-hexyl-N'-(4-vinylbenzyl)-4,4'-bipyridinium bromide chloride (HVV), was synthesized and graft copolymerized with commercial PET films . The surface graft concentration of HVV on the PET film is easily controlled by varying the monomer concentration used in the UV-induced graft copolymerization process . The HVV surface functionalized PET film functions as a smart window whose transmittance is reduced upon exposure to light . Concomitantly, the film possesses antibacterial activity, as shown by its bactericidal effect on Escherichia coli (E . coli) . The antibacterial activity depends on the concentration of pyridinium groups on the surface and a surface concentration of 25 nmol/cm2 on PET has been shown to be highly effective in killing the bacteria.

Eur J Med Chem, 2004 Aug, 39(8), 699 - 705
Synthesis and antibacterial activity of 2-(4-substituted phenyl)-3(2H)-isothiazolones; Khalaj A et al.; Several new and known 2-(4-substituted phenyl)-3(2H)-isothiazolone derivatives with or without chloro substituent at C-5 position were synthesized and their in vitro antibacterial activity against selected Gram-negative and Gram-positive bacteria were evaluated using agar dilution method . Most of compounds exhibited moderate to high activities against tested microorganisms, and in comparison with the reference drugs some compounds showed comparable or higher activities . In contrast to results of the previous studies, some 5-chloro derivatives showed lower or comparable activities against some tested microorganism, in comparison with analogues without C-5 substitution . In general, most of the compounds bearing electron withdrawing group at 4-position of the phenyl ring were more active against Gram-positive and most of those having piperazine derivatives were more active against Gram-negative bacteria.

Parasitol Today, 1994, 10(4), 132 - 139
The inducible antibacterial peptides of insects; Cociancich S et al.; Insects respond to bacterial challenge by the rapid and transient synthesis of a large number of potent antibacterial peptides that are active against many different bacteria . Two families of inducible antibacterial peptides are well characterized: the cecropins and the insect defensins . A rapidly increasing number of proline- and glycine-rich peptides are reported from various insect species together with cecropins and insect defensins . In this review, Stephane Cociancich, Philippe Bulet, Charles Hetru and Jules A . Hoffmann give an update of our current information on the induced antibacterial peptides.

Langmuir, 2004 Aug 3, 20(16), 6847 - 52
Surface-grafted viologen for precipitation of silver nanoparticles and their combined bactericidal activities; Shi Z et al.; A viologen, N-hexyl-N'-(4-vinylbenzyl)-4,4'-bipyridinium dinitrate (HVVN), was synthesized and subsequently graft-copolymerized on poly(ethylene terephthalate) (PET) films . Silver nanoparticles can be deposited on the surface of the HVVN-PET film through photoinduced reduction of the silver ions in salt solution . The size and distribution of the silver nanoparticles can be varied by changing the reaction time . The pyridinium groups of the HVVN graft-copolymerized on the surface of the substrate possess bactericidal effects on Escherichia coli, and this antibacterial effect can be very significantly enhanced by the incorporation of silver nanoparticles on the HVVN-PET film . The dual functionalities of HVVN and silver remain stable after prolonged immersion in phosphate buffer solution and after aging in a weathering chamber.

Klin Monatsbl Augenheilkd, 2004 Jul, 221(7), 539 - 45
{Anti-infective drug therapy in ophthalmology -- Part 1: bacterial infections}; Behrens-Baumann W; This review presents a rational antibacterial therapy . First, systemic versus topical administration of the drugs is discussed including substances specific for the respective routes . Secondly, ocular diseases requiring systemic therapy are presented followed by a discussion of infections suitable for topical administration . Finally, the pros and cons of a combined antibiotic-steroid therapy are discussed and examples described.

J Endod, 2004 Aug, 30(8), 593 - 6
Lack of genotoxicity of formocresol, paramonochlorophenol, and calcium hydroxide on mammalian cells by comet assay; Ribeiro DA et al.; Formocresol, paramonochlorophenol, and calcium hydroxide are widely used in dentistry because of their antibacterial activities in root canal disinfection . However, the results of genotoxicity studies using these materials are inconsistent in literature . The goal of this study was to examine the genotoxic potential of formocresol, paramonochlorophenol, and calcium hydroxide using mouse lymphoma cells and human fibroblasts cells in vitro by the comet assay . Data were assessed by Kruskal-Wallis nonparametric test . The results showed that all compounds tested did not cause DNA damage for the tail moment or tail intensity parameters . These findings suggest that formocresol, paramonochlorophenol, and calcium hydroxide do not promote DNA damage in mammalian cells and that the comet assay is a suitable tool to investigate genotoxicity.

J Med Microbiol, 2004 Aug, 53(Pt 8), 727 - 33
Legionella-induced acute lung injury in the setting of hyperoxia: protective role of tumour necrosis factor-alpha; Nara C et al.; Among the main characteristics of Legionella pneumophila pneumonia are acute lung injury and severe hypoxemia . Although high oxygen supplementation is a valuable supportive therapy in these patients, oxygen itself is known to be a risk factor for acute lung injury . The effects of hyperoxia on lung injury of mice with Legionella pneumonia were examined . Hyperoxia treatment reduced survival of the infected mice in an oxygen concentration- and exposure time-dependent manner . The enhanced lethality was associated with an increase in total lung weight and apoptosis markers, but not with bacterial burden in the lungs . Hyperoxia decreased the levels of the antioxidant glutathione (GSH) in infected lungs . Exogenous tumour necrosis factor-alpha (TNF-alpha) improved the survival of infected mice kept under hyperoxia . TNF-alpha effects were associated with restoration of total lung weight and histone DNA and GSH levels on day 2, whereas the lung bacterial burden did not differ significantly . Moreover, upregulation of GSH by TNF-alpha was observed in the lungs of mice without infection . These results demonstrate that hyperoxia exacerbates L . pneumophila pneumonia . The data suggest that TNF-alpha may be a potential therapeutic candidate for these individuals, not only through modulating host antibacterial systems, but also by mediating induction of the antioxidant GSH .

J Inorg Biochem, 2004 Aug, 98(8), 1271 - 83
Copper(II) Schiff base coordination compounds of dien with heterocyclic aldehydes and 2-amino-5-methyl-thiazole: synthesis, characterization, antiproliferative and antibacterial studies . Crystal structure of CudienOOCl2; Chaviara AT et al.; A new series of coordination compounds of the starting materials {Cu(dienX(2)Y(2))} and their adducts {Cu(dienXXY(2))(2a-5mt)} (where dien=diethylenetriamine, dienXX=Schiff bases of diethylenetriamine with 2-furaldehyde or 2-thiophene-carboxaldehyde, X=O, S, Y=Cl, Br, NO(3) and 2a-5mt=2-amino-5-methylthiazole) were synthesized by stepwise reactions and their structures were established by C, H, N, Cu analysis, spectroscopic, magnetic and molar conductivity measurements . The isolated compounds are monomers, paramagnetic and electrolytic compounds of the type 1:1 . In all cases, the pentadentate Schiff base (dienXX) is bonded in a tridentate fashion through the 3 N atoms . In the CudienXXY(2) compounds the coordination sphere is completed by two Cl or Br or NO(3) groups in a square pyramidal arrangement . The proposed structure for this type of compound was further supported by X-ray diffraction analysis of the compound {Cu(dienOO)Cl(2)} . Its basal plane consists of three Cu-N contacts {2.017(2), 2.025(2) and 2.012(2) A} from dienOO, and the Cl(1) atom, while the Cl(2) atom possesses the apical position, the relevant distances being 2.2732(7) A for Cu-Cl(1) and 2.6051(7) A Cu-Cl(2) . In the CudienX(2)Y(2).2a-5mt adducts the coordination sphere of copper is further completed by the nitrogen ring atom of the 2a-5mt, forming an octahedral configuration . The study of the biological activity of the compounds synthesized against a panel of different normal and cancer cell lines (MRC5, HeLa, MCF7, HT-29, OAW42, T47D) and bacteria (E . coli, B . cereus, B . subtilis) showed that the adducts of the type {Cu(dienXXY(2))(2a-5mt)} exhibit increased activity both in cancer cells and in bacteria, compared to the starting material of type {Cu(dienXXY(2))}.

Insect Mol Biol, 2004 Aug, 13(4), 399 - 405
Baculovirus and dsRNA induce Hemolin, but no antibacterial activity, in Antheraea pernyi; Hirai M et al.; Hemolin is one of the haemolymph proteins most strongly induced upon bacterial infection in Lepidoptera . When we applied RNA interference (RNAi) to suppress Hemolin expression in the Chinese oak silk moth Antheraea pernyi, we discovered that Hemolin is induced by double-stranded RNA (dsRNA) per se . As dsRNA is recognized as a virus pattern molecule, we then investigated the effect of a baculovirus (ApNPV) infection . We found that Hemolin is induced and expressed with similar kinetics as upon dsRNA injection . Notably, no Attacin gene expression or antibacterial activity was recorded . When baculovirus and high amounts of dsRNA were coinjected, the viral symptoms appeared earlier with Hemolin dsRNA than with GFP dsRNA . This indicates that silencing of hemolin affected the progress of the viral infection.

Rev Neurol (Paris), 2004 May, 160(5 Pt 1), 597 - 605
{Cerebral aspergillosis}; Tattevin P et al.; INTRODUCTION: The brain is almost always a localization of invasive aspergillosis, after hematogenous spread from pulmonary aspergillosis . Brain aspergilosis is not rare and is one of the worst prognosis factors of invasive aspergillosis . STATE OF ART: The incidence of this severe mycosis is currently on the rise due to the development of major immunosuppressive treatments . Brain aspergillosis is noteworthy for its vascular tropism, leading to infectious cerebral vasculitis, mainly involving thalamoperforating and lenticulostriate arteries, with a high frequency of thalamic or basal nuclei lesions . Extra-neurologic features that suggest this diagnosis are: i) risk factors for invasive aspergillosis (major or prolonged neutropenia, hematologic malignancies, prolonged corticosteroid treatment, bone marrow or solid organ transplant, AIDS); ii) persistent fever not responding to presumptive antibacterial treatment; iii) respiratory signs (brain aspergillosis is associated with pulmonary aspergillosis in 80 to 95 p . 100 of cases) . Perspectives . Two recent major improvements in brain aspergillosis management must be outlined: i) for diagnostic purposes, the development of testing for Aspergillus antigenemia (a non-invasive procedure with good diagnostic value for invasive aspergillosis); ii) for therapeutic purposes, the demonstration that voriconazole is better than amphotericin B in terms of clinical response, tolerance and survival, for all types of invasive aspergillosis, the benefit being probably even greater in case of brain aspergillosis because of the good diffusion of voriconazole into the central nervous system . CONCLUSIONS: Brain aspergillosis is a severe emerging opportunistic infection for which diagnostic and therapeutic tools have recently improved . Thus, this diagnostic must be suspected early, especially in the immunocompromised patient, in the event of respiratory symptoms and when the brain lesions are localized in the central nuclei and the thalamus.

Br J Community Nurs, 2004 Jun, Suppl, S21 - 7
Evaluation of a honey-impregnated tulle dressing in primary care; Stephen-Haynes J; Honey has been used for its healing properties for centuries and has been used to dress wounds with favourable results . The emergence of antibiotic resistance and growing interest in "natural" or "complementary" therapies has led to an interest in honey dressings . Much of the research to date has been related to honey's antibacterial properties . However, the healing properties claimed for honey also include stimulating new tissue growth, moist wound healing, fluid handling and promoting epithelialization . Until recently, honey had not been developed as a wound management product and was not a certified pharmaceutical device . Activon Tulle is a sterile, non-adherent dressing impregnated with Leptospermum scoparium hone . The claimed properties of honey dressings would make this a valuable addition to the dressing currently available in the primary care setting . An evaluation was undertaken involving 20 patients with a variety of wounds . A conclusion is drawn that while further research is needed, medical grade honey does appear to be a valuable addition to the wound management formulary.

Biotechnol Lett, 2004 Jun, 26(12), 953 - 7
Expression of a human lactoferrin N-lobe in Nicotiana benthmiana with potato virus X-based agroinfection; Li Y et al.; A DNA fragment encoding the N-terminal half (N-lobe) of the human lactoferrin (hLfN) gene has now been cloned into recombinant Potexvirus potato virus X (PVX) vector and expressed in Nicotiana benthmiana using agroinfection . Western blot analysis showed the recombinant protein with an apparent molecular mass on electrophoresis of ca . 40 kDa, corresponding to the predicted size of the hLfN . The yield of hLfN reached a maximum (up to 0.6% of total soluble proteins) when recombinant PVX systemically infected an entire plant . Protein extracts from infected plants had antibacterial activity.

Drug Metab Dispos, 2004 Oct, 32(10), 1162 - 9 Epub 2004 Jul 21.
Triclosan as a substrate and inhibitor of 3'-phosphoadenosine 5'-phosphosulfate-sulfotransferase and UDP-glucuronosyl transferase in human liver fractions; Wang LQ et al.; Triclosan is a broad spectrum antibacterial agent used in many household products . Due to its structural similarity to polychlorobiphenylols, which are potent inhibitors of the sulfonation and glucuronidation of 3-hydroxy-benzo{a}pyrene, it was hypothesized that triclosan would inhibit these phase II enzymes . This study was designed to assess the interactions of triclosan as a substrate and inhibitor of 3'-phosphoadenosine 5'-phosphosulfate-sulfotransferases and UDP-glucuronosyltransferases in human liver cytosol and microsomes . Triclosan was sulfonated and glucuronidated in human liver . The apparent Km and Vmax values for triclosan sulfonation were 8.5 microM and 0.096 nmol/min/mg protein, whereas Km and Vmax values for glucuronidation were 107 microM and 0.739 nmol/min/mg protein . Triclosan inhibited the hepatic cytosolic sulfonation of 3-hydroxybenzo(a)pyrene (3-OH-BaP), bisphenol A, p-nitrophenol, and acetaminophen with IC50 concentrations of 2.87, 2.96, 6.45, and 17.8 microM, respectively . Studies of 3-OH-BaP sulfonation by expressed human SULT1A1*1, SULT1A1*2, SULT1B1, and SULT1E1 showed that triclosan inhibited the activities of each of these purified enzymes with IC50 concentrations between 2.09 and 7.5 microM . Triclosan was generally a less potent inhibitor of microsomal glucuronidation . IC50 concentrations for triclosan with 3-OH-BaP, acetaminophen, and bisphenol A as substrates were 4.55, 297, and >200 microM, respectively . Morphine glucuronidation was not inhibited by 50 microM triclosan . The kinetics of 3-OH-BaP sulfonation and glucuronidation were examined in the presence of varying concentrations of triclosan: the inhibition of sulfonation was noncompetitive, whereas that of glucuronidation was competitive . These findings reveal that the commonly used bactericide triclosan is a selective inhibitor of the glucuronidation and sulfonation of phenolic xenobiotics.

Expert Opin Investig Drugs, 2004 Aug, 13(8), 1045 - 63
Preclinical evaluation of novel antibacterial agents by microbiological and molecular techniques; O'Neill AJ et al.; The defining property of an antibacterial agent is its ability to selectively interfere with bacterial growth and/or survival . Consequently, a considerable and crucial part of the preclinical evaluation of any novel antibacterial drug involves judging and characterising its effects on bacteria in vitro . These critical stages in drug development are sometimes made to appear somewhat trivial, sandwiched as they are between the highly demanding antibacterial discovery process and the formidable task of demonstrating safety and efficacy in vivo . However, careful biological evaluation in vitro is key to quantifying and understanding the basis of the antibacterial activity, providing preliminary indications and evaluations of therapeutic potential, assessing the likelihood for the development of bacterial resistance, guiding chemical refinement and assisting subsequent stages of the appraisal of any new antibacterial drug . This review covers concepts in, and strategies for, the in vitro microbiological and molecular evaluation of antibacterial drug candidates.

J Small Anim Pract, 2004 Jul, 45(7), 368 - 71
Phalangeal fractures and metacarpophalangeal luxations subsequent to post-traumatic osteomyelitis and cellulitis in a dog; Langley-Hobbs SJ et al.; A working Border collie suffered a puncture wound to the metacarpal pad . No fractures or luxations were identified at initial presentation . Treatment was instigated with various antibacterials for a period of months . At subsequent visits, the dog's condition progressed with development of metacarpophalangeal joint luxation and phalangeal fractures secondary to cellulitis and chronic osteomyelitis . Amputation was curative . Prompt treatment of the acute condition with debridement and drainage may have prevented osteomyelitis becoming established in the first instance.

J Basic Microbiol, 2004, 44(4), 317 - 9
Lignoren, a new sesquiterpenoid metabolite from Trichoderma lignorum HKI 0257; Berg A et al.; The new compound lignoren (1) was isolated from Trichoderma lignorum HKI 0257 by chromatographic methods . This metabolite has a santalane-like structure, which was elucidated by mass spectrometric and NMR spectroscopic investigations . Lignoren (1) shows a moderate narrow-spectrum of antibacterial and antifungal activity .

Minerva Stomatol, 2004 Jun, 53(6), 355 - 9
{Antibacterial effect of Nd:YAG laser in periodontal pockets decontamination: a in vivo study}; Grassi RF et al.; AIM: Tha aim of this paper is to assess the effects in vivo of the Nd: Yag laser on gingival microflora in patients periodontally at risk . METHODS: An investigation has been carried out on 5 patients suffering from serious periodontal disease, with a sub-gingival check-up a week after the treatment . The selected patients presented either a relapse after the raising of a traditional flap, or showed acute phenomena and were, therefore, treated with a laser with the propedeutic intention of surgery; or they refused traditional surgical therapy or presented systematic pathologies that could not be included in the appropriate protocol . Pockets were chosen that had a probe depth of between 5-8 mm, an optic fibre probe was pushed as far as possible into the probe depth, for about 1 minute per site, 5 times, at 30 second intervals . The samples, taken in order to calculate bacteria colonies, were carried out before using the laser, immediately after and, again, 1 week later . RESULTS: All the sites showed a slight reduction in the quantity of colonies forming immediately after the Nd:Yag laser application, while a week later, only if clinical inflammation appeared to be resolved, the bacteria forming colonies seemed to be reduced . CONCLUSION: From this study it can be concluded that the use of the Nd:Yad laser represents, in mild and average periodontitis, a therapeutic aid to scaling and root planing and, in the same way, in serious periodontitis for traditional surgical therapy.

Curr Med Res Opin, 2004 Jul, 20(7), 969 - 80
Hospitalization rates among patients with community-acquired pneumonia treated with telithromycin vs clarithromycin: results from two randomized, double-blind, clinical trials; Niederman MS et al.; AIMS: To compare hospitalization rates among patients with community-acquired pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on pooled data from two randomized, double-blind, multinational clinical trials . PATIENTS AND METHODS: Adult patients with CAP eligible for oral therapy (Study 1, n = 448; Study 2, n = 575) received telithromycin 800 mg once daily for 10 (Study 1, 2-arms), 5 or 7 (Study 2, 3-arms) days, or clarithromycin 500 mg twice daily for 10 days . Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use, as well as CAP-related length of hospital stay and hospitalization costs, were compared by treatment group (intent to treat populations) up until the late post-therapy visit (Days 31-36) . Study investigators blinded to treatment regimen assessed whether hospital admissions were CAP related . RESULTS: Despite equivalent clinical efficacy for telithromycin vs clarithromycin in the clinically evaluable per-protocol populations (n = 784) (88.8% {428/482} vs 90.1% {272/302}--difference: -1.3%; 95% CI: -6.0, 3.4), telithromycin treatment for 5, 7, or 10 days was associated with significantly fewer CAP-related hospitalizations (p = 0.023) and CAP-related hospital days (p = 0.025) vs clarithromycin (reduction of 2.3 hospitalizations and 23.4 hospital days per 100 patients) . Accordingly, estimated CAP-related hospitalization costs were significantly lower (p = 0.025) for telithromycin recipients (30,231 US dollars less per 100 patients) . CAP-related hospitalizations, duration of hospital stay, and hospitalization costs for 7- to 10-day telithromycin--the approved dosing regimen for CAP--were significantly lower (p = 0.023, 0.025, and 0.025, respectively) than for clarithromycin . CONCLUSIONS: Data from this study indicate that telithromycin 800 mg once daily for 5, 7, or 10 days provides an effective therapy for patients with CAP, and may be associated with fewer CAP-related hospitalizations and hospital days than clarithromycin 500 mg twice daily for 10 days . Treatment with telithromycin could, therefore, potentially translate into cost savings in the management of CAP.

Acta Crystallogr C, 2000 Mar 15, 56(Pt 3), E115 - 6 Epub 2000 Mar 15.
Sparfloxacin, an antibacterial drug; Sivalakshmidevi A et al.; The title compound, sparfloxacin or cis-5-amino-1-cyclopropyl-7-(3,5-dimethylpiperazin-1-yl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid trihydrate, C(19)H(22)F(2)N(4)O(3).3H(2)O, is an antibacterial drug . The molecule, which crystallizes as a trihydrate, is in the zwitterionic form in the solid state . Hydrogen bonds stabilize the molecules in the lattice.

Clin Ther, 2004 Jun, 26(6), 915 - 24; discussion 904
Review of antibiotic drug use in a surgical ICU: management with a patient data management system for additional outcome analysis in patients staying more than 24 hours; Hartmann B et al.; BACKGROUND: A number of developments have been made in computerized patient data management systems (PDMSs), making them of interest to medical and nursing staff as a means of improving patient care . OBJECTIVES: The aim of this study was to assess the capability of a PDMS to record and provide drug-administration data and to investigate whether the PDMS may be used as a means of support for clinical audits and quality control . Furthermore, we assessed whether antibiotic therapy as a surrogate for infections correlates with hospital mortality in patients staying >24 hours in a surgical intensive care unit (SICU) . METHODS: Because of its medical and economic importance in ICU treatment, we chose to use the field of antibiotic therapy as an example . A PDMS was used in a 14-bed SICU (Department of Anesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Giessen, Giessen, Germany) to record relevant patient data, including therapeutic, diagnostic, and nursing actions . During a 15-month period (April 1, 2000 to June 30, 2001), antibiotic drug therapy was electronically analyzed and presented using the anatomic therapeutic chemical (ATC) category for antibacterials (ATC group, J01) with daily defined doses . Furthermore, the correlation of antibiotic therapy with patient outcome (hospital mortality) was tested using logistic regression analysis . RESULTS: A total of 2053 patients were treated in the SICU . Of these, 58.0% (1190 patients) received antibiotics (4479 treatment days; 13,145 single doses) . Cephalosporins (ATC category, J01DA) were used most frequently (1785 treatment days {39.9% of treatment days}), followed by combinations of penicillins with beta-lactam inhibitors (ATC category, J01CR; 1478 treatment days {33.0%}) and imidazole derivatives (ATC category, J01XD; 667 treatment days {14.9%}) . The antibiotic therapy lasted <3 days in 65.6% of cases . In 13.8% of cases, the treatment lasted >1 week . A total of 36.7% of cases were treated with only 1 antibiotic agent, 14.1% were given a combination of 2, and 7.2% were given a combination of > or =3 antibiotic agents . Seven hundred twenty-six patients remained in the SICU for >24 hours; 143 (19.7%) died during their hospital stay; 110 (15.2%) in the SICU . The duration of antibiotic therapy (odds ratio {OR}, 1.46) and number of different antibiotic drugs used (OR, 2.15) significantly correlated with hospital mortality . CONCLUSIONS: Antibiotic therapy in a SICU can be assessed and analyzed in detail using a PDMS . Furthermore, in this study, the duration of antibiotic therapy and the number of antibiotic agents used correlated with hospital mortality . In further developing PDMSs, it is important for quality-assurance purposes to document the reasons for giving antibiotics and for changing prescriptions . It would also be helpful to integrate certain therapy standards and reminder functions for the duration of therapy in the PDMS.

Vet Immunol Immunopathol, 2004 Sep, 101(1-2), 123 - 30
Impairment of oxidative burst in porcine neutrophils induced by pseudorabies virus; Yang JW et al.; Industrial swine production is affected by several serious viral diseases, such as pseudorabies, hog cholera, porcine reproductive and respiratory syndrome, which are frequently complicated with the increased incidence of bacterial complications such as Actinobacillus pleuropneumoniae (APP) . This clinical observation is suggestive of a virus-bacteria synergism on the pathogenesis . One hypothesis is that viruses induce polymorphonuclear cell (PMNs, primarily neutrophils) dysfunction resulting in defective antibacterial resistance . The purpose of this study was to use the pseudorabies virus (PrV) as a model to explore the possibility of virus-induced PMN dysfunctions in pigs . The goals were to evaluate, in ex vivo settings, the oxidative burst (OB) function of pig PMNs, and to evaluate whether PrV could affect these responses to APP . We found that PrV served as a mild OB stimulant (2-fold) to pig PMNs, which also launched a significant burst to phorbol 12-myristate 13-diacetate (PMA; 61-fold), to non-opsonized, heat-killed and formaldehyde-fixed APP (8-fold), and to normal pig serum-opsonized APP (34-fold) . Interestingly, the PMA-induced OB could be reduced 50-70% by preincubating PMNs with PrV, and the critical target was not likely the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase itself . Inactivated PrV was as efficient as viable PrV at exerting the inhibitory effect . On the other hand, PrV exerted a primarily additive effect on APP-induced OB, when the cytotoxic effect of APP on PMNs was avoided . The current finding suggests the possibility that activated PMNs are susceptible to PrV-induced dysfunction, and that the PrV-APP synergism may require upstream stimuli of PMNs to be initiated.

Fitoterapia, 2004 Jul, 75(5), 510 - 3
Antibacterial activity and cytotoxicity of extractives from Ravenia spectabilis; Sohrab MH et al.; A methanolic extract of Ravenia spectabilis, an isolated alkaloid, arborinine plus a fraction comprising arborinine and gamma-fagarine (VLC), showed mild to significant in vitro antibacterial activity . In a brine shrimp lethality bioassay, the extract and the fraction were found to exhibit moderate cytotoxicity having LC50 of 76.26 microg/ml and 14.98 microg/ml, respectively.

Fitoterapia, 2004 Jul, 75(5), 494 - 6
Antibacterial activity of Galeola foliata; Khan MR et al.; Galeola foliata leaves and stem bark were successively extracted with petrol, dichloromethane, ethyl acetate, butanol and methanol . A broad spectrum antibacterial activity (24 bacteria and protozoan) was exhibited by both parts . A very good level of activity was demonstrated by the CH2Cl2 and EtOAc fractions . None of the fractions were active against the moulds.

Fitoterapia, 2004 Jul, 75(5), 451 - 6
Anti-Helicobacter pylori metabolites from Rhizoctonia sp . Cy064, an endophytic fungus in Cynodon dactylon; Ma YM et al.; A new benzophenone, named rhizoctonic acid (1), together with three known compounds monomethylsulochrin (2), ergosterol (3) and 3beta,5alpha,6beta-trihydroxyergosta-7,22-diene (4) were isolated through bioassay-guided fractionations from the culture of Rhizoctonia sp . (Cy064), an endophytic fungus in the leaf of Cynodon dactylon . The structure of the new acid 1 was elucidated to be 5-hydroxy-2-(2-hydroxy-6-methoxy-4-methylbenzoyl)-3-methoxybenzoic acid by a combination of spectral analyses . Furthermore, the structure of monomethylsulochrin 2 was confirmed by 13C-NMR analysis . All four metabolites were subjected to a more detailed in vitro assessment of their antibacterial action against five clinically isolated and one reference (ATCC 43504) Helicobacter pylori strains.

Bioorg Med Chem Lett, 2004 Aug 16, 14(16), 4213 - 6
Synthesis of 7 alpha- and 7 beta-spermidinylcholesterol, squalamine analogues; Choucair B et al.; Stereoselective synthesis of squalamine dessulfates analogues, 7 alpha and 7 beta-N-{3N-(4-aminobutyl) aminopropyl}aminocholesterol are reported, using 7 alpha and 7 beta-aminocholesterol as a key intermediate . It's the first example in which the position of spermidine is modified at the steroid ring . These molecules showed a comparable antibacteria and fungi activities to squalamine . Then, they have a cytotoxic activity on a human non-small cell bronchopulmonary carcinoma line (NSCLC-N6).

Indian J Exp Biol, 2004 Jun, 42(6), 589 - 94
Antibacterial and antidiarrhoeal effects of alkaloids of Holarrhena antidysenterica WALL; Kavitha D et al.; The alkaloids from the ethanolic extract of H . antidysenterica seeds were evaluated for their antibacterial activity against clinical isolates of enteropathogenic Escherichia coli (EPEC) in vitro, and their antidiarrhoeal activity on castor oil-induced diarrhoea in rats, in vivo . The plasmid DNA, whole cell lysate and outer membrane protein profile of a clinical isolate of EPEC was determined in presence of alkaloids of H . antidysenterica . The disc diffusion and agar well diffusion methods were used to evaluate the antibacterial efficacy . The alkaloids showed strong antibacterial activity against EPEC strains . In castor oil-induced diarrhoea, alkaloids reduced the diarrhoea with decrease in the number of wet faeces in pretreated rats at a dose of 200-800 mg/kg . The loss of plasmid DNA and suppression of high molecular weight proteins were observed on alkaloids treatment . Taking into account the multiple antibiotic resistance of EPEC, the results suggest usefulness of alkaloids of H . antidysenterica seeds as antibacterial and antidiarrhoeal agents.

Biol Pharm Bull, 2004 Jul, 27(7), 1116 - 20
Evaluation of synergism between the aminoglycoside antibiotic streptomycin and the cardiovascular agent amlodipine; Asok Kumar K et al.; Amlodipine, a cardiovascular drug, exhibited remarkable antibacterial action in vitro against 504 bacterial strains belonging to both Gram positive and Gram negative genera, as well as in vivo against a mouse-virulent bacterium . Based on such findings, the present study was undertaken to determine whether the efficacy of this non-antibiotic drug could be enhanced in the presence of any antibiotic . Twelve bacterial strains, sensitive to amlodipine as well as to 6 antibiotics, viz., benzyl penicillin, streptomycin, chloramphenicol, tetracycline, erythromycin and ciprofloxacin were chosen . Disc diffusion test with amlodipine and streptomycin revealed marked synergism between the combination, compared with their individual effects . The synergism was found to be statistically significant (p<0.01) . To assess the degree of synergy, the checkerboard analysis was performed . The fractional inhibitory concentration (FIC) index of this combination turned out to be 0.24, which confirmed synergism . This antibiotic-non-antibiotic pair was then administered to mice, challenged with S . typhimurium to determine whether this was effective in vivo . Statistical analysis of the mouse protection tests suggested that the combination was highly synergistic (p<0.001), according to Student's t-test . This synergistic drug combination may help us in enhancing the scope of prolonged antibiotic therapy in various types of infections, and might open a new therapeutic approach to combat drug resistance in bacterial diseases.

Toxicol In Vitro, 2004 Oct, 18(5), 581 - 92
6-Aminoquinolones: photostability, cellular distribution and phototoxicity; Viola G et al.; Three selected aminoquinolones endowed with a potent antibacterial (compounds 1 and 2) and antiviral activity (compound 3) have been evaluated for their phototoxic properties in vitro . Photostability studies of these compounds indicate that compound 3 is photostable whereas compound 1 and in particular, compound 2 are rapidly photodegraded upon UVA irradiation, yielding a toxic photoproduct . Intracellular localization of these compounds has been evaluated by means of fluorescence microscopy using tetramethylrhodamine methyl ester and acridine orange, which are specific fluorescent probes for mitochondria and lysosomes, respectively . No co-staining was observed with lysosomal stain for all the test compounds . On the contrary compound 3 was found to be specifically incorporated in mitochondria . The compounds exhibited remarkable phototoxicity in two cell culture lines: human promyelocytic leukaemia (HL-60) and human fibrosarcoma (HT-1080) . The quinolone-induced photodamage was also evaluated measuring the photosensitizing cross-linking in erythrocyte ghost membranes, the strand breaks activity and oxidative damage on plasmid DNA . The results show that these derivatives are able to photoinduce crosslink of erythrocytes spectrin, whereas do not significantly photocleavage DNA directly, but single strand breaks were observed after treatment of photosensitized DNA with two base excision repair enzymes, Fpg and Endo III respectively.

Pharmacoeconomics, 2004, 22(11), 751 - 7
Resource use and cost of care for patients hospitalised with community acquired pneumonia: impact of adherence to infectious diseases society of america guidelines; Orrick JJ et al.; OBJECTIVE: The objective of this study was to compare the inpatient resource use and cost of care for patients hospitalised with community-acquired pneumonia (CAP) who were treated with preferred antibacterial therapy according to the 1998 Infectious Diseases Society of America (IDSA) guidelines with those who were not treated with preferred therapy . METHODS: A multicentre, observational study was conducted in Florida between 1999 and 2000 . Hospitalised adult patients (aged > or = 18 years) started on antibacterial therapy for suspected or confirmed CAP were enrolled in the study . Data collected included patient demographic characteristics, pneumonia risk class, resource use (pharmacy, laboratory, radiology, respiratory services, hospital room and board) and economic data . Risk classification according to Fine et al.'s criteria was determined for each patient . Patient's antibacterial therapy was classified as being preferred or non-preferred according to the 1998 IDSA guidelines . Resource utilisation and cost of care were compared between these two groups . RESULTS: Ninety-nine patients were enrolled in the study . The average age was 60.6 years +/- 20.5 years . The percentage of patients in each risk class (according to Fine et al.) were 11.1% in class I, 39.4% in class II, 29.3% in class III, 16.2% in class IV and 4% in class V.The mean cost of hospitalisation per admission (excluding physician cost) was US 3,490 dollars +/- US 3,058 dollars (median US 2,430 dollars) with hospital room/board accounting for the largest percentage (83.7%), followed by laboratory (8.1%), antibacterial (4.6%), radiology (2.6%) and respiratory (0.9%) cost centres {year 2000 values} . The majority of patients (75.8%) received preferred antibacterials according to the IDSA guidelines . The group treated with preferred antibacterials had a shorter mean length of hospital stay (4.5 vs 6.8 days, p = 0.002), a lower total cost of hospitalisation (mean US 3,009 dollars +/- US 2,682 dollars vs US 4,992 dollars +/- US 3,686 dollars; median US 2,047 dollars vs US 3,805 dollars, p = 0.021) and lower antibacterial costs (mean US 117 dollars +/- US 79 dollars vs US 301 dollars +/- US 409 dollars; median US 97 dollars vs US 171 dollars, p = 0.038) compared with patients who did not receive preferred therapy . CONCLUSION: Implementation of protocols according to IDSA guidelines may result in cost savings to institutions wishing to reduce the economic burden associated with treating hospitalised patients for CAP.

Pharmacoeconomics, 2004, 22(11), 719 - 40
Economic aspects of pneumococcal pneumonia: a review of the literature; De Graeve D et al.; In this review, the economic aspects of pneumococcal pneumonia are analysed, including the costs, cost effectiveness and cost benefit of treatment and prevention . We identified eight cost-of-illness studies, 15 analyses comparing the costs of different treatment options and 15 economic evaluations of prevention that met our search criteria . The studies were conducted largely in Europe and the US . Most pertained to community-acquired pneumonia (CAP) in general, without specific analysis of pneumococcus-related illness . Many of the studies were considered to be of poor quality for the following reasons: comparison without randomisation or control variables, disregard of health outcomes, small sample size, restriction of costs to drug costs and vague or disputable sources of cost information . In the US, hospitalisation costs resulting from CAP can be estimated to be between US 7,000 dollars and US 8,000 dollars per admission or US 4 million dollars per 100,000 population . Hospitalisation costs are significant (representing about 90% of total costs), but are much lower in Europe than in the US (one-third to one-ninth of the US estimates in the UK and Spain, respectively) . In general, economic studies of treatment for pneumococcal pneumonia are in line with clinical evidence . A drug with proven clinical effectiveness would also appear to be supported from an economic stand point . Furthermore, economic data support an early switch from an intravenous to an oral antibacterial, the use of quinolones for inpatients with CAP, and also the use of guidelines built on clinical evidence . Of all the possible preventive strategies for pneumococcal pneumonia, only vaccination has been subjected to economic evaluation . Pneumococcal polysaccharide vaccine seems relatively cost effective (and potentially cost saving) for those between 65 and 75 years of age, for military recruits and for HIV positive patients with a sufficiently high CD4 cell count . Evaluations of the pneumococcal conjugate vaccine (PCV) indicate the price of the vaccine to be the main determinant of cost effectiveness . As the current price is high (in the order of US 50 dollars per dose), the economic attractiveness of the universal PCV vaccination strategies hinges on the potential for price reductions and the willingness of decision makers to adopt a societal perspective.

Spectrochim Acta A Mol Biomol Spectrosc, 2004 Jul, 60(8-9), 1917 - 24
Tautomeric structures, electronic spectra, acid-base properties of some 7-aryl-2,5-diamino-3(4-hydroxyphenyazo)pyrazolo{1,5-a}pyrimidine-6-carbonitriles, and effect of their copper(II) complex solutions on some bacteria and fungi; Rageh NM; Infrared and electronic spectra were used to investigate the tautomerism of some azo compounds, in both the solid and solution states . It was found that the compounds exist in azo<==>hydrazone tautomeric equilibrium in solid and in solutions . The different bands displayed in the electronic spectra of the compounds in various organic solvents are assigned to the suitable electronic transitions . The solvatochromic behavior of the compounds was investigated by studying their visible spectra in pure and mixed organic solvents . DeltaG and formation constant, Kf, values of the molecular complexes formed in solution have been determined . Effect of concentration of the compounds in DMF and EtOH solutions has been investigated . The basicity and acidity constants of the different compounds were determined from the spectra of these compounds in aqueous-ethanolic solutions of varying pH values . Some complexes of copper(II) with these compounds in solution were tested as for their antibacterial and antifungal activity.

Nat Prod Res, 2004 Oct, 18(5), 397 - 401
A new approach towards ikimine A analogues; Krauss J et al.; An analogon of the alkylpyridine alkaloid ikimine A (1) was prepared in six steps starting from undec-10-ynoic acid . A key step in this synthesis was a Sonogashira coupling of the alkyne and 3-iodopyridine, followed by hydrogenation of the alkyne, reduction of the ester to the primary alcohol and oxidation to the corresponding aldehyde . This aldehyde was converted to the ikimine A analogon with O-methyl hydroxylamine hydrochloride . This product and the intermediate alkylpyridines were tested in the agar diffusion assay for antibacterial and antifungal activities.

Asian Pac J Cancer Prev, 2004 Apr-Jun, 5(2), 196 - 204
Comparative evaluation of antiproliferative activity and induction of apoptosis by some fluoroquinolones with a human non-small cell lung cancer cell line in culture; Mondal ER et al.; Lung cancer is the leading cause of cancer- related death in the world today . Since the effective management of drug resistant lung cancer, and particularly non-small cell lung carcinomas is a major problem, attempts need to be made to identify new potential anticancer drugs that can kill non-small cell lung cancer cells efficiently . In the present study, a human non-small cell lung carcinoma NCI-H460 cell line was used to evaluate the antiproliferative activity of Fluoroquinolones like Enoxacin, Norfloxacin, Ciprofloxacin and Levofloxacin . As determined by Sulphorodhamine B assay (SRB assay), all Fluoroquinolones caused cellular growth inhibition in a concentration and time-dependent manner . Enoxacin was found to be the most effective Fluoroquinolone followed by Norfloxacin, Ciprofloxacin and Levofloxacin . Growth inhibitory effects were also found to be independent of the concentrations of serum growth factors in culture medium or variation of initial cell seeding density and proved to be irreversible in nature . Appearance of rounded cells with altered morphology and cell surface blebbing indicated cell killing by apoptosis . Cell shrinkage, nuclear condensation & fragmentation, and cytoplasmic blebbing as indicated by MGG staining confirmed this to be the case . Thus, this investigation clearly demonstrated that the NCI-H460 human non-small cell lung carcinoma cell line is highly sensitive to Fluoroquinolone treatment . The Fluoroquinolones used in this study which are clinically used as antibacterial agents, can also inhibit tumor cell growth suggesting their potential use in a strategy for cancer treatment which might help in controlling cancer.

J Infect Dis, 2004 Aug 1, 190(3), 519 - 26 Epub 2004 Jun 30.
Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza; McCullers JA; Secondary bacterial pneumonia is an important cause of influenza-associated death . Although antibacterial therapy is standard, antiviral therapy has been ignored because viral infections usually resolve by the time bacterial pneumonia presents . In the present study, antiviral compounds were tested in a mouse model of secondary pneumococcal pneumonia after influenza . Treatment with oseltamivir improved survival in mice from 0% to 75%, even when therapy was delayed for up to 5 days after infection with influenza virus . In mice, treatment with rimantadine had no effect on survival . Treatment with ampicillin cleared infection but, in the absence of treatment with oseltamivir, did not improve survival . Pneumonia developed in only 7 of the 22 mice receiving oseltamivir, and subsequent treatment with ampicillin resulted in cure (100% survival) . Treatment of the predisposing influenza-virus infection with inhibitors specific for the viral neuraminidase may improve the efficacy of antibiotics and increase survival in persons who are at high risk for complications and mortality during influenza.

J Antimicrob Chemother, 2004 Aug, 54(2), 524 - 8 Epub 2004 Jul 08.
No significant decrease in antibiotic use from 1992 to 2000, in the French community; Sommet A et al.; OBJECTIVES: To analyse trends in antibiotic exposure of the French population from 1992 to 2000 . METHODS: The analysis used data provided by a representative annual nationwide survey of health care consumption in the community . RESULTS: The frequency of antibiotic use increased from 4.7 per 100 person-months in 1992 to 7.3 in 1995, and remained stable from 1998 to 2000 . Children under 7 years of age were three times more strongly exposed to antibiotics than older subjects . Respiratory tract infections of probable viral aetiology and sore throat accounted for >50% of antibacterial prescriptions . CONCLUSIONS: We identified two major priorities for campaigns designed to reduce antibiotic exposure of the French population in the community, namely respiratory tract infections of presumed viral origin, and children under 7 years of age.

Clin Diagn Lab Immunol, 2004 Jul, 11(4), 742 - 51
Bacterial clearance and cytokine profiles in a murine model of postsurgical nosocomial pneumonia; Manderscheid PA et al.; The development of a nosocomial pneumonia is facilitated by alterations in host innate pulmonary antibacterial defenses following surgical trauma, which can result in decreased pulmonary bacterial clearance and increased morbidity and mortality . In a murine model of postoperative nosocomial infection, surgical stress (laparotomy) decreased Escherichia coli clearance from the lungs of animals that underwent surgery . Consistent with previous studies, (i) pulmonary levels of tumor necrosis factor alpha at 6 h and of interleukin-1beta (IL-1beta), IL-6, and gamma interferon (IFN-gamma) at 24 h post-bacterial infection (PBI) were decreased in animals that underwent laparotomy 24 h prior to E . coli infection (LAP/E . coli) compared to animals that received E . coli only; (ii) KC and macrophage inhibitory protein 2 were elevated at 6 h PBI in LAP/E . coli animals compared to E . coli-only animals; however, at 24 h PBI, levels were higher in the E . coli-only group; (iii) at 24 h PBI, monocyte chemoattractant protein 1 was lower in the LAP/E . coli group compared to the E . coli-only group; (iv) IL-10 levels were unaffected at all time points evaluated; and (v) the total number of neutrophils present in the lungs of LAP/E . coli animals at 6 h PBI was decreased in comparison to that in E . coli-only animals, resulting in decreased bacterial clearance and increased mortality in LAP/E . coli animals by 24 h PBI . Similar changes in cytokine profiles, pulmonary bacterial clearance, and mortality were consistent with reported findings in patients following surgical trauma . This model, therefore, provides a clinically relevant system in which the molecular and cellular mechanisms that lead to the development of nosocomial pneumonia can be further explored.

Structure (Camb), 2004 Jul, 12(7), 1257 - 68
The solution structure of type III effector protein AvrPto reveals conformational and dynamic features important for plant pathogenesis; Wulf J et al.; Pseudomonas syringae pv . tomato, the causative agent of bacterial speck disease of tomato, uses a type III secretion system (TTSS) to deliver effector proteins into the host cell . In resistant plants, the bacterial effector protein AvrPto physically interacts with the host Pto kinase and elicits antibacterial defense responses . In susceptible plants, which lack the Pto kinase, AvrPto acts as a virulence factor to promote bacterial growth . The solution structure of AvrPto reveals a functional core consisting of a three-helix bundle motif flanked by disordered N- and C-terminal tails . Residues required for Pto binding lie in a 19 residue Omega loop . Modeling suggests a hydrophobic patch involving the activation loop of Pto forms a contact surface with the AvrPto Omega loop and that helix packing mediates interactions between AvrPto and putative virulence targets Api2 and Api3 . The AvrPto structure has a low stability that may facilitate chaperone-independent secretion by the TTSS.

Z Naturforsch {C}, 2004 Mar-Apr, 59(3-4), 244 - 8
Oxygenated bisabolane fucosides from Carthamus lanatus L; Mikhova B et al.; The aerial parts of Carthamus lanatus (Asteraceae) afforded four new oxygenated bisabolane fucosides, 10-hydroperoxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside, 11-hydro-peroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside, 10-hydroxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside and 11-hydroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside together with the known compounds a-bisabolol beta-D-fucopyranoside, asperuloside, sitosterol 3-O-beta-D-glucoside and stigmasterol 3-O-beta-D-glucoside . Asperuloside appears to be the second representative of the iridoid monoterpene group found in the plant family Asteraceae, which until recently was considered to lack iridoids . The main constituent a-bisabolol fucoside exhibited noticeable antibacterial and cytotoxic activities.

J Biomed Biotechnol, 2004, 2004(2), 93 - 98
Novel Marine Compounds: Anticancer or Genotoxic?
Arif JM, Al-Hazzani AA, Kunhi M, Al-Khodairy F.
In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials . But till date only few anticancer drugs (cytarabine, vidarabine) have been commercially developed from marine compounds while several others are currently in different clinical trials . Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials . This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers.

Hepatogastroenterology, 2004 Jul-Aug, 51(58), 941 - 5
Ceftriaxone is twice as cost-effective as standard therapy in biliary tract infection; Zoepf T et al.; BACKGROUND/AIMS: Various antibiotics, mainly cephalosporins and broad-spectrum penicillins, are indicated in biliary tract infection . The primary endpoint was to compare the cost-effectiveness of ceftriaxone (Rocephin) 1 g once daily vs . standard therapy two or three times daily . METHODOLOGY: A prospective multicenter observational study, matched-pair analysis of 902 patients receiving ceftriaxone or standard therapy (second-generation cephalosporin, broad-spectrum penicillin or a combination of aminopenicillin and beta-lactamase inhibitor) in 75 hospitals yielded 173 pairs matched for definite risk criteria . Both groups received comparable accompanying endoscopic antiobstructive treatment . Cost parameters included primary antibiotic purchase, total antibiotic purchase (including combination and second-line drugs), and infusion preparation and administration . RESULTS: 87.9% of patients in the ceftriaxone group vs . 73.4% in the standard group received antibacterial monotherapy, for 7.5 vs . 9.1 days respectively (p=0.001) . Therapy was equally effective in both groups . Overall treatment costs, including antibiotic purchase and infusion preparation/administration, were 170.84 vs . 320.46, respectively (p=0.0001) . CONCLUSIONS: Ceftriaxone 1 g once daily is approximately twice as cost-effective as standard therapy in biliary tract infection: lower concomitant medication costs, a shorter treatment course, and lower antibiotic administration costs achieved an approximate 50% saving.

J Am Anim Hosp Assoc, 2004 Jul-Aug, 40(4), 270 - 84
Correlations of Fatty Acid supplementation, aeroallergens, shampoo, and ear cleanser with multiple parameters in pruritic dogs; Nesbitt GH et al.; Seventy-two pruritic dogs were fed one of four diets controlled for n-6:n-3 fatty acid ratios and total dietary intake of fatty acids . Multiple parameters were evaluated, including clinical and cytological findings, aeroallergen testing, microbial sampling techniques, and effects of an anti-fungal/antibacterial shampoo and ear cleanser . Significant correlations were observed between many clinical parameters, anatomical sampling sites, and microbial counts when data from the diet groups was combined . There were no statistically significant differences between individual diets for any of the clinical parameters . The importance of total clinical management in the control of pruritus was demonstrated.

Arch Pharm (Weinheim), 2004 Jul, 337(7), 391 - 7
Synthesis and antibacterial evaluation of 1beta-methyl-2-(5-substituted heterocyclic carbamoyl)pyrrolidin-3-ylthio)carbapenem derivatives; Lee JS et al.; The synthesis of a new series of 1beta-methylcarbapenems having a substituted heterocyclic carbamoyl pyrrolidine moiety is described . Their in vitro antibacterial activity against both gram-positive and gram-negative bacteria was tested, and the effect of heterocyclic substituents on the pyrrolidine was investigated . One particular compound (III(d)) having a substituted oxadiazole moiety showed the most potent antibacterial activity.

J Ethnopharmacol, 2004 Aug, 93(2-3), 331 - 5
Antibacterial, antifungal, antiplasmodial, and cytotoxic activities of Albertisia villosa; Lohombo-Ekomba ML et al.; Albertisia villosa (Menispermaceae) is a subtropical medicinal plant that is widely used in traditional African medicines against various diseases . Three known bisbenzylisoquinoline alkaloids; cycleanine, cocsoline, and N-desmethylcycleanine have been identified . Cycleanine, the most abundant (85%) of all identified bisbenzylisoquinoline alkaloids, accounts for all of the activity of the crude drug . The biological screening of cycleanine and the root bark alkaloidal extract revealed potent antibacterial, antifungal, antiplasmodial, and cytotoxic activities . These results may partly explain and support the use of Albertisia villosa root barks for the treatment of malaria and other infectious diseases in traditional Congolese medicine.

J Chromatogr A, 2004 Jun 4, 1038(1-2), 157 - 70
Simultaneous extraction of tetracycline, macrolide and sulfonamide antibiotics from agricultural soils using pressurised liquid extraction, followed by solid-phase extraction and liquid chromatography-tandem mass spectrometry; Jacobsen AM et al.; The veterinary antibacterial agents chlortetracycline (CTC), oxytetracycline (OTC), sulfadiazine (SDZ), erythromycin (ERY) and tylosin (TYL A, B, C and D) were extracted from soil using pressurized liquid extraction (PLE) . Citric acid (pH 4.7) and methanol was used as extraction buffer, followed by tandem-solid-phase extraction (SPE) clean-up (SAX + HLB) for all compounds . For quantification two slightly different methods were employed using LC-MS-MS with MRM detection . The soil extraction method was validated using a loamy sand soil and a sandy soil, representing two typical Danish agricultural soils . Recoveries were 50-80% for the tetracyclines (CTC and OTC) and sulfadiazine (SDZ) and 60-100% for the macrolides (TYL and ERY) . Limits of detection for the soil extraction method (LOD(soil)) were 0.6-5.6 microg kg(-1) soil for CTC and OTC, 0.9-2.9 microg kg(-1) soil for SDZ and 2.4-5.5 microg kg(-1) soil for TYL A and ERY . Furthermore, the method was applied to field samples taken from two agricultural fields fertilised with liquid manure containing CTC and TYL A . These results showed a decline in the content of antibacterial agents throughout the sampling period of 155 days from 10 to 15 microg CTC kg(-1) soil and 20-55 microg TYL A kg(-1) soil to below or near the LOD(soil) listed above . Finally, the method was applied to barley grains harvested from the fields . None of the antibacterial agents were measured in grain samples, but recoveries for spiked grain samples were similar to soil recoveries.

J Antimicrob Chemother, 2004 Aug, 54(2), 553 - 6 Epub 2004 Jul 01.
In vitro antibacterial activity of fluoroquinolones against Porphyromonas gingivalis strains; Eick S et al.; OBJECTIVES: The objective of the study was to evaluate the in vitro activity of ciprofloxacin, gatifloxacin and moxifloxacin against 16 Porphyromonas gingivalis strains . METHODS: MICs of the quinolones were established by Etest and the agar dilution technique . Experiments focused on determination of the spontaneous mutation rate and the induction of resistant strains, using 0.25-fold MIC of antibiotic . Fragments of gyrA and gyrB as well as of parC were sequenced . RESULTS: Moxifloxacin and gatifloxacin had very low MIC values . Subinhibitory concentrations of the fluoroquinolones rapidly induced mutations . The spontaneous mutation rate was strain- and quinolone-dependent; the lowest rate was encountered after moxifloxacin . The predicted serum concentrations of the quinolones were bactericidal to wild-type strains, but 100 mg/L of each tested quinolone was insufficient to kill a mutant exhibiting moderate resistance . Often the mutants exhibited high resistance to >/=32 mg/L . All these mutants bore a Ser-83-->Phe substitution in GyrA . CONCLUSIONS: DNA gyrase is the primary target of fluoroquinolones in P . gingivalis . In terms of the achievable level in the gingival fluid and the MICs, moxifloxacin might prevent the development of resistance and may be an alternative in the antibiotic treatment of P . gingivalis-associated periodontitis.

Klin Med (Mosk), 2004, 82(5), 51 - 4
{Anti-Helicobacter therapy for duodenal peptic ulcer complicated by pyloroduodenal stenosis}; Mirodzhov GK et al.; The rate of persistence of and susceptibility of Helicobacter pylori (HP) to antibacterial drugs (ABDs) and the results of eradication therapy were studied in patients with duodenal peptic ulcer complicated by pyloroduodenal stenosis (PDS) . The patients with PDS exhibited a high (97.1%) rate of anthral mucosal infection with HP showing a high resistance to ABDs . The efficiency of eradication therapy performed with the susceptibility of HP to ABDs kept in mind was 92.5% . The use of eradication therapy in the complex preoperative preparation of patients with ulcerative PDS increases the latter.

Biol Reprod, 2004 Nov, 71(5), 1453 - 60 Epub 2004 Jun 30.
Differential expression and antibacterial activity of epididymis protein 2 isoforms in the male reproductive tract of human and rhesus monkey (Macaca mulatta); Avellar MC et al.; The epididymis protein 2 (EP2) gene, the fusion of two ancestral beta-defensin genes, is highly expressed in the epididymis and subject to species-specific regulation at the levels of promoter selection, transcription, and mRNA splicing . EP2 mRNA expression is also androgen dependent, and at least two of the secreted proteins bind spermatozoa . Alternative splicing produces more than 17 different EP2 mRNA variants . In this article, the expression of EP2 variants was profiled in different tissues from the human and rhesus monkey (Macaca mulatta) male reproductive tract using reverse transcriptase-polymerase chain reaction . Different EP2 mRNA variants were identified not only in human and rhesus testis and epididymis but also in the novel sites, seminal vesicle and prostate . Immunolocalization of EP2 protein in epithelial cells from rhesus and human seminal vesicle demonstrated that EP2 transcripts are translated in these tissues . In addition, two novel splicing variants, named EP2R and EP2S, were discovered . EP2C was the only splice variant expressed in all tissues tested from rhesus monkey . However, expression was not detected in human testis or seminal vesicle . For the first time, bactericidal function was demonstrated for EP2C, EP2K, and EP2L . Taken together, the results indicate that EP2 expression is more widespread in the male reproductive tract than realized previously . Whereas the activity of every EP2 variant tested thus far is antibacterial, further investigation may reveal additional physiological roles for EP2 peptides in the primate male reproductive tract.

Mol Microbiol, 2004 Jul, 53(2), 697 - 706
Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system; Touze T et al.; The major Escherichia coli multidrug efflux pump AcrAB-TolC expels a wide range of antibacterial agents . Using in vivo cross-linking, we show for the first time that the antiporter AcrB and the adaptor AcrA, which form a translocase in the inner membrane, interact with the outer membrane TolC exit duct to form a contiguous proteinaceous complex spanning the bacterial cell envelope . Assembly of the pump appeared to be constitutive, occurring in the presence and absence of drug efflux substrate . This contrasts with substrate-induced assembly of the closely related TolC-dependent protein export machinery, possibly reflecting different assembly dynamics and degrees of substrate responsiveness in the two systems . TolC could be cross-linked independently to AcrB, showing that their large periplasmic domains are in close proximity . However, isothermal titration calorimetry detected no interaction between the purified AcrB and TolC proteins, suggesting that the adaptor protein is required for their stable association in vivo . Confirming this view, AcrA could be cross-linked independently to AcrB and TolC in vivo, and calorimetry demonstrated energetically favourable interactions of AcrA with both AcrB and TolC proteins . AcrB was bound by a polypeptide spanning the C-terminal half of AcrA, but binding to TolC required interaction of N- and C-terminal polypeptides spanning the lipoyl-like domains predicted to present the intervening coiled-coil to the periplasmic coils of TolC . These in vivo and in vitro analyses establish the central role of the AcrA adaptor in drug-independent assembly of the tripartite drug efflux pump, specifically in coupling the inner membrane transporter and the outer membrane exit duct.

Pharmacol Res, 2004 Sep, 50(3), 211 - 22
Antibacterial macrolides: a drug class with a complex pharmacological profile; Abu-Gharbieh E et al.; Macrolides are widely used antibacterial agents . Although generally well tolerated, they have a number of important additional pharmacological effects, which can sometimes result in significant adverse reactions . This review focuses on three of these side effects: the prokinetic action associated with stimulation of motilin receptors, the proarrhythmic effect due to prolongation of the QT interval of the electrocardiogram and the potential for drug interactions due to inhibition of drug metabolising enzymes . For macrolides that have obtained marketing authorisation in Italy, United Kingdom or United States of America, we also considered whether these actions are properly reported in the approved summaries of the product characteristics and tried to provide strategies to identify patients at risk of significant side effects when macrolides are administered.

Planta, 2004 Aug, 219(4), 561 - 78 Epub 2004 Jun 24.
Exploitation of marine algae: biogenic compounds for potential antifouling applications; Bhadury P et al.; Marine algae are one of the largest producers of biomass in the marine environment . They produce a wide variety of chemically active metabolites in their surroundings, potentially as an aid to protect themselves against other settling organisms . These active metabolites, also known as biogenic compounds, produced by several species of marine macro- and micro-algae, have antibacterial, antialgal, antimacrofouling and antifungal properties, which are effective in the prevention of biofouling, and have other likely uses, e.g . in therapeutics . The isolated substances with potent antifouling activity belong to groups of fatty acids, lipopeptides, amides, alkaloids, terpenoids, lactones, pyrroles and steroids . These biogenic compounds have the potential to be produced commercially using metabolic engineering techniques . Therefore, isolation of biogenic compounds and determination of their structure could provide leads for future development of, for example, environmentally friendly antifouling paints . This paper mainly discusses the successes of such research, and the future applications in the context of understanding the systems biology of micro-algae and cyanobacteria.

J Antimicrob Chemother, 2004 Aug, 54(2), 311 - 20 Epub 2004 Jun 23.
Resistance in the environment; Kummerer K; Antibiotics, disinfectants and bacteria resistant to them have been detected in environmental compartments such as waste water, surface water, ground water, sediments and soils . Antibiotics are released into the environment after their use in medicine, veterinary medicine and their employment as growth promoters in animal husbandry, fish farming and other fields . There is increasing concern about the growing resistance of pathogenic bacteria in the environment, and their ecotoxic effects . Increasingly, antibiotic resistance is seen as an ecological problem . This includes both the ecology of resistance genes and that of the resistant bacteria themselves . Little is known about the effects of subinhibitory concentrations of antibiotics and disinfectants on environmental bacteria, especially with respect to resistance . According to the present state of our knowledge, the impact on the frequency of resistance transfer by antibacterials present in the environment is questionable . The input of resistant bacteria into the environment seems to be an important source of resistance in the environment . The possible impact of resistant bacteria on the environment is not yet known . Further research into these issues is warranted.

J Med Chem, 2004 Jul 1, 47(14), 3693 - 6
Synthesis and antibacterial activity of a novel series of potent DNA gyrase inhibitors . Pyrazole derivatives; Tanitame A et al.; We have previously found that a pyrazole derivative 1 possesses antibacterial activity and inhibitory activity against DNA gyrase and topoisomerase IV . Here, we synthesized new pyrazole derivatives and found that 5-{(E)-2-(5-chloroindol-3-yl)vinyl}pyrazole 16 possesses potent antibacterial activity and selective inhibitory activity against bacterial topoisomerases . Many of the synthesized pyrazole derivatives were potent against clinically isolated quinolone- or coumarin-resistant Gram-positive strains and had minimal inhibitory concentration values against these strains equivalent to those against susceptible strains.

J Med Chem, 2004 Jul 1, 47(14), 3487 - 90
Hydrophobic acetal and ketal derivatives of mannopeptimycin-alpha and desmethylhexahydromannopeptimycin-alpha: semisynthetic glycopeptides with potent activity against Gram-positive bacteria; Dushin RG et al.; The effect of introducing hydrophobic groups onto the disaccharide portion of the mannopeptimycins has been examined . Under acid-catalyzed conditions dimethyl acetals and ketals react on the terminal mannose of the disaccharide moiety of mannopeptimycin-alpha and the cyclohexylalanyl analogue 2 . The preferentially formed monofunctionalized 4,6-acetals and -ketals display potent antibacterial activities against Gram-positive microorganisms, including MRSA, PRSP, and VRE pathogens.

Drug Ther Bull, 2004 Jun, 42(6), 43 - 7
Antibacterial prophylaxis in surgery: 3--Arterial surgery in the abdomen, pelvis and lower limbs; Preparation of endotoxin-free bacteriophages; Laboratory of Biomedical Chemistry, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland . borat@iitd.pan.wroc.pl

Bacteriophages (phages) are bacterial viruses that interact with bacterial walls and invade bacterial cells . Moreover, they disturb bacterial metabolism and lead to bacteria lysis . In the case of Gram-negative bacteria crude phage cultures, apart from the phages themselves, the bacterial debris, bacterial proteins and nucleic acids contain endotoxins . These endotoxins (lipopolysaccharides) posses a high degree of toxicity in vitro and in vivo, and their removal is essential for safety in antibacterial bacteriophage therapy . An effective, scaleable purification of bacteriophages from endotoxins was accomplished by sequential ultrafiltration through polysulfone membrane (30 nm) followed by chromatography on sepharose 4B and Matrex Cellulofine Sulfate . The phage fraction after gel filtration chromatography routinely contained endotoxins in the 150-2500 EU/ml range . The procedure yielded bacteriophages contaminated with as little as 0.4-7 EU/ml (Limulus assay) . This value lies within the permitted level for intravenous applications (5 EU/kg/h by European Pharmacopoeia, 1997).

Chemosphere, 2004 Aug, 56(6), 549 - 59
Enhanced microbial degradation of cadusafos in soils from potato monoculture: demonstration and characterization; Karpouzas DG et al.; Rapid degradation of cadusafos was evident in soils collected from previously-treated field sites from a potato monoculture area in northern Greece . The slower degradation of cadusafos observed in corresponding antibiotic-treated soils as well as in soils from an adjacent previously-untreated field demonstrated the microbial involvement in the rapid degradation of cadusafos in the soils from the previously-treated sites . Application of the non-specific antibacterial antibiotic chloramphenicol or of the Gram+ bacteria-inhibiting antibiotics penicillin + lyncomycin + vancomycin significantly inhibited the rapid biodegradation of cadusafos suggesting that soil bacteria and probably Gram+ bacteria are mainly responsible for the rapid biodegradation of cadusafos in the specific soil . Further experiments showed that the bacterial population of the cadusafos-adapted soil was also able to rapidly degrade the chemically related nematicide ethoprophos but not fenamiphos and oxamyl . This is the first report of the occurrence of enhanced biodegradation of cadusafos in potato fields . In addition, the finding of cross-enhancement between cadusafos and ethoprophos significantly reduces the number of available chemicals which could be alternated to prevent the development of enhanced biodegradation and thus intensifies the problem in potato monoculture areas like the one in northern Greece.

Khirurgiia (Mosk), 2004, (6), 36 - 8
{Lactation mastitis: problems and perspectives}; Kulakov AA et al.; Results of treatment of 664 patients with lactation mastitis were analyzed . It was demonstrated that Staph . aureus was the main infectious agent of the disease . Antibacterial therapy must be started with cephalosporins and aminoglycosides and corrected after tests for antibiotics sensitivity . In purulent mastitis breast feeding must be stopped, and drugs suppressing lactation should be added . In severe forms of intramammary purulent mastitis semi-oval incision by Rovinsky is recommended . In infiltrative-purulent mastitis it is better to resect the affected part of the mammary gland and apply delayed sutures in 5-7 days . Surgery must be performed by an experienced surgeon and assistant under general anesthesia.

Acta Pharmacol Sin, 2004 Jul, 25(7), 932 - 6
Relationship between antibacterial activity of chitosan and surface characteristics of cell wall; Chung YC et al.; AIM: Five representative waterborne pathogens were used to illustrate the relationship between chitosan's antibacterial activity and the surface characteristics of the bacterial cell wall . METHODS: Chitosan was prepared with averaged 75% or 95% deacetylated degree to examine its antibacterial activity against waterborne pathogens . Fresh microbial inoculants for the antibacterial assessment were prepared on nutrient agar at 37 degrees for 24 h . The evaluation items of antibacterial mechanism included hydrophilicity and negative charge analysis of cell surface, and adsorptive characteristics of chitosan to bacterial cell . All the experiments were applied in triplicate tests at least . RESULTS: Although cell wall hydrophilicity was similar among Gram-negative bacteria, the distribution of negative charge on their cell surfaces was quite different . More negatively charged cell surfaces had a greater interaction with chitosan, a phenomenon further confirmed by transmission electron micrography (TEM) . CONCLUSION: Results showed the hydrophilicity in Gram-negative bacteria was much higher than in Gram-positive ones . The correlation coefficient 0.988 between the amount of absorbed chitosan and its inhibition efficiency indicated a close relationship.

Artif Organs, 2004 Jul, 28(7), 604 - 10
Large bore catheters with surface treatments versus untreated catheters for vascular access in hemodialysis; Bambauer R et al.; Infection, thrombosis, and stenosis are among the most frequent complications associated with blood-contacting catheters . Complications resulting from infection remain a major problem for hemodialysis catheters, with significant numbers of catheters being removed due to catheter-related sepsis . Numerous strategies have been employed to reduce the occurrence of infection and im-prove long-term outcomes, with varying degrees of success . The most important is the careful and sterile handling by the attending staff of the catheters during hemodialysis treatments to minimize or stop a microbial colonization of the skin and the catheter . Another approach is coating the external surface of the catheters with substances which are antibacterial like silver and/or substances with low thrombogenicity like silicone . This investigation reviews results of animal and clinical experiments conducted to assess the efficacy and biocompatibility of silver and silicone coated dialysis catheters . It is concluded that silver coatings can reduce bacterial colonization and occurrence of infection associated with these devices . The catheters employing ion implantation of silicone rubber showed low thrombogenicity . Results of the studies indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters . A new development is the microdomain structured surface (PUR-SMA coated catheters) . Preliminary results with these catheters are very encouraging.

Anesteziol Reanimatol, 2004 Mar-Apr, (2), 52 - 4
{In Process Citation}; Contamination of honey by the herbicide asulam and its antibacterial active metabolite sulfanilamide; Official Food Control Authority of the Canton of Zurich (Kantonales Laboratorium Zurich), CH-8030 Zurich, SwitzerlandA number of antibacterial drugs (antibiotics) like sulfonamides, tetracyclines and streptomycin are used for the treatment of bacterial diseases in beehives . Yet, the finding of sulfanilamide residues in some 15 Swiss honeys out of some 350 samples could not be explained by such apicultural practice . Bees occasionally collect nectar from meadows treated with the herbicide asulam . Such honey is not only contaminated by asulam, but also by its degradation product sulfanilamide . This is the first report that the use of a herbicide causes the appearance of residues of an antibacterial active metabolite belonging to the category of sulfonamide drugs in food . The relevance of this finding lies in the fact that the use of the herbicide asulam might cause unacceptable residue levels of sulfanilamide in a product fbr human consumption.

Bioorg Med Chem Lett, 2004 Jul 16, 14(14), 3809 - 13
Synthesis and antibacterial activity of novel bifunctional macrolides; Akritopoulou-Zanze I et al.; We report the discovery of a novel class of macrolide antibiotics that have improved antibacterial activity against Ery-resistant organisms.

Bioorg Med Chem Lett, 2004 Jul 16, 14(14), 3743 - 6
Synthesis and antibacterial activity of O-substituted nocathiacin I derivatives; Naidu BN et al.; The synthesis and antibacterial activity of a series of new nocathiacin I derivatives (1-12) containing polar water solubilizing groups is described . Most of these compounds exhibited potent antibacterial activity and have improved water solubility . In addition, compounds 5, 7-9 also exhibited potent in vivo activity.

Mol Cell, 2004 Jun 18, 14(6), 739 - 51
Antibacterial Peptide Microcin J25 Inhibits Transcription by Binding within and Obstructing the RNA Polymerase Secondary Channel; Mukhopadhyay J et al.; The antibacterial peptide microcin J25 (MccJ25) inhibits transcription by bacterial RNA polymerase (RNAP) . Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP . Genetic results indicate that inhibition of transcription requires an extensive determinant, comprising more than 50 amino acid residues, within the RNAP secondary channel (also known as the "NTP-uptake channel" or "pore") . Biophysical results indicate that inhibition of transcription involves binding of MccJ25 within the RNAP secondary channel . Molecular modeling indicates that binding of MccJ25 within the RNAP secondary channel obstructs the RNAP secondary channel . We conclude that MccJ25 inhibits transcription by binding within and obstructing the RNAP secondary channel-acting essentially as a "cork in a bottle." Obstruction of the RNAP secondary channel represents an attractive target for drug discovery.

J Clin Pharmacol, 2004 Jul, 44(7), 689 - 95
Effects of a new antibacterial, telavancin, on cardiac repolarization (QTc interval duration) in healthy subjects; Barriere S et al.; Telavancin is a rapidly bactericidal antibiotic with multiple mechanisms of action against gram-positive bacteria . Preclinical and early clinical data suggested possible effects on cardiac repolarization requiring the conduct of a definitive evaluation of QT effects in healthy subjects . A total of 160 subjects were randomized into four groups to receive placebo (telavancin vehicle), telavancin at a dose of 7.5 mg/kg or 15 mg/kg, or moxifloxacin 400 mg (positive control) . All medications were administered once daily for 3 days as 60-minute IV infusions . Sixteen ECGs were obtained over 24 hours following an infusion of D5W (baseline) and following Day 3 infusions of each medication . ECGs were analyzed digitally in a blinded fashion by a validated core ECG laboratory . The primary endpoint was QT data corrected for heart rate by the Fridericia formula (QTcF) . Placebo-corrected mean changes in QTcF values for 7.5 mg/kg telavancin, 15 mg/kg telavancin, and moxifloxacin were 4.1 msec, 4.5 msec, and 9.2 msec, respectively . The mean change from baseline in QTcF for moxifloxacin, which served as the assay-sensitive positive control in the study, helped to establish that telavancin had a minimal effect on QT prolongation . No subject had a QTcF > or = 450 msec, and none experienced clinically significant ECG abnormalities . The telavancin treatment groups were not significantly different from each other . There was no correlation of the magnitude of change in QTc and plasma concentrations of telavancin . Telavancin has a < 5-msec mean effect on cardiac repolarization, with a flat-dose response over a two-fold exposure range.

J Control Release, 2004 Jun 18, 97(2), 313 - 20
Controlled release of a model antibacterial drug from a novel self-lubricating silicone biomaterial; Malcolm RK et al.; There is considerable interest in developing medical devices that provide controlled delivery of biologically active agents, for example, to reduce the incidence of device-related infection . Silicone elastomers are one of the commonest biomaterials used in medical device production . However, they have a relatively high coefficient of friction and the resulting lack of lubricity can cause pain and tissue damage on device insertion and removal . Novel silicone cross-linking agents have recently been reported that produce inherently 'self-lubricating' silicone elastomers with very low coefficients of friction . In this study, the model antibacterial drug metronidazole has been incorporated into these self-lubricating silicone elastomers to produce a novel bioactive biomaterial . The in vitro release characteristics of the bioactive component were evaluated as a function of cross-linker composition and drug loading . Although conventional matrix-type release kinetics were observed for metronidazole from the silicone systems, it was also observed that increasing the concentration of the cross-linking agent responsible for the lubricious character (tetra(oleyloxy)silane) relative to that of the standard non-lubricious cross-linking agent (tetrapropoxysilane) produced an increase in the metronidazole flux rate by up to 65% for a specified drug loading . The results highlight the potential for developing lubricious silicone medical devices with enhanced drug release characteristics .

Biochemistry, 2004 Jun 22, 43(24), 7892 - 8
Characterization of full length and truncated type I human methionine aminopeptidases expressed from Escherichia coli; Li JY et al.; Methionine aminopeptidase (MetAP) carries out an essential posttranslational modification of nascent proteins by removing the initiator methionine and is recognized as a potential target for developing antibacterial, antifungal, and anticancer agents . We have established an Escherichia coli expression system for human type I MetAP (HsMetAP1) and characterized the full length HsMetAP1 and its N-terminal-truncated mutants HsMetAP1(Delta1-66) and HsMetAP1(Delta1-135) for hydrolysis of several thiopeptolide and peptide substrates and inhibition by a series of nonpeptidic inhibitors . Although the N-terminal extension with zinc finger motifs in HsMetAP1 is not required for enzyme activity, it has a significant impact on the interaction of the enzyme with substrates and inhibitors . In hydrolysis of the thiopeptolide substrates, a relaxation of stringent specificity for the terminal methionine was observed in the truncated mutants . However, this relaxation of specificity was not detectable in hydrolysis of tripeptide or tetrapeptide substrates . Several nonpeptidic inhibitors showed potent inhibition of the mutant HsMetAP1(Delta1-66) but exhibited only weak or no inhibition of the full length enzyme . With the recombinant HsMetAP1 available, we have identified several MetAP inhibitors with submicromolar inhibitory potencies against E . coli MetAP (EcMetAP1) that do not affect HsMetAP1 . These results have demonstrated the possibility of developing MetAP inhibitors as antibacterial agents with minimum human toxicity . In addition, micromolar inhibitors of HsMetAP1 identified in this study can serve as tools for investigating the functions of HsMetAP1 in physiological and pathological processes.

Tidsskr Nor Laegeforen, 2004 Jun 3, 124(11), 1518 - 20
{Acute bacterial conjunctivitis}; Hovding G; Acute infectious conjunctivitis is the eye disease most commonly seen by general practitioners, and is estimated to represent 2-3% of their total number of consultations . The present paper gives a review of the epidemiology, etiology, clinical picture, complications, differential diagnoses and therapy of acute bacterial conjunctivitis . The condition has an excellent prognosis with a high frequency of spontaneous remission . However, topical antibacterial therapy should always be instituted, because this will shorten the course of the disease and reduce the risk of epidemic outbreaks, particularly in institutions for children.

Int J Antimicrob Agents, 2004 Jun, 23(6), 631 - 3
Inhibitory action of a new proton pump inhibitor, trifluoromethyl ketone derivative, against the motility of clarithromycin-susceptible and-resistant Helicobacter pylori; Spengler G et al.; We previously reported that a trifluoromethyl ketone derivative, 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18), exhibited the potent antibacterial activity against Helicobacter pylori, but had no urease activity . In order to clarify the mechanism of anti-H . pylori action of TF18, we evaluated the growth and motility of TF18 on clarithromycin-susceptible H . pylori (CSHP) and -resistant H . pylori (CRHP) . An effective proton pump inhibitor (TF18) had remarkable dose-dependent antibacterial activity and was able to inhibit the flagellar motor of both CSHP and CRHP isolates . The antimotility effect of TF18 was more pronounced at subinhibitory concentration in CRHP than in CSHP . The swimming (the forward motion) was more sensitive to the inhibition than the tumbling . Based on the results, it is supposed that TF18 works as an uncoupler similar to the 'clutch' in a biological motor, in which counterclockwise rotation is more sensitive to the effect of TF18 than the clockwise rotation .

Int J Antimicrob Agents, 2004 Jun, 23(6), 613 - 9
In vitro activity of extracts and constituents of Pelagonium against rapidly growing mycobacteria; Seidel V et al.; Extracts of the roots of plants of the Geraniaceae family have been used for many years in South Africa as native herbal remedies and there is circumstantial evidence for efficacy in the treatment of pulmonary tuberculosis . We have examined dried roots of Pelargonium reniforme and P . sidoides for antibacterial activity against rapidly growing mycobacteria . Fractions with activity against Mycobacterium aurum and M . smegmatis were obtained from both plant species by bioassay-guided fractionation of n-hexane extracts and were found to contain mixtures of straight-chain fatty acids . Analysis by gas chromatography-mass spectrometry (GC-MS) of the corresponding fatty acid methyl esters revealed structures with chain lengths ranging from C12 to C26 . Unsaturated compounds were analysed as the corresponding dimethyl disulfide adducts to determine double-bond positions . Active mixtures differed in the relative abundance of their components, but all contained 16:0 (palmitic), Delta9-18:1 (oleic) and Delta9,12-18:2 (linoleic acid) as the major components . When tested against M . aurum, M . smegmatis and other rapidly growing mycobacteria (M . fortuitum, M . abscessus and M . phlei), all saturated compounds except 12:0 were devoid of antimycobacterial activity, whereas unsaturated compounds showed antimycobacterial activity related to their degree of unsaturation, their chain length and the bacterial species tested . The most potent compound was linoleic acid, with MIC of 2 mg/l against M . aurum .

Clin Microbiol Infect, 2004 Jun, 10(6), 499 - 501
Fusarium fungaemia in immunocompromised patients; Jensen TG et al.; Fusarium spp . cause infections only rarely in immunologically competent hosts, but disseminated infection may occur in severely immunocompromised patients . Symptoms of disseminated infection are persistent fever, despite broad-spectrum antibacterial and antifungal treatment, associated with skin lesions, most commonly on the extremities, in 60-80% of patients . A mortality rate of 50-75% has been reported for patients with disseminated fusariosis . Despite treatment failures, amphotericin B remains the preferred drug, in part because of lack of alternatives . Voriconazole is a promising new agent, but more clinical experience is required.

Annu Rev Biochem, 2004, 73, 467 - 89
Structure and function of TolC: the bacterial exit duct for proteins and drugs; Koronakis V et al.; The bacterial TolC protein plays a common role in the expulsion of diverse molecules, which include protein toxins and antibacterial drugs, from the cell . TolC is a trimeric 12-stranded alpha/beta barrel, comprising an alpha-helical trans-periplasmic tunnel embedded in the outer membrane by a contiguous beta-barrel channel . This structure establishes a 140 A long single pore fundamentally different to other membrane proteins and presents an exit duct to substrates, large and small, engaged at specific inner membrane translocases . TolC is open to the outside medium but is closed at its periplasmic entrance . When TolC is recruited by a substrate-laden translocase, the entrance is opened to allow substrate passage through a contiguous machinery spanning the entire cell envelope, from the cytosol to the external environment . Transition to the transient open state is achieved by an iris-like mechanism in which entrance alpha-helices undergo an untwisting realignment, thought to be stabilized by interaction with periplasmic helices of the translocase . TolC family proteins are ubiquitous among gram-negative bacteria, and the conserved entrance aperture presents a possible cheomotherapeutic target in multidrug-resistant pathogens.

Biol Pharm Bull, 2004 Jun, 27(6), 899 - 902
Biological activity of alpha-thujaplicin, the isomer of hinokitiol; Morita Y et al.; alpha-Thujaplicin, a minor component of Aomori Hiba (Thujopsis dolabrata SIEB . et ZUCC . var . hondai MAKINO), showed rather strong antifungal activity against seven kinds of plant-pathogenic fungi, their minimum inhibitory concentrations (MICs) being in the range of 12.0-50.0 microg/ml . alpha-Thujaplicin and hinokitiol (the major component of Aomori Hiba) also showed clear antibacterial activity against Legionella pneumophila SG 1 and L . pneumophila SG 3, and their MICs are in the range of 6.25-50 microg/ml . This compound showed strong insecticidal activity against Reticulitermes speratus {50%-lethal concentration (LC(50)): 0.02 g/m(2)}, and it also had clear acaricidal activity against Dermatophagoides farinae (LC(50): 0.66 g/m(2)) . At 24 h after treatment, alpha-thujaplicin at 0.63 microg/ml inhibited the cell growth of murine P388 lymphocytic leukemia by 78%, and its cytotoxic activity at a concentration higher than 0.63 microg/ml was as high as that of vincristine, used as a positive control . On the other hand, the cytotoxic effect of alpha-thujaplicin at 0.63 microg/ml was weaker than that of vinblastine . In this respect, the strong cytotoxic effect of alpha-thujaplicin on murine P388 lymphocytic leukemia cell line should be emphasized, considering that it has recently been found to be low in toxicity to mice.

Int Endod J, 2004 Jun, 37(6), 408 - 16
Prognosis of large cyst-like periapical lesions following nonsurgical root canal treatment: a clinical review; Caliskan MK; AIM: To evaluate clinically and radiographically the long-term clinical outcome of nonsurgical root canal treatment using calcium hydroxide in teeth with large cyst-like periapical lesions . SUMMARY: A total of 42 mature anterior teeth with large periapical lesions ranging in size from 7 to 18 mm in diameter were included in this study . Fluid samples from the lesions contained cholesterol crystals, which were identified by light microscopy . After adequate draining, the teeth were treated endodontically using calcium hydroxide as the intracanal medicament . All cases were followed up for a period of 2-10 years . Complete healing was observed in 73.8% and incomplete healing in a further 9.5% of cases . KEY LEARNING POINTS: Root canal treatment using calcium hydroxide as an antibacterial dressing was successful in healing large cyst-like periapical lesions . This study suggests that the size of a periapical lesion is not a major determining factor in the decision to perform conventional root canal treatment or surgical removal of the lesion . Even large cyst-like periapical lesions containing cholesterol crystals can heal following nonsurgical root canal treatment.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2004 Jun, 97(6), 714 - 7
Effect of antibacterial therapy and salivary secretion on the efficacy of Helicobacter pylori eradication in duodenal ulcer patients; Namiot Z et al.; OBJECTIVE: Oral health status may play a role in Helicobacter pylori eradication . Because adequate secretion of saliva promotes oral health, the aim of the study was to assess the effect of salivary secretion on the efficacy of H pylori eradication from the stomach . STUDY DESIGN: The study involved 90 H pylori-positive subjects with duodenal ulcer (68 men, 22 women, aged 20-70 years) in whom saliva was collected under basal conditions for 45 min before antibacterial treatment began . They received no drugs for at least 3 days prior to saliva collection . A 7-day course of either of 2 eradication regimens--omeprazole, amoxicillin, and tinidazole (OAT); or omeprazole, amoxicillin, and clarithromycin (OAC)--was used . The efficacy of eradication therapy was evaluated 30 days after its completion . RESULTS: The efficacy of H pylori eradication from the stomach (per protocol analysis) was 77.5% in the group of subjects treated with OAT and 81.6% with OAC . Combined analysis of both groups (OAT+OAC) showed reduced salivary secretion in subjects with eradication failure (0.395 +/- 0.266 vs 0.25 +/- 0.176 mL/min, P=.042) . A similar outcome was obtained when the OAT group was analyzed separately (0.436 +/- 0.316 vs 0.211 +/- 0.216 mL/min, P=.022), but in the OAC group the difference was not significant . In the combined analysis, the efficacy of eradication therapy was lower in women than in men (52.9% vs 86.9%, P=.005) . In women, it corresponded to salivary secretion (successful eradication 0.337 +/- 0.133 mL/min, unsuccessful eradication 0.180 +/- 0.144 mL/min, P=.043); whereas in men, the difference was not significant (successful eradication 0.405 +/- 0.282 mL/min, unsuccessful eradication 0.321 +/- 0.186 mL/min) . CONCLUSION: Low salivary secretion may contribute to the decrease in efficacy of H pylori eradication from the stomach, at least in subjects treated with certain drug regimens .

Appl Environ Microbiol, 2004 Jun, 70(6), 3313 - 20
Evaluation of Nostoc strain ATCC 53789 as a potential source of natural pesticides; Biondi N et al.; The cyanobacterium Nostoc strain ATCC 53789, a known cryptophycin producer, was tested for its potential as a source of natural pesticides . The antibacterial, antifungal, insecticidal, nematocidal, and cytotoxic activities of methanolic extracts of the cyanobacterium were evaluated . Among the target organisms, nine fungi (Armillaria sp., Fusarium oxysporum f . sp . melonis, Penicillium expansum, Phytophthora cambivora, P . cinnamomi, Rhizoctonia solani, Rosellinia, sp., Sclerotinia sclerotiorum, and Verticillium albo-atrum) were growth inhibited and one insect (Helicoverpa armigera) was killed by the extract, as well as the two model organisms for nematocidal (Caenorhabditis elegans) and cytotoxic (Artemia salina) activity . No antibacterial activity was detected . The antifungal activity against S . sclerotiorum was further studied with both extracts and biomass of the cyanobacterium in a system involving tomato as a host plant . Finally, the herbicidal activity of Nostoc strain ATCC 53789 was evaluated against a grass mixture . To fully exploit the potential of this cyanobacterium in agriculture as a source of pesticides, suitable application methods to overcome its toxicity toward plants and nontarget organisms must be developed.

J Insect Physiol, 2004 Jun, 50(6), 489 - 96
An entomopathogenic bacterium, Xenorhabdus nematophila, inhibits the expression of an antibacterial peptide, cecropin, of the beet armyworm, Spodoptera exigua; Ji D et al.; An entomopathogenic bacterium, Xenorhabdus nematophila, is known to depress hemocyte nodule formation of target insects by inhibiting eicosanoid biosynthesis . This study analyzed the inhibitory effect of X . nematophila on the humoral immunity of the target insects and tested its association with the host eicosanoid pathway . Plasma collected from the fifth instar larvae of Spodoptera exigua, when they were injected with X . nematophila, did not show antibacterial activity against Escherichia coli by a growth inhibition zone assay . In comparison, heat-killed X . nematophila induced significant antibacterial activity in the plasma . The antibacterial humoral activity was further demonstrated by examining a specific potent antibacterial peptide, cecropin . Two cecropin genes ('A' and 'B') were partially cloned from the fifth instar larvae of S . exigua by conserved degenerate primers using nested reverse transcriptase-polymerase chain reaction (RT-PCR) . They showed high homologies with known cecropins from other lepidopteran species . Northern analysis using the cecropin probe showed that the injection of the heat-killed X . nematophila induced significant expression of a cecropin mRNA transcript (approximately 1.1 kb), but the larvae injected with the live bacteria did not show the corresponding transcript . Injection of arachidonic acid did not rescue the inhibition of X . nematophila based on either antibacterial activity or cecropin gene expression . The addition of dexamethasone, a specific phospholipase A2 inhibitor, did not inhibit antibacterial activity or cecropin gene expression when the larvae were injected with heat-killed X . nematophila . These results suggest that X . nematophila inhibits the antibacterial humoral immune reaction as well as the cellular immune reaction in S . exigua and that the inhibition of X . nematophila on the expression of the antibacterial peptide is not associated with inhibition of the eicosanoid pathway.

J Ethnopharmacol, 2004 Jul, 93(1), 123 - 32
Pharmacological actions and potential uses of Momordica charantia: a review; Grover JK et al.; Since ancient times, plants and herbal preparations have been used as medicine . Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine . Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant . Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient . Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori . Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease) . There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results.

SADJ, 2004 Mar, 59(2), 51 - 3
Compressive strength of glass ionomer cements with dental antibacterial agents; Botelho MG; Glass ionomer cements have been suggested for obturating carious teeth that have been prepared with dental hand instruments . In such cases, carious dentine may be inadvertently or deliberately left in situ . The residual bacteria may, over time, lead to secondary caries and restoration failure . Benefit may be gained from combining antibacterial agents with the glass ionomer cement to control residual bacteria . The aim of this study was to investigate the effects on the compressive strength of glass ionomer cement combined with oral antibacterial agents . Cationic antibacterial agents; chlorhexidine hydrochloride, cetylpyridinium chloride and cetrimide were added to the powder and benzalkonium chloride, a liquid, to the liquid of Fuji IX glass ionomer cement . These were prepared to concentrations of 1, 2 and 4 per cent by weight of the glass ionomer cement and compared to Fuji IX with no antibacterial agent . Test specimens were subjected to a compressive force to failure . Multiple analysis of variance showed highly significant reductions in compressive strength (p < 0.01) between the test materials and control group apart from one per cent benzalkonium chloride . Increasing concentration of the antibacterial agent had increasing adverse effects on the physical properties . The addition of the antibacterial agents tested to Fuji IX reduces the seven-day compressive strength which may affect the clinical performance of the material.

J Infect Dis, 2004 Jun 15, 189(12), 2308 - 17 Epub 2004 May 25.
Inhibition of the tissue factor/factor VIIa pathway does not influence the inflammatory or antibacterial response to abdominal sepsis induced by Escherichia coli in mice; Weijer S et al.; BACKGROUND: Anticoagulants have gained increasing attention for the treatment of sepsis . Inhibition of the tissue factor (TF)/factor (F) VIIa pathway has been shown to attenuate the activation of coagulation and to prevent death in a primate model of sepsis caused by gram-negative bacteria . METHODS: To determine the role of the TF/FVIIa complex in the host response to peritonitis, mice received an intraperitoneal injection of live Escherichia coli with or without concurrent treatment with recombinant nematode anticoagulant protein c2 (rNAPc2), a selective inhibitor of the TF/FVIIa pathway . RESULTS: Peritonitis was associated with an increase in the expression of TF at the tissue level and activation of coagulation, as reflected by elevated levels of thrombin-antithrombin complexes and by increased fibrin(ogen) deposition in the liver and lungs . rNAPc2 strongly attenuated this procoagulant response but did not influence the inflammatory response (histopathology, leukocyte recruitment to the peritoneal cavity, and cytokine and chemokine levels) . Moreover, rNAPc2 did not alter bacterial outgrowth locally or dissemination of the infection, and survival was not different between rNAPc2-treated mice and control mice . CONCLUSIONS: These data suggest that TF/FVIIa activity contributes to the activation of coagulation during E . coli peritonitis but does not play a role in the inflammatory response or antibacterial host defense.

Zhong Yao Cai, 2004 Jan, 27(1), 20 - 2
{Phenolic acid from culture broth of fungus Cephalosporium sp . AL031}; Bi Y et al.; Three phenolic acids were isolated from the culture broth of the fungus Cephalosporium sp . AL031 whose metabolites have been proven to possess antifungal and antibacterial activities . Their structures were elucidated as 2,4-dihydroxy-3,6-dimethyl-benzoic acid (1),3,6-dihydroxy-2,4-dimethylbenzoic acid(2) and 4-hydroxy-phenylacetic acid(3) by IR, EIMS, 1HNMR, 13CNMR, DEPT, HMQC and HMBC.

Drug News Perspect, 2004 Apr, 17(3), 187 - 94
The potential of bacterial fatty acid biosynthetic enzymes as a source of novel antibacterial agents; Payne DJ; Bacteria can produce new progeny in only 20 minutes (500,000 times faster than humans), enabling them to rapidly mutate and evolve ingenious methods to outwit just about all of the currently available antibiotics . These mechanisms can then disseminate rapidly through bacterial populations via transmissible pieces of DNA such as transposons, integrons and plasmids . This leads to resistance mechanisms becoming geographically dispersed and has resulted in the overall decrease in the susceptibility of microorganisms to antibiotics that used to be highly efficacious . There is an obvious need for new antibiotics that kill bacteria via novel mechanisms not previously exploited by existing agents; this will provide new generations of antibiotics unlikely to be compromised by preexisting resistance mechanisms . The fatty acid biosynthetic pathway is an essential metabolic process in bacteria and presents several novel targets for antibiotic development . (c) 2004 Prous Science . All rights reserved.

Expert Opin Investig Drugs, 2004 Jun, 13(6), 715 - 21
Antibacterial drug discovery & development summit; Barrett JF et al.; Over 100 senior researchers and managers from academic and industrial research organisations attended this 2-day annual international discovery summit on antibacterial R&D . A number of firms, particularly biotechnology firms, presented compounds that are advancing through clinical development . In addition, areas for basic research and development included metallo-beta-lactamases, ribosomal structural studies and phage-selected targets were described.

Treat Respir Med, 2004, 3(1), 59 - 65
The effect of oral clarithromycin on bronchial airway inflammation in moderate-to-severe stable COPD: a randomized controlled trial; Banerjee D et al.; INTRODUCTION: COPD is characterized by bronchial neutrophilic inflammation . Clarithromycin is a macrolide antibiotic that has antibacterial and anti-inflammatory properties . Macrolide antibiotics have been shown to improve airway inflammation in diffuse pan-bronchiolitis but their role in COPD is undetermined . The aim of the study was to determine if 3 months of therapy with modified-release oral clarithromycin (Klaricid XL) 500 mg/day reduced bronchial airway inflammation in patients with moderate-to-severe stable COPD compared with placebo.METHODS: A prospective, double-blind controlled trial randomized patients with moderate-to-severe stable COPD to 3 months' therapy with oral modified-release clarithromycin 500 mg/day or placebo . Patients underwent saline sputum induction before and after treatment with clarithromycin . The effects of clarithromycin on sputum total cell and neutrophil counts, supernatant interleukin-8 (IL-8), leukotriene B(4) (LTB(4)), tumor necrosis factor (TNF)-alpha, neutrophil elastase (NE), and neutrophil chemotaxis were assessed in comparison with placebo . RESULTS: Of a total of 67 patients included in the trial, 31 were treated with clarithromycin and 36 with placebo . The groups were similar in age, body mass index, history of smoking, and spirometry . Of 60 evaluable patients, 26 and 34 completed 3 months' therapy with clarithromycin and placebo, respectively . Clarithromycin had no significant effect on sputum total cell count, neutrophil count, IL-8, LTB(4), TNFalpha levels or neutrophil elastase . However, clarithromycin did cause a small reduction in the neutrophil differential (p = 0.04 relative to placebo) and neutrophil chemotaxis (p = 0.058 relative to placebo) . CONCLUSIONS: Oral clarithromycin 500 mg/day administered for 3 months had no significant effect on sputum neutrophil numbers or cytokine levels in patients with moderate-to-severe stable COPD . However, clarithromycin did cause a small reduction in the neutrophil differential and neutrophil chemotaxis . Further studies may be warranted to determine the clinical significance of these findings.

Nutr Health, 2004, 17(4), 335 - 41
The under utilization of honey in a deprived environment; Ojofeitimi EO et al.; The study investigated the utilization of honey in the treatment and prevention of illness amongst 400 respondents in Oranfe Community, Ile-Ife, Osun State Nigeria . Data were collected by employing a structured and pretested open ended questionnaire . The data indicated that 21%, 17% and less than 5% of the respondents had used honey for wounds, respiratory tract infections and gastroenteritis respectively . Neither educational nor professional status had any significant influence on the usage of honey in the treatment and prevention of common illness (p > 0.05) . The vast majority (55%) preferred refined sugar to honey . The study has some policy implications . The first is the need for an intensive nutrition education programme that will disseminate the health benefits of honey as a source of energy, essential nutrients and its antioxidant properties . The second is the need to promote its usage in clinical trials because of its antibacterial properties.

Phytother Res, 2004 May, 18(5), 358 - 61
In vitro anti-Helicobacter pylori potential of methanol extract of Allium ascalonicum Linn . (Liliaceae) leaf: susceptibility and effect on urease activity; Adeniyi BA et al.; The crude methanol extract of the leaf of Allium ascalonicum was screened in vitro against fi ve strains of Helicobacter pylori (Hp) (ATCC 24376, UCH 97001, UCH 97009, UCH 98026 and UCH 99039) for antibacterial activity by the agar diffusion method in Mueller-Hinton agar supplemented with de fi brinated horse blood . All the strains were inhibited by the extract to varying degrees . The minimum inhibitory concentrations (MICs) of the extract against all the tested strains ranged from 6.25 to 12.5 mg/mL . The effects of increasing concentrations of the extract on the urease activity of three of the Helicobacter pylori strains were investigated further . The results showed that increasing the concentration of the extract decreased the urease activity of all the strains tested . Phytochemical screening of the plant showed that it contains alkaloids, cardiac glycosides and saponins . The anti-Hp activity observed is discussed in relation to the chemical constituents reportedly isolated from these plants and their traditional uses . The result of this work suggests that Allium ascalonicum has some therapeutic potential against Helicobacter pylori infection, which could be explored for patients with gastroduodenal disorders .

JAMA, 2004 Jun 2, 291(21), 2547 - 54
Effect of intensive handwashing promotion on childhood diarrhea in high-risk communities in Pakistan: a randomized controlled trial; Luby SP et al.; CONTEXT: Washing hands with soap prevents diarrhea, but children at the highest risk of death from diarrhea are younger than 1 year, too young to wash their own hands . Previous studies lacked sufficient power to assess the impact of household handwashing on diarrhea in infants . OBJECTIVE: To evaluate the effect of promoting household handwashing with soap among children at the highest risk of death from diarrhea . DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized controlled trial of 36 low-income neighborhoods in urban squatter settlements in Karachi, Pakistan . Field workers visited participating households at least weekly from April 15, 2002, to April 5, 2003 . Eligible households located in the study area had at least 2 children younger than 15 years, at least 1 of whom was younger than 5 years . INTERVENTIONS: Weekly visits in 25 neighborhoods to promote handwashing with soap after defecation and before preparing food, eating, and feeding a child . Within intervention neighborhoods, 300 households (1523 children) received a regular supply of antibacterial soap and 300 households (1640 children) received plain soap . Eleven neighborhoods (306 households and 1528 children) comprised the control group . MAIN OUTCOME MEASURE: Incidence density of diarrhea among children, defined as the number of diarrheal episodes per 100 person-weeks of observation . RESULTS: Children younger than 15 years living in households that received handwashing promotion and plain soap had a 53% lower incidence of diarrhea (95% confidence interval {CI}, -65% to -41%) compared with children living in control neighborhoods . Infants living in households that received handwashing promotion and plain soap had 39% fewer days with diarrhea (95% CI, -61% to -16%) vs infants living in control neighborhoods . Severely malnourished children (weight for age z score, <-3.0) younger than 5 years living in households that received handwashing promotion and plain soap had 42% fewer days with diarrhea (95% CI, -69% to -16%) vs severely malnourished children in the control group . Similar reductions in diarrhea were observed among children living in households receiving antibacterial soap . CONCLUSION: In a setting in which diarrhea is a leading cause of child death, improvement in handwashing in the household reduced the incidence of diarrhea among children at high risk of death from diarrhea.

Ann Transplant, 2003, 8(4), 27 - 30
Similar response of dendritic cells to bacterial and allogeneic antigens; Stanislawska J et al.; The dendritic cells (DC) of an allograft recipients become engaged not only in an allogeneic but also antibacterial reaction . They react to the alloantigens and microorganisms which colonize the rejecting grafts . This leads to overstimulation of DCs what may non-specifically intensity the rejection process . We investigated the effects of allogeneic and bacterial antigens on splenic DCs phenotypes . In vitro stimulation of spleen DC-enriched population by E . coli, LPS and CpG DNA brought about an increase in expression of OX6 (MHC class II) from 47.4% in the control population to 65% in the E . coli stimulated group (p < 0.05) and to 85% in the LPS and CpGDNA groups (p < 0.05) . Interestingly, a significant drop in the frequency of OX62+ antigen was observed after incubation with LPS . Allogeneic heart transplants brought about an increase of OX6+ (MHC class II) DCs to 100% and a decrease of EDI+ cells . Simultaneously, an increase in expression of W3/13 on DC-enriched splenic cells was observed . There was no significant change in the frequency of OX62+ expression in conclusion, both bacterial and alloantigens strongly activate splenic DCs what may add to the intensity of the rejection process.

Eur J Clin Pharmacol, 2004 Jul, 60(5), 355 - 61 Epub 2004 May 28.
Medication use during pregnancy: data from the Avon Longitudinal Study of Parents and Children; Headley J et al.; OBJECTIVE: To present data on the self-reported use of all types of medicinal products collected during pregnancy in a large cohort in southwest England . METHODS: Pregnant women with a delivery date during 1991-1992 and forming part of the prospective, population-based Avon Longitudinal Study of Parents and Children (ALSPAC) were sent up to four self-completion postal questionnaires during pregnancy . Text data collected from the questions on drug usage were coded using an ALSPAC drug dictionary based on the World Health Organization Drug Dictionary . RESULTS: At least one antenatal self-completion questionnaire was completed for 14,119 pregnancies, and 11,545 women completed all four . The data included prescription, over-the-counter, herbal and homeopathic products as well as iron, vitamins and other supplements . Only 7.6% did not report use of any medicinal product throughout their entire pregnancy . The remaining 92.4% used at least one product at some stage . After exclusion of iron, folate, vitamins, supplements, herbal and homeopathic products and skin emollients, 83% of those completing all questionnaires had used conventional therapeutic drugs . Analgesics were reported by approximately one-third of women at each stage during pregnancy, and paracetamol was the most frequently reported substance . Iron preparations were reported by 33% of the full cohort, at some stage, and folate by 21.9% . Use of anti-anaemic products increased during pregnancy with the greatest incidence at 32 weeks . Other vitamins and supplements were taken by 17.4% at some stage . Use of vitamins decreased throughout pregnancy from 9.6% in early pregnancy to 5% at 32 weeks . Antacids were reported by 23% at 32 weeks . The reported incidence of antibiotic use decreased slightly during pregnancy from 8% early on to 5.8% at 32 weeks; amoxicillin was the most frequently reported antibacterial . CONCLUSION: Use of medicinal products was high during pregnancy in the ALSPAC cohort . This finding is consistent with data from recent publications.

Curr Opin Otolaryngol Head Neck Surg, 2004 Jun, 12(3), 237 - 42
Categorization of eosinophilic chronic rhinosinusitis; Ferguson BJ; PURPOSE OF REVIEW: The presence of eosinophilia histopathologically in sinusitis is frequently associated with greater disease objectively and a decreased likelihood of surgical success . Eosinophilic chronic rhinosinusitis encompasses a wide variety of etiologies and associations that can be grouped under this umbrella term . In addition, this term can be further divided into those patients with no polyps and those with polyps . The purpose of this review is to detail the epidemiology of eosinophilic chronic rhinosinusitis, to define known and potential subcategories, and to discuss targeted therapeutic interventions . Eosinophilia is frequently, but not exclusively, caused by IgE-mediated hypersensitivity and is dominated by the associated cytokine milieu of Th2 inflammation . Thus, allergic rhinitis or allergy is a subcategory and not synonymous with eosinophilic chronic rhinosinusitis . RECENT FINDINGS: Recent findings supporting mechanisms that promote eosinophilic infiltration are discussed and include the following subcategories: super antigen-induced eosinophilic chronic rhinosinusitis, allergic fungal sinusitis, nonallergic fungal eosinophilic chronic rhinosinusitis, and aspirin-exacerbated eosinophilic chronic rhinosinusitis . Undoubtedly there are other mechanisms and categorizations of eosinophilic chronic rhinosinusitis as yet unknown . It is possible, and in fact probable, that some patients may have overlapping mechanisms for eosinophilia . Corticosteroid therapy is an important treatment across all eosinophilic disorders and a profoundly potent but nonspecific antiinflammatory agent . Within each subcategory a specific antibacterial, antifungal, or immune modulation may be indicated . SUMMARY: The subcategories of eosinophilic chronic rhinosinusitis are discussed in light of recent findings and treatment recommendations.

J Clin Laser Med Surg, 2004 Apr, 22(2), 87 - 9
Cleaning of the root canal using Nd:YAP laser and its effect on the mineral content of the dentin; Moshonov J et al.; OBJECTIVE: To compare the efficacy of root canal cleanliness with and without Nd:YAP laser and to assess the effect of the laser on the mineral content of the dentin . BACKGROUND DATA: A high degree of cleanliness of the canal when using Nd:YAG laser has been shown while the laser had been in contact with the canal wall . A new Nd:YAP laser has been studied recently, which is considered to be superior to Nd:YAG with regard to antibactericidal ability due to its 1.34-mu wavelength, which is in the infra red range . This wavelength is absorbed better in water that of Nd:YAG . MATERIALS AND METHODS: Fourteen extracted single rooted premplars were divided into two groups . In group 1, canals were cleaned, instrumented and shaped with K files . In group 2, initial preparation was done using K files and completed with a Nd:YAP laser . Teeth were then split longitudinally and submitted to SEM . RESULTS: The cleanliness of the laser treated teeth was significantly greater than teeth treated with K files alone (p<0.05) . No difference in Ca and P content was detected when the use of K files was compared to the use of laser . CONCLUSIONS: It appears that Nd:YAP laser improves the cleanliness of the root canal . However, since Nd:YAP laser serves as an addition to K files, its clinical value for replacing conventional root canal instrumentation remains to be determined.

Biomed Pharmacother, 2004 Apr, 58(3), 183 - 93
Organosulfur compounds from alliaceae in the prevention of human pathologies; Tapiero H et al.; A strong association between elevated plasma low-density-lipoprotein (LDL) and the development of cardiovascular diseases (CVD) has been established . Oxidation of LDL (Ox-LDL) promotes vascular dysfunction, enhances the production and release of inflammatory mediators such as reactive oxygen species and contribute to the initiation and progression of atherosclerosis . In addition, Ox-LDL enhances the production and release of tumor necrosis factor (TNF-alpha), interleukin (IL)-6, arachidonic acid metabolites and nitric oxide (NO) that are responsible for various human pathologies including cancer . Organosulfur compounds (OSC) from alliaceae modulate the glutathione (GSH) redox cycle and inhibits NFkappa-B activation in human T cells . Furthermore, OSC bioactivities include antioxidant, antibacterial, anticarcinogenic, antiatherogenic, immunostimulatory, and liver protection potential.

Antibiot Khimioter, 2004, 49(1), 30 - 4
{Analysis of parameters of the antibacterial treatment of acute otitis media in adults: results of a multicenter study}; Kozlov SN et al.; The programme was aimed at audit of the parameters of antibacterial therapy for acute otitis media in adult outpatients in 8 cities of Russia (Smolensk, Volgograd, Ekaterinburg, Yaroslavl, Nizhny Novgorod, Tyumen, Ryazan, Vladivostok) . The information sources were the case records . The data from the records were structurally fixed in specially designed individual registration charts for further computer processing . The analysis of the results showed that the real practice of the antibacterial therapy for acute otitis media was not based on a unique approach and did not mainly correspond to the present standards . Ampicillin proved to be preferential, whereas it is known that the drug of choice for such cases is amoxicillin . Antibacterial agents with low activity against the basic pathogens of the infection (doxycycline and others) and high toxicity (co-trimoxazol) were often prescribed, while the recommended up-to-date antibiotics (amoxicillin/clavulanate and others) were prescribed extremely rare or not prescribed at all . Scientifically unreasonable combined antibiotic therapy and prescription of parenteral drugs not rational for the treatment of outpatients were practiced.

J Med Chem, 2004 Jun 3, 47(12), 2965 - 8
Synthesis and antibacterial activity of a novel class of 4'-substituted 16-membered ring macrolides derived from tylosin; Phan LT et al.; Novel 4'-substituted 16-membered ring macrolides were synthesized by the cleavage of the mycarose sugar of tylosin and subsequent modification of 4'-hydroxyl group . This new class of macrolide antibiotics exhibited potent activity against some key erythromycin-resistant pathogens.

Rev Biol Trop, 2003 Sep-Dec, 51(3-4), 647 - 73
Phytomedicinal potential of tropical cloudforest plants from Monteverde, Costa Rica; Setzer MC et al.; A pharmacological survey of plants from Monteverde, Costa Rica, including 165 species representing 61 families has been carried out . Crude plant extracts have been tested for in-vitro bactericidal and fungicidal activity as well as cytotoxic and anti-herpes activity . Of these, 123 extracts exhibited notable cytotoxicity, 62 showed antibacterial activity, 4 showed antifungal activity, and 8 showed promising antiviral activity . Thus, 101 of the plant species examined in this work, or 62%, showed marked bioactivity in one or more bioassays . These results underscore the phytomedicinal potential of Neotropical cloud forests.

J Agric Food Chem, 2004 Jun 2, 52(11), 3486 - 91
Composition and functional properties of the essential oil of amazonian basil, Ocimum micranthum Willd., Labiatae in comparison with commercial essential oils; Sacchetti G et al.; Wild Amazonian basil Ocimum micranthum Willd . (O . campechianum Mill.) Labiatae essential oil was analyzed by GC and GC-MS: 31 compounds were identified . The main components were eugenol (46.55 +/- 5.11%), beta-caryophyllene (11.94 +/- 1.31%), and beta-elemene (9.06 +/- 0.99%), while a small amount of linalool (1.49 +/- 0.16%) was detected . The oil was tested for its in vitro food-related biological activities and compared with common basil Ocimum basilicum and Thymus vulgaris commercial essential oils . Radical scavenging activity was evaluated employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay . The oil exerted a good capacity to act as a nonspecific donor of hydrogen atoms or electrons when checked in the diphenylpicrylhydrazyl assay, quenching 76,61 +/- 0.33% of the radical, with values higher than those reported by reference oils . In the beta-carotene bleaching test, the oil provided an antioxidant efficacy comparable with that of O . basilicum and T . vulgaris essential oils . These data were confirmed by photochemiluminescence, where the oil showed a remarkable antioxidant capacity (2.39 +/- 0.1), comparable to that of Trolox and vitamin E, and higher than the other essential oils . Antibacterial activity of O . micranthum essential oil was evaluated against Gram positive and Gram negative bacterial strains . The oil showed a dose-dependent antifungal activity against pathogenic and food spoiling yeasts.

J Biol Chem, 2004 Jul 30, 279(31), 32684 - 91 Epub 2004 May 24.
The position of a key tyrosine in dTDP-4-Keto-6-deoxy-D-glucose-5-epimerase (EvaD) alters the substrate profile for this RmlC-like enzyme; Merkel AB et al.; Vancomycin, the last line of defense antibiotic, depends upon the attachment of the carbohydrate vancosamine to an aglycone skeleton for antibacterial activity . Vancomycin is a naturally occurring secondary metabolite that can be produced by bacterial fermentation . To combat emerging resistance, it has been proposed to genetically engineer bacteria to produce analogues of vancomycin . This requires a detailed understanding of the biochemical steps in the synthesis of vancomycin . Here we report the 1.4 A structure and biochemical characterization of EvaD, an RmlC-like protein that is required for the C-5' epimerization during synthesis of dTDP-epivancosamine . EvaD, although clearly belonging to the RmlC class of enzymes, displays very low activity in the archetypal RmlC reaction (double epimerization of dTDP-6-deoxy-4-keto-D-glucose at C-3' and C-5') . The high resolution structure of EvaD compared with the structures of authentic RmlC enzymes indicates that a subtle change in the enzyme active site repositions a key catalytic Tyr residue . A mutant designed to re-establish the normal position of the Tyr increases the RmlC-like activity of EvaD.

Fitoterapia, 2004 Jun, 75(3-4), 412 - 6
Antibacterial and antifungal activities of Euroschinus papuanus; Khan MR et al.; The crude methanolic extracts of the leaves, stem bark, stem heart wood, root bark and root heart wood of Euroschinus papuanus and the fractions obtained on partitioning with petrol, dichloromethane (D), ethyl acetate (E) and butanol (B), exhibited a broad spectrum antibacterial activity . Fractionation drastically enhanced the activity . Excellent activity was demonstrated by the E fractions of stem heart wood, D of root bark, and E of root heart wood . Antifungal activity was exhibited by the B fractions of leaves, stem heartwood and root bark .

Fitoterapia, 2004 Jun, 75(3-4), 371 - 4
Variability in the content of active constituents and biological activity of Glycyrrhiza glabra; Statti GA et al.; Nine samples of Glycyrrhiza glabra were collected in various sites of Calabria, Italy, with the aim to determine the variability in the confront of active constituents and in antibacterial and antifungal activities of the extracts . The samples showed remarkable differences in chemical composition and biological activity .

Fitoterapia, 2004 Jun, 75(3-4), 360 - 3
Antibacterial and brine shrimp lethality tests of biflavonoids and derivatives of Rheedia gardneriana; Verdi LG et al.; The hydroalcoholic extract of the leaves from Rheedia gardneriana yielded volkensiflavone (1), fukugetin (2), fukugiside (3), GB2a-I-7-O-glucoside (4) and epicatechin (5) . Compounds 1-5, and some derivatives of 1 and 2 were evaluated for lethality to brine shrimp larvae and for antibacterial activity .

Fitoterapia, 2004 Jun, 75(3-4), 355 - 9
Cytotoxicity and antibacterial activity of extractives from Wedelia calendulacea; Mottakin AK et al.; The cytotoxicity and antibacterial activity of petroleum ether, chloroform and methanol extracts of Wedelia calendulacea were assayed by brine shrimp lethality bioassay and standardized disk diffusion method against 19 bacterial strains . Three diterpenes isolated from the plant were also evaluated for in vitro antibacterial activities . The LC50 for the crude extracts against the brine shrimp nauplii were found to be 4.59 microg/ml, 7.99 microg/ml and 14.88 microg/ml, respectively, whereas the positive control, vincristine sulfate showed an LC50 of 0.58 microg/ml . Among the crude extracts and pure compounds tested, (-)-kaur-16-en-19-oic acid isolated from the chloroform extract showed the highest inhibitory activity against most of the bacterial strains with mean zone of inhibition of 10-21 mm at 200 microg/disc .

Chem Biol, 2004 May, 11(5), 655 - 62
New aminocoumarin antibiotics formed by a combined mutational and chemoenzymatic approach utilizing the carbamoyltransferase NovN; Xu H et al.; Five new aminocoumarin antibiotics were produced by a combined mutational and chemoenzymatic approach . For this purpose, the 3"-carbamoyltransferase NovN from the novobiocin producer Streptomyces spheroides was overexpressed in the heterologous host S . lividans as an N-terminal His(6) fusion protein and purified by nickel affinity chromatography . Five different 3"-unsubstituted aminocoumarin derivatives were isolated from mutants of the clorobiocin producer S . roseochromogenes, carrying single or multiple gene defects . All five compounds were readily accepted as substrates by NovN, and the 3"-carbamoylated products were isolated on a preparative scale . Their structures were elucidated by (1)H-NMR and mass spectroscopy, and their inhibitory activity on gyrase in vitro as well as their antibacterial activity was determined . The results give further insight into the structure-activity relationships of aminocoumarin antibiotics.

Biochim Biophys Acta, 2004 May 25, 1678(2-3), 85 - 93
Characterization of a homologue of the Rel/NF-kappaB transcription factor from a beetle, Allomyrina dichotoma; Sagisaka A et al.; A cDNA encoding a Rel/NF-kappaB homologue was cloned from a beetle, Allomyrina dichotoma, by reverse transcriptase-polymerase chain reactions (RT-PCR) taking advantage of the conserved Rel homology domain (RHD) to synthesize primers . The Rel/NF-kappaB homologue was designated A . dichotoma (A.d.) Rel A . The amino acid sequence of the A.d . Rel A RHD was compared with those of insect RHDs . The result showed that it has 70% identity with Tribolium castaneum Dorsal, 66% with Drosophila melanogaster Dorsal, 61% with Anopheles gambiae Gambif1, and 55% with D . melanogaster Dif . A putative phosphorylation site in the RHD, RRPS, and two putative nuclear localization signals were conserved in A.d . Rel A . A recombinant fusion protein containing the A.d . Rel A RHD was confirmed to bind specifically to the NF-kappaB site of a gene encoding A.d . coleoptericin A, an antibacterial peptide from A . dichotoma . The activity of A.d . Rel A in modulating a gene construct of the A.d . coleoptericin A promoter-luciferase reporter by expressing the A.d . coleoptericin A cDNA in a Bombyx mori cell line was analyzed . The result showed that A.d . Rel A strongly activates the A.d . coleoptericin A gene construct, whereas A.d . Rel A failed to activate the gene construct containing the mutated NF-kappaB site, suggesting the importance of the interaction between the NF-kappaB site and A.d . Rel A in the signal transduction for gene expression of antibacterial peptides in A . dichotoma.

Antimicrob Agents Chemother, 2004 Jun, 48(6), 2179 - 84
Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936); Hirata T et al.; The activity of tigecycline, 9-(t-butylglycylamido)-minocycline, against Escherichia coli KAM3 (acrB) strains harboring plasmids encoding various tetracycline-specific efflux transporter genes, tet(B), tet(C), and tet(K), and multidrug transporter genes, acrAB, acrEF, and bcr, was examined . Tigecycline showed potent activity against all three Tet-expressing, tetracycline-resistant strains, with the MICs for the strains being equal to that for the host strain . In the Tet(B)-containing vesicle study, tigecycline did not significantly inhibit tetracycline efflux-coupled proton translocation and at 10 microM did not cause proton translocation . This suggests that tigecycline is not recognized by the Tet efflux transporter at a low concentration; therefore, it exhibits significant antibacterial activity . These properties can explain its potent activity against bacteria with a Tet efflux resistance determinant . Tigecycline induced the Tet(B) protein approximately four times more efficiently than tetracycline, as determined by Western blotting, indicating that it is at least recognized by a TetR repressor . The MICs for multidrug efflux proteins AcrAB and AcrEF were increased fourfold . Tigecycline inhibited active ethidium bromide efflux from intact E . coli cells overproducing AcrAB . Therefore, tigecycline is a possible substrate of AcrAB and its close homolog, AcrEF, which are resistance-modulation-division-type multicomponent efflux transporters.

Antimicrob Agents Chemother, 2004 Jun, 48(6), 2061 - 8
Novel pharmacokinetic-pharmacodynamic model for prediction of outcomes with an extended-release formulation of ciprofloxacin; Meagher AK et al.; The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers . The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation . The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma . A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes . A "mixture model" was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment . Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter . At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect: the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively . The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios.

J Chem Inf Comput Sci, 2004 May-Jun, 44(3), 1031 - 41
Artificial neural networks and linear discriminant analysis: a valuable combination in the selection of new antibacterial compounds; Murcia-Soler M et al.; A set of topological descriptors has been used to discriminate between antibacterial and nonantibacterial drugs . Topological descriptors are simple integers calculated from the molecular structure represented in SMILES format . The methods used for antibacterial activity discrimination were linear discriminant analysis (LDA) and artificial neural networks of a multilayer perceptron (MLP) type . The following plot frequency distribution diagrams were used: a function of the number of drugs within a value interval of the discriminant function and the output value of the neural network versus these values . Pharmacological distribution diagrams (PDD) were used as a visualizing technique for the identification of antibacterial agents . The results confirmed the discriminative capacity of the topological descriptors proposed . The combined use of LDA and MLP in the guided search and the selection of new structures with theoretical antibacterial activity proved highly effective, as shown by the in vitro activity and toxicity assays conducted.

Anticancer Res, 2004 Mar-Apr, 24(2C), 1143 - 7
Treatment of glioblastoma with intravenous taurolidine . First clinical experience; Stendel R et al.; BACKGROUND: Despite progress in diagnosis and therapy, the prognosis of patients with glioblastoma remains poor . Recently it has been found that the antibacterial agent taurolidine has a direct and selective antineoplastic effect on brain tumor cells by the induction of programmed cell death . This paper reports on intravenous taurolidine treatment in two patients with a progressive glioblastoma despite conventional therapy . PATIENTS AND METHODS: Two male patients with histopathologically diagnosed glioblastoma were included . The tumors were progressive despite conventional therapy . Intravenous taurolidine treatment was initiated . RESULTS: The neurological condition and quality of life improved in both patients such that they could be discharged for further outpatient treatment . Follow-up demonstrated partial remission of the tumor in both patients . However, both patients died about 4 months following the start of taurolidine treatment, from pneumonia and acute thrombembolism, respectively . CONCLUSION: Both patients achieved a transient, marked improvement in quality of life and partial tumor remission . There was a clear response to the taurolidine treatment.

Am J Dent, 2004 Apr, 17(2), 89 - 93
Bonding to root caries by a self-etching adhesive system containing MDPB; Doi J et al.; PURPOSE: To evaluate the bonding of an experimental antibacterial fluoride-releasing adhesive system (ABF) to normal and carious dentin in human teeth with Class V root caries . METHODS: Mesiodistal sectioning removed the buccal enamel, superficial dentin and much of the carious dentin in 21 extracted human bicuspids with root surface caries . The surfaces of normal coronal and root dentin, and caries-affected and caries-infected dentin were ground with wet 600-grit SiC paper to create a standardized smear layer . Tooth surfaces were treated with the ABF according to manufacturer's instructions, and then covered with excess resin composite . After immersion in 37 degrees C water for 24 hours, the restored teeth were horizontally sectioned into serial slabs that were trimmed into hourglass shapes to isolate the bonded area to the test substrates, and then their bond strengths were measured by the microtensile bond test, and the interfaces examined by SEM and TEM . The bond strengths were statistically compared with ANOVA and Fisher's PLSD (P < 0.05) . RESULTS: The bond strengths of ABF to caries-affected and caries-infected dentin were significantly lower than those to normal coronal and root dentin . SEM micrographs revealed that the hybrid layers in caries-affected and caries-infected dentin were more porous compared to the hybrid layer in normal coronal and root dentin . TEM micrographs showed that bacteria that had invaded the dentin were embedded in this adhesive monomer in caries-infected dentin . CLINICAL SIGNIFICANCE: Although the bond strength of ABF adhesive system to root carious dentin is lower than that of normal dentin, the antibacterial and fluoride-releasing properties of ABF may contribute to prevent caries progression and inhibit secondary caries.

J Antimicrob Chemother, 2004 Jun, 53 Suppl 2, ii7 - 9
Ertapenem: a Group 1 carbapenem with distinct antibacterial and pharmacological properties; Hammond ML; Ertapenem, a Group 1 carbapenem, is the most recent beta-lactam antibiotic to enter clinical practice in the USA and Europe . While structurally a carbapenem, the overall molecular structure of ertapenem has been modified to focus its antibacterial spectrum on important community-acquired aerobic and anaerobic pathogens, and to increase its plasma half-life, permitting once-a-day dosing for this parenteral antibiotic . A number of chemical features are responsible for the unique properties of ertapenem . The inclusion of a trans-1-hydroxyethyl group in the structure of ertapenem enables the drug to maintain antibacterial efficacy against the vast majority of beta-lactamase-producing organisms . A critical 1beta-methyl substituent shields the beta-lactam carbonyl group and serves to reduce dehydropeptidase (DHP)-1 catalysed hydrolysis of the beta-lactam, enabling ertapenem to be administered without a DHP-1 inhibitor . A meta-substituted benzoic acid substituent increases the molecular weight and lipophilicity of the molecule, and the carboxylic acid moiety, ionized at physiological pH, results in ertapenem having a net negative charge . As a result, ertapenem is highly protein bound and has an extended half-life, permitting a once-a-day treatment regimen.

J Inorg Biochem, 2004 Jun, 98(6), 1054 - 60
Involvement of reactive oxygen species in the bactericidal activity of activated carbon fibre supporting silver; Bactericidal activity of ACF(Ag) mediated by ROS; Le Pape H et al.; An activated carbon fibre supporting silver (ACF(Ag)) was tested for its antibacterial capacity against Escherichia coli (E . coli) . Water that has passed through ACF(Ag) demonstrated strong bactericidal ability . This activity decreased over the time suggesting that generated bactericidal species were short lifespan . Since formation of reactive oxygen species (ROS) might be catalysed by silver impregnated and/or ACF itself, implication of ROS and silver was evaluated by the use of ROS scavengers and a silver ions neutralizing agent . The role of ROS in the E . coli mortality was confirmed by the use of a molecular approach which revealed a strong expression of oxidative stress genes.

Bioorg Med Chem Lett, 2004 Jun 21, 14(12), 3299 - 302
Novel inhibitors of bacterial protein synthesis: structure-activity relationships for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants; Clark RF et al.; Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated . Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues . A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent.

Bioorg Med Chem Lett, 2004 Jun 21, 14(12), 3189 - 93
Synthesis and structure-activity relationships of 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines as novel antitumor agents; Tsuzuki Y et al.; In order to obtain clinically useful antitumor agent, we have designed and synthesized various 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines, and evaluated their cytotoxic activity . The series of novel 3-substituted derivatives synthesized in this study showed good antitumor activity against murine P388 leukemia . Particularly, the 3-formyl 1,8-naphthyridine displayed an antitumor activity equal to that of the 3-carboxy 1,8-naphthyridine against murine and human tumor cell lines as well as in vivo test for mouse leukemia . These results demonstrate that the carboxy group at the C-3 position of 1,8-naphthyridine ring is not essential for antitumor activity . In addition, the trend of cytotoxic activity for the 3-substituted 1,8-naphthyridines was different from that of antibacterial activity.

Bioorg Med Chem Lett, 2004 Jun 21, 14(12), 3161 - 4
A new 2-carbamoyl pteridine that inhibits mycobacterial FtsZ; Reynolds RC et al.; The preparation of a new 2-carbamoyl pteridine, its activity data against FtsZ from M . tuberculosis (Mtb), and in vitro antibacterial data against Mtb strain H37Ra are presented.

Bioorg Med Chem Lett, 2004 Jun 21, 14(12), 3139 - 42
Oxazolidinone: search for highly potent antibacterial; Lohray BB et al.; A number of substituted piperazinyl oxazolidinone derivatives have been synthesized and their antibacterial activities were evaluated by MIC determination . A systematic SAR was carried out to get highly potent oxazolidinone derivatives.

Prescrire Int . 2004 Apr;13(70):53.
Nifuroxazide: licence modification . New restrictions in children; Combined Assessment of beta- d-Glucan and Degree of Candida Colonization before Starting Empiric Therapy for Candidiasis in Surgical Patients; Department of Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, 2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, JapanThe purpose of the study was to investigate whether examination for plasma beta- d-glucan, a cell wall constituent of fungi, is useful for selecting surgical patients with Candida colonization who would benefit from empiric antifungal therapy . We administered fluconazole to postoperative patients with Candida colonization who have risk factors for candidemia and complained of persistent fever despite prolonged antibacterial therapy . We then analyzed the clinical outcomes regarding the number of sites colonized with Candida spp . and plasma beta- d-glucan . Of the 32 patients positive for beta- d-glucan, 15 (46.9%) responded to the empiric therapy; only 9% of those who were negative responded ( p < 0.01) . In the multiple logistic regression analysis, being positive for beta- d-glucan was a significant factor predicting response, with an adjusted odds ratio of 12.9 in patients with Candida colonization {95% confidence interval (CI) 2.07-80.73) ( p < 0.01) . In addition, the number of sites colonized with Candida spp . was a significant factor predicting response, with an estimated exposure odds ratio of 7.57 for those who were colonized at three or more sites compared with those colonized at one site (95% CI 1.20-47.70) ( p = 0.031) . In patients with Candida colonization, assessment of beta- d-glucan was useful for deciding whether to start empiric therapy for suspected candidiasis in surgical patients.

Methods Mol Biol, 2004, 266, 231 - 59
Genomic approaches to antibacterial discovery; Payne DJ et al.; This chapter describes two key strategies for the discovery of new antibacterial agents and illustrates the critical role played by genomics in each . The first approach is genomic target-based screening . Comparative genomics and bioinformatics are used to identify novel, selective antibacterial targets of the appropriate antibacterial spectrum . Genetic technologies integral for the success of this approach, such as essentiality testing, are also described . An unprecedented number of novel targets have been discovered via this approach, and a plethora of examples are discussed . This section concludes with the case history of a target successfully progressed from identification by genomics, to high-throughput screening, and onto proof of concept in curing experimental infections . The second approach is based on screening for compounds with antibacterial activity and then employing a broad variety of newer technologies to identify the molecular target of the antibacterial agent . The advantage of this approach is that compounds already possess antibacterial activity, which is a property often challenging to engineer into molecules obtained from enzyme-based screening approaches . The recent development of novel biochemical and genomic technologies that facilitate identification and characterization of the mode of action of these agents has made this approach as attractive as the genomic target-based screening strategy.

Vestn Khir Im I I Grek, 2004, 163(1), 16 - 9
{Surgical strategy in active infective endocarditis}; Viaznikov VA et al.; In the cardio-surgical department of the regional clinical hospital of Kirov oblast 117 patients (83 men and 34 women) with active infective endocarditis of native heart valves were operated upon: with injury of the aortal valve (61), mitral (37), mitral and aortal (16), tricuspidal (2), mitral, aortal and tricuspidal (1) . During 10 days the patients were examined and prepared for operation which included intensive antibacterial, cardiotropic and immunomodulating therapy . Then the operation of prosthesing the valve, mainly with domestic prostheses "LIKS-2" and Karboniks-1 was performed . Lethality was 7.6% . Recurrent endocarditis took place in 6% of cases . In reoperations cannulation of the femoral artery and retrograde cardioplegia were used . In repeated mitral prosthesing right side thoracotomy in the 4th intercostal area was used as the approach . The surgical strategy for active infective endocarditis should consist of maximally rapid examination of the patient, rapid intensive preparation for the operation performed in maximally early terms.

Bioorg Med Chem, 2004 Jun 1, 12(11), 3047 - 54
Antibacterial chalcones--bioisosteric replacement of the 4'-hydroxy group; Nielsen SF et al.; Hydroxy chalcones, for example, Licochalcone A, has for several years been known to be antibacterial . The low aqueous solubility and the medium antibacterial potency have limited the usefulness of the compounds . We describe the bioisosteric replacement of the essential 4'-hydroxy group in the hydroxy chalcones with bioisosters of varied degrees of acidity resulting in both more potent and more soluble compounds . The more acidic 4'-hydroxy analogues (e.g., 3'-fluoro- or 3',5'-difluoro-) gave almost inactive compounds whereas exchanging the hydroxy group with a carboxy group resulted in a potent compound with a high aqueous solubility . Further optimisation and SAR-analysis resulted in soluble and potent carboxy chalcones {e.g., 3,5-dibromo- and 3,5-di(trifluoromethyl)-}.

Bioorg Med Chem, 2004 Jun 1, 12(11), 3027 - 35
QSPR of 3-aryloxazolidin-2-one antibacterials; Katritzky AR et al.; A QSPR treatment has been applied to a data set consisting of 60 3-aryloxazolidin-2-one antibacterials to relate the in vitro minimum inhibitory concentration (MIC) (required to inhibiting growth of S . aureus) with theoretical molecular and fragment descriptors . The treatment using codessa pro descriptors leads to a seven-parameter model with r2 = 0.820 and r2cv = 0.758.

Comp Biochem Physiol B Biochem Mol Biol, 2004 May, 138(1), 53 - 64
Two novel muramidases from skin mucosa of rainbow trout (Oncorhynchus mykiss); Fernandes JM et al.; Two novel antibacterial muramidases were purified to homogeneity from skin exudates of rainbow trout (Oncorhynchus mykiss) . Unusually, one has an acidic isoelectric point and it is the first anionic muramidase to be reported for fish . Its molecular mass is 14,268 Da, as determined by mass spectrometry . The other muramidase is cationic with a mass of 14,252 Da . Partial N-terminal amino acid sequencing and peptide mapping strongly point to it being a c-type lysozyme, the first to be purified and characterised from skin of a salmonid . Its optimum pH ranges from 4.5 to 5.5 and its optimum temperature, at pH 5.0, is 33-49 degrees C, although it still exhibits activity at 5 degrees C . It is strongly bactericidal to the Gram-(+) bacterium Planococcus citreus, with a minimum bactericidal concentration of 100 U ml(-1), but is neither chitinolytic nor haemolytic . These two muramidases probably contribute to epithelial defence of the fish against microbes, either alone or in synergism with antibacterial peptides.

J Pharm Pharmacol, 2004 May, 56(5), 677 - 81
Melissa officinalis L . essential oil: antitumoral and antioxidant activities; de Sousa AC et al.; Melissa officinalis L (lemon balm) is a traditional herbal medicine used widely as a mild sedative, spasmolytic and antibacterial agent . This paper focuses on the analysis of the chemical composition and the biological activities of M . officinalis essential oil obtained under controlled harvesting and drying conditions . An in-vitro cytotoxicity assay using MTT indicated that this oil was very effective against a series of human cancer cell lines (A549, MCF-7, Caco-2, HL-60, K562) and a mouse cell line (B16F10) . This oil possessed antioxidant activity, as evidenced by reduction of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) . These results pointed to the potential use of M . officinalis essential oil as an antitumoral agent.

J Pharm Pharmacol, 2004 May, 56(5), 565 - 71
Ca(2+), calpain and 3-phosphorylated phosphatidyl inositides; decision-making signals in neutrophils as potential targets for therapeutics; Tian W et al.; The chemical signals within neutrophils that control their behaviour are complex and these signals control the complex activity of neutrophils with precision . Failure of neutrophils to reform their antibacterial activity would lead to infection, while over-activity of neutrophils may lead to tissue damage and inflammatory disease . The identity of some of the intracellular signals is becoming clear and insights into the potential for interplay between them are being sought . Although it is well established that cytosolic free Ca(2+) plays a role, it is only recently that the importance of intracellular protease, calpain, and the 3-position phosphorylated phosphatidyl inositides is becoming recognised . In this review these three key signals are discussed as potential therapeutic targets for the modulation of neutrophil activity.

Poult Sci, 2004 May, 83(5), 726 - 31
Influence of hard water on the bioavailability of enrofloxacin in broilers; Sumano LH et al.; To define the impact that use of different levels of hard water has on the bioavailability of the antibacterial, enrofloxacin, in poultry, an oral bioavailability-pharmacokinetic study of the drug was carried out . Two hundred fifty clinically healthy broilers, divided into 5 groups, were individually dosed orally with 10 mg/kg of enrofloxacin diluted to 0.1% . The enrofloxacin was diluted with water of increasing hardness in accordance with an international grading system . After dosing, blood samples were obtained at predetermined times . Serum was recovered and quantified for enrofloxacin by means of an agar diffusion bacteriological method . The composite serum concentrations of enrofloxacin and metabolites vs . time relationships were analyzed using software for compartmental pharmacokinetics . Results show that there were statistically significant differences in the following pharmacokinetic variables: maximal serum concentrations (Csmax), area under the time vs . concentration curves, and half-lives of the elimination phases . The means of these values showed a linear decay of Csmax from one group to the next as water hardness increased . Chemical analysis of water calcium and magnesium ions revealed the formation of coordination groups . Lack of interference with the microbiological activity in vitro of enrofloxacin diluted in hard water indicated that diminished absorption may be partly responsible for reduction in bioavailability . These results stress the need for proper water supply when enrofloxacin is used and point out a factor that must be taken into account when clinical outcomes do not comply with expectations.

Curr Med Res Opin, 2004 May, 20(5), 749 - 56
Comparison of hospitalization rates in patients with community-acquired pneumonia treated with 10 days of telithromycin or clarithromycin; Niederman MS et al.; AIMS: To compare the impact on hospitalization rates and the clinical efficacy of oral telithromycin and clarithromycin treatment in patients with community-acquired pneumonia (CAP) . PATIENTS AND METHODS: Outpatients aged >or= 18 years (n = 448) with CAP were enrolled in a randomized, double-blind, multinational study and received telithromycin 800 mg once daily (n = 224) or clarithromycin 500 mg twice daily (n = 224) for 10 days . The primary outcome measure was clinical efficacy at post-therapy/test of cure (Days 17-24) in the per-protocol population . Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use were compared by treatment group (intent to treat population) up to the late post-therapy visit (Days 31-36) . Study investigators who were blinded to the treatment arm assessed whether hospital admissions were CAP related or not . Hospitalization costs (USdollars) associated with telithromycin and clarithromycin treatment were compared . RESULTS: Per-protocol clinical cure rates for telithromycin and clarithromycin were statistically reduced number of hospitalizations/days required equivalent (88.3% {143/162} vs 88.5% {138/156} - difference: -0.2%; 95% CI: -7.8, 7.5) . There were four CAP-related hospitalizations (1.8 events/100 patients) among patients treated with telithromycin vs eight (3.6 events/100 patients) among clarithromycin patients (p = 0.281) . Total CAP-related hospitalization costs for telithromycin and clarithromycin patients were $25 360 vs $70 567, respectively (difference: -20 182 per 100 patients; 95% CI: -49 531; 9168) {corrected} . CONCLUSIONS: This study demonstrates that telithromycin is an effective therapy for outpatients with CAP.There were no significant differences in hospitalization rates between treatments; however, a tendency towards a numerically in hospital among telithromycin patients was observed . This could potentially translate into reduced hospitalization costs for telithromycin vs clarithromycin in the treatment of CAP.

Curr Med Res Opin, 2004 May, 20(5), 739 - 47
Comparison of hospitalization rates in patients with community-acquired pneumonia treated with telithromycin for 5 or 7 days or clarithromycin for 10 days; Tellier G et al.; AIMS: To compare the impact on hospitalization rates and the clinical efficacy of oral telithromycin and clarithromycin treatment in patients with community-acquired pneumonia (CAP) . METHODS: A total of 581 patients with CAP were enrolled in this randomized, double-blind, parallel group, multinational study, of whom 575 were evaluated for healthcare resource utilization from a payer perspective (intent to treat {ITT} population) . Patients received telithromycin 800 mg once daily for 5 (n = 193) or 7 (n = 195)days, or clarithromycin 500 mg once daily for 10 days (n = 187) . The primary efficacy endpoint was clinical outcome at test of cure (Days 17-24) in the per-protocol population . Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use were compared by treatment group (ITT) up to late post- for clarithromycin vs dollars 37930 (difference: -26446; therapy (Days 31-36) . Study investigators blinded to treatment assessed whether hospital admissions were CAP-related or not . CAP-related hospitalization costs (USdollars) for telithromycin and clarithromycin were compared . RESULTS: Clinical cure rates were similar in patients who received clarithromycin for 10 days and telithromycin for 5 or 7 days: 91.8% (134/146), 89.3% (142/159), and 88.8% (143/161), respectively, and both 5- and 7-day telithromycin were statistically equivalent to clarithromycin (difference: -2.5 and -3.0%, respectively; 95% CI: -9.7, 4.7 and -10.2, 4.3, respectively) . There were 7 CAP-related hospital admissions among clarithromycin patients vs 3 (p = 0.283) and 1 (p = 0.021) admissions among 5- and 7-day telithromycin patients, respectively . The number of hospital days/100 patients was 40.1 for clarithromycin vs 17.1 and 7.2 for 5- and 7-day telithromycin, respectively . Projected hospitalization costs/100 patients were dollars 86205 95% CI: -66 654; 13 762) and dollars 16 091 (difference: -37 847; 95% CI: -77953; 2259) for 5- and 7-day telithromycin, respectively . CONCLUSIONS: Data from this study demonstrate that telithromycin 800 mg once daily for 5 or 7 days with fewer hospital days and potentially lower is an effective treatment for CAP,and that telithromycin treatment of CAP may be associated hospitalization costs than clarithromycin treatment.

Biochem J, 2004 Aug 1, 381(Pt 3), 735 - 41
Mutational analysis of the triclosan-binding region of enoyl-ACP (acyl-carrier protein) reductase from Plasmodium falciparum; Kapoor M et al.; Triclosan, a known antibacterial, acts by inhibiting enoyl-ACP (acyl-carrier protein) reductase (ENR), a key enzyme of the type II fatty acid synthesis (FAS) system . Plasmodium falciparum, the human malaria-causing parasite, harbours the type II FAS; in contrast, its human host utilizes type I FAS . Due to this striking difference, ENR has emerged as an important target for the development of new antimalarials . Modelling studies, and the crystal structure of P . falciparum ENR, have highlighted the features of ternary complex formation between the enzyme, triclosan and NAD+ {Suguna, A . Surolia and N . Surolia (2001) Biochem . Biophys . Res . Commun . 283, 224-228; Perozzo, Kuo, Sidhu, Valiyaveettil, Bittman, Jacobs, Fidock, and Sacchettini (2002) J . Biol . Chem . 277, 13106-13114; and Swarnamukhi, Kapoor, N . Surolia, A . Surolia and Suguna (2003) PDB1UH5} . To address the issue of the importance of the residues involved in strong specific and stoichiometric binding of triclosan to P . falciparum ENR, we mutated the following residues: Ala-217, Asn-218, Met-281, and Phe-368 . The affinity of all the mutants was reduced for triclosan as compared with the wild-type enzyme to different extents . The most significant mutation was A217V, which led to a greater than 7000-fold decrease in the binding affinity for triclosan as compared with wild-type PfENR . A217G showed only 10-fold reduction in the binding affinity . Thus, these studies point out significant differences in the triclosan-binding region of the P . falciparum enzyme from those of its bacterial counterparts.

Zhongguo Zhong Yao Za Zhi, 2003 Jul, 28(7), 593 - 7
{Advances in studies on flavonoids of licorice}; Xing GX et al.; The progress in the research of the active ingredients of licorice flavonoid and the pharmacological activities was reviewed . Licorice flavonoid constituents mainly included flavones, flavonals, isoflavones, chalcones, bihydroflavones and bihydrochalcones . Pharmacological investigation concluded that they had antioxidant, antibacterial, antitumer and inhibiting HIV activities . It is important to study further the flavonoid constituents and pharmacological activities.

Acta Neuropathol (Berl), 2004 Jul, 108(1), 65 - 8 Epub 2004 May 08.
Rifampicin inhibits neurodegeneration in the optic nerve transection model in vivo and after 1-methyl-4-phenylpyridinium intoxication in vitro; Kilic U et al.; Rifampicin is an antibacterial drug which is highly effective in the treatment of tuberculosis and leprosy . It has been shown to exert antioxidative as well as anti-apoptotic effects . In this study, the neuroprotective effect of rifampicin was examined after 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic cell death in vitro, and on the survival of retinal ganglion cells after optic nerve transection in vivo . Rifampicin administration significantly increased the number of surviving dopaminergic neurons after MPP+ intoxication as compared to control cultures . No cytotoxic effects were noted even at final rifampicin concentrations of 100 microM . In the rifampicin-treated group, retinal ganglion cell survival was significantly increased after axotomy as compared with vehicle-treated and phosphate-buffered saline-treated control animals . These results suggest that rifampicin is able to prevent neuronal degeneration in cell death paradigms involving oxidative stress and activation of apoptotic pathways . It may thus play a role in the future treatments of neurodegenerative disorders.

Pharmacoeconomics, 2004, 22(7), 413 - 20
Adherence to guidelines for community-acquired pneumonia: does it decrease cost of care?
Brown PD.
Community-acquired pneumonia (CAP) is a common diagnosis and care of CAP is responsible for significant healthcare expenditures, the majority of which are for patients who require hospitalisation . Studies have shown that significant variation exists among institutions with respect to antibacterial costs and length of stay (LOS) for CAP . These variations do not appear to be associated with significant differences in patient outcomes . This information has stimulated the development of practice guidelines and critical pathways to optimise the care of patients with CAP . The central focus of guidelines is recommendations for antibacterial therapy; critical pathways include recommendations for therapy, but focus on the process of care for patients with CAP . Guidelines and critical pathways are time consuming to develop and their implementation requires significant institutional resources . Therefore, it is essential that they are shown to be effective, and there has been significant interest in determining if guidelines and pathways can improve the cost effectiveness of care . In the past several years, a number of studies have evaluated the impact of treatment consistent with guidelines on outcomes for patients with CAP . These studies have shown that antibacterial therapy that is consistent with guidelines can reduce LOS, decrease costs, and several have shown a favourable impact on mortality . The majority of these studies have been retrospective reviews . One multicenter prospective, randomised trial of a critical pathway for CAP revealed significant reductions in the hospital admission of patients, LOS and cost of care . Other studies of processes of care have been mainly 'before and after' interventions; many have shown reductions in LOS and costs.Based on the available data, it is reasonable to expect that adherence to guidelines and critical pathways can reduce the cost of care for CAP; however, randomised controlled trials that include a formal cost-effectiveness analysis are needed . Even if the data to support the use of guidelines and pathways are robust, those who develop and implement them need to anticipate and understand barriers to physician adherence .

Proc Natl Acad Sci U S A, 2004 May 18, 101(20), 7821 - 6 Epub 2004 May 10.
Arabidopsis thaliana DNA gyrase is targeted to chloroplasts and mitochondria; Wall MK et al.; DNA gyrase is the bacterial DNA topoisomerase (topo) that supercoils DNA by using the free energy of ATP hydrolysis . The enzyme, an A(2)B(2) tetramer encoded by the gyrA and gyrB genes, catalyses topological changes in DNA during replication and transcription, and is the only topo that is able to introduce negative supercoils . Gyrase is essential in bacteria and apparently absent from eukaryotes and is, consequently, an important target for antibacterial agents (e.g., quinolones and coumarins) . We have identified four putative gyrase genes in the model plant Arabidopsis thaliana; one gyrA and three gyrB homologues . DNA gyrase protein A (GyrA) has a dual translational initiation site targeting the mature protein to both chloroplasts and mitochondria, and there are individual targeting sequences for two of the DNA gyrase protein B (GyrB) homologues . N-terminal fusions of the organellar targeting sequences to GFPs support the hypothesis that one enzyme is targeted to the chloroplast and another to the mitochondrion, which correlates with supercoiling activity in isolated organelles . Treatment of seedlings and cultured cells with gyrase-specific drugs leads to growth inhibition . Knockout of A . thaliana gyrA is embryo-lethal whereas knockouts in the gyrB genes lead to seedling-lethal phenotypes or severely stunted growth and development . The A . thaliana genes have been cloned in Escherichia coli and found to complement gyrase temperature-sensitive strains . This report confirms the existence of DNA gyrase in eukaryotes and has important implications for drug targeting, organelle replication, and the evolution of topos in plants.

Biochim Biophys Acta, 2004 May 6, 1698(2), 167 - 74
Biochemical characterization of an inhibitor of Escherichia coli UDP-N-acetylmuramyl-l-alanine ligase; Ehmann DE et al.; UDP-N-acetylmuramyl-l-alanine ligase (MurC) is an essential bacterial enzyme involved in peptidoglycan biosynthesis and a target for the discovery of novel antibacterial agents . As a result of a high-throughput screen (HTS) against a chemical library for inhibitors of MurC, a series of benzofuran acyl-sulfonamides was identified as potential leads . One of these compounds, Compound A, inhibited Escherichia coli MurC with an IC(50) of 2.3 microM . Compound A exhibited time-dependent, partially reversible inhibition of E . coli MurC . Kinetic studies revealed a mode of inhibition consistent with the compound acting competitively with the MurC substrates ATP and UDP-N-acetyl-muramic acid (UNAM) with a K(i) of 4.5 microM against ATP and 6.3 microM against UNAM . Fluorescence binding experiments yielded a K(d) of 3.1 microM for the compound binding to MurC . Compound A also exhibited high-affinity binding to bovine serum albumin (BSA) as evidenced by a severe reduction in MurC inhibition upon addition of BSA . This finding is consistent with the high lipophilicity of the compound . Advancement of this compound series for further drug development will require reduction of albumin binding.

Mini Rev Med Chem, 2004 May, 4(4), 437 - 59
Bioactive carbohydrates and recently discovered analogues as chemotherapeutics; Wrodnigg TM et al.; Infectious diseases such as tuberculosis, malaria, the "simple flu" or HIV and HBV, are killing more than 50,000 people a day according to estimations by the World Health Organisation (WHO) . Consequently, the development of biologically active agents in general, such as antibiotics and chemotherapeutics, is of great importance . Hand in hand with the understanding of the mechanisms of biological agents, structures carrying sugar moieties have become increasingly important during the last decades . This review will cover the most recent developments in the field of new antibiotics and synthetic agents containing carbohydrates which are active against tuberculosis and malaria . In addition, compounds having antiviral, antibacterial and anticancer properties will be examined . Compounds such as aminoglycosides, iminosugars, carbacycles, nucleosides, and other selected substance classes will be considered.

Urol Int, 2004, 72 Suppl 1, 34 - 9
Pain killers and antibacterial therapy for kidney colic and stones; Porena M et al.; In 85% of patients, renal colic is caused by renal-ureteral stones with extrinsic obstructions such as pelvic, retroperitoneal or intestinal abnormalities, and intrinsic reno-ureteral obstructions, e.g . junction pathologies and malformation, accounting for only 10 and 5%, respectively . The objectives of therapy for renal colic therapy are to eliminate pain, preserve renal function and eliminate the obstruction by the excretory pathway . Many drugs can be used to relieve pain: non-steroid anti-inflammatory agents (NSAIDs), opioid analgesics, antidiuretic hormone (ADH), loco-regional anesthesia and acupuncture . Opiates are the first-choice therapy during pregnancy as no other drug is indicated because of tetragenic potential . Paracetamol (N-acetyl-p-aminophenol) is the only NSAID that is registered for pediatric use because it has none of the adverse side effects that are associated with NSAIDs . Tamsulosin, an alpha-lithic drug, has very recently been included among the drugs that are used for stone expulsion . The rationale underlying its use is that a high concentration of alpha-1D adrenergic receptors has been recently detected in the terminal ureter, especially in the intramural tract . Inhibition of alpha-1D receptor stimulation should relax smooth muscle in the intramural ureteral tract, making stone expulsion easier .

Biol Pharm Bull, 2004 May, 27(5), 652 - 6
Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones; Alagarsamy V et al.; A variety of novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with a variety of amines, the starting material dithiocarbamate was synthesized from methylanthranilate . The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities . While the test compounds exhibited significant activity, the compounds A1, A2, A3 and A4 shown more potent analgesic activity, and the compound A4 shown more potent anti-inflammatory activity than the reference diclofenac sodium.

J Biol Chem, 2004 Jul 23, 279(30), 30994 - 1001 Epub 2004 May 07.
Evaluation of epigallocatechin gallate and related plant polyphenols as inhibitors of the FabG and FabI reductases of bacterial type II fatty-acid synthase; Zhang YM et al.; Epigallocatechin gallate (EGCG) is the major component of green tea extracts and possesses antibacterial, antiviral, and antitumor activity . Our study focused on validating the inhibition of the bacterial type II fatty acid synthesis system as a mechanism for the antibacterial effects of EGCG and related plant polyphenols . EGCG and the related tea catechins potently inhibited both the FabG and FabI reductase steps in the fatty acid elongation cycle with IC(50) values between 5 and 15 microm . The presence of the galloyl moiety was essential for activity, and EGCG was a competitive inhibitor of FabI and a mixed type inhibitor of FabG demonstrating that EGCG interfered with cofactor binding in both enzymes . EGCG inhibited acetate incorporation into fatty acids in vivo, although it was much less potent than thiolactomycin, a validated fatty acid synthesis inhibitor, and overexpression of FabG, FabI, or both did not confer resistance . A panel of other plant polyphenols was screened for FabG/FabI inhibition and antibacterial activity . Most of these inhibited both reductase steps, possessed antibacterial activity, and inhibited cellular fatty acid synthesis . The ability of the plant secondary metabolites to interfere with the activity of multiple NAD(P)-dependent cellular processes must be taken into account when assessing the specificity of their effects.

Drugs Aging, 2004, 21(7), 427 - 35
Life-threatening idiosyncratic drug-induced agranulocytosis in elderly patients; Andres E et al.; Agranulocytosis is a life-threatening disorder in any age, but particularly so in elderly patients who are receiving, on average, a larger number of drugs than younger patients . Drug-induced agranulocytosis still remains a rare event, with an annual incidence rate of approximately 3-12 cases per million population . This disorder frequently occurs as an adverse reaction to drugs, particularly antibacterials, antiplatelet agents, antithyroid drugs, antipsychotics or antiepileptic drugs, and NSAIDs . Although patients experiencing drug-induced agranulocytosis may initially be asymptomatic, the severity of the neutropenia usually translates into the onset of severe sepsis that requires intravenous broad-spectrum antibacterial therapy . In this setting, haematopoietic growth factors have been shown to shorten the duration of neutropenia . Thus, with appropriate management, the mortality rate of idiosyncratic drug-induced agranulocytosis is now 5-10% . However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management .

J Comb Chem, 2004 May-Jun, 6(3), 398 - 406
Optimization of antibacterial cyclic decapeptides; Qin C et al.; A previously developed method for cyclic peptide synthesis was demonstrated to be able to provide convenient access to large combinatorial libraries of analogues, and this methodology was applied to the optimization of natural product cyclic decapeptides . Using this method, a 192-member library was designed and successfully constructed on the basis of the natural products tyrocidines, streptocidins, and loloatins to increase the therapeutic indices of these antibiotics . Library screening identified nine analogues whose therapeutic indices were increased by up to 90-fold in comparison to the natural products . Three of these analogues showed significant increase in antibacterial potency and concurrent drastic decrease in hemolytic activity . Since the natural products target the bacterial cell wall, the newly discovered analogues are promising leads for drug development against drug-resistant bacteria.

J Allergy Clin Immunol, 2004 May, 113(5), 973 - 6
Distribution of peanut allergen in the environment; Perry TT et al.; BACKGROUND: Patients with peanut allergy can have serious reactions to very small quantities of peanut allergen and often go to extreme measures to avoid potential contact with this allergen . OBJECTIVE: The purpose of this study was to detect peanut allergen under various environmental conditions and examine the effectiveness of cleaning agents for allergen removal . METHODS: A monoclonal-based ELISA for Arachis hypogaea allergen 1 (Ara h 1; range of detection, 30-2000 ng/mL) was used to assess peanut contamination on cafeteria tables and other surfaces in schools, the presence of residual peanut protein after using various cleaning products on hands and tabletops, and airborne peanut allergen during the consumption of several forms of peanut . RESULTS: After hand washing with liquid soap, bar soap, or commercial wipes, Ara h 1 was undetectable . Plain water and antibacterial hand sanitizer left detectable Ara h 1 on 3 of 12 and 6 of 12 hands, respectively . Common household cleaning agents removed peanut allergen from tabletops, except dishwashing liquid, which left Ara h 1 on 4 of 12 tables . Of the 6 area preschools and schools evaluated, Ara h 1 was found on 1 of 13 water fountains, 0 of 22 desks, and 0 of 36 cafeteria tables . Airborne Ara h 1 was undetectable in simulated real-life situations when participants consumed peanut butter, shelled peanuts, and unshelled peanuts . CONCLUSION: The major peanut allergen, Ara h 1, is relatively easily cleaned from hands and tabletops with common cleaning agents and does not appear to be widely distributed in preschools and schools . We were not able to detect airborne allergen in many simulated environments.

Pediatr Res, 2004 Jul, 56(1), 99 - 103 Epub 2004 May 05.
Labor promotes neonatal neutrophil survival and lipopolysaccharide responsiveness; Molloy EJ et al.; Labor is a mild proinflammatory state that is associated with fetal leukocytosis . Elective cesarean section has been linked with increased neonatal morbidity, which may be partially immune mediated . We hypothesized that labor may alter neutrophil phenotype and thereby decrease neonatal complications . We characterized neutrophil function and survival in normal neonates after either uncomplicated vaginal delivery (VD) or elective cesarean section (CS) without labor . Spontaneous neutrophil apoptosis is delayed in cord blood neutrophils of neonates after normal labor (VD) compared with CS, as assessed by propidium iodide DNA incorporation using flow cytometry . This demonstrates their ability to maintain an inflammatory response . CD11b expression on neonatal neutrophils after CS is decreased, providing further evidence of altered activation or priming . Lipopolysaccharide responsiveness, characterized by CD11b and apoptosis, is similar in VD and adults, but CS-derived neutrophils are unresponsive . Baseline TLR-4 levels are elevated in CS in contrast to the other groups, although expression is not up-regulated by lipopolysaccharide co-incubation . Neonatal neutrophil survival and function are altered by labor and may increase antibacterial function and neutrophilia . This suggests that labor of any duration may be immunologically beneficial to the normal term neonate.

Appl Environ Microbiol, 2004 May, 70(5), 2816 - 22
Transposon mutagenesis of the obligate intracellular pathogen Rickettsia prowazekii; Qin A et al.; Genetic analysis of Rickettsia prowazekii has been hindered by the lack of selectable markers and efficient mechanisms for generating rickettsial gene knockouts . We have addressed these problems by adapting a gene that codes for rifampin resistance for expression in R . prowazekii and by incorporating this selection into a transposon mutagenesis system suitable for generating rickettsial gene knockouts . The arr-2 gene codes for an enzyme that ADP-ribosylates rifampin, thereby destroying its antibacterial activity . Based on the published sequence, this gene was synthesized by PCR with overlapping primers that contained rickettsial codon usage base changes . This R . prowazekii-adapted arr-2 gene (Rparr-2) was placed downstream of the strong rickettsial rpsL promoter (rpsL(P)), and the entire construct was inserted into the Epicentre EZ::TN transposome system . A purified transposon containing rpsL(P)-Rparr-2 was combined with transposase, and the resulting DNA-protein complex (transposome) was electroporated into competent rickettsiae . Following selection with rifampin, rickettsiae with transposon insertions in the genome were identified by PCR and Southern blotting and the insertion sites were determined by rescue cloning and inverse PCR . Multiple insertions into widely spaced areas of the R . prowazekii genome were identified . Three insertions were identified within gene coding sequences . Transposomes provide a mechanism for generating random insertional mutations in R . prowazekii, thereby identifying nonessential rickettsial genes.

Eur J Biochem, 2004 May, 271(10), 2012 - 7
Transport of the phosphonodipeptide alafosfalin by the H+/peptide cotransporters PEPT1 and PEPT2 in intestinal and renal epithelial cells; Neumann J et al.; The interaction of the antibacterial phosphonodipeptide alafosfalin with mammalian H(+)/peptide cotransporters was studied in Caco-2 cells, expressing the low-affinity intestinal type peptide transporter 1 (PEPT1), and SKPT cells, expressing the high-affinity renal type peptide transporter 2 (PEPT2) . Alafosfalin strongly inhibited the uptake of {(14)C}glycylsarcosine with K(i) values of 0.19 +/- 0.01 mm and 0.07 +/- 0.01 mm for PEPT1 and PEPT2, respectively . Saturation kinetic studies revealed that in both cell types alafosfalin affected only the affinity constant (K(t)) but not the maximal velocity (V(max)) of glycylsarcosine (Gly-Sar) uptake . The inhibition constants and the competitive nature of inhibition were confirmed in Dixon-type experiments . Caco-2 cells and SKPT cells were also cultured on permeable filters: apical uptake and transepithelial apical to basolateral flux of {(14)C}Gly-Sar across Caco-2 cell monolayers were reduced by alafosfalin (3 mm) by 73% . In SKPT cells, uptake of {(14)C}Gly-Sar but not flux was inhibited by 61% . We found no evidence for an inhibition of the basolateral to apical uptake or flux of {(14)C}Gly-Sar by alafosfalin . Alafosfalin (3 mm) did not affect the apical to basolateral {(14)C}mannitol flux . Determined in an Ussing-type experiment with Caco-2 cells cultured in Snapwells trade mark, alafosfalin increased the short-circuit current through Caco-2 cell monolayers . We conclude that alafosfalin interacts with both H(+)/peptide symporters and that alafosfalin is actively transported across the intestinal epithelium in a H(+)-symport, explaining its oral availability . The results also demonstrate that dipeptides where the C-terminal carboxyl group is substituted by a phosphonic function represent high-affinity substrates for mammalian H(+)/peptide cotransporters.

J Am Dent Assoc, 2004 Apr, 135(4), 484 - 7
Combating antibiotic resistance; American Dental Association Council on Scientific Affairs; BACKGROUND: The ADA Council on Scientific Affairs developed this report to provide dental professionals with current information on antibiotic resistance and related considerations about the clinical use of antibiotics that are unique to the practice of dentistry . OVERVIEW: This report addresses the association between the overuse of antibiotics and the development of resistant bacteria . The Council also presents a set of clinical guidelines that urges dentists to consider using narrow-spectrum antibacterial drugs in simple infections to minimize disturbance of the normal microflora, and to preserve the use of broad-spectrum drugs for more complex infections . CONCLUSIONS AND PRACTICE IMPLICATIONS: The Council recommends the prudent and appropriate use of antibacterial drugs to prolong their efficacy and promotes reserving their use for the management of active infectious disease and the prevention of hematogenously spread infection, such as infective endocarditis or total joint infection, in high-risk patients.

Br J Nurs, 2004 Mar, 13(6 Suppl), S6 - 19
A review of the use of silver in wound care: facts and fallacies; Lansdown AB; This review traces the use of silver in wound care, discussing its merits as an antibacterial agent and constituent of many new dressings, which are increasingly tailored to the treatment of wounds ranging from acute surgical lesions to chronic and diabetic leg ulcers . Misconceptions regarding the biological properties of silver, its possible physiological value in the human body and wound bed, absorption through the skin, and safety factors are addressed . The article aims to present silver and the new range of sustained silver-release dressings as important features in the management of skin wounds, providing effective control of wound infections while ensuring patient comfort and quality of life.

Bioorg Med Chem Lett, 2004 Jun 7, 14(11), 2901 - 4
Synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antiviral, antifungal and anticancer agents; Tandon VK et al.; The synthesis and evaluation of some 2-substituted-1,4-naphthoquinones 2, S-(1,4-naphthoquinon-2-yl)-mercaptoalkanoic acid amides 4, related benzoquinone and naphthoquinone derivatives 6-9 and 2,3-disubstituted 1,4-naphthoquinones 10-11 were carried out . The antifungal, antibacterial, antiviral and anticancer activities were determined by using the standard assay . The results show that compounds 2b and 10a showed in vitro antiviral activity against Influenza-A Virus and Herpes Simplex Virus and possess pronounced antifungal profile whereas 4a showed anticancer activities against Lymphoid Leukaemia P 388.

Klin Khir, 2004 Feb, (2), 26 - 8
{Cardiac valve prosthesis in patients with infective endocarditis and chronic renal insufficiency in terminal stage on a programmable hemodialysis}; Todurov BM et al.; Mechanical cardiac valve implantation was performed in 3 patients with infective endocarditis, sepsis, chronical renal insufficiency of terminal stage, to whom the programmed dialysis was conducted . The operation was performed for vital indications . All the patients after the operation are alive, their treatment was continued, using programmed hemodialysis, effect of operation is good . The success of treatment of infective endocarditis in patients with chronical renal insufficiency of terminal stage depends on timely radical elimination of the infection foci in endocardium, the intracardial and systemic hemodynamics normalization, application of etiotropic antibacterial therapy, an adequate programmed hemodialysis.

J Leukoc Biol, 2004 Aug, 76(2), 368 - 73 Epub 2004 May 03.
CCL2, a product of mice early after systemic inflammatory response syndrome (SIRS), induces alternatively activated macrophages capable of impairing antibacterial resistance of SIRS mice; Tsuda Y et al.; Infection associated with systemic inflammatory response syndrome (SIRS) is a major cause of morbidity and mortality in patients with major surgery, polytrauma, and severe burn injury . In previous studies, mice with severe pancreatitis (a mouse model of SIRS, SIRS mice) have been shown to be greatly susceptible to various infections . In the present study, a mechanism involved in the impaired resistance of SIRS mice to infectious complications was investigated . Sera from SIRS mice impaired the resistance of normal mice to infectious complications induced by cecal ligation and puncture (CLP) . CC chemokine ligand 2 (CCL2) was detected in sera of SIRS mice . Resident macrophages (RMphi) cultured with SIRS mouse sera converted to alternatively activated macrophages (AAMphi), which were also demonstrated in mice treated with recombinant murine CCL2 . However, AAMphi were not demonstrated in mice injected with SIRS mouse sera and anti-CCL2 monoclonal antibody (mAb) in combination . Furthermore, normal mice that received SIRS mouse sera and anti-CCL2 mAb resisted CLP-induced infectious complications . These results indicate that the resistance of SIRS mice to infectious complications is impaired by AAMphi generated from RMphi in response to SIRS-associated CCL2 production.

Pediatrics, 2004 May, 113(5), 1451 - 65
Diagnosis and management of acute otitis media; American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media; This evidence-based clinical practice guideline provides recommendations to primary care clinicians for the management of children from 2 months through 12 years of age with uncomplicated acute otitis media (AOM) . The American Academy of Pediatrics and American Academy of Family Physicians convened a committee composed of primary care physicians and experts in the fields of otolaryngology, epidemiology, and infectious disease . The subcommittee partnered with the Agency for Healthcare Research and Quality and the Southern California Evidence-Based Practice Center to develop a comprehensive review of the evidence-based literature related to AOM . The resulting evidence report and other sources of data were used to formulate the practice guideline recommendations . The focus of this practice guideline is the appropriate diagnosis and initial treatment of a child presenting with AOM . The guideline provides a specific definition of AOM . It addresses pain management, initial observation versus antibacterial treatment, appropriate choices of antibacterials, and preventive measures . Decisions were made based on a systematic grading of the quality of evidence and strength of recommendations, as well as expert consensus when definitive data were not available . The practice guideline underwent comprehensive peer review before formal approval by the partnering organizations . This clinical practice guideline is not intended as a sole source of guidance in the management of children with AOM . Rather, it is intended to assist primary care clinicians by providing a framework for clinical decision-making . It is not intended to replace clinical judgment or establish a protocol for all children with this condition . These recommendations may not provide the only appropriate approach to the management of this problem.

Jpn J Antibiot, 2004 Feb, 57(1), 118 - 23
{Transfer of cadrofloxacin, a novel fluoroquinolone antibacterial, into the gallbladder tissue and bile}; Tanimura H et al.; Clinical pharmacological studies of a novel fluoroquinolone antibacterial drug, cadrofloxacin, were performed in 12 surgical patients by investigating the transfer of cadrofloxacin into the gallbladder tissue and bile . They were scheduled for cholecystectomy (n = 6) or had undergone a percutaneous transhepatic biliary drainage (n = 5) or gallbladder drainage (n = 1) at the Second Department of Surgery, Wakayama Medical University . A single dose of cadrofloxacin was orally administered to all patients at a dose of 200 mg . The results were as follows: 1) Serum and gallbladder tissue levels of cadrofloxacin after 2.9-5.7 hours were 0.6-2.5 micrograms/ml and 0.6-8.6 micrograms/ml, respectively . The gallbladder/serum ratios of drug concentration were 0.6-3.4 . 2) Levels of cadrofloxacin in bile reached a peak of 2.5-12.9 micrograms/ml after individually different period of time . Cumulative bile recoverlies of cadrofloxacin (unchanged compound + glucuronide conjugate) within the first 6 hours were 0.02-0.49%, and 0.08-0.75% within 0-12 hours . The mean value of {glucuronide conjugate/unchanged compound} in bile was 37%, although the values depended on the patients.

Vet Clin North Am Small Anim Pract, 2004 May, 34(3), 655 - 68
Antibacterial agents for ocular therapeutics; Kern TJ; Ocular bacterial infections of animals take a variety of forms . The eyelid, external ocular surface, anterior segment, posterior segment,and orbit are all frequent targets . Effective management of ocular bacterial infections requires specific identification of the offending organism(s) combined with knowledge of the mechanisms of action and the therapeutic characteristics of available antibiotics.

Phytochemistry, 2004 Apr, 65(8), 1185 - 91
A benzil and isoflavone derivatives from Derris scandens Benth; Mahabusarakam W et al.; A benzil derivative: scandione, 2',2"-dihydroxy-4'-methoxy-4",5"-methylenedioxybenzil and two isoflavones: scandenal, 3'-formyl-4',5-dihydroxy-2",2"-dimethylchromeno-{6,7:5",6"}isoflavone and scanderone, 4',5-dihydroxy-3'-prenyl-2",2"-dimethylchromeno-{7,8:6",5"}isoflavone together with fifteen known compounds were isolated from the stem of D . scandens . Their structures were determined by spectroscopic methods . Radical scavenging, antibacterial and hypertensive activities of some of the compounds were investigated.

Transplant Proc, 2004 Apr, 36(3), 703 - 4
Hematologic toxicity of immunosuppressive treatment; Danesi R et al.; The administration of immunosuppressive agents may be associated with the occurrence of hematologic toxicity, such as anemia, due to bone marrow suppression or hemolysis, leukopenia, and thrombocytopenia . The administration of azathioprine and mycophenolate mofetil is more frequently associated with bone marrow suppression, while hemolytic-uremic syndrome may occur after administration of cyclosporine, tacrolimus, or muromonab (OKT3) and may be associated with the loss of the allograft . Moreover, microangiopathic hemolytic anemia and thrombocytopenia are rare, but potentially severe, complications of immunosuppressive treatment with tacrolimus and cyclosporine; they are characterized by intravascular hemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels . Viral infections (cytomegalovirus), administration of antiviral agents (gancyclovir), inhibitors of angiotensin-converting enzyme and angiotensin II receptor antagonists, antibacterial agents (sulfamethoxazole and trimethoprim), and allopurinol may aggravate bone marrow suppression, particularly when administered with agents that interfere with purine biosynthesis, including azathioprine and mycophenolate mofetil.

Biochim Biophys Acta, 2004 May 3, 1672(2), 120 - 9
Enzymatic description of the anhydrofructose pathway of glycogen degradation; I . Identification and purification of anhydrofructose dehydratase, ascopyrone tautomerase and alpha-1,4-glucan lyase in the fungus Anthracobia melaloma; Yu S et al.; The anhydrofructose pathway describes the degradation of glycogen and starch to metabolites via 1,5-anhydro-d-fructose (1,5AnFru) . The enzyme catalyzing the first reaction step of this pathway, i.e., alpha-1,4-glucan lyase (EC 4.2.1.13), has been purified, cloned and characterized from fungi and red algae in our laboratory earlier . In the present study, two 1,5AnFru metabolizing enzymes were discovered in the fungus Anthracobia melaloma for the formation of ascopyrone P (APP), a fungal secondary metabolite exhibiting antibacterial and antioxidant activity . These are 1,5AnFru dehydratase (AFDH) and ascopyrone tautomerase (APTM) . AFDH catalyzed the conversion of 1,5AnFru to ascopyrone M (APM), a compound that has been earlier presumed to occur biologically, while APTM isomerized the APM formed to APP . Both enzymes were purified 400-fold by (NH(4))(2)SO(4) fractionation, hydrophobic interaction, ion-exchange and gel filtration chromatography . The purified AFDH showed a molecular mass of 98 kDa on SDS-PAGE and 230 kDa by gel filtration . The corresponding values for APTM was 60 and 140 kDa . Spectrophotometric and HPLC methods were developed for the assay of these two enzymes . To confirm that A . melaloma possessed all enzymes needed for conversion of glycogen to APP, an alpha-1,4-glucan lyase from this fungus was isolated and partially sequenced . Based on this work, a scheme of the enzymatic description of the anhydrofructose pathway in A . melaloma was proposed.

Bioorg Med Chem Lett, 2004 May 17, 14(10), 2489 - 92
Design and synthesis of bridged gamma-lactams as analogues of beta-lactam antibiotics; Aszodi J et al.; Anti-Bredt bridged bicyclo{3.2.1} gamma-lactams were designed as inhibitors of penicillin binding proteins (PBPs) . The compounds were prepared by a carbenoid insertion into a lactam N-H bond . Their weak antibacterial activity could either be explained by a poor chemical stability or by unfavorable steric interactions of the methylene bridge of the gamma-lactam with the targeted enzymes.

Bioorg Med Chem Lett, 2004 May 17, 14(10), 2417 - 21
Synthesis and antibacterial activity of 6-O-arylpropargyl-9-oxime-11,12-carbamate ketolides; Beebe X et al.; A series of novel 6-O-arylpropargyl-9-oxime-ketolides was synthesized and evaluated against various pathogens . These new compounds show promising in vitro antibacterial potency and in vivo efficacy against macrolide resistant strains.

Microbiol Immunol, 2004, 48(4), 251 - 61
Antibacterial activity of hydrolyzable tannins derived from medicinal plants against Helicobacter pylori; Funatogawa K et al.; Helicobacter pylori is a major etiological agent in gastroduodenal disorders . In this study, we isolated 36 polyphenols and 4 terpenoids from medicinal plants, and investigated their antibacterial activity against H . pylori in vitro . All hydrolyzable tannins tested demonstrated promising antibacterial activity against H . pylori . Monomeric hydrolyzable tannins revealed especially strong activity . Other compounds demonstrated minimal antibacterial activity with a few exceptions . A monomeric hydrolyzable tannin, Tellimagrandin I demonstrated time- and dose-dependent bactericidal activity against H . pylori in vitro . On the other hand, hydrolyzable tannins did not affect the viability of MKN-28 cells derived from human gastric epithelium . Hydrolyzable tannins, therefore, have potential as new and safe therapeutic regimens against H . pylori infection . Furthermore, we investigated effects of hydrolyzable tannins on lipid bilayer membranes . All the hydrolyzable tannins tested demonstrated dose-dependent membrane-damaging activity . However, it remains to be elucidated whether their membrane-damaging activity directly contributes to their antibacterial action.

Org Biomol Chem, 2004 May 7, 2(9), 1368 - 75 Epub 2004 Apr 01.
Synthesis and bioactivity of linear oligomers related to polymeric alkylpyridinium metabolites from the Mediterranean sponge Reniera sarai; Mancini I et al.; Dimers and tetramers of linear 3-alkylpyridinium salts have been synthesized by an efficient synthetic pathway, which is also applicable to the preparation of higher oligomers . Mono-, di- and tetrameric compounds have been tested for antibacterial and hemolytic activities and for the inhibition of acetylcholinesterase and protein phosphatase 2A . Their activities were compared to those of the natural poly-3-octylpyridinium alkaloids isolated from the Mediterranean sponge Reniera sarai . Relatively high antibacterial and anti-acetylcholinesterase activities were observed that increase with higher degrees of oligomerization.

Reumatismo, 2004 Jan-Mar, 56(1), 51 - 6
{Autologous peripheral stem cell transplantation in a patient with diffuse systemic sclerosis: our experience}; Giorgetti F et al.; The diffuse form of systemic sclerosis (SSc) can often lead to a rapidly progressive course with the involvement of the visceral organs which causes a severe prognosis . The 5-years cumulative mortality is between 30 and 60%, depending on the clinic form at the onset . Until now, no drug treatment has been proved to be efficacious against the progression of the disease or the regression of the fibrosis . Recently autologous peripheral blood stem cell (PBSC) transplantation has been found to be promising . We introduce the case of a patient, male, 56 years old, who came under our observation on February 2001, suffering from a SSc with a severe multisystem involvement of lungs, skin, heart and gastrointestinal tract, and a positive antibodies anti-Scl-70 . The 8 months therapy, at first with iloprost and cyclophosphamide, then with bolus of cyclophosphamide, was ineffective, with a rapid worsening of the cutaneous and pulmonary involvement . Under the patient agreement we decided to carry out an autologous PBSC transplantation . On December 2001, we obtained the PBSC mobilization after the administration of cyclophosphamide and lenograstim and the PBSC recovery with two leucoaferesis procedures . On February 2002, we gave the conditioning therapy with: thiotepa, cyclophosphamide, fludarabine, rabbit antilymphocytic globulin; then we made the infusion of PBSC . The bone marrow recovery (GN >500 and PLT >20.000) arrived at the day + 10 . For three months after the transplantation we made an antibacterial, antiviral and antifungin prophylaxis with valacocyclovir, co-trimoxazole and fluconazole . The one-year follow-up has shown an essentially good response with the improving of the skin involvement and of the subjective indicators of the disease, while the pulmonary involvement don't seen modified from the high dose therapy.

Antimicrob Agents Chemother, 2004 May, 48(5), 1581 - 5
Molecular mechanisms of anti-inflammatory action of erythromycin in human bronchial epithelial cells: possible role in the signaling pathway that regulates nuclear factor-kappaB activation; Desaki M et al.; Long-term macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis . Although its mechanisms remain unknown, previous studies have suggested the effects of macrolide might be anti-inflammatory rather than antibacterial . To elucidate the molecular mechanisms of its action, we studied here the effects of erythromycin (EM) and its new derivative, EM703, which shows no antibacterial action, on the activation of the transcription factor nuclear factor-kappaB (NF-kappaB) in human bronchial epithelial cells . Western blotting analysis showed that EM did not inhibit the degradation of IkappaBalpha, suggesting the molecular target for EM was not the dissociation of NF-kappaB from IkappaB . An electrophoretic mobility shift assay showed that EM did not interrupt the NF-kappaB DNA-binding activity in the nucleus under the conditions tested . Moreover, not only EM but also EM703 suppressed the activation of NF-kappaB and the production of interleukin-8, demonstrating that the anti-inflammatory action of the macrolide is independent of its antibacterial activity . Taken together, these data suggest EM has an anti-inflammatory action, presumably via an interaction with the NF-kappaB signaling pathway in the downstream of the dissociation from IkappaB, resulting in the inhibition of NF-kappaB.

J Antimicrob Chemother, 2004 Jun, 53(6), 981 - 8 Epub 2004 Apr 21.
Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes; Prior S et al.; OBJECTIVES: The intracellular antibiotic efficiency of gentamicin-loaded microspheres in the context of Brucella-infected murine monocytes was examined in vitro with a view to developing improved therapies for the treatment of brucellosis . METHODS: Biodegradable microspheres made of end-group capped and uncapped poly(lactide-co-glycolide) 50:50 (PLGA 50:50 and PLGA 50:50H) and containing gentamicin sulphate were used to target Brucella abortus-infected J774 monocyte-macrophages . The infected cells were treated with 15 micro g of free or microencapsulated gentamicin and the efficacy of the treatments was measured after 24 h . RESULTS: The particle sizes were below 8 micro m and in vitro release of gentamicin from the microspheres followed a continuous (PLGA 50:50H) or a multiphasic (PLGA 50:50) pattern over 50 days . Treatment with gentamicin microencapsulated into the end-group uncapped PLGA 50:50H microspheres, decreased significantly the number of intracellular bacteria (typically by 2 log(10)) in comparison with untreated infected cells . Addition of 2% poloxamer 188 to the microsphere dispersion medium further reduced the infection (3.5 log(10)) . Opsonization of the particles with non-immune mouse serum had no effect on the antibacterial efficacy of the microspheres . End-group capped PLGA 50:50 type microspheres containing the antibiotic were less effective at reducing intracellular bacteria ( approximately 1 log(10) reduction), although addition of poloxamer 188 to the dispersion medium again enhanced their intracellular antibacterial activity . Placebo PLGA 50:50 and PLGA 50:50H microspheres had no bactericidal activity . CONCLUSIONS: The results indicate that PLGA 50:50-microencapsulated gentamicin sulphate may be suitable for efficient drug targeting and delivery to reduce intracellular Brucella infections.

Org Lett, 2004 Apr 29, 6(9), 1381 - 4
Application of glycodiversification: expedient synthesis and antibacterial evaluation of a library of kanamycin B analogues; Li J et al.; {reaction: see text} The expedient synthesis of a library of kanamycin B analogues is reported . The revealed SAR will guide future designs in developing kanamycin-type aminoglycoside antibiotics against drug-resistant bacteria.

Voen Med Zh, 2004 Feb, 325(2), 33 - 9, 96
{Optimization of empirical antibacterial therapy of diffuse purulent peritonitis during the stage of multiple organ failure}; Efimenko NA et al.; The experience of optimization of empirical antibacterial therapy of diffuse purulent peritonitis at toxic and terminal stages is presented . The treatment results were compared in main (209) and control (130) patient groups taking into account the clinical and bacteriological efficiency . The technology of combined antibacterial multi-component retroperitoneal lymphotropic therapy was used that included the following drugs: novocain, haemodesum, trisaminum, hydrocortison hemisuccinas, heparin, tripsinum and antibacterial group (kanamicini, levomycetinum, natrii hemisuccinas, dioxydinum, metronidazole) for abdominal and retroperitoneal treatment . 96.7% from the main group and 74.6% from the control group recovered, lethal outcomes and complications decreased in 2.78 and 4 times respectively.

Vestn Ross Akad Med Nauk, 2004, (2), 29 - 34
{The structural and functional analysis of the biological activity of acridine derivatives}; Deeva EG et al.; The paper contains an analysis of research on designing drugs based on acridine derivatives . The discussed series of compounds is of essential value since acridines belong to the group of natural compounds with the pronounced antibacterial and anti-tumor activity . Improved chemical-synthesis techniques made it possible to synthesize both simple and complex compounds of the acridine series; they displayed a clear pharmacological activity as anti-proliferative, anti-tumor and antiparasitic preparations . The ability to induce interferons (INF), type 1, is an expected property of simple acridine derivatives . A variety of INF inducers, now used clinically, have been designed recently on the basis of the above compounds . The most well-known acridine derivatives, their pharmacological properties, action mechanisms and outlooks for practical application are described in the paper . The unique qualities of acridines are primarily attractive due to the possibility of using them for the purpose-oriented designing of drugs . Thus, acridines were used as a basis to create the specific regulatory HIV-1 elements, proliferation inhibitors of leukemia cells and new anti-tumor drugs . The elaboration of complexes of acridines derivatives combined with peptides intercalating specifically into the DNA big or small grooves is the most outstanding trend of acridines' research--it opens up prospects for using them in the synthesis of compounds regulating the gene expression.

Clin Infect Dis, 2004 Apr 15, 38(8), 1058 - 64 Epub 2004 Mar 26.
Similar hematologic effects of long-term linezolid and vancomycin therapy in a prospective observational study of patients with orthopedic infections; Rao N et al.; Linezolid is an alternative to vancomycin for the long-term treatment of gram-positive bacterial orthopedic infections because of its antibacterial spectrum and oral bioavailability, but duration-related myelosuppression could offset its advantages . To evaluate the hematologic effects of these agents, we prospectively studied 65 consecutive adults with gram-positive bacterial orthopedic infections requiring > or =2 weeks of vancomycin therapy (n=52) or linezolid therapy (n=20) . Trends suggesting higher incidence of hematologic effects among the patients receiving vancomycin were not significant, regardless of whether the end point was lowest cell count during therapy or change from baseline . The only difference was a higher incidence of thrombocytopenia (<150x10(9) platelets/L) in the subset of the linezolid recipients who had received vancomycin within 2 weeks before starting linezolid therapy than in the linezolid recipients who had not received vancomycin (5 {71%} of 7 patients vs . 2 {15%} of 13; P=.02) . All hematologic effects were reversible . In conclusion, hematologic effects were detectable through weekly monitoring and were reversible; therefore, concern about myelosuppression need not preclude linezolid use for orthopedic infections requiring long-term therapy.

Crit Care Med, 2004 Mar, 32(3), 747 - 54
Gastric acid and particulate aspiration injury inhibits pulmonary bacterial clearance; Rotta AT et al.; OBJECTIVE: To establish a model of secondary bacterial pneumonia following gastric aspiration and to identify possible mechanisms involved in the suppressed antibacterial defenses following the initial pulmonary insult . DESIGN: A controlled, in vivo laboratory study . SETTING: Research laboratory of a health sciences university . SUBJECTS: Ninety-five Long-Evans rats . INTERVENTIONS: Animals were anesthetized for neck dissection and placement of a 14-gauge catheter in the trachea . Gastric aspirate (1.2 mL/kg of saline, pH 1.25, and 40 mg/mL sterile rat gastric particles) or an equal amount of normal saline (pH 5.3) was instilled intratracheally . One minute after this insult, animals received an intratracheal instillation of either 5.6 x 10 colony-forming units of Escherichia coli or an equal volume of normal saline . The animals remained in room air until kill at 4 hrs or 24 hrs after the intratracheal instillation . The lungs were homogenized for quantitative bacterial cultures . Bronchoalveolar lavage fluid was obtained for cell counts and measurements of albumin, tumor necrosis factor-alpha, interleukin-1 beta, cytokine-induced neutrophil chemoattractant-1, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, and interleukin 10 . MEASUREMENTS AND MAIN RESULTS: Animals that received gastric aspirate (followed by normal saline or E . coli) had increased injury as assessed by significant reductions in oxygenation and elevations in bronchoalveolar lavage albumin . At 24 hrs, animals that received gastric aspirate inoculation followed by E . coli had significantly higher pulmonary bacterial counts compared with animals that received E . coli alone . Gastric aspiration injury followed by bacterial inoculation also resulted in acute, but transient, increases in tumor necrosis factor-alpha, interleukin-1 beta, cytokine-induced neutrophil chemoattractant-1, and macrophage inflammatory protein-2 and more sustained elevations of monocyte chemoattractant protein-1 and interleukin-10 . CONCLUSIONS: Lung injury increases and bacterial clearance decreases in this experimental model of E . coli pneumonia following gastric aspiration . Cytokine profiles suggest possible mechanisms for the impaired antibacterial host defense.

J Cell Mol Med, 2004 Jan-Mar, 8(1), 77 - 84
Role of human prostasomes in the activation of spermatozoa; Arienti G et al.; Prostasomes are small vesicles of prostatic origin contained in human semen . Their composition is peculiar under many aspects . Cholesterol is abundant and many proteins are endowed with enzymatic or other activities . The function of prostasomes has been amply debated and several hypotheses have been put forward . The liquefaction of semen, spermatozoa motility, antibacterial activity and immunological functions have been related to prostasomes . Under certain aspects, prostasomes resemble synaptosomes . The fusion of prostasomes to spermatozoa enriches spermatozoa with cholesterol and causes bursts of cytoplasmic sperm calcium . The interaction of spermatozoa and prostasomes should be limited to vagina since prostasomes are immobile and do not follow spermatozoa in the superior female genital tract . Calcium bursts would increase spermatozoa motility, where cholesterol would decapacitate spermatozoa, so preventing untimely activation . Since spermatozoa receive many different molecules from prostasomes, additional effects are also possible . Prostasomes makes spermatozoa more apt to be activated by progesterone in the proximity of the ovum . Therefore, the fusion between spermatozoa and prostasomes would influence spermatozoa behaviour under many aspects and might be relevant for fecundation . The richness of molecular species in prostasomes is amazing and these small vesicles are expected to lead to many more discoveries in the field of human reproduction.

Br J Clin Pharmacol, 2004 May, 57(5), 563 - 8
Tissue pharmacokinetics of levofloxacin in human soft tissue infections; Bellmann R et al.; AIMS: The present study addressed the ability of levofloxacin to penetrate into subcutaneous adipose tissues in patients with soft tissue infection . METHODS: Tissue concentrations of levofloxacin in inflamed and healthy subcutaneous adipose tissue were measured in six patients by microdialysis after administration of a single intravenous dose of 500 mg . Levofloxacin was assayed by high-performance liquid chromatography . RESULTS: The mean concentration vs time profile of free levofloxacin in plasma was identical to that in inflamed and healthy tissues . The ratios of the mean area under the free levofloxacin concentration vs time curve from 0 to 10 h (AUC(0,10 h)) in tissue to that in plasma were 1.2 +/- 1.0 for inflamed and 1.1 +/- 0.6 for healthy subcutaneous adipose tissue (mean +/- SD) . The mean difference in the ratio of the AUC(tissue) : AUC(plasma) for inflamed and healthy tissue was 0.09 (95% confidence interval -0.58, 0.759, P > 0.05) . Interindividual variability in tissue penetration was high, as indicated by a coefficient of variation of approximately 82% for AUC(tissue) : AUC(plasma) ratios . CONCLUSIONS: The penetration of levofloxacin into tissue appears to be unaffected by local inflammation . Our plasma and tissue data suggest that an intravenous dose of 500 mg levofloxacin provides effective antibacterial concentrations at the target site . However, in treatment resistant patients, tissue concentrations may be sub-therapeutic.

Drug Dev Ind Pharm, 2004 Feb, 30(2), 195 - 203
Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases; Jadhav BK et al.; Eugenol is the principle chemical constituent of clove oil and has been used to cure dental problems for ages . Eugenol is an integral part of the dentist's kit due to its analgesic, local anesthetic, anti-inflammatory, and antibacterial effects . It is used in the form of a paste or mixture as dental cement, filler, and restorative material . This study reports the development and evaluation of controlled-release mucoadhesive tablets for gingival application, containing eugenol, which are prepared by taking carbopol 934 P and Hydroxypropyl methylcellulose (HPMC) K4M in the ratio of 1:2, 1:1, and 2:1 . Incorporation of eugenol (10 mg) in a mucoadhesive formulation provides controlled release for a period of 8 hours, which is advantageous over conventional use . In vitro mucoadhesion measured as detachment force in grams and the formulations show good correlation in vivo . The release study indicates that increase in carbopol increases the release rate of eugenol from the formulation whereas HPMC retards it . Increased in vitro bioadhesion is related to HPMC content of the formulation . The release kinetics of eugenol in vitro correlates with the in vivo results . This indicates the increased potential of eugenol as antibacterial, local analgesic, and anaesthetic treatment.

Bioorg Med Chem Lett, 2004 May 3, 14(9), 2035 - 40
Highly diastereoselective inverse electron demand (IED) Diels-Alder reaction mediated by chiral salen-AlCl complex: the first, target-oriented synthesis of pyranoquinolines as potential antibacterial agents; Magesh CJ et al.; The first, target-oriented synthesis of pyranoquinolines as potential antibacterial agents by inverse electron demand (IED) Diels-Alder reaction using chiral salen-AlCl complex has been accomplished, the reactions proceed with moderate yields, and a very high degree of diastereoselectivity (>90%) . The diastereoselectivity-enhanced pyranoquinolines exhibit potential bactericidal activity against seven strains of pathogenic gram-negative bacteria.

Acta Pol Pharm, 2003 Nov-Dec, 60(6), 487 - 92
The synthesis and antibacterial activity of 3-alkyl derivatives of some pyrimido{4,5-d} pyrimidine; Cieplik J et al.; The synthesis of 4,5-diamino derivatives of pyrimidine and pyrimido{4,5-d}pyrimidines is presented . The antibacterial and antifungal activity of the compounds was investigated on nine selected bacterial species, comparing the changes in the chemical structure with increase in the bioactive properties . The investigations have shown that the obtained derivatives of pyrimido{4,5-d}pyrimidines and especially the compounds reveal interesting antibacterial 6e and antifungal 6d activity.

Acta Pol Pharm, 2003 Nov-Dec, 60(6), 451 - 6
Synthesis and biological action of 1-substituted-3-R-4-phenyl-delta 2-1,2,4-triazoline-5-thione; Wujec M et al.; Using common substitution reactions, several 4-phenyl-delta2-1,2,4-triazoline-5-thione {I} and 4-phenyl-3-(pyridin-3-yl)-delta2-1,2,4-triazoline-5-thione {II} derivatives of 1-substituted-3-R-4-phenyl-delta2-1,2,4-triazoline-5-thione were obtained . These new compounds were screened for their antibacterial activities.

Protein Pept Lett, 2004 Apr, 11(2), 115 - 24
Conformation of the cecropin-melittin hybrid, cecropin A(1-8)-melittin (1-18) antibacterial Peptide; Tauro S et al.; Cecropin A (1-8)-Melittin (1-18) is a synthetic cecropin A-melittin hybrid peptide with leishmanicidal activity . The primary sequence of the peptide is as follows: KWKLPKKIGIGAVLKVLTTGLPALIS-NH2 . 1H and 13C 2D NMR techniques were used to deduce the conformational parameters of chemical shift, 3JNHalpha coupling constants, temperature coefficients of NH chemical shifts and the pattern of intra and inter-residue nOe's . NMR studies were carried out in water (pH 6.0) and hexafluoroacetone (HFA) . The peptide was found in a beta-pleated structure in water, and in HFA it adopts a right-handed alpha-helix conformation . Solution structures generated using restrained molecular dynamics simulations were refined by Mardigras to R factors ranging from 0.5 to 0.6.

J Chemother, 2004 Feb, 16(1), 70 - 6
Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations; Meloni F et al.; Rates of acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections were determined in 115 adults hospitalized for community-acquired pneumonia (CAP), purulent exacerbations of COPD and acute exacerbations of bronchial asthma, by means of serology and molecular methods . Results were compared with those obtained in a matched control group . Common respiratory pathogens were isolated by cultures in 22.5% and 22.2% of CAP and exacerbated COPD patients, respectively . Cultures from exacerbated asthma patients were always negative . Serological and molecular evidence of current C . pneumoniae infection was obtained in 10.0%, 8.9% and 3.3% of CAP, COPD and asthma cases . The corresponding rates of acute M . pneumoniae infection were 17.5%, 6.7% and 3.3%, respectively . Finally, no difference was found between typical and atypical pathogen rates . These findings highlight the importance of taking into account C . pneumoniae and M . pneumoniae infections in guiding the choice of empirical antibacterial treatment for CAP and purulent exacerbations of COPD.

Klin Khir, 2003 Dec, (12), 18 - 20
{Antibiotic prophylaxis in the abdominal surgery in children at an early age}; Horbatiuk OM et al.; Conduction of antibioticoprophylaxis (ABP) promotes the lowering of frequency of purulent-septic complications occurrence after performance of urgent intervention on organs of abdominal cavity in children aged up to 3 years, prevention of nosocomial infection occurrence, ABP is necessary to conduct, taking into account the microbes strain resistance to antibacterial preparations, defining possible "microbe--leader" . During performance of conditionally clean operation ABP is conducted using intravenous injection of the antibiotic daily dose while doing premedication . For this the cephalosporines of II generation, aminoglycosides, metronidazole, are applied . High clinical efficacy of the ABP chart proposed, essential improvement of the treatment of patients results were noted.

Pharmacoepidemiol Drug Saf, 1999 Apr, 8 Suppl 1, S27 - 35
Hospital-based survey of doctors' attitudes to adverse drug reactions and perception of drug-related risk for adverse reaction occurrence; Cosentino M et al.; Doctors' attitudes to adverse drug reactions (ADRs) and perception of drug-related risk for ADR occurrence were investigated in four hospitals in Northern Italy using an interviewer-administered questionnaire . ADRs were a relevant concern in medical practice for 80% of the respondents and had been observed by 87% . ADRs were perceived to occur in no more than 5% of hospitalized patients and serious ADRs in less than 1% . The response patterns, however, differed according to the ward of work and the year of graduation of the doctors . Antibacterials, NSAIDs and antiarrhythmics were rated as higher risk drugs, while diuretics, lipid lowering agents, antihistamines, antiemetics and antispasmodics were rated as lower risk drugs . Risk perception was dishomogeneous mainly with respect to the ward of work . The estimated frequency of ADR occurrence, the perception of drug-related risk and previous ADR reporting behaviour were clearly correlated . The present results suggest that personal factors affect doctors' attitudes to ADRs, perception of drug-related risk and ADR reporting behaviour and may thus be relevant in developing and targeting educational strategies aimed at increasing awareness of ADRs and at encouraging ADR reporting .

Proc Natl Acad Sci U S A, 2004 Mar 30, 101(13), 4578 - 83 Epub 2004 Mar 15.
Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells; Chou WC et al.; Arsenic has played a key medicinal role against a variety of ailments for several millennia, but during the past century its prominence has been displaced by modern therapeutics . Recently, attention has been drawn to arsenic by its dramatic clinical efficacy against acute promyelocytic leukemia . Although toxic reactive oxygen species (ROS) induced in cancer cells exposed to arsenic could mediate cancer cell death, how arsenic induces ROS remains undefined . Through the use of gene expression profiling, interference RNA, and genetically engineered cells, we report here that NADPH oxidase, an enzyme complex required for the normal antibacterial function of white blood cells, is the main target of arsenic-induced ROS production . Because NADPH oxidase enzyme activity can also be stimulated by phorbol myristate acetate, a synergism between arsenic and the clinically used phorbol myristate acetate analog, bryostatin 1, through enhanced ROS production can be expected . We show that this synergism exists, and that the use of very low doses of both arsenic and bryostatin 1 can effectively kill leukemic cells . Our findings pinpoint the arsenic target of ROS production and provide a conceptual basis for an anticancer regimen.

J Biomater Appl, 2004 Apr, 18(4), 291 - 303
Norfloxacin-loaded chitosan sponges as wound dressing material; Denkbas EB et al.; The aim of this study was the preparation and characterization of chitosan sponges including a model antibiotic (i.e., norfloxacin) . The chitosan sponges were prepared by a solvent evaporation method . The matrix was also cross-linked during the preparation . The results indicated that the chitosan sponges were in the fibrillar structure . The swelling behavior, norfloxacin loading, in vitro release characteristics, and antibacterial activity were determined . The effects of cross-linker concentration, norfloxacin/chitosan ratio, chitosan molecular weight, and base concentration were investigated . The most effective parameter was found to be the degree of neutralization . It was also observed that the equilibrium swelling ratio decreased with increasing cross-linking density . The norfloxacin release was found to be swelling controlled initially and diffusion controlled at the extended release periods . It was also found that the antibacterial activity was directly proportional to the release rate.

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2004 Apr, 16(4), 198 - 201
{An early comprehensive prevention and treatment of sepsis in severely burned patients with delayed fluid resuscitation}; Wu ZH et al.; OBJECTIVE: To study an early comprehensive prevention and treatment of sepsis in severely burned patients with delayed fluid resuscitation . METHODS: From January 1990 to December 2001, 72 cases of patients with delayed fluid resuscitation were admitted to our burn department . Two different periods were divided and analyzed retrospectively . The first period was from January 1990 to December 2001 and the span of the second period was from January 1995 to December 2001 . RESULTS: (1)The mortality rate and incidence of sepsis in the second period (6.5 percent and 17.4 percent) were significantly lower than those of the first period (23.0 percent and 57.7 percent, P<0.05 and P<0.01) . (2)The time of wound healing in the second period was (1.9+/-0.9) hours, it was lower than that of the first period (6.6+/-2.5) hours . (3)The serum contents of tumor necrosis factor (TNF) and blood lactic acid (BLA) were increased at all times in two periods and were markedly increased in the first period (all P<0.01) . CONCLUSION: Our data demonstrated that measures adopted in the second period for patients with delayed fluid resuscitation, including early excision, early rapid adequate resuscitation, early enteral feeding, increased immunity function, early applying antibactials, xenotransfusion of ultraviolet-irradiated blood, application of recombinant human-growth factor (rh-GH), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), are beneficial to the prevention and treatment of sepsis in severely burned patients with delayed fluid resuscitation.

Helicobacter, 2004 Apr, 9(2), 146 - 51
Anti-Helicobacter pylori activities of six Iranian plants; Nariman F et al.; BACKGROUND: Helicobacter pylori is the major worldwide cause of bacterial gastrointestinal infections in adults and children . Antibiotic therapy and a combination of two or three drugs have been widely used to eradicate these infections . However, development of drug resistance in bacteria calls for new sources of drugs, and plants seem to be a logical source of new antibacterial compounds . METHODS: The anti-H . pylori activities of six native Iranian plants (Glycyrrhiza aspera, Juglans regia, Ligustrum vulgare, Thymus kotschyanus, Trachyspermum copticum and Xanthium brasilicum) and seven antibiotics were determined against 70 clinical isolates from children using the disk susceptibility assay . Minimum inhibitory concentrations were also measured for the biologically active extracts . One extract with the best anti-H . pylori activity was fractionated by silica gel and thin layer chromatography and the active compounds were identified by hydrogen nuclear magnetic resonance ((1)HNMR) spectroscopy . RESULTS: All plant extracts showed anti-H . pylori activity by the disk sensitivity method, but the most active extracts were those from X . brasilicum and T . copticum . In fact, the anti-H . pylori activities of the two extracts were superior to the disk antibiotic susceptibility profile . Minimum inhibitory concentrations were within the range of 31.25-250 micro g/ml . Fractionation and chemical identification of the extract from X . brasilicum showed the presence of two substances, a flavonoid and a xanthanolide . CONCLUSIONS: Due to the rise in antibiotic resistance, new sources of anti-H . pylori drugs are needed . The use of medicinal plants and/or their chemical components may have potential benefit in eradicating such problems.

Drug Ther Bull, 2004 Feb, 42(2), 9 - 13
Antibacterial prophylaxis in surgery: 2--Urogenital, obstetric and gynaecological surgery; Evaluation of a scanner-assisted colorimetric MIC method for susceptibility testing of gram-negative fermentative bacteria; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden . mokhlasur.rahman@mtc.ki.se

We describe the ScanMIC method, a colorimetric MIC method for susceptibility testing of gram-negative fermentative bacteria . The method is a slight modification of the National Committee for Clinical Laboratory Standards (NCCLS) recommended broth microdilution method that uses a redox indicator 2,3,5-triphenyltetrazolium chloride (TTC) to enhance the estimate of bacterial growth inhibition in a microplate and a flatbed scanner to capture the microplate image . In-house software was developed to transform the microplate image into numerical values based on the amount of bacterial growth and to generate the MICs automatically . The choice of indicator was based on its low toxicity and ease of reading by scanner . We compared the ScanMIC method to the NCCLS recommended broth microdilution method with 197 coliform strains against seven antibacterial agents . The interpretative categorical agreement was obtained in 92.4% of the assays, and the agreement for MIC differences (within +/-1 log(2) dilution) was obtained in 96% for ScanMIC versus broth microdilution and 97% for a two-step incubation colorimetric broth microdilution versus the broth microdilution method . The method was found to be labor-saving, not to require any initial investment, and to show reliable results . Thus, the ScanMIC method could be useful for epidemiological surveys that include susceptibility testing of bacteria.

Eur J Pharm Sci, 2004 Apr, 21(5), 589 - 96
Evaluation of the antibacterial efficacy of diesters of azelaic acid; Charnock C et al.; A number of diesters of the topical dermatosis treatment azelaic (nonanedioic) acid were prepared and tested for antibacterial effect . Two esters, bis-{(hexanoyloxy)methyl} nonanedioate and especially bis-{(butanoyloxy)methyl} nonanedioate showed promising activity against acne related bacteria in vitro . No activity of azelaic acid was detected in Mueller Hinton II agar at pH 7.3 when using the agar diffusion method, whereas both esters gave zones of growth inhibition . At pH 5.6, activity of azelaic acid was detected . At this pH, the zones of inhibition and MIC values obtained with azelaic acid were smaller than those of bis-{(butanoyloxy)methyl} nonanedioate for all test organisms . A preparation for topical use containing 20% (w/w) bis-{(butanoyloxy)methyl} nonanedioate, and the commercially available Skinoren (20% (w/w) azelaic acid), were compared for antibacterial effect against cutaneous bacteria using contact plate analyses of the skin . Though Skinoren was usually most effective, the differences were not statistically significant . Furthermore, bacteria surviving contact with the topical preparations were invariably more sensitive to the ester than to azelaic acid upon subculturing onto agar (pH 5.6) containing either preparation at 0.2-0.7 mg/ml . This might indicate that other factors, such as the composition of the cream base, mitigate the antibacterial activity of the ester . It is proposed that the pharmacological and microbiological properties of bis-{(butanoyloxy)methyl} nonanedioate are worthy of further study based on an extended screening of acne sufferers.

Biochem Biophys Res Commun, 2004 Apr 30, 317(2), 618 - 24
Suppression of angiogenesis by the plant alkaloid, sanguinarine; Eun JP et al.; Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis . Its principal pharmacologic use is in dental products where it has antibacterial, antifungal, and anti-inflammatory activities that reduce gingival inflammation and supragingival plaque formation . Angiogenesis is indispensable for inflammation, and most angiogenesis is dependent on vascular endothelial growth factor (VEGF) . However, the effect of sanguinarine on angiogenesis is not known . In the present study, we examined the effect of sanguinarine on VEGF-induced angiogenesis in vitro and in vivo . Interestingly, sanguinarine markedly suppressed VEGF-induced endothelial cell migration, sprouting, and survival in vitro in a dose-dependent manner at nanomolar concentrations . Furthermore, sanguinarine potently suppressed blood vessel formation in vivo in mouse Matrigel plugs and the chorioallantoic membrane of chick embryos . Our biochemical assays indicated that sanguinarine strongly suppressed basal and VEGF-induced Akt phosphorylation, while it did not produce any changes in VEGF-induced activation of ERK1/2 and PLCgamma1 . Therefore, we conclude that sanguinarine is a potent antiangiogenic natural product, and its mode of action could involve the blocking of VEGF-induced Akt activation . Thus, in addition to antibacterial, antifungal, and anti-inflammatory activities, sanguinarine has a novel antiangiogenic role.

Biochem Biophys Res Commun, 2004 Apr 30, 317(2), 527 - 30
NMR evidence for independent domain structures in zoocin A, an antibacterial exoenzyme; Liang Q et al.; NMR was used to obtain spectroscopic evidence supporting a two domain model for zoocin A in which an N-terminal catalytic domain is linked by a threonine-proline rich linker to a target recognition domain responsible for recognizing the cell wall of bacteria susceptible to the bacteriolytic action of the enzyme . When cloned and separately expressed, each domain retains the folding found in the whole enzyme . Additionally, spectroscopy suggests that the target recognition domain has a conformation typical of a soluble globular protein, while the catalytic domain aggregates at low millimolar concentrations.

Jpn J Ophthalmol, 2004 Mar-Apr, 48(2), 93 - 6
The effect of the corneal epithelium on the intraocular penetration of fluoroquinolone ophthalmic solution; Fukuda M et al.; PURPOSE: Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes . In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed . METHODS: We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 microl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals . The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography . RESULTS: The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 +/- 1.56 microg/ml (60 min, OFLX), 2.57 +/- 1.00 microg/ml (30 min, LVFX), and 0.42 +/- 0.12 microg/ml (120 min, NFLX) . The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 +/- 5.62 microg/ml (30 min, OFLX), 9.02 +/- 2.45 microg/ml (60 min, LVFX), and 8.54 +/- 5.17 microg/ml (30 min, NFLX) . The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea . CONCLUSION: Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas.

Res Microbiol, 2004 Apr, 155(3), 136 - 43
Leishmanicidal activity of polyphenolic-rich extract from husk fiber of Cocos nucifera Linn . (Palmae); Mendonca-Filho RR et al.; The available therapy for leishmaniasis, which affects 2 million people per annum, still causes serious side effects . The polyphenolic-rich extract from the husk fiber of Cocos nucifera Linn . (Palmae) presents antibacterial and antiviral activities, also inhibiting lymphocyte proliferation, as shown by our group in previous works . In the present study, the in vitro leishmanicidal effects of C . nucifera on Leishmania amazonensis were evaluated . The minimal inhibitory concentration of the polyphenolic-rich extract from C . nucifera to completely abrogate parasite growth was 10 microg/ml . Pretreatment of peritoneal mouse macrophages with 10 microg/ml of C . nucifera polyphenolic-rich extract reduced approximately 44% the association index between these macrophages and L . amazonensis promastigotes, with a concomitant increase of 182% in nitric oxide production by the infected macrophage in comparison to nontreated macrophages . These results provide new perspectives on drug development against leishmaniasis, since the extract of C . nucifera at 10 microg/ml is a strikingly potent leishmanicidal substance which inhibited the growth of both promastigote and amastigote developmental stages of L . amazonensis after 60 min, presenting no in vivo allergenic reactions or in vitro cytotoxic effects in mammalian systems.

Zhonghua Yi Xue Za Zhi, 2004 Feb 2, 84(3), 242 - 7
{Anti-endotoxin effect of lanthanum chloride in vivo: an experimental study of mice}; Wang Y et al.; OBJECTIVE: Lanthanum is one of rare earth with extremely active chemical property and has been evidenced to possess antibacterial effect as well as the function of blocking calcium flux and regulating cellular immunity . Our previous studies showed that lanthanum could affect the biological activity of LPS and inhibit the activity in vitro . In this study, we explored the anti-LPS effects of lanthanum chloride in vivo so as to provide evidence in searching for new anti-endotoxic agents for the prevention and treatment of endotoxemia . METHODS: (1) 96 BALB/c mice were divided into 2 groups: experimental group including 84 mice injected intraperitoneally with 17.5 mg/kg, LD(50) dose, of LPS mixed with lanthanum chloride of the dosages of 1 mg/kg, 2 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, 40 mg/kg, and 80 mg/kg respectively; and control group including 12 mice injected intraperitoneally with 17.5 mg/kg of LPS . The mortality rates of different mice within 7 days were observed so as to observe the protective effect of lanthanum chloride . (2) 40 BALB/c mice were randomly divided into 2 group 2: experimental group injected intraperitoneally with lanthanum chloride of the dosages 10 mg/kg for 3 days and then injected with 1 LD(50) dosage of LPS 30 minutes after the last injection of lanthanum chloride of the dosages 10 mg/kg; and control group injected intraperitoneally with normal saline for 3 days and then with 1 LD(50) dosage of LPS 30 minutes after the last injection of normal saline . The mortality rates of different mice within 7 days were observed . (3) 40 BALB/c mice were randomly divided into 4 groups: LPS group, injected intraperitoneally with LPS of sublethal dosage (12.5 mg/kg), lanthanum chloride treatment group, injected intraperitoneally with LPS of sublethal dosage 1 hour after the venous injection of 10 mg/kg lanthanum chloride, lanthanum chloride control group, injected intravenously with 10 mg/kg lanthanum chloride, and NS control group, injected intraperitoneally with NS . Four hours after the intraperitoneal injection blood sample were collected to detect the plasma tumor necrosis factor-alpha (TNFalpha) and liver and thymus tissues were collected to examine the expression of TNFalpha mRNA and apoptosis of thymocytes by Rt-PCR and flow cytometry so as to observe the effects of lanthanum chloride on LPS-induced reaction in vivo . RESULTS: The mortality rates of the mice administrated with LD(50) dosage of LPS combined with 5, 10, and 20 mg/kg lanthanum chloride were 0, 0, and 8% respectively, all significantly lower than that of the control group (67%, all P < 0.01) . The mortality rate of the LPS-challenged mice that were pretreated with 10 mg/kg of lanthanum chloride was 20%, significantly lower than that of the control group (55%, P < 0.05) . (2) In the mice with endotoxemia that were pretreated with lanthanum chloride the plasma TNFalpha level was 0.44 +/- 0.22 ng/ml and the TNFalpha mRNA expression in liver was (3.93 +/- 0.62) x 10(5) copies/ micro g RNA, both significantly lower than those of the mice with endotoxemia without pretreatment of lanthanum chloride, 0.99 +/- 0.24 ng/ml and (1.9 +/- 0.33) x 10(7) copies/ micro g RNA (both P < 0.001) . The percentage of DNA fragmentation of thymocytes in the mice challenged with LPS and pretreated with lanthanum chloride was 14.77% +/- 1.0%, significantly lower than that of the untreated mice (55.38% +/- 3.88%, P < 0.001), the percentage of hypodiploidy in thymocytes of the mice challenged with LPS was 15.56% +/- 0.59%, significantly higher than that of the lanthanum chloride treated mice (6.05% +/- 0.71%, P < 0.001) . (3) Morphologic observation showed that pathological changes of the thymocytes and liver and lung tissues were remarkably milder in the lanthanum chloride-treated mice than in the mice challenged only by LPS . CONCLUSIONS: (1) Lanthanum chloride can bind LPS and reduce its toxicity, which shows protective effects on mice challenged by lethal dose LPS . (2) Lanthanum chloride can greatly decrease the secretion of TNFalpha and TNFalpha mRNA expression in the mice the secretion of TNFalpha and TNFalpha mRNA expression in the mice challenged with LPS . Furthermore, LPS-induced apoptosis of thymocyte and damage of liver and lungs are inhibited by lanthanum chloride.

Zhonghua Shao Shang Za Zhi, 2004 Feb, 20(1), 10 - 3
{Investigation on the antibiotic resistance and risky factors of nosocomial infections caused by Stenotrophomonas maltophilia}; Zhuo C et al.; OBJECTIVE: To investigate the antibiotic resistance and risky factors of nosocomial infections caused by Stenotrophomonas maltophilia, so as to help elucidate the difference of drug resistance between metallic beta-lactamase (MBL) producing and non-MBL producing strains . METHODS: Standard agar dilution method of NCCLS was employed in the isolation of 36 strains of Stenotrophomonas maltophilia from patients with nosocomial infection with respect to their in vitro antibiotic resistance to 18 kinds of antibiotics . MBL strains were identified by MBL-E test method . RESULTS: Stenotrophomonas maltophilia in our hospital was mainly identified in the lower respiratory tract (88.9%), in which 88.2% (30/34) of the patients had serious original diseases, 50% of whom had received Imipenem/cilastatin sodium treatment . Thirty-six strains of Stenotrophomonas maltophilia were susceptible to new types of fluoquinolone antibiotics, i.e . Sparfloxacin, levofloxacin, gatifloxacin and doxycycline, with inhibitory rate ranging 97.2%, 94.4%, 91.7% to 83.3%, respectively . They could also be inhibited by SMZ/TMP and Ticarcillin/Lavulanic acid with inhibitory rate of 63.9% and 58.3%, respectively . There were 16 strains out of 36 of MBL bacteria with complete resistance to Imipenem/cilastatin sodium, but with higher susceptibility to aztreonam than those non-MBL producing strains . CONCLUSION: The nosocomial infection in our hospital caused by Stenotrophomonas maltophilia seemed to be related with severe primary disease and the use of Imipenem/cilastatin sodium . The newly developed fluoroquinolones possessed powerful antibacterial potency on Stenotrophomonas maltophilia found in nosocomial infection.

J Org Chem, 2004 Mar 19, 69(6), 1872 - 9
Model studies and first synthesis of the antifungal and antibacterial agent cladobotryal; Clive DL et al.; The antifungal and antibacterial agent cladobotryal (1) was synthesized by a convergent route from lactone 31 and aldehyde 13, a key step in the elaboration of the pyridinone ring being conversion of a Boc group on nitrogen into a CO(2)SiPr-i(3) group . The simple model compounds 9 and 10, representing the core of cladobotryal and of 5, respectively, were prepared as support studies for making the natural product.

Infection, 2004 Apr, 32(2), 98 - 108
Therapeutic implications of antibacterial resistance in community-acquired respiratory tract infections in children; Cunha BA; The global spread of antibacterial resistance has important implications for the current and future management of bacterial respiratory tract infections in children . Data suggest that emerging resistance to commonly prescribed antibacterials, such as macrolides and trimethoprim-sulfamethoxazole, is beginning to impact the treatment of these infections, which include acute otitis media, tonsillitis/pharyngitis and community-acquired pneumonia . There is, therefore, a need for additional agents that are active against common respiratory tract pathogens, including resistant strains and are suitable for use in children . Infection control measures to curb the clonal spread of antibacterial resistance are also extremely important.

J Invertebr Pathol, 2004 Feb, 85(2), 112 - 9
Antibacterial activities in various tissues of the horse mussel, Modiolus modiolus; Haug T et al.; A search for antibacterial activity in different organs/tissues of the horse mussel, Modiolus modiolus, was conducted . Dried samples were extracted with 60% (v/v) acetonitrile, containing 0.1% (v/v) trifluoroacetic acid . Due to high salt content, two liquid phases were obtained; an acetonitrile-rich phase (ACN extract) and an aqueous phase . The aqueous phase was further subjected to solid phase extraction (SPE) . Eluates from SPE and ACN extracts were tested for antibacterial, lysozyme, and toxic activity . Antibacterial activity was demonstrated in extracts from several tissues, including plasma, haemocytes, labial palps, byssus, mantle, and gills . Some of the extracts were sensitive to proteinase K treatment, indicating antibacterial peptides and/or proteins . Lysozyme-like activity and toxic activity against Artemia salina nauplii was detected in fractions from the gills, mantle, muscle, and haemocytes . Results from this study indicate that M . modiolus is a promising source for identifying novel drug lead compounds.

J Biochem (Tokyo), 2004 Feb, 135(2), 171 - 7
Binding between azurocidin and calreticulin: its involvement in the activation of peripheral monocytes; Okuyama Y et al.; We found that azurocidin, a secretory protein in neutrophils, binds to calreticulin, a multifunctional chaperone of the endoplasmic reticulum . Azurocidin is known to induce cytokine production in monocytes, but the mechanism of monocyte activation by azurocidin remains unknown . On the other hand, an antibacterial peptide, KLKLLLLLKLK-NH(2) (L5), is known to bind to cell surface calreticulin of human neutrophils, resulting in their activation to produce O(2)(-) . Therefore, we examined whether cell surface calreticulin is involved in the activation of human monocytes by azurocidin to produce IL-6 . We found that carlreticulin is in fact located on the surface of monocytes and that the IL-6 production stimulated by an azurucidin is inhibited by anti-calreticulin antibody . Possibly, binding between cell surface calreticulin and azurocidin is prerequisite for the activation of monocytes by azurocidin to produce IL-6.

Biomaterials, 2004 Aug, 25(18), 4383 - 91
An in vitro assessment of the antibacterial properties and cytotoxicity of nanoparticulate silver bone cement; Alt V et al.; Infections with multiresistant bacteria have become a serious problem in joint arthroplasty . This study reports about in vitro antibacterial activity against multiresistant bacteria and in vitro cytotoxicity of polymethylmetacrylate bone cement loaded with metallic silver particles with a size of 5-50 nm called NanoSilver . In vitro antibacterial activity against S . epidermidis, methicillin-resistant S . epidermidis (MRSE), and methicillin-resistant S . aureus (MRSA) was studied by microplate proliferation tests . Quantitative elution testing and qualitative ongrowth of human osteoblasts was done to study in vitro cytotoxicity . Only NanoSilver cement showed high-antibacterial activity against all strains, including MRSE and MRSA . Gentamicin cement was not effective against MRSA and MRSE due to the high-level gentamicin resistance of the tested strains . Plain cement did not inhibit proliferation of any strains . There was no significant difference regarding in vitro cytotoxicity between NanoSilver and the non-toxic control . Cytotoxicity of cement loaded with silver salts made this kind of silver unsuitable for all day clinical use in the past . This new form of silver called NanoSilver was free of in vitro cytotoxicity and showed high effectiveness against multiresistant bacteria . If the results can be confirmed in vivo NanoSilver may have a high interest in joint arthroplasty.

FEBS Lett, 2004 Mar 26, 562(1-3), 129 - 33
Peroxynitrite formation from the simultaneous reduction of nitrite and oxygen by xanthine oxidase; Millar TM; One electron reductions of oxygen and nitrite by xanthine oxidase form peroxynitrite . The nitrite and oxygen reducing activities of xanthine oxidase are regulated by oxygen with K(oxygen) 26 and 100 microM and K(nitrite) 1.0 and 1.1 mM with xanthine and NADH as donor substrates . Optimal peroxynitrite formation occurs at 70 microM oxygen with purine substrates . Kinetic parameters: V(max) approximately 50 nmol/min/mg and K(m) of 22, 36 and 70 microM for hypoxanthine, pterin and nitrite respectively . Peroxynitrite generation is inhibited by allopurinol, superoxide dismutase and diphenylene iodonium . A role for this enzyme activity can be found in the antibacterial activity of milk and circulating xanthine oxidase activity.

J Nat Prod, 2004 Mar, 67(3), 466 - 8
New peptaibols from Mycogone cervina; Wilhelm C et al.; From cultures of Mycogone cervina, a mycophilic fungus growing on the fruit bodies of ascomycete Paxina acetabulum, two new peptaibols (cervinin, N-Ac-Leu-Aib-Pro-Aib-Leu-Aib-Pro-Ala-Aib-Pro-Val-red-Leu (1) and the red-Leu O-acetylated derivative 2) were isolated . The structures of 1 and 2 were elucidated by spectroscopic techniques . They exhibited weak antibacterial as well as cytotoxic activities . They are the first secondary metabolites described from M . cervina.

J Nat Prod, 2004 Mar, 67(3), 448 - 50
Periconicins, two new fusicoccane diterpenes produced by an endophytic fungus Periconia sp . with antibacterial activity; Kim S et al.; Two new fusicoccane diterpenes, named periconicins A (1) and B (2), with antibacterial activities have been isolated by bioassay-guided fractionation from an endophytic fungus Periconia sp., collected from small branches of Taxus cuspidata . The structures of the new compounds were determined by combined spectroscopic methods.

What Is Listeria Monocytogenes?, What Is Bioremediation?, What Is Bioassay?, What Is Staphylococcus Aureus?, What Is Nitrification?, c, Bacteria, a, Microorganisms, o, Bacteriology, r, Bacterium, i, Microbiology, i, Escherichia coli, o, Pseudomonas aeruginosa, c, Salmonella, r, Enterobacteriacea, r, Microflora, o, Bactericidal, a, Shigella, c, Meningococcus, n, Escherichia coli, s, Vibriosis, r, Cell suspensions, e, Microbiological, a, Microbial, a, Cell cultures, r, Candida albicans, r, Candida albicans, o, Denitrificans, i, Microorganism, e, Rhodotorula, r, Staphylococcus aureus, c, Gram negative

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005