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 a