Antimicrobial

Phytochemistry, 2001 Dec, 58(7), 1107 - 11
Taraxastane-type triterpenoids from Saussurea petrovii; Dai J et al.; Two taraxastane triterpenoids, i.e . taraxast-20-ene-3beta,30-diol (1) and 20alpha,21alpha-epoxy-taraxastane-3beta,22alpha-diol (2), as well as four known triterpenes taraxast-20(30)ene-3beta,21alpha-diol (3), taraxast-20(30)-ene-3beta-ol (4), taraxast-20-ene-3beta-ol (5) and taraxastane-3beta,20alpha-diol (6) were isolated from the Chinese medicinal plant Saussurea petrovii . Their structures were elucidated by spectroscopic methods . These compounds, especially 1 and 2, exhibit significant antitumor and antibacterial activity.

Int Arch Allergy Immunol, 2001 Oct, 126(2), 173 - 8
Equal allergenic potency of beta-lactam antibiotics produced by chemical or enzymatic manufacturing--mouse IgE test; Coenen TM et al.; BACKGROUND: Cephalexin and amoxicillin are semisynthetic beta-lactam antibiotics with a broad spectrum of antibacterial activity against gram-positive and gram-negative microorganisms . Both antibiotics are produced by a new 'green' process in which enzyme technology is used to combine the intermediate structure and the side chain in an aqueous medium to yield cephalexin or amoxicillin, thus avoiding the use of several chemical reagents and volatile organic solvents . As a result of the enzyme technology a new residual protein impurity has been identified . To check for the sensitizing capacity of the residual protein, a mouse IgE test was used to detect differences in the production of specific IgE by chemical or enzymatic preparations of the antibiotics . METHODS: Balb/c female mice were immunized intraperitoneally with alum and conjugates of different amoxicillins or cephalexins with ovalbumin (OVA) . After 16 days, the amoxicillin mice were injected with one half the original amount of antigen . After 19-23 days, the sera were tested for specific IgE by the passive cutaneous anaphylaxis assay in Sprague-Dawley rats . The greatest dilution of sera which resulted in a positive response was the titer of specific IgE . RESULTS: No significant differences were found between the titers of specific IgE caused by the chemically and enzymatically produced beta-lactam antibiotics, indicating that the antibiotics are equal in allergenicity . CONCLUSIONS: The data show that a residual level of 35 ppm protein did not affect the allergenic potency of these beta-lactam antibiotics as determined by the mouse allergenicity model .

Trends Microbiol, 2001 Dec, 9(12), 611 - 7
Exploiting genomics to discover new antibiotics; McDevitt D et al.; There is an urgent need to develop new classes of antibiotics to tackle the increase in resistance in many common bacterial pathogens . One strategy to develop new antibiotics is to identify and exploit new molecular targets and this strategy is being driven by the wealth of new genome sequence information now available . Additionally, new technologies have been developed to validate new antibacterial targets, for example, new technologies have been developed to enable rapid determination of whether a gene is essential and to assess the transcription status of a putative target during infection . As a result, many novel validated targets have now been identified and for some, appropriate high-throughput screens against diverse compound collections have been carried out . Novel antibiotic leads are emerging from these genomics-derived targeted screens and the challenge now is to optimize and develop these leads to become part of the next generation of antibiotics.

FEMS Microbiol Lett, 2001 Nov 27, 205(1), 1 - 7
Macrolide antibiotics and pulmonary inflammation; Hoyt JC et al.; Many clinically effective therapeutic agents can exhibit localized and systemic effects that are manifestly different from their intended primary pharmacological mode of action . Macrolide antibiotics such as erythromycin and its derivatives are no exception . In addition to their antibacterial action, this class of antibiotics exhibits anti-inflammatory activity in a variety of airway diseases such as asthma and diffuse panbronchiolitis that is separate and distinct from a direct antibacterial action . A variety of erythromycin derivatives have been shown to be clinically beneficial in these airway diseases . The anti-inflammatory activities of these macrolide antibiotics are becoming a research topic of intense interest . Recent work in this field has led to the understanding of the various physiological, cellular and molecular processes of the inflammatory response that are inhibited or suppressed by these compounds . This review presents a brief summary of the fascinating recent work in this active research area.

Adv Exp Med Biol, 2001, 493, 207 - 14
Cannabinoid-mediated inhibition of inducible nitric oxide production by rat microglial cells: evidence for CB1 receptor participation; Cabral GA et al.; Activated brain microglial cells release inflammatory mediators such as nitric oxide (NO) that may play important roles in central nervous system antibacterial, antiviral, and antitumor activities . However, excessive release of these factors has been postulated to elicit immune-mediated neurodegenerative inflammatory processes and to cause brain injury . Recent studies using the rat animal model indicate that select cannabinoids may modulate production of these inflammatory factors . Treatment of neonatal rat brain cortical microglial cells with the cannabinoid paired enantiomers CP55940 and CP56667 resulted in a stereoselective differential effect on inducible NO production . The analog CP55940 exerted a dose-dependent inhibition of interferon gamma (IFNy)/bacterial lipopolysaccharide (LPS)-inducible NO production which was significantly greater than that exerted by CP56667 . Pretreatment of microglial cells with the CB1 cannabinoid receptor-selective antagonist SR141716A reversed this CP55940-mediated inhibition . MRT-PCR demonstrated the presence of CB1 receptor mRNA within microglial cells consistent with the presence of CB1 receptors . Collectively, these results indicate that the cannabinoid analog CP55940 selectively inhibits inducible NO production by microglial cells and that this inhibition is effected, at least in part, through the CB1 receptor.

Anal Biochem, 2001 Dec 1, 299(1), 31 - 6
A method for identification of inhibitors of the phosphorylation reactions of bacterial response regulator proteins using (31)P nuclear magnetic resonance spectroscopy; Hubbard JA et al.; Bacterial response regulators are attractive targets for antibacterial drug development, yet random screening against these targets has failed as yet to identify chemicals that constitute viable leads . Alternative methods to provide leads for drug development based on identification and optimization of low affinity ligands from NMR screens have been described . However, leads from these processes still require verification in a bioassay, which is often problematic if compounds have unfavorable optical and solubility properties . A simple method, based on using NMR to observe the activity of the target, is described . It has the advantages of being able to characterize both low affinity leads and a wider selection of compounds in a structure activity relationships series, without the problems affecting a fluorescence assay . In this example we use (31)P to monitor the turnover of a bacterial response regulator, but the generic approach could be applied to other nuclei and thus a range of biological systems.

Z Naturforsch {C}, 2001 Sep-Oct, 56(9-10), 731 - 8
Composition and antibacterial activity of the essential oils from Satureja wiedemanniana (Lallem.) Velen; Baser KH et al.; Satureja wiedemanniana (Lallem.) Velen (Lamiaceae) is an endemic species of Turkey . Aerial parts of the plant collected from eleven different localities in Turkey were subjected to hydrodistillation to yield essential oils which were analysed by a GC/MS system . Carvacrol, thymol, p-cymene and gamma-terpinene were found as the main constituents . Antibacterial evaluation of the oils was also carried out.

Eur J Surg Suppl, 2001, (586), 82 - 8
Helicobacter pylori: today's treatment, and possible future treatment; Trust TJ et al.; Helicobacter pylori induces chronic superficial gastritis which in some patients may lead to peptic ulcer disease, while a subset of infected individuals develop gastric cancer or gastric lymphoma . Consensus guidelines recommend that patients with a known H . pylori infection receive eradication treatment . Successful treatment requires that antibiotics be used in combination with acid suppressants or bismuth, and although the list of effective antibacterials is short, regimens such as amoxicillin and clarithromycin or metronidazole and clarithromycin with the proton pump inhibitor omeprazole have achieved eradication rates of approximately 90% in trials . However lower eradication rates are probably more common, and strains resistant to clarithromycin or metronidazole, or both, are of concern . Stable amoxycillin resistance has also been reported . Efforts are underway to discover and develop novel therapeutics, both H . pylori specific antibacterial drugs and a therapeutic vaccine . Impetus to these efforts has been provided by the availability of the genome sequences of two different H . pylori isolates . In the case of drug discovery, a genome-based strategy facilitates the expeditious selection of novel lethal targets not used by today's antibiotics, providing the opportunity to identify novel classes of antibacterials . Vaccine discovery and development has largely focused on a small number of antigens selected by conventional means . Recent reports that mucosal and serum antibody titers do not appear to be essential for protection against H . pylori in murine models suggest that that a wider range of H . pylori proteins than those previously considered may be able to induce protective immunity . Progress towards development of new H . pylori therapeutics is discussed.

Zhonghua Wai Ke Za Zhi, 1998 Feb, 36(2), 110 - 2
{The relationship between severe burn injury and systemic inflammatory response syndrome}; Sun Y et al.; OBJECTIVE: To study course of systemic inflammatory response syndrome (SIRS) . METHODS: The relationship was observed between SIRS and the effect of burn injury on cellular and humoral immunity between survivors . Nonsurvivors were also compared . The gastric mucosal pHi was measured . RESULTS: The SIRS initiated 22 hours after burn injury and peaked 3 days to 7 days postburn . Compared to the survivors significan increase of content of TNF and decrease of content of G-CSF were detected in the nonsurvivors serum . Obvious immunosuppression could be found . In patients with SIRS accompanied with infection or organ failure, marked increase of mortality was seen . The value of pHi was very low . CONCLUSION: Severe burn injury can lead to the release of massive inflammatory mediators . The second insult such as infection can further amplify the process leading to a vicious cycle of inflammation which cause tissue damage and immunosuppression . To prevent MODS, early diagnosis and treatment including organ supply, use of antibacterial agents, oxygen supply and immunity therapy were necesary.

Zhong Yao Cai, 2001 Aug, 24(8), 568 - 9
{Studies on chemical constituents of mycelium of fungus Cephalosporium sp . AL031(I)}; Bi Y et al.; Five compounds were isolated from the mycelium of the fungus Cephalosporium sp . AL031 whose metabolites have been proven to possess antifungal and antibacterial activities . Based on the spectral data and elemental analysis, they were identified as ergosterol(I), 2,4,6-octatrienoic acid(II), succinic acid(III), uracil(IV), and D-mannitol(V) . All of these compounds were obtained from the culture of this fungus for the first time.

J Invest Dermatol, 2001 Nov, 117(5), 1206 - 11
Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy; Tokura Y et al.; Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten . In a murine model of quinolone photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells . The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells . On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin . An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide . CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide . These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin . Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of photoallergy evoked with systemic ofloxacin and ultraviolet A light . This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone photoallergy.

Antimicrob Agents Chemother, 2001 Dec, 45(12), 3616 - 22
In vitro antibacterial activities of AF 3013, the active metabolite of prulifloxacin, against nosocomial and community Italian isolates; Montanari MP et al.; AF 3013, the active metabolite of prulifloxacin, was tested to determine its inhibitory and bactericidal activities against 396 nosocomial and 258 community Italian isolates . Compared with that of ciprofloxacin, its activity (assessed in MIC and minimal bactericidal concentration tests) was generally similar or greater against gram-positive bacteria and greater against gram-negative bacteria . In time-kill assays using selected isolates, its bactericidal activity was comparable to that of ciprofloxacin.

Enferm Infecc Microbiol Clin, 2001 Nov, 19(9), 422 - 7
{Infection in patients with neutropenia that undergo an autologous peripheral blood stem cell transplant due to breast cancer}; Palau J et al.; BACKGROUND: The extent and duration of neutropenia and the characteristics of the underlying disease are determinant factors for the prognosis of febrile syndromes . Despite the fact that traditionally the peripheral blood stem cell transplantation (PBSCT) were considered to cause high risk neutropenia, in all probability the neutropenia observed in the PBSCT in some solid tumours could be considered moderate risk . Febrile episodes in patients with these characteristics were evaluated . METHODS: We prospectively analysed 132 autologus PBSCT in patients with breast cancer (1994-1999).Conditioning regime: STAMP V . Antibacterial prophylaxis: ofloxacin (400 mg/12 hrs PO) . Classification of the febrile syndrome: bacteremia, microbiologically documented infection withut bacteremia, clinical infection and a fever of unknown origin . RESULTS: 122 patients had a fever (92%), mean age: 45 years (range: 27-61) . There were 32 (26%) bacteremias, 13 (11%) microbiologically documented infections without bacteremia and 54 (44%) clinical infections . The mean number of days with a neutrophil count of <1x109/1 was 14 (range: 11-20) . In the 74 patients (61%) that had a granulocyte colony stimulating factor (G-CSF), the mean number of days to reach a 0,5x109/I neutrophil count (7,6) and the average number of days in hospital (26) were significantly less . There was a main infectious point in 80 patients (65%): the most frequent being oropharynx in 33 cases (46%) and digestive in 29 cases (41%) . 48 gram negative (GN) 29 gram positive (GP) bacteria were isolated (71% of the GN's were resistant to ofloxacin) . Between 1997-1999 the GN/GP ratio was 2,3 . There were no deaths related to the infection . CONCLUSIONS: Given the excellent evolution of our patients we can consider their neutropenia to be moderate or low risk, and they are a long way from the death rates caused by infections published by other types of hemopoietic transplants . The predominance of GN over the last few years and their limited sensitivity to quinolones means that their prophylactic use in these patients should be reconsidered.

Trans R Soc Trop Med Hyg, 2001 Sep-Oct, 95(5), 524 - 8
Therapeutic responses to antibacterial drugs in vivax malaria; Pukrittayakamee S et al.; Some antibacterial drugs have antimalarial activity that can be exploited for the prevention or treatment of malaria . Monotherapy with tetracycline, doxycycline, clindamycin or azithromycin was assessed in 1995-98 in 92 adult patients in Thailand with Plasmodium vivax malaria . All patients recovered following treatment and the early therapeutic responses were similar among the 4 groups . The overall median fever clearance time was 57 h and the mean (SD) overall time to parasite clearance was 134 (48) h . Of 66 patients who completed a 28-day follow-up, reappearances of vivax infection occurred in 27 patients (41%) from all groups; delayed appearances of falciparum malaria occurred in 6 patients (9%), only from the azithromycin group . The overall mean (SD) time to reappearance of P . vivax was 23 (5) days and time taken for detection of falciparum malaria was 13 (4) days after starting treatment for vivax malaria . The 28-day cumulative cure rates of clindamycin (n = 12), tetracycline (n = 18) and doxycycline (n = 18) groups were similar (P > or = 0.14) and all were significantly higher compared to the azithromycin group (n = 18; P < or = 0.04) . The intervals until vivax reappearance were also significantly shorter in the azithromycin group {mean (SD) = 21 (6) vs 25 (3) days, P < 0.05} suggesting that some of these were recrudescences . The apparent success rate (no subsequent appearances of either vivax or falciparum infection) was significantly lower for the azithromycin group (11%) compared to the other groups (34-78%; P < 0.01) . In current antibacterial treatment regimens, short-course azithromycin has inferior antimalarial activity compared to clindamycin or the tetracyclines.

Plant Physiol, 2001 Nov, 127(3), 711 - 9
Rapid isolation of monoclonal antibodies . Monitoring enzymes in the phytochelatin synthesis pathway; Li Y et al.; Genomics projects have identified thousands of interesting new genes whose protein products need to be examined at the tissue, subcellular, and molecular levels . Furthermore, modern metabolic engineering requires accurate control of expression levels of multiple enzymes in complex pathways . The lack of specific immune reagents for characterization and monitoring of these numerous proteins limits all proteomic and metabolic engineering projects . We describe a rapid method of isolating monoclonal antibodies that required only sequence information from GenBank . We show that large synthetic peptides were highly immunogenic in mice and crude protein extracts were effective sources of antigen, thus eliminating the time-consuming step of purifying the target proteins for antibody production . A case study was made of the three-enzyme pathway for the synthesis of phytochelatins . Enzyme-linked immunosorbent assays and western blots with the recombinant proteins in crude extracts demonstrated that the monoclonal antibodies produced to synthetic peptides were highly specific for the different target proteins, gamma-glutamyl cysteine synthetase, glutathione synthetase, and phytochelatin synthase . Moreover, immunofluorescence localization studies with antibacterial gamma-glutamyl cysteine synthetase and antiglutathione synthetase antibodies demonstrated that these immune reagents reacted strongly with their respective target proteins in chemically fixed cells from transgenic plants . This approach enables research to progress rapidly from the genomic sequence of poorly characterized target genes, to protein-specific antibodies, to functional studies.

Am J Clin Dermatol, 2001, 2(4), 219 - 27
Clinical applications for maggots in wound care; Mumcuoglu KY; Maggot debridement therapy (MDT) was first introduced in the US in 1931 and was routinely used there until mid-1940s in over 300 hospitals . With the advent of antibacterials, maggot therapy became rare until the early 1990s, when it was re-introduced first in the US, and later in Israel, the UK, Germany, Sweden, Switzerland, Ukraine and Thailand . Sterile maggots of the green bottle fly, Lucilia (Phaenicia) sericata, are used for MDT . Up to 1000 maggots are introduced in the wound and left for 1 to 3 days . MDT could be used for any kind of purulent, sloughy wound on the skin, independent of the underlying diseases or the location on the body for ambulatory as well as for hospitalized patients . One of the major advantages of MDT is that the maggots separate the necrotic tissue from the living tissue, making a surgical debridement easier . In 80 to 95% of the cases, a complete or significant debridement of the wound is achieved . As therapy progresses, new layers of healthy tissue are formed over the wounds . The offensive odor emanating from the necrotic tissue and the intense pain accompanying the wound decrease significantly . In a significant number of patients, an immediate amputation can be prevented as a result of MDT . In other cases, a more proximal amputation could be avoided . It is also possible that in patients with deep wounds, where septicemia is a serious threat, this can be prevented as a result of MDT . The majority of patients do not complain of any major discomfort during the treatment . Psychological and esthetic considerations are obvious . Maggots can occasionally cause a tickling or itching sensation . Approximately 20 to 25% of the patients with superficial, painful wounds, complain of increased pain during treatment with maggots, and are treated with analgesics . MDT has been proven to be an effective method for cleaning chronic wounds and initiating granulation . It is a simple, efficient, well tolerated and cost-effective tool for the treatment of wounds and ulcers, which do not respond to conventional treatment and surgical intervention.

Value Health, 2001 Sep-Oct, 4(5), 370 - 5
The excess cost of acute exacerbations of chronic bronchitis in patients aged 45 and older in England and Wales; McGuire A et al.; INTRODUCTION: Chronic Bronchitis is a serious and costly health problem . Prevalence is estimated at 45 per 10,000 persons in the United Kingdom . Approximately 120,000 Pounds would be saved for every 100 hospital admissions avoided . A reduction in acute exacerbations of chronic bronchitis (AECB), treatment failures, and subsequent hospital admission could have a significant impact on the burden of AECB borne by secondary care facilities in the UK National Health Service (NHS) . OBJECTIVE: The aim of this study is to provide an economic assessment of the direct cost to the health care system associated with the management of chronic bronchitis and its acute exacerbations . DESIGN: A prevalence-based, excess-cost-of-illness analysis is undertaken from the perspective of the UK NHS . Disease prevalence data, primary health care resource utilization, hospital inpatient and outpatient resource utilization, and costs of health care were taken from a variety of data sources, including a large UK national survey of general practice (GP) consultations, the General Practice Research Database, a survey from a single NHS hospital trust, and the national health-care resource and cost statistics . RESULTS: From 1994 to 1995, approximately 233,000 cases of chronic bronchitis were detected in the persons aged 45 and older in the United Kingdom . Prevalence peaked at 204 per 10,000 in the group of subjects aged 75 to 84 years . During that same period, the total excess cost of primary care associated with AECB was calculated at 35.7 million Pounds . The largest component of primary care costs was the excess cost of all prescription medicines, which totaled 27.8 million Pounds . The excess cost attributed to antibacterial and respiratory prescription medications alone was estimated at 9 million Pounds . Excess costs attributed to GP consultations and hospital emergency room visits were 6.5 million Pounds and 1.3 million Pounds, respectively . The excess costs arising from inpatient hospital episodes included 8.3 million Pounds for hospital admissions, 660,000 Pounds for outpatient costs, and 225,000 Pounds for day care . CONCLUSIONS: These results suggest that improving the management of AECB with the objective of reducing the number of AECB treatment failures and the associated hospital admissions could significantly reduce expenditures by the UK NHS.

Rev Esp Quimioter, 2001 Jun, 14(2), 165 - 71
{Effect of anti-inflammatory drugs, alone and combined with ofloxacin, on the respiratory burst of human polymorphonuclear leukocytes}; Cabrera E et al.; The antibacterial activity of polymorphonuclear leukocytes (PMNs) is based on the production of superoxide anion and H(2)O(2) in the respiratory burst and can be impaired in different ways . The combination of an antibacterial agent and an antiinflammatory drug is quite common in immunodepressed patients whose respiratory burst of PMN could be impaired . In this study we examine in vitro the effect of pretreating (35 degrees C for 30 min) PMNs with the antiinflammatory drugs dexamethasone (0.4, 4 and 40 microgram/ml), methylprednisolone (0.37, 3.7 and 37 microgram/ ml), hydrocortisone (0.048, 0.48 and 4.8 microgram/ml), betamethasone (0.1, 1, 5 and 10 mg/ml), phenylbutazone (1000 microgram/ml) and acetylsalicylic acid (25, 250, 2500 microgram/ml) alone, and combined with 10 mg/ml of ofloxacin on the respiratory burst . Superoxide anion was measured by the cytochrome c reduction microtechnique and H(2)O(2) by phenol red . The antiinflammatory drugs alone decreased the production of H(2)O(2) (except dexamethasone and methylprednisolone) and superoxide anion (except betamethasone) from 15-45%, depending on the antiinflammatory drug and concentration, while ofloxacin increased the production of superoxide anion (20.2 +/- 6.7%) . The combination of antiinflammatory drugs with ofloxacin neutralizes the inhibitory effect of the former on the respiratory burst of PMNs . It is therefore important to know the effect of drugs on the respiratory burst in order to choose those that have the same therapeutic effect without interfering with PMN functions.

Dev Cell, 2001 Oct, 1(4), 503 - 14
Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis; Georgel P et al.; We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila . imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis . We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes . Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35 . We also show that imd is involved in the apoptotic response to UV irradiation . These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila.

Am J Clin Dermatol, 2001, 2(1), 21 - 5
Laser removal of tattoos; Kuperman-Beade M et al.; Tattoos are placed for different reasons . A technique for tattoo removal which produces selective removal of each tattoo pigment, with minimal risk of scarring, is needed . Nonspecific methods have a high incidence of scarring, textural, and pigmentary alterations compared with the use of Q-switched lasers . With new advances in Q-switched laser technology, tattoo removal can be achieved with minimal risk of scarring and permanent pigmentary alteration . There are five types of tattoos: amateur, professional, cosmetic, medicinal, and traumatic . Amateur tattoos require less treatment sessions than professional multicolored tattoos . Other factors to consider when evaluating tattoos for removal are: location, age and the skin type of the patient . Treatment should begin by obtaining a pre-operative history . Since treatment with the Q-switched lasers is painful, use of a local injection with lidocaine or topical anaesthesia cream may be used prior to laser treatment . Topical broad-spectrum antibacterial ointment is applied immediately following the procedure . Three types of lasers are currently used for tattoo removal: Q-switched ruby laser (694 nm), Q-switched Nd:YAG laser (532 nm, 1064 nm), and Q-switched alexandrite laser (755 nm) . The Q-switched ruby and alexandrite lasers are useful for removing black, blue and green pigments . The Q-switched 532 nm Nd:YAG laser can be used to remove red pigments and the 1064 nm Nd:YAG laser is used for removal of black and blue pigments . The most common adverse effects following laser tattoo treatment with the Q-switched ruby laser include textural change, scarring, and pigmentary alteration . Transient hypopigmentation and textural changes have been reported in up to 50 and 12%, respectively, of patients treated with the Q-switched alexandrite laser . Hyperpigmentation and textural changes are infrequent adverse effects of the Q-switched Nd:YAG laser and the incidence of hypopigmentary changes is much lower than with the ruby laser . The development of localized and generalized allergic reactions is an unusual complication following tattoo removal with the Q-switched ruby and Nd:YAG lasers . Since many wavelengths are needed to treat multicolored tattoos, not one laser system can be used alone to remove all the available inks and combination of inks . While laser tattoo removal is not perfect, we have come a long way since the advent of Q-switched lasers . Current research is focusing on newer picosecond lasers, which may be more successful than the Q-switched lasers in the removal of the new vibrant tattoo links.

Am J Clin Dermatol, 2000 Nov-Dec, 1(6), 349 - 60
Drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis; Fritsch PO et al.; Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare (occurring in approximately 2 to 3 people/million population/year in Europe and the US), life-threatening, intolerance reaction of the skin . It is most often caused by drugs (most commonly sulfonamides, nonsteroidal anti-inflammatory drugs, antimalarials, anticonvulsants, and allopurinol) . SJS/TEN is characterized by a macular exanthema ('atypical targets') which focusses on the face, neck, and the central trunk regions . Lesions show rapid confluence, a positive Nikolsky's sign, and quickly result in widespread detachment of the epidermis and erosions . Mucosal, conjunctival, and anogenital mucous membranes are prominently involved . Histopathology shows satellite cell necrosis in the early stages progressing to full thickness necrosis of the epidermis, contrasting with rather inconspicuous inflammatory infiltrates of the dermis . Damage to the skin is thought to be mediated by cytotoxic T lymphocytes and mononuclear cells which induce apoptosis in keratinocytes expressing drug-derived antigens at their surfaces . No guidelines for the treatment of SJS/TEN exist since no controlled clinical trials have ever been performed . The controversy over whether systemic corticosteroids should be used to curtail progression is still unresolved; while many authors agree that corticosteroids do in fact suppress progression, it is obvious that they also greatly enhance the risk of infection, the complication which most frequently leads to a fatal outcome . It appears reasonable to only administer corticosteroids in the phase of progression and to withdraw them as soon as possible, and to add antibacterials for prophylaxis . Recently, in a small series of patients, intravenous immunoglobulins were presumed to be effective by the blockade of lytic Fas ligand-mediated apoptosis in SJS/TEN . However, these results have to be confirmed by large clinical trials . Supportive treatment and monitoring of vital functions is of utmost importance in SJS/TEN, and out-patient treatment is unacceptable . Recovery is usually slow, depending on the extent and severity and the presence of complications, and may take 3 to 6 weeks . Skin lesions heal without scars as a rule, but scarring of mucosal sites is a frequent late complication, potentially leading to blindness, obliteration of the fornices and anogenital strictures . There is no reliable laboratory test to determine the offending drug; diagnosis rests on the patient's history and the empirical risk of drugs to elicit skin SJS/TEN . Provocation tests are not indicated since re-exposure is likely to elicit a new episode of SJS/TEN of increased severity.

Am J Clin Dermatol, 2000 Mar-Apr, 1(2), 81 - 8
alpha-Hydroxy acid-based cosmetic procedures . Guidelines for patient management; Tung RC et al.; alpha-Hydroxy acid (AHA) peels and home regimens have recently been recognized as important adjunctive therapy in a variety of conditions including photodamage, actinic damage, melasma, hyperpigmentation disorders, acne, and rosacea . Overall in our experience and in the literature, AHAs have a proven level of safety and efficacy in a variety of skin types . Although their exact mechanism of action is unknown, it has been demonstrated that AHAs improve these disorders by thinning the stratum corneum, promoting epidermolysis, dispersing basal layer melanin, and increasing collagen synthesis within the dermis . In patients with photodamage, AHA peels and topical products are often combined with retinoids and other antioxidants for maximum benefit . Similarly, synergistic effects of fluorouracil and glycolic acid are observed in the treatment of diffuse actinic keratoses . For patients with melasma, AHA peels and combination products containing bleaching agents such as hydroquinone, kojic acid, and glycolic acid seem to have increased efficacy . Acne and rosacea patients can see improved results when standard regimens like antibacterials and topical retinoids are supplemented with AHA peels and lotions . However, care should always be taken prior to commencing treatment with AHA peels and topical products . By obtaining a thorough history and physical examination, the physician will identify any specific factors like medications, prior procedures and medical conditions which can affect the outcome of the peel . During the interview, there should be open discussion of patient questions and concerns so that realistic expectations can be made . Pre- and post-peel regimens should also be reviewed in full as patient compliance is essential to ensure the success of a series of AHA peels.

Am J Clin Dermatol, 2000 May-Jun, 1(3), 191 - 9
Topical metronidazole . A review of its use in rosacea; McClellan KJ et al.; Topical application of the antibacterial agent metronidazole is effective in the treatment of moderate to severe rosacea, although its mechanism of action has yet to be clearly established . Metronidazole preparations (0.75 and 1% cream, 0.75% gel and 0.75% lotion) were significantly more effective than placebo in patients with moderate to severe rosacea when administered to the affected area once or twice daily for 7 to 12 weeks . The mean number of papules and pustules decreased by between 48 and 65.1% during the treatment period . Reductions were fairly consistent regardless of formulation, strength or application frequency and were significant compared with placebo (p < 0.05) . In 1 study, most of the overall effects of metronidazole were observed within the first 3 weeks . Although data are limited, topical metronidazole appears to improve inflammatory lesions and erythema as effectively as oral tetracyclines . Like tetracyclines, however, metronidazole has no effect on telangiectasia . Metronidazole 0.75% gel seems to be effective in maintaining remission of rosacea symptoms in patients successfully treated with both oral tetracycline and topical metronidazole . In the only study, 77% of patients treated with metronidazole gel compared with 58% of placebo recipients (p < 0.05) remained in remission 6 months after the tetracycline was stopped . The effects of topical metronidazole preparations on rosacea symptoms are palliative, not curative, but preliminary data suggest that relapse rates after cessation of therapy are no worse than those after cessation of oral oxytetracycline . Topical metronidazole formulations are generally well tolerated locally, with stinging, dryness, burning and itching reported in < or = 2% of patients . Because minimal concentrations of metronidazole are absorbed after topical administration, systemic adverse events and drug interactions seen with oral or intravenous metronidazole are unlikely . CONCLUSIONS: Topical metronidazole formulations are significantly more effective than placebo when used in the initial treatment of patients with moderate to severe rosacea . Furthermore, limited evidence suggests that the use of topical metronidazole alone may be as effective as oral tetracyclines against the disorder's inflammatory component . Therefore, for those patients with a preference for topical rather than oral therapy, the use of a topical metronidazole formulation must be a consideration.

Eur J Clin Pharmacol, 2001 Sep, 57(6-7), 547 - 51
Use of systemic anti-infective agents in Iran during 1997-1998; Ansari F; OBJECTIVE: Conduction of standardized national drug utilization review to investigate the pattern of systemic anti-infective agent use in Iran . METHODS: The wholesale data were used . The Anatomical Therapeutic Chemical (ATC) classification and the defined daily dose (DDD) methodology was employed . Data were presented as DDD/1,000 inhabitants"day . Results were compared using national drug statistics of Norway, Sweden, and Denmark . RESULTS: The overall sales of systemic anti-infective agents was 43.5 DDD/1,000 inhabitants/day . The parenteral form of drug accounted for 4.20% and broad-spectrum systemic antibacterial agents accounted for 86.2% . The three most commonly used agents, accounting for 74.1% of total sales, were amoxicillin, co-trimoxazole, and ampicillin . Seven kinds of anti-infective agents (17% of total available agents) accounted for 90% of antibacterial use, with dominance of broad-spectrum agents . Comparison showed differences in pattern and intensity of use . The sales of systemic anti-infective agents in general, particularly antibacterials and anti-tuberclotics, were greater in Iran than in three European countries . Broad-spectrum antibacterial agents accounted for a larger proportion of total sales in Iran . CONCLUSION: The high use of systemic antibacterial agents in general, particularly broad-spectrum agents, suggest the possibility of irrational prescribing, higher prescribed daily doses than DDDs, and a drug wastage . This survey, as a first attempt, provided an overview of anti-infective use in Iran . Thus, it may serve as a basis for further investigative studies and advanced drug policies.

Vestn Otorinolaringol, 2001, (5), 29 - 32
{Comparative clinical efficacy and tolerance of cefuroxime axetil (zinnat) and ceftibuten (cedex) in patients with acute sinusitis}; Otvagin IV et al.; The aim of the study was to substantiate clinically and microbiologically administration of such oral cephalosporins as cefuroxime axetil and ceftibuten in acute sinusitis . The spectrum of causative agents of acute sinusitis was determined, most common pathogens were identified and their sensitivity to antibiotics was tested . The conclusion is made that cephalosporins of the II-III generation meet the requirements to antibacterial drugs for treatment of acute sinusitis.

Eur J Pharmacol, 2001 Oct 19, 429(1-3), 209 - 29
Anti-inflammatory effects of macrolide antibiotics; Culic O et al.; Macrolides are widely used as antibacterial drugs . Clinical and experimental data, however, indicate that they also modulate inflammatory responses, both contributing to the treatment of infective diseases and opening new opportunities for the therapy of other inflammatory conditions . Considerable evidence, mainly from in vitro studies, suggests that leukocytes and neutrophils in particular, are important targets for modulatory effects of macrolides on host defense responses . This underlies the use of the 14-membered macrolide erythromycin for the therapy of diffuse panbronchiolitis . A variety of other inflammatory mediators and processes are also modulated by macrolides, suggesting that the therapeutic indications for these drugs may be extended significantly in future.

J Pharm Pharmacol, 2001 Oct, 53(10), 1303 - 10
Human lactoferrin: a novel therapeutic with broad spectrum potential; Weinberg ED; Lactoferrin (Lf), a natural defence iron-binding protein, has been found to possess antibacterial, antimycotic, antiviral, antineoplastic and anti-inflammatory activity . The protein is present in exocrine secretions that are commonly exposed to normal flora: milk, tears, nasal exudate, saliva, bronchial mucus, gastrointestinal fluids, cervico-vaginal mucus and seminal fluid . Additionally, Lf is a major constituent of the secondary specific granules of circulating polymorphonuclear neutrophils (PMNs) . The apoprotein is released on degranulation of the PMNs in septic areas . A principal function of Lf is that of scavenging free iron in fluids and inflamed areas so as to suppress free radical-mediated damage and decrease the availability of the metal to invading microbial and neoplastic cells . Mechanisms of action of Lf in addition to iron deprivation are also described . Administration of exogenous human or bovine Lf to hosts with various infected or inflamed sites has resulted in some prophylactic or therapeutic effects . However, an adverse response to the protein might occur if it were to stimulate antibody production or if it were to provide iron to the invading pathogen . The recombinant form of human Lf has become available and development of the product for use in a wide range of medical conditions can now be anticipated.

Stomatologiia (Mosk), 2001, 80(5), 22 - 5
{Insulating polymeric film in comprehensive prevention of complications of mandibular fractures}; Korotkikh NG et al.; A method for prevention of inflammatory complications of mandibular fractures making use of insulating polymer-based bioactive film was studied on 48 mice . Antibacterial and osteoregeneratory activities of the therapeutic film were assessed.

Stomatologiia (Mosk), 2001, 80(5), 14 - 7
{Ozone therapy of chronic mandibular osteomyelitis}; Agapov VS et al.; Clinical picture, bacterial passage, and immune status were studied in patients with chronic traumatic and chronic odontogenic mandibular osteomyelitis . The deepest disorders of biocenosis and the highest incidence of immunodeficiencies were observed in patients with chronic odontogenic osteomyelitis . Local and total ozone therapy is suggested for antibacterial and immunomodulating treatment . Medical ozone exposure promoted more complete and rapid normalization of nonspecific resistance and T-cellular immunity, thus accelerating clinical cure and reducing the incidence of complications.

Aust Dent J, 2001 Sep, 46(3), 166 - 73
Oral hygiene measures and promotion: review and considerations; Choo A et al.; Current mechanical and chemotherapeutic approaches to oral hygiene aim to modify the oral microflora to promote healthy periodontal and dental tissues . Current oral hygiene measures, appropriately used and in conjunction with regular professional care, are capable of virtually preventing caries and most periodontal disease and maintaining oral health . Toothbrushing and flossing are most commonly used, although interdental brushes and wooden sticks can offer advantages in periodontally involved dentitions . Chewing sugar-free gums as a salivary stimulant is a promising caries-preventive measure . Despite new products and design modifications, mechanical measures require manual dexterity and cognitive ability . Chemotherapeutic supplementation of mechanical measures using dentifrices, mouthrinses, gels and chewing gums as delivery vehicles can improve oral hygiene . The list includes anticalculus, antibacterial and cariostatic agents . For the population at large to make effective use of these oral hygiene measures, oral hygiene promotion needs to be implemented . Considerations include the role of parents, school and the media for children and the workplace, social environments . nursing homes and trained carers for adults and the elderly . Community oral hygiene promotion must attempt to maximise opportunities for oral health for all and reduce inequalities by removing financial and other barriers . Oral health approaches should be tailored to lifestyles and abilities of children, adults and the elderly in order to enable them to make decisions to improve personal oral hygiene and oral health.

J Ethnopharmacol, 2001 Dec, 78(2-3), 133 - 7
Immunomodulatory activity of alcoholic extract of Mangifera indica L . in mice; Makare N et al.; Mangifera indica Linn, a plant widely used in the traditional medicinal systems of India, has been reported to possess antiviral, antibacterial and anti-inflammatory activities . In the present study, the alcoholic extract of stem bark of Mangifera indica Linn (Extract I containing mangiferin 2.6%), has been investigated for its effect on cell mediated and humoral components of the immune system in mice . Administration of test extract I produced increase in humoral antibody (HA) titre and delayed type hypersensitivity (DTH) in mice . It is concluded that test extract I is a promising drug with immunostimulant properties.

Indian J Biochem Biophys, 2001 Jun, 38(3), 142 - 8
Effects of salt and denaturant on structure of the amino terminal alpha-helical segment of an antibacterial peptide dermaseptin and its binding to model membranes; Thennarasu S et al.; The amino terminal 1-18 domain of dermaseptin s is an important determinant of its structure as well as the antibacterial activity . A thorough investigation on the structure of the 18-residue peptide (D18) and its binding to model membranes in presence of salt and denaturant guanidinium chloride has been carried out . In presence of salt, there is an increase in the fraction of peptide molecules in helical conformation . In presence of the denaturant, D18 is unordered, but addition of the structure-promoting solvent trifluoroethanol results in a transition to the helical conformation . In presence of denaturant, the peptide is unordered, but binding to lipid vesicles is not abolished . Investigation of model membrane permeabilizing ability of the peptide in solutions containing various proportions of sodium chloride and guanidinium chloride indicates that vesicle permeabilization parallels extent of binding . The peptide thus binds to lipid vesicles in an unfolded state . Since the peptide has propensity to fold into a helical conformation, lipid induced transition to a helical structure occurs, followed by membrane permeabilization as a result of pore formation.

Arch Toxicol, 2001 Sep, 75(7), 395 - 9
Phototoxic retinal degeneration and toxicokinetics of sitafloxacin, a quinolone antibacterial agent, in mice; Shimoda K et al.; We examined drug concentrations and the incidence of retinal degeneration in the eyes of albino BALB/c mice after a single intravenous administration of sitafloxacin plus a 4 h period of UVA irradiation . Retinal degeneration was induced at 40 mg/kg or more plus UVA irradiation, and there was little decrease in ocular sitafloxacin concentration under UVA irradiation . We then examined the incidence of retinal degeneration with various periods of UVA irradiation in BALB/c mice given a single intravenous administration of 40 mg/kg sitafloxacin . Retinal degeneration occurred in all the groups receiving UVA irradiation immediately after sitafloxacin administration, whereas no retinal degeneration occurred in the groups receiving UVA irradiation starting 30 min or later after administration . In addition, we examined both the retinal degeneration and auricular inflammation in BALB/c mice given a 7-day repeated administration of sitafloxacin at 1, 3.3 and 10 mg/kg per day, which never induce retinal or auricular change by a single administration . Retinal degeneration was not induced at any dose level, although auricular skin inflammation was augmented by repeated administration . These results suggest that the occurrence of retinal degeneration depends on maximum ocular sitafloxacin concentration during UVA irradiation, whereas the severity of auricular inflammation is directly proportional to the total decrease in area under the drug concentration curve for auricular sitafloxacin under UVA irradiation . This difference between retinal degeneration and auricular inflammation may derive from their respective mechanisms of pathogenesis.

Clin Diagn Lab Immunol, 2001 Nov, 8(6), 1044 - 8
STAT4 is required for antibacterial defense but enhances mortality during polymicrobial sepsis; Godshall CJ et al.; The signal transducer and activator of transcription factor 4 (STAT4) pathway mediates the intracellular effects of interleukin-12 (IL-12), leading to the production of gamma interferon, induction of a T helper type 1 response, and increased natural killer cell cytotoxicity . The purpose of this study was to determine the role of the STAT4 pathway during polymicrobial peritonitis in the cecal ligation and puncture (CLP) model . CLP was performed on STAT4-deficient (STAT4(-/-)) and wild-type control (BALB/c) mice . At 4 h after CLP, STAT4(-/-) mice had significantly higher bacterial counts in the peritoneal lavage fluid, liver, and blood . This difference persisted for 18 h in the peritoneal lavage fluid and blood . Neutrophil migration to the site of infection and into remote tissues was unaffected . Despite higher bacterial counts locally and systemically, STAT4(-/-) mice had a lower mortality rate than BALB/c controls . In contrast, blockade of IL-12 in BALB/c mice was detrimental to host survival . A blunted serum IL-12 response at 18 h after CLP was exhibited in STAT4(-/-) mice . These results suggest several critical roles for the STAT4 pathway in the resolution of polymicrobial infections . Additionally, the disparate effects observed with IL-12 blockade and STAT4 deficiency on host survival suggest that IL-12 may activate alternate pathways promoting survival.

Pharm Res, 2001 Sep, 18(9), 1310 - 4
Penetration of cefaclor into the interstitial space fluid of skeletal muscle and lung tissue in rats; De La Pena A et al.; PURPOSE: To measure and compare the penetration of cefaclor from the plasma compartment into the interstitial space of lung and skeletal muscle in rats and to integrate the data in a pharmacokinetic model . METHODS: Unbound interstitial concentrations in muscle and lung were measured by in vivo microdialysis following i.v . bolus doses of 50 and 75 mg/kg cefaclor . Unbound muscle concentrations were also measured after a primed, continuous i.v . infusion at an infusion rate of 0.3 mg/kg/min . RESULTS: The cefaclor half-life in plasma, muscle and lung was approximately 1 h . Unbound cefaclor concentrations in muscle and lung were found to be virtually identical . A 2-compartment body model was fitted to the data with a tissue penetration factor (AUC(tissue(unbound)))/AUC(plasma(unbound))) of approximately 0.26 independent of dose, tissue and mode of administration . CONCLUSIONS: Unbound concentrations of cefaclor in the interstitial space fluid of lung and skeletal muscle are of similar magnitude and lower than those in plasma . Using total plasma concentrations would overestimate the antibacterial activity of the drug and therefore its clinical efficacy . Instead, therapeutically active levels of cefaclor at the site of action should be taken into account . Microdialysis allows direct measurement of these unbound concentrations.

J Pharm Biomed Anal, 2002 Jan 1, 27(1-2), 133 - 42
Spectrophotometric determination of ciprofloxacin, enrofloxacin and pefloxacin through charge transfer complex formation; Mostafa S et al.; A spectrophotometric method was described for the determination of the antibacterial quinolone derivatives, ciprofloxacin, enrofloxacin and pefloxacin through charge transfer complex formation with three different acceptors . Chloranilic acid (CL) was utilized for their determination, forming charge transfer complex with lambdamax 520 nm . The proposed method was applied for determination of Ciprocin tablets, Enroxil oral solution, Peflacin ampoules and Peflacin tablets, with mean percentage accuracies, 99.58+/-1.25,99.94+/-0.96,100.91+/-1.59 and 99.86+/-1.003 . Also, tetracyanoethylene (TCNE) was utilized in the determination of the concerned compounds forming charge transfer complexes with maximum absorbances at lambdamax 335 nm for ciprofloxacin and at lambdamax 290 nm for both enrofloxacin and pefloxacin . The procedure was applied for determination of Ciprocin tablets, Enroxil 10% oral solution, Peflacine tablets and Peflacine ampoules with mean percentage accuracies 99.40+/-1.27,99.95+/-0.90,98.98+/-1.565 and 99.88+/-0.998, respectively . Also, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) was utilized for determination of pefloxacin forming charge transfer complex with maximum absorbance at lambdamax 460 nm . The procedure was applied for determination of peflacine tablets and peflacine ampoules with mean percentage accuracies 100.40+/-0.76 and 99.91+/-0.623, respectively . Statistical analysis of the obtained results showed no significant difference between the proposed method and other official and reported methods as evident from the t-test and variance ratio.

Farmaco, 2001 Sep, 56(9), 665 - 75
Synthesis and antibacterial activity of 2-substituted 6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids; Jung JC et al.; A series of 2-substituted 6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids was prepared and evaluated for antibacterial activity . The 6-fluoro-2-methyl-1-prenyl-1,4-dihydro-7-(3,5-dimethylpiperazinyl)-4-oxo-3-quinolinecarboxylic acid (14f) exhibited the most potent antibacterial activity against gram-positive bacteria among the total 32 derivatives . The synthetic strategies involve the use of well known keto ester condensation of benzoyl chloride and reductive cyclization of intermediates (4a-d) to afford 4-hydroxy-1,2-dihydro-2-oxo-quinoline derivatives (5a,b) or 1-hydroxy-1,4-dihydro-4-oxo-quinoline derivatives (6a,b).

Adv Immunol, 2001, 79, 225 - 59
Regulation of antibacterial and antifungal innate immunity in fruitflies and humans; Williams MJ; Insects have been very successful in adapting to their environment, and the ability of the insect immune system to detect and elicit the appropriate response against various invading pathogens has helped in this success . Unlike the vertebrate immune system, which consists of both innate and adaptive components, insect immunity probably consists entirely of an innate immune response, as no evidence of an adaptive response has been found . The innate immune response is described as either a reaction against "lack of self," or the interaction between host germline-encoded receptors and molecules unique to a particular class of invading organisms . Once the invading organism is recognized, the host immune response can be activated via signaling pathways that lead to the appropriate reaction . This review endeavors to put forth how through genetic, molecular, and biochemical studies of the fruit fly Drosophila melanogaster, as well as other insects, it is now understood that aspects of the insect and vertebrate innate immune system are very similar.

Acta Crystallogr D Biol Crystallogr, 2001 Nov, 57(Pt 11), 1677 - 9 Epub 2001 Oct 25.
Expression, purification, crystallization and preliminary X-ray analysis of the cathelicidin motif of the protegrin-3 precursor; Sanchez JF et al.; Numerous precursors of antibacterial peptides with unrelated sequences share a similar prosequence which belongs to the cathelicidin family of proteins . The three-dimensional structure of this cathelicidin motif, which contains two disulfide bonds, has not yet been reported . The cathelicidin motif (ProS) of the protegrin-3 precursor was overexpressed in Escherichia coli as a His-tagged protein . The His(6) tag was removed by thrombin cleavage . ProS was purified to homogeneity and single crystals were obtained by the hanging-drop vapour-diffusion method at pH 3-4 . Preliminary X-ray diffraction analysis indicated that these crystals belong to the hexagonal space group P6(1)22 or P6(5)22, with unit-cell parameters a = b = 51.42, c = 134.25 A . These crystals diffracted beyond 2.75 A (1.9 A at ESRF) and contain one molecule per asymmetric unit.

Bioorg Med Chem Lett, 2001 Nov 19, 11(22), 2931 - 4
Enols as potent antibacterial agents; Thorarensen A et al.; This paper describes the discovery of alpha-trifluoroketoacetamides as potent antibacterial agents against Gram-positive organisms . The initial SAR indicates that the aryl ethyl side chain is essential in maintaining antibacterial activity . The SAR observations have been utilized to design a bioisostere for the alpha-trifluoroketoacetamide with good activity against Gram-positive organisms.

Fitoterapia, 2001 Nov, 72(7), 810 - 7
Sudanese plants used in folkloric medicine: screening for antibacterial activity . Part X; Elegami AA et al.; The results of the screening for antibacterial activity of 30 medicinal plants from north, east and central Sudan are reported.

Fitoterapia, 2001 Nov, 72(7), 807 - 9
Antibacterial activity of Caesalpinia bonducella seeds; Saeed MA et al.; The methanol extract and four triterpenoids isolated from the seeds of Caesalpinia bonducella showed a wide range of inhibiting activity against both gram-positive and gram-negative bacteria.

Biosci Biotechnol Biochem, 2001 Sep, 65(9), 1965 - 9
The relationship between a leaf-rolling moth (Dactylioglypha tonica) and fungi covering the cocoon; Imamura N et al.; To discover the relationship between a leaf-rolling moth and the fungi densely covering its cocoons, the rolled nest leaves were collected in two districts in Japan and antibacterial properties of the fungi were examined . Cocoons and fungi isolated from the nest were classified into 5 categories by the growth stages of the insects, and 7 categories based on taxonomic properties and pigment productivity, respectively . The dominant genus was Penicillium in each location . However, the composition of the fungal categories was different and seemed to depend on their circumstances . From all cocoons with larvae, the strains that belonged to the same fungal category and produced the same antibiotic (deoxyherqueinone) were isolated . From these results, the species-specific relationship between the insect and fungi or fungal products was considered to be not extremely tight, and it was suggested the period of the larval spinning of the cocoon is a key stage of this unique relationship.

J Org Chem, 1999 Jul 23, 64(15), 5388 - 5395
Photoinduced C-F Bond Cleavage in Some Fluorinated 7-Amino-4-quinolone-3-carboxylic Acids; Fasani E et al.; The photochemistry of some fluorinated 7-amino-4-quinolone-3-carboxylic acids used in therapy as antibacterials and known to be phototoxic has been investigated in water . All of them undergo heterolytic defluorination, and this appears to be a path for the generation of aryl cations in solution . 6-Fluoro derivatives such as norfloxacin (Phi(dec) = 0.06) and enoxacin (Phi(dec) = 0.13) give the corresponding phenols . Insertion of an electron-donating substituent makes defluorination inefficient; thus, ofloxacin, an 8-alkoxy derivative, is found to be rather photostable (Phi(dec) = 0.001) and reacts in part via a process different from defluorination (degradation of the N-alkyl side chain) . With a 6,8-difluoro derivative, lomefloxacin, the reaction is more efficient (Phi = 0.55) and selective for position 8 . Contrary to the previous cases, the aryl cation undergoes insertion in the neighboring N-ethyl group rather than solvent addition (a carbene-like chemistry) . With all of the above fluoroquinolones an intensive triplet-triplet absorption is detected and is quenched by sulfite (k(q) = (1-5) x 10(8) M(-)(1) s(-)(1)) . Under this condition, reductive defluorination via the radical anion takes place . The relation of the above chemistry to the phototoxicity of these drugs is commented upon briefly.

J Org Chem, 1997 Nov 14, 62(23), 8177 - 8181
Solid-Phase Synthesis of beta-Sultams; Gordeev MF et al.; Solid-phase synthesis of beta-sultams amenable for construction of sulfonyl beta-lactam analogue combinatorial libraries is reported . Imine intermediates generated from polymer-immobilized amino acids and aldehydes are reacted with (chlorosulfonyl)acetates in the presence of pyridine to afford the solid-phase-tethered beta-sultam products . The latter can be released from support by acidic cleavage (TFA) or photocleavage, depending on the nature of the linker employed (acid-labile or photolabile linkers) . Immobilized 4-(9-fluorenyl)methoxycarbonyl beta-sultams are further functionalized on supports to afford, upon cleavage, the respective carboxy and amido thiazetidine derivatives . The method can be employed in production of beta-sultam libraries for identification of new antibacterial agents.

J Org Chem, 1996 Jun 14, 61(12), 3983 - 3986
Solid-Phase Total Synthesis of Bacitracin A; Lee J et al.; An efficient solid-phase method for the total synthesis of bacitracin A is reported . This work was undertaken in order to provide a general means of probing the intriguing mode of action of the bacitracins and exploring their potential for use against emerging drug-resistant pathogens . The synthetic approach to bacitracin A involves three key features: (1) linkage to the solid support through the side chain of the L-asparaginyl residue at position 12 (L-Asn(12)), (2) cyclization through amide bond formation between the alpha-carboxyl of L-Asn(12) and the side chain amino group of L-Lys(8), and (3) postcyclization addition of the N-terminal thiazoline dipeptide as a single unit . To initiate the synthesis, Fmoc L-Asp(OH)-OAllyl was attached to a PAL resin . The chain of bacitracin A was elaborated in the C-to-N direction by sequential piperidine deprotection/HBTU-mediated coupling cycles with Fmoc D-Asp(OtBu)-OH, Fmoc L-His(Trt)-OH, Fmoc D-Phe-OH, Fmoc L-Ile-OH, Fmoc D-Orn(Boc)-OH, Fmoc L-Lys(Aloc)-OH, Fmoc L-Ile-OH, Fmoc D-Glu(OtBu)-OH, and Fmoc L-Leu-OH . The allyl ester and allyl carbamate protecting groups of L-Asn(12) and L-Lys(8), respectively, were simultaneously and selectively removed by treating the peptide-resin with palladium tetrakis(triphenylphosphine), acetic acid, and triethylamine . Cyclization was effected by PyBOP/HOBT under the pseudo high-dilution conditions afforded by attachment to the solid support . After removal of the N-terminal Fmoc group, the cyclized peptide was coupled with 2-{1'(S)-(tert-butyloxycarbonylamino)-2'(R)-methylbutyl}-4(R)-carboxy-Delta(2)-thiazoline (1) . The synthetic peptide was deprotected and cleaved from the solid support under acidic conditions and then purified by reverse-phase HPLC . The synthetic material exhibited an ion in the FAB-MS at m/z 1422.7, consistent with the molecular weight calculated for the parent ion of bacitracin A (MH(+) = C(73)H(84)N(10)O(23)Cl(2), 1422.7 g/mol) . It was also indistinguishable from authentic bacitracin A by high-field (1)H NMR and displayed antibacterial activity equal to that of the natural product, thus confirming its identity as bacitracin A . The overall yield for the solid-phase synthesis was 24%.

Drug Saf, 2001, 24(11), 843 - 53
Preventing and managing drug-induced anaphylaxis; Drain KL et al.; Drug-induced anaphylaxis and anaphylactoid reactions have increased in frequency with more widespread use of pharmaceutical agents . Anaphylaxis is a systemic, severe immediate hypersensitivity reaction caused by immunoglobulin (Ig) E-mediated immunological release of mediators of mast cells and basophils . An anaphylactoid reaction is an event similar to anaphylaxis but is not mediated by IgE . The incidence of anaphylactic or anaphylactoid reactions differs amongst classes of medications . Antibacterials are the most usual offenders, and penicillins are the most studied . Other compounds commonly causing reactions include non-steroidal anti-inflammatory drugs, anaesthetics, muscle relaxants, latex and radiocontrast media . Prevention, if possible, is the purpose of detailed patient history taking and physical examination . Simple strategies can be employed to decrease the risk of anaphylaxis . These include consideration of the route of drug administration, identification of patients with known causes of anaphylaxis, and the knowledge that certain medications cross react and are contraindicated in those with known history of anaphylaxis . Tests are available, and include IgE-specific skin tests and radioallergosorbent tests . Penicillins are the only compounds whose antigenic determinants are well documented, it is therefore difficult to determine the negative predictive value of other compounds tested . Oral challenge remains an alternative, though entails risk . Desensitisation procedures, as well as gradual dose escalation protocols, are available and can be implemented based on patient history and diagnostic testing . The management of anaphylaxis is based on control of the airway, breathing and circulation . Treatment consists of epinephrine (adrenaline) and supportive measures . Rapid diagnosis and intervention are important in these life-threatening reactions . After stabilisation, all individuals with a documented history of anaphylaxis require a Medic-Alert bracelet or necklace, and an identification card for their wallet or purse.

Pharmacotherapy, 2001 Oct, 21(10 Pt 2), 224S - 232S
Mechanism of action of and resistance to quinolones; Bearden DT et al.; A topoisomerase was identified as the bacterial target site for quinolone action in the late 1970s . Since that time, further study identified two bacterial topoisomerases, DNA gyrase and topoisomerase IV, as sites of antibacterial activity DNA gyrase appears to be the primary quinolone target for gram-negative bacteria . Topoisomerase IV appears to be the preferential target in gram-positive organisms, but this varies with the drug . Three mechanisms of resistance against quinolones are mutations of topoisomerases, decreased membrane permeability, and active drug efflux . Although these mechanisms occur singly, several resistance factors are often required to produce clinically applicable increases in minimum inhibitory concentrations . Appropriate drug selection and dosage and prudent human and veterinary interventions are important factors in controlling the emergence of resistance.

Pathol Biol (Paris), 2001 Sep, 49(7), 576 - 82
{Chronic experimental bacteremia in Yucatan micropigs}; Peter JD et al.; The Yucatan micropig has been used to develop an experimental model of chronic bacteremia . This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man . Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria . During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters . A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease . In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate . In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8 . At day five, all animals are alive, and five micropigs have positive blood cultures . This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Caries Res, 2001 Sep-Oct, 35(5), 331 - 7
The effects of benzoate and fluoride on dental caries in intact and desalivated rats; Davis BA et al.; The decline in prevalence of dental caries in some segments of the population has been attributed mainly to extensive exposure to fluoride . Over the past decades, the use of fluoridated products has increased . During the same period, the consumption of food preservatives such as benzoates and sorbates has also increased substantially . Benzoates, in vitro, possess antibacterial properties similar to those of fluoride and in combination with fluoride could affect caries development . In the present study we explored the effects of sodium benzoate and fluoride in combination and alone on dental caries in our animal model . The results showed a combination of benzoate and fluoride reduced caries activity more effectively in rodents fed a cariogenic diet ad libitum than fluoride alone (p = 0.038).

Rev Hist Pharm (Paris), 1997, 45(314), 171 - 8
{A hundred years pharmaceutical research performed in the Rhône-Poulenc groups}; Barral E; The main discoveries performed by scientists working the Rhone-Poulenc groups are listed, from 1895, date of the creation of Societe chimique des usines du Rhone, to 1996 . Analgesics, hypnotics, drugs useful for surgery, Tropical diseases, antihistaminics, neuroleptics, antibacterial agents, drugs acting in the cardio-vascular system, anti-cancer agents and drugs discovered by companies who joined the groups are briefly presented . Biotechnologies are also evoked.

Nord Medicinhist Arsb . 1996;:81-90.
{The history of toothcleaning}; Hanstrom L et al.; A short historical review of toothcleaning with primitive and manufactured toothbrushes, toothpicks and thread of waxed silk . Mouthrinses, toothpowders or soaps and toothpastes and chewing gums composed of ingredients from nature are presented . Antibacterial and pharmacological effects are discussed.

Genetics, 2001 Oct, 159(2), 659 - 71
Evidence for recurrent paralogous gene conversion and exceptional allelic divergence in the Attacin genes of Drosophila melanogaster; Lazzaro BP et al.; Insects produce a limited variety of antibacterial peptides to combat a wide diversity of pathogens . These peptides are often conserved across evolutionarily distant taxa, but little is known about the level and structure of polymorphism within species . We have surveyed naturally occurring genetic variation in the promoter and coding regions of three Attacin antibacterial peptide genes from 12 lines of Drosophila melanogaster . These genes exhibit high levels of silent nucleotide variations (1-3% per nucleotide heterozygosity), but are not excessively polymorphic at the amino acid level . There is extensive variation in the Attacin promoters, some of which may affect transcriptional efficiency, and one line carries a deletion in the Attacin A coding region that renders this gene nonfunctional . Two of the genes, Attacins A and B, are arranged in tandem and show evidence of repeated interlocus gene conversion . Attacin C, more divergent and located 1.3 Mbp upstream of Attacins A and B, does not appear to have been involved in such exchanges . All three genes are characterized by divergent haplotypes, and one Attacin AB allele appears to have recently increased rapidly in frequency in the population.

J Am Coll Nutr, 2001 Oct, 20(5 Suppl), 389S - 395S; discussion 396S-397S
Antiinflammatory activities of lactoferrin; Conneely OM; Lactoferrin is a non-heme iron binding glycoprotein produced during lactation and by epithelial cells at mucosal surfaces . The protein is a prominent component of the first line of mammalian host defense and its expression is upregulated in response to inflammatory stimuli . In this paper, the antibacterial and immune modulatory properties of lactoferrin that contribute to host defense are reviewed . In addition, the results of recent preclinical and clinical studies demonstrating that lactoferrin acts as an inhibitor of dermal inflammatory cytokine production are summarized . The results indicate that lactoferrin may act as a potent anti-inflammatory protein at local sites of inflammation including the respiratory and gastrointestinal tracts.

Dev Comp Immunol, 2001 Oct-Dec, 25(8-9), 827 - 39
Innate host defense mechanisms of fish against viruses and bacteria; Ellis AE; The integumental defenses provide a physical and chemical barrier to the attachment and penetration of microbes . Besides the entrapping and sloughing of microbes in the mucus, the latter contains many antibacterial substances including anti-bacterial peptides, lysozyme, lectins and proteases.The gastro-intestinal tract is a hostile environment of acids, bile salts and enzymes able to inactivate and digest many viruses and bacteria . In most cases the integumental defenses are sufficient to protect against even quite virulent organisms which often only produce disease when the integument has been physically damaged . If a microbe gains access to the tissues of the fish, it is met with an array of soluble and cellular defenses . The complement system, present in the blood plasma, plays a central role in recognising bacteria and its activated products may lyse the bacterial cells, initiate inflammation, induce the influx of phagocytes and enhance their phagocytic activity . Complement can be activated directly by bacterial products and constituents and also indirectly by other factors, principally C-reactive protein and lectins, which can also bind to the bacterial surface . Plasma also contains a number of factors which inhibit bacterial growth(e.g . transferrin and anti-proteases) or which are bactericidal e.g . lysozyme . Following the infection of fish with virus pathogens, infected cells produce interferon . This induces antiviral defenses in neighbouring cells which are then protected from becoming infected . Anti-viral cytotoxic cells are able to lyse virally infected cells and thus reduce the rate of multiplication of virus within them . Innate defenses thus provide a pre-existing and fast-acting system of protection which is non-specific and relatively temperature-independent and thus has several advantages over the slow-acting and temperature-dependent specific immune responses.

J Food Prot, 2001 Oct, 64(10), 1579 - 83
Heated scallop-shell powder slurry treatment of shredded cabbage; Sawai J et al.; The main component of scallop-shell powder is calcium carbonate (CaCO3) . Through heat treatment, CaCO3 in the shell is converted to CaO, which exhibits antibacterial activity . The disinfecting effect of heated scallop-shell powder on shredded cabbage was investigated for various powder concentrations (0.1 to 1.0 g dm(-3)) and treatment temperatures (10 to 40 degrees C) . Scallop-shell powder treatment was found to reduce the aerobic bacteria count in cabbage, with increasing effectiveness at higher powder concentrations and treatment temperatures . Coliforms were completely eliminated within 5 min with as little as 0.1 g dm(-3) powder treatment . During storage at 4 degrees C, aerobic bacterial counts did not increase after powder treatment, whereas counts increased with water-washing or sodium hypochlorite treatment at 200 microg dm(-3) . The inactivation pattern of bacterial cells in shredded cabbage involved an accelerated decline followed by an extended tail at powder concentrations of 0.1 and 0.5 g dm(-3) . We postulate that a fraction of bacterial cells in the initial population becomes tolerant to the shell powder . A proposed model accurately predicts the reducing bacterial counts on shredded cabbage by scallop-shell powder treatment . The decrease in the L-ascorbic acid content of shredded cabbage was approximately 20 to 30% for scallop-shell powder treatment at 0.1 and 0.5 g dm(-3) (20 degrees C), which is almost identical to that by sodium hypochlorite treatment at 200 micorg dm(-3).

Farmaco, 2001 Aug, 56(8), 565 - 70
Synthesis of some halogen-containing 1,2,4-triazolo-1,3,4-thiadiazines and their antibacterial and anticancer screening studies--part I; Holla BS et al.; A series of 7-arylidene-6-(2,4-dichloro-5-fluorophenyl)-3-substituted-1,2,4-triazolo{3,4-b}-1,3,4-thiadiazines (3) were prepared by the condensation of 4-amino-5-mercapto-3-substituted-1,2,4-triazoles (1) and 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-2-propen-1-one (2) . An alternative route for the synthesis of the title compound 3 has been described . The newly synthesised compounds were characterised on the basis of N-analyses, IR, 1H NMR and mass spectral data . Some of the newly synthesised compounds were tested for their antibacterial activities against Gram + ve and Gram - ve bacteria . Among the tested compounds 3n showed the highest degree of antibacterial activity against S . aureus and evaluation of the LD50 value of this compound was carried out . Some of the newly synthesised compounds were also screened for their anticancer activities . Among these, compounds 3b, 3g, 3n and 3p are found to be active against NCI-H460 (lung), MCF7 (breast), SF 268 (CNS) in the preliminary anticancer screening studies . Further, 60-cell-line anticancer studies of these compounds were carried out . The results of such studies are discussed in this paper.

Farmaco, 2001 Aug, 56(8), 549 - 54
Synthesis and biological evaluation of some differently substituted 9,10-anthracenediones; Cardia MC et al.; 9,10-Anthracenedione derivatives are known to exhibit a quite potent anticancer activity . It has also been reported that these compounds can be effectively employed in both antibacterial and antitrypanosomal therapy . Anthraquinones also exhibit some undesirable side effects, like cardiotoxicity . So many interactions seem to demonstrate that 9,10-anthracenediones strongly interact with a number of biological sites . In this paper we wish to report on the synthesis and the pharmaceutical activity of some newly synthesised derivatives containing the anthraquinone pharmacophore.

Nucleic Acids Res, 2001 Oct 15, 29(20), 4224 - 30
The topoisomerase II poison clerocidin alkylates non-paired guanines of DNA: implications for irreversible stimulation of DNA cleavage; Gatto B et al.; Clerocidin, a diterpenoid with antibacterial and antitumor activity, stimulates in vitro DNA cleavage mediated by mammalian and bacterial topoisomerase (topo) II . Different from the classical topoisomerase poisons, clerocidin-stimulated breaks at guanines immediately preceding the sites of DNA cleavage are not resealed upon heat or salt treatment . To understand the mechanism of irreversible trapping of the topo II-cleavable complex, we have investigated the reactivity of clerocidin per se towards DNA . We show here that the drug is able to nick negatively supercoiled plasmids . DNA cleavage by clerocidin in enzyme-free medium is due to the ability of the drug to form covalent adducts with guanines . Indeed, clerocidin was able to specifically react with short oligonucleotides when the guanines were unpaired and exposed as in bulges or in the single-strand form . The clerocidin epoxy group attacks the nitrogen at position 7 of guanines, leading to strand scission at the modified site . Our findings also demonstrate that trapping of topoisomerases by clerocidin is specific for type II enzymes . The guanine-alkylating ability of clerocidin suggests an unprecedented mechanism of topo II poisoning, according to which the enzyme renders the drug reactive toward DNA by distorting the double-helical structure of the nucleic acid at the cleavage site.

Eur J Med Chem, 2001 Jul-Aug, 36(7-8), 615 - 25
Synthesis and antibacterial screening of hydrazones, Schiff and Mannich bases of isatin derivatives; Sridhar SK et al.; Schiff bases and hydrazones of substituted isatins (1-28) were prepared by reacting isatin and aromatic primary amines/hydrazines . A new series of the corresponding N-Mannich base (29-35) was synthesised by reacting them with formaldehyde and diphenyl amine . The chemical structures were confirmed by means of 1H-NMR, IR spectral data and elemental analysis . The compounds were screened for antibacterial activity against seven Gram (+) and seven Gram (-) standard and pathological bacterial strains by the paper disc diffusion technique . The minimum inhibitory concentrations of the active compounds were determined . 1-Diphenyl amino-methyl-3-(4-bromo phenylimino)-1,3-dihydro-indol-3-one (30) and 3-(4-bromo phenylimino)-5-nitro-1,3-dihydro-indol-3-one (13) were found to be the most active compounds of the series . Mannich bases exhibited higher activity than the corresponding Schiff bases.

Chem Res Toxicol, 2001 Oct, 14(10), 1453 - 64
Absolute rate constants for the reaction of hypochlorous acid with protein side chains and peptide bonds; Pattison DI et al.; Hypochlorous acid (HOCl) is a potent oxidant, which is produced in vivo by activated phagocytes . This compound is an important antibacterial agent, but excessive or misplaced production has been implicated in a number of human diseases, including atherosclerosis, arthritis, and some cancers . Proteins are major targets for this oxidant, and such reaction results in side-chain modification, backbone fragmentation, and cross-linking . Despite a wealth of qualitative data for such reactions, little absolute kinetic data is available to rationalize the in vitro and in vivo data . In this study, absolute second-order rate constants for the reactions of HOCl with protein side chains, model compounds, and backbone amide (peptide) bonds have been determined at physiological pH values . The reactivity of HOCl with potential reactive sites in proteins is summarized by the series: Met (3.8 x 10(7) M(-1) x s(-1)) > Cys (3.0 x 10(7) M(-1) x s(-1)) >> cystine (1.6 x 10(5) M(-1) x s(-1)) approximately His (1.0 x 10(5) M(-1) x s(-1)) approximately alpha-amino (1.0 x 10(5) M(-1) x s(-1)) > Trp (1.1 x 10(4) M(-1) x s(-1)) > Lys (5.0 x 10(3) M(-1) x s(-1)) >> Tyr (44 M(-1) x s(-1)) approximately Arg (26 M(-1) x s(-1)) > backbone amides (10-10(-3) M(-1) x s(-1)) > Gln(0.03 M(-1) x s(-1)) approximately Asn (0.03 M(-1) x s(-1)) . The rate constants for reaction of HOCl with backbone amides (peptide bonds) vary by 4 orders of magnitude with uncharged peptide bonds reacting more readily with HOCl than those in a charged environment . These kinetic parameters have been used in computer modeling of the reactions of HOCl with human serum albumin, apolipoprotein-A1 and free amino acids in plasma at different molar excesses . These models are useful tools for predicting, and reconciling, experimental data obtained in HOCl-induced oxidations and allow estimations to be made as to the flux of HOCl to which proteins are exposed in vivo.

Cell Stress Chaperones, 2001 Apr, 6(2), 148 - 52
Activation of human monocyte cell line U937 via cell surface calreticulin; Cho JH et al.; U937 cells were found to be activated by an antibacterial peptide, KLKLLLLLKLK-NH2 (L5), to generate superoxide anion (O2-)-like peripheral neutrophils . However, the state of cell surface calreticulin, a possible receptor for L5, was suggested to differ between neutrophils and U937 cells . Unlike the former, the latter ones were activated by anti-C-domain peptide antibody of calreticulin even in the absence of L5 and generated O2- in a GTP-binding protein (G-protein)-dependent manner.

Dtsch Tierarztl Wochenschr, 2001 Sep, 108(9), 393 - 6
Pharmacodisposition of thiamphenicol in rabbits; el-Aty AM et al.; The pharmacokinetic parameters of thiamphenicol (TAP) were studied in New Zealand white rabbits . Five rabbits were each given thiamphenicol as a single 30 mg/kg of body weight dosage by intravenous (i.v.), intramuscular (i.m.) and oral routes . Serum antibacterial concentrations were determined for 72 h after dosing . Compartmental modeling of the i.v . administration indicated that a 2-compartment open model best described the disposition of thiamphenicol in rabbits . Serum thiamphenicol concentrations after i.m . and oral dosing were best described by a 1- and 2-compartment model, respectively . Overall elimination half-lives for i.v., i.m . and oral routes of administration were 1.39, 2.45, and 1.44 h, respectively . The half-life of absorption for oral dosing was 1.2 times the half-life of absorption after i.m . dosing (0.49 h vs 0.40 h) . The calculated time to maximal serum concentration was 1.25 h after i.m . dosing and 1.17 h after oral administration . The calculated serum concentrations at these times were 80.4 and 69.8 micrograms/ml, respectively . Mean residence time's were 1.89 h for i.v . injection, 2.78 h for i.m . dosing and 4.11 h for oral administration . Thiamphenicol was widely distributed in the rabbit as suggested by the volume of distribution value at steady state of 1.47 l/kg calculated from the i.v . study . Bioavailability was 101.4% after i.m . dosing and 64.2% for oral absorption.

J Biomol Screen, 2000 Dec, 5(6), 435 - 40
Isolation of peptide ligands that inhibit glutamate racemase activity from a random phage display library; Kim WC et al.; Several new antibacterial agents are currently being developed in response to the emergence of bacterial resistance to existing antibiotic substances . The new agents include compounds that interfere with bacterial membrane function . The peptidoglycan component of the bacterial cell wall is synthesized by glutamate racemase, and this enzyme is responsible for the biosynthesis of d-glutamate, which is an essential component of cell wall peptidoglycan . In this study, we screened a phage display library expressing random dodecapeptides on the surface of bacteriophage against an Escherichia coli glutamate racemase, and isolated specific peptide sequences that bind to the enzyme . Twenty-seven positive phage clones were analyzed, and seven different peptide sequences were obtained . Among them, the peptide sequence His-Pro-Trp-His-Lys-Lys-His-Pro-Asp-Arg-Lys-Thr was found most frequently, suggesting that this peptide might have the highest affinity to glutamate racemase . The positive phage clones and HPWHKKHPDRKT synthetic peptide were able to inhibit glutamate racemase activity in vitro, implying that our peptide inhibitors may be utilized for the molecular design of new potential antibacterial agents targeting cell wall synthesis.

Pharmacoeconomics, 2001, 19(8), 831 - 43
Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for Helicobacter pylori eradication; Agro K et al.; OBJECTIVE: To assess the cost effectiveness of a multidrug prepackaged regimen for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg, amoxicillin 1 g, all twice daily), relative to alternative pharmacological strategies in the management of confirmed duodenal ulcer over a 1-year period from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry of Health) excluding the patient copayment; and (ii) a healthcare payer perspective including the patient copayment . DESIGN: A decision-analytical model was developed to estimate expected per patient costs {1998 Canadian dollars ($ Can)}, weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA), PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM) and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT) . MAIN OUTCOME MEASURES AND RESULTS: All PPI-based regimens had higher expected costs but better outcomes relative to RAN-BMT . From a strict healthcare payer perspective, PPI-CM ($Can 209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs than Hp-PAC ($Can 211) . However, these 3 regimens all shared identical outcomes (51.2 weeks without ulcer) . When the current Ontario, Canada, $Can 2 patient copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214) than PPI-CM ($Can 216) . CONCLUSION: From a strict healthcare payer perspective, Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness (relative to RAN-BMT) of $Can 5.77 per ulcer week averted . When the patient copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5 per ulcer week averted) . Regardless of perspective, Hp-PAC and PPI-CM differed by only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2 weeks for both . More data on the clinical and statistical differences in H . pylori eradication with Hp-PAC and PPI-CM would be useful . This analysis does not in clude the possible advantage of Hp-PAC in terms of compliance and antibacterial resistance.

Yao Xue Xue Bao, 1997 Nov, 32(11), 844 - 51
{Studies on pyridonecarboxylic acids as antibacterial agents . XII . Synthesis and antibacterial activity of 6-chloro-1-cyclopropyl-7-(1-piperazinyl)-1, 4-dihydro-4-oxo-quinoline-3-carboxylic acid and analogues}; Li XH et al.; Sixteen pyridonecarboxylic acids, characterized by having a chlorine atom and a cyclopropyl group at the 6- and 1-position respectively, substituted amino groups at the 7-position, and some substituted groups (chloro, nitro, amino, dimethylamino) at the 8-position, were synthesized . In vitro antibacterial activities of these compounds were tested . The fluoroquinolones ciprofloxacin and norfloxacin were included for comparative purposes . The results showed that both 11 Ca and 11 Cc were 4-8 times more active than ciprofloxacin and norfloxacin against S . aureus-15 in vitro, but with the same activity as ciprofloxacin against E . coli-22 and P . aeruginosa-29.

Curr Med Res Opin, 1999, 15 Suppl 1, S1 - 45
A critical analysis of the pharmacology of AZT and its use in AIDS; Papadopulos-Eleopulos E et al.; The triphosphorylated form of the nucleoside analogue 3'-azido-3'-deoxythymidine (Zidovudine, AZT) is claimed to interrupt the HIV replication cycle by a selective inhibition of viral reverse transcriptase, thereby preventing the formation of new proviral DNA in permissive, uninfected cells . Given that initial HIV infection of an individual instigates abundant HIV replication from inception until death, and that the life of infected T-cells is only several days, the administration of AZT should lead both in vitro and in vivo (i) to decreased formation of proviral DNA; and thus (ii) to decreased frequencies of 'HIV isolation' (detection of p24 or reverse transcription or both) in stimulated cultures/cocultures of T-cells from seropositive individuals; (iii) to decreased synthesis of HIV p24 and RNA ('antigenaemia', 'plasma viraemia', 'viral load') ultimately resulting in low or absent levels of all three parameters; and (iv) to a perfect and direct correlation between all these parameters . A critical analysis of the presently available data shows that no such evidence exists, an outcome not unexpected given the pharmacological data on AZT . HIV experts all agree that only the triphosphorylated form of AZT (AZTTP) and not the unphosphorylated form administered to patients, nor its mono- or diphosphate, is the active agent . Furthermore, the mechanism of action is the ability of AZTTP to halt the formation of HIV-DNA (chain termination) . However, although this claim was posited from the outset, AZT underwent clinical trials and was introduced as a specific anti-HIV drug many years before there were any data proving that the cells of patients are able to triphosphorylate the parent compound to a level considered sufficient for its putative pharmacological action . Notwithstanding, from the evidence published since 1991 it has become apparent that no such phosphorylation takes place and thus AZT cannot possess an anti-HIV effect . However, the scientific literature does elucidate: (i) a number of biochemical mechanisms which predicate the likelihood of widespread, serious toxicity from use of this drug; (ii) in vitro data proving that AZT has significant antibacterial and antiviral properties which confound interpretation of its effects when administered to patients . Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug.

J Endod, 2001 Oct, 27(10), 610 - 2
Radiographic evaluation of periradicular repair after endodontic treatment of dog's teeth with induced periradicular periodontitis; Grecca FS et al.; Eighty-four root canals of premolars from six dogs were left open for 7 days, and then sealed and followed for 45 days until periradicular periodontitis developed . The root canals were then treated endodontically using 5.25% sodium hypochlorite as the irrigating solution . After instrumentation, all root canals were filled with a calcium hydroxide-based antibacterial dressing (Calen PMCC or Calasept) that was left in place for 30 days . After this period the root canals were filled with gutta-percha cones and a root canal sealer (Sealapex or AH Plus)--group I: Calen PMCC + Sealapex; group II: Calasept + Sealapex; group III: Calen PMCC + AH Plus; and group IV: Calasept + AH Plus . Periapical radiographs of the teeth were made after root canal filling and after 90, 180, 270, and 360 days . Radiographic images were digitalized by scanning, and the Mocha program was used to measure the periapical lesions . Analysis showed that the lesions of groups I to III were statistically similar reduction in size, whereas group IV had a smaller reduction in lesion size (p < 0.05).

Peptides, 2001 Oct, 22(10), 1675 - 81
N-terminal modifications of Polymyxin B nonapeptide and their effect on antibacterial activity; Tsubery H et al.; Polymyxin B (PMB) is a potent antibacterial lipopeptide composed of a positively charged cyclic peptide ring and a fatty acid containing tail . Polymyxin B nonapeptide (PMBN), the deacylated amino derivative of polymyxin B, is much less bactericidal but able to permeabilize the outer membrane of Gram-negative bacteria and to neutralize the toxic effects of lipopolysaccharide (LPS) . In this study, we synthesized and evaluated the antibacterial and LPS neutralizing activities of four PMBN analogs modified at their N-terminal . Our results suggest that oligoalanyl substitutions of PMBN do not effect most of PMBN activities . However, a hydrophobic aromatic substitution generated a PMB-like molecule with high antibacterial activity and significant reduced toxicity.

Perit Dial Int, 2001 Jul-Aug, 21(4), 372 - 7
Azithromycin: an assessment of its pharmacokinetics and therapeutic potential in CAPD; Kent JR et al.; BACKGROUND: Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity . Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin . This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis . OBJECTIVE: This study aimed to define the potential role of azithromycin in treating CAPD peritonitis . DESIGN: The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin . Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography . SETTING: The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom . PATIENTS: Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day) . RESULTS: Peak plasma concentrations occurred at 2-3 hours with 0.35-1.35 microg/mL (mean 0.75) . The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour . This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers . After 8 hours, the mean dialysate concentration was 0.07 microg/mL; PD clearance was 0.06 L/hr . CONCLUSION: Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present . However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported . Future research should address this possibility.

Chemotherapy, 2001, 47 Suppl 4, 47 - 52; discussion 53-4
Optimal treatment strategies for acute exacerbations of chronic bronchitis: high-risk patients; Norrby SR; Diagnosis of high-risk patients with acute exacerbations of chronic bronchitis (AECB) should include an evaluation of the patient's respiratory function, chest X-ray to exclude pneumonia, and sputum culture . Increasing resistance to amoxicillin, cephalosporins, macrolides, trimethoprim-sulfamethoxazole, and doxycycline means that fluoroquinolones are often the only oral empiric treatment available . Levofloxacin, a new respiratory fluoroquinolone with a wide spectrum of antibacterial activity and no cross-resistance with other classes of antibiotics, can be administered as an intravenous formulation as well as orally . Sequential therapy is easily administered due to its high oral bioavailability, and the dosing schedule can be a convenient once-daily dose . Clinical trials have established that levofloxacin is effective in AECB and is well tolerated .

Biochemistry, 2001 Oct 9, 40(40), 11995 - 2003
Solution structures of the antifungal heliomicin and a selected variant with both antibacterial and antifungal activities; Lamberty M et al.; In response to an experimental infection, the lepidopteran Heliothis virescens produces an antifungal protein named heliomicin . Heliomicin displays sequence similarities with antifungal plant defensins and antibacterial or antifungal insect defensins . To gain information about the structural elements required for either antifungal or antibacterial activity, heliomicin and selected point-mutated variants were expressed in yeast as fusion proteins . The effects of mutations, defined by comparing the primary structure of heliomicin with the sequences of members of the insect defensin family, were analyzed using antibacterial and antifungal assays . One of the variants shows significant activity against Gram-positive bacteria while remaining efficient against fungi . The three-dimensional structures of this variant and of the wild-type protein were determined by two-dimensional (1)H NMR to establish a correlation between structure and antibacterial or antifungal activity . Wild-type and mutated heliomicins adopt a similar scaffold, including the so-called cysteine-stabilized alphabeta motif . A comparison of their structures with other defensin-type molecules indicates that common hydrophobic characteristics can be assigned to all the antifungal proteins . A comparative analysis of various structural features of heliomicin mutant and of antibacterial defensins enables common properties to be assessed, which will help to design new mutants with increased antibacterial activity.

Drugs, 2001, 61(11), 1581 - 91
Optimising outcomes in acute pancreatitis; Norton ID et al.; Acute pancreatitis is a common cause for presentation to emergency departments . Common causes in Western societies include biliary pancreatitis and alcohol (the latter in the setting of chronic pancreatitis) . Acute pancreatitis also follows endoscopic retrograde pancreatography in 5 to 10% of patients, a group that could potentially benefit from prophylactic treatment . Although episodes of pancreatitis usually run a relatively benign course, up to 20% of patients have more severe disease, and this group has significant morbidity and mortality . Therefore, attempts have been made to identify, at or soon after presentation, those patients likely to have a poor outcome and to channel resources to this group . The mainstay of treatment is aggressive support and monitoring of those patients likely to have a poor outcome . Pharmacotherapy for acute pancreatitis (both prophylactic and in the acute setting) has been generally disappointing . Efforts initially focused on protease inhibitors, of which gabexate shows some promise as a prophylactic agent . Agents that suppress pancreatic secretion have produced disappointing results in human studies . Infection of pancreatic necrosis is associated with high mortality and requires surgical intervention . In view of the seriousness of infected necrosis, the use of prophylactic antibacterials such as carbapenems and quinolones has been advocated in the setting of pancreatic necrosis . Similarly, data are accumulating to support the use of prophylactic antifungal therapy . Recently, it has become apparent that the intense inflammatory response associated with acute pancreatitis is responsible for much of the local and systemic damage . With this realisation, future efforts in pharmacotherapy are likely to focus on suppression or antagonism of pro-inflammatory cytokines and other inflammatory mediators . Similarly, animal studies have demonstrated the importance of oxidative stress in acute pancreatitis, although to date there is a paucity of information regarding the efficacy of antioxidants . Although the clinical course for most patients with acute pancreatitis is mild, severe acute pancreatitis continues to be a clinical challenge, requiring a multidisciplinary approach of physician, intensivist and surgeon.

Chemistry, 2001 Sep 3, 7(17), 3824 - 43
Synthesis and biological evaluation of vancomycin dimers with potent activity against vancomycin-resistant bacteria: target-accelerated combinatorial synthesis; Nicolaou KC et al.; Based on the notion that dimerization and/or variation of amino acid 1 of vancomycin could potentially enhance biological activity, a series of synthetic and chemical biology studies were undertaken in order to discover potent antibacterial agents . Herein we describe two ligation methods (disulfide formation and olefin metathesis) for dimerizing vancomycin derivatives and applications of target-accelerated combinatorial synthesis (e.g . combinatorial synthesis in the presence of vancomycin's target Ac2-L-Lys-D-Ala-D-Ala) to generate libraries of vancomycin dimers . Screening of these compound libraries led to the identification of a number of highly potent antibiotics effective against vancomycin-suspectible, vancomycin-intermediate resistant and, most significantly, vancomycin-resistant bacteria.

Biomaterials, 2001 Nov, 22(22), 2999 - 3004
Design and evaluation of drug-loaded wound dressing having thermoresponsive, adhesive, absorptive and easy peeling properties; Lin SY et al.; In order to develop a novel unique wound dressing, a combination of self-adhesive Eudragit E film with antibacterial drug-loaded poly (N-isopropyl-acrylamide) (PNIPAAm) microgel beads was designed . The result indicates that the tack property of Eudragit E film increased with an increase of the PNIPAAm microgel beads added, but there was no significant difference between the dried PNIPAAm microgel beads with or without adsorbing drug . In addition, the peel strength of Eudragit E film initially decreased with the addition of PNIPAAm microgel beads, but increased to a maximum value when PNIPAAm microgel beads were added from 4% to 7.6% . then decreased again after 7.6% . The optimal concentration of PNIPAAm microgel beads was 7.6% (w/v) which had better tack and peel adhesive properties . The water uptake ratio of Eudragit E film containing PNIPAAm microgel beads was found to be temperature-dependent, suggesting that the Eudragit E film containing PNIPAAm microgel beads enabled to absorb the wound fluid . Eudragit E film containing PNIPAAm microgel beads with or without adsorbing drug had significantly reduced peel strength after 12 h-immersion in solution . All these results suggest that a novel drug-loaded wound dressing has been developed by binding a self-adhesive Eudragit E film with an antibacterial drug-loaded PNIPAAm microgel beads to achieve thermo-responsive, adhesive, absorptive and easy peeling functions.

Org Lett, 2001 Oct 4, 3(20), 3189 - 91
Total synthesis of (+/-)-hapalindole Q; Kinsman AC et al.; {reaction: see text} The total synthesis of the antibacterial and antimycotic alkaloid hapalindole Q has been achieved in eight steps and 12.4% overall yield . The key step involves a regio- and diastereoselective Diels-Alder reaction to afford a bicyclo{2.2.2}oct-2-ene . This cycloadduct was subsequently dihydroxylated, cleaved, and converted to the natural product.

Arch Toxicol, 2001 Aug, 75(6), 369 - 74
Biochemical changes in Achilles tendon from juvenile dogs after treatment with ciprofloxacin or feeding a magnesium-deficient diet; Shakibaei M et al.; Quinolones are antibacterial agents that have the potential to induce Achilles tendon disorders - such as tendinitis or even ruptures - in patients treated with these drugs . We studied the effects of ciprofloxacin on several proteins of Achilles tendons from immature dogs, 10- to 11-weeks-old . The dogs were treated orally for 5 days with 30 or 200 mg ciprofloxacin/kg body weight or with the vehicle alone . Since quinolone-like alterations in joint cartilage were observed in magnesium-deficient animals, another group was fed a magnesium-deficient diet for 6 weeks . At necropsy, tendons (n=3 from each group) were frozen and stored until analysis when they were homogenized in a lysis buffer to release a soluble fraction of the tendon proteins . Densitometric analysis of the immunoblots with anticollagen type I, anti-elastin, anti-fibronectin, and antiintegrin antibodies showed a significant reduction of all proteins . For example, collagen type I concentrations (mean +/-SD, arbitrary densitometric units) were 3190+/-217 (controls), 1890+/-468 (30mg/kg), 1695+/-135 (200mg/kg) and 2053+/-491 in the magnesium-deficient dogs . The differences between concentrations in controls and all treated groups were statistically significant (P<0.01, t-test) . Similarly, compared with control samples, relative concentrations of other proteins in tendons from ciprofloxacin-treated dogs (30 mg/kg) decreased by 73% (elastin), 88% (fibronectin), and 96% (beta1 integrin) (data from low-dose group only) . A very similar pattern of protein alterations was detected in samples from magnesium-deficient dogs . In conclusion, rather low doses of a fluoroquinolone or a diet-induced magnesium deficiency caused similar biochemical alterations in the soluble fraction of proteins from canine tendons . These findings support our hypothesis that quinolone-induced toxic effects on connective tissue structures are due to the magnesium-antagonistic effects of these antibacterial agents . They also indicate that patients with a latent magnesium deficiency could be at an increased risk of quinolone-induced tendon disorders.

Boll Chim Farm, 2001 Jul-Aug, 140(4), 215 - 20
Simple and convenient preparation of 1-(arylamino)methylbenzotriazoles and -(arylamino)methylbenzimidazoles; Milata V et al.; The preparation of 1-(arylamino)methylbenzotriazoles 1a-17a and benzimidazoles 1b-17b is described and their antibacterial activity evaluated . 1-Hydroxymethylbenzazo-les react with the appropriate aniline to yield the target compounds . These were characterized using 1H NMR, IR, UV spectra . The compounds displayed no significant antibacterial activity.

Infect Dis Clin North Am, 2001 Sep, 15(3), 983 - 1002, xi
Use of antibacterial agents in renal failure; Livornese LL Jr et al.; This article reviews the pharmacokinetics of antibacterial agents in patients with normal and decreased renal function . The concepts of volume and distribution, rate of elimination, loading and maintenance doses, and therapeutic drug monitoring are delineated . Special reference is made to the intermittent dosing of cefazolin with hemodialysis . Newer, as well as traditional methods of extracorporeal circulation and the resultant changes in antibacterial agent pharmacodynamics are discussed.

Vestn Oftalmol, 2001 Jul-Aug, 117(4), 29 - 32
{Effects of gaseous flow containing nitric oxide on the eyeball structures (an experimental study)}; Gundarova RA et al.; Nitric oxide is one of the main factors of intra- and intercellular regulation in the organism . Its vasodilating, antiaggregant, antithrombogenic, antibacterial, anticarcinogenic, and immunogenic effects are well known . It stimulates the reparative processes in soft tissue injuries . We failed to find reports about the role of NO in the wound process in the eyes . The source of NO in our experiments was medical air-plasma device Plason . Exposure of the eye to NO-containing gaseous flow did not cause changes in the lacrimal pH; NO penetrated through the cornea and sclera, exerted no appreciable cytotoxic effect on the surface epithelium of the eye, did not change the intraocular pressure, and caused no morphological changes in ocular tissues . On the other hand, NO-containing gaseous flow had an appreciable lasting effect on the diameter of the conjunctival vessels, this effect being dose-dependent . The doses of NO-containing gaseous flow which can be used in the treatment of eye wounds were determined.

J Antimicrob Chemother, 2001 Sep, 48 Suppl T1, 25 - 31
Activity of telithromycin, a new ketolide antibacterial, against atypical and intracellular respiratory tract pathogens; Hammerschlag MR et al.; Atypical respiratory pathogens such as Mycoplasma pneumoniae and intracellular pathogens such as Legionella spp . and Chlamydia spp . form a significant proportion of the aetiological agents underlying community-acquired pneumonia (CAP) . The clinical signs or radiological features of atypical pneumonia are generally insufficient to predict accurately the pathogen involved; in addition, high costs and a considerable length of time are involved in the identification of atypical pathogens . Treatment is, therefore, most often empirical, and it is important that the activity of antibacterial agents available to treat CAP is sufficiently broad to eradicate infection with both common and atypical bacterial pathogens . Telithromycin (HMR 3647) is the first of a new family of antibacterials, the ketolides, and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs) . The excellent activity of telithromycin against the respiratory tract bacterial pathogens most commonly associated with community-acquired RTIs, including resistant strains, is well established . This review examines the considerable body of evidence showing that telithromycin also has a high level of activity against atypical and intracellular respiratory tract bacterial pathogens.

Int J Pharm, 2001 Oct 4, 227(1-2), 149 - 56
Investigation of Smith's quinolone killing mechanisms during the PAE of ciprofloxacin on Escherichia coli; Wickens HJ et al.; Quinolone antibacterials interact with the DNA-DNA gyrase complex, but subsequent events that lead to cell death are unresolved . Three distinct mechanisms of quinolone lethality have been identified by Smith and co-workers: Mechanism A, which requires RNA and protein synthesis and cell division for expression; Mechanism B, which remains active when these functions are precluded; and Mechanism C, which is active on non-dividing cells . Exposure to 4x MIC ciprofloxacin (Cip) in nutrient broth (NB) for 3 h reduced the viability of Escherichia coli AB1157 to 0.25% . Addition of rifampicin (Rif) or chloramphenicol (Cm), to inhibit RNA or protein synthesis, respectively, increased survival 70-fold . Treatment of cells with Cip in phosphate-buffered saline (PBS), to inhibit cell division, increased survival 20-fold . No further cell death occurred once the various drug combinations or PBS had been washed out and cells resuspended in drug-free nutrient broth . These latter conditions allow expression of the post-antibiotic effect (PAE) . PAE was lengthened in cells exposed to Cip in the presence of Rif or Cm, probably as a result of delay in the initiation of inducible DNA repair.

Aliment Pharmacol Ther, 2001 Oct, 15(10), 1543 - 7
Review article: alternative antibacterial agents for Helicobacter pylori eradication; Guslandi M; Standard eradication therapies against Helicobacter pylori appear to be effective in most cases, but in clinical practice a failure rate higher than the 5-10% reported in clinical trials is often observed . Among the various reasons responsible for therapeutic failure, antibiotic resistance is becoming a major issue in some countries . A range of different antibacterial agents is currently under investigation: several macrolides, new fluoroquinolones, furazolidone and rifabutin . Although not formally tested in refractory cases, azithromycin, spiromycin, levofloxacin and furazolidone represent the most promising antibacterial agents for possible inclusion in eradication regimens . Rifabutin has been evaluated in H . pylori infections resistant to standard therapies . Although very effective, the drug is expensive and its use should be restricted to the most difficult cases to avoid the development of rifabutin resistance in Mycobacterium spp.

Curr Pharm Des, 2001 Nov, 7(17), 1703 - 24
Interest of acridine derivatives in the anticancer chemotherapy; Demeunynck M et al.; DNA is considered as one of the main targets for anticancer drug design . The planar structure of acridines confers to the molecules the ability to bind DNA by intercalation and therefore to interfere with metabolic processes . A large number of natural alkaloids and synthetic acridine derivatives have been tested as anticancer agents . So far, a few molecules have entered clinical trials and have been approved for chemotherapy . The mechanisms of action are not fully understood . Cytotoxicity may be related to potent enzyme inhibition . Topoisomerase and telomerase activities may be strongly affected by acridines . The affinity of acridines for DNA has also been used to design new active compounds in which a DNA modifying group is tethered to the acridine nucleus . Acridine derivatives display other pharmacological properties such as antibacterial and antimalarial activities . They are also tested for Alzheimer's disease.

Curr Med Chem, 2001 Dec, 8(14), 1775 - 93
Quinolone, everninomycin, glycylcycline, carbapenem, lipopeptide and cephem antibacterials in clinical development; Bronson JJ et al.; The development of antibacterials was a very successful endeavor in the pharmaceutical company repertoire through the late 1970s, when interest in investing in antibiotic research and development temporarily waned . More recently, there have been a number of failures in late stage development or post-launch of human antibiotics . The answer to the dilemma of less-than-desired success may be the introduction of novel classes of agents, as well as development of new agents in traditional classes . This review provides an overview of the various "miscellaneous" antibacterials in development, excluding glycopeptides, macrolides, ketolides, and oxazolidinones . Among the agents highlighted in this review are the clinical candidates of quinolones, everninomycins, carbapenems, lipopeptides, glycylcyclines, and cephems . In several cases, certain quinolone agents described in this review will have been approved for marketing before press time.

Curr Med Chem, 2001 Dec, 8(14), 1727 - 58
Recent developments on ketolides and macrolides; Wu YJ et al.; Recent semi-synthetic studies of erythromycin A culminated in the discovery of two ketolide drug candidates, HMR-3647 and ABT-773, for the treatment of community-acquired bacterial infections caused by both macrolide- and beta-lactam-susceptible and -resistant S . pneumoniae, gram negative bacteria, and intracellular atypical pathogens . The discovery of ketolides has rekindled interest in macrolides, and recent efforts have also led to a novel class of 4''-carbamates with activity against macrolide-resistant organisms . This review is an account of recent developments on ketolides and macrolides in terms of both chemistry and antibacterial activity.

Curr Med Chem, 2001 Dec, 8(14), 1699 - 711
Efflux pumps: their role in antibacterial drug discovery; Lomovskaya O et al.; The emergence of active efflux as a major causative factor in antibiotic resistance has been one of the most significant trends in antiinfective chemotherapy over the last decade . The phenomenon affects virtually all classes of antibiotics and frequently results in multi-drug resistant phenotypes . This review analyzes efflux pumps of clinical significance and examines their impact on different antibiotic classes relative to other mechanisms of resistance . Progress in strategies to combat efflux-mediated resistance by modification of existing antibiotics or identification of efflux pump inhibitors is also reviewed.

Biochemistry, 2001 Sep 25, 40(38), 11344 - 52
Role of S65, Q67, I68, and Y69 residues in homotetrameric R67 dihydrofolate reductase; Strader MB et al.; R67 dihydrofolate reductase (DHFR) shares no sequence or structural homology with chromosomal DHFRs . This enzyme arose recently in response to the clinical use of the antibacterial drug trimethoprim . R67 DHFR is a homotetramer possessing a single active site pore . A high-resolution crystal structure shows the homotetramer possesses exact 222 symmetry {Narayana, N., et al . (1995) Nat . Struct . Biol . 2, 1018-1025} . This symmetry dictates four symmetry-related binding sites must exist for each substrate as well as each cofactor . Isothermal titration calorimetry studies, however, indicate only two molecules bind: either two dihydrofolate molecules, two NADPH molecules, or one substrate and one cofactor {Bradrick, T . D., et al . (1996) Biochemistry 35, 11414-11424} . The latter is the productive ternary complex . To evaluate the role of S65, Q67, I68, and Y69 residues, located near the center of the active site pore, site-directed mutagenesis was performed . One mutation in the gene creates four mutations per active site pore which typically result in large cumulative effects . Steady state kinetic data indicate the mutants have altered K(m) values for both cofactor and substrate . For example, the Y69F R67 DHFR displays an 8-fold increase in the K(m) for dihydrofolate and a 20-fold increase in the K(m) for NADPH . Residues involved in ligand binding in R67 DHFR display very little, if any, specificity, consistent with their possessing dual roles in binding . These results support a model where R67 DHFR utilizes an unusual "hot spot" binding surface capable of binding both ligands and indicate this enzyme has adopted a novel yet simple approach to catalysis.

Ann Intern Med, 2001 Sep 18, 135(6), 412 - 22
Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy . A randomized, controlled trial; Boogaerts M et al.; BACKGROUND: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy . However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting . OBJECTIVE: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy . DESIGN: An open randomized, controlled, multicenter trial, powered for equivalence . SETTING: 60 oncology centers in 10 countries . PATIENTS: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy . INTERVENTION: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution . MEASUREMENTS: Defervescence, breakthrough fungal infection, drug-related adverse events, and death . RESULTS: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively . The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points {95% CI, -0.8 to 19.5 percentage points}) . Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs . 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs . 38%; P = 0.001) . Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001) . Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar . Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days . CONCLUSIONS: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer . However, itraconazole is associated with significantly less toxicity.

Lik Sprava, 2001 May-Jun, (3), 143 - 5
{Sensitivity of Helicobacter pylori to antibacterial drug preparations in potential military recruits with duodenal peptic ulcer}; Kharchenko NV et al.; Results are submitted of bacteriological investigations in those persons with duodenal peptic ulcer who had been called up . The presence of regional strains of H . pylori is ascertained together with their sensitivity to certain antibacterial drug preparations . A rational antihelocobactertherapy schedule is proposed.

Gut, 2001 Oct, 49(4), 481 - 7
Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori; Hamanaka Y et al.; BACKGROUND: Human beta-defensin 2 (hBD-2) plays a role in the innate defence system at mucosal surfaces . Colonisation of Helicobacter pylori in the stomach is an important pathological factor in gastrointestinal illnesses, including gastritis, peptic ulcer, and gastric adenocarcinoma . AIMS: To evaluate the antibacterial role of hBD-2 against H pylori infection in the gastric mucosa . SUBJECTS: Biopsied gastric mucosa specimens from H pylori positive (n=6) and H pylori negative (n=6) individuals were used . H pylori was determined by the presence of urease activity and microscopic examination . METHODS: The specimens were examined for hBD-2 expression by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridisation . The antibacterial effect of hBD-2 against H pylori was evaluated by the number of colony forming units of H pylori after incubation with 0, 10(-9), 10(-8), 10(-7), 10(-6), or 10(-5) M of hBD-2 peptide . RESULTS: All six H pylori positive specimens expressed a high level of hBD-2 mRNA while hBD-2 mRNA was not detected in the H pylori negative specimens by RT-PCR . Immunohistochemistry using anti-hBD-2 antiserum revealed that hBD-2 was expressed in the surface epithelium of H pylori infected specimens . In gastric specimens obtained after H pylori eradication, hBD-2 immunoreactivity had dramatically decreased . In situ hybridisation confirmed that hBD-2 transcripts were localised in the epithelium of H pylori infected gastric specimens . Incubation with hBD-2 reduced the growth rate of cultured H pylori in a dose dependent manner, and incubation with 10(-5) M hBD-2 completely inhibited the proliferation of H pylori . CONCLUSIONS: H pylori infection induces hBD-2 expression in the human gastric epithelium . hBD-2 inhibited the growth of H pylori in vitro, suggesting that hBD-2 plays an antibacterial role in H pylori induced gastritis.

Curr Infect Dis Rep, 2001 Oct, 3(5), 407 - 412
Bactericidal/Permeability-increasing Protein in Host Defense and Its Efficacy in the Treatment of Bacterial Sepsis; Levy O et al.; The 55-kD bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived polypeptide belonging to a family of lipid and endotoxin binding proteins . BPI is composed of two functionally distinct structural domains: a potently antibacterial and antiendotoxin ~ 20-kD amino-terminal half, and an opsonic carboxy-terminal portion . In multiple animal models, a recombinant amino-terminal fragment of BPI (rBPI(21)) is nontoxic and protects against gram-negative bacteria and endotoxin . In humans, rBPI(21) is also nontoxic and nonimmunogenic and has undergone phase II/III clinical trials with apparent therapeutic benefit.

Drugs, 2001, 61(10), 1455 - 500
Cefuroxime axetil: an updated review of its use in the management of bacterial infections; Scott LJ et al.; Cefuroxime axetil, a prodrug of the cephalosporin cefuroxime, has proven in vitro antibacterial activity against several gram-positive and gram-negative organisms, including those most frequently associated with various common community-acquired infections . In numerous randomised, controlled trials, 5 to 10 days' treatment with oral cefuroxime axetil (250 or 500 mg twice daily) was an effective treatment in patients with upper (URTI) and lower respiratory tract infections (LRTI) as assessed by clinical and bacteriological criteria . The drug was as effective as several other cephalosporins, quinolones, macrolides and amoxicillin/clavulanic acid . Shorter courses (5 to 10 days') of cefuroxime axetil were at least as effective as a 10 day course . Furthermore, sequential therapy with intravenous cefuroxime (750 mg 2 or 3 times daily for 2 to 5 days) followed by oral cefuroxime axetil (500 mg twice daily for 3 to 8 days) proved an effective treatment in adult patients with community-acquired pneumonia (CAP) . This approach provided similar efficacy to intravenous ampicillin/sulbactam followed by oral amoxicillin/clavulanic acid, a full parenteral course of cefuroxime, or intravenous then oral azithromycin or clarithromycin . Additionally, cefuroxime axetil was an effective treatment in patients with genitourinary, skin and soft-tissue infections, and erythema migrans associated with early stage Lyme disease . The drug is well tolerated by adult and paediatric patients, with adverse effects that are consistent with those of other cephalosporins . The majority of adverse events (primarily gastrointestinal disturbances) were mild to moderate in intensity and reversible upon discontinuation of treatment, with very few serious adverse events reported . Conclusions: Cefuroxime axetil is a broad spectrum antibacterial agent with a pharmacokinetic profile that permits convenient twice-daily administration . The drug is an effective and well tolerated treatment in patients with various infections, including otitis media, pharyngitis, sinusitis, CAP and acute exacerbations of chronic bronchitis . Cefuroxime axetil proved effective as a component of intravenous/oral sequential therapy in the treatment of CAP, although there are currently no dosage recommendations available for this regimen in some countries . Cefuroxime axetil may be considered as an empirical therapy for a range of community-acquired infections, including those in which beta-lactamase-producing strains of common respiratory pathogens are identified as the causative organisms . In an era of rapidly emerging bacterial resistance, empirical treatment with bacterial agents, potentially preventing the emergence of bacterial resistance to agents such as cefuroxime axetil may ensure the appropriate use of newer antibacterial agents, potentially preventing the emergence of bacterial resistance to these newer drugs.

Drugs, 2001, 61(10), 1379 - 85
New and emerging therapies for pulmonary complications of cystic fibrosis; Tonelli MR et al.; In the decade since the gene for cystic fibrosis (CF) was discovered, research into potential therapeutic interventions has progressed on a number of different fronts . The vast majority of morbidity and mortality in CF results from inflammation and infection of the airways . Direct delivery of antibacterials to the airway secretions via a nebuliser is an attractive therapeutic option, and a novel formulation of tobramycin designed for such a purpose has been demonstrated to improve spirometry and decrease the need for intravenous antibacterials . In addition, early clinical trials are studying the effects of small peptides with antibiotic properties (defensins) delivered directly to the airways . Inflammation, whether secondary to infection or an independent feature of CF, leads to progressive bronchiectasis . Anti-inflammatories such as prednisone and possibly ibuprofen have been shown to decrease the rate of respiratory decline in patients with CF but have tolerability profiles that limit clinical usefulness . Macrolides also have anti-inflammatory properties and clinical trials are now ongoing to assess the efficacy of these agents in CF . Multiple agents, including uridine triphosphate (UTP), genistein, phenylbutyrate and CPX (cyclopentyl dipropylxanthine), have been demonstrated in cell culture to at least partially correct the primary defect of ion transport related to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) . No agent of this class has yet demonstrated clinical effectiveness, but several are in preclinical and early clinical trials . Finally, gene therapy that allows for the incorporation and expression of wild-type CFTR in respiratory epithelial cells would be definitive therapy for CF . However, multiple barriers to delivery and expression need to be overcome . With research proceeding on these multiple fronts, new therapies for pulmonary complications promise to continue to increase the life expectancy of individuals with CF.

Antibiot Khimioter, 2001, 46(5), 24 - 7
{Efficacy of pefoxacin (abactal) in the complex treatment of patients with pancreonecrosis}; Gel'fand BR et al.; The efficacy of pefloxacin in the complex treatment of 28 patients with pancreatonecrosis of various etiology was estimated in a prospective trial . The diagnosis of pancreatonecrosis was verified by the data of the disease clinical progress, laboratory findings and instrumental examination . Pefloxacin (Abactal; LEK) was administered intravenously in a dose of 400 mg every 8 hours (1200 mg) in combination with metronidazole in a dose of 1.5-2.0 g a day intravenously . When indicated 3 days after the start of the pefloxacin therapy, the treatment was switched to the oral use of the drug in the same dosage . The positive clinical effect (cure and improvement) at the end of the treatment with pefloxacin was stated in 78 per cent of the patients in spite of the initial severity state of above 15 APACHE II . It was shown that in the treatment of patients with pancreatonecrosis when the severity state was not above 12 APACHE II the antibacterial therapy with pefloxacin in combination with metronidazole was optimal.

Am J Physiol Lung Cell Mol Physiol, 2001 Oct, 281(4), L776 - 85
Interaction of bacterial lipopolysaccharide with mouse surfactant protein C inserted into lipid vesicles; Augusto L et al.; Infection of the respiratory tract is a frequent cause of lung pathologies, morbidity, and death . When bacterial endotoxin {lipopolysaccharide (LPS)} reaches the alveolar spaces, it encounters the lipid-rich surfactant that covers the epithelium . Although binding of hydrophilic surfactant protein (SP) A and SP-D with LPS has been established, nothing has been reported to date on possible cross talks between LPS and hydrophobic SP-B and SP-C . We designed a new binding technique based on the incorporation of surfactant components to lipid vesicles and the separation of unbound from vesicle-bound LPS on a density gradient . We found that among the different hydrophobic components of mouse surfactant separated by gel filtration or reverse-phase HPLC, only SP-C exhibited the capacity to bind to a tritium-labeled LPS . The binding of LPS to vesicles containing SP-C was saturable, temperature dependent, related to the concentrations of SP-C and LPS, and inhibitable by distinct unlabeled LPSs . Unlike SP-A and SP-D, the binding of SP-C to LPS did not require calcium ions . This LPS binding capacity of SP-C may represent another antibacterial defense mechanism of the lung.

Phytochemistry, 2001 Oct, 58(3), 517 - 23
Halogenated metabolites with antibacterial activity from the Okinawan Laurencia species; Vairappan CS et al.; The chemical compositions of five species of the red algal genus Laurencia from coastal waters of Okinawa Prefecture, Japan, have been investigated . A halogenated C(15) acetogenin, (12E)-lembyne-A, was isolated from L . mariannensis, and a halogenated sesquiterpene, (6R,9R,10S)-10-bromo-9-hydroxy-chamigra-2,7(14)-diene, was first found from L . majuscula as a naturally occurring compound . Laurencia nidifica yielded previously known laurinterol and isolaurinterol . Samples of L . cartilaginea and L . concreta afforded no halogenated metabolites . The structures of these halogenated metabolites as well as their antibacterial activity against some marine bacteria are reported.

Lett Appl Microbiol, 2001 Sep, 33(3), 196 - 200
The mechanism of carbonate killing of Escherichia coli; Jarvis GN et al.; AIMS: To define the mechanism of carbonate killing in Escherichia coli . METHODS AND RESULTS: Sodium carbonate (150 mM) and ethylenediaminetetracetic acid (EDTA, 60 mM) both killed E . coli K-12 when the pH was 8.5, but ammonium chloride (150 mM) was ineffective . EDTA was a 5-fold more potent agent than carbonate, but some of this difference could be explained by ionization . At pH 8.5, only 1.6% of the carbonate is CO(-2), but nearly 100% of the EDTA is EDTA(-2) . CONCLUSION: As carbonate and EDTA had similar effects on viability, cellular morphology, protein release and enzymatic activities, the antibacterial activity of carbonate seems to be mediated by divalent metal binding . SIGNIFICANCE AND IMPACT OF THE STUDY: Cattle manure is often used as a fertilizer, and E . coli from manure can migrate through the soil into water supplies . Previous methods of eradicating E . coli were either expensive or environmentally unsound . However, cattle manure can be treated with carbonate to eliminate E . coli, and the cost of this treatment is less than $0.03 per cow per day.

Bioorg Med Chem Lett, 2001 Oct 8, 11(19), 2585 - 8
Asymmetric synthesis of BB-3497--a potent peptide deformylase inhibitor; Pratt LM et al.; By screening a library of metalloenzyme inhibitors, the N-formyl-hydroxylamine derivative BB-3497 was identified as a potent inhibitor of Escherichia coli peptide deformylase with antibacterial activity both in vitro and in vivo . The homochiral synthesis of BB-3497, involving a novel asymmetric Michael addition reaction is described.

Phytochemistry, 2001 Sep, 58(2), 291 - 7
Antibacterial halogenated metabolites from the Malaysian Laurencia species; Vairappan CS et al.; Two halogenated C15 acetogenins, named lembyne-A and lembyne-B, have been isolated from an unrecorded Laurencia species collected off the Malaysian waters . Their structures were deduced on the basis of spectroscopic evidence . Previously known elatol and iso-obtusol showed potent antibacterial activity against some marine bacteria.

Am J Ther, 2001 Sep-Oct, 8(5), 321 - 8
Boron therapeutics on the horizon; Groziak MP; No pharmaceutical based on boron has yet made it to market, but this may soon change . The new millennium has brought with it some unique classes of bioactive boron compounds that are sufficiently mature in development to be considered significant and timely advances in their respective chemotherapeutic areas . Because boron is seldom seen as a constituent of a bioactive agent, this review relates some of the pertinent biologic and physiologic properties of boron and then describes in detail those boron-based agents clearly visible on the therapeutic horizon . Highlighted agents include boronic acids and boron heterocycles as potent proteasome inhibitors, beta-lactamase inhibitors, dipeptidyl peptidase inhibitors, inositol trisphosphate receptor modulators, antibacterials, and antiestrogens . As these new agents are welcomed into the therapeutic armamentarium, others will surely follow and the prescribing clinician will already have an awareness and appreciation of the unique benefits that these compounds have to offer.

MedGenMed . 2001 Mar 06;3(2):3.
Evaluating the role of alternative therapy in burn wound management: randomized trial comparing moist exposed burn ointment with conventional methods in the management of patients with second-degree burns; Ang ES et al.; CONTEXT: Moist exposed burn ointment (MEBO), from China, has been said to revolutionize burn management . OBJECTIVE: Our study was conducted to compare MEBO with conventional management (C) with respect to the rate of wound healing, antibacterial and analgesic effect, and hospital costs . DESIGN: This is a prospective, randomized, controlled clinical trial conducted between 1 March 1997 and 24 October 1998 . SETTING: The trial was conducted in a specialized burn facility located in a tertiary referral hospital in a developed and industrialized island-state in Southeast Asia . PATIENTS: We randomly assigned 115 consecutive patients between the ages of 12 and 80 who had partial-thickness thermal burns covering less than 40% of body surface area (BSA) to receive either MEBO or C . Fifty-seven patients were assigned to MEBO and 58 patients to C . The latter group received twice-daily dressing changes; MEBO patients received MEBO every 4 hours . MAIN OUTCOME MEASURES: Patients were hospitalized until 75% BSA had healed . BSA was determined by visual inspection and charted on Lund and Browder charts regularly . Wound healing rate, bacterial infection rate, pain score, and hospitalization costs were recorded . RESULTS: The median time to 75% healing was 17.0 and 20.0 days with MEBO and C, respectively (HR = 0.67, 95% CI = 0.41-1.11, P =.11), suggesting similar efficacy between the 2 modalities . Bacterial infection rates were similar between the 2 groups (HR = 1.10, 95% CI = 0.59-2.03, P =.76) . MEBO imparted a greater analgesic effect in the first 5 days of therapy and reduced hospital costs by 8% . CONCLUSIONS: MEBO is as effective as conventional management but is not the panacea for all burn wounds . The use of MEBO eases the management of face and neck burns and facilitates early institution of occupational therapy in hand burns . It confers better pain relief such that fewer opiates are used during the first 5 days after burn injury.

Eur J Clin Pharmacol, 2001 Jul, 57(4), 333 - 41
Personal formularies . An index of prescribing quality?
Robertson J, Fryer JL, O'Connell DL, Smith AJ, Henry DA.
OBJECTIVES: (1) To determine the extent to which Australian general practitioners (GPs) restrict the numbers of agents they prescribe within a drug class ('personal formularies'); (2) To assess concordance of these drug choices with standards based on established guidelines or recognised good prescribing practices; (3) To assess the potential of these measures as indicators of the quality of prescribing . METHODS: Australian Health Insurance Commission (HIC) prescription data (1994 1997) for around 15,400 GPs providing 1500 or more Medicare services per year were analysed . Measures of an individual GP's use of a personal formulary (determined by number of agents) and concordance with prescribing criteria based on specified drugs for five classes of commonly prescribed drugs were derived . RESULTS: Non-steroidal anti-inflammatory drugs (NSAIDs): GP concordance was higher with a non-specified personal formulary (any five NSAIDs) than with a list of specified drugs (five NSAIDs of 'low' or 'medium' risk of gastrointestinal toxicity), and concordance with both increased over time . In 1997, around 70% of GPs used five or fewer NSAIDs for 90% of their prescribing; 47% of GPs had 90% of prescribing from five selected agents . Angiotensin converting enzyme inhibitors/angiotensin-II receptor antagonists: The introduction of new agents appeared to increase the size of the GPs' personal formularies, and concordance with defined standards decreased over time . Antibacterial agents: Concordance with a specified drug standard (nine drugs listed in the Australian Antibiotic Guidelines) increased substantially over time but was largely due to increased prescribing of two heavily promoted drugs . Beta-blocking agents: Over time, GPs restricted most prescribing to two agents, atenolol and metoprolol . Calcium channel blockers: GPs did not appear to restrict prescribing of these drugs; most GPs prescribed all five agents available . CONCLUSIONS: Australian GPs use 'personal formularies' . Formulary size varies with the drug class, can change over time as new agents become available, and its contents can be influenced by promotional activities . Prescribing standards based on numbers of drugs used may not always reflect rational prescribing choices . Criteria based on specified drugs provide more rigorous prescribing standards, but may give a misleading picture of prescribing quality in the absence of information on patients and the indications for treatment . Personal formulary measures are potentially useful prescribing indicators but need to be carefully defined and interpreted . GPs should be encouraged to identify their personal formularies and review the drugs included in them.

Stomatologiia (Mosk), 2001, 80(3), 23 - 7
{Ozone therapy in treatment of local sluggish suppurative inflammation of maxillofacial soft tissues}; Agapov VS et al.; Combined local and general ozone therapy was used in 30 patients with local sluggish pyoinflammatory diseases of the maxillofacial soft tissues . The results were compared to those in 33 patients administered no ozone therapy . Ozone therapy decreased the duration of treatment more than 2-fold due to antibacterial effect and stimulation of nonspecific and immunological reactivity . Lack of obvious contraindications and selective activity and universal immunocorrective effect recommend ozone therapy for wide use in this patient population irrespective of the type of inflammatory reaction.

Nat Prod Lett, 2001, 15(1), 9 - 12
Biologically active metabolites from fungi 14 3-chloro-4-hydroxy-5-(3,7,11-trimethyldodeca-2,6,10-trienyl)-benzamide, a new antibacterial agent from a soil fungus; Krohn K et al.; The antibacterial 3-chloro-4-hydroxy-5-(3,7,11-trimethyldodeca-2,6,10-trienyl)-benzamide, and the antifungal strobilurins B and D were isolated from an unidentified South African soil fungus.

Drug Discov Today, 2001 Sep 15, 6(18), 954 - 961
Deformylase as a novel antibacterial target; Yuan Z et al.; Bacterial genomics has revealed a plethora of previously unknown targets of potential use in the discovery of novel antibacterial drugs . However, so far little has emerged from this approach . Peptide deformylase is an interesting target that was discovered more than 30 years ago, but was not exploited until recently . The reawakening of interest in this target resulted from an improved understanding of the enzyme, making it a more tractable and attractive target . Information on the properties of the enzyme, such as its three-dimensional structure, the activity of inhibitors, its resistance and suitability as a target are discussed.

Infection, 2001 Aug, 29(4), 222 - 7
Pharmacokinetic basis for oral perioperative prophylaxis with ofloxacin in general surgery; Schwarz M et al.; BACKGROUND: Perioperative prophylaxis is recommended to be administered intravenously which, compared to oral prophylaxis, is more expensive . However, pharmacokinetic data on oral perioperative prophylaxis in patients with preoperative surgical and anesthesiological preparation are not available . PATIENTS AND METHODS: 40 patients with open hernial repair or cholecystectomy (low-risk group), colonic or pancreatic resection (high-risk group) received a standard single-dose perioperative prophylaxis with 4.5 g mezlocillin and 0.5 g metronidazole intravenously in addition to 400 mg ofloxacin orally 2 h prior to surgery . Antibiotic concentrations were measured perioperatively and pharmacokinetic data calculated . RESULTS: Serum and tissue concentrations of ofloxacin were above the MIC90 of the potential bacterial spectrum for surgical infection throughout the entire operation . Pharmacokinetic data were not influenced by preoperative surgical or anesthesiological preparation . CONCLUSION: Tissue and serum concentrations and the antibacterial spectrum of orally administered ofloxacin suggest effective protection against perioperative infection . Pharmacokinetic data confirm that oral ofloxacin may be used effectively as single-dose perioperative antibiotic prophylaxis . Since there are no clinical data comparing oral and intravenous singLe-dose prophylaxis, a prospective randomized clinical trial should be performed.

Int J Food Microbiol, 2001 Aug 15, 68(1-2), 83 - 91
Observation of everyday hand-washing behavior of Japanese, and effects of antibacterial soap; Toshima Y et al.; People wash their hands only for a short time outside the home and when preparing meals at home . This may not be sufficient for those who prepare meals because of possible secondary contamination from food . Although washing with a placebo soap for a short period (lathering 3 s and rinsing 8 s) cleansed from hands about 95% of the total coliforms transferred from ground meat, an antibacterial soap further reduced the coliform count significantly (p < 0.01) . To effectively avoid secondary contamination, it is recommended that people should more frequently wash their hands, using an antibacterial soap on the areas that have been in contact with raw meat, poultry, seafood, eggs, vegetables and other foods.

Annu Rev Microbiol, 2001, 55, 437 - 51
Bacteriophage therapy; Summers WC; In 1917, bacteriophages were recognized as epizootic infections of bacteria and were almost immediately deployed for antibacterial therapy and prophylaxis . The early trials of bacteriophage therapy for infectious diseases were confounded, however, because the biological nature of bacteriophage was poorly understood . The early literature reviewed here indicates that there are good reasons to believe that phage therapy can be effective in some circumstances . The advent of antibiotics, together with the "Soviet taint" acquired by phage therapy in the postwar period, resulted in the absence of rigorous evaluations of phage therapy until very recently . Recent laboratory and animal studies, exploiting current understandings of phage biology, suggest that phages may be useful as antibacterial agents in certain conditions.

Annu Rev Microbiol, 2001, 55, 305 - 32
Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery; Campbell JW et al.; The increase in drug-resistant pathogenic bacteria has created an urgent demand for new antibiotics . Among the more attractive targets for the development of new antibacterial compounds are the enzymes of fatty acid biosynthesis . Although a number of potent inhibitors of microbial fatty acid biosynthesis have been discovered, few of these are clinically useful drugs . Several of these fatty acid biosynthesis inhibitors have potential as lead compounds in the development of new antibacterials . This review encompasses the known inhibitors and prospective targets for new antibacterials.

J Immunol, 2001 Sep 15, 167(6), 3329 - 38
Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells; Nagaoka I et al.; Mammalian myeloid and epithelial cells express several kinds of antibacterial peptides (alpha-/beta-defensins and cathelicidins) that contribute to the innate host defense by killing invading micro-organisms . In this study we evaluated the LPS-neutralizing activities of cathelicidin peptides human CAP18 (cationic antibacterial proteins of 18 kDa) and guinea pig CAP11 using the CD14(+) murine macrophage cell line RAW264.7 and the murine endotoxin shock model . Flow cytometric analysis revealed that CAP18 and CAP11 inhibited the binding of FITC-conjugated LPS to RAW264.7 cells . Likewise, Northern and Western blot analyses indicated that CAP18 and CAP11 suppressed LPS-induced TNF-alpha mRNA and protein expression by RAW264.7 cells . Interestingly, CAP18 and CAP11 possessed LPS-binding activities, and they strongly suppressed the interaction of LPS with LPS binding protein that mediates the transport of LPS to CD14 to facilitate the activation of CD14(+) cells by LPS . Moreover, when CAP18 and CAP11 were preincubated with RAW264.7 cells, they bound to the cell surface CD14 and inhibited the binding of FITC-LPS to the cells . Furthermore, in the murine endotoxin shock model, CAP18 or CAP11 administration inhibited the binding of LPS to CD14(+) cells (peritoneal macrophages) and suppressed LPS-induced TNF-alpha expression by these cells . Together these observations indicate that cathelicidin peptides CAP18 and CAP11 probably exert protective actions against endotoxin shock by blocking the binding of LPS to CD14(+) cells, thereby suppressing the production of cytokines by these cells via their potent binding activities for LPS and CD14.

Fitoterapia, 2001 Aug, 72(6), 695 - 7
Antibacterial activity of Vitex trifolia; Hossain MM et al.; The petroleum ether and ethanol extracts of Vitex trifolia leaves exhibited moderate inhibiting activity against both gram-positive and gram-negative bacteria.

Fitoterapia, 2001 Aug, 72(6), 689 - 91
Antibacterial activity of Rhizophora mangle bark; Melchor G et al.; The aqueous extract of Rhizophora mangle bark, also formulated to ensure physical and chemical stability, was found to inhibit the growth of seven bacteria frequent in infected wounds.

Fitoterapia, 2001 Aug, 72(6), 662 - 5
Anti-microbial activity of Bidens pilosa, Bischofia javanica, Elmerillia papuana and Sigesbekia orientalis; Khan MR et al.; The ethanol extracts of Bidens pilosa (whole plant), Bischofia javanica (leaves), Elmerillia papuana (root bark) and Sigesbekia orientalis (whole plant) were partitioned (petrol, dichloromethane, ethyl acetate) . The crude ethanolic extracts and all the obtained fractions showed a broad spectrum of antibacterial activity, the ethyl acetate fractions and the petrol fraction of E . papuana being the most effective . No activity was observed against the tested moulds.

J Med Chem, 2001 Sep 13, 44(19), 3125 - 31
Synthesis and conformational analysis of fusidic acid side chain derivatives in relation to antibacterial activity; Duvold T et al.; Novel fusidic acid type antibiotics having flexible side chains are described . Saturation of the double bond between C-17 and C-20 of fusidic acid produces four stereoisomers differing in the configuration at C-17 and C-20 . The structure-activity relationship of the stereoisomers was studied using computer-assisted analyses of low-energy conformations and crystallographic data . Only one of the four stereoisomers showed potent antibiotic activity comparable with that of fusidic acid, whereas the other three stereoisomers retained little or no activity . The orientation of the side chain is crucial, and there is only a limited space for bioactive side chain conformations . This investigation demonstrates the essential role of the side chain conformations in relation to antibacterial activity and contradicts earlier assumptions that the Delta17(20) bond is an essential feature in the molecule.

Arch Pharm Res, 2001 Aug, 24(4), 263 - 9
Facile synthesis and biological evaluation of heterocyclic compounds containing diazepam; Berghot MA; Diazepamoxadiazoles 4, 5, 6, 12, 14 and 22 were prepared with the binary form system . Diazepamthiadiazoles 15, 20 and Diazepamtriazoles 7, 8, 9, 17, 18, 19 and 21 were also shapely synthesized . Some of these compounds were screened to test their antibacterial activity against E . coli and B . subtilis compounds 15 and 20 show potent activity against these bacteria.

Mol Gen Mikrobiol Virusol, 2001, (3), 3 - 8
{Active membrane transport and bacterial multiple antibiotic resistance}; Viktorov DV et al.; Multiple drug resistance can form in bacteria by functioning the membrane transport systems, responsible for release of antibacterial compounds from the cell into the environment . These transport mechanisms activated in the majority of cases by energy of proton transmembrane gradient are presented by solitary membrane transporting proteins and by functionally related transporter groups, periplasma proteins, and external membrane porines . Many bacterial drug transporters can bind and transfer a number of structurally heterogeneous substrates . Drug transporters known today have different origin and primary physiological functions . The genetic system of transporter type drug resistance is as a rule characterized by a cluster structure and related to mobile genetic elements . Transport mechanisms of drug resistance create an extra adaptation potential of microorganisms under conditions of selective pressure.

Z Naturforsch {C}, 2001 Jul-Aug, 56(7-8), 593 - 6
New bioactive chalcones in propolis from El Salvador; Popova M et al.; 2',3'-Dihydroxy-4,4'-dimethoxychalcone (1) and 2',3',4-trihydroxy-4'-methoxy-chalcone, two new chalcones, were isolated from propolis from El Salvador . The compounds showed significant antibacterial and antifungal activity and moderate toxicity to Artemia salina nauplii.

Vestn Otorinolaringol, 2001, (4), 46 - 7
{Orbital and intracranial complications of rhinosinusitis}; Kuranov NI; Rhinogenic orbital and intracranial complications occur in 0.8 and 0.01% of patients with rhinosinusitis, respectively . The author recognizes 9 and 8 forms of rhinogenic orbital and intracranial complications, respectively . Conservative treatment is preferable in non-purulent orbital and intracranial complications resultant from acute inflammation of the paranasal sinuses . In the above complications taking place in chronic paranasal inflammation it is valid to conduct a sanitizing operation on the paranasal sinuses . Purulent intracranial and orbital complications dictate the necessity of major surgical treatment of the affected paranasal sinuses and intracranial focus in active antibacterial, dehydration, desensitizing and strengthening therapy . Prognosis of the orbital and intracranial complications at present is more favourable.

Bioorg Med Chem Lett, 2001 Sep 3, 11(17), 2397 - 9
Synthesis and biological properties of new 1beta-methylcarbapenems containing heteroaromatic thioether moiety; Shin KJ et al.; The synthesis and biological activities of a series of new 1beta-methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of pyrrolidine were described . Among these compounds, 1,2,3-thiadiazole derivative 1h showed the most potent antibacterial activity and advanced pharmacokinetics in comparison with meropenem.

Antivir Chem Chemother, 2001 Mar, 12(2), 125 - 31
Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins; Lampi G et al.; Some enzymes present in biological fluids, such as lysozyme (LYS) and lactoferrin (LAC), are known to possess antibacterial and antiviral activity, against herpesviruses in particular . It will be shown in this paper that their combination with a natural triterpene, namely glycyrrhizic acid (GLA), gives significant results in enhancing the antagonistic activity on HSV1 in in vitro assays . Data elaboration was carried out by calculation of the FIC index (fractional inhibitory concentration) for each combination of the three compounds and by a three-dimensional evaluation of the inhibiting combinatory effects, which indicated the percentage of the synergistic action . A FIC index equal to or below 0.5 demonstrated a significant synergistic effect between two substances . Considering each single compound, the 50% inhibiting doses on viral replication (ID50) were 252+/-53 microg/ml for LAC, 497+/-165 microg/ml for LYS and 740+/-125 microg/ml for GLA . The combination of LAC and GLA showed a clear synergistic effect, with a FIC index of 0.08 and a potentiating activity which, for some doses, was up to 1.5 log10 of difference (from about 5.5x10(6) to 10(5) pfu/ml) . The combinations of GLA and LYS, and LYS and LAC showed a less significant synergistic activity . These findings led to the conclusion that some physiological proteins, even at concentrations usually present in some body fluids, may enhance the anti-herpetic activity of a natural compound such as GLA.

Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S214 - 20
In vitro models, in vivo models, and pharmacokinetics: what can we learn from in vitro models?
MacGowan A, Rogers C, Bowker K.
In vitro pharmacokinetic models of infection can make an important contribution to the study of the pharmacodynamic properties of an antibacterial agent . In conjunction with animal and human pharmacodynamic evaluations, they provide data to allow for the optimization of drug dosing regimens . In vitro models can be used simply to describe the effect of a drug on a bacterial population as well as to provide data for more-analytical studies, including hypothesis testing . Analytical study designs provide information on the pharmacodynamic parameter best related to the chosen outcome, as well as its magnitude . Factors such as the characteristics of the model (method of drug removal, inoculum density, and growth phase), doses simulated, species and susceptibility range of bacteria, and methods and analytical tools used to measure antibacterial effect will have an effect on the conclusions drawn . In vitro models have an important future role in ensuring antibiotic efficacy and in reducing the risks of resistance.

Anesth Analg, 2001 Sep, 93(3), 641 - 4
A comparison of atenolol, labetalol, esmolol, and landiolol for altering human neutrophil functions; Nishina K et al.; IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system . Atenolol, labetalol, esmolol, and landiolol at clinically relevant concentrations failed to change neutrophil functions . Our findings indicate that we may be able to use these beta-antagonists without great caution in clinical settings.

J Biol Chem, 2001 Nov 2, 276(44), 41377 - 82 Epub 2001 Aug 24.
Structure of the induced antibacterial protein from tasar silkworm, Antheraea mylitta . Implications to molecular evolution; Jain D et al.; The crystal structure of an antibacterial protein of immune origin (TSWAB), purified from tasar silkworm (Antheraea mylitta) larvae after induction by Escherichia coli infection, has been determined . This is the first insect lysozyme structure and represents induced lysozymes of innate immunity . The core structure of TSWAB is similar to c-type lysozymes and alpha-lactalbumins . However, TSWAB shows significant differences with respect to the other two proteins in the exposed loop regions . The catalytic residues in TSWAB are conserved with respect to the chicken lysozyme, indicating a common mechanism of action . However, differences in the noncatalytic residues in the substrate binding groove imply subtle differences in the specificity and the level of activity . Thus, conformational differences between TSWAB and chicken lysozyme exist, whereas functional mechanisms appear to be similar . On the other hand, alpha-lactalbumins and c-type lysozymes exhibit drastically different functions with conserved molecular conformation . It is evident that a common molecular scaffold is exploited in the three enzymes for apparently different physiological roles . It can be inferred on the basis of the structure-function comparison of these three proteins having common phylogenetic origin that the conformational changes in a protein are minimal during rapid evolution as compared with those in the normal course of evolution.

Khirurgiia (Mosk), 2001, (7), 39 - 41
{Correction of hyperglycemia in diabetic patients with postinjection abscesses}; Kurlaev PP et al.; Local use of oxytocin-antibacterial complexes in combination with treatment of diabetes including divided insulinotherapy in patients with postinjection abscesses and non-insulin-dependent diabetes led to compensation of diabetes and earlier sanation of suppurative focus compared with patients treated by local antibiotics only.

J Endotoxin Res, 2001, 7(1), 3 - 23
Lipopolysaccharide biosynthesis: which steps do bacteria need to survive?
Gronow S, Brade H.
A detailed knowledge of LPS biosynthesis is of the utmost importance in understanding the function of the outer membrane of Gram-negative bacteria . The regulation of LPS biosynthesis affects many more compartments of the bacterial cell than the outer membrane and thus contributes to the understanding of the physiology of Gram-negative bacteria in general, on the basis of which only mechanisms of virulence and antibiotic resistance can be studied to find new targets for antibacterial treatment . The study of LPS biosynthesis is also an excellent example to demonstrate the limitations of "genomics" and "proteomics", since secondary gene products can be studied only by the combined tools of molecular genetics, enzymology and analytical structural biochemistry . Thus, the door to the field of "glycomics" is opened.

J Nat Prod, 2001 Aug, 64(8), 1093 - 4
Verbalactone, a new macrocyclic dimer lactone from the roots of Verbascum undulatum with antibacterial activity; Magiatis P et al.; A novel macrocyclic dimer lactone, named verbalactone, was isolated from the roots of Verbascum undulatum and exhibited interesting antibacterial activity . It is the first time that 1,7-dioxacyclododecane is reported as the ring system of a natural product . The structure and the absolute stereochemistry of the new compound were determined by spectral methods and chemical correlation.

J Dairy Sci, 2001 Aug, 84(8), 1829 - 35
Analysis time and lactation stage influence on lactoperoxidase system components in dairy ewe milk; Althaus RL et al.; To study the effect of time elapsed from the moment of taking samples on lactoperoxidase system components, we analyzed the activity of the lactoperoxidase enzyme and the concentrations of thiocyanate and hydrogen peroxide in 46 individual samples of Manchega ewe milk . Samples were maintained at a temperature of 4 degrees C until analysis, which took place at 6, 12, 24, and 48 h after extraction . Decreases were observed in lactoperoxidase activity when the analyses were performed at 48 h and in the thiocyanate and hydrogen peroxide concentrations at 12 h compared with those carried out earlier . Consequently, when the components of the lactoperoxidase system or its antibacterial activity are studied, the time elapsed since the sampling commenced must be taken into account . Similarly, the time elapsed is important when carrying out bacterial counts or residue screening by microbiological methods, during which the lactoperoxidase system may interfere . To study the component changes in the lactoperoxidase system during lactation, samples obtained 15, 30, 45, 60, 75, 90, 105, 120, and 135 d postpartum from 48 Manchega ewes were used . Average lactoperoxidase activity, thiocyanate, and hydrogen peroxide concentrations were 3.46 U/ml, 6.89 mg/L, and 0.39 mg/L, respectively, with significant variations throughout lactation . The thiocyanate and hydrogen peroxide levels at different lactation stages seemed to be insufficient to activate the lactoperoxidase system . Nevertheless, this could be achieved by adding 5 mg/L of thiocyanate and 8 mg/L of hydrogen peroxide at any time during lactation.

J Control Release, 2001 Jun 15, 73(2-3), 205 - 11
Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system; Srividya B et al.; The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac . The present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, ofloxacin, based on the concept of pH-triggered in situ gelation . Polyacrylic acid (Carbopol 940) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel E50LV) which acted as a viscosity enhancing agent . The developed formulation was therapeutically efficacious, stable, non-irritant and provided sustained release of the drug over an 8-h period . The developed system is thus a viable alternative to conventional eye drops.

Bioorg Med Chem Lett, 2001 Aug 20, 11(16), 2111 - 5
Stereoselective synthesis and antibacterial evaluation of 4-amido-isothiazolidinone oxides; Chen Z et al.; Two well-defined oxidative chlorination-cyclization processes have been developed for the stereoselective synthesis of a variety of 4-amido-isothiazolidinone oxide derivatives . The stereochemistry of the cyclization products was confirmed by X-ray crystallography . These new compounds were designed as bacterial serine protease inhibitors . In tests, some of them showed weak antibacterial activity.

J Agric Food Chem, 2001 Aug, 49(8), 3746 - 52
Hypervalent iodine compounds as potent antibacterial agents against ice nucleation active (INA) Pseudomonas syringae; Menkissoglu-Spiroudi U et al.; Twenty-three hypervalent iodine compounds belonging to aryliodonium salts, 1, aryliodonium ylides, 2, and (diacyloxyiodo)arenes, 3, were tested for their antibacterial activities against ice nucleation active (INA) Pseudomonas syringae, and the MIC and EC(50) values were determined . All of the compounds examined caused a dose-dependent decrease in bacterial growth rates . Aryliodonium salts, especially those with electron-withdrawing groups, exhibit higher antibacterial activities with MIC = 8-16 ppm, whereas the nature of the anion does not seem to affect the activities of the diaryliodonium salts.

J Antibiot (Tokyo), 2001 Jun, 54(6), 506 - 9
3-Keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A synthesis and in vitro activity; Shengxi C et al.; A series of 3-keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A were prepared with a novel synthetic route, which include 6 reaction steps--oximation, protection, hydrolysis, oxidation, deprotection and addition . The antibacterial activity of these compounds were tested in vitro against both erythromycin-susceptible and erythromycin-resistant organisms . Several of these derivatives showed improved antibacterial activity against some erythromycin-resistant organisms as compared to erythromycin A.

Drug Resist Updat, 2001 Apr, 4(2), 93 - 105
Low-level antibacterial resistance: a gateway to clinical resistance; Baquero F; The huge amount of antibiotic substances released in the human environment has probably resulted in an acceleration in the rate of bacterial evolution . It is to note that most interactions between chemotherapeutic agents and microbial populations occur at very low antibiotic concentrations . Thus, natural selection is expected to act on very small increases in the bacterial ability to resist to antibiotic inhibitory effects . On the other hand, there is a wealth of mechanisms to resist to these low antibiotic concentrations . The progressive enrichment in low-level resistant populations favours secondary selections for more specific and effective mechanisms of resistance, particularly in treated patients . These adaptations may have a biological cost in the absence of antibiotics, but frequently compensatory mutations occur, minimizing such genetic burden . In this way, a phenomenon of directional selection takes place, with low possibilities of return to susceptibility . Moreover, low antibiotic concentrations are not only able to select low-level antibiotic resistant variants, but may produce a substantial stress in bacterial populations, that eventually influences the rate of genetic variation and the diversity of adaptive responses . More attention should be devoted to the mechanisms of low-level resistance in microorganisms, as they can serve as stepping stones to develop high level, clinically relevant resistance . These mechanisms should be identified early in the development of drugs in order to adapt the therapeutic strategies (for instance dosage) to minimize the selection of low-level resistant variants, as frequently they emerge by means of concentration-specific selection . At the same time, conventional susceptibility testing should probably be able to detect low-level resistance, and not only clinically-relevant resistance . We should be vigilant of the evolutionary trends of microorganisms; for that a purpose, knowledge of the biology and epidemiology of low-level resistance is becoming a real need.

J Am Acad Dermatol, 2001 Sep, 45(3), 420 - 34
Dapsone and sulfones in dermatology: overview and update; Zhu YI et al.; In their 60-year history, dapsone and the sulfones have been used as both antibacterial and anti-inflammatory agents . Dapsone has been used successfully to treat a range of dermatologic disorders, most successfully those characterized by abnormal neutrophil and eosinophil accumulation . This article reviews and updates the chemistry, pharmacokinetics, clinical application, mechanism of action, adverse effects, and drug interactions of dapsone and the sulfones in dermatology.

Anal Chem, 2001 Aug 1, 73(15), 3716 - 22
High-throughput liquid chromatography/mass spectrometry method for the determination of the chromatographic hydrophobicity index; Camurri G et al.; A fast gradient reversed-phase liquid chromatography (LC) method, using an acetonitrile gradient was developed to determine the chromatographic hydrophobicity index (CHI), as reported by Valco et al . (Anal . Chem . 1997, 69, 2022-2029).The analytical method provides retention times, based on UV detection at two different wavelengths, which then are converted into CHI values after calibration with a set of test compounds . The CHI of each compound is measured at three different pH values, 2.0, 7.4, and 10.5; so using an 8-min gradient at each pH value one compound can be analyzed in approximately 24 min . The aim of this work is to improve the throughput of the CHI screening using a LC/MS approach, so the application of the LC/MS technique is an extension of the LC/UV approach previously reported by Valco et al . This approach allows contemporary injection of N compounds into the LC/MS system, the retention time of each compound can be then extracted from the selected ion recording chromatograms . The throughput of the existing screening method could be increased by N times, where N is the number of compounds injected, so only three runs are needed to determine the CHI at three different pH values for a set of N compounds . The highest value of N depends on the total number of channels that can be monitored simultaneously; in the present work, 32 channels were used . This LC/MS method has been tested for a number of commercial products analyzed as mixtures, and data obtained were compared with those coming from the classical LC/UV approach . In the same way, the method was tested for a number of compounds associated with two GlaxoWellcome projects in the antibacterial area . Data reported show that the LC/MS method can be successfully applied for analyzing compounds in mixtures and for compounds with poor UW absorption, which cannot be analyzed with the standard LC/UV method.

Anal Chem, 2001 Aug 1, 73(15), 3632 - 8
Trace determination of fluoroquinolone antibacterial agents in urban wastewater by solid-phase extraction and liquid chromatography with fluorescence detection; Golet EM et al.; Fluoroquinolones (FQs) are among the most important antibacterial agents (synthetic antibiotics) used in human and veterinary medicine . An analytical method based on reversed-phase liquid chromatography with fluorescence detection was developed and validated for the simultaneous determination of nine FQs and the quinolone pipemidic acid in urban wastewater . Aqueous samples were extracted using mixed-phase cation-exchange disk cartridges that were subsequently eluted by ammonia solution in methanol . Recoveries were above 80% at an overall precision of better than 10% . Instrumental quantification limits varied between 150 and 450 pg injected . The presented method was successfully applied to quantify FQs in effluents of urban wastewater treatment plants . The two most abundant human-use FQs, ciprofloxacin and norfloxacin, occurred in primary and tertiary waste-water effluents at concentrations between 249 and 405 ng/L and from 45 to 120 ng/L, respectively . The identity of FQs in urban wastewater was confirmed by recording full fluorescence spectra and liquid chromatography directly coupled to tandem mass spectrometry . These results indicate that conventional environmental risk assessment overestimates FQ concentrations in surface waters by 1 to 2 orders of magnitude.

Dtsch Tierarztl Wochenschr, 2001 Jul, 108(7), 311 - 4
Non-bioequivalence of various trademarks of enrofloxacin and Baytril in cows; Sumano LH et al.; Including Baytril, in various parts of the world many commercial preparations of enrofloxacin for parenteral administration are being employed for the treatment of bacterial diseases in cows . To optimize clinical responses and to minimize development of bacterial resistance to this agent, the copied pharmaceutical preparations must comply with some key pharmacokinetic features when bioequivalence studies are performed . To assess whether or not there was bioequivalence among nine commercial preparations of enrofloxacin and the original one, a controlled pharmacokinetic study was carried out . These was done utilizing the microbiological agar-diffusion test as quantitative/qualitative analytical method . A non-compartmental model defined kinetic variables . Results for Baytril revealed that maximal serum concentration (Csmax) was only matched by one preparation while area under the curve (AUC) of the serum concentration/activity of enrofloxacin and metabolites in time was not matched by any preparation . Time to Csmax (Tmax), elimination half-life, and shape of the time-serum concentrations of enrofloxacin profiles obtained for the nine generic preparations differ significantly somehow from the corresponding data obtained for the reference enrofloxacin . The need for studies to demonstrate bioequivalence becomes mandatory if similar preparations of enrofloxacin become commercially available . Enrofloxacin should be used selectively and cautiously to limit development of bacterial resistance . Non-bioequivalence of relevant pharmacokinetic values, such as Csmax and bioavailability (AUC) would facilitate development of bacterial resistance and limit the useful life span of this antibacterial agent.

Arzneimittelforschung, 2001, 51(7), 582 - 7
Evaluation of cardiac subacute toxicity of ciprofloxacin in rats using serum biochemical parameters; Pispirigos K et al.; Cardiac subacute toxicity induced by ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid, CAS 86393-32-0) a relatively new quinolone carboxylic acid derivative with an extensive antibacterial spectrum was investigated in healthy rats using serum biochemical parameters . Toxicological evaluation was performed in serum samples following the administration of the therapeutic dose regimens of the compound . Cardiac subacute toxicity was evaluated by measuring serum enzyme activity of creatine kinase, creatine kinase isoenzyme-MB (muscular-brain), lactate dehydrogenase and aspartate aminotransferase . The serum biochemical parameters indicated that the cardiac subactue toxicity of ciprofloxacin was: Cipro 1.2 (250 mg) = Cipro 2.4 (500 mg) < Cipro 4.3 (750 mg).

Prescrire Int, 1999 Dec, 8(44), 170 - 2
Nifuroxazide in acute diarrhoea: OTC preparation . Irrational.
{Tumescence local anesthesia in venous surgery}
Selzle K, Kamionek I, Kuropka R, Schonath M.

Diagnose- und Therapiezentrum fur Haut und Gefasse, Artemed Fachklinik MunchenAfter the long standing application of the tumescent solution with percutaneous sticks the tumescent technique in combination with the Rofil Medro-pump represents at the moment a very elegant and innovative method of local anesthesia in the field of phlebosurgery . Since 1997 the tumescent technique has been used in our hospital for all major surgeries in the field of phlebosurgery . Even more difficult operations like inguinal relapse-varicosis or acute thrombophlebitis are successfully performed with this method . From our experience the advantages of this method are a reduced bleeding, less hematomas, an insignificant risk of thrombosis and embolism, an antibacterial effect, the hydrodissection and anodynia . Using very large volumes painless surgical treatment of complicated and extended findings is possible . Essential disadvantages (like a wet surgical field, which needs to get used to) hardly exist neither for the patient nor for the surgeon . Therefore, the tumescent technique represents a safe, comfortable and almost painless kind of local anesthesia of the skin and the subcutaneous fatty tissue.

Biol Chem, 2001 Jun, 382(6), 947 - 51
Purification of chrysancorin, a novel antifungal protein with mitogenic activity from garland chrysanthemum seeds; Wang H et al.; A novel antifungal protein, designated chrysancorin, was isolated from seeds of Chrysanthemum coronarium var . spatiosum with a procedure involving ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue resin, ion exchange chromatography on SP-Sepharose and FPLC-gel filtration on Superdex 75 . The N-terminus of chrysancorin displays sequence similarity to the genomic sequence of chromosome 1 from Arabidopsis thaliana BAC T19E23 . Chrysancorin exhibits a molecular mass of 13.4 kDa in gel filtration and SDS-polyacrylamide gel electrophoresis . It stimulates the proliferation of mouse splenocytes and inhibits the activity of human immunodeficiency virus-1 reverse transcriptase . The protein possesses antifungal activity against Botrytis cinerea, Mycosphaerella arachidicola and Physalospora piricola, but not against Rhizoctonia solani, Fusarium oxysporum and Coprinus comatus . However, we could not detect antibacterial activity against a variety of bacteria.

Photodermatol Photoimmunol Photomed, 2001 Aug, 17(4), 172 - 7
Pefloxacin and ciprofloxacin increase UVA-induced edema and immune suppression; Sun YW et al.; BACKGROUND: Quinolone antibiotics are popularly prescribed antibiotics because of their wide antibacterial spectrum and lowered bacterial resistance . Quinolone antibiotics are one of the well-known photosensitizers that induce phototoxicity . Their role in photocarcinogenesis has been suggested in some studies . MATERIAL AND METHODS: Mice were treated with two quinolone antibiotics (ciprofloxacin, which is less phototoxic, and pefloxacin, which is more phototoxic) to study the effect of the antibiotics on sunburn and immune suppression by ultraviolet A (UVA) irradiation . The effects of a combined treatment with UVA and these quinolone antibiotics were measured on back skin swellings, sunburn cell formations, depletion of epidermal Langerhans cells, and local and systemic suppression of contact hypersensitivity . RESULTS: Mice treated with both UVA and quinolone showed significantly increased back skin swellings and decreased epidermal Langerhans cells than mice treated with UVA only . Sunburn cells were increased significantly in mice treated with pefloxacin and 50 J/cm2 of UVA . Combination of pefloxacin and UVA suppressed local contact hypersensitivity significantly, but not systemic contact hypersensitivity . CONCLUSION: Phototoxic quinolones augmented the effect of UVA by increasing sunburn and apoptosis, depleting Langerhans cells and suppressing local immune response . By affecting apoptosis and immune suppression, they may facilitate photocarcinogenesis caused by UVA.

Yao Xue Xue Bao, 1997 May, 32(5), 347 - 52
{Synthesis and antibacterial activity of tricycic fluoroquinolones}; Xiong WN et al.; Twelve new analogues of new tricyclic rufloxacin were prepared and their MIC were evaluated against thirteen kinds of bacteria . As a result of these studies: the polarity of C10-side chain was found to exert greater positive effect on G- than on G+ bacteria.

Otolaryngol Pol, 2001, 55(2), 217 - 21
{The use of benzydamine Hcl -- Tantum Verde -- in otolaryngology}; Szmeja Z; Benzydamine HCL--Tantum Verde is a non-steroid drug of anti-inflammatory, pain-killing and antibacterial activity . The preparation is very easy to use in the form of mouth and throat wash, nebuliser or 3 mg lozenges . It is non-toxic and does not have side-effects . It allows the patients to improve their ability to eat foods and reduces throat discomfort and pain . On the basis of literature and own observation it is to be stated that Tantum Verde has substantial usefulness in the treatment of various, inflammatory conditions, radiotherapy induced mucositis in anti-neoplastic induced stomatitis, in angina, in neoplasms with necrosis, after surgical operation of the mouth and pharynx, after intubation and endoscopic surgery in the larynx.

J Nat Toxins, 2001 Aug, 10(3), 181 - 91
Antibacterial and anticholinesterase activities of aplysamine-4, a bromotyrosine-derived metabolite of a Red Sea marine sponge; Sepcic K et al.; Aplysamine-4, a metabolite of likely bromotyrosine biogenesis, was isolated from an unidentified verongid sponge from the Red Sea . The compound was identified by heteronuclear magnetic resonance experiments, and by electrospray ionization tandem mass spectrometry . The compound exhibited moderate inhibitory activity on several Gram positive and Gram negative bacteria, and was also found to be a non-competitive reversible inhibitor of acetylcholinesterase . At pH 7.4, a Ki value of 16 and 2 microM was determined with electric eel and insect recombinant acetylcholinesterase, respectively . A deprotonated form of aplysamine-4 was obtained by alkaline treatment of the natural compound and it was shown to be less active than the protonated form.

J Mol Biol, 2001 May 25, 309(1), 171 - 80
A study of the structure-activity relationship for diazaborine inhibition of Escherichia coli enoyl-ACP reductase; Levy CW et al.; Enoyl acyl carrier protein (ACP) reductase catalyses the last reductive step of fatty acid biosynthesis, reducing the enoyl group of a growing fatty acid chain attached to ACP to its acyl product using NAD(P)H as the cofactor . This enzyme is the target for the diazaborine class of antibacterial agents, the biocide triclosan, and one of the targets for the front-line anti-tuberculosis drug isoniazid . The structures of complexes of Escherichia coli enoyl-ACP reductase (ENR) from crystals grown in the presence of NAD+ and a family of diazaborine compounds have been determined . Analysis of the structures has revealed that a mobile loop in the structure of the binary complex with NAD+ becomes ordered on binding diazaborine/NAD+ but displays a different conformation in the two subunits of the asymmetric unit . The work presented here reveals how, for one of the ordered conformations adopted by the mobile loop, the mode of diazaborine binding correlates well with the activity profiles of the diazaborine family . Additionally, diazaborine binding provides insights into the pocket on the enzyme surface occupied by the growing fatty acid chain.

Klin Med (Mosk), 2001, 79(3), 40 - 3
{Pneumonia in patients with terminal renal failure on programmed hemodialysis}; Potekhin NP; Of 183 patients with terminal renal failure (TRF) on programmed hemodialysis 12(6.5%) were diagnosed to have acute pneumonia . As a rule, the disease develops in hyperhydration and hypertension of the lesser circulation, more rarely concomitant heart disease is diagnosed which runs with general circulation insufficiency . This indicates that pneumonia in dialysis patients is secondary . Pulmonary congestion in pneumonia debut may mask infiltrative alterations . Therefore, in obscure cases it is desirable to combine x-ray examination with polyposition tomoscintigraphy of the lungs . The agent was verified in 33.3% cases . The sputum contained for the most part gram-positive bacteria . Antibacterial therapy was combined with measures against hyperhydration and hypertension . Mean duration of the treatment was 21.25 +/- 13.6 days.

J Chromatogr B Biomed Sci Appl, 2001 Jul 15, 758(2), 323 - 5
Fast analysis of antibacterial isothiazolones by capillary electrophoresis; Bartak P et al.; Some technical aspects influencing the total time of CE analysis are discussed . A high throughput electrophoretic system based on micellar electrokinetic chromatography (MEKC) is demonstrated as an example . A short capillary, strong electric field, alkaline buffer (pH 9.5) generating strong electroosmotic flow, and parallel hydrodynamic pressure allow the separation of two uncharged isothiazolone derivatives within 45 s.

Boll Chim Farm, 2001 May-Jun, 140(3), 195 - 200
Polycyclic 4(3h)-quinazolinones survey of biological properties (Part II); Nawrocka W et al.; The authors present examples of polycyclic 4(3H)-quinazolinones of natural origin . Structures and syntheses of pharmacologically active (antibacterial, antifungal, antihypertensive and cardiovascular, antiasthmatic, anti-inflamatory, CNS-depresant, secretion of gastric acid inhibitors) compounds are described.

Eur J Med Res, 2001 Jul 30, 6(7), 306 - 8
Therapeutic and prophylactic effects of crude honey on chronic seborrheic dermatitis and dandruff; Al-Waili NS; Honey has antibacterial, antifungal and antioxidants activities and has high nutrient value . In this study we investigated the potential use of topical application of crude honey in the management of seborrheic dermatitis and dandruff . Thirty patients with chronic seborrheic dermatitis of scalp, face and front of chest were entered for study . Twenty patients were males and 10 were females, their ages ranged between 15 and 60 years . The patients had scaling, itching and hair loss . The lesions were scaling macules, papules and dry white plaques with crust and fissures . The patients were asked to apply diluted crude honey (90% honey diluted in warm water) every other day on the lesions with gentle rubbing for 2-3 mins . Honey was left for 3 hr before gentle rinsing with warm water . The patients were followed daily for itching, scaling, hair loss and the lesions were examined . Treatment was continued for 4 weeks . The improved patients were included in a prophylactic phase, lasting six months . Half patients were treated with the topical honey once weekly and the other half served as control . All the patients responded markedly with application of honey . Itching was relieved and scaling was disappeared within one week . Skin lesions were healed and disappeared completely within 2 weeks . In addition, patients showed subjective improvement in hair loss . None of the patients ( 15 patients) treated with honey application once weekly for six months showed relapse while the 12/15 patients who had no prophylactic treatment with honey experienced a relapse of the lesions 2-4 months after stopping treatment . It might be concluded that crude honey could markedly improve seborrheic dermatitis and associated hair loss and prevent relapse when applied weekly.

Emerg Infect Dis, 2001, 7(3 Suppl), 512 - 5
Antibacterial household products: cause for concern; Levy SB; The recent entry of products containing antibacterial agents into healthy households has escalated from a few dozen products in the mid-1990s to more than 700 today . Antibacterial products were developed and have been successfully used to prevent transmission of disease-causing microorganisms among patients, particularly in hospitals . They are now being added to products used in healthy households, even though an added health benefit has not been demonstrated . Scientists are concerned that the antibacterial agents will select bacteria resistant to them and cross-resistant to antibiotics . Moreover, if they alter a person's microflora, they may negatively affect the normal maturation of the T helper cell response of the immune system to commensal flora antigens; this change could lead to a greater chance of allergies in children . As with antibiotics, prudent use of these products is urged . Their designated purpose is to protect vulnerable patients.

J Virol Methods, 2001 Sep, 97(1-2), 77 - 85
'RETCIF': a rapid, sensitive method for detection of viruses, applicable for large numbers of clinical samples; Alexander R et al.; Rapid detection of viruses in clinical samples is important for continuing appropriate antiviral treatment and discontinuing unnecessary antibacterial treatment, as well as for excluding viral pathogens . Yet detection of viral agents may require numerous susceptible cell lines . Even with the shell vial culture method, it is cumbersome for handling large volumes of specimens . A procedure has been developed, which is time and cost-saving and uses specific cell lines in a 96-well microtitre plate and monoclonal antibodies (RETCIF-rapid enhanced tissue culture immunofluorescence) . Each clinical sample was inoculated into 12 different wells with five different cell lines . Enhancement was achieved by sonication, centrifugation and hormonal supplementation to the medium used . Cytomegalovirus (CMV), herpes simplex virus (HSV) and respiratory viruses were detected by monoclonal antibodies on day 2, whilst varicella zoster virus (VZV) and enteroviruses were detected on days 5 and 7, respectively . During July-December 1998, 3298 patient specimens were compared by RETCIF and a modified shell vial method . Either or both methods isolated 779 viruses (24% positivity rate), whilst both methods detected 621 . Of the 779 viruses, 87% (679) were isolated by the shell vial method in an average time of 4.9 days . For RETCIF the respective rate was 92.5% (721), in an average time of 3.0 days . The RETCIF method is a time-saving procedure, with higher isolation rates than the shell vial method.

Drugs Aging, 2001, 18(7), 487 - 94
Helicobacter pylori-associated peptic ulcer disease in older patients: current management strategies; Pilotto A; The incidence of peptic ulcer and its severe complications, i.e . bleeding or perforation, is increasing in elderly patients worldwide . The prevalence of Helicobacter pylori infection in patients with peptic ulcer aged over 65 years has been reported to range from 58 to 78% . However, in elderly patients hospitalised for ulcer disease, the rate of diagnostic screening or treatment for H . pylori infection was less than 60%, and only 50 to 73% of patients who had a positive H . pylori test were treated with antibacterials . The eradication of H . pylori infection is known to be of proven benefit for elderly patients with H . pylori-associated ulcer disease . Significant improvement of the clinical outcome, and reduction of ulcer recurrences, symptoms and histological signs of ulcer-associated chronic gastritis activity, as well as decreased costs in elderly healthcare, all result from successful therapy . Proton pump inhibitor (PPI)-based triple therapy regimens including clarithromycin, amoxicillin and/or nitroimidazoles are highly effective and well tolerated in elderly patients, particularly if therapy is of a short duration and low doses of both the PPI and clarithromycin are used . Resistance of H . pylori to antibacterials and low compliance are the major reasons for treatment failure . Surveillance of H . pylori susceptibility to antibacterials at the regional level and enhanced compliance programmes give promising results that suggest new approaches to anti-H . pylori treatment, especially in elderly patients . The role of H . pylori infection in nonsteroidal anti-inflammatory drug (NSAID)-related peptic ulcer still remains controversial . At present, no clear evidence supports the testing and treatment of H . pylori infection for the prevention of drug-related peptic ulcer in elderly patients receiving an NSAID or aspirin (acetylsalicylic acid) . After therapy, elderly patients with peptic ulcer may be re-evaluated by invasive methods, i.e . endoscopy and gastric biopsies . or by noninvasive methods . In elderly patients, the 13C-urea breath test demonstrated significantly higher sensitivity, specificity and diagnostic accuracy for detecting H . pylori infection than anti-H . pylori antibodies.

Klin Khir, 2001 Feb, (2), 50 - 2
{Microbiological monitoring of the microbic strain stability to antibacterial preparations in surgical in-patient clinics}; Demikhovskaia EV et al.; While performing of microbiological monitoring, conducted in surgical stationaries of Dnepropetrovsk, of 775 cultures, isolated during one year from patients and outer space, the S . aureus cultures were revealed, resistant to methicillin were 23.6%, to gentamycin 12.3% culture of all Gram-negative bacteria . Most effective preparation, which is recommended for the empirical antibacterial therapy conduction, is meronem, to whom the sensitivity of 87.5% for Gram-positive and 92.1% for Gram-negative cultures of conventionally pathogenic microorganism were established.

Klin Khir, 2001 Feb, (2), 43 - 6
{Microbiological aspects of application of fluoroquinolones in surgery}; Gorshevnikova EV; Antimicrobic activity of fluorochinolons with regard to pathogenic organisms of purulent-septic surgical infection was studied . In comparison with cephalosporins of the third generation, higher activity of fluorochinolons is noted with regard to majority aerobic microorganisms, and to pseudomonads, in particular . Optimal pharmacokinetics properties, good compliance, wide antimicrobic spectrum permits to use fluorochinolons in conduction of empirical antibacterial therapy for the infection occurrence prophylaxis in surgical practice, and for the selective intestinal decontamination, in particular.

Klin Khir, 2001 Feb, (2), 13 - 6
{Application of endoscopic laser irradiation and antibacterial therapy in surgical treatment of duodenal ulcer disease}; Grushka VA et al.; For duodenal ulcer disease there were performed an isolated selective proximal vagotomy--in 63 patients, vagotomy with various kinds of drainage operations--in 32, gastric resection according to Billroth-II--in 19 . The expediency of application of endoscopic laser irradiation and antibacterial therapy in preoperative preparation complex for prophylaxis of early postoperative complications and the ulcer recurrences occurrence was noted . Among the patients operated on without the preoperative preparation conduction the inflammatory complications in early postoperative period occurred in 19.3% of them and the ulcer recurrence--in 11.5%; after preoperative preparation conduction--in 8.6 and 4.8% accordingly.

Adverse Drug React Toxicol Rev, 2001 Jun, 20(2), 89 - 103
Adverse and beneficial effects of plant extracts on skin and skin disorders; Mantle D et al.; Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively . Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care . Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs . The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials . In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature . Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g . psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice) . Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants or plant products (e.g . peanut allergy, poison ivy (Toxicodendron) poisoning).

J Biochem (Tokyo), 2001 Aug, 130(2), 313 - 8
Identification and characterization of an antibacterial peptide of the 26-kDa protease of Sarcophaga peregrina with antibacterial activity; Tsuji Y et al.; Previously, we purified a serine protease with a molecular mass of 26 kDa that exhibits potent antibacterial activity from a pupal extract of Sarcophaga peregrina (flesh fly) . We divided this protease into 12 peptides and examined their antibacterial activity . A peptide corresponding to residues 155 to 174 (peptide 9) was found to exhibit antibacterial activity comparable to that of the 26-kDa protease . When Escherichia coli was treated with peptide 9, the permeability of both the outer and inner membranes increased, and substrates for beta-lactamase and beta-galactosidase entered the cells, but beta-galactosidase did not leak out of the cells under these conditions . It was suggested that residues 6 to 18 of peptide 9 form an amphiphilic alpha-helix under hydrophobic conditions with an N-terminal basic loop and then interact with acidic phospholipids in the bacterial membranes.

Drug Saf, 2001, 24(8), 575 - 85
Is gender a risk factor for adverse drug reactions? The example of drug-induced long QT syndrome; Drici MD et al.; Drug-induced torsade de pointes is a rare life-threatening adverse drug reaction (ADR) which is strongly influenced by gender . Drugs that prolong cardiac repolarisation include antiarrhythmics, gastrokinetics, antipsychotics, antihistamines and antibacterials . Such drugs share the potential to block cardiac voltage-gated potassium channels, particularly the rapid component (I(Kr)) of the delayed rectifier potassium current (I(K)) . By doing so, such drugs usually, but not always, prolong the QT interval . Even if the electrocardiographic signs are subdued, the underlying blockade of I(Kr) current may precipitate the occurrence of arrhythmia . Women are perceived to be more prone to ADRs than men . Such a propensity may result from gender-associated differences in drug exposure, in the number of drugs prescribed (polypharmacy), in drug pharmacology, as well as from possible differences in the way the adverse event is perceived . A prolonged QT interval on the electrocardiogram (time that elapses from the onset of the cardiac ventricular depolarisation to the completion of its repolarisation) is associated with the occurrence of torsade de pointes and related ventricular arrhythmias . The QT interval is influenced by heart rate, autonomic nervous system, electrolyte disturbances and above all, drugs that block potassium channels . Two-thirds of the cases of drug-induced torsade de pointes occur in women . Therefore, this adverse effect represents a perfect example of gender differences impairing women's health . Clinical and experimental studies show that female gender is associated with a longer corrected QT interval at baseline and a greater response to drugs that block I(Kr), both of which facilitate the emergence of arrhythmia . This results most likely from a specific regulation of ionic channel expression (potassium, calcium, etc) by sex steroids, even though nongenomic effects may play a role as well . Estrogens facilitate bradycardia-induced prolongation of the QT interval and the emergence of arrhythmia whereas androgens shorten the QT interval and blunt the QT response to drugs . Hence, underlying genetic defects of potassium channels that may be asymptomatic in normal conditions, may precipitate drug-induced arrhythmia in women more frequently than in men . Even in the presence of a drug that mildly blocks I(Kr) and seldom prolongs the QT interval, women are still more prone to drug-induced torsade de pointes, due to their reduced cardiac 'repolarisation reserve' . This is an important aspect of I(Kr) blockade to be aware of during the development of new drugs.

Bioinformatics, 2001, 17 Suppl 1, S253 - 61
Designing better phages; Skiena SS; We propose a method to engineer the genome of bacteriophages to increase their effectiveness as antibacterial agents . Specifically, we exploit the redundancy of the triplet code to design genomes that avoid restriction sites while producing the same proteins as wild-type phages . We give an efficient algorithm to minimize the number of restriction sites against sets of cutter sequences, and demonstrate that that phage genomes can be significantly protected against surprisingly large sets of enzymes with no loss of function . Finally, we develop a model to explain why evolution has failed to eliminate many possible restriction sites despite selective pressure, thus motivating the need for genome-level sequence engineering.

Int J Pharm, 2001 Aug 14, 224(1-2), 177 - 83
The formulation of an effective topical antibacterial product containing Ocimum gratissimum leaf essential oil; Orafidiya LO et al.; The antibacterial potential of Ocimum gratissimum essential oil was explored . Liquid and semisolid formulations of the oil were designed in a variety of bases for topical antiseptic medication . The products were evaluated by agar diffusion assay against type strains and clinical isolates from boil, wound and pimples . Remarkable antibacterial effects, higher than those of commercial antiseptic products, were demonstrated at 2% Ocimum oil concentration in some bases . The properties of base into which the oil was incorporated affected its activity . It was more effective in hydrophilic bases than in lipophilic bases . Solubilization and microemulsification grossly reduced its activity.

Eur J Surg, 2001 Jun, 167(6), 426 - 32
Secondary peritonitis: severity of disease and activation of peritoneal cells; Sendt W et al.; OBJECTIVE: To compare the degree of the inflammatory response of human peritoneum with the severity of peritonitis . DESIGN: Clinical laboratory study . SETTING: University hospital, Germany . SUBJECTS: 15 patients with diffuse secondary peritonitis and 5 having conventional cholecystectomy (controls) had peritoneal specimens taken from the site of incision . MAIN OUTCOME MEASURES: Correlation between presence of indicators of the inflammatory response: interleukin 1 (IL-1), interleukin 6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), antibacterial protein (defensin 3 reflecting the activation of granulocytes), the antibody clone HAM 56 (for detection of local macrophages), and antibodies against macrophage migration inhibiting factor (MIF)-related proteins 8 and 14 (MRP 8 and 14), and clinical state evaluated by the Mannheim Peritonitis Index (MPI), the Peritonitis Index Altona II (PIA II) and the Acute Physiology Score (APS) . C-reactive protein (CRP) concentrations were measured preoperatively in the serum . RESULTS: Expression of MRP 8 and 14, HAM 56, and defensin 3 was significantly higher in patients with peritonitis than in controls (p < 0.05) . Expression of IL-1 and IL-6 was almost undetectable . ICAM-1 expression correlated significantly with phagocytic activation . There was no correlation between clinical scores, CRP, and immunohistochemically detectable variables . CONCLUSION: The pattern of peritoneal inflammatory reactions is relatively uniform and does not correlate with the clinical grading of severity.

J Endod, 2000 Dec, 26(12), 751 - 5
Reduction of intracanal bacteria using nickel-titanium rotary instrumentation and various medications; Shuping GB et al.; The purpose of this study was to evaluate the extent of bacterial reduction with nickel-titanium rotary instrumentation and 1.25% NaOCl irrigation . Also, the additional antibacterial effect of calcium hydroxide for >1 wk was tested . Forty-two subjects with radiographic and clinical signs of chronic apical periodontitis were recruited . The canals were sampled before treatment, during and after instrumentation, and after treatment with calcium hydroxide and the samples incubated anaerobically for 7 days at 37 degrees C . The bacteria from each sample were quantified and the log10 values were used for calculations and comparisons . The initial sample confirmed infection of the canals . There was a significantly greater pattern of reduction of bacteria when NaOCl was used as an irrigant, compared with sterile saline (p < 0.05) . After instrumentation with NaOCl irrigation, 61.9% of canals were rendered bacteria-free . The placement of calcium hydroxide for at least 1 wk rendered 92.5% of the canals bacteria free . This was a significant reduction, compared with NaOCl irrigation alone (p = 0.0001) . The results of this study indicate that NaOCl irrigation with rotary instrumentation is an important step in the reduction of canal bacteria during endodontic treatment . However this method could not consistently render canals bacteria-free . The addition of calcium hydroxide intracanal medication should be used to more predictably attain this goal.

Biochim Biophys Acta, 2001 Aug 6, 1513(2), 83 - 94
Morphology of fast-tumbling bicelles: a small angle neutron scattering and NMR study; Luchette PA et al.; Bilayered micelles, or bicelles, which consist of a mixture of long- and short-chain phospholipids, are a popular model membrane system . Depending on composition, concentration, and temperature, bicelle mixtures may adopt an isotropic phase or form an aligned phase in magnetic fields . Well-resolved (1)H NMR spectra are observed in the isotropic or so-called fast-tumbling bicelle phase, over the range of temperatures investigated (10-40 degrees C), for molar ratios of long-chain lipid to short-chain lipid between 0.20 and 1.0 . Small angle neutron scattering data of this phase are consistent with the model in which bicelles were proposed to be disk-shaped . The experimentally determined dimensions are roughly consistent with the predictions of R.R . Vold and R.S . Prosser (J . Magn . Reson . B 113 (1996)) . Differential paramagnetic shifts of head group resonances of dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC), induced by the addition of Eu(3+), are also consistent with the bicelle model in which DHPC is believed to be primarily sequestered to bicelle rims . Selective irradiation of the DHPC aliphatic methyl resonances results in no detectable magnetization transfer to the corresponding DMPC methyl resonances (and vice versa) in bicelles, which also suggests that DHPC and DMPC are largely sequestered in the bicelle . Finally, (1)H spectra of the antibacterial peptide indolicidin (ILPWKWPWWPWRR-NH(2)) are compared, in a DPC micellar phase and the above fast-tumbling bicellar phases for a variety of compositions . The spectra exhibit adequate resolution and improved dispersion of amide and aromatic resonances in certain bicelle mixtures.

J Mol Biol, 2001 Aug 3, 311(1), 195 - 203
Ciprofloxacin affects conformational equilibria of DNA gyrase A in the presence of magnesium ions; Sissi C et al.; The conformational equilibria of the A subunit of DNA gyrase (GyrA), of its 59 kDa N-terminal fragment (GyrA59) and of the quinolone-resistant Ser-Trp83 mutant (GyrATrp83), were investigated in the presence of mono- and divalent metal ions and ciprofloxacin, a clinically useful antibacterial quinolone . The stability of the proteins was estimated from temperature denaturation, monitoring unfolding with circular dichroism spectroscopy . Two transitions were observed in GyrA and GyrATrp83, which likely reflect unfolding of the N and C-terminal protein domains . Accordingly, one thermal transition is observed for GyrA59.The melting profile of the GyrA subunit is dramatically affected by monovalent and divalent metal ions, both transitions being shifted to lower temperature upon increasing salt concentration . This effect is much more pronounced with divalent ions (Mg(2+)) and cannot be accounted for by changes in ionic strength only . The presence of ciprofloxacin shifts the melting transitions of the wild-type subunit to higher temperatures when physiological concentrations of Mg(2+) are present . In contrast, both the mutant protein and the 59 kDa fragment do not show evidence for quinolone-driven changes . These data suggest that ciprofloxacin binds to the wild-type subunit in an interaction that involves Ser83 of GyrA and that both C and N-terminal domains may be required for effective drug-protein interactions . The bell-shaped dependence of the binding process upon Mg(2+) concentration, with a maximum centred at 3-4 mM {Mg(2+)}, is consistent with a metal-ion mediated GyrA-quinolone-interaction . Affinity chromatography data fully support these findings and additionally confirm the requirement for a free carboxylate to elicit binding of the quinolone to GyrA.We infer that the Mg(2+)-GyrA interaction at physiological metal ion concentration could bear biological relevance, conferring more conformational flexibility to the active enzyme . The results obtained in the presence of ciprofloxacin additionally suggest that the Mg(2+)-mediated quinolone binding to the enzyme might be involved in the mechanism of action of this family of drugs .

Curr Pharm Biotechnol, 2000 Dec, 1(4), 355 - 95
Structure alteration of polyketides by recombinant DNA technology in producer organisms--prospects for the generation of novel pharmaceutical drugs; Mendez C et al.; Actinomycetes are gram-positive bacteria and commercially important microorganisms . They are producers of approximately two thirds of all bioactive compounds known and they produce a great variety of compounds which have clinical application on the basis of their activity against different kinds of organisms and cells as antibacterial (macrolides, avermectins), antitumor (anthracyclines, angucyclines, aureolic acid group) and also compounds showing immunosuppresant activity (rapamycin, FK506) . Most of these clinically useful pharmaceuticals produced by actinomycetes belong to the polyketide family . Polyketides comprise a wide family of chemically diverse compounds, many of which have shown bioactivity . The development of recombinant DNA technology has opened a new and exciting field of research for the generation of new bioactive compounds through genetic manipulation of the biosynthetic pathways . Researchers in this area are trying to take advantage of the enormous capability of actinomycetes to produce pharmaceutically useful compounds in order to manipulate the different biosynthetic pathways and subsequently generate novel drugs . Combinatorial biosynthesis is now emerging as a powerful tool to generate novel families of compounds by interchanging secondary metabolism genes between bioactive producing actinomycetes . Novel compounds will be the consequence of the concerted action of enzymes from different, but related, biosynthetic pathways . Insertional inactivation of selected genes and tailoring modification may also produce novel compounds that can be useful pharmaceuticals or lead compounds for further chemical modification . This minireview will present the state of the art in this field showing the different polyketides biosynthetic pathways so far characterized and how the identified genes are being used to generate structural biodiversity . Emphasis will be made on the polyketide family including type I and type II polyketides.

Pharm Res, 2001 May, 18(5), 573 - 8
Transport of levofloxacin in the OK kidney epithelial cell line: interaction with p-aminohippurate transport; Matsuo Y et al.; PURPOSE: To evaluate the mechanism of renal transport of quinolone antibacterial drugs, we examined the interaction of levofloxacin with p-aminohippurate (PAH) transport systems and the transport of levofloxacin in renal epithelial cells . METHODS: Transport of {14C}PAH or {14C}levofloxacin was measured using OK cell monolayers grown on microporous membrane filters . RESULTS: Transcellular transport from the basolateral to the apical side and cellular accumulation of {14C}PAH were inhibited by levofloxacin . Both the initial uptake of {14C}PAH from the basolateral side and the efflux to the apical side were inhibited by levofloxacin . The basolateral-to-apical transcellular transport of {14C}levofloxacin was greater than that in the opposite direction . {14C}Levofloxacin efflux to the apical side was greater than that to the basolateral side . Unlabeled levofloxacin and grepafloxacin inhibited the transcellular transport of {14C}levofloxacin, accompanied by an increase of cellular accumulation . However, neither PAH nor an anion transport inhibitor 4-4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) affected the basolateral-to-apical transport of {14C}levofloxacin nor its uptake from the basolateral side . CONCLUSIONS: These results indicated that levofloxacin inhibits PAH transport across both the basolateral and apical membranes of OK cells, but are not transported via the systems for PAH transport . The existence of a specific transport system for quinolones was indicated in OK cells.

Nefrologia, 2001 Mar-Apr, 21(2), 209 - 12
{Ciprofloxacin-induced vasculitis with cutaneous and renal involvement}; Pons R et al.; Quinolone antibiotics are frequently used in the practice of medicine . Nephrotoxic side effects related to the use of quinolones are uncommon . We report a patient in treatment with ciprofloxacin who presented with purpuric skin lesions and alteration of renal function . We review these antibacterial agents with special attention on associated adverse reactions, and present-day experience with the newer quinolone antibiotics.

Eur Urol, 2001 May, 39(5), 538 - 43
Prostate-specific antigen (PSA) value change after antibacterial therapy of prostate inflammation, as a diagnostic method for prostate cancer screening in cases of PSA value within 4-10 ng/ml and nonsuspicious results of digital rectal examination; Karazanashvili G et al.; OBJECTIVES: Investigation of the possibilities of improving the accuracy of prostate cancer (PC) screening among patients with a PSA value of 4-10 ng/ml and nonsuspicious results of digital rectal examination (DRE), using as diagnostic method the PSA value change (PSA-VCh) after antibacterial treatment of prostate inflammation . METHODS: The study included 61 patients with PSA 4-10 ng/ml, nonsuspicious DRE and inflammation in expressed prostate secretion (EPS) . All these patients underwent antibacterial therapy with the following repeated PSA determination and PSA-VCh assessment . RESULTS: Antibacterial therapy led to PSA decrease in 80% of cases . Effectiveness of PSA-VCh in PC screening was estimated . Sensitivity of PSA-VCh (with cut-off point -0.1.100%) equaled 85%, specificity 96%, positive predictive value 85% and negative predictive value 96% . CONCLUSIONS: Prostate inflammation proves to be a significant factor contributing to serum PSA elevation up to 10 ng/ml among patients with nonsuspicious DRE . Assessment of PSA-VCh after antibacterial treatment can improve PC screening accuracy in cases of PSA 4-10 ng/ml, nonsuspicious DRE and inflammation in EPS.

Int J Antimicrob Agents, 2001 Jul, 18(1), 85 - 8
Antibacterial activity of black myrobalan (Terminalia chebula Retz) against Helicobacter pylori; Malekzadeh F et al.; The effect of ether, alcoholic and water extracts of black myrobalan (Teminalia chebula Retz) on Helicobactor pylori were examined using an agar diffusion method on Columbia Agar . Water extracts of black myrobalan showed significant antibacterial activity and had a minimum inhibitory concentration (MIC) and minimum bacteriocidal concentration (MBC) of 125 and 150 mg/l, respectively . The extract was active after autoclaving for 30 min at 121 degrees C . Plant powder (incorporated in agar) gave higher MIC and MBC values (150 and 175 mg/l, respectively) . Water extracts of the black myrobalan at a concentration of 1-2.5 mg/ml inhibited urease activity of H . pylori . The results show that black myrobalan extracts contain a heat stable agent(s) with possible therapeutic potential . Other bacterial species were also inhibited by black myrobalan water extracts.

J Pept Sci, 2001 Jun, 7(6), 297 - 304
Antibacterial activity of bactenecin 5 fragments and their interaction with phospholipid membranes; Tokunaga Y et al.; Bactenecin 5 (Bac 5) is an antibacterial 43mer peptide isolated from bovine neutrophils . It consists of an Arg-rich N-terminal region and successive repeats of Arg-Pro-Pro-Ile (or Phe) . We synthesized Bac 5(1-23) and several related peptides to clarify the roles these regions play in antibacterial activity . An assay of antibacterial activity revealed that such activity requires the presence of Arg residues at or near the N-terminus, as well as a chain length exceeding 15 residues . None of the peptides exhibited haemolytic activity . Polyproline II-like CD curves were observed for most of the peptides . Measurements of the membrane perturbation and fusion indicated that the perturbation and fusogenic activities of the peptides were, generally, parallel to their antibacterial activities . Amino acid substitution in the repeating region had some effect on antibacterial activity.

CNS Drugs, 2001, 15(2), 105 - 18
Clinically significant drug interactions with agents specific for migraine attacks; Eadie MJ; The drugs which provide specific relief from migraine attacks, the ergopeptides (ergotamine and dihydroergotamine) and the various 'triptans' (notably sumatriptan), are often prescribed for persons already taking various migraine preventative agents, and sometimes drugs for other indications . As a result, migraine-specific drugs may become involved in drug-drug interactions . The migraine-specific drugs all act as agonists at certain subclasses of serotonin (5-hydroxytryptamine; 5-HT) receptor, particularly those of the 5-HT1D subtype, and produce vasoconstriction through these receptor-mediated mechanisms . The oral bioavailabilities of these drugs, particularly those of the ergopeptides, are often incomplete, due to extensive presystemic metabolism . As a result, if migraine-specific agents are coadministered with drugs with vasoconstrictive properties, or with drugs which inhibit the metabolism of the migraine-specific agents, there is a risk of interactions occurring which produce manifestations of excessive vasoconstriction . This can also occur through pharmacodynamic mechanisms, as when ergopeptides or triptans are coadministered with methysergide or propranolol (although a pharmacokinetic element may apply in relation to the latter interaction), or if one migraine-specific agent is used shortly after another . When ergopeptide metabolism is inhibited by the presence of macrolide antibacterials, particularly troleandomycin and erythromycin, the resultant interaction can produce ergotism, sometimes leading to gangrene . Similar pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably apply to combination of the ergopeptides with HIV protease inhibitors (indinavir and ritonavir), heparin, cyclosporin or tacrolimus . Inhibition of triptan metabolism by monoamine oxidase A inhibitors, e.g . moclobemide, may raise circulating triptan concentrations, although this does not yet seem to have led to reported clinical problems . Caffeine may cause increased plasma ergotamine concentrations through an as yet inadequately defined pharmacokinetic interaction . However, a direct antimigraine effect of caffeine may contribute to the claimed increased efficacy of ergotamine-caffeine combinations in relieving migraine attacks . Serotonin syndromes have been reported as probable pharmacodynamic consequences of the use of ergots or triptans in persons taking serotonin reuptake inhibitors . There have been two reports of involuntary movement disorders when sumatriptan has been used by patients already taking loxapine . Nearly all the clinically important interactions between the ergopeptide antimigraine agents and currently marketed drugs are likely to have already come to notice . In contrast, new interactions involving the triptans are likely to be recognised as additional members of this family of drugs, with their different patterns of metabolism and pharmacokinetics, are marketed.

Acta Cient Venez, 2000, 51(4), 257 - 63
{Changes in serum enzymes in rats treated with sodium bisulfite}; Alarcon-Corredor OM et al.; Inorganic sulfites are chemical compounds with antioxidative, antibacterial and antimycotic properties diffusely employed in agro-food and pharmaceutical industries . In spite of their continuous use there still are many questions regarding their safety, and their possible influence in several nutrients and enzymatic systems, as according to reports in the literature cited . In this study it is determined the effect of increasing doses of sodium bisulphite, 10 to 50 mg/kg/day, injected intramuscularly during seven days on the activity of the following serum enzymes: phosphohexoseisomerase (PHI), gamma-glutamyltranspeptidase (gamma-GT), cholinesterase (CHE), arginase, acid maltase (AM), alkaline phosphatase (AIP), lactic dehydrogenase (LDH), transaminases (GOT and GPT) and 5'-nucleotidase (5'-N) on male Wistar rats (treated groups) . The results indicate that in rats treated with sodium bisulphite there is a significant increase (p < 0.05) in the activity of PHI, gamma-GT, arginase, AIP, GOT, GPT and 5'-N as well as an equally significant decrease (p < 0.05) in the activity of LDH, AM and CHE; these variations are proportional to the doses of the compound applied . These findings indicate there is cellular damage to rat liver, kidney or others organs as a result of bisulphite injected or by its metabolic derivatives . It is suggested that measurements of serum levels of LDH, AM and CHE are particularly helpful in the clinical assessment of pathologies caused by sulfites in allergology.

Mar Environ Res, 2000 Jul-Dec, 50(1-5), 153 - 6
Developmental evaluation of a potential non-steroidal estrogen: triclosan; Foran CM et al.; Triclosan is an antibacterial agent commonly used in industry and often detected in waste-water effluent . The potential of triclosan to act as an endocrine disruptor was examined because its chemical structure closely resembles known non-steroidal estrogens (e.g . DES, bisphenol A) . Japanese medaka fry (Oryzias latipes) were exposed for 14 days beginning 2 days post-hatch to triclosan (100, 10, 1 micrograms/l), 17-beta estradiol (E2; 1 microgram/l), or a solvent control (ethanol) . Two months post-exposure, the phenotypic sex of each adult was assessed visually using sexually dimorphic fin shape and size . The proportion of females in each group was similar for triclosan-exposed animals and solvent-treated controls (ethanol 53%, 1 ppb 58%, 10 ppb 45%, 100 ppb 36%) although E2 treatment did produce 92% female adults . Sexually dimorphic fin traits were quantified to look for potential effects of triclosan and E2 on the development of secondary sexual characters . These results do not support the hypothesis that triclosan is potently estrogenic . However, changes in fin length and non-significant trends in sex ratio suggest triclosan is potentially weakly androgenic.

Bioorg Med Chem Lett, 2001 Jul 23, 11(14), 1903 - 6
3-Arylpiperidines as potentiators of existing antibacterial agents; Thorarensen A et al.; Important resistance patterns in Gram-negative pathogens include active efflux of antibiotics out of the cell via a cellular pump and decreased membrane permeability . A 3-arylpiperidine derivative (1) has been identified by high-throughput assay as a potentiator with an IC(50) approximately 90 microM . This report details the evaluation of the tether length, aryl substitution and the importance of the fluorine on antibiotic accumulation . Evaluation of various tether lengths demonstrated that the two-carbon tethered analogues are optimal . Removal of the fluorine has a modest effect on antibiotic accumulation and the defluorinated analogue 17 is equally potent to the original lead 1.

Bioconjug Chem, 2001 Jul-Aug, 12(4), 464 - 9
Syntheses of Curcumin Bioconjugates and Study of Their Antibacterial Activities against beta-Lactamase-Producing Microorganisms; Kumar S et al.; In the present study curcumin bioconjugates, viz . di-O-glycinoylcurcumin (I), di-O-glycinoyl-C(4)-glycylcurcumin (II), 5'-deoxy-5'-curcuminylthymidine (5'-cur-T) (IV), and 2'-deoxy-2'-curcuminyluridine (2'-cur-U) (V) have been synthesized and characterized by elemental analysis and (1)H NMR . The turmeric peptide (Tp) was isolated from the aqueous turmeric extract of the turmeric rhizome . The antibacterial activity of these four bioconjugates and also of the turmeric peptide and sodium salt of curcumin (III) have been tested particularly for beta-lactamase-producing microorganisms.

Zhonghua Yi Xue Za Zhi (Taipei), 2001 Mar, 64(3), 133 - 40
Preventive dental care for children and adolescents; Drummond BK; Preventive dental care for children and adolescents requires a good understanding of the dental caries process and the particular relationships that exist throughout childhood and young adulthood . Only when these relationships are understood can they be used to diagnose dental caries risk and apply appropriate preventive therapies and restorative care that is effective . The need to diagnose risk when applying preventive care is as important for individual patients as it is for population groups . At the individual level, the aim is to aid the development of a healthy functioning dentition for life . This applies in the population group level but the cost benefits also become important in justifying the funding to carry out preventive practices . Risk can be determined by general factors including the socioeconomic status, access to optimally fluoridated drinking water and age . Specific factors include the microbiology of the dental plaque, dietary practices, oral hygiene practices, individual fluoride use and previous dental caries history . Once the risk has been diagnosed and the related factors identified, the best preventive approach can be selected . This may include oral hygiene, dietary change, fluoride recommendations, restorative care using fluoride releasing materials or antibacterial mouthwashes . The dentist may play several roles in preventive dental care . The first is as the giver of advice and care for the individual child patient; the second is as an advocate to help the child get the care by getting the consent and support of the parents; and the third may be to lobby for the appropriate funding to obtain this care in publicly funded programs.

Acta Vet Scand, 2001, 42(1), 189 - 98
Antibacterial drugs prescribed for dogs and cats in Sweden and Norway 1990-1998; Odensvik K et al.; The usage of veterinary antibacterial drugs in dogs and cats in Sweden and Norway for the period 1990-1998 was investigated by use of drug wholesalers' statistics . Additionally, usage of human antibacterial drugs in these species in Sweden was investigated by use of prescription data for the period 1996-1998 . On average, more than 50% of the prescribed veterinary antibacterials in Sweden were beta-lactam antibiotics . In Norway, about 75% of the preparations prescribed for dogs and cats contained sulfonamides and trimethoprim . Furthermore, the prescription data from Sweden showed a reduced usage of human antibacterials prescribed for dogs and cats since the beginning of the 1980s . Approximately 20% of the prescribed packages for dogs in the years 1996-1998 were human approved drugs . The corresponding figure for cats was 13% . The differences between the countries in the choice of antibacterial drugs can be explained by differences in the availability of approved preparations during the study period . The consumption of veterinary antibacterials in dogs and cats in Sweden during the period was in the range of 3% to 8% of the total use of veterinary antibacterials . The corresponding figures in Norway were in the range of 3% to 7% . It is of vital importance to study usage patterns of antibacterial drugs in dogs and cats in surveillance and control of bacterial resistance, but also in discussions of therapeutic appropriateness . Therefore, further research is needed in this area.

Ann Acad Med Singapore, 2001 May, 30(3), 226 - 33
Perioperative treatment with bactericidal/permeability-increasing protein (rBPI21) in major liver surgery: a concise summary; Wiezer MJ et al.; INTRODUCTION: Major hepatic resections are still associated with considerable morbidity . Gut-derived bacteria and bacterial endotoxin are considered to play a central role in the pathophysiology of complications . Experimental studies suggest that bactericidal/permeability-increasing protein (BPI), which has both antibacterial and endotoxin-neutralising properties, can reduce postoperative complications . MATERIAL AND METHODS: A phase II, double-blind, placebo-controlled, multicentre, dose escalation trial was conducted in patients undergoing major liver resection, and clinical outcome, infectious complications, plasma amino acid patterns, coagulation and fibrinolytic cascade systems and neutrophil functions were compared between the two treatment groups and an extra group of patients undergoing major abdominal non-hepatic surgery . RESULTS: Drug administration in this patient group was safe, and resulted in a significant reduction of infectious complications . Furthermore, beneficial effects were found in the postoperative amino acid ratio and fibrinolytic cascades, and rBPI21 preserved leukocyte functions . CONCLUSION: Administration of rBPI21 in patients undergoing major liver resection is well tolerated and results in improvement of both clinical and biochemical parameters.

Arzneimittelforschung, 2001, 51(6), 501 - 5
In vivo susceptibility of Mycobacterium ulcerans to KRM-1648, a new benzoxazinorifamycin, in comparison with rifampicin . Anti-mycobacterial activity of KRM-1648; Dhople AM; The antibacterial effects of a new benzoxazinorifamycin, KRM-1648 (3'-hydroxy-5'-(4-isobutyl-1-piperazinyl, CAS 129791-92-0), against Mycobacterium ulcerans were evaluated in vivo in mouse foot pads, and the results were compared against those obtained with rifampicin (rifampin, CAS 13292-46-1) . When mice were fed with the drugs from the day of footpad inoculations, KRM-1648, at concentrations of 0.001% and higher, mixed in mouse food, was effective in inhibiting the growth of M . ulcerans in the foot pads, and the effects were bactericidal . Effects of KRM-1648 at 0.0005% were bacteriostatic . Similar results were obtained with rifampicin, but only at concentrations of 0.008% and above . In established infection, i.e., when M . ulcerans were growing actively in footpads, bactericidal effects were observed with KRM-1648 at concentrations of 0.002% and above; to obtain similar results with rifampicin, the minimum dose was 0.032% . Thus, the results suggest the superiority of KRM-1648 over rifampicin in the treatment of M . ulcerans infection . The possibility of using KRM-1648 in combination with other antimycobacterial agents is discussed.

Curr Opin Cell Biol, 2001 Aug, 13(4), 412 - 6
Protein export and drug efflux through bacterial channel-tunnels; Andersen C et al.; The bacterial protein TolC assembles into an alpha-helical trans-periplasmic tunnel, which is embedded in the outer membrane by a contiguous beta-barrel channel . TolC and its homologues thus provide large exit ducts for a wide range of substrates, including protein toxins and antibacterial drugs, that are engaged by specific recognition proteins in the cytosolic membrane.

J Agric Food Chem, 2001 Jul, 49(7), 3145 - 50
Determination of sulfamethazine and trimethoprim in liquid feed premixes by HPLC and diode array detection, with an analysis of the uncertainty of the analytical results; Cancho Grande B et al.; Sulfamethazine (SMZ) and trimethoprim (TMP) are antibacterials used in veterinary practice . This paper describes a method for their determination in veterinary liquid feed premixes that is based on liquid chromatography with diode array detection . Gradient elution with methanol and ammonium acetate achieved excellent separation of the two analytes within 15 min without any interference from the matrix . Absorbance of the column effluent was monitored at 264 nm for SMZ and at 230 nm for TMP . Detailed analyses of the uncertainties of determinations afford estimated expanded uncertainties of, respectively, 0.2 and 0.1 w/v % for typical SMZ and TMP concentrations of 10.7 and 2.1 w/v %, respectively . At the lower end of the calibrated range of the method, the dominant source of uncertainty is the preparation of standards and the construction of the calibration line.

Eur J Clin Microbiol Infect Dis, 2001 May, 20(5), 346 - 9
Risk factors for esophageal candidiasis in a large cohort of HIV-infected patients treated with nucleoside analogues; Abgrall S et al.; To assess the risk factors for esophageal candidiasis (EC), a cohort study and a case-control study were conducted using 1,368 French patients who were already participating in the Delta trial (which compared different types of antiretroviral therapy in HIV-infected patients) and who had no previous history of EC . During a median follow-up period of 19 months, 87 (6%) patients developed EC . The results of the cohort study showed an increased risk of EC associated with a low baseline CD4+ cell count (P<0.0001), a high baseline plasma HIV RNA level (P < 0.0001) and prior zidovudine therapy (P = 0.02) at entry to the study . The case-control study revealed an increased risk of EC in patients with a recent low CD4+ cell count (P < 0.0002), recent antibacterial chemotherapy (P = 0.01) and oral candidiasis (P < 0.05) . Cotrimoxazole prophylaxis also increased the risk of EC (P = 0.04) in the case-control study.

Lik Sprava, 2000 Sep, (6), 74 - 7
{Acute pyelonephritis associated with intestinal dysbacteriosis: incidence and enhancement of efficiency of treatment}; Ukhal' EM et al.; A study was made on the incidence rate of acute pyelonephritis associated with intestinal dysbacteriosis in urological patients (n = 68) . Prehospitalization and precombined-treatment duration of the illness came up to one to four days . It has been ascertained as a result of the conducted study that under present ecological conditions, acute pyelonephritis runs its course in the presence in patients of dysbacteriosis of the intestines even before the start of treatment in an urological clinic setting . Antibacterial treatment of patients with acute pyelonephritis without simultaneous action on the pathogenic intestinal microflora and normalization of colonizing normoflora was found to produce profound aggravation of dysbacteriosis and to result in the development of candidasis . Extermination with the aid of the intestinal antibiotic intetrix of the pathogenic microflora in the intestines together with achieving of normalization of intestinal normoflora by way of the enteral intake by patients with acute pyelonephritis of eubiotics permit the marked improvement to be achieved in results of combined treatment thereof.

J Chemother, 2001 Jun, 13(3), 255 - 9
Antibacterial activity and post-antibiotic effect of flurithromycin compared with other macrolides and penicillins against periodontal pathogens; Lo Bue AM et al.; In this study the authors examined the activity of flurithromycin compared to that of erythromycin, spiramycin and penicillin against 107 strains of various species supposed to cause periodontitis . The range of MICs of flurithromycin was: < or =0.06-2 mg/l for P . gingivalis (28 isolates), 0.06-2 mg/l for P . melaninogenica (7), 0.5-4 mg/l for P . intermedia (5), 0.25-8 mg/l for Prevotella sp . (8), 1-16 mg/l for F . nucleatum (14), 0.12-0.5 mg/l for W . recta (2), 0.5-32 mg/l for E . corrodens, 0.5-2 mg/l for B . forsythus (2); < or =0.06-64 mg/l for Peptostreptococcus sp . (11), < or =0.06-1 mg/l for A . odontolyticus (11) and for A . naeslundii (7) and < or =0.06-16 mg/l for A . viscosus (7) . Macrolide activity was ranked in decreasing order from flurithromycin to erythromycin to spiramycin . Beta-lactamase production was demonstrated in Prevotella sp . (20%) and in F . nucleatum (7%) . Isolates which were beta-lactamase negative but resistant to penicillin were found among Peptostreptococcus sp . and Actinomyces sp . A post-antibiotic effect of 2 hours was seen for flurithromycin on P . gingivalis and E . corrodens . The good in vitro activity of flurithromycin against bacteria supposed to cause periodontitis suggests clinical potential in the treatment of these diseases.

Fitoterapia, 2000 Sep, 71(5), 559 - 61
Antibacterial activity and cytotoxicity of Miliusa velutina; Jumana S et al.; Goniothalamusin and two mixtures, acetogenins-A and acetogenins-B, isolated from a petroleum ether extract of the stem bark of Miliusa velutina exhibited significant antibacterial and cytotoxic activities.

Fitoterapia, 2000 Feb, 71(1), 69 - 71
Antibacterial activity of the essential oil of Cymbopogon densiflorus; Takaisi-Kikuni NB et al.; The essential oil of Cymbopogon densiflorus showed a wide spectrum of activity against Gram-positive and Gram-negative bacteria.

Cytokine, 2001 May 21, 14(4), 240 - 2
Stimulation of TNF-alpha release in monocytes by honey; Tonks A et al.; Although evidence exists for the antibacterial effects of honey there is limited objective evidence for direct promotion of healing . We investigated the effect of manuka, pasture and an artificial honey on macrophage function . Reactive oxygen intermediate (ROI) production was assessed by luminol enhanced chemoluminescence and tumour necrosis factor-alpha (TNF-alpha) release was determined by immunoassay . ROI production was significantly (P<0.001) decreased by pasture honey and manuka honey . TNF-alpha release was significantly enhanced (P<0.001) in unprimed MM6 cells by manuka and pasture honey but was not altered in primed cells . These results could explain the suggested therapeutic properties of honey in promoting wound healing .

Infect Immun, 2001 Aug, 69(8), 4823 - 30
Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages; Jubier-Maurin V et al.; Brucella spp . can establish themselves and cause disease in humans and animals . The mechanisms by which Brucella spp . evade the antibacterial defenses of their host, however, remain largely unknown . We have previously reported that live brucellae failed to induce tumor necrosis factor alpha (TNF-alpha) production upon human macrophage infection . This inhibition is associated with a nonidentified protein that is released into culture medium . Outer membrane proteins (OMPs) of gram-negative bacteria have been shown to modulate macrophage functions, including cytokine production . Thus, we have analyzed the effects of two major OMPs (Omp25 and Omp31) of Brucella suis 1330 (wild-type {WT} B . suis) on TNF-alpha production . For this purpose, omp25 and omp31 null mutants of B . suis (Deltaomp25 B . suis and Deltaomp31 B . suis, respectively) were constructed and analyzed for the ability to activate human macrophages to secrete TNF-alpha . We showed that, in contrast to WT B . suis or Deltaomp31 B . suis, Deltaomp25 B . suis induced TNF-alpha production when phagocytosed by human macrophages . The complementation of Deltaomp25 B . suis with WT omp25 (Deltaomp25-omp25 B . suis mutant) significantly reversed this effect: Deltaomp25-omp25 B . suis-infected macrophages secreted significantly less TNF-alpha than did macrophages infected with the Deltaomp25 B . suis mutant . Furthermore, pretreatment of WT B . suis with an anti-Omp25 monoclonal antibody directed against an epitope exposed at the surface of the bacteria resulted in substancial TNF-alpha production during macrophage infection . These observations demonstrated that Omp25 of B . suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages.

Pharmacotherapy, 2001 Jul, 21(7 Pt 2), 100S - 104S
The use of fluoroquinolones as antiinfective transition-therapy agents in community-acquired pneumonia; Press RA; The newer quinolone antibiotics, including levofloxacin, moxifloxacin, and gatifloxacin, offer coverage of the likely pathogens in community-acquired pneumonia (CAP) and have been shown to be safe and effective treatments for CAP . Two of these agents, levofloxacin and gatifloxacin, have pharmacokinetic and antibacterial properties that are similar in both oral and intravenous formulations . As such, they may be excellent candidates for transition therapy involving early switch from intravenous to oral therapy followed by early hospital discharge for patients with CAP

Drug Discov Today, 2001 Jul 1, 6(14), 721 - 727
Phage display for target-based antibacterial drug discovery; Christensen DJ et al.; Increasing bacterial drug resistance and hard-to-eradicate opportunistic infections have created a need for new antibiotics . Sequencing of microbial genomes has yielded many new potential targets for antibacterial drug discovery . However, little is known about the biochemical activities of many of these targets, making it difficult to develop HTS assays for them . Peptides isolated by phage display can be used as 'surrogate ligands' in competition assays for screening of targets of unknown function with small-molecule libraries . These screening assays can be adapted into a variety of high-throughput formats, including those based on radioactive, luminescence or fluorescence detection.

Peptides, 2001 Jul, 22(7), 1093 - 8
MALDI-PSD-MS analysis of the phosphorylation sites of caseinomacropeptide; Talbo GH et al.; Caseinomacropeptide (CMP) is a 64 amino acid polypeptide corresponding to kappa-casein 106-169 . CMP naturally exists in several forms due to extensive posttranslational modifications including glycosylation and phosphorylation . The aglycosylated, phosphorylated form of CMP has been shown to exhibit antibacterial activity . The aim of this study was to use matrix assisted laser desorption/ionization post source decay mass spectrometry (MALDI-PSD-MS) to identify the phosphorylation sites in the CMP sequence . CMP was isolated from a chymosin digest of casein by HPLC and then digested with endoproteinase Glu-C to generate peptides suitable for MALDI-PSD-MS analysis . This analysis showed that CMP is fully phosphorylated at Ser(149) and only partially phosphorylated at Ser(127.) Dehydroalanyl residues corresponding to the phosphoserines of CMP were detected upon MALDI-PSD-MS analysis suggesting that the phosphoryl bond in phosphoserine is very labile during PSD analysis such that the phosphoryl group may be lost before backbone fragmentation.

J Vet Pharmacol Ther, 2001 Jun, 24(3), 187 - 92
Comparison of cefepime pharmacokinetics in neonatal foals and adult dogs; Gardner SY et al.; The pharmacokinetics of cefepime, a new fourth generation cephalosporin with enhanced antibacterial activity, was examined in neonatal foals and adult dogs . Cefepime was administered intravenously (i.v.) at a dose of 14 mg/kg to five neonatal foals and six adult dogs . Blood samples were collected in both groups of animals and plasma cefepime concentrations measured by reverse-phase high-performance liquid chromatography (HPLC) . Cefepime concentrations in both groups of animals were described by a two-compartment pharmacokinetic model with elimination half-lives of 1.65 and 1.09 h for the foal and dog, respectively . We tested whether or not pharmacokinetic parameters for cefepime could be scaled across species using principles of allometry . The parameters of elimination half-life (t(1/2)beta), apparent volume of distribution (VDarea), and systemic clearance (CL) were scaled linearly to body weight on a double logarithmic plot with allometric exponents for body weight of 0.26, 1.08 and 0.72, respectively . This study further determined doses for cefepime, a potentially useful antibiotic for neonatal foals and dogs, from the pharmacokinetic values . An i.v . dose of cefepime estimated from this study for treating sensitive bacteria was 11 mg/kg every 8 h for neonatal foals and 40 mg/kg every 6 h for dogs.

J Vet Pharmacol Ther, 2001 Apr, 24(2), 111 - 6
Absorption, tissue distribution and excretion of flumequine and oxolinic acid in corkwing wrasse (Symphodus melops) following a single intraperitoneal injection or bath treatment; Samuelsen OB et al.; The pharmacokinetic properties of the antibacterial agents oxolinic acid and flumequine were studied in corkwing wrasse (Symphodus melops) after either intraperitoneal injection or bath treatment . Following intraperitoneal administration the peak plasma concentrations (Cmax) and the time to peak plasma concentrations (Tmax) were estimated to be 2.0 microg/mL and 12 h, respectively, for oxolinic acid and 2.6 microg/mL and 12 h, respectively, for flumequine . In muscle, Cmax and Tmax were estimated to 6.7 microg/g and 12 h, respectively, for oxolinic acid with corresponding values of 8.5 microg/g and 13 h, respectively, for flumequine . In liver, Cmax and Tmax were calculated to 7.0 microg/g and 12 h, respectively, for oxolinic and 12.2 microg/g and 11 h, respectively, for flumequine . Elimination half-lives (t1/2 beta) of 26, 24 and 29 h, respectively, for plasma, muscle and liver were calculated for flumequine . For oxolinic acid two distinct elimination phases were found and calculated to be 16 h (t1/2 beta) and 57 h (t1/2 gamma) in plasma, 15 and 59 h, respectively, in muscle and 20 and 72 h, respectively, in liver . Bath treatment using 150 mg/L of flumequine or 200 mg/L of oxolinic acid for 72 h resulted in flumequine concentrations of 1.0 microg/mL in plasma, 5.0 microg/g in muscle and 12.4 microg/g in liver . Corresponding values for oxolinic acid were 1.0 microg/g in plasma, 2.5 microg/g in muscle and 4.9 microg/g in liver.

J Clin Periodontol, 2001 Aug, 28(8), 776 - 81
Effects of metal salts on the oral production of volatile sulfur-containing compounds (VSC); Young A et al.; BACKGROUND, AIM: Halitosis, mainly caused by bacteria located on the posterior dorsum of the tongue and in periodontal pockets, is due to formation of volatile sulfur compounds (VSC) . The hypothesis to be tested was that the affinity of a metal for sulfur determines its anti-VSC activity . METHOD: Clinical tests were carried out on 12 subjects who rinsed with cysteine to induce halitosis (baseline) before rinsing with 7.34 mM ZnCl2, SnF2 and CuCl2 . Mouth air VSC analyses were repeated following cysteine rinses at 1 h, 2 h and 3 h using a gas chromatograph . In vitro experiments tested toxic metals Hg2+, Pb2+ and Cd2+ . 10-microl aliquots of metal salts were added to 1-ml aliquots of human whole saliva from 30 subjects . Samples were incubated overnight at 37oC and saliva headspace was analyzed for VSC in a gas chromatograph . CLINICAL RESULTS: Cu2+>Sn2+>Zn2+ (supports hypothesis) . Zn2+ had significantly less anti-VSC effect compared with Cu2+ and Sn2+ at 1, 2 and 3 h . In vitro results indicated that Hg2+, Cu2+ and Cd2+ had close to 100% anti-VSC effect, and that Pb2+ was less effective and Cd2+ more effective than expected in inhibiting VSC . CONCLUSIONS: Apart from Hg2+ and Cu2+, the metals had a significantly greater effect on H2S than on CH3SH . Cu2+ and Hg2+ have well-known antibacterial activity and may presumably also operate by this mechanism.

J Comb Chem, 2001 Jul-Aug, 3(4), 346 - 53
Parallel synthesis and biocatalytic amplification of a cross-conjugated cyclopentenone library; Jang WB et al.; A combination of parallel chemical synthesis and biocatalysis has been used to prepare and amplify a library of cross-conjugated cyclopentenones . A number of marine and terrestrial natural products with antibiotic activity are known to incorporate this pharmacophore . The library was screened for anticancer, antimycobacterial, antifungal, and antibacterial activity . The positive results from the screens provide an indication of the structural features that are associated with activity in the various assays and suggest promising avenues for further inquiry.

J Chromatogr A, 2001 Jun 15, 919(2), 395 - 406
Prediction of electrophoretic behaviour of a series of quinolones in aqueous methanol; Barron D et al.; Quinolones are a family of antibacterial agents used in human and veterinary clinics . The examination of protonation equilibria is essential because their antibacterial activity is pH-dependent . In this work, dissociation constants of quinolones in MeOH-water mixtures were obtained using capillary electrophoresis . The method is based on a model that relates electrophoretic mobility of the solute with pH . The effect of pH, pKa and activity coefficient on electrophoretic behaviour was considered . Standard pH values for buffer solutions were previously determined in MeOH-water mixtures, and the pH can thus be measured in these media as in water . This model is also used to obtain the optimum conditions for the separation of a series of substances because it allows one to predict the resolution between adjacent peaks from a few experimental data.

Am J Ther, 2001 Jul-Aug, 8(4), 243 - 6
Some plasma pharmacokinetic parameters of isoniazid in the presence of a fluoroquinolone antibacterial agent; Ofoefule SI et al.; The effects of ciprofloxacin (CP), a fluoroquinolone antibacterial agent, on the extent of absorption of isoniazid (INH) and on some of its pharmacokinetic parameters were investigated in six healthy female volunteers between the ages of 23 and 32 years . The presence of CP led to increase in the amount of INH and to a slight reduction in its peak plasma concentration (Cmax) . There was a 1-hour increase in the time to attain Cmax (tmax) of INH, indicating absorption interaction between the two drugs . This absorption interaction was related to inhibition of cholinergic neurotransmission caused by CP, which is capable of inhibiting gastric motility, leading to a delay in gastric emptying . The rate of elimination (K) and plasma half-life (t1/2) of INH were not significantly affected (P = 0.05) . The extent of absorption interaction that may have occurred (based on values of 24-hour values for area under the concentration curve, Cmax, Tmax, K, and t1/2) was considered to be of no therapeutic consequence, and the coadministration of the two drugs may be recommended in clinical practice.

J Invertebr Pathol, 2001 May, 77(4), 237 - 42
Purification and characterization of a natural agglutinin in the hemolymph of the prawn Penaeus indicus H . Milne Edwards; Jayasree S; A natural agglutinin in the hemolymph of the marine prawn Penaeus indicus was isolated by gel filtration chromatography, purified using polyacrylamide gel electrophoresis, and characterized . Prawn agglutinin has a native molecular mass of 181 kDa and consists of two monomeric units (97 and 84 kDa), maintains some agglutinating activity over a wide pH range (7-9), and is inactivated at 85 degrees C . The agglutinin was denatured upon mixing with trichloroacetic acid, phenol, chloroform, and 45% ammonium sulfate . It was also sensitive to trypsin digestion . The results indicate that prawn agglutinin is proteinaceous in nature, with agglutinating, hemolytic, and antibacterial properties against marine bacteria and erythrocytes with carbohydrate binding sites .

J Urol, 2001 Jul, 166(1), 240 - 3
Parental preferences in the management of vesicoureteral reflux; Ogan K et al.; PURPOSE: We determined parental preferences for the treatment of vesicoureteral reflux in their child . MATERIALS AND METHODS: Parents of children with vesicoureteral reflux were prospectively recruited to evaluate choices in reflux management . In each case a standard questionnaire that described the treatment options for reflux was administered . Parents were asked to choose between long-term antibacterial prophylaxis with annual radiography studies and open or endoscopic treatment at each of 1 to 5 years of followup . They were also given the choice between open or endoscopic treatment . Annual resolution and/or correction rates provided for medical, surgical and endoscopic management were 20%, 95% to 100% and 80% after 1 or 2 injections, respectively . RESULTS: We queried 91 families of female (81%) and male (19%) patients . Average duration of reflux followup was 2 years and mean patient age was 49.8 months . At diagnosis reflux was grades I to II in 65% of cases, grade III in 26% and grades IV to V in 9% . The majority of parents chose daily antibiotics over surgery if the child was predicted to have vesicoureteral reflux for 1 to 4 years . However, the majority chose ureteral reimplantation over daily antibiotics and yearly x-ray if a 5-year course was predicted . In contrast, parents chose daily antibiotics rather than endoscopic treatment if the anticipated interval was 1 to 3 years . After 3 years the majority preferred the endoscopic approach . Also, 60% of parents stated that they would choose endoscopic treatment over reimplantation, although the child may require repeat endoscopic treatment and there was a 20% chance of persistent vesicoureteral reflux . CONCLUSIONS: Parents of children with vesicoureteral reflux prefer antibiotic prophylaxis as initial treatment . However, when daily antibiotics and yearly cystography may be required beyond 3 to 4 years, most parents would choose definitive correction . While endoscopic treatment is less effective than surgery, parents prefer endoscopic treatment, most likely because it is less invasive . Also, when compared directly against each other, the majority of parents stated that they would choose endoscopic treatment over surgery, although it has a lower success rate.

Am J Physiol Lung Cell Mol Physiol, 2001 Aug, 281(2), L309 - 13
X-ray microanalysis of airway surface liquid collected in cystic fibrosis mice; Zahm JM et al.; The airway surface liquid (ASL) that lines the airway surface epithelium plays a major role in airway antibacterial defense and mucociliary transport efficiency, two key factors in cystic fibrosis (CF) disease . A major difficulty is to collect ASL in native conditions without stimulation or alteration of the underlying airway epithelium . Using a cryoprobe specifically adapted to collect native ASL from the tracheal mouse surface, we analyzed by X-ray microanalysis the complete ASL and plasma ion content in Cftr(tm1Hgu)/Cftr(tm1Hgu) mice compared with that in control littermates . ASL ion content from eight Cftr(tm1Hgu)/Cftr(tm1Hgu) mice and eight control littermates did not appear significantly different . The mean (+/-SE) concentrations were 2,352 +/- 367 and 2,058 +/- 401 mmol/kg dry weight for Na, 1,659 +/- 272 and 1,448 +/- 281 mmol/kg dry weight for Cl, 357 +/- 57 and 337 +/- 38 mmol/kg dry weight for S, 1,066 +/- 220 and 787 +/- 182 mmol/kg dry weight for K, 400 +/- 82 and 301 +/- 58 mmol/kg dry weight for Ca, 105 +/- 31 and 105 +/- 20 mmol/kg dry weight for Mg, 33 +/- 15 and 29 +/- 9 mmol/kg dry weight for P in non-CF and CF mice, respectively . This cryotechnique appears to be a promising technique for analyzing the complete elemental composition of native ASL in CF and non-CF tissues.

Biochemistry, 2001 Jul 10, 40(27), 7973 - 83
Solution structure of the squash trypsin inhibitor MCoTI-II . A new family for cyclic knottins; Heitz A et al.; The "knottin" fold is a stable cysteine-rich scaffold, in which one disulfide crosses the macrocycle made by two other disulfides and the connecting backbone segments . This scaffold is found in several protein families with no evolutionary relationships . In the past few years, several homologous peptides from the Rubiaceae and Violaceae families were shown to define a new structural family based on macrocyclic knottin fold . We recently isolated from Momordica cochinchinensis seeds the first known macrocyclic squash trypsin inhibitors . These compounds are the first members of a new family of cyclic knottins . In this paper, we present NMR structural studies of one of them, MCoTI-II, and of a beta-Asp rearranged form, MCoTI-IIb . Both compounds display similar and well-defined conformations . These cyclic squash inhibitors share a similar conformation with noncyclic squash inhibitors such as CPTI-II, and it is postulated that the main effect of the cyclization is a reduced sensitivity to exo-proteases . On the contrary, clear differences were detected with the three-dimensional structures of other known cyclic knottins, i.e., kalata B1 or circulin A . The two-disulfide cystine-stabilized beta-sheet motif {Heitz et al . (1999) Biochemistry 38, 10615-10625} is conserved in the two families, whereas in the C-to-N linker, one disulfide bridge and one loop are differently located . The molecular surface of MCoTI-II is almost entirely charged in contrast to circulin A that displays a well-marked amphiphilic character . These differences might explain why the isolated macrocyclic squash inhibitors from M . cochinchinensis display no significant antibacterial activity, whereas circulins and kalata B1 do.

J Nat Prod, 2001 Feb, 64(2), 196 - 9
A facile synthetic approach to prenylated flavanones: first total syntheses of (+/-)-bonannione A and (+/-)-sophoraflavanone A; Wang Y et al.; A facile and efficient approach for the syntheses of both C-8 and C-6 prenylated flavonoids has been developed that features a highly regioselective prenylation of 2,4,6-trihydroxyacetophenone and regioselective cyclization of prenylated polyhydroxy chalcones . Thus, the first efficient total syntheses of (+/-)-sophoraflavanone A (1) and (+/-)-bonannione A (2), two naturally occurring geranylated flavanones with antibacterial activities, have been achieved starting from the key intermediate 3 via regioselective cyclization of geranylated tetrahydroxychalcone 4.

Fitoterapia, 2001 Jun, 72(5), 558 - 60
Antibacterial spectrum of Hypericum hookerianum; Mukherjee PK et al.; The antibacterial activity of the chloroform, acetone and methanol extracts of Hypericum hookerianum leaves and stems was evaluated . All extracts showed antibacterial activity against six different gram-positive and gram-negative bacteria, the methanol extracts exhibiting the maximum inhibitory activity at 400 microg/ml.

Fitoterapia, 2001 Jun, 72(5), 555 - 7
Constituents of Coriaria ruscifolia fruits; Valencia E et al.; Corianin (1) and ellagic acid 3,3'-dimethylether (2) were obtained from the methanol extract of powdered fruits of Coriaria ruscifolia . Biological screening of both compounds and of the methanol extract revealed slight antibacterial activity and cytotoxicity.

Fitoterapia, 2001 Jun, 72(5), 550 - 2
Antibacterial activity of Bergenia ciliata rhizome; Sinha S et al.; The methanol extract of Bergenia ciliata (tested at 200--1000 microg/disc) showed a wide spectrum of concentration-dependent antibacterial activity.

Fitoterapia, 2001 Jun, 72(5), 547 - 9
Antibacterial activity of Clausena heptaphylla; Sohrab MH et al.; The antibacterial activity of different crude extracts of Clausena heptaphylla leaves as well as three purified coumarins, obtained from the cold methanol extract, is reported.

Fitoterapia, 2001 Jun, 72(5), 544 - 6
Antibacterial activity of Jatropha multifida roots; Aiyelaagbe OO; Hexane, ethyl acetate, chloroform and methanol successive extracts of Jatropha multifida yellow rootbark, red rootbark and rootwood effectively inhibited the growth of B . subtilis and S . aureus at concentration of 200 microg/disk.

Biomaterials, 2001 Jul, 22(14), 2043 - 8
Influence of surface modifications to titanium on antibacterial activity in vitro; Yoshinari M et al.; The antibacterial effect of surface modifications to titanium on Porphyromonas gingivalis ATCC 33277 and Actinobacillus actinomycetemcomitans ATCC 43718 was evaluated . Surface modifications were performed with dry processes including ion implantation (Ca+, N+, F+), oxidation (anode oxidation, titania spraying), ion plating (TiN, alumina), and ion beam mixing (Ag, Sn, Zn, Pt) with Ar+ on polished pure titanium plates . F+-implanted specimens significantly inhibited the growth of both P . gingivalis and A . actinomycetemcomitans than the polished titanium . The other surface-modified specimens did not exhibit effective antibacterial activity against both bacteria . No release of the fluorine ion was detected from F-implanted specimens under dissolution testing . This result and the characterization of the F+-implanted surfaces suggested that the possible antibacterial mechanism of the F+-implanted specimen was caused by the formation of a metal fluoride complex on the surfaces . In addition, F+-implanted surfaces did not inhibit the proliferation of fibroblast L929-cells . These findings indicate that surface modification by means of a dry process is useful in providing antibacterial activity of oral bacteria to titanium implants exposed to the oral cavity.

Leuk Lymphoma, 2000 Dec, 40(1-2), 105 - 12
Vasculitis and leukemia; Paydas S et al.; Vasculitis may accompany neoplasias and be of paraneoplastic type or associated with drugs used in patient treatment . We evaluated skin biopsies of twenty-eight cases with vasculitis accompanying leukemias reviewed and clinical outcome was evaluated . Eleven of the 28 cases had paraneoplastic vasculitis and 17 had vasculitis associated with various drugs including chemotherapy, cytokines and antibacterial agents . Paraneoplastic vasculitis was seen in 3 cases with chronic myelocytic leukemia in blastic phase, 5 patients with acute myeloblastic leukemia, and 3 with myelodysplastic syndrome . Drugs responsible for the 17 cases of vasculitis included hydroxyurea, vincristine, cytosine-arabinoside, methotrexate, all-trans retinoic acid, granulocyte-colony stimulating factor, interferon and antibiotics . Paraneoplastic vasculitis is not rare in leukemias and may be a manifestation of the blastic phase of chronic myeloid leukemia . Furthermore paraneoplastic vasculitis can be fatal in myelodysplastic syndromes and may be present clinically before the specific diagnosis is made . Drugs used in routine therapy may be the cause of the vasculitis, thus skin biopsy should be performed in all cutaneous lesions in patients with hemopoietic neoplasias.

Bioorg Med Chem, 2001 Jul, 9(7), 1781 - 91
Synthesis of plaunotol derivatives and their antibacterial activities against Helicobacter pylori; Tago K et al.; Plaunotol, a known antiulcer drug, has antibacterial activities against Helicobacter pylori . Plaunotol thiourea derivatives 2--4 and diol derivatives 6--10 were designed in search for a compound with high antibacterial activities . Thiourea derivatives 2--4 were synthesized regioselectively using our effective synthetic route for plaunotol (1), and diol derivatives 6--10 were also synthesized . Their antibacterial activities against H . pylori are described and we found that the most potent antibacterial agent was C1-thiourea derivative 2c.

J Ind Microbiol Biotechnol, 1999 Oct, 23(4-5), 414 - 424
Interaction of peptides and proteins with bacterial surface glycolipids: a comparison of glycosphingolipids and lipopolysaccharides; Wiese A et al.; The bacterial cell wall of Gram-negative bacteria consists, in addition to the cytoplasmic membrane, of another permeability barrier, the outer membrane . The lipid distribution between both sides of this membrane is strictly asymmetric . The outer leaflet is made up of glycolipids, usually lipopolysaccharides . In Sphingomonas spp glycosphingolipids were found to substitute for lipopolysaccharides . In this review, it is shown by an electrophysiological approach that glycosphingolipid can replace lipopolysaccharide with respect to its function as antigenic surface structure as well as to its contribution to the diffusion barrier properties of the outer membrane . This review is focused on: (i) the function of porins, as examples of transmembrane proteins, in the different glycolipid environments; (ii) the interaction of polymyxin B with the outer membrane, as an example of polycationic antibacterial peptides; and (iii) the activation of the human complement system by lipopolysaccharides and glycosphingolipids.

Carbohydr Res, 2001 Jun 22, 333(1), 1 - 6
Synthesis and antibacterial activities of quaternary ammonium salt of chitosan; Jia Z et al.; Chitosan derivatives with quaternary ammonium salt, such as N,N,N-trimethyl chitosan, N-N-propyl-N,N-dimethyl chitosan and N-furfuryl-N,N-dimethyl chitosan were prepared using different 96% deacetylated chitosan of M(v) 2.14x10(5), 1.9x10(4), 7.8x10(3) . Amino groups on chitosan react with aldehydes to from a Schiff base intermediate . Quaternized chitosan were obtained by reaction of a Schiff base with methyl iodide . The yields, degree of quaternization and water-solubility of quaternized chitosan were influenced by the molecular weight of the chitosan sample . The antibacterial activities of quaternized chitosan against Escherichia coli were explored by calculation of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in water, 0.25 and 0.50% acetic acid medium . Results show the antibacterial activities of quaternized chitosan against E . coli is related to its molecular weight . Antibacterial activities of quaternized chitosan in acetic acid medium is stronger than that in water . Their antibacterial activities is increased as the concentration of acetic acid is increased . It was also found that the antibacterial activity of quaternized chitosan against E . coli is stronger than that of chitosan.

J Nat Prod, 2001 Jun, 64(6), 809 - 12
Bombardolides: new antifungal and antibacterial gamma-lactones from the coprophilous fungus Bombardioidea anartia; Hein SM et al.; Chemical studies of organic extracts from cultures of the coprophilous fungus Bombardioidea anartia have led to the discovery of bombardolides A--D (1--4), a series of new antifungal and antibacterial metabolites . Three of these metabolites (1--3) were obtained as inseparable pairs of geometric isomers . A new 3-substituted phenol (5) and the known compound asterriquinone B4 were also encountered . The structures of compounds 1--5 were determined by analysis of NMR and MS data.

J Nat Prod, 2001 Jun, 64(6), 701 - 6
New prenylated bi- and tricyclic phloroglucinol derivatives from Hypericum papuanum; Winkelmann K et al.; Five new prenylated tricyclic and three new bicyclic acylphloroglucinol derivatives have been isolated by bioactivity-guided fractionation of the petroleum ether extract of the dried aerial parts of Hypericum papuanum . The tricyclic compounds (1--5) were named papuaforins A--E . The bicyclic compounds were isolated together with their corresponding tautomers and were named hyperguinones A and B (6/6a,7/7a) and hyperpapuanone (8/8a), respectively . Their structures were elucidated on the basis of extensive 1D and 2D NMR experiments, as well as mass spectrometry . Furthermore, the cytotoxicity toward KB nasopharyngeal carcinoma cells and the antibacterial activity of the isolated compounds were determined.

Farmaco, 2001 Apr, 56(4), 331 - 4
Synthesis and biological evaluation of pseudostellarin B; Poojary B et al.; A new potent bioactive cyclic peptide pseudostellarin B has been synthesised . The structure was elucidated by elemental analyses, IR, 1H NMR, 13C NMR and FAB mass spectral data . The synthesised compound was also screened for its antibacterial, antifungal, antiinflammatory and anthelmintic activities.

Respir Med, 2001 Jun, 95 Suppl A, S20 - 5; discussion S26-7
The hidden impact of antibacterial resistance in respiratory tract infection . Steering an appropriate course: principles to guide antibiotic choice; Cars O; The prevalence and degree of antibacterial resistance in common respiratory pathogens are increasing worldwide . The health impact of resistance is not yet fully understood . However, once the impact of resistance becomes measurable, it may be too late to apply interventions to reduce resistance levels and regain previous quality and cost of care . We should address resistance now, before patient care is irreversibly compromised . The association between antibiotic consumption and the prevalence of resistance is widely assumed . However, evidence suggests that there is a more complex . multifactorial relationship between antibiotic use and resistance . It is also assumed that there is an adaptive fitness cost for bacterial resistance mutations . However, in some cases, bacteria are able to acquire 'compensatory genes' negating any negative impact of resistance mutations . Mathematical modeling indicates that the timescale for the emergence of resistance is typically shorter than the decay time following a decline in antibiotic consumption . Against this background, a general principle is proposed: to maximize patient outcome whilst minimizing the potential for selection and spread of resistance . This may be achieved through the use of agents that fulfill defined pharmacodynamic and pharmacokinetic parameters and elicit rapid eradication of the bacterial population, including emerging resistant mutants, from the site of infection . The choice of agent may not be the same in all regions, as selection will depend on local resistance patterns and disease etiology; however, the application of this principle may help to preserve the benefits of antibiotic therapy.

Ter Arkh, 2001, 73(3), 40 - 4
{Effects of bacterial extract IRS-19 on the concentration of hydrogen peroxide and myeloperoxidase activity in nasal washings of patients with chronic bronchitis}; Nowak D et al.; AIM: To determine the effect of intranasal treatment with IRS-19, an immunomodulating agent, on the number of polymorphonuclear leukocytes (PMNL), H2O2 concentration and myeloperoxidase (MPO) activity in nasal washings . MATERIAL AND METHODS: 28 adult patients of both sexes with chronic bronchitis participated in an open study of intranasal treatment with IRS-19 . RESULTS: The number of PMNL recovered from nasal spaces increased from 4460 +/- 3960 to 10,490 +/- 10,950 cells/ml (p < 0.02) after two month administration of IRS-19 . It was accompanied by 2.6- and 1.4-fold increase (p < 0.001) in MPO activity and H2O2 concentration, respectively . However, no correlation was found between increments in these three variables . CONCLUSION: Since PMNL and MPO--H2O2--Cl- system are involved in the first line of defense against invading pathogens it is suggested that the above mentioned changes may represent one among mechanisms leading to enhancement of antibacterial defence in the airways in response to treatment with IRS-19.

Proc Natl Acad Sci U S A, 2001 Jul 3, 98(14), 7904 - 9 Epub 2001 Jun 19.
Increased sexual activity reduces male immune function in Drosophila melanogaster; McKean KA et al.; Despite the benefits of resistance, susceptibility to infectious disease is commonplace . Although specific susceptibility may be considered an inevitable consequence of the co-evolutionary arms race between parasite and host, a more general constraint may arise from the cost of an immune response . This "cost" hypothesis predicts a tradeoff between immune defense and other components of fitness . In particular, a tradeoff between immunity and sexually selected male behavior has been proposed . Here we provide experimental support for the direct phenotypic tradeoff between sexual activity and immunity by studying the antibacterial immune response in Drosophila melanogaster . Males exposed to more females showed a reduced ability to clear a bacterial infection, an effect that we experimentally link to changes in sexual activity . Our results suggest immunosuppression is an important cost of reproduction and that immune function and levels of disease susceptibility will be influenced by sexual selection.

Microbios, 2001, 105(412), 183 - 9
Antibacterial activity of Karanj (Pongamia pinnata) and Neem (Azadirachta indica) seed oil: a preliminary report; Baswa M et al.; The antibacterial activity of Karanj (Pongamia pinnata) and Neem (Azadirachta indica) seed oil in vitro against fourteen strains of pathogenic bacteria was assessed . Using the tube dilution technique, it was observed that 57.14 and 21.42% of the pathogens were inhibited at 500 microl/ml; 14.28 and 71.42% at 125 microl/ml; and 28.57 and 7.14% at 250 microl/ml of Karanj and Neem oils, respectively . The activity with both the oils was bactericidal and independent of temperature and energy . Most of the pathogens were killed more rapidly at 4 degrees C than 37 degrees C . The activity was mainly due to the inhibition of cell-membrane synthesis in the bacteria.

Environ Sci Technol, 2001 Jun 1, 35(11), 2388 - 94
Hybrid organic/inorganic reverse osmosis (RO) membrane for bactericidal anti-fouling . 1 . Preparation and characterization of TiO2 nanoparticle self-assembled aromatic polyamide thin-film-composite (TFC) membrane; Kwak SY et al.; Hybrid organic/inorganic reverse osmosis (RO) membranes composed of aromatic polyamide thin films underneath titanium dioxide (TiO2) nanosized particles have been fabricated by a self-assembly process, aiming at breakthrough of biofouling problems . First, positively charged particles of the colloidal TiO2 were synthesized by a sol-gel process, and the diameter of the resulting particles in acidic aqueous solution was estimated to be approximately 2 nm by analyzing the UV-visible absorption characteristics with a quantum mechanical model developed by Brus . Transmission electron microscopy (TEM) further confirmed the formation of the quantum-sized TiO2 particles (approximately 10 nm or less) . The TiO2 particles appeared to exist in the crystallographic form of anatase as observed with the X-ray diffraction (XRD) pattern in comparison with those of commercial 100% rutile and commercial 70:30% anatase-to-rutile mixture . The hybrid thin-film-composite (TFC) aromatic polyamide membranes were prepared by self-assembly of the TiO2 nanoparticles on the polymer chains with COOH groups along the surface . They showed improved RO performance in which the water flux even increased, though slightly . Field-emission scanning electron microscopy (FESEM) exhibited the TiO2 nanoparticles well adsorbed onto the surface . X-ray photoelectron spectroscopy (XPS) demonstrated quantitatively that a considerable amount of the adsorbed particles were tightly self-assembled at the expense of the initial loss of those that were loosely bound, and became stabilized even after exposure to the various washing and harsh RO operating conditions . The antibacterial fouling potential of the TiO2 hybrid membrane was examined and verified by measuring the viable numbers and determining the survival ratios of the Escherichia coli (E . coli) as a model bacterium, both with and without UV light illumination . The photocatalytic bactericidal efficiency was remarkably higher for the TiO2 hybrid membrane under UV illumination, compared to that of the same membrane in darkness, as well as those for the neat membranes under either light condition.

Arzneimittelforschung, 2001, 51(5), 425 - 32
Four-week oral toxicity studies of the new quinolone antibacterial agent cetefloxacin tosylate in rats and marmoset monkeys; Guzman A et al.; Four-week oral toxicity studies with cetefloxacin tosylate ((-)-7{3-(R)-amino-2-(S)-methyl-1-azetidinyl}-1-(2,4- difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid tosylate, CAS 141725-88-4 (base), E-4868.Ts) a new quinolone antibacterial agent, were performed in Sprague-Dawley rats and marmoset monkeys at doses of 100, 450, 2000 mg/kg/d and 25, 50, 125, 300 mg/kg/d, respectively . In rats, due to its toxicity the high dose was decreased to 1000 mg/kg/d after 3 days of treatment . Mortality was recorded among high dose rats receiving 2000 or 1000 mg/kg/d . Rats receiving dosages of 450 or 2000/1000 mg/kg/d showed less activated mandibular lymph nodes, cortical lymphocyte depletion of mandibular and/or mesenteric lymph nodes, atrophy of the white pulp of the spleen, cortical atrophy of thymus and thymic apoptosis . Enlarged caeca, increased water consumption and variations in plasma electrolyte levels were observed in animals receiving these dosages and in male rats receiving 100 mg/kg/d . Low neutrophil counts were observed in rats receiving dosages of 100 or 450 mg/kg/d, and increased alkaline phosphatase and alanine transaminase plasma levels and slightly decreased plasma protein levels in females receiving 450 or 2000/1000 mg/kg/d . Marmosets receiving dosages of 50 mg/kg/d and above displayed several clinical signs which included emesis, diarrhoea, ptosis, occasional episodes of under- and overactivity, and excessive scratching activity . Skin reddening was observed during the first week of treatment in marmosets receiving 300 mg/kg/d . On the basis of the results obtained it can be concluded that the non-toxic doses of E-4868 . Ts after 4-week oral administration in rats and marmoset monkeys were 100 and 25 mg/kg/d, respectively.

J Chem Inf Comput Sci, 2001 May-Jun, 41(3), 791 - 7
3D connectivity indices in QSPR/QSAR studies; Estrada E et al.; Topographic (3D) molecular connectivity indices based on molecular graphs weighted with quantum chemical parameters are used in QSPR and QSAR studies . These descriptors were compared to 2D connectivity indices (vertex and edge ones) and to quantum chemical descriptors in modeling partition coefficient (log P) and antibacterial activity of 2-furylethylene derivatives . In describing log P the 3D connectivity indices produced a significant improvement (more than 29%) in the predictive capacity of the model compared to those derived with topological and quantum chemical descriptors . The best linear discriminant model for classifying antibacterial activity of these compounds was also obtained with the use of 3D connectivity indices . The global percent of good classification obtained with 3D and 2D connectivity as well as quantum chemical descriptors were 94.1, 91.2, and 88.2, respectively . In general, all these models predict correctly the antibacterial activity of a set of nine new 2-furylethylene derivatives . The best result is obtained with 3D connectivity indices that classified correctly 100% of these compounds versus 88.9% obtained with 2D connectivity or quantum chemical descriptors.

Bioorg Med Chem Lett, 2001 Jun 18, 11(12), 1545 - 8
Amidino benzimidazole inhibitors of bacterial two-component systems; Weidner-Wells MA et al.; Amidino benzimidazoles have been identified as inhibitors of the bacterial KinA/Spo0F two-component system (TCS) . Many of these inhibitors exhibit good in vitro antibacterial activity against a variety of susceptible and resistant Gram-positive organisms . The moiety at the 2-position of the benzimidazole was extensively modified . In addition, the regioisomeric benzoxazoles, heterocyclic replacements for the benzimidazole, have been synthesized and their activity against the TCS evaluated.

Chem Pharm Bull (Tokyo), 2001 Jun, 49(6), 711 - 5
Studies on chemical modification of monensin IX . Synthesis of 26-substituted monensins and their Na+ ion transport activity; Tanaka R et al.; The C-26 modified monensin derivatives, 26-O-benzoylmonensin (3), 26-O-benzylmonensin (4) and 26-phenylaminomonensin (5) were prepared from monensin (1) . Na+ ion transport activity through biological membrane and antibacterial activity of 3-5 were evaluated and compared with the activities reported for a 26-phenylurethane derivative (2) . Among these compounds, 5 showed the largest Na+ ion transport and antibacterial activities . In these compounds, the formation of head-to-tail hydrogen bonds was suggested to be an important factor for Na+ ion transport and antibacterial activities.

Sheng Wu Gong Cheng Xue Bao, 2001 Mar, 17(2), 207 - 10
{Cloning and expression of a synthetic gene encoding magainin-melittin hybrid peptide in Escherichia coli and studies on its antibacterial activity}; Huang Y et al.; A hybrid peptide gene was designed and synthesized . Its encoding peptide is constructed from residues 3-14 of magainin and residues 1-13 of melittin . The MA-E gene was cloned into plasmids pUC18 and pBV220 . By DNA sequencing, the whole sequences of this gene is confirmed to be correct . The recombinant plasmid pBMA-E was expressed in E . coli DH5 alpha . A gene product band can be seen with Tricine-SDS-PAGE . The MA-E hybrid peptide was purified by immobilized metal affinity chromatography . Bioactivity assay was carried out in liquid turbidity method . The bactericide value to E . coli K12D31 is 0.182.

Cochrane Database Syst Rev . 2001;(2):CD002987.
Troleandomycin as an oral corticosteroid steroid sparing agent in stable asthma; Evans DJ et al.; BACKGROUND: Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids . The use of steroids is associated with serious side effects . Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids . troleandomycin is a compound that is established as an effective antibiotic but may also have non antibacterial actions that may be useful in the treatment of asthma . OBJECTIVES: The objective of this review was to assess the effects of adding troleandomycin to oral steroids in the treatment of chronic steroid dependent asthmatics . SEARCH STRATEGY: The Cochrane Airways Group trials register and reference lists of identified articles were searched . SELECTION CRITERIA: Randomised trials looking at the addition of troleandomycin compared to placebo in adult steroid dependent asthmatics . DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was carried out by two reviewers independently . Study authors were contacted for missing information . MAIN RESULTS: Three trials fulfilled the criteria for inclusion in the review and a total of 112 patients were recruited into these studies . Data from 90 patients were analysed . There was no treatment effect for troleandomycin in terms of steroid dose reduction (SMD -0.29, 95% CI -0.75, 0.17) . For measures of lung function a meta-analysis of data derived from two of the included studies showed no benefits for added troleandomycin (SMD 0.06 95% CI -0.8, 0.9) . REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of troleandomycin in the treatment of steroid dependent asthma.

Antimicrob Agents Chemother, 2001 Jul, 45(7), 1994 - 2000
Interaction between DNA gyrase and quinolones: effects of alanine mutations at GyrA subunit residues Ser(83) and Asp(87); Barnard FM et al.; DNA gyrase is a target of quinolone antibacterial agents, but the molecular details of the quinolone-gyrase interaction are not clear . Quinolone resistance mutations frequently occur at residues Ser(83) and Asp(87) of the gyrase A subunit, suggesting that these residues are involved in drug binding . Single and double alanine substitutions were created at these positions (Ala(83), Ala(87), and Ala(83) Ala(87)), and the mutant proteins were assessed for DNA supercoiling, DNA cleavage, and resistance to a number of quinolone drugs . The Ala(83) mutant was fully active in supercoiling, whereas the Ala(87) and the double mutant were 2.5- and 4- to 5-fold less active, respectively; this loss in activity may be partly due to an increased affinity of these mutant proteins for DNA . Supercoiling inhibition and cleavage assays revealed that the double mutant has a high level of resistance to certain quinolones while the mutants with single alanine substitutions show low-level resistance . Using a drug-binding assay we demonstrated that the double-mutant enzyme-DNA complex has a lower affinity for ciprofloxacin than the wild-type complex . Based on the pattern of resistance to a series of quinolones, an interaction between the C-8 group of the quinolone and the double-mutant gyrase in the region of residues 83 and 87 is proposed.

Clin Pharmacol Ther, 2001 Jun, 69(6), 451 - 7
Drug interactions as a cause of overanticoagulation on phenprocoumon or acenocoumarol predominantly concern antibacterial drugs; Penning-van Beest FJ et al.; BACKGROUND: The risk of hemorrhage when coumarin anticoagulants are used sharply increases when the international normalized ratio (INR) is > or = 6.0 . Such overanticoagulation may be caused by drug interactions . We performed a case-control study among previously stable outpatients of an anticoagulation clinic using phenprocoumon or acenocoumarol to identify changes in the use of potentially interacting drugs related to overanticoagulation . METHODS: Three hundred case patients with INR values > or = 6.0 were compared with 302 randomly selected matched control subjects with INR values within the target zone . Information on changes in the use of 87 potentially interacting drugs in the 4 weeks before the index day was collected by interviewing patients and by reviewing the anticoagulant medical record . RESULTS: Forty-five potentially interacting drugs were not used in the 4-week study period, and only 15 drugs were used by at least 10 patients . For a number of drugs, too few patients had a relevant change in use to judge their association with overanticoagulation . A course of a combination product of sulfamethoxazole and trimethoprim strongly increased the risk of overanticoagulation (adjusted odds ratio, 24.2; 95% confidence interval {CI}, 2.8 to 209.1; population attributable risk percentage {PAR%}, 5.7%), especially in patients receiving acenocoumarol . Penicillins were associated with a risk of overanticoagulation of 2.4 (95% CI, 1.00 to 5.5); the corresponding PAR% was 3.4% . The effect was confined to amoxicillin (INN, amoxicilline) plus clavulanic acid . CONCLUSION: Drug interactions as a cause of overanticoagulation predominantly concerned antibacterial drugs . If possible, the use of sulfamethoxazole-trimethoprim and amoxicillin plus clavulanic acid should be avoided in patients receiving coumarins . If there is no therapeutic alternative available, increased monitoring of INR values is warranted to prevent overanticoagulation and potential bleeding complications.

J Biomater Sci Polym Ed, 2001, 12(2), 137 - 48
Controlled release of lysozyme from succinylated gelatin microspheres; Srinivas SS et al.; Gelatin was anionized to increase the carboxylic acid groups through succinylation . Succinylation of gelatin was performed using varying amounts of succinic anhydride . This gave various percentages of substitution . Lysozyme, a cationic antibacterial enzyme, which has important applications in the reduction of prosthetic valve endocarditis, was chosen as a model protein drug . Microspheres were prepared using unmodified gelatin and succinylated gelatin (SG) and lysozyme was incorporated into them . The percentage loading and release profiles of lysozyme for gelatin and SG microspheres were evaluated and compared . It was found that the SG microspheres exhibited higher loading efficiency for lysozyme (50%) than the unmodified gelatin microspheres . The in vitro release of lysozyme from SG microspheres occurred up to 122 h, compared to 96 h for gelatin microspheres, for the release of most of the lysozyme incorporated . This prolonged release of lysozyme from SG microspheres was attributed to the electrostatic interaction between the cationic lysozyme and the anionic SG microsphere carrier.

Drugs, 2001, 61(6), 713 - 21
Aminoglycoside adaptive resistance: importance for effective dosage regimens; Barclay ML et al.; There are various pharmacodynamic features of the aminoglycosides that are thought to contribute to the benefits of once-daily administration, of which the ability to induce adaptive resistance is the least understood and discussed . However, this may be the most important characteristic conferring increased efficacy with extended interval dose administration . Adaptive resistance describes a reversible refractoriness to the bactericidal effect of an antibacterial agent . It is well documented for the aminoglycosides but has also been seen with the quinolones . It does not appear to be caused by a genetic mutational change but rather by a protective phenotypic alteration in bacterial characteristics . This includes reversible down-regulation of the active transport of aminoglycosides into gram-negative bacteria . In vitro, animal and clinical studies have shown that marked adaptive resistance of gram-negative bacteria to aminoglycosides occurs within 1-2 hours of the first dose . The duration of adaptive resistance relates directly to the half-life of elimination of the aminoglycoside . With normal human aminoglycoside pharmacokinetics, the resistance may be maximal for up to 16 hours after a single dose of aminoglycoside, followed by partial return of bacterial susceptibility at 24 hours and complete recovery at around 40 hours . With conventional dosage regimens, second and subsequent doses of aminoglycoside are given at the time of maximal resistance and this practice is also likely to reinforce the resistance . Dose administration at 24 hour intervals, or longer, may increase efficacy by allowing time for adaptive resistance to reverse.

Food Chem Toxicol, 2001 Jul, 39(7), 641 - 7
Luteolin-inhibited arylamine N-acetyltransferase activity and DNA-2-aminofluorene adduct in human and mouse leukemia cells; Li YC et al.; N-Acetyltransferase enzyme is an important enzyme in the first step of arylamine compounds metabolism . Luteolin has been shown to exit antibacterial and antineoplastic activity . The purpose of this present study is to evaluate the question of whether luteolin could affect arylamine N-acetyltransferase (NAT) activity and DNA-2-aminofluorene adduct formation in human (HL-60) and mouse (L1210) leukemia cells . By using HPLC, N-acetylation of 2-aminofluorene was determined . Luteolin displayed a dose-dependent inhibition to cytosolic NAT activity and intact human and mice leukemia cells . Time-course experiments showed that N-acetylation of 2-aminofluorene measured from intact human and mice leukemia cells were inhibited by luteolin for up to 24 hours . Using standard steady-state kinetic analysis, it was demonstrated that luteolin was a possible uncompetitive inhibitor to NAT activity in cytosols . The DNA-2-aminofluorene adduct formation in human and mouse leukemia cells were inhibited by luteolin . This report is the first demonstration to show that luteolin affects human and mice leukemia cells NAT activity and DNA-2-aminofluorene on adduct formation.

J Pediatr Gastroenterol Nutr, 2001 Apr, 32(4), 449 - 53
Absence of Toll-like receptor 4 explains endotoxin hyporesponsiveness in human intestinal epithelium; Naik S et al.; BACKGROUND: The Toll protein in Drosophila regulates dorsal ventral patterning during embryogenesis, and participates in antibacterial and antifungal host defense . Mammalian homologues are termed Toll-like receptors and, to date, nine have been cloned (TLRI-9) in humans . They are characterized by extracellular leucine-rich repeats and a cytoplasmic domain similar to the interleukin 1 receptor . Both TLR2 and TLR4 recognize various bacterial cell wall components including lipopolysaccharide (LPS) . This results in the activation of the NFkappaB pathway . Peripheral blood mononuclear cells (PBMCs) express both TLR2 and TLR4 . The authors hypothesized that the expression of TLR 2 and TLR4 in human intestinal epithelial cells differs from PBMCs because of the abundance of LPS in the intestinal lumen . METHODS: Epithelial cells were isolated from Caco-2 cells, fetal gut explants, and small bowel resection specimens using Hanks/ethylenediamine tetraacetic acid solution . PBMCs were used as positive controls . Ribonucleic acid (RNA) was isolated using the TRIzol method . Standard reverse transcription-polymerase chain reaction examined TLR2 and TLR4 messenger RNA (mRNA) expression . NFkappaB expression was determined using a luciferase reporter assay . RESULTS: TLR2 mRNA was highly expressed in PBMCs and was present in all human intestinal epithelial cells . TLR4 mRNA was detected only in PBMCs . TLR4 is not present in epithelium from children with inflammatory bowel disease . In Caco-2 cells, significant NFkappaB activation in response to LPS occurred only in the presence of TLR4 introduced by complementary deoxyribonucleic acid transfection . CONCLUSION: Absence of TLR4 is associated with endotoxin hyporesponsiveness of intestinal epithelial cells . TLR4 is not directly involved in inflammation of the intestinal epithelium . Although TLR2 is normally present in the epithelial cell, it plays a limited role in inflammation . It may be activated during conditions in which bacterial cell wall concentrations within the intestine are pathologically high.

Fitoterapia, 2001 May, 72(4), 418 - 20
Antibacterial activity of the resinous exudates from Haplopappus uncinatus and Haplopappus foliosus; Urzua A et al.; The antibacterial activities of the resinous exudates from Haplopappus uncinatus and H . foliosus are reported . The results provide a justification to the traditional use of the resinous exudates of Haplopappus spp as an antiseptic.

Fitoterapia, 2001 May, 72(4), 412 - 4
Antibacterial activity and cytotoxicity of Nyctanthes arbor-tristis flowers; Khatune NA et al.; The flowers of Nyctanthes arbor-tristis showed interesting antibacterial activity against some gram-positive and gram-negative microorganisms (chloroform and ethyl acetate extracts) and significant cytotoxic activity (petroleum ether, chloroform and ethyl acetate extracts).

Fitoterapia, 2001 May, 72(4), 409 - 11
Antibacterial activity of luteoforol from Bridelia crenulata; Ramesh N et al.; The methanol extract of Bridelia crenulata stem bark (50-1.5625 mg/ml) and its isolated luteoforol (2-0.25 mg/ml) showed concentration-dependent inhibiting activity against all 10 tested bacteria.

Fitoterapia, 2001 May, 72(4), 406 - 8
Antibacterial activity of Picrasma javanica; Khan MR et al.; The methanol extracts of Picrasma javanica, leaves, seeds, stem and root barks were partitioned (petrol, dichloromethane, ethyl acetate, butanol) . All obtained extracts and fractions showed a broad spectrum of antibacterial activity, while none was active against the tested moulds.

Bull Exp Biol Med, 2001 Feb, 131(2), 132 - 5
Efficiency of magnesium-containing preparation polykatan in therapy of purulent wounds; Spasov AA et al.; Local treatment with polykatan, a magnesium-containing drug based on bischofite mineral, promoted healing of infected skin wounds . Wound cleansing from bacteria was due to a direct antibacterial effect of the drug.

J Ethnopharmacol, 2001 Jul, 76(2), 183 - 6
Antibacterial and antifungal activity of the essential oils of Thymus revolutus Celak from Turkey; Karaman S et al.; The chemical composition of the volatile constituent from flowering parts of Thymus revolutus C., an endemic plant of Turkey, were analysed by GC/MS . Twenty-two components were identified, and carvacrol was found as a predominant compound in the oil . Furthermore, the essential oil was tested against 11 bacteria and four fungi at different concentrations . Results showed that the oil exhibited a significant antibacterial and antifungal activity.

Clin Infect Dis, 2001 Jul 1, 33 Suppl 1, S26 - 31
Prophylaxis strategies for solid-organ transplantation; Soave R; In addition to the net state of immunosuppression, the risk of infection after transplantation is largely determined by the transplant recipient's epidemiologic exposures . Potential sources of infection in the transplant recipient include the environment and the recipient's endogenous flora . This article presents aspects of prevention of infection after solid-organ transplantation such as avoidance of epidemiologic exposures, antibacterial prophylaxis, prophylaxis for tuberculin-positive transplant recipients, and prophylaxis against infections with Pneumocystis carinii and Toxoplasma gondii.

Curr Opin Pediatr, 2001 Jun, 13(3), 280 - 8
Updates in pediatric nutrition; Oken E et al.; Ongoing research in several areas of pediatric nutrition has new practical applications for community-based pediatricians . For example, a fresh understanding of risk factors for rickets persuades pediatricians to recognize and treat this disease, which was thought to be nearly extinct in the modern industrialized world . Similarly, an expanded awareness of the antibacterial components of breast milk encourages a more complete dialogue between pediatricians and new mothers about the potential benefits of breast-feeding . For those infants with feeding intolerance, new data help to refine the indications for hypoallergenic formulas, which are increasingly recommended for children with a variety of symptoms . The past year also has seen breakthroughs in our understanding of supplemental nutrition for children . Vitamin A may provide direct benefits for the most vulnerable of children, namely premature infants at high risk for lung disease . At the other end of the pediatric spectrum, adolescent athletes seeking to enhance their performance are consuming poorly studied sports supplements that may not be beneficial and may even be toxic . Finally, a greater appreciation for the epidemic of obesity that is sweeping the United States and other countries suggests that children at high risk may represent a far more diverse population than had been recognized previously.

Biosci Biotechnol Biochem, 2001 Apr, 65(4), 966 - 8
Antibacterial activity of S-methyl methanethiosulfinate and S-methyl 2-propene-1-thiosulfinate from Chinese chive toward Escherichia coli O157:H7; Seo KI et al.; S-Methyl methanethiosufinate (1) and S-methyl 2-propene-1-thiosulfinate (2) were easily seperated from Chinese chive (Allium tuberosum L.) using simple column chromatography . Both compounds showed significant antibacterial activities against E . coli O-157:H7 including spoilage microorganism in food . Structural assignment was based on Mass and NMR-spectroscopic methods.

J Med Chem, 2001 Jun 7, 44(12), 1847 - 52
2-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)- and 2-(2,2-dioxo-1,4-dihydro-2H-2lambda6-benzo{1,2,6}thiadiazin-3-yl)-N-hydroxy-acetamides as potent and selective peptide deformylase inhibitors; Apfel C et al.; Potent, selective, and structurally new inhibitors of the Fe(II) enzyme Escherichia coli peptide deformylase (PDF) were obtained by rational optimization of the weakly binding screening hit (5-chloro-2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid hydrazide (1) . Three-dimensional structural information, gathered from Ni-PDF complexed with 1, suggested the preparation of two series of related hydroxamic acid analogues, 2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-N-hydroxy-acetamides (A) and 2-(2,2-dioxo-1,4-dihydro-2H-2lambda(6)-benzo{1,2,6}thiadiazin-3-yl)-N-hydroxy-acetamides (B), among which potent PDF inhibitors (37, 42, and 48) were identified . Moreover, two selected compounds, one from each series, 36 and 41, showed good selectivity for PDF over several endoproteases including matrix metalloproteases . However, these compounds showed only weak antibacterial activity.

Immunology, 2001 May, 103(1), 113 - 21
Mycobacterium avium infection in CD14-deficient mice fails to substantiate a significant role for CD14 in antimycobacterial protection or granulomatous inflammation; Ehlers S et al.; CD14 is a pattern-recognition receptor implicated in the inflammatory response to microbial components such as lipopolysaccharide, peptidoglycan and lipoarabinomannan . In this work, we made use of CD14-deficient (CD14-/-) mice to evaluate the relative importance of CD14 in response to infection with viable, intact cells of Mycobacterium avium in vitro and in vivo . Following co-incubation of either bone marrow-derived macrophages (Mphi) or thioglycollate-elicited peritoneal Mphi from CD14-/- mice with viable M . avium, tumour necrosis factor (TNF) production was significantly reduced and delayed compared to TNF secretion by infected CD14+/+ Mphi . However, following intravenous infection with a M . avium strain of either high virulence (TMC724) or intermediate virulence (SE01), there was no difference in the bacterial loads of lungs, livers or spleens at 3, 5 and 8 weeks postinfection in CD14-/- mice when compared with syngeneic CD14+/+ mice . At these time-points, TNF and interferon-gamma (IFN-gamma) mRNA expression in the liver was similar in infected CD14+/+ and CD14-/- mice, and granuloma formation and expression of inducible nitric oxide synthase within granuloma Mphi was the same in both mouse groups . In conclusion, although the absence of CD14 results in significantly reduced and delayed TNF production in response to stimulation with M . avium in vitro, there is no evidence that CD14 plays a significant role in either the antibacterial defence or the chronic granulomatous reaction to M . avium infection in vivo.

J Vet Med A Physiol Pathol Clin Med, 2001 Apr, 48(3), 129 - 36
Disposition kinetics of florfenicol in goats by using two analytical methods; Atef M et al.; Florfenicol, a monofluorinated analogue of thiamphenicol, has antibacterial activity against a broad spectrum of bacterial strains, including enteric bacteria that are resistant to chloramphenicol and thiamphenicol . The pharmacokinetics of florfenicol was studied following a single intravenous bolus or intramuscular injections at a dose of 20 mg/kg body weight, in five healthy goats . Serum florfenicol concentrations were determined using two analytical methods: microbiological assay and high-performance liquid chromatography (HPLC) . Pharmacokinetic analysis was performed using redundant routine equations and the results derived from each method were compared . While florfenicol was detected for up to 4 and 8 h after administration by the bioassay, the drug was recovered in serum after 12 and 24 h by HPLC following intravenous and intramuscular injections, respectively . Comparison of the concentration profiles obtained by the two methods revealed substantial differences in the resultant kinetic data . Values for the initial serum concentration, elimination half-life, the area under the serum concentration-time curve, the mean residence time, and the systemic bioavailability were significantly (P < 0.01) higher when florfenicol concentrations were determined using HPLC . In conclusion, differences between analytical methodologies should be considered when interpreting the kinetic data for clinical use . However, both the hepatic biotransformations and the interchangeability of enantiomers need further investigation.

Insect Biochem Mol Biol, 2001 Jun 22, 31(8), 747 - 51
Two isoforms of a member of the arthropod defensin family from the soft tick, Ornithodoros moubata (Acari: Argasidae); Nakajima Y et al.; We previously purified and determined the partial amino acid sequence of a 4 kDa peptide having high homology with scorpion defensin from the hemolymph of adult fed female soft ticks, Ornithodoros moubata . In this study, the full length sequences of two defensin isoforms were obtained . Deduced amino acid sequences reveal a precursor protein of 73 amino acid residues with a mature portion consisting of 37 amino acid residues . This mature peptide contains six cysteine residues conserved in the same location as other invertebrate defensins . Phylogenetic analysis reveals that Ornithodoros defensin is most closely related to scorpion defensin and other more ancient arthropods . Ornithodoros defensin mRNA is constitutively expressed and up-regulated by blood-feeding and bacterial injection . Ornithodoros defensin gene expression occurs mainly in the midgut . This is the first report of the cloning and gene expression of an antibacterial peptide from the Acari.

Bioorg Med Chem Lett, 2001 Jun 4, 11(11), 1461 - 4
Fine Tuning of physico-chemical parameters to optimise a new series of novobiocin analogues; Schio L et al.; A novel series of novobiocin analogues has been synthesised by removing the lipophilic aryl chain in novobiocin and introducing an amino substituent . The structural modifications have been dictated by the control of lipophilicity and the dissociation constant of the resulting compounds . Antibacterial activity of the new coumarin derivatives could be correlated with the amount of uncharged form in physiological conditions.

J Ethnopharmacol, 2001 Jun, 76(1), 87 - 91
Purification and identification of active antibacterial components in Carpobrotus edulis L; van der Watt E et al.; Very little is known about the chemical composition of Carpobrotus edulis, also known as Hotnotsfig or sourfig . However, some claims have been made in the past by traditional healers, regarding its usage as a medicinal plant . In this investigation it was initially illustrated that a crude methanolic extract of the plant exhibits strong anti-bacterial activity . Subsequently, the crude extract was fractionated by means of liquid-liquid chromatography, tannins removed by means of LH20 column chromatography and bioactive fractions with antibacterial properties isolated by means of preparative thin layer chromatography . Five bioactive compounds, individually or collectively responsible for the antibacterial property of C . edulis, were purified from an active ethyl acetate fraction . These compounds were initially identified as flavanoids using standard fingerprinting methods and eventually identified as rutin, neohesperidin, hyperoside, cactichin and ferulic acid using flavanoid standards . A sixth flavanoid with antibacterial activity was also purified but could not be identified in this way . The latter is currently isolated in larger volume for identification through nuclear magnetic resonance spectroscopy.

Bioorg Med Chem, 2001 May, 9(5), 1221 - 31
Pleuromutilins . Part 1 . The identification of novel mutilin 14-carbamates; Brooks G et al.; A novel series of mutilin 14-carbamates has been discovered as a result of structure-activity studies on the naturally occurring antibiotic pleuromutilin (1) . In particular, the 4-methoxybenzoylcarbamate, SB-222734 (15o) displays potent antibacterial activity against a number of bacterial pathogens which are resistant to currently used agents and shows enhanced metabolic stability when compared to earlier pleuromutilin derivatives . Such derivatives therefore have the potential to provide a new class of antibacterial agents for human therapy which address the threat of bacterial resistance.

Gene, 2001 May 16, 269(1-2), 27 - 32
The gene of chlamysin, a marine invertebrate-type lysozyme, is organized similar to vertebrate but different from invertebrate chicken-type lysozyme genes; Nilsen IW et al.; In a recent publication we reported the protein purification, characterization, and the gene isolation of a cDNA encoding the antibacterial cold-active lysozyme-like protein chlamysin from the marine bivalve Chlamys islandica . A 4.2 kb genomic chlamysin gene has now been amplified and sequence-analyzed . By comparison to the cDNA sequence and its translation product, the coding region was found separated in four exons of 38-252 bp . The introns range in size from 0.8 to 1.5 kb, and have traditional spliceosomal intron 5'-GT donor and 3'-AG acceptor sites for splicing . Two of the introns contain multiple copies of three sequence motifs not found repeated in other published genes . The over-all gene organization of chlamysin resembles chicken-type (c-type) lysozyme genes in vertebrates, but is different from the three-exon structure in invertebrate c-type lysozyme genes . A phylogenetic analysis of invertebrate-type (i-type) and c-type lysozyme proteins demonstrated a large evolutionary distance between the i-type and the c-type enzyme classes . Exons of the i-type genes are not equally organized according to their homolog protein domains.

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