Clin Infect Dis, 1998 Jul, 27(1), 23 - 7 The pharmacodynamics of aminoglycosides; Lacy MK et al.; Recently, a more complete understanding of the pharmacodynamics of aminoglycosides has been recognized, indicating that this class of antibiotics exhibits both concentration-dependent bactericidal activity and a postantibiotic effect . This pharmacodynamic information, along with better knowledge of the mechanisms responsible for aminoglycoside toxicity, established the foundation for once-daily aminoglycoside dosing regimens . This new approach to aminoglycoside dosing appears to be safe, efficacious, and cost-effective, resulting in its increasing popularity in clinical practice. Clin Pharmacokinet, 1998 Jul, 35(1), 65 - 77 Community-based parenteral anti-infective therapy (CoPAT) . Pharmacokinetic and monitoring issues; Williams DN et al.; Community-based parenteral anti-infective therapy (CoPAT) has, over the past 20 years, increased rapidly in many parts of the world including North America, Europe, South America and Australia . CoPAT is a multidisciplinary activity demanding close cooperation between nurses, pharmacists and physicians, as well as with the patient . The selection of an anti-infective drug for use outside the hospital setting must take into account not only the therapeutic effectiveness, cost effectiveness and safety of the drug, but also pharmacological factors such as the dosage schedule and the stability of the drug . Dosage schedules vary with pharmacokinetic factors (e.g . the use of drugs with long half-lives are favoured by CoPAT programmes) and pharmacodynamic features (e.g . once daily gentamicin therapy is attractive and practical because of concentration-dependent bactericidal killing and prolonged post-antibiotic effect) . With selected drugs, the renal and, to a lesser degree, liver function of the patient will influence the dosage schedule . The mode of intravenous (i.v.) drugs administration will vary with volume considerations (limiting the use of syringe-infusion therapy for some drugs), stability issues (prevents drugs that are stable at room temperature for less than 24 hours from being used in multidose computerised delivery systems), as well as patient factors (ability to self administer an i.v . drug) . Monitoring serum anti-microbial concentrations is undertaken to assure effectiveness and avoid toxicity, and is indicated for drugs with a narrow therapeutic window, such as the aminoglycosides . With the advent of the single daily dose administration of aminoglycosides, checking serum concentrations at the mid-point, i.e . 6 to 14 hours following administration of the first dose, is one approach . Because the toxic effects of vancomycin have been overstated, serum concentrations should only be obtained for defined indications primarily to assure therapeutic effectiveness. Infect Immun, 1998 Aug, 66(8), 3656 - 65 Cloning and expression of the Moraxella catarrhalis lactoferrin receptor genes; Du RP et al.; The lactoferrin receptor genes from two strains of Moraxella catarrhalis have been cloned and sequenced . The lfr genes are arranged as lbpB followed by lbpA, a gene arrangement found in lactoferrin and transferrin receptor operons from several bacterial species . In addition, a third open reading frame, orf3, is located one nucleotide downstream of lbpA . The deduced lactoferrin binding protein A (LbpA) sequences from the two strains were found to be 99% identical, the LbpB sequences were 92% identical, and the ORF3 proteins were 98% identical . The lbpB gene was PCR amplified and sequenced from a third strain of M . catarrhalis, and the encoded protein was found to be 77% identical and 84% similar to the other LbpB proteins . Recombinant LbpA and LbpB proteins were expressed from Escherichia coli, and antisera raised to the purified proteins were used to assess antigenic conservation in a panel of M . catarrhalis strains . The recombinant proteins were tested for the ability to bind human lactoferrin following gel electrophoresis and electroblotting, and rLbpB, but not rLbpA, was found to bind lactoferrin . Bactericidal antibody activity was measured, and while the anti-rLbpA antiserum was not bactericidal, the anti-rLbpB antisera were found to be weakly bactericidal . Thus, LbpB may have potential as a vaccine candidate. Eur J Biochem, 1998 Apr 15, 253(2), 452 - 61 Bactericidal activity of Lys49 and Asp49 myotoxic phospholipases A2 from Bothrops asper snake venom--synthetic Lys49 myotoxin II-(115-129)-peptide identifies its bactericidal region; Paramo L et al.; Mammalian group-II phospholipases A2 (PLA2) of inflammatory fluids display bactericidal properties, which are dependent on their enzymatic activity . This study shows that myotoxins II (Lys49) and III (Asp49), two group-II PLA2 isoforms from the venom of Bothrops asper, are lethal to a broad spectrum of bacteria . Since the catalytically inactive Lys49 myotoxin II isoform has similar bactericidal effects to its catalytically active Asp49 counterpart, a bactericidal mechanism that is independent of an intrinsic PLA2 activity is demonstrated . Moreover, a synthetic 13-residue peptide of myotoxin II, comprising residues 115-129 (common numbering system) near the C-terminal loop, reproduced the bactericidal effect of the intact protein . Following exposure to the peptide or the protein, accelerated uptake of the hydrophobic probe N-phenyl-N-naphthylamine was observed in susceptible but not in resistant bacteria, indicating that the lethal effect was initiated on the bacterial membrane . The outer membrane, isolated lipopolysaccharide (LPS), and lipid A of susceptible bacteria showed higher binding to the myotoxin II-(115-129)-peptide than the corresponding moieties of resistant strains . Bacterial LPS chimeras indicated that LPS is a relevant target for myotoxin II-(115-129)-peptide . When heterologous LPS of the resistant strain was present in the context of susceptible bacteria, the chimera became resistant, and vice versa . Myotoxin II represents a group-II PLA2 with a direct bactericidal effect that is independent of an intrinsic enzymatic activity, but adscribed to the presence of a short cluster of basic/hydrophobic amino acids near its C-terminal loop. J Exp Med, 1998 Jul 6, 188(1), 49 - 60 Phase-variable expression of lipopolysaccharide contributes to the virulence of legionella pneumophila; Luneberg E et al.; With the aid of monoclonal antibody (mAb) 2625, raised against the lipopolysaccharide (LPS) of Legionella pneumophila serogroup 1, subgroup OLDA, we isolated mutant 811 from the virulent wild-type strain RC1 . This mutant was not reactive with mAb 2625 and exhibited an unstable phenotype, since we observed an in vitro and in vivo switch of mutant 811 to the mAb 2625-positive phenotype, thus restoring the wild-type LPS . Bactericidal assays revealed that mutant 811 was lysed by serum complement components, whereas the parental strain RC1 was almost serum resistant . Moreover, mutant 811 was not able to replicate intracellularly in macrophage-like cell line HL-60 . In the guinea pig animal model, mutant 811 exhibited significantly reduced ability to replicate . Among recovered bacteria, mAb 2625-positive revertants were increased by fourfold . The relevance of LPS phase switch for pathogenesis of Legionella infection was further corroborated by the observation that 5% of the bacteria recovered from the lungs of guinea pigs infected with the wild-type strain RC1 were negative for mAb 2625 binding . These findings strongly indicate that under in vivo conditions switching between two LPS phenotypes occurs and may promote adaptation and replication of L . pneumophila . This is the first description of phase-variable expression of Legionella LPS. Biochim Biophys Acta, 1998 Jun 24, 1372(1), 78 - 90 Membrane permeabilisation and antimycoplasmic activity of the 18-residue peptaibols, trichorzins PA; Beven L et al.; The membrane permeabilisation properties of six linear natural 18-residue peptaibols, termed trichorzins PA, have been assessed on liposomes and on mollicutes (trivial name, mycoplasmas), a class of parasitic bacteria characterized by a small genome, the lack of a cell wall, a minute cell size, and the incorporation in their plasma membrane of exogenously supplied cholesterol . The trichorzins PA used in this study (PA II, PA IV-VI, PA VIII, and PA IX) differ between them by amino acid or amino alcohol substitutions at positions 4, 7, and 18, and form slightly amphipathic alpha-helices . They proved bactericidal for mollicutes belonging to the genera Acholeplasma, Mycoplasma, and Spiroplasma, with minimal inhibitory concentrations (3.12</=MICs</=50 microM) generally 2 to 4 fold higher than those of alamethicin F50, a related 20-residue peptide (1.56</=MICs</=12.5 microM) . Spiroplasma cells were apparently not protected by the presence of spiralin on their surface . The activities of the six trichorzins PA were not influenced by their sequence variations and no synergistic effect was observed . Consistent with the marginal effect of cholesterol on the incorporation of the trichorzins PA into liposome bilayers, the antibiotic activity was independent of the amount of cholesterol in the membranes of the different mollicutes . The trichorzins PA and alamethicin inhibited the motility of Spiroplasma melliferum, the helical cells being deformed and split into coccoid forms . Membrane potential measurements in Acholeplasma laidlawii and S . melliferum showed that trichorzin PA V and alamethicin F50 very efficiently depolarized the plasma membrane of mollicutes . This was consistent with fluorescence and 23Na NMR measurements on liposomes that revealed the permeabilisation of the lipid bilayer and the nonselective ionophoric activity of the trichorzins PA . These data suggest that the bactericidal activity exhibited by the trichorzins PA on mollicutes is due to the permeabilisation of the plasma membrane . J Autoimmun, 1998 Apr, 11(2), 185 - 90 Antineutrophil cytoplasmic autoantibodies (ANCA) in children with cystic fibrosis; Sediva A et al.; Anti-neutrophil cytoplasmic antibodies (ANCA) represent a useful diagnostic tool in patients with small vessel vasculitis . Circulating ANCA specific for bactericidal/permeability increasing protein (BPI) have been recently reported in adult patients with cystic fibrosis (CF), an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene with consequent impaired function of a transmembrane chloride channel . To contribute to the better understanding of the significance of ANCA in this disease, we investigated ANCA presence and antigenic specificity in children with CF . Results were correlated with clinical status, immunological data, age and genotype . The indirect immunofluorescence pattern of a total of 71 children with CF indicated that 31 were c-ANCA positive, while seven were p-ANCA positive . In further ELISA studies of ANCA antigenic specificity, 51 out of 66 investigated samples were positive for BPI, and 14 out of 28 were positive for proteinase 3 (PR3) . We found an association between levels of antibodies against PR3 with age and Pseudomonas infection . We did not, however, find any correlation between CFTR genotypes, Pseudomonas infection or paediatric parameters and the level of anti-BPI antibodies . High positivity of anti-BPI antibodies were seen even among the youngest CF patients, before the development of clinical signs of CF, indicating that formation of ANCA might be a very early event in the disease . Both anti-BPI and anti-PR3 antibodies may play a significant, although variable role, in the pathogenesis of CF. Bull Acad Natl Med, 1998, 182(2), 285 - 97; discussion 297-8 {Recent aspects of monitoring the dosage of aminoglycosides and vancomycin}; Cheymol G et al.; The narrow range of therapeutic serum concentrations of aminoglycosides and vancomycin and the great variations in their pharmacokinetics from one person to another makes it important to monitor patients at risk that are treated with them . The technique of customizing dosages based on the population pharmacokinetics enables an effective treatment to be rapidly established from a few measurements of serum concentrations . Aminoglycosides may be given as single daily doses because of their concentration-dependent activity . The high peak concentration produces an enhanced, prolonged bactericidal activity, while a low residual concentration reduces the risk of toxicity . The effect of vancomycin is time-dependent . Giving it by continuous i.v . infusion maximizes the time during which the serum antibiotic concentration is effective but non-toxic . Monitoring serum concentrations can help reduce health care costs . But medical training in pharmacokinetics is needed for the optimal use of these therapeutic tools. Infect Immun, 1998 Jul, 66(7), 3113 - 9 Phenotypic effect of isogenic uspA1 and uspA2 mutations on Moraxella catarrhalis 035E; Aebi C et al.; The UspA surface antigen of Moraxella catarrhalis was recently shown to be comprised of two different proteins (UspA1 and UspA2) which share an internal region containing 140 amino acids with 93% identity (C . Aebi, I . Maciver, J . L . Latimer, L . D . Cope, M . K . Stevens, S . E . Thomas, G . H . McCracken, Jr., and E . J . Hansen, Infect . Immun . 65:4367-4377, 1997) . Isogenic uspA1, uspA2, and uspA1 uspA2 mutants were tested in a number of in vitro systems to determine what effect these mutations, either individually or together, might exert on the phenotype of M . catarrhalis 035E . Monoclonal antibodies specific for UspA1 or UspA2 were used in an indirect antibody accessibility assay to prove that both of these proteins were expressed on the surface of M . catarrhalis . All three mutants grew in vitro at the same rate and did not exhibit autoagglutination or hemagglutination properties that were detectably different from those of the wild-type parent strain . When tested for the ability to adhere to human epithelial cells, the wild-type parent strain and the uspA2 mutant readily attached to Chang conjunctival cells . In contrast, the uspA1 mutant and the uspA1 uspA2 double mutant both attached to these epithelial cells at a level nearly 2 orders of magnitude lower than that obtained with the wild-type parent strain, a result which suggested that expression of UspA1 by M . catarrhalis is essential for attachment to these epithelial cells . Both the wild-type parent strain and the uspA1 mutant were resistant to the bactericidal activity of normal human serum, whereas the uspA2 mutant and the uspA1 uspA2 double mutant were readily killed by this serum . This latter result indicated that the presence of UspA2 is essential for expression of serum resistance by M . catarrhalis. J Trauma, 1998 Jun, 44(6), 1047 - 54; discussion 1054-5 Recombinant human granulocyte colony-stimulating factor attenuates inflammatory responses in septic patients with neutropenia; Ishikawa K et al.; OBJECTIVE: The objective of this study was to determine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in septic patients with neutropenia . METHODS: Twenty consecutive septic patients were administered rhG-CSF subcutaneously (2 microg x kg(-1) x d(-1)) for 5 days (group G) . They were compared with 14 septic patients treated earlier without rhG-CSF (group N) . All patients in both groups met the criteria of total leukocyte count (TLC) less than 5,000/mm3 and C-reactive protein (CRP) more than 10 mg/dL . Changes in TLC, absolute neutrophil count (ANC), CRP, respiratory index (RI), Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Goris's Multiple Organ Failure (MOF) index were evaluated . In addition, nucleated cell count (NCC), differentiation in bone marrow aspiration, neutrophil phagocytic and bactericidal activity, serum concentrations of interleukin-6 (IL-6) and IL-8 as inflammatory markers, and plasma concentration of leukocyte elastase (LE) as an indicator of the tissue injury were evaluated in group G . RESULTS: In group G, TLC, ANC, NCC, and neutrophil functions increased significantly, whereas CRP, IL-6, and IL-8 decreased reciprocally . There was no deterioration of LE and RI . Consequently, the APACHE II score and MOF index improved . In group N, however, CRP showed no change concomitant with the APACHE II score and MOF index . CONCLUSION: Administration of rhG-CSF attenuates inflammatory responses without inducing tissue injury in septic patients with neutropenia. Scand J Med Sci Sports, 1998 Apr, 8(2), 91 - 7 Aspects of leukocyte function and the complement system following aerobic exercise in young female gymnasts; Wolach B et al.; Recent studies have reported reduced immunity in trained athletes . Scant information exists on changes in the immune function among trained children . The purpose of this study was to assess the effect of aerobic exercise on the phagocytic process of neutrophils and the complement system in young athletes . Subjects included prepubertal elite female gymnasts (n = 7) and untrained girls (n = 6) aged 10-12 years . Venous blood was withdrawn before, immediately post and 24 h following a 20-min run at a heart rate of 170-180 beats.min-1 . Neutrophil random migration, chemotactic activity, bactericidal function and PMA/FMLP-stimulated superoxide anion release as well as various complement components were assessed . Net chemotaxis was found reduced (P < 0.05) 24 h following exercise (58 +/- 11 vs . 36 +/- 11 cells/field in gymnasts and 47 +/- 7 vs . 42 +/- 8 cells/field in untrained girls pre- and 24 h post-exercise, respectively) . The basal values, as well as post-exercise values of bactericidal activity were lower (P < 0.05) in gymnasts as compared with the control group (0.8 +/- 0.3, 0.8 +/- 0.2 and 0.8 +/- 0.1 log decrease of colonies in gymnasts at pre-, immediately post-, and 24 h post-exercise, respectively and 1.1 +/- 0.1, 1.1 +/- 0.1 and 1.0 +/- 0.2 log decrease of colonies in controls, respectively) . No significant effect on the bactericidal activity was observed in either group following exercise . The addition of homologous sera did not correct the bactericidal activity . PMA-stimulated superoxide anion release decreased (P < 0.05) among gymnasts immediately following exercise (5.7 +/- 0.4 vs . 4.4 +/- 1.0 mmol O2/10(6) PMN.min) and remained low 24 h later . The same trend was observed in FMLP-stimulated neutrophils but the data were not significant . Significantly decreased levels (P < 0.05) of the early complement components (C1Q, C1R) were also found following exercise (1.34 +/- 0.64 vs . 1.27 +/- 0.28 and 1.09 +/- 0.07 vs . 1.02 +/- 0.06 pre- and post-exercise in gymnasts and untrained, respectively) . Furthermore, consistently lower C2 and C3 were observed in gymnasts compared with controls . Neutrophil dysfunction as well as impairment of the complement system seem to occur following exercise. FEMS Microbiol Lett, 1998 May 15, 162(2), 331 - 7 Variation in Bordetella bronchiseptica lipopolysaccharide during human infection; Gueirard P et al.; We previously reported the case of a human chronic Bordetella bronchiseptica respiratory infection, due to contact with infected rabbits . Lipopolysaccharides of the human isolates, of one rabbit isolate and of isolate from other origins were analyzed with sera from infected mice, rabbit and human . Antigenicity and length of the lipopolysaccharide molecules varied between isolates . We showed a progressive loss of O-chain during infection, associated with an enhanced susceptibility of the isolates to the bactericidal effect of normal serum . This observation suggests the existence of an intracellular niche which selects for strains with distinct lipopolysaccharide types. Br J Biomed Sci, 1997 Dec, 54(4), 260 - 6 Polymorphonuclear neutrophils in saliva and blood: a comparative study of morphology, function and phenotype; Takubo T et al.; The morphology, phagocytic activity, production of hydrogen peroxide (H2O2) and expression of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), complement receptor type 3 (CR3; CD11b/CD18), p150,95 (CD11c/CD18), and platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) by oral polymorphonuclear neutrophils (PMN) are assessed and the results compared with those of blood PMN . There were no differences in the morphology and phagocytic activity between oral and blood PMN . H2O2 production was measured following stimulation with phorbol myristate acetate (PMA) and N-formyl-L-leucyl-L-phenylalanine (FMLP) as indicators of bactericidal activity . There was a significant difference in the H2O2 production by the two groups when stimulated with FMLP; the level of H2O2 production by oral PMN was significantly higher than that by blood PMN . However, there was no significant difference in H2O2 production between oral and blood PMN when stimulated with PMA . The percentage of CD11a- and CD11c-positive concentrated oral PMN was significantly lower than that seen in blood PMN, as was the percentage of CD31-positive cells . Higher H2O2 production by oral PMN following stimulation with FMLP may result in enhanced bactericidal activity . Low expression of CD31 may lead to the accumulation of PMN in the mouth by blocking their return to the bloodstream . These phenomena may be necessary for oral PMN to protect periodontal tissues from bacteria in the mouth. Clin Infect Dis, 1998 Apr, 26(4), 874 - 7 Activity of amoxicillin/clavulanate in patients with tuberculosis; Chambers HF et al.; Some beta-lactam antibiotics are active in vitro against Mycobacterium tuberculosis . There are anecdotal reports of successful treatment of tuberculosis caused by multiple-drug-resistant strains of M . tuberculosis with regimens that included amoxicillin/clavulanate . Reduction of M . tuberculosis in the sputum of patients with pulmonary tuberculosis during administration of amoxicillin/clavulanate was measured by a quantitative culture method to determine the activity in vivo . Patients were randomized to receive isoniazid, ofloxacin, or amoxicillin/clavulanate for 7 days . Isoniazid was the most effective agent, reducing M . tuberculosis after 2 days at a mean rate (+/- standard deviation) of 0.60 +/- 0.30 log10 cfu/mL per day, compared with 0.32 +/- 0.05 and 0.34 +/- 0.03 for ofloxacin and amoxicillin/clavulanate, respectively . The early bactericidal activity of amoxicillin/clavulanate was comparable to that reported for antituberculous agents other than isoniazid . Further studies of beta-lactam antibiotics with in vitro activity against M . tuberculosis are warranted to define their role in treatment of tuberculosis. Autoimmunity, 1998, 27(4), 231 - 8 Anti-neutrophil cytoplasm autoantibodies (ANCA) . The need for specific and sensitive assays; Baslund B et al.; Anti-neutrophil cytoplasm antibodies (ANCA) are a group of autoantibodies primarily associated with systemic vasculitis . Hitherto, the method of choice for ANCA detection has been indirect immunofluorescence (IIF) . By this method two major patterns can be seen: a cytoplasmic pattern (cANCA) or a perinuclear pattern (pANCA) . The cANCA pattern is most often caused by antibodies directed against proteinase-3 (PR3) and in rare cases it is caused by anti-myeloperoixdase (MPO) antibodies . The pANCA pattern can de caused by antibodies directed against a large group of proteins i.e . MPO, lactofenin and bactericidal/permeability-increasing protein . Often there is a discrepancy between the results obtained by IIF and those reported from the use of assays with purified antigens . This causes confusion . Until now only anti-PR3 and anti-MPO have been found of any clinical value . Therefore, it would be more proper to use assays with these highly purified antigens instead of an unspecific method like IIF. Eksp Klin Farmakol, 1998 Mar-Apr, 61(2), 48 - 50 {The effect of the immunostimulating agent trimezon on the cells of the mononuclear phagocytosing system}; Liubin GS et al.; The effect of the immunostimulator trimeson of the 8-aza-gomogonan series on the cells of the mononuclear monocyte system was studied in C3H and ICR mice in vitro . Intraperitoneal injection of trimeson (50 mg/kg 1 x 10(-7)-1 x 10(6) M) inhibits, as a rule, the initial stages of the phagocytizing process but stimulates the bactericidal properties of the peritoneal phagocytes and their mechanisms of processing and destruction of the antigen material . In the system of adaptive transfer of donor splenocytes and peritoneal macrophages to recipients exposed to lethal radiation, trimeson (20 mg/kg intravenously, 50 mg/kg per os) increases the immunogenic function of the mononuclear phagocytes in formation of the primary immune response to sheep erythrocytes. J Biol Chem, 1998 Jun 5, 273(23), 14071 - 3 Helicobacter pylori generates superoxide radicals and modulates nitric oxide metabolism; Nagata K et al.; During studies of the bactericidal action of nitric oxide (NO), we found that it reversibly inhibited the respiration of Escherichia coli and irreversibly inhibited the respiration of Helicobacter pylori . Peroxynitrite, a reaction product of NO and superoxide, irreversibly inhibited the respiration of both H . pylori and E . coli . H . pylori, but not E . coli, generated substantial amounts of superoxide radicals . These results suggest that NO directly inhibits the respiration of E . coli whereas it rapidly reacts with endogenously generated superoxide radicals in H . pylori . The resulting peroxynitrite inactivates the respiration of H . pylori. Cell Mol Biol (Noisy-le-grand), 1998 May, 44(3), 521 - 6 Streptomycin bactericidal action is dependent on polyamine endogenous levels in E . coli; Diniello GB et al.; E . coli polyamine-supplemented and depleted cultures showed an important difference in survival to streptomycin; the bactericidal effect of the antibiotic was remarkably higher in cells with normal levels of polyamines . Similar results were observed with kanamycin . Analysis of the polyamine-containing cells pulse-labelled with 35S-methionine during streptomycin action indicated that the amounts of newly-synthesized peptides in various subcellular fractions was different from the amounts formed in the untreated controls; the most dramatic change was found in the residual particulate fraction where the antibiotic treatment caused a 3-fold increase of radioactive proteins . On the contrary, equivalent amounts of labelled peptides were detected in the different fractions prepared from polyamine-depleted bacteria incubated with or without antibiotic . In this case the corresponding residual fraction was only slightly increased . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the different fractions showed some changes elicited by streptomycin in the protein patterns of polyamine-containing bacteria, especially in the residual fractions . The electrophoretic profile corresponding to deprived cells was very similar in all cases . The role of polyamines in the conformation of the outer membrane and in the correct assembly of ribosomes is discussed on account of the enhancing effect of these polycations on the bactericidal action of streptomycin. J Bone Joint Surg Br, 1998 May, 80(3), 527 - 30 Treatment of osteomyelitis with antibiotic-soaked porous glass ceramic; Kawanabe K et al.; We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis . A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum . We evaluated the release concentrations of the antibiotics from the blocks . The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days . The concentrations of CMZ from both materials were lower than those of ISP . An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation . Osteoconduction of the A-W GC block was good . Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results. Dev Comp Immunol, 1998 Jan-Feb, 22(1), 55 - 61 A comparison of the chemiluminescent response of Crassostrea virginica and Morone saxatilis phagocytes to zymosan and viable Listonella anguillarum; Bramble LH et al.; If reactive oxygen species (ROS) produced by hemocytes of the eastern oyster, Crassostrea virginica, impart bactericidal activity, exposure of hemocytes to bacteria should result in increased ROS generation . In an earlier study, this hypothesis was tested using luminol- and lucigenin-augmented chemiluminescence (CL) to measure ROS production . The bacterium Listonella anguillarum did not stimulate a net increase in hemocyte-derived CL, and it was suggested that bacterial antioxidants might suppress hemocyte CL . In the present study a comparison was made, under identical assay conditions, of the zymosan- and bacteria-enhanced luminol CL produced by eastern oyster hemocytes and by striped bass (Morone saxatilis) macrophages, for which L . anguillarum has been shown to be a stimulus in CL reactions . The response to zymosan produced by bass phagocytes was two orders of magnitude greater than that generated by eastern oyster hemocytes . Whereas an increase in net ROS production was not evident when oyster hemocytes were exposed to L . anguillarum, significant stimulation of striped bass macrophage-derived CL occurred . These data suggest that striped bass macrophages have a greater capacity to generate ROS than oyster hemocytes, enabling them to surpass the antioxidant capability of L . anguillarum and produce a luminol CL response. Antiviral Res, 1998 Apr, 38(1), 25 - 30 Activity of N-chlorotaurine against herpes simplex- and adenoviruses; Nagl M et al.; N-chlorotaurine, an essential weak oxidant produced by stimulated human leukocytes, is known to have bactericidal, fungicidal and vermicidal properties . This study for the first time demonstrates its virucidal activity . By viral suspension tests at incubation times between 5 and 60 min, virus titers of both Herpes simplex virus type 1 and 2 were reduced about 1.3-2.9 log10 and 2.8-4.2 log10 by 0.1 and 1%, (5.5 and 55 mM) N-chlorotaurine, respectively . Virus titer reduction of adenovirus type 5 between 15 and 60 min was 0.5-2.0 and 0.6-4.0 log10, respectively, by the same concentrations of N-chlorotaurine . These findings support a contribution of N-chlorotaurine in destruction of pathogens during inflammatory reactions and also the possibility of its application as an antiviral agent in human medicine. Australas J Dermatol, 1998 May, 39(2), 96 - 9 Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leucocytoclastic vasculitis associated with antithyroid therapy in Graves' disease; Miller RM et al.; Presented is a case of a 27-year-old male with Graves' disease on long-term propylthiouracil treatment who, when changed to carbimazole, rapidly developed a petechial and purpuric eruption on the legs, which subsequently flared on treatment with radioiodine . The clinical diagnosis of leucocytoclastic vasculitis was confirmed on skin biopsy . High-titre antineutrophil cytoplasmic antibodies in a perinuclear pattern (P-ANCA) were identified . No anti-myeloperoxidase activity was noted; therefore, the P-ANCA were classified in the atypical group . The target antigens, as determined by enzyme-linked immunosorbent assay, were lysozyme, lactoferrin and bactericidal/permeability increasing protein . Propylthiouracil and carbimazole are chemically related antithyroid drugs . There are reports of typical and atypical P-ANCA-positive cutaneous vasculitis due to propylthiouracil . Cutaneous vasculitis associated with atypical P-ANCA has not been noted previously to be temporally related to carbimazole use . The consideration of thionamides as possible aetiological agents in cases of P-ANCA-positive drug-induced vasculitis is suggested. Am J Respir Crit Care Med, 1998 May, 157(5 Pt 1), 1436 - 40 Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice; Grosset J et al.; The bactericidal activities of several once-weekly rifapentine (P)-containing combination regimens against Mycobacterium tuberculosis, and their ability to prevent the selection of rifampin (R)-resistant mutants, were compared with those of the standard six-times-weekly regimen consisting of R, isoniazid (H), and pyrazinamide (Z) in a mouse experiment . Mice were infected intravenously with 1.3 x 10(7) cfu of M . tuberculosis strain H37Rv, and 8 wk of treatment began on Day 14 after infection, when mice were randomly allocated to an untreated control group and nine treatment groups of 30 mice each . At the end of 8 wk of treatment, all the tested regimens showed promising bactericidal activities . Once-weekly P alone was less bactericidal than six-times-weekly R alone; likewise, the once-weekly P-containing combined regimens were less bactericidal than the six-times-weekly standard regimen . However, the difference in killing was about 1 log10, which represented only a fraction of the overall 4 log10 to 5 log10 magnitude of killing effects . The addition of streptomycin (S) improved the bactericidal effect of once-weekly PHZ, and the effect of once-weekly PHZS was further enhanced when it was preceded by 2 wk of daily HZS . The latter regimen achieved the same level of activity as the standard six-times-weekly regimen . All of the once-weekly P-containing combined regimens were able to prevent the selection of R-resistant mutants, whereas monotherapy with R or P selected resistant mutants in approximately 50% of animals. Chest, 1998 May, 113(5), 1290 - 5 Systemic inflammation present in patients undergoing CABG without extracorporeal circulation; Fransen E et al.; STUDY OBJECTIVES: This study was conducted to evaluate to what extent the cardiopulmonary bypass (CPB) procedure in patients undergoing coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response . Therefore, we measured bactericidal permeability increasing protein (BPI) as an indicator of neutrophil activation, interleukin 6 as inducer of the acute phase response, and lipopolysaccharide binding protein and C-reactive protein as parameters of the acute phase response in patients undergoing CABG either with or without the use of CPB . DESIGN: Prospective study . SETTING: Cardiopulmonary surgery department in a university hospital . PATIENTS: Sixteen patients undergoing elective CABG were included . Eight patients underwent surgery with CPB, and eight patients underwent surgery without CPB (non-CPB) . INTERVENTIONS: In the CPB group, blood samples were taken upon induction of anesthesia, at the start of aortic cross-clamping, at aortic unclamping, and 0.5, 4, 8, and 18 h thereafter . In the non-CPB group, blood samples were taken upon induction of anesthesia, and 0.5, 4, 8, and 18 h after completion of the bypass graft anastomoses . MEASUREMENTS AND RESULTS: BPI release from neutrophil granules markedly increased during surgery in CPB patients but not in non-CPB patients . The increase in acute phase reactants, however, was the same in both patient groups . CONCLUSIONS: These data indicate that the acute phase response in CABG patients, which has historically been ascribed to the CPB procedure, is predominantly caused by the surgical procedure per se . Early neutrophil activation, however, is seen only when extracorporeal circulation is used. FEMS Microbiol Lett, 1998 May 1, 162(1), 117 - 22 Physiological consequences of the over-production of E . coli truncated molecular chaperone DnaJ; al-Herran S et al.; In Escherichia coli one of the main molecular chaperones is DnaJ (hsp40) which mediates in a variety of highly conserved cellular process including protein folding reactions and assembly/disassembly of protein complexes . In this study we have investigated the toxicity of the over-production of DnaJ and two truncated polypeptides by examining growth rates, cell morphology and cell viability . Full-length DnaJ (1-375 amino acids) and truncated polypeptides, corresponding to the last 176 (containing the substrate binding domain) and 266 (containing the zinc finger-like domain) amino acids of the C-terminus of DnaJ, DnaJ delta 1-199 and delta 1-108 respectively, were over-produced via IPTG induction . High levels of synthesis were determined by SDS-PAGE and Western blotting using anti-DnaJ antibodies . The over-production of full-length DnaJ resulted in a low degree of filamentation and a decrease in cell viability . However, over-production of DnaJ truncated polypeptides, especially DnaJ delta 1-108, was bactericidal and resulted in a loss of viability and defective septation. Antimicrob Agents Chemother, 1998 May, 42(5), 1115 - 20 Bactericidal activity of a single-dose combination of ofloxacin plus minocycline, with or without rifampin, against Mycobacterium leprae in mice and in lepromatous patients; Ji B et al.; To develop a fully supervisable, monthly administered regimen for treatment of leprosy, the bactericidal effect of a single-dose combination of ofloxacin (OFLO) and minocycline (MINO), with or without rifampin (RMP), against Mycobacterium leprae was studied in the mouse footpad system and in previously untreated lepromatous leprosy patients . Bactericidal activity was measured by the proportional bactericidal method . In mouse experiments, the activity of a single dose of the combination OFLO-MINO was dosage related; the higher dosage of the combination displayed bactericidal activity which was significantly inferior to that of a single dose of RMP, whereas the lower dosage did not exhibit a bactericidal effect . In the clinical trial, 20 patients with previously untreated lepromatous leprosy were treated with a single dose consisting of either 600 mg of RMP plus 400 mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of MINO . The OFLO-MINO combination exhibited definite bactericidal activity in 7 of 10 patients but was less bactericidal than the RMP-OFLO-MINO combination . Both combinations were well tolerated . Because of these promising results, a test of the efficacy of multiple doses of ROM in a larger clinical trial appears justified. Antimicrob Agents Chemother, 1998 May, 42(5), 1022 - 7 Modulation of gyrase-mediated DNA cleavage and cell killing by ATP; Li TK et al.; An uncoupler of oxidative phosphorylation, 2,4-dinitrophenol, and an aconitase inhibitor, fluoroacetic acid, both of which are known to lower the cellular ATP pool, protected Escherichia coli cells from the bactericidal actions of gyrase poisons including quinolone antibiotics, nalidixic acid and ciprofloxacin, and the epipodophyllotoxins VP-16 and VM-26 . Using purified E . coli DNA gyrase, we examined the effect of ATP on gyrase-mediated DNA cleavage in the presence of these gyrase poisons . ATP was shown to stimulate gyrase-mediated DNA cleavage from 10- to more than 100-fold in the presence of these gyrase poisons . ADP antagonized the stimulatory effect of ATP . Consequently, gyrase-mediated DNA cleavage induced by gyrase poisons is modulated by the ATP concentration/ADP concentration ({ATP}/{ADP}) ratio . Coumermycin A1, an inhibitor of the ATPase subunit of DNA gyrase, like ADP, also effectively antagonized the stimulatory effect of ATP on gyrase-mediated DNA cleavage induced by gyrase poisons . Furthermore, coumermycin A1, like DNP and fluoroacetic acid, also protected cells from the bactericidal action of gyrase poisons . In the aggregate, our results are consistent with the notion that the {ATP}/{ADP} ratio, through its modulatory effect on the gyrase-mediated DNA cleavage, is an important determinant of cellular susceptibility to gyrase poisons. Am J Hematol, 1998 May, 58(1), 8 - 15 Neonatal neutrophil inflammatory responses: parallel studies of light scattering, cell polarization, chemotaxis, superoxide release, and bactericidal activity; Wolach B et al.; Neutrophil dysfunction among newborn infants, especially those born prematurely, is well recognized, but the mechanism responsible for this phenomenon is yet to be clarified . In this study, we evaluated the stimulus response coupling in neutrophils from 90 healthy newborns and 96 healthy adults in an effort to establish whether defective neonatal neutrophil function is a result of impaired signal perception or immature responsiveness . Measurement of rapid- and slow-light scattering responses (LSR) to 1 microM FMLP stimulation revealed that neonatal neutrophils have about one-half the corresponding responsiveness of adult cells (rapid-LSR: 6.1 +/- 3.1 arbitrary light intensity units vs . 12.0 +/- 2.8, P < .001; and slow-LSR: 5.0 +/- 2.5 vs . 9.1 +/- 2.0; P < .001) . The same markedly reduced activity was observed in newborn neutrophil chemotaxis and bactericidal activity in comparison with adult cells . Nevertheless, low FMLP concentrations (less than 1 nM) induced no difference in cell polarization between newborn and adult neutrophils, yet at higher FMLP concentrations, the newborn revealed significantly reduced cell polarization . Our data suggest that newborn infants bear a fully functional FMLP signal perception but lack the full capacity of inflammatory responsiveness. Am J Med Sci, 1998 May, 315(5), 307 - 13 Complement component C9 enhances the capacity of beta-lactam antibiotics to kill Escherichia coli in vitro and in vivo; Jung E et al.; Complement component C9 is required for rapid complement-mediated killing of Escherichia coli . In this report, the influence of supplemental C9 on the bactericidal and protective effects of beta-lactam antibiotics in neonates was assessed . By rocket immunoelectrophoresis, the intrinsic C9 concentrations of pooled serum from both human and rat neonates was less than 20% of adult levels . Supplemental C9 purified from human plasma enhanced the capacity of ampicillin-treated serum from human neonates to impair the survival of E coli O7:K1:NM (P < 0.02) . Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05) . Moreover, the intraperitoneal administration of C9 enhanced the survival of cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05) . These observations may contribute to the development of new strategies, such as augmentation of complement component serum concentrations, to reduce the morbidity and mortality of neonatal E coli sepsis. Kansenshogaku Zasshi, 1998 Mar, 72(3), 211 - 7 {Bactericidal and anti-toxin activities of catechin on enterohemorrhagic Escherichia coli}; Okubo S et al.; We examined the bactericidal activity of catechin, an astringent ingredient of tea, on enterohemorrhagic Escherichia coli (EHEC) O157:H7 and the anti-toxin activity of catechin on vero toxin (VT), the main pathogenic factor of EHEC O157:H7 . To examine bactericidal activity, we added 1 X 10(4) CFU/ml bacteria to 1.25 to 20 W/V% of green tea extract or the PBS solution containing 25 to 400 micrograms/ml of (-) epigallocatechin gallate (EGCg), which is the main catechin ingredient of green tea leaf, and counted the number of live bacteria at various intervals . After 3 to 5 hours, no live bacteria were seen in 1.25 to 2.5 (regular drinking concentration) % green tea extract . In the high concentrations of 100 to 400 micrograms/ml EGCg the number of live bacteria decreased with time and after 24 hours no survivors were seen . In the low concentrations of 25 to 50 micrograms/ml EGCg, however, no change was observed in the number of live bacteria during 5 hours . After 24 hours the bacteria in 50 micrograms/ml were killed and the number of bacteria in 25 micrograms/ml decreased to one tenth of that at the start . To examine the anti-toxin activity, we mixed equal volumes of 2 ng/0.1 ml VT2 and 0.5 to 2 mg/0.1 ml catechin in vitro and incubated them at 37 degrees C for various times . Then we inoculated 0.2 ml of the mixture intraperitonealy to BALB/c mice . One mg of catechin inhibited by 100% the lethal toxicity of 2 ng of VT2 (LD 100) to mice . The inhibition of lethal toxicity of VT2 by catechin depended on the incubation time . The rate of inhibition was 0, 40 and 100% for 9, 12 and 18-24 hours incubation, respectively . These results suggest that catechin has not only bactericidal activity on EHEC O157:H7 but also anti-toxin activity on vero toxin. Proc Natl Acad Sci U S A, 1998 Apr 14, 95(8), 4321 - 6 Translocation of inserted foreign epitopes by a channel-forming protein; Jakes KS et al.; Certain bacterial protein toxins are able to insert themselves into, and at least partially across, lipid bilayer membranes in the absence of any auxiliary proteins, by using unknown mechanisms to overcome the high energy barrier presented by the hydrophobic bilayer core . We have previously shown that one such toxin, colicin Ia, translocates a large, hydrophilic part of itself completely across a lipid bilayer in conjunction with the formation of an ion-conducting channel . To address the question of whether the colicin can translocate any arbitrary amino acid sequence, we have altered the translocated segment by inserting, singly, two different foreign epitopes . Colicins containing either epitope retain significant bactericidal activity and form channels of normal conductance in planar bilayers . Furthermore, antibodies added on the side of the bilayer opposite that to which the colicin was added interact specifically with the corresponding epitopes, producing an inhibition of channel closing . Thus, the inserted epitopes are translocated along with the rest of the segment, suggesting that a surprisingly small part of colicin Ia, located elsewhere in the molecule, acts as a nonspecific protein translocator. Rocz Akad Med Bialymst, 1997, 42(1), 141 - 7 The bactericidal activity of blood platelets in patients infested with Entamoeba histolytica/Entamoeba dispar; Matowicka-Karna J et al.; Blood platelets participate actively in organism defensive reactions and particularity in antiparasitic immunity . Platelets stimulation can be the result of contact with a parasite, the presence of immunoglobulins, complement and lymphokines . The aim of the study was to evaluate the blood platelets bactericidal activity in the course of amoebiasis . The examination was carried out in the group of 22 patients with E . histolytica/E . dispar, diagnosed on the basis of cyst forms presence in faeces . The results show that blood platelets bactericidal activity is significantly impaired in the course of amoebiasis. J Antimicrob Chemother, 1998 Mar, 41 Suppl B, 23 - 7 The comparative in-vitro activity of roxithromycin and other antibiotics against Bordetella pertussis; Brett M et al.; In spite of vaccination programmes, whooping cough epidemics continue to occur . The disease affects all age groups, although its severity is greatest in the young, with infants being particularly vulnerable . Erythromycin is generally accepted as the drug of choice both for treatment and for prophylaxis during epidemics . Roxithromycin is a macrolide with pharmacokinetic advantages over erythromycin; it is well absorbed, produces high serum concentrations, has a long half-life and penetrates respiratory secretions well . There are no accepted standards for testing the sensitivity of Bordetella pertussis to antibiotics, and reports of the activity of roxithromycin and erythromycin are variable . Using Isosensitest agar supplemented with 5% horse blood and an inoculum of 10(4) cfu, 88 strains of B . pertussis were tested for their sensitivity to roxithromycin, erythromycin, rifampicin and trimethoprim/sulphamethoxazole . The range of MICs was 0.12-0.5 mg/L for both roxithromycin and erythromycin . Roxithromycin was bactericidal, with an MBC of 1 mg/L (as compared with 0.5 mg/L for erythromycin) . Since roxithromycin is well tolerated by children when used for respiratory tract infections, the good in-vitro activity against B . pertussis, combined with its favourable pharmacokinetics, suggest it may be a good candidate for use in the treatment and prophylaxis of whooping cough. LDA J, 1997 Fall, 56(3), 16 - 8 Efficacy of topical disinfectants; Oeschger MP et al.; A comparison of bactericidal activity of two surface disinfectants showed that both were highly effective . The glutaraldehyde-based disinfectant showed higher efficacy on roughed surfaces than the alcohol-based disinfectant . The study used a novel, and generally applicable, method to evaluate the surface killing potential of disinfectants. Int J Biochem Cell Biol, 1997 Dec, 29(12), 1401 - 18 IL-6-regulated transcription factors; Akira S; Through the cloning of two transcription factors named NF-IL6 and STAT3/APRF, two types of IL-6 signal transduction pathways from the cell surface to the nucleus have been revealed . NF-IL6 is phosphorylated and activated by a Ras-dependent MAP kinase cascade, while STAT3/APRF is directly tyrosine-phosphorylated by JAK kinases that associate with the cytoplasmic portion of the receptor, and translocates to the nucleus and activates transcription (JAK-STAT pathway) . STAT3 is also tyrosine phosphorylated in response to epidermal growth factor (EGF), granulocyte colony-stimulating factor (G-CSF), leptin and other IL-6-type cytokines including ciliary neurotrophic factor (CNTF), oncostatin M and leukemia inhibitory factor (LIF) . Mice deficient in the genes for NF-IL6 and STAT3 were generated . NF-IL6 mice were highly susceptible to facultative intracellular bacteria owing to ineffective killing of the pathogens by the macrophages . Futhermore, the tumor cytotoxicity of macrophages from NF-IL6 KO mice was severely impaired . These results demonstrate a crucial role of NF-IL6 in macrophage bactericidal and tumoricidal activities . The target disruption of STAT3 resulted in embryonic lethality prior to gastrulation, demonstrating that STAT3 is essential for the early development of mouse embryos. Lett Appl Microbiol, 1998 Mar, 26(3), 194 - 8 Effects of tea tree oil on Escherichia coli; Gustafson JE et al.; Tea tree oil (TTO) stimulates autolysis in exponential and stationary phase cells of Escherichia coli . Electron micrographs of cells grown in the presence of TTO showed the loss of electron dense material, coagulation of cell cytoplasm and formation of extracellular blebs . Stationary phase cells demonstrated less TTO-stimulated autolysis and also had greater tolerance to TTO-induced cell death, compared to exponentially grown cells . It was also revealed that subpopulation of stationary phase cells demonstrated increased tolerance to TTO-bactericidal effects. Clin Exp Immunol, 1998 Apr, 112(1), 10 - 6 Catalase and alpha-enolase: two novel granulocyte autoantigens in inflammatory bowel disease (IBD); Roozendaal C et al.; In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies . In this study, we identify the target antigens of ANCA in large groups of patients with ulcerative colitis (UC) and Crohn's disease (CD) . Apart from antibodies against lactoferrin and bactericidal/permeability-increasing protein (BPI), which have been reported before, antibodies against two novel granulocyte antigens were identified: antibodies against a 57/56-kD doublet were found in 38% of samples from UC patients and in 26% of samples from CD patients, whereas antibodies against a 47-kD protein were found in 10% of samples from UC patients and in 18% of samples from CD patients . Partial purification and amino acid sequence analysis identified the 57-kD protein as catalase and the 47-kD protein as alpha-enolase . This study is the first to report catalase and alpha-enolase as granulocyte antigens for autoantibodies in IBD. Diagn Microbiol Infect Dis, 1998 Feb, 30(2), 135 - 7 Timed kill kinetic studies of levofloxacin, ofloxacin, and ciprofloxacin against Moraxella catarrhalis; Barrett MS et al.; Levofloxacin bactericidal activity was compared to ciprofloxacin and ofloxacin against 10 strains of Moraxella catarrhalis . The cidal action (by kill-curve analysis) was slightly more rapid for levofloxacin, but all tested fluoroquinolones were considered bactericidal for all strains tested, including those producing BRO-1 and 2 beta-lactamases. Int J Antimicrob Agents, 1997 Jan, 9(3), 169 - 73 The activity of rifabutin against Mycobacterium leprae in armadillos; Dhople AM et al.; The activity of rifabutin (LM 427) against Mycobacterium leprae was evaluated in armadillos inoculated earlier with human-derived M . leprae . Rifabutin was administered daily at a dose of 6 mg/kg body weight/day . The effect of rifabutin on M . leprae harvested from armadillos was determined by measuring the intracellular levels of ATP (an indicator of metabolic activity) of M . leprae and also their ability to multiply in the mouse footpads and in vitro in DH medium . Within 2 weeks of initiating the treatment, ATP levels declined to 21% of the original (pre-treatment level) and these M . leprae failed to multiply in the footpads of mice as well as in the in vitro culture system . This suggests that rifabutin was able to kill all M . leprae within 2 weeks . After 8 weeks the treatment was terminated and results showed that M . leprae from the treated armadillos remained non-viable in the mouse footpad system as well as in the in vitro system, indicating bactericidal action of rifabutin . The results suggest that rifabutin can be a substitute for rifampin in the leprosy multi-drug therapy regimen. PDA J Pharm Sci Technol, 1998 Jan-Feb, 52(1), 37 - 42 Bacterial cell size and surface charge characteristics relevant to filter validation studies; Mittelman MW et al.; There are two recognized mechanisms whereby organisms are retained by liquid filters; namely, sieve-retention and adsorption . The efficiency of each may be influenced by the organism, suspending milieu, and by the filtration conditions . Validations of sterilizing filtrations require the use of organism suspensions in product-specific media . However, where the product is bactericidal to the challenge organism(s), surrogate solutions may be required . The ideal surrogate solution would minimize adsorptive retention, ensuring that the sterilizing action of the filter under consideration is the consequence of sieve-retention . This review explores the impact that various physicochemical factors may have on bacterial cell size and cell surface characteristics . An understanding of interactions among challenge bacteria, suspending fluid, and filter medium is essential for the development of surrogate solutions that provide a "worst case" mileu for filter validation studies or a "placebo," non-inhibitory challenge solution. Helicobacter, 1998 Mar, 3(1), 21 - 7 Growth inhibitory and bactericidal activities of lansoprazole compared with those of omeprazole and pantoprazole against Helicobacter pylori; Nakao M et al.; BACKGROUND: Helicobacter pylori plays a role in the pathogenesis of both duodenal and gastric ulcers . The aim of this study was to evaluate the effect of the proton pump inhibitor (PPI), lansoprazole, commonly used in eradication regimens, on growth, bactericidal activity and morphology of H . pylori in vitro in comparison with other PPIs . MATERIALS AND METHODS: Growth inhibitory activity of each of the PPIs was evaluated by determining minimum inhibitory concentrations using an agar dilution method . Bactericidal activity was determined by analysis of the viable cells in culture at various time points after incubation with different concentrations of the PPIs . Bacterial morphology was examined using scanning electron microscopy of fixed cells after exposure to the test substances . Urease activity in cell extracts of H . pylori that had been incubated with increasing concentrations of the PPIs was determined by colorimetry . RESULTS: The growth inhibitory activity of lansoprazole was significantly more potent than that of omeprazole or pantoprazole (MIC90 6.25 vs . 25 and 100 micrograms/ml, respectively) . Exposure of H . pylori to lansoprazole produced loss of viability and an aberrant bacterial morphology, which was more extensive than seen with omeprazole or pantoprazole . Lansoprazole dose dependently inhibited urease activity; its effectiveness was comparable with omeprazole but more potent than pantoprazole . CONCLUSIONS: The mechanism of action that leads to loss of viability of H . pylori cells appears to differ between the three PPIs investigated; lansoprazole was the most potent of the three agents in terms of growth inhibition and disruption of bacterial morphology. J Antimicrob Chemother, 1998 Feb, 41(2), 171 - 7 Flavodoxin-dependent pyruvate oxidation, acetate production and metronidazole reduction by Helicobacter pylori; Kaihovaara P et al.; Helicobacter pylori flavodoxin was purified to homogeneity from cell extracts of strain NCTC 11637 . The molecular weight of the protein was estimated by gel electrophoresis to be 18 kDa . Oxidized flavodoxin showed an absorption spectrum with maxima at 378 nm and 453 nm, and it was reduced to a neutral form of flavin semiquinone by the electrons generated in the oxidation of pyruvate . This coenzyme A dependent pyruvate:flavodoxin oxidoreductase activity of H . pylori was also detected as a reduction of methyl viologen or cytochrome c by bacterial extracts . The apparent Km of pyruvate was 310 microM . Anaerobically incubated bacteria (10{9}) of strain NCTC 11637 produced acetate (96 +/- 16 nmol/h) from pyruvate concomitantly reducing metronidazole (17 +/- 5 nmol/h) . In anaerobic conditions both sensitive and resistant H . pylori strains reduced metronidazole, and there was a significant positive correlation between acetate production and metronidazole activation (r = 0.77, P < 0.01, n = 11) . In the presence of atmospheric oxygen, H . pylori excreted twice as much acetate but metronidazole was not activated . These results suggest that the pyruvate:flavodoxin oxidoreductase complex catalyses pyruvate oxidation in H . pylori . Electrons generated in this reaction are transferred to flavodoxin and under anaerobic conditions further to metronidazole (imidazoles) thus reducing the drug to its bactericidal form. Cent Eur J Public Health, 1998 Feb, 6(1), 51 - 6 Long-term monitoring of the immune reactivity of stainless steel welders; Hanovcova I et al.; The immune reactivity of stainless steel welders (n = 22-53) was evaluated in a three year's study . The results (phagocytic activity, cellular and humoral immunity) were statistically compared with those in control group of non-exposed persons from the same plant (n = 14-23) and with long-term laboratory reference values (LRV) (n = 14-311) . In welders several changes were found when compared to the LRV: in humoral response there were higher prealbumin, lysozyme, circulating immune complexes and lower IgG . In phagocytic tests there were lower ingestion, bactericidal activity and higher metabolic activity of peripheral mononuclear leucocytes . In cellular immunity the marked lymphocytosis, higher counts of T-lymphocytes, CD4+ and CD8+ lymphocytes were noticed . After lowering the concentrations of metals in the working area there were trends to normal values in some parameters {relative numbers of T-lymphocytes, relative number of CD4+ lymphocytes, phagocytic activity, metabolic activity of leucocytes (INT index), IgA, complement C3, transferrin} . The extent and the length of the exposure to welding fumes, smoking and changed conditions at working place were followed as well. J Cell Biochem, 1998 Mar 1, 68(3), 355 - 65 Analysis of differential gene expression in rat tibia after an osteogenic stimulus in vivo: mechanical loading regulates osteopontin and myeloperoxidase; Miles RR et al.; The skeleton has the ability to alter its mass, geometry, and strength in response to mechanical stress . In order to elucidate the molecular mechanisms underlying this phenomenon, differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR) was used to analyze gene expression in endocortical bone of mature female rats . Female Sprague-Dawley rats, approximately 8 months old, received either a sham or bending load using a four-point loading apparatus on the right tibia . RNA was collected at 1 h and 24 h after load was applied, reverse-transcribed into cDNA, and used in DDRT-PCR . Parallel display of samples from sham and loaded bones on a sequencing gel showed several regulated bands . Further analysis of seven of these bands allowed us to isolate two genes that are regulated in response to a loading stimulus . Nucleotide analysis showed that one of the differentially expressed bands shares 99% sequence identity with rat osteopontin (OPN), a noncollagenous bone matrix protein . Northern blot analysis confirms that OPN mRNA expression is increased by nearly 4-fold, at 6 h and 24 h after loading . The second band shares 90% homology with mouse myeloperoxidase (MPO), a bactericidal enzyme found primarily in neutrophils and monocytes . Semiquantitative PCR confirms that MPO expression is decreased 4- to 10-fold, at 1 h and 24 h after loading . Tissue distribution analysis confirmed MPO expression in bone but not in other tissues examined . In vitro analysis showed that MPO expression was not detectable in total RNA from UMR 106 osteoblastic cells or in confluent primary cultures of osteoblasts derived from either rat primary spongiosa or diaphyseal marrow . Database analysis suggests that MPO is expressed by osteocytes . These findings reinforce the association of OPN expression to bone turnover and describes for the first time, decreased expression of MPO during load-induced bone formation . These results suggest a role for both OPN and MPO expression in bone cell function. Microb Pathog, 1998 Jan, 24(1), 57 - 63 Antibodies to lipopolysaccharide block adherence of Shiga toxin-producing Escherichia coli to human intestinal epithelial (Henle 407) cells; Paton AW et al.; Shiga toxin-producing Escherichia coli (STEC) are a diverse group of organisms known to cause diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome (HUS) in humans . During the early stage of infection, numbers of STEC in the gut may be very high (of the order of 10(9)/g faeces), but as disease progresses, the numbers may drop rapidly such that STEC are undetectable within a week . Convalescent sera from patients recovering from HUS frequently contain high levels of antibody to E . coli lipopolysaccharide (LPS) of the infecting serotype, and it is possible that a local immune response to LPS contributes to elimination of the organism from the gut . We have recently demonstrated that STEC strains isolated from HUS cases have enhanced adherence to a human intestinal epithelial cell line (Henle 407) compared with STEC strains from non-human sources . In this study, we examined the capacity of STEC strains belonging to O-antigen types O111 and O157 to adhere to human intestinal epithelial (Henle 407) cells in the presence or absence of anti-LPS . Adherence was inhibited by up to 95% by anti-LPS of the homologous, but not heterologous serotype . This effect was not an artefact of serum bactericidal or agglutinating activity . Preincubation with purified homologous or heterologous LPS did not prevent adherence, suggesting that LPS was not acting as an adhesin per se . Nevertheless, these findings raise the possibility that oral administration of preparations containing anti-LPS may interfere with colonization of the human gut by STEC, and therefore could be of potential therapeutic value if administered early in the course of infection . EMBO J, 1998 Feb 16, 17(4), 1141 - 51 Evidence for in vivo ribosome recycling, the fourth step in protein biosynthesis; Janosi L et al.; Ribosome recycling factor (RRF) catalyzes the fourth step of protein synthesis in vitro: disassembly of the post-termination complex of ribosomes, mRNA and tRNA . We now report the first in vivo evidence of RRF function using 12 temperature-sensitive Escherichia coli mutants which we isolated in this study . At non-permissive temperatures, most of the ribosomes remain on mRNA, scan downstream from the termination codon, and re-initiate translation at various sites in all frames without the presence of an initiation codon . Re-initiation does not occur upstream from the termination codon nor beyond a downstream initiation signal . RRF inactivation was bacteriostatic in the growing phase and bactericidal during the transition between the stationary and growing phase, confirming the essential nature of the fourth step of protein synthesis in vivo. J Bacteriol, 1998 Mar, 180(6), 1402 - 10 Balance between endogenous superoxide stress and antioxidant defenses; Gort AS et al.; Cells devoid of cytosolic superoxide dismutase (SOD) suffer enzyme inactivation, growth deficiencies, and DNA damage . It has been proposed that the scant superoxide (O2-) generated by aerobic metabolism harms even cells that contain abundant SOD . However, this idea has been difficult to test . To determine the amount of O2- that is needed to cause these defects, we modulated the O2- concentration inside Escherichia coli by controlling the expression of SOD . An increase in O2- of more than twofold above wild-type levels substantially diminished the activity of labile dehydratases, an increase in O2- of any more than fourfold measurably impaired growth, and a fivefold increase in O2- sensitized cells to DNA damage . These results indicate that E . coli constitutively synthesizes just enough SOD to defend biomolecules against endogenous O2- so that modest increases in O2- concentration diminish cell fitness . This conclusion is in excellent agreement with quantitative predictions based upon previously determined rates of intracellular O2- production, O2- dismutation, dehydratase inactivation, and enzyme repair . The vulnerability of bacteria to increased intracellular O2- explains the widespread use of superoxide-producing drugs as bactericidal weapons in nature . E . coli responds to such drugs by inducing the SoxRS regulon, which positively regulates synthesis of SOD and other defensive proteins . However, even toxic amounts of endogenous O2- did not activate SoxR, and SoxR activation by paraquat was not at all inhibited by excess SOD . Therefore, in responding to redox-cycling drugs, SoxR senses some signal other than O2-. Vestn Ross Akad Med Nauk, 1998, (1), 50 - 5 {Criteria for prognosis of infectious complications of radiation injuries}; Alekseev GI et al.; The results of comprehensive study of clinical, hematological, immunological, and bacteriological parameters in irradiated rats and dogs are presented . There is a growth of the automicroflora with decreases in leukocytes by 30-40%, lysozyme, beta-lysine, phagocytosis, total serum bactericidal activity by 10-20% . The appearance of pathogenic properties and resistance of Escherichia coli to antibiotics was observed with 60-70% reductions in the activity of nonspecific antiinfectious resistance and with 75-85% falls in neutrophils . This causes clinical manifestations of infectious complications . The appearance of hemolytic properties of Escherichia coli promotes the development of hemorrhagic complications at the sites of its natural habitation . The changes found in different periods after irradiation in the hematologic, immunological, and particularly bacteriological parameters may be criteria for predicting infectious complications and using therapeutical features in time. Klin Khir, 1997, (9-10), 42 - 3 {Characteristics of the myeloperoxidase-dependent bactericidal system of blood neutrophil granulocytes in patients with suppurative-septic diseases}; Tumasova EP; It was established on the ground of comparative analysis of the blood neutrophils oxidant activity (OA), estimated on the reason of chemoluminescence index and morphometric determination of bactericidal enzyme myeloperoxidase activity in 150 patients with septic-purulent diseases and 30 healthy persons, that frequent association of high indexes of the neutrophils OA and the low enzyme activity don't reflect the functional full value of myeloperoxidase system of the neutrophils bactericidal activity. Lepr Rev, 1997 Dec, 68(4), 350 - 66 The impact of multiple drug therapy on leprosy disabilities; Willcox ML; In an overview of controlled trials, it is shown that bactericidal drugs increase the short-term risk of Type I reactions, but prevent the long-term development of new impairments caused by bacterial proliferation . Clinical experience suggests that the clofazimine component of multiple drug therapy (MDT) has reduced the incidence of Type II reactions or erythema nodosum leprosum (ENL) . The principal impact of MDT, compared with monotherapy, has been to reduce the duration of active disease, thus preventing the deterioration of disability scores . Reduction of population disability rates is mainly achieved by earlier detection and treatment . MDT has a number of indirect benefits such as improved compliance, decreased cost, and increased motivation and availability of leprosy workers . However, MDT must be supplemented by other measures to prevent and treat disabilities. FEMS Microbiol Lett, 1998 Feb 15, 159(2), 261 - 6 Rapid accumulation of intracellular 2-keto-3-deoxy-6-phosphogluconate in an Entner-Doudoroff aldolase mutant results in bacteriostasis; Fuhrman LK et al.; The accumulation of 2-keto-3-deoxy-6-phosphogluconate, the key intermediate of the Entner-Doudoroff pathway, has long been thought to inhibit growth of bacteria, but careful measurements of 2-keto-3-deoxy-6-phosphogluconate accumulation by growing cells and the correlation of intracellular 2-keto-3-deoxy-6-phosphogluconate levels to growth inhibition had not been made . A system designed for this purpose was developed in Escherichia coli strains, allowing 2-keto-3-deoxy-6-phosphogluconate accumulation to be experimentally induced and measured by extraction of the cell pool . Addition of gluconate to a strain which lacked 2-keto-3-deoxy-6-phosphogluconate aldolase and overproduced 6-phosphogluconate dehydratase resulted in an increase in the intracellular concentration of 2-keto-3-deoxy-6-phosphogluconate from undetectable levels to 2.0 mM within 15 s, as measured by anion-exchange HPLC . The accumulation of 2-keto-3-deoxy-6-phosphogluconate was correlated with an immediate and significant decrease in growth; this inhibition was determined to be bacteriostatic and not bactericidal . It had been proposed that the mechanism of 2-keto-3-deoxy-6-phosphogluconate toxicity involves competitive inhibition of 6-phosphogluconate dehydrogenase and the consequent block of the pentose phosphate pathway . An experiment addressing this hypothesis failed to provide any supporting data. J Heart Valve Dis, 1998 Jan, 7(1), 72 - 4 Application of cyanoacrylate adhesive (Krazy Glue) in critical cardiac injuries; Eastman DP et al.; BACKGROUND AND AIMS OF THE STUDY: Although small lacerations of the myocardium may be repaired easily using conventional methods, larger tears or ruptures, especially if they occur in infarcted myocardial tissue, may create formidable technical challenges . Described is a method for applying sutureless pericardial patches for control of hemorrhage . METHODS: A sutureless pericardial patch was glued to the myocardium with commercially available household cyanoacrylate (Krazy Glue) in seven patients . RESULTS: No patient in this series developed any evidence of mediastinal infection as a result of this technique . Six patients were discharged home without any long-term sequelae noted . One patient developed reinfarction and died of arrhythmia two weeks following surgery . Autopsy revealed that the laceration had healed and that the patch was closely adherent . Bacteriology studies revealed that different brands of cyanoacrylate are not only bacterium-free but also exhibit a bactericidal effect . CONCLUSIONS: Sutureless pericardial patches fastened to the myocardium with cyanoacrylate glue to control hemorrhage under critical situations were easy to apply, safe and effective in this series of patients. Acupunct Electrother Res, 1997, 22(3-4), 191 - 206 Acupuncture enhances the efficacy of antibiotics treatment for canine otitis crises; Sanchez-Araujo M et al.; External bacterial otitis is a very frequent dog's recurrent complaint and should be useful for studying acupuncture effects in infectious disease . Conventional treatment based on antibiotics, washes and bactericidal ointments, solves most cases within 1 to 6 weeks . To establish if the well known effect of this conventional treatment could be modified by acupuncture as additional treatment, a comparative randomized placebo controlled study was performed . From a sample of 25 dogs, two groups were selected at random . In addition to a conventional treatment, each group also received real acupuncture or placebo acupuncture . A veterinarian M.D . and the animal's owner evaluated at blind, through a Visual Analogous Scale, (VAS) the clinical signs and symptoms of otitis . The results show a significant difference in the complete recovery time (p < 0.01); in the disappearance period of the pain (p < 0.01) in the disappearance period of the secretion (p < 0.001) and in the animal's owner evaluation of symptoms (p < 0.001) by 6th . day of treatment . These results suggest that acupuncture stimulates animal defensive systems increasing the conventional treatment effect, which seems to work mainly against the invading agent while acupuncture seems to act by reinforcing the host's defensive barriers . Combination of both shows a synergistic effect capable of empowering the anti-infectious therapy . A three months follow-up revealed all animals were without symptoms . Further evaluation of both groups after a one year follow up will allow us to establish if relapse incidence is also modified by acupuncture, and the potential usefulness of this complementary treatment on recurrent infectious pathology. Anticancer Res, 1997 Nov-Dec, 17(6D), 4403 - 6 Correlation between structure and diverse biological activities of "half-mustard type" phenothiazines; Motohashi N et al.; The structure and activity relationship of fifteen "half-mustard type" phenothiazines and related compounds were investigated . These compounds did not show any direct bactericidal activity, possibly due to the lack of radical generation activity . Pretreatment with phenothiazines significantly reduced the lethality of Escherichia coli GN2411 infection, possibly due to activation of the host defense mechanism . Higher concentrations of these compounds showed cytotoxic activity against several cultured tumor cell lines . However, no clear-cut relationship was established between biological activity and two dipole moments (mu g, mu e). Mikrobiologiia, 1997 Nov-Dec, 66(6), 785 - 9 {Detection of two new extracellular adaptogenic factors in Escherichia coli K-12}; Nikolaev IuA; The culture liquid of Escherichia coli K-12 was able to promote the adaptation of this bacterium to various stress factors . Exponentially growing E . coli cells were found to secrete an extracellular "factor of accelerated adaptation to new media," capable of shortening by several hours the lag phase of LB-grown cells transferred to minimal medium with glucose . At sublethal temperatures, E . coli cells secreted a "growth rate reducer," capable of slowing down the growth rate and enhancing the resistance of cells to bactericidal concentrations of N-ethylmaleimide . Such factors have not yet been described in the literature. Microbiol Immunol, 1997, 41(12), 909 - 16 Growth inhibition of Helicobacter pylori by monoclonal antibody to heat-shock protein 60; Yamaguchi H et al.; The H20mAb recognizing the 60-kilodalton protein, which existed in the outer membrane and was induced by heat shock at 42 C, was established . The molecule recognized with the mAb was a heat-shock protein 60 (HSP60) of Helicobacter pylori . To understand the role of HSP60 on the cell surface of H . pylori, whether or not H20mAb affects the growth of H . pylori was investigated . When bacteria were cultured with H20mAb, growth was markedly inhibited after 24 hr, although an initial 5 hr-incubation with the mAb induced no significant inhibition of H . pylori growth . The 24- and 48 hr growth of the bacteria after washing to remove the mAb at 5 hr was also inhibited though the inhibitory effect was not strong . In electron microscopical analysis, the spots with high electron density in the cytoplasm of the bacteria treated with H20mAb were increased, depending on the length of incubation time from 5 to 24 hr . After 24 hr treatment with H20mAb, bacterial destruction was also observed, indicating bactericidal activity by H20mAb . These results suggest that the HSP60 on the cell surface of H . pylori might have an essential role in the growth of the bacteria. J Microw Power Electromagn Energy, 1997, 32(4), 205 - 14 Modification of bactericidal effects of microwave heating and hyperthermia by hydrogen peroxide; Kuchma T; Two different approaches for studying of bactericidal effects of microwave heating and hyperthermia were introduced . Low concentration of hydrogen peroxide (0.05%) was used to modify the sensitivity of isogenous strains of Escherichia coli K-12 to microwave heating and hyperthermia with the following assessment of their combined action . This was carried out simulataneously and successively under equal conditions of temperature rise at 50 degrees C . A method of anomalous viscosity time dependencies (AVTD) was used for measurement of the changes in genome conformational state simultaneously with bacterial survival determination . Experiments were performed to study isolated effects of hyperthermia and microwave heating over a range of temperatures from 40 to 80 degrees C and hydrogen peroxide concentrations from 0.05 to 0.3% during 10-minute exposures and their combined action . No difference was found between isolated effects of microwave heating and hyperthermia when survival of E . coli AB 1157 cells was determined . It was shown by the AVTD method that microwave heating at a temperature increase of 6 degrees C per second caused greater damage to cell genome than hyperthermia . The synergistic interaction of microwave heating and low concentrations of hydrogen peroxide was found in simulataneous and successive exposures . The essential distinctions observed in recognition of the action of microwave heating and hyperthermia combined with hydrogen peroxide in various sequences on cellular and molecular levels were attributed to the different effects of microwave and conventional heating on the systems of DNA repair. Vopr Kurortol Fizioter Lech Fiz Kult, 1997 Nov-Dec, (6), 18 - 9 {The effect of sanatorium-health resort treatment on the function of the bactericidal oxidative mechanism of the blood neutrophils in patients with different forms of chronic bronchitis}; Iarosh AM et al.; The authors' studies show that sanatorium treatment contributes to normalization of bactericidal oxidant mechanism (BOM) of blood neutrophils in patients with chronic bronchitis . In a complete remission this normalization is complete, in partial remission positive trends were seen . In chronic obstructive bronchitis the effect was minor. Anesth Analg, 1998 Feb, 86(2), 422 - 6 Propofol and thiopental in a 1:1 volume mixture is chemically stable; Lazar ER et al.; Propofol and thiopental have been used clinically in combination for induction of anesthesia . Studies suggest that this mixture has synergistic activity, recovery characteristics similar to propofol alone, and bactericidal effects on multiple organisms . It may therefore be both clinically useful and cost-effective . In this study, we examined the chemical stability of this mixture . We used high-performance liquid chromatography to quantify the concentration of both propofol and thiopental in a given sample . This technique allows the detection of loss in total drug mass and of the appearance of breakdown products resulting from drug interaction . Ten samples of a 1:1 mixture by volume were prepared and assayed at Time 0 and Days 1, 3, and 7 . Half the samples were incubated at 23 degrees C and the rest were stored at 4 degrees C . Other mixtures were assayed before and after filtration at Time 0 and Days 1 and 7 after storage at 23 degrees C . The assay was able to measure accurately the quantity of drug present in the samples . There was no significant decrease in the quantities of either propofol or thiopental in the mixture over the 7-day period . We conclude that the 1:1 volume mixture of propofol and thiopental is chemically stable for 1 wk at room temperature . Implications: A mixture of propofol and thiopental has been used to induce anesthesia . We investigated the chemical stability of this mixture using high-performance liquid chromatography and found it to be stable for at least 24 h. Vestn Otorinolaringol, 1997, (5), 50 - 1 {The use of xenon irradiator in otology}; Kulakova LA et al.; Xenon irradiator " " (Yakhont-F) has been used in combined treatment of chronic purulent diseases of the external and middle ear in 50 patients . The unit is supplied with flexible multifiber light guides which can operate in the sites not easily accessible for other instruments . Such radiation leads to good bactericidal, antiinflammatory and antiedema effects . In reconstructive and cleansing surgery on the middle ear the transplant retension and epidermization of the postoperative cavity took less time . The technique is proposed for wide otiatric practice. Infect Immun, 1998 Feb, 66(2), 540 - 8 Mapping of a protective epitope of the CopB outer membrane protein of Moraxella catarrhalis; Aebi C et al.; A monoclonal antibody (MAb) (MAb 10F3) directed against the CopB outer membrane protein of Moraxella catarrhalis previously was found to enhance pulmonary clearance of M . catarrhalis in an animal model (M . Helminen, I . Maciver, J . L . Latimer, L . D . Cope, G . H . McCracken, Jr., and E . J . Hansen, Infect . Immun . 61:2003-2010, 1993) . In the present study, this same MAb was shown to exert complement-dependent bactericidal activity against this pathogen in vitro . Nucleotide sequence analysis of the copB gene from two MAb 10F3-reactive and two MAb 10F3-unreactive strains of M . catarrhalis revealed that the deduced amino acid sequences of these four CopB proteins were at least 90% identical . Comparison of the amino acid sequences of these proteins allowed localization of possible MAb 10F3 binding sites to five relatively small regions of the CopB protein from M . catarrhalis O35E . When five synthetic peptides representing these regions were tested for their ability to bind MAb 10F3 in a direct enzyme-linked immunosorbent assay system, an oligopeptide containing 26 amino acids was shown to bind this MAb . The actual binding region for MAb 10F3 was localized further through the use of overlapping decapeptides that spanned this 26-mer . A fusion protein containing the same 26-mer readily bound MAb 10F3 and was used to immunize mice . The resultant antiserum contained antibodies that reacted with the CopB protein of the homologous M . catarrhalis strain in Western blot analysis and bound to the surface of both homologous and heterologous strains of M . catarrhalis. Infect Immun, 1998 Feb, 66(2), 486 - 91 Lactoferrin inhibits the endotoxin interaction with CD14 by competition with the lipopolysaccharide-binding protein; Elass-Rochard E et al.; Human lactoferrin (hLf), a glycoprotein released from neutrophil granules during inflammation, and the lipopolysaccharide (LPS)-binding protein (LBP), an acute-phase serum protein, are known to bind to the lipid A of LPS . The LPS-binding sites are located in the N-terminal regions of both proteins, at amino acid residues 28 to 34 of hLf and 91 to 108 of LBP . Both of these proteins modulate endotoxin activities, but they possess biologically antagonistic properties . In this study, we have investigated the competition between hLf and recombinant human LBP (rhLBP) for the binding of Escherichia coli 055:B5 LPS to the differentiated monocytic THP-1 cell line . Our studies revealed that hLf prevented the rhLBP-mediated binding of LPS to the CD14 receptor on cells . Maximal inhibition of LPS-cell interactions by hLf was raised when both hLf and rhLBP were simultaneously added to LPS or when hLf and LPS were mixed with cells 30 min prior to the incubation with rhLBP . However, when hLf was added 30 min after the interaction of rhLBP with LPS, the binding of the rhLPS-LBP complex to CD14 could not be reversed . These observations indicate that hLf competes with rhLBP for the LPS binding and therefore interferes with the interaction of LPS with CD14 . Furthermore, experiments involving competitive binding of the rhLBP-LPS complex to cells with two recombinant mutated hLfs show that in addition to residues 28 to 34, another basic cluster which contains residues 1 to 5 of hLf competes for the binding to LPS . Basic sequences homologous to residues 28 to 34 of hLf were evidenced on LPS-binding proteins such as LBP, bactericidal/permeability-increasing protein, and Limulus anti-LPS factor. Anaesth Intensive Care, 1997 Dec, 25(6), 640 - 2 Do intensive care drug infusions support microbial growth? Graystone S, Wells MF, Farrell DJ. The potential for commonly infused drug solutions to support or inhibit microbial growth was explored in this study . Drugs examined were midazolam HCl, morphine sulphate, fentanyl citrate, pethidine HCl, bupivacaine HCl, atracurium besylate, vecuronium bromide, adrenaline, dopamine, dobutamine, noradrenaline, isoprenaline, glyceryl trinitrate, sodium nitroprusside and propofol . All drugs were studied in both diluted and undiluted forms . Of the 15 medications investigated, all except propofol were found to be bactericidal and to reduce fungal growth. Antimicrob Agents Chemother, 1998 Jan, 42(1), 154 - 60 The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II; Brotz H et al.; The lantibiotic mersacidin exerts its bactericidal action by inhibition of peptidoglycan biosynthesis . It interferes with the membrane-associated transglycosylation reaction; during this step the ultimate monomeric peptidoglycan precursor, undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)-GlcNAc (lipid II) is converted into polymeric nascent peptidoglycan . In the present study we demonstrate that the molecular basis of this inhibition is the interaction of mersacidin with lipid II . The adsorption of {14C}mersacidin to growing cells, as well as to isolated membranes capable of in vitro peptidoglycan synthesis, was strictly dependent on the availability of lipid II, and antibiotic inhibitors of lipid II formation strongly interfered with this binding . Direct evidence for the interaction was provided by studies with isolated lipid II . {14C}mersacidin associated tightly with {14C}lipid II micelles; the complex was stable even in the presence of 1% sodium dodecyl sulfate . Furthermore, the addition of isolated lipid II to the culture broth efficiently antagonized the bactericidal activity of mersacidin . In contrast to the glycopeptide antibiotics, complex formation does not involve the C-terminal D-alanyl-D-alanine moiety of the lipid intermediate . Thus, the interaction of mersacidin with lipid II apparently occurs via a binding site which is not targeted by any antibiotic currently in use. Int J Tuberc Lung Dis, 1997 Oct, 1(5), 460 - 7 Activity of KRM 1648 or rifabutin alone or in combination with clarithromycin against Mycobacterium avium complex in human alveolar macrophages; Suzuki K et al.; SETTING: The activity of KRM 1648 (KRM), a new benzoxazinorifamycin, and rifabutin (RBT), alone or in combination with clarithromycin (CLA), was evaluated against Mycobacterium avium complex (MAC) that multiplied in human alveolar macrophages (AM) . DESIGN: AM were recovered by bronchoalveolar lavage, incubated in RPMI 1640 medium with 10% human AB serum, infected with four strains of MAC (of non-acquired immune deficiency syndrome {AIDS} origin), and then treated with each drug alone or in combination . After incubation for 7 days, colony forming units in each well were counted on 7H10 agar . RESULTS: Although concentrations between 0.2 microgram/ml and 20 micrograms/ml of both rifamycins showed clear dose-dependent activities against all MAC strains tested, only 20 micrograms/ml of each drug had modest bactericidal effect . In combination with 2.0 micrograms/ml of CLA, however, 0.2 microgram/ml of both drugs caused a bactericidal response against two of the four MAC strains examined . CONCLUSION: According to this human alveolar macrophage model of MAC infection, KRM and RBT in combination with CLA was found to be a promising candidate against human pulmonary MAC infection, and deserves clinical evaluation. Scand J Immunol, 1997 Dec, 46(6), 609 - 18 Activated human gamma delta T lymphocytes express functional lactoferrin receptors; Mincheva-Nilsson L et al.; Lactoferrin (Lf), an iron-binding protein in milk, mucosal secretions and neutrophil granules has bactericidal properties and is a source of iron for breast-fed infants . In this paper the authors show that most in vivo activated lymphocytes, i.e . freshly isolated lymphocytes from first trimester human decidua, and most in vitro activated human blood lymphocytes, express lactoferrin receptors (Lf-R), while unstimulated blood lymphocytes do not . All major lymphocyte subsets, i.e . alpha beta T cells, gamma delta T cells, CD8+ T cells, CD4+ T cells, B cells and NK cells, express Lf-R after activation . The proportion of Lf-R expressing activated gamma delta T cells is significantly larger than that of activated alpha beta T cells . Lf-R and transferrin receptors (Tr-R/CD71) show the same kinetics of appearance on activated blood lymphocytes and are, to a large extent, expressed on the same cells . However, 35% of decidual lymphocytes and 15% of activated blood lymphocytes express Lf-R only . Addition of Lf to cultures containing an optimal concentration of Tr augments the proliferative response to polyclonal T cell activators and alloantigens, suggesting that presently used standard culture conditions for in vitro activation are suboptimal in particular for gamma delta T cells . Lf-R on decidual lymphocytes contain bound Lf, which probably is produced locally . The results suggest that Lf is a growth-supporting factor, especially important in local immune responses in the mucosa. J Trauma, 1997 Dec, 43(6), 875 - 9 Effects of exogenous cytokines on intravascular clearance of bacteria in normal and splenectomized mice; Hebert JC et al.; BACKGROUND: Pretreatment with interleukin-1 (IL-1), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) can improve alveolar macrophage bactericidal activity against pneumococci . These effects vary in eusplenic and asplenic mice . Likewise, these cytokines have been shown to improve survival after an aerosol pneumococcal challenge . Mice dying in these studies had positive blood cultures and disseminated infection . The purpose of this study was to determine the effect of cytokine pretreatment on intravascular clearance of bacteria from eusplenic and asplenic mice . METHODS: Two weeks after splenectomy or sham operation, mice were pretreated for various times with IL-1, G-CSF, or GM-CSF or their corresponding vehicles . Mice then received tail-vein injections of bacteria (0.1 mL), and quantitative blood cultures were performed 15 and 30 minutes thereafter . RESULTS: Splenectomized mice had impaired clearance of both pneumococci and Pseudomonas compared with sham-operated mice (p < 0.05) . IL-1 enhanced clearance in splenectomized mice (p < 0.001) but not in sham-operated mice (p not significant) . G-CSF enhanced bacterial clearance in sham-operated mice (p < 0.01) but not in splenectomized mice (p not significant) . GM-CSF enhanced clearance in both groups (p < 0.001) . CONCLUSION: The net effects of exogenous cytokine therapy for infections depends on the state of the host defenses at the time of therapy . These agents may be useful as adjuvants for the treatment of infections, but further study is warranted. Antimicrob Agents Chemother, 1997 Dec, 41(12), 2786 - 9 Antipneumococcal activity of BAY 12-8039, a new quinolone, compared with activities of three other quinolones and four oral beta-lactams; Visalli MA et al.; Activities of BAY 12-8039 against 205 pneumococci were tested by agar dilution . MICs (in micrograms per milliliter) at which 50 and 90% of the isolates are inhibited (MIC50s and MIC90s, respectively) were 0.125 and 0.25 (BAY 12-8039), 2.0 and 4.0 (ciprofloxacin and ofloxacin), and 0.25 and 0.5 (sparfloxacin) . Beta-lactam MIC50s and MIC90s for penicillin-susceptible, -intermediate, and -resistant strains, in that order, were 0.016 and 0.03, 0.25 and 2.0, and 2.0 and 4.0 (amoxicillin); 0.03 and 0.06, 0.25 and 4.0, and 4.0 and 8.0 (ampicillin); 0.03 and 0.06, 0.5 and 4.0, and 4.0 and 8.0 (cefuroxime); and 0.03 and 0.125, 0.25 and 2.0, and 4.0 and 8.0 (cefpodoxime) . At two times their MICs after 24 h, BAY 12-8039, ciprofloxacin, ampicillin, and cefuroxime were uniformly bactericidal (99.9% killing) against 12 strains; other compounds were bactericidal at four times their MICs. Antimicrob Agents Chemother, 1997 Dec, 41(12), 2699 - 704 Inhibition of the multiple antibiotic resistance (mar) operon in Escherichia coli by antisense DNA analogs; White DG et al.; The multiple antibiotic resistance operon (marORAB) in Escherichia coli controls intrinsic susceptibility and resistance to multiple, structurally different antibiotics and other noxious agents . A plasmid construct with marA cloned in the antisense direction reduced LacZ expression from a constitutively expressed marA::lacZ translational fusion and inhibited the induced expression of LacZ in cells bearing the wild-type repressed fusion . The marA antisense construction also decreased the multiple antibiotic resistance of a Mar mutant . Two antisense phosphorothioate oligonucleotides, one targeted to marO and the other targeted to marA of the mar operon, introduced by heat shock or electroporation reduced LacZ expression in the strain having the marA::lacZ fusion . One antisense oligonucleotide, tested against a Mar mutant of E . coli ML308-225, increased the bactericidal activity of norfloxacin . These studies demonstrate the efficacy of exogenously delivered antisense oligonucleotides targeted to the marRAB operon in inhibiting expression of this chromosomal regulatory locus. Optom Vis Sci, 1997 Oct, 74(10), 865 - 7 Sterility of ophthalmic drugs dispensed from spray bottles; Kim GE et al.; BACKGROUND: Spray application of cycloplegics and mydriatics is efficacious and frequently easier to use than a standard dropper bottle in the pediatric population . However, no documentation regarding the sterility of drugs dispensed from spray bottles is available . This study was conducted to determine whether contamination of ophthalmic drugs occurs with spray bottle use . METHODS: Fifteen milliliters of 1% cyclopentolate hydrochloride or 0.5% tetracaine hydrochloride were transferred to each of 15 disinfected spray bottles, stored at room temperature or refrigerated, and sprayed three times weekly for 12 weeks . Cultures were obtained from the spray bottles and drugs before transfer of the drug and from spray bottle contents at 0, 2, 4, and 6 to 12 weeks of storage . RESULTS: No cultures showed significant bacterial growth . The bactericidal action of the preservative and sterility of the drugs were maintained . CONCLUSIONS: Despite the transfer to and use of a spray bottle there appears to be minimal risk of instilling contaminated diagnostic drugs using the spray method when a single drug is stored in a spray bottle. Int Urol Nephrol, 1997, 29(4), 473 - 8 Chemiluminescence response of whole blood in patients undergoing urological operations; Sakumoto M et al.; Polymorphonuclear leukocytes (PMNs) are one of the most important components of the defence mechanisms against bacterial infection . The functions of PMNs are believed to be impaired in patients during the perioperative period . Bactericidal function of PMNs was investigated together with the luminol-dependent chemiluminescence (CL) reaction of whole blood in 23 patients, 12 undergoing open surgery and 11 undergoing endoscopic surgery . Blood samples were collected one day before surgery (day -1) and 2 hours (day 0), 24 hours (day 1) and 7 days (day 7) after surgery . Counts of whole white blood cells (WBCs), PMNs and lymphocytes were not different between the two surgery groups . CL responses in the open surgery group were increased on days 0, 1 and 7 . In the endoscopic surgery group, CL response was increased on day 1, but not on day 0 or day 7 . These results suggest that the PMN function during the perioperative period was not impaired, but increased just after surgery, mainly due to an increasing number of WBC caused by the surgical intervention. C R Seances Soc Biol Fil, 1997, 191(4), 617 - 25 {Modulation of respiratory activity of renal macrophages in sea bass (Dicentrarchus labrax) by chronic exposure to sublethal concentration of ammonia}; Gourdon I et al.; Sea bass (Dicentrarchus labrax) were exposed for 71 days to three different ammonia concentrations corresponding to 0, 15 and 25% of the lethal threshold concentration causing the death of half a fish population in 96 hours . The study of the respiratory burst from sea bass renal macrophages showed that the luminol dependent chemiluminescence (CL) emitted following stimulation with mezerein is higher when fishes were previously exposed to ammonia . Therefore, it seemed that chronically exposure of fishes to sublethal concentrations of ammonia primed their renal macrophages to secrete higher amounts of oxygen activated species during respiratory burst, even several days after the transfer of fishes into a standard environment . The stimulated-macrophage CL was partially inhibited by sodium azide, superoxide dismutase and a nitric oxide-synthesis inhibitor, the N5-(-1-iminoethyl)-L-ornithine monochloride, showing that hydrogen peroxide, superoxide anions and nitric oxide were released by renal macrophages from sea bass during the respiratory burst . These reactive species could react together to generate peroxynitrite, a strong bactericidal agent. Clin Infect Dis, 1997 Nov, 25(5), 1213 - 21 The clinical use of fluoroquinolones for the treatment of mycobacterial diseases; Alangaden GJ et al.; Mycobacterial diseases often require prolonged therapy with multidrug regimens . Fluoroquinolones have excellent bactericidal activity against many mycobacteria; achieve effective serum, tissue, and intracellular levels following oral administration; and produce few adverse effects . These properties have led to the increasing use of fluoroquinolones for the treatment of mycobacterial infections . We reviewed clinical studies and reports involving the use of fluoroquinolones for mycobacterial diseases . Ofloxacin, ciprofloxacin, sparfloxacin, and pefloxacin exhibit clinical efficacy against mycobacterial diseases, especially tuberculosis and leprosy . Fluoroquinolones have generally been administered in regimens that include other agents . However, when a fluoroquinolone has been found to be the sole active agent in a multidrug regimen, the ready emergence of resistance to fluoroquinolones has been recognized, just as when they have been used as monotherapy . Therefore, to forestall the emergence of resistance to fluoroquinolones during the treatment of mycobacterial diseases, these drugs should always be used in combination with at least one other active agent, and they should be used only when effective alternative drugs are not available. Helicobacter, 1996 Mar, 1(1), 28 - 33 Susceptibility of Helicobacter pylori to the bactericidal activity of human serum; Gonzalez-Valencia G et al.; BACKGROUND: Human serum represents an important barrier to the entry of most mucosal organisms into tissues and to the systemic circulation . If at all present, Helicobacter pylori within gastric tissue is rare, and bacteremia for this organism has been described only once . METHODS: To assess the susceptibility of H . pylori to the bactericidal activity present in normal human serum (NHS), we examined 13 H . pylori isolates . To assess the contributions of the classical and alternative complement pathways to killing, we added either C2-deficient or factor B-deficient serum, respectively, to heat-inactivated NHS . Also we assessed the ability of the strains to bind 125I-C3 . RESULTS: After incubation for 60 minutes at 37 degrees C, all 13 H . pylori strains were killed by NHS; heating to 56 degrees C for 30 minutes ablated killing, indicating complement dependence for this phenomenon . In the absence of an antibody source, there was no killing when either an alternative or classical complement pathway source was used . Adding B-deficient serum to heat-inactivated normal human serum did not restore killing, but adding C2-deficient serum permitted partial killing . All of the 13 strains bound 125I-C3 . Although the kinetics varied from strain to strain, C3 bound was significantly correlated (r = 0.61, p = 0.03) with serum susceptibility . CONCLUSIONS: H . pylori are susceptible to complement, alternative pathway activation appears critical, and C3 binding is a major locus of variability. Kekkaku, 1997 Oct, 72(10), 579 - 85 {Basic and clinical studies on pathogenesis of pulmonary Mycobacterium avium complex disease}; Suzuki K; I have studied pathogenesis of pulmonary Mycobacterium avium complex disease (PMAC), using mouse and human alveolar macrophage (PAM) model of the infection as well as clinical evaluations . The mouse model revealed no relation between natural resistance against the bacteria and the activation of macrophages which was evaluated on the basis of releasing capacities of prostaglandin E2 and superoxide anion . The PAM model suggested that TNF-alpha and GM-CSF could activate PAM to restrict the intracellular growth of the bacteria, probably not through the superoxide anion release, but through the myeloperoxidasae-halide system . It was also found that rifamycins in combination with clarithromycin could have a good bactericidal effect in the PAM-model of the infection . Clinical evaluations suggested that defect in local pulmonary defense, such as healed pulmonary tuberculous lesions, pneumoconiosis, and COPD was more important predisposing factor than defect in systemic defense in the development of PMAC . Most patients having PMAC without predisposing factors are elderly women, the reason of which is the most important question to be answered in the future studies. Biochim Biophys Acta, 1997 Oct 23, 1329(2), 357 - 69 Effects on mollicutes (wall-less bacteria) of synthetic peptides comprising a signal peptide or a membrane fusion peptide, and a nuclear localization sequence (NLS) -- a comparison with melittin; Beven L et al.; In order to investigate the effect of primary amphipathic peptides on mollicutes (wall-less bacteria), we have synthesised five molecules (P1, P2, P3, JM123, and JM133) comprising a 16 to 18-residue hydrophobic sequence and the nuclear localization sequence (NLS) PKKKRKV of simian virus 40 large-T antigen, C-terminated by a cysteamide group . The hydrophobic cluster was in P1 the signal sequence of the heavy chain of Caiman crocodilus immunoglobulin G and in JM123 the fusion peptide of human immunodeficiency virus 1 glycoprotein gp41 in which phenylalanine7 was replaced by a tryptophan residue . The homologues P2, P3, and JM133 were obtained by slight alterations of these sequences . Circular dichroism spectroscopy revealed that, in liposomes, P-series peptides were mainly under the form of beta-sheets whereas JM-series peptides displayed a high proportion of turns . These peptides proved to be bactericidal for some mollicutes, notably Acholeplasma laidlawii, but were much less potent than melittin . Furthermore, their antibiotic activity was independent of the average thickness of the plasma membrane hydrophobic core whilst that of melittin was inversely related to the thickness . Melittin and the synthetic peptides abolished spiroplasma cell motility and helicity, but only melittin and P-series peptides split the cells into globular forms displaying an average diameter of ca . 1 microm . In contrast to melittin, the synthetic peptides agglutinated spiroplasmas, suggesting that their polycationic NLS was exposed on the cell surface . P-series peptides decreased, though less efficiently than melittin, A . laidlawii and Spiroplasma melliferum membrane potential (delta psi) and transmembrane pH gradient (delta pH), at concentrations much lower than their minimal inhibitory concentrations whilst JM-series peptides had no effect on delta psi and delta pH in the same conditions . Actually, the bactericidal activity of these peptides towards mollicutes was proportional to their ability to collapse the electrochemical transmembrane potential. Cancer, 1997 Nov 15, 80(10), 1897 - 903 Vitamin C inhibits the growth of a bacterial risk factor for gastric carcinoma: Helicobacter pylori; Zhang HM et al.; BACKGROUND: Helicobacter pylori infection is a risk factor for gastric carcinogenesis . High dietary vitamin C intake appears to protect against gastric carcinoma . It has been suggested that vitamin C exerts the protective effect by scavenging free radicals that may be enhanced by H . pylori . However, vitamin C has not been investigated in relation to the direct action on H . pylori . In this study, the authors attempted to clarify this possibility both in vitro and in vivo . METHODS: Susceptibility testing of H . pylori (64 strains) was performed by the agar dilution method . Bactericidal actions were determined by a broth cultivation technique . The effect of vitamin C on in vivo H . pylori colonization was evaluated by using the Mongolian gerbil model . RESULTS: At concentrations of 2048, 512, and 128 microg/mL (minimum inhibitory concentrations {MICs}), vitamin C could inhibit the growth of 90% of the bacterial stains incubated at pH values of 7.4, 6.0, and 5.5, respectively . The broth cultures exposed to the MICs of vitamin C displayed a 1.57 approximately 2.5-log decrease in the number of viable bacteria, and the loss of viability was observed in 24 hours at concentrations 8-fold higher than the MICs . In an in vivo experiment, H . pylori colonies decreased significantly in animals treated with vitamin C after oral administration of vitamin C (10 mg/head/day) for 7 days . CONCLUSIONS: High doses of vitamin C inhibit the growth of H . pylori in vitro as well as in vivo. J Immunol, 1997 Nov 15, 159(10), 5079 - 83 Two functionally independent pathways for lipopolysaccharide-dependent activation of mouse peritoneal macrophages; Amura CR et al.; We have investigated the effects of human LPS-binding protein (LBP) and human bactericidal/permeability-increasing protein (BPI) on LPS-dependent activation of mouse thioglycolate-elicited peritoneal macrophages in vitro, in comparison with human PBMCs . Confirming earlier published studies, BPI inhibited, and LBP enhanced, the ability of LPS to stimulate PBMC production of the cytokines TNF-alpha and IL-6 . In marked contrast to these results, under identical conditions of in vitro culture, both LBP and BPI suppressed, in a dose-dependent manner, the ability of LPS to stimulate cytokine production in mouse macrophages . Further, while human BPI also suppressed LPS-dependent NO secretion in mouse macrophages, human LBP had no inhibitory effect on NO secretion under conditions that inhibited TNF-alpha secretion . These data provide the first direct evidence that mouse macrophages may utilize two independent pathways in response to LPS, thus leading to different phenotypic responses. Nutrition, 1997 Oct, 13(10), 863 - 9 Glutamine-enhanced bacterial killing by neutrophils from postoperative patients; Furukawa S et al.; Neutrophils play an important role in host defense by phagocytosing and destroying invading bacteria . A recent investigation revealed that glutamine (Gln) augmented the in vitro bactericidal activity of neutrophils from burn patients . However, it is unclear whether Gln enhances the function of neutrophils in postoperative patients . This study was designed to investigate the effect of Gln on the in vitro Escherichia coli-killing activity of neutrophils from postoperative patients . Nine randomly selected patients were included in this study . On the morning of the first postoperative day, blood was drawn and neutrophils were isolated . Eight healthy volunteers served as controls . E . coli was opsonized with pooled normal serum . Neutrophils (5 x 10(6)), together with opsonized E . coli (5 x 10(5)), were incubated for 2 h at 37 degrees C in Hanks' balanced salt solution supplemented with 0, 100, 500, or 1000 nmol/mL of Gln . The bactericidal function of neutrophils was determined by counting the number of viable bacteria . Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, and granulocyte elastase levels in the cell culture supernatant were measured . Plasma C-reactive protein (CRP), cortisol, and amino acids were also analyzed . The plasma concentration of Gln was significantly lower in the postoperative patients than in the controls . Following culture with patient neutrophils, the number of viable E . coli decreased by 26% as the in vitro Gln concentration was increased from 500 to 1000 nmol/mL (P < 0.01) . We defined the Gln 1000/Gln 500 ratio of the number of viable bacteria as the number of viable E . coli at an in vitro Gln concentration of 1000 nmol/mL divided by the number of viable E . coli at an in vitro Gln concentration of 500 nmol/mL . A positive correlation was thus demonstrated between the plasma Gln level and the Gln 1000/Gln 500 ratio of the number of viable bacteria in the patients (r = 0.69, P = 0.04) . This finding indicated that as plasma Gln fell, there was an enhancement of neutrophil E . coli-killing activity by neutrophils in in vitro tests when the Gln concentration was increased from 500 to 1000 nmol/mL . Gln supplementation caused no appreciable changes in TNF-alpha, IL-1 beta, IL-8, or granulocyte elastase levels in cell culture supernatants . A negative correlation was recognized between the patient plasma Gln level and the Gln 1000/Gln 500 ratio of the cell culture supernatant IL-8 level (r = -0.73, P = 0.025) . In conclusion, Gln supplementation enhanced the in vitro bactericidal function of neutrophils from postoperative patients. Microbiology, 1997 Oct, 143 ( Pt 10), 3367 - 73 The pncA gene from naturally pyrazinamide-resistant Mycobacterium avium encodes pyrazinamidase and confers pyrazinamide susceptibility to resistant M . tuberculosis complex organisms; Sun Z et al.; The antituberculosis drug pyrazinamide (PZA) needs to be converted into pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZas