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PubMed1989

The use of Streptococcus zymogenes for estimating tryptophan and methionine bioavailability in 17 foods.

As part of a cooperative study assessing amino acid bioavailability and/or protein quality, the provisional method of Boyne et al. (Brit J Nutr 21: 181-206) was used to assay 17 protein sources for methionine and tryptophan availability with S. zymogenes. Pronase was used as the predigesting enzyme. Product composition was found to affect reproducibility. The microbial assay results correlated positively with results from rat growth studies on the same foods (p = 0.05), and were generally accurate in identifying products of lower protein quality. Defatting four high-fat products increased microbial values in the methionine assay, but only the chicken franks and the sausage values in the tryptophan assay. Heating non-fat milk increased methionine values slightly. Low values for rolled oats were further reduced by finer grinding.

Biological Assay↗
PubMed1990

The synthesis and antibacterial activities of quinolones containing five- and six-membered heterocyclic substituents at the 7-position.

A series of 6-fluoro-7-substituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared. The substituents at the 7-position included five- and six-membered heterocyclic rings such as oxazoline and oxazine as well as five-membered heteroaromatic rings such as oxazoles and imidazoles. The structure--activity relationships (SAR) of these compounds indicated that oxazole substituents containing a 2-methyl group had the greatest in vitro potency. The compounds showed greater in vitro antibacterial activity against Gram-positive organisms than against Gram-negative organisms.

4-Quinolones↗
PubMed1992

In-vitro activity of PD 131628, a new quinolone antimicrobial agent.

The in-vitro activity of PD 131628, the active metabolite of the prodrug PD 131112, was compared with that of ciprofloxacin and members of other groups of antimicrobial agents against 701 recent clinical isolates and strains with known mechanisms of resistance. The MIC90s of PD 131628 against the Enterobacteriaceae were between 0.008 and 0.5 mg/L; PD 131628 was one- to four-fold more active than ciprofloxacin against these strains and was four-fold more active than ciprofloxacin against Pseudomonas aeruginosa. Against the Gram-positive species tested, PD 131628 was two- to four-fold more active than ciprofloxacin, inhibiting all strains of Staphylococcus aureus and Streptococcus pneumoniae with 0.5 mg/L or less. PD 131628 was very active against Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis, with MIC90s ranging from 0.004 to 0.008 mg/L. Organisms with decreased susceptibility to other quinolones had decreased susceptibility to PD 131628, but there was no cross-resistance between this class of antimicrobial and other classes. The protein binding of PD 131628 was at most 25% across a broad range of concentrations. The addition of 70% human serum had little effect on the MICs, but caused a two- to eight-fold increase in MBCs.

Anti-Infective Agents↗
PubMed1983

Two new monobactam antibiotics produced by a Flexibacter sp. I. Taxonomy, fermentation, isolation and biological properties.

Two new beta-lactam antibiotics, namely SQ 28,502 and SQ 28,503, have been isolated from fermentations of a Flexibacter sp. They are demethoxy monobactams with oligopeptide side chains and have molecular weights of 1,462 and 1,446, respectively. These beta-lactams show a high degree of stability to a variety of beta-lactamases and act as potent irreversible inactivators of P99 beta-lactamase from Enterobacter cloacae. They exhibit weak antibacterial activity.

Anti-Bacterial Agents↗
PubMed1988

Protective immunity to experimental tuberculosis by mannophosphoinositides of mycobacteria.

Mannophosphoinositides isolated from mycobacterial cells were found to induce both humoral and cell-mediated immune responses in mice when injected as mannoside-methylated bovine serum albumin (MBSA) complexes. Immunization of mice with mannoside-MBSA complexes elicited significant protection against challenge with LD50 dose of M. tuberculosis H37Rv as revealed by high survival rate, low values of root-specific lung weight, lung densities and colony forming units recovered from lung, liver and spleen, compared to the nonimmunized group. These observations were further substantiated by histopathological studies. The protective immunity elicited by mannoside-MBSA complexes against challenge with M. tuberculosis H37Rv was mediated by the cooperation of T-B cells, as shown by the passive transfer of immune cells/sera into syngeneic sublethally irradiated recipient mice.

Animals↗
PubMed1994

Do intensive hospital antibiotic control programs prevent the spread of antibiotic resistance?

The relation between antibiotic control and resistance was assessed by review of selected journal articles from 1988 through 1994. Most studies of control or monitoring do not report susceptibility pattern as an outcome measure. Several aspects of bias and confounding prevent more than analysis of temporal association between antibiotic use restriction and resistance pattern. However, in a few institutions there has been an increase in susceptibility to antimicrobials following intensive control or monitoring. Moreover, in a few hospitals, intensive antibiotic control for selected drug-organism pairs was associated with a high prevalence of susceptibility, and the proportion susceptible fell abruptly when control or monitoring was relaxed or removed. These examples, coupled with the recent emergence of new resistant organisms, justify attempts to determine the value of intensive antibiotic control as a preventive practice. Because these studies were performed in single institutions, their power to distinguish associations was poor. Cooperative multicenter studies are needed in which selection and classification biases are addressed prospectively, and in which confounding factors are controlled.

Anti-Bacterial Agents↗
PubMed1986

Effects of cations, polyamines and other aminoglycosides on gentamicin C2. Binding to ribosomes from sensitive and resistant Escherichia coli strains.

Gentamicin C2 interacts cooperatively with ribosomes from a sensitive Escherichia coli strain in a multiphasic way with several classes of sites. It is shown that this binding is highly-dependent on Mg++ and natural endogenous polyamine concentrations. The differences observed between ribosomes from sensitive and resistant strains may be explained by the absence of specific cooperative gentamicin interactions with resistant ribosomes. The effects of other aminoglycoside antibiotics are discussed in terms of structure-activity relationships.

Aminoglycosides↗
PubMed1981

[Insulin binding to isolated thyroid plasma membrane].

Binding sites of insulin were detected in plasmic membranes isolated from bovine thyroid. Membrane 123I-insulin binding was inhibited by unlabelled insulin, at a lower degree by proinsulin, not at all by TSH and GH. Binding dissociation appeared to be consistent with the process of cooperative negativity. These data suggest that specific receptors binding to insulin are present in thyroid isolated plasmic membranes.

Animals↗
PubMed1990

In-vitro activity of sparfloxacin, a new quinolone antimicrobial agent.

The in-vitro activity of sparfloxacin (AT-4140), a new difluorinated quinolone, was compared with those of ciprofloxacin, temafloxacin and selected members of other groups of antimicrobial agents, against 651 recent distinct clinical isolates and strains with known mechanisms of resistance. Three strains of Chlamydia trachomatis were also studied. The MICs for 90% of the Enterobacteriaceae were between 0.06 and 1 mg/l; for Pseudomonas aeruginosa the MIC90 was 2 mg/l. Sparfloxacin was 16-fold more active against Acinetobacter spp. than ciprofloxacin. For Staphylococcus spp., Streptococcus, spp. and Enterococcus faecalis the MIC90 was between 0.25 and 1 mg/l; sparfloxacin was four-fold more active against Str. pneumoniae than ciprofloxacin. Ninety percent of strains of Haemophilus influenzae, Branhamella catarrhalis and Neisseria spp. were inhibited by less than 0.03 mg/l; for Bacteroides fragilis the MIC90 was 1 mg/l. The three strains of Chl. trachomatis were susceptible to 0.06-0.12 mg/l sparfloxacin, which was 16-fold more active than ciprofloxacin. There was cross resistance among the quinolones, but not between the quinolones and other groups of antimicrobials. The protein binding of sparfloxacin was 40% and serum had little effect on its activity.

Anti-Bacterial Agents↗
PubMed2006

Dendritic cells: the commanders-in-chief of mucosal immune defenses.

PURPOSE OF REVIEW: Intestinal dendritic cells have emerged as key regulators of immunity to pathogens, oral tolerance and intestinal inflammation. Studies have begun to elucidate the regulatory mechanisms responsible for defining region- and compartment-specific phenotypes and functions of dendritic cells in mucosal tissues. RECENT FINDINGS: Specific subsets of dendritic cells appear to be associated with the various routes for antigen acquisition in the intestine. The constant sampling of intestinal antigenic content ensures establishment of tolerance to commensal bacteria and food antigens. Tolerance development to oral antigens is restricted to the mucosal immune system. Other advances have provided insight into the molecular basis of microbial recognition and innate immune responses by intestinal dendritic cells. Differences in the involvement of dendritic cells have begun to emerge in Crohn's disease and ulcerative colitis and link gene regulation in dendritic cells to therapeutic responses. SUMMARY: A major focus of mucosal immunology will be to understand how diverse dendritic cell subsets cooperate in regulating homeostasis and host defense in the different intestinal immune compartments. This will be pivotal to understanding how the mucosal immune system makes the distinction between commensal microbiota, pathogens and self antigens.

Animals↗
PubMed2003

Catalytic properties of an endogenous beta-lactamase responsible for the resistance of Azospirillum lipoferum to beta-lactam antibiotics.

Azospirillum lipoferum RG20, a nitrogen-fixing bacterium found in all kind of soils, was found to be naturally resistant to penicillins and cephalosporins. 6-beta-Bromopenicillanic acid, an irreversible inhibitor of serine-beta-lactamases, completely abolished this resistance. A beta-lactamase was purified 518-fold from a cell-free extract of A. lipoferum RG20. A single band on SDS-PAGE (apparent molecular mass 31000 Da) and on isoelectric focussing (pI9.35) was observed with the purified protein. The enzyme hydrolysed benzylpenicillin, ampicillin, cephalothin and cephaloridine with comparable k(cat) values and catalytic efficiencies. However, carbenicillin and cefotaxime were hydrolysed with significantly lower kinetic parameters and oxacillin was hydrolysed at a rate 100 times slower. The purified beta-lactamase was inhibited by clavulanic acid and sulbactam but not by EDTA or aztreonam. Its substrate and inhibitor profiles are consistent with those of the broad-spectrum beta-lactamases inhibited by clavulanic acid (group 2b of the Bush-Jacoby-Medeiros scheme). The effect of pH on k(cat) and K(m) values for benzylpenicillin hydrolysis was studied. The dependence of k(cat) on pH suggests that the enzyme-substrate (ES) complex must be in at least three protonation states: two with k(cat) values equal to 2800 and 1450 s(-1) and a third inactive one [pK(1(ES)) 4.7 and pK(2(ES)) 7.9]. Similarly, the dependence of k(cat)/K(m) on pH can be explained by postulating that the enzyme free form can be at least in three different protonation states: two of them with k(cat)/K(m) values equal to 2.7 x 10(6) and 3.7 x 10(8) M(-1) s(-1) and a third one unable to productively bind substrate. Interestingly, the dependence of k(cat)/K(m) on pH is consistent with positive cooperativity for proton binding to the enzyme free form [pK(1(E)) 8.5 and pK(2(E)) 7.2].

Anti-Bacterial Agents↗
PubMed1975

Anacystis nidulans mutants resistant to aromatic amino acid analogues.

Three classes of mutants of Anacystis nidulans were selected on the basis of resistance to fluorophenylalanine and 2-amino-3-phenylbutanoic acid. The most frequent type exhibited DAHP synthetase (7-phospho-2-keto-3-deoxy-D-arabino-heptonate-D-erythrose-4-phosphate-lyase [pyruvate phosphorylating], EC 4.1.2.15) activity identical to that of the parental strain. The second type was characterized by extremely low levels of the activity. The third type had a DAHP synthetase showing decreased sensitivity to inhibition by L-tyrosine. The enzyme was purified 140-fold from wild-type and feedback-insensitive strains, and the kinetics of the reaction was examined. The activity of the wild-type enzyme was inhibited 75% in the presence of 2.0 X 10-3 M tyrosine, and the altered enzyme was inhibited 10%. The following apparent constants were obtained from kinetic studies with partially purified wild-type enzyme: S0.5 for D-erythrose-4-phophate equal to 7.1 X 10-4 M; S0.5 for phosphoenolpyruvate equal to 1.4 X 10-4 M. Inhibition by tyrosine was mixed with respect to binding of both D-erythrose-4-phosphate and phosphoenolpyruvate. In addition, tyrosine promoted cooperative interactions in the binding of phosphoenolpyruvate. For the altered enzyme the following apparent constants were obtained: S0.5 for D-erythrose-4-phosphate equal to 7.1 X 10-4 M; S0.5 for phosphoenolpyruvate equal to 2.9 X 10-4 M. Inhibition by tyrosine was mixed with respect to D-erythrose-4-phosphate and competitive with respect to phosphoenolpyruvate. Tyrosine did not promote cooperative effects in the binding of phosphoenolpyruvate to the altered enzyme.

4-Aminobutyrate Transaminase↗
PubMed2000

[Dominant etiological factors of urinary tract infections in various hospital departments and their resistance to chemotherapeutic agents].

PURPOSE: The purpose of this study was the determination of the incidence of urinary tract infection (UTI) in patients hospitalized in specific wards, and the analysis of the factors influencing the incidence of infection. METHODS: 329,608 hospital infection registration cards taken from the Polish national program for registration of hospital infections were analysed. This programme is based on a unified registration card system and on the definitions of particular types of hospital-acquired infections provided by the CDC (Centers for Disease Control, Atlanta, Georgia, USA). Statistical analysis was performed using the Statistica programme. RESULTS: 1,422 cases of hospital-acquired UTI, making up 21% of total hospital-acquired infections, were found. Six hundred sixty-six microbes were isolated from this total number of cases. The dominant pathogens were: Escherichia coli (31%), followed by Pseudomonas aeruginosa (13%), and Enterococcus sp. (12%). Hospital-acquired UTI occurred most often in maternity wards, gynaecology departments and intensive care units. Microbiological confirmation was obtained for only 45% of the clinically diagnosed cases of UTI. A disquieting increase of Pseudomonas aeruginosa resistant to chinolones was observed as well as extremely high resistance to aminoglycosides in Enterococcus sp. CONCLUSIONS: Urinary tract infections (UTIs) are the second most common form of hospital-acquired infection. Causal agents of hospital-acquired UTIs differed, depending upon the specific ward to which the patient is admitted. The most frequently isolated pathogens were Escherichia coli, Pseudomonas aeruginosa and Enterococcus sp. Microbiological confirmation of the clinically diagnosed cases of urinary tract infection is absolutely necessary, as well as a better cooperation between practicing physicians and microbiologists in the detection of hospital-acquired infection and interpretation of results.

Bacteria↗
PubMed1977

[Involvement of veterinary medicine in, and its responsibility for, the microbiological safety of foods of animal origin (author's transl)].

Epidemiological data indicate that, in the majority of outbreaks, the aetiology of diseases of microbial origin transmitted by foods is the "dual failure": poor sanitary handling in addition to storage of perishable items at temperatures allowing of microbial proliferation. For statistical reasons, sampling and examination of final products is completely ineffective as a means to obtain safe foods and meals. Dependable assurance of microbiological safety of foods should rather be attained by the application of Good Manufacturing Practices. The shared responsibility for reliable, uninterrupted preventive safeguarding of the food chain calls for cooperation between line workers of various disciplines. Microbiological examination of final product samples is still meaningful in order to monitor Good Manufacturing Practices. Reference values ("standards" with which data obtained can be compared are essential for this purpose. Theri establishment, based on product sample surveys of factories previously examined for reliable operation of approved procedures, is outlined.

Bacterial Infections↗
PubMedDate not supplied

Microbial resistance to drugs--a universal problem in urgent need of a comprehensive approach.

The last two decades have seen an increase in bacterial resistance to commonly used antibiotics all over the world. In the past five years the emergence of vancomycin-resistant Enterococcus and multidrug-resistant Streptococcus pneumoniae was particularly notable. Several factors have contributed to this, including inappropriate use of readily available antibiotics, survival of high-risk patients in critical care units, burn wards and cancer centres following treatment with multiple antibiotic combinations, increasing poverty and worsening of living conditions. The data available from South-east Asia, albeit limited, indicate that prevalence of antibiotic resistance in bacteria isolated from human and animal sources is higher than that reported from western countries. To combat this global problem, a multi-pronged approach is needed. Accurate antibiotic susceptibility data will be required to define the extent of the problem. Medical experts and scientific organizations will have to develop guidelines for the use of antibiotics in ambulatory, inpatient and animal husbandary areas. Cooperation between the medical community, regulating agencies and pharmaceutical industry will be needed to define policies governing the sale of antibiotics, drug promotional materials, physician education programmes and consumer education regarding the hazards of inappropriate antibiotic use. For long term control of infectious diseases, it is imperative that existing vaccines be appropriately utilized and new vaccines developed.

Anti-Bacterial Agents↗