Production of Bacteriocins in a Liquid Medium by Streptococcus mutans

A sterile-filtered, liquid medium composed of one-half-strength APT broth and 4% (wt/vol) yeast extract was found to support the production of bacteriocins by Streptococcus mutans strains BHT and GS-5. Culture supernatants, adjusted to pH 7.0 and sterilized by filtration, contained bacteriocin-like activity, which could be demonstrated by spotting dilutions onto top agar lawns seeded with Streptococcus pyogenes as the sensitive indicator and by adding dilutions to log-phase indicator broth cultures. A quantitative assay was developed for BHT bacteriocin, based on its lethal effects. Bacteriocin production did not occur until after the log phase of growth had ceased and was not inducible by ultraviolet irradiation or treatment with mitomycin C. Non-bacteriocinogenic clones of strain BHT occurred spontaneously at high frequency, suggesting control by a plasmid, but this frequency was not increased by treatment with the plasmid-curing agents acridine orange and ethidium bromide.     

Bacteriostatic activity and killing curves of eight antibiotics against seven strains of penicillin G-resistant pneumococci]

Increasing resistance to multiple antimicrobial agents including penicillins is a current problem with Streptococcus pneumoniae. Seven cases of severe infection due to penicillin G-resistant pneumococci were seen in two teaching hospitals in Paris (France) during the first half of 1991; six of the strains were recovered from pulmonary secretions (protected brush specimens) and one from cerebrospinal fluid (CSF). The bacteriostatic activity and killing curves of eight antimicrobials against these seven strains were studied. Antimicrobial agents tested included penicillin G (PEN), amoxicillin (AMX), cefotaxime (CTX), imipenem (IPM), rifampin (RIF), vancomycin (VAN), fosfomycin (FOS), and erythromycin (ERO). MICs were determined using the agar dilution method. Killing curves were obtained using a liquid medium inoculated with 10(5) to 10(6) CFU/ml and subjected to continuous agitation; survivors were counted at baseline and after 1, 3 and 5 hours incubation. MICs of each antimicrobial (mg/l) for the seven strains were in the following ranges: PEN: 0.5-2, AMX: 0.5-2; CTX: 0.125-1; IPM: 0.03-0.25; RIF: 0.12-0.25; VAN: 0.25-1; FOS: 16; ERO: 0.06 greater than 4. Overall, bactericidal activity was greatest with vancomycin, followed by imipenem, then amoxicillin. The cefotaxime-fosfomycin combination proved synergistic and exhibited bactericidal activity (2MIC + 2MIC) for three of the seven strains. This study demonstrated the value of the cefotaxime-fosfomycin combination. Both these antimicrobials seem appropriate for the treatment of meningitis caused by penicillin G-resistant pneumococci provided their dosage is adjusted to achieve adequate drug levels in the cerebrospinal fluid.     

Growth trajectories are influenced by breast-feeding and infant health in an afro-colombian community

We conducted a longitudinal study among an Afro-Colombian population to investigate the influence of feeding practices and child morbidity on linear and ponderal growth during infancy. We enrolled 133 children at 5-7 mo and followed them until 18 mo. Repeated anthropometric measures were taken every 2-3 mo, with monthly interviews on feeding practices and daily self-reports on morbid conditions by the mothers of the infants. Mothers' social conditions and infants' fixed variables (gender and gestational age at birth) were measured at baseline. Growth starting points and trajectories were modeled via Hierarchical Linear Models (HLM). Children started with a mean length of 64.8 cm (95% CI: 59.8-69.7) and a mean weight of 7.68 kg (95% CI: 5.37-9.9), and gained length at a rate of 1.13-1.70 cm/mo, and weight at 66.5-319 g/mo. Breast-feeding, defined as receiving breast milk at any time within a 2-3-mo interval, was positively related to length gain (regression coefficient = 0.27 cm/mo; P = 0.04), after adjusting for social conditions and food consumption. Among mothers with low levels of education, breast-feeding had a positive effect on weight gain (regression coefficient = 0.30 kg/mo; P = 0.04); among nonbreast-fed infants, complementary food diversity generated a positive effect on weight (regression coefficient = 0.14 kg/mo; P = 0.03). Mean differences in length were related to the total proportion of healthy time (regression coefficient = 3.1; P = 0.02), whereas weight-gain rates were negatively associated with changes during illness (regression coefficient = -0.70; P = 0.04 for fever). No association was found between diarrhea episodes and infant growth. Our study confirms that breast-feeding after 6 mo of life is important for nutrition and health, likely by mitigating the negative effects of poor social conditions and diarrhea on infant growth.     

Chronic adult cerebral infarction studied by phosphorus NMR spectroscopy

Spatially localized phosphorus (P-31) nuclear magnetic resonance (NMR) spectra were recorded in vivo from the brains of nine healthy adults and of four adult patients examined 10 weeks to 7 years following cerebral infarction. Spectra from the healthy adult subjects showed reduced inorganic phosphate (Pi) and phosphoester resonances compared with earlier such measurements in infants. Spectra from subjects with chronic cerebral infarction exhibited no significant differences in the ratios of high-energy phosphate metabolites, Pi, or pH compared with the spectra of the healthy adults, although decreases of up to about 40% in the total P-31 NMR signal from infarcted tissue were noted. These results are consistent with a reduction in the number of metabolically active brain cells and/or a decrease in cellular functional activity in chronic infarction. Phosphorus metabolite ratios do not appear to be a sensitive indicator of abnormal energy reserve in chronic brain infarction in adults.     

Multifactorial analysis of survival in thyroid cancer. Pitfalls of applying the results of published studies to another population

Multifactorial analyses (MFAs) of survival data of thyroid carcinoma patients have already been published by the European Organization for Research and Treatment of Cancer EORTC, the Institut Curie (IC), and the Institut Gustave Roussy (IGR). The aim of this study was to find out if the results obtained in these MFAs could be applied to a new population of 480 patients. To determine this, three MFAs were carried out on the new population. Each of these MFAs is based on exactly the same methodology as one of the three reference studies. Using the EORTC methodology, five significant factors were retained: age, principal cell type, anaplastic, T-category, and metastatic sites (The significant factors in the EORTC study also included the sex factor, which was not significant for the current study). Using their own prognostic index instead of the EORTC index, gave the authors a better classification of the patients and better survival prediction. Using the IC methodology, four significant factors were retained: age, histology, T-category, and metastatic sites (the significant factors in the IC study were age, histology and sex). Using the IGR methodology, two significant factors were retained: age and N-category (the significant factors in the IGR study also included sex and histology). The authors' results differ from those published by the previous groups. Therefore, one should hesitate before applying the results obtained by other groups for thyroid carcinoma to another population. It would seem necessary to carry out one's own MFA before determining a prognostic index.     

Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy

beta-Blockers are widely used in the treatment of cardiovascular diseases. However, their effects on HERG channels at comparable conditions remain to be defined. We investigated the direct acute effects of beta-blockers on HERG current and the molecular basis of drug binding to HERG channels with mutations of putative common binding site (Y652A and F656C). beta-Blockers were selected based on the receptor subtype. Wild-type, Y652A and F656C mutants of HERG channel were stably expressed in HEK293 cells, and the current was recorded by using whole-cell patch-clamp technique (23 degrees C). Carvedilol (nonselective), propranolol (nonselective) and ICI 118551 (beta(2)-selective) inhibited HERG current in a concentration-dependent manner (IC(50) 0.51, 3.9 and 9.2 microM, respectively). The IC(50) value for carvedilol was a clinically relevant concentration. High metoprolol (beta(1)-selective) concentrations were required for blockade (IC(50) 145 microM), and atenolol (beta(1)-selective) did not inhibit the HERG current.Inhibition of HERG current by carvedilol, propranolol and ICI 118551 was partially but significantly attenuated in Y652A and F656C mutant channels. Affinities of metoprolol to Y652A and F656C mutant channels were not different compared with the wild-type. HERG current block by all beta-blockers was not frequency-dependent. Drug affinities to HERG channels were different in beta-blockers. Our results provide additional strategies for clinical usage of beta-blockers. Atenolol and metoprolol may be preferable for patients with type 1 and 2 long QT syndrome. Carvedilol has a class III antiarrhythmic effect, which may provide the rationale for a favourable clinical outcome compared with other beta-blockers as suggested in the recent COMET (Carvedilol Or Metoprolol European Trial) substudy.     

The role of NGOs in global health research for development

Background  

Global health research is essential for development. A major issue is the inequitable distribution of research efforts and funds directed towards populations suffering the world's greatest health problems. This imbalance is fostering major attempts at redirecting research to the health problems of low and middle income countries. Following the creation of the Coalition for Global Health Research – Canada (CGHRC) in 2001, the Canadian Society for International Health (CSIH) decided to review the role of non-governmental organizations (NGOs) in global health research. This paper highlights some of the prevalent thinking and is intended to encourage new thinking on how NGOs can further this role.