Effect of severe protein-calorie malnutrition on the penetration kinetics of trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats

This study shows the effect that severe malnourishment has on the kinetics of antibiotic penetration in tissues. A total of 104 male Wistar rats, 21 days old, were randomly divided into eight groups. Five groups of experimental rats were severely malnourished (SM) and three further groups were considered well-nourished control groups (WN). A single dose of trimethoprim-sulfamethoxazole (TMP-SMX) was administered intraperitoneally. Blood samples were taken by heart puncture and five organs were extracted 0-24 h after the administration of the drug. HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in fluids. The elimination half-life for trimethoprim from plasma was longer in SM rats with a median of 3.15 h; in WN rats, it was 0.390 h. Clearance was slower in SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P < 0.05). Tissue penetration was much higher for trimethoprim, with penetration indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats. In the case of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657 for SM rats. Similarly, the penetration ratio to muscle and heart tissue was lower in SM rats. However, penetration to kidney, lung, liver and spleen was greater in SM rats. It is evident that severe SM decreases the capacity of trimethoprim more importantly than sulfamethoxazole biotransformation.     

An outbreak due to Serratia marcescens in a neonatal intensive care unit typed by 2-day pulsed field gel electrophoresis protocol

BACKGROUND: Serratia marcescens is a well-recognized nosocomial pathogen. The objective of the study was to describe typing results using a rapid pulsed field gel electrophoresis (PFGE) protocol and infection control measures during an outbreak of Serratia marcescens in a 24-bed, referral, neonatal intensive care unit (NICU) of a tertiary-care pediatric hospital. METHODS: Two patients with S. marcescens sepsis were identified in the NICU. Health care personnel of the unit were requested to reinforce infection control measures. Active surveillance was established to detect infected and/or colonized patients and environmental and staff reservoirs. Infected and colonized patients were cohorted on one side of the unit; admissions to NICU were limited. Isolates were typed with a short 2-day pulsed-field gel electrophoresis (PFGE) protocol. RESULTS: Thirty three patients were exposed during a period of 20 days. Ten S. marcescens isolates were obtained from six patients, in two from blood culture and in three from stool culture; a single clone was identified in four. S. marcescens was not isolated from environmental or staff cultures. CONCLUSIONS: PFGE results were obtained in 2 days, infection control measures were reinforced, outbreak was promptly interrupted, and the NICU remained opened.     

Uptake of serotonin by adult rat corpus callosum is partially reduced by common antidepressants

The corpus callosum (CC) is the main white matter tract involved in interhemispheric brain communication. We establish that uptake of [3H]5-hydroxytryptamine (5-HT) in CC is partially inhibited by some antidepressants. Slices of the adult rat CC had a high-affinity uptake of 5-HT. About 80% of this uptake was Na+ dependent, with a Michaelis-Menten constant, Km, of 420 +/- 80 nM and a rate of 5-HT uptake, Vmax, of 9.5 +/- 0.8 pmol/mg protein/min. The 5-HT uptake was reduced approximately 60% at pH 5 compared with that at pH 7. Fluoxetine (Prozac) inhibited only 43% of 5-HT uptake in a concentration-dependent manner, with an affinity constant, Ki, of 44.7 +/- 10.0 nM. We also studied the effects of other monoamine uptake inhibitors, all at 10 microM, and found that zimelidine, imipramine, and clomipramine inhibited 5-HT uptake in the CC by approximately 30-40%. The fluoxetine-insensitive 5-HT uptake was not altered by high concentrations of dopamine plus norepinephrine. The present data show that Na(+)-dependent 5-HT uptake occurs in the CC and optic nerve and that this uptake is partially sensitive to antidepressants and probably mediated by the serotonin transporter, which may be relevant during depression.     

Occupational disease. Burnout syndrome

This theoretical article, which includes a bibliographical summary, analyzes the burnout syndrome in all its aspect. The author presents ways to diagnose and prevent this syndrome and presents a series of extremely useful and interesting recommendations for professionals as well as businesses and organizations where these professionals work. This article is written from the viewpoint of preventing risks in the workplace.     

In vitro resistance to 5-nitroimidazoles and benzimidazoles in Giardia duodenalis: Variability and variation in gene expression

The susceptibility of Giardia duodenalis trophozoites exposed in vitro to sublethal concentrations of metronidazole (MTZ) and albendazole (ABZ) may exhibit inter-culture (variability) and intra-culture (variation) differences in drug susceptibility. It was previously reported that MTZ-resistant trophozoites may display changes in pyruvate:ferredoxin oxidoreductase (PFOR) expression while changes at the β-tubulin molecule are apparently absent in ABZ-resistant cultures. To assess the levels of gene expression of these molecules, we obtained cloned cultures growing at concentrations up to 23 μM MTZ (WBRM23) and up to 8 μM ABZ (WBRA8) and gene sequence and expression of pfor and β-tubulin loci were compared with these of drug-susceptible clone WB1. Neither the pfor nor the β-tubulin genes showed changes at sequence level but the MTZ-resistant clones WBRM21 and WBRM23 showed up-regulation of the pfor RNA using the gdh gene as reference. By using WB1 and WBRA8 clones in representational difference analyses of gene expression (RDA) an insert referred to as ARR-VSP was selected and sequenced. It showed the highest homology to one VSP molecule in the Giardia Genome Database (orf GL50803_101765). This isogene was up-regulated in five ABZ-resistant clones and the clone WBRA8 exhibited the highest RNA expression level. When successive progenies of clones WB1, WBRM23 and WBRA8 were analyzed in Northern blot assays to detect pfor and ARR-VSP RNAs respectively, the expression patterns showed variation for both genes but it was much lower in the clone WBRA8. These results suggest that G. duodenalis cultures either susceptible or resistant to MTZ and ABZ may display variability and variation at RNA expression levels albeit these were more marked in the MTZ-resistant parasites. These data might have further implications defining major mechanisms involved in drug resistance of Giardia.     

Healthcare Use Among California Farmworkers: Predisposing and Enabling Factors

Farmworkers are at risk for developing occupation-related health conditions, yet healthcare use is limited. National Agricultural Workers Survey data were used to test a modification of the Behavioral Model for Vulnerable Populations on use of healthcare in the past two years and type of healthcare used. Barriers to care were examined to determine associations with use and type of use. The farmworkers (N = 2,291) were primarily foreign-born Latino/Hispanic married males who reported limited ability to read and speak English. Healthcare use in the past two years was more likely among females, those with more than six years of education, who earned an annual income of more than $15,000 annually, were authorized, non-migrant, insured, and who reported living in the US for more than two years. Healthcare system barriers were most prominent. This study provides important targets for policy and health promotion initiatives to reduce health disparities in this marginalized community.     

Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites

³²P-labelled oligonucleotides complementary to rat 5-HT₂ receptor mRNA were used as probes to study the distribution of cells in rat brain containing the mRNA coding for this receptor by in situ hybridization histochemistry. 5-HT₂ receptor binding sites were visualized by autoradiography using [¹²⁵I]DOI as ligand. Both distributions were comparable, demonstrating that 5-HT₂ receptors are expressed by cells intrinsic to the neocortex (lamina Va), claustrum, olfactory bulb and several nuclei of the brainstem.