Acetylation of sulfamethazine in a Nigerian population

Sulfamethazine (syn. sulfadimidine) is inactivated by conversion to its N-acetyl derivative. Individuals are phenotyped as either “rapid” or “slow” acetylators. We have tested the validity of this theory in a Nigerian population. The frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum were found to be bimodal, indicating the existence of a genetic polymorphism as observed by earlier workers. A plot of the percentage of the drug acetylated in serum against that in urine of the same individual results in a satisfactory separation of the rapid and slow acetylator phenotypes. An incidence of the slow acetylator phenotype of 41% was observed in the Nigerian population tested. How this observation fits into the hypothesis that the slow frequency of the allele increases from the Arctic Circle toward the Equator is discussed.     

Mitochondrial dysfunction due to in vitro exposure to atrazine and its metabolite in striatum

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) has been described as a potential toxic for dopaminergic metabolism both in vivo and in vitro. Its main metabolite diamino-chloro triazine (DACT) has been shown to achieve higher levels in brain tissue than atrazine. The aim of this study was to evaluate the in vitro effects of atrazine and DACT on striatal mitochondrial function, active oxygen species generation, and nitric oxide (NO) content. Incubation of mitochondria with atrazine (10 µM) was not able to modify oxygen consumption. However, a 50% increase in malate-glutamate state 4 respiratory rates was observed after DACT treatment (100 µM) without changes in respiratory state 3. Atrazine was able to inhibit complex I–III activity by 30% and DACT induced a tendency to decrease by 17% in the striatum. Regarding reactive oxygen species (ROS), DACT increased H₂O₂ production by 43%. Also, superoxide anion levels were higher (14%) after atrazine exposure than in control mitochondria. Incubation of striatal mitochondria with atrazine and DACT induced membrane depolarization by 15% and 19%, respectively. Also, atrazine increased NO content by 10% but no significant changes were observed after exposure of mitochondria to DACT. Glutathione peroxidase activity was inhibited (56%) by DACT and atrazine inhibited superoxide dismutase activity by 60%. Also, cardiolipin oxidation (15%) was observed after atrazine treatment. Summing up, the obtained results suggest that in vitro atrazine and DACT induce ROS production affecting striatal mitochondrial function. The atrazine effects would be attributed to a direct effect on the mitochondrial respiratory chain and superoxide dismutase activity while DACT appears to disturb glutathione-related enzyme system.     

The relationship between the antiviral action of interferon and prostaglandins in virus-infected murine cells

The relationship between prostaglandins (PG) and interferon (IFN) was investigated. IFN induced the synthesis of immunoreactive PGE and PGA at early and late stages, respectively, of vaccinia virus infection in mouse L fibroblasts. Only species-specific IFN possessed this activity and PG synthesis was stimulated in virus-infected cells, while normal L cells were not affected. The vaccinia virus infection did not significantly alter PG synthesis in the absence of IFN. Indomethacin increased the rate of vaccinia virus replication and partially inhibited the IFN-induced protection of L cells. The addition of exogenous PGA1 only partially reversed this effect. Finally, short-term PGA treatment induced the synthesis of two enzymes (protein kinase and 2,5A synthetase) thought to be partially responsible for the antiviral action of interferon. These findings suggest that a prostaglandin or PG-related compound seems to mediate at least one aspect of IFN action.     

Norepinephrine,dopamine, and 5-HT release from perfused hypothalamus of the rat during feeding induced by neuropeptide Y

In the unrestrained rat, the hyperphagic-like ingestion of food evoked by the sustained elevation of neuropeptide-Y (NPY) in the hypothalamus was correlated with the release and turnover of monoaminergic transmitters in this structure. A single guide tube was implanted stereotaxically in the perifornical region of the hypothalamus for localized push-pull perfusion of an artificial CSF vehicle or NPY_1–36 in a concentration of 10, 50, or 100 ng/1.0 l. After the rat was fully satiated, a site reactive to NPY was perfused repeatedly at a rate of 20 l/min for 6.0 min with an interval of 6.0–12 min elapsing between each perfusion. Samples of perfusate were analyzed by HPLC with coulometric detection for DA, HVA, DOPAC, NE, MHPG, 5-HT, and 5-HIAA. Although control perfusions were without effect on feeding or monoamine activity, NPY evoked mean cumulative intakes of food of 14±2.4, 25.6±3.0 and 26.5±3.2 g in response to 10, 50, or 100 ng/l concentrations of NPY, respectively, over the 4.0–5.0 hr test interval. HPLC analyses showed that during feeding the release of both NE and DA was enhanced significantly. The turnover of both catecholamines likewise increased significantly as reflected by the elevated levels of MHPG, DOPAC and HVA. However, neither the basal efflux of 5-HT nor its turnover, as reflected by the output of 5-HIAA, was affected during feeding induced by NPY perfused in the hypothalamus. These results suggest that a sustained elevation of NPY in the hypothalamus causes a perturbation in the basal activity of NE and DA which are both implicated in the neuronal mechanism regulating normal eating behavior. Thus, these catecholamine neurotransmitters are envisaged to comprise an intermediary step in the functional role played by NPY in the hypothalamus in integrating the control of energy metabolism and caloric intake.     

Comparison of Respiratory Disease Prevalence among Voluntary Monitoring Systems for Pig Health and Welfare in the UK

Surveillance of animal diseases provides information essential for the protection of animal health and ultimately public health. The voluntary pig health schemes, implemented in the United Kingdom, are integrated systems which capture information on different macroscopic disease conditions detected in slaughtered pigs. Many of these conditions have been associated with a reduction in performance traits and consequent increases in production costs. The schemes are the Wholesome Pigs Scotland in Scotland, the BPEX Pig Health Scheme in England and Wales and the Pig Regen Ltd. health and welfare checks done in Northern Ireland. This report set out to compare the prevalence of four respiratory conditions (enzootic pneumonia-like lesions, pleurisy, pleuropneumonia lesions and abscesses in the lung) assessed by these three Pig Health Schemes. The seasonal variations and year trends associated with the conditions in each scheme are presented. The paper also highlights the differences in prevalence for each condition across these schemes and areas where further research is needed. A general increase in the prevalence of enzootic pneumonia like lesions was observed in Scotland, England and Wales since 2009, while a general decrease was observed in Northern Ireland over the years of the scheme. Pleurisy prevalence has increased since 2010 in all three schemes, whilst pleuropneumonia has been decreasing. Prevalence of abscesses in the lung has decreased in England, Wales and Northern Ireland but has increased in Scotland. This analysis highlights the value of surveillance schemes based on abattoir pathology monitoring of four respiratory lesions. The outputs at scheme level have significant value as indicators of endemic and emerging disease, and for producers and herd veterinarians in planning and evaluating herd health control programs when comparing individual farm results with national averages.     

Some properties of liver alkaline phosphatase from the goat Capra hircus.

1. Gel-filtration of an extract from the liver of the local Hausa goat Capra hircus indicated the presence of two molecular forms of alkaline phosphatase (orthophosphoric monoester phosphohydrolase, E.C. 3.1.3.1.). 2. Cellulose acetate electrophoresis showed that the lower-molecular-weight form had a similar electrophoretic mobility to alpha 2-globulin from goat serum, whereas the higher-molecular-weight form had a similar electrophoretic mobility to gamma-globulin. 3. Only the lower-molecular-weight form was detected on electrophoresis of a liver extract which contained some residual n-butanol used in the extraction procedure, whereas dialysed acetone powder obtained from the liver extract contained both molecular-weight forms. 4. The partially purified enzyme showed maximum activity at pH 9.8, and was stimulated by Mg2+. 5. The enzyme was heat-labile, and was competitively inhibited by phosphate ions but uncompetitively inhibited by L-phenylalanine. 6. These results are discussed in terms of the properties of the enzyme from other sources.     

Secure Surveillance of Antimicrobial Resistant Organism Colonization or Infection in Ontario Long Term Care Homes

Background

There is stigma attached to the identification of residents carrying antimicrobial resistant organisms (ARO) in long term care homes, yet there is a need to collect data about their prevalence for public health surveillance and intervention purposes.

Objective

We conducted a point prevalence study to assess ARO rates in long term care homes in Ontario using a secure data collection system.

Methods

All long term care homes in the province were asked to provide colonization or infection counts for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended-spectrum beta-lactamase (ESBL) as recorded in their electronic medical records, and the number of current residents. Data was collected online during the October-November 2011 period using a Paillier cryptosystem that allows computation on encrypted data.

Results

A provably secure data collection system was implemented. Overall, 82% of the homes in the province responded. MRSA was the most frequent ARO identified at 3 cases per 100 residents, followed by ESBL at 0.83 per 100 residents, and VRE at 0.56 per 100 residents. The microbiological findings and their distribution were consistent with available provincial laboratory data reporting test results for AROs in hospitals.

Conclusions

We describe an ARO point prevalence study which demonstrated the feasibility of collecting data from long term care homes securely across the province and providing strong privacy and confidentiality assurances, while obtaining high response rates.     

Basilar membrane velocity in a cochlea with a modified organ of Corti

Many cochlear models assign zero longitudinal coupling in the cochlea. Although this is consistent with the transverse basilar membrane (BM) fibers, the cochlear partition contains cellular longitudinal coupling. In cochlear models, longitudinal coupling diminishes passive BM tuning; however, it has recently been employed in theories of active mechanics to enhance tuning. Our goal in this study was to probe passive longitudinal coupling by comparing BM responses in damaged cochleae with passive responses in normal cochleae. The cochleae of gerbils were damaged with intratympanic neomycin followed by a waiting period to ensure that all of the cells of the partition were missing or severely disrupted. We then measured BM motion and examined the cochleae histologically. In comparison with passive responses in normal cochleae, we observed a downward shift in characteristic frequency, an expected consequence of reduced stiffness from cellular damage. However, we did not observe enhanced passive tuning in the damaged cochleae, as would be expected if longitudinal coupling were substantially greater in the normal cochleae. Thus, we conclude that cell-based longitudinal coupling is not large enough to influence passive cochlear mechanics. This finding constrains theories of active mechanics.