Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects.

The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 x 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG.

Sex determination in dioecious Mercurialis annua and its close diploid and polyploid relatives.

Separate sexes have evolved on numerous independent occasions from hermaphroditic ancestors in flowering plants. The mechanisms of sex determination is known for only a handful of such species, but, in those that have been investigated, it usually involves alleles segregating at a single locus, sometimes on heteromorphic sex chromosomes. In the genus Mercurialis, transitions between combined (hermaphroditism) and separate sexes (dioecy or androdioecy, where males co-occur with hermaphrodites rather than females) have occurred more than once in association with hybridisation and shifts in ploidy. Previous work has pointed to an unusual 3-locus system of sex determination in dioecious populations. Here, we use crosses and genotyping for a sex-linked marker to reject this model: sex in diploid dioecious M. annua is determined at a single locus with a dominant male-determining allele (an XY system). We also crossed individuals among lineages of Mercurialis that differ in their ploidy and sexual system to ascertain the extent to which the same sex-determination system has been conserved following genome duplication, hybridisation and transitions between dioecy and hermaphroditism. Our results indicate that the male-determining element is fully capable of determining gender in the progeny of hybrids between different lineages. Specifically, males crossed with females or hermaphrodites always generate 1:1 male:female or male:hermaphrodite sex ratios, respectively, regardless of the ploidy levels involved (diploid, tetraploid or hexaploid). Our results throw further light on the genetics of the remarkable variation in sexual systems in the genus Mercurialis. They also illustrate the almost identical expression of sex-determining alleles in terms of sexual phenotypes across multiple divergent backgrounds, including those that have lost separate sexes altogether.

Development of genital plates in nymphs of Triatoma pallidipennis, Stål 1872, (Hemiptera: Reduviidae) and its application as sexing method

Searching for morphometric differences between sexes in immature forms, the development of genital plates in the exuviae of Triatoma pallidipennis Stål 1872nymphs was studied. Differences were found in the form and size of the 9th genital urosternite, it is larger and wider in males as compared to females. This difference is reported in several South American Triatoma species. From our results it is possible to sex early stages from microscopic observation of genital plates in whole insects.

Leishmanial infection: analysis of its first steps. A review

The first steps in leishmaniasis are critical in determining the evolution of the disease. Major advances have recently been done in understanding this crucial moment. Fundamental research in parasite-vector interaction, parasite biology, insect saliva, and vertebrate host response have shed new light and uncovered a most fascinating and complex moment in leishmaniasis. We review here some of these aspects and we try to connect them in a logical framework.

Ecological characteristics of Triatoma patagonica at the Southern limit of its distribution (Chubut, Argentina)

This study aimed at identifying the ecological characteristics of Triatoma patagonica Del Ponte 1929 (Hemiptera: Reduviidae) and evaluating the epidemiological importance of this species at its southernmost distribution limit. We carried out two surveys in the Province of Chubut, in summer and in spring, 1998. In each survey, we interviewed local health care agents for triatomine recognition and reports of the bugs, followed by entomological searches in houses and peridomestic and silvatic biotopes. The presence of T. patagonica was confirmed in two of the five localities indicated by interview. In agreement with previous studies, all these positive localities were east of the 11°C isotherm, within the Monte phytogeographic province. Triatomine abundance and infestation levels (in peridomiciles and peridomestic biotopes) were higher in summer than in spring, possibly reflecting adverse environmental conditions such as flood and cold winter weather. In the silvatic environment, we found three adult bugs under rocks in summer. In peridomestic sites bugs were only found associated with chickens, which were also the only blood meal source identified. Infection by Trypanosoma cruzi was not detected. We conclude that T. patagonica at its southernmost distribution limit does not represent a risk to public health due to its low abundance, lack of association with humans, and absence of T. cruzi infection.

Random amplified polymorphic DNA analysis of DNA extracted from Trichuris trichiura (Linnaeus, 1771) eggs and its prospective application to paleoparasitological studies

Random amplified polymorphic DNA analysis was applied to DNAs extracted from Trichuris trichiura eggs recovered from human fecal samples. Four out of 6 primers tested displayed 18 distinct and well defined polymorphic patterns, ranging from 650 to 3200 base pairs. These results, upon retrieval and DNA sequencing of some of these bands from agarose gels, might help in establishing T. trichiura specific genetic markers, not available yet, and an important step to design primers to be used in molecular diagnosis approaches.

TB: the disease, its treatment and prevention (English and 10 translations)

This booklet offers general advice on the control of tuberculosis (TB)

Molluscicidal effect of nicotinanilide and its intermediate compounds against a freshwater snail Lymnaea luteola, the vector of animal schistosomiasis

The molluscicidal effect of nicotinanilide was evaluated and compared with niclosamide (2',5-dichloro-4'-nitrosalicylanilide, ethanolamide salt) against different stages of the freshwater snail Lymnaea luteola i.e., eggs, immature, young mature, and adults. Calculated values of lethal concentrations (LC50 and LC90 ) showed that both nicotinanilide and niclosamide as toxic against eggs, immature, and adults. The young mature stage of the snails was comparatively more tolerant to both molluscicides than the other stages. The toxicity of the intermediate compounds of nicotinanilide against the young mature stage of the snails showed them as ineffective. The mortality pattern of the snails exposed to LC90 concentration of these molluscicides showed niclosamide to kill faster (within 8 to 9 h) than nicotinanilide (26 to 28 h). In view of the above studies it may be concluded that both molluscicides are toxic against all the stages of the L. luteola snails.

Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component.

State-of-the-art production technologies for conjugate vaccines are complex, multi-step processes. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. The C. jejuni N-glycosylation system has been successfully transferred into Escherichia coli, enabling in vivo production of customized recombinant glycoproteins. However, some antigenic bacterial cell surface polysaccharides, like the Vi antigen of Salmonella enterica serovar Typhi, have not been reported to be accessible to the bacterial oligosaccharyltransferase PglB, hence hamper development of novel conjugate vaccines against typhoid fever. In this report, Vi-like polysaccharide structures that can be transferred by PglB were evaluated as typhoid vaccine components. A polysaccharide fulfilling these requirements was found in Escherichia coli serovar O121. Inactivation of the E. coli O121 O antigen cluster encoded gene wbqG resulted in expression of O polysaccharides reactive with antibodies raised against the Vi antigen. The structure of the recombinantly expressed mutant O polysaccharide was elucidated using a novel HPLC and mass spectrometry based method for purified undecaprenyl pyrophosphate (Und-PP) linked glycans, and the presence of epitopes also found in the Vi antigen was confirmed. The mutant O antigen structure was transferred to acceptor proteins using the bacterial N-glycosylation system, and immunogenicity of the resulting conjugates was evaluated in mice. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with E. coli O121 LPS. One animal developed a significant rise in serum immunoglobulin anti-Vi titer upon immunization.

The prevalence of erectile dysfunction and its association with antiretroviral therapy in HIV-infected men: the Swiss HIV Cohort Study.

BACKGROUND: Here, we aimed to determine the prevalence of erectile dysfunction (ED) among HIV-infected men and its association with components of antiretroviral therapy. METHODS: Cross-sectional data on sexual dysfunction were collected in the Swiss HIV Cohort Study (SHCS) between December 2009 and November 2010. Multilevel logistic regression models were used to estimate the association between ED and exposure to 24 different antiretroviral drugs from four drug classes. RESULTS: During the study period, 5,194 of 5,539 eligible men in the SHCS had a follow-up visit; 4,064 men answered a question on ED for the first time. Among these men, ED was experienced often by 459 (11%), sometimes by 543 (13%), rarely by 389 (10%), never by 2,526 (62%) and 147 (4%) did not know. ED was associated with older age, an earlier HIV diagnosis and depression. No association was found with any drug class; however, ED was associated with cumulative exposure to either zalcitabine (OR 1.29 per year of use; 95% CI 1.07, 1.55) or enfuvirtide (OR 1.28; 95% CI 1.08, 1.52). CONCLUSIONS: Around 1 in 10 men in the SHCS reported often experiencing ED. We found no association between ED and any drug class, but those exposed to zalcitabine or enfurvitide (drugs no longer or rarely used) were more likely to report ED; this second association was probably not causal.

Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis

While dementia affects 6-10% of persons 65 years or older, industrialized countries have witnessed an alarming rise in obesity. However, obesity's influence on dementia remains poorly understood. The conducted a systematic review and meta-analysis. PUBMED search (1995-2007) resulted in 10 relevant prospective cohort studies of older adults (40-80 years at baseline) with end points being dementia and predictors including adiposity measures, such as body mass index (BMI) and waist circumference (WC). There was a significant U-shaped association between BMI and dementia (P= 0.034), with dementia risk increased for obesity and underweight. Pooled odds ratios (OR) and 95% confidence intervals (CI) for underweight, overweight and obesity compared with normal weight in relation to incident dementia were: 1.36 (1.07, 1.73), 0.88 (0.60, 1.27) and 1.42 (0.93, 2.18) respectively. Pooled ORs and 95% CI for obesity and incident Alzheimer's disease (AD) and vascular dementia were 1.80 (1.00, 3.29) vs. 1.73 (0.47, 6.31) and were stronger in studies with long follow-up (>10 years) and young baseline age (

Development of a Bacillus sphaericus tablet formulation and its evaluation as a larvicide in the biological control of Culex quinquefasciatus

This study aimed to analyze the final fermentation culture of Bacillus sphaericus 2362, standardize it and develop an active tablet formulation for use in urban mosquito breeding sites. It was performed in three phases: analysis and standardization of a B. sphaericus fermented culture; physical, chemical, and biological analysis of the active powder (solubility, residual humidity, particle size, resting angle, flowing off time, compacted density, and biological activity against Culex quinquefasciatus larvae); and the development of fast-disintegrating tablets. Five formulations with differing compositions were developed and a UV protector was added to the selected formulation. The formulation products with or without UV protector, as well as the active powder caused 100% larval mortality from 1 day to 2 months after a single treatment under simulated field conditions. These results show that the UV protector does not affect the initial larvicide activity of B. sphaericus, nor its persistence over a period of two months.