Synthesis and evaluation of phenylcarbamate derivatives as ligands for nicotinic acetylcholine receptors

Phenylcarbamate derivatives were synthesized and evaluated in radioligand binding assays for different nicotinic acetylcholine receptor (nAChR) subtypes. Carbamate derivatives bearing a pyrrolidine or piperidine moiety 8-20 exhibited much lower affinity for alpha7* nAChR than the analogues in the quinuclidine series 21-25, although the same structural elements are present. Furthermore, in contrast to the quinuclidine analogues 21-25, all (S)-pyrrolidine derivatives 8-12 and the piperidine analogues 15 and 16 exhibited higher affinities for alpha4beta2* nAChR.     

Capillary plexus development in the day five to day six chick chorioallantoic membrane is inhibited by cytochalasin D and suramin

The chick chorioallantoic membrane (CAM) is a valuable model for evaluating angiogenesis and vasculogenesis. Our purpose was to characterize the formation of the CAM vasculature, in particular the capillary plexus, between days five and six after fertilization and to examine the mode of action of cytochalasin D and suramin on vascular development during this interval. The CAM increased 20-fold in size between days five and six, during which time the capillary plexus forms by both migration of mesodermal blood vessels toward the ectoderm and by the formation of new vessels from angioblasts near the ectoderm. Between days five and six, the CAM becomes thinner, and the density of the mesodermal cells decreases. To determine the mode of action of anti-angiogenic drugs on the day five to day six CAM, various concentrations of cytochalasin D or suramin were added directly to day five CAMs, and their effects were evaluated on day six. Both drugs significantly inhibited CAM growth, altered branching patterns of the major vessels, decreased area of the major vessels, and inhibited the formation of the capillary plexus by inhibiting both vasculogenesis and the migration of mesodermal blood vessels to the ectoderm. Cytochalasin D also inhibited compartmentalization of the plexus. Cytochalasin D and suramin were inhibitory at similar doses. This study provides new information on early CAM development, establishes the mode of action and dose dependency of cytochalasin D and suramin on day five to day six CAMs, and demonstrates that the day five to day six CAM provides a useful assay to examine the effect of anti-angiogenic drugs on blood vessel development, including capillary plexus formation.     

The Distribution of Ocular Chlamydia Prevalence across Tanzanian Communities Where Trachoma Is Declining

BackgroundMathematical models predict an exponential distribution of infection prevalence across communities where a disease is disappearing. Trachoma control programs offer an opportunity to test this hypothesis, as the World Health Organization has targeted trachoma for elimination as a public health concern by the year 2020. Local programs may benefit if a single survey could reveal whether infection was headed towards elimination. Using data from a previously-published 2009 survey, we test the hypothesis that Chlamydia trachomatis prevalence across 75 Tanzanian communities where trachoma had been documented to be disappearing is exponentially distributed.Methods/FindingsWe fit multiple continuous distributions to the Tanzanian data and found the exponential gave the best approximation. Model selection by Akaike Information Criteria (AIC_c) suggested the exponential distribution had the most parsimonious fit to the data. Those distributions which do not include the exponential as a special or limiting case had much lower likelihoods of fitting the observed data. 95% confidence intervals for shape parameter estimates of those distributions which do include the exponential as a special or limiting case were consistent with the exponential. Lastly, goodness-of-fit testing was unable to reject the hypothesis that the prevalence data came from an exponential distribution.ConclusionsModels correctly predict that infection prevalence across communities where a disease is disappearing is best described by an exponential distribution. In Tanzanian communities where local control efforts had reduced the clinical signs of trachoma by 80% over 10 years, an exponential distribution gave the best fit to prevalence data. An exponential distribution has a relatively heavy tail, thus occasional high-prevalence communities are to be expected even when infection is disappearing. A single cross-sectional survey may be able to reveal whether elimination efforts are on-track.     

A procedure to remove protease activities from Bacillus subtilis sporulating cells and their crude extracts.

A simple procedure was developed to remove both extracellular and intracellular proteases associated with aporulating Bacillus subtilis cells. Cells are washed four times with 1 m KCl before breakage and their crude extracts are treated with 2 mm diisopropylfluorophosphate before passage through a hemoglobin-Sepharose affinity column. RNA polymerase in crude B. subtilis extracts treated by this procedure was stable, functionally and structurally, for more than 1 month at 4°C. This process for removing all proteases should work essentially with any crude extracts containing proteolytic activities.     

Common mental health problems in immigrants and refugees: general approach in primary care

Background:

Recognizing and appropriately treating mental health problems among new immigrants and refugees in primary care poses a challenge because of differences in language and culture and because of specific stressors associated with migration and resettlement. We aimed to identify risk factors and strategies in the approach to mental health assessment and to prevention and treatment of common mental health problems for immigrants in primary care.

Methods:

We searched and compiled literature on prevalence and risk factors for common mental health problems related to migration, the effect of cultural influences on health and illness, and clinical strategies to improve mental health care for immigrants and refugees. Publications were selected on the basis of relevance, use of recent data and quality in consultation with experts in immigrant and refugee mental health.

Results:

The migration trajectory can be divided into three components: premigration, migration and postmigration resettlement. Each phase is associated with specific risks and exposures. The prevalence of specific types of mental health problems is influenced by the nature of the migration experience, in terms of adversity experienced before, during and after resettlement. Specific challenges in migrant mental health include communication difficulties because of language and cultural differences; the effect of cultural shaping of symptoms and illness behaviour on diagnosis, coping and treatment; differences in family structure and process affecting adaptation, acculturation and intergenerational conflict; and aspects of acceptance by the receiving society that affect employment, social status and integration. These issues can be addressed through specific inquiry, the use of trained interpreters and culture brokers, meetings with families, and consultation with community organizations.

Interpretation:

Systematic inquiry into patients’ migration trajectory and subsequent follow-up on culturally appropriate indicators of social, vocational and family functioning over time will allow clinicians to recognize problems in adaptation and undertake mental health promotion, disease prevention or treatment interventions in a timely way.Changing patterns of migration to Canada pose new challenges to the delivery of mental health services in primary care. For the first 100 years of Canada’s existence, most immigrants came from Europe; since the 1960s, there has been a marked shift, with greater immigration from Asia, Africa, and Central and South America.¹ The mix differs across the provinces, although nearly all immigrants settle in Canada’s largest cities.² The task of preventing, recognizing and appropriately treating common mental health problems in primary care is complicated for immigrants and refugees because of differences in language, culture, patterns of seeking help and ways of coping.^3–6In consultation with experts in immigrant and refugee mental health, we reviewed the literature to determine associated risks and clinical considerations for primary care practitioners in the approach to common mental health problems among new immigrant or refugee patients.^7–10 In this paper, we review the effect of migration on mental health, use of health care and barriers to care. We outline basic clinical strategies for primary mental health care of migrants including the use of interpreters, family interaction and assessment, and working with community resources.     

Evaluation of matrix-assisted laser desorption ionization-time of flight whole cell profiles for assessing the cultivable diversity of aerobic and moderately halophilic prokaryotes thriving in solar saltern sediments

The moderately halophilic, cultivable fraction of prokaryotes thriving in hypersaline sediments of a solar saltern in Mallorca, Spain, has been studied by means of different cultivation media. A set of 374 isolates retrieved with six different culture conditions was screened, using whole-cell MALDI-TOF MS analysis to classify them into 25 phenotypic clusters at 52% similarity. The phylogenetic inference, made from comparative sequence analyses of the 16S rRNA genes of selected strains, indicated that each phenotypic cluster was comprised of a genealogically homogeneous set of strains. DNA-DNA hybridization (DDH) results among selected strains confirmed that each MALDI-TOF cluster encompassed members of the same species. On the other hand, the intra-cluster diversity, measured by several RAPD (Random Amplified Polymorphic DNA) amplifications, indicated that the clusters corresponded to several populations of the same phylogenetic unit coexisting in the same environment. The results encourage the use of MALDI-TOF MS for further exhaustive studies of the cultivable diversity of hypersaline environments.     

Acetazolamide: maternal toxicity, pattern of malformations, and litter effect

Thirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.: Teratology 6:239-240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A "litter effect" was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fetuses.