Effect of prostaglandin A1, arsenite and aspirin on stress proteins response in mosquito cells

The stress response of eukaryotic cells is characterized by changes in the metabolism of responding cells, most notably by increased synthesis of a group of proteins known as heat shock (HSP) proteins In this paper the effect of prostaglandin A1 (PGA1), arsenite and aspirin in Aedes albopictus cells was investigated. In cells treated with PGA1 (10 microg/ml) we observed the induction of several polypeptides with molecular masses of 87, 80, 70, 57, 29 and 23 kDa. Immunoblot analysis revealed that arsenite induces a marked synthesis of HSP70, and aspirin administered during the hyperthermic treatment caused a small increase of HSP70 synthesized.     

The metastable state of nucleocapsids of enveloped viruses as probed by high hydrostatic pressure

Enveloped viruses fuse their membranes with cellular membranes to transfer their genomes into cells at the beginning of infection. What is not clear, however, is the role of the envelope (lipid bilayer and glycoproteins) in the stability of the viral particle. To address this question, we compared the stability between enveloped and nucleocapsid particles of the alphavirus Mayaro using hydrostatic pressure and urea. The effects were monitored by intrinsic fluorescence, light scattering, and binding of fluorescent dyes, including bis(8-anilinonaphthalene-1-sulfonate) and ethidium bromide. Pressure caused a drastic dissociation of the nucleocapsids as determined by tryptophan fluorescence, light scattering, and gel filtration chromatography. Pressure-induced dissociation of the nucleocapsids was poorly reversible. In contrast, when the envelope was present, pressure effects were much less marked and were highly reversible. Binding of ethidium bromide occurred when nucleocapsids were dissociated under pressure, indicating exposure of the nucleic acid, whereas enveloped particles underwent no changes. Overall, our results demonstrate that removal of the envelope with the glycoproteins leads the particle to a metastable state and, during infection, may serve as the trigger for disassembly and delivery of the genome. The envelope acts as a "Trojan horse," gaining entry into the host cell to allow release of a metastable nucleocapsid prone to disassembly.     

Effects of creatine supplementation on the performance and body composition of competitive swimmers

The objective of this study was to determine the effect of creatine supplementation on performance and body composition of swimmers. Eighteen swimmers were evaluated in terms of post-performance lactate accumulation, body composition, creatine and creatinine excretion, and serum creatinine concentrations before and after creatine or placebo supplementation. No significant differences were observed in the marks obtained in swimming tests after supplementation, although lactate concentrations were higher in placebo group during this period. In the creatine-supplemented group, urinary creatine, creatinine, and body mass, lean mass and body water were significantly increased, but no significant difference in muscle or bone mass was observed. These results suggest that creatine supplementation cannot be considered to be an ergogenic supplement ensuring improved performance and muscle mass gain in swimmers.     

Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase

Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics. Compound 30 has an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this compound has micromolar potency. Furthermore, two compounds (16 and 30) demonstrate a reasonable pharmacokinetic profile in rodents. The synthesis, SAR, and biological activity of this novel class of compounds is described.     

Do mental health professionals use diagnostic classifications the way we think they do? A global survey

We report on a global survey of diagnosing mental health professionals, primarily psychiatrists, conducted as a part of the development of the ICD‐11 mental and behavioural disorders classification. The survey assessed these professionals' use of various components of the ICD‐10 and the DSM, their attitudes concerning the utility of these systems, and usage of “residual” (i.e., “other” or “unspecified”) categories. In previous surveys, most mental health professionals reported they often use a formal classification system in everyday clinical work, but very little is known about precisely how they are using those systems. For example, it has been suggested that most clinicians employ only the diagnostic labels or codes from the ICD‐10 in order to meet administrative requirements. The present survey was conducted with clinicians who were members of the Global Clinical Practice Network (GCPN), established by the World Health Organization as a tool for global participation in ICD‐11 field studies. A total of 1,764 GCPN members from 92 countries completed the survey, with 1,335 answering the questions with reference to the ICD‐10 and 429 to the DSM (DSM‐IV, DSM‐IV‐TR or DSM‐5). The most frequent reported use of the classification systems was for administrative or billing purposes, with 68.1% reporting often or routinely using them for that purpose. A bit more than half (57.4%) of respondents reported often or routinely going through diagnostic guidelines or criteria systematically to determine whether they apply to individual patients. Although ICD‐10 users were more likely than DSM‐5 users to utilize the classification for administrative purposes, other differences were either slight or not significant. Both classifications were rated to be most useful for assigning a diagnosis, communicating with other health care professionals and teaching, and least useful for treatment selection and determining prognosis. ICD‐10 was rated more useful than DSM‐5 for administrative purposes. A majority of clinicians reported using “residual” categories at least sometimes, with around 12% of ICD‐10 users and 19% of DSM users employing them often or routinely, most commonly for clinical presentations that do not conform to a specific diagnostic category or when there is insufficient information to make a more specific diagnosis. These results provide the most comprehensive available information about the use of diagnostic classifications of mental disorders in ordinary clinical practice.