Risk Categories Disclosed in the Administration Reports of Brazilian Companies with ADRs

The study aims to find the categories of risks disclosed in the Administration Reports of Brazilian companies with the issuance of ADR`s. The research is characterized as descriptive, accomplished through doucmentary analysis. The sample includes 28 Brazilian companies with the issuance of American Depository Receipt (ADR`s) in the Stock Exchange of New York (USA). We have tried to identify the categories of risk, presented by the companies surveyed in the Administration Reports (AR) of 2007. Seven categories of corporate risks were considered, identified through COSO (2004) methodology strategic risks, operational risks, legal risks and image risks,. The survey results show that in general there is no standaardization of the types sof risks disclosed by the companies. A total of 14 types of risks havd been identified. The predominant category in the disclosure was the operational risk, with 20.72% of the observations. There was no disclosre of image risk in the AR of the companies surveyed. It was found that 19 companies, 67.86% of the surveyed companies, demonstrate some kind of risk to which they are exposed. On the other hand, nine companies (32.14%) did not show any kind of risk.

Protection against Paracoccidioides brasiliensis infection conferred by the prophylactic administration of native and recombinant ArtinM

We determined the prophylactic effect of both the d-mannose-binding lectin ArtinM extracted from the seeds of Artocarpus integrifolia (jackfruit) and its recombinant counterpart during the course of experimental paracoccidioidomycosis induced in BALB/c mice. Four experimental protocols of prophylaxis were employed to evaluate the most protective regimen of ArtinM administration. It was demonstrated that the best effect was obtained by administration of two ArtinM doses on days 10 and 3 before the challenge with Paracoccidioides brasiliensis. By following this protocol, the lungs of mice that received native or recombinant ArtinM exhibited reduced fungal burden and granuloma incidence. In addition, the protocol augmented contents of IL-12, IFN-gamma, TNF-alpha and NO. On the other hand, the control group consisting of untreated infected mice had higher pulmonary levels of IL-4 and IL-10. In conclusion, prophylaxis with ArtinM significantly reproduces the effect of its therapeutic administration, i.e, it confers resistance to P. brasiliensis infection in mouse models by promoting IL-12 production and favours Th1-immunity.

Therapeutic administration of KM+ lectin protects mice against Paracoccidioides brasiliensis infection via interleukin-12 production in a Toll-like receptor 2-dependent mechanism

KM+ is a mannose-binding lectin from Artocarpus integrifolia that induces interleukin (IL)-12 production by macrophages and protective T helper I immune response against Leishmania major infection. in this study, we performed experiments to evaluate the therapeutic activity of jackfruit KM+ (jfKM(+)) and its recombinant counterpart (rKM(+)) in experimental paracoccidioidomycosis. To this end, jfKM(+) or rKM(+) was administered to BALB/c mice 10 days after infection with Paracoccidiodes brasiliensis. Thirty days postinfection, lungs from the KM+-treated mice contained significantly fewer colony-forming units and little to no organized granulomas compared to the controls. In addition, lung homogenates from the KM+-treated mice presented higher levels of nitric oxide, IL-12, interferon-gamma, and tumor necrosis factor-a, whereas higher levels of IL-4 and IL-10 were detected in the control group. With mice deficient in IL-12, Toll-like receptor (TLR) 2, TLR4, or TLR adaptor molecule MyD88, we demonstrated that KM+ led to protection against P. brasiliensis infection through IL-12 production, which was dependent on TLR2. These results demonstrated a beneficial effect of KM+ on the severity of P. brasiliensis infection and may expand its potential use as a novel immunotherapeutic molecule.

Disposition of MDMA and Metabolites in Human Sweat Following Controlled MDMA Administration

BACKGROUND: Understanding the excretion of 3,4-methylenedioxymethamphetamine (MDMA) and metabolites in sweat is vital for interpretation of sweat tests in drug treatment, criminal justice, and workplace programs. METHODS: Placebo, low (1.0 mg/kg), and high (1.6 mg/kg) doses of oral MDMA were given double-blind in random order to healthy volunteers (n = 15) with histories of MDMA use. Participants resided on the closed clinical research unit for up to 7 days after each dose. Volunteers wore PharmChek (R) sweat patches (n = 640) before, during, and after controlled dosing. Patches were analyzed by solid phase extraction and GC-MS for MDMA, methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA), and 4hydroxy-3-methoxymethamphetamine (HMMA). Limits of quantification (LOQ) were 2.5 ng/patch for MDMA and 5 ng/patch for HMA, HMMA, and MDA. RESULTS: MDMA was the primary analyte detected in 382 patches (59.7%), with concentrations up to 3007 ng/patch. MDA was detected in 188 patches (29.4%) at <172 ng/patch, whereas no HMMA or HMA was detected; 224 patches (35.0%) and 60 patches (9.4%) were positive for MDMA and MDA, respectively, at the 25-ng/patch threshold proposed by the Substance Abuse and Mental Health Services Administration. CONCLUSIONS: Sweat testing was shown to be an effective and reliable method for monitoring MDMA use in this controlled MDMA administration study. However, variability in sweat excretion suggests that results should be interpreted qualitatively rather than quantitatively. These data provide a scientific database for interpretation of MDMA sweat test results. (C) 2008 American Association for Clinical Chemistry

Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development

A dendritic cell (DC) imbalance with a marked deficiency in CD4(-)8(+) DC occurs in non-obese diabetic (NOD) mice, a model of human autoimmune diabetes mellitus. Using a NOD congenic mouse strain, we find that this CD4(-)8(+) DC deficiency is associated with a gene segment on chromosome 4, which also encompasses non-MHC diabetes susceptibility loci. Treatment of NOD mice with fms-like tyrosine kinase 3 ligand (FL) enhances the level of CD4(-)8(+) DC, temporarily reversing the DC subtype imbalance. At the same time, fms-like tryosine kinase 3 ligand treatment blocks early stages of the diabetogenic process and with appropriately timed administration can completely prevent diabetes development. This points to a possible clinical use of FL to prevent autoimmune disease.

Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production

The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology.

Transitions between routes of benzodiazepine administration among heroin users in Sydney

A sample of 312 heroin users were interviewed regarding their benzodiazepine use. The majority (94%) had used benzodiazepines, 72% in the 6 months prior to interview. Benzodiazepine injecting was common, with 28% of the sample having injected these drugs, 13% in the 6 months preceding interview. Current benzodiazepine injectors showed greater polydrug use, injection-related HIV risk-taking behaviour, criminal involvement, psychological distress and injection-related health problems, as well as poorer general health, and an increased risk of having overdosed than other users of benzodiazepines. Of those subjects who had injected benzodiazepines, 55% were no longer current benzodiazepine injectors. Concern for general health emerged as the most common reason for having made a transition away from injecting, and for being likely to make such a transition.

Timing-dependent protection of hypertonic saline solution administration in experimental liver ischemia/reperfusion injury

Background. Diving liver ischemia, the decrease in mitochondrial energy causes cellular damage that is aggravated after reperfusion. This injury can trigger a systemic inflammatory syndrome, also producing remote organ damage. Several substances have been employed to decrease this inflammatory response during liver transplantation, liver resections, and hypovolemic shock. The aim of this study was to evaluate the effects of hypertonic saline solution and the best timing of administration to prevent organ injury during experimental liver ischemia/reperfusion. Methods. Rats underwent 1 hr of warm liver ischemia followed by reperfusion. Eighty-four rats Were allocated into 6 groups: sham group, control of ischemia group) (C), pre-ischemia treated NaCl 0.9% (ISS) and NaCl 7.5% (HTS) groups, pre-repefusion ISS, and HTS groups. Blood and tissue samples were collected 4 hr after reperfusion. Results. HTS showed beneficial effects in prevention of live ischemia/reperfusion injury. HTS groups developed increases in AST and ALT levels that were significantly less than ISS groups; however, the HTS pre-reperfusion group showed levels significantly less than the HTS pre-ischemia group. No differences in IL-6 and IL-10 levels, were observed. A significant decrease in mitochondrial dysfunction as well as hepatic edema was observed in the HTS pre-reperfusion group. Pulmonary vascular permeability Was significantly less in the pre-reperfusion HTS group compared to the ISS group. No differences in myeloperoxidase activity were observed. The liver histologic score was significantly less in the pre-reperfusion HTS group compared to the pre-ischemia I-ITS group. Conclusion. HTS ameliorated local and systemic injuries in experimental liver ischemia/reperfusion. Infusion of HTS in the pre-reperfusion period may be an important adjunct to accomplish the best results. (Surgery 2010;147:415-23.)

Sexual behavior and knowledge of sexually transmitted infections among university students in Sao Paulo, Brazil

Objective: To investigate the sexual behavior and knowledge about sexually transmitted infections (STIs) among undergraduate students in Sao Paulo, Brazil. Methods: Self-reported questionnaires were used. Results: Most of the 447 students in the study were single (97.3%), in their first year of university (87.7%), and the mean ages were 20.4 years (males) and 19.8 years (females). Vaginal intercourse was practiced by 69.7% of males and 48.4% of females, oral sex by 64.5% of males and 43.7% of females, and anal sex by 18.4% of males and 14.1% of females. Use of a condom during vaginal sex was practiced by 80.4% of males and 74.8% of females and during anal sex by 47.8% of males and 30.0% of females. Knowledge of transmission of STIs was greater than 90% for HIV, syphilis, genital herpes, and gonorrhea; 63%-76% for HPV and genital warts; 30%-34% for Trichomonas and only 16% for Chlamydia. Only 25%-34% knew that HIV was transmitted by breastfeeding; 56%-60% knew that HIV was transmitted by anal sex. Conclusion: Many students engage in high-risk sexual behavior with multiple partners and use condoms inconsistently. Knowledge of the acquisition and modes of sexual and vertical transmission of HIV are strikingly deficient. (C) 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Dose-dependent hepatic response to subchronic administration of nandrolone decanoate

Background: Androgenic anabolic steroids (AAS) are synthetic hormone derivatives of testosterone and are mainly used to enhance athletic performance and muscle mass, but medical applications also have been described. Short- and long-term side effects have been demonstrated in many organs, but the liver adverse effects are the most common and serious ones associated with AAS use. However, these effects have been supported by few clinical and experimental studies. Objective: To evaluate the hepatic function and structure after 5 wk of nandrolone decanoate administration at three different doses. Methods: Twenty-seven adult male Wistar rats were randomly assigned to the following groups: control, clinical, intermediate, and suprapharmacological doses of nandrolone decanoate during 5 wk. Results: The biochemical studies showed that nandrolone decanoate administration leads to a dose-dependent increase in serum levels of the aspartate aminotransferase (AST) (P < 0.05), alanine aminotransferase (ALT) (P < 0.01), and alkaline phosphatase (ALP) (P < 0.001), as well as a significant decrease in total proteins (P < 0.01), bilirubin (P < 0.05), total cholesterol and fractions (P < 0.05), and triglycerides (P < 0.05). Although a significant statistical difference was found for AST, ALT, and ALP when compared with the control group, their values remained within the normal range. The number of Kupffer cells was increased in the liver parenchyma (P < 0.05), and the content of collagen was increased in the central lobular vein wall, in the hepatic parenchyma, and in the portal space (P < 0.05). Conclusions: These results suggest that subchronic treatment with nandrolone decanoate, mainly administered at higher-than-clinical doses, are potentially deleterious to the liver, leading to incipient fibrosis.