Clustering of modifiable cardiovascular risk factors in adults living in Salvador (BA), Brazil]

OBJECTIVE: To estimate the frequency of modifiable cardiovascular risk factors, with and without inclusion of arterial hypertension, occurring simultaneously in a racially-mixed population. METHOD: A cross-sectional study was carried out with 1,298 adults aged > or = 20 years in the city of Salvador, Brazil, in 2000. Eight modifiable cardiovascular risk factors were assessed, in any combination: total cholesterol > or = 240 mg/dL; high density-lipoprotein cholesterol (HDL-c) < 40 mg/dL; triglycerides > or = 200 mg/dL; glycemia > or = 126 mg/dL + well-controlled diabetes; body mass index > or = 25 kg/m2, waist > or = 102 cm for males and > or = 88 cm for females, smoking and alcoholism. The results were stratified according to the number of simultaneous risk factors (zero to five or more and two or more risk factors). The data were analyzed in terms of estimated proportions and 95% confidence intervals (95%CI), with and without the inclusion of arterial hypertension (VI Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC-VI], United States of America), ratio of proportions and chi-square for proportions as a measure of association. RESULTS: Among men (41.4% of participants), 7.5% (95%CI: 2.5 to 9.7) did not present risk factors; 68.8% (95%CI: 65.0 to 72.8) presented two or more risk factors, not including hypertension. After inclusion of hypertension, 73.4% (95%CI: 69.7 to 77.1) presented two or more risk factors. Among women, 11.6% did not present risk factors. The presence of two or more risk factors, not including hypertension, was observed in 67.7% (95%CI: 64.8 to 71.4). After inclusion of hypertension, 71.7% (95%CI: 68.5 to 74.9) of the women presented two or more risk factors. Significant differences were observed for the presence of two or more risk factors in men with not more than 4 years of schooling vs. 5 to less than 11 years of schooling (P < 0.05); in women with not more than 4 years of schooling vs. 5 to less than 11 years of schooling; in women with not more than 4 years of schooling vs. 11 or more years of schooling (P < 0.01); and in black vs. white women (P < 0.01). CONCLUSIONS: The high proportion of clustering cardiovascular risk factors in Salvador, with or without hypertension, especially in the population with little schooling and in black individuals, suggests the need for broad social strategies to reduce social inequality, promote health, and facilitate the treatment of cardiovascular risk factors.     

Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.

Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.     

Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients.

PURPOSE: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. PATIENTS AND METHODS: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m(2) every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 microg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). RESULTS: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G(2)M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. CONCLUSION: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment.     

PSTPIP1‐associated myeloid‐related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia

Neutropenia in pediatric patients can be due to a variety of disorders. We describe two patients who underwent extensive evaluation over many years for arthralgias and moderate neutropenia of unclear etiology. Genetic testing identified a pathogenic variant in PSTPIP1 (proline‐serine‐threonine phosphatase‐interacting protein 1) in both patients. Markedly elevated inflammatory markers and zinc levels confirmed the rare diagnosis of PSTPIP1‐associated myeloid‐related proteinemia inflammatory (PAMI) syndrome, tailoring treatment. Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in PAMI syndrome may account for the specific phenotypic features of this disorder.     

Anatoxin-a(s), an anticholinesterase from the cyanobacterium Anabaena flos-aquae NRC-525-17

Anatoxin a(s) [antx-a(s)] given intraperitoneally to Sprague-Dawley rats at different doses (0.1-1.0 mg/kg) caused signs of severe cholinergic overstimulation. Assays of rat blood acetylcholinesterase (AChE) revealed a dose-dependent inhibition. The in vitro inhibition of electric eel acetylcholinesterase (AChE, E.C. 3.1.1.7) and horse serum butyrylcholinesterase (BUChE, E.C. 3.1.1.8) by antx-a(s) was time- and concentration-dependent. The inhibition of electric eel AChE follows first order kinetics, indicative of irreversible inhibition. The irreversibility of electric eel AChE inhibition was confirmed by a plot of Vmax versus total enzyme concentration [ET]. The kinetics of inhibition of cholinesterase by antx-a(s) supports the previous pharmacological findings that antx-a(s) is an anticholinesterase and that signs of intoxication by it are primarily due to cholinesterase inhibition.     

Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial

While Ayurvedic medicine has touted the cognitive enhancing effects of Bacopa monniera for centuries, there is a need for double-blind placebo-controlled investigations. One hundred and seven healthy participants were recruited for this double-blind placebo-controlled independent group design investigation. Sixty-two participants completed the study with 80% treatment compliance. Neuropsychological testing using the Cognitive Drug Research cognitive assessment system was conducted at baseline and after 90 days of treatment with a special extract of Bacopa monniera (2 x 150 mg KeenMind) or placebo. The Bacopa monniera product significantly improved performance on the 'Working Memory' factor, more specifically spatial working memory accuracy. The number of false-positives recorded in the Rapid visual information processing task was also reduced for the Bacopa monniera group following the treatment period. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monniera extract. Further studies are required to ascertain the effective dosage range, the time required to attain therapeutic levels and the effects over a longer term of administration.