Recombinogenic, genotoxic, and cytotoxic effects of azathioprine using in vivo assays.

Azathioprine (Aza) is a purine antimetabolite immunosuppressant that is widely employed for immunosuppressive therapy in post-transplant recipients or patients with autoimmune diseases. Chronic use of immunosuppressants might produce several side effects, including a high rate of neoplasms in these patients. Considering that genotoxic effects are associated with an increased risk of developing cancer, the aim of this study was to examine the recombinogenic, genotoxic, and cytotoxic effects of Aza using Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster, as well as comet and micronucleus assays in mouse bone marrow cells. Further, the adverse effects of Aza were determined in mouse hepatic and renal tissues using histopathological analysis. Data demonstrated that Aza induced significant increased genotoxicity in D. melanogaster and mouse bone marrow cells at all concentrations tested. Homologous recombination was the predominant genotoxic event noted for the first time to be initiated by Aza in SMART. In histopathological analysis, Aza did not show any marked toxic activity in mouse hepatic and renal tissues. Therefore, the high rate of neoplasms reported in patients with long-term use of Aza may be attributed, at least partially, to the genotoxic action of this drug.

Toxicity and genotoxicity induced by abacavir antiretroviral medication alone or in combination with zidovudine and/or lamivudine in Drosophila melanogaster.

Abacavir (ABC), zidovudine (AZT), and lamivudine (3TC) are nucleoside analog reverse transcriptase inhibitors (NRTIs) widely used as combination-based antiretroviral therapy against human immunodeficiency virus. Despite effective viral suppression using NRTI combinations, genotoxic potential of NRTIs can be increased when administered in combination. This study investigated the toxic and genotoxic potential of ABC when administered alone or in combination with AZT and/or 3TC using the somatic mutation and recombination test in Drosophila melanogaster. This test simultaneously evaluated two events related to carcinogenic potential: mutation and somatic recombination. The results indicated that ABC was responsible for toxicity when administered alone or in combination with AZT and/or 3TC. In addition, all treatment combinations increased frequencies of mutation and somatic recombination. The combination of AZT/3TC showed the lowest genotoxic activity compared to all combinations with ABC. Therefore, our results indicated that ABC was responsible for a significant portion of genotoxic activity of these combinations. Somatic recombination was the main genetic event observed, ranging from 83.7% to 97.7%.

Phenotypic aspects of oral strains of Candida albicans in children with Down's syndrome.

The aim of this article is to characterize the biological aspects of oral strains of C. albicans in children with Down's syndrome. These yeasts were analyzed as to their macromorphological and enzymatic aspects and were tested as to their in vitro susceptibility to antifungal drugs using broth microdilution to determine the minimum inhibitory concentration (MIC). The morphotyping revealed that all oral C. albicans isolates from children with Down's syndrome promoted the formation of fringes regardless of size, while the control group presented smaller fringes. All oral C. albicans strains produced proteinase, but those with phospholipolytic activity showed greater enzyme capacity in the test group. In vitro susceptibility showed that all oral C. albicans isolates were sensitive to the drugs used.

Phenotypic aspects of oral strains of Candida albicans in children with down's syndrome / Aspectos fenotípicos de cepas de Candida albicans orais em crianças com síndrome de down

The aim of this article is to characterize the biological aspects of oral strains of C. albicans in children with Down's syndrome. These yeasts were analyzed as to their macromorphological and enzymatic aspects and were tested as to their in vitro susceptibility to antifungal drugs using broth microdilution to determine the minimum inhibitory concentration (MIC). The morphotyping revealed that all oral C. albicans isolates from children with Down's syndrome promoted the formation of fringes regardless of size, while the control group presented smaller fringes. All oral C. albicans strains produced proteinase, but those with phospholipolytic activity showed greater enzyme capacity in the test group. In vitro susceptibility showed that all oral C. albicans isolates were sensitive to the drugs used.

O objetivo deste artigo foi caracterizar os aspectos biológicos de cepas de C. albicans orais em crianças com síndrome de Down. Estas leveduras foram analisadas quanto aos seus aspectos macromorfológicos e enzimáticos e foram testadas quanto a sua suscetibilidade in vitro a drogas antifúngicas, usando a microdiluição em caldo para a determinação da concentração inibitória mínima (CIM). A morfotipagem revelou que todos os isolados de C. albicans orais de crianças com síndrome de Down induziram à formação de franjas independente do tamanho, enquanto o grupo controle teve franjas menores. Todas as cepas de C. albicans orais produziram proteinase, mas aquelas com atividade fosfolipidolítica mostraram maior capacidade enzimática no grupo teste. A suscetibilidade in vitro mostrou que todos os isolados de C. albicans orais foram sensíveis a drogas empregadas.

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.

Postexercise hypotension and hemodynamics: the role of exercise intensity.

AIM: Although postexercise hypotension (PEH) has already been extensively demonstrated, the influence of exercise intensity on its magnitude and mechanisms is still controversial. METHODS: Twenty-three normotensive subjects were submitted to a control (45 minutes of rest) and 3 exercise sessions (cycle ergometer, 45 minutes at 30%, 50% and 75% of .VO(2peak)) to investigate the role of exercise intensity on PEH. Blood pressure (BP - auscultatory), heart rate (HR - ECG), and cardiac output (CO - CO2 rebreathing) were measured before and after the control and exercise sessions. RESULTS: Systolic BP decreased significantly after exercise at 50% and 75% of .VO(2peak). Diastolic BP increased significantly during the control session, did not change after exercise at 30% of .VO(2peak), and decreased significantly after exercise at 50% and 75% of .VO(2peak). This fall was greater and longer after more intense exercise. CO and systemic vascular resistance (SVR) responses were similar between sessions, CO increased whereas SVR decreased significantly. Stroke volume (SV) increased and heart rate (HR) decreased following control and exercise at 30% of .VO(2peak) whereas SV decreased and HR increased after exercise at 50% and 75% of .VO(2peak). CONCLUSION: PEH is greater and longer after more intense exercise. BP profile is followed by a decrease in SVR and an increase in CO, what was not influenced by previous exercise. The increase in CO is caused by an increase in SV after rest and low intensity exercise and by an increase in HR after moderate and more intense aerobic exercise.