Alendronate therapy in cyclosporine-induced alveolar bone loss in rats

Background and Objective: Cyclosporine A is an immunosuppressive drug that is widely used in organ transplant patients as well as to treat a number of autoimmune conditions. Bone loss is reported as a significant side-effect of cyclosporine A use because this can result in serious morbidity of the patients. As we have shown that cyclosporine A-associated bone loss can also affect the alveolar bone, the purpose of this study was to evaluate the effect of the concomitant administration of alendronate on alveolar bone loss in a rat model.Material and Methods: Forty Wistar rats (10 per group) were given cyclosporine A (10 mg/kg, daily), alendronate (0.3 mg/kg, weekly), or both cyclosporine A and alendronate, for 60 d. The control group received daily injections of sterile saline. The expression of proteins associated with bone turnover, including osteocalcin, alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP), and also the calcium levels, were evaluated in the serum. Analysis of the bone volume, alveolar bone surface, the number of osteoblasts per bone surface and the number of osteoclasts per bone surface around the lower first molars was also performed.Results: the results indicate that cyclosporine A treatment was associated with bone resorption, represented by a decrease in the bone volume, alveolar bone surface and the number of osteoblasts per bone surface and by an increase in the number of osteoclasts per bone surface and TRAP-5b. These effects were effectively counteracted by concomitant alendronate administration.Conclusion: It is concluded that concomitant administration of alendronate can prevent cyclosporine A-associated alveolar bone loss.

Effect of salt stress on polyamine metabolism in bean cell culture

The adaptive capacity of bean (Phaseolus vulgaris L.) calluses (cultivars IAC-carioca, JALO EEP-558, BAT-93 and IAPAR-14) to salt stress (0-80 mM) was verified to determine the existence of biochemical markers such as organic and inorganic compounds, and metabolism of polyamines. The results obtained demonstrate that salt (NaCl) interfered with all the parameters analyzed and its intensity ranged due to the salt concentration and the cultivars used.

Enzymatic variability among venoms from different subspecies of Apis mellifera (Hymenoptera: Apidae)

The enzymatic variability was analyzed in venom extracts from bees reared in different colonies of the Africanized, A. m. ligustica and A. m. carnica subspecies. The implications of this variation focused on the biochemistry differentiation and immunogenicity of these venoms. The results showed the existence of a huge variability among the subspecies as well as among the colonies for three out of the six tested components - hyaluronidase, acid phosphatase and proteases - suggesting the utilization of these features as possible biochemical markers. Furthermore, although not statistically significant, it was found that the Africanized bee venom presented slightly higher levels of protein content and esterase activity, when compared to the other subspecies. If the esterase plays a role in the pain intensity caused by the sting, as suggested elsewhere, this might suggest a reason for a bigger algogenicity of this venom in relation to that of European bees. On the other hand, A. m. ligustica bees presented the highest levels of proteolytic and acid phosphatase activities, whose functions are not enlightened in Hymenoptera venoms. The A. m. carnica workers presented the highest hyaluronidase and the lowest acid phosphatase activity levels. The extremely variable results among colonies of the same subspecies and among subspecies, for the tested venom components, justify the absence of correlation between allergic reactions and tests with pooled venom.

Influência das concentrações de marcadores bioquímicos de supertreinamento sobre as performances aeróbia e anaeróbia durante periodização em natação

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Impacto da desnutrição fetal/neonatal e do exercício durante a recuperação nutricional sobre lipídios teciduais e homeostase glicêmica de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da remodelação óssea após a interrupção do tratamento com bifosfonato por um período prolongado e seu efeito sobre a osseointegração

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação dos efeitos de Baccharis dracunculifolia DC na prevenção e tratamento de colite induzida por ácido trinitrobenzenosulfônico em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação dos marcadores de injúria miocárdica induzida pela exposição ao metilmercúrio em modelos experimentais de primatas do novo mundo (Cebus Apella)

Este estudo teve como objetivo analisar os efeitos dos mecanismos de injúria celular que produzem lesão no coração do macaco Cebus apella expostos durante 120 dias consecutivos com doses diárias de 1,5 mg de metilHg, através de alterações detectadas no marcador bioquímico de lesão miocárdica CK-MB, nos achados histopatológicos assim como pela técnica de imuno-marcação de células apoptóticas. Para tanto foram relacionados os perfis séricos da CK-MB, CK total, AST, ALT, uréia, creatinina e bilirrubina total com os achados histopatológicos e imunohistoquímicos no processo de acometimento do músculo cardíaco durante a exposição ao metilHg, comparando com o grupo controle. O método utilizado para dosagem e análise das substâncias bioquímicas séricas e para a dosagem de mercúrio no sangue foi o cinético ultravioleta e espectrometria de absorção atômica, respectivamente; para análise histopatológica utilizou-se a técnica de Hematoxilina Eosina e para detecção dos perfis apoptóticos o método APOPTAG. Foram obtidas consideráveis informações que permitem correlacionar as alterações bioquímicas, histopatológicas e os perfis apoptóticos ao mecanismo do acometimento cardíaco nos três animais expostos ao metilHg comparando-os com o grupo controle. Verificou-se que de todas as substâncias bioquímicas analisadas, houve apenas acentuado aumento sérico da enzima CK-MB, enquanto que na histopatologia observou-se lesão celular reversível por acúmulo de água nos três órgãos analisados (coração, fígado e rim). Destaca-se também a observação de uma nítida marcação células apoptóticas no tecido cardíaco, hepático e renal dos animais expostos, evidenciando-se maior número de células positivas nas células dos túbulos renais, ressaltando que não se observou infiltrado inflamatório em torno destes elementos descritos em nenhum dos tecidos analisados e ausência das referidas lesões nos tecidos dos três animais controle. Concluiu-se que a enzima CK-MB, a degeneração hidrópica e o mecanismo de apoptose podem ser indicadores de lesão miocárdica na exposição aguda ao metilHg, cuja etiopatogenia pode estar relacionada a descompensação mitocondrial pelo comprometimento maciço na bomba de Na+ / K+ e Ca++. Fazendo-se necessário um maior aporte de estudos experimentais que venham esclarecer com precisão a etiopatogenia, o mecanismo de agressão e injúria celular em indivíduos expostos a doses tóxicas de metilHg.

Densidade mineral óssea de adolescentes do sexo feminino e suas relaçoes com biomarcadores ósseos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determinantes genéticos, bioquímicos e clínicos na resposta ao uso de hidroxiureia na doença falciforme

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Resistance training with excessive training load and insufficient recovery alters skeletal muscle mass-related protein expression

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Phenotypic expression of homozygous hemoglobin S in relation to β-globin haplotypes, glutathione S-transferase polymorphisms and detoxification enzymes

Sickle cell anemia (SCA) shows a pathophysiology that involves multiple changes in sickle cell erythrocytes, vaso-occlusive episodes, hemolysis, activation of inflammatory mediators, endothelial cell dysfunction, and oxidative stress. These events complicate treatment and culminate in the development of manifestations such as anemia, pain crises and multiorgan dysfunction. The aim of this study was to evaluate, in SCA patients, oxidative stress and antioxidant capacity markers, correlating them to treatment with hydroxyurea (HU), β-globin haplotypes and glutathione S-transferase polymorphisms (GSTT1, GSTM1 and GSTP1), in comparison to a control group (CG). The study groups were composed of 48 individuals without hemoglobinopathies (CG), SCA patients treated with HU [AF (+HU), N = 13] and untreated SCA patients [AF (-HU), N = 15], after informed consent. The groups were analyzed using cytological, electrophoretic, chromatographic and molecular methods and information from medical records. The GSTM1 and GSTT1 polymorphisms were determined by multiplex PCR, while the GSTP1 polymorphism by PCR-RFLP. Biochemical parameters were measured using spectrophotometric methods [TBARS, TEAC and catalase (CAT) and GST activities] and a chromatographic method [glutathione (GSH)]. The fetal Hb (Hb F) levels observed in the SCA (+HU) group (10.9%) confirmed the already well-described pharmacological effect of HU, but the SCA (-HU) group also had high Hb F levels (6.1%), which may have been influenced by genetic factors not targeted in this study. We found a higher frequency of the Bantu haplotype (48.2%), followed by the Benin (32.1%) and also Cameroon haplotypes, rare in our population, and 19.7% of atypical haplotypes. The presence of Bantu haplotype was related to higher lipid peroxidation levels in patients, but also, it conferred a differential response to HU treatment, raising Hb F levels in 52.6% (P = 0.03). The protective effect of Hb F was confirmed, because the increase in their levels resulted in a 41.3% decrease in lipid peroxidation levels (r = -0.74, P = 0.0156). The genotypic frequency of the GST polymorphisms observed was similar to that of other studies in the Brazilian population, and its association with biochemical markers revealed a significant difference only for the GSTP1 polymorphism, where patients with genotype V/V showed higher GSH and TEAC levels (P = 0.04 and P = 0.03, respectively) compared to patients with genotype I/I. The TBARS levels were about five to eight times higher in the SCA (+HU) and SCA (-HU) groups, respectively, compared to controls, and HU produced a 35.2% decrease in lipid peroxidation levels in the SCA (+HU) group (P < 0.0001). Moreover, the SCA (+HU) group showed higher TEAC levels when compared to CG (P = 0.002). We did not find any significant difference in GST activity between the groups studied (P = 0.76), but CAT activity was about 17 and 30% lower in SCA (+HU) and SCA (-HU) groups, respectively (P < 0.00001). Plasma GSH levels were ~2 times higher in SCA patients than in the control group (P = 0.0005) and showed a positive correlation with TBARS levels, confirming its antioxidant function. HU treatment contributed to higher CAT activity and TEAC levels and lower lipid peroxidation, and its pharmacological effect showed a “haplotype-dependent” response. These findings may contribute to elucidating the potential of HU in ameliorating oxidative stress in SCA subjects.

Efeitos da redução da concentração de sódio na solução de hemodiálise e no conteúdo de sódio da dieta sobre a resposta inflamatória de pacientes com doença renal crônica

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Avaliação do efeito do óleo essencial de Citrus Auratium L. no infarto do miocárdio em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)