Lactate modulates cardiac gene expression in mice during acute physical exercise

The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.

Avaliação da atividade antimicrobiana in vitro do extrato de Tabernaemontana catharinensis A. DC / Evaluation of in vitro antimicrobial activity of Tabernaemontana catharinensis A. DC. extract

Diversas espécies de Tabernaemontana têm sido estudadas devido a diversidade de alcalóides com atividade farmacológica. O objetivo desse trabalho foi avaliar a capacidade antimicrobiana in vitro do extrato das cascas do caule de Tabernaemontana catharinensis A. DC.em cepas de Staphylococcus aureus e Pseudomonas aeruginosa, microrganismos causadores de diversas infecções. Os testes de susceptibilidade bacteriana foram realizados usando o método de Kirby Bauer, consistindo na difusão em disco do antibiótico em meio de cultivo Mueller Hinton. Os testes de inibição foram realizados com soluções do extrato bruto seco de T. catharinensis dissolvido em etanol 70 por cento (v/v) na concentração 1,0 mg mL-1, que aplicada nos discos de área 20 mm², apresentaram concentração de 0,005 mg mm-2. Como controle negativo, realizou-se ensaios com placas contendo P. aeruginosa, e discos com etanol 70 por cento (v/v), e como controle positivo, discos com os antibióticos ceftriaxona sódica (0,25 mg mm-2 de área do disco), tetraciclina (0,005 mg mm-2) e cefalexina (0,005 mg mm-2). A solução do extrato na concentração de 0,005 mg mm-2 inibiu o Staphylococcus aureus, com diâmetro médio do halo de 0,6 cm. O halo de inibição para o Pseudomonas aeruginosa foi em média 1,2 cm. A tetraciclina, a cefalexina, e o controle negativo (etanol 70 por cento v/v) não demonstraram ação antimicrobiana. O halo de inibição usando ceftriaxona foi em média 2,2 cm para P. aeruginosa e 1,0 cm para Staphylococcus aureus.

Several Tabernaemontana species have been studied due to their several alkaloids with pharmacological activity. The aim of this work was to evaluate the in vitro antimicrobial action of the extract from stem barks of Tabernaemontana catharinensis A. DC. against strains of Staphylococcus aureus and Pseudomonas aeruginosa, microorganisms that cause several infections. Bacterial susceptibility tests were performed by the Kirby-Bauer method, consisting in antibiotic disk diffusion in Mueller Hinton medium. Inhibition tests were performed with solutions of T. catharinensis dry crude extract dissolved in ethanol 70 percent (v/v) at 1.0 mg mL-1, which became 0.005 mg mm-2 when applied to 20 mm² disks. As negative control, assays were carried out in plates containing P. aeruginosa and disks with ethanol 70 percent (v/v). Positive control consisted of disks containing the antibiotics ceftriaxone sodium (0.25 mg mm-2 disk area), tetracycline (0.005 mg mm-2) and cephalexin (0.005 mg mm-2). Extract solution at 0.005 mg mm-2 inhibited Staphylococcus aureus, with 0.6cm halo mean diameter. The inhibition halo for Pseudomonas aeruginosa was on average 1.2 cm. Tetracycline, cephalexin and negative control (ethanol 70 percent v/v) did not show antimicrobial action, whereas ceftriaxone sodium resulted in 2.2 and 1.0cm mean inhibition halo diameters for P. aeruginosa and Staphylococcus aureus, respectively.

Effect of (-)- Δ9 -tetrahydrocannabinoid on the hepatic redox state of mice

(-)-∆9-Tetrahydrocannabinol (∆9-THC), a psychoactive component of marijuana, has been reported to induce oxidative damage in vivo and in vitro. In this study, we administered (∆9-THC to healthy C57BL/6J mice aged 15 weeks in order to determine its effect on hepatic redox state. Mice were divided into 3 groups: (∆9-THC (N = 10), treated with 10 mg/kg body weight (∆9-THC daily; VCtrl (N = 10), treated with vehicle [1:1:18, cremophor EL® (polyoxyl 35 castor oil)/ethanol/saline]; Ctrl (N = 10), treated with saline. Animals were injected ip twice a day with 5 mg/kg body weight for 10 days. Lipid peroxidation, protein carbonylation and DNA oxidation were used as biomarkers of oxidative stress. The endogenous antioxidant defenses analyzed were glutathione (GSH) levels as well as enzyme activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase, and glutathione peroxidase (GPx) in liver homogenates. The levels of mRNA of the cannabinoid receptors CB1 and CB2 were also monitored. Treatment with ∆9-THC did not produce significant changes in oxidative stress markers or in mRNA levels of CB1 and CB2 receptors in the liver of mice, but attenuated the increase in the selenium-dependent GPx activity (∆9-THC: 8 percent; VCtrl: 23 percent increase) and the GSH/oxidized GSH ratio (∆9-THC: 61 percent; VCtrl: 96 percent increase), caused by treatment with the vehicle. ∆9-THC administration did not show any harmful effects on lipid peroxidation, protein carboxylation or DNA oxidation in the healthy liver of mice but attenuated unexpected effects produced by the vehicle containing ethanol/cremophor EL®.

Hanseníase no ambiente de trabalho / Leprosy in the workplace

Apesar de ser uma doença conhecida há milhares de anos, e de atualmente ter tratamento que leva à cura, a hanseníase continua a se espalhar principalmente nos países mais pobres. O Brasil ocupa o primeiro lugar em número de casos da América, aproximadamente 13 por 10 mil habitantes, dados de 1993. Desde 1986 o Ministério da Saúde vem priorizando este agravo, tendo como objetivo atingir a meta de reduzir os coeficientes de prevalência a níveis inferiores a um paciente em cada 10.000 habitantes até o ano 2.000. Em 1996 o Ministério da Saúde, junto com a OMS, elegeu a empresa como um local a mais em que se pode diagnosticar novos casos de hanseníase. Um trabalho que deve ser desenvolvido em conjunto com os Centros de Referência em Saúde dos Trabalhadores e Centros de Vigilância Epidemiológica.