Self-assembly of 6-thioguanine and 6-thioguanosine monolayers on the mercury electrode: effects of oxygen and applied potential

The formation of self-assembled monolayers (SAMs) of 6-thioguanine and 6-thioguanosine on mercury from deaerated and air-saturated aqueous solutions has been studied. The self-assembly process was investigated using chronoamperometry, cyclic voltammetry and open circuit potential (ocp) measurements. The presence of dissolved oxygen is a necessary condition for the formation of full SAMs on a hanging mercury drop electrode (HMDE) at ocp. In the absence of oxygen, the formation of such SAMs requires application of an appropriate potential to the HMDE during a certain period of time. The effects of oxygen and applied potential are explained on the basis of the charge-transfer reaction involved in the self-assembly process.     

Dengue emergence and adaptation to peridomestic mosquitoes

Phylogenetic evidence suggests that endemic and epidemic dengue viruses (DENV), transmitted among humans by the anthropophilic mosquitoes Aedes aegypti and Ae. albopictus, emerged when ancestral, sylvatic DENV transmitted among nonhuman primates by sylvatic Aedes mosquitoes adapted to these peridomestic vectors. We tested this hypothesis by retrospectively examining evidence for adaptation of epidemic and endemic versus sylvatic strains of DENV-2 to Ae. albopictus and Ae. aegypti. First and second-generation offspring of mosquitoes from different geographic regions in the Americas and Southeast Asia were tested for their susceptibility to epidemic/endemic and sylvatic DENV-2 isolates from West Africa, Southeast Asia, and Oceania. Both Aedes species were highly susceptible (up to 100% infected) to endemic/epidemic DENV-2 strains after ingesting artificial blood meals but significantly less susceptible (as low as 0%) to sylvatic DENV-2 strains. Our findings support the hypothesis that adaptation to peridomestic mosquito vectors mediated dengue emergence from sylvatic progenitor viruses.     

Disease-related outcomes influence prevalence of falls in people with rheumatoid arthritis

Background

Patients with rheumatoid arthritis (RA) are at increased risk of falls, with potential adverse outcomes. There is a considerable variation across studies regarding the prevalence of falls and its correlation with clinical data, disease-related outcomes and physical performance tests.

Interaction between arachidonic acid and cAMP signaling pathways enhances steroidogenesis and StAR gene expression in MA-10 Leydig tumor cells

Previous studies have demonstrated that trophic hormone stimulation induced cyclic AMP (cAMP) formation and arachidonic acid (AA) release from phospholipids and that both these compounds were required for steroid biosynthesis and steroidogenic acute regulatory (StAR) gene expression in MA-10 mouse Leydig tumor cells. The present study further investigates the synergistic effects of the AA and cAMP interaction on steroidogenesis. To demonstrate cAMP-induced AA release, MA-10 cells were pre-loaded with 3H-AA and subsequently treated with dibutyryl cyclic AMP (dbcAMP). Stimulation with dbcAMP significantly induced AA release in MA-10 cells to a level 145.7% higher than that of controls. Lowering intracellular cAMP concentration by expressing a cAMP-phosphodiesterase significantly reduced human chorionic gonadotrophin (hCG)-induced AA release. The dbcAMP-induced AA release was inhibited significantly by the phospholipase A(2) (PLA(2)) inhibitor dexamethasone (Dex) and also by the protein kinase A (PKA) inhibitor H89, suggesting the involvement of PKA phosphorylation and/or PLA(2) activation in cAMP-induced AA release. The effect of the interaction between AA and cAMP on StAR gene expression and steroid production was also investigated. While 0.2 mM dbcAMP induced only very low levels of StAR protein, StAR mRNA, StAR promoter activity and steroid production, all of these parameters increased dramatically as AA concentration in the culture medium was increased from 0 to 200 microM. Importantly, AA was not able to induce a significant increase in steroidogenesis at any concentration when used in the absence of dbcAMP. However, when used in concert with submaximal concentrations of dbcAMP (0.05 mm to 0.5 mm), AA was capable of stimulating StAR gene expression and increasing steroid production significantly. The results from this study demonstrate that AA and cAMP act in a highly synergistic manner to increase the sensitivity of steroid production to trophic hormone stimulation and probably do so by increasing StAR gene expression.     

Long-term comparative pharmacovigilance of orally transmitted Chagas disease: first report

Background: Two old drugs are the only choice against Trypanosoma cruzi and little is known about their secondary effects in the acute stage of oral-transmitted Chagas disease (ChD).

Methods: A cross-sectional analytical surveillance study was conducted in a sizable cohort of patients seen during the largest acute foodborne ChD microepidemic registered so far. Individuals were treated with benznidazole (BNZ) or nifurtimox (NFX). ‘Common Terminology Criteria for Adverse Events’ was assessed to categorize side effects according to severity.

Results: Out of 176 treatments applied, 79% had one or more adverse effects, which predominated in adults (97.8%) as compared to children (75.5%). Risk of side effects with NFX was significantly higher than BNZ. Four adults and a child treated with NFX had severe side effects (pulmonary infarction, facial paralysis, neutropenia, blurred vision, bone marrow hypoplasia) warranting hospitalization, and drug suspension. Adverse effects frequently reported with NFX were abdominal pain, hyporexia, weight loss, headache, nausea and lymphocytosis, whereas skin rash, neurosensory effects, hyporexia, fatigue, pyrosis, abdominal pain and eosinophilia were observed with BNZ.

Conclusions: Frequency and severity of side effects during treatment of acute oral infection by T. cruzi demand direct supervision and close follow-up, even in those asymptomatic, to prevent life-threatening situations.