Surveillance,health promotion and control of Chagas disease in the Amazon Region - Medical attention in the Brazilian Amazon Region: a proposal

We refer to Oswaldo Cruz''s reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients'' samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care.     

COMMD1 regulates the delta epithelial sodium channel (δENaC) through trafficking and ubiquitination

The delta subunit of the epithelial sodium channel (δENaC) is a member of the ENaC/degenerin family of ion channels. δENaC is distinct from the related α-, β- and γENaC subunits, known for their role in sodium homeostasis and blood pressure control, as δENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate δENaC activity. Here, we show that COMMD1 interacts with δENaC through its COMM domain. Co-expression of δENaC with COMMD1 significantly reduced δENaC surface expression, and led to an increase in δENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of δENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates δENaC activity by reducing δENaC surface expression through promoting internalization of surface δENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.     

Optimization of Ionic Liquid Pretreatment of Mixed Softwood by Response Surface Methodology and Reutilization of Ionic Liquid from Hydrolysate

We investigated the feasibility of producing bioethanol from mixed softwood pretreated with the ionic liquid 1-butyl-3-methylimidazolium acetate ([Bmim]Ac). The optimal pretreatment conditions were determined by response surface methodology to be 100°C for 15 h, and the fermentable sugar yield was estimated to be 92.5%. Efficient pretreatment of softwood was maintained even after reutilizing [Bmim]Ac up to four times. Through the enzymatic saccharification and subsequent fermentation, bioethanol was produced with 0.42 g/g of yield and 0.24 g/L/h of productivity, which clearly suggests that efficient and economical bioethanol production can be achieved by optimizing pretreatment processes and reutilizing ionic liquid.     

Cartilage stress-relaxation proceeds slower at higher compressive strains

Articular cartilage is the connective tissue which covers bone surfaces and deforms during in vivo activity. Previous research has investigated flow-dependent cartilage viscoelasticity, but relatively few studies have investigated flow-independent mechanisms. This study investigated polymer dynamics as an explanation for the molecular basis of flow-independent cartilage viscoelasticity. Polymer dynamics predicts that stress-relaxation will proceed more slowly at higher volumetric concentrations of polymer. Stress-relaxation tests were performed on cartilage samples after precompression to different strain levels. Precompression increases the volumetric concentration of cartilage biopolymers, and polymer dynamics predicts an increase in relaxation time constant. Stress-relaxation was slower for greater precompression. There was a significant correlation between the stress-relaxation time constant and cartilage volumetric concentration. Estimates of the flow-dependent timescale suggest that flow-dependent relaxation occurs on a longer timescale than presently observed. These results are consistent with polymer dynamics as a mechanism of cartilage viscoelasticity.     

Effects of the calcium antagonist, diltiazem on in vitro and in vivo/in vitro bone resorption

The effect of the calcium antagonist diltiazem on bone resorption in organ culture has been investigated. It was found that diltiazem was ineffective alone but that in concentrations above 5 mumol/l it reduced mineral and organic resorption induced in vitro by 1.25 dihydroxycholecalciferol (1.25 (OH)2D3). No additivity with calcitonin effects was observed. Diltiazem did not significantly affect bone resorbing activity stimulated by 24,25(OH)2D3. Bone resorption was measured by an in vivo/in vitro technique using 45Ca prelabelled mice. Compared with 1.25(OH)2D3 alone treated group (0.480 pmol/g), it was found that diltiazem (100 nmol/g) reduced bone resorption without effect on calcium and phosphorus plasmatic concentrations at death. These data suggest that such a calcium antagonist is able to inhibit 1.25-(OH)2D3-increased-bone resorption either in vitro or in vivo/in vitro.     

Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors.

Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious i.v. antithrombotic agents.     

Comparative effects of the ionophore A23187 and vitamin D metabolites on 45Ca desaturation curves derived from bone cells: interaction of a calcium channel channel inhibitor diltiazem

The effects of diltiazem, a calcium channel inhibitor, on the cellular transport of calcium were studied in isolated heterogenous rat bone cells. Efflux was measured after equilibrating the cells with 45Ca and adding the vitamin D metabolite (1,25dihydroxycholecalciferol-1,25(OH)2D3 or 24,25dihydrocholecalciferol-24,25(OH)2D3), the ionophore A23187 and/or diltiazem. Results were analysed by fitting the desaturation curve to a model of two exponential terms. Kinetic analyses of curve indicated the presence of 2 exchangeable pools with different rate constants of exchange between the medium and cells (expressed by K.). After incubation of bone cells with diltiazem (20 nmol/10(6) cells) the following changes were recorded: a marked decrease in the rate constant of efflux from the fast turnover calcium pool (K12) and a reduction of the calcium pool sizes. Incubation of 10(6) cells with 0.5 ng 1,25(OH)2D3 plus diltiazem significantly reduced K12 compared to incubation with 1,25(OH)2D3 alone. In presence of 24,25(OH)2D3, diltiazem did not significantly alter K12 which was raised by incubation with the metabolite alone. Ionophore A23187 (0.5 micrograms/10(6) cells) increased the value of slow turnover constants of efflux whose values were affected by diltiazem. The possible involvement of Ca movements in bone resorption does not seem confirmed in the present experiment since in vitro effects of diltiazem in organ culture (observed in an initial previous experiment) were not reflected in the calcium 45 desaturation kinetics in heterogenous bone cells.