Tetravalent Vanadium Releases Ferritin Iron which Stimulates Vanadium-Dependent Lipid Peroxidation

The iron storage protein, ferritin, represents a possible source of iron for oxidative reactions in biological systems. It has been shown that superoxide and several xenobiotic free radicals can release iron from ferritin by a reductive mechanism. Tetravalent vanadium (vanadyl) reacts with oxygen to generate superoxide and pentavalent vanadium (vanadate). This led to the hypothesis that vanadyl causes the release of iron from ferritin. Therefore, the ability of vanadyl and vanadate to release iron from ferritin was investigated. Iron release was measured by monitoring the generation of the Fe²⁺-fcrrozine complex. It was found that vanadyl but not vanadate was able to mobilize ferritin iron in a concentration dependent fashion. Initial rates. and iron release over 30 minutes. were unaffected by the addition of superoxide dismutase. Glutathione or vanadate added in relative excess to the concentration of vanadyl, inhibited iron release up to 45%. Addition of ferritin at the concentration used for measuring iron release prevented vanddyl-induced NADH oxidation. Vanadyl promoted lipid peroxidation in phospholipid liposomes. Addition of ferritin to the system stimulated lipid peroxidation up to 50% above that with vanadyl alone. Fcrritin alone did not promote significant levels of lipid peroxidation.     

Patients' costs and cost-effectiveness of tuberculosis treatment in DOTS and non-DOTS facilities in Rio de Janeiro, Brazil

Background

Costs of tuberculosis diagnosis and treatment may represent a significant burden for the poor and for the health system in resource-poor countries.

Objectives

The aim of this study was to analyze patients'' costs of tuberculosis care and to estimate the incremental cost-effectiveness ratio (ICER) of the directly observed treatment (DOT) strategy per completed treatment in Rio de Janeiro, Brazil.

Methods

We interviewed 218 adult patients with bacteriologically confirmed pulmonary tuberculosis. Information on direct (out-of-pocket expenses) and indirect (hours lost) costs, loss in income and costs with extra help were gathered through a questionnaire. Healthcare system additional costs due to supervision of pill-intake were calculated considering staff salaries. Effectiveness was measured by treatment completion rate. The ICER of DOT compared to self-administered therapy (SAT) was calculated.

Principal Findings

DOT increased costs during the treatment phase, while SAT increased costs in the pre-diagnostic phase, for both the patient and the health system. Treatment completion rates were 71% in SAT facilities and 79% in DOT facilities. Costs per completed treatment were US$ 194 for patients and U$ 189 for the health system in SAT facilities, compared to US$ 336 and US$ 726 in DOT facilities. The ICER was US$ 6,616 per completed DOT treatment compared to SAT.

Conclusions

Costs incurred by TB patients are high in Rio de Janeiro, especially for those under DOT. The DOT strategy doubles patients'' costs and increases by fourfold the health system costs per completed treatment. The additional costs for DOT may be one of the contributing factors to the completion rates below the targeted 85% recommended by WHO.     

Engineering grapevine for increased resistance to fungal pathogens without compromising wine stability

The vast majority of wine proteins have recently been identified as pathogenesis-related (PR) proteins. During the growing season, these proteins are expressed in developmentally dependent and inducible manners in grapevine leaves and grape berries, in which they are believed to play an important role in protection against fungal pathogens and possibly other stresses. Because of their inherent resistance to proteolytic attack and to the low pH values characteristic of wines, vinification can be seen as a "purification strategy" for grape PR proteins. The inevitable consequent accumulation of these proteins in wines becomes a technological nuisance because they adversely affect the clarity and stability of wines. Genetically modified vines underexpressing PR proteins would certainly lead to stable wines but would increase the plant susceptibility to fungal attack, and the actual trend seems to be in the opposite direction, that is overexpressing these proteins to obtain plants with enhanced resistance to pathogens--a trend that will probably augment problems associated with protein instability in the resulting wines.     

Size and fecundity variation in populations of Poecilia vivipara Block & Schneider (Teleostei; Poeciliidae) inhabiting an environmental gradient

The reproductive variables [female size (geometric centroid size), fecundity and offspring size (longest diameter of the embryo)] of the livebearer Poecilia vivipara in the quaternary lagoons of northern Rio de Janeiro State varied significantly among sites and were partially associated within and among sites. Mean female size was directly related to salinity. Fecundity (number of offspring) was directly related to female size both within and among sites. The female size × fecundity relationship, however, was not constant among sites. Offspring size was partially and directly associated with female size and salinity. The relationship between fecundity and female size was positively related with fecundity, suggesting a non-linear relationship of these variables when the total sample was considered. The results suggest that life-history differences among sites were more related to different predation regimes than to simple effects of plasticity caused by increased growth in saltwater environments.     

The Active and the Inactive Form of the hAT1 Receptor Have an Identical Ligand-Binding Environment: An MPA Study on a Constitutively Active Angiotensin II Receptor Mutant

Several models of activation mechanisms were proposed for G protein-coupled receptors (GPCRs), yet no direct methods exist for their elucidation. The availability of constitutively active mutants has given an opportunity to study active receptor conformations within acceptable limits using models such as the angiotensin II type 1 (AT₁)¹ receptor mutant N111G-hAT₁ which displays an important constitutive activity. Recently, by using methionine proximity assay, we showed for the hAT₁ receptor that TMD III, VI, and VII form the ligand-binding pocket of the C-terminal amino acid of an antagonistic AngII analogue. In the present contribution, we investigated whether the same residues would also constitute the ligand-binding contacts in constitutively activated mutant (CAM) receptors. For this purpose, the same Met mutagenesis strategy was carried out on the N111G double mutants. Analysis of 43 receptors mutants in the N111G-hAT₁ series, photolabeled and CNBr digested, showed that there were only subtle structural changes between the wt-receptor and its constitutively active form.     

3D conformal hypofractionated radical radiotherapy in early glottic cancer

Aim

The purpose of this study was to evaluate acute and late toxicity and the locoregional control in patients treated with hypofractionated radical radiotherapy 2.25 Gy/fraction/day for early glottic carcinoma.

Materials and methods

A retrospective analysis was performed of 27 patients, stage T1–T2 N0 glottic squamous cell carcinoma, that underwent radical RT from April 2008 to October 2011. The mean age was 64.6 years (range 36–81). Seventeen patients were staged T1a, 3 patients T1b and 7 patients T2. All patients were 3D planned and treated in a 6 MV LINAC, 2.25 Gy/fraction/5 days per week, to a total dose between 63 Gy and 67.5 Gy. Biological Effective Dose (BED (α/β = 10)) ranged from 77.18 Gy to 82.69 Gy and EQD2 from 64.31 Gy to 68.91 Gy. Patients were evaluated in periodic follow-up. Toxicity was evaluated according to RTOG Toxicities Scales.

Results

With a median follow-time of 24.7 months (range 3.6–44.2 months), no evidence of locoregional recurrence was observed. The treatment was well tolerated and no unscheduled interruptions in treatments for toxicity were documented, with the median overall treatment time of 41 days (range 38–48). Only grades 1 and 2 acute toxicity were observed and no evidence of severe late toxicity.

Conclusion

The authors believe that this moderately hypofractionated scheme can provide a good locoregional control for T1–T2 glottic carcinomas with no increase of toxicity. As the limitation of this work is the reduced number of patients and the lack of long term follow-up, the authors hope to update this retrospective study in the future in order to improve the power of the results.     

Wear analysis in anatomical and reversed shoulder prostheses

This paper describes the development of a computational model to calculate wear rates in total shoulder prostheses, for a 5-150 degrees arm abduction. Anatomical keeled and pegged prosthesis as well as reversed prosthesis were the studied implants. The bone models were built based on computed tomography (CT) images and using a computer aided design-based modelling pipeline. The finite element method was used to solve the contact problem between the surface of the polyethylene (PE) components and the corresponding articular component. The aim of this work was to determine linear and volumetric PE wear, for several radial mismatches, in conditions of pathological (rheumatoid arthritis) and non-pathological bone. Results showed that contact pressures and linear wear developed in anatomical prosthesis were higher than those visualised in reversed prosthesis. However, anatomical prosthesis exhibited a better volumetric wear performance. Moreover, our findings indicated higher values of volumetric wear in higher congruent models and on pathological bone conditions.     

From endosperm to triploid plants: a stepwise characterization of the de novo shoot organogenesis and morpho-agronomic aspects of an ornamental passion fruit (Passiflora foetida L.)

Plant Cell, Tissue and Organ Culture (PCTOC) - Somaclonal variation during in vitro culture is often an undesirable phenomenon but may also be a source of genetic variation useful for breeders. The...