Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction

Exercise training reduces renin-angiotensin system (RAS) activation, decreases plasma and tissue oxidative stress and inflammation in hypertension. However, the temporal nature of these phenomena in response to exercise is unknown. We sought to determine in spontaneously hypertensive rats (SHR) and age-matched WKY controls the weekly effects of training on blood pressure (BP), plasma and left ventricle (LV) Ang II and Ang-(1–7) content (HPLC), LV oxidative stress (DHE staining), gene and protein expression (qPCR and WB) of pro-inflammatory cytokines, antioxidant enzymes and their consequence on hypertension-induced cardiac remodeling. SHR and WKY were submitted to aerobic training (T) or maintained sedentary (S) for 8 weeks; measurements were made at weeks 0, 1, 2, 4 and 8. Hypertension-induced cardiac hypertrophy was accompanied by acute plasma Ang II increase with amplified responses during the late phase of LV hypertrophy. Similar pattern was observed for oxidative stress markers, TNF alpha and interleukin-1β, associated with cardiomyocytes’ diameter enlargement and collagen deposition. SHR-T exhibited prompt and marked decrease in LV Ang II content (T1 vs T4 in WKY-T), normalized oxidative stress (T2), augmented antioxidant defense (T4) and reduced both collagen deposition and inflammatory profile (T8), without changing cardiomyocytes’ diameter and LV hypertrophy. These changes were accompanied by decreased plasma Ang II content (T2-T4) and reduced BP (T8). SHR-T and WKY-T showed parallel increases in LV and plasma Ang-(1–7) content. Our data indicate that early training-induced downregulation of LV ACE-AngII-AT1 receptor axis is a crucial mechanism to reduce oxidative/pro-inflammatory profile and improve antioxidant defense in SHR-T, showing in addition this effect precedes plasma RAS deactivation

Influence of isolated cleft palate and palatoplasty on the face

INTRODUCTION: The literature has demonstrated that alterations in craniofacial morphology characterizing individuals with cleft palate are observed in both operated and unoperated patients. OBJECTIVE: This study evaluated the influence of isolated cleft palate and palatoplasty on the face, based on facial analysis. MATERIAL AND METHODS: Lateral facial photographs of the right side of 85 young adult patients with cleft palate were analyzed, of whom 50 were operated on and 35 had never received any previous surgical treatment. The nasolabial angle and zygomatic projection were used to define the maxillary position in the face. Mandibular positioning was classified as Pattern I, II and III. RESULTS: Patients were distributed into 54.12% as Pattern I, 32.94% Pattern II and 12.94% Pattern III. Distribution of facial patterns did not show statistically significant differences between groups (p>;0.05). Although palatoplasty did not influence the facial pattern, the zygomatic projection was vulnerable to plastic surgeries. Twenty-eight percent of the patients in the operated group showed zygomatic deficiency, compared to only 8.5% in the unoperated group. CONCLUSIONS: In patients with isolated cleft palate, palatoplasty may influence negatively the sagittal behavior of the maxilla, according to the zygomatic projection of the face, though without compromising the facial pattern

Study of ph effect on AZ31 magnesium alloy corrosion for using in temporary implants

Currently, magnesium alloys are gaining great interest for medical applications due to their degrading properties in the human body ensuring a great biocompatibility. These alloys also provide profitable mechanical properties due similarities with human bone.  However, a difficulty in applying these materials in the biomaterials industries is the corrosion prior to cell healing. The effect of the chemical composition of Mg alloys on their corrosion behavior is well known. In this study, samples of AZ31 magnesium alloy were cut into chips for elemental chemical analysis by neutron activation analysis (NAA). Concentrations of the elements As, La, Mg, Mn, Na, Sb and Zn were determined in the AZ31 alloy. Visualization tests of agar corrosion development in various media, of 0.90% sodium chloride solution (mass), phosphate buffer saline (PBS) and simulated body fluid (SBF) were performed. Visualizations of the effect of agar gel corrosion revealed pH variation during the corrosion process due to the released into the cathode. The highest released of hydroxyl ions occurred in NaCl solution compared to PBS and SBF solutions indicating that NaCl solution was much more aggressive to the alloy compared to the others

4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.

BackgroundChagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice.Methodology/principal findingsBoth acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart.Conclusions/significanceThe positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life

Revisiting the drivers of acoustic similarities in tropical anuran assemblages

Acoustic signaling is key in mediating mate-choice, which directly impacts individual fitness. Because background noise and habitat structure can impair signal transmission, the acoustic space of mixed-species assemblages has long been hypothesized to reflect selective pressures against signal interference and degradation. However, other potential drivers that received far less attention can drive similar outputs on the acoustic space. Phylogenetic niche conservatism and allometric constraints may also modulate species acoustic features, and the acoustic space of communities could be a side-effect of ecological assembly processes involving other traits (e.g. environmental filtering). Additionally, the acoustic space can also reflect the sorting of species relying on public information through extended communication networks. Using an integrative approach, we revisit the potential drivers of the acoustic space by addressing the distribution of acoustic traits, body size, and phylogenetic relatedness in tropical anuran assemblages across gradients of environmental heterogeneity in the Pantanal wetlands. We found the overall acoustic space to be aggregated compared with null expectations, even when accounting for confounding effects of body size. Across assemblages, acoustic and phylogenetic differences were positively related, while acoustic and body size similarities were negatively related, although to a minor extent. We suggest that acoustic partitioning, acoustic adaptation, and allometric constraints play a minor role in shaping the acoustic output of tropical anuran assemblages and that phylogenetic niche conservatism and public information use would influence between-assemblage variation. Our findings highlight an overlooked multivariate nature of the acoustic dimension and underscore the importance of including the ecological context of communities to understand drivers of the acoustic space

Phallus glutinolens

Phallus glutinolens is a species endemic to Brazil, occurring in fragments of Atlantic Forest in southern and southeastern regions. Up to now, there are only a few records of the species from six different sites. The total population is estimated at around 4,800 mature individuals, in one subpopulation. Based on the habitat decline within the area, we suspect a population decline around 10% in the last three generations (20 years). Phallus glutinolens is, therefore, assessed as Vulnerable C2a(ii).Fil: Trierveiler Pereira, Larissa. Universidade de Sao Paulo; BrasilFil: Vieira de Miranda, M.. Universidade de Sao Paulo; BrasilFil: Hernández Caffot, María Luciana. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Baltazar, J. M.. Universidade Federal do São Carlos; BrasilFil: Martins da Cuña, K.. Universidade Federal do Rio Grande do Sul; BrasilFil: Alves Silva, G.. Universidade de Sao Paulo; BrasilFil: Kossmann, T.. Universidade Federal de Santa Catarina; BrasilFil: Palacio, M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Drechsler Santos, E. R.. Universidade Federal de Santa Catarina; Brasi

The stress responsive and morphologically regulated hsp90 gene from Paracoccidioides brasiliensis is essential to cell viability

<p>Abstract</p> <p>Background</p> <p><it>Paracoccidioides brasiliensis </it>is a dimorphic fungus that causes the most prevalent systemic mycosis in Latin America. The response to heat shock is involved in pathogenesis, as this pathogen switches from mycelium to yeast forms in a temperature dependent fashion that is essential to establish infection. HSP90 is a molecular chaperone that helps in the folding and stabilization of selected polypeptides. HSP90 family members have been shown to present important roles in fungi, especially in the pathogenic species, as an immunodominant antigen and also as a potential antifungal therapeutic target.</p> <p>Results</p> <p>In this work, we decided to further study the <it>Pbhsp90 </it>gene, its expression and role in cell viability because it plays important roles in fungal physiology and pathogenesis. Thus, we have sequenced a <it>Pbhsp90 </it>cDNA and shown that this gene is present on the genome as a single copy. We have also confirmed its preferential expression in the yeast phase and its overexpression during dimorphic transition and oxidative stress. Treatment of the yeast with the specific HSP90 inhibitors geldanamycin and radicicol inhibited growth at 2 and 10 μM, respectively.</p> <p>Conclusion</p> <p>The data confirm that the <it>Pbhsp90 </it>gene encodes a morphologically regulated and stress-responsive protein whose function is essential to cell viability of this pathogen. This work also enforces the potential of HSP90 as a target for antifungal therapies, since the use of HSP90 inhibitors is lethal to the <it>P. brasiliensis </it>yeast cells in a dose-responsive manner.</p