Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

Caryocar brasiliense Camb. "pequi" is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway.

Regioregular improvement on the oxidative polymerization of poly-3-octylthiophenes by slow addition of oxidant at low temperature

Many pathways can be used to synthesize polythiophenes derivatives. The polycondensation reactions performed with organometallics are preferred since they lead to regioregular polymers (with high content of heat-to-tail coupling) which have enhanced conductivity and luminescence. However, these pathways have several steps; the reactants are highly moisture sensitive and expensive. On the other hand, the oxidative polymerization using FeCl3 is a one-pot reaction that requires less moisture sensitive reactants with lower cost, although the most common reaction conditions lead to polymers with low regioregularity. Here, we report that by changing the reaction conditions, such as FeCl3 addition rate and reaction temperature, poly-3-octylthiophenes with different the regioregularities can be obtained, reaching about 80% of heat-to-tail coupling. Different molar mass distributions and polydispersivities were obtained. The preliminary results suggest that the oxidative polymerization process could be improved to yield polythiophenes with higher regioregularity degree and narrower molar mass distributions by just setting some reaction conditions. We also verified that it is possible to solvent extract part of the lower regioregular fraction of the polymer further improving the regioregularity degree. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

The polysaccharide fraction of Propionibacterium acnes modulates the development of experimental focal segmental glomerulosclerosis

The pathogenesis of focal segmental glomerulosclerosis (FSGS) appears to be associated with type-2 cytokines and podocyte dysfunction. In this study, we tested the hypothesis that immunization with the polysaccharide fraction of Propionibacterium acnes (PS), a pro-Th1 agonist, may subvert the type-2 profile and protect podocytes from adriamycin-induced glomerulosclerosis. Adriamycin injection resulted in albuminuria and increased serum creatinine in association with loss of glomerular podocin and podoplanin expression, which is consistent with podocyte dysfunction. Renal tissue analysis revealed the expression of transcripts for GATA3 and fibrogenic-related proteins, such as TGF-beta, tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase 9 (MMP9). In association with the expression of fibrogenic transcripts, we observed peri-glomerular expression of a-smooth muscle actin (alpha-SMA), indicating epithelial-to-mesenchymal transition, and increased expression of proliferating cell nuclear antigen (PCNA) in tubular cells, suggesting intense proliferative activity. Previous immunization with PS inhibited albuminuria and serum creatinine in association with the preservation of podocyte proteins and inhibition of fibrogenic transcripts and the expression of alpha-SMA and PCNA proteins. Tissue analysis also revealed that PS treatment induced expression of mRNA for GD3 synthase, which is a glycosiltransferase related to the synthesis of GD3, a ganglioside associated with podocyte physiology. In addition, PS treatment inhibited the influx of inflammatory CD8(pos) and CD11b(pos) cells to kidney tissue. Finally, PS treatment on day 4 post-ADM, a period when proteinuria was already established, was able to improve renal function. Thus, we demonstrate that the PS fraction of P. acnes can inhibit FSGS pathogenesis, suggesting that immunomodulation can represent an alternative approach for disease management. (C) 2011 Elsevier GmbH. All rights reserved.

Black carbon affects the cycling of non-black carbon in soil

Black carbon (BC) is an important fraction of many soils worldwide and plays an important role in global C biogeochemistry. However, few studies have examined how it influences the mineralization of added organic matter (AOM) and its incorporation into soil physical fractions and whether BC decomposition is increased by AOM. BC-rich Anthrosols and BC-poor adjacent soils from the Central Amazon (Brazil) were incubated for 532 days either with or without addition of (13)C-isotopically different plant residue. Total C mineralization from the BC-rich Anthrosols with AOM was 25.5% (P < 0.05) lower than with mineralization from the BC-poor adjacent soils. The AOM contributed to a significantly (P < 0.05) higher proportion to the total C mineralized in the BC-rich Anthrosols (91-92%) than the BC-poor adjacent soils (69-80%). The AOM was incorporated more rapidly in BC-rich than BC-poor soils from the separated free light fraction through the intra-aggregate light fraction into the stable organo-mineral fraction and up to 340% more AOM was found in the organo-mineral fraction. This more rapid stabilization was observed despite a significantly (P < 0.05) lower metabolic quotient for BC-rich Anthrosols. The microbial biomass (MB) was up to 125% greater (P < 0.05) in BC-rich Anthrosols than BC-poor adjacent soils. To account for increased MB adsorption onto BC during fumigation extraction, a correction factor was developed via addition of a (13)C-enriched microbial culture. The recovery was found to be 21-41 % lower (P < 0.05) for BC-rich than BC-poor soils due to re-adsorption of MB onto BC. Mineralization of native soil C was enhanced to a significantly greater degree in BC-poor adjacent soils compared to BC-rich Anthrosols as a result of AOM. No positive priming by way of cometabolism due to AOM could be found for aged BC in the soils. (C) 2009 Elsevier Ltd. All rights reserved.

Anti-Atherogenic Effects of a Phenol-Rich Fraction from Brazilian Red Wine (Vitis labrusca L.) in Hypercholesterolemic Low-Density Lipoprotein Receptor Knockout Mice

Moderate wine intake (i.e., 1-2 glasses of wine a day) is associated with a reduced risk of morbidity and mortality from cardiovascular disease. The aim of this study was to evaluate the anti-atherosclerotic effects of a nonalcoholic ethyl acetate fraction (EAF) from a South Brazilian red wine obtained from Vitis labrusca grapes. Experiments were carried out on low-density lipoprotein (LDL) receptor knockout (LDLr-/-) mice, which were subjected to a hypercholesterolemic diet and treated with doses of EAF (3, 10, and 30 mg/kg) for 12 weeks. At the end of the treatment, the level of plasma lipids, the vascular reactivity, and the atherosclerotic lesions were evaluated. Our results demonstrated that the treatment with EAF at 3 mg/kg significantly decreased total cholesterol, triglycerides, and LDL plus very low-density lipoprotein levels compared with control hypercholesterolemic mice. The treatment of mice with EAF at 3 mg/kg also preserved the vasodilatation induced by acetylcholine on isolated thoracic aorta from hypercholesterolemic LDLr-/- mice. This result is in agreement with the degree of lipid deposit on arteries. Taken together, the results show for the first time that the lowest concentration of an EAF obtained from a red wine produced in southern Brazil significantly reduced the progression of atherosclerosis in mice.

THE LOG-BURR XII REGRESSION MODEL FOR GROUPED SURVIVAL DATA

The log-Burr XII regression model for grouped survival data is evaluated in the presence of many ties. The methodology for grouped survival data is based on life tables, where the times are grouped in k intervals, and we fit discrete lifetime regression models to the data. The model parameters are estimated by maximum likelihood and jackknife methods. To detect influential observations in the proposed model, diagnostic measures based on case deletion, so-called global influence, and influence measures based on small perturbations in the data or in the model, referred to as local influence, are used. In addition to these measures, the total local influence and influential estimates are also used. We conduct Monte Carlo simulation studies to assess the finite sample behavior of the maximum likelihood estimators of the proposed model for grouped survival. A real data set is analyzed using a regression model for grouped data.

A multiple time scale survival model with a cure fraction

Many recent survival studies propose modeling data with a cure fraction, i.e., data in which part of the population is not susceptible to the event of interest. This event may occur more than once for the same individual (recurrent event). We then have a scenario of recurrent event data in the presence of a cure fraction, which may appear in various areas such as oncology, finance, industries, among others. This paper proposes a multiple time scale survival model to analyze recurrent events using a cure fraction. The objective is analyzing the efficiency of certain interventions so that the studied event will not happen again in terms of covariates and censoring. All estimates were obtained using a sampling-based approach, which allows information to be input beforehand with lower computational effort. Simulations were done based on a clinical scenario in order to observe some frequentist properties of the estimation procedure in the presence of small and moderate sample sizes. An application of a well-known set of real mammary tumor data is provided.

Thyroid hormones are involved in 5 '-nucleotidase modulation in soluble fraction of cardiac tissue

Aims: To investigate the role of TH (thyroid hormones) in 5'-nucleotidase activity and expression in cardiac soluble fraction (SF). Main methods: Male Wistar rats received daily injections of 14 (10, 25 or 50 mu g T4/100 g body weight) for 14 days to develop a hyperthyroidism condition. Thyroidectomy was performed in other animals to mimic hypothyroidism, and 14 days after surgery they were submitted to TH replacement therapy. Key findings: T4 reduced the 5'-nucleotidase activity (T4-25. P<0.05 and 14-50, P<0.01) in the SF. Conversely, hypothyroidism significantly increased the 5'-nucleotidase activity in this fraction (P<0.001) and TH replacement therapy reversed the latter result (P<0.001 compared to hypothyroid group). The analysis of protein expression in the SF showed that 5'-nucleotidase was more expressed in hypothyroid than in the control group and that the phosphorylated state of PKC observed in this condition may contribute to a possible mechanism of 5'-nucleotidase modulation by thyroid status. Significance: Taken together, these data reveal that TH can influence adenosine production by modulating 5'-nucleotidase activity and expression, which may contribute to the cardioprotective effect and the maintenance of cardiac function under TH privation. (C) 2012 Elsevier Inc. All rights reserved.

Effect of Si addition on Ca- and P-impregnated implant surfaces with nanometer-scale roughness: an experimental study in dogs

Objectives: To investigate the effect of Si addition on a nanometer-scale roughness Ca and P implant surfaces in a canine tibia model by biomechanical and histomorphometric evaluations. Material and methods: The implant surfaces comprised a resorbable media CaP microblasted (control) and a CaP resorbable media + silica-boost microblasted (experimental) surfaces. Surfaces were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and optical interferometry (IFM) down to the nanometric level. The animal model involved the bilateral placement of control (n = 24) and experimental surface (n = 24) implants along the proximal tibiae of six dogs, remaining in vivo for 2 or 4 weeks. After euthanization, half of the specimens were torquedto- interface failure, and the other half was subjected to histomorphologic and bone-to-implant contact (BIC) evaluation. Torque and BIC statistical evaluation was performed by the Friedman test at 95% level of significance, and comparisons between groups was performed by the Dunn test. Results: IFM and SEM observations depicted comparable roughness parameters for both implant surfaces on the micrometer and nanometer scales. XPS analysis revealed similar chemical composition, except for the addition of Si on the experimental group. Torque-to-interface failure and BIC mean values showed no significant differences (P = 0.25 and 0.51, respectively) at both 2- and 4-week evaluation points for experimental and control groups. Early bone healing histomorphologic events were similar between groups. Conclusions: The experimental surface resulted in not significantly different biomechanical fixation and BIC relative to control. Both surfaces were biocompatible and osseoconductive.

Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of Diabetes

Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p < 0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p < 0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p < 0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p < 0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p < 0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.

Cerebral amyloid angiopathy impact on endothelium

Cerebral amyloid angiopathy (CAA) is an age-associated disease characterized by amyloid deposition in cerebral and meningeal vessel walls. CAA is detected in the majority of the individuals with dementia and also in a large number of non-demented elderly individuals. In addition, CAA is strongly associated with Alzheimer's disease (AD) pathology. Mechanical consequences including intra-cerebral or subarachnoid hemorrhage remains CAA most feared complication, but only a small fraction of CAA results in severe bleeding. On the hand the non-mechanical consequences in cerebrovascular regulation are prevalent and may be even more deleterious. Studies of animal models have provided strong evidence linking the vasoactive A beta 1-40, the main species found in CAA, to disturbances in endothelial-dependent factors, disrupting cerebrovascular regulation Here, we aimed to review experimental findings regarding the non-mechanical consequences of CAA for cerebrovascular regulation and discuss the implications of these results to clinical practice. (C) 2012 Elsevier Inc. All rights reserved.

Footprints of a trypanosomatid RNA world: pre-small subunit rRNA processing by spliced leader addition trans-splicing

The addition of a capped mini-exon [spliced leader (SL)] through trans-splicing is essential for the maturation of RNA polymerase (pol) II-transcribed polycistronic pre-mRNAs in all members of the Trypanosomatidae family. This process is an inter-molecular splicing reaction that follows the same basic rules of cis-splicing reactions. In this study, we demonstrated that mini-exons were added to precursor ribosomal RNA (pre-rRNA) are transcribed by RNA pol I, including the 5' external transcribed spacer (ETS) region. Additionally, we detected the SL-5' ETS molecule using three distinct methods and located the acceptor site between two known 5' ETS rRNA processing sites (A' and A1) in four different trypanosomatids. Moreover, we detected a polyadenylated 5' ETS upstream of the trans-splicing acceptor site, which also occurs in pre-mRNA trans-splicing. After treatment with an indirect trans-splicing inhibitor (sinefungin), we observed SL-5' ETS decay. However, treatment with 5-fluorouracil (a precursor of RNA synthesis that inhibits the degradation of pre-rRNA) led to the accumulation of SL-5' ETS, suggesting that the molecule may play a role in rRNA degradation. The detection of trans-splicing in these molecules may indicate broad RNA-joining properties, regardless of the polymerase used for transcription.

Peel bond strength of resilient liner modified by the addition of antimicrobial agents to denture base acrylic resin

In order to prolong the clinical longevity of resilient denture relining materials and reduce plaque accumulation, incorporation of antimicrobial agents into these materials has been proposed. However, this addition may affect their properties. Objective: This study evaluated the effect of the addition of antimicrobial agents into one soft liner (Soft Confort, Dencril) on its peel bond strength to one denture base (QC 20, Dentsply). Material and Methods: Acrylic specimens (n=9) were made (75x10x3 mm) and stored in distilled water at 37 degrees C for 48 h. The drug powder concentrations (nystatin 500,000U - G2; nystatin 1,000,000U - G3; miconazole 125 mg - G4; miconazole 250 mg - G5; ketoconazole 100 mg - G6; ketoconazole 200 mg - G7; chlorhexidine diacetate 5% - G8; and 10% chlorhexidine diacetate - G9) were blended with the soft liner powder before the addition of the soft liner liquid. A group (G1) without any drug incorporation was used as control. Specimens (n=9) (75x10x6 mm) were plasticized according to the manufacturers' instructions and stored in distilled water at 37 degrees C for 24 h. Relined specimens were then submitted to a 180-degree peel test at a crosshead speed of 10 mm/min. Data (MPa) were analyzed by analysis of variance (alpha=0.05) and the failure modes were visually classified. Results: No significant difference was found among experimental groups (p=0.148). Cohesive failure located within the resilient material was predominantly observed in all tested groups. Conclusions: Peel bond strength between the denture base and the modified soft liner was not affected by the addition of antimicrobial agents.

Influence of titanium and lutetium on the persistent luminescence of ZrO2

Non-doped as well as titanium and lutetium doped zirconia (ZrO2) materials were synthesized via the sol-gel method and structurally characterized with X-ray powder diffraction. The addition of Ti in the zirconia lattice does not change the crystalline structure whilst the Lu doping introduces a small fraction of the tetragonal phase. The UV excitation results in a bright white-blue luminescence at ca. 500 nm for all the materials which emission could be assigned to the Ti3+ e(g) -> t(2g) transition. The persistent luminescence originates from the same Ti3+ center. The thermoluminescence data shows a well-defined though rather similar defect structures for all the zirconia materials. The kinetics of persistent luminescence was probed with the isothermal decay curve analyses which indicated significant retrapping. The short duration of persistent luminescence was attributed to the quasi-continuum distribution of the traps and to the possibility of shallow traps even below the room temperature. (C) 2012 Optical Society of America

INSECTICIDAL AND BEHAVIORAL EFFECTS OF SECONDARY METABOLITES FROM MELIACEAE ON BEMISIA TABACI (HEMIPTERA: ALEYRODIDAE)

We studied the effects of crude extracts and fractions of Azadirachta indica, Melia azedarach, Toona ciliata and Trichilia pallida on both egg and nymph mortality and embryonic development of Bemisia tabaci B biotype, using tomato plants grown in a greenhouse. Next, we studied the host selection behavioral effects on the adult whitefly under laboratory conditions. The dichloromethane extracts from all plant species and fractions of the extract from branches of T. pallida (EBTPD) and of the extract from leaves of T. ciliata (ELTCD) in dichloromethane caused mortality of nymphs, but neither affected egg viability. However, the branches of the ethanolic extract of A. indica increased the period of embryonic development of the B. tabaci. In addition, the tomato leaflets treated with the fraction of ELTCD dichloromethane (0.28%) were the least preferred by adults, reducing the number of insects resting on the tomato leaflets. The ELTCD methanol and EBTPD dichloromethane fractions inhibited B. tabaci oviposition. Thus, Meliaceae derivatives can contribute to the reduction of the B. tabaci population. The susceptibility of the B. tabaci to Meliaceae derivatives and the relevant behavioral changes of this pest are discussed.