Nicorandil protects cardiac mitochondria against permeability transition induced by ischemia-reperfusion

Ischemia followed by reperfusion is known to negatively affect mitochondrial function by inducing a deleterious condition termed mitochondrial permeability transition. Mitochondrial permeability transition is triggered by oxidative stress, which occurs in mitochondria during ischemia-reperfusion as a result of lower antioxidant defenses and increased oxidant production. Permeability transition causes mitochondrial dysfunction and can ultimately lead to cell death. A drug able to minimize mitochondrial damage induced by ischemia-reperfusion may prove to be clinically effective. We aimed to analyze the effects of nicorandil, an ATP-sensitive potassium channel agonist and vasodilator, on mitochondrial function of rat hearts and cardiac HL-1 cells submitted to ischemia-reperfusion. Nicorandil decreased mitochondrial swelling and calcium uptake. It also decreased reactive oxygen species formation and thiobarbituric acid reactive substances levels, a lipid peroxidation biomarker. We thus confirm previous reports that nicorandil inhibits mitochondrial permeability transition and demonstrate that nicorandil inhibits this process by preventing oxidative damage and mitochondrial calcium overload induced by ischemia-reperfusion, resulting in improved cardiomyocyte viability. These results may explain the good clinical results obtained when using nicorandil in the treatment of ischemic heart disease.

Optimisation of solid-phase microextraction combined with gas chromatography–mass spectrometry based methodology to establish the global volatile signature in pulp and skin of Vitis vinifera L. grape varieties

The volatiles (VOCs) and semi-volatile organic compounds (SVOCs) responsible for aroma are mainly present in skin of grape varieties. Thus, the present investigation is directed towards the optimisation of a solvent free methodology based on headspace-solid-phase microextraction (HS-SPME) combined with gas chromatography–quadrupole mass spectrometry (GC–qMS) in order to establish the global volatile composition in pulp and skin of Bual and Bastardo Vitis vinifera L. varieties. A deep study on the extraction-influencing parameters was performed, and the best results, expressed as GC peak area, number of identified compounds and reproducibility, were obtained using 4 g of sample homogenised in 5 mL of ultra-pure Milli-Q water in a 20 mL glass vial with addition of 2 g of sodium chloride (NaCl). A divinylbenzene/carboxen/polydimethylsiloxane fibre was selected for extraction at 60 °C for 45 min under continuous stirring at 800 rpm. More than 100 VOCs and SVOCs, including 27 monoterpenoids, 27 sesquiterpenoids, 21 carbonyl compounds, 17 alcohols (from which 2 aromatics), 10 C13 norisoprenoids and 5 acids were identified. The results showed that, for both grape varieties, the levels and number of volatiles in skin were considerably higher than those observed in pulp. According to the data obtained by principal component analysis (PCA), the establishment of the global volatile signature of grape and the relationship between different part of grapes—pulp and skin, may be an useful tool to winemaker decision to define the vinification procedures that improves the organoleptic characteristics of the corresponding wines and consequently contributed to an economic valorization and consumer acceptance.

Effects of the basic fibroblast growth factor and its anti-factor in the healing and collagen maturation of infected skin wound

PURPOSE: The infection is one of the main factors that affect the physiological evolution of the surgical wounds. The aim of this work is to evaluate the effects of fibroblast growth factor (FGFâ) and anti-FGFâ in the healing, synthesis and maturation of collagen when topically used on infected skin wounds of rats. METHODS: An experimental study was perfomed in 60 male Wistar rats. All animals were divided in two groups (A and B). Each group was divided in three subgroups A1, B1; A2, B2 and A3, B3. After anesthesia with pentobarbital, two open squared wounds (1cm2), 4cm distant to each other, were done in the dorsal skin of all the rats. In group A (n=30) the wounds were contaminated with multibacterial standard solution, and in group B(n=30) the wounds were maintained sterile. These wounds were named F1 (for inflammation analysis) and F2 (for collagen study). The open wounds of A1 and B1 rats were topically treated with saline solution, A2 and B2 were treated with FGFâ and subgroups A3 and B3 were treated with FGFâ and anti-FGFâ. The rats were observed until complete epitelization of F2 wounds for determination of healing time and the expression of types I and III collagen, using Picro Sirius Red staining. Inflammatory reaction in F1 wounds was studied using hematoxilineosin staining. The three variable was measured by the Image Pro-Plus Média Cybernetics software. The statistical analysis was performed by ANOVA and Tukey test, considering p<0.05 as significant. RESULTS: It was observed that infection retarded significantly (p<0.05) the time of wound scarring and the topical application of FCFb reverted the inhibition of healing caused by bacteria. The inflammatory reaction was greater in the subgroup B2 than in B1 and A3, and the difference was significant (p<0.05). It was observed greater expression of type I collagen in all the subgroups treated with FCFb, when compared with the untreated subgroups. Type III collagen was significantly decreased in wounds of B3 rats, comparing to the other subgroups. CONCLUSIONS: The FCFb accelerated the healing of open infected wounds and contributed with maturation of collagen, enhancing the type I collagen density. The anti-FCFb antibody was able to attenuate the production of both type I and III collagen

Simvastatin improves the healing of infected skin wounds of rats

This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. Methods: Fourteen Wistar rats weighing 285±12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of sinvastatina microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by imunohistochemical technique, and histological analysis by HE stain were performed. Results: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 ± 74.7 ìm2) than in saline (2120.0 ± 327.1 ìm2). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherchia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. Conclusion: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising

Detection of Leishmania (L.) chagasi in canine skin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of the season of the year, truck type and location on truck on skin bruises and meat quality in pigs

The purpose of this study was to evaluate the effect of the season of the year (summer vs winter), type of truck (A: single decker vs B : double-decker) and pig location on the truck (front, middle, rear) on the incidence of skin bruising and pork quality variation. For this purpose, 2660 gilts of an average weight of 126.7 (+/- 6.6) kg originating from 19 different farms were used. No interaction between season of the year, type of truck and location on truck was observed. A higher number of bruises on the body at unloading and slaughter (P < 0.0001) and a higher number of bruises on the carcass (P < 0.01) were observed in winter. At unloading a higher number of bruises on the body and on the carcass after slaughter was observed in pigs transported on Truck A (P=0.004 and P=0.05). A higher, although not significant, number of bruises was found on the body of pigs transported in the rear compartment of both trucks. Higher paleness value was found in the longissimus and semimembranosus muscles in summer (P=0.0001) than in winter. Cold and heat stress have a negative influence on skin bruises and meat quality, respectively. Poor vehicle design increases the incidence of bruised carcasses without detracting from pork quality regardless of the climate conditions tested and location of the animal it] the truck. (c) 2006 Elsevier B.V. All rights reserved.

The field resistance of potato cultivars to foliar late blight and its relationship with foliage maturity type and skin type in Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Comparison of the properties of compacted and porous lamellar chitosan-xanthan membranes as dressings and scaffolds for the treatment of skin lesions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of isocoumarins isolated from Paepalanthus bromelioides on mitochondria: Uncoupling, and induction/inhibition of mitochondrial permeability transition

Isolated mitochondria may undergo uncoupling, and in presence of Ca2+ at different conditions, a mitochondrial permeability transition (MPT) linked to protein,thiol oxidation, and demonstrated by CsA-sensitive mitochondrial swelling; these processes may cause cell death either by necrosis or by apoptosis. Isocoumarins isolated from the Brazilian plant Paepalanthus bromelioides (Eriocaulaceae) paepalantine (9,10-dihydroxy-5,7-dimethoxy-1H-naptho(2,3c)pyran-1-one), 8,8'-paepalantine dimer, and vioxanthin were assayed at 1-50 mu M on isolated rat liver mitochondria, for respiration, MPT, protein thiol oxidation, and interaction with the mitochondrial membrane using 1,6-diphenyl-1,3,5-hexatriene (DPH). The isocoumarins did not significantly affect state 3 respiration of succinate-energized mitochondria; they did however, stimulate 4 respiration, indicating mitochondrial uncoupling. Induction of MPT and protein thiol oxidation were assessed in succinate-energized mitochondria exposed to 10 mu M Ca2+; inhibition of these processes was assessed in non-energized organelles in the presence of 300 mu M t-butyl hydroperoxide plus 500 mu M Ca2+. Only paepalantine was an effective MPT/protein thiol oxidation inducer, also releasing cytochrome c from mitochondria; the protein thiol oxidation, unlike mitochondrial swelling, was neither inhibited by CsA nor dependent on the presence of Ca2+. Vioxanthin was an effective inhibitor of MPT/protein thiol oxidation. All isocoumarins inserted deeply into the mitochondrial membrane, but only paepalantine dimer and vioxantin decreased the membrane's fluidity. A direct reaction with mitochondrial membrane protein thiols, involving an oxidation of these groups, is proposed to account for MPT induction by paepalantine, while a restriction of oxidation of these same thiol groups imposed by the decrease of membrane fluidity, is proposed to account for MPT inhibition by vioxanthin. (c) 2006 Published by Elsevier B.V..

Nanotechnology-based Drug Delivery Systems for Dermatomycosis Treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of Formulations Containing Dimethylaminoethanol (DMAE) Acetoamidobenzoate and Pidolate on the Skin

The aim of this study was to analyze the effects of formulations containing DMAE pidolate and DMAE acetoamidobenzoate on the skin. Four areas of five swines were submitted to following treatments during 15 days: C (Control), S (Silicone = 80 % DC*LC Blend (R)), F1 (DMAE acetoamidobenzoate), F2 (DMAE pidolate). Measures of the thickness of epidermis and stratum corneum, and the density population of fibroblasts and leukocytes in papillary dermis were obtained. We also assessed possible variations in birefringence of dermis collagen bundles. Means of the data was compared using ANOVA followed by the Tukey test. The F1 and F2 groups showed a thicker epidermis than the control group (p < 0.01), but did not demonstrate a significant difference in the number of fibroblasts and leukocytes, as well as in the birefringent areas of collagen bundles, in comparison with the control groups. The DMAE-supplemented formulations enhanced viable epidermis thickness, but did not modify structures related with mechanical properties of the skin.

Interações entre a carboximetilcelulose, carbonato de cálcio e bentonita: repercussões sobre as propriedades dos fluidos de perfuração aquosos

The role of carboxymethylcellulose (CMC) in association to calcium carbonate particles (CaCO3) in most water-based drilling fluids is to reduce the fluid loss to the surrounding formation. Another essential function is to provide rheological properties capable of maintaining in suspension the cuttings during drilling operation. Therefore, it is absolutely essential to correlate the polymer chemical structure (degree of substitution, molecular weight and distribution of substituent) with the physical-chemical properties of CaCO3, in order to obtain the better result at lower cost. Another important aspect refers to the clay hydration inhibitive properties of carboxymethylcellulose (CMC) in drilling fluids systems. The clay swelling promotes an undesirable damage that reduces the formation permeability and causes serious problems during the drilling operation. In this context, this thesis consists of two main parts. The first part refers to understanding of interactions CMC-CaCO3, as well as the corresponding effects on the fluid properties. The second part is related to understanding of mechanisms by which CMC adsorption occurs onto the clay surface, where, certainly, polymer chemical structure, ionic strength, molecular weight and its solvency in the medium are responsible to affect intrinsically the clay layers stabilization. Three samples of carboximetilcellulose with different molecular weight and degree of substitution (CMC A (9 x 104 gmol DS 0.7), CMC B (2.5 x 105 gmol DS 0.7) e CMC C (2.5 x 105 gmol DS 1.2)) and three samples of calcite with different average particle diameter and particle size distribution were used. The increase of CMC degree of substitution contributed to increase of polymer charge density and therefore, reduced its stability in brine, promoting the aggregation with the increase of filtrate volume. On the other hand, the increase of molecular weight promoted an increase of rheological properties with reduction of filtrate volume. Both effects are directly associated to hydrodynamic volume of polymer molecule in the medium. The granulometry of CaCO3 particles influenced not only the rheological properties, due to adsorption of polymers, but also the filtration properties. It was observed that the lower filtrate volume was obtained by using a CaCO3 sample of a low average size particle with wide dispersion in size. With regards to inhibition of clay swelling, the CMC performance was compared to other products often used (sodium chloride (NaCl), potassium chloride (KCl) and quaternary amine-based commercial inhibitor). The low molecular weight CMC (9 x 104 g/mol) showed slightly lower swelling degree compared to the high molecular weight (2.5 x 105 g/mol) along to 180 minutes. In parallel, it can be visualized by Scanning Electron Microscopy (SEM) that the high molecular weight CMC (2.5 x 105 g/mol e DS 0.7) promoted a reduction in pores formation and size of clay compared to low molecular weight CMC (9.0 x 104 g/mol e DS 0.7), after 1000 minutes in aqueous medium. This behavior was attributed to dynamic of interactions between clay and the hydrodynamic volume of CMC along the time, which is result of strong contribution of electrostatic interactions and hydrogen bounds between carboxylate groups and hydroxyls located along the polymer backbone and ionic and polar groups of clay surface. CMC adsorbs on clay surface promoting the skin formation , which is responsible to minimize the migration of water to porous medium. With the increase of degree of substitution, it was observed an increase of pores onto clay, suggesting that the higher charge density on polymer is responsible to decrease its flexibility and adsorption onto clay surface. The joint evaluation of these results indicate that high molecular weight is responsible to better results on control of rheological, filtration and clay swelling properties, however, the contrary effect is observed with the increase of degree of substitution. On its turn, the calcite presents better results of rheological and filtration properties with the decrease of average viii particle diameter and increase of particle size distribution. According to all properties evaluated, it has been obvious the interaction of CMC with the minerals (CaCO3 and clay) in the aqueous medium

Preoperative warming combined with intraoperative skin-surface warming does not avoid hypothermia caused by spinal anesthesia in patients with midazolam premedication

CONTEXTO E OBJETIVO: Hipotermia inadvertida no perioperatório é freqüente durante anestesia subaracnóidea e após a administração de midazolam. O objetivo foi avaliar os efeitos do aquecimento da pele no intra-operatório, associado ou não ao aquecimento da pele durante o período de 45 minutos no pré-operatório, na prevenção de hipotermia intra- e pós-operatória determinada pela anestesia subaracnóidea em pacientes com medicação pré-anestésica com midazolam. TIPO DE ETUDO E LOCAL: Estudo prospectivo e aleatório, realizado no Hospital das Clínicas, Universidade Estadual Paulista (Unesp), Botucatu, SP. MÉTODOS: O estudo foi realizado em 30 pacientes com estado físico ASA (da Sociedade Norte-americana de Anestesiologistas) I e II submetidos à cirurgia eletiva do abdômen. Como medicação pré-anestésica, utilizou-se o midazolam, 7,5 mg via intramuscular (IM) e anestesia subaracnóidea padrão. em 10 pacientes (Gcontrole) utilizou-se isolamento térmico passivo; 10 pacientes (Gpré+intra) foram submetidos a aquecimento ativo no pré- e intra-operatório; e 10 pacientes (Gintra) foram aquecidos ativamente somente no intra-operatório. RESULTADOS: Após 45 minutos de aquecimento no pré-operatório, os pacientes do Gpré+intra apresentaram temperatura central mais elevada em relação aos dos grupos não aquecidos antes da anestesia (p < 0,05) mas não no início da cirurgia (p > 0,05). Os pacientes que receberam aquecimento no intra-operatório apresentaram temperatura central mais elevada no final da cirurgia em relação aos de Gcontrole (p < 0,05). Todos os pacientes estavam hipotérmicos na admissão da sala de recuperação pós-anestésica (temperatura central < 36º C). CONCLUSÕES: 45 minutos de aquecimento no pré-operatório combinado com aquecimento no intra- operatório não evita, mas minimiza a ocorrência de hipotermia determinada pela anestesia subaracnóidea em pacientes que receberam midazolam como medicação pré-anestésica.