Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

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

Dor: aspectos atuais da sensibilização periférica e central

JUSTIFICATIVA E OBJETIVOS: As pesquisas recentes têm focalizado a plasticidade bioquímica e estrutural do sistema nervoso decorrente da lesão tissular. Os mecanismos envolvidos na transição da dor aguda para crônica são complexos e envolvem a interação de sistemas receptores e o fluxo de íons intracelulares, sistemas de segundo mensageiro e novas conexões sinápticas. O objetivo deste artigo foi discutir os novos mecanismos que envolvem a sensibilização periférica e central. CONTEÚDO: A lesão tissular provoca aumento na resposta dos nociceptores, chamada de sensibilização ou facilitação. Esses fenômenos iniciam-se após a liberação local de mediadores inflamatórios e a ativação de células do sistema imune ou de receptores específicos no sistema nervoso periférico e central. CONCLUSÕES: As lesões do tecido e dos neurônios resultam em sensibilização de nociceptores e facilitação da condução nervosa central e periférica.

Efeitos de concentrações crescentes de lidocaína hiperbárica, administradas no espaço subaracnóideo, sobre a medula espinhal e as meninges: estudo experimental em cães

JUSTIFICATIVA E OBJETIVOS: Ainda não está bem estabelecida a concentração de lidocaína que é potencialmente capaz de determinar lesão no tecido nervoso. O objetivo desta pesquisa foi estudar os efeitos sobre a medula espinhal e as meninges, de concentrações crescentes de lidocaína administrada por via subaracnóidea, em injeção única através de agulha de Quincke. MÉTODO: Após a aprovação da Comissão de Ética em Experimentação Animal, 40 cães adultos foram anestesiados com fentanil e etomidato e submetidos a punção subaracnóidea com agulha de Quincke 22G 21/2 para introdução de 1 mL, em 10 segundos, de solução glicosada a 7,5% - Grupo 1; lidocaína a 5% em solução glicosada a 7,5% - Grupo 2; lidocaína a 7,5% em solução glicosada a 7,5% - Grupo 3; lidocaína a 10% em solução glicosada a 7,5% - Grupo 4. Após a recuperação da anestesia venosa, foram observados, no período em que os animais estavam em vigência do bloqueio subaracnóideo, a presença de bloqueio motor, o tônus do esfíncter anal (normal ou relaxado) e o nível de bloqueio sensitivo nos diferentes dermátomos das regiões cervical, torácica, lombar e sacral. Os animais permaneceram em cativeiro por 72 horas. Foram avaliados o tônus do esfíncter anal, a motricidade das patas posteriores, a sensibilidade dolorosa nas patas anteriores e posteriores e nos dermátomos sacrais, lombares e torácicos. Após serem sacrificados por eletrocussão sob anestesia, foram retiradas porções lombar e sacral da medula espinhal e das meninges para exame histológico por microscopia óptica. RESULTADOS: Nenhum animal dos Grupos 1 e 2 apresentou lesões clínicas ou histológicas. Três animais do Grupo 3 apresentaram alterações motoras nas patas posteriores e relaxamento do esfíncter anal. Nestes, foram observados focos de necrose na região posterior (dois cães) e necrose em faixa em toda a superfície medular (um cão). em um outro animal deste grupo, no qual foram notados focos de necrose, em área inferior a 5% do campo histológico não foram encontradas alterações clínicas. Sete animais do Grupo 4 apresentaram alterações clínicas (paralisia ou diminuição de força muscular nas patas posteriores, relaxamento do esfíncter anal) e histológicas (necrose na faixa da superfície medular ou focos de necrose de tecido nervoso). CONCLUSÕES: Neste estudo, a lidocaína em concentrações superiores a 7,5%, em injeção única, administrada no espaço subaracnóideo por meio de agulha de Quincke, determinou alterações histológicas sobre a medula espinhal, mas não sobre as meninges.

Perfil eletroforético e concentração de imunoglobulinas G (IgG) do soro sanguíneo de cabras Saanen com mastite experimental induzida por Staphylococcus aureus suplementadas com vitamina E

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

Tropical dermatology: Venomous arthropods and human skin Part II. Diplopoda, Chilopoda, and Arachnida

Members of arthropod classes Chilopoda (centipedes), Diplopoda (millipedes), and Arachnida (spiders and scorpions) cause tissue injury via bites, stings, and/or a release of toxins. A few members of the Acari subclass of Arachnida (mites and ticks) can transmit a variety of infectious diseases, but this review will cover the noninfectious manifestations of these vectors. Dermatologists should be familiar with the injuries caused by these arthropods in order to initiate proper treatment and recommend effective preventative measures. (J Am Acad Dermatol 2012;67:347.e1-9.)

Espécies reativas do oxigênio e as doenças respiratórias em grandes animais

As espécies reativas do oxigênio (ERO) são moléculas instáveis e extremamente reativas capazes de transformar outras moléculas com as quais colidem. As ERO são geradas em grande quantidade durante o estresse oxidativo, condição em que são afetadas moléculas como proteínas, carboidratos, lipídeos e ácido nucleicos. Neste trabalho, são discutidos os principais conceitos sobre os radicais livres e as ERO: principais tipos, sua formação e a forma como atuam sobre as estruturas celulares, provocando lesão tecidual significativa. Os principais sistemas de defesa antioxidantes e a influência do aumento na produção dessas ERO no trato respiratório de grandes animais também são discutidos, dando ênfase ao envolvimento das ERO em doenças como a pneumonia em ruminantes e na obstrução recorrente das vias aéreas e a hemorragia pulmonar induzida por exercício em equinos.

Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries

Background: Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis.Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A(2) (PLA(2)). Pancreatitis was induced by administration of TAU or PLA(2) from Naja mocambique mocambique into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC(50)) and maximal responses (E(MAX)) were determined. Blood samples were collected for biochemical analysis.Results: In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA(2) (about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC(50) nor E(MAX) values for Ach were altered in pulmonary rings in any group. Similarly, the pEC(50) and the E(MAX) values for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the E(MAX) for PHE. The nitrite/nitrate (NO(x)(-)) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA(2) protocol, respectively.Conclusion: Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NO(x)(-) levels as consequence of intense inflammatory responses. Furthermore, the subsensitivity of contractile response to PHE in both mesenteric and pulmonary rings might be due to the complications of this pathological condition in the early stage of pancreatitis.

Efeitos cardiovascular e metabólico da reposição volêmica com solução salina hipertônica 7,5% associada ou não ao hidroxietilamido 130/0,4 em gatas com hipovolemia induzida

A hipovolemia é caracterizada por uma perda de fluido corpóreo, cursando com inadequado fluxo circulatório e consequentemente lesão tecidual. Neste trabalho, objetivou-se comparar a expansão volêmica resultante da administração de solução salina hipertônica (NaCl 7,5%), isolada ou em associação com hidroxietilamido 130/0,4 (HES 130/0,4), em gatas com hipovolemia induzida, sob anestesia geral inalatória com isofluorano. Foram utilizadas 12 gatas, sem raça definida, adultas, com massa corporal média de 3,07±0,56kg. Os animais foram anestesiados com isofluorano e, após a preparação cirúrgica, foram mantidos em 1CAM sob ventilação controlada. Após a estabilização do plano anestésico, foram avaliados os parâmetros basais. em ato contínuo, iniciou-se a fase de hipovolemia, por meio da retirada de 30ml kg-1 de sangue da artéria femoral. Após 60 minutos da estabilização do quadro de hipovolemia, foi realizada nova mensuração dos dados, alocando-se os animais aleatoriamente em dois grupos: GSH (grupo solução hipertônica, n=6), que receberam, na fase de expansão volêmica, NaCl 7,5% isolada, na dose de 4ml kg-1, e GSHC (grupo salina hipertônica associado ao coloide, n=6), que receberam NaCl 7,5%, na mesma dose citada, em associação com HES 130/0,4, na dose de 30ml kg-1. Após realização do tratamento, foram avaliados novamente os efeitos cardiovasculares e hemogasométricos por 120 minutos. As pressões arteriais média (PAM), sistólica (PAS) e diastólica (PAD) foram maiores logo após a expansão volêmica (T0) para o GSH. de T45 até T120, as PAM, PAS e PAD foram maiores para o GSHC, em comparação com o GSH. A pressão venosa central foi maior no GSHC até T60. Não foram observadas diferenças entre grupos para frequência cardíaca e respiratória, íons sódio e potássio, déficit de base, bicarbonato, saturação de oxigênio na hemoglobina, glicose, PaCO2, PaO2 e pH. Conclui-se que a administração de NaCl 7,5% isoladamente aumenta rapidamente a PAM, PAS e PAD em gatos com hipovolemia induzida, mantendo esse efeito por apenas 30 minutos, enquanto que a administração de hidroxietilamido 130/0,4 associado à NaCl 7,5% promove reestabelecimento mais tardio (após 30 minutos), porém mais duradouro (até 120 minutos) da PAM, PAS e PAD em gatas com hipovolemia induzida. A administração de HES 130/0,4 associada à NaCl 7,5% promove aumento acentuado da PVC por até 60 minutos após a administração.

Eucalyptus ESTs related to genes for oxidative stress

Oxidative stress generating active oxygen species has been proved to be one of the underlying agents causing tissue injury after the exposure of Eucalyptus (Eucalyptus spp.) plants to a wide variety of stress conditions. The objective of this study was to perform data mining to identify favorable genes and alleles associated with the enzyme systems superoxide dismutase, catalase, peroxidases, and glutathione S-transferase that are related to tolerance for environmental stresses and damage caused by pests, diseases, herbicides, and by weeds themselves. This was undertaken by using the eucalyptus expressed-sequence database (https//forests.esalq.usp.br). The alignment results between amino acid and nucleotide sequences indicated that the studied enzymes were adequately represented in the ESTs database of the FORESTs project.

Effects of monocrotaline on energy metabolism in the rat liver

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

Acute, subchronic and chronic 2,4-dichlorophenoxyacetic acid (2,4-D) intoxication in rats

The acute, subchronic and chronic toxicities of 2,4- dichlorophenoxyacetic acid (2,4-D) were studied in rats. Animals were exposed acutely (600 mg/kg), subchronically (200 ppm for 30 d) and chronically (200 ppm for 180 d) to 2,4-D by the oral route. Clinical, laboratory and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased locomotor activity and induced ataxia, sedation, muscular weakness (mainly of the hind quarters) and gasping for breath; increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), amylase activities and creatinine levels; decreased total protein (TP) and glucose levels; and increased hematocrit values. Subchronic and chronic 2,4-D exposures did not induce overt clinical signs or symptoms of intoxication. However, subchronic herbicide exposure increased AST activity and albumin and hematocrit values, and chronic exposure increased AST, AP and LDH activities, decreased amylase and glucose levels, but did not change hematocrit values. Chromatographic analysis of the serum of chronically exposed rats showed the presence of the herbicide; the amount found (3.76 ± 1.16 mg/ml) suggested the absence of 2,4-D accumulation within the body. Although macroscopic or histopathological lesions were not observed in acutely, subchronically or chronically 2,4-D exposed rats, the laboratory data obtained suggest tissue injuries after dosing, since the results are considered early indicators of primarily hepatic and muscle tissue damage.

Free radical production by azomethine H: Effects on pancreatic and hepatic tissues

The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TEARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O-2(.-)), since Cu-Zn superoxide dismutase activities were increased by azomethine I-I treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O-2(.-)) maybe produced as a mediator of azomethine H action.

Effect of α-tocopherol on superoxide radical and toxicity of cadmium exposure

Contamination with cadmium compounds poses high potential risk for the health of populations and for this reason the treatment of their toxic effects should urgently be established. The present study was carried out to determine whether α-tocopherol intake can protect tissues against damage induced by cadmium, and to clarify the contribution of superoxide radicals (O 2 -) in this process. Cadmium chloride was tested for tissue damage by a single intraperitoneal injection of Cd 2+ ions (2 mg Kg -1). To determine the potential therapeutic effect of vitamin E, a group of Cd 2+-treated rats received a drinking solution of α-tocopherol (40 mg l -1) for 15 days. Cadmium induced increased serum creatinine and total lactate dehydrogenase, reflecting renal and cardiac damage. The increased lipoperoxide and decreased Cu-Zn superoxide dismutase levels indicated the generation of superoxide radicals in cadmium-treated rats. Tocopherol induced increased serum high-density lipoprotein and depressed the toxic effects of Ca 2+ alone, since creatinine and lactate dehydrogenase determinations were recovered to the control values. Tocopherol decreased lipoperoxide and led the superoxide dismutase activities to approach those of the control values. We concluded that superoxide radicals are produced as mediators of cadmium toxicity. Tocopherol possesses a significant anti-radical activity and inhibits the cadmium effect on superoxide dismutase activity. Tocopherol also protected tissues from the toxic effects of cadmium by a direct antioxidant action which decreased lipoperoxide formation.

The role of myofibroblasts and interstitial fibrosis in the progression of membranous nephropathy

Renal interstitial fibrosis has been observed in a large number of nephropathies and contributes to the progressive deterioration of renal function. Myofibroblasts have been implicated in the reparative process of tissue injury, including renal scarring secondary to glomerular diseases. We performed a retrospective study on 28 patients with biopsy-proven primary membranous nephropathy, to determine whether interstitial myofibroblasts and tubulointerstitial lesions correlated with renal function at follow-up. Tubulointerstitial pathology was evaluated by morphometric and semiquantitative methods. Interstitial myofibroblasts were counted; 24-hour urinary protein and serum creatinine at the time of diagnosis and at the end of follow-up were available for all the patients. There were 20 males and 8 females, age 2-67 years (mean 42.3±153), most of them with nephrotic syndrome (78.6%). The final renal function had deteriorated in 16 patients (57.1%) and in 5 patients (17.8%) reached end-stage. The renal outcome was correlated with histological changes. We found a positive correlation between the severity of tubulointerstitial damage and the deterioration of the final serum creatinine (r 2=0.185; p=0.016). Myofibroblasts did not predict impaired renal function at the final follow-up. The current data do not support previous suggestions that myofibroblasts are a useful a predictor of end-stage renal disease.

Arthrodesis tarsocrural or tarsometatarsal in 2 dogs using circular external skeletal fixator

An external fixation technique, using a circular fixator, to obtain arthrodesis was evaluated in 2 dogs with infected open lesions and soft tissue damage. In both cases, articular cartilage was curetted, and devitalized bone and necrotic soft tissue were removed. No bone graft was used. The wounds were maintained open and the dogs received postoperative antibiotic therapy. The arthrodesis site was compressed progressively as needed. Infection was eradicated and bony union was obtained in both dogs. It was concluded that the use of a circular fixator is an effective method to achieve arthrodesis.