987 resultados para PURINE LESIONS
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The effects of massive lesions of the telencephalon on the behavioral repertoire of captive pigeons were investigated. The behavior of four birds with an intact telencephalon was compared to that of four birds submitted to ablation of telencephalic structures. Behavioral audio recording was done according to previously defined categories in three daily sessions for fifteen days. Experimental birds were followed up for one month. Immediately after the lesion, operated birds showed decreases in the occurrence of different behaviors such as coordinated movements, feeding, interaction, preening, maintenance, exploration and vocalization and increases in locomotion and discrete movements of the body when compared to the control birds (P < 0.05). Recovery of exploration (P < 0.05), feeding and localization was observed during the follow-up period. These data are interpreted as suggestive of a functional role of the telencephalon in the organization of behavior and a long-term recovery of behavior after detelencephalation.
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Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell and Apicomplexan parasites-mediated diseases.
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Studies investigating the immunopathological aspects of Jorge Lobo's disease have shown that the inflammatory infiltrate consists mainly of histiocytes and multinucleated giant cells involving numerous yeast-like cells of Lacazia loboi, with the T lymphocytes more common than B lymphocytes and plasma cells. The quantification of cytokines in peripheral blood mononuclear cells culture supernatant has revealed alterations in the cytokines profile, characterized by predominance of a Th2 profile. In view of these findings and of the role of cytokines in cell interactions, the objective of the present study was to investigate the presence of the cytokines IL-10, TGF-ss 1 and TNF-alpha, as well as iNOS enzyme in granulomas induced by L. loboi. Histological sections obtained from skin lesions of 16 patients were analyzed by immunohistochemistry for the presence of these cytokines and iNOS. The results showed that TGF-ss 1 was the cytokine most frequently expressed by cells present in the inflammatory infiltrate, followed by IL-10. There was a minimum to discrete positivity of cells expressing TNF-alpha and iNOS. The results suggest that the presence of immunosuppressive cytokines in skin lesions of patients with the mycosis might be responsible for the lack of containment of the pathogen as demonstrated by the presence of numerous fungi in the granuloma.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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The purpose of this study was to observe and characterize colonic and lung lesions in horses subjected to experimental distension and decompression of the small colon. Sixteen healthy adult horses were divided into 2 groups: 9 horses that were subjected to distension of the small colon by means of a latex balloon surgically implanted in the lumen and inflated to a pressure of 40 mm Hg for 4 h, and 7 horses in which the balloon was implanted but not inflated. Colonic biopsy specimens were collected before balloon implantation, at the end of the period of obstruction, and 1.5 and 12 h after decompression and were examined for hemorrhage, edema, and neutrophil infiltration; myeloperoxidase (MPO) activity and hemoglobin concentration were measured as well. At the end of the experiment, lung samples were also collected and examined for neutrophil accumulation and MPO activity. The mucosa was not affected by luminal distension; lesions were restricted to the seromuscular layer. Neutrophil accumulation and edema were observed in the samples from both groups of horses but were greater in those from the distension group, in which there was also hemorrhage, fibrin deposition, and increased MPO activity in the seromuscular layer. Similarly, there was greater accumulation of neutrophils in the lung samples from the distension group than in those from the sham-operated group, as determined by histologic evaluation and MPO assay. These findings provide new evidence of reperfusion injury and a systemic inflammatory response, followed by remote lesions, in horses with intestinal obstruction.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Objective: To verify a potential association between the presence of noncarious cervical lesions, parafunctional habits, and temporomandibular disorder (TMD) diagnosis. Method and Materials: Sample-size calculation provided a value of 130 participants with a confidence level of 95% and an error margin of 5%. A population of 132 volunteers (30 men: mean age, 23.7 +/- 3.05 years; 102 women: mean age, 24.9 +/- 5.86 years) underwent an oral examination and was interviewed by a trained dentist. The following parameters were registered: personal details, TMD diagnosis, parafunctional habits, and noncarious cervical lesion presence. The population was then divided into a noncarious cervical lesion group and a control group and subjected to the t test, chi-square test, Fisher exact test, and Spearman correlation (alpha = .05). Results: Noncarious cervical lesions were present in 39% of the population, with the largest concentrations found in the maxillary premolars (32%). The data showed a significant association between noncarious cervical lesion presence, tooth clenching (P = .03), and nail biting (P = .02), as well as a relation with TMD diagnosis (Fonseca Index [P = .01] and Research Diagnostic Criteria for TMD (RDC/TMD) [P = .004] ). In the noncarious cervical lesion group, direct rank correlation was found between maxillary premolars and clenching (P = .03), mandibular canines and nail biting (P = .05), and mandibular incisors and parafunctional habits without dental contacts (P = .02). Conclusion: Parafunctional habits and TMD presence should be taken into account in the diagnosis and treatment plan of noncarious cervical lesions.
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The present work evaluated the pathological effects in both dams and their fetuses of cyanide ingestion during pregnancy using goat as animal model. From the Day 24 of pregnancy, three pregnant goats were dosed by gavage with 3.0 mg KCN/kg bw/day, and two others received only tap water. All dams were euthanized and necropsied at Day 120 of pregnancy. The fetuses were examined carefully for gross abnormalities. Determinations of cyanide and thiocyanate were performed in maternal and fetal blood and in amniotic fluid. Samples of several organs were collected for histopathologic evaluation. No clinical changes were seen in any animal throughout the pregnancy. No malformations or dead fetuses were observed: however, placenta from one treated goat presented increased cotyledon surface area occupied by vascular lumina. Histological lesions in KCN-treated dams consisted of vacuolation of hepatocytes and thyroid follicular cells, increased number of vacuoles on thyroid follicular colloid. and spongiosis of cerebral, internal capsule, and cerebellar peduncles tracts. Fetuses from these mothers showed vacuolation of hepatocytes and thyroid follicular cells, and spheroids in the cerebellar white matter. Levels of cyanide and thiocyanate were higher in maternal than fetal blood, which suggests that these substances were largely but not freely transferred from mothers to fetuses. (C) 2009 Elsevier B.V. All rights reserved.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Background: The World Health Organization (WHO) advises treatment of Mycobacterium ulcerans disease, also called Buruli ulcer'' (BU), with a combination of the antibiotics rifampicin and streptomycin (R+S), whether followed by surgery or not. In endemic areas, a clinical case definition is recommended. We evaluated the effectiveness of this strategy in a series of patients with large ulcers of >= 10 cm in longest diameter in a rural health zone of the Democratic Republic of Congo (DRC).Methods: A cohort of 92 patients with large ulcerated lesions suspected to be BU was enrolled between October 2006 and September 2007 and treated according to WHO recommendations. The following microbiologic data were obtained: Ziehl-Neelsen (ZN) stained smear, culture and PCR. Histopathology was performed on a sub-sample. Directly observed treatment with R+S was administered daily for 12 weeks and surgery was performed after 4 weeks. Patients were followed up for two years after treatment.Findings: Out of 92 treated patients, 61 tested positive for M. ulcerans by PCR. PCR negative patients had better clinical improvement than PCR positive patients after 4 weeks of antibiotics (54.8% versus 14.8%). For PCR positive patients, the outcome after 4 weeks of antibiotic treatment was related to the ZN positivity at the start. Deterioration of the ulcers was observed in 87.8% (36/41) of the ZN positive and in 12.2% (5/41) of the ZN negative patients. Deterioration due to paradoxical reaction seemed unlikely. After surgery and an additional 8 weeks of antibiotics, 98.4% of PCR positive patients and 83.3% of PCR negative patients were considered cured. The overall recurrence rate was very low (1.1%).Interpretation: Positive predictive value of the WHO clinical case definition was low. Low relapse rate confirms the efficacy of antibiotics. However, the need for and the best time for surgery for large Buruli ulcers requires clarification. We recommend confirmation by ZN stain at the rural health centers, since surgical intervention without delay may be necessary on the ZN positive cases to avoid progression of the disease. PCR negative patients were most likely not BU cases. Correct diagnosis and specific management of these non-BU ulcers cases are urgently needed.