44 resultados para antithrombotic agents, development for clinical use
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Use of clays as catalyzers in heterogeneous processes has increased significantly given their low cost, safety and commercial availability. However, interconnected political, economic, social, environmental, geological, and chemical aspects should be considered for chemical processes to satisfy sustainable development concepts. This concept requires complex thinking involving different areas of knowledge in dialogue, contrasting with classical thought, which is linear and Cartesian. Thus, this paper discusses the principles of complex thought in the concept of sustainable development exemplified by use of clay as a clean technology in organic synthesis.
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Abstract: The knowledge of anatomical structures found in wild animals is important for the practice of medical and surgical clinic. Thus, the aim of this study was to describe the osteology and radiographic anatomy of the femur, patella, tibia, fibula, tarsal, metatarsal and phalanges of the Marshdeer Blastocerus dichotomus as a reference for clinical use and species identification. Most structures were similar to those found in domestic animals, with special features of this species. Noteworthy is, for example, the absence of the third trochanter of the femur. Although a ruminant, the Marshdeer has a fibuyla similar to the one described for the horse. B. dichotomus has four fingers on each limb, formed through three phalanges, only the third and fourth finger touch the ground, and the second and fifth finger is rudimentary. It has four proximal and two distal sesamoid bones, and sesamoid bones near the gastrocnemius muscle do not exist.
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Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT) using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 µg/ml) was only 4.88-fold higher than that of the low molecular weight heparin Clexane® (4.1 µg/ml), whereas 80 µg/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.
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The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.
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Tuberculosis is one of the most frequent opportunistic infections after renal transplantation and occurred in 30 of 1264 patients transplanted between 1976 and 1996 at Hospital São Paulo - UNIFESP and Hospital Dom Silvério, Brazil. The incidence of 2.4% is five times higher than the Brazilian general population. The disease occurred between 50 days to 18 years after the transplant, and had an earlier and worse development in patients receiving azathioprine, prednisone and cyclosporine, with 35% presenting as a disseminated disease, while all patients receiving azathioprine and prednisone had exclusively pulmonary disease. Ninety percent of those patients had fever as the major initial clinical manifestation. Diagnosis was made by biopsy of the lesion (50%), positivity to M. tuberculosis in the sputum (30%) and spinal cerebral fluid analysis (7%). Duration of treatment ranged from 6 to 13 months and hepatotoxicity occurred in 3 patients. The patients who died had a significant greater number of rejection episodes and received higher doses of corticosteroid. In conclusion, the administration of cyclosporine changed the clinical and histopathological pattern of tuberculosis occurring after renal transplantation.
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INTRODUCTION: The fishes of continental Brazil have socioeconomic importance due to their potential for sport fishing and commercial and subsistence uses, as seen in the Upper Paraguay River Basin, particularly in the municipalities of the Pantanal region, where it is the second largest economic activity. Injuries caused in professional fishermen are common and poorly studied, as in other regions of the country. METHODS: Data were obtained from questionnaires and interviews with 100 professional fishermen, 50 in each municipality, between December 2008 and October 2009. RESULTS: All the fishermen reported some kind of injury caused by fish stings (78% of injuries) and fish, alligator and snake bites (22%) on the hands (46% of cases) and feet (35% of cases). Most of the patients had mild symptoms. The most severe cases were associated with secondary bacterial infections and required specific treatment and prolonged recovery associated with social and economic losses. CONCLUSIONS: The results of this study indicate that the stressful work conditions, inattention to basic preventive measures and carelessness were factors that contributed to accidents and that the toxicity and ability to inflict mechanical trauma of some aquatic species, plus the ineffective use of first aid and hospital treatment, contributed to the high morbidity and complications in many cases. Data from this study are relevant to the fishing communities of the Pantanal region, since they reveal high rates of accidents, lack of knowledge concerning first aid, initial treatment, injury prevention and lack of medical follow-up of the population.
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Candida parapsilosis, currently divided into three distinct species, proliferates in glucose-rich solutions and has been associated with infections resulting from the use of medical devices made of plastic, an environment common in dialysis centres. The aims of this study were (i) to screen for Candida orthopsilosis and Candida metapsilosis (100 environmental isolates previously identified as C. parapsilosis), (ii) to test the ability of these isolates to form biofilm and (iii) to investigate the in vitro susceptibility of Candida spp biofilms to the antifungal agents, fluconazole (FLC) and amphotericin B (AMB). Isolates were obtained from a hydraulic circuit collected from a haemodialysis unit. Based on molecular criteria, 47 strains were re-identified as C. orthopsilosis and 53 as C. parapsilosis. Analyses using a formazan salt reduction assay and total viable count, together with microscopy studies, revealed that 72 strains were able to form biofilm that was structurally similar, but with minor differences in morphology. A microtitre-based colorimetric assay used to test the susceptibility of fungal biofilms to AMB and FLC demonstrated that the C. parapsilosis complex displayed an increased resistance to these antifungal agents. The results from these analyses may provide a basis for implementing quality controls and monitoring to ensure the microbiological purity of dialysis water, including the presence of yeast.
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There is insufficient evidence of the usefulness of dengue diagnostic tests under routine conditions. We sought to analyse how physicians are using dengue diagnostics to inform research and development. Subjects attending 14 health institutions in an endemic area of Colombia with either a clinical diagnosis of dengue or for whom a dengue test was ordered were included in the study. Patterns of test-use are described herein. Factors associated with the ordering of dengue diagnostic tests were identified using contingency tables, nonparametric tests and logistic regression. A total of 778 subjects were diagnosed with dengue by the treating physician, of whom 386 (49.5%) were tested for dengue. Another 491 dengue tests were ordered in subjects whose primary diagnosis was not dengue. Severe dengue classification [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5], emergency consultation (OR 1.9; 95% CI 1.4-2.5) and month of the year (OR 3.1; 95% CI 1.7-5.5) were independently associated with ordering of dengue tests. Dengue tests were used both to rule in and rule out diagnosis. The latter use is not justified by the sensitivity of current rapid dengue diagnostic tests. Ordering of dengue tests appear to depend on a combination of factors, including physician and institutional preferences, as well as other patient and epidemiological factors.
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Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.
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A survey for canine tegumentary leishmaniasis (CTL) has been carried out between 1986 and 1993 in seven endemic localities for American cutaneous leishmaniasis in the State of Rio de Janeiro. 270 dogs have been examined for their clinical aspects, the development of delayed hypersensitivity (DHS) with Immunoleish antigen and with immunofluorescent antibody research of IgG (IF). 28.2% of them had ulcer lesions and 3.3% had scars. The lesions consisted of single (39.5%) and mucocutaneous lesions (31.6%), multiple cutaneous (25.0%) and mucocutaneous lesions associated with cutaneous ulcers (4.0%). Twelve (15.8%) isolates from biopsies were analyzed by zimodeme and schizodeme and identified as L. (V.) braziliensis. The overall prevalence of canine infection that was evaluated with the skin test was of 40.5% and with IF it was of 25.5%. Both tests showed a high positive rate with relation to the animals with mucosal lesions, as in the case of human mucocutaneous leishmaniasis. The comparison of the two tests showed the skin test to have a better performance although there was no statistical difference (p>0.05) between them. The proportional sensitivity and specificity was of 84.0% and 74.0%, respectively. The Immunoleish skin test and IF are useful tools to be employed in CTL field epidemiological surveys.
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The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.
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The purpose of the present study was to compare the susceptibility to four antifungal agents of 69 Cryptococcus neoformans strains isolated from AIDS patients with that of 13 C. neoformans strains isolated from the environment. Based on the NCCLS M27-A methodology the Minimal Inhibitory Concentrations (MICs) obtained for amphotericin B, itraconazole and ketoconazole were very similar for clinical and environmental isolates. Clinical isolates were less susceptible to fluconazole than environmental isolates. The significance of these findings and aspects concerning the importance, role and difficulties of C. neoformans susceptibility testing are also discussed.
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SUMMARYDuring recent decades, antifungal susceptibility testing has become standardized and nowadays has the same role of the antibacterial susceptibility testing in microbiology laboratories. American and European standards have been developed, as well as equivalent commercial systems which are more appropriate for clinical laboratories. The detection of resistant strains by means of these systems has allowed the study and understanding of the molecular basis and the mechanisms of resistance of fungal species to antifungal agents. In addition, many studies on the correlation of in vitro results with the outcome of patients have been performed, reaching the conclusion that infections caused by resistant strains have worse outcome than those caused by susceptible fungal isolates. These studies have allowed the development of interpretative breakpoints for Candida spp. and Aspergillus spp., the most frequent agents of fungal infections in the world. In summary, antifungal susceptibility tests have become essential tools to guide the treatment of fungal diseases, to know the local and global disease epidemiology, and to identify resistance to antifungals.
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The clinical manifestations and prognosis of cutaneous leishmaniasis (CL) can be influenced by the immune response of the patient and the species of the parasite. A case of atypical clinical presentation of CL, with development of non-characteristic lesions, poor response to therapy, and a long time to resolution is reported. Confirmatory laboratory tests included parasite detection, indirect immunofluorescence, Montenegro skin test, polymerase chain reaction, and parasite identification by multilocus enzyme electrophoresis. The parasite was identified as Leishmaniabraziliensis. The lesion was unresponsive to three complete courses of N-methylglucamine antimoniate intramuscular, and to treatment with pentamidine. The patient did not tolerate amphotericin B. The lesion finally receded after treatment with intravenous N-methylglucamine antimoniate. It is essential to ensure the accuracy of diagnosis and the appropriate treatment, which can include the use a second choice drug or a different route of administration.