813 resultados para Pankratz, Marcia
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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The Topliss method was used to guide a synthetic path in support of drug discovery efforts toward the identification of potent antimycobacterial agents. Salicylic acid and its derivatives, p-chloro, p-methoxy, and m-chlorosalicylic acid, exemplify a series of synthetic compounds whose minimum inhibitory concentrations for a strain of Mycobacterium were determined and compared to those of the reference drug, p-aminosalicylic acid. Several physicochemical descriptors (including Hammett's sigma constant, ionization constant, dipole moment, Hansch constant, calculated partition coefficient, Sterimol-L and -B-4 and molecular volume) were considered to elucidate structure-activity relationships. Molecular electrostatic potential and molecular dipole moment maps were also calculated using the AM1 semi-empirical method. Among the new derivatives, m-chlorosalicylic acid showed the lowest minimum inhibitory concentration. The overall results suggest that both physicochemical properties and electronic features may influence the biological activity of this series of antimycobacterial agents and thus should be considered in designing new p-aminosalicylic acid analogs.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Purpose: This paper focuses on the characterization of polymeric micelle-forming tuberculostatic prodrugs and the antimycobacterial activity of these prodrugs.Method: By the condensation of hydroxymethylpyrazinamide, isoniazid and rifampin with free carboxyl groups on the copolymer poly(ethyleneglycol)-poly(aspartic acid), micelle-forming carrier-drug conjugates were obtained. These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric measurement, to determine the stability of micelles. These micelles were tested in vitro against several Mycobacterium strains.Results: As expected, the size and distribution of the micelle-forming tuberculostatic prodrugs found to be small (78.2nm, 84.2nm and 98.9 nm) while the level of the drug conjugated was high (65.02-85.7%). Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger antimycobacterial activity than the original drugs.Conclusion: the results demonstrate that polymeric micelles can be used as efficient carriers for drugs, which alone, exhibit undesired pharmacokinetics, poor solubility, and low stability. The synthesized micelle-forming tuberculostatic prodrugs opens a perspective of alternative prodrugs that prolong action and decrease the toxicity of the tuberculostatic drugs of choice.
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Background: Hyperglycemia, insulin resistance and hyperleptinemia are some of the consequences of obesity. Gastric bypass for morbid obesity provides gastric restriction with decreased energy absorption. To confirm and extend previous reports in the literature, We evaluated the plasma glucose, serum insulin and leptin and insulin resistance of patients preoperatively and 1 and 3 months after Roux-en-Y gastric bypass (RYGBP).Methods: We determined body mass index (BMI), plasma glucose (glucose-oxidase method), serum leptin (immunoassay) and insulin (chemiluminescent immunometric assay), and insulin resistance index (IRI) by Homeostasis Model Assessment (HOMA) of 20 patients with morbid obesity both preoperatively and 1 and 3 months after RYGBP.Results: Patients showed a mean decrease in weight of 8 kg/month. Glycemia was above reference levels in 65% of the preoperative patients but dropped significantly 1 month postoperatively, serum insulin and leptin levels and the HOMA index also decreasing significantly in the same period. The percentage of patients with preoperative elevated serum insulin and leptin relative to reference levels decreased significantly following RYGBP. We also observed a weak but significant correlation between BMI and glucose, BMI and insulin, and leptin and insulin.Conclusions: the beneficial effects of bariatric surgery are already noticeable 1 month postoperatively, the reduction in insulin levels being more important for leptin reduction than decreased BMI. Leptin appeared to be subject to multifactorial control and showed a larger reduction than body weight.
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The antifungal susceptibility profiles and the genetic variability of 83 sequential clinical isolates of Cryptococcus neoformans, including four Cryptococcus gattii isolates, obtained from 38 São Paulo AIDS patients with cryptococcal meningitis were assessed by electrophoretic karyotyping and random amplified polymorphic DNA (RAPD) analysis. The majority of the Cryptococcus neoformans isolates were highly susceptible to amphotericin B and fluconazole. Twenty percent of the minimum inhibitory concentration values for amphotericin B varied from 0.5 to 1 mu g mL(-1). For fluconazole, 22% occurred in the range 8-16 mu g mL(-1). Sequential isolates from nine patients showed a trend towards lower susceptibility to fluconazole, flucytosine, itraconazole and amphotericin B. The results of molecular typing by electrophoretic karyotyping and RAPD analysis showed the presence of 22 electrophoretic karyotypes (EK) and 15 RAPD profiles that were highly correlated. Our results provided evidence for the occurrence of genetic changes in some strains associated with microevolution during the course of infection. We also observed both microevolution and simultaneous coinfection with two distinct Cryptococcus neoformans strains in one patient. In some patients, we found changed EK- and RAPD patterns in association with increased MIC values.
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One of the high tuberculosis (TB) incidence countries in the world, Brazil is characterized by considerable differences in TB incidence on regional and state level. In the present study, we describe Brazilian spoligotypes of 1991 Mycobacterium tuberculosis complex (MTC) clinical isolates from patients residents of 11 states from different regions of the country, diagnosed between 1996 and 2005. By performing spoligotyping on a large number of M. tuberculosis clinical isolates, one of the main objectives of this study was to determine the major genotype families causing TB in Brazil and to verify the region-associated genotype distribution. We observed a total of 577 distinct spoligopatterns, 12.6% of these corresponded to orphan patterns while 87.4% belonged to 326 shared-types (SITs). Among the latter, 86 SITs (isolated from 178 patients) had been observed for the first time in this study, the most frequent being SIT2517 which belonged to the T3-ETH lineage and was exclusively found among patients residents of Belem, the capital of the state of Para (n = 8 isolates). Irrespective of shared-type labeling, a total of 19.5% strains were unique (unclustered) in our study as opposed to 80.5% clustered isolates (189 clusters, size range from 2 to 205 isolates). The three largest clusters were SIT42 of the Latin-America & Mediterranean (LAM) 9 clade (10.3%), SIT53 of the T clade (7.6%), and SIT50 of the Haarlem clade (5.4%). The predominant MTC lineages in Brazil in decreasing order belonged to the LAM (46%); the ill-defined T (18.6%); the Haarlem (12.2%), the X (4.7%), the S (1.9%), and the East African Indian (EAI) (0.85%) families. The rest of clades grouped together as Mycobacterium africanum, Mycobacterium bovis, Beijing, Central Asian (CAS), and the Manu types, represented less than 1% of the strains. Finally, about 15% of the isolates showed spoligotype signatures that were not yet classified among well-defined lineages. In conclusion, we provide hereby a first insight into the population structure of MTC isolates in Brazil, showing the predominance of both LAM and T family and the existence of region-associated genotypes. (C) 2011 Elsevier B.V. All rights reserved.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Les initiatives du gouvernement ayant pour finalité une réorganisation de la structure urbaine de la ville au début du XXème siècle reflètent le désir vécu par les membres de l'élite locale d'encadrer Natal dans les moules des grands centres urbains de la même période. Les élites désiraient transformer Natal dans une ville moderne. Dans ce but, le gouvernement s'est engagé dans la reformulation de quelques espaces physiques de la ville. Néanmoins, il fallait aussi d autres que les transformations urbaines, la ville devrait passer par des réformes sociales. De cette façon, ces groupes ont créées des nouvelles institutions et espaces de sociabilité qui affirmeraient la capitale de l'État comme une ville moderne. Les institutions formelles avaient un rôle imortant dans la construction de cette nouvelle ville convoitée par l'élite locale. Ainsi, à travers celles-ci, se diffusaient des nouvelles pratiques sociales qui seraient reflétées dans les espaces urbains. Dans des places tels, des cafés, des clubs et associations sportives, l'élite se distinguait du populaire. Dans ces places, leurs pratiques étaient légitimées, en contrepoint avec les pratiques populaires. C était dans les clubs et par les activités pratiquées par leurs membres que les idéals de l'élite circulaient, c était par là que l'élite se formait et se transformait. De cette façon, les aspirations d'un groupe social reflétaient dans l'organisation sociale des espaces de la ville
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Yoga has been studied and practiced for over three thousand years and nowadays it is widely adopted as a mean to assist the health of individuals. Additionally, numerous benefits to the health rehabilitation and quality of life of elderly individuals has been attributed to this set of techniques. In women, the aging process is characterized by the interruption on ovarian follicular activity (menopause) characterized by a number of neuroendocrine and physiologic changes. Those changes are frequently accompanied by uncomfortable and occasionally debilitating symptoms. Although there is profuse clinical information about menopause, studies on the potential therapeutic application of yoga during the climacteric period are scarce. The objective of this research was to investigate the psychophysiological effects of 12 weeks of yoga practice in 88 postmenopausal women. The volunteers were divided into a control group (no intervention), exercise group and yoga group. Instruments were applied for the evaluation of climacteric syndrome, stress, depression, quality of life, and anxiety. In addition, the determination of hormonal levels of FSH, LH, estradiol, cortisol and progesterone, and biochemical levels of glucose, cholesterol, triglycerides, HDL, LDL, urea, creatinine, AST and ALT were conducted. Our results showed that the yoga group had significantly lower scores after the regular practice of yoga for menopausal symptoms. Besides, those changes were accompanied by a statistical significant improvement in the stress levels, decrease in depression scores, and higher scores in quality of life when compared with the control group and the exercise group. As well, the regular practice of yoga promoted the maintenance of cortisol levels compared to control group after 12 weeks. Regarding the biochemical parameters yoga practitioners presented lower levels of LDL in the blood. These results are supported by previous studies which found that regular practice of yoga improves quality of life of subjects, Thus, herein we propose that yoga can be a non-pharmacological alternative to management of menopausal symptoms and stress in postmenopausal women
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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One of the Psychology challenges, especially among the assessment and educational areas, is to understand and predict individual differences. In this context, this research aimed to verify the personality styles of students with high and low academic performance. The study included 236 university students from Petrolina-PE and Juazeiro-BA campus of the UNIVASF (Universidade Federal do Vale do São Francisco). They were uniformly distributed in four disciplines (medicine, psychology, administration and civil engineering), 10 students from each semester (five highest scores average students and five lowest scores average students) took place of the sample. The Millon Index Personality Styles (MIPS) was applied to analyze the personality/behavioral styles of the students. The MIPS is a 180 dichotomous (true/false) item scale. It was also developed and applied a questionnaire about the students characteristics and their academic information. Descriptive and central tendency statistics analysis (mean, standard deviation, frequency and percentage) were done to provide sample information. Then we performed a Mann-Whitney test in the overall sample and in each course and a factorial ANOVA. The results suggest that the university population is heterogeneous and there are significant differences (p <0.05) between the personality styles of students with high and low academic performance, when analyzing the overall sample and in courses of different areas of knowledge. Students of Medicine who have higher performance as personality styles prevalent the conformism and compliance, while students with lower income in this course, the styles are: innovation and discrepancy. Psychology students with higher income are more systematic and lower income students to score significantly on accommodation. The civil engineering students of the two groups differed only in personality style intuition, being such a style more characteristic of higher income students. Students of Management with higher yield stand out more in the style of the doubt and lower yields in these styles: individual, reflection and discrepancy. This study is correlational, but had an exploratory nature because there are no studies about this relationship in Brazil. Therefore, it provided a better understanding of the action characteristics of students with high and low academic performance. Further studies using the Big Five Personality Factors instruments are required because it is the most used model in understanding the influence of personality on students performance. This way, the relation between personality and academic performance will be better discussed. Otherwise, it will be possible to compare with the existing studies in the area