975 resultados para Androstane-3,17-diol -- metabolism
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El propósito de esta monografía es comprender cuál ha sido el rol de la Unión Africana (UA), dentro de la misión de paz AMISOM en el periodo de 2007- 2013. Por ello, el trabajo abarca aspectos geopolíticos e históricos, que han influido en la configuración del conflicto armado de Somalía y que han llevado progresivamente a la creación, evolución e implementación de mecanismos como las misiones de paz. Además, se abarcan los planteamientos del neo-funcionalismo y el neo-regionalismo para comprender las estructuras y las dinámicas propias de la UA y así, comprender la naturaleza tanto de sus acciones, como de sus propósitos; propósitos que aclaman el fomento del panafricanismo. Desde aquí se puede entender como su rol ha contribuido con el crecimiento del mercado de la industria militar en la región, a costa de la responsabilidad de proteger. Por último, se concluye que dichas dinámicas han llevado a la creación de comunidades de inseguridad.
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Este proyecto se origina en el interés de analizar las estrategias actuales de promoción de productos farmacéuticos, en el marco del debate sobre el efecto persuasivo o informativo que la publicidad directa tiene sobre los consumidores. El objetivo es determinar el efecto de las estrategias de promoción directa para consumidores (Direct to Consumer Advertising [DTCA]) sobre el comportamiento de compra de pacientes y las prescripciones que formulan los médicos en el mercado de productos bajo receta en Estados Unidos. Para tal fin se propuso realizar una monografía que incluyera una revisión de literatura de carácter argumentativo, consultando información de nivel secundario en bases de datos científicas cuyos contenidos obedecieran a criterios metodológicos determinados por la naturaleza argumentativa del estudio. Adicionalmente, se analizó el debate sobre estos anuncios a la luz de dos estudios realizados a pacientes con cáncer de seno, próstata y colon, liderados por el Pennsylvania Cancer Registry con los productos biofarmacéuticos Avodart® y Flomax®. Finalmente, la investigación se fundamentó en la relación del mercado farmacéutico en Estados Unidos con cada uno de los agentes que interactúan en él; consumidores, médicos prescriptores y empresas farmacéuticas, así como el valor que estos comparten través de dichas interacciones. Se concluye que el comportamiento de compra de los consumidores está determinado por la naturaleza de la patología que padecen y el comportamiento de los profesionales que prescriben a sus pacientes se ve influenciado por los anuncios DTCA.
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As capacidades produtivas dos animais dependem de diversos fatores: genéticos e ambientais. O conhecimento da forma como os referidos fatores afetam a produtividade dos animais, carne e leite, permite ao produtor tomar as decisões técnicas necessárias para atingir um melhor índice de produtividade e rentabilidade da sua exploração. Este trabalho teve como objetivo principal evidenciar alguns dos fatores que afetam as características creatopoiéticas e lactopoiéticas da Serpentina e a forma como atuam sobre as mesmas, usando dados recolhidos pela APCRS, desde 1991 a 2014, em efetivos dos seus associados, explorados em sistemas de produção tradicionais. Foram estudados os pesos ao nascimento (PN) (3,17 kg), ajustado aos 30 dias (P30) (6,47 kg) e aos 70 dias (P70) (10,51 kg), bem como os diferentes modos de cria dos cabritos. Considerando as diversas modalidades de cria, o potencial de crescimento observado foi: (i) aleitamento natural os machos cresceram 0,108 kg e as fêmeas 0,095 kg; (ii) aleitamento em boxes os machos cresceram 0,109 kg e as fêmeas 0,099 kg; (iii) aleitamento em grupo os machos cresceram 0,141 kg e as fêmeas 0,119 kg; (iv) aleitamento em cornadi os machos cresceram 0,106 kg e as fêmeas 0,100 kg; (v) aleitamento artificial os machos cresceram 0,095 kg e as fêmeas 0,085 kg. A análise das diferentes características lactopoiéticas basearam-se na duração da lactação (DL), duração da ordenha (DO), produção total de leite (PTL), produção de leite comercializável (PLC), teor de matéria gorda (TMG) e teor de matéria proteica (TMP). Analisando os resultados de produção verificou-se: (i) duração da lactação de 207,18 dias; (ii) produção total de leite 167,81 L; (iii) produção de leite ajustado aos 210 dias de 118,46 L; (iv) teor butiroso ajustado aos 210 dias de 4,91 %; teor proteico ajustado aos 210 dias de 3,78 %. Verificou-se que os caracteres de crescimento e de produção de leite estudados apresentaram diferenças altamente significativas (P < 0,01) de forma generalizada, como consequência das diferenças técnicas e condições ambientais existentes nas diferentes explorações. Os valores médios obtidos, bem como a sua variabilidade, para as características creatopoiéticas e lactopoiéticas, revelam que a aptidão da raça para a produção de carne e leite tem um peso considerável na sua viabilidade produtiva. A existência de animais com valores produtivos elevados incute a esperança que através de um maneio mais cuidado e de um melhoramento genético mais criterioso, será possível obterem-se valores médios mais elevados aos obtidos neste estudo.
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Le neoplasie cutanee di tipo non-melanoma (non-melanoma skin cancers, NMSCs), quali il carcinoma a cellule basali (basal cell carcinoma, BCC) e il carcinoma a cellule squamose (squamous cell carcinoma, SCC) possono mostrare invasività locale e alto tasso di recidiva. La chirurgia microscopicamente controllata di Mohs (Mohs micrographic surgery, MMS) permette di eseguire una valutazione istologica immediata dei margini chirurgici delle neoplasie contestualmente alla loro escissione. Nel nostro studio abbiamo valutato del ruolo delle tecnologie in vivo (dermatoscopia e microscopia confocale a riflettanza, MCR) nella definizione dei margini preoperatori di NMSC ad alto rischio del volto e descritto la nostra esperienza con chirurgia tradizionale e MMS. Sono stati valutati 234 pazienti operati nel triennio 2019-2021: 39 con MMS e guida videodermatoscopica (Gruppo 1) e 195 con chirurgia tradizionale e guida videodermatoscopica (Gruppo 2). I pazienti operati nel periodo 2013-2018 (con MMS, Gruppo 3 (n = 241), e con chirurgia tradizionale, Gruppo 4 (n = 1086)) sono stati usati come confronto. La radicalità chirurgica è stata ottenuta nel Gruppo 1 nel 92,3% dei casi, con 1,2 steps in media di MMS (versus 1,7 nel Gruppo 3), nel Gruppo 2 nell’84,5% dei casi. La percentuale di non radicalità è stata: 7,7% nel Gruppo 1, 15,9% nel Gruppo 2, 6,2% nel Gruppo 3, 17,9% nel Gruppo 4. I tassi di recidiva sono stati: 5,1% nel Gruppo 1, 3,6% nel Gruppo 2, 4,1% nel Gruppo 3, 5,9% nel Gruppo 4, soprattutto in BCC di tipo sclerodermiforme e infiltrante. La MCR prechirurgica è stata utilizzata in 11 pazienti, con alcuni limiti nel delineare BCC di tipo sclerodermiforme e infiltrante. In conclusione, la videodermatoscopia e la MCR appaiono valide tecniche ancillari alla MMS e anche alla chirurgia tradizionale nel trattamento dei NMSCs. La MMS appare indicata soprattutto nei pazienti giovani e salvaguarda l’outcome estetico e funzionale.
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BETANCOURT, Ana Yajaira Gil. Melhoria da atenção à saúde da pessoa com hipertensão arterial sistêmica e/ou diabetes mellitus na UBS Aldo Arioli, Erechim/RS. 2015. 80f. Trabalho de Conclusão de Curso (Curso de Especialização em Saúde da Família) - Departamento de Medicina Social, Faculdade de Medicina, Universidade Federal de Pelotas, Pelotas, 2015. A hipertensão arterial sistêmica e o diabetes mellitus são considerados como grave problema de saúde pública. A primeira é a porta de entrada para múltiplas doenças como cardiopatias hipertensivas, aterosclerose, trombose, doença isquêmica cardíaca, cerebrovascular, vascular periférica e renal. Já entre as complicações do diabetes, as doenças cardiovasculares e renais estão entre as mais custosas, em termos de sofrimento humano como de gastos para os sistemas de saúde. O presente trabalho caracteriza-se como uma intervenção típica em Atenção Primária à Saúde na UBS Aldo Arioli, Erechim RS, Brasil. O trabalho foi desenvolvido em doze semanas. O objetivo principal foi melhorar a atenção à saúde das pessoas com hipertensão e/ou diabetes baseado nas orientações das proposições e Protocolos do Ministério da Saúde (2013) sobre as referidas doenças. As ações foram traçadas dentro dos quatro eixos pedagógicos como qualificação da prática clínica, engajamento público, monitoramento e avaliação e organização da gestão do serviço. A intervenção motivou grandemente a especializanda, pois uma alta porcentagem dos usuários da UBS são portadores de hipertensão e/ou diabetes e somente ao solicitar o sedimento urinário e a microalbuminuria como exames laboratoriais de rotina podemos prevenir complicações graves como a insuficiência renal. O indicador de cobertura do Programa de atenção à saúde da pessoa com hipertensão alcançou no mês 1 da intervenção 5,8% (35), no mês 2 um total de 8,6% (52) e no mês 3 alcançamos 11,5% (70) do total de 608. Já o indicador de cobertura do programa de atenção à saúde da pessoa com diabetes no mês 1 atingiu 10,0% (15), no mês 2 foi de 11,3% (17) e no mês 3 alcançamos 14,7% (22) do total de 150. Junto à comunidade foram realizadas diversas atividades de promoção à saúde relacionadas ao manejo adequado das doenças crônicas como hipertensão e/ou diabetes. Os usuários foram educados e orientados para o (re)conhecimento das mesmas quanto aos riscos derivados do controle inadequado. Com este trabalho buscamos educar a população para que possa desfrutar de uma qualidade de vida melhorada com mudanças de hábitos alimentares, realização de prática regular de atividade física de acordo com as limitações de cada um. Ao final percebemos uma melhoria significativa, tanto no nível de conhecimento, como na adoção de estilos de vida saudáveis, cumprimento regular e estável dos tratamentos prescritos, com consequente melhoria da qualidade de vida e uma ótima preparação para evitar os riscos e as complicações destas doenças. Palavras-chave: atenção primária à saúde; saúde da família; doença crônica; hipertensão; diabetes mellitus.
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The objective of the present study was to evaluate the effect of 17ß-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17ß-estradiol at a dose of 30 µg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17ß-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass.
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Background: Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing. Methods: We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area - BA22p) identifying by mass spectrometry several protein expression alterations that could be related to the disease. Results: Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6) and glial fibrillary acidic protein (GFAP) were confirmed by western blot in schizophrenia prefrontal cortex. Conclusion: Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.
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Background: Melatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation. Methods: Twenty-four adult Wistar rats, 60 days old (+/-250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [ 100 mu g/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a. m. Results: Melatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated. Conclusions: We suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.
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The mechanism of uptake of anthocyanins (as well as the type) from food in the intestine is not clear. Anthocyanin-rich extract from wild mulberry, composed of cyanidin-3-glucoside (79%) and cyanidin-3-rutino side (cy-3-rut) (19%), was orally administered to Wistar rats, and their concentrations were determined in plasma, kidney, and the gastrointestinal (GI) tract. The 2 glycosylated forms showed maximum concentration at 15 minutes after oral administration, both in plasma and kidney. The cyanidin-3-glucoside and cy-3-rut were found in plasma as glucuronides, as sulfates of cyanidin, and as unchanged forms. The area under the curve of concentration vs time (AUC(0-8h)) was 2.76 +/- 0.88 mu g hour/mL and 9.74 +/- 0.75 mu g hour/g for plasma and kidney, respectively. In spite of the low absorption, the increase in plasma anthocyanin level resulted in a significant increase in antioxidant capacity (P < .05). In the GI tract (stomach and small and large intestines), cyanidin glycosides were found unchanged, but a low amount of the aglycone form was present. Anthocyanin glycosides were no longer detected in the GI tract after 8 hours of administration. In vitro fermentation showed that the 2 cyanidin glycosides were totally metabolized by the rat colonic microflora, explaining their disappearance. In addition, the 2 products of their degradation, cyanidin and protocatechuic acid, were not detected in plasma and probably do not influence plasma antioxidant capacity. As found by the everted sac model, anthocyanins were transported across the enterocyte by the sodium-dependent glucose transporter. (c) 2008 Elsevier Inc. All rights reserved.
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In this study, twenty hydroxylated and acetoxylated 3-phenylcoumarin derivatives were evaluated as inhibitors of immune complex-stimulated neutrophil oxidative metabolism and possible modulators of the inflammatory tissue damage found in type III hypersensitivity reactions. By using lucigenin- and luminol-enhanced chemiluminescence assays (CL-luc and CL-lum, respectively), we found that the 6,7-dihydroxylated and 6,7-diacetoxylated 3-phenylcoumarin derivatives were the most effective inhibitors. Different structural features of the other compounds determined CL-luc and/or CL-lum inhibition. The 2D-QSAR analysis suggested the importance of hydrophobic contributions to explain these effects. In addition, a statistically significant 3D-QSAR model built applying GRIND descriptors allowed us to propose a virtual receptor site considering pharmacophoric regions and mutual distances. Furthermore, the 3-phenylcoumarins studied were not toxic to neutrophils under the assessed conditions. (C) 2007 Elsevier Masson SAS. All rights reserved.
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A new nitrosyl ruthenium complex [Ru(NH center dot NHq)(terpy)NO](3+) nitric oxide donor was recently developed and due to its excellent vasodilator activity, it has been considered as a potential drug candidate. Drug metabolism is one of the main parameters that should be evaluated in the early drug development, so the biotransformation of this complex by rat hepatic microsomes was investigated. In order to perform the biotransformation study, a simple, sensitive and selective HPLC method was developed and carefully validated. The parameters evaluated in the validation procedure were: linearity, recovery, precision, accuracy, selectivity and stability. Except for the stability study, all the parameters evaluated presented values below the recommended by FDA guidelines. The stability study showed a time-dependent degradation profile. After method validation, the biotransformation study was accomplished and the kinetic parameters were determined. The biotransformation study obeyed the Michaelis-Menten kinetics. The V(max) and K(m) were, respectively, 0.1625 +/- 0.010 mu mol/mg protein/min and 79.97 +/- 11.52 mu M. These results indicate that the nitrosyl complex is metabolized by CYP450. (C) 2009 Elsevier Inc. All rights reserved.
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Double aneuploidy, (48,XXY,+21) of maternal origin in a child born to a 13-year-old mother: evoluation of the maternal folate metabolism: The occurrence of non-mosaic double trisomy is exceptional in newborns. In this paper, a 48,XXY,+21 child, the parental origin of the extra chromosomes and the evaluation of the maternal folate metabolism are presented. The infant was born to a 13-year-old mother and presented with the typical clinical features of Down syndrome (DS). The origin of the additional chromosomes was maternal and most likely resulted from errors during the first meiotic division. Molecular analysis of 12 genetic polymorphisms involved in the folate metabolism revealed that the mother is heterozygous for the MTHFR C677T and TC2 A67G polymorphisms, and homozygous for the mutant MTRR A66G polymorphism. The maternal homocysteine concentration was 4.7 mu mol/L, a value close to the one considered as a risk factor for DS in our previous study. Plasma methylmalonic acid and serum folate concentrations were 0.17 mu mol/L and 18.4 ng/mL, respectively. It is possible that the presence of allelic variants for the folate metabolism and Hey concentration might have favored errors in chromosomal disjunction (hiring gametogenesis in this young mother. To our knowledge, this is the first patient with non-mosaic Down-Klinefelter born to a teenage mother, resulting from a rare fertilization event combining an abnormal 25,XX,+21 oocyte and a 23,Y spermatozoon.
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center dot Pharmacokinetic interactions between albendazole and praziquantel are based on plasma concentrations of the enantiomeric mixture of both drugs with contradictory data, although the antiparasitic activity arises from (-)-(R)-praziquantel and (+)-albendazole sulfoxide. WHAT THIS STUDY ADDS center dot The pharmacokinetic interaction between albendazole and praziquantel is enantioselective. Praziquantel increased the plasma concentrations of (+)-albendazole sulfoxide more than those of (-)-albendazole sulfoxide and the administration of albendazole did not change the kinetic disposition of (+)-(S)-praziquantel, but increased the plasma concentration of (-)-(R)-praziquantel. AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0-48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P < 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 mu g ml-1 h), (-)-ASOX by 358% (0.14 vs. 0.50 mu g ml-1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 mu g ml-1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (-)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (-)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 mu g ml-1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (-)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination.
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1. Eight human cytochrome P4501B1 (CYP1B1) allelic variants, namely Arg(48)Ala(119)Leu(432), Arg(48)Ala(119)Val(432), Gly(48)Ala(119)Leu(432), Gly(48)Ala(119)Val(432), Arg(48)Ser(119)Leu(432), Arg(48)Ser(119)Val(432), Gly(48)Ser(119)Leu(432) and Gly(48)Ser(119)Val(432) (all with Asn(453)), were expressed in Escherichia coli together with human NADPH-P450 reductase and their catalytic specificities towards oxidation of 17 beta -oestradiol and benzo[a]pyrene were determined. 2. All of the CYP1B1 variants expressed in bacterial membranes showed Fe2+. CO versus Fe2+ difference spectra with wavelength maxima at 446 nm and they reacted with antibodies raised against recombinant human CYP1B1 in immunoblots. The ratio of expression of the reductase to CYP1B1 in these eight preparations ranged from 0.2 to 0.5. 3. CYP1B1 Arg(48) variants tended to have higher activities for 17 beta -oestradiol 4-hydroxylation than Gly(48) variants, although there were no significant variations in 17 beta -oestradiol 2-hydroxylation activity in these eight CYP1B1 variants. Interestingly, ratios of formation of 17 beta -oestradiol 4-hydroxylation to 2-hydroxylation by these CYP1B1 variants were higher in all of the Val(432) forms than the corresponding Leu(432) forms. 4. In contrast, Leu(432) forms of CYP1B1 showed higher rates of oxidation of benzo[a]pyrene (to the 7, 8-dihydoxy-7,8-dihydrodiol in the presence of epoxide hydrolase) than did the Val(432) forms. 5. These results suggest that polymorphic human CYP1B1 variants may cause some altered catalytic specificity with 17 beta -oestradiol and benzo[a]pyrene and may influence susceptibilities of individuals towards endogenous and exogenous carcinogens.
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The title compound (3) has been synthesized and its presence sought in the urinary metabolites of the brushtail possum. © CSIRO 2001