Conservation of the cardiostimulant effects of (-)-Norepinephrine across Ser49Gly and Gly389Arg Beta1-adrenergic receptor polymorphisms in human right atrium in vitro

OBJECTIVES The goal of this study was to determine whether the cardiostimulant effects of the endogenous beta(1)-adrenergic receptor (AR) agonist, (-)-norepinephrine are modified by polymorphic (Serine49Glycine [Ser49Gly], Glycine389Arginine [Gly389Arg]) variants of beta(1)-ARs in the nonfailing adult human heart. BACKGROUND Human heart beta(1)-ARs perform a crucial role in mediating the cardiostimulant effects of (-)-norepinephrine. An understanding of the significance of Ser49Gly and Gly389Arg polymorphisms in the human heart is beginning to emerge, but not as yet in adult patients who have coronary artery disease (CAD). METHODS The potency and maximal effects of (-)-norepinephrine at beta(1)-ARs (in the presence of beta(2)-AR blockade with 50 nM ICI 118,551 [erythro-DL-1(7-methylindan-4-yloxy)-3-isopropylamino-butan-2-ol]) for changes in contractile force and shortening of contractile cycle duration were determined in human right atrium in vitro from 87 patients undergoing coronary artery bypass grafting who were taking beta-blockers before surgery. A smaller sample of patients (n = 20) not taking beta-blockers was also investigated. Genotyping for two beta(1)-AR polymorphisms (Ser49Gly and Gly389Arg) was determined from a sample of blood taken at the time of surgery. RESULTS (-)-Norepinephrine caused concentration-dependent increases in contractile force and reductions in time to reach peak force and time to reach 50% relaxation. There were no differences in the potency or maximal effects of (-)-norepinephrine in the right atrium from patients with different Ser49Gly and Gly389Arg polymorphisms. CONCLUSIONS The cardiostimulant effects of (-)-norepinephrine at beta(1)-ARs were conserved across Ser49Gly and Gly389Arg polymorphisms in the right atrium of nonfailing hearts from patients with CAD managed with or without beta-blockers. (C) 2002 by the American College of Cardiology Foundation.

Dietary supplementation with vitamin E modulates avian intestinal immunity

The effect of dietary vitamin E on immunoglobulin A (IgA) antibody production, which acts as the first line of defence at the intestinal mucosa, has not been evaluated in chickens. In the present study the impact of the inclusion of supplementary levels of vitamin E to the diet, on total and antigen-specific IgA antibody titres, T-cell subsets and Ia+ cells, was assessed. From hatching, chickens received a maize-based diet which was supplemented with either 25, 250, 2500 or 5000 mg dl-alpha-tocopherol acetate/kg. Primary immunisation with tetanus toxoid (T. toxoid) emulsified in a vegetable oil-in-water adjuvant was administered by the intraperitoneal route at 21 d of age. At 35 d of age all birds received an oral booster vaccination of T. toxoid. Significantly higher total IgA antibody titres were present in the day 42 intestinal scrapings of birds receiving the 5000 mg/kg vitamin E-supplemented diet (VESD) (P=0.05) and a notable increase was observed in birds receiving the 250 mg/kg VESD (P=0.06). At days 21 and 42 total serum IgA antibody titres of birds receiving the 250 mg/kg VESD was significantly higher (P

Effects of dietary level of protein, lysine and methionine and strain of bird on production and egg yolk cholesterol

The effects of dietary level of protein (151, 181 g/kg), lysine (nil, 10g L-lysine hydrochloride/kg) and methionine (nil, 5g DL-methionine/kg) on the production performance and egg yolk cholesterol of two strains of birds were studied for 12 weeks. Birds fed on the high protein diet had higher body weight gain, feed conversion ratio (FCR), rate of lay, egg weight and mass and yolk weight and mass. A high lysine diet decreased feed intake and improved FCR. High dietary level of methionine increased egg yolk cholesterol. There were differences between strains of laying bird in feed intake, rate of lay, egg and yolk weights and egg cholesterol content. It is concluded that strain of bird and dietary level of protein and lysine influenced the production performance of birds. Whilst, egg yolk cholesterol was not reduced by any of the factors studied.

Ocular melanoma is not associated with CDKN2A or MC1R variants - a population-based study

Germline variants in the melanocortin 1 receptor gene (MC1R) and the p16 gene (CDKN2A) are associated with an increased risk of cutaneous melanoma. The frequency of these germline variants was examined in a population-based, incident series of 62 ocular melanoma cases and ethnicity-matched population controls. In both cases and controls, 59% of individuals carried at least one MC1R variant and there were no significant differences in the frequency of any of the five most common variants of MC1R. We also found no significant differences between cases and controls in the frequency of any of the four most common variants of CDKN2A, and no melanoma case carried a deleterious germline CDKN2A mutation. Our findings argue against an important predisposing effect of the MC1R and CDKN2A genes for ocular melanoma.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Effects of heat treatment on the nutritional value of raw soybean selected for low trypsin inhibitor activity

1. Two broiler experiments and a layer experiments were conducted on Kunitz trypsin inhibitor (Kti) soybeans (SB) of low trypsin inhibitor (TI) activity to determine their nutritive value when included as mash in least-cost poultry diets. 2. Experiment 1 compared chick performance on the Kti or raw SB using a commercial full-fat SB meal (FFSBM) and a solvent extracted SB meal (SBM) as controls during a 20 d experimental period. Broiler experiment 2 compared Kti and raw SB, non-steamed, or steam-pelleted with and without DL-methionine supplementation added to every treatment containing 170 g SB/kg. For each broiler experiment the levels of each SB were 70, 120 and 170 g/kg with the control birds fed only 170 g SB/kg. 3. The layer experiment, compared steam-pelleted Kti and raw SB against a non-steamed Kti and raw SB each fed at two levels (70 and 110 g/kg) x 30 replicates from 29 weeks of age for 19 weeks in a completely randomised design. Production parameters were measured when diets were formulated to contain minimum required specifications and calculated apparent metabolisable energy (AME). At the completion of each trial, 2 broiler birds from each cage and 5 layer birds per treatment were killed, weighed, and their liver and pancreas weighed. 4. Both broiler experiments indicated that production parameters on the Kti SB treatments were significantly lower (P < 0.05) than on the two commercial control SB treatments. However, the Kti treatments were superior to the raw SB treatments. 5. Pancreas weight increased with increasing inclusion of both raw and Kti SB, suggesting that a TI was causing the depression in performance. The AME of the Kti SB was similar to that of commercial FFSB meal. After steam conditioning, the raw SB meal AME value of 9.5 MJ/kg dry matter (DM) was improved to 14.1 MJ/kg DM by reduced TI activity, but this AME improvement with TI activity reduction, plus the supplementation with DL-methionine on birds fed the raw SB had no effect (P > 0.05) on any parameter evaluated in experiment 2. 6. The layer experiment showed that hens on the Kti SB treatments had significantly greater live weight gain (LWG), egg weight and daily egg mass than birds given raw SB. A reduced food intake (FI) was observed in the Kti treatments but egg mass was generally similar to that on the FFSB control diet, indicating that Kti SB supported excellent egg production at an inclusion of 110 g/kg. The depressed performance observed for broiler chicks suggest that younger birds are more susceptible to the effects of SB TI.

Matriz de capacita????o modelada por compet??ncias para atuar em programas de educa????o a dist??ncia: uma proposta para as escolas de governo

This study discusses distance learning (DL) as a corporate education strategy in the scope of National Policy on Staff Development. The purpose was to identify, along with managers and specialists of National Network of Schools of Government in Brazil (RNEG), demanded competencies for DL professionals acting in continued education to service public. Part of the research is based in official documents and in related capacity-building initiatives of Schools of Government in the last three years. Through questionnaire sent to managers of institutions of RNEG, we identified existing infrastructure, teams profile, actions developed in DL and training needs. The research allowed to map the critical competencies to work in DL programs and to create a proposal from a Competency-Based Training Matrix for school teams in order to leverage continuing education programs to public servants in three spheres of government. The results revealed the key technological, pedagogical, management and communication skills, as well as the critical activities and content to be included in the training plans. It was found that 88% of institutions have already implemented or are in the process of implementing DL, and the other 12% are deficient in qualified staff to make regulations on hiring personnel or in technology fluency. This corroborates the importance and the contribution of Competency-Based Training Matrix for RNEG

Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice

The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response: 51 ± 8 vs 53 ± 5%, respectively) and SNP-induced vasorelaxation (maximal response: 73 ± 6 vs 74 ± 6%, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm2 x 103). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.

O Papel do Agente de Execução na Fase da Penhora-Determinação dos Bens a Penhorar

A penhora é, no contexto actual de crise económica, uma realidade frequente, sendo o ato executivo por excelência no âmbito das execuções para o pagamento de quantia certa, que consiste na apreensão de bens, num desapossamento de bens do devedor, com vista á satisfação do credito adequando. Previamente á realização á realização deste ato processual, terão de ser determinados os bens que do mesmo serão objecto, devendo ser consideradas as limitações legais e, eventualmente, convencionais. Os poderes de indicação dos bens a penhorar sofreram alterações desde o Código de Processo Civil de 1939 ate ao actualmente em vigor, que tem a redacção do DL nº 226/2008, de 20 de novembro, tendo sido atribuído ao Agente de Execução, com a reforma de 2003, o poder de determinar os bens a penhorar.O objectivo principal desta dissertação é, precisamente determinar qual o papel do Agente de Execução na fase da penhora, em especial na determinação dos bens a penhorar, com analise de todos os aspectos relacionados, e aferir a interpretação e aplicação do regime em vigor por aqueles que lidam diariamente com os processos executivos. Para o efeito, alem da analise teórica da matéria, foi realizado um estudo empírico, mediante a aplicação e tratamento de um inquérito por questionário ministrado a todos os Agentes de Execução a exercer funções nas comarcas abrangidas pelo Conselho Regional do Norte da Câmara dos Solicitadores. Genericamente, no presente estudo, concluímos que apesar da atribuição ao Agente de Execução do poder de determinar quais os bens que ira penhorar, esse poder esta vinculado, designadamente por critérios e imperativos legais. E o Agente de Execução deve, ainda, ter em consideração a vontade manifestada pelo exequente, o que, como resulta do estudo empírico realizado, é, na pratica, frequente. Paralelamente e de forma a garantir a legalidade da penhora determinada pelo gente de Execução, ao juiz de execução é atribuída competência para controlada este seu poder.

A Normalização Contabilística das Pequenas e Microentidades: implicações contabilísticas e fiscais no processo de transição

O Sistema de Normalização Contabilística(SNC, aprovado pelo Decreto-Lei(DL) numero(nº) 158/2009, de 13 de Julho, atendeu ás diversas necessidades de relato financeiro. Por isso, prevê a adopção das Normas Contabilísticas e de Relato Financeiro(NCRF´S), para as empresas com maiores necessidades de relato financeiro, um regime simplificado correspondente a uma Norma Contabilística e de Relato Financeiro para as Pequenas Entidades(NCRF-PE), para as entidades mais pequenas, e inclui também uma norma para as entidades do sector não lucrativo.

Legalidade do Júri do Doutoramento

Qualquer coincidência com a realidade é pura coincidência, ciência. Chegou-nos aos ouvidos por voz credível que haveria quem no Minho defendesse, e passamos a citar, qualquer coisa como: os professores dos institutos politécnicos e os professores de universidades de baixa reputação não deverão fazer parte de júris para provas de doutoramento em determinada Universidade…. Se isto é verdade – além da difamação que pode gerar responsabilidade judicial e civil para os seus autores (quem te avisa, teu amigo é!) -, salvo o devido respeito e amizade, é violador da legislação que, no Estado de Direito, regula a constituição de júris para provas de doutoramento. Se dúvidas existirem, veja-se o art. 34º do DL nº 115/2013, de 7/8 § Any coincidence with reality is purely coincidental, science. We reached our ears by credible voice that there would be anyone in the Minho defend, and we quote, something like: teachers of polytechnics and teachers of low-reputation universities should not be part of juries for PhD exams in certain University .... If this is true - in addition to the defamation that can generate judicial and civil liability for their authors (who warns you, your friend is!) - Unless due respect and friendship, is in breach of legislation, the rule of law, regulates the constitution of juries for doctoral exams. If doubts exist, see art. 34 of DL No. 115/2013, 7/8.

Fatores prognósticos da doença meningocócica: estudo relativo a 254 casos

Analisa-se, em relação a 254 casos de doença meningocócica, a variação da letalidade sob a influência dos seguintes fatores que, segundo a literatura, agravam-lhe o prognóstico: grupos de idade extrema, tempo curto de história antes da admissão, presença de púrpuras e/ou petéquias na admissão, ocorrência de choque ou de coma, número de leucócitos normal ou diminuído no sangue periférico na admissão, líquido cefalorraquidiano normal na admissão, número de leucócitos normal ou diminuído no sangue periférico na admissão, número de leucócitos menor que 100/mm³, proteinorraquia maior que 300 mg/dl, ou glicorraquia menor que 10 mg/dl, no líquido cefalorraquidiano colhido na admissão. Dentre esses fatores, aqueles para os quais se demonstrou influência estatisticamente significativa sobre a letalidade foram: 1) idades extremas: maior letalidade em crianças com menos de um ano de idade e em adultos com mais de 40 anos; 2) tempo de história, antes da admissão hospitalar, menor que 48 horas; 3) presença de coma ou 4) choque na admissão; 5) número de leucócitos, no sangue periférico colhido na admissão, igual ou menor que 10.000/mm³. A combinação desses fatores evidenciou que, quanto maior o número deles associados, mais alto o índice de letalidade.

Avaliação da concentração de ferro orgânico em uma população de grávidas

Objetivou-se conhecer as alterações da concentração de hemoglobina (Hb), hematócrito (Ht), ferro sérico (FS), capacidade total de ligação de ferro (CTLF) e saturação de transferrina (ST) durante a gestação normal em mulheres não anêmicas (H > 11,0g/dl). Verificou-se, entre as 250 mulheres selecionadas, diminuição dos valores de Hb e Ht até o 7.° mês de gravidez quando houve aumento nesses valores até o final do processo gravídico; o mesmo foi observado com relação aos valores do FS. A CTLF apresentou um aumento durante todo o período considerado enquanto a ST diminuiu. Os resultados observados justificam o uso de suplementação de ferro como uma estratégia de saúde pública a ser utilizada no controle da deficiência de ferro, mesmo entre mulheres não anêmicas.

Diagnóstico de deficiência de ferro na infância

Com o objetivo de enfatizar a importância da escolha adequada de um parâmetro foi analisado o diagnóstico de deficiência de ferro de 855 crianças, com 60 meses e menos de idade, utilizando o padrão proposto pela OMS (11,0 g/dl) e outros. A inclusão de maior número de "falsos-positivos", resultante de parâmetros de maior sensibilidade do que o da OMS, é compensada pela garantia de tratamento à maior parte das crianças ferro-deficientes. Ao mesmo tempo que tal ampliação de programa é importante em sociedades de países em desenvolvimento, onde a prevalência de anemia é elevada, esta extensão é factível de ser executada dado o baixo custo do suplemento de ferro.

A anemia nutricional entre gestantes atendidas em centros de saúde do Estado de São Paulo (Brasil)

Com o objetivo de estimar a prevalência de anemia entre a clientela do Programa de Atendimento à Gestante (PAG), da Secretaria de Saúde do Estado de São Paulo (Brasil), e de analisar o item referente à suplementação de ferro, do mesmo programa, estudaram-se os prontuários de 4.539 gestantes, matriculadas nos PAGs de 15 Centros de Saúde (CS), escolhidos através de amostragem, probabilística. Observou-se anemia (hemoglobina - Hb - < 11,0 g/dl) em 35,1% das gestantes, valor que sugere constituir essa deficiência problema de saúde pública em relação à clientela dos Centros de Saúde estudados. É destacada a necessidade de incluir, na rotina do PAG, a medida da concentração de Hb e de referi-la conjuntamente com a idade gestacional propiciando conhecer a necessidade de ferro suplementar específica de cada grávida, aumentando, com isso, a eficiência do programa de combate à anemia e, conseqüentemente, a do PAG. Sugere-se também que a avaliação da suplementação seja feita em Centros de Saúde que tenham facilidade para tal.