Influence of the polymorphisms of the α-major regulatory element HS-40 on in vitro gene expression

The α-MRE is the major regulatory element responsible for the expression of human α-like globin genes. It is genetically polymorphic, and six different haplotypes, named A to F, have been identified in some population groups from Europe, Africa and Asia and in native Indians from two Brazilian Indian tribes. Most of the mutations that constitute the α-MRE haplotypes are located in flanking sequences of binding sites for nuclear factors. To our knowledge, there are no experimental studies evaluating whether such variability may influence the α-MRE enhancer activity. We analyzed and compared the expression of luciferase of nine constructs containing different α-MRE elements as enhancers. Genomic DNA samples from controls with A (wild-type α-MRE) and B haplotypes were used to generate C-F haplotypes by site-directed mutagenesis. In addition, three other elements containing only the G→A polymorphism at positions +130, +199, and +209, separately, were also tested. The different α-MRE elements were amplified and cloned into a plasmid containing the luciferase reporter gene and the SV40 promoter and used to transiently transfect K562 cells. A noticeable reduction in luciferase expression was observed with all constructs compared with the A haplotype. The greatest reductions occurred with the F haplotype (+96, C→A) and the isolated polymorphism +209, both located near the SP1 protein-binding sites believed not to be active in vivo. These are the first analyses of α-MRE polymorphisms on gene expression and demonstrate that these single nucleotide polymorphisms, although outside the binding sites for nuclear factors, are able to influence in vitro gene expression.

Optimization of the HS-SPME-GC/MS technique for the analysis of volatile compounds in caprine Coalho cheese using response surface methodology

Abstract Caprine Coalho cheese presents great potential for a typical protected designation of origin, considering that this traditional Brazilian cheese presents a slightly salty and acid flavor, combined with a unique texture. This study optimized the HS-SPME-GC-MS methodology for volatile analysis of Coalho cheese, which can be used as a tool to help in the identification of the distinctive aroma profile of this cheese. The conditions of equilibrium time, extraction temperature and time were optimized using the statistical tool factorial experimental design 23, and applying the desirability function. After the evaluation, it was concluded that the optimum extraction conditions comprised equilibrium and extraction time of 20 and 40 minutes, respectively; and ideal extraction temperature of 45 °C. The optimum extraction of volatile compounds in goat Coalho cheese captured 32 volatile compounds: 5 alcohols, 5 esters, 3 ketones, 6 acids, 3 aldehydes, 3 terpenes, and 7 hydrocarbons.

40 anos de política externa brasileira, 1958-1998: três inflexões

A política externa brasileira, de 1958 a 1998, atravessa três grandes períodos ou mudanças em suas orientações e formas de atuação. Numa primeira fase, herdada ainda do período anterior do imediato pós-guerra e mesmo anterior a ela, ela vive ainda o "paradigma Rio Branco", isto é, orienta-se basicamente e busca manter relações especiais com a principal potência hemisférica. No período do regime militar, assiste-se a uma ampliação do quadro de relacionamento externo, contemporaneamente a grandes mudanças na estrutura econômica do País. Na fase recente, finalmente, emerge a importância do multilateralismo econômico, no contexto da globalização. Essas inflexões são analisadas colocando-se lado a lado mudanças na conjuntura internacional e nas condições políticas e econômicas do País.

Comparación de ranking del Ministerio de Salud (Minsal) e impacto financiero de las 40 primeras patologías Auge-GES vigentes en Chile

El presente artículo compara el ranking Minsal de 40 patologías Auge-GES con el determinado por impacto financiero. Se elaboró una base de datos homogénea, se estandarizaron datos y se aplicaron correlaciones Pearson y Spearman. Se concluye que el criterio de impacto financiero cambia efectivamente las prioridades y modifica la congruencia social de la política de Estado.

Mammography in asymptomatic women aged 40-49 years

OBJECTIVE To assess findings of mammography of and interventions resulting from breast cancer screening in women aged 40-49 years with no increased risk (typical risk) of breast cancer. METHODS This cross-sectional study evaluated women aged 40-49 years who underwent mammography screening in a mastology reference center in Recife, PE, Northeastern Brazil, between January 2010 and October 2011. Women with breast-related complaints, positive findings in the physical examination, or high risk of breast cancer were excluded. RESULTS The 1,000 mammograms performed were classified into the following Breast Imaging-Reporting and Data System (BI-RADS) categories BI-RADS 0, 232; BI-RADS 1, 294; BI-RADS 2, 294; BI-RADS 3, 16; BI-RADS 4A, 2; BI-RADS 5, 1. There was one case of grade II invasive ductal carcinoma and various interventions, including 469 ultrasound scans, 53 referrals to mastologists, 11 cytological examinations, and 8 biopsies. CONCLUSIONS Mammography screening in women aged 40-49 years with typical risk of breast cancer led to the performance of other interventions. However, it also resulted in increased costs without demonstrable efficacy in decreasing mortality.

Multiple skin neoplasms in subjects under 40 years of age in Goiania, Brazil

OBJECTIVE To describe the trend for malignant skin neoplasms in subjects under 40 years of age in a region with high ultraviolet radiation indices.METHODS A descriptive epidemiological study on melanoma and nonmelanoma skin cancers that was conducted in Goiania, Midwest Brazil, with 1,688 people under 40 years of age, between 1988 and 2009. Cases were obtained fromRegistro de Câncer de Base Populacional de Goiânia(Goiania’s Population-Based Cancer File). Frequency, trends, and incidence of cases with single and multiple lesions were analyzed; transplants and genetic skin diseases were found in cases with multiple lesions.RESULTS Over the period, 1,995 skin cancer cases were observed to found, of which 1,524 (90.3%) cases had single lesions and 164 (9.7%) had multiple lesions. Regarding single lesions, incidence on men was observed to have risen from 2.4 to 3.1/100,000 inhabitants; it differed significantly for women, shifting from 2.3 to 5.3/100,000 (Annual percentage change – [APC] 3.0%, p = 0.006). Regarding multiple lesions, incidence on men was observed to have risen from 0.30 to 0.98/100,000 inhabitants; for women, it rose from 0.43 to 1.16/100,000 (APC 8.6%, p = 0.003). Genetic skin diseases or transplants were found to have been correlated with 10.0% of cases with multiple lesions – an average of 5.1 lesions per patient. The average was 2.5 in cases without that correlation.CONCLUSIONS Skin cancer on women under 40 years of age has been observed to be increasing for both cases with single and multiple lesions. It is not unusual to find multiple tumors in young people – in most cases, they are not associated with genetic skin diseases or transplants. It is necessary to avoid excessive exposure to ultraviolet radiation from childhood.

Avaliação de três esquemas terapêuticos com o antimoniato de N-metil-glucamina no tratamento da leishmaniose visceral no estado do Pará, Brasil

Avaliaram-se, de forma retrospectiva, três esquemas terapêuticos à base do antimoniato de N-metil-glucamina (Glucantime) usados no tratamento de 43 casos autóctones de leishmaniose visceral (Estado do Pará), observados em crianças de 1 a 12 anos de idade, no período de 1985 a 1990. Dos 43 casos, 28 (grupo A) foram tratados com 40 mg/SbV/kg administrados IV a intervalos de 48 hs, em séries de 15 doses (esquema I); 8 (grupo B) receberam 40mg/SbV/kg administrados IV diariamente, durante 15 dias (esquema II), e 7 (grupo C) receberam 20 mg/SbV/kg administrados IV diariamente, durante 15 dias (esquema III). Considerando que o controle de cura da doença foi essencialmente clínico, admitiu-se que o esquema III representaria a melhor opção terapêutica, em razão de: a) ter promovido taxa de cura equivalente aos esquemas que usaram o dobro dessa dose, b) a relação custo-benefício desse esquema torna-o menos dispendioso, c) pode ser usado durante período mais prolongado, com menor risco de produzir efeitos de toxicidade, e d) não existem, a nível local (Pará), relatos de casos de resistência da doença associados ao uso desse esquema.

EXPERIENCE IN THE EVALUATION OF CHILDREN WITH HEPATOSPLENOMEGALY AT A TEACHING AMBULATORY, SÃO PAULO, BRAZIL

Objectives: Describe cases of children with hepatosplenomegaly (HS) attended at the General Pediatric Teaching Ambulatory (AGER) of Instituto da Criança, São Paulo, identifying the main causes, evolution, necessity for hospitalization and/or referral to specialists. Methodology: Retrospective analysis of the records of children presenting HS on admission at AGER from September 1, 1993 to August 31, 1996. Results: Of the 89 children included (age range, 1 to 148 months; median, 24 months), 64 (72%) were referred from other services for HS investigation. Most common presenting complaints were: fever - 39 (44%); pallor - 26 (29%); weight loss - 21 (24%) and jaundice - 14 (16%). Main alterations noticed on physical examination were: pallor - 47 (53%) and short stature - 17 (19%). Anemia was diagnosed in 70 children (79%); 35 children (39%) had infections; 7 (8%) metabolic disorders and 5 (6%) neoplastic disorders. The most frequent infections were of the urinary tract - 9 (10%) and hepatitis A - 6 (7%).Thirty six children (40%) were referred to specialists, 17 of which were already diagnosed. Conclusions: Most of the children with HS present deficiency anemia associated with infections which the general pediatrician is able to diagnose. Persistence of unexplained HS for more than 2 months, especially when there is substantial volume enlargement or alteration in the organs consistency, is an indication for referral to specialists.

Tratamento da esquistossomose mansônica na criança com oxamniquine sob forma de xarope

São apresentados os resultados preliminares do tratamento da esguistossomose mansônica com oxamniquine, sob forma de xarope, em 40 crianças, com idade variando de 5 a 14 anos. 18 pertenciam ao sexo masculino e 22 ao feminino. A dose utilizada foi de 20 mg/k em uma única aplicação - 25 pacientes (Grupo A) ou em 2 tomadas com intervalo de 12 hs - 15 pacientes (Grupo B). A tolerância foi em geral boa, sobretudo no Grupo B de pacientes, onde 73,3% não apresentou qualquer sintoma colateral, em comparação com 44% do Grupo A. 0s sintomas mais freqüentes foram tontura (22,5%) e sonolência (20%). 5 pacientes do Grupo A apresentaram distúrbio de conduta sob forma de excitação psíquica ou agressividade passageiras. A cura parasitológica (comprovação entre o 4º e o 6º mês pós-tratamento) foi observada em 70% dos pacientes tratados (90% no Grupo A e 50% no Grupo B). O baixo índice, nesse último Grupo, possivelmente deveu-se ao longo intervalo entre as 2 tomadas (12hs). Houve grande redução do número de ovos eliminados nos pacientes não curados.

A retrospective study of 40 victims of Crotalus snake bites: analysis of the hepatic necrosis observed in one patient

Forty patients with a diagnosis of snake bite were studied at the Infectious and Parasitic Disease Service of the Faculty of Medicine of Botucatu. Thirty were males and 10 females, ranging in age from 16 to 70 years. All were farm laborers and 35 of them were bitten in the lower limbs. Two of the 9 patients seen more than 6 hours after the bite died. The low mortality rate (5%) observed could be explained by the early care provided, by the use of appropriate doses of anti-crotalus serum, parenteral hydration, urine alkalinization with sodium bicarbonate and induction of osmotic diuresis with a mannitol solution. Anatomopathological examination of one of the patients who died revealed extensive hepatic necrosis. The authors discuss the possibility of the effect of a factor of snake venom in the genesis of hepatic necrosis and in the increased transaminase levels.

Hedylidae (Lepidoptera: Hedyloidea) coletados à luz a 40 metros de altura no dossel da floresta da Estação Experimental de Silvicultura Tropical em Manaus, Amazonas, Brasil

Os Hedylidae constituem um grupo de lepidópteros exclusivamente neotropical com 35 espécies conhecidas em um gênero, Macrosoma Hübner, 1818. Antes classificados entre as mariposas Geometridae, agora são considerados um grupo basal e noturno de borboletas. Foram realizadas coletas mensais de janeiro a dezembro de 2004 no dossel de uma floresta em área de terra-firme, utilizando um lençol branco iluminado por luz mista de mercúrio e outra luz negra UV-BLB, instalado a 40 m de altura em uma torre. As coletas foram realizadas das 18:00 às 6:00 h do dia seguinte. Foram coletados 55 exemplares , a maioria machos, somente dois exemplares fêmeas pertencentes a nove espécies, uma delas provavelmente nova, a saber: M. hedylaria Warren (1894), M. bahiata (Felder & Rogenhofer, 1875), M. conifera (Warren, 1897), M. heliconiaria (Guenée, 1857), M. hyacinthina (Warren, 1905), M. klagesi (Prout, 1916), M. lucivittata (Walker, 1863) M. nigrimacula (Warren, 1897) e Macrosoma sp. Os Hedylidae foram mais abundantes na estação mais chuvosa, dezembro a maio, com 65,5% dos espécimes coletados. O horário de maior atividade foi entre 19:00 e 22 h com 80% dos espécimes coletados.

Do estigma da psicose maníaco-depressiva ao incentivo ao tratamento do transtorno bipolar: a evolução da abordagem em dois veículos midiáticos nos últimos 40 anos

OBJETIVO: Investigar a evolução ao longo dos últimos 40 anos da assimilação midiática do transtorno bipolar. MÉTODOS: Foram pesquisadas referências sobre os termos "transtorno bipolar" e "maníaco-depressivo" na revista Veja e no jornal The New York Times e analisada uma amostra de 40 textos de cada veículo. Os textos foram divididos em dois grupos, o primeiro reunindo aqueles datados dos anos entre 1970 e 1999 e o segundo, 2000 a 2009. RESULTADOS: Entre os anos de 1970 e 1999 é mais utilizado o termo "maníaco-depressivo", porém na década de 2000-2009 a expressão "transtorno bipolar" predomina amplamente. Além disso, artigos mais antigos, que utilizam principalmente o termo "maníaco-depressivo", tendem a ser mais estigmatizantes e com menor pretensão informativa. Já artigos mais recentes, em que a expressão "transtorno bipolar" é mais utilizada, tendem a incentivar a busca de tratamento. CONCLUSÃO: Sugere-se que a abordagem midiática do transtorno bipolar, comparada ao tratamento recebido pela psicose maníaco-depressiva, é marcada pela maior assimilação do referencial biomédico.