RESUMO
A procedure for the determination of (210)Pb, and alpha-emitting radioisotopes of uranium, thorium, and radium from the same aliquot of a sample has been proposed. The key step consisted in the recovery of Pb(II) and Ra by precipitation of insoluble Pb(NO(3))(2), the uranium and thorium radioisotopes remaining in solution. Afterwards, the fractions were handled by specific, well consolidated procedures. Lead-210 was determined by the LSC technique while the uranium, thorium, and radium radioisotopes were measured with silicon alpha-spectrometers. The procedure was applied to a reference sample and several environmental samples obtaining satisfactory results.
Assuntos
Algoritmos , Misturas Complexas/análise , Radioisótopos/análise , Radiometria/métodos , Análise Espectral/métodos , Partículas alfa , Doses de Radiação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
In the late 1980's child malnutrition was still prevalent in Brazil, and child obesity was beginning to rise in the richest regions of the country. To assess the extent of the nutritional transition during the period and the influence of birth weight and maternal smoking on the nutritional condition of schoolchildren, we estimated the prevalence of excess weight and malnutrition in a cohort of Brazilian schoolchildren from 1987 to 1989. We calculated the body mass index (BMI) of 8- to 10-year-old schoolchildren born in Ribeirão Preto in 1978/79. We considered children with a BMI <5th percentile (P5) to be malnourished, children with P5³BMIAssuntos
Criança
, Feminino
, Humanos
, Recém-Nascido
, Masculino
, Gravidez
, Peso ao Nascer
, Transtornos da Nutrição Infantil/epidemiologia
, Sobrepeso/epidemiologia
, Efeitos Tardios da Exposição Pré-Natal/epidemiologia
, Fumar
, Índice de Massa Corporal
, Brasil/epidemiologia
, Estudos de Coortes
, Transtornos da Nutrição Infantil/etiologia
, Recém-Nascido de Baixo Peso
, Sobrepeso/etiologia
, Prevalência
, Fatores de Risco
, Fatores Socioeconômicos
, População Urbana
RESUMO
In the late 1980's child malnutrition was still prevalent in Brazil, and child obesity was beginning to rise in the richest regions of the country. To assess the extent of the nutritional transition during the period and the influence of birth weight and maternal smoking on the nutritional condition of schoolchildren, we estimated the prevalence of excess weight and malnutrition in a cohort of Brazilian schoolchildren from 1987 to 1989. We calculated the body mass index (BMI) of 8- to 10-year-old schoolchildren born in Ribeirão Preto in 1978/79. We considered children with a BMI <5th percentile (P5) to be malnourished, children with P5 > or = BMI
Assuntos
Peso ao Nascer , Transtornos da Nutrição Infantil/epidemiologia , Sobrepeso/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar , Índice de Massa Corporal , Brasil/epidemiologia , Criança , Transtornos da Nutrição Infantil/etiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Sobrepeso/etiologia , Gravidez , Prevalência , Fatores de Risco , Fatores Socioeconômicos , População UrbanaRESUMO
Isolation and biological characterization of pure compounds was used to identify and characterize estrogenic activity and estrogen receptors (ER) preference in chemical components of Achillea millefolium. This medicinal plant is used in folk medicine as an emmenagogue. In vitro assay, based on recombinant MCF-7 cells, showed estrogenic activity in a crude extract of the aerial parts of A. millefolium. After fractionation of the crude extract with increasing polar solvents, estrogenic activity was found in the methanol/water fraction. Nine compounds were isolated and characterized by HR-MS spectra and 1D- and 2D-NMR techniques. In particular, dihydrodehydrodiconiferyl alcohol 9-O-beta-D-glucopyranoside - a glycosyl-neolignan - was isolated for the first time from the genus Achillea in addition to six flavone derivatives, apigenin, apigenin-7-O-beta-D-glucopyranoside, luteolin, luteolin-7-O-beta-D-glucopyranoside, luteolin-4'-O-beta-D-glucopyranoside, rutin, and two caffeic acid derivatives, 3,5-dicaffeoylquinic acid and chlorogenic acid. Apigenin and luteolin, the most important estrogenic compounds among those tested, were studied for their ability to activate alpha or beta estrogen receptors (ERalpha, ERbeta) using transiently transfected cells. Our results suggest that isolation and biological characterization of estrogenic compounds in traditionally used medicinal plants could be a first step in better assessing further (e.g. in vivo) tests of nutraceutical and pharmacological strategies based on phytoestrogens.
Assuntos
Achillea , Receptor alfa de Estrogênio/efeitos dos fármacos , Receptor beta de Estrogênio/efeitos dos fármacos , Fitoestrógenos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Células Cultivadas/efeitos dos fármacos , Feminino , Humanos , Técnicas In Vitro , Fitoestrógenos/administração & dosagem , Fitoestrógenos/química , Fitoestrógenos/uso terapêutico , Componentes Aéreos da Planta , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/uso terapêuticoRESUMO
A selection of wild plants collected in Valsesia (Northwest Italy) was screened for their in vitro antioxidant activity. Aerial parts of selected plants were dried at room temperature and powdered. Then, four sequential extractions were performed with increasing polarity solvents, i.e. n-hexane, chloroform, chloroform-methanol (9:1, v/v) and methanol. By employing different assays, it was shown that all the methanol extracts of the samples collected were endowed with antioxidant activity, though, as expected, their potency varied according to the different tests. In particular, plants of the Thymus and Achillea genus displayed the highest activity. Given that a diet rich in wild plants is associated with a reduced incidence of degenerative diseases, such as atherosclerosis and cancer, this study suggests that some Valsesia plants could be pharmaceutically exploited.
Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Plantas/química , Achillea/química , Artemisia/química , Cardamine/química , Gentiana/química , Itália , Extratos Vegetais/química , Timo/química , Valeriana/químicaRESUMO
We used the yeast estrogen screen (YES) containing a human estrogen receptor to evaluate the estrogenic activity of extracts obtained from Nigella damascena seeds. Alcohol extracts obtained by direct extraction of seeds showed a low estrogenic activity, while the alcohol extract obtained after extraction with solvents of increasing polarity showed a strong estrogenic activity. This suggests the presence in Nigella of polar components whose activity can be clearly demonstrated after previous elimination of interacting apolar components that may mask the activity of more polar components. The response of both alcohol fractions follow a bell-shaped curve indicating a concentration-dependent relationship.
Assuntos
Estrogênios não Esteroides/isolamento & purificação , Estrogênios não Esteroides/farmacologia , Nigella damascena/química , Receptores de Estrogênio/metabolismo , Saccharomyces cerevisiae/genética , Expressão Gênica , Genes Reporter , Genisteína/farmacologia , Humanos , Isoflavonas/farmacologia , Fitoestrógenos , Extratos Vegetais/farmacologia , Preparações de Plantas , Plantas Medicinais/química , Receptores de Estrogênio/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Sementes/químicaRESUMO
The activity concentrations of soil and sediment samples are determined by alpha spectrometry with a sample size usually < 1 g. Hence, a systematic and careful procedure must be followed in the sampling and pre-treatment of the sample in order to ensure that the aliquot analysed represents the activity concentration of the entire sample. Statistical analyses of the activity concentrations of uranium and thorium isotopes in soil and sediment samples were performed to study the activity variation due to the lack of the representativity of the sample. These studies showed that, although some uncertainty in the determination of the sample activity concentration may be due to the lack of representativity (about 10%), the procedure followed for the pre-treatment of the sample can be considered adequate, providing an acceptable level of representativity.
RESUMO
The linearity assumption for soil and plant concentrations of radionuclides is usually a good approximation for use in food-chain models. To verify this assumption, different samples of plant and substrate were collected from a granitic zone located near a disused uranium mine in order to cover a large range of concentrations. In all of the samples, the activity concentration of 226Ra and of different isotopes of uranium (238U and 234U) and thorium (232Th, 230Th and 228Th) were determined. The results indicate that the linearity assumption can be considered valid when the range of concentrations taken into account is large (approx. two orders of magnitude). Otherwise, there is a clear deviation from linearity. Also, the influence of different stable elements on the soil-plant transfer factors was studied by using multivariate regression methods. The uptake of uranium, thorium and radium was found to be mainly associated with the concentration of iron in the plant and the phosphorus and alkaline earths in the substrate.
Assuntos
Cadeia Alimentar , Radônio/farmacocinética , Poluentes Radioativos do Solo/farmacocinética , Modelos Teóricos , Fósforo/química , Tório/farmacocinética , Distribuição Tecidual , Urânio/farmacocinéticaRESUMO
The authors report a case of congenital muscular dystrophy with mild nonprogressive muscle weakness, white matter hypodensity, and absence of the laminin alpha2 chain in muscle fibers with two antibodies, but not with four others. They identified mutations in LAMA2, which explain the partial laminin alpha2 deficiency. Analysis of this case and two others allows us to refine the epitopes of two of the commercial antibodies, and illustrate the importance of using antibodies directed against different domains of the protein.
Assuntos
Laminina/genética , Distrofias Musculares/genética , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Biópsia , Criança , Pré-Escolar , Epitopos/imunologia , Humanos , Imuno-Histoquímica , Laminina/deficiência , Laminina/imunologia , Masculino , Músculo Esquelético/patologia , Distrofias Musculares/congênito , Distrofias Musculares/patologia , Mutação , FenótipoRESUMO
We used a yeast estrogen screen (YES) containing human estrogen receptor to evaluate the estrogenic activity of both crude extracts and simple pure phenolic compounds from Nigella damascena seeds. Estrogenic activity was established in the methanolic and aqueous extracts of the seeds as well as in two simple phenolic compounds isolated from the methanolic extract, 2,4-dihydroxyphenylacetic acid, 3,4-dihydroxy-beta-phenethyl alcohol.
Assuntos
Estrogênios/farmacologia , Magnoliopsida/química , Fenilacetatos/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Fatores Estimuladores de Colônias/efeitos dos fármacos , Estrogênios/química , Estrogênios/isolamento & purificação , Humanos , Óperon Lac , Fenilacetatos/química , Fenilacetatos/isolamento & purificação , Álcool Feniletílico/química , Álcool Feniletílico/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes , Saccharomyces cerevisiaeRESUMO
A quantitative analysis of deltoid muscle biopsy specimens was performed by light microscopy in 26 males and 25 females aged 50-79 years without known neuromuscular disease. Muscle fibre size, fibre type distribution and increase in mitochondrial content in muscle fibres were examined using a semi-automatic image analysis system. This study showed significant age- and gender-related differences. In females, there was marked atrophy of type II fibres with increasing age, specially of type IIb fibres, but no significant change in muscle fibre type distribution. In males, there was diminution in the relative proportion of type IIb fibres with increasing age but no significant muscle fibre atrophy. Mitochondrial aggregates increased with age, and this increase was observed earlier in females than in males. The gender-related morphological changes observed in the present study differ somewhat from those reported in the literature. The differences between males and females may be partially related to gender differences in muscular activity and may reflect an earlier decline in deltoid muscle strength in females. The existence of these age and gender changes should be taken into account in the interpretation of muscle biopsies of aged individuals.
Assuntos
Desenvolvimento Muscular , Músculo Esquelético/crescimento & desenvolvimento , Fatores Etários , Idoso , Biópsia , Tamanho Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/ultraestrutura , Fibras Musculares Esqueléticas/ultraestrutura , Músculo Esquelético/ultraestrutura , Valores de Referência , Fatores Sexuais , Coloração e RotulagemRESUMO
The very low yields obtained in a common method of alpha-particle spectrometry for the determination of uranium and thorium in soil and sediment samples of environmental origin were investigated. Several experiments were performed to determine the cause. The results suggest that aluminium may cause major chemical interference in the electrodeposition process, and can be considered to be primarily responsible for the low recoveries found. A procedure is proposed to resolve this problem.
Assuntos
Sedimentos Geológicos/análise , Poluentes Radioativos do Solo/análise , Solo/análise , Tório/análise , Urânio/análise , Partículas alfa , Alumínio , Artefatos , Eletroquímica/métodos , Reprodutibilidade dos Testes , Análise EspectralRESUMO
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. The autosomal dominant form of the disease is caused by short (GCG)(8-13) expansions in the PABP2 gene. This gene encodes the poly(A) binding protein 2 (PABP2), an abundant nuclear protein that binds with high affinity to nascent poly(A) tails, stimulating their extension and controlling their length. In this work we report that PABP2 is detected in filamentous nuclear inclusions, which are the pathological hallmark of OPMD. Using both immunoelectron microscopy and fluorescence confocal microscopy, the OPMD-specific nuclear inclusions appeared decorated by anti-PABP2 antibodies. In addition, the inclusions were labeled with antibodies directed against ubiquitin and the subunits of the proteasome and contained a form of PABP2 that was more resistant to salt extraction than the protein dispersed in the nucleoplasm. This suggests that the polyalanine expansions in PABP2 induce a misfolding and aggregation of the protein into insoluble inclusions, similarly to events in neurodegenerative diseases caused by CAG/polyglutamine expansions. No significant differences were observed in the steady-state poly(A) tail length in OPMD and normal myoblasts. However, the nuclear inclusions were shown to sequester poly(A) RNA. This raises the possibility that in OPMD the polyalanine expansions in the PABP2 protein may interfere with the cellular traffic of poly(A) RNA.
Assuntos
Núcleo Celular/patologia , Corpos de Inclusão/patologia , Distrofias Musculares/patologia , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Núcleo Celular/química , Núcleo Celular/ultraestrutura , Cisteína Endopeptidases/metabolismo , Humanos , Hibridização In Situ , Corpos de Inclusão/química , Corpos de Inclusão/ultraestrutura , Microscopia Imunoeletrônica , Complexos Multienzimáticos/metabolismo , Distrofias Musculares/metabolismo , Proteínas de Ligação a Poli(A) , Complexo de Endopeptidases do Proteassoma , Ligação Proteica , RNA Mensageiro/química , Proteínas de Ligação a RNA/químicaRESUMO
Autosomal recessive limb girdle muscular dystrophies 2C-2F represent a family of diseases caused by primary mutations in the sarcoglycan genes. We show that sarcospan, a novel tetraspan-like protein, is also lost in patients with either a complete or partial loss of the sarcoglycans. In particular, sarcospan was absent in a gamma-sarcoglycanopathy patient with normal levels of alpha-, beta- and delta-sarcoglycan. Thus, it is likely that assembly of the complete, tetrameric sarcoglycan complex is a prerequisite for membrane targeting and localization of sarcospan. Based on our findings that sarcospan is integrally associated with the sarcoglycans, we screened >50 autosomal recessive muscular dystrophy cases for mutations in sarcospan. Although we identified three intragenic polymorphisms, we did not find any cases of muscular dystrophy associated with primary mutations in the sarcospan gene. Finally, we have identified an important case of limb girdle muscular dystrophy and cardiomyopathy with normal expression of sarcospan. This patient has a primary mutation in the gamma-sarcoglycan gene, which causes premature truncation of gamma-sarcoglycan without affecting assembly of the mutant gamma-sarcoglycan into a complex with alpha-, beta- and delta-sarcoglycan and sarcospan. This is the first demonstration that membrane expression of a mutant sarcoglycan-sarcospan complex is insufficient in preventing muscular dystrophy and cardiomyopathy and that the C-terminus of gamma-sarcoglycan is critical for the functioning of the entire sarcoglycan-sarcospan complex. These findings are important as they contribute to a greater understanding of the structural determinants required for proper sarcoglycan-sarcospan expression and function.
Assuntos
Proteínas de Transporte/metabolismo , Aberrações Cromossômicas/genética , Proteínas do Citoesqueleto/metabolismo , Distrofina/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Distrofias Musculares/genética , Proteínas de Neoplasias , Adulto , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Proteínas de Transporte/genética , Aberrações Cromossômicas/metabolismo , Transtornos Cromossômicos , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Éxons , Feminino , Imunofluorescência , Genes Recessivos , Humanos , Masculino , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Distrofias Musculares/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo Genético , Ligação Proteica , SarcoglicanasRESUMO
The preparation of a range of open analogues of arcyriaflavin A is described. The synthetic approach is based on the use of perhydroisoindole-1,3,5-triones as key intermediates, which were obtained via Diels-Alder methodology using 1-aryl-3-siloxy-1, 3-butadienes as starting materials. Fischer indolization and aromatization processes afforded different methoxy-substituted arylpyrrolocarbazoles. The stereochemistry and conformation of the Diels-Alder products and the regiochemistry of the indolization reactions are supported by NMR and molecular modeling studies.
Assuntos
Antineoplásicos/síntese química , Butadienos/síntese química , Carbazóis/síntese química , Maleimidas/química , Benzaldeídos/química , Hidrazinas/química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Streptomyces/químicaRESUMO
Two familial cases of a myopathy remarkable by the presence of a granulo-filamentar, electron dense material were reported in 1978. In a second step, in 1988, it was demonstrated that this material contained an abnormally-phosphorylated desmin. During the last twenty years, the occurrence of new cases in this family confirmed the autosomal dominant inheritance of the disease, and made it potentially informative for molecular genetics studies. This allowed first to map the disease on chromosome11q21-23, and afterwards to identify a mutation within a gene coding for a chaperone protein, alphaBcrystallin. An extensive clinical, pathological and genetic study of this princeps family is herein reported in detail. First, it showed the possible detection of histopathological changes in presymptomatic patients. Second, it allowed to demonstrate the simultaneous occurrence of both alphaBcrystallin and desmin in the granulo-filamentar aggregates. Third, this study provided a precise knowledge of the evolution rate of the disease. The analysis of similar observations reported in the literature clearly shows the clinical, pathological and genetic heterogeneity of this new neuro-muscular disorder.
Assuntos
Citoesqueleto de Actina/genética , Cristalinas/genética , Grânulos Citoplasmáticos/genética , Desmina/genética , Miopatias Congênitas Estruturais/genética , Citoesqueleto de Actina/patologia , Adulto , Idoso , Biópsia , Grânulos Citoplasmáticos/patologia , Feminino , Seguimentos , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Miopatias Congênitas Estruturais/diagnóstico , Miopatias Congênitas Estruturais/patologia , LinhagemRESUMO
We report 21 French patients (12 males and 9 females), presenting a distal myopathy of Miyoshi type. The main clinical features of these patients were 1) onset in late adolescence or early adulthood (mean age: 20.3 years), 2) early and predominant involvement of the posterior compartment muscles of legs, 3) marked elevation of serum CK (from 10 to 50 times the normal value), 4) dystrophic features with a necrotic regeneration pattern without vacuole in muscle biopsy. All cases were sporadic and a consanguinity of parents was found in five cases. The clinical course was relatively mild: twelve patients could walk without aid; However four patients were severely disabled. Four patients were initially considered as having polymyositis; corticosteroids and immunosuppressive drugs were always inefficient. A genetic linkage to chromosome 2 was ascertained in five cases. In our experience the Miyoshi distal myopathy is the most common form of distal myopathy, particularly in young patients.
Assuntos
Distrofias Musculares/diagnóstico , Distrofias Musculares/epidemiologia , Adolescente , Adulto , Idade de Início , Feminino , França/epidemiologia , Humanos , Incidência , Perna (Membro) , Masculino , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofias Musculares/fisiopatologia , CaminhadaRESUMO
A new procedure for the determination of uranium, thorium and 226Ra from the same aliquot of an aqueous sample using extractant scintillators and liquid scintillation alpha spectrometry is proposed. The procedure is designed such that the same aqueous phase can be used in all the stages, with slight modifications. The procedure is thus very simple, requiring little manipulation of the sample. Testing of the procedure was performed obtaining satisfactory results and high reproducibility.
Assuntos
Monitoramento Ambiental/métodos , Nêutrons , Espectrometria gama/métodosRESUMO
Rigid spine syndrome is a neuromuscular disorder characterised by early rigidity of the spine due to axial muscle contractures, generally associated with muscle weakness, limb-joint contractures, and often respiratory failure. This phenotype may be associated with several muscular diseases. In cases of merosin-positive congenital muscular dystrophies (CMD) with rigid spine syndrome, we have recently identified a new locus (RSMD1) on chromosome 1p35-36. In the present study, we report the clinical, morphological and genetic analysis of other patients affected by a CMD with rigid spine syndrome from nine consanguineous families. Homozygosity mapping showed that the disease was linked to RSMD1 in one of the nine families. The other families were excluded from RSMD1, and the patients presented highly variable phenotypes suggesting the involvement of more than one gene defect in rigid spine syndrome. Nevertheless, a subgroup of patients who never walked, and had very early rigidity of the spine and scoliosis, may be considered for further genetic analysis.
Assuntos
Cromossomos Humanos Par 1 , Rigidez Muscular/genética , Distrofias Musculares/genética , Escoliose/genética , Doenças da Coluna Vertebral/genética , Adulto , Idade de Início , Biópsia , Criança , Mapeamento Cromossômico , Consanguinidade , DNA/sangue , DNA/genética , Feminino , Homozigoto , Humanos , Masculino , Rigidez Muscular/patologia , Distrofias Musculares/complicações , Distrofias Musculares/patologia , Núcleo Familiar , Linhagem , Escoliose/complicações , Doenças da Coluna Vertebral/patologia , SíndromeRESUMO
Laminin-2 is part of the basement membrane of the skeletal muscle fibers. The laminin alpha 2 chain is absent or drastically reduced in a subgroup of congenital muscular dystrophy patients, and in the severely affected dystrophic dy/dy mouse. We previously reported that heterogeneous primary mouse muscle cell cultures conferred laminin alpha 2 chain expression in dy/dy mice muscles upon cell transplantation. In the present study we investigated whether pure myoblast cell lines were able to confer laminin alpha 2 chain expression in vivo. We observed that: (1) xeno-transplantation of non-immortalized human myoblast in SCID mouse muscles allows human laminin alpha 2 chain expression; (2) allotransplantation of the permanent G8 mouse myoblast cell line in dy/dy muscles allows the expression of the murine laminin alpha 2 chain; and (3) allo-transplantation of the D7 dystrophic dy/dy cell line allows the formation of new and hybrid muscle fibers in dy/dy muscle in the absence of laminin alpha 2 chain expression. We conclude that normal myoblasts are able to restore the expression of an extracellular skeletal muscle protein and that the absence of laminin-2 does not prevent transplanted muscle cells from participating in the formation of myofibers. Myoblasts are, therefore, attractive tools for further exploration of gene complementation strategies in the animal models of congenital muscular dystrophy.