RESUMO
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The penetrance is incomplete and it is age and gender dependent. It is accepted as a disease of the sarcomere. Sixty percent of HCM cases carry mutations in 1 of 8 sarcomere protein genes, mainly non-sense MYBPC3 and missense MYH7 variants. Young patients with severe phenotype and other clinical features are included in proposed scores for prediction of high positive genetic result. The number of genes reported as disease-causing has increased in the last few years, in some cases without robust evidence. Currently available in silico tools are not always useful for differentiation between benign and deleterious variants. There is enough information on genotype-phenotype correlations to start understanding the mechanisms of the disease. Genetic and environmental modifiers have been explored with some interesting insights from miRNA studies with potential as biomarkers and therapeutic agents. There is an additional value of genetic testing in HCM for prognosis. Knowledge about genetics and functional studies are the basis of near future therapies.
Assuntos
Cardiomiopatia Hipertrófica/genética , Predisposição Genética para Doença/genética , Mutação , Sarcômeros/genética , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Morte Súbita Cardíaca/etiologia , Estudos de Associação Genética , Testes Genéticos , HumanosRESUMO
Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The heart was the main organ involved. Affected adult males had mild hypertrophy, systolic dysfunction and restriction with non-dilated ventricles. Carriers had significant QTc prolongation. The proband presented with resuscitated cardiac arrest. There were two transplants. Pathological study of explanted heart showed fibrofatty replacement and scarring consistent with arrhythmogenic cardiomyopathy and prominent left ventricular trabeculations. Myopathic involvement was evident in all males. Females had no significant neuromuscular disease. Mutations in FHL1 cause unclassifiable cardiomyopathy with coexisting EDMD. Prognosis is poor and systolic impairment and arrhythmias are frequent. Thrombopenia and raised creatine phosphokinase should raise suspicion of an FHL-1 disorder in X-linked cardiomyopathy.
Assuntos
Arritmias Cardíacas/genética , Cardiomiopatia Dilatada/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas com Domínio LIM/genética , Proteínas Musculares/genética , Distrofia Muscular de Emery-Dreifuss/genética , Mutação , Adolescente , Adulto , Idoso , Arritmias Cardíacas/complicações , Arritmias Cardíacas/patologia , Arritmias Cardíacas/cirurgia , Biomarcadores/sangue , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/cirurgia , Criança , Pré-Escolar , Creatina Quinase/sangue , Análise Mutacional de DNA , Feminino , Expressão Gênica , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular de Emery-Dreifuss/complicações , Distrofia Muscular de Emery-Dreifuss/patologia , Distrofia Muscular de Emery-Dreifuss/cirurgia , Miocárdio/metabolismo , Miocárdio/patologia , Linhagem , Fatores Sexuais , Trombocitopenia/fisiopatologia , Remodelação VentricularRESUMO
Maternal milk is the first source of exogenous polyamines for the newborn. Polyamines modulate gut maturation in neonates, but no studies are available on polyamine concentration in human milk of preterm babies, even though they could be important for their immature gut. The present study aimed to determine polyamine concentration in human breast milk of mothers with preterm or term infants during the first month of lactation. Human milk samples were obtained during the first month of lactation from twenty-seven mothers with preterm babies and twelve mothers with babies born at term. The polyamine concentration in human milk was quantified by HPLC. During the first month of lactation, the total polyamine concentration was significantly higher in preterm milk than in term milk samples (7590 (SD 4990) v. 4660 (SD 4830) nmol/l, respectively (P » 0·034)), as well as individual polyamine concentrations. Polyamine concentration in mature milk for preterm babies was significantly higher than that in mature milk for babies at term, and a similar trend was observed in colostrum and transition human milk. The spermidine/spermine ratio was higher in transition milk in preterm v. term samples, while in mature milk, the ratio was significantly lower in preterm than in term babies. In conclusion, the polyamine concentration was significantly higher in human milk for preterm than for term infants. This and the different spermidine/spermine ratios could influence the gut development of premature babies.
Assuntos
Aleitamento Materno , Recém-Nascido Prematuro , Lactação , Leite Humano/química , Poliaminas/análise , Espermidina/análise , Espermina/análise , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Fructooligosaccharides (FOS) are oligosaccharides that occur naturally in plants such as onion, chicory, garlic, asparagus, banana, artichoke, among many others. They are composed of linear chains of fructose units, linked by beta (2-1) bonds. The number of fructose units ranges from 2 to 60 and often terminate in a glucose unit. Dietary FOS are not hydrolyzed by small intestinal glycosidases and reach the cecum structurally unchanged. There, they are metabolized by the intestinal microflora to form short-chain carboxylic acids, L -lactate, CO(2), hydrogen and other metabolites. FOS have a number of interesting properties, including a low sweetness intensity; they are also calorie free, non-cariogenic and are considered as soluble dietary fibre. Furthermore, FOS have important beneficial physiological effects such as low carcinogenicity, a prebiotic effect, improved mineral absorption and decreased levels of serum cholesterol, triacylglycerols and phospholipids. Currently FOS are increasingly included in food products and infant formulas due to their prebiotic effect stimulate the growth of nonpathogenic intestinal microflora. Their consumption increases fecal bolus and the frequency of depositions, while a dose of 4-15 g/day given to healthy subjects will reduce constipation, considered one of the growing problems of modern society, and newborns during the first months of life.
Assuntos
Carboidratos da Dieta/farmacologia , Oligossacarídeos/farmacologia , Oligossacarídeos/uso terapêutico , Prebióticos , Glicemia/efeitos dos fármacos , Sequência de Carboidratos , Neoplasias do Colo/prevenção & controle , Constipação Intestinal/tratamento farmacológico , Ácidos Graxos Voláteis/metabolismo , Humanos , Sistema Imunitário/efeitos dos fármacos , Lactente , Fórmulas Infantis/química , Recém-Nascido , Insulina/sangue , Absorção Intestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Leite Humano , Minerais/metabolismoRESUMO
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Fructooligosaccharides (FOS) are oligosaccharides that occur naturally in plants such as onion, chicory, garlic, asparagus, banana, artichoke, among many others. They are composed of linear chains of fructose units, linked by beta (2-1) bonds. The number of fructose units ranges from 2 to 60 and often terminate in a glucose unit. Dietary FOS are not hydrolyzed by small intestinal glycosidases and reach the cecum structurally unchanged. There, they are metabolized by the intestinal microflora to form short-chain carboxylic acids, L -lactate, CO2, hydrogen and other metabolites. FOS have a number of interesting properties, including a low sweetness intensity; they are also calorie free, non-cariogenic and are considered as soluble dietary fibre. Furthermore, FOS have important beneficial physiological effects such as low carcinogenicity, a prebiotic effect, improved mineral absorption and decreased levels of serum cholesterol, triacylglycerols and phospholipids. Currently FOS are increasingly included in food products and infant formulas due to their prebiotic effect stimulate the growth of nonpathogenic intestinal microflora. Their consumption increases fecal bolus and the frequency of depositions, while a dose of 415 g/day given to healthy subjects will reduce constipation, considered one of the growing problems of modern society, and newborns during the first months of life (AU)