RESUMO
The reactivity of 6-(nitrophenyl or trimethoxyphenyl)-4-tert-butyldimethyl- siloxy-1,2,3,6-tetrahydropyridine derivatives with hydrazines under acid conditions is described. The structure of the products isolated - hydrazones, pyrazolines or pyridazinones - depended on the conditions used. In addition, a systematic study of the reaction outcomes was carried out by introducing variations on the substituents of the tetrahydropyridine ring.
Assuntos
Hidrazinas/química , Piridinas/química , Siloxanas/química , Isótopos de Carbono , Espectroscopia de Ressonância Magnética , PrótonsRESUMO
The congenital muscular dystrophies (CMD) are clinically and genetically heterogeneous. The merosin (laminin alpha2 chain) deficient form (MDC1A), is characterized clinically by neonatal hypotonia, delayed motor milestones and associated contractures. It is caused by deficiency in the basal lamina of muscle fibers of the alpha2 chain of laminins 2 and 4 (LAMA2 gene at 6q22-23). Laminin alpha2 chain is also expressed in fetal trophoblast, which provides a suitable tissue for prenatal diagnosis in families where the index case has total deficiency of the protein. This article reports the collective experience of five centers over the past 10 years in 114 prenatal diagnostic studies using either protein analysis of the chorionic villus (CV) of the trophoblast plus DNA molecular studies with markers flanking the 6q22-23 region and intragenic polymorphisms (n=58), or using only DNA (n=44) or only protein (n=12) approaches. Of the 102 fetuses studied by molecular genetics, 27 (26%) were predicted to be affected while 75 (74%) were considered as unaffected, with 52 (51%) being heterozygous, thus conforming closely to an autosomal recessive inheritance. In 18 of the 27 affected fetuses, the trophoblast was studied by immunocytochemistry and there was a total or only traces deficiency of the protein in CV basement membrane in all. In 10 cases material from the presumably affected fetus was available for analysis after termination of the pregnancy and immunohistochemical study confirmed the diagnosis in all of them. Prenatal studies of 'at risk' pregnancies in the five centers produced neither false negative (merosin-deficiency in CVs in a normal fetus), nor false positive (normal merosin expression in CVs and affected child), indicating the reliability of the technique, when all the necessary controls are done. Our experience suggests that protein and DNA analysis can be used either independently or combined, according to the facilities of each center, to provide accurate prenatal diagnosis of the MDC1A, and have an essential role in genetic counseling.
Assuntos
Laminina/deficiência , Laminina/genética , Distrofias Musculares/genética , Líquido Amniótico/citologia , Feminino , Triagem de Portadores Genéticos , Aconselhamento Genético , Humanos , Recém-Nascido , Masculino , Distrofias Musculares/congênito , Distrofias Musculares/etiologia , Linhagem , Polimorfismo de Nucleotídeo Único , Gravidez , Diagnóstico Pré-NatalRESUMO
Several hydroindenic derivatives (7a-methyl-2,3,5,6,7,7a-hexahydro-1H-indenes), bearing an amidinohydrazone at C-5 and different moieties at C-1, have been synthesized and evaluated for their inotropic and chronotropic effects on right- and left-guinea-pig-atria activity. Three of them showed the same profile as digoxin, although with lower potency. The effect on Na(+),K(+)-ATPase (NKA) was also evaluated for these three compounds, observing that two of them, with the same absolute configuration as natural cardenolides, are also NKA inhibitors, while the compound with the opposite configuration lacks such an effect. More interestingly, both active compounds act without affecting the cardiac rhythm. This could be related to the selective inhibition of the human alpha2beta1 isozyme (associated with the inotropic effect) with respect to the alpha1beta1 isozyme (associated with the maintenance of basal ionic levels in the cell and the toxic effect of cardenolides).
Assuntos
Cardiotônicos/síntese química , Hidrazonas/síntese química , Indenos/síntese química , Amidinas/síntese química , Amidinas/química , Amidinas/farmacologia , Animais , Transporte Biológico , Cardiotônicos/química , Cardiotônicos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Feminino , Cobaias , Coração/efeitos dos fármacos , Coração/fisiologia , Frequência Cardíaca , Humanos , Hidrazonas/química , Hidrazonas/farmacologia , Técnicas In Vitro , Indenos/química , Indenos/farmacologia , Isoenzimas/metabolismo , Masculino , Contração Miocárdica , Oócitos/metabolismo , Ratos , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Transfecção , Xenopus laevisRESUMO
We report the case of a patient followed since childhood for congenital complete atrioventricular block. At 28 years of age, atrioventricular conduction through an accessory pathway with long conduction times was detected. Periods of atrioventricular conduction alternated with periods of atrioventricular block. Sinus tachycardia and 1:1 exclusive conduction through the accessory pathway developed with increased sympathic activity (exercise, isoproterenol infusion). We discuss the special features of this case.
Assuntos
Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/complicações , Síndrome de Wolff-Parkinson-White/congênito , Síndrome de Wolff-Parkinson-White/complicações , Adulto , Eletrocardiografia , Bloqueio Cardíaco/fisiopatologia , Humanos , Masculino , Síndrome de Wolff-Parkinson-White/fisiopatologiaRESUMO
An array of 4-(aryl or indolyl)pyrrolo[3,4-c]carbazole-1,3-diones (open analogues of indolocarbazole alkaloids), 10-(aryl or indolyl)pyrrolo[3,4-b]carbazole-1,3-diones, and different derivatives have been prepared using a Diels-Alder plus Fischer indolization approach and tested as cytotoxic agents. Some representative compounds display interesting cytotoxic profiles.