RESUMO
Glypicans represent a family of cell surface proteoglycans. Loss-of-function mutations in the human glypican-3 (GPC3) gene results in the Simpson-Golabi-Behmel syndrome, characterized by severe malformations and pre- and postnatal overgrowth. Because the expression of GPC3 during human embryonic and fetal periods remains largely unknown, we investigated by immunohistochemistry its pattern of expression during four periods of human development covering the embryonic period (P1) from 5 to 8 weeks of development, and the fetal periods (P2, P3 and P4) from 9 to 28 weeks of development. Hepatocytes were homogeneously positive for GPC3 during the four periods while pancreatic acini and ducts showed a rather high staining only during P1. GPC3 was also detected in several kidney structures and in the genital system where the sex cords were weakly positive in P1 and P2. In later developmental stages the male's genital system expressed GPC3 while the female's did not. While the mesenchyme in the limbs showed positive staining in P1, GPC3 was not detected during the following stages. The mesenchymal tissue localized between the most caudal vertebrae was also positive in P1. A strong GPC3 signal was observed in neurons of the spinal cord and dorsal root ganglia in P2 and P3, while the brain was negative. In sum our studies revealed that GPC3 expression is highly tissue- and stage-specific during human development. The expression pattern of GPC3 is consistent with the abnormalities seen in the Simpson-Golabi-Behmel syndrome.
Assuntos
Embrião de Mamíferos/metabolismo , Feto/metabolismo , Glipicanas/metabolismo , Anormalidades Múltiplas/metabolismo , Animais , Feminino , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Idade Gestacional , Humanos , Imuno-Histoquímica , Masculino , Mesoderma/metabolismo , Camundongos , Músculo Esquelético/embriologia , Músculo Esquelético/metabolismo , Sistema Nervoso/embriologia , Sistema Nervoso/metabolismo , Sistema Respiratório/embriologia , Sistema Respiratório/metabolismo , Síndrome , Fatores de Tempo , Sistema Urogenital/embriologia , Sistema Urogenital/metabolismoRESUMO
The concentrations of lopinavir and ritonavir in seminal and blood plasma and the seminal human immunodeficiency virus (HIV) viral load were quantified by HPLC and the Nuclisens assay, respectively, in a cross-sectional study of 16 HIV-1-infected Brazilian men under stable treatment with a lopinavir/ritonavir containing antiretroviral regimen. Semen and blood samples were collected on 2 occasions: at 6 to 60 minutes before ("trough"), and 5 to 6 hours after ("peak") ingestion of regular doses of lopinavir/ritonavir. Median seminal lopinavir levels were 120.6 ng/mL (range, <20-1481.8 ng/mL) and 233.1 ng/mL (range, 48.4-1133.4 ng/mL) at trough and peak points, respectively. The corresponding values for ritonavir were 9.2 ng/mL (range, <5-47 ng/mL) and 17.1 ng/mL (range, 6.6-66.7 ng/mL). The median concentrations of lopinavir and ritonavir in semen were, respectively, 1.9% to 3% and 3.7% to 4.4% of those measured in blood plasma samples collected within 30 minutes. HIV-1 viral load was detectable in the semen of 2 and in the blood of 6 of 16 patients. These results may have implications for drug-resistant HIV-1 evolution and transmission.
Assuntos
Infecções por HIV/tratamento farmacológico , Pirimidinonas/farmacocinética , Ritonavir/farmacocinética , Sistema Urogenital/metabolismo , Disponibilidade Biológica , Brasil , Estudos Transversais , Infecções por HIV/sangue , Infecções por HIV/virologia , Inibidores da Protease de HIV/sangue , Inibidores da Protease de HIV/farmacocinética , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/crescimento & desenvolvimento , Humanos , Lopinavir , Masculino , Pirimidinonas/sangue , Pirimidinonas/uso terapêutico , Análise de Regressão , Ritonavir/sangue , Ritonavir/uso terapêutico , Sêmen/química , Sêmen/efeitos dos fármacos , Fatores de Tempo , Sistema Urogenital/efeitos dos fármacos , Carga ViralRESUMO
It is well conceived that the intention of man in trying to solve human kind ailments, is being a long standing biological rule to give rational solutions at any rate. The response to the current problem studied, approaches a different view of the peripheral and local deteriorating phenomena and offers--in a non classical way--how to maintain the well-being of a population of otherwise healthy women, in trying to defer the degenerative cellular process. Interesting, as the proximity of the XXI century arrives, the technology and the biomedical level of progress seems to be for a way from the ideal, particularly when dealing with a process initiated years before the menopause. This critical period of hormonal imbalance makes also a definite++ e social change for women; such a combination of facts, prompt us to be aware that in society, a women is no longer biologically reproductive but certainly, productive, as an economical drive digure. Needless to say that we must be protective to her and to realize that the number of them will continue to an increase in the years to come. The following two comments intended to associate various levels of the current knowledge of one of the Public Health problems in women.