RESUMO
Crystallographic structures of NGF/p75NTR and proNGF/p75NTR were previously obtained in 2:1 and 2:2 stoichiometries, respectively. However, evidence shows that both stoichiometries can occur for mature neurotrophins and pro-neurotrophins. We used Molecular Dynamics (MD) simulations to examine the energetic and structural characteristics of these two complete systems as well as the uncomplexed forms of NGF and understand how these could translate in a new view of different biological outcomes. Here, we show that one chain at the 2:2 proNGF complex seems to be preferentially lost creating a 2:1 structure able to interact with sortilin. We also demonstrated that the structure of the neurotrophin dimers is not pre-established and suffers large structural modifications upon p75NTR binding. Moreover, our data suggests an elegant explanation for the dual role of NGF in neuronal cell death and survival, where different stoichiometries induce conformational changes that might be the basis for the different biological outcomes observed with the mature and proforms of neurotrophins.
Assuntos
Simulação de Dinâmica Molecular , Fator de Crescimento Neural/química , Fator de Crescimento Neural/metabolismo , Multimerização Proteica , Precursores de Proteínas/química , Precursores de Proteínas/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Ligação Proteica , Estrutura Quaternária de Proteína , Receptor de Fator de Crescimento Neural/química , TermodinâmicaRESUMO
The authors illustrate the possibilities for intrauterine diagnosis of congenital heart disease stressing limits and possibilities.
Assuntos
Doenças Fetais/diagnóstico , Cardiopatias Congênitas/diagnóstico , Diagnóstico Pré-Natal/métodos , Feminino , Humanos , GravidezRESUMO
The authors studied a case of idiopathic hypereosinophilic syndrome emphasizing clinical manifestations and therapy.
Assuntos
Eosinofilia/etiologia , Eosinofilia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , SíndromeRESUMO
A qualitative and quantitative assessment of respiratory deficiency in patients with N.Y.H.A. Class II mitral stenosis is presented with the standard screening of respiratory mechanics providing the parameters.
Assuntos
Estenose da Valva Mitral/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Fluxo Expiratório Máximo , Pessoa de Meia-Idade , Estenose da Valva Mitral/complicações , Insuficiência Respiratória/etiologia , Capacidade VitalRESUMO
The actual practice of immunoprophylaxis in a Sanitary District of Campania (Italy) is described. As everywhere in Italy, in subjects at risk (wounded) the passive immunoprophylaxis by human specific immunoglobins is currently applied: at very high cost and with unreliable protection. The Authors suggest to implement antitetanus mass vaccination, with benefits incoming from lower expenses and higher protection.
Assuntos
Toxoide Tetânico/uso terapêutico , Tétano/prevenção & controle , Vacinação , Adolescente , Adulto , Feminino , Política de Saúde , Humanos , Imunização Passiva , Masculino , Toxoide Tetânico/imunologiaAssuntos
Pancreatite/cirurgia , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnósticoAssuntos
Diafragma/lesões , Hérnia Diafragmática Traumática/etiologia , Adolescente , Adulto , Idoso , Criança , Diafragma/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , RupturaAssuntos
Doenças Cardiovasculares/etiologia , Hiperlipidemias/complicações , Hipertensão/etiologia , Lipídeos/sangue , Menopausa , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , Estrogênios/sangue , Feminino , Humanos , Lipoproteínas/sangue , Pessoa de Meia-Idade , Fosfolipídeos/sangue , RiscoRESUMO
The people influence of body weight on the climacteric symptoms of 618 selected women in spontaneous post-menopause has been studied bases on data collected at a Geriatric Centre and subsequently incorporated into a postal questionnaire. These cases were divided into 3 groups according to the "obesity degree": (I) less than 5 kg (53.1% of the cases);(II) between 5 and 15 kg (31.7%); and (III) greater than 15 kg (15.2%). The data were also analysed according to the socio-economic groups to which the women belonged. Overweight women, compared with thin women, seemed to suffer less "somatic" symptoms such as hot flushes and perspiration, independently of their socio-economic level. This might well be a consequence of the higher endogenous oestrogen activity. On the contrary, "psychic" symptoms (anxiety, depression, irritability, crying spells) seemed to be more frequent and severe (a) in the "obesity degree" sub-group III, compared with sub-groups I and II, in the women belonging to the higher socio-economic group, and (b) in the sub-groups I and III, compared with sub-group II, in the women belonging to the lower socio-economic group. Such a difference between the socio-economic groups is possibility due to cultural factors. The effects of endogenous oestrogens in the overweight women seem to be easily overruled by the influence of psychological factors.
Assuntos
Peso Corporal , Climatério , Classe Social , Idoso , Estrogênios/fisiologia , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Obesidade/psicologia , Inquéritos e QuestionáriosRESUMO
The effects on blood-clotting factors, plasma lipids and endometrial proliferation of two types of oral oestrogen therapy (a) cyclical therapy with 0.625 mg/day conjugated equine oestrogens for 3 wk followed by 1 wk without treatment, and (b) continuous therapy with 2 mg/day oestriol) were investigated in a 5-mth study involving 22 post-menopausal women. Assays were performed in order to measure blood-clotting factors (activity of the factor II-VII-X complex, anti-thrombin III, euglobulin lysis time) and plasma lipids (total cholesterol, triglycerides, lipoprotein electrophoresis) before treatment and after 3 and 4 mth of treatment. The only significant change found to have occurred was a decrease in the beta: alpha lipoproteins ratio; this was greater in the group treated with conjugated equine oestrogens, but was also statistically significant in the group treated with oestriol. Endometrial proliferation was investigated indirectly by means of the medroxyprogesterone acetate (MPA) test before treatment and after 5 mth of treatment. The response to MPA at the end of 5 mth of treatment in patients previously unresponsive, showed endometrial proliferation to have occurred during treatment with conjugated equine oestrogens but not during treatment with oestriol.