RESUMEN
Our objective was to investigate the phenotype of helper T cells in the peripheral blood of patients with systemic sclerosis (SSc). PBMC from 15 patients with SSc and 15 sex- and age-matched controls were investigated for lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16/CD56, CD3-DR); IL-2, IL-4, and IFN-gamma mRNAs; and the relative cytokines in their cytoplasm. The last assay was carried out both in unstimulated and in PMA-activated PBMC. SSc patients presented a higher percentage of activated T cells, CD3+ DR+ (19.7 +/- 9.9 vs 5.1 +/- 2.5%; P < 0.0001); 12 of them presented IFN-gamma mRNA-positive cells; and none IL-2 or IL-4 mRNAs. Under basal conditions, PBMC from six SSc patients contained IL-2, IL-4, and IFN-gamma (i.e., they showed both Th1 and Th2 activation), and 1 IFN-gamma only. PMA-stimulated PBMC of patients differed from those of controls only in the increased percentage of IFN-gamma positive cells (52 +/- 12 vs 37 +/- 11%; P < 0.01). Our study demonstrates that Thl activation occurs in the peripheral blood of SSc patients. This evidence must be faced with from both a pathogenetic and a therapeutical point of view.
Asunto(s)
Esclerodermia Sistémica/inmunología , Células TH1/inmunología , Células Th2/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Técnicas In Vitro , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Activación de Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Esclerodermia Sistémica/genética , Acetato de Tetradecanoilforbol/farmacología , Células TH1/efectos de los fármacos , Células Th2/efectos de los fármacosRESUMEN
Allopregnanolone is a neuroactive steroid synthesized in rat gonads, adrenal cortex, and central nervous system. It has been suggested that sex steroid hormones might influence allopregnanolone concentrations but no clear data have ever been reported. The aim of the present study was to investigate the effects of administration of 17beta-estradiol (17beta-E2), the raloxifene analog LY-117018 or their combination on allopregnanolone levels in fertile and ovariectomized (OVX) rats. Thirteen groups of 12 Wistar female rats each received either 17beta-E2 (0.1 or 1 microg/day) or LY-117018 (25, 250, and 1,250 microg/day), or 17beta-E2 1 microg/day plus LY-117018: 25, 250, and 1,250 microg/day for 14 days. The rats were then sacrificed and allopregnanolone content was assessed in the hypothalamus, hippocampus, pituitary, adrenals, and serum. Ovariectomy determined a significant decrease in allopregnanolone content in the hypothalamus, hippocampus, pituitary, and serum, while increasing it in the adrenals (p<0.01). In OVX rats, the administration of either 17beta-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17beta-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17beta-E2 in the hippocampus, hypothalamus, and pituitary, but not in the adrenals and serum. In fertile rats, the administration of LY-117018 reproduced the effects of ovariectomy. This study shows that the raloxifene analog LY-117018 has an estrogen-like action on the central nervous system of OVX rats when administered alone, while it acts as an antiestrogen in the presence of 17beta-E2, both in OVX animals treated with 17beta-E2 and in fertile rats. A different effect was observed in the adrenal glands. The mechanism of action of this compound has still to be clarified.
Asunto(s)
Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Estradiol/metabolismo , Antagonistas de Estrógenos/farmacología , Pregnanolona/sangre , Pirrolidinas/farmacología , Tiofenos/farmacología , Animales , Combinación de Medicamentos , Interacciones Farmacológicas/fisiología , Estradiol/farmacología , Femenino , Fertilidad/efectos de los fármacos , Fertilidad/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Ovariectomía/efectos adversos , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Pregnanolona/biosíntesis , Clorhidrato de Raloxifeno/análogos & derivados , Ratas , Ratas WistarRESUMEN
BACKGROUND: The increasing use of analogs of Gn-RH during treatment of some benign gynaecological diseases, has induced the authors to investigate the principal collateral effects, fixing one's attention on the loss of bony mass. METHODS: This perspective research has considered 38 patients selected for two diseases "endometriosis" and "uterine fibromyomatosis". The therapy has been effected with triptorelin intramuscularly in a dose of 3.75 mg every 28 days for six months, in all six phials. RESULTS: After a half-yearly cycle of therapy, the loss of bony mass was valued about 3% medium. CONCLUSIONS: In the light of other studies too, it was decided to confirm the necessity of associating other medicines able to prevent the side effects caused by their analogs of Gn-RH.