RESUMO
BACKGROUND: Hypercholesterolemia causes alterations in platelet function. Platelet hyperaggregation is considered a predisposing factor for atherosclerosis. In this paper, the antiaggregating effect of the polyamines putrescine, spermidine, and spermine was studied on platelets of normal and hypercholesterolemic rabbits. METHODS: New Zealand rabbits were fed with a cholesterol-enriched diet for 10 weeks. Lipids and glucose were determined in serum. The assays of platelet aggregation were carried out using platelet-rich plasma (PRP) obtained from both control and cholesterol-fed rabbits. We used 2.5 micromol /mL ADP and 2 microg/mL collagen as inductors of platelet aggregation. In addition, arginase activity and L-arginine content were determined in PRP. RESULTS: Serum total cholesterol and LDL-cholesterol concentrations were increased from 26.3 +/- 8.1 to 1,485.0 +/- 26.8 mg/dL and from 15.9 +/- 5.9 to 1,383.8 +/- 58.9 mg/dL, respectively, whereas triglyceride concentration increased from 88.3 +/- 35.6 to 411.0 +/- 154.5 mg/dL upon cholesterol feeding. Seventy-five percent of platelet aggregation inhibition was observed with 10 microM of polyamines in PRP of normal rabbits. Spermine inhibited platelet aggregation by 54% in PRP of hypercholesterolemic rabbits when ADP was used as agonist. The order of polyamine action was spermine > spermidine > putrescine. In addition, we found that platelet arginase activity and L-arginine content were unaltered upon hypercholesterolemia. CONCLUSIONS: These results show that the polyamines putrescine, spermidine, and spermine have antagonist action in platelet aggregation and suggest a key role of polyamines in platelet aggregation under normal and hypercholesterolemic conditions.
Assuntos
Hipercolesterolemia/sangue , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Putrescina/uso terapêutico , Espermidina/uso terapêutico , Espermina/uso terapêutico , Animais , Arginase/sangue , Arginina/sangue , Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Glicemia/análise , Plaquetas/química , Plaquetas/enzimologia , Proteínas Sanguíneas/análise , Colesterol/sangue , Colesterol na Dieta/toxicidade , LDL-Colesterol/sangue , Dieta Aterogênica , Avaliação Pré-Clínica de Medicamentos , Hipercolesterolemia/complicações , Masculino , Inibidores da Agregação Plaquetária/farmacologia , Putrescina/farmacologia , Coelhos , Espermidina/farmacologia , Espermina/farmacologia , Triglicerídeos/sangueRESUMO
OBJECTIVE: Our purpose was to determine the effectiveness of 5-fluorouracil (5-FU) in the treatment of vaginal intraepithelial neoplasia (VaIN) in a Mexican population. MATERIALS AND METHODS: The study was performed in 30 patients with a mean age of 54 years and previous diagnoses from reviewed records and histopathology slides selected from a group of 65 patients with VaIN from 1980 to 1997. Patients received intravaginal treatment with 5-FU, 1.5 g once weekly for 10 weeks, and all patients were followed up for a 1-year minimum. Papanicolaou smear and colposcopy were performed, as was biopsy when indicated. RESULTS: Twenty-eight (93%) patients with VaIN had prior or concurrent anogenital squamous neoplasia, including 5 with invasive cervical carcinoma and 23 with cervical intraepithelial neoplasia. In 23 of 30 treated patients (77%), VaIN went into remission after a single treatment; in 3, (10%), it went into remission after two treatments; 3 (10%) had recurrent VaIN 3; and in 1 (3%), it progressed to invasive vaginal cancer. The treatment was well tolerated. CONCLUSIONS: We conclude that 5-FU is an option choice for VaIN treatment. It is effective, with minimal side effects. Its use should be confined to treating extensive or multifocal high-grade VaIN.
RESUMO
At the Colposcopy Clinic, Hospital "Luis Castelazo Ayala", from January 1990 to May, 1991, 24 cases of vaginal intraepithelial neoplasia, were diagnosed. The average age of the patients was 54.2 years. Twenty had antecedents of previous hysterectomy; seven (29%) with benign pathology, and twelve (50%) with malignant pathology. Only four patients (17%) presented with symptomatology. In all the cases it was suspected by abnormal cytology. Colposcopy was done, as well as directed biopsy, finding that the pointillism and white epithelium, were the most frequent findings, with localization mainly in the vaginal cupule and vaginal upper third. Histopathological correlation showed NIVa I in three cases (13%) NIVa II in six cases (25%), and NIVa III in 15 (62%). Treatment was done with cryotherapy in 10 patients; with 5-fluorouracil in eight; cryotherapy plus 5-fluorouracil in three; radiotherapy in two, and it was not done in one. It was found persistent lesion in two cases treated with cryotherapy, and in one case with radiotherapy; there was a complication in one case after cryotherapy (retrovaginal fistula). Vaginal cytology should be done in every patient after hysterectomy, by benign or malignant pathology. In NIVa the colposcopic study is mandatory for the adequate diagnosis. 5-Fluorouracil showed to be an adequate treatment.