ABSTRACT
OBJECTIVE: To compare the effects of the abrupt discontinuation of postmenopausal hormone therapy (HT) and reduction of the daily dosage of the hormone on climacteric symptoms. METHODS: The study included Brazilian postmenopausal women who were using estrogen-progestogen hormone therapy in full doses previously prescribed for vasomotor symptoms. The patients were randomized to receive one of three treatments: placebo for 6 months; estradiol (E2) 1 mg/day + norethisterone acetate (NETA) 0.5 mg/day for 2 months, followed by placebo for 4 months; or E2 1 mg/day + NETA 0.5 mg/day for 4 months, followed by placebo for 2 months. The climacteric symptoms were assessed by the Blatt-Kupperman Menopausal Index at baseline and at 2, 4 and 6 months. Statistical evaluation was performed using the chi(2) or Fisher's test for categorical data, the Kruskal-Wallis test for numerical data, and ANOVA for time and group relationship with the Blatt-Kupperman Menopausal Index. RESULTS: We randomized 60 women (20 in each group), and 54 completed the study. It was observed that both the full Blatt-Kupperman Menopausal Index and the hot flush score did not change significantly in the HT group during low-dose therapy compared with baseline; however, the evaluation performed at 2 months after low-dose-HT cessation showed that the full Blatt-Kupperman Menopausal Index and the hot flush score were similar to those of the group who stopped HT abruptly and significantly higher than at baseline (hot flush scores: p < 0.001 for all three groups at months 2, 4 and 6, respectively, vs. baseline). CONCLUSION: Discontinuation of HT by reducing the daily dose of estrogen for a period of 2 or 4 months did not differ in its effect from that of abrupt cessation with regard to vasomotor symptoms.
Subject(s)
Estradiol/administration & dosage , Estrogen Replacement Therapy/methods , Hot Flashes/epidemiology , Female , Hot Flashes/drug therapy , Humans , Middle Aged , Norethindrone/administration & dosage , Norethindrone/analogs & derivatives , Norethindrone Acetate , Placebos , Time FactorsABSTRACT
BACKGROUND: Granulocytes from healthy subjects and from patients suffering from diabetes mellitus present differences in reactivity to stimulation with cyclic nucleotide-elevating agents. The production of reactive oxygen species (ROS) is inhibited in cells from non-diabetic subjects following such stimulation, but activated through a PKA-independent signaling pathway in granulocytes from type 1 and type 2 diabetic patients. The aim of the present study was to understand better the changes in signaling mechanisms induced by the disease. METHODS: ROS production in granulocytes from healthy subjects and from type 1 and type 2 diabetic patients was measured using a luminol-dependent chemiluminescence assay. Granulocytes were stimulated by the addition of the cAMP-elevating agent dibutyryl cAMP. In some experiments, granulocytes were pre-treated with an inhibitor of PKA or Akt/PKB prior to cAMP stimulation. RESULTS: Intracellular elevation of cAMP induced a PKA-dependent and Akt/PKB-independent inhibition of ROS production in granulocytes from healthy subjects, but a significant activation in cells from both type 1 and type 2 diabetic patients. Most significantly, activation of ROS generation in cells from diabetic patients was shown to be Akt/PKB-dependent and PKA-independent. CONCLUSIONS: These results suggest that chronic hyperglycaemia could induce metabolic adaptation in cAMP-related signaling mechanisms. Epac (exchange protein directly activated by cAMP) is a novel cAMP receptor besides PKA involved in different signaling pathways. The cAMP-stimulated inverse ROS response in granulocytes from type 1 and type 2 diabetic patients may be due to a change in signaling pathways from cAMP/PKA to cAMP/Epac/Akt/PKB. These preliminary results require further studies in order to evaluate their consequences on innate immunity and pathogenesis of diabetes mellitus.
Subject(s)
Bucladesine/pharmacology , Cyclic AMP/blood , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Granulocytes/metabolism , Proto-Oncogene Proteins c-akt/blood , Reactive Oxygen Species/blood , Adult , Female , Granulocytes/drug effects , Humans , Male , Proto-Oncogene Proteins c-akt/drug effects , Reference ValuesABSTRACT
Os autores apresentam um caso de fistula utero-cutanea observado apos operacao cesariana, e tratada na Clinica Ginecologica do Hospital Barao de Lucena _ Recife. Justificam a apresentacao pela raridade deste tipo de fistula e fazem comentarios a respeito da etiologia, do diagnostico e do tratamento, enfatizando que o tratamento clinico conservador levou a cura completa e ao retorno de ciclos menstruais normais da paciente