RESUMEN
PURPOSE: Kososan (KSS), a traditional Japanese medicine with a distinct aroma, is clinically used to treat affective disorders but its antidepressant-like effect has not been thoroughly investigated. In this study, we investigated the effects of inhaled and orally administered KSS on sleep disturbances in socially isolated mice. METHODS: Four-weeks-old male ddy mice were housed either in social isolation or in groups for 4-6 weeks before the experiment. KSS was orally administered (0.5 or 1.0 g/kg) or inhaled (0.5, 1.0, or 2.5 g/0.125 m(3)) 60 min before pentobarbital administration. Stress levels in mice were evaluated by the duration of pentobarbital-induced sleeping time. RESULTS: Sleeping time was shorter in socially-isolated mice than in group-housed mice. Oral and inhaled KSS prolonged sleeping time in stressed mice, but had no effect on sleeping time of group-housed mice. Prolonged sleeping time after oral KSS was significantly inhibited (p<0.05) by bicuculline (3 mg/kg, i.p.), a GABAA antagonist, but not by flumazenil (3 mg/kg, i.p.), a selective benzodiazepine antagonist. Prolonged sleeping time after KSS inhalation was significantly inhibited (p<0.05) by flumazenil but not by bicuculline. CONCLUSIONS: Our findings suggest that KSS activates GABAA-benzodiazepine receptor complex and reverses shortened pentobarbital-induced sleep caused by social isolation.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Agonistas de Receptores de GABA-A/uso terapéutico , Fitoterapia/métodos , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Aislamiento Social , Administración por Inhalación , Administración Oral , Animales , Medicamentos Herbarios Chinos/farmacología , Antagonistas de Receptores de GABA-A , Masculino , Medicina Tradicional de Asia Oriental , Ratones , Fenobarbital , Sueño/efectos de los fármacosRESUMEN
We report 2 elderly patients with fulminant type 1 diabetes mellitus. Case 1: A 61-year-old-man was admitted because of hyperglycemia (blood glucose level, 1,071 mg/dl) and metabolic acidosis. His hemoglobin A1c level was almost normal (5.8%), glutamic acid decarboxylase (GAD) antibody was not detected, and a low level of C-peptide (CPR) was excreted in his urine. We diagnosed his condition as diabetic ketoacidosis, and administered intensive insulin therapy. Case 2: A 77-year-old-man was admitted because of hyperglycemia (blood glucose level, 925 mg/dl). His hemoglobin A1c level was slightly high (5.9%), GAD antibody was not detected, and low levels of CPR were excreted in his urine. He showed no signs of metabolic acidosis, but showed metabolic ketosis. The findings of these cases were consistent with those of fulminant type 1 diabetes mellitus. Thus, it is necessary to consider the possibility of this disease in elderly people.
Asunto(s)
Diabetes Mellitus Tipo 1 , Anciano , Diabetes Mellitus Tipo 1/fisiopatología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We have recently demonstrated that serotonin (5-HT) increases the production of type 4 collagen by cultured human mesangial cells. Here we examined the clinical effects of a 5-HT(A2) receptor antagonist whether it would prevent the development or progression of diabetic nephropathy. We compared the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the major metabolite of 5-HT, in 24-h urine samples of patients with type 2 diabetes (n=110) and normal subjects (n=40). We then investigated the effects of 24-month treatment with sarpogrelate hydrochloride, a 5-HT(A2) receptor antagonist, on urinary albumin level in 10 type 2 diabetics with microalbuminuria, compared with not treated control group. Urinary 5-HIAA in diabetic patients was significantly higher (3.44+/-1.43 mg/day) than in normal subjects (1.62+/-0.50 mg/day, P<0.001), and correlated significantly with hemoglobin A1c (r=0.56, P<0.001) and with fasting blood glucose (r=0.37, P<0.001). Sarpogrelate significantly reduced urinary albumin excretion level within 3 months of commencement of treatment (24.3+/-8.58 mg/g Cr, P<0.05), which was persistently seen during the treatment, while no such change was noted in the control group (32.2+/-13.4 mg/g Cr). Our study indicate that high levels of 5-HT in type 2 diabetics may be one of the underlying mechanisms of diabetic nephropathy, and that treatment with 5-HT(A2) receptor antagonists may reduce or inhibit the development of nephropathy.