Pharmacokinetics of gliclazide in healthy and diabetic subjects

The pharmacokinetics of total and free gliclazide, 1-(3-azabicyclo[3,3,0]oct-3-yl)-3-(p-tolylsulfonyl)urea, a potential hypoglycemic drug, was studied in healthy (n = 12) and diabetic (n = 12) subjects. The serum level of gliclazide was determined by a high-performance liquid chromatographic method (HPLC). The free fraction of gliclazide was obtained from serum by an ultrafiltration technique using a collodion membrane. The mean adsorption of gliclazide to the membrane was approximately 50% when the membrane was used more than twice. Therefore, the gliclazide level in the filtrate was corrected by doubling the apparent value. The ratio of gliclazide-protein binding remained constant at approximately 92% in serum after administration to healthy and diabetic subjects. The mean pharmacokinetic parameters of elimination rate (ke), time to reach the peak level (tmax), elimination half-life (t 1/2), and volume of distribution (Vd) were 0.07 h-1, 2.8 h, 12.3 h, and 17.4 L, respectively. The parameters did not differ significantly between healthy and diabetic subjects or between single and successive administrations; moreover, they did not differ between the free and total drug level. Although there were intersubject variations, the therapeutic effects of oral administration of gliclazide on serum glucose and insulin levels were found in four diabetic patients. The results of this study show that the pharmacokinetics of the total gliclazide level reflect those of the free gliclazide in serum.     

Aneurysm of the anterior inferior cerebellar artery at the internal auditory meatus

An aneurysm of the anterior inferior cerebellar artery extending into the internal auditory meatus is reported. The patient developed headache and vomiting caused by a subarachnoid hemorrhage, and rapidly showed signs and symptoms of a lesion in the cerebellopontine angle soon after the onset. At operation, a clip was successfully applied to the neck of the aneurysm. The characteristic clinical findings are briefly reviewed.     

Effects of lactulose on blood ammonia levels in beagles with end-to-side portacaval shunt

The effects of lactulose on blood ammonia and fecal pH in beagles with an end-to-side portacaval shunt were investigated. Concentrations of blood ammonia before and two weeks after the operation were 4.65 +/- 0.34 micrograms/ml (N = 12) and 8.66 +/- 0.60 micrograms/ml (N = 6), respectively (P less than 0.01), while there was no significant difference in fecal pH values before and after the operation. The blood ammonia concentrations in the control and lactulose-treated (2.1 g/kg, p.o.) groups after administration of meat were 12.65 +/- 1.64 micrograms/ml (N = 8) and 8.45 +/- 0.90 micrograms/ml (N = 8), respectively (P less than 0.05). The fecal pH values in the control and lactulose-treated (2.1 g/kg, p.o.) beagles were 6.24 +/- 0.09 (N = 8) and 5.58 +/- 0.08 (N = 8), respectively (P less than 0.01). The lowering effect of lactulose on the blood ammonia levels could not be ascribed to its laxative action alone, because the oral administration of lactulose at doses less than 2.1 g/kg induced no fluid evacuation. The present studies in the beagle suggest that the action of lactulose produce a lowering of fecal pH, causing an increase in the concentration of less absorbable ammonium ions and a decrease in the production of toxic nitrogenous compounds such as ammonia, resulting in a reduction in blood ammonia levels.     

Thymolipoma: A report of three cases

Three cases of thymolipoma, seen in a 6 year old boy, a 34 year old woman and a 24 year old man are presented herein. The weight of each tumor was 1380 g, 670 g and 560 g respectively. The 2 male patients had no symptoms and the woman only complained of a fever. On CT scan the thymic tissue was recognized as islands of soft tissue density within a fatty mass, and T1 weighted MRI was helpful in demonstrating the predominant fatty nature of this tumor. Thus, our experience demonstrates that CT and MRI are valuable for establishing a diagnosis of thymolipoma. In a review of the literature on the subject, some clinical features of this non-malignant tumor in the mediastinum are discussed. Although rare, thymolipoma should be considered in the differential diagnosis of mediastinal tumors.     

Antihypertensive therapy reduces increased plasma levels of adrenomedullin and brain natriuretic peptide concomitant with regression of left ventricular hypertrophy in a patient with malignant hypertension.

We investigated the potential role of increased plasma adrenomedullin and brain natriuretic peptide (BNP) levels in a patient with malignant hypertension. A 51-year-old man was admitted to our hospital with a chief complaint of visual disturbance. His blood pressure was 270/160 mmHg on admission. Papillary edema associated with retinal bleeding was observed. Echocardiography revealed marked concentric left ventricular hypertrophy with mild systolic dysfunction. Plasma levels of adrenomedullin and BNP were markedly elevated. Antihypertensive therapy reduced the plasma levels of adrenomedullin in association with a concomitant decrease in blood pressure. The plasma level of BNP also decreased and regression of left ventricular hypertrophy and normalization of left ventricular systolic function were observed. Our findings suggest that adrenomedullin may be involved in the defense mechanism against further elevations in blood pressure in patients with hypertension and that the plasma level of BNP may reflect left ventricular systolic dysfunction, left ventricular hypertrophy, or both, in patients with severe hypertension.     

Granulomatous Pigmented Purpuric Dermatosis

We report two cases of brown pigmentation accompanied by hemorrhagic papules. A 61-year-old woman and a 53-year-old woman presented with brown pigmentation accompanied with hemorrhagic papules occurring bilaterally from the dorsal aspect of the feet to the lower legs. The clinical picture was of pigmented purpuric dermatosis, but histopathologically, they were hemorrhagic granulomatous inflammation of the upper dermis. As no systemic granulomatous lesions were observed, these cases were considered to be granulomatous pigmented purpuric dermatosis.     

Characteristics of antinociception induced by noncatecholic phenylethylamine derivatives: the relation of endogenous norepinephrine to phenylethylamine analog-induced antinociception

Characteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, beta-phenylethylamine (PEA) and beta-hydroxyphenylethylamine (OHPEA), were examined. The pain threshold of mice was measured by using the hot plate method. Intraperitoneal administration of alpha-methyl-p-tyrosine inhibited antinociception induced by PEA and OHPEA, and intracisternal administration of norepinephrine increased antinociception induced by PEA and OHPEA. Intracisternal administration of phentolamine inhibited the antinociception induced by PEA derivatives. The levels of norepinephrine and normetanephrine in the brain were determined by using HPLC. PEA derivatives decreased norepinephrine in the brain and tended to increase normetanephrine at 15 min after the administration of PEA derivatives. These findings indicate that PEA derivatives cause the release of norepinephrine in the central nervous system, and the released norepinephrine induces antinociception.     

First-stage palliation of hypoplastic left heart syndrome--experience in three cases]

We administered palliative procedures for hypoplastic left heart syndrome in three cases. One case underwent Van Prragh's procedure and two cases were subjected to Jonas's modification of Norwood's procedure. One of the latter cases with AS and MS survived. The pulmonary blood flow of the survivor was secured through a hole of 3 mm in diameter made between the posterior wall of the newly constructed pulmonary-aortic common tract and the heterogeneous pericardial patch used to close the distal end of the transected main pulmonary artery. The pulmonary blood flow had been maintained adequately for 15 months after the operation but the flow was decreased thereafter. Consequently, a modified Blalock-Taussig shunt was added at the age of 21 months. The patient is now waiting for Fontan procedure in the near future. We used a heterogeneous pericardium to supplement an anastomosis connecting ascending aorta, aortic arch, and proximal descending aorta with transected proximal main pulmonary artery. This procedure also served to supplement the defect of the distal end of the transected main pulmonary artery. The sufficient removal of coarctation of aorta is very important. No aneurysmal change of this pericardium has been recognized. However there still remains a slight stenosis at the proximal anastomosis between the pulmonary artery and the newly constructed common tract. To avoid this stenosis, we recommend an anastomosis of the transected proximal main pulmonary artery to the ascending aorta and then to the proximal end of the heterogeneous pericardial tract.(ABSTRACT TRUNCATED AT 250 WORDS)