Acarbose improved severe postprandial hypotension in a patient with diabetes mellitus.

Postprandial hypotension (PPH) is defined as a decrease of systolic blood pressure by more than 20 mmHg after meals. Severe PPH is a troublesome diabetic complication, which has no established means of treatment. We encountered a patient who had diabetes mellitus complicated by severe PPH and attempted to treat this problem using several medications (octreotide, midodrine hydrochloride, and acarbose). A 58-year-old male with diabetic triopathy complained of orthostatic dizziness and vertigo after meals. The blood pressure was monitored for 24 h with an ambulatory blood pressure monitor, revealing that the systolic blood pressure decreased markedly after breakfast and dinner by 45 and 50 mmHg, respectively. PPH was not improved by a subcutaneous injection of octreotide. Administration of midodrine hydrochloride reduced the frequency of hypotensive episodes from twice to once daily, but the magnitude of the postprandial fall in blood pressure was still around 30 mmHg. After the patient started to receive acarbose therapy, the postprandial fall in blood pressure was diminished to 18 mmHg and his symptoms largely disappeared. For the treatment of PPH in diabetic patients, our experience suggests that it may be appropriate to try first on alpha-glucosidase inhibitor like acarbose.

In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans.

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.

[Itraconazole-induced hypokalemia in a patient with pulmonary aspergilloma].

An 80-year-old man was admitted to the hospital with a diagnosis of pulmonary aspergilloma. A new azole antifungal agent, D 0870, was administered to the patient for 7 days orally, and itraconazole (400 mg/day) was started on March 5, 1997. After 1 month of chemotherapy, facial and pretibial edema were observed and the patient's serum potassium concentration decreased to 2.5 mEq/l. A chest radiograph disclosed cardiomegaly with cardiac effusion and right pleural effusion on admission. The serum potassium concentration rose after the cessation of itraconazole therapy. The serum ITCZ concentration remained high for 2 weeks after admission. Although reports of hypopotassemia induced by ITCZ are rare, we concluded that blood concentrations should be monitored more carefully when treating pulmonary aspergilloma patients with high-dose regimens of ITCZ.

Change in hepatic antioxidant defense system with liver injury development in rats with a single alpha-naphthylisothiocyanate intoxication.

The change in hepatic antioxidant defense system with the development of alpha-naphthylisothiocyanate (ANIT)-induced liver injury was examined in rats injected once with the toxicant (75 mg/kg body weight). Liver injury with cholestasis did not occur 12 h after ANIT injection, but appeared at 24 h, progressed at 48 h, and recovered at 72 h, judging from the serum levels of marker enzymes and components. Liver lipid peroxide content increased 12 h after ANIT injection and further increased 24 and 48 h, but this increase was attenuated at 72 h. Liver superoxide dismutase and catalase activities decreased 24 and 48 h, respectively, after ANIT injection, although the catalase activity increased at 12 h, but these decreases were attenuated at 72 h. Liver Se-glutathione peroxidase activity remained unchanged 24, 48, and 72 h after ANIT injection, although the activity increased at 12 h. Liver reduced glutathione content increased 24 h after ANIT injection, but the increase was reduced time dependently thereafter. Liver ascorbic acid content increased 12 h after ANIT injection and further increased at 24 h, but the increase was reduced time dependently thereafter. These results indicate that the change in hepatic antioxidant defense system occurs before and with the development of ANIT-induced liver injury in rats, and suggest that the reduction of hepatic antioxidant defense system mediated by SOD and catalase could contribute to the liver injury development through an enhancement of hepatic lipid peroxidation.

Preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on the development of stress-induced acute gastric mucosal lesions in rats.

The preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15), a traditional Chinese herbal medicine for the therapies of gastric ulcers and gastritis, on the development of stress-induced acute gastric mucosal lesions was examined in rats with water immersion restraint (WIR) stress. Simultaneous p.o. administration of TJ-15 at a dose of 20, 100 or 250 mg/kg prevented dose-dependently gastric mucosal lesion development in rats subjected to WIR stress over a 6-h period. In the gastric mucosa of rats with WIR stress alone, lipid peroxide concentration and xanthine oxidase (XOD) and myeloperoxidase--an index of neutrophil infiltration--activities increased with lesion development, while nonprotein SH concentration decreased. The simultaneous administration of TJ-15 attenuated all these changes with gastric mucosal lesion development in a dose-dependent manner. These results indicate that simultaneously administered TJ-15 exerts a preventive effect on the development of WIR stress-induced acute gastric lesions in rats, and suggest that the preventive effect of TJ-15 could be due to its preventive actions on enhanced sulfhydryl oxidation and lipid peroxidation via oxygen free radicals generated by the xanthine-xanthine oxidase system and infiltrated neutrophils in the gastric mucosa and on neutrophil infiltration into the tissue.

Inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on hepatic triglyceride accumulation with the progression of carbon tetrachloride-induced acute liver injury in rats.

The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). TJ-15 at a dose of 100, 250 or 500 mg/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl4 (1.0 ml/kg BW) at which time apparent liver injury and hepatic TG accumulation occurred. TJ-15 significantly prevented not only the progression of liver injury but also inhibited hepatic TG accumulation with the progression of the injury in a dose-dependent manner when these effects were examined 24 h after CCl4 injection. In CCl4-untreated rats with oral administration of TJ-15 at a dose of 100, 250 or 500 mg/kg BW, liver and serum TG concentrations decreased depending on the dose of the herbal medicine. These results indicate that in rats intoxicated once with CCl4, orally administered TJ-15 can inhibit hepatic TG accumulation with the progression of acute liver injury by its decreasing action on serum and liver TG levels, leading to a prevention of the progression of the liver injury.

Preventive effect of oren-gedoku-to (huanglian-jie-du-tang) extract on progression of carbon tetrachloride-induced acute liver injury in rats.

The effect of oral administration of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). When TJ-15 at a dose of 500 mg/kg body weight (b.w.) was administered to male Wistar rats aged seven weeks 6 hours after i.p. injection of CCl4 (1.0 ml/kg b.w.), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found 24 hours after the injection judging from the activities of serum transaminases and other indices of liver cell damage. An increase in lipid peroxide level and decreases in reduced glutathione level and superoxide dismutase (SOD) activity occurred in the liver at 6 and 24 hours after CCl4 injection. Serum SOD activity increased 24 hours after CCl4 injection. Post-oral TJ-15 administration significantly ameliorated all these changes found at 24 hours after CCl4 injection. An increase in liver triglyceride level and a decrease in serum triglyceride level also occurred 6 and 24 hours after CCl4 injection. Post-oral TJ-15 administration prevented the increase in liver triglyceride level at 24 hours after CCl4 injection. Although the activity of liver tryptophan 2,3-dioxygenase (TDO), a marker of the inhibition of liver protein synthesis by CCl4, decreased 6 and 24 hours after injection of the toxicant, post-oral TJ-15 administration had no effect on this decrease in TDO activity at 24 hours after the injection. These results indicate that oral TJ-15 administration can prevent the progression of acute liver injury in CCl4-injected rats, and suggest that this prevention could be due to the action of TJ-15 to scavenge free radicals formed in the liver and to inhibit triglyceride accumulation in the liver.

Comparative study of oral and parenteral administration of sho-saiko-to (xiao-chaihu-tang) extract on D-galactosamine-induced liver injury in rats.

The preventive effect of Sho-saiko-to (Xiao-Chaihu-Tang) extract (TJ-9) on the progression of D-galactosamine (GaIN)-induced liver injury was examined in five week-old male Wistar rats with oral (p.o.) or intraperitoneal (i.p.) administration of the same dose of TJ-9. Rats treated once with GaIN (500 mg/kg body weight, i.p.) received TJ-9 at a dose of 1.0 g/kg body weight (p.o. or i.p.) 2 hours after GaIN treatment at which time an apparent liver injury occurred. Both p.o. and i.p. administration of TJ-9 showed similar significant prevention against the progression of liver injury 24 hours after GaIN injection. Although total protein and albumin concentrations in serum and protein concentration in the liver decreased with the progression of GaIN-induced liver injury, oral or i.p. administration of TJ-9 prevented these decreases in similar degree. However, decreases in serum and liver triglyceride concentration with the progression of liver injury were not attenuated after p.o. or i.p. administration of TJ-9. The activities of liver 5'-nucleotidase and glucose-6-phosphatase, marker enzymes of liver plasma and microsomal membranes, respectively, decreased during the progression of liver injury. A similar preventive effect on the decrease of both enzyme activities was found after p.o. or i.p. administration of TJ-9. These results indicate that the preventive effect on progression of GaIN-induced liver injury by oral or i.p. administration is approximately equal, and that the effect may be through improving the impaired liver protein synthesis and disrupted liver plasma and microsomal membranes in a similar degree.

Preventive effect of dai-saiko-to (da-chai-hu-tang) extract on disrupted hepatic active oxygen metabolism in rats with carbon tetrachloride-induced liver injury.

In order to clarify the preventive action of Dai-Saiko-to (Da-Chai-Hu-Tang) extract (TJ-8) on the progression of acute liver injury in rats intoxicated with carbon tetrachloride (CCl4), we examined the effect of post-oral TJ-8 administration on hepatic active oxygen metabolism following the progression of this liver damage. When TJ-8 (1.0 g/kg body weight) was administered orally to male Wistar rats aged five weeks 2 hrs after i.p. injection of CCl4 (1.0 ml/kg body weight), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found at 24 hrs after injection, judging from the activities of serum transaminases, indexes of liver cell damage. Liver cytosolic superoxide dismutase (SOD) activity decreased 2 and 24 hrs after CCl4 injection, while liver cytosolic catalase and glutathione reductase (GSSG-R) activities decreased 24 hrs after the injection. At 2 and 24 hrs after CCl4 treatment, liver cytosolic Se-containing glutathione peroxidase (GSH-px) activity did not change and liver cytosolic glucose-6-phosphate dehydrogenase (G-6-PDH) activity increased. Post-oral TJ-8 administration significantly ameliorated decreases in liver SOD, catalase, and GSSG-R activities at 24 hrs after CCl4 injection, but did not affect liver Se-GSH-px and increased liver G-6-PDH activities at 24 hrs after the injection. Although increased liver lipid peroxide level and decreased liver reduced glutathione and ascorbic acid levels were observed 2 and 24 hrs after CCl4 injection, post-oral TJ-8 administration significantly prevented these changes found at 24 hrs after injection. These results indicate that post-oral TJ-8 administration can prevent the progression of acute liver injury in CCl4-injected rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.

Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats.

A(-)-epicatechin (EC) and (-)-epigallocatechin (EGC) mixture and a mixture of their gallates (ECG and EGCG, respectively) markedly lowered lymphatic cholesterol absorption in rats with a cannulated thoracic duct. A mixture of ECG and EGCG was more effective in reducing cholesterol absorption than the EC and EGC mixture. These catechins also tended to decrease lymphatic absorption of triacylglycerols, although not so pronounced as in cholesterol absorption. An in vitro study on micellar solubility of cholesterol showed that these catechin mixtures precipitated cholesterol solubilized in mixed bile salt micelles in a dose-dependent manner. A mixture of ECG and EGCG more effectively precipitated micellar cholesterol than a mixture of EC and EGC. When purified EC, EGC, ECG and EGCG were used, EGCG was more effective in precipitating micellar cholesterol than ECG. The effect of EC and EGC was comparable and weaker than their gallate esters. The bile acid concentration in the micelles was not affected by these catechins. A positive correlation was observed between the amount of coprecipitated EGCG and cholesterol. These results clearly show that tea catechins, in particular their gallate esters, effectively reduce cholesterol absorption from the intestine by reducing solubility of cholesterol in mixed micelles. The observation accounts for the hypocholesterolemic effect of tea catechins.

Determination of uranium in human teeth, bones and tissues by the fission track method.

The uranium content of several human tooth, bone and soft tissue samples was determined by the fission tract method. The average uranium content in teeth, bones and soft tissues were 6.7, 8.4 and 64 ppb ash, respectively. The distribution of uranium in bones is less uniform than that of teeth, and the uranium content of soft tissues is generally higher than that of teeth and bone. The presence of thorium does not interfere with the uranium determination in most cases.