Amitriptyline-induced constipation in cynomolgus monkeys is beneficial for the evaluation of laxative efficacy.

In an attempt to create an animal model of constipation in monkeys, amitriptyline was administered to cynomolgus monkeys at doses of 10-160 mg/kg body weight via a nasogastric tube. Normal control monkeys excreted feces frequently throughout the day. Monkeys treated with amitriptyline at doses of 10-40 mg/kg showed delays in feces excretion. The 60 mg/kg treated monkeys for the most part did not excrete feces during the 24 h after amitriptyline administration. The 80 and 120 mg/kg treated monkeys did not excrete feces until 24 h from administration of amitriptyline, and also showed prolonged crouching and lethargy. On the other hand, 160 mg/kg treated monkeys died within 24 h after administration. We therefore felt that the optimal dose for creating constipation in the monkeys was 60 mg/kg. We tested the appropriateness of this amitriptyline-induced constipated monkey model by observing the effects of a new laxative, the herbal medicine ND-10 and the commercially available laxative bisacodyl. Control monkeys (those not receiving ND-10 or bisacodyl) treated with 60 mg/kg amitriptyline did not excrete feces up to 32 h after amitriptyline administration in 2 of 3 monkeys. However, all monkeys treated with one tablet of ND-10 excreted feces. Also, in 4 monkeys administrated with bisacodyl, 3 excreted feces. In this study, we confirmed that constipation can be caused in cynomolgus monkeys by oral administration of amitriptyline. This model may also be useful for the evaluation of laxatives.

Water extract of defatted rice bran suppresses visceral fat accumulation in rats.

Rice bran has been reported to inhibit pancreatic lipase activity in vitro. This action shows that administration of rice bran may result in a decrease in plasma triglyceride levels and suppress accumulation of fat in vivo. We administered water extract of defatted rice bran (WED-rice bran) to rats to determine its effects. Single administration of WED-rice bran at a dose of 1 g/kg body weight caused a decrease in plasma triglyceride levels in fat emulsion induced hypertriglyceridemic rats. Four week administration of WED-rice bran suppressed accumulation of visceral fat and body weight gain without influencing food consumption, liver function, and renal function. These results indicate that a reduction of plasma triglycerides and suppression of visceral fat accumulation may be induced by pancreatic lipase inhibition caused by administration of WED-rice bran.

Nutritional therapy of chronic hepatitis by whey protein (non-heated).

In an open study the clinical efficacy of milk serum (whey) protein (Immunocal; cysteine content: 7.6-fold higher than that of casein) isolated from fresh milk and purified without heating was evaluated in 25 patients with chronic hepatitis B or C. Immunocal (12 g as protein) food (mousse) was given twice a day, in the morning and evening, for 12 weeks (test period). Casein (12 g as protein) food (mousse) was similarly given for two weeks prior to the start of the supplement with Immunocal food (induction period) and for four weeks after the end of the supplement with Immunocal food (follow-up period). Serum alanine aminotransferase (ALT) activity was reduced, and plasma glutathione (GSH) levels increased in six and five of eight patients with chronic hepatitis B, respectively, 12 weeks after the start of the supplement with Immunocal food. Serum lipid peroxide levels significantly decreased, and interleukin (IL)-2 levels and natural killer (NK) activity significantly increased. However, there were no significant Immunocal-related changes in 17 patients with chronic hepatitis C. These findings suggest that the long-term supplement with Immunocal alone may be effective for improving liver dysfunctions in patients with chronic hepatitis B.

Determination of absorption and endogenous excretion of iron in man by monitoring fecal excretion of a stable iron isotope (58Fe).

The absorption and endogenous excretion of iron in man was studied by monitoring the fecal excretion of a stable iron isotope (58Fe). The study was carried out for 12 healthy volunteers who were divided into two groups. Group I received 58Fe-labeled ferric ammonium citrate (III) (58FeAC) equivalent to 6 mg of iron as a control, and group II received a combination of 500 mg of vitamin C and 58FeAC. A new formula was used to calculate the 58Fe absorption ratio reflecting the pool of iron in the intestinal cells, and the ratio was compared with that obtained from Janghorbani's formula, which has been used as one of the common methods. As a result, the 58Fe absorption ratio in group II was statistically significantly higher than that of group I (34.4 +/- 6.1% vs. 15.0 +/- 5.5%, M +/- SD) using Janghorbani's formula. The similar absorption ratio (34.1 +/- 6.0% vs. 14.8 +/- 5.5%) was also obtained by our new formula. Our results confirmed the previous findings that the availability of iron is stimulated by the supplementation of vitamin C. Both formulae agreed in the absorption of iron, indicating that the endogenous excretion of iron (caused by the desquamated cells) in the intestine does not disguise the iron absorption.