Eugenol, an active principle of clove, is an effective secretagogue in rats, causing dose-dependent augmentation of gastric secretion. Eugenol, when administered intragastrically at 100μg/kg body weight, stimulated maximum secretion of gastric free acid and serum pepsinogen. However, at higher concentrations it had an inhibitory effect on gastric secretion. Long-term oral treatment with eugenol at a dose of 100μg/kg body weight per day for three weeks significantly increased the serum pepsinogen levels, which positively correlated with gastric free acid secretion. The levels of serum mucoprotein and α-antitrypsin remained unchanged. Histopathological examination of the stomach of experimental animals did not show any damage to mucosal cells. Thus, stimulation of gastric secretion at a low concentration of eugenol, i. e., 100μg/kg body weight and below, should facilitate digestion.
The effect of mannose grafting to the surface of Amphotericin B (Amp-B)-containing liposomes with and without cholesterol on the toxicity, therapeutic efficacy, and altered tissue distribution was studied in normal and infected mice. The inclusion of cholesterol in the mannose-grafted liposomes bearing Amp-B increased the LD50 from 8.4mg/kg to 20.3mg/kg body weight. Cholesterol was found to enhance the therapeutic efficacy of mannosylated liposomes. The tissue distribution studies indicated that incorporation of cholesterol in mannose-grafted liposomal formulation of Amp-B increased the tissue concentration in various organs of both healthy and infected mice. A significant increase in concentration of Amp-B in the lungs of infected animals was observed when mannosylated liposomes having cholesterol were administered. Inhibition of mannosylated liposomal formulation of Amp-B by mannan was observed in normal animals, but in infected animals there was no inhibition.
Pharmacokinetics and antineoplastic effect of adriamycin (ADM) entrapped in multilamellar vesicles of liposomes composed of egg phosphatidylcholine (PC), cholesterol (Chol), and cholesterol sulfate (CholSO4) in a molar ratio of 6:3:1 were studied. Upon its intravenous injection, the blood level of ADM remained higher for 24h than that of ADM entrapped in liposomes composed of PC, Chol, and sulfatide (CSE) in a molar ratio of 5:4:1 and than that of free ADM. Entrapment of ADM in liposomes containing either CholSO4 or CSE reduced the concentration of ADM in the heart and kidney compared with free ADM. In the liver, however, the level of ADM, when the drug entrapped in CholSO4-containing liposomes was injected, was similar to that of ADM injected in free form, while the drug markedly accumulated in this organ, when ADM was entrapped in CSE-containing liposomes. By using P388 leukemia of mice, we demonstrated that ADM entrapped in CholSO4-containing liposomes has higher antineoplastic activity than free ADM.
We investigated the effects of TJ-35 (Shigyaku-san) on gastric mucosal injury induced by ischemia-reperfusion in rats; and using the electron spin resonance (ESR) spin trapping method, we also assessed its oxygen-derived free radical-scavenging activities. The increase in mucosal lesions and in thiobarbituric acid-reactive substances (as an index of lipid peroxidation) was significantly inhibited by the oral administration of 500mg/kg of TJ-35; and in addition, TJ-35 demonstrated superoxide and hydroxyl radical-scavenging activities in vitro. These results suggest the possibility that the effects of TJ-35 on gastric mucosal injury induced by ischemia-reperfusion may be the result of its free radical-scavenging activities.
When administered to mice, enzyme inhibitors exert extensive effects that cannot be expected from their direct actions. On the basis of our previous observations , we tested how glycosidase inhibitors influence the intracerebral activities of various hydrolytic enzymes including glycosidases. The results showed that, when administered intraperitoneally, mannostatin and nagstatin stimulated, while siastatin and pyridindolol suppressed, intracerebral activities of glycosidases. The effects showed dose dependency. Although the above inhibitors influenced various other enzymatic activities as well, no particular significance could be attached to such effects because of the absence of dose dependency.
Muscular dystrophy is known to occur mainly in hindlimb muscle, rather than in forelimb muscle, of dystrophic mice. In order to explain this phenomenon, we measured the activities of 12 hydrolytic enzymes, including exopeptidases, endopeptidases, and glycosidases, in muscle of forelimb and hindlimb. In spite of similar enzymatic changes in both limbs, multivariate analysis enabled us to extract two important factors that may explain the difference in the metabolism between forelimb muscle and hindlimb muscle of dystrophic mice. Of the two factors, one was closely correlated to mannosidase, DPP-IV, PEP, and cathepsin B, while the other was correlated to DPP-III, kallikrein, and AP-A. Of these enzymes, DPP-III was particular in that its activity was decreased in forelimb, but not in the hindlimb, muscle of dystrophic mice. The lack of a significant decrease in this enzymatic activity may prompt the muscular breakdown in the hindlimb of dystrophic mice.
Iron absorption from three typical Central African meals was measured in 15 Zairian volunteers by use of the extrinsic tag technique with 59Fe and 55Fe. Meals were prepared in Zaire under realistic conditions from locally grown foods. Two of them were meals (based on rice or cassava as the staple food) usually eaten by a large fraction of the population in the Kinshasa area and one (based on plantain as the staple food) was eaten especially during periods of festivities. Among non-heme iron in the meals, 54-76% did not exchange with the added inorganic radio-iron tracer, depending on the degree of iron contamination of meals. The non-heme iron absorption coefficient was low in usual meals, but was higher for the special meal eaten during festive periods. When heme iron absorption was included, 85μg to 1.2mg iron was absorbed according to the type of meal. While the total iron absorption coefficient in the different meals varied up to 5-fold (between 1.4 and 5.1%), the bioavailable iron density varied up to 10-fold (between 17 and 184μg/100kcal).
Low levels of blood ascorbate in pregnant women had been thought to have a role in incidence of premature rupture of membranes (PROM). In this study, maternal and fetal blood levels of ascorbate were surveyed in term and preterm labor. Each group was subdivided according to the presence of PROM. Placental ascorbate levels were also studied. Since ascorbate is known to be involved in the synthesis of collagen, hydroxyproline content of the amnion was also measured and taken as an index for collagen production. Amnionic membranes from births with PROM showed relatively low levels of hydroxyproline. Preterm newborns with PROM also exhibited a significantly low ascorbate concentration as compared with preterm controls. In conclusion, ascorbate in the fetal compartment appears to be important for the occurrence of PROM.