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High Oral Doses (high + oral_dose)
Selected AbstractsClinical effects of high oral dose of donepezil for patients with Alzheimer's disease in JapanPSYCHOGERIATRICS, Issue 2 2009Motohiro NOZAWA Abstract Background:, Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimer's disease. Methods:, We evaluated the efficacy and adverse effects of donepezil when the dose was increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease. Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and mini-mental state examination at the day before starting, and at 4, 8 and 24 weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4 was also investigated. Results:, The Revised Hasegawa Dementia Scale and mini-mental state examination scores were not statistically significantly different at any time after starting donepezil 10 mg/day. It can be anticipated that donepezil 10 mg/day will especially inhibit deterioration of cognitive function in advanced Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the rate of 40% or higher recorded during previous clinical trials. Conclusions:, The progression of cognitive dysfunction could be inhibited by increasing the dose of donepezil to 10 mg/day. It was suggested that longer-term treatment with 5 mg/day might lead to fewer adverse events when the dose is increased to 10 mg/day. [source] The Influence of Lactobacillus brevis on Ornithine Decarboxylase Activity and Polyamine Profiles in Helicobacter pylori -Infected Gastric MucosaHELICOBACTER, Issue 2 2004Michele Linsalata ABSTRACT Background., Functional probiotics may prevent Helicobacter pylori infection, and some evidence suggests that they also possess antitumor properties. Lactobacillus brevis (CD2) is a functional Lactobacillus strain with peculiar biochemical features, essentially related to the activity of arginine deiminase. This enzyme catalyzes the catabolism of arginine and affects the biosynthesis of polyamines (putrescine, spermidine, and spermine). Polyamines are polycations found in high concentrations in both normal and neoplastic cells. Our aims were: 1, to assess whether oral administration of L. brevis (CD2) affects H. pylori survival in the human gastric mucosa; 2, to evaluate the effects of L. brevis (CD2) on polyamine biosynthesis in gastric biopsies from H. pylori- positive patients. Materials and Methods., For 3 weeks before endoscopy, 22 H. pylori- positive dyspeptic patients randomly received (ratio 1 : 1) high oral doses of L. brevis (CD2) or placebo. Before and after treatment, H. pylori infection was determined by urea breath test (UBT). In gastric biopsies, ornithine decarboxylase activity and polyamine levels were, respectively, evaluated by a radiometric technique and high-pressure liquid chromatography (HPLC). Results.,L. brevis (CD2) treatment did not eradicate H. pylori. However, a reduction in the UBT delta values occurred, suggesting a decrease in intragastric bacterial load. Significantly, L. brevis (CD2) induced a decrease in gastric ornithine decarboxylase activity and polyamine levels. Conclusions., Our data support the hypothesis that L. brevis (CD2) treatment decreases H. pylori colonization, thus reducing polyamine biosynthesis. Alternatively, the arginine deiminase activity following L. brevis (CD2) administration might cause arginine deficiency, preventing polyamine generation from gastric cells. [source] Absorption, disposition and metabolism of di-isononyl phthalate (DINP) in F-344 ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2002R. H. McKee Abstract Di-isononyl phthalate (DINP; CAS no. 68515-48-0) is a general-purpose plasticizer for polyvinyl chloride. It produced liver and kidney effects when given to rodents at high oral doses, but there were no target organ effects in primates treated under similar conditions. To assist in understanding the basis for these species differences, the pharmacokinetic properties of DINP were evaluated in rodents following both oral and dermal administration. These studies demonstrated that the pharmacokinetic properties of DINP are similar to those of other high-molecular-weight phthalates. When orally administered to rodents, DINP is rapidly metabolized in the gastrointestinal tract to the corresponding monoester, absorbed and excreted, primarily in the urine. Shortly after administration, DINP is found primarily in liver and kidneys, but it does not persist or accumulate in any organ or tissue. It is very poorly absorbed from the skin, but once absorbed it behaves in the same way as the orally administered material. The results of these rodent studies contrast with data from studies involving humans or other primates, which indicate low absorption at low oral doses and much more limited total absorption at high doses. It appears that many, if not all, of the effects of DINP in rodent studies are associated with internal doses that would be difficult, if not impossible, to achieve in humans under any circumstances. Thus, the results of rodent studies may not be very useful in assessing the potential risks to humans from high-molecular-weight phthalates. Copyright © 2002 John Wiley & Sons, Ltd. [source] Dietary fiber, low-molecular-weight food constituents and colo-rectal inflammation in animal models , A reviewMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 10 2009Dieter Schrenk Abstract This review provides an overview over studies in experimental animals aimed at elucidating the influence of dietary constituents on colo-rectal inflammation. Human studies as well as in vitro investigations will not be covered. In experimental animals, a variety of chemical treatments and genetic modifications, lead to various types of gut inflammation. In a number of these models, there is good evidence for an anti-inflammatory action of dietary tocopherols, certain polyphenols, and curcumin at relatively high oral doses. It has also been established, that oral application of fats and oils rich in n-3 PUFAs and/or conjugated linoleic acid (CLA) can attenuate certain types of colitis in experimental animal models. While the effect of dietary calcium on experimental colitis is less clear, there are hints indicating that certain high-fiber diets or diets rich in digestion-resistant carbohydrates ("fiber") can attenuate experimental colitis in animals, although contradictory results have been reported. In summary, the anti-inflammatory potency of dietary constituents on colon inflammation in experimental animals seems to be rather limited. The reasons for this lack of activity seem to be manifold including pharmacokinetic limitations and intestinal degradation of the compounds, in particular insufficient local, i. e., intra- or sub-mucosal levels of the effective compounds, and general limitations of animal models. [source] | ||||||||||