Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury.

Design of the Women's Health Initiative clinical trial and observational study

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)61452-9.pdf

Selenium and human health

Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy for smoking cessation, a potential medication for several diseases, and a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). We review current knowledge about the metabolism and disposition kinetics of nicotine, some other naturally occurring tobacco alkaloids, and nicotine analogs that are under development as potential therapeutic agents. The focus is on studies in humans, but animal data are mentioned when relevant to the interpretation of human data. The pathways of nicotine metabolism are described in detail. Absorption, distribution, metabolism, and excretion of nicotine and related compounds are reviewed. Enzymes involved in nicotine metabolism including cytochrome P450 enzymes, aldehyde oxidase, flavin-containing monooxygenase 3, amine N-methyltransferase, and UDP-glucuronosyltransferases are represented, as well as factors affecting metabolism, such as genetic variations in metabolic enzymes, effects of diet, age, gender, pregnancy, liver and kidney diseases, and racial and ethnic differences. Also effects of smoking and various inhibitors and inducers, including oral contraceptives, on nicotine metabolism are discussed. Due to the significance of the CYP2A6 enzyme in nicotine clearance, special emphasis is given to the effects and population distributions of CYP2A6 alleles and the regulation of CYP2A6 enzyme.

Metabolism and Disposition Kinetics of Nicotine

Physiological Parameter Values for Physiologically Based Pharmacokinetic Models

OBJECTIVE To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. RESULTS Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. CONCLUSIONS Ginseng may be a useful therapeutic adjunct in the management of NIDDM.

Ginseng therapy in non-insulin-dependent diabetic patients.

Objectives
The effect of aging on drug metabolism in humans has not yet been completely described.

Methods
Two hundred twenty-six patients with equal histopathologic conditions were investigated. The cytochrome P450 contents in the liver biopsy samples, the plasma antipyrine clearance rates after oral administration and, as an independent control of vitality, serum testosterone levels were determined.

Results
Cytochrome P450 content in subjects from 20 to 29 years of age was 7.2 ± 2.6 nmol · gm−1, increased during the fourth decade (+ 7.2%, p = NS), declined after 40 years (−16%, p < 0.01) to a level that remained unaltered up to 69 years, and declined further after 70 years (−32%, p < 0.001). The antipyrine (phenazone) clearance rate in young subjects was 46.4 ± 18.5 ml · min−1, remained unaltered during the fourth decade, and declined after 40 years by a rate of 0.34 ml · min−1 per year toward old age (−29%, p < 0.001). The half-life in young subjects was 9.5 ± 2.0 hours and increased after 30 years toward old age (+26%, p < 0.001). The volume of antipyrine distribution, 0.46 ± 0.12 L · kg−1 in young subjects, decreased after 30 years (−11%). In line with the testosterone content, the decrease in drug metabolism was equal in both sexes.

Conclusion
This study shows a reduction of in vitro and in vivo drug metabolism with age in humans. The data suggest that at least three age groups—young, middle-aged, and elderly—should be included in the evaluation of the pharmacokinetics of a new drug. The reduction of drug metabolism (−30%) after 70 years of age indicates that care is needed in the prescription of drugs for elderly subjects.

Clinical Pharmacology & Therapeutics (1997) 61, 331–339; doi:

Age and cytochrome P450-linked drug metabolism in humans: An analysis of 226 subjects with equal histopathologic conditions

Immunochemical and catalytical studies on hepatic coumarin 7-hydroxylase in man, rat, and mouse.

. The two major constituents of basement membranes are type IV collagen and laminin. Specific radioimmunoassays are described here for two structural domains of these proteins (7-S collagen and the fragment PI, respectively) that allow the related antigens to be quantified in human serum. The serum 7-S collagen antigen was uniform in size, whereas the laminin PI antigenicity was heterogeneous. These proteins were measured in sera from sixty-three alcoholics, divided on the basis of liver histology into four groups: normal light microscopy, fatty liver, alcoholic cirrhosis with hepatitids and inactive cirrhosis. The group with cirrhosis and hepatitis had clearly elevated values in both assays, differing significantly from the others. A few pathological results were also seen in the other groups. The increases noted in 7-S collagen concentration were larger than those in laminin PI. During follow-up of a patient with cirrhosis and hepatitis the 7-S collagen level in particular seemed to reflect the course of the disease. The elevated basement membrane protein concentrations in serum may be associated with the formation of real basement membranes in the perisinusoidal space, a process known as capillarization of the sinusoids which is found during the development of liver cirrhosis.

Type IV collagen and laminin‐related antigens in human serum in alcoholic liver disease

The effect of cimetidine on human microsomal drug metabolism was studied. In five of six healthy volunteers therapeutic doses of cimetidine prolonged the half-life of antipyrine (range 12–37%; p<0.05). Its clearance was decreased in five subjects (range 2–18%) and was increased in one subject (15%), the changes not being statistically significant. The volume of distribution increased on average by about 14% (range 9–19%; p<0.001). Cimetidine in vitro inhibited the hydroxylation of benzo(a)pyrene and coumarin, as well as the O-deethylation of 7-ethoxycoumarin, by homogenised liver biopsies. The in vitro studies suggest that the effect of cimetidine on antipyrine elimination is due to inhibition of microsomal drug metabolism, which may prove an important drug interaction.

Eero A. Sotaniemi

Papers

Ginseng therapy in non-insulin-dependent diabetic patients.

Age and cytochrome P450-linked drug metabolism in humans: An analysis of 226 subjects with equal histopathologic conditions

Immunochemical and catalytical studies on hepatic coumarin 7-hydroxylase in man, rat, and mouse.

Type IV collagen and laminin‐related antigens in human serum in alcoholic liver disease

Effect of cimetidine on microsomal drug metabolism in man.