Biochemical effects of two promoters of hepatocarcinogenesis in rats

The effects of two promoters of hepatocarcinogenesis--phenobarbital and butylated hydroxytoluene (BHT)--on five hepatic biochemical parameters were examined in adult female rats. Phenobarbital given orally in two doses each of 110 mg/kg 21 and 4 hr before the rats were killed caused large increases in hepatic ornithine decarboxylase (ODC) activity and cytochrome P-450 content. Extending the number of phenobarbital treatments to five increased the hepatic enzyme induction and also caused a minor decrease in hepatic glutathione and a small increase in serum alanine aminotransferase activity. Two oral doses of 700 mg BHT/kg (20% of the LD50) caused hepatic DNA damage and induction of both ODC activity and cytochrome P-450 content. When the dose of BHT was reduced from 700 to 140 mg/kg no significant effects on the biochemical parameters were found. Both promoters of hepatocarcinogenesis were identified by their induction of ODC, a marker for promotional potential, but only BHT showed a potential for carcinogenic initiation. The biochemical parameters examined, particularly the alkaline elution technique for DNA damage, ornithine decarboxylase activity and serum alanine aminotransferase, may constitute a useful assay system for examining a compound's potential for carcinogenic initiation, carcinogenic promotion and cellular toxicity.     

Obese, overweight, desirable, ideal: where to draw the line in 1986?

In February 1985, the National Institutes of Health sponsored the Consensus Development Conference on the Health Implications of Obesity. The panel of experts concluded that height and weight tables based on mortality data and the body mass index (BMI) are helpful measures to determine the presence of obesity and the need for treatment. For the dietitian, however, practical concerns arise regarding which index to select. The usefulness of the BMI in patient education and contradictions between the 1959 and 1983 Metropolitan Life Insurance height-weight tables are discussed. A temporary solution is offered in light of the need for further investigation into morbidity experience at weights recommended in the 1983 table.     

Modelling the interaction of small organic molecules with biomacromolecules. III. Interaction of benzoates with anti-p-(p'-azophenylazo)benzoate antibody

A novel approach for modelling the biological activity of organic molecules, which requires simultaneous consideration of the influence of all factors (topological, steric, hydrophobic, and electronic) that determine the bioactivity, is used to study the interaction of a series of benzoates with anti-p-(p'-azophenylazo)benzoate antibody. The results obtained suggest that this biological interaction proceeds by a two-step stereospecific mechanism. The first step requires a geometrical correspondence between the benzoates and the cavity in the biomacromolecule, which enables the pharmacophore to come into close contact with the receptor. The second step is the orbitally controlled electronic interaction between the active parts of the benzoates and the antibody. The electronic interaction results from pi-charge transfer from the pharmacophore to the biomacromolecule and from the formation of pi-complexes. A proposed mathematical model for this biological interaction exhibits some statistical advantages over existing models.     

Bioavailability of mefenamic acid: influence of food and water intake

The influence of food and water intake on mefenamic acid (N-2,3-xylylanthranilic acid) bioavailability from commercial capsules of high bioavailability was studied in four healthy male volunteers. The drug was administered as a single oral dose of 250 mg, under fasting or nonfasting conditions, and a 4 X 4 Latin-square design was used. Eight blood samples were collected over a 24-h period following drug administration, and the drug plasma concentrations were determined by HPLC. The bioavailability of mefenamic acid from capsules was markedly influenced in the fasting subjects by the water but not by the food intake. A good correlation was found between the bioavailability and amount of water ingested with the drug in the fasting subjects. The area under the plasma concentration-time curve (AUC0-infinity) of mefenamic acid was highest when the capsule was taken with 50 mL of water or immediately after a meal. Increasing the amount of water from 50 to 500 mL in the fasting subjects caused a significant reduction in AUC0-infinity.     

Analysis of the activities of a geriatric assessment and rehabilitation unit

In a four month period 228 patients were admitted to the Wakari assessment and rehabilitation unit in Dunedin, New Zealand. One hundred and seventy subjects came from the community, 35 were transferred from the local public hospital, and 23 were readmitted. Median lengths of stay were 13, 26 and 10 days respectively. Assessment of activities of daily living (ADL) dependency on admission and discharge showed a significant improvement in ability by discharge, which correlated closely with place to which subjects were discharged, and with survival. There was 5% inpatients death rate which cumulated to 18%, 23%, 34%, 39% and 46% by six weeks, three months, six months, nine months and one year respectively. High discharge dependency was closely related to poor survival after discharge. Use of domiciliary services did not change because the savings from those who moved into institutions were cancelled out by those who were discharged back to the community being in need of increased social support.