Mathematical modeling of nicotine and cotinine as biological markers of environmental tobacco smoke exposure

Computer software developed in our laboratory (CMATRIX) was used to design a physiological pharmacokinetic model of nicotine absorption, distribution, metabolism and excretion in man. The model accommodates inhalation of nicotine from various environmental settings and physiological conditions in man. It was also used to predict pharmacokinetic behavior of cotinine arising from nicotine metabolism. Model-predicted variations in body-fluid nicotine levels confirm that nicotine is not an acceptable quantitative marker of environmental tobacco smoke (ETS) exposure. Though cotinine provides a more stable pattern, predicted interindividual variation suggests the need for specific strict sampling and monitoring guidelines for cotinine to be a reliable quantitative marker.     

The state of sulphydryl groups in proteins isolated from normal and cataractous human lenses

Individual crystallins, urea-soluble and urea-insoluble proteins were isolated from the nucleus and cortex of types I-IV cataractous lenses and normal lenses. The levels of protein sulphydryls (P-SH), disulphides (S-S), as well as surface (F-SH) and buried (S-SH) in these proteins were determined by reaction with 5, 5'-dithiotris- (2-nitrobenzoic acid) or performic acid oxidation followed by amino acid analysis. During nuclear colour development there is a progressive decrease in the sulphydryl content of the crystallins. In the nuclei of advanced cataractous lenses, the P-SH decreases to 10% of the levels found in the normal nucleus. Similar but smaller changes take place in the cortex. No specific changes were found between the crystallins, with the exception of beta S crystallin. The cysteine remains constant in all lens types suggesting no higher oxidation products are formed. There is a significant shift in the distribution of cysteine in the nucleus of type III and IV lenses. Urea-insoluble proteins are the predominant species, accounting for about 70% of the total cysteine pool. This is consistent with the accumulation of modified insoluble polypeptides during senile nuclear cataract formation.     

The development of neurons in the cat perigeniculate nucleus and reticular nucleus of the thalamus

The postnatal development of soma size and cytochrome oxidase activity was examined in the perigeniculate nucleus (PGN) and reticular nucleus of the thalamus (RNT). Neurons in the PGN and RNT exhibited a rapid increase in soma size between 2 and 4 weeks of age. During this period of cell growth there is an increase in the intensity of cytochrome oxidase staining within the cell body. Cells in both the PGN and RNT decrease in size after 4 weeks of age, and become very fusiform in shape. During this postnatal period, there is also a shift in cytochrome oxidase staining from the cell body to the dendrites.     

An epidemic of cirrhosis in Danish women revisited

Between 1944 and 1947 the mortality statistics for the Danish population show an epidemic increase of liver diseases: subacute necrosis and cirrhosis. The epidemic only affected female mortality rates. Mortality due to cirrhosis remained at a higher rate for women than men until 1970 as a result of an excess mortality in the cohort of women who in 1945 were over the age of 45. Up to 1981 this group showed an excess of 4,000 fatalities. A reevaluation of medico-statistical data shows that the disease cannot be explained by the epidemic hepatitis occurring in 1942-1944 or by increased consumption of alcohol. Possible causes could be pharmaceutical products or additives, perhaps hormone preparations.