Effects of ethanol administration on components of the ubiquitin proteolytic pathway in rat liver

Hepatic protein accumulation during ethanol administration may result partly from an ethanol-elicited decline in hepatic protein degradation, which we have previously shown. We conducted the current studies to examine the effects of ethanol administration on the levels of hepatic ubiquitin, an 8.5-kd protein which is an important mediator of extralysosomal protein catabolism. Rats were pair-fed liquid diets containing either ethanol (36% of calories) or isocaloric maltose-dextrin for 1 to 5 weeks. Ubiquitin was immunochemically quantified by competitive enzyme-linked immunosorbent assay (ELISA) in crude cytosol fractions from whole liver and in 12,000g supernatants of hepatocyte lysates. Ubiquitin levels in hepatic cytosol fractions of ethanol-fed rats exceeded those of controls by about 30%. Isolated hepatocytes from ethanol-fed animals also showed a 40% to 75% elevation of ubiquitin above that in cells of pair-fed controls and this difference exceeded the relative rise in hepatocellular protein. In hepatocyte lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting, we detected monomeric ubiquitin and higher molecular mass ubiquitin-protein conjugates. However, the immunoblot analyses revealed no quantitative changes in the level of either free or conjugated ubiquitin. The ubiquitin conjugating activity of crude and diethyl aminoethyl-fractionated liver cytosols of ethanol-fed rats had equal capacities to those from controls in catalyzing the formation of ubiquitin-protein conjugates. Our findings indicate that chronic ethanol consumption increased the level of immunoreactive ubiquitin in rat liver. This may have resulted from enhanced ubiquitin production because of an ethanol-elicited stress response and/or decreased catabolism of ubiquitin and its conjugates. Our findings also provide no indication that the ethanol-elicited reduction in hepatic proteolysis is because of a ubiquitin-mediated mechanisms.     

Effect of cortisone on post-traumatic regeneration of mammalian skeletal muscle

Prolonged administration of cortisone to sexually immature rabbits and rats, in which m. tibialis anterior was injured preliminarily, inhibited the process of regeneration of the skeletal muscle tissue; this was expressed in the retarded growth of myosymplasts and of the muscle tubes. By the 15th postoperative day experimental rabbits (in comparison with control) showed a lesser area of muscle component of the regenerated tissue. Analysis of the intensity of methionine-H3 incorporation into the regenerating elements of the muscle tissue demonstrated a significant reduction of the label incorporation into the nuclear and cytoplasmic proteins of the myosymplasts of rats to which cortisone was given. Inhibition of the protein synthesis at the early stage of differentiation of the muscle tissue was expressed to a lesser extent than in the mature differentiated muscle fibers of the intact muscle.     

Effect of adrenaline on the secretory activity of the ocular ciliary body in rabbits

In intact rabbits and in rabbits with intracerebral unilateral section of the n. oculomotorius, instillation of 2 drops of 0.1% adrenaline into the conjunctival sack increased and then decreased the intraocular pressure (IOP); i.v. administration of adrenaline (50 mcg) or electrophoresis decreased IOP. In conditions of disturbed parasympathetic innervation of the eye its sensitivity to adrenaline increased as revealed by a sharper lowering of IOP.     

A case-control study of menopausal estrogen therapy and breast cancer

The association between estrogen replacement therapy and female breast cancer was studied in two Los Angeles area retirement communities. The 138 study cases of breast cancer occurring in residents younger than 75 years were compared with age- and race-matched community control subjects. The risk ratio for a total cumulative dose in excess of 1,500 mg was estimated to be 2.5 in women with intact ovaries. This increase was present using various independent sources of drug usage information but was inconsistent at low dose and undetectable in oophorectomized women. No important sources of confounding could be identified, and no risk modifiers could be identified except for a history of surgically confirmed benign breast disease. In such women with intact ovaries, the risk ratio for a high cumulative dose rose to 5.7 relative to nonusers with normal breasts.     

Initial experience of clinical pharmacology and clinical pharmacy interactions in a clinical pharmacokinetics consultation service

International statistics indicate that there is a close correlation between the consumption of saturated fats (dairy fats and meat fats) and the mortality from coronary heart disease (CHD), and this conception has been confirmed by many epidemiological studies. Such studies alone, however, cannot prove the existence of a cause-and-effect relationship between these two variables; dietary intervention trials are needed. The Finnish Mental Hospital Study was such a trial, conducted in two hospitals near Helsinki in 1959--1971. Practically total replacement of dairy fats by vegetable oils in the diets of these hospitals was followed by a substantial reduction in the mortality of men from CHD. Total mortality also appeared to be reduced. As to the causes of death other than CHD, none was significantly influenced by dietary change. This was also true for malignant neoplasms. To alleviate the burden of CHD on public health, many investigators have recommended important changes in the quantity and quality of dietary fats.     

The fluoride content of teeth in the canton of Vaud 5 years after the introduction of salt fluoridation

Fluroide concentrations in teeth from the canton of Vaud were about at the same level reported from regions with 1,0 ppm F in the drinking water and from children receiving fluoride tablets during tooth formation age.