Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane- induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.      

The treatment of acute cholecystitis

The authors treated 462 patients with acute cholecystitis. Operated on were 220 patients. Of them, 53.6%--at the first 24 hours after admission. In 26.3% of the patients, peritonitis was an indication for the operation. The postoperative lethality was 4.1%.     

The clinical importance of atrial fibrillation-flutter induced by electric transesophageal stimulation of the heart

A study was made of the clinical importance of atrial fibrillation-flutter (AFF) induced by using different modes of left atrium stimulation via the esophagus. Ninety-eight patients were entered into the study including 40 patients with a history of AFF paroxysms, 24 with risk factors of AFF development, and 27 practically normal persons. The stimulation modes applied permitted reproducing stable paroxysms of AFF in 85 percent of the patients with a history of arrhythmias and in none of the normal persons. As for the patients with risk factors, stable paroxysms of AFF could be induced in 33 percent of the cases. The specificity and sensitivity of transesophageal electrophysiologic stimulation (TEES) with the modes applied were 100 and 82 percent, respectively. The investigations have demonstrated that TEES appeared most effective when applied in the mode of an even increase of the frequency of the set pace up to 300 imp/min.     

Dual effects of endogenous DNases on transcriptionally active and inactive chromatin

Experiments on resting hepatocytes with inactive c-fos gene and active albumin gene. We revealed that DNA of the transcribed gene is less susceptible to the influence of endogenous Ca2+/Mg(2+)-dependent DNases in matrix-associated and highly soluble chromatin fractions. In the fraction of low soluble chromatin active gene was more accessible for DNases. Our results indicate that activity of endogenous DNases can change in the transcribed gene locus.