Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with antioxidants was investigated. Adult female Sprague-Dawley rats were injected sc with 5 micromol CdCl2/kg/day, 5 times a week, for up to 22 weeks. Serum alanine amino transferase and lactate dehydrogenase activities were elevated after 9 weeks of Cd administration, indicating hepatic damage. Renal toxicity, indicated by elevation in urinary lactate dehydrogenase activity and protein, was also observed around this time. Chronic Cd administration resulted in a gradual rise in hepatic as well as renal cortex glutathione levels. In spite of this, lipid peroxidation increased in both tissues, particularly during the second half of the Cd exposure period. Depletion of glutathione following buthionine sulfoximine administration at the end of Week 5, or inhibition of catalase by aminotriazole at the end of Week 7, resulted in the development of acute nephrotoxicity within 6 h. Coadministration of antioxidants, N-acetylcysteine (50-100 mg/kg, sc), or vitamin E (100-150 mg/kg, sc) with Cd, starting from the early phases of Cd exposure, controlled Cd-induced lipid peroxidation and protected the animals against hepatic as well as renal toxicity. A Japanese hepatoprotective drug, Stronger Neo-Minophagen C, containing glycyrrhizin, glycine, and cysteine, was also effective in reducing the chronic Cd nephrotoxicity. In conclusion, oxidative stress appears to play a major role in chronic Cd-induced hepatic and renal toxicity since inhibition of components of the antioxidant defense system accelerated and administration of antioxidants protected against Cd toxicity.     

Synthesis and properties of mixed ribodeoxyribooligonucleotide duplexes containing an internucleotide trisubstituted pyrophosphate bond

To assess the early stage of atherosclerosis of the thoracic descending aorta, we evaluated morphological atheromatous lesions (atherosis) and the stiffness parameter of the artery (beta; sclerosis) in 24 male rabbits using echography. Male Japanese white rabbits weighing 2.5-3.0 kg were fed a diet containing 1% cholesterol for 7 (n = 8) or 14 weeks (n = 8). Rabbits fed a normal diet were used as controls (n = 8). Atheromatous lesions were evaluated with intravascular ultrasound (IVUS: Aloka, 20 MHz, 6F). We also calculated beta using M-mode echography (7.5 or 10 MHz) and direct aortic pressure measurement. Thickening of the intima-media complex was clearly observed with IVUS in the 14-week group but was not detected in the others. Histologically, only a thin layer of foamy cells on the intima (thickness < 20 microns) was observed in the 7-week group. The value of beta was significantly increased in both the 7-week (4.7 +/- 2.2) and 14-week groups (4.5 +/- 0.8) compared with controls (1.7 +/- 0.9, both p < 0.01). These results suggest that the development of atherosis might be preceded by vascular sclerosis during the early stage of atherosclerosis when the serum cholesterol level is high: at a time when the thin layer of foamy cells could not be detected by conventional IVUS.     

Immune status indices during the combined treatment of patients with duodenal peptic ulcer

Indices were studied of the immunological status (cell-mediated, humoral immunity) before and after the multimodality pathogenetic treatment of patients with duodenal ulcer. Noted in the course of the complex treatment were changes in the immunoregulatory index, NK-cells, IgM. The findings obtained suggest that the immune defence may be depressed, with the vascular factor, infection (Helicobacter pylori) having their part in the genesis of duodenal ulcer.     

Influence of dietary protein, energy and corticosteroids on protein turnover, proteoglycan sulphation and growth of long bone and skeletal muscle in the rat

Ratings of temperament for 32 children with Down syndrome and 44 children who were developing normally over the developmental range from 12 to 36 months were compared. Mothers completed the Toddler Temperament Scales and/or the Bates Infant/Child Characteristics Questionnaire at two time points. Analyses tested for diagnostic group differences in temperament ratings. Multivariate repeated measures analyses of variance, with diagnosis and developmental age as grouping variables, were run for both instruments. For the Toddler Temperament Scales, no between-subjects main effects of diagnosis or interactions were significant; however, a significant multivariate main effect for diagnosis was obtained for the Bates Scales. Ordering consistency for the two samples was considered separately. Cross-time correlations were generally significant; however, relations tended to be of greater magnitude in the normally developing group. Results suggest that the development of temperament, as assessed with maternal ratings, follows a common path in these two groups.     

Serum immunoglobulins, rheumatoid factor, and pneumoconiosis in coal miners with rheumatoid arthritis

The occurrence and severity of pneumoconiosis were studied in 100 coal miners with rheumatoid arthritis (RA) and compared to findings in a geographically relevant survey of coal workers' pneumoconiosis. Contrary to European reports, miners with RA were not found to have an excessive frequency or severity of pneumoconiosis. In 55 of these men, serum immunoglobulin levels and rheumatoid factor were compared with data from matched RA patients with no history of silica exposure. The immunochemical results were unrelated to the stage of pneumoconiosis, nor did they differ from those in the control group.     

Synthesis and properties of covalently-closed DNA duplexes containing pyrophosphate and and substituted pyrophosphate internucleotide groups

A new method for the efficient synthesis of covalently closed DNA duplexes (DNA dumbbells) and the introduction of pyrophosphate and substituted pyrophosphate internucleotide groups into their structure is proposed. The method is based on chemical ligation in DNA duplexes that are formed by a polynucleotide the ends of which are brought together due to the introduction of the minihairpin structure [sequence: see text]. DNA dumbbells containing a pyrophosphate (substituted pyrophosphate) group result from the interaction as being between the 3'-terminal phosphate (methylphosphate) group of the polynucleotide and the 5'-terminal phosphate group of deoxyguanosine of the minihairpin sequence, which flanks the polynucleotide from the 5' end. 1-Ethyl-3-(3'-dimethylaminopropyl) carbodiimide was used as a condensing agent. The yield of covalently closed 42-mer DNA duplexes containing a pyrophosphate group was 98%, that of duplexes with a substituted pyrophosphate group was 25%. The reactivity of the substituted pyrophosphate group incorporated into DNA dumbbells was studied. It is shown that the group efficiently interacts with nucleophiles in an aqueous medium at pH 8.0.