Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation.

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40-60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs-Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL.

Cardiovascular drug utilisation and socio-economic inequalities in 20 districts of the Czech Republic.

OBJECTIVE: To analyse whether there exists a socio-economic gradient in utilisation of cardiovascular drugs at the district level in the Czech Republic. METHODS: The aggregated data on drug utilisation during the period 1997-2000, expressed in defined daily doses per 1000 inhabitants per day, were obtained from the General Health Insurance Company. Socio-economic characteristics of the districts in year 2000 (percentage of university-educated inhabitants, percentage of single-member households, number of ambulatory physicians per 10,000 inhabitants, unemployment rate and mean monthly income) were used as single unadjusted predictor variables. Partial correlation controlling for age in districts was used to analyse the relationship of cardiovascular disease (CVD) drug utilisation and several socio-economic variables. RESULTS: There were considerable differences in the utilisation of CVD drugs within the districts studied. Significantly higher utilisation of dihydropyridine Ca-channel blockers and statins was found in the districts with a higher percentage of university-educated inhabitants and more ambulatory physicians. CVD drug utilisation (nitrates, fibrates, selective beta-blockers, verapamil and diltiazem and statins) correlated significantly with the percentage of single-member households. The five socio-economic variables explained more than 60% of the variability in use of dihydropyridine Ca-channel blockers, verapamil and diltiazem, ACE inhibitors and statins. CONCLUSION: There exists a significant gradient in the utilisation of mainly newer CVD drug groups within districts of the Czech Republic that can be, at least partly, explained by social characteristics of the districts.

Effects of proteasome inhibitors MG132, ZL3VS and AdaAhx3L3VS on protein metabolism in septic rats.

Proteasome inhibitors are novel therapeutic agents for the treatment of cancer and other severe disorders. One of the possible side effects is influencing the metabolism of proteins. The aim of our study was to evaluate the influence of three proteasome inhibitors MG132, ZL(3)VS and AdaAhx(3)L(3)VS on protein metabolism and leucine oxidation in incubated skeletal muscle of control and septic rats. Total proteolysis was determined according to the rates of tyrosine release into the medium during incubation. The rates of protein synthesis and leucine oxidation were measured in a medium containing L-[1-(14)C]leucine. Protein synthesis was determined as the amount of L-[1-(14)C]leucine incorporated into proteins, and leucine oxidation was evaluated according to the release of (14)CO(2) during incubation. Sepsis was induced in rats by means of caecal ligation and puncture. MG132 reduced proteolysis by more than 50% and protein synthesis by 10-20% in the muscles of healthy rats. In septic rats, proteasome inhibitors, except ZL(3)VS, decreased proteolysis in both soleus and extensor digitorum longus (EDL) muscles, although none of the inhibitors had any effect on protein synthesis. Leucine oxidation was increased by AdaAhx(3)L(3)VS in the septic EDL muscle and decreased by MG132 in intact EDL muscle. We conclude that MG132 and AdaAhx(3)L(3)VS reversed protein catabolism in septic rat muscles.