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Biomedical subjects

V R Preedy

Publications and source records attributed to V R Preedy.

At least 55 records · Page 3Linked to original sources
PubMed2000

Alcohol-induced reductions in cardiac protein synthesis in vivo are not ameliorated by treatment with the dihydropyridine calcium channel blocker amlodipine.

BACKGROUND: Various studies have indicated that acute ethanol dosage perturbs cardiac function and/or structure with concomitant reductions in protein synthesis. Cellular calcium homeostasis is also perturbed, which may contribute to altered protein synthesis. This is supported by the observation that calcium channel blockers can prevent numerous features of alcohol-induced pathology. However, many of these studies have been carried out in vitro, employing supraphysiological levels of alcohol, or have failed to address whether their results obtained in isolated systems have direct relevance in vivo. The aim of the present investigation was to examine the response of cardiac protein synthesis in vivo due to a physiologically relevant dose of ethanol and determine whether a calcium channel antagonist could prevent these effects. METHODS: Changes in cardiac protein synthesis rates in vivo were assessed by measuring the fractional rates of protein synthesis (i.e., ks) using a "flooding dose" of [3H]phenylalanine. Rats were treated either acutely (10 mg/kg body weight, 3 hr) or chronically (10 mg/kg body weight/day, 30 days) with amlodipine, a dihydropyridine-type calcium channel blocker, before dosing with ethanol (75 mmol/kg body weight, 2.5 hr). RESULTS: Ethanol (75 mmol/kg body weight) inhibited cardiac protein synthesis after 1 hr. Similar responses were recorded at 2.5 and 6 hr after ethanol dosage. At 24 hr, ethanol decreased food intakes. However, a direct comparison between pair-fed controls and alcohol-dosed rats also showed a decrease in cardiac protein synthesis after 24 hr. Acute alcohol dosage reduced cardiac protein synthesis in mixed, myofibrillary, and sarcoplasmic protein fractions. Similar results were obtained when data were expressed relative to ribonucleic acid (i.e., kRNA). Neither acute nor chronic treatments with the calcium antagonist amlodipine ameliorated the deleterious actions of ethanol on protein synthesis. CONCLUSIONS: Ethanol may affect cardiac protein synthesis independently of altered calcium entry.

Amlodipine↗
PubMed2000

Carbonyl levels in type I and II fiber-rich muscles and their response to chronic ethanol feeding in vivo and hydroxyl and superoxide radicals in vitro.

BACKGROUND: Chronic alcoholic myopathy is characterized by selective reductions in the size of Type II skeletal muscle fibers (i.e., glycolytic, anaerobic fast-twitch). Type I (i.e., oxidative, aerobic, slow twitch) fibers are relatively resistant. It is possible that reactive oxygen species may preferentially damage the Type II fibers because the concentrations of several antioxidant enzymes are lower in Type II compared with Type I fibers. METHODS: To test the hypothesis, we measured protein carbonyl levels in Type I (i.e., soleus) and Type II (i.e., plantaris) fiber-rich muscles of rats subjected to chronic alcohol dosage with the Lieber-DeCarli regimen. Muscles were also exposed to hydroxyl or superoxide radicals in vitro. RESULTS: The Type I fiber-predominant soleus of control animals had less carbonyl than the Type II fiber-predominant plantaris. In rats that were fed ethanol for 6 weeks, the weights of the plantaris muscle were preferentially reduced but changes in soleus weight did not achieve significance. However, carbonyl levels were not significantly altered in any muscle in response to alcohol feeding. Calculation of the data in terms of total carbonyl per whole muscle showed decreases in both soleus and plantaris at the end of the 6-week alcohol feeding period. In response to hydroxyl radical (OH*) generation in vitro, protein carbonyl increased substantially in both soleus and plantaris muscles, but more so in the soleus. The increase in carbonyl in control soleus muscles in response to OH* was significantly lower than in soleus muscles from alcohol-fed animals. The increase in control plantaris muscle was not significantly different from the increase in carbonyl in corresponding muscles from ethanol-fed rats in response to OH*. In response to superoxide radicals, carbonyl in control soleus increased, an effect similar to that recorded in the soleus from ethanol-fed rats. In control plantaris, carbonyl increased in response to superoxide radicals, an effect not significantly different to the increase in plantaris from alcohol-fed rats. CONCLUSIONS: Using increased carbonyl concentrations as an indicator of muscle damage by reactive oxygen species, we concluded (1) there is no evidence of enhanced reactive oxygen species-induced damage to mixed muscle proteins in either Type I or Type II muscles in response to alcohol feeding; (2) Type II muscles have a greater capacity than Type I muscles to protect against damage (as indicated by carbonyl formation) by both hydroxyl and superoxide radicals in vitro; (3) alcohol reduces the capacity of Type I muscle to resist hydroxyl radical-induced protein damage, a mechanism that may arise through impairment of other antioxidant systems or other process not yet elucidated.

Alcoholism↗
PubMed1999

Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle.

The chronic form of alcoholic skeletal myopathy is characterized by selective atrophy of Type II fibers and affects up to two thirds of all alcohol misusers. Plasma selenium and alpha-tocopherol are reduced in myopathic alcoholics compared to alcoholic patients without myopathy. Plasma carnosinase is also reduced in myopathic alcoholics, implicating a mechanism related to reduced intramuscular carnosine, an imidazole dipeptide with putative antioxidant properties. Together with the observation that alcoholic patients have increased indices of lipid peroxidation, there is evidence suggestive of free radical (i.e., unpaired electrons or reactive oxygen species) mediated damage in the pathogenesis of alcohol-induced muscle disease. Protein synthesis is a multi-step process that encompasses amino acid transport, signal transduction, translation and transcription. Any defect in one or more of the innumerable components of each process will have an impact on protein synthesis, as determined by radiolabelling of constituent proteins. Both acute and chronic alcohol exposure are associated with a reduction in skeletal muscle protein synthesis. Paradoxically, alcohol-feeding studies in rats have shown that the imidazole dipeptide concentrations are increased in myopathic muscles though alpha-tocopherol contents are not significantly altered. In acutely dosed rats, where protein synthesis is reduced, protein carbonyl concentrations (an index of oxidative damage to muscle) also decline slightly or are unaltered, contrary to the expected increase. Alcoholic cardiomyopathy can ensue from heavy consumption of alcohol over a long period of time. The clinical features include poor myocardial contractility with reduced left ventricular ejection volume, raised tissue enzymes, dilation of the left ventricle, raised auto- antibodies and defects in mitochondrial function. Whilst oxidant damage occurs in experimental models, however this issues remains to be confirmed in the clinical setting. In the rat, circulating troponin-T release increases in the presence of ethanol, a mechanism ascribed to free radical mediated damage, as it is prevented with the xanthine oxidase inhibitor and beta-blocker, propranolol. However, whilst propranolol prevents the release of troponin-T, it does not prevent the fall in whole cardiac protein synthesis, suggestive of localized ischemic damage due to ethanol.

Animals↗
PubMed1999

Effect of ethanol and acetaldehyde on intracellular protease activities in human liver, brain and muscle tissues in vitro.

The effect of ethanol and acetaldehyde on the activity of a range of intracellular cytoplasmic and lysosomal proteolytic enzymes has been determined in human brain, liver and skeletal muscle tissues in vitro. There was a substantial degree of inhibition for most protease types in all tissues if sufficiently high concentrations of ethanol (10%, v/v; 1.7 mol/L) or acetaldehyde (1%, v/v; 0.17 mol/L) were used in the assay media. However, it was concluded that direct inhibition of proteases in vivo by ethanol or acetaldehyde is improbable, at the concentrations of these agents likely to pertain in vivo, and that any effect of these agents on intracellular protein catabolism must occur via a more subtle biochemical mechanism.

Acetaldehyde↗
PubMed1999

Free radicals as mediators of alcohol toxicity.

In this article we have reviewed recent evidence in support of the hypothesis that acute/chronic alcohol toxicity is mediated primarily via the generation of damaging free radical species in various tissues. Studies in man, animal model or in vitro experimental systems have shown: (1) the demonstration of alcohol-induced free radical species directly via esr spectroscopic analysis; (2) increases in indirect markers of ethanol-induced free radical damage in tissues, such as lipid peroxides and protein carbonyl; (3) ethanol-induced alterations in the levels of endogenous tissue antioxidants. These data show the induction of free radicals by ethanol to be a complex interactive process. The classical pathway for ethanol metabolism, catalysed by alcohol dehydrogenase to form acetaldehyde, results in the formation of free radicals, resulting from concomitant changes in NADH levels and NADH/NAD+ redox ratios, which in turn modulate the activity of the free radical generating enzyme xanthine oxidase. The induction of CYP 2E1 in the microsomes results in the generation of HER, another major route by which ethanol induces free radical formation. In addition to the above, ethanol may also induce free radical formation via the reaction of aldehyde oxidase with acetaldehyde or NADH to generate oxyradicals via disturbance in the metabolism of the pro-oxidant iron, or via increased efflux from mitochondria following altered mitochondrial oxidative metabolism.

Alcoholism↗
PubMed1998

Metabolic consequences of alcohol ingestion.

Many of the pathophysiological effects of alcohol ingestion relate to the pathways of ethanol metabolism. However, some of the acute and chronic effects of ethanol use are also attributable to the direct effects of ethanol, e.g. on membrane fluidity. Oxidation of ethanol to acetaldehyde is catalysed by alcohol dehydrogenase (ADH). There are at least six classes of ADH, some of which show inter-individual variation, i.e. genetic polymorphism, that influences the rate of ethanol oxidation. A consequence of ethanol oxidation is an increase in the NADH/NAD redox potential within the cytosol and mitochondria with subsequent alteration in several tissue metabolites. The popular hypothesis that most, if not all, of the consequences of chronic alcohol ingestion can be explained by these redox changes is still unproven. This should be considered in the context that most metabolic pathways of the liver are affected by alcohol, as are several endocrine axes in the whole body. In fact most, if not all, tissues and organs are deleteriously affected by chronic ingestion. Acetaldehyde, the product of ethanol oxidation, is chemically highly reactive, toxic and immunogenic. However, the concentrations achieved in vivo usually fall short of those used to produce these toxic effects in experimental situations. Oxidation of acetaldehyde is also coupled to redox changes, although primarily affecting the intra-mitochondrial redox. In addition, further oxidative pathways of ethanol metabolism can lead to the formation of fatty acid ethyl esters, hydroxyethyl free radicals and reactive oxygen species via the ethanol-specific cytochrome P450-2E1 system. There is no conclusive evidence that nutrient supplementation has beneficial effects on overall ethanol-mediated tissue damage.

Alcohol Drinking↗
PubMed1998

Alcohol and the myocardium.

Structural and functional abnormalities are prominent in alcoholic cardiomyopathy (ACM). Histological features in affected subjects are almost identical to the characteristics of dilated cardiomyopathy. Quantitative morphometry, however, can distinguish between ACM and dilated cardiomyopathy. Biopsies from patients with ACM show increases in the activities of some myocardial enzymes (alpha-hydroxybutyric dehydrogenase, creatine kinase, lactate dehydrogenase, malic dehydrogenase) which are correlated with the bimodal distribution of alcohol intake and may represent an adaptive response. One-third of patients with ACM have serum antibodies against cardiac acetaldehyde-protein adducts. Animal models of ethanol toxicity have shown that acutely, alcohol and acetaldehyde reduce the synthesis of cardiac contractile proteins in vivo. Two-dimensional SDS-PAGE has also shown that in rats chronically fed alcohol, the relative amounts of over 10% of heart muscle proteins are altered. The heat shock proteins (HSP) Hsp60 and Hsp70 are decreased in alcohol-fed rats, as is desmin. Reduction in HSPs may indicate reduced myocardial protection whilst a fall in desmin may indicate structural defects. In conclusion, ACM is a complex process that is due to altered protein synthesis, the formation of acetaldehyde adducts and a reduction of cardiac HSPs and desmin. Both acetaldehyde and alcohol are myocardial perturbants.

Alcohol Drinking↗
PubMed1998

Skeletal muscle ribonuclease activities in chronically ethanol-treated rats.

Alcoholic myopathy occurs in up to two thirds of alcohol misusers and is characterized by selective atrophy of type II (anaerobic, fast-twitch) fibers; type I (aerobic, slow twitch) fibers are relatively unaffected. Both clinical and animal studies have indicated that skeletal muscle RNA content is reduced in response to ethanol exposure, and contributes to impaired protein synthesis. We hypothesized that the reduction in muscle RNA may be due to raised ribonuclease (RNase) activities that enhance RNA catabolism. To test this hypothesis, we measured the total tissue and plasma RNase activities as well as the activities of general (RNase A) and specific or "restriction" RNases (T1L, T2L) in ethanol-treated rats. Chronically treated rats were fed a nutritionally complete liquid diet with 35% of calories as ethanol. Weight-matched controls were pair-fed with isocaloric glucose. Rats were killed at time-points up to 6 weeks. For comparative purposes, the effect of acute (24 hr) starvation was also analyzed in a second group of rats relative to a group of control rats allowed free access to food and water over 24 hr. Results showed that the type II fiber-predominant plantaris muscle exhibited a significant increase in total RNase, RNase A and RNase T1L activities (increases ranged from +59% to +196%; P-values between 0.025 and 0.01) concomitant with large falls in RNA and protein content. In contrast, none of the RNase activities measured in the type I fiber-predominant soleus muscles were significantly affected; compositional changes were also smaller in the soleus. This effect was independent of reduced nutrition. In conclusion, the raised total RNase, RNase A and RNase T1L activities may contribute to the type II fiber-specific reduction in total RNA in chronically ethanol-treated rats. In turn, this may contribute to the alterations in cellular protein metabolism seen under these treatments.

Alcoholism↗
PubMed1997

Protein profiling in cardiac tissue in response to the chronic effects of alcohol.

An investigation was made into cardiac protein levels after chronic ethanol consumption to examine whether specific proteins are affected by alcohol. Ethanol was administered for six weeks to male Wistar rats which were fed a nutritionally complete liquid diet containing 35% of total calories as ethanol. Controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose; thus both groups had identical nutritional intakes, albeit differences in ethanol or carbohydrate. After six weeks' feeding, cardiac tissue was removed and analyzed by two-dimensional electrophoresis, where equal amounts of proteins were studied. Protein patterns were analyzed by computerized densitometry and characterized by comparison with a database of known cardiac proteins. Chronic alcohol feeding caused significant decreases in the relative amounts of various proteins, including several tentatively identified as heat shock protein (HSP) 60, HSP70, and desmin. The relative proportions of actin, vimentin, myosin light chain 1, myosin light chain 2, and albumin, remained unchanged. Examination of antibodies raised against HSP65 showed no overt differences in plasma levels following chronic alcohol consumption, and liver changes as assessed by histology were mild. In conclusion, chronic alcohol appears to have selective effects on particular proteins, and the effects were not directly ascribed to overt liver dysfunction or malnutrition. This may explain some of the functional and morphological characteristics observed in alcohol-induced heart muscle disease, including reduced contractility.

Alcoholism↗
PubMed1997

Effects of the dihydropyridine calcium channel blocker amlodipine on ventricular and atrial protein synthesis in an aortic constriction model of hypertension and, following chronic treatment, in the left ventricle of SHR rats.

The dihydropyridine calcium channel blocking agent amlodipine is an effective anti-hypertensive agent and its use (in doses of 5 or 10 mg/day/kg body weight) was investigated in male Wistar rats with hypertension induced by aortic constriction. Controls were sham-operated and pair-fed. At the end of the study, rates of protein synthesis were measured with radiolabelled phenylalanine to calculate fractional rates of protein synthesis (ks), absolute rates of protein synthesis (Vs) and synthesis rates relative to RNA (kRNA). After 30 days of aortic constriction, weights of the left ventricle and left atrium were significantly increased by hypertension. The weights of the right ventricle and right atrium were relatively unaffected. Hypertension was accompanied by significant increases in the protein and RNA contents of the left ventricle and left atrium. The contractile and non-contractile protein contents were also increased in the left ventricles of hypertensive rats as were total proteins and total RNA. In the myofibrillary fraction, ks decreased. The right ventricle and right atrium were generally unaffected except for a decline in mixed protein ks. Many of these changes in hypertension were ameliorated by treatment with amlodipine, particularly at the higher dose (i.e. 10 mg/kg body weight/day) implicating an effect on protein metabolism. In the left ventricle these included amelioration of the increases in mixed and contractile proteins, total RNA contents, mixed Vs and Vs for sarcoplasmic and stromal proteins. The ameliorating effects of amlodipine were moderate in the left atrium. Furthermore, amlodipine also retarded the hypertension-induced reduction in right ventricule rates of protein synthesis. Although the preceding study emphasises the preventative aspects of amlodipine's efficacy, an additional study was carried out in SHR rats to ascertain the applicability for regression per se. Amlodipine (10 mg/kg/body weight) therapy for 30 weeks caused regression of LV mass, total protein, RNA and DNA contents. We conclude that amlodipine, is an efficient agent in ameliorating the hypertension-induced changes in protein metabolism in an aortic constriction model.

Amlodipine↗
PubMed1997

The effects of alcohol on the heart.

We have discussed in this review many features and possible mechanisms responsible for the development of alcoholic cardiomyopathy. The evidence suggests that defects in myofibrillar protein turnover occur in both acute and chronic alcohol studies. Possible mechanisms to explain poor contractile function include alterations in cellular calcium, magnesium or phosphate homeostasis. The toxic effects of acetaldehyde or the formation of fatty acid ethyl esters may cause impairment of mitochondrial oxidative phosphorylation. Alternatively, reduced amounts of heat shock proteins may result in poor assembly and protection of proteins. In acute ethanol toxicity ischaemia may occur, possibly due to increased xanthine oxidase activity or beta-adrenergic stimulation. Chronic alcohol consumption can also lead to the development of hypertension via magnesium loss and consequent alterations in peripheral vascular calcium regulation. However, these are only a few facets of a complex relationship between alcohol and the cardiovascular system.

Alcohol Drinking↗
PubMed1997

Studies on the time-course of ethanol's acute effects on skeletal muscle protein synthesis: comparison with acute changes in proteolytic activity.

A study of the effects of ethanol on skeletal muscle protein synthesis and protease activities was carried out in young male Wistar rats (150 g) for up to 24 hr after a single intraperitoneal dose of 75 mmol of ethanol/kg of body weight. At 20 min, the mean blood ethanol levels were 448 mg/dl. This level dropped steadily to zero through the following 24 hr. Compared with pair-fed controls, significant reductions in total protein, RNA, and DNA contents were seen only after 24 hr in all skeletal muscles studied: changes were more marked in the muscles containing large proportions of type II fibers. In plantaris muscle, the fractional rate of protein synthesis (ks, %/day) did not fall 20 min after dosage but was reduced after 1 hr by 23% (p < 0.001), and by 63% after 24 hr, compared with control saline-injected rats (p < 0.001). This effect was independent of dietary intake because, compared with the pair-fed group, the 24-hr ethanol-treated rats still showed a 52% decrease in fractional rates of protein synthesis (p < 0.001). Smaller reductions in ks were seen in soleus muscles in response to ethanol at 24 hr (-39%, p < 0.001). The activities of a variety of lysosomal and nonlysosomal proteases in plantaris muscle of 24-hr treated rats were not significantly affected by ethanol. Only alanyl- and tripeptidyl-aminopeptidase activities were reduced significantly (26%, p < 0.05 and 39%, p < 0.01, respectively). These results suggest that the muscle compositional changes seen over acute periods of ethanol toxicity are predominantly associated with impaired synthesis of protein and that the contribution of cellular proteolytic systems may be minimal. The effects of ethanol on skeletal muscle protein metabolism are greater in muscles containing a predominance of type II fibers than in those containing mainly type I fibers. Ethanol's effects on muscle may be influenced by hormonal changes after 24 hr, because protein synthesis is still compromised and free plasma T3 and corticosterone are altered at this time-point.

Alcoholism↗
PubMed1997

Metabolic consequences of alcohol dependency.

Alcohol dependency leads to a variety of biochemical adaptations and morphological changes which may be considered as either adaptive or destructive. This ranges from the utilization of ethanol as a metabolic fuel, to overt tissue and cellular damage, and may lead to increases in morbidity and mortality. Virtually every organ system is affected by either acute and chronic ethanol exposure and numerous metabolic pathways are altered. As a consequence of these wide ranging effects, it is extremely difficult to cover every aspect of alcohol toxicity in a single review. Instead, attention is focussed on selected areas, such as nutrition and protein metabolism in the liver and bone (and to a lesser extent, skeletal muscle and the gastrointestinal tract). The aim is to illustrate the numerous ways in which alcohol affects the body.

Alcohol-Related Disorders↗
PubMed1996

Application of proton NMR spectroscopy to measurement of whole-body RNA degradation rates: effects of surgical stress in human patients.

The urinary catabolites, N2,N2-dimethylguanosine (DMG), pseudouridine (PSU) and 7-methylguanine (m7-Gua) are formed from post-transcriptional methylation of RNA bases and are not reincorporated into RNA upon its degradation. Their quantitative urinary excretion may be used to determine rates of whole body degradation of individual RNA species since DMG occurs exclusively in tRNA, PSU occurs in rRNA and tRNA and m7-Gua occurs in all RNA species. Conventional HPLC analysis has several drawbacks since pre-analytical steps may involve selective losses and, under certain conditions, other urinary analytes may co-elute. In the present paper, we report analysis of these compounds by high-field 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. Urinary concentrations of these metabolites were found to be in agreement with previously published HPLC and ELISA determinations. However, NMR analysis required minimal sample preparation (other than lyophilisation and reconstitution) and was capable of the simultaneous determination of other relevant analytes such as creatinine. This technique was therefore applied to urine samples from patients who had undergone surgical stress and insulin-like growth factor-1 (IGF-I) therapy. Surgical stress increased the excretion of DMG and m7-Gua. Degradation rates for tRNA and mRNA were also higher in surgically stressed subjects when compared with controls but degradation rates of rRNA decreased by approx. 30%. However, injection of IGF-I (40 micrograms/kg s.c.) had no significant effect on the excretion of these nucleosides. These data indicated that IGF-I therapy has no marked effects on RNA turnover following trauma. We suggest that this technique can be applied to study of RNA metabolism in any surgical or medical condition. Furthermore, since only 0.6 ml of urine is required, studies in neonates seem to be feasible.

Adult↗
PubMed1996

Protein synthesis during regression of left ventricular hypertrophy with lisinopril in abdominal aortic constriction model of hypertension.

The use of lisinopril was assessed in inducing regression of established left ventricular hypertrophy. Left ventricular hypertrophy was achieved by aortic constriction in the rat. Lisinopril was administered in drinking water (5 mg/kg body weight/day) to aortic constricted rats starting from Day 30 for a period of further 30 days. At the end of 60 days the rates of protein synthesis were measured using the flooding dose technique. Lisinopril reduced the mixed protein contents of the regressed left ventricle from 223 +/- 7 mg to 175 +/- 10 mg/left ventricle in the aortic constricted rats; P < 0.01, all data are means +/- SEM, n = 5-8. The regression of left ventricular mass occurred along with simultaneous decrease in the rate of protein synthesis (i.e., 6.56 +/- 0.33 in aortic constricted rats versus 4.40 +/- 0.44%/day, in lisinopril treated left ventricles, P < 0.05). However, the expanded cardiocyte fiber thickness remained unchanged despite lisinopril treatment (i.e., 20.4 +/- 0.7 in aortic constricted rats versus 19.5 +/- 0.6 microm in regressed left ventricles, P > 0.05). The results indicate that regression of pressure overloaded hypertrophy with lisinopril primarily occurs by a decrease in protein synthesis in the connective tissue components of the left ventricle, although cytoskeletal components may be unaffected.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

The effect of endotoxin on skeletal muscle protein gene expression in the rat.

Sepsis is associated with net breakdown of skeletal muscle protein, mediated partly by reduced rates of muscle protein synthesis. This study investigated the role of altered gene expression for specific muscle proteins in mediating reduced protein synthesis in a rat model of acute severe sepsis. Adult rats were given a single sublethal intraperitoneal dose of endotoxin (bacterial lipopolysaccharide). Protein, RNA and DNA contents of muscle were measured and changes in expression of mRNA in tibialis anterior and extensor digitorum longus muscles were detected by quantification of Northern blots at 6, 24, 48 and 72 hr after endotoxin and in animals starved for 24 hr. Results showed that at 24 hr after endotoxin there was a loss of about 14% of muscle protein content. No reduction in mRNA was found at any time point for beta-myosin heavy chain (MHC), fast-MHC, alpha-actin, skeletal muscle troponin or carbonic anhydrase III (CA III); rather, at 48 hr there was increased expression of beta-MHC (224 +/- 123% control) and CA III (202 +/- 56%). Blocking TNF-alpha by pre-treatment with a monoclonal antibody did not appear to influence this. Total RNA content of muscle was reduced to 67% of the control values 24 hr after LPS, although this was no different to pair-fed animals starved for 24 hr. It is concluded that reduced protein synthesis in skeletal muscle in early acute sepsis is not primarily associated with reduced muscle protein gene expression.

Actins↗