Utility of biological markers during outpatient treatment of alcohol-dependent subjects: carbohydrate-deficient transferrin responds to moderate changes in alcohol consumption.

A group of 25 alcohol-dependent subjects in outpatient treatment were monitored for a period of 4 weeks. They were weekly interviewed for their alcohol consumption and their serum levels of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) were analyzed. The majority of the patients reported an excessive and fairly constant alcohol intake during the observation period. When selecting those patients that reported periods of 1 or 2 weeks with moderate changes in alcohol consumption, corresponding changes in CDT were demonstrated. Thus, of 14 patients reporting an increased alcohol consumption for 2 weeks (mean values increased from 57 to 101 g/day), 11 showed an increase in CDT at the end of the period. The mean CDT value of all 14 increased from 5.5 to 6.7% (p < 0.05). Slight, but not significant, increases were noted in GT, indicating that CDT is more sensitive than GT in detecting increased alcohol consumption. Furthermore, of 17 patients that reported decreased alcohol consumption for one or several weeks, 14 showed decreased CDT and GT values. The mean values of all 17 were reduced from 5.1% to 4.5% (CDT) and from 126 units/liter to 97 units/liter (GT) (p < 0.05 for both parameters). The results indicate that CDT responds to moderate changes in alcohol consumption in alcohol-dependent patients and may thus be useful as a corrective tool to self-reports of alcohol consumption during outpatient treatments.

Substrate preference of isolated perfused rat hearts during hypothermia and rewarming.

Fatty acid and glucose oxidation rates were measured in isolated rat hearts undergoing hypothermia and rewarming. The hearts were perfused in the Langendorff mode with Krebs-Henseleit bicarbonate buffer containing 11.1 mM glucose plus 0.6 mM albumin-bound oleic acid as energy substrates. The hearts were stabilized at 37 degrees C and thereafter cooled progressively to 15 degrees C over a period of 60 min. The hearts were kept at this temperature for 10 min and then rewarmed to 37 degrees C during the next 30 min. Control hearts were perfused at 37 degrees C throughout the whole perfusion period. Trace amounts of [14C]glucose or [14C]oleic acid were included in the perfusate, and the rate of substrate oxidation was determined on the basis of the radioactive CO2 production. In normothermic hearts steady state oxidation rates of glucose and oleate were found to be 0.17 +/- 0.01 and 0.51 +/- 0.07 mumol min-1 g-1 dry wt, respectively (mean +/- SEM). In response to hypothermia (15 degrees C) glucose oxidation was reduced by 76% (from 0.17 +/- 0.01 to 0.04 +/- 0.01 mumol min-1 g-1 dry wt) and oleate oxidation by 47% (from 0.51 +/- 0.07 to 0.27 +/- 0.02 mumol min-1 g-1 dry wt). Upon rewarming glucose and fatty acid oxidation rates returned to essentially the same values (0.12 +/- 0.02 and 0.45 +/- 0.04 mumol min-1 g-1 dry wt) as those observed under steady state normothermic conditions. The molar ratio between glucose and fatty acid oxidation was, however, significantly (P < 0.05) lower in hypothermic than in normothermic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphatidylcholine metabolism in hypoxic and phospholipase C exposed rat ventricular myocytes.

A phospholipase C specific for choline and ethanolamine acyl and plasmalogen glycerophospholipids (PC-PLC) has been described in myocardial tissue. In the present study we investigated whether an endogenous PC-PLC is activated in hypoxic, substrate-free incubations of rat ventricular myocytes. The phosphatidylcholine pool of the myocytes was prelabelled with [14C]choline during a 4-h preincubation (pulse) period. The myocytes were subsequently washed and incubated for another 2 h (chase period) in normoxic, hypoxic, or hypoxic buffer supplemented with PC-PLC from Bacillus cereus. We hypothesized that an increase in the total (intracellular plus extracellular) content of [14C]phosphocholine (one of the products resulting from PC-PLC action on phosphatidylcholine) throughout the chase period would indicate PC-PLC activity. Instead, an apparent decrease was observed for this parameter in all myocyte groups (17-29%), even in the one exposed to exogenous PC-PLC. However, 60 min after the start of the chase period, the level of total [14C]phosphocholine was higher in hypoxic (p = 0.022) and hypoxic + PC-PLC exposed (p = 0.013) myocytes compared with normoxic controls. The total content of [14C]choline increased significantly (p < 0.017) in all myocyte groups during the incubation period (98-153%) as a result of an increment of this metabolite in the buffer. Furthermore, the values measured in hypoxic and hypoxic + PC-PLC exposed myocytes during the first hour of the chase period were significantly (p < 0.017) higher than the corresponding values in normoxic myocytes. The present results do not allow firm conclusions regarding endogenous PC-PLC activation in energy-depleted rat cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of reduced joint mobility and training on Na,K-ATPase and Ca-ATPase in skeletal muscle.

In guinea pigs, the ankle joint was partly immobilized in a position reducing dorsiflection to 105 degrees (as compared to the normal value of 30 degrees). When compared with the contralateral unrestrained leg, this led to a significant atrophy and a decrease in contractile force (-23%) of the gastrocnemius muscle. This was associated with a significant decrease in the total concentration of [3H]ouabain binding sites in gastrocnemius and plantaris muscle reaching minimum (-19% and -23%) after 3 weeks, but no evidence of degenerative changes. Total contents of Ca and Ca-ATPase were increased by 27% and 22%, respectively. After 4 to 5 weeks of reduced mobility, the concentration of [3H]ouabain binding sites in gastrocnemius muscle returned to control level. The lowest concentration of [3H]ouabain binding sites reached during reduced mobility was 258 +/- 13 pmol/g wet wt., and the maximum value attained following 3 weeks of reduced mobility and 3 weeks of training by running was 498 +/- 25 pmol/g wet wt., i.e, 93% higher. In soleus, training produced an increase of 25%. Clinically, it is important to realize that movable braces cannot prevent the development of muscular atrophy. The observed spontaneous recovery of the Na,K-pump concentration may partly explain why patients using movable casts show a better capacity for physical performance than those treated with complete immobilization. In conclusion, the total concentration of Na,K-pumps in guinea pig skeletal muscle undergoes downregulation and upregulation as a function of contractile activity as well as muscle length under conditions mimicking the constraints on mobility frequently used in the clinical treatment of lesions.