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Biomedical subjects

D Lester

Publications and source records attributed to D Lester.

At least 901 records · Page 50Linked to original sources

Task-dependent ethanol effects on escape in rats bred for ethanol sensitivity.

Lines of rats selectively bred for differences in degree of locomotor depression by ethanol were tested for ethanol-induced impairment of jumping to a descending platform to escape 0.3 mA shock. The MA ("most affected") line showed greater decreases in height jumped than the LA ("least affected") line at IP doses of 1.25, 1.75, and 2.25, but not at 0.75 g ethanol/kg. MA rats also showed greater increases in latency to first jump (at 1.75 and 2.25 g/kg) which largely accounted for the line difference in decrease in height jumped. Males showed greater impairment than females on both measures. While extending the greater ethanol sensitivity of MA than LA rats to impairment of an escape response, the results contrast with previous studies of water escape where the LA line showed greater impairment than the MA line.

Animals↗

Evidence for increased proteolysis in intact beta thalassemia erythroid cells.

Much excess alpha chain is synthesized, but little accumulates in the erythroid cells of patients with homozygous beta thalassemia. To determine if the proteases known to exist in erythroid cells play a role in the destruction or alteration of any of this excess alpha chain, thalassemic and nonthalassemic erythroid cells were incubated for 90 minutes with 3H-leucine. The cells were then washed, and incubated twice for 15 minutes in 100 volumes of cold leucine-rich media, a procedure which eliminates almost all intracellular TCA soluble radioactivity. After these incubations levels of TCA soluble and TCA precipitable radioactivity in the cell lysates were determined, and the cells incubated for 120 minutes more in two volumes of leucine-rich media. At the end of this incubation, total TCA soluble and precipitable radioactivity was again determined in the cell lysate, and also in the two hour incubation media. The total increase in TCA soluble radioactivity in the cells and their media was divided by the 0 time TCA precipitable radioactivity, to determine the percent proteolysis labelled globin chains. In five control patients percent proteolysis ranged from 0 to 3.10 (mean = 1.50); in four severe and three mild thalassemia patients percent proteolysis ranged from 5.80 to 14.1 (mean = 11.0). The difference between the control and thalassemic groups was significant at a p of less than 0.001. This data is the first direct evidence that more proteolysis takes place in intact thalassemic cells than in non-thalassemic cells.

Adolescent↗

Distribution of ethanol between blood and dorsal subcutaneous air of the rat and the feasibility of using this distribution coefficient to estimate blood ethanol.

Equilibration of ethanol between dorsal subcutaneous air and blood is rapid, a steady state being already present in 60 seconds after air injection in the rat. The mean in vivo partition coefficient (blood/air) is 2,875, the linear regression coefficient having a standard error of 112, the high F value of this regression indicating the linearity and reliability of the estimates of calculated blood ethanol; the variance arises mainly from temperature variance of the air bleb. Although the concentration of alcohol in the blood must remain the standard of comparison, the production of the air bleb and its subsequent serial sampling is a virtually noninvasive technique which yields an almost immediate result at a sensitivity and specificity greater than that from the usual enzymatic determination of ethanol in blood.

Air↗

Significance of the gastrointestinal tract in the in vivo metabolism of ethanol in the rat.

The rate of ethanol metabolism and the extrapolated zero time blood ethanol concentration (C0) were compared in naive and ethanol-fed rats following intracardiac or ingastric administration of a test dose of ethanol (3 g/kg). If the gastrointestinal tract is involved in the disposition of ethanol, intragastric administration should result in a lower C0 and a faster overall rate of metabolism than intracardiac administration, since part of the dose would be metabolized in the gastrointestinal tract without having been absorbed and thereby entering the blood. However, no significant differences were observed in C0. The rate of metabolism was substantially higher in the ethanol-fed rats, but was uninfluenced by route of administration. Thus, the gastrointestinal tract plays no significant role in the metabolism of ethanol.

Alcohol Drinking↗

Tolerance to ethanol-induced impairment of water escape in rats bred for ethanol sensitivity.

Rats selectively bred for ethanol (EtOH)- induced reductions in locomotor activity ("least affected" = MA) showed a reversed order of senstivity (i.e., LA more sensitive) to EtOH-induced (1.75 g/kg, IP) impairment of swimming. Thirty days of daily EtOH intubation began the next day, starting at 3.5 g/kg for 4 days, and increasing by 0.5 g/kg after 4 days at each dose, until 6.0 and 6.5 g/kg were given for 5 days each. Subjects were retested on the swim task (1.75 g/kg, IP) following 10, 20, and 30 days of chronic EtOH, and at 10, 20, and 30 days after cessation of EtOH treatment. Rats of each line and sex showed progressively decreasing peak impairment during the chronic treatment period; impairment increased toward initial levels during the post-treatment period. LA rats were more impaired than MA rats prior to, throughout, and subsequent to the chronic treatment period; a significant positive correlation between initial impairment and impairment after 30 days of chronic EtOH was found. No line differences in rates of tolerance acquisition or loss, or in final levels of tolerance as indicated by post-treatment impairment relative to initial impairment were observed. The similarity of the dynamics of EtOH tolerance in rats selectively bred for sensitivity to its acute effects suggests independent genetic influences upon initial ethanol sensitivity as opposed to acquired ethanal tolerance.

Animals↗