Biomedical subjects

A C Collins

Publications and source records attributed to A C Collins.

222 records · Page 13Linked to original sources

PubMedDate not supplied

Ethanol's behavioral effects may be partly due to increases in brain prostaglandin production.

Prostaglandin synthesis inhibitors antagonize behavioral responses to ethanol. The dose of inhibitor (e.g., indomethacin or aspirin) required to block ethanol's effects is directly proportional to the ethanol sensitivity of the organism. Animals selectively bred for differential response to ethanol provide a useful tool in exploring the biochemical substrates of ethanol-related behavior. This study shows that ethanol increases brain prostaglandin levels in a dose-, sex-, and genotype-dependent manner consistent with the hypothesis that part of ethanol's mechanism of action is to increase the production of prostaglandins.

Animals↗

PubMedDate not supplied

Indomethacin pretreatment blocks the effects of high concentrations of ethanol.

Previous reports from our laboratory have indicated that the responses to ethanol following intraperitoneal (i.p.) injection increase as the concentration of the ethanol solution increases. We have also presented evidence which indicates that pretreatment with drugs such as indomethacin (a prostaglandin synthetase inhibitor) decreases the response of mice to ethanol injected i.p. The results reported here corroborate our earlier findings in that the sleep time response of C57BL and DBA mice was greater following injection with a 40% (w/v) ethanol solution than that seen following i.p. injection with a 20% (w/v) ethanol solution. The increase in sleep time does not appear to be due to alterations in the rates of absorption or elimination of ethanol. Pretreatment with indomethacin reduced sleep time in those animals injected with the 40% solution but was without effect in the animals injected with the 20% solution. Both C57BL and DBA mice pretreated with indomethacin exhibited an increase in waking blood and brain ethanol, an indicant of altered central nervous system sensitivity. In addition, both DBA and C57BL mice exhibited an increase in the linear rate of ethanol elimination if pretreated with indomethacin before injection with the 40% ethanol solution. Indomethacin did not affect ethanol elimination rates of animals injected with the 20% ethanol solution. These data indicate that high concentrations of ethanol when injected into the peritoneal cavity promote the production of prostaglandins which serve to enhance the behavioral response to ethanol. This enhancement may be due to altered pharmacokinetics as well as central nervous system effects.

Analysis of Variance↗

PubMedDate not supplied

Dose and route of administration alter the relative elimination of ethanol by long-sleep and short-sleep mice.

The elimination of ethanol following the intravenous and intraperitoneal administration of five ethanol doses was measured in two mouse lines, the long-sleep (LS) and short-sleep (SS), that differ markedly in central nervous system sensitivity to ethanol. Both dose and route of administration affected the relative ethanol elimination in these two mouse lines. When the ethanol was given i.v., a steady increase in elimination rate was seen in the SS mice as the dose was increased. In the LS mice, consistent changes in rate with dose were not seen. At the lower doses tested, the LS eliminated ethanol more rapidly than did the SS but at higher doses the mouse lines did not differ. When the ethanol was given i.p., increases in rate with dose were not seen. Rather, the SS elimination rate remained constant as the dose was increased, whereas in the LS a decrease in rate was observed. As a consequence, the SS eliminated ethanol more rapidly than did the LS at higher doses. A potential explanation for these results is that ethanol elimination, following the administration of large doses, is affected by both enzymological factors and central nervous system sensitivity to ethanol. The central nervous system factors may be mediated via ethanol-induced hypothermia.

Alcohol Oxidoreductases↗

PubMedDate not supplied

Rarity of a marked "dawn phenomenon" in diabetic subjects treated by continuous subcutaneous insulin infusion.

We assessed the quality of overnight glycemic control and the frequency of the "dawn phenomenon" (nadir-0800 h glycemic increase) in 41 insulin-dependent diabetic patients treated by continuous subcutaneous insulin infusion (CSII). Mean plasma glucose levels were near-normal during the 24 h and, in particular, constant throughout the night. In a subset of six patients overnight plasma free insulin concentrations were also constant during CSII. The majority of profiles (88%) showed a glucose nadir from 2.0 to 5.9 mmol/L (most frequently at 0600 h) and had an 0800 h value from 2.0 to 6.9 mmol/L (92%). A large proportion (46%) of profiles showed a zero or negative nadir-0800 h glycemic increase. In 22 patients with three or more profiles recorded at the same basal insulin infusion rate, only one of 103 profiles had a fasting glycemic increase greater than an arbitrary value of 5.0 mmol/L (5.3), although many patients exhibited small dawn glycemic increases (e.g., 14 of 22 had a mean increase of from 0 to 2 mmol/L). In 12 subjects a 15% reduction in basal insulin infusion rate increased the mean +/- SEM dawn glycemic increase from 0.58 +/- 0.25 mmol/L to 2.7 +/- 0.76 mmol/L (P less than 0.025) as well as significantly increasing the nocturnal nadir and 0800 h plasma glucose concentrations. Thus, a marked dawn phenomenon is rare when a single but adequate basal infusion rate is used for CSII, and this questions the need in the majority of patients for preprogrammable pumps with nocturnal infusion rate changes.

Adult↗

PubMedDate not supplied

Hypoglycemia and counterregulation in insulin-dependent diabetic patients: a comparison of continuous subcutaneous insulin infusion and conventional insulin injection therapy.

Eleven insulin-dependent diabetic patients were treated in random order by 2-mo continuous subcutaneous insulin infusion (CSII) or 2-mo conventional injection treatment (CIT) with crossover to the alternative regimen. Mean plasma glucose concentrations throughout the day were significantly lower during CSII than during CIT, but the percentage of plasma glucose values less than 2.5 mmol/L, obtained from outpatient self-collected diurnal profiles, was similar for both treatments (CSII vs. CIT: 5.9 and 4.8%, respectively). Reported symptomatic hypoglycemia at home was not significantly different in the whole group of patients treated by CSII or CIT but was reduced by a mean of 57% (P less than .02) in the five patients on CSII who experienced frequent symptomatic hypoglycemic episodes (greater than 4/2 mo) during CIT. Neither the plasma glucose concentration at which the patients recognized induced hypoglycemia nor the glycemic or counterregulatory hormone responses for 60 min thereafter were changed by CSII treatment.

Adult↗

PubMedDate not supplied

Genetic influences on tobacco use: a review of human and animal studies.

This paper provides an overview of the literature which indicates that genetic factors regulate the use of alcohol and tobacco by humans. The methods used to make genetic assessments in humans and the results obtained are discussed. Studies using animals have been helpful in identifying simpler behavioral components of the dependence process that are regulated by genetic factors. An overview of the genetic methods used most often in animal studies is presented along with an in-depth discussion of how these methods have been useful in uncovering genetic influences on nicotine responses in animals. Data which indicate that genetic factors regulate brain nicotinic receptor numbers and response to nicotine are also included as examples of how genetic strategies have been useful in increasing our understanding of how genes may influence behavior.

Alcohol Drinking↗