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Biomedical subjects

M C Wilson

Publications and source records attributed to M C Wilson.

At least 163 records · Page 9Linked to original sources

The anorexic and actometric effects of cocaine and two coca extracts.

The effects of cocaine and two extracts of the coca leaf were compared using locomotor activity and limited access food consumption paradigms. The three treatments were tested using both IP and PO routes of administration. The extracts were prepared by first extracting the powdered leaves with 95% ethanol, evaporating the ethanol and then partitioning the residue between water and chloroform. The doses of the extracts studied were 60, 120, 240, and 480 mg/kg. The doses of cocaine studied were 3.45, 6.9, 13.8 and 27.6 mg/kg. These doses corresponded to the amount of cocaine contained in the four doses of the chloroform layer. Cocaine and the chloroform layer (via both routes) produced dose related increases in locomotor activity and dose related decreases in food consumption. The water layer (containing only trace amounts of cocaine) produced no changes in locomotor activity; however, the highest IP dose did significantly reduce food consumption. Furthermore two of the doses (one IP, one PO) of the chloroform layer produced significantly greater effects than an equivalent amount of cocaine. These data suggest that plant constitutents other than cocaine may contribute to the overall effect achieved by chewing the leaf.

Animals↗

Obstructive uropathy after pan-proctocolectomy for ulcerative colitis.

We report two cases of pan-proctocolectomy for ulcerative colitis who some time postoperatively developed an obstructive uropathy with the clinical and radiological features of retroperitoneal fibrosis. The incidence of this complication appears to be around 10% and the possibility of such a diagnosis should be borne in mind in any patient who has non-specific symptoms after surgery for ulcerative colitis.

Adult↗

Successful treatment of genetically hypophosphatemic mice by 1 alpha-hydroxyvitamin D3 but not 1,25-dihydroxyvitamin D3.

The X-linked hypophosphatemia (Hyp) mutation in the mouse, a model for X-linked familial hypophosphatemic rickets in man, is characterized by defective phosphate transport. The role of vitamin D3 in the defective phosphate transport was investigated in three experiments by treatment of mutant mice with the natural hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3, or its potent synthetic analog, 1 alpha-hydroxyvitamin D3. The results showed that both compounds were able to increase urinary phosphate conservation and improve rachitic bone morphology. Only 1 alpha-hydroxyvitamin D3, however, repaired the critically important hypophosphatemia and significantly increased intestinal transport of phosphate. These results indicate that defective phosphate transport in genetic hypophosphatemia is amenable to effective treatment. We hypothesize that the intestinal phosphate transport system is not genetically deleted but, instead, is unable to respond to 1,25-dihydroxyvitamin D3. Elucidation of the mechanism whereby 1 alpha-hydroxyvitamin D3 is able to stimulate the defective phosphate transport may provide fresh insight into the metabolic basis of the disease.

Animals↗

Regulation of the primary expression of the early adenovirus transcription units.

The time course of appearance of transcriptional activity from five early adenovirus type 2 transcription units has been determined. RNA complementary to region 1A (1-4.4 map units), the first region to be transcribed, was detectable at 45 min after infection; a maximal rate of RNA synthesis was reached at 3 h after infection and was maintained thereafter for at least 6 h. RNA from region 2 (75-56 map units), which encodes the mRNA for the 72,000-dalton DNA-binding protein, was the last to be synthesized; transcription commenced at about 2 h postinfection, reached a maximum at 7 h, and then declined. Transcription of regions 3 (76-86 map units) and 4 (99-91 map units) reached a maximal value at 3 h postinfection. The rates of RNA synthesis from these regions then declined over the next 6 h. The decline of transcription from regions 2 and 4 appeared to be a specific repression of these transcription units. The repression did not occur in the absence of protein synthesis, suggesting that a viral protein might be involved. Transcription of all early regions was initiated and continued for at least 2 to 3 h in cells that were treated with cycloheximide or emetine before and during infection, suggesting that at least the initiation of RNA synthesis from the five early adenovirus type 2 transcription units does not depend on the formation of a viral protein. Moreover, mRNA was formed in the absence of protein synthesis that hybridized to DNA fragments representing each of the five early transcription units. The increase in mRNA accumulation in the presence of cycloheximide (or emetine) does not appear to be due to increased RNA synthesis; thus, either increased mRNA stability or increased efficiency of nuclear RNA processing must occur.

Adenoviruses, Human↗

Actometric effects of intravenous cocaine in rats.

Intravenous infusions of cocaine, in dosages which have been reported to maintain self-administration behavior, were administered to cannulated rats. Ten identical infusions were administered at 6 min intervals within a session. The activity occuriring in the initial minute following infusions was compared to that produced by saline infusions. Dosages of 200, 400, 800 and 1200 microgram/kg significantly increased activity. However, this effect was not maintained throughout the session. The tenth infusion no longer increased activity as compared to the initial infusion. Therefore these data would not support the hypothesis that cocaine-induced activity was responsible for maintaining cocaine self-administration behavior in this species. Pretreatment with agents which disrupt the synthesis of dopamine and/or norepinephrine failed to antagonize this initial increase in activity. These data would suggest that the activity effect of cocaine is not dependent on newly synthesized pools of the catecholamines.

Animals↗

Brief communication. Comparative pharmacology of norcocaine in M. mulatta and M. fascicularis.

Norcocaine was administered intravenously (0.05, 0.5, 5.0 mg/kg) to three chaired unanesthetized male rhesus monkeys and to three chaired male cynomolgus monkeys. Respiration rate, heart rate and rectal temperature were monitored. In the rhesus monkeys tachycardia and hyperventilation resulted. However, similar qualitative and quantitative changes were not observed in the cynomolgus species. There was a statistically significant difference in the response to norcocaine across species. These results indicate that cynomolgus monkeys are either less sensitive or respond differently than rhesus monkeys to some of the pharmacological effects of norcocaine. Furthermore, these data confirm that norcocaine is an active derivative of cocaine in both rhesus and cynomolgus monkeys.

Animals↗

Cocaine reinforced progressive ratio performance in the rhesus monkey.

A series of experiments were conducted to determine the effectiveness of a progressive ratio (PR) procedure in measuring the relative reinforcing efficacy of several intravenous doses of cocaine. In Experiment 1, utilizing much smaller increases in the ratio requirement than previously reported, the animals generally displayed increases in breaking point with increases in the cocaine unit dose up to 0.4 mg/kg/inj. The highest dose studied (0.8 mg/kg/inj.) engendered breaking points lower than the 0.4 mg/kg dose but higher than the remaining lower doses. Experiment 2 was conducted utilizing the same reinforcement schedule as in Experiment 1 but with liquid Tang as the reward. The results demonstrated that this procedure would function to discriminate reinforcing strength with a more traditional reward. Experiment 3 examined a more expedient procedure to see if results similar to those seen in Experiment 1 could be obtained in a shorter period of time. However, the shorter procedure engendered excessive intrasubject variability, suggesting that some intermediate level of baseline experience between the 5-7 days used in Experiment 1 and the 50 reinforced responses used in Experiment 3 would be necessary to obtain consistent breaking point-unit dose functions.

Animals↗