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Biomedical subjects

W M Davis

Publications and source records attributed to W M Davis.

At least 55 records · Page 3Linked to original sources

Premature mortality among prominent American authors noted for alcohol abuse.

An array of 27 American authors noted in the literature for their excessive drinking was compared for their longevity to a control group of 54 writers. The latter were selected for having similar sex distribution and distribution of dates of birth, as well as for their peer recognition among American writers. The median (and range) for the alcohol-abusing writers was 65 (33-77) years, whereas the control group survived to a median of 76 years (range 32-90). This difference was highly significant (p less than 0.001). Thus, data from American authors support those epidemiologic studies reporting alcohol abuse to be a cause of premature mortality, rather than others that have failed to demonstrate such a relationship. The social cost of an alcohol-related decrement in lifespan is emphasized by these data from a highly talented selection of American writers.

Adult↗

Effects of anesthesia and phenoxybenzamine on responses of dogs to IV subtoxic doses of 3,4-methylenedioxyamphetamine (MDA).

Racemic 3,4-methylenedioxyamphetamine HCl (MDA) was tested for acute intravenous (i.v.) lethality in mongrel dogs. The LD50 and 95% confidence limits were 8.1 (7.0-9.4) mg/kg, and the LD1 and LD99 were approximately 5 and 14 mg/kg. Subtoxic doses (0.1, 0.3, 1.0 and 3.0 mg/kg, i.v.) were tested for acute effects on cardiovascular and respiratory functions in conscious dogs prepared surgically under local anesthesia and also in dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Four experimental groups were constituted, by pretreating or not, both conscious and anesthetized dogs with phenoxybenzamine HCl (15 mg/kg, i.v.). Arterial and left ventricular pressures tended to be elevated more by MDA in the anesthetized than in the conscious dogs. These and other cardiovascular parameters tended to be more fully antagonized by phenoxybenzamine in anesthetized than in conscious dogs. Respiratory rate was increased by higher doses, more so in the conscious group, but the increase was fully blocked by phenoxybenzamine. Possible clinical implications of the data are suggested.

3,4-Methylenedioxyamphetamine↗

Dynamic organ culture of precision liver slices for in vitro toxicology.

The lack of a reproducible method for the production of thin tissue slices has hindered the use of liver slices as an in vitro tool for hepatotoxicity studies. Fresh human, rat, and rabbit liver was processed using a mechanical slicer. With this instrument, precision (5% of thickness) liver slices in the submillimeter range could be produced at a rapid rate. Slices were prepared from fresh livers in chilled, oxygenated buffer to minimize trauma. Following incubation for up to 20 h in a dynamic organ culture system, histology of incubated slices suggested that 250 m precision-cut slices were optimum in regard to morphology relative to liver slices incubated under conventional organ culture conditions. Addition of bromobenzene to the culture showed time-dependent hepatotoxicity based on two classic parameters of cell degeneration. Histological evidence is presented which suggests the usefulness of this system for hepatotoxicity studies and the production of focal necrosis in vitro.

Animals↗

Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse liver preparations.

Using a mouse liver microsomal preparation, it was found that the heterocyclic ring system of MPTP underwent an initial alpha-oxidation to give chemically reactive metabolites that may be associated with the induction of Parkinsonism by MPTP. Subsequent oxidative metabolic transformations of these intermediates were found to give a lactam metabolite and a pyridone metabolite that potentially may interact with the neurotransmitter system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Pharmacologic investigation of compounds related to 3,4-methylenedioxyamphetamine (MDA).

The 3-aminobutane homolog (HMDA) of 3,4-methylenedioxyamphetamine (MDA) was synthesized and compared to MDA for acute pharmacologic/toxicologic properties in mice. The lethality of intraperitoneal doses of HMDA equalled or exceeded that of MDA, depending on whether mice were grouped or isolated after dosing. All deaths with HMDA occurred by 6 hours, while many were delayed to 6-24 hours for MDA, particularly in the aggregated condition. Rather similar response patterns were seen for the N-methylated derivatives of MDA and HMDA. Catecholaminergic receptor blockers, haloperidol, propranolol and phenoxybenzamine, which previously were found protective against MDA lethality, were ineffective against HMDA. However, phenoxybenzamine supplemented a protective action of phenobarbital toward HMDA lethality. The dose-related pattern of locomotor activity effects of HMDA differed from the one seen for MDA, which has been suggested to characterize hallucinogenic agents. Thus, HMDA differs qualitatively in actions from MDA and tends to be more toxic acutely for mice.

3,4-Methylenedioxyamphetamine↗

Neurobehavioral actions of cannabichromene and interactions with delta 9-tetrahydrocannabinol.

1. Neither cannabichromene (CBC) nor delta 9-tetrahydrocannabinol (THC) protected mice from electroshock-induced seizures, although THC inhibited postictal mortality. Minor effects were produced on seizure latency and duration. 2. CBC had a weak analgetic action in mice; THC had a moderate and lengthy effect, which was potentiated at 2 hr by concurrent CBC. 3. Both CBC (10-75 mg/kg, i.p.) and THC (20 mg/kg) reduced motility of mice, the THC equalling the highest dose of CBC. 4. Performance of a conditioned avoidance response was strongly impaired by THC, but not by CBC, nor did CBC combined with THC have influence on the effects of THC.

Analgesics↗

Parental methadone treatment: a multigenerational study of development and behavior in offspring.

After 60 days of treating both sexes with daily oral doses of 15 mg/kg methadone hydrochloride, Wistar rats were mated. Drug treatment of females continued until the weaning of their pups. The body weight of pups was reduced compared to controls up to weaning, and viability was significantly decreased. Ontogeny of reflexes was delayed, and exploration in an open-field arena was reduced up to 2 weeks of age, but then increased above controls. Defecation in the open-field arena was lessened. When only the sire received methadone, only the increase in exploratory behavior and the decrease in defecation occurred. Breeding offspring (F1) of which both parents had methadone treatment gave F2 generation offspring for which neonatal mortality was significantly elevated and defecation in the open-field arena was lessened at 21 days. No changes clearly traceable to methadone were found in the subsequent F3 generation. Some F3 generation rats were treated with methadone and bred in the same manner as the original parental generation. The resulting pups, having the genealogy twice-exposed to methadone, were not significantly different from those whose immediate parents only received the drug.

Animals↗

Motility response of rats to chronic constant-dose treatment with narcotics.

The changes in effects on motor activity of rats upon repeated (48 day) dosing with four narcotic analgesics were determined. The following were administered IP once daily in a.m.: morphine sulfate (MOR), 20 mg/kg: dl-methadone HCl (MET), 5 mg/kg: meperidine HCl (MEP), 10 mg/kg; and pentazocine lactate (PEN), 20 mg/kg. Motility was measured in photocell actometers every 4 days for 6 hr after dosing. Activity was elevated after the initial dose as follows: for MOR at hours 3-5, for MET at hours 2-5, for MEP and PEN at hours 2-3. Time of peak response showed no systematic change over days. For all 4 drugs there occurred, upon repeated dosing, a considerable increase in motility over the initial acute response. For MOR the greatest increment occurred between days 12 and 16, but regression analysis showed a strong linear trend of increasing activity from day 1 through day 48. For MET and MEP, activity rose considerably between days 4 and 12 to a maximum, after which the activity trended downward for MET, but showed no continuing fall or climb for MEP. For PEN the greatest increases were from days 4 to 8 and 44 to 48, with an intervening period of relative stability. These results seem to be more readily explainable in terms of increasing sensitivity to the motor excitatory actions of these agents than merely by a development of tolerance to motor-inhibitory actions.

Animals↗

LSD or DOB?

Explore the source record for details and available documents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Intragastric drug self-administration by rats exposed successively to morphine and ethanol.

Male Sprague-Dawley rats were implanted with intragastric cannulas for self-administration of drug solutions by bar-pressing on a continuous reinforcement schedule in 10-hour daily sessions. Similar levels of responding were observed for doses per infusion of 3.0 mg/kg morphine sulfate and 25 mg/kg ethanol in separate groups of rats. When rats that showed self-administration of a morphine solution over a 5-day period were than given access instead to ethanol for 5 days, the number of infusions taken did not deviate significantly between the two periods. However, rats selected from a small minority that failed to take morphine under these conditions also failed to manifest ethanol self-administration behavior. The data can be seen to support a possible concurrence or similarity between innate factors determining acceptance or rejection of morphine and ethanol as objects of self-administration behavior.

Alcoholism↗

Perinatal exposure to cannabichromene and delta 9-tetrahydrocannabinol: separate and combined effects on viability of pups and on male reproductive system at maturity.

The effects of cannabichromene (CBC), delta 9-tetrahydrocannabinol (delta 9-THC) and their combination (all doses 50 mg/kg orally) were determined after being administered to female mice for 7 days beginning on the 20th day of gestation. The THC treatment reduced postnatal viability, impaired male reproductive behavior at maturity and significantly reduced seminal vesicle weights. No changes from control values occurred after CBC or CBC + THC. Thus, CBC alone at this dosage did not act like THC; moreover, it antagonized the effects of THC when the two were given in combination.

Animals↗

Effect of light on biomass and community structure of estuarine detrital microbiota.

Comparison of estuarine detrital microbiota grown with and without light in the absence of macroscopic grazing showed shifts in the community structure that enabled correlation between various biochemical measures. Analysis of these biochemical measures showed that growth in light induces the smallest increases in procaryotic attributes such as muramic acid; wall glucosamine; lipid phosphate; total extractable adenosine nucleotides; short-branched, cyclopropane, and cis-vaccenic fatty acids; lipid glucose and mannose; the incorporation of acetate into lipid; and the formation of deoxyribonucleic acid from thymidine. Measures of the microfauna such as lipid inositol and the gamma-linolenic series of polyenoic fatty acids also increased minimally in the light-grown microbiota. Measures of sulfo-lipid synthesis, lipid glycerol, total extractable palmitate, 18-carbon polyenoic fatty acids, and total polyenoic fatty acids longer than 20 carbons increased 10- to 15-fold in algae and fungi. Chlorophyll a, lipid galactose, and the 16- and 20- carbon polyenoic fatty acids characteristic of diatoms increased maximally in the light. This increase of diatom measure correlated with the sheets of diatoms detected by scanning electron microscopy.

Journal Article↗