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Biomedical subjects

M L Reid

Publications and source records attributed to M L Reid.

7 recordsLinked to original sources
PubMed2002

Neurological evaluation of toxic axonopathies in rats: acrylamide and 2,5-hexanedione.

This research was conducted to determine which neurological test or combination of tests can provide sufficient functional information to compliment biochemical or morphological endpoints in mechanistic studies of toxic axonopathies. Using several neurological indices, we evaluated the effects of two prototypical neurotoxicants that cause distal axonopathy: acrylamide monomer (ACR) and 2,5-hexanedione (HD). For each toxicant, rats were exposed to two daily dosing rates (ACR, 50 mg/kg per day i.p. or 21 mg/kg per day, p.o.; HD, 175 or 400 mg/kg per day, p.o.) and neurological endpoints were determined two to three times per week. Specific tests included observations of spontaneous locomotion in an open field, and measurements of hindlimb landingfoot splay, forelimb and hindlimb grip strength and the hindlimb extensor thrust response. For all neurological parameters, the magnitude of defect induced by either neurotoxicant was not related to daily dose-rate, e.g. both the lower and higher ACR dose-rates produced the same degree of neurological dysfunction. Instead, dose-rate determined onset and progression of neurotoxicity, e.g. the higher ACR dose-rate produced moderate neurotoxicity after approximately 8 days of intoxication, whereas the lower dose-rate caused moderate neurotoxicity after 26 days. Regardless of dose-rate, ACR-exposed rats exhibited gait abnormalities (ataxia, splayed hindlimbs), in conjunction with increased landing hindfoot spread and decreased hindlimb grip strength and extensor thrust HD intoxicated rats exhibited hindlimb muscle weakness as indicated by a gait abnormality (dropped hocks) and decreases in grip strength and the extensor thrust response. However, hindlimb landingfoot spread was not affected by HD exposure. For both neurotoxicants, gait changes preceded or coincided with alterations in other neurologic indices. These results suggest that observations of spontaneous behavior in an open field represent a practical approach to assessing temporal development and extent of neurological dysfunction induced by axonopathic toxicants such as ACR and HD.

Acrylamide↗
PubMed2001

Research with rats germane to medication for alcoholism: consequences of noncompliance.

Results of prior work indicate that (a) rats take stable, toxic levels of ethanol when they receive a daily regimen of limited opportunities to take both water and sweetened ethanol solution and (b) the combination of isradipine plus naltrexone persistently reduces those intakes. What are the effects of periodically missing doses of isradipine, naltrexone, or both? That is, what are the effects of differing levels of compliance? To get relevant information, rats were placed on a daily regimen, leading them to take, by choice, large amounts of ethanol (>2.0 g of ethanol per kilogram of body weight during 2 h a day). After being on this regimen for more than 60 days and after 28 days of no opportunity to take ethanol, 55 rats were divided into five groups. The opportunity to drink was then reinstated. One group received placebos, and another group received the combination of isradipine plus naltrexone daily. The other three groups received doses periodically, thereby conforming to good, moderate, and poor compliance. After abstinence, the intakes for rats receiving placebos rapidly returned to high levels. Intakes for rats receiving daily isradipine plus naltrexone did not return to high levels. The intakes for the other three groups were intermediate to intakes of the reference groups, corresponding to frequency of medication. When medication was not given, intakes approached placebo control levels, but the combination of isradipine plus naltrexone was effective when given subsequently. Daily dosing clearly is effective in reducing intakes, and suspension of dosing leads to higher intakes. A missed day of dosing, however, has limited consequences, provided that administration of medication is resumed.

Alcohol Drinking↗
PubMed1999

Amlodipine, a calcium channel inhibitor, and cocaine and ethanol's reinforcing effects.

The effects of amlodipine (from 0.1 to 3.0 mg/kg) on rats' pressing for rewarding brain stimulation, with and without cocaine administration, were assessed. None of the doses reliably modified the effects of cocaine. Also, amlodipine was given to two groups of rats taking alcohol: one group that was regularly taking a sweetened alcoholic beverage and the other taking an unsweetened alcoholic beverage. The only discernible effects of amlodipine on alcohol intake were associated with the highest dose and only with rats taking the sweetened beverage. The effects of this high dose could easily be attributable to behavioral toxicity elicited by the dose. In contrast, and confirming previous work, isradipine, another calcium channel inhibitor, produced reliable reductions on both cocaine's and alcohol's reinforcing effects. Despite the similarity of isradipine and amlodipine, isradipine apparently has some unique features with respect to cocaine and alcohol.

Amlodipine↗
PubMed1983

Antibody-induced cell-cycle synchrony.

Synergism between specific antibodies and cytotoxic drugs in killing tumor cells is an established phenomenon. When cells grown in a suspension culture are treated with antibody, a subsequent increase in susceptibility to cytosine arabinoside has been shown to be due to the induction of cell-cycle synchrony. This observation may lead to a novel way of investigating cell-cycle-dependent processes and also an aspect of tumor-antibody interactions that is not generally recognized.

Animals↗
PubMed1979

Perinatal care and cost effectiveness: changes in health expenditures and birth outcome following the establishment of a nurse-midwife program.

Estimates of infant health status and expenditures for perinatal care are presented for periods of time before and after implementation of a nurse-midwife program in rural Georgia. As the program developed, the infant mortality rate of the four counties served by the program showed a decrease. Similarly, the target population (pregnant women of low to moderate income who had no private physician) experienced decreases in the rate of neonatal mortality, low birthweight, and short gestational age. Estimated expenditures for perinatal care in the four counties decreased as well. These results are examined from the perspective of the National Health Planning and Resources Development Act of 1974 and the utility of using an epidemiologic approach for estimating the output of health services in terms of health status is emphasized.

Cost-Benefit Analysis↗
PubMed1978

Vitamin K dependence of a calcium-binding protein containing gamma-carboxyglutamic acid in chicken bone.

Bone contains a small protein, osteocalcin, rich in the amino acid gamma-carboxyglutamate (gammaCGlu), which is dependent on vitamin K for its synthesis. The vitamin K dependence of osteocalcin biosynthesis has been studied both in the developing chicken embryo and in the skeletons of young chicks. Osteocalcin formation, assessed by quantitation of gammaCGlu in whole bone, begins in the 8-day embryonic skeleton and increases dramatically until hatching. Biosynthesis of gammaCGlu is warfarinsensitive; time- and dose-related inhibition of up to 75% is observed. Vitamin K deficiency reduces bone gammaCGlu concentrations by 50% in 3-week-old chicks, and this is totally corrected by including vitamin K1 in the diet. Feeding the vitamin K antagonist dicumarol decreases the bone gammaCGlu level 80% after 6 weeks, but no corresponding alterations are observed in the calcium and phosphorous content of the bone ash. Osteocalcin purified from bones of dicumoral-fed chicks exhibits several electrophoretically variant undercarboxylated protein species containing 2 and 3 gammaCGlu/57 amino acid residues rather than the normal complement of 4 gammaCGlu/57 residues.

1-Carboxyglutamic Acid↗