PubMed HealthSearch

Biomedical subjects

W A Reynolds

Publications and source records attributed to W A Reynolds.

At least 19 recordsLinked to original sources

Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking versus nasal spray.

Nicotine is the primary psychoactive constituent of tobacco smoke, but it is not clear whether the reinforcing effects of cigarette smoking can be attributed solely to nicotine intake. In this study, two groups of male and female smokers participated in three sessions involving intermittent exposure to moderate low, or no nicotine doses via controlled tobacco smoking ("smoke," n = 20) or measured-dose nasal spray ("spray," n = 16). Visual analog scales of subjective effects (VAS) and heart rate (HR) were obtained within 5 min of each dosing. Plasma nicotine levels indicated comparable dosing between methods. For both methods, there were significant nicotine dose effects for most subjective measures and HR. More importantly, the pattern of effects across doses was virtually identical between methods, as nicotine intake via smoking or spray significantly increased HR and the VAS scales of Head Rush and Dizzy, decreased Hunger and Desire to Smoke, and had no effect on Comfortable, Jittery, or Relaxed. These results suggest that rapid nicotine uptake by novel methods may provide effects very similar to nicotine intake by smoking.

Administration, Intranasal

Chronic and acute tolerance to subjective, behavioral and cardiovascular effects of nicotine in humans.

Understanding tolerance to effects of nicotine in humans may elucidate processes involved in the onset and maintenance of tobacco dependence. Subjective, behavioral and cardiovascular responses to nicotine were examined as a function of past history of nicotine exposure (i.e., smokers vs. nonsmokers, chronic tolerance) and of immediately preceding nicotine exposure (acute tolerance). Dose-effect relationships between nicotine (0-2 micrograms/kg via measured-dose nasal spray) and each response were determined in male and female smokers (n = 17) and nonsmokers (n = 18), with different doses presented on different days. Each day, subjects also received a challenge dose of 20 micrograms/kg 30 min after the previous dosing to assess acute tolerance. Plasma nicotine concentrations were 30% lower in nonsmokers compared with smokers and analyses were adjusted to control for this difference. Results showed significant changes in nearly all responses as a function of nicotine dose. Dose-effect curves were shifted to the right or dampened in smokers relative to nonsmokers for most subjective and some behavioral responses, consistent with chronic tolerance, but there was less evidence of chronic tolerance to other behavioral effects or to cardiovascular responses. A pattern of acute tolerance generally similar to that of chronic tolerance was observed across response domains (i.e., clear acute tolerance to subjective measures but less to behavioral or cardiovascular effects). These results support the notions that regular use of nicotine is associated with chronic functional tolerance and that repeated nicotine exposure during a single episode produces acute tolerance. A similar pattern of chronic vs. acute tolerance suggests similarity of mechanisms responsible for both "types" of tolerance. However, variability in tolerance magnitude across subjective, behavioral and cardiovascular response domains indicates that different mechanisms may be responsible for these different effects of nicotine.

Adult

Fibrocartilaginous dysplasia of bone.

Fibrocartilaginous dysplasia is a benign, unusual complication of fibrous dysplasia occurring in the lower extremities, especially the femoral neck. Rapid growth and chondroid features may cause fibrocartilaginous dysplasia to be misdiagnosed as malignant. True chondrosarcomatous transformation of fibrous dysplasia is probably very rare. A recent case of fibrocartilaginous dysplasia is presented.

Adolescent

Inhibition of the enzymes of glutathione metabolism by mercuric chloride in the rat kidney: reversal by selenium.

The treatment of rats with 10 mumoles/kg (s.c.) of mercuric chloride (Hg2+) caused time-dependent decreases in the activities of the enzymes of the glutathione (GSH) metabolism pathway in the kidney. Twenty-four hours after administration of Hg2+, the activities of gamma-glutamylcysteine synthetase and glutathione disulfide (GSSG)-reductase in the kidney were decreased by 50-60%, and the activities of the GSH catabolic enzymes, gamma-glutamyl transpeptidase and GSH-peroxidase, were decreased by 25-35%. In the liver, only the activity of GSSG-reductase was decreased at this time. The observed decreases in the enzyme activities were not accompanied by a depression in the cellular protein concentration. The same pattern of enzyme response was noted when rats were given 30 mumoles/kg Hg2+; however, the decreases in the specific activity of the enzymes were accompanied by great losses in the cellular protein concentrations in both the liver and the kidney (35-40%). This dose of Hg2+ also caused significant decreases in the concentration of GSH in both organs. In vitro, Hg2+ only inhibited the activity of GSSG-reductase. When rats were given sodium selenite (Na2SeO3; 5, 10 or 20 mumoles/kg, s.c.) 30 min after Hg2+ treatment (10 mumoles/kg), the Hg2+-related depressions in the activities of the enzymes of GSH metabolism in the liver and the kidney were blocked. Also, in rats treated with 30 mumoles/kg Hg2+, the administration of 10 mumoles/kg selenium significantly decreased the magnitude of depression in the concentration of GSH in the kidney.

Animals

Calcitropic hormone responsiveness during pregnancy.

Release of the calcitropic hormones parathyroid hormone (PTH) and calcitonin (CT) in-response to provocative stimuli was assessed in pregnant rhesus monkeys tested three times during gestation (corresponding to the end of each trimester) and again 6 weeks post partum. In the case of PTH, although basal levels were higher during pregnancy than post partum and tended to increase with advancing gestation, similar to observations in human subjects, the incremental response of the hormone to a hypocalcemic stimulus was diminished in pregnant animals and tended to lessen with advancing gestation. Basal CT levels were also increased during pregnancy but, in contrast to PTH, the incremental CT response to a provocative stimulus was generally greater during pregnancy than post partum and tended to increase with advancing gestation. The explanation of these findings may lie in differing degrees of hormone storage. These adjustments in maternal endocrine physiology regulating calcium metabolism would have the net effect of tending to preserve the maternal skeleton by protecting it from excessive resorption at times of hypocalcemia and promoting increased calcium storage during episodes of hypercalcemia.

Animals

Microsurgical ovarian transplantation in the primate.

We have developed a technique for orthotopic transplantation of ovaries by microsurgical reanastomosis of the ovarian blood vessels in rhesus monkeys. Four monkeys receiving autografts resumed cyclic menses and had postoperative circulating luteinizing hormone (LH) and progesterone concentrations consistent with developing follicles and corpus luteum function. Postoperative luteal phase ovarian biopsies were indicative of ovulation in three of the four animals. However, in a fifth recipient an ovarian allograft from an unrelated donor was rejected despite the use of a standard immunosuppressive regimen. This study suggests that ovarian transplantation by direct vascular anastomosis is a technically feasible surgical procedure in the human, where the vascular anatomy is similar and the caliber of the ovarian vessels if greater than in the rhesus monkey.

Animals

Placental transfer of taurine in the rhesus monkey.

Maternal to fetal transfer of taurine was examined in 10 pregnant monkeys infused with taurine. In four animals infused at 15 mg/kg body weight, maternal plasma taurine concentration increased from preinfusion values of 8.82 +/- 2.61 to 28.0 +/- 6.00 mumol/dl (mean +/- SD) by the end of the 2-h infusion period. Mean (+/- SD) fetal plasma taurine concentration increased concomitantly, rising from preinfusion values of 13.3 +/- 2.61 to 36.6 +/- 17.8 mumol/dl at the end of the infusion, maintaining the normal fetal to maternal plasma ratio of 1.3 to 1.5. Maternal infusion of larger quantities of taurine increased both maternal and fetal plasma taurine levels; however, the placenta was unable to maintain the normal fetal to maternal gradient. In four monkeys infused with taurine at 25 mg/kg body weight over a 2-h period, mean (+/- SD) maternal plasma taurine concentration increased from 10.0 +/- 1.33 to 43.5 +/- 11.0 mumol/dl. Fetal plasma concentration increased from 13.6 +/- 1.05 to 34.9 +/- 5.89 mumol/dl. However, the maternal to fetal plasma taurine ratio fell from 1.36 to 0.80. Similar results were noted in single animals infused with taurine at 50 and 250 mg/kg body weight. Maternal and fetal plasma concentrations of most other amino acids were not affected by taurine infusion. Fetal, but not maternal, plasma alanine concentration increased after taurine infusion. These data indicate that taurine is efficiently concentrated to the fetal circulation at postprandial maternal plasma taurine concentrations.

Alanine