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D J Nichols

Publications and source records attributed to D J Nichols.

35 records · Page 2Linked to original sources

A demonstration of pharmacokinetics and physiological modelling using a microcomputer for data capture and analysis.

We describe a simple and inexpensive demonstration of mass transport and exchange using dye clearance from a hydrodynamic model. A microcomputer was used for data acquisition and storage, non-linear least squares curve fitting, compartmental analysis and parameter estimation. The system is useful for demonstrating the indicator-dilution technique for fluid volume measurement and compartmental analysis in pharmacokinetics.

Algorithms↗

Cortisol dynamics during seawater adaptation of Atlantic salmon Salmo salar.

We examined plasma cortisol concentration (PCC), cortisol metabolism, and cortisol protein binding (CPB) in chronically cannulated Atlantic salmon (Salmo salar) during seawater (SW) adaptation. PCC rose significantly 2 h after freshwater (FW) to SW changeover but tended to be lower for 6 days thereafter. Plasma chloride concentrations began to stabilize 24-48 h after entry to SW. Cortisol metabolic clearance rate (MCR) was significantly higher 24 h after SW transfer than in FW; CPB and plasma protein concentration were significantly lower, but cortisol production rate was unchanged. The change in plasma chloride after 24 h in SW was negatively correlated with the change in plasma protein (r = -0.915, n = 9, P less than 0.001). The changes in CPB and plasma protein were correlated with the change in MCR (r = -0.643, n = 14, P less than 0.02; r = -0.850, n = 9, P less than 0.005). We hypothesize that these changes in protein concentration reflect an ion-induced expansion of extracellular volume and lead to increased MCR.

Adaptation, Physiological↗

Cortisol kinetics and fluid distribution in brook trout (Salvelinus fontinalis).

Cortisol kinetics were examined in brook trout (Salvelinus fontinalis) to assess possible relationships with body fluid distribution during acclimation to sea water (SW). The disappearance curve of [3H]cortisol in plasma, after a bolus injection, was analysed by compartmental analysis using a three-pool mammillary model. The results indicated that only approximately 10% of the total exchangeable cortisol was located in the plasma pool. Over 75% of the total cortisol was associated with a large slowly exchanging pool and the remaining cortisol was located in a second extravascular tissue pool which was in rapid exchange with the plasma pool. Two days after transfer of trout from fresh water to SW, when plasma chloride concentration was at a new steady state, body weight, intracellular fluid volume, haematocrit and inulin clearance rate were lowered but plasma, blood and extracellular volumes were unaltered. Cortisol plasma clearance rate was unaltered but plasma cortisol concentration, cortisol secretion rate, total cortisol pool size and interpool transport rates were increased. These results are consistent with an acute role for cortisol in SW adaptation of brook trout. The fraction of the total cortisol cleared was smaller and the average time that cortisol spent in the tissue pools was slightly longer in trout after transfer to SW, possibly reflecting altered fluid dynamics. The fractional disappearance rate was larger at higher plasma cortisol concentrations in the SW trout. This relationship is compatible with the hypothesis that cortisol protein binding protects cortisol from metabolism.

Adaptation, Physiological↗

Plasma cortisol concentrations in Atlantic salmon, Salmo salar: episodic variations, diurnal change, and short term response to adrenocorticotrophic hormone.

Short term episodic peaks 1-2 hr in duration in plasma cortisol levels were observed in adult Atlantic salmon. These results support the concept that episodic secretion of corticosteroids may be a characteristic feature of the vertebrate adrenal/interrenal regulatory system and provide an explanation for the variability frequently observed in plasma cortisol concentrations in salmonids. Plasma cortisol levels also varied throughout the light-dark cycle and mean concentrations were higher during the night. High frequency variations in plasma cortisol levels (with a time scale of minutes rather than hours) were not observed. Porcine adrenocorticotrophic hormone (ACTH) and ACTH1-24 but not alpha-melanocyte-stimulating hormone (alpha-MSH) increased plasma cortisol levels 10 min after injection. The change in plasma cortisol levels after injection of 1 mU/kg porcine ACTH was of similar magnitude and duration as endogenous episodic variations. Plasma cortisol levels during episodic peaks, circadian changes, or after ACTH injection were less than the binding capacity of the "high" affinity protein binding system for cortisol. Hence, the unbound cortisol concentration is a linear function of the total cortisol concentration. Whereas episodic release of cortisol is indicated here, the physiological importance of this mode of hormone secretion is unclear. Plasma glucose levels were unaffected up to 2 hr after injection of ACTH and did not show close temporal correlation with endogenous episodic peaks in plasma cortisol.

Adrenocorticotropic Hormone↗

Adrenocortical responses and changes during the oestrous cycle in mice: effects of male presence, male urine and housing conditions.

Male urine applied daily to their bedding raised the basal levels of plasma corticosterone in individually housed, virgin female mice, when compared with females (grouped or individually housed) living with male mice or with group-housed females exposed daily to male urine. Values were not affected during ether-induced stress. A single application of male urine raised plasma levels 30 min later regardless of housing conditions; but after 4 and 24 h levels had fallen to normal. The results are discussed in terms of sensitization of the pituitary-adrenal system and of stress and reproductive pheromones. Male urine was less effective than male presence at inducing 4-day oestrous cycles. Length and type of cycle varied continuously under the influence of a spectrum of environmental signals.

Adrenal Cortex↗

Pharmacokinetics and fate of [3H]trospectomycin sulfate, a novel aminocyclitol antibiotic, in male and female dogs and rabbits. Allometric scaling with human.

The pharmacokinetics and fate of [3H]trospectomycin sulfate, a novel aminocyclitol antibiotic, were examined in male and female dogs and rabbits. Total radioactivity levels in plasma were associated with unchanged trospectomycin in both dog and rabbit. No unchanged drug was found in rabbit urine. Two radioactive components were found in dog urine; one was indistinguishable from trospectomycin and the other was probably a degradation product. The disappearance of drug from plasma followed a biphasic pattern and was well described by a bi-exponential function with half-lives of 0.4-0.8 and 30-70 hr in the dog and 0.4 and 90-120 hr in the rabbit. There was a large distribution volume (Vss), which indicated some retention of drug by tissues. The clearance (CL) for both animals was within the normal range for glomerular filtration rate. CL and Vss were not different between the sexes in the dog or rabbit. Excretion in both animals was initially rapid (greater than 40% by 4 hr) and mainly by the urinary route (fecal excretion less than 10%). Urinary excretion was not significantly different between the sexes. Over the dose range of 25-100 mg/kg, the plasma pharmacokinetics in the dog were linear. However, the recovery of radioactivity in the urine was significantly reduced at the highest dose. Trospectomycin CL in rat, human (obtained from previous studies), dog, and rabbit was described by the allometric equation, CL (ml/hr) = 132 x M0.91 where M is the body mass in kg.

Animals↗

Perceptions and practices relating to condom use among urban men in Haiti.

This report is based on a survey conducted in 1986-87 of sexually active adult male residents in a low-income community of Port-au-Prince, Haiti. The objectives were to investigate knowledge of and attitudes toward condoms; to evaluate the effectiveness of the existing condom distribution program; and to obtain information that can be used in the design of strategies to increase condom acceptance and use among men throughout Haiti. A final sample of 706 sexually active adult male residents in stable unions, including a specially drawn sample of male partners of condom acceptors, were interviewed in their homes. Although condoms are almost universally known, they are rarely used. The majority felt that the responsibility for family planning should be borne by the woman. Whereas condoms may be of limited popularity for family planning purposes in Haiti, it should be determined whether they might be more acceptable as an effective means of controlling the spread of AIDS and other STDs.

Adolescent↗