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Biomedical subjects

J R King

Publications and source records attributed to J R King.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of lewisite toxicity in isolated perfused skin.

Lewisite (L) is a potent organic arsenical that causes rapid onset of pain and severe vesication on contact with epithelial tissues. The isolated perfused porcine skin flap (IPPSF) is an in vitro model that has shown potential as a model for cutaneous vesicant research. The objective of this study was to characterize IPPSF responses after topical exposure to six concentrations of L ranging from 0.07 to 5.0 mg/ml (n = 4/treatment plus controls). Biochemical markers of viability (glucose utilization (CGU) and lactate dehydrogenase (LDH) release), vascular resistance (VR), venous arsenic flux, and morphological parameters (light and electron microscopy) were evaluated. In addition, lewisite lesions were characterized at 1, 3, 5, and 8 hr after exposure (n = 4/time plus controls) using these morphological parameters, as well as enzyme histochemistry. Macroscopic and microscopic lesions caused by L exposure were dose related. Mild decreases in CGU were noted with the higher concentrations of L, while generally increased responses in LDH release and VR were seen. Marked increases in LDH activity were noted in the blister fluid of IPPSFs treated with 5.0 mg/ml of L. Also, significant cutaneous arsenic flux was noted at the 5.0 mg/ml dose of L. The formation of gross blisters, the location and characterization of epidermal-dermal junction separation, and the time course of lesion production paralleled the description of L-induced lesions in humans. The sensitivity of the IPPSF to L exposure and the similarity of lesions to those described for humans suggests that this model provides a relevant in vitro model with which to study mechanisms of chemical vesication and arsenic toxicity, as well as protective and therapeutic intervention for vesicant exposure.

Administration, Topical↗
PubMed1991

Effects of organic solvent vehicles on the viability and morphology of isolated perfused porcine skin.

Although many organic solvents are known to be cutaneous irritants, they are commonly utilized as vehicles in percutaneous absorption and toxicity studies. The isolated perfused porcine skin flap (IPPSF) is an alternative animal model that has been used to study percutaneous absorption and cutaneous toxicity. The purpose of this study was to evaluate the effect of five organic solvents (ethanol, acetone, dimethyl sulfoxide (DMSO), toluene, and cyclohexane) on biochemical viability parameters, vascular response, and epidermal morphology of the IPPSF. Cumulative glucose utilization (CGU), the ratio of lactate production/glucose utilization (L/CGU ratio), and the leakage of lactate dehydrogenase (LDH) were used as biochemical indicators of alterations in glucose metabolism and flap viability. Only ethanol resulted in a statistically significant decrease in the average rate of CGU over the perfusion period. All of the solvent treatments resulted in slight increases in LDH release versus the controls. Vascular resistance (VR) was measured to examine the response of the cutaneous vasculature to these solvents, and most treatments resulted in a decreased VR in the terminal phases of perfusion. Ethanol was the only solvent to cause an apparent increase in terminal VR. Light microscopy demonstrated a moderate increase in intracellular edema in the DMSO, toluene, and acetone flaps. Ultrastructural evaluation showed focal blebbing of the nuclear envelope and vesiculation of the rough endoplasmic reticulum in cells of the stratum basale and stratum spinosum layers with DMSO treatment. The IPPSF allowed the evaluation of subtle biochemical, vascular, and morphological changes associated with non-occlusive topical exposure to these organic solvents. These findings support the necessity of documenting vehicle effects which might mask or otherwise alter subtle, but potentially important, compound-specific responses.

Acetone↗
PubMed1990

Cutaneous toxicity of 2-chloroethyl methyl sulfide in isolated perfused porcine skin.

Previous research has shown the isolated perfused porcine skin flap (IPPSF) to be a novel in vitro experimental model for investigating xenobiotic percutaneous absorption. In this study, the IPPSF was used to biochemically and morphologically assess the dermatotoxicity of 2-chloroethyl methyl sulfide (CEMS), a monofunctional analog of the vesicant, sulfur mustard. IPPSFs were perfused in a recirculating perfusion system and were treated with 97% CEMS (n = 4) or served as controls (n = 4). Additional IPPSFs were perfused in a nonrecirculating perfusion system and were treated with CEMS (n = 4) or were controls (n = 4). After dosing, each IPPSF was perfused for 8 hr. Cumulative glucose utilization (GU) and lactate production/glucose utilization ratio (L/GU ratio) were used as viability parameters. The average rate of GU for CEMS was significantly lower than control (p less than 0.05) in the recirculating and nonrecirculating IPPSFs. The L/GU ratio for CEMS was not significantly different (p greater than 0.05) from control for either perfusion system. CEMS resulted in a marked increase in vascular resistance versus control in both perfusion systems. Gross vesicles and bullae formation occurred in six of the CEMS-treated IPPSFs. Light microscopy revealed subepidermal vesicle formation above the basement membrane and extensive basal cell pyknosis in all IPPSFs treated with CEMS. No macroscopic or microscopic lesions were noted in the control flaps. Transmission electron microscopy revealed separation between the lamina lucida and the lamina densa of the basal lamina, with intracellular vacuolization and mitochondrial swelling occurring in the stratum basale and stratum spinosum cells of IPPSFs treated with CEMS. These lesions are similar to those described after human exposure to sulfur mustard. Full characterization of the morphological and biochemical changes seen after topical exposure of the IPPSF to vesicants may shed light on the pathogenesis of cutaneous toxicity of these compounds in vivo and serve as a relevant model to assess protective strategies against vesicant exposure.

Animals↗
PubMed1990

Pharmacokinetics of lithium in patients treated with controlled release lithium formulations.

There has long been discussion as to the relative merits of the lithium formulations available in the UK. Two of these have been shown to exhibit similar pharmacokinetics in normal volunteers and both are now marketed as controlled release formulations. In this study the serum lithium profiles of these formulations were compared in patients at two centres during the first 4 h after the dose, and at 24 h. We were unable to show any significant difference between the formulations in respect of maximum serum lithium concentrations or the concentration at each time point.

Adult↗
PubMed1989

Sparrows discriminate between diets differing in valine or lysine concentrations.

White-crowned Sparrows (WCS) were given free access to pairs of semisynthetic diets that were either adequate or subadequate (25% of requirement) in valine or lysine. Within 2 to 4 days WCS chose a ratio of the paired diets that allowed them to maintain body mass or restore any losses quickly. On the initial choice days the birds transiently reduced total daily food intake (TDFI) roughly in proportion to their intake of the subadequate diet. The initial decrease of TDFI was greater and the latency in choosing an effective ratio of the paired diets was 2-3 days longer with valine than with lysine diets in well-nourished test birds. In malnourished birds fed only the subadequate test diet for 3 days, valine-deficient birds increased TDFI and body mass more promptly than did lysine-deficient birds when offered a choice of adequate and subadequate diets. The form of the test amino acid (CAA = crystalline, PB = protein-bound) had little effect on choice behavior, but sudden transfer of WCS from a PB acclimation diet to test diets with a large total CAA concentration increased the latency of effective choice by 2-3 days. A brief acclimation (2-3 days) to a CAA diet precludes any bias between nutritionally equivalent CAA and PB diets. The small differences in choice dynamics between valine and lysine and between dietary forms may help to identify mechanisms involved in food choice but are probably ecologically insignificant to free-living WCS. These birds are very adept at selecting diets that satisfy their amino acid requirements.

Animals↗
PubMed1987

Temperature and humidity dynamics of cutaneous and respiratory evaporation in pigeons, Columba livia.

Using a two-compartment metabolism chamber, we measured oxygen consumption simultaneously with evaporative water loss (EWL) separately from the skin and respiratory tract of pigeons exposed to various air temperatures and humidities. Both respiratory (REWL) and cutaneous (CEWL) water loss increased markedly with increasing air temperature, and latent heat loss through both routes dissipated large fractions of internal heat production during mild heat stress. CEWL as a percentage of total EWL significantly exceeded REWL (60 +/- 1.5%) at thermoneutral air temperatures, and was also a substantial fraction of total EWL at lower and higher temperatures. Both REWL and CEWL were inverse functions (apparently linear) of ambient humidity at 20 and 30 degrees C. These observations verify suggestions by other investigators that CEWL in birds plays a greater role in water balance and in counteracting heat stress than was previously believed.

Animals↗
PubMed1985

Side-effects of lithium at lower therapeutic levels: the significance of thirst.

The prevalence of thirst, subjective polyuria and related side-effects was investigated in 87 patients attending a lithium clinic and in a group of 52 controls. Thirst was surprisingly common, occurring in 67% of patients, in spite of the fact that they had been maintained on relatively low levels of lithium, and was due principally to the lithium rather than to other psychotropic drugs. Urine flow and impaired renal water absorption correlated with the serum lithium level and the length of treatment in the patients, despite the fact that few were clinically polyuric. The pattern of the results confirms previous suggestions that lithium may stimulate the thirst mechanism directly as well as via an increased renal resistance to vasopressin. The possible implications in terms of clinical response are discussed.

Bipolar Disorder↗
PubMed1985

Nutritional state of elderly women on admission to mental hospital.

Since nutritional deficiencies might worsen the severity of symptoms and prolong the length of illness in non-nutritional disorders, particularly in the elderly, we examined the nutritional status of 216 elderly women newly admitted to a mental hospital. Compared to healthy elderly women, they had lower values for plasma prealbumin, vitamin C, and B vitamins. This was particularly common in senile dementia, and appeared to be the result of inadequate intake of protein or vitamins. Regular hospital diet for one month corrected the very low levels of prealbumin, but supplements were essential to remove deficiency of the water-soluble vitamins. Although vitamin supplements did not influence the length of stay in hospital, we did not exclude the possibility that nutritional deficiencies have a significant effect on the severity of mental illness.

Aged↗
PubMed1979

Energetic cost of terrestrial locomotion: biped and quadruped runners compared.

Reanalysis of empirical data relating the energetic ost of running (Erun = cm3 02 g-1 km-1) to body mass (g) indicate the slopes of these regression analyses are indistinguishable when bipeds and quadrupeds are compared. The results agree with previous theoretical conclusions that the cost of transport in all runners scales on body mass (g) raised to the -1/3 power. The comparison also suggests that there is no difference between the energetic cost of maintaining a running posture for bipeds and quadrupeds and this postural cost is much less than original estimates.

Animals↗
PubMed1977

Trace analysis of diethylstilbestrol [DES] in animal chow by parallel high-speed liquid chromatography, electron-capture gas chromatography, and radioassays.

An analytical method is described for determining residues of the synthetic estrogen diethylstilbestrol (DES) in animal chow at levels as low as 1 ppb. A methanol extract of the chow is subjected to a 3-step cleanup procedure including a Sephadex LH-20 column, liquid-liquid partitioning at pH 14 and 10.2, and a silica gel column. Residues of DES in the cleaned-up extract are analyzed directly by high-speed liquid chromatography or derivatized to pentafluoropropionyl-DES and assayed by electron-capture gas chromatography. Tests with 14C-DES were used to develop and validate the procedure. Ancillary data concerning extraction efficiencies of various solvents, comparisons of various derivatizing reagents, rates of trans-cis isomerization in two solvents, P-values of DES in various solvent-systems and thin-layer chromatographic behavior i

Animal Feed↗
PubMed1976

Benzidine and congeners: analytical chemical properties and trace analysis in five substances.

Spectrophotofluorimetric (SPF) methods are described for the trace analysis of benzidine, 3,3'-dimethylbenzidine, 3,3'-dimethoxybenzidine, and their dihydrochloride salts in microbiological growth media, waste water, potable water, human urine, and rat blood. The salient elements of the methods for these known or suspected carcinogens are: extraction of the residues as the free amine with benzene, rapid cleanup on an alumina column, and quantification of the free amine in methanol via SPF. Potable water solutions of the salts are diluted with buffer (pH-4) and quantified directly by SPF. Ancillary analytical information concerning the solubility and stability of these compounds in water, p-values, gas chromatographic analysis of the free amines, and thin layer chromatographic data in ten solvent systems are also presented.

Animals↗
PubMed1976

4-aminobiphenyl, 2-naphthylamine, and analogs: analytical properties and trace analysis in five substrates.

Methods for monitoring trace levels of 4-aminobiphenyl, 2-naphthylamine, and their hydrochloride salts in waste water, microbiological growth media, potable water, human urine, and mouse blood utilizing spectrophotofluorometry (SPF) are described. The salient elements of the methods are extraction of the residues as the free amine with benzene, rapid cleanup on an alumina column, and quantification of the free amine in methanol via SPF. Potable water solutions of the salts are diluted with 0.01 N aqueous HCL and quantified directly by SPF. Ancillary analytical information concerning gas chromatography of the free amines, partitioning properties of the compounds between solvent pairs, their solubility and stability in water, and thin-layer chromatographic data is presented. The compositions of various admixtures of 1- and 2-naphthylamine or their salts were determined by using SPF with calculations based on simultaneous equations.

2-Naphthylamine↗