Search PubMed⌕ Search

Biomedical subjects

T W Jones

Publications and source records attributed to T W Jones.

162 records · Page 9Linked to original sources
PubMed1967

The molluscicidal activity of N-tritylmorpholine.

N-Tritylmorpholine (Frescon, WL 8008) is highly toxic to the intermediate-host snails of the Schistosomatidae. Molluscicidal concentrations range from 0.1 ppm to 0.5 ppm for 1-hour exposures and from 0.01 ppm to 0.05 ppm for 24-hour exposures. Under these conditions the compound is not toxic to snail eggs; recent work, however, shows that longer exposures are toxic. It has been successfully used to control snails in large-scale trials in several countries with very short exposures (4 ppm for 15 min), as well as in prolonged treatments (0.025 ppm for 16 days).These treatments have remarkably little effect on other forms of aquatic life; plants, insects and the microfauna and flora are unaffected, and in certain circumstances it has proved possible to control snails without harming fish populations. A detailed study of the toxicology of N-tritylmorpholine in mammals has shown that it does not present any toxic hazards.N-Tritylmorpholine can be formulated in a variety of ways, e.g., as emulsifiable concentrates, water-dispersible powders and granules, as well as some specialized types of formulations, such as baits and spreading oils. Laboratory and field studies have shown that environmental factors such as mud, light and vegetation have little effect on the performance of N-tritylmorpholine, but hydrolysis and loss of activity may occur in acid water.

Animals↗
PubMedDate not supplied

Gastrointestinal metabolism of N-acetylcysteine in the rat, including an assay for sulfite in biological systems.

The intestinal metabolism of N-acetylcysteine was studied in the rat. Isolated intestinal epithelial cells were shown to rapidly deacetylate [14C]-N-acetylcysteine to [14C]-cysteine, with slight oxidation of the latter to disulfide species. The cells did not accumulate reduced or oxidized cysteine, and N-acetylcysteine itself was not detected either free or in oxidized species intracellularly. Further metabolism of this NAC-derived cysteine to inorganic sulfite or glutathione was not detected. Following the administration of [14C]-N-acetylcysteine (50 mg/kg; 25 microCi) in vivo into the ilium, small quantities of both reduced and oxidized [14C]-N-acetylcysteine were demonstrated in hepatic portal vein plasma. [14C]-cysteine and inorganic sulfite were demonstrated as the major metabolites of N-acetylcysteine. These were present in the portal vein plasma at levels five and three times greater than the parent drug, respectively, 30 min after dosing. Additionally, [14C]-glutathione was shown to be a minor metabolite of N-acetylcysteine accumulating in portal vein plasma. These results may provide an explanation for the apparent low bioavailability of N-acetylcysteine when administered orally in humans and are discussed in terms of the origins of the protective effect of the drug in cases of paracetamol intoxication in humans.

Acetylcysteine↗
PubMedDate not supplied

The effect of age on the plasma protein binding of pentobarbitone in the mouse. A brief note.

Old mice show an increased sensitivity to parenteral pentobarbitone compared with young adult mice, despite similar plasma concentrations of the drug. One factor may be an alteration in the binding of barbiturate to the plasma protein, perhaps consequent on reduced hepatic synthesis of plasma protein with advancing age. As part of a study of the effect of age upon the pharmacological and adaptive response to barbiturates, binding of pentobarbitone to plasma proteins from mice of different ages was measured by equilibrium dialysis in the presence of a standard concentration of the drug. The total plasma protein concentration was measured and found to be the same in both age groups. The plasma protein binding of pentobarbitone was found to correlate significantly with the plasma albumin concentration, which was lower in the older mice. However, there was no significant overall difference in pentobarbitone binding between old and young mice. Pretreatment of the mice with phenobarbitone for 21 days had no effect upon the capacity for plasma protein binding of pentobarbitone in either age group. Thus, it seems unlikely that the increased sensitivity of older mice to pentobarbitone can be explained in terms of altered plasma protein binding of the drug.

Aging↗
PubMedDate not supplied

The effect of age and pentobarbitone tolerance on pentobarbitone depression of calcium-45 uptake by mouse brain synaptosomes.

Nerve terminals (synaptosomes) isolated from mouse brains accumulate 45Ca2+ at a rate which can be stimulated to increase by immersion in a high K+ saline. Low concentrations of pentobarbitone depress stimulated 45Ca2+ accumulation in a dose-dependent manner. We investigated the effect of 1 mM pentobarbitone on calcium accumulation by synaptosomes isolated from the brains of young and old mice, some of which had been made tolerant to barbiturates, to see if age and tolerance to barbiturate would modify 45Ca2+ accumulation. In the absence of barbiturate, neither advancing age nor barbiturate tolerance could be associated with any significant change in 45Ca2+ uptake by potassium-stimulated or non-stimulated synaptosomes. However, both factors modified the depressant effect of barbiturate. Age and tolerance did not influence resting or potassium-stimulated 45Ca2+ uptake, nor did they influence the suppression by pentobarbitone of resting 45Ca2+ uptake. However, when correcting for suppression of resting uptake by barbiturate, age significantly reduced barbiturate suppression of potassium-stimulated 45Ca2+ uptake. Tolerance significantly reduced this corrected effect of barbiturate in synaptosomes from the 3-month old but not the 24-month-old mice.

Aging↗
PubMedDate not supplied

N-methyl-D-aspartate mediated responses decrease with age in Fischer 344 rat brain.

N-Methyl-D-aspartate (NMDA) receptor-mediated responses were studied in hippocampus, cortex, and striatum of Fischer 344 rats of various ages (3-5, 12-14, or 24-28 months old; young, middle-aged, and senescent or old, respectively) to determine whether aging alters the function of NMDA receptors. NMDA-induced inhibition of muscarinic-stimulated phosphoinositide hydrolysis in hippocampus, and NMDA-stimulated release of [3H]norepinephrine (NE) or [3H]dopamine (DA) were used as indices of NMDA receptor function. The muscarinic agonist carbachol (1 mM) stimulated PI hydrolysis in hippocampi from all three age groups with no significant differences between the groups. NMDA inhibited the carbachol-evoked PI response in a concentration-dependent manner (10-100 microM) in all age groups. However, the NMDA-induced (100 microM) inhibition of the carbachol-stimulated response was markedly reduced in an age-dependent manner with losses of 25% and 53% in middle-aged and senescent rats compared to young. Concentration-effect curves for NMDA-stimulated [3H]NE release were determined using hippocampal and cortical slices from rats of the three age groups. In the hippocampus the maximal response for NMDA was significantly decreased from 6.55 fractional [3H]NE release in young to 4.51 and 4.18 in middle-aged and old rats, respectively, with no age-related changes in the potency of NMDA or slope of the curves. In cortical slices the maximal response was significantly reduced in an age-dependent manner by 23% in the senescent rats compared to the young rats. NMDA-stimulated [3H]DA release from striatal slices was significantly lower in the senescent rats at concentrations of NMDA from 500-2000 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

In vitro studies of mechanisms of cytotoxicity.

A variety of model systems has been used to study mechanisms of cytotoxicity in vitro. These include purified enzymes, subcellular fractions, freshly isolated cells and perfused organs. Freshly isolated cells provide a number of distinct advantages and have become a popular experimental model in many laboratories. This paper discusses some of the advantages and disadvantages of isolated cell preparations for studies of cytotoxicity and summarizes the results of recent work in which isolated hepatocytes and renal epithelial cells have been used to examine the metabolism and toxicity of menadione and hexachloro-1,3-butadiene.

Animals↗
PubMedDate not supplied

Alcohol inhibition of NMDA-stimulated catecholamine efflux in aging brain.

The influence of aging on the ability of ethanol to inhibit N-methyl-D-aspartate-stimulated catecholamine overflow in rat brain was examined. Alcohol effects on N-methyl-D-aspartate stimulated [3H]norepinephrine or [3H]dopamine overflow from the cortex, hippocampus, and striatum of aged (24-28 months) middle aged (12-14 months), and young (3-5 months) rats were examined. N-methyl-D-aspartate (500 microM) stimulated catecholamine overflow in all brain regions, with aged rats showing declines in overflow of 33% in the hippocampus and 41% in the striatum. Alcohol (30-200 mM) produced a concentration-dependent inhibition of overflow at all ages and brain regions tested. The IC50 for alcohol inhibition of NMDA-stimulated catecholamine release was not significantly different in aged brain or across brain regions. These results indicate that alcohol's ability to inhibit NMDA-stimulated catecholamine release is not significantly altered with aging.

Aging↗
PubMedDate not supplied

D, L-(tetrazol-5-yl)glycine stimulation of NMDA receptors in neonatal dissociated neurons: inhibition by ethanol.

Ethanol inhibition of NMDA receptor stimulation by the high-affinity selective agonist D, L-(tetrazol-5-yl)glycine (T5G) was studied using acutely dissociated neonatal whole-brain neurons loaded with the fluorescent indicator fura-2. T5G induced a concentration-dependent increase in intracellular calcium with a maximal increase above basal of 70nM at 16 microM T5G (EC50 of 0.66 +/- 0.18 microM). T5G agonist specificity was verified using the NMDA antagonists MK-801 (40 nM), APV (100 microM), and Mg2+ (1 mM). The T5G stimulation of calcium entry was both blocked and reversed by these antagonists. Ethanol significantly inhibited the T5G-mediated increase in intracellular calcium only at concentrations > or = 100 mM. In addition, the effect of increasing concentrations of ethanol in the presence of the glycine-site antagonist 5, 7-dichlorokynurenic acid (DCKA, 0.37 microM) on T5G-stimulated calcium entry was examined. A significant inhibition of the T5G-stimulated response in the presence of DCKA was observed at ethanol concentrations as low as 20 mM. These results support previous findings that T5G is a potent agonist of the NMDA receptor and indicate that stimulation of calcium entry by this agonist is less sensitive to ethanol inhibition than stimulation by NMDA.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Acute hyperglycaemia impairs cognitive function in children with IDDM.

OBJECTIVE: The effects of acute hyperglycaemia on cognitive function in children remain controversial. This study was designed to investigate the suggestion that acute hyperglycaemia impairs cognition in IDDM children. DESIGN: To examine this question we studied 12 randomly selected children with IDDM (6 boys, 6 girls, mean age 12.4 years). Cognitive performance was assessed on two occasions at least six months apart (7.4 +/- 1.4 mths, range: 6.3-11.1 mths) under randomised conditions of hyperglycaemia (20-30 mmol/l) on one occasion and euglycaemia (5-10 mmol/l) on the other. Target glucose levels were achieved using a modified clamp technique with subjects and psychologist blinded to the glycaemic level. Cognitive tests chosen to assess performance skills were subtests from the Wechsler Intelligence Scale for Children-3rd Edition (WISC-111). RESULTS: No significant learning effect was present. However, there was a reduction in performance IQ at hyperglycaemia compared with euglycaemia (106 +/- 4.3 vs 112 +/- 4.5 IQ points respectively, p < 0.05). Under hyperglycaemic conditions the mean decrease in percentile score for performance IQ was 9.5%. Of the 12 children tested, 8 had a decrease in IQ when hyperglycaemic, which was independent of duration of diabetes and long term metabolic control assessed by HbA1c. CONCLUSION: Acute hyperglycaemia results in impairment of complex cognitive function in children with IDDM. This may have important implications for school performance.

Adolescent↗