Biomedical subjects

A J Kennedy

Publications and source records attributed to A J Kennedy.

At least 19 recordsLinked to original sources

PubMed2005

Evaluation of ionic contribution to the toxicity of a coal-mine effluent using Ceriodaphnia dubia.

The United States Environmental Protection Agency has defined national in-stream water-quality criteria (WQC) for 157 pollutants. No WQC to protect aquatic life exist for total dissolved solids (TDS). Some water-treatment processes (e.g., pH modifications) discharge wastewaters of potentially adverse TDS into freshwater systems. Strong correlations between specific conductivity, a TDS surrogate, and several biotic indices in a previous study suggested that TDS caused by a coal-mine effluent was the primary stressor. Further acute and chronic testing in the current study with Ceriodaphnia dubia in laboratory-manipulated media indicated that the majority of the effluent toxicity could be attributed to the most abundant ions in the discharge, sodium (1952 mg/L) and/or sulfate (3672 mg/L), although the hardness of the effluent (792 +/- 43 mg/L as CaCO3) ameliorated some toxicity. Based on laboratory testing of several effluent-mimicking media, sodium- and sulfate-dominated TDS was acutely toxic at approximately 7000 microS/cm (5143 mg TDS/L), and chronic toxicity occurred at approximately 3200 microS/cm (2331 mg TDS/L). At a lower hardness (88 mg/L as CaCO3), acute and chronic toxicity end-points were decreased to approximately 5000 microS/cm (3663 mg TDS/L) and approximately 2000 microS/cm (1443 mg TDS/L), respectively. Point-source discharges causing in-stream TDS concentrations to exceed these levels may risk impairment to aquatic life.

Animals↗

PubMed2004

Evaluation of ecologically relevant bioassays for a lotic system impacted by a coal-mine effluent, using Isonychia.

Many studies investigating the ecotoxicological impacts of industrial effluents on fresh-water biota utilize standardized test species such as the daphnids, Ceriodaphnia dubia, Daphnia magna, and the fathead minnow, Pimephales promelas. Such species may not be the most predictive or ecologically relevant gauges of the responses of instream benthic macroinvertebrates to certain stressors, such as total dissolved solids. An indigenous species approach should be adopted, using a sensitive benthic collector-filterer following development of practical laboratory bioassays. In the Leading Creek Watershed (southeast Ohio), an aggregated approximately 99% reduction in mean mayfly abundance for all impacted sites was observed below a coal-mine effluent with mean specific conductivity (SC) of 8,109 (7,750-8,750) microS cm(-1). The mayfly, Isonychia, was exposed for 7-days to a simulation of this effluent, in lotic microcosms. Based on lowest observable adverse effect concentrations, Isonychia survival was a more sensitive endpoint to SC (1,562 microS cm(-1)) than were 7-day C. dubia survival and fecundity (3,730 microS cm(-1)). Isonychia molting, a potentially more sensitive endpoint, was also examined. Using traditional test species to assess discharges to surface water alone may not adequately protect benthic macroinvertebrate assemblages in systems impaired by discharges high in SC.

Animals↗

PubMed2003

Field and laboratory assessment of a coal processing effluent in the Leading Creek Watershed, Meigs County, Ohio.

The U.S. Environmental Protection Agency has not recommended water quality criteria (WQC) to protect aquatic life from elevated sodium and sulfate concentrations, such as those associated with the coal-processing effluent of Meigs County Mine #31. This discharge, received by a tributary of the Leading Creek Watershed (SE Ohio), had a mean specific conductivity (SC) of 8,109 (7,750-8,750) microS/cm and total metal concentrations below acute WQC. The mean 48-h LC(50) for Ceriodaphnia dubia in the effluent was 6,713 +/- 99 microS/cm; mean 48-h survival was 44% for study sites downstream of the effluent. The best indicators of impairment used in this study were Ceriodaphnia fecundity, in situ Corbicula fluminea growth, EPT minus Hydropsychidae (richness and relative abundance), and relative Ephemeroptera abundance. Mayflies, reduced by more than 99% below the effluent, were absent from all but the furthest downstream study site. SC was strongly correlated with Corbicula growth (r = -0.9755, p = 0.0009) and EPT minus Hydropsychidae richness (r = -0.8756, p < 0.0001), suggesting the effluent was primarily responsible for biotic impairment. Our results indicated that SC levels, a measure of dissolved solids, in the Leading Creek Watershed that exceeded approximately 3,700 microS/cm impaired sensitive aquatic fauna.

Animals↗

PubMed1998

GDNF and its receptor component Ret in injured human nerves and dorsal root ganglia.

Glial cell line-derived neurotrophic factor (GDNF) is trophic to motor and sensory neurones in animal models. GDNF mRNA is up-regulated in Schwann cells after peripheral nerve injury in rats. We have quantified and localized GDNF and its receptor component Ret, for the first time in any species, in injured human peripheral nerves and dorsal root ganglia (DRG) avulsed from the spinal cord. Significantly higher levels of GDNF were found in nerve distal to the site of the injury than in proximal or intact nerve, and in avulsed DRG than in post-mortem control DRG. GDNF immunostaining was seen in Schwann cells and in DRG neurones, especially of small and medium size, with significantly increased numbers of medium sized sensory neurones immunoreactive for GDNF after avulsion. Ret immunoreactivity was restricted to DRG neurones and axons, with no significant changes in numbers of positive DRG cells after injury. Our findings suggest that GDNF may play a role in injured human nerves and sensory ganglia, particularly in medium sized sensory neurones.

Adolescent↗

PubMed1998

Neurotrophin-3 is increased in skin in human diabetic neuropathy.

Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been shown to be necessary for the development of muscle spindle and Merkel cell afferent nerve fibres in animal models. The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres terminate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of endogenous NT-3 in skin of 24 patients at different stages of diabetic polyneuropathy have been investigated. NT-3 concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32 (1.18) pg/mg v control skin 1.28 (0.05) (mean (SEM)); p<0.004, Mann-Whitney U test), particularly in the later stages. The optical density of NT-3-immunostaining was also significantly greater in the epidermis in diabetic patients (diabetic epidermis 0.30 (0.06) v controls 0.24 (0.01); p<0.02). No correlation was found between individual quantitative sensory tests and the increase of NT-3 concentration. The increase of NT-3 seems to reflect the degree of skin denervation in diabetic neuropathy, and may represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.

Adult↗

PubMed1993

d-Fenfluramine- and d-norfenfluramine-induced hypophagia: differential mechanisms and involvement of postsynaptic 5-HT receptors.

Severe depletion of 5-hydroxytryptamine (5-HT) by para-chlorophenylalanine (pCPA, 150 mg/kg per day x3) did not alter the hypophagic effect of d-fenfluramine (1-3 mg/kg i.p.) 1 h after food presentation in 24-h food-deprived rats, and moderately and comparably increased the hypophagic effects of its metabolite, d-norfenfluramine (0.35-1.0 mg/kg i.p.), and of the 5-HT1C receptor agonist, 1-(3-chlorophenyl)piperazine (mCPP; 1.5, 2.0 mg/kg i.p.). Chronic treatment with mCPP (2.5 mg/kg i.p. x 14) attenuated the hypophagia induced by d-norfenfluramine (1, 1.5 mg/kg) but not d-fenfluramine (1, 3 mg/kg). 1-(1-Naphthyl)piperazine (3, 8 mumol/kg s.c.), which has greater affinity for 5-HT1C than for 5-HT2 receptors, had no effect on the hypophagia induced by d-fenfluramine (1.25, 2.0 mg/kg), but 1.3 and 3 mumol/kg 1-(1-naphthyl)piperazine largely and comparably attenuated the substantial hypophagic effect of d-norfenfluramine (0.75 mg/kg). The essentially complete hypophagic action of d-norfenfluramine (1.25 mg/kg) was inhibited by 1-(1-naphthyl)piperazine with ID50 = 2.13 mumol/kg. Ketanserin, which binds more weakly than 1-(1-naphthyl)piperazine to 5-HT1C receptors and more strongly to 5-HT2 receptors, attenuated weaker but not stronger hypophagic effects of d-fenfluramine (1.25, 2.0 mg/kg) when given at high dosage (8, 16 mumol/kg s.c.). Ketanserin (16 mumol/kg) also weakly attenuated the hypophagia due to d-norfenfluramine (0.75 mg/kg), but not the essentially complete hypophagia due to d-norfenfluramine (1.25 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of housing, restraint and chronic treatments with mCPP and sertraline on behavioural responses to mCPP.

The effects of pretreatments on behavioural responses to activation of 5-HT1C receptors by m-chlorophenylpiperazine (mCPP) were investigated. The hypo locomotor and anxiogenic effects of mCPP (social interaction test) were influenced neither by previous housing (single versus grouped) nor by restraint (2 h, 24 h previously). In the absence of mCPP, 24 h group housing led to decreased social interaction and the restraint procedure led to significant decreases of feeding and locomotion. The hypophagic effect of mCPP was unaffected by previous restraint. However, chronic pretreatment with mCPP (2.5 mg/kg per day IP x 14) or with the antidepressant 5-HT reuptake inhibitor sertraline (5 mg/kg per day SC x 14) attenuated all three behaviours. The above findings are discussed with respect to published data on effects of pretreatments on responses to the activation of 5-HT1C receptors.

1-Naphthylamine↗

PubMed1987

The effect of a peptide aldehyde reversible inhibitor of elastase on a human leucocyte elastase-induced model of emphysema in the hamster.

The peptide aldehyde Ro 31-3537, N alpha-(1-adamantanesulphonyl)-N epsilon-(4-carboxybenzoyl)-L-lysyl-L-alanyl-L- valinal, is a reversible competitive, hydrophilic, specific inhibitor of elastase. Its Ki against human leucocyte elastase is 6 x 10(-8) M. The effect of this compound has been studied on a model of emphysema in the hamster induced by multiple sequential intratracheal doses of human leucocyte elastase. Concomitant intratracheal dosing of 200 micrograms of inhibitor with the enzyme significantly reduces lung damage as measured by quasi-static lung compliance and by histological assessment of the emphysema.

Adamantane↗

PubMed1985

A new class of inhibitors of human leucocyte elastase.

Studies of the inhibition of elastases at a molecular level have resulted in the identification of protected dipeptides which are reversible and highly specific inhibitors of human leucocyte elastase (HLE). These have been further developed by increasing their hydrophilicity and potency to give a new family of elastase inhibitors, typically N alpha-(1-adamantanesulphonyl)-N epsilon-(4-carboxybenzoyl)-L-lysyl-L-alanyl-L-valinal. These compounds are active in pharmacological models designed to detect compounds of potential therapeutic value in the treatment of emphysema.

Adamantane↗

PubMed1984

Pharmacological and biochemical activities of tenoxicam (Ro 12-0068), a new non-steroidal anti-inflammatory drug.

Tenoxicam, a new non-steroidal anti-inflammatory drug has been compared with piroxicam and indomethacin in a range of pharmacological and biochemical inflammation test systems. In a chronic (17-day) adjuvant arthritis in the rat, tenoxicam and piroxicam were equally effective in reducing several indices of inflammation and were less ulcerogenic and better tolerated than indomethacin. The oxicams reduced the oedematous and cellular components of a carrageenan pleurisy at 4 hours while at 24 hours they increased exudate volume and selectively inhibited the accumulation of mononuclear cells. These agents also reduced the inflammatory component of a delayed hypersensitivity response to methylated bovine serum albumin in the mouse. The oxicams were about 100-fold less active than indomethacin as inhibitors of prostaglandin synthetase but all three compounds reduced about equally the release of prostaglandin E2 from phagocytosing rat PMN and interleukin 1-stimulated human rheumatoid synovial cells. The compounds had no effect on the release of superoxide anion, lysosomal enzymes or collagenase from cultured cells, neither did they inhibit isolated collagenase. Only indomethacin stabilized albumin against heat denaturation.

Adrenal Cortex Hormones↗

PubMed1982

Assessment of drugs for activity in established type II collagen arthritis.

Arthritis was induced in a proportion of rats sensitized with type II collagen and Freund's incomplete adjuvant. Rats which developed arthritis had significantly higher antibody titres and significantly greater delayed hypersensitivity responses to type II collagen than rats which did not develop arthritis. Anti-inflammatory and anti-rheumatic drugs were evaluated against type II collagen arthritis. Dexamethasone reduced inflammatory swelling, reduced both the antibody titre and delayed hypersensitivity to type II collagen and exerted joint protection. Indomethacin reduced inflammatory swelling. Azathioprine, Clozic, Levamisole, D-Penicilamine and Sulphapyridine did not exert significant beneficial activity in this test.

Animals↗

PubMed1979