PubMed Health⌕ Search

Biomedical subjects

C Pinsky

Publications and source records attributed to C Pinsky.

At least 19 recordsLinked to original sources
PubMed1998

Increased apoptosis, changes in intracellular Ca2+, and functional alterations in lymphocytes and macrophages after in vitro exposure to static magnetic field.

Electromagnetic-related alteration of cellular functions is well documented for extremely low-frequency low-energy pulsing electromagnetic fields (ELF-EMF). In this study we examined the in vitro effects of static magnetic fields (SMF) on the cellular immune parameters of the C57BI/6 murine macrophages, spleen lymphocytes, and thymic cells. The cells were exposed in vitro for 24 h at 37 degrees C, 5% CO2, to 250-1500 G SMF. Exposure to the SMF resulted in the decreased phagocytic uptake of fluorescent latex microspheres, which was accompanied by an increased intracellular Ca2+ level in macrophages. Exposure to SMF decreased mitogenic responses in lymphocytes, as determined by incorporation of [3H]thymidine into the cells. This was associated with the increased Ca2+ influx in concanavalin A-stimulated lymphocytes. Furthermore, exposure to SMF produced markedly increased apoptosis of thymic cells, as determined by flow cytometry. Overall, in vitro exposure of immunocompetent cells to 250-1500 G SMF altered several functional parameters of C57BI/6 murine macrophages, thymocytes, and spleen lymphocytes.

Animals↗
PubMed1994

Kynurenic acid distribution into brain and peripheral tissues of mice.

Kynurenic acid (KYN), an antagonist of excitatory amino acid receptors, is a putative antidote against neuroexcitatory amino acid toxicity. We studied various doses (0.05-3.17 mmol/kg, i.p.) and the effects of probenecid coadministration (0.70 mmol/kg, i.p.) on tissue distribution of KYN in male and female Swiss-Webster mice. After injection of [3H]KYN, samples of brain, heart, liver, kidney, skeletal muscle, and gut were collected at selected times and assayed for KYN by liquid scintillation counting. The substance was absorbed rapidly and distributed into all tissues. Its content (nmol/g, mean +/- SE) at 60 min was 0.26 +/- 0.05, 1.80 +/- 0.05, and 40.4 +/- 8.1 in brain (for 0.05, 0.53, and 3.17 mmol/kg), 1.43 +/- 0.11, 14.3 +/- 3.7, and 212 +/- 32 in heart, 1.16 +/- 0.21, 10.6 +/- 2.6, and 254 +/- 21 in liver, and 7.41 +/- 2.65, 180 +/- 63, and 1899 +/- 254 in kidney. Net accumulation of KYN in brain was much lower than in other tissues. Probenecid increased KYN concentration in brain 2.5-fold. Peak brain:blood concentration ratio occurred between 60 and 180 min, was inversely associated with dose, and was not affected by probenecid. Although brain content was similar, female mice had an earlier peak brain:blood ratio (120 min) than males (180 min) for the 0.05 mmol/kg dose. Our results suggest the presence of a restricted transfer process for KYN with delayed egress from brain.

Animals↗
PubMed1992

Pyridine and other coal tar constituents as inhibitors of potato polyphenol oxidase: a non-animal model for neurochemical studies.

Potato polyphenol oxidase activity was strongly and noncompetitively inhibited by the "Perov mixture" of coal tar components and by pyridine alone, while phenol competitively inhibited the enzyme. These two inhibitors are structural components of the parkinsonogenic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). By extension, dopamine and neuromelanin synthesis in the brain may be influenced by the inhibitory effects of such compounds upon the copper-dependent steps of tyrosine metabolism. The non-animal model used in this study may represent an alternative to the use of animal tissues in neurodegenerative disease research.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Parenteral domoic acid impairs spatial learning in mice.

The present study is the first to examine the effect of a single intraperitoneal injection of the neuroexcitotoxin domoic acid on learning in mice. Compared to saline controls, animals exposed to domoic acid (2.0 mg/kg) showed significant impairment on the acquisition of the place task in the Morris water maze. Observation of swim paths taken by mice searching for the underwater platform revealed a failure on the part of the domoic acid-exposed mice to select the appropriate problem solving strategies. The results, along with neuroanatomic work done here and elsewhere, suggest that impairment of acquisition and retention of this spatial navigation task by domoic acid, involves a neuropathology that includes not only the hippocampus, but other limbic, and possibly extralimbic brain regions.

Animals↗
PubMed1992

Effects of excitotoxins on free radical indices in mouse brain.

Excitotoxins and free radicals individually have been implicated in several neurological disorders including those associated with aging. We observed that systemically administered domoic acid enhanced mouse brain superoxide dismutase activity with either an associated decrease or no change in mouse brain lipid peroxidation. These findings reflect a state of adequately compensated oxidative stress induced by excitotoxins. In homogenates containing disrupted cells from various regions of mouse brain, however, kainic acid produced a 2 to 5-fold increase in lipid peroxidation. This suggests that excitotoxins cause lipid peroxidation possibly by acting at intracellular loci which become more accessible following disruption of cells in vitro and by extrapolation, possibly in vivo due to cellular permeability changes during the edematous stage of ischemic and other related neuropathological conditions.

Animals↗
PubMed1991

Global elevation of brain superoxide dismutase activity following forebrain ischemia in rat.

Regional superoxide dismutase (SOD) activity and lipid peroxidation (as reflected by thiobarbituric acid-reactive substances (TBARS)) have been measured at increasing post-ischemic time intervals following a (10 min) forebrain ischemic insult in rat. All brain regions showed significant progressive increases in SOD activity with increasing post-ischemic time intervals. Lipid peroxidation also was significantly increased in frontal and parietal/occipital regions at 1 and 24 h post-ischemia, although this was several orders of magnitude less than the increase in SOD activity. By 7 days post-ischemia lipid peroxidation had returned to control values for all regions. These data are consistent with the hypothesis that cerebral ischemia is accompanied by glial activation with an associated increase in SOD activity. Global increases in SOD activity may protect the brain from free radicals, thereby preventing large increases in lipid peroxidation.

Animals↗
PubMed1991

Circumventricular organ origin of domoic acid-induced neuropathology and toxicology.

The neuroexcitotoxin, domoic acid, was responsible for an episode of mussel poisoning in Eastern Canada in 1987. Severe neurologic impairment and some deaths occurred. We have characterized the nature of domoate-induced neuropathology in the mouse brain. Domoic acid was administered intraperitoneally at doses of 2, 3 or 7 mg/kg to Swiss-Webster mice. Brains were examined at 0.5, 1, 24, 48 or 72 h postinjection for evidence of damage. Significant pathologic changes occurred only after the largest dose of domoic acid. Damage was confined to circumventricular organs lacking a blood-brain barrier and their environs, including the organon vasculosum of the lamina terminalis, subfornical organ, mediobasal hypothalamus and area postrema. The neural damage induced by domoic acid was evident at as early as 30 min after injection and increased by 60 min postinjection. The loci of domoic acid-induced neuropathological changes accounts for several central and peripheral effects and toxicities observed following systemic domoate treatment, these included gastroduodenal lesions, hypodipsia, analgesia, and blood pressure fluctuations.

Animals↗
PubMed1990

Effects of metkephamid (LY127623), a selective delta opioid receptor agonist, on gastric function.

Metkephamid, a delta opioid receptor agonist, blocked cold-restraint stress ulcers, reduced absolute ethanol-induced gastric ulcers and, at the lowest and highest doses examined, reduced basal gastric acid secretion in conscious rats, all to a significant degree. The dose effects on stress ulcer formation parallel those seen against maximal electroshock seizures and suggest that both central as well as peripheral delta opioid receptors mediate gastrointestinal responses to stress.

Animals↗
PubMed1990

Domoic acid-induced neurovisceral toxic syndrome: characterization of an animal model and putative antidotes.

A rodent model of neurovisceral toxic syndrome induced by the neuroexcitant amino acid, domoic acid, is described, along with the activity of a putative antidote, the nonselective excitotoxin antagonist, kynurenic acid. Both an extract of contaminated mussels and pure domoic acid induced a characteristic syndrome including: sluggishness, scratching stereotypy, convulsions and death. Autopsy revealed gastric and duodenal lesions and peritoneal ascites. Kynurenic acid significantly obtunded these behavioral and physiological effects, particularly when given 60-75 min after the toxic insult. Probenecid, a blocker of organic acid transport, and tryptophan, a precursor of endogenous brain kynurenic acid, increased the time frame in which kynurenic acid exerted its protective effects. Kynurenic acid alone, in nontoxin-challenged animals significantly blocked cold-stress gastric lesions, significantly reduced basal gastric acid secretion and was protective to a lesser degree against ethanol-induced gastric mucosal injury. The murine model of domoate toxicity represents an inexpensive, reliable and sensitive biological assay for screening commercial shellfish for excitotoxin contamination. We are currently exploring kynurenic acid and other compounds for possible therapeutic use in both current and any future victims of neuroexcitant amino acid toxicosis.

Animals↗
PubMed1990

The effects of naloxone on the changes in breathing and behaviour induced by morphine in the foetal sheep.

In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.

Animals↗
PubMed1990

Gastrointestinal effects of contaminated mussels and putative antidotes thereof.

A recent outbreak of amnesic shellfish poisoning (ASP) in Atlantic Canada was characterized by severe gastrointestinal and central nervous system pathology. We examined the gastrointestinal effects of an acidic extract of blue mussels contaminated with domoic acid, the suspected toxin responsible for the ASP. We also tested the gastric effects pure domoic acid as well as a putative antagonist of neuroexcitant amino acid receptors, kynurenic acid. Mussel extract produced gastric (antral) ulcers, duodenal ulcers, gastric and duodenal hyperemia and bleeding, as well as peritoneal ascites. Kynurenic acid protected significantly against extract-induced gastropathy, particularly when given 60 or 75 minutes after extract. Pure domoic acid resulted in fatalities in all infant mice tested. These animals exhibited gastric bleeding and hemorrhage, especially at the higher doses employed. In otherwise untreated rats, kynurenic acid exerted significant anti-stress ulcer and anti-gastric secretory effects, but was less effective at blocking ethanol-induced gastric lesions. We suggest that there may be both peripheral as well as central effects of kynurenic acid in modulating normal and pathological gastric function.

Animals↗
PubMed1990

Sensitive murine model and putative antidotes for behaviorial toxicosis from contaminated mussel extracts.

The recent outbreak of "amnesic" mussel poisoning syndrome, attributed to domoic acid contamination of edible mussels claimed several lives and left many victims impaired with a peculiar loss of memory. We administered the whole mussel extract (WMX) and the mussel hepatopancreas extract (MHX, hepatopancreas being the major site for sequestration of domoic acid in mussels) in Swiss-Webster mice. A characteristic syndrome featuring sluggishness, scratching stereotypy, convulsions and death was noticed. Infant mice were some 3- to 4-fold more sensitive to the WMX toxicity. Kynurenic acid (KYN), an endogenous nonselective excitotoxin antagonist offered significant protection against the toxicosis after its onset had been provoked by the mussel extract. This observation emphasizes the feasibility of using KYN or related compounds in the therapy of poisoning from excitotoxins. As a logical extension of this possibility we examined the possibility that endogenous KYN could be exploited for similar protection against domoate toxicosis in our murine model. The time frame during which KYN was protective was increased by probenecid, a blocker of organic acid transport and by tryptophan, a precursor of endogenous KYN. We examined also the classical anticonvulsants phenytoin and ethosuximide, as well as dextromethorphan at its excitotoxin antagonistic dose. The infant mouse model of domoate-toxicity holds promise for being developed into a rapid, sensitive, reliable and inexpensive biological assay for screening commercial batches of mussel for excitotoxin contamination. Kynurenic acid and dextromethorphan should be further examined as antidotes for possible therapeutic use in existing victims and in the treatment of future domoate toxicosis occurring here or elsewhere.

Age Factors↗
PubMed1989

Biological and methodological implications of prostaglandin involvement in mouse brain lipid peroxidation measurements.

Enhanced cyclooxygenase-mediated prostaglandin (PG) turnover occurring during sacrifice and biochemical processing of tissues also generates malondialdehyde (MDA), a product of lipid peroxidation (LPO). Studies reporting on LPO estimated by thiobarbituric acid reactive substances (TBARS) have failed to consider such artefactual increases. This study reports the relative proportion of PG metabolism-derived MDA (PG-MDA) in mouse brain regions during the TBARS assay. The cyclooxygenase inhibitor indomethacin significantly lowered MDA in fronto-parietal cortex and corpus striatum. Indomethacin (50-800 micrograms/ml, in vitro) increased estimated TBARS in whole brain. Such enhancement was absent when indomethacin (20-80 micrograms/sample) was added to the MDA standard curve, reflecting its interaction with TBARS other than MDA. PG-MDA contributes as much as 15% to the total estimated value of MDA in fronto-parietal cortex and corpus striatum and must be corrected for in LPO studies.

Animals↗