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Biomedical subjects

C Pinsky

Publications and source records attributed to C Pinsky.

At least 37 records · Page 2Linked to original sources
PubMed1989

Neurotoxicity and lethality of toxic extracts from Atlantic coast shellfish.

1. HCl-extract of poisonous shellfish was injected i.p. into Swiss-Webster mice. 2. Behavioral effects (sluggishness, scratching, huddling, clonic convulsions, respiratory distress and mortality) were noted. 3. Infant mice were more sensitive than were the adults to XTRT toxicity. Estimated LD50 values were; adult: 34.8 ml/kg i.p., infant: 9.6 ml/kg i.p. 4. The mouse model of shellfish-toxicity offers the advantages of a degree of similarity with the human clinical situation and a rapid time course for screening antagonists against shellfish poisoning.

Aging↗
PubMed1989

Kynurenic acid protects against gastroduodenal ulceration in mice injected with extracts from poisonous Atlantic shellfish.

1. Mice were treated with an extract prepared from poisonous Atlantic mussels. 2. Gastric and duodenal ulcers, duodenal hyperemia and peritoneal ascites resulted from administration of the shellfish extract, with an LD84 of 1.0 ml. 3. Kynurenic acid, an antagonist at excitatory amino acid receptors, protected significantly against gastroduodenal ulcers, ascites and hyperemia when given at 60 or 75 min post-extract. 4. It is likely that the gastrointestinal damage evoked by this extract is due to its domoic acid content and that kynurenic acid may prove useful against domoic acid-induced gastropathy.

Animals↗
PubMed1989

Kynurenic acid protects against neurotoxicity and lethality of toxic extracts from contaminated Atlantic coast mussels.

1. An aqueous acidic extract from poisonous Atlantic coast mussels was injected i.p. into groups of Swiss-Webster mice at the LD84 value (= 40 ml of extract/kg). Body-scratching, clonic convulsions and death were consistently observed in response to XTRT injection. These results are consistent with the presumed presence of the neuroexcitant amino acid, domoic acid, in the contaminated mussels. 2. Kynurenic acid at 300 and 600 mg/kg i.p. protected powerfully and significantly against extract-induced neurotoxicity. Greatest protection was observed when the antidote was administered between 30 and 90 min after injection of the toxic extract.

Animals↗
PubMed1989

Kynurenic acid attenuates experimental ulcer formation and basal gastric acid secretion in rats.

Kynurenic acid is a broad spectrum antagonist at neuroexcitant amino acid receptors in the mammalian brain. Preliminary data indicated that kynurenic acid attenuates domoic acid-induced central nervous system pathology, lethality and gastrointestinal pathology. We now show that kynurenic acid significantly blocks restraint-cold stress ulcers, ethanol ulcers and basal, non-stimulated gastric acid secretion in normal rats not subjected to neurotoxin challenge. There may be peripheral actions, in addition to the central effects of kynurenic acid, in modulating normal and pathological gastric function.

Animals↗
PubMed1988

Randomized trial of combined modality therapy with and without thymosin fraction V in the treatment of small cell lung cancer.

A randomized trial of thymosin fraction V (60 mg/m2 s.c. twice weekly) given during induction chemotherapy and radiation therapy was performed in 91 patients with small cell carcinoma of the lung. Induction chemotherapy consisted of four cycles of an alternating combination of drugs (cyclophosphamide/Adriamycin/vincristine and cisplatin/etoposide). Radiation to the primary complex was given to patients with limited disease. All patients received prophylactic cranial irradiation. There were 35 patients with limited disease (18 randomized to thymosin and 17 to no thymosin) and 56 with extensive disease (28 thymosin and 28 no thymosin). Pretreatment immunological parameters were comparable between the two groups. For limited disease patients the overall response rate was 100%, including 66% (21 of 32) complete responders. The median duration of response was 19 mo (range, 5-57 mo) and survival 21 mo (range, 4 days to 57 mo). The 3-yr survival was 32%. For ED patients the overall response rate was 95% with 29% (13 of 48) complete. The median duration of response was 10 mo and the median duration of survival 12 mo with 13% alive at 2 yr. A comparison of the thymosin-versus no thymosin-treated patients revealed no difference in response rate, response duration, or survival whether analyzed as a whole or by extent of disease. An analysis based on pretreatment immune function and total white blood cell and absolute lymphocyte count revealed no difference in the survival distributions. No differences in the pattern of toxicity were observed between the thymosin- versus no thymosin-treated patients. The addition of thymosin fraction V during induction chemotherapy and consolidation radiotherapy did not alter outcome.

Carcinoma, Small Cell↗
PubMed1988

Effects of 4-acetylpyridine on stress ulcer formation in mice.

4-Acetylpyridine, earlier reported by us to be an anticonvulsant, offers long-lasting protection after a single administration against hypothermic restraint stress-induced gastric ulceration in mice. Electroshock convulsions, marginally but not significantly protective against such ulcers themselves, when coupled with 4-acetylpyridine administration fully prevented gastric ulcers from occurring in this murine model of experimentally induced stress.

Animals↗
PubMed1988

Pyridine and other coal tar constituents as free radical-generating environmental neurotoxicants.

We have tested the hypothesis that chronic exposure to the principal constituents of the aqueous fraction of coal tar extracts can lead to the in vivo formation of substances which may produce neurological damage as the result of free radical generation and lipid peroxidation, these may be involved in the etiology of some neurological disorders. Artificial mixtures of the aqueous fraction of coal tar extracts were given in low concentrations to pigmented mice in their drinking water over a 3-month period. This resulted in significant increases in lipid peroxidation in the striatum, cerebellum and liver of the mice under test, the rank order being striatum greater than cerebellum greater than liver. These results are compatible with the possibility that coal tar emissions (as would be recovered or liberated in the burning, refining or beneficiation of coal) constitute a potential source of neurotoxicants with a predilection for damaging the nigrostriatal neuronal pathway. Our observations may thus have identified an important and hitherto unsuspected environmental source of neurotoxic chemicals, a possibility consistent with the proposed involvement of an environmental chemical factor in Parkinson's disease and perhaps in other neurological disorders.

Animals↗
PubMed1988

Effect of morphine on breathing and behavior in fetal sheep.

To define the dose response of apnea and breathing to morphine we studied 12 fetuses at 116-141 days of gestation using our window technique. We instrumented the fetus to record electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (integral of EMGdi), heart rate, carotid blood pressure, and amniotic pressure. Saline and morphine in doses of 0.03, 0.1, 0.5, 1, and 3 mg/kg were injected in random order in the jugular vein of the fetus during low-voltage ECoG. Fetuses were videotaped for evaluation of fetal behavior. We found 1) that saline did not elicit a response; 2) apnea, associated with a change from low- to high-voltage ECoG, increased from 2.2 +/- 1.5 (SE) min in two fetuses at a dose of 0.03 mg to 20 +/- 6.3 min in seven fetuses at 3 mg/kg (P less than 0.005); 3) the length of the breathing responses, associated with a change from high- to low-voltage ECoG, were 15 +/- 1.8 and 135.9 +/- 18.1 min (P less than 0.0005); 4) integral of EMGdi X frequency, an index equivalent to minute ventilation, increased from 1,763 +/- 317 arbitrary units to 10,658 +/- 1,843 at 1.0 mg/kg and then decreased to 7,997 +/- 1,335 at 3.0 mg/kg. These changes were related to a steady increase in integral of EMGdi, whereas frequency decreased at 3 mg/kg. There was an increase in breathing response to morphine plasma concentrations or morphine doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

L-deprenyl attenuates stress ulcer formation in rats.

Both intraperitoneal and intracerebroventricular (i.c.v.) administration of the monoamine oxidase-B inhibitor L-deprenyl markedly attenuated restraint stress-induced gastric ulcers in rats. L-Deprenyl given i.c.v. attenuated stress ulcers in microgram doses and virtually abolished ulcer formation at a dose of 2.0 micrograms. These data suggest that intact or augmented central dopaminergic function may be an essential component of gastric mucosal protection.

Animals↗
PubMed1986

Mu- and delta-opioid modulation of electrically-induced epileptic seizures in mice.

Graded seizure responses to suprathreshold cerebral electroshock in mice were modified by drugs acting at mu- and at delta-opioid receptors. Morphine exerts a proconvulsant effect at a non-mu opioid receptor and may exert a simultaneous anticonvulsant effect at a mu-opioid receptor. Delta-opioid receptor blockade increases seizure severity, suggesting a predominantly anticonvulsant nature of the delta-opioid system in the seizure model tested here.

Animals↗
PubMed1986

The BRMP IL-2 reference reagent.

The BRMP has established an interim IL 2 Reference Reagent. Unitage was assigned after a collaborative, 7 laboratory study. The standard has been distributed to over 350 investigators to date.

Indicators and Reagents↗
PubMed1985

Increased survival with high-dose multifield radiotherapy and intensive chemotherapy in limited small cell carcinoma of the lung.

From June 1979 through April 1982, we treated 35 patients with limited small cell carcinoma on an intensive chemo-radio-immunotherapy regimen, consisting of induction with cyclophosphamide, doxorubicin, and vincristine, alternately cycled with VP-16 and cisplatin. Patients were stratified by performance status and randomized to thymosin, fraction V, or no thymosin. Induction was followed by consolidation, consisting of prophylactic whole-brain radiotherapy and multifield radiotherapy to the primary and mediastinum with cyclophosphamide and vincristine. Patients who were complete responders (CRs) postconsolidation resumed maintenance immediately. Patients were followed from 1 to 3.8 years (median, 2.2 years) at the time of analysis. After induction, 35% (12/34) had become CRs; after consolidation radiotherapy, an additional 10/34 became CRs for a total CR rate of 65% (22/34). There were only 9/34 local failures (26%), of which all but one were impatients who had not become CRs. A prolonged median survival (21 months) has been obtained in patients with limited small cell carcinoma of lung treated with an intensive combined modality regimen. At 1 year, survival is 83%; at 2 years, 46%. There is a 33% long-term survival (greater than 3 years). There is no difference in survival or recurrence rate between patients treated with or without thymosin.

Adult↗
PubMed1985

Peptidases that terminate the action of enkephalins. Consideration of physiological importance for amino-, carboxy-, endo-, and pseudoenkephalinase.

The term "enkephalinase" has been frequently applied to enzyme activity in a variety of tissue preparations. In some cases there has been the implication that cleavage of a specific peptide bond in the enkephalin molecule results from the action of a single enzyme with the major responsibility of inactivating synaptic enkephalin. It is not known to what extent diverse enkephalin-degrading enzymes, with differing peptide bond specificities, may act in concert at any given synapse. There do exist, however, enzymes having known characteristic specificities with respect both to peptide substrates, including enkephalins, and to identifiable peptide bonds. Thus, at any given site of enkephalin release there probably resides a characteristic assembly of peptidases concerned with inactivation of this neuromediator. We propose that the term "enkephalinase" be used to encompass the entire family of enkephalin-degrading enzymes, and that "aminoenkephalinase", "carboxyenkephalinase", "endoenkephalinase" and "pseudoenkephalinase" should designate enzymes of known specificities with respect to both peptide substrates and particular peptide bonds.

Aminopeptidases↗
PubMed1985

Mu- and delta-opioid receptor-mediated epileptoid responses in morphine-dependent and non-dependent rats.

In 3 different models of opioid epileptogenesis we have utilized opioid receptor antagonists to differentiate the nature and role of opioid receptor subtypes involved in opioid agonist-induced epileptoid responses in rats. Selective mu-opioid receptor agonism can initiate epileptoid responses in non-dependent rats. Delta-opioid agonism is important in sustaining mu-initiated epileptoid responses. A role for mu-opioid receptor stimulation in delta-opioid initiated epileptoid responses remains yet to be clarified. Delta-opioid antagonism does not precipitate classic autonomic and behavioral signs of withdrawal in morphine-dependent rats but blocks epileptoid responses in naloxone-precipitated morphine withdrawal without affecting autonomic and behavioral components of an ongoing withdrawal reaction.

Animals↗
PubMed1985

delta-Opioid modulation of striatal dopaminergic activity in mice.

Mu- and delta-opioid subtype receptor antagonists were tested in the mouse for their effects on vertical climbing activity, an index of striatal dopaminergic activity. The selective delta-opioid antagonist ICI 154 129 (I/l) by itself enhanced vertical climbing activity in a dose-related manner, whereas the mu-opioid antagonist naloxone by itself was inactive on climbing behavior. Naloxone increased the climbing-stimulant effect of I/l. Unstimulated vertical climbing activity was reduced, and all opioid-antagonist enhancement of climbing behavior was antagonized, by the competitive dopamine antagonist haloperidol in dose-related fashion. The observed motor-enhancement effect of a selective delta-opioid receptor antagonist is the first demonstration of physiologically-significant tonic activity on a central opioid receptor. Our observations suggest that I/l may be useful clinically in striatal dopamine-deficient disease conditions such as parkinsonism.

Animals↗
PubMed1985

Dynamic studies of positron-emitting putative tumor marker 132Cs in mice show differential tumor and regional uptake.

Positron-emitting 132Cs (t1/2 = 6.47 days) was generated from stable 133CsCl via the 133Cs (p,pn) 132Cs reaction. BALB/c mice, bearing implanted MT296 mammary tumors, were given 4.6 mEq kg-1 of 132CsCl via a single intraperitoneal injection. Postinjection uptake of 132Cs into body regions was monitored in vivo with external detectors. Positron emission from the tumor region was continuously greater than that from the head, the numerical ratio of mean emission intensities being fourfold at 10 min postinjection. Tissues excised from these mice postmortem showed sequence of relative tissue cesium uptake rates to be kidney 1.8, small intestine 1.7, tumor 1.0, skin 0.75, liver 0.75, skeletal muscle 0.4, and brain 0.28. Comparative studies with multiple injections of stable cesium and rubidium showed this sequence to be ion-specific. These observations suggest that positron-emitting isotopes of cesium could provide useful markers for tumors of several tissues.

Animals↗
PubMed1984

Central depressant action of cesium in mice.

Cesium chloride (CsCl) at several dose levels (1.25-20.0 mEq/kg IP) was administered acutely to albino mice whose behavior was compared with that in corresponding saline controls. Motor activity decreased and Straub tail occurred in a dose-related manner. Signs of autonomic disturbance, diarrhea, and salivation were seen with toxic doses. Subchronic administration of CsCl (5.0 mEq/kg/day IP for 7 days) exerted a phenothiazine-like effect in mice, reducing amphetamine-induced aggregation toxicity and enhancing pentobarbital-induced hypnosis. The antinociceptive action of morphine was unaltered by identical multiple administrations of CsCl. These results indicate a specific neurosuppressant action of CsCl on mouse CNS and suggest exploration of this alkali earth metal for antipsychotic-like activity.

Amphetamine↗