PubMed Health⌕ Search

Biomedical subjects

C Pinsky

Publications and source records attributed to C Pinsky.

At least 55 records · Page 3Linked to original sources
PubMed1984

Pharmacological and toxicological investigations of cesium.

Cesium, a mineral resource abundantly present in Manitoba with important existing and potential industrial applications was investigated to study its effects on biological systems. Several rodent models of pharmacological activities were utilized. The profile that emerged indicated that cesium is only moderately toxic and exerts salubrious effects which could be gainfully investigated for application in the treatment of certain psychological disorders and some tumors. Its conjunction with existing pharmacological agents for these two types of disorders could yield a pharmacologically active yet less toxic therapeutic combination.

Animals↗
PubMed1983

Newer concepts of analgesia and anesthesia.

Intracerebroventricular (ICV) administration of the peptidase inhibitors amastatin, trasylol, bacitracin, or phe-D-ala and systemic administration of phenylmethylsulfonyl fluoride resulted in one or more of the following responses: analgesia, reduced withdrawal severity in opiate tolerant rats, alterations in motor activity and behavior, hypo- and hyperthermia and others; some of these effects were antagonized by naloxone, suggesting participation of opioid and other endogenous peptides. In addition, peptidase inhibitors enhanced analgesic and other responses to opioid peptides given ICV. Peptidase inhibition affords another method of inducing selective pharmacological responses such as pain relief in individuals resistant to other forms of therapy. ICV administration of beta-endorphin in the rat induces general anesthesia that is instantly reversed by systemic naloxone. Extensions of this work include identification of specific neural pathways that mediate anesthesia and characterization of opiate receptor subtype(s) at these sensitive loci. This approach offers the potential for the design of systemically effective opioid peptide anesthetics with little or no secondary effects and rapid reversibility.

Analgesia↗
PubMed1983

Cesium attenuates conditioned avoidance response in rats and mice.

The pole-climbing conditioned avoidance response (CAR) was attenuated in rats after four once-daily injections of CsCl intraperitoneally at 3.0 mEq kg-1 and in mice after seven such injections at 5.0 mEq kg-1. Suppression of CAR increased with increasing numbers of injections. Treatment with cesium did not attenuate the unconditioned pole-climbing escape response to mild footshock. The cesium effect on CAR resembles that of antidopaminergic phenothiazine like agents, in concordance with our earlier studies which showed cesium potentiation of pentobarbital sleeping time and antagonism of amphetamine toxicity.

Animals↗
PubMed1982

Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

Animals↗
PubMed1982

Hyperactivity versus explosive motor behavior induced by opioids in the rat. Mechanisms elucidated with enkephalin-tyrosine-o-sulfate and morphine congeners.

A relatively mild hyperactive state (HAS), characterized by agitation and hypermotility, is induced by opiate drugs and opioid peptides in general and is blocked by naloxone. HAS can be distinguished from the profound hyperresponsiveness of an explosive motor behavior (EMB). Sulfation of the phenolic moiety in morphine or in methionine enkephalin essentially abolishes opiate receptor binding activity. The sulfated peptide lacks detectable pharmacological activity in the rat, whereas sulfated morphine is several hundred-fold more potent than morphine in eliciting (EMB). Thus, EMB is elicited only by congeners of morphine having appropriate hydrophilic substitution at C-6 and which is mediated through a receptor that is insensitive to naloxone.

Animals↗
PubMed1980

Antibody responses to mycobacterial antigens in patients immunized with BCG for the treatment of neoplastic disease.

Precipitin and agglutination antibody response to antigens of Mycobacterium tuberculosis was measured in 43 patients with neoplastic disease who were treated with weekly BCG or intratumor BCG vaccination. Resuspended freeze-dried Tice vaccine was shown to contain soluble mycobacterial antigens. Fourteen patients receiving weekly BCG vaccination developed intense precipitin and agglutination antibody response over the course of several months. Twenty-nine patients receiving intratumor and oral vaccination developed less intense antibody response. Twenty-one of 28 purified protein derivative (PPD)-negative patients converted their PPD. No correlation between antibody, PPD response and antitumor effect could be identified. The importance of identifying the soluble antigen in BCG and of defining the humoral response to purified antigens is discussed.

Agglutination Tests↗
PubMed1980

Primary hepatocellular carcinoma with hepatitis B antigenemia: effects of chemotherapy.

Eight patients with primary hepatocellular carcinoma (PHC) whose blood was positive for hepatitis B surface antigen (HBsAg) received treatment with cyclophosphamide, adriamycin, and 5-fluorouracil. In 4 cases, a rise in serum HBsAg titer occurred after chemotherapy. In 2 cases involving drug-related leukopenia, the rise in HBsAg titer was marked and associated with a sharp rise in the serum transaminase level (SGOT), up to 1700 in 1 case. Lower-dosage chemotherapy was safely resumed after SGOT had returned to pretreatment levels. No evidence of immunodeficiency after chemotherapy was revealed by in vitro testing of lymphocyte and granulocyte function, percentage of circulating T-cells, and immunoglobulin and complement levels. All 8 cases were negative for e antigen (eAg) and 4 were anti-positive. In 3 of 4 cases, anti-e became negative after chemotherapy, but all remained eAg negative. The negative eAg tests in these cases of PHC suggest they are not highly infectious, in spite of increased HBsAg titers in blood following chemotherapy.

Adult↗
PubMed1980

Effects of morphine and naloxone on the K+-stimulated release of methionine-enkephalin from slices of rat corpus striatum.

Methionine-enkephalin (ME) released from superfused slices of rat corpus striatum was estimated by radioimmunoassay (RIA). The basal release of 2.5 +/- 0.2 pmol/g/min (0.15% of content per min) was increased approximately 3-fold upon exposure of tissue to 30 mM K+ for 5 min. This increase in release was not observed in the absence of Ca2+. Both morphine (10(-5) M) and (-)-naloxone (10(-5) and 10(-6) M) significantly depressed the release of ME evoked by 30 mM K+ did not alter basal release. The (+)-isomer of naloxone, which lacks opiate antagonist activity, did not affect basal or evoked release. A consistent depression of release was not observed when 47 mM K+ was used to evoke the release of ME. The issue of whether a feedback mechanism controls the release of ME from the striatum cannot be resolved until it is known whether the effect of morphine and naloxone on ME release are mediated by opiate or non-opiate mechanisms.

Animals↗
PubMed1980

beta-Endorphin induces general anaesthesia by an interaction with opiate receptors.

beta-endorphin, administered into the cerebral ventricles of rats, provokes a sequence of behavioural and electroencephalographic (EEG) responses similar to those observed with general anaesthetics used clinically. Initial behavioural and EEG excitation, motor incoordination and exaggerated responsiveness to sensory stimuli are followed by a stage of rigid immobility with maintenance of local reflexes (withdrawal, corneal) and EEG arousal in response to stimulation. Finally, there is immobility associated with both EEG and behavioural unresponsiveness to severely noxious stimuli. Such a state of unconsciousness with complete analgesia defines general anaesthesia. This state was completely and rapidly reversed by the specific opiate antagonist, naloxone. The induction of general anaesthesia by a water-soluble neurohormonal peptide acting at specific receptor sites has important implications for traditional theories of anaesthesia.

Anesthesia, General↗
PubMed1979

Morphine derivatives with diminished opiate receptor potency show enhanced central excitatory activity.

Central excitatory potency of morphine administered by cerebroventricular infusion in enhanced in derivatives substituted at the 3-position (phenolic group) and/or 6-position (alcoholic group). Morphine-3-glucuronide is several hundred times more potent than morphine in evoking dose-related hyperactive motor behavior which can progress to lethal convulsions. Excitatory potencies in decreasing order are: (1) 3-glucuronide; (2) 3-SO4; (3) 3-OAc, 6-OAc (heroin); (4) 6-OAc; (5) 3-OAc; (6) 3-OH, 6-OH (morphine); (7) 3-OCH3 (codeine); (8) 3-OCH3, 6-OCH3 (thebaine). Levorphanol, lacking a 6-OH group, is devoid of excitatory actions. In this series of substituted morphines, there is an inverse relationship between opiate receptor binding potency and central excitatory potency, but codeine and thebaine behave anomalously. These findings are compatible with the hypothesis that morphine acts upon a species of receptor which mediates behavioral and EEG excitation and is distinct from the recognized opiate receptor mediating sedation and analgesia.

Animals↗
PubMed1979

Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly.

Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates.

Aggression↗
PubMed1979

The effect of morphine on human neuromuscular transmission.

By utilizing high frequency nerve stimulation, we observed the effects of morphine sulphate, 0.5 mg.kg-1 on human neuromuscular transmission. Tetanic fade at 50, 100 and 200 hz did not change during the one hour period after infusion of morphine. Post-tetanic depression (PTD) of single twitch response increased progressively with time over the one-hour study period. This was most marked with the 100 and 200 hz tetanic frequencies. In contrast, control subjects displayed either no change, or a slight increase (post-tetanic facilitation; PTF), over a similar one-hour test period. We believe these results are best explained by a presynaptic action of morphine, whereby intraterminal mobilization of acetylcholine is impaired by the opiate narcotic drug.

Acetylcholine↗
PubMed1978

Opiate properties of SKF 525A.

SKF 525A, a classical inhibitor of microsomal drug-metabolizing enzymes, is structurally similar to the diphenylpropylamine analgesics, and certain reported effects in animals resemble those produced by opiate drugs. In an opiate radioreceptor assay, SKF 525A was 50 times less potent than methadone in the absence of sodium and 10 times less potent in the prescence of sodium. The nature of the sodium effect indicates SKF 525A to have less opiate agonist character than does methadone. In mice, 2 mg of SKF 525A given intraperitoneally induced less profound analgesia on a hot plate (44 degrees C) than did 0.1 mg of methadone. Analgesia by SKF 525A was prevented by pretreatment of the mice with naloxone. In rats, 50 microgram of SKF 525A given intracerebroventricularly was analgesic.

Analgesia↗
PubMed1978

Opiate-like naloxone-reversible effects of androsterone sulfate in rats.

Androsterone sulfate (5alpha-androstan-3alpha-ol-17-one, 3-sodium sulfate) administered to freely moving rats via cerebroventricular cannulae induced analgesia, wet-dog shakes, body jerks, rigidity, Straub tail, hypermotility, excessive grooming, hyperreactivity to stimuli, aggression, escape behavior, EEG spiking, and behavioral and EEG seizures. These responses resemble those produced by certain opiate drugs and by beta-endorphin, an endogenous peptide; they appear during the 5-min infusion period, persist in some cases for several hours, and are diminished by pretreatment with the narcotic antagonist naloxone. These findings indicate that steroid hormones can act upon at least some of the same central pathways influenced by recognized opiate compounds.

Androsterone↗