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Biomedical subjects

L Shuster

Publications and source records attributed to L Shuster.

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

Cocaine-induced changes in perfusion pressure and bile flow in perfused rat livers.

Cocaine produces hepatotoxicity. To study the acute effect of cocaine on the liver, we used the isolated, single-pass perfused rat liver. When perfusion pressure was measured in a constant flow system, a 15-min infusion of cocaine (1.47 mM) increased perfusion pressure (136 +/- 15%), decreased bile flow (61 +/- 5%), and decreased oxygen uptake (82 +/- 5%). The vasoconstriction was concentration-dependent and reversible. The pressure increase elicited by cocaine was not inhibited by the alpha-receptor antagonists phentolamine, prazosin, or yohimbine. These antagonists did inhibit phenylephrine-induced increases in perfusion pressure. Neither serotonin at concentrations up to 1 mM nor lidocaine or procaine in concentrations equimolar to cocaine increased the perfusion pressure. Indomethacin (5 microM), SKF-525A, and chloramphenicol also failed to block vasoconstriction induced by cocaine. High concentrations of cocaine were cholestatic, while concentrations lower than 0.6 mM were choleretic. These results indicate that cocaine-induced vasoconstriction in the liver is not mediated by alpha-receptor activation or prostaglandins and does not require metabolic activation of cocaine. The acute effects of cocaine in the perfused liver are vascular (vasoconstriction) and functional (alteration in bile formation).

Anesthetics, Local↗
PubMed1989

Effect of naltrexone on relaxation induced by flank pressure in pigs.

Twenty, 6 to 9 kg Yorkshire piglets were used in 2 trials. Ten piglets received an IM injection of naltrexone at a dose of 1 to 1.3 mg/kg. Ten control pigs received saline. Blind behavioral testing in a "squeeze chute" was conducted 40 minutes after injection. The "squeeze chute" consists of two padded plywood panels hinged on a base to form a V. Each pig was squeezed for 60 seconds. After release, each pig remained in the padded V for 10 minutes. There was sufficient room for the pigs to walk a few steps. Both naltrexone- and saline-treated pigs eventually crouched down in the chute and relaxed against the padded sides of the V. Naltrexone-pretreated pigs had a longer latency to achieve relaxation--311.8 +/- 47.8 seconds vs. 161.8 +/- 30.38 seconds (SE) (p less than 0.02). Each stage of relaxation at induction was rated on a 1-4 scale (1 = squealing and jumping, 4 = relaxed quietly). Naltrexone-treated pigs had significantly lower relaxation ratings than saline-treated pigs (1.90 vs. 3.20) (p less than 0.01). Treatment had no effect on the final degree of relaxation. Naltrexone partially blocked the relaxation response.

Animals↗
PubMed1988

Use of narcotic antagonists to modify stereotypic self-licking, self-chewing, and scratching behavior in dogs.

We evaluated 2 narcotic antagonists, naltrexone and nalmefene, for treatment of refractory self-licking, self-chewing, and scratching behavior in dogs. Eleven dogs with various irritative or pruritic disorders were medicated with naltrexone (1 mg/kg of body weight, sc) or nalmefene (1 to 4 mg/kg, sc), after a period of control observation during which the dogs had not been medicated. The time for which the dogs were involved in self-licking, self-chewing, or scratching was determined retrospectively by analysis of videotapes. The rates of involvement in either activity before and after treatment were calculated and compared statistically. Treatment with a narcotic antagonist significantly reduced the time spent self-licking, self-chewing, or scratching in 7 of 11 dogs, was partially effective in 3 dogs, and was ineffective in one dog. Dogs with acral lick dermatitis responded most to treatment.

Animals↗
PubMed1988

Use of a narcotic antagonist (nalmefene) to suppress self-mutilative behavior in a stallion.

Nalmefene, an opioid antagonist, caused a decrease in self-mutilative behavior in a 500-kg stallion. Self-mutilative attempts were counted during a control period and on 4 subsequent occasions after the IM administration of 100 mg, 200 mg, 400 mg, or 800 mg of nalmefene. The frequency of self-mutilation decreased with increasing doses of nalmefene and was virtually abolished with the 800-mg dose.

Animals↗
PubMed1988

Analgesia in defeated mice: evidence for mediation via central rather than pituitary or adrenal endogenous opioid peptides.

Mice subjected to defeat in a social conflict paradigm display an analgesic response that is apparently mediated by endogenous opioids. It is blocked by naloxone and shows full cross-tolerance to and from morphine. The present study investigated the contribution of sources of endogenous opioids outside of the central nervous system, namely the pituitary and adrenal glands. Treatment known to enhance (metyrapone pretreatment), reduce (2% saline in the drinking water) or block (dexamethasone pretreatment) the release of beta-endorphin from the anterior pituitary did not affect the display of analgesia in defeated mice. Similarly, treatments known to enhance (reserpine pretreatment) or block release of enkephalins (removal of the adrenals or hexamethonium pretreatment) from the adrenal medulla also failed to influence defeat-induced analgesia in the expected manner. If anything, adrenalectomy enhanced and reserpine pretreatment suppressed the analgesic response to defeat. The data are discussed in terms of providing evidence that defeat-induced analgesia is mediated primarily by endogenous opioids released and acting within the central nervous system.

Animals↗
PubMed1987

Investigation into the use of narcotic antagonists in the treatment of a stereotypic behavior pattern (crib-biting) in the horse.

Crib-biting in horses is a repetitive behavior pattern which may involve the activation of both narcotic receptors and dopamine receptors in the CNS. Crib-biting frequency, determined in 7 nontreated horses under controlled conditions, was usually linear for many hours and ranged from 0.3 to 14.9 bites/min. Intravenous or IM injections of narcotic antagonists decreased these rates to almost zero by about 20 minutes after the injection was given. The duration of the response to a single injection ranged from 20 minutes for naloxone to 4 hours or more for nalmefene and diprenorphine. Effective doses were 0.02 to 0.04 mg of naloxone/kg, 0.04 mg of naltrexone/kg, 0.08 mg of nalmefene/kg, and 0.02 to 0.03 mg of diprenorphine/kg. Crib-biting could be prevented completely for up to a week by continuous infusion of 5 to 10 mg of nalmefene/hr. Crib-biting resumed when the infusion was discontinued, and plasma nalmefene concentrations decreased to below 5 ng/ml. Doses of nalmefene as large as 0.4 mg/kg, IV, produced only minor side effects. These side effects included some passage of semifluid fecal material, intermittent penile relaxation, and mild sedation. Treated horses responded normally to external stimuli, retained their appetites, and performed appropriately when ridden. Sedation wore off during the course of prolonged infusions. Narcotic antagonists may provide a novel and effective treatment of stereotypic behavior disorders.

Animals↗
PubMed1985

Electrochemistry of norcocaine nitroxide and related compounds: implications for cocaine hepatotoxicity.

Norcocaine nitroxide, a free radical metabolite of cocaine, displays a reversible one-electron cyclic voltammogram which is abolished by the addition of reduced glutathione. The corresponding nitrosonium ion was synthesized. It showed the same electrochemical characteristics as the nitroxide. The spin label 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPOL) and its nitrosonium ion behaved like morcocaine nitroxide and its nitrosonium ion. The nitrosonium ion of TEMPOL caused hemolysis of red blood cells, but TEMPOL did not. These observations suggest that the highly reactive nitrosonium ion may be involved in the production of cocaine-induced hepatic necrosis in mice.

Animals↗
PubMed1985

Naloxone injections into the periaqueductal grey area and arcuate nucleus block analgesia in defeated mice.

In a situation of social conflict, mice that are defeated by an opponent exhibit a marked analgesia. Microinjections of naloxone (1 or 10 micrograms) into the periaqueductal grey area (PAG) or into the region of the arcuate nucleus prior to the defeat prevented the emergence of analgesia. Microinjections of morphine (5 micrograms) into these sites had previously been shown to produce profound analgesia. Mice whose adrenals were removed rapidly developed analgesia when attacked by a stimulus animal. Injection of naloxone into PAG also antagonized defeat-induced analgesia in adrenalectomized mice. These observations indicate that sites and processes in the brain rather than in the periphery are responsible for the development of analgesia in mice that are subjected to social defeat.

Analgesia↗
PubMed1984

Sex and strain differences in response to cocaine.

After pretreatment with phenobarbital, female B6AF1 mice showed considerably higher serum glutamic oxaloacetic transaminase (SGOT) elevations and more periportal necrosis from a single injection of cocaine than males. This sex difference was androgen dependent. Castration or treatment with flutamide made males respond like females, while testosterone made females behave like males. There was no significant sex difference in enzymes of cocaine metabolism. When the mice were induced by exposure to pine bedding, males showed higher SGOT elevations and more centrilobular necrosis after cocaine than females. In this case, the sex difference could be attributed to increased levels of cytochrome P-450 and cocaine N-demethylase in liver microsomes. BALB/cBy mice on pine bedding showed much less liver damage from cocaine than B6AF1 mice, but they were more sensitive to norcocaine and N-hydroxynorcocaine. This difference was correlated with low levels of cocaine N-demethylase in the BALB/cBy mice. Liver microsomes from phenobarbital-induced BALB/cBy mice had less norcocaine N-hydroxylase activity than those from B6AF1 mice. These studies demonstrate that the pattern of sex and strain differences in liver damage from cocaine depends on the inducing agent and can be related to a large extent to the microsomal enzymes induced by that agent.

Aging↗
PubMed1984

Encephalitis and aseptic meningitis, Olmsted County, Minnesota, 1950-1981: I. Epidemiology.

All cases fulfilling stated criteria for encephalitis and aseptic meningitis in Olmsted County, Minnesota, for the period 1950 through 1981 were identified. This is, to our knowledge, the first such incidence and trend study in a delineated population, providing rates per 100,000 person-years of 7.4 for encephalitis (189 cases) and 10.9 for aseptic meningitis (283 cases). These are about twelve and six times higher, respectively, than the rates reported by the Centers for Disease Control. The rates have been stable over successive 5- or 10-year periods except for a recent increase in aseptic meningitis. Both conditions were more common in the summer months, in childhood, and among males. Viral identification using conventional laboratory tests has improved with time; in the period 1970 through 1981, virus type was specified in about one-fourth of the cases. The most common agents identified were California and mumps viruses in encephalitis, and entero and mumps viruses in aseptic meningitis. Antecedent and/or concurrent infections were noted in 42 and 35% of encephalitis and aseptic meningitis cases, respectively. No case due to mumps, measles, or rubella viruses has occurred since 1972, reflecting the impact of immunizations. Recovery was reported at the end of the acute phase in 95% of patients with aseptic meningitis, and there were no deaths. Seventy-eight percent of encephalitis patients recovered completely; the case fatality rate was 3.8%. Of the encephalitis cases, 2% were diagnosed initially postmortem.

Adolescent↗
PubMed1984

Effects of naloxone and naltrexone on drug-induced hypothermia in mice.

The hypothermia produced by injecting apomorphine into mice was potentiated by morphine; it was antagonized by haloperidol, by naloxone and by naltrexone. The hypothermic responses to morphine, chlorpromazine and ethanol were also blocked by naltrexone. However, naltrexone potentiated the hypothermic response to pentobarbital. Tolerance to morphine, produced by subcutaneous implantation of a morphine pellet, was accompanied by cross-tolerance to apomorphine-induced hypothermia. Animals made tolerant to apomorphine were not tolerant to morphine-induced hypothermia. The dopamine supersensitivity resulting from chronic treatment with haloperidol potentiated the hypothermic response to apomorphine but not to morphine. These results suggest that endogenous opioids may serve as mediators in the control of thermoregulation by dopamine.

Animals↗
PubMed1983

Metabolism of cocaine and norcocaine to N-hydroxynorcocaine.

The mixed function oxidase system of mouse liver microsomes converts norcocaine to N-hydroxynorcocaine (NHNC). This metabolite can be measured by high performance liquid chromatography (HPLC) using an electrochemical detector. Experiments with inducers and inhibitors suggested that the cytochrome P-450 system was responsible for most of the formation of NHNC. NHNC was relatively unstable under physiological conditions, with a T 1/2 of 17 min at pH 7.4 and 37 degrees. HPLC with the electrochemical detector was also used to demonstrate the formation of NHNC in vivo when mice were injected with norcocaine or cocaine.

Animals↗