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Biomedical subjects

A Goldstein

Publications and source records attributed to A Goldstein.

At least 145 records · Page 8Linked to original sources
PubMed1984

Naltrexone treatment of heroin addiction: one-year follow-up.

Pre-treatment characteristics and post-treatment outcome measures were compared for 40 patients who began naltrexone maintenance and 77 who did not after a 6-month period of temporary maintenance on L-alpha-acetylmethadol (methadyl acetate LAAM). Patients who chose to begin naltrexone were younger, had fewer incarcerations and fewer months incarcerated prior to LAAM treatment, had fewer opiate-free months following previous treatments, and were more likely to be of Caucasian ethnicity. One year later, significantly more patients who had received any naltrexone than those who had not were no longer in any treatment program and were opiate-free. We found no significant correlations between total duration of naltrexone-treatment and post-treatment outcome variables such as heroin use, arrests, incarcerations or enrollment in a treatment program.

Adult↗
PubMed1984

Opioid receptor reserve in normal and morphine-tolerant guinea pig ileum myenteric plexus.

We have measured the opioid receptor reserve in the guinea pig ileum myenteric plexus by means of the site-directed alkylating agent, beta-chlornaltrexamine. Treatment of the tissue with low (less than 10 nM) concentrations of beta-chlornaltrexamine caused a parallel shift of the log concentration-response curves for both normorphine and dynorphin A-(1-13). Analysis of the resulting curves indicated that the Kd values were 1.5 +/- 0.5 X 10(-6) and 10 +/- 4 X 10(-9), respectively. Using the naloxone Ke to distinguish between the mu and kappa receptors in this tissue, we found that the receptor selectivities of normorphine and dynorphin A-(1-13) were unchanged after a maximum parallel shift, thus demonstrating that there are both spare mu and spare kappa receptors present. The spare-receptor fraction for both receptor types was about 90%. In morphine-tolerant preparations (chronic pellet implantation), there was an apparent reduction in the fraction of spare mu receptors without any change in the apparent affinity of normorphine. Reduction in the spare receptor fraction does not necessarily imply reduction in the number of binding sites. We suggest that this reduction in receptor reserve is the basis of opioid tolerance, since the agonist concentration needed to produce a given effect is expected to increase as the receptor reserve decreases.

Animals↗
PubMed1984

Dynorphin converting enzyme with unusual specificity from rat brain.

A rat brain membrane extract was shown to convert synthetic dynorphin B-29 ("leumorphin") to dynorphin B [dynorphin B-29-(1-13), "rimorphin"]. This represents a "single arginine cleavage" at Thr-Arg at positions 13 and 14 of the substrate. The product was identified by immunoprecipitation with a highly specific dynorphin B antiserum and by coelution with radiolabeled dynorphin B on reversed-phase high-performance liquid chromatography. The converting activity exhibits a pH optimum of 8. It is inhibited by a thiol protease inhibitor but not by inhibitors of cathepsin B or of serine proteases. It is inhibited by dynorphin A but not by various dynorphin A fragments. These results suggest that the converting activity is due to a novel thiol protease distinct from any known protease believed to function in the processing of biologically active peptides.

Animals↗
PubMed1984

Nicotine self-administration in rats.

Female Wistar rats were allowed to self-administer nicotine solutions through indwelling jugular vein cannulae for 23 h per day for periods from three to five weeks. Two response levers were available to the rats; responding on one lever, designated the active lever, produced an immediate infusion of nicotine solution or saline. A second lever for which responding had no programmed consequences was introduced as a control for the locomotor stimulant action of low doses of nicotine. Baseline lever response rates were determined over a period of one week, in which active lever responding produced an infusion of saline. Rats were then allowed access to varying doses of nicotine or saline for a further two or three weeks. Response rates on the active lever increased significantly in rats with access to nicotine at a dose of 30 micrograms kg-1 per response. However, control lever response rates were also significantly elevated. The role of nicotine-induced locomotor stimulation in the self-administration behaviour was further evaluated in a dose-reduction experiment, in which the dose of nicotine available to rats responding for 30 micrograms kg-1 per response was reduced to 3 micrograms kg-1 per response. This resulted in a significant differential increase in active lever responding relative to control lever responding. The results suggest that nicotine is positively reinforcing in rats which had not previously been deprived of food or water or received prior drug treatment, but also indicate that nicotine induced locomotor stimulation may contribute to the observed increases in lever response rates when rats self-administer nicotine.

Animals↗
PubMed1984

Opioid receptor selectivity of dynorphin gene products.

In the guinea-pig ileum myenteric plexus-longitudinal muscle preparation, products from the dynorphin gene fell into three groups according to their potency. Dynorphin A was the most potent; dynorphin-32, dynorphin B, dynorphin B-29 and alpha-neo-endorphin were about equipotent and 10 to 20 times less potent than dynorphin A; dynorphin A-(1-8) and beta-neo-endorphin were about 200 times less potent than dynorphin A. Dynorphin A (a kappa agonist) was about 10 times less sensitive to antagonism by naloxone (as measured by naloxone Ke) than was normorphine (a mu agonist). Ke values for dynorphin-32, dynorphin B and alpha-neo-endorphin were the same as for dynorphin A, indicating that these peptides are also highly selective kappa agonists. Dynorphin A-(1-8), dynorphin B-29 and beta-neo-endorphin had Ke values intermediate between dynorphin A and normorphine, suggesting that they interact at both kappa and mu receptors. Addition of peptidase inhibitors to the bathing medium increased the potencies of dynorphin B, dynorphin B-29, alpha-neo-endorphin, dynorphin A-(1-8) and beta-neo-endorphin, but not of dynorphin A, dynorphin-32 or normorphine. The inhibitors did not change the naloxone Ke for dynorphin A or normorphine, or for dynorphin B-29, dynorphin A-(1-8) and beta-neo-endorphin, suggesting that the intermediate values were not caused by degradation to products with different receptor selectivities from the parent compounds. Ke for dynorphin-32, dynorphin B and alpha-neo-endorphin changed from being the same as dynorphin A in the absence of inhibitors to intermediate between dynorphin A and normorphine in the presence of inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Site-directed alkylation of multiple opioid receptors. I. Binding selectivity.

We report a method for measuring and expressing the binding selectivity of ligands for mu, delta, and kappa opioid binding sites. We used radioligands that are partially selective for these sites in combination with membrane preparations enriched in each site. Enrichment was obtained by treatment of membranes with the alkylating agent beta-chlornaltrexamine in the presence of appropriate protecting ligands, sufentanil for mu sites, [D-Ala2, D-Leu5] enkephalin for delta sites, and dynorphin A for kappa sites. After enrichment for mu receptors, [3H] dihydromorphine bound to a single type of site as judged by the slope of competition binding curves. After enrichment for delta or kappa receptors, binding sites for [3H] [D-Ala2, D-Leu5]enkephalin and [3H]ethylketocyclazocine, respectively, were still not homogeneous. There were residual mu sites in delta-enriched membranes but we found no evidence for residual mu or delta sites in kappa-enriched membranes. We used this method to identify ligands that are highly selective for each of the three types of sites: Tyr-D-Ala-Gly-(Me)Phe-Gly-ol, sufentanil, and morphiceptin for mu sites; (D- Pen2 , D- Pen5 ]enkephalin and [D- Pen2 ,L- Pen5 ]enkephalin for delta sites; and tifluadom and U50 ,488 for kappa sites.

Alkylation↗
PubMed1984

Site-directed alkylation of multiple opioid receptors. II. Pharmacological selectivity.

A site-directed alkylating agent was used to inactivate one or more types of opioid receptor in two bioassay preparations in the presence of type-selective ligands as protectors of other opioid receptor types. Since the pharmacological potency of an agonist is decreased when the receptor type through which it acts has been inactivated, the method can be used to characterize the pharmacological selectivity of opioid agonists. All of the smaller opioid products of the enkephalin gene were found to be delta-selective in the mouse vas deferens, but BAM-12P, BAM- 22P , and Peptide E were not. In the same tissue, beta c-endorphin was not mu-selective, but in the guinea pig ileum preparation it evidently combined with mu and kappa receptors. The presence of functional epsilon receptors, however, could not be ruled out. The approach described here is applicable to any pharmacologically active receptors of which there are multiple types, and for which site-directed alkylating agents and type-selective protector ligands are available.

Alkylation↗
PubMed1984

[Efficacy of medical treatment (isoproterenol + aminophylline) of aneurysm rupture spasm].

Efficiency against spasm of a combined therapy by Isoproterenol Aminophylline is discussed from 97 operated cases (118 aneurysms) and 30 non operated cases (32 aneurysms). This treatment seems efficient and best results are achieved when therapy is started as soon as possible or systematically after surgery. Analysis of spasm and of its treatment is based on criterions which vary from one author to another, and comparison between different series is difficult. In the series here reported, one group with treatment is compared to another one without treatment. This method seems the most reliable. This treatment cannot be considered as the lone efficient therapy against spasm and is usually used beside other techniques such as ICP and Arterial pressure management or early surgery.

Aminophylline↗
PubMed1984

[Does the ferritin level have a practical value in chronically hemodialized patients?].

In order to determine whether serum ferritin assay has any advantages compared with usual hematologic parameters, serum ferritin was assessed in 70 hemodialysed patients. It was positively correlated with the number of blood units infused, but there was no correlation with iron treatment, serum iron or the degree of anemia. However, the interpretation of the results is difficult, because of the large dispersion of serum ferritin levels. Therefore, the determination of serum ferritin concentration cannot be recommended as a current method to follow-up and manage anemic chronic hemodialysed patients, especially when the cost of the test is taken into account.

Female↗
PubMed1983

Methadyl acetate (LAAM) in the treatment of heroin addicts. II. Double-blind comparison of gradual and abrupt detoxification.

One hundred nineteen patients were admitted to a six-month (26-week) prenaltrexone detoxification program comparing abrupt and gradual withdrawal from methadyl acetate (LAAM) therapy. All patients were brought to a maintenance level of 50, 50, and 65 mg (Monday, Wednesday, and Friday). Patients randomly assigned to the gradual group (group G) began 4-mg/wk reduction the Monday of week 9 and reached zero dosage (placebo) the Monday of week 23; patients in the abrupt group (group A) continued to receive 50, 50, and 65 mg until the Monday of week 23, when their dosage was dropped to zero (placebo). All patients were given placebo for four weeks. This study showed the superiority of abrupt withdrawal over this gradual-withdrawal schedule. Forty-six percent of group P compared with 28% of group G made the transition to naltrexone treatment. Severity of withdrawal problems was in no case significantly greater in group A.

Adolescent↗
PubMed1983

Immunoreactive dynorphin in rat tissues and plasma.

Distribution of immunoreactive dynorphin (ir-dyn) has been determined in rat tissues using a highly specific antiserum. Concentrations are highest in the pituitary, brain and spinal cord, as previously reported. In peripheral tissues highest levels occur in the stomach and upper intestine, but ir-dyn has also been detected in several other tissues, including heart and skeletal muscle. Unilateral vagotomy did not affect the amount of ir-dyn in heart or stomach, and denervation did not affect the amount in skeletal muscle. Gel permeation chromatography of the ir-dyn in gastrointestinal tract, heart, and skeletal muscle revealed a larger apparent molecular weight than that of the 17-residue dynorphin. Using octadecylsilyl-silica cartridges, it was possible to extract and concentrate ir-dyn from rat plasma. By gel permeation chromatography plasma immunoreactivity was found in two peaks, both of higher apparent molecular weight than dynorphin. This immunoreactivity was unaltered by hypophysectomy or adrenalectomy.

Animals↗
PubMed1983

Episodes of heroin use during maintenance treatment with stable dosage of (-)-alpha-acetylmethadol (methadyl acetate, LAAM).

The phenomenon of episodic heroin use by patients maintained on a surrogate opiate has been noted by clinical investigators since the early 1970s. Several investigators have hypothesized that relapse to heroin use is related to stressful events in the patient's life, and retrospective studies give some support to this hypothesis. In the present study, we asked patients every month to rate their situation with respect to 11 life areas. There were significant negative correlations between the absolute scores in most life areas and the amount of heroin use. However, the relationship between changes in life-area scores and changes in heroin use was less clear. Our data indicate that of patients who have substantial increases in heroin use, many do have negative changes in one or more life areas. However, not all patients who have such negative changes in life-area scores respond by increasing their heroin use.

Family↗
PubMed1983

Dynorphin is contained within hippocampal mossy fibers: immunochemical alterations after kainic acid administration and colchicine-induced neurotoxicity.

Antisera raised against synthetic dynorphin or [Leu5]enkephalin demonstrate immunostaining in hippocampal mossy fibers and in dentate granule cells. However, dynorphin immunoreactivity (ir) appears to be denser in immunocytochemical preparations and is quantitatively greater by radioimmunoassay than enkephalin-ir. Immunostaining with dynorphin antisera is eliminated by adsorption with 1-100 microM dynorphin-17 whereas immunostaining with enkephalin antisera is eliminated by adsorption with 1-100 microM [Leu5]enkephalin, dynorphin-17, dynorphin-(1-13), or alpha-neo-endorphin. Intrahippocampal colchicine injections, which selectively destroy dentate granule cells, significantly decrease the dynorphin-ir and enkephalin-ir levels in rat hippocampus. Intraventricularly administered kainic acid, which selectively destroys CA3-4 pyramidal cells, results in an increase of enkephalin immunostaining in mossy fibers and a significant increase in enkephalin-ir by radioimmunoassay in whole hippocampus. The enkephalin-ir cells and fibers in entorhinal/perirhinal cortex, which innervate rat hippocampus and dentate gyrus, do not contain dynorphin-ir.

Animals↗