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Biomedical subjects

M A Marrazzi

Publications and source records attributed to M A Marrazzi.

At least 19 recordsLinked to original sources
PubMed1997

Endogenous codeine and morphine in anorexia and bulimia nervosa.

The endogenous plasma alkaloids codeine and morphine were shown to be elevated in patients with anorexia nervosa and bulimia nervosa compared to control subjects. The role of these opioids in the pathophysiology of these eating disorders is discussed in relation to an auto-addiction opioid model. This model proposes that endogenous opioids are released during an initial period of dieting and reinforce a state of starvation dependence [1,2].

Adolescent↗
PubMed1997

High-dose naltrexone and liver function safety.

Studies have found naltrexone useful in the treatment of diseases other than opiate addiction in which endogenous opioids presumably play a role, such as alcoholism and eating disorders. Some of these studies involve high doses (100-200 mg bid). Because investigational studies with high doses (300 mg/day) reported clinically significant increases in liver enzyme levels, the authors measured a spectrum of liver function parameters in response to high doses of naltrexone in a double-blind, crossover trial (100 mg bid) followed by an open-label period (200 mg bid). They observed no adverse clinical or laboratory changes in liver function in association with high-dose naltrexone therapy in eating disorders.

Adult↗
PubMed1996

Male/female comparison of morphine effect on food intake--relation to anorexia nervosa.

We have proposed that endogenous opioids play a critical role in the etiology of anorexia nervosa by mediating an auto-addiction. A biological predisposition may result from an atypical endogenous opioid system. Morphine activation of the system increases food intake in most species, including normal humans and rats, but decreases food intake in mice. The atypical opioid system in mice may be representative of that in anorexia nervosa patients, causing the biological predisposition. Anorexia nervosa is 10 times more prevalent in females than males. In the context of this auto-addiction opioid model, it was interesting to determine if the effects of morphine on food intake were markedly different between the two sexes. Full dose-response curves were done of the effects of morphine on food intake in males and females in both rats and mice, representing the typical and atypical responses, respectively. Differences between the sexes were not found to explain the marked prevalence of anorexia nervosa for females. The marked preference is probably at some other step.

Animals↗
PubMed1995

Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa.

Our auto-addiction model suggests that opiate blockade may be therapeutically useful in anorexia nervosa and bulimia nervosa. Naltrexone was administered to out-patient subjects in double-blind clinical trials with randomized cross-over designs. Reduction in binge-purge symptomatology was evident in the naltrexone period over placebo for 18 out of 19 subjects with either bulimia or anorexia nervosa of the bulimic subtype. In every case, the decoding of drug or placebo double blinding confirmed the assessments of both the investigator and the subjects, based on the blind analysis of the data and on their therapeutic response, respectively. Statistical analysis done on the total population and two diagnostic subgroups found highly significant differences.

Adult↗
PubMed1995

A detailed longitudinal analysis on the use of naltrexone in the treatment of bulimia.

In accord with our auto-addiction opioid model, naltrexone was previously reported to be effective in the treatment of bulimia in a controlled double-blind clinical trial with a randomized cross-over design. This is a detailed longitudinal analysis over a 16 month period of one subject from that study. Attenuation in bulimic symptoms in two-drug as compared to no-drug periods was demonstrated. The duration for which the drug was needed was also addressed. The subject is an illustration of a therapeutic response on multiple parameters including binges, purges, urges to perform both behaviors, eating patterns, scaled feelings and Eating Disorder Inventory questionnaire scores. A rare allergic reaction to the drug is reported. It appeared to be heat and photosensitive, even in the presence of sun screen, occurred after a delay and did not appear immediately on skin testing. Use of naltrexone after desensitization is also reported.

Adult↗
PubMed1995

Binge eating disorder: response to naltrexone.

Binge eating disorder (BED) is characterized by a bulimic binge eating pattern without the compensatory behaviors of purging or laxative abuse. It is often associated with obesity. The treatment response characteristics are more like bulimia than other forms of obesity. We have shown the opiate antagonist naltrexone to attenuate bulimia nervosa in controlled clinical trials. We report here a response to naltrexone in a subject with BED similar to that previously reported for the larger population of bulimic subjects. Three consecutive periods of drug, placebo and double dose drug were used, with the order of the first two periods double blind until after the data analysis. Symptoms were reduced in the naltrexone compared to placebo period. Statistical significance was demonstrated using time series analysis for this 'n of one' study. Psychotherapy was carried out throughout all periods. Naltrexone plus psychotherapy may be more efficient than psychotherapy alone.

Adult↗
PubMed1990

Atypical endogenous opioid systems in mice in relation to an auto-addiction opioid model of anorexia nervosa.

We have proposed that the atypical opioid system in the mouse may be representative of that in the anorexia nervosa patient and may account for a biological predisposition to the disorder. This is in the context of our auto-addiction model of anorexia nervosa in which endogenous opioids play a critical role in its etiology. Morphine activation of the endogenous opioid systems increases food intake and causes sedation in most species, including normal humans and rats. In contrast in BALB/C mice, morphine causes anorexia and hyperactivity, which we suggest may be true in the anorexia nervosa patient. A variety of atypical opioid systems have been demonstrated in different mouse strains, based on other responses. The present study examines these strains with reference to the responses relevant to our anorexia nervosa model. Three patterns are described--anorexia with hyperactivity (BALB/C and C57BL/6J mice), anorexia without hyperactivity (DBA/J mice), and a biphasic curve with hyperphagia at low doses and anorexia and hyperactivity at higher doses (CF-1 mice). Only female mice were used. These atypical opioid systems may reflect a spectrum of biological predispositions to the disorder. These strain differences may also provide useful correlations of the genetic determinants of various opiate responses and provide useful comparisons in characterizing the essential features responsible for the atypical responses.

Animals↗
PubMed1990

Effects of U50,488, a selective kappa agonist, on atypical mouse opiate systems.

We have proposed that endogenous opioids play a critical role in the etiology of anorexia nervosa, mediating an auto-addiction, and that atypical opioid systems in mice may be representative of those in anorexia nervosa patients, in contrast to normal humans and rats. A biological predisposition to eating disorders may result from these atypical opioid systems. Definition of these systems as atypical is based on their responses to morphine, which are preferential for the mu receptor subtype. Three patterns have been described in four strains of mice: anorexia with hyperactivity (BALB/C and C57BL/J), anorexia without hyperactivity (DBA/J), and a biphasic curve (CF-1). The latter showed anorexia and hyperactivity at high doses but increased food intake without a change in motor activity at low doses. These patterns contrast to the increase in food intake and sedation in typical species, including rats and normal humans. In the present study, U50,488, a selective kappa agonist, increases food intake in all four mouse strains, as previously reported in rats. Thus, these two agonists have opposite effects on the atypical mouse systems, but similar effects on the typical rat system. The typical and atypical opioid systems respond oppositely to morphine but similarly to U50,488.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Atypical responses to morphine in mice: a possible relationship to anorexia nervosa?

According to our previously proposed auto-addiction hypothesis of chronic anorexia nervosa, patients become addicted to an initial period of dieting through endogenous opioid mediated mechanisms. Morphine causes hyperactivity and anorexia in the mouse, symptoms of anorexia nervosa but responses opposite to those of most species including rats and normal human subjects. This suggests that the atypical opioid systems in the mouse may resemble those of the chronic anorexia nervosa patient in contrast to those of most species including the normal human. Characterization of this atypical opioid system may be useful in understanding the pathophysiology of anorexia nervosa.

Animals↗
PubMed1986

Effects of thioglucoses on sensitivity to insulin hypoglycemic convulsions.

Based on the effects of gold thioglucose (GTG), we have previously proposed a regulatory center in brain which adjusts the convulsive response to insulin hypoglycemia. The sensitivity to insulin hypoglycemic convulsions is decreased 24 hr and increased 1 week after a single i.p. injection of GTG. The differences are in the brain's convulsive response to equal hypoglycemia, as the blood glucose response to insulin is unchanged. The generalized convulsive threshold, reflected in the sensitivity to nonmetabolic pentylenetetrazol (Metrazol) convulsions, is not altered. Despite its systemic administration, GTG causes lesions focused in the ventromedial hypothalamus. In the present study, this regulatory center was explored further by the ability of two thioglucoses to substitute for GTG. beta-D-Thioglucose had no effect. 5-Thioglucose simulated the early (24 hr) action of GTG but had no effect at 1 week. However, unlike GTG, 5-thioglucose did not cause the ventromedial hypothalamus lesion. The early (24 hr) and late (1 week) components are thus dissociated. The early effect on insulin hypoglycemic convulsions does not require a ventromedial hypothalamus lesion. Structure-activity relationships and relationships to glucoregulatory systems are discussed.

Animals↗
PubMed1985

Thioglucose interactions with a "gold thioglucose-lesioned glucostat".

Our previous studies suggest a central nervous system regulatory center that adjusts the brain's convulsive response to the insulin hypoglycemia based on decreased sensitivity to insulin hypoglycemic convulsions 24 hr after a single i.p. injection of gold thioglucose (GTG). This decrease is a change in the convulsive response to equal hypoglycemia and is not a change in the generalized convulsive threshold. GTG simultaneously causes a cytotoxic lesion focused in the ventromedial-arcuate hypothalamus (VMH), and the proposed regulatory center may be thought of as a "GTG-lesioned glucostat." However, 5-thioglucose (5TG) substitutes for GTG in decreasing the sensitivity to insulin hypoglycemic convulsions but does not lesion the VMH. In the present study, two possible explanations were explored for this previously reported dissociation of the 5TG functional effect and the VMH lesion. First, an interaction of 5TG with the GTG-lesioned glucostat in the VMH, without itself causing a lesion, was not supported by competition experiments, i.e., GTG lesion formation was not inhibited by appropriate 5-TG pretreatment. beta-D-Thioglucose, for which the sulfur substitution is more like GTG, is also compared. Two indices of GTG lesion formation were used, histology and the increased body weight that eventually results from a VMH lesion. Second, no 5-TG-induced lesion was found anywhere in the brain. Thus, no support was found for the possibility that 5-TG and GTG share a common lesion at some site other than the main VMH lesion of GTG. Other explanations must be sought.

Animals↗
PubMed1982

Effects of bipiperidyl mustard (BPM) lesions on insulin hypoglycemic convulsions.

Systemic gold thioglucose (GTG) is well known to produce hyperphagia, resulting in obesity, and histological damage focused relatively selectively in the ventromedial hypothalamus (VMH). Although structurally very different, bipiperidyl mustard (BPM) produces apparently similar effects. However, a proposed mechanism for concentration and hence localization of GTG toxicity depends on its structural similarity to glucose, binding it to glucoreceptors and focusing the cytotoxicity of the gold thio-portion. We recently showed that GTG treatment also produces an early decrease and a later increase in sensitivity to insulin hypoglycemic convulsions. We report here that BPM also produces a similar biphasic change in sensitivity to insulin hypoglucemic convulsions. For both, the differences are in the brain's convulsive response to hypoglycemia, rather than in the degree of hypoglycemia in response to insulin. Thus, GTG and BPM cytotoxic lesions appear similar in this regard as well. BPM is another way of producing a relatively discrete brain lesion which alters the brain's functional adjustment to hypoglycemia. The significance of this control center and its relationship to the control(s) of feeding and systemic metabolism are discussed.

Animals↗
PubMed1982

Blood glucose profiles in surgically prepared flaxedilized and anesthetized rats.

Blood glucose profiles were monitored over an extended period of time in surgical rat preparations which included femoral artery and vein cannulations, tracheotomy, carotid artery cannulation and a craniotomy to expose the brain. Rats were under pentobarbital anesthesia, urethane anesthesia or Flaxedil neuromuscular blockage and local anesthesia, Fasted and unfasted rats were compared. These profiles are a foundation for studies of the central nervous system control of feeding behavior and metabolic homeostasis and of hypothalamic glucoreceptors, for which knowledge of the baseline blood glucose profile is particularly important. Such studies utilize the surgical preparations examined here. The importance of rapid "on the spot" "moment to moment" monitoring of blood glucose during the course of an experiment and adjustment of the experiment accordingly is demonstrated. Methods for such monitoring are evaluated in comparison with the standard enzymatic fluorometric assay for glucose. The YSI Glucose Analyzer seems to be a suitable one and is feasible for physiological and psychological laboratories without biochemical expertise.

Anesthesia, General↗