Sarcopenia in cirrhosis: from pathogenesis to interventions

Journal of Gastroenterology - Sarcopenia (severe muscle depletion) is a prevalent muscle abnormality in patients with cirrhosis that confers poor prognosis both pre- and post-liver transplantation....     

Presence of a metallothionein-like protein in the bovine pineal gland

Summary The high concentration of zinc in the bovine pineal gland prompted us to investigate the existence of a zinc-binding protein in this organ. In this study, we report that the subcellular distribution of zinc in the bovine pineal gland is nonuniform, with the crude nuclear, mitochondrial, microsomal, and supernatant fractions having 0.264±0.038, 0.160±0.019, 0.130±0.016, and 0.287±0.010 g zinc/mg protein, respectively. Furthermore, gel filtration studies using Sephadex G-75 and a 105,000 g supernatant fraction revealed two zinc binding protein peaks that bind 1.7 and 3.7 g Zn⁺⁺/mg protein, respectively. Furthermore, purification of the protein peak with an elution volume (ve/vo) of 2.06 on anion exchange chromatography (DEAE-A 25) yielded a single protein peak which binds 10 g zinc/mg protein. The comparative high performance liquid Chromatographic (HPLC) profiles of the zinc-induced hepatic metallothionein isoform I (retention time=17.39 min) and of the bovine pineal metallothionein-like protein isoform I (retention time=17.49 min) are similar. Since zinc is a potent inhibitor of sulfhydryl-containing enzymes and receptor sites, we investigated the effects of zinc and found that it inhibited the binding of [³H]glutamate (IC 50=80 M) and of [³H]spiroperidol (IC 50=0.6 mM) to the pineal membranes. The results of these studies are interpreted to indicate that the bovine pineal gland possesses an active and dynamic zinc homeostatic mechanism, whose precise function(s) remain(s) to be delineated.     

Pathogenesis and treatment of neuroleptic malignant syndrome

1. Neuroleptic drugs (antipsychotics) produce numerous side effects which include serious extrapyramidal symptoms consisting of akathisia, dystonia, neuroleptic malignant syndrome, parkinsonian reactions such as postural abnormality, tremor, akinesia or bradykinesia, rigidity, and tardive dyskinesia. 2. Among the complications of neuroleptic chemotherapy, the most serious and potentially fatal complication is malignant syndrome, which is characterized by extreme hyperthermia, "lead pipe" skeletal muscle rigidity causing dyspnea, dysphagia, and rhabdomyolysis, autonomic instability, fluctuating consciousness, leukocytosis, and elevated creatine phosphokinase. 3. Neuroleptic malignant syndrome should be differentiated from malignant hyperthermia, lethal catatonia, and other pathological states producing some of these same symptoms. 4. In addition to neuroleptics, malignant syndrome has been caused by thymoleptics (antidepressants), metoclopramide (antiemetic), metoclopramide combined with cimetidine, tetrabenazine, overdosage of benzodiazepine, phenelzine, dothiepin and alcohol, and amphetamine. 5. Factors leading to and/or facilitating the emergence of neuroleptic malignant syndromes are reportedly organic brain syndrome, dehydration, exhaustion, external heat load, excessive sympathetic discharge, use of long acting neuroleptics, high doses of neuroleptics, rapid dose titration with neuroleptics, abrupt discontinuation of antiparkinsonism agents, and concurrent lithium therapy. 6. Although, the pathogenesis of neuroleptic malignant syndrome is not understood completely, a blockade of dopaminergic receptors in the hypothalamus, spinal cord and striatum, an alteration of dopaminergic-serotonergic transmission in the body, an enhanced synthesis and action of prostaglandin E1 and E2, and a modification of calcium-mediated signal transduction in the body have been suggested. 7. The treatment of malignant syndrome includes immediate withdrawal of neuroleptic drugs, i.v. infusion of dantrolene, and oral administration of bromocriptine; or alternatively i.v. infusion of dantrolene and the combination of levodopa-carbidopa. 8. Other measures to enhance the therapeutic effectiveness of the aforementioned regimens are to include the use of anticholinergic drugs such as benztropine to enhance the effectiveness of bromocriptine, of lorazepam if catatonic symptoms persist, or of electroconvulsive therapy (ECT) if psychotic symptoms persist. 9. These treatments, however, must be "active" rather than "passive", in order to avert fatalities and/or unfortunate sequelae from this iatrogenic and incompletely understood disease.     

Severe Hypoglycemia Due to Cryptic Insulin Use in a Bodybuilder

Background

Bodybuilding is a demanding sport, which requires high-volume, high-resistance weight training and augmented nutritional intake, toward an increase of overall body muscle mass accompanied by an overall decrease of body fat percentage and mass. Among bodybuilders, the use of various legal and illegal supplements is common. These supplements may be naturally occurring or man-made.

Patterns of marriage and reproductive practices: is there any relationship?

Today, a transition from traditional to modern marriages can be observed in many countries. This shift in patterns of marriage has evidently affected childbearing and reproductive practices. This study aimed to examine the relationship between patterns of marriage and reproductive practices in Iran. Hence, 880 married women, aged 15–49 years old, living in the North of Iran were selected using a multi-stage cluster sampling strategy and their patterns of marriage and reproductive practices were cross sectionally studied. The results revealed that there were no significant differences in the reproductive practices by three main patterns of marriage in Babol, Iran. The study also indicated that there were no significant differences in reproductive practices in three patterns of marriage after controlling for socio-economic variables. It seems that apart from the patterns of marriage, other influencing factors are the determinants of fertility in women, and the policy-makers of Iran need to pay attention to these determinants before making any decisions in this area.     

The presence and actions of opioid receptors in bovine pineal gland

The mammalian pineal gland and its main hormone, melatonin, working in conjunction with the hypothalamic suprachiasmatic nuclei, synchronize circadian rhythm and hence refine numerous physiological and biochemical parameters. An interaction among melatonin, opioids, and analgesia has been suspected for many years, since during nighttime, when the level of melatonin is high, the mammals are less sensitive to pain. In studying this phenomenon further, we have identified a single population of opioid receptors in the bovine pineal gland using [3H]-diprenorphine and other ligands. The receptors have a dissociation equilibrium constant (Kd) of 1.36 +/- 0.31 nM and a density (Bmax) of 17.93 +/- 5.22 fmol/mg protein. In competitive experiments, the concentration of drugs required to inhibit 50% of the [3H]-diprenorphine binding (IC50) in descending order of potency was found to be naltrexone > fentanyl > naloxone > nalbuphine > morphine > nalorphine > DAGO > dynorphin > metenkephalin. In order to delineate the function of the opioid system in the pineal gland, the effects of both opioid receptor agonists and antagonists on the basal activity of N-acetyltransferase were examined in the bovine pineal explants in culture. Morphine, an opioid receptor agonist, increased significantly the activity of N-acetyltransferase in a dose-dependent fashion. In addition, the stimulatory effect of morphine was inhibited by naloxone, an opioid receptor antagonist. The results of these studies indicate the existence of pineal opioid receptors, which play a pivotal role in the synthesis of melatonin and its action in synchronizing pineal events.     

Should Sarcopenia Increase Priority for Transplant or Is It a Contraindication?

Purpose of Review

The purpose of this review is to discuss the current evidence regarding the impact of sarcopenia on patients with cirrhosis awaiting liver transplantation and to determine if its presence should be considered a criterion for expedited transplantation or a contraindication for transplantation.

Recent Findings

Sarcopenia is a negative predictor of survival in patients on a waiting list and after liver transplant. The gut-liver axis and the liver-muscle axis have been explored to understand the complex pathophysiology of sarcopenia.

Summary

Sarcopenia is a frequent finding in patients with cirrhosis. The diagnosis is ideally based on cross-sectional image analysis (CT or MRI) and treatment consists of optimization of caloric and protein intake. To date, prioritizing tools for liver transplantation have not included nutrition or sarcopenia parameters. Patients with a low Model for End-Stage Liver Disease (MELD) or MELD-Na score and sarcopenia would benefit from prioritization for transplant in order to reduce time on waiting list and therefore mortality.