scholarly journals Association of alcohol withdrawal severity with MTNR1A (rs34532313) and MTNR1B (rs10830963) genes polymorphisms

2021 ◽  
Vol 1 (2) ◽  
pp. 111-116
Author(s):  
I. S. Efremov ◽  
D. R. Tukhvatullina ◽  
U. S. Efremova ◽  
V. R. Gashkarimov ◽  
N. R. Tulbaeva ◽  
...  
Keyword(s):  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Melatonin Receptors ◽  
Research Centre ◽  
Melatonin Receptor ◽  
Saint Petersburg ◽  
Severe Withdrawal ◽  
Final Sample ◽  
Threatening Condition ◽  
Polymorphic Variants

Alcohol withdrawal is the most threatening condition encountered in patients with alcohol use disorder. Our study aimed to investigate the association of alcohol withdrawal severity with polymorphic variants in melatonin receptor genes. Methods. The clinical study was carried out on the basis of the Republican Narcological Dispensary №1 in Ufa and the Republican Narcological Dispensary №2 in Sterlitamak. Genetic analysis was performed at the Department of Personalised Psychiatry and Neurology at the V.M. Bekhterev Research Centre, Saint Petersburg. The final sample consisted of 307 subjects. Results. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were found to have less hypertension during alcohol withdrawal than carriers of the other genotypes. In comparison, carriers of the GG genotype of the MTNR1B gene (rs10830963) experienced more symptoms than other genotypes: paroxysmal sweating, visual hallucinations, anxiety, and overall CIWA-Ar score. Conclusions. Thus, it can be concluded that the TT genotype of MTNR1A gene (rs34532313) is associated with a lower risk of hypertension during alcohol withdrawal compared to carriers of other gene genotypes. The GG genotype of MTNR1B gene (rs10830963) is associated with severe withdrawal. In general, it can be concluded that melatonin receptors are involved in the pathogenesis of alcohol withdrawal and the severe of some of its symptoms. 

scholarly journals Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents

2021 ◽  
Vol 7 (15) ◽  
pp. eabf6780
Author(s):  
Corinde E. Wiers ◽  
Leandro F. Vendruscolo ◽  
Jan-Willem van der Veen ◽  
Peter Manza ◽  
Ehsan Shokri-Kojori ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Anterior Cingulate ◽  
Dorsal Anterior Cingulate Cortex ◽  
Beneficial Effects ◽  
Alcohol Cues ◽  
History Of ◽  
To Receive

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower “wanting” and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.

scholarly journals Sugar intake and craving during alcohol withdrawal in alcohol use disorder inpatients

2020 ◽  
Author(s):  
Régis Alarcon ◽  
Margaux Tiberghien ◽  
Raphael Trouillet ◽  
Stéphanie Pelletier ◽  
Amandine Luquiens ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Sugar Intake

scholarly journals What is the role of melatonin within the anterior pituitary?

2001 ◽  
Vol 170 (3) ◽  
pp. 493-501 ◽  
Author(s):  
DG Hazlerigg
Keyword(s):  
Anterior Pituitary ◽  
Cellular Level ◽  
Prolactin Secretion ◽  
Receptor Expression ◽  
Melatonin Receptors ◽  
Seasonal Effects ◽  
Pars Tuberalis ◽  
Melatonin Receptor ◽  
Functional Studies

The pineal hormone, melatonin, is uniquely defined by its role as hormonal time, but the processes whereby cells extract temporal information from the melatonin signal are not understood. Melatonin receptors are expressed in the pars tuberalis (PT) and, during fetal and perinatal life, in the pars distalis (PD). Functional studies suggest that the PT mediates the seasonal effects of melatonin on prolactin secretion, whilst the PD may be involved in photoperiodic programming of the developing gonadotrophic axis. To understand these effects at the cellular level we need to know the phenotype of melatonin-responsive cells. This review summarises current understanding in this area, and highlights present shortcomings. A case is presented for exploring the hypothesis that there is a functional association between melatonin receptor expression and cell differentiation in the anterior pituitary.

Reproductive phase dependent variation in lung-associated immune system (LAIS) and expression of melatonin receptors (Mel1a and Mel1b) in the lung of the Jungle-Bush Quail (Perdicula asiatica)

2011 ◽  
Vol 89 (1) ◽  
pp. 10-18 ◽  
Author(s):  
R. K. Kharwar ◽  
C. Haldar
Keyword(s):  
Immune System ◽  
Significant Variation ◽  
Active Phase ◽  
Melatonin Receptors ◽  
Melatonin Receptor ◽  
Reproductive Phase ◽  
Inactive Phase ◽  
Avian Lung ◽  
Circulatory Level ◽  
Reproductive Phases

The present study was performed to assess the variation of the lung-associated immune system (LAIS) in the Jungle-Bush Quail ( Perdicula asiatica (Latham, 1790)) during two different reproductive phases when differences in the circulatory level of hormones (melatonin and gonadal steroid) and environmental conditions were maximum. We noted high significant variation in size and number of bronchus-associated lymphoid tissue (BALT) nodules, as well as in the size and number of non-BALT nodules, during the reproductively inactive phase (RIP; December) compared with the active phase (RAP; June). We also noted high significant variation in the percent stimulation ratio of lung lymphocyte, as well as in the concentrations of plasma melatonin and melatonin receptors, during RIP compared with RAP. Testosterone level and number of macrophages in lungs were high during RAP. Thus, we suggest that the LAIS had reproductive phase dependent variation, which could be due to (i) variation in environmental factors (photoperiod, temperature, and humidity) and (ii) circulatory level of hormones (melatonin and testosterone). Because of the importance of melatonin in avian immune regulation, we assess and document the expression of melatonin receptor types Mel1a and Mel1b in the avian lung, which suggest that the lung is a target organ for melatonin and that melatonin is an immunomodulator for lung-associated immunity in birds.

Alcohol Withdrawal Syndrome in Critically Ill Patients: Identification, Assessment, and Management

2016 ◽  
Vol 36 (1) ◽  
pp. 28-38 ◽  
Author(s):  
Lynsey J. Sutton ◽  
Annemarie Jutel
Keyword(s):  
At Risk ◽  
Alcohol Consumption ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Delirium Tremens ◽  
Alcohol Withdrawal Syndrome ◽  
Rapid Identification ◽  
Severe Withdrawal

Management of alcohol withdrawal in critically ill patients is a challenge. The alcohol consumption histories of intensive care patients are often incomplete, limiting identification of patients with alcohol use disorders. Abrupt cessation of alcohol places these patients at risk for alcohol withdrawal syndrome. Typically benzodiazepines are used as first-line therapy to manage alcohol withdrawal. However, if patients progress to more severe withdrawal or delirium tremens, extra adjunctive medications in addition to benzodiazepines may be required. Sedation and mechanical ventilation may also be necessary. Withdrawal assessment scales such as the Clinical Institute of Withdrawal Assessment are of limited use in these patients. Instead, general sedation-agitation scales and delirium detection tools have been used. The important facets of care are the rapid identification of at-risk patients through histories of alcohol consumption, management with combination therapies, and ongoing diligent assessment and evaluation. (Critical Care Nurse. 2016;36[1]:28–39)

Chronobiological features of melatonin receptors (MT1) expression in breast cancer cells.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12581-e12581
Author(s):  
Alexandre Tavartkiladze ◽  
Ani Gvajaia ◽  
Pati Revazishvili
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Venous Blood ◽  
Receptor Expression ◽  
Melatonin Receptors ◽  
Breast Cancer Patients ◽  
Melatonin Receptor ◽  
Circadian Expression ◽  
Immunocytochemical Method

e12581 Background: According to WHO data, Breast Cancer is the most prevalent malignancy in women. The biological role of Melatonin in the etiology and pathogenesis of the tumour disease has already been approved by a number of research studies. The purpose of our investigation was the assessment of features of Melatonin receptor circadian expression in circulating tumour cells of breast cancer (CTCs). Methods: We observed 34 patients (aged 36-68) with breast cancer (various immunophenotypes). CTCs were separated from patients’ venous blood every third day, in 02:00-04:00 pm and in 02:00-04:00 am intervals. The cells were taken from each patient 4 times. On CTCs, MT1 – receptor expression was assessed using immunocytochemical method. Results: Results of the study revealed that Melatonin receptor expression in breast cancer patients is characterised by the noticable circadian rhythmics. MT1–receptor expression peak by CTCs was detected at 02:00-04:00 am i.e. at night. The less aggressive tumor the higher is the extent of the receptor expression (density). Respectively, in hormone dependent and Her2/neu (negative) tumors the highest expression of the MT1–receptor occurs in hormone dependent and Her2/neu(positive) tumors–medium expression and in triple negative breast Cancer (TNBC) cells–the lowest expression, while in some TNBC–circulating tumor cells MT1 receptor expression has not been detected at all. Conclusions: Hence, based on our the results, we can conclude that Melatonin as the expression of main biochemical marker receptors of bio-rhythms in breast cancer cells, has highly expressed chronobiological nature and directly correlates with histological types of tumor, that provides conditions for the development of new chronotherapeutic strategies in breast cancer treatment.

Approach to the Complicated Alcohol Withdrawal Patient

2016 ◽  
Vol 32 (1) ◽  
pp. 3-14 ◽  
Author(s):  
Jason A. Ferreira ◽  
Patrick M. Wieruszewski ◽  
David W. Cunningham ◽  
Kimberly E. Davidson ◽  
Stephanie F. Weisberg
Keyword(s):  
Alcohol Withdrawal ◽  
Care Setting ◽  
Treatment Approach ◽  
Standard Of Care ◽  
Aminobutyric Acid ◽  
Multimodal Approach ◽  
Gaba Agonists ◽  
Severe Withdrawal ◽  
Common Causes ◽  
Withdrawal Syndromes

Alcohol withdrawal syndromes are common causes for admission to the intensive care unit. As many as one-fifth of the admitted patients have an alcohol-associated disorder. Identifying the benefit of the γ-aminobutyric acid (GABA) agonists has shifted toward methods to improve benzodiazepine (BZD) utilization. Literature validating this treatment approach in severe withdrawal, especially in the critical care setting, is limited, and extrapolation to this population may be dangerous. Multiple therapies have been suggested or utilized in the literature including continuous infusion of GABA agonists, ethanol, dexmedetomidine, antiepileptics, and antipsychotics, introducing a significant amount of variability into clinical practice. This variability in treatment approaches highlights the lack of uniformity and recommendations available for the treatment of severe refractory patients. In patients progressing to severe withdrawal, it may be warranted to escalate care with adjunctive or more aggressive therapies. Although multiple practices are commonly used, the evidence supporting their use after failing symptom-triggered or aggressive therapy with BZDs is virtually nonexistent. These patients commonly receive a multimodal approach, which varies substantially between providers and institutions. Further literature should be directed at the approach most likely to provide benefit when standard of care has failed.

scholarly journals Dexmedetomidine infusions and phenobarbital in the treatment of an unusual presentation of benzodiazepine-resistant alcohol withdrawal

2019 ◽  
Author(s):  
Neil Shah
Keyword(s):  
Alcohol Withdrawal ◽  
Critical Role ◽  
Delirium Tremens ◽  
Seizure Threshold ◽  
First Line ◽  
Keywords Alcohol ◽  
Threatening Condition ◽  
Life Threatening ◽  
Hospital Stays ◽  
High Doses

Background: Alcohol withdrawal is a life-threatening condition characterized by a myriad of physiologic changes including tachycardia, hypertension, lowered seizure threshold, hallucinations, and potential for delirium tremens. Benzodiazepines remain the gold standard for treatment of alcohol withdrawal, although few studies have compared barbiturates to benzodiazepines as first-line treatment. Methods: This study is a single patient chart review. Results: Over the course of his hospital stay, in addition to receiving a continuous infusion of dexmedetomidine, the patient received a total of 389 mg lorazepam, 650 mg phenobarbital, 40 mg haloperidol, 25 mg quetiapine, 5 mg midazolam, and 75 mg diphenhydramine. Conclusion: Phenobarbital is an effective first line agent for management of alcohol withdrawal and may be a safer and more effective treatment with lower rates of intubation and shorter hospital stays than benzodiazepines. It is particularly successful in patients who require high doses of benzodiazepines or ICU admission. Furthermore, the role of dexmedetomidine infusions in alcohol withdrawal remains unclear but may play a critical role in mitigating tachycardia and hypertension though it poses a risk of bradycardia and hypotension. Keywords: Alcohol withdrawal, Dexmedetomidine, Precedex, Phenobarbital, Ativan, Lorazepam, CIWA, GABA channel.

scholarly journals Hyperphosphorylation of Tau Due to the Interference of Protein Phosphatase Methylesterase-1 Overexpression by MiR-125b-5p in Melatonin Receptor Knockout Mice

2021 ◽  
Vol 22 (21) ◽  
pp. 11850
Author(s):  
Han Zhao ◽  
Lingyan Feng ◽  
Wei Zhong ◽  
Hongyan Zhen ◽  
Qingjia Chi ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Knockout Mice ◽  
Protein Phosphatase ◽  
Glycogen Synthase ◽  
Melatonin Receptors ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tau Hyperphosphorylation ◽  
Melatonin Receptor ◽  
Receptor Signal

Melatonin has been indicated to ameliorate tau hyperphosphorylation in the pathogenesis of tau diseases, but the role of melatonin-receptor signal transduction has not been clearly discovered. In this study, we found intensive tau hyperphosphorylation in melatonin receptor knockout mice. Bielschowsky silver staining showed ghostlike neurofibrillary tangles in melatonin receptor-2 knockout (MT2KO) as well as melatonin receptors-1 and -2 knockout (DKO) mice, and an argyrophilic substance was deposited in melatonin receptor-1 knockout (MT1KO) mice. Furthermore, we found significantly decreased activity of protein phosphatase 2A (PP2A) by Western blot and enzyme-linked immunosorbent assay (ELISA), which was partly due to the overexpression of protein phosphatase methylesterase-1 (PME-1), but not glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (CDK5) or protein kinase B (Akt). Finally, we observed a significant increase in cyclic adenosine monophosphate (cAMP) and a decrease in miR-125b-5p levels in MT1KO, MT2KO and DKO mice. Using a luciferase reporter assay, we discovered that miR-125b-5p largely decreased the expression of firefly luciferase by interfering with the 3′UTR of PME-1. Furthermore, miR-125b-5p mimics significantly decreased the expression of PME-1, while miR-125b-5p inhibitor induced tau hyperphosphorylation. These results show that melatonin-receptor signal transduction plays an important role in tau hyperphosphorylation and tangle formation.

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