Role of neuropeptide tyrosine (NPY) in ethanol addiction

Here, an overview of neurophysiological, pharmacological and genetic research on the role of neuropeptide tyrosine (NPY) in ethanol consumption and withdrawal is presented. NPY is abundantly expressed in the extended amygdala and is critically involved in the regulation of negative affective states in rats, also is involved with neurobiological responses to ethanol and other drug of abuse. Genetic, molecular and pharmacological evidences suggest that NPY is an important neurobiological substrate for the predisposition to alcoholism. Administration, as well as the withdrawal of ethanol, alters central NPY expression. Alcohol- preferring rats exhibit basal NPY deficits in central amygdala. In the latter, NPY may rescue dependence-induced increases in anxiety and alcohol drinking. Low NPY levels in some brain regions following ethanol withdrawal contribute to the increased sensitivity to seizure and the heightened levels of anxiety characteristic of withdrawal responses. Mice with deletion of NPY gene exhibit a high-anxiety, high-alcohol-drinking phenotype. Pharmacological and genetic manipulations suggest that central NPY signaling modulates ethanol consumption via Y1, Y2, and Y5 receptors. Analysis of chromosomal regions (QTLs) associated with alcohol consumption identified NPY as one of the genes that influence alcohol dependence and as a promising target for pharmacotherapeutics to combat alcohol associated disorders. Consequently, NPY is a potentially new pharmacological target for the treatment of alcohol diseases

Role of Neuropeptide Tyrosine (NPY) in Ethanol Addiction

Here, an overview of neurophysiological, pharmacological and genetic research on the role of neuropeptide tyrosine (NPY) in ethanol consumption and withdrawal is presented. NPY is abundantly expressed in the extended amygdala and is critically involved in the regulation of negative affective states in rats, also is involved with neurobiological responses to ethanol and other drug of abuse. Genetic, molecular and pharmacological evidences suggest that NPY is an important neurobiological substrate for the predisposition to alcoholism. Administration, as well as the withdrawal of ethanol, alters central NPY expression. Alcohol-preferring rats exhibit basal NPY deficits in central amygdala. In the latter, NPY may rescue dependence-induced increases in anxiety and alcohol drinking. Low NPY levels in some brain regions following ethanol withdrawal contribute to the increased sensitivity to seizure and the heightened levels of anxiety characteristic of withdrawal responses. Mice with deletion of NPY gene exhibit a high-anxiety, high-alcohol-drinking phenotype. Pharmacological and genetic manipulations suggest that central NPY signaling modulates ethanol consumption via Y1, Y2, and Y5 receptors. Analysis of chromosomal regions (QTLs) associated with alcohol consumption identified NPY as one of the genes that influence alcohol dependence and as a promising target for pharmacotherapeutics to combat alcohol associated disorders. Consequently, NPY is a potentially new pharmacological target for the treatment of alcohol diseases

Investigating alcohol consumption during pregnancy for the prevention of Fetal Alcohol Spectrum Disorders (FASD)

The term FASD (Fetal Alcohol Spectrum Disorders) is used to describe the entire spectrum of pathologies and disorders caused by alcohol exposure in uterus. Alcohol assumed in pregnancy passes directly through the placental barrier causing a broad range of symptoms whose severity can greatly vary in degree. The alcohol teratogenic effect may result in physical damage and specific facial anomalies, growth delays, neurological defects along with intellectual disabilities and behavioral problems. Children affected show difficulties in verbal learning, memory, visual-spatial abilities, attention, logic and math abilities, information processing, executive functions as well as in many other domains and in general coping with daily life. Total abstention from alcohol during pregnancy is strongly recommended, as a safe threshold of consumption has not been established yet. Hence, the early identification of alcohol consumption in pregnancy is crucial. Specific methodologies to overcome difficulties related to the identification of alcohol behavior in pregnant women are needed and intervention protocols should be implemented to prevent damage in offsprings. This paper gives an overview on this pathology, from clinical delineation to epidemiology and risk factors with a special focus to promote alcohol-free pregnanc

Caesarean section in preventing stillbirths in pregnancy complicated with COVID-19. A narrative review

Introduction: COVID-19 is a complex syndrome caused by SARS-Cov-2. It mainly affects the respiratory system, but it could cause serious harm during pregnancy. An increase in stillbirths and preterm births has been highlighted by many authors. Although WHO and Royal College of Obstetrics and Gynecology don't recommend elective cesarean section in women with confirmed infection, cesarean sections were performed by many clinicians. This short narrative review aims to analyze pieces of evidence found in literature about the effectiveness of cesarean section in preventing stillbirths in COVID-19 positive mothers. Methods: Studies included in the present review were retrieved searching MEDLINE (last access August 5th, 2021) with the following keywords: "pregnant woman with covid-19", "Caesarean section", "Ab-dominal Delivery" and "Stillbirth". Studies regarding the mode of delive-ry in pregnant women infected with COVID-19 and neonatal outcomes were included. Studies about biology, anesthesiology and necroscopy were excluded. Filters for "human" and "English" were applied. Results: Searching MEDLINE, 24 references were found. Other 103 articles were found searching bibliography. Two references were excluded after duplicate removal, 77 references after the title screen and 27 after the abstract screen. The final number of references included was 23. Most of the included studies were case reports. Most of them were from China. Discussion: Many authors highlighted the increased risk of fetal death in pregnancies complicated with SARS-Cov-2 infection, but it is not clear if Caesarean Section could reduce this risk. Pieces of evidence show that most clinicians choose to perform an elective cesarean section mostly because of maternal conditions or the fear of possible vertical transmission. Data show that mode of delivery doesn't affect the neonatal outcome and Caesarean Section doesn't reduce the positivity rate among neonates. Different opinions were found about the possible infection of amniotic fluid, cord blood and placenta. The risk of vertical transmission is considered moderate or low by most of the authors. Positivity to SARS-Cov-2 isn't an indication of elective cesarean section by itself, but this mode of delivery should be optioned in patients with other obstetrical indications or with severe conditions due to COVID. The recent increase in stillbirths could be related to the overall deterioration of maternal conditions

Acute alcohol intoxication: a clinical overview

Alcohol is a legal and yet detrimental psychoactive substance, capable of establishing addiction and impacting the physical, mental, social, and economic health of people. Alcohol intake causes a large variety of tissue damages severely impacting the nervous system, digestive and cardiovascular systems and causing oral cavity, oropharyngeal, hypopharyngeal, esophageal, colon-rectal, laryngeal, liver and intrahepatic bile duct, and breast cancers. Alcohol can also play a role in the pathogenesis of diabetes mellitus, cardiomyopathy and hemorrhagic strokes. When drunk during pregnancy it is proved to be responsible for serious damage to fetuses causing a wide range of pathological conditions from miscarriage to Fetal Alcoholic Spectrum Disorder (FASD). Acute ethanol intoxication happens when the amount of alcohol consumed is greater than the disposal capacity of the liver, causing an accumulation of its metabolites displayed by initial dysphoria and disinhibition. Nausea, vomiting, memory loss could happen. Although, it can lead to more serious conditions like impaired speaking, impaired coordination, unstable gait, nystagmus, stupor, or coma. Respiratory depression and death could also happen in such cases. Unfortunately, diagnosis of acute alcohol intoxication is difficult because most of the drinkers deny or minimize their assumption. It is dramatically important to assess when the last intake happened to avoid withdrawal syndrome. Alcohol acute intoxication can be considered a serious harm to health and a relevant issue for healthcare provid-ers working in emergency rooms. Differential diagnosis is crucial to avoid serious outcomes. There is no consensus about therapies for acute intoxication, but supportive and symptomatic treatments were proved effective. The repercussions of alcohol misuse over drinkers' social, familiar, economical and working life enhance the importance of a multidisciplinary approach in such cases

Motivational enhancement therapy versus cognitive behavioral therapy in a cohort of men and women with alcohol use disorder

The clinical manifestations of alcohol dependence are not homogeneous. Many studies described both cognitive impairments and psychiatric disorders among people with Alcohol use disorder (AUD). However, AUD can be present without comorbid psychiatric disorders or severe cognitive deficits, namely, “pure alcoholics”. Until now, knowledge about effective treatments for this typology of AUD patients remains unknown. The aim of the present study was to assess two psychological methods of intervention: Cognitive-behavioral treatment (CBT) in the short format and the Motivational enhancement therapy (MET). We then opted to compare the efficacy of methods in treating AUD in both men and women pure alcoholics. We performed a controlled and randomized study consisting of 325 people affected by AUD (244 men, 81 women). 72.3% (n=235; 181 men 54 women) were excluded according to selection criteria. The major percentage of exclusion (38.7%; n=91; 63 men 28 women) regarded patients with comorbid psychiatric disorders. Only the 90 remaining test subjects (27.7% of the sample population; 63 men and 27 women) classified as pure alcoholics were eligible for this study. The test subjects were divided into two groups. One group underwent MET (n=47; 35 men and 12 women) and the other underwent CBT (n=43; 28 men and 15 women). We found a significant adherence to the treatment in the CBT group (19 men and 9 women) compared to the MET group (3 men and 1 woman). At the end of treatment, the dropout rates for the CBT and MET therapy groups were 34.9% and 91.5%, respectively. Moreover, we found no differences in the percentage of abstinent days between CBT and MET groups at three months (CBT: n=36; mean 91.40±15.34; MET: n=18; mean 93.90±11.95; t(52)= 0.605, p=0.550), at six months (CBT: N=30; mean 85.00±30.71; MET: n=9; mean 87.78±33.08; t(37)=-0.234, p=0.820) and at twelve months from the beginning of treatment (CBT: n=28; mean 90.14±22.06; MET: n=4; mean 100±0; t(30)=-0.881, p=0.838). In conclusion, we disclose that CBT in the short format could be an effective treatment strategy for pure alcoholics without psychiatric disorders or severe cognitive deficits

Oxidative stress inhibition by resveratrol in alcohol dependent mice

Objective uncontrolled ingestion of alcohol has dramatic consequences on the entire organism also associated with the oxidation process induced by alcohol by elevating radical oxygen species (ROS). Resveratrol, a non-flavonoid phenol, shows well-documented antioxidant properties. We investigated the potential antioxidant ability of this natural compound in a mouse model of alcohol addiction. Methods we administered (per os) for two months 10 mg/kg/day of resveratrol in alcoholic adult male mice. Oxidative stress was evaluated by measuring serum free oxygen radicals defense (FORD) and free oxygen radicals (FORT) levels. Resveratrol metabolites were measured in the serum of mice administered with resveratrol. Finally, the effect of resveratrol on alcohol-induced alteration of BDNF in the liver was investigated. Results prolonged consumption of resveratrol strongly counteracts serum ROS formation caused by chronic alcohol intake, without effects on natural, free oxygen radical defense. The presence of resveratrol metabolites only in the serum of animals supplemented with resveratrol potentiates the evidence that the antioxidant effect observed is due to the ingestion of the natural compound. Moreover, resveratrol supplementation can counteract alcohol-induced BDNF elevation in the liver, the main target of organ alcohol-induced damage. Conclusion the consumption of resveratrol through metabolite formation may play a protective role, by decreasing free radical formation, and by modulating BDNF involved in hepatic disruption induced by chronic alcohol consumption. Further investigation about the mechanism underlying the protective effect could reinforce the potential use of resveratrol as a dietary supplement to prevent damage associated with chronic alcohol abuse

Behavioral responses in people affected by alcohol use disorder and psychiatric comorbidity: correlations with addiction severity

Aim. In this study, we investigated in people suffering from alcohol use disorder (AUD) with or without dual diagnosis (concomitant psychiatric disability) how they feel their dependence condition. We predicted that AUD people with a dual diagnosis could feel potentiated their addiction.Methods. Alcohol habits and psychiatric conditions of 183 AUD men and 62 AUD women were measured by using the DSM-5, the severity of alcohol dependence questionnaire (SADQ), the alcohol anamnesis and psychiatric examination by the symptom check list 90-R (SCL-90-R).Results. We have shown that alcohol drinking does not correlate with both psychiatric examination and self-reported psychopathology. SADQ shows that severe alcohol dependence correlates with highest psychiatric symptoms and with the levels of alcohol consumption.Conclusions. This finding suggests that high SADQ scores may represent a tool to early disclose only patients with dual diagnosis. SADQ may provide information to address pharmacological interventions because revealing aspects of the dark side of addiction potentiated by AUD associated psychopathology.

Nerve growth factor in brain diseases

The nerve growth factor (NGF) belongs to a family of proteins termed neurotrophins, consisting of NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5 and NT-6. Today, NGF is well recognized to mediate a large number of trophobiological actions resulting in neurotrophic, immunotrophic and/or metabotrophic effects. The pathobiology of neurodegenerative diseases, including Alzheimer disease, psychiatric disorders (e.g. depression and schizophrenia) and brain parasitic infections have in common the effect of altering the brain levels of neurotrophins and in particular NGF. The involvement of NGF and its TrkA receptor in these pathologies and the recent promising results of NGF therapies are presented and discussed