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Manon Auffret, Sophie Drapier, Marc Vérin
Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges...
March 15, 2018: Drugs in R&D
Emmanuelle A D Schindler, Ryan M Wallace, Jordan A Sloshower, Deepak C D'Souza
Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class...
2018: Frontiers in Pharmacology
Hetal Patel, Manikandan Periyasamy, Georgina P Sava, Alexander Bondke, Brian W Slafer, Sebastian H B Kroll, Marion Barbazanges, Richard Starkey, Silvia Ottaviani, Alison Harrod, Eric O Aboagye, Laki Buluwela, Matthew J Fuchter, Anthony G M Barrett, Charles Coombes, Simak Ali
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942...
March 15, 2018: Molecular Cancer Therapeutics
Lauren Brinkley-Rubinstein, Nickolas Zaller, Sarah Martino, David H Cloud, Erin McCauley, Andrew Heise, David Seal
The United States (US) is in the midst of an epidemic of opioid use; however, overdose mortality disproportionately affects certain subgroups. For example, more than half of state prisoners and approximately two-thirds of county jail detainees report issues with substance use. Overdose is one of the leading causes of mortality among individuals released from correctional settings. Even though the criminal justice (CJ) system interacts with a disproportionately high number of individuals at risk of opioid use and overdose, few CJ agencies screen for opioid use disorder (OUD)...
February 24, 2018: Addictive Behaviors
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Atul Ambekar, Monica Mongia
A number of research designs have been used to study the efficacy of psychosocial interventions in addictive disorders, including open label studies and randomised controlled trials. Only through a rigorously conducted research, evidence base for effectiveness of a psychosocial intervention can be established. However, research on these interventions are fraught with a number of challenges. It is imperative for researchers to ask appropriate research questions based on sound theoretical understanding of psychiatric disorders, psychosocial interventions and research designs...
February 2018: Indian Journal of Psychiatry
Sunita Simon Kurpad
It is important for health professionals to have an ethical framework to help take decisions regarding psychosocial interventions in patients with addictive disorders. As patients with addictive disorders are vulnerable to unethical actions in the name of treatment, therapists need to aware of their role in delivering ethical care - not just in their own clinical practice but in the setting in which they deliver the interventions. This article aims to sensitize the health professional to the various arenas in which ethical challenges may arise...
February 2018: Indian Journal of Psychiatry
Reshma Malick
Prevention in the community and at the workplace is a vital component in substance use disorder treatment and management. Mobilizing the community, creating awareness that addiction to substances is a disease, that it is treatable and that treatment is available are all essential. A cost-effective prevention and treatment approach plays a major role in creating drug free communities. Workplace prevention policies to prevent and manage substance use disorders leads to safer work environments, better motivated teams of workers and a productive workforce...
February 2018: Indian Journal of Psychiatry
Manoj Kumar Sharma, Thamil Selvan Palanichamy
Increase in the use of technology has led to an increase in various kinds of technological addictions. A range of psychological and behavioural theories has been proposed to explain technology addictions. These include learning theories, reward-deficiency hypothesis, impulsivity, cognitive-behavioural models and social skills deficiency theories. While no particular form of psychological intervention has been suggested as being the golden standard for its treatment, the most frequently investigated approaches have been cognitive behavioural therapy (CBT) and motivational enhancement therapy...
February 2018: Indian Journal of Psychiatry
Mrunal Bandawar, Venkata Lakshmi Narasimha, Prabhat Chand
The expanding use of digital technology in mental health has widened the scope of emerging addiction interventions. This review focus on the use of technological advances in the field of addiction and mental health. We discuss about how these advances has been implemented in addiction treatment and research. Further, we also mention about the utilisation of these services in India.
February 2018: Indian Journal of Psychiatry
Gitanjali Narayanan, Shaima Naaz
Recent research points to a shift from categorical diagnoses to a dimensional understanding of psychopathology and mental health disorders. In parallel, there has been a rise in newer psychosocial treatment modalities, which are inherently transdiagnostic. Transdiagnostic approaches are those that identify core vulnerabilities and apply universal principles to therapeutic treatment. As treatment of substance use disorders (SUD) must invariably accommodate such vulnerabilities, clinicians are finding such interventions useful...
February 2018: Indian Journal of Psychiatry
T S Sathyanarayana Rao, Shreemit Maheshwari, Manju George, Suhas Chandran, Shivanand Manohar, Suman S Rao
Substance abuse and addictive disorders are very common in the community. Patients with addictive disorders frequently experience sexual dysfunctions and chronic use of substances tends to adversely affect all stages of sexual response, in both male and female abusers. An important aspect in the management of sexual dysfunction is psychosocial intervention. In addictive disorders, sexual dysfunction is of high clinical relevance, as it often leads to treatment non adherence and sexual or marital disharmony...
February 2018: Indian Journal of Psychiatry
Malika Verma, Ajay Vijayakrishnan
Psychoanalytic psychotherapy can afford a viable treatment option for certain carefully chosen patients whose needs go beyond the immediate control of substance use. Though the evidence base specifically for addictions is lacking, an emerging body of evidence has demonstrated good effect in the commonly seen co-morbid conditions such as depression, anxiety and personality pathology.
February 2018: Indian Journal of Psychiatry
Rakesh K Chadda, Biswadeep Chatterjee
Addictive disorders have a strong psychosocial component in their etiogenesis, and hence psychosocial approaches form a significant part of management planning with a role in prevention, treatment, relapse prevention and long term rehabilitation. Due to a number of myths and misconceptions associated with addictive disorders, there is often strong resistance from the patients as well as the families towards treatment. The disorder is often perceived as a bad habit and hence not requiring treatment. It is very important to break this barrier to bring the patient and the family in treatment engagement...
February 2018: Indian Journal of Psychiatry
Catherine F Moore, Valentina Sabino, Pietro Cottone
Eating disorders and some forms of obesity are characterized by addictive-like, compulsive eating behavior which contains numerous similarities with compulsive drug use. Food intake is in part mediated by reward and reinforcement processes that can become dysregulated in these disorders. Additionally, impairments in inhibitory control regulation of reward-related responding can cause or further exacerbate binge and compulsive eating. Dysfunctions in two neurotransmitter systems in the mesocorticolimbic pathway, dopamine and glutamate, are thought to contribute to maladaptive eating behaviors...
2018: Frontiers in Pharmacology
Stephen Brimijoin, Yang Gao, Liyi Geng, Vicky P Chen
Butyrylcholinesterase (BChE), a plasma enzyme that hydrolyses the neurotransmitter, acetylcholine relatively well, with far lower efficiency than acetylcholinesterase (AChE) but with the capability to degrade a broad range of bioactive esters. AChE is universally understood as essential to cholinergic neurotransmission, voluntary muscle performance, and cognition, among other roles, and its catalytic impact is essential for life. A total absence of BChE activity, whether by enzyme inhibition or simple lack of enzyme protein is not only compatible with life, but does not lead to obvious physiologic disturbance...
2018: Frontiers in Pharmacology
Peiye Shen, Ying Jing, Ruiyun Zhang, Mei-Chun Cai, Pengfei Ma, Haige Chen, Guanglei Zhuang
Neuroendocrine bladder cancer is a relatively rare but often lethal malignancy, with cell of origin, oncogenomic architecture and standard treatment poorly defined. Here we performed comprehensive whole-genome and transcriptome sequencing on a unique cohort of genitourinary neuroendocrine neoplasms, mainly small cell carcinomas of the urinary bladder. The mutational landscape and signatures of neuroendocrine bladder cancer strikingly resembled those in conventional urothelial carcinoma, along with typically mixed histologies, supporting a common cellular origin...
March 14, 2018: Oncogene
Can Sarica, Mazhar Ozkan, Husniye Hacioglu Bay, Umit Sehirli, Filiz Onat, M Ibrahim Ziyal
BACKGROUND: Binge eating (BE) involves the consumption of a large amount of food in a short period of time and a loss of control during the binge episode. It is a key feature of the major subtypes of eating disorders like bulimia nervosa, BE disorder, anorexia nervosa binge/purge type. Alterations in the mesocorticolimbic pathway play a crucial role in its pathophysiology. OBJECTIVES: We hypothesized that BE rats receiving deep brain stimulation (DBS) in the prelimbic cortex, a functional analog of the dorsolateral prefrontal cortex in humans, would have a reduced binge size compared with those receiving sham stimulation...
March 13, 2018: Stereotactic and Functional Neurosurgery
John R Fedota, Xiaoyu Ding, Allison L Matous, Betty Jo Salmeron, Michael R McKenna, Hong Gu, Thomas J Ross, Elliot A Stein
BACKGROUND: Insular subdivisions show distinct patterns of resting-state functional connectivity (rsFC) with specific brain regions, each with different functional significance. Seeds in these subdivisions are employed to characterize the effects of acute nicotine abstinence on rsFC between insula subdivisions and brain networks implicated in addiction and attentional control. METHODS: In a within-subjects design, resting-state blood oxygen level-dependent data were collected from treatment-seeking smokers (N= 20) following smoking satiety and again following 48 hours of nicotine abstinence...
February 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Terril L Verplaetse, Kelly E Moore, Brian P Pittman, Walter Roberts, Lindsay M Oberleitner, Philip H Smith, Kelly P Cosgrove, Sherry A McKee
Background: Stress contributes to the development and maintenance of substance use disorders (SUD), with some research suggesting that the impact of stress on SUD is greater in women. However, this has yet to be evaluated in a national dataset, across major substances of abuse. Methods: Using data from the newly available U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 3; n =36,309) we evaluated relationships among past year stressful life events (0 or 1 vs...
January 2018: Chronic Stress
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