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Long term drug affect studies

Anna Wallerstedt, Peter Strom, Henrik Gronberg, Tobias Nordstrom, Martin Eklund
Background: Studies have shown that 5α-reductase inhibitors (5-ARIs) decrease the risk for low-grade prostate cancer (PC), but results are conflicting concerning high-grade PCs. The objective of the present study is to evaluate the association between 5-ARI treatment for lower urinary tract symptoms and the risk for PC. Methods: This is a population-based prospective study on all men age 40 years and older with at least one prostate-specific antigen (PSA) test in Stockholm County from January 2007 until December 2015...
March 14, 2018: Journal of the National Cancer Institute
Charles V Vorhees, Jenna N Sprowles, Samantha L Regan, Michael T Williams
High throughput screens for developmental neurotoxicity (DN) will facilitate evaluation of chemicals and can be used to prioritize those designated for follow-up. DN is evaluated under different guidelines. Those for drugs generally include peri- and postnatal studies and juvenile toxicity studies. For pesticides and commercial chemicals, when triggered, include developmental neurotoxicity studies (DNT) and extended one-generation reproductive toxicity studies. Raffaele et al. (2010) reviewed 69 pesticide DNT studies and found two of the four behavioral tests underperformed...
March 12, 2018: Toxicology and Applied Pharmacology
Liv Weichien Chen, Feng-Cheng Liu, Li-Feng Hung, Chuan-Yueh Huang, Shiu-Bii Lien, Leou-Chyr Lin, Jenn-Haung Lai, Ling-Jun Ho
Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study...
March 12, 2018: International Journal of Molecular Sciences
V Hoerr, M Franz, M W Pletz, M Diab, S Niemann, C Faber, T Doenst, P C Schulze, S Deinhardt-Emmer, B Löffler
Infective endocarditis (IE) is a life-threatening disease, caused by septic vegetations and inflammatory foci on the surface of the endothelium and the valves. Due to its complex and often indecisive presentation the mortality rate is still about 30%. Most frequently bacterial microorganisms entering the bloodstream are the underlying origin of the intracardiac infection. While the disease was primarily restricted to younger patients suffering from rheumatic heart streptococci infections, new at risk categories for Staphylococcus (S...
February 21, 2018: International Journal of Medical Microbiology: IJMM
Sareh Shahmohammadi, Mohammad Ali Sahraian, Abootorab Shahmohammadi, Rozita Doosti, Ali Zare-Mirzaie, Abdorreza Naser Moghadasi
Multiple sclerosis (MS) is one of the most important demyelinating diseases that affects the central nervous system. Its treatment often involves a long-term disease modifying therapy. According to some studies, the prevalence of autoimmune disorders, such as autoimmune hepatitis (AIH) and ulcerative colitis (UC) is higher in MS patients than in the normal population. There are also few studies that have reported the onset of UC after rituximab therapy. The present study presents a report of a 31-years old female patient suffering from aggressive multiple sclerosis, which developed into autoimmune hepatitis during the MS therapy...
March 1, 2018: Multiple Sclerosis and related Disorders
Rocco Gogliotti, Nicole Fisher, Branden Stansley, Carrie Jones, Craig Lindsley, Jeffrey Conn, Colleen Niswender
Mutations in the Methyl CpG Binding Protein 2 (MECP2) gene are responsible for the neurodevelopmental disorder Rett syndrome (RTT). MeCP2 is a DNA-binding protein whose abundance and ability to complex with HDAC3 is linked to the regulation of chromatin structure. Consequently, loss-of-function mutations in MeCP2 are predicted to have broad effects on gene expression. However, to date, studies in mouse models of RTT have identified a limited number of gene or pathway-level disruptions, and even fewer genes have been identified that could be considered amenable to classical drug discovery approaches...
March 9, 2018: Journal of Pharmacology and Experimental Therapeutics
Agostinho Lemos, Rita Meloc, Antonio J Preto, Jose G Almeida, Irina S Moreira, M Natalia D S Cordeiro
Parkinson's Disease (PD) is a long-term neurodegenative brain disorder that mainly affects the motor system. The causes are still unknown, and even though currently there is no cure, several therapeutic options are available to manage its symptoms. The development of novel anti-parkinsonian agents and an understanding of their proper and optimal use are, indeed, highly demanding. For the last decades, L-3,4-DihydrOxyPhenylAlanine or levodopa (L-DOPA) has been the gold-standard therapy for the symptomatic treatment of motor dysfunctions associated to PD...
March 8, 2018: Current Neuropharmacology
J J Garcia-Penas
INTRODUCTION: Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. AIM: To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals...
March 1, 2018: Revista de Neurologia
S D Dolzani, M V Baratta, J M Moss, N L Leslie, S G Tilden, A T Sørensen, L R Watkins, Y Lin, S F Maier
Stress is a potent etiological factor in the onset of major depressive disorder and posttraumatic stress disorder (PTSD). Therefore, significant efforts have been made to identify factors that produce resilience to the outcomes of a later stressor, in hopes of preventing untoward clinical outcomes. The NMDA receptor antagonist ketamine has recently emerged as a prophylactic capable of preventing neurochemical and behavioral outcomes of a future stressor. Despite promising results of preclinical studies performed in male rats, the effects of proactive ketamine in female rats remains unknown...
January 2018: ENeuro
Shijie Ren, Iñigo Bermejo, Emma Simpson, Ruth Wong, David L Scott, Adam Young, Matt Stevenson
As part of its single technology appraisal process, the National Institute for Health and Care Excellence invited the manufacturer (Eli Lilly) of baricitinib (BARI; Olumiant® ; a Janus kinase inhibitor that is taken orally) to submit evidence of its clinical and cost effectiveness for the treatment of moderate to severe rheumatoid arthritis (RA) after the failure of disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
March 3, 2018: PharmacoEconomics
Young Choi, Sungmin Lim, Kwan Yong Lee, Ha-Wook Park, Jaeho Byeon, Byung-Hee Hwang, Jin Jin Kim, Yong-Seog Oh, Ho-Joong Youn, Wook Sung Jung, Ki-Bae Seung, Kiyuk Chang
BACKGROUND: The effects of renin-angiotensin system (RAS) blockade on the clinical outcome in patients with stable coronary artery disease (SCAD) are conflicting. We evaluated the long-term effects of RAS blockers (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker) on the clinical outcomes in patients with SCAD without heart failure (HF) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent using a large-scale, multicenter, prospective cohort registry...
February 27, 2018: Coronary Artery Disease
Alice E Berizzi, Christina J Perry, David M Shackleford, Craig W Lindsley, Carrie K Jones, Nicola A Chen, Patrick M Sexton, Arthur Christopoulos, Christopher J Langmead, Andrew J Lawrence
Despite the cost to both individual and society, alcohol use disorders (AUDs) remain a major health risk within society, and both relapse and heavy drinking are still poorly controlled with current medications. Here we demonstrate for the first time that a centrally active and selective negative allosteric modulator for the rat M5 muscarinic acetylcholine receptor (mAChR), ML375, decreases ethanol self-administration and attenuates cue-induced reinstatement of ethanol seeking in ethanol-preferring (iP) rats...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Seokho Kang
Patients with type 2 diabetes mellitus are generally under continuous long-term medical treatment based on anti-diabetic drugs to achieve the desired glucose level. Thus, each patient is associated with a sequence of multiple records for prescriptions and their efficacies. Sequential dependencies are embedded in these records as personal factors so that previous records affect the efficacy of the current prescription for each patient. In this study, we present a patient-level sequential modeling approach utilizing the sequential dependencies to render a personalized prediction of the prescription efficacy...
February 23, 2018: Artificial Intelligence in Medicine
Emma E McGinty, Elizabeth A Stuart, G Caleb Alexander, Colleen L Barry, Mark C Bicket, Lainie Rutkow
BACKGROUND: The U.S. opioid epidemic has been driven by the high volume of opioids prescribed by healthcare providers. U.S. states have recently enacted four types of laws designed to curb high-risk prescribing practices, such as high-dose and long-term opioid prescribing, associated with opioid-related mortality: (1) mandatory Prescription Drug Monitoring Program (PDMP) enrollment laws, which require prescribers to enroll in their state's PDMP, an electronic database of patients' controlled substance prescriptions, (2) mandatory PDMP query laws, which require prescribers to query the PDMP prior to prescribing an opioid, (3) opioid prescribing cap laws, which limit the dose and/or duration of opioid prescriptions, and (4) pill mill laws, which strictly regulate pain clinics to prevent nonmedical opioid prescribing...
February 26, 2018: Implementation Science: IS
Lotte Ramerman, Pieter J Hoekstra, Gerda de Kuijper
BACKGROUND: Many people with intellectual disabilities use long-term antipsychotics for challenging behaviour and experience side-effects from these drugs, which may affect Health-related Quality of Life (HQoL). AIMS: This study aimed to investigate HQoL in people with intellectual disabilities who use long-term antipsychotics and to investigate its associations with challenging behaviour and physical symptoms often associated with antipsychotics. MATERIALS AND METHODS: We used baseline data of two studies of long-term used antipsychotics...
February 23, 2018: Research in Developmental Disabilities
M Espadas, I Insa, M Chamorro, J A Alda-Diez
INTRODUCTION: The use of psychostimulants has been present in common medical practice since the 20th century and has undergone an exponential growth in terms of the number of prescriptions. AIM: To review the current state of knowledge about the side effects of psychostimulants in the child and teen populations. DEVELOPMENT: A review was performed by searching in different databases and included clinical analyses, observational prospective studies and systematic reviews...
March 1, 2018: Revista de Neurologia
Panagiotis Karyofyllis, Varvara Papadopoulou, Vassilis Voudris, Hiromi Matsubara
PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH) is the only potentially curable form of precapillary pulmonary hypertension. Although pulmonary endarterectomy (PEA) is the preferred management strategy, a significant number of CTEPH patients will have an inoperable disease. As drug therapy is not expected to offer relief from the mechanical component of the disease, the novel technique of balloon pulmonary angioplasty (BPA) has provided a new therapeutic option for patients with inoperable CTEPH...
February 24, 2018: Current Treatment Options in Cardiovascular Medicine
Benedetta Grancini, Vera De Carlo, Mariacarlotta Palazzo, Matteo Vismara, Chiara Arici, Laura Cremaschi, Beatrice Benatti, A Carlo Altamura, Bernardo Dell'Osso
It is established that delayed effective pharmacotherapy plays a significant role in the overall burden of psychiatric disorders, which are often treated with symptomatic drugs, that is benzodiazepines (BZDs), in relation to their rapid onset of action and safety, despite long-term side effects. We aimed to assess the influence of initial treatment with BZDs on the duration of untreated illness (DUI) and whether specific sociodemographic and clinical factors could influence the choice of BZDs as first treatment in 545 patients affected by schizophrenia, mood and anxiety spectrum disorders...
February 15, 2018: International Clinical Psychopharmacology
Sara Gandini, Domenico Palli, Giuseppe Spadola, Benedetta Bendinelli, Emilia Cocorocchio, Ignazio Stanganelli, Lucia Miligi, Giovanna Masala, Saverio Caini
INTRODUCTION: Several anti-hypertensive drugs have photosensitizing properties, however it remains unclear whether long-term users of these drugs are also at increased risk of skin malignancies. We conducted a literature review and meta-analysis on the association between use of anti-hypertensive drugs and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). METHODS: We searched PubMed, EMBASE, Google Scholar and the Cochrane Library, and included observational and experimental epidemiological studies published until February 28th, 2017...
February 2018: Critical Reviews in Oncology/hematology
Nadia Steiner, Clara Rossetti, Takeshi Sakurai, Masashi Yanagisawa, Luis de Lecea, Pierre J Magistretti, Olivier Halfon, Benjamin Boutrel
Compelling evidence indicates that hypocretin/orexin signaling regulates arousal, stress and reward-seeking behaviors. However, most studies on drug reward-related processes have so far described the effects of pharmacological blockers disrupting hypocretin/orexin transmission. We report here an extensive study on cocaine-related behaviors in hypocretin/orexin-deficient mice (KO) and their heterozygous (HET) and wildtype (WT) littermates. We evaluated behavioral sensitization following repeated administrations and preference for an environment repeatedly paired with cocaine injections (15 mg/kg)...
February 15, 2018: Neuropharmacology
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