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Clinic pharmacology

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https://www.readbyqxmd.com/read/29346775/brd4-promotes-dna-repair-and-mediates-the-formation-of-tmprss2-erg-gene-rearrangements-in-prostate-cancer
#1
Xiangyi Li, GuemHee Baek, Susmita G Ramanand, Adam Sharp, Yunpeng Gao, Wei Yuan, Jon Welti, Daniel N Rodrigues, David Dolling, Ines Figueiredo, Semini Sumanasuriya, Mateus Crespo, Adam Aslam, Rui Li, Yi Yin, Bipasha Mukherjee, Mohammed Kanchwala, Ashley M Hughes, Wendy S Halsey, Cheng-Ming Chiang, Chao Xing, Ganesh V Raj, Sandeep Burma, Johann de Bono, Ram S Mani
BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346639/comparison-of-dopamine-d3-and-d2-receptor-occupancies-by-a-single-dose-of-blonanserin-in-healthy-subjects-a-positron-emission-tomography-study-with-11c-phno
#2
Amane Tateno, Takeshi Sakayori, Woo-Chan Kim, Kazuyoshi Honjo, Haruo Nakayama, Ryosuke Arakawa, Yoshiro Okubo
Background: Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Methods: Six healthy males (mean 35...
January 13, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29346311/apoptotic-and-nonapoptotic-activities-of-pterostilbene-against-cancer
#3
REVIEW
Rong-Jane Chen, Hsiao-Che Kuo, Li-Hsin Cheng, Yu-Hsuan Lee, Wen-Tsan Chang, Bour-Jr Wang, Ying-Jan Wang, Hung-Chi Cheng
Cancer is a major cause of death. The outcomes of current therapeutic strategies against cancer often ironically lead to even increased mortality due to the subsequent drug resistance and to metastatic recurrence. Alternative medicines are thus urgently needed. Cumulative evidence has pointed out that pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, PS) has excellent pharmacological benefits for the prevention and treatment for various types of cancer in their different stages of progression by evoking apoptotic or nonapoptotic anti-cancer activities...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29345985/cyp3a-activity-and-rivaroxaban-serum-concentrations-in-russian-patients-with-deep-vein-thrombosis
#4
Dmitriy Alexeyevich Sychev, Arshak Vardanyan, Aleksandr Rozhkov, Edita Hachatryan, Ani Badanyan, Valery Smirnov, Anna Ananichuk, Natalya Denisenko
BACKGROUND: Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome involved in the metabolism of nearly 50% of all medications. Thus, its effective concentration depends on multiple pharmacologic parameters. METHODS: The primary goal of our research was to study the correlation between the CYP3A family activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83 years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days after diagnosis and 20 mg/day for the follow-up period of 6 months...
January 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29345866/cognitive-impairment-in-patients-with-depression-awareness-assessment-and-management
#5
REVIEW
Larry Culpepper, Raymond W Lam, Roger S McIntyre
​​ Cognitive impairment is a common, often persistent, symptom of major depressive disorder (MDD) that is disproportionately represented in patients who have not returned to full psychosocial functioning. The ultimate goal of treatment in depression is full functional recovery, and assessing patients for cognitive impairment and selecting treatments that address cognitive dysfunction should lead to improved functional outcomes. Unfortunately, many clinicians use screening and assessment tools that are not suited for measuring cognitive impairment in patients with depression...
November 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29345589/neonatal-systemic-thrombosis-an-updated-overview
#6
Salvatore Santo Signorelli, Gea Oliveri Conti, Angelo Claudio Molinari, Martino Ruggieri, Alfina Grasso, Margherita Ferrantea
Thromboembolic disease is a complex disorder with a multifactorial aetiology and a severe outcome. In newborns and children it may be missed or diagnosed late, thus worsening the prognosis. The neonatal disease is different from the disorder affecting older children and adults. However, scant epidemiological data and few randomised clinical trials regarding paediatric patients are available, and treatment recommendations are largely based on adult guidelines. Younger patients then have several decades over which they will suffer from the complications of thrombosis and risk of a new thrombotic episode...
January 16, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29345505/the-pharmacological-management-of-metabolic-syndrome
#7
Julie Rask Larsen, Lorena Dima, Christoph U Correll, Peter Manu
Introduction The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice...
January 18, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29345193/serotonin-2a-receptor-inhibition-protects-against-the-development-of-pulmonary-hypertension-and-pulmonary-vascular-remodeling-in-neonatal-mice
#8
Cassidy Delaney, Laurie Sherlock, Susan Fisher, Joanne K Maltzahn, Clyde J Wright, Eva Nozik-Grayck
Pulmonary hypertension (PH) complicating bronchopulmonary dysplasia (BPD) worsens clinical outcomes in former preterm infants. Increased serotonin (5-hydroxytryptamine, 5-HT) signaling plays a prominent role in PH pathogenesis and progression in adults. We hypothesized that increased 5-HT signaling contributes to the pathogenesis of neonatal PH complicating BPD and neonatal lung injury. Thus, we interrogated 5-HT signaling in neonatal mice exposed to bleomycin, previously demonstrated to induce PH and alveolar simplification...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29345040/assessing-and-addressing-cognitive-impairment-in-bipolar-disorder-the-international-society-for-bipolar-disorders-targeting-cognition-task-force-recommendations-for-clinicians
#9
REVIEW
K W Miskowiak, K E Burdick, A Martinez-Aran, C M Bonnin, C R Bowie, A F Carvalho, P Gallagher, B Lafer, C López-Jaramillo, T Sumiyoshi, R S McIntyre, A Schaffer, R J Porter, S Purdon, I J Torres, L N Yatham, A H Young, L V Kessing, E Vieta
OBJECTIVES: Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and address cognitive impairment. METHODS: The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face-to-face meeting, telephone conference call and email exchanges...
January 18, 2018: Bipolar Disorders
https://www.readbyqxmd.com/read/29344814/nutritional-therapy-in-autosomal-dominant-polycystic-kidney-disease
#10
REVIEW
Biagio R Di Iorio, Adamasco Cupisti, Claudia D'Alessandro, Antonio Bellasi, Vincenzo Barbera, Luca Di Lullo
CKD-related nutritional therapy (NT) is a crucial cornerstone of CKD patients' treatment, but the role of NT has not been clearly investigated in autosomal dominant polycystic kidney disease (ADPKD). Several clinical studies have focused on new pharmacological approaches to delay cystic disease progression, but there are no data on dietary interventions in ADPKD patients. The aim of this paper is to analyze the evidence from the literature on the impact of five nutritional aspects (water, sodium, phosphorus, protein intake, and net acid load) in CKD-related ADPKD extrapolating-where information is unavailable-from what occurs in CKD non-ADPKD patients Sodium intake restriction could be useful in decreasing the growth rate of cysts...
January 17, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29344438/new-therapeutic-approaches-in-obesity-and-metabolic-syndrome-associated-with-polycystic-ovary-syndrome
#11
REVIEW
Fatima Saleem, Syed W Rizvi
Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting reproductive and metabolic indices. PCOS is commonly associated with a high prevalence of insulin resistance and obesity; this association carries an increased risk of developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. Guidelines recommend lifestyle modification, metformin, hormonal contraceptives (HCs), and bariatric surgery as the main treatment options in obese patients with PCOS. Studies are being conducted to test the efficacy of existing treatment options as well as to discover new therapies...
November 13, 2017: Curēus
https://www.readbyqxmd.com/read/29344421/anti-aging-implications-of-astragalus-membranaceus-huangqi-a-well-known-chinese-tonic
#12
REVIEW
Ping Liu, Haiping Zhao, Yumin Luo
Owing to a dramatic increase in average life expectancy and the Family Planning program of the 1970s - 1990s, China is rapidly becoming an aging society. Therefore, the investigation of healthspan-extending drugs becomes more urgent. Astragalus membranaceus (Huangqi) is a major medicinal herb that has been commonly used in many herbal formulations in the practice of traditional Chinese medicine (TCM) to treat a wide variety of diseases and body disorders, or marketed as life-prolonging extracts for human use in China, for more than 2000 years...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344420/the-effects-of-baicalin-and-baicalein-on-cerebral-ischemia-a-review
#13
REVIEW
Wei Liang, Xiaobo Huang, Wenqiang Chen
Ischemic stroke, producing a high mortality and morbidity rate, is a common clinical disease. Enhancing the prevention and control of ischemic stroke is particularly important. Baicalin and its aglycon baicalein are flavonoids extracted from Scutellaria baicalensis, an important traditional Chinese herb. In recent years, a growing body of evidences has shown that baicalin and baicalein could be effective in the treatment of cerebral ischemia. Pharmacokinetic studies have shown that baicalin could penetrate the blood-brain barrier and distribute in cerebral nuclei...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344418/advances-in-the-studies-of-ginkgo-biloba-leaves-extract-on-aging-related-diseases
#14
REVIEW
Wei Zuo, Feng Yan, Bo Zhang, Jiantao Li, Dan Mei
The prevalence of degenerative disorders in public health has promoted in-depth investigations of the underlying pathogenesis and the development of new treatment drugs. Ginkgo biloba leaves extract (EGb) is obtained from Ginkgo biloba leaves and has been used for thousands of years. In recent decades, both basic and clinical studies have established the effects of EGb. It is widely used in various degenerative diseases such as cerebrovascular disease, Alzheimer's disease, macroangiopathy and more. Here, we reviewed several pharmacological mechanisms of EGb, including its antioxidant properties, prevention of mitochondrial dysfunctions, and effect on apoptosis...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344416/lycium-barbarum-a-traditional-chinese-herb-and-a-promising-anti-aging-agent
#15
REVIEW
Yanjie Gao, Yifo Wei, Yuqing Wang, Fang Gao, Zhigang Chen
Lycium barbarum has been used in China for more than 2,000 years as a traditional medicinal herb and food supplement. Lycium barbarum contains abundant Lycium barbarum polysaccharides (LBPs), betaine, phenolics, carotenoids (zeaxanthin and β-carotene), cerebroside, 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG), β-sitosterol, flavonoids and vitamins (in particular, riboflavin, thiamine, and ascorbic acid). LBPs are the primary active components of Lycium barbarum. In this review, we discuss the pharmacological activities of LBPs and other major components...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344414/herba-cistanches-anti-aging
#16
REVIEW
Ningqun Wang, Shaozhen Ji, Hao Zhang, Shanshan Mei, Lumin Qiao, Xianglan Jin
The Cistanche species ("Rou Cong Rong" in Chinese) is an endangered wild species growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been used as a tonic in China for many years. Modern pharmacological studies have since demonstrated that Herba Cistanches possesses broad medicinal functions, especially for use in anti-senescence, anti-oxidation, neuroprotection, anti-inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti-osteoporosis and the promotion of bone formation...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344413/therapeutic-potential-and-cellular-mechanisms-of-panax-notoginseng-on-prevention-of-aging-and-cell-senescence-associated-diseases
#17
REVIEW
Haiping Zhao, Ziping Han, Guangwen Li, Sijia Zhang, Yumin Luo
Owing to a dramatic increase in average life expectancy, most countries in the world are rapidly entering an aging society. Therefore, extending health span with pharmacological agents targeting aging-related pathological changes, are now in the spotlight of gerosciences. Panax notoginseng (Burk.) F. H. Chen, a species of the genus Panax, has been called the "Miracle Root for the Preservation of Life," and has long been used as a Chinese herb with magical medicinal value. Panax notoginseng has been extensively employed in China to treat microcirculatory disturbances, inflammation, trauma, internal and external bleeding due to injury, and as a tonic...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344342/frontotemporal-dementia-latest-evidence-and-clinical-implications
#18
REVIEW
Juan Joseph Young, Mallika Lavakumar, Deena Tampi, Silpa Balachandran, Rajesh R Tampi
Background: Frontotemporal dementia (FTD) describes a cluster of neurocognitive syndromes that present with impairment of executive functioning, changes in behavior, and a decrease in language proficiency. FTD is the second most common form of dementia in those younger than 65 years and is expected to increase in prevalence as the population ages. This goal in our review is to describe advances in the understanding of neurobiological pathology, classification, assessment, and treatment of FTD syndromes...
January 2018: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/29344341/treatment-of-adult-adhd-a-clinical-perspective
#19
REVIEW
Josh Geffen, Kieran Forster
Adult attention deficit/hyperactivity disorder (ADHD) has moved from the blurred edge of clinical focus to clear recognition as a prevalent and significant disorder in its own right. It is a relatively common comorbidity which if identified and treated may open the door to better outcomes for hard-to-treat patients. Conversely, failure to identify and treat adult ADHD is linked to negative outcomes. The recognition of the importance of adult ADHD in a subset of our patients challenges us to overcome our anxiety about this diagnosis and prevent the societal marginalization of vulnerable patients...
January 2018: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/29344328/management-of-functional-dyspepsia-state-of-the-art-and-emerging-therapies
#20
REVIEW
Hiroshi Yamawaki, Seiji Futagami, Mako Wakabayashi, Noriko Sakasegawa, Shuhei Agawa, Kazutoshi Higuchi, Yasuhiro Kodaka, Katsuhiko Iwakiri
Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS...
January 2018: Therapeutic Advances in Chronic Disease
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