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Clinical pharmacology

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https://www.readbyqxmd.com/read/28735109/design-and-rationale-for-a-real-world-observational-cohort-of-patients-with-nonalcoholic-fatty-liver-disease-the-target-nash-study
#1
A Sidney Barritt, Norman Gitlin, Samuel Klein, Anna S Lok, Rohit Loomba, Laura Malahias, Margaret Powell, Miriam B Vos, L Michael Weiss, Kenneth Cusi, Brent A Neuschwander-Tetri, Arun Sanyal
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. NAFLD comprises the spectrum from simple steatosis (nonalcoholic fatty liver, NAFL), to steatosis with inflammation (nonalcoholic steatohepatitis, NASH). Current primary therapy recommended for NAFLD is weight loss induced by lifestyle modification. The difficulty in achieving this has led to robust pharmacological therapy development. While new drugs may show efficacy in selected phase II/III clinical trial populations, their real-world effectiveness is unknown...
July 19, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28735000/application-of-pharmacometrics-and-quantitative-systems-pharmacology-to-cancer-therapy-the-example-of-luminal-a-breast-cancer
#2
REVIEW
Brett Fleisher, Kayla Andrews, Ashley A Brown, Sihem Ait-Oudhia
Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline bridging systems biology with pharmacokinetics (PK) and pharmacodynamics (PD) leveraging the systematic understanding of drugs' efficacy and toxicity. Despite numerous challenges in applying computational methodologies for QSP and mechanism-based PK/PD models to biological, physiological, and pharmacological data, bridging these disciplines has the potential to enhance our understanding of complex disease systems such as BC...
July 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28734960/pharmacokinetic-interactions-of-curcuminoids-with-conventional-drugs-a-review
#3
REVIEW
Roodabeh Bahramsoltani, Roja Rahimi, Mohammad Hosein Farzaei
ETHNOPHARMACOLOGICAL RELEVANCE: Herb-drug interactions are of great concern in health practices. Curcumin is a natural polyphenol extracted from turmeric, a spice widely used all over the world. Curcumin is clinically used due to its acceptable safety profile and therapeutic efficacy. AIM OF THE STUDY: Current paper aims to highlight the effect of curcumin on concomitantly used drugs. METHODS: Electronic databases including PubMed, Scopus and Science Direct were searched with the keywords "curcumin" in the title/abstract and "drug interaction," "drug metabolism," "cytochrome," "P-glycoprotein" and "P450" in the whole text...
July 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28734639/ffa4-gpr120-pharmacology-and-therapeutic-opportunities
#4
REVIEW
Graeme Milligan, Elisa Alvarez-Curto, Brian D Hudson, Rudi Prihandoko, Andrew B Tobin
Free Fatty Acid receptor 4 (FFA4), also known as GPR120, is a G-protein-coupled receptor (GPCR) responsive to long-chain fatty acids that is attracting considerable attention as a potential novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). Although no clinical studies have yet been initiated to assess efficacy in this indication, a significant number of primary publications and patents have highlighted the ability of agonists with potency at FFA4 to improve glucose disposition and enhance insulin sensitivity in animal models...
July 19, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28734089/dementia-risk-and-prevention-by-targeting-modifiable-vascular-risk-factors
#5
REVIEW
Sana Tariq, Philip A Barber
The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society. The most common type of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) often co-exists in the brain and shares common, modifiable risk factors, which are targeted in numerous secondary prevention trials...
July 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28733984/implant-treatment-in-pharmacologically-immunosuppressed-liver-transplant-patients-a-prospective-controlled-study
#6
Víctor Paredes, Rosa María López-Pintor, Jesús Torres, Juan Carlos de Vicente, Mariano Sanz, Gonzalo Hernández
OBJECTIVES: The main objective of this prospective study was to evaluate the long-term outcome of implant therapy in liver transplant patients (LTP). The secondary goal was to assess several implant- and patient-dependent variables, such as peri-implantitis (PI), peri-implant mucositis (PIM), bone loss (BL), and immediate postoperative complications. MATERIAL AND METHODS: Two groups, including 16 pharmacologically immunosuppressed LTP and 16 matched controls, received 52 and 54 implants, respectively, between 1999 and 2008...
July 21, 2017: Clinical Oral Implants Research
https://www.readbyqxmd.com/read/28733905/glp-1-glucagon-receptor-co-agonism-for-treatment-of-obesity
#7
REVIEW
Miguel A Sánchez-Garrido, Sara J Brandt, Christoffer Clemmensen, Timo D Müller, Richard D DiMarchi, Matthias H Tschöp
Over a relatively short period, obesity and type 2 diabetes have come to represent a large medical and economic burden to global societies. The epidemic rise in the prevalence of obesity has metabolic consequences and is paralleled by an increased occurrence of other diseases, such as diabetes, cancer and cardiovascular complications. Together, obesity and type 2 diabetes constitute one of the more preventable causes of premature death and the identification of novel, safe and effective anti-obesity drugs is of utmost importance...
July 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28733759/management-of-gait-changes-and-fall-risk-in-mci-and-dementia
#8
REVIEW
Gilles Allali, Joe Verghese
Gait disorders and falls are very prevalent in aging, especially in older adults with cognitive impairment: older adults with dementia are 2-3 times more likely to fall than their non-demented counterparts. The management of gait disorders and falls in older adults with mild cognitive impairment (MCI) or dementia begins by their identification with the use of specific screening tools, such as measuring gait speed, use of dual-task gait tests, or diagnosing motoric cognitive risk syndrome, a newly described pre-dementia syndrome...
September 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28733468/management-impact-effects-on-quality-of-life-and-prognosis-in-men1
#9
Francesca Marini, Francesca Giusti, Francesco Tonelli, Maria Luisa Brandi
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant endocrine tumor syndrome, caused by inactivating mutations of the MEN1 tumor suppressor gene at 11q13 locus, which predisposes to develop tumors in target neuroendocrine tissues. Since the positional cloning and identification of the causative gene in 1997, genetic diagnosis, by the sequencing-based research of gene mutations, has become an important tool in the early and differential diagnosis of the disease. Application of the genetic test, in MEN1 index cases and in first degree relatives of mutated patients, has been constantly increasing during the last two decades, also thanks to the establishment of multidisciplinary referral centers and specific genetic counselling, and thanks to the wide availability of high throughput instruments for gene sequencing and gene mutation identification...
July 21, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28733448/pathophysiology-of-cardiorenal-syndrome-in-patients-with-heart-failure-potential-therapeutic-targets
#10
Hiroyuki Takahama, Masafumi Kitakaze
Despite the development of pharmacological inventions and new non-pharamacological techniques to prevent and treat HF, the mortality rate in patients with symptomatic HF remains high. To conquer these difficulties, the pathophysiology of HF should be considered within a wide range of views. Given the diverse mechanisms of HF pathophysiology, renal and cardiac functions have close and complementary interconnections. Recent studies suggest that communication between kidney and heart through bidirectional pathways causes significant pathological changes...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28733142/deprescribing-for-frail-older-people-learning-from-the-case-of-mrs-hansen
#11
Anne Gerd Granas, Marit Stendal Bakken, Sabine Ruths, Katja Taxis
Drug treatment is often an essential part in treatment and prevention of diseases in older people, but there is much concern about inappropriate medication use. This paper aims to describe the complexity of medication safety issues and clinical judgments when optimizing prescribing in older individuals. It uses the case of Mrs. Hansen, an aged nursing home resident, to illustrate the facilitators and barriers of this process. With decreasing life expectancy, medication use should shift from cure to care, focusing on symptomatic treatment to increase the patient's well-being...
July 13, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28732252/update-on-medical-treatment-of-uterine-fibroids
#12
REVIEW
Fátima Faustino, Margarida Martinho, José Reis, Fernanda Águas
OBJECTIVES: In this review paper, the pros and cons of the available pharmacological options for the treatment of uterine fibroids are explored, including oral progestogens, levonorgestrel intra-uterine device, gonadotropin-releasing hormone analogs and progesterone receptor modulators with an emphasis on ulipristal acetate. STUDY DESIGN: The choice of the appropriate therapeutic approach for uterine fibroids depends on several factors, including women's age, parity, childbearing aspirations and wish to preserve fertility, extent and severity of symptoms, size, number and location of myomas, risk of malignancy and proximity to menopause...
July 8, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28730281/pk-pd-studies-on-non-selective-pde-inhibitors-in-rats-using-camp-as-a-marker-of-pharmacological-response
#13
Artur Świerczek, Elżbieta Wyska, Sebastian Baś, Marta Woyciechowska, Jacek Mlynarski
In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats. Male Wistar rats were administered LPS (1 mg kg(-1), i...
July 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28729967/tesevatinib-ameliorates-progression-of-polycystic-kidney-disease-in-rodent-models-of-autosomal-recessive-polycystic-kidney-disease
#14
William E Sweeney, Philip Frost, Ellis D Avner
AIM: To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). METHODS: We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation...
July 6, 2017: World Journal of Nephrology
https://www.readbyqxmd.com/read/28729866/cytokine-induced-killer-cells-as-pharmacological-tools-for-cancer-immunotherapy
#15
REVIEW
Xingchun Gao, Yajing Mi, Na Guo, Hao Xu, Lixian Xu, Xingchun Gou, Weilin Jin
Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3(+)CD56(+) natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28729850/drug-resistant-epilepsy-multiple-hypotheses-few-answers
#16
REVIEW
Fei Tang, Anika M S Hartz, Björn Bauer
Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28729837/optimization-and-in-vivo-profiling-of-a-refined-rat-model-of-walker-256-breast-cancer-cell-induced-bone-pain-using-behavioral-radiological-histological-immunohistochemical-and-pharmacological-methods
#17
Priyank Shenoy, Andy Kuo, Irina Vetter, Maree T Smith
In the majority of patients with advanced breast cancer, there is metastatic spread to bones resulting in pain. Clinically available drug treatments for alleviation of breast cancer-induced bone pain (BCIBP) often produce inadequate pain relief due to dose-limiting side-effects. A major impediment to the discovery of novel well-tolerated analgesic agents for the relief of pain due to bony metastases is the fact that most cancer-induced bone pain models in rodents relied on the systemic injection of cancer cells, causing widespread formation of cancer metastases and poor general animal health...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28729815/symposium-report-an-evidence-based-approach-to-ibs-and-cic-applying-new-advances-to-daily-practice-a-review-of-an-adjunct-clinical-symposium-of-the-american-college-of-gastroenterology-meeting-october-16-2016-%C3%A2-las-vegas-nevada
#18
William D Chey
Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials...
February 2017: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#19
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729304/effectiveness-of-the-management-of-major-depressive-episodes-disorder-in-adults-with-comorbid-chronic-physical-diseases-a-protocol-for-a-systematic-review-and-meta-analysis
#20
Pablo Martínez, Ariel Castro, Diego Alonso, Paul A Vöhringer, Graciela Rojas
INTRODUCTION: Depression is a global-scale public health problem, and a significant association has been established between depression and chronic physical diseases. This growing comorbidity poses a challenge to healthcare systems. We aim to assess the effectiveness of the management of major depressive episodes/disorder in adults with comorbid chronic physical diseases. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of randomised clinical trials...
July 20, 2017: BMJ Open
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