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Pharmacological Research: the Official Journal of the Italian Pharmacological Society

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https://www.readbyqxmd.com/read/28943224/the-effect-of-lipophilicity-and-dose-on-the-frequency-of-statin-associated-muscle-symptoms-a-systematic-review-and-meta-analysis
#1
REVIEW
Jordon C Irwin, Saman Khalesi, Andrew S Fenning, Rebecca K Vella
Addressing the factors which lead to the development of statin-associated muscle symptoms (SAMS) is vital for maintaining patient compliance with these pharmaceuticals, and thus improving patient outcomes. This study aimed to clarify the relationship between statin lipophilicity, or dose, and the frequency of adverse muscle symptoms using a systematic review of randomised controlled trials (RCTs). RCTs, including statin monotherapy and placebo groups, which reported data on muscle adverse events were identified through the PubMed and Scopus databases...
September 21, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28941781/glucocorticoids-and-toll-like-receptor-2-cooperatively-induce-acute-phase-serum-amyloid-a
#2
Qi Su, Günther Weindl
Serum amyloid A (SAA) is a highly conserved acute-phase protein and extrahepatic produced SAA1/2 contributes to cutaneous inflammation. Prolonged systemic or topical treatment with glucocorticoids can provoke skin diseases such as steroid-induced acne. Glucocorticoids increase Toll-like receptor 2 (TLR2) expression, however, an inflammatory mediator linked to this side effect remains elusive. We report that TLR2 agonists in combination with dexamethasone substantially increase SAA expression and production in human keratinocytes and epithelial cells...
September 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28939201/combination-drug-treatment-in-hypertension
#3
REVIEW
Costas Tsioufis, M D Costas Thomopoulos
Combination treatment of hypertension has been introduced almost 50 years ago, because of the marked blood pressure (BP) elevation of recruited patients in the early randomized controlled trials of BP lowering. However, in all subsequent trials combination treatment was per protocol anticipated irrespectively of the initial randomized treatment to ensure either a desirable BP lowering or a comparable level of BP reduction among arms. Beyond clinical trials, combination treatment is mainly used in the clinical practice to reinforce ongoing single-agent treatment to achieve hypertension control...
September 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28928073/timing-of-food-intake-sounding-the-alarm-about-metabolic-impairments-a-systematic-review
#4
REVIEW
Guglielmo Beccuti, Chiara Monagheddu, Andrea Evangelista, Giovannino Ciccone, Fabio Broglio, Soldati Laura, Simona Bo
Growing evidence points to an association between timing of food intake and obesity in humans, raising the question if when to eat matters as much as what and how much to eat. Based on the new definition of obesity as a chronobiological disease, an unusual or late meal timing represent a circadian chronodisruption, leading to metabolic impairments. Preliminary data from cross-sectional and experimental studies suggest that changes in meal timing can influence obesity and success of weight loss therapy, independently from total energy intake, dietary composition and estimated energy expenditure...
September 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28928074/curcumin-or-combined-curcuminoids-are-effective-in-lowering-the-fasting-blood-glucose-concentrations-of-individuals-with-dysglycemia-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#5
Ingrid Sofia Vieira de Meloa, Aldenir Feitosa Dos Santosb, Nassib Bezerra Buenoc
Curcuminoids have received considerable attention as therapeutical adjuvants in the treatment of dysglycemia. The purpose of this meta-analysis was to evaluate whether the supplementation of turmeric extract, curcuminoids and/or isolated curcumin is more effective than placebo in decreasing fasting blood glucose (FBG) in adults. MEDLINE, CENTRAL, ScienceDirect and gray literature databases were searched. Randomized controlled trials with the following criteria were included: (1) studied individuals older than 18 years, supplemented with curcumin, curcuminoids and/or turmeric extract (2) had a follow-up ≥4 weeks (3) used a placebo group...
September 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28923544/modulation-of-oncogenic-transcription-factors-by-bioactive-natural-products-in-breast-cancer
#6
REVIEW
Mohadeseh Hasanpourghadi, Ashok Kumar Pandurangan, Mohd Rais Mustafa
Carcinogenesis, a multi-step phenomenon, characterized by alterations at genetic level and affecting the main intracellular pathways controlling cell growth and development. There are growing number of evidences linking oncogenes to the induction of malignancies, especially breast cancer. Modulations of oncogenes lead to gain-of-function signals in the cells and contribute to the tumorigenic phenotype. These signals yield a large number of proteins that cause cell growth and inhibit apoptosis. Transcription factors such as STAT, p53, NF-κB, c-JUN and FOXM1, are proteins that are conserved among species, accumulate in the nucleus, bind to DNA and regulate the specific genes targets...
September 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28923543/selective-glucocorticoid-receptor-modulation-inhibits-cytokine-responses-in-a-canine-model-of-mild-endotoxemia
#7
J Bartko, U Derhaschnig, T Neels, G H Nabozny, C Harcken, J Leuschner, F De Vries, B Jilma
Selective glucocorticoid receptor modulators (GRMs) promise to reduce adverse events of glucocorticoids while maintaining anti-inflammatory potency. The present study tested the anti-inflammatory activity of two novel non-steroidal GRMs (GRM1: BI 607812 BS, GRM2: BI 653048 BS*H3PO4) in comparison to prednisolone in a canine model of low dose endotoxemia. This study compared the anti-inflammatory and pharmacokinetic profile of escalating daily oral doses of GRM1 (1, 2.5, 5 and 10mg/kg) and GRM2 (0.1, 0.25 and 1mg/kg) with prednisolone (0...
September 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28918174/14-3-3-adaptor-protein-protein-interactions-as-therapeutic-targets-for-cns-diseases
#8
REVIEW
Andrew Kaplan, Christian Ottmann, Alyson E Fournier
14-3-3s are a family of ubiquitously expressed adaptor proteins that regulate hundreds of functionally diverse 'client proteins.' In humans, there are seven isoforms with conserved structure and function. 14-3-3s typically bind to client proteins at phosphorylated serine/threonine motifs via a linear binding groove. Binding can have a variety of effects on the stability, activity and/or localization of the client protein. 14-3-3s are generating significant interest as potential drug targets for their involvement in cellular homeostasis and disease...
September 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28918173/edited-course-of-biomedical-research-leaping-forward-with-crispr
#9
REVIEW
Patrick J Collins, Christopher M Hale, Han Xu
Within the short few years since the report of its application in precise genome editing, CRISPR technology has become the method of choice to modify and modulate gene expression in biomedical research and therapeutic development. Subsequently, a variety of research, diagnostic, and therapeutic tools have been developed based upon CRISPR's mechanism of action. Such tools have helped to deepen the understanding of fundamental biology and broaden the horizon in the search for treatments for diseases that have been considered hard or impossible to cure...
September 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28918172/melatonin-and-periodontal-tissues-molecular-and-clinical-perspectives
#10
REVIEW
Agata Rita Carpentieri, María Elena Peralta Lopez, Javier Aguilar, Verónica Mariana Solá
Periodontal disease is a frequent chronic inflammatory pathology that implies the destruction of the tissues supporting the teeth, which represents a high sanitary cost. It usually appears associated with other systemic conditions such as diabetes, metabolic syndrome, depression and Alzheimer disease among others. The presence of melatonin and its receptors in the oral cavity supports the hypothesis that this hormone could play a role in homeostasis of periodontal tissues. In the present review we will discuss the potential role of melatonin, a circadian synchronizing hormone, with proved antiinflammatory and antioxidant profile, in the pathogenesis and treatment of periodontitis...
September 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28899790/alisporivir-rescues-defective-mitochondrial-respiration-in-duchenne-muscular-dystrophy
#11
Marco Schiavone, Alessandra Zulian, Sara Menazza, Valeria Petronilli, Francesco Argenton, Luciano Merlini, Patrizia Sabatelli, Paolo Bernardi
Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtained from muscle biopsies of DMD patients display a decrease of the respiratory reserve, a consequence of inappropriate opening of the permeability transition pore (PTP). Treatment with the cyclophilin inhibitor alisporivir - a cyclosporin A derivative that desensitizes the PTP but does not inhibit calcineurin - largely restored the maximal respiratory capacity without affecting basal oxygen consumption in cells from patients, thus reinstating a normal respiratory reserve...
September 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28893628/a-combination-of-nanosystems-for-the-delivery-of-cancer-chemoimmunotherapeutic-combinations-1-methyltryptophan-nanocrystals-and-paclitaxel-nanoparticles
#12
P Calleja, J M Irache, C Zandueta, C Martínez-Oharriz, S Espuelas
IDO is an enzyme that tumors use to create a state of immunosupression. 1-D-methyltryptophan (1-MT) is an IDO pathway inhibitor. After being successfully evaluated in preclinical studies, current clinical trials are actually analyzing its efficacy as monotherapy or in combination with multiple chemotherapeutic agents such as paclitaxel. 1-MT very poor solubility in water and many other solvents precludes its ease parenteral administration. It is currently administered by oral route because high daily doses were well-tolerated and effectively inhibited the IDO activity although only 25% of dose was recovered in plasma...
September 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28889972/the-emerging-role-of-amp-activated-protein-kinase-in-cholestatic-liver-diseases
#13
REVIEW
Xiaojiaoyang Li, Runping Liu, Luyong Zhang, Zhenzhou Jiang
AMP-activated protein kinase (AMPK), recognized as an energy sensor with three heterotrimeric subunits (α, β and γ), not only maintains basal intracellular adenosine triphosphate levels but also regulates energy-intensive pathological responses, such as neurodegenerative and metabolic diseases, through multiple signaling pathways. Recent studies open a new direction for AMPK research and demonstrate that AMPK is a critical player in the pathogenesis of cholestatic liver injury and plays paradoxical roles in the regulation of different pathological processes, including the disruption of bile acid homeostasis and the regulation of hepatic polarity, inflammation and fibrosis...
September 7, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28882690/toxicogenomic-and-bioinformatics-platforms-to-identify-key-molecular-mechanisms-of-a-curcumin-analogue-dm-1-toxicity-in-melanoma-cells
#14
Érica Aparecida de Oliveira, Diogenes Saulo de Lima, Lucas Esteves Cardozo, Garcia Ferreira de Souza, Nayane de Souza, Debora Kristina Alves-Fernandes, Fernanda Faião-Flores, José Agustín Pablo Quincoces, Silvia Berlanga de Moraes Barros, Helder I Nakaya, Gisele Monteiro, Silvya Stuchi Maria-Engler
Melanoma is a highly invasive and metastatic cancer with high mortality rates and chemoresistance. Around 50% of melanomas are driven by activating mutations in BRAF that has led to the development of potent anti-BRAF inhibitors. However resistance to anti-BRAF therapy usually develops within a few months and consequently there is a need to identify alternative therapies that will bypass BRAF inhibitor resistance. The curcumin analogue DM-1 (sodium 4-[5-(4-hydroxy-3-methoxy-phenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate) has substantial anti-tumor activity in melanoma, but its mechanism of action remains unclear...
September 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28873339/non-invasive-strategies-for-stimulating-endogenous-repair-and-regenerative-mechanisms-in-the-damaged-heart
#15
REVIEW
Fiona C Lewis, Siri Deva Kumar, Georgina M Ellison-Hughes
The adult myocardium, including human, harbours a population of resident multi-potent cardiac stem cells (CSCs), which when stimulated under the right conditions can give rise to new cardiomyocytes and vasculature. Elucidation of the cellular and molecular mechanisms that govern CSC biology and their role in myocardial regeneration will allow the design and development of optimal therapeutic interventions. It is now evident that different growth factors and cytokines govern CSC survival, proliferation, migration and differentiation, as well as playing a role in activating cardiac repair mechanisms such as improving angiogenesis, cardiomyocyte survival and limiting fibrosis...
September 2, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28870498/drug-adherence-in-hypertension
#16
REVIEW
M Burnier
Blood pressure control remains unsatisfactory in all countries of the world with at best 60% of treated hypertensive patients reaching recommended therapeutic goals. Several factors have been identified which may explain why the rate of blood pressure control remains low. Among them, one can cite medical inertia and a poor adherence to drug therapies. In the absence of new drugs to control blood pressure, drug adherence has become a major issue in the management of hypertensive patients. Numerous studies have demonstrated that the major problem is the lack of persistence followed by a poor day to day execution of the prescribed regimens...
September 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28867639/animal-models-of-pulmonary-arterial-hypertension-a-systematic-review-and-meta-analysis-of-data-from-6126-animals
#17
Katarzyna Sztuka, Magdalena Jasińska-Stroschein
Numerous animal models of pulmonary hypertension are currently available. A systematic review and meta-analysis was performed of a number of experimental studies of disease induction based on several animal models. A meta-analysis was performed of 291 publications discussing the efficacy of 611 interventions to introduce disease pulmonary hypertension in 6126 animals. A meta-regression analysis was done to assess the effect of prolonged periods of disease induction on the outcomes. A random-effects meta-analysis was used to assess the impact of study characteristics and seek evidence of publication bias...
September 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28867637/sinomenine-induced-histamine-release-like-anaphylactoid-reactions-are-blocked-by-tranilast-via-inhibiting-nf-%C3%AE%C2%BAb-signaling
#18
Lufen Huang, Yan Dong, Jianlin Wu, Peixun Wang, Hua Zhou, Ting Li, Liang Liu
Zhengqing Fengtongning (ZQFTN), the pharmaceutical preparation of sinomenine (SIN) derived from the medicinal plant Sinmenium acutum, is well-known in China as an effective treatment for rheumatoid arthritis (RA). However, its histamine-release anaphylactoid reactions (HRARs) occur often in some patients. Therefore, it is desirable to establish effective clinical protocols to manage such HRARs. In the study, rat models with systemic HRARs and local HRARs of the skin were established. The level of vascular permeability and mast cell numbers was determined by quantitative analysis using Evans blue dye and histological assays...
September 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28867638/zebrafish-a-promising-in-vivo-model-for-assessing-the-delivery-of-natural-products-fluorescence-dyes-and-drugs-across-the-blood-brain-barrier
#19
REVIEW
Ye Li, Tongkai Chen, Xiaoqing Miao, Xiang Yi, Xueqing Wang, Haitao Zhao, Simon Ming-Yuen Lee, Ying Zheng
The blood brain barrier (BBB) is the network of capillaries that controls the passage of substances from the blood into the brain and other parts of the central nervous system (CNS). As this barrier is the major obstacle for drug delivery into CNS, a credible BBB model is very necessary to assess the BBB permeability of novel neuroactive compounds including thousands of bioactive compounds which have been extracted from medicinal plants and have the potential for the treatment of CNS diseases. Increasing reports indicated that zebrafish has emerged as a timely, reproducible model for BBB permeability assessment...
August 31, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28860008/a-signalome-screening-approach-in-the-autoinflammatory-disease-tnf-receptor-associated-periodic-syndrome-traps-highlights-the-anti-inflammatory-properties-of-drugs-for-repurposing
#20
Ian Todd, Ola H Negm, Jenna Reps, Paul Radford, Grazziela Figueredo, Elizabeth M McDermott, Elizabeth Drewe, Richard J Powell, Susan Bainbridge, Mohamed Hamed, Sharon Crouch, Jon Garibaldi, Steve St-Gallay, Lucy C Fairclough, Patrick J Tighe
TNF receptor associated periodic syndrome (TRAPS) is an autoinflammatory disease caused by mutations in TNF Receptor 1 (TNFR1). Current therapies for TRAPS are limited and do not target the pro-inflammatory signalling pathways that are central to the disease mechanism. Our aim was to identify drugs for repurposing as anti-inflammatories based on their ability to down-regulate molecules associated with inflammatory signalling pathways that are activated in TRAPS. This was achieved using rigorously optimized, high through-put cell culture and reverse phase protein microarray systems to screen compounds for their effects on the TRAPS-associated inflammatory signalome...
August 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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