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https://www.readbyqxmd.com/read/29049116/basic-translational-development-of-forthcoming-opioid-and-nonopioid-targeted-pain-therapeutics
#1
Nebojsa Nick Knezevic, Ajay Yekkirala, Tony L Yaksh
Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management has limitations, and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of reinforcing activity in the absence of a pain state...
November 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29048637/leptin-induces-ros-via-nox5-in-healthy-and-neoplastic-mammary-epithelial-cells
#2
Sinda Mahbouli, Audrey Der Vartanian, Sophie Ortega, Stéphanie Rougé, Marie-Paule Vasson, Adrien Rossary
NADPH oxidase (NOX) complexes (a family of seven isoforms) drive cellular ROS production in patho-logical processes such as cancer. NOX-driven ROS production is involved in cell mechanisms from signalling to oxidative stress. Leptin, an adipokine overexpressed in obese patients, has been investigated in studies on breast carcinogenesis, but its effects on oxidative stress remain largely unexplored, especially in breast cancer. The study used three human mammary epithelial cell models presenting different neoplastic status (healthy primary HMECs, neoplastic MCF-7 cells and neoplastic MDA-MB-231 cells) to determine the effects of leptin on short-term ROS production and to characterize the enzymes involved...
September 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29046519/the-effects-of-anti-hypertensive-drugs-and-the-mechanism-of-hypertension-in-vascular-smooth-muscle-cell-specific-atp2b1-knockout-mice
#3
Yuki Okuyama, Nobuhito Hirawa, Megumi Fujita, Akira Fujiwara, Yosuke Ehara, Keisuke Yatsu, Koichiro Sumida, Minako Kagimoto, Mari Katsumata, Yusuke Kobayashi, Sanae Saka, Satoshi Umemura, Kouichi Tamura
ATP2B1 is a gene associated with hypertension. We reported previously that mice lacking ATP2B1 in vascular smooth muscle cells (VSMC ATP2B1 KO mice) exhibited high blood pressure and increased intracellular calcium concentration. The present study was designed to investigate whether lack of the ATP2B1 gene causes a higher response to calcium channel blockers (CCBs) than to other types of anti-hypertensive drugs. Both VSMC ATP2B1 KO and control mice were administered anti-hypertensive drugs while monitoring blood pressure shifts...
October 19, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29046002/-optimal-diagnostics-and-therapy-for-microvascular-angina-pectoris
#4
Peter Ong, Udo Sechtem
Patients with microvascular angina are characterized by angina pectoris with proof of myocardial ischemia in the absence of any relevant epicardial stenosis and without myocardial disease (type 1 coronary microvascular dysfunction according to Crea and Camici). Structural and functional alterations of the coronary microvessels (diameter < 500 µm) are the reason for this phenomenon. Frequently such alterations are associated with cardiovascular risk factors. Patients with angina pectoris without epicardial stenoses represent for 10 - 50 % of all patients undergoing coronary angiography depending on the clinical presentation...
October 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29045341/effect-of-antihypertensive-treatment-on-24-h-blood-pressure-variability-pooled-individual-data-analysis-of-ambulatory-blood-pressure-monitoring-studies-based-on-olmesartan-mono-or-combination-treatment
#5
Stefano Omboni, Kazuomi Kario, George Bakris, Gianfranco Parati
OBJECTIVE: To evaluate the impact of olmesartan alone or combined with one to three antihypertensive drugs on 24-h blood pressure variability (BPV) and on distribution of BP reduction in a pooled individual data analysis of 10 double-blind, randomized, ambulatory BP monitoring (ABPM) studies. METHODS: ABPMs were performed before and after 6-12 weeks of treatment with placebo (n = 119), active control monotherapy [n = 1195, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers (DCCBs)], or DCCBs), olmesartan monotherapy (n = 1410), active control dual combination [n = 79, DCCB + thiazide diuretic (TD)], olmesartan dual combination (n = 637, DCCB or TD), and triple combination therapy (n = 102, DCCB+TD)...
October 16, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29044427/genomic-identification-expression-profiling-and-functional-characterization-of-catsper-channels-in-the-bovine
#6
Gillian P Johnson, Anne-Marie English, Sinead Cronin, David A Hoey, Kieran G Meade, Sean Fair
Cation channels of sperm (CatSper) are sperm-specific calcium channels with identified roles in the regulation of sperm function in humans, mice, and horses. We sought to employ a comparative genomics approach to identify conserved CATSPER genes in the bovine genome, and profile their expression in reproductive tissue. We hypothesized that CATSPER proteins expressed in bull testicular tissue mediates sperm hyperactivation and their rheotactic response in the reproductive tract of the cow. Bioinformatic analysis identified all four known CATSPER genes (CATSPER 1-4) in the bovine genome, and profiling by quantitative real-time polymerase chain reaction identified site-specific variation in messenger ribonucleic acid (mRNA) expression for all four genes along the reproductive tract of the bull...
August 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29043521/initiation-of-antihypertensive-monotherapy-and-incident-fractures-among-medicare-beneficiaries
#7
Jennifer L Hargrove, Yvonne M Golightly, Virginia Pate, Carri H Casteel, Laura R Loehr, Stephen W Marshall, Til Stürmer
BACKGROUND: Research suggests antihypertensive medications are associated with fractures in older adults, however results are inconsistent and few have examined how the association varies over time. We sought to examine the association between antihypertensive class and incident non-vertebral fractures among older adults initiating monotherapy according to time since initiation. METHODS: We used a new-user cohort design to identify Medicare beneficiaries (≥ 65 years of age) initiating antihypertensive monotherapy during 2008-2011 using a 20% random sample of Fee-For-Service Medicare beneficiaries enrolled in parts A (inpatient services), B (outpatient services), and D (prescription medication) coverage...
October 18, 2017: Injury Epidemiology
https://www.readbyqxmd.com/read/29042318/mechanisms-of-%C3%AE-opioid-receptor-inhibition-of-nmda-receptor-induced-substance-p-release-in-the-rat-spinal-cord
#8
Wenling Chen, Helena S Ennes, James A McRoberts, Juan Carlos Marvizon
The interaction between NMDA receptors and μ-opioid receptors in primary afferent terminals was studied by using NMDA to induce substance P release, measured as neurokinin 1 receptor internalization. In rat spinal cord slices, the μ-opioid receptor agonists morphine, DAMGO and endomorphin-2 inhibited NMDA-induced substance P release, whereas the antagonist CTAP right-shifted the concentration response of DAMGO. In vivo, substance P release induced by intrathecal NMDA after priming with BDNF was inhibited by DAMGO...
October 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29041894/-clinical-features-of-arterial-hypertension-in-the-elderly-and-senile-age-and-the-rationale-for-using-the-combination-of-amlodipine-indapamide-retard
#9
D Z Kobalava, K E Shavarova
The proportion of elderly in the population is growing. The two-thirds of those over the age of 65 has arterial hypertension (AH). There is a significant increase in the incidence of isolated systolic hypertension with age. The relationship between increased pulse pressure, arterial stiffness and aging processes has been repeatedly confirmed in population epidemiological studies. Some evidence has been found that the treatment of AH in the elderly is accompanied by a reduction in the risk of cardiovascular diseases...
August 2017: Kardiologiia
https://www.readbyqxmd.com/read/29038363/moderate-exercise-training-does-not-prevent-the-reduction-in-myocardial-l-type-ca-2-channels-protein-expression-at-obese-rats
#10
Vitor L da Silva, Ana P Lima-Leopoldo, Artur J T Ferron, Jóctan P Cordeiro, Paula P Freire, Dijon H S de Campos, Carlos R Padovani, Mário M Sugizaki, Antonio C Cicogna, André S Leopoldo
Authors have showed that obesity implicates cardiac dysfunction associated with myocardial L-type calcium channels (LTCCs) activity impairments, as well as moderate exercise training (MET) seems to be an important therapeutic tool. We tested the hypothesis that MET promotes improvements on LTCCS activity and protein expression at obesity induced by unsaturated high-fat diets, which could represent a protective effects against development of cardiovascular damage. Male Wistar rats were randomized in control (C, n = 40), which received a standard diet and obese (Ob; n = 40), which received high-fat diet...
October 2017: Physiological Reports
https://www.readbyqxmd.com/read/29038242/activity-dependent-facilitation-of-cav1-3-calcium-channels-promotes-kca3-1-activation-in-hippocampal-neurons
#11
Giriraj Sahu, Hadhimulya Asmara, Fang-Xiong Zhang, Gerald W Zamponi, Ray W Turner
CaV1 L-type calcium channels are key to regulating neuronal excitability, with the range of functional roles enhanced by interactions with calmodulin, accessory proteins, or CaMKII that modulate channel activity. In hippocampal pyramidal cells a prominent elevation of CaV1 activity is apparent in late channel openings that can last for seconds following a depolarizing stimulus train. The current study tested the hypothesis that a reported interaction between CaV1.3 channels, the scaffolding protein densin, and CaMKII could generate a facilitation of channel activity that outlasts a depolarizing stimulus...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29036189/inhibition-of-cug-binding-protein-1-and-activation-of-caspases-are-critically-involved-in-piperazine-derivative-bk10007s-induced-apoptosis-in-hepatocellular-carcinoma-cells
#12
Ju-Ha Kim, Hee Young Kwon, Dong Hoon Ryu, Min-Ho Nam, Bum Sang Shim, Jin Han Kim, Jae Yeol Lee, Sung-Hoon Kim
Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/29033611/stable-ischemic-heart-disease-in-women-current-perspectives
#13
REVIEW
Fatima Samad, Anushree Agarwal, Zainab Samad
Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD) in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m(2)), smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/29032888/calcium-channel-blockers-for-lung-function-improvement-in-asthma-a-systematic-review-and-meta-analysis
#14
Kam Yu Chiu, Jian Guo Li, Ying Lin
BACKGROUND: For decades, calcium channel blockers (CCBs) have been believed to play a role in asthma treatment. However, the clinical efficacy of CCBs for lung function improvement in patients with asthma has not been qualitatively evaluated. OBJECTIVE: To assess the effect of CCBs vs placebo on lung function test results in adults with asthma. METHODS: Various databases were systematically searched to identify all randomized clinical trials with adults with asthma...
October 9, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29031978/monitoring-the-phase-behavior-of-supersaturated-solutions-of-poorly-water-soluble-drugs-using-fluorescence-techniques
#15
Francesco Tres, Stephen D Hall, Michael A Mohutsky, Lynne S Taylor
Phase transformations of poorly water-soluble drugs, in low concentration, supersaturated aqueous solutions are of considerable interest. Herein, fluorescence lifetime and steady-state fluorescence spectroscopy were employed to investigate the fluorescence properties of the autofluorescent compound, felodipine (a 1,4-dihydropyridine calcium channel blocker), when present as free drug in solution, drug-rich aggregates and crystals. Measurements were also performed in the absence and presence of liver microsomes...
October 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29026579/amlodipine-induced-gingival-enlargement
#16
Abhilash Koratala, Indirakshi Jamalpur, Harikrishna Reddy Mogili
The three most common classes of medications implicated in drug-induced gum enlargement are anticonvulsives, calcineurin inhibitors, and calcium channel blockers. Treatment primarily consists of withdrawing the offending agent whenever possible, in addition to maintaining good oral hygiene. Gingivectomy or flap surgery may be needed in resistant cases.
October 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29026201/dual-contribution-of-trpv4-antagonism-in-the-regulatory-effect-of-vasoinhibins-on-blood-retinal-barrier-permeability-diabetic-milieu-makes-a-difference
#17
David Arredondo Zamarripa, Ramsés Noguez Imm, Ana María Bautista Cortés, Osvaldo Vázquez Ruíz, Michela Bernardini, Alessandra Fiorio Pla, Dimitra Gkika, Natalia Prevarskaya, Fernando López-Casillas, Wolfgang Liedtke, Carmen Clapp, Stéphanie Thébault
Breakdown of the blood-retinal barrier (BRB), as occurs in diabetic retinopathy and other chronic retinal diseases, results in vasogenic edema and neural tissue damage, causing vision loss. Vasoinhibins are N-terminal fragments of prolactin that prevent BRB breakdown during diabetes. They modulate the expression of some transient receptor potential (TRP) family members, yet their role in regulating the TRP vanilloid subtype 4 (TRPV4) remains unknown. TRPV4 is a calcium-permeable channel involved in barrier permeability, which blockade has been shown to prevent and resolve pulmonary edema...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29022231/calcium-channel-blockers-for-the-clinical-management-of-hypertension
#18
EDITORIAL
Massimo Volpe
No abstract text is available yet for this article.
October 11, 2017: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
https://www.readbyqxmd.com/read/29020410/the-requirement-of-l-type-voltage-dependent-calcium-channel-l-vdcc-in-the-rapid-acting-antidepressant-like-effects-of-scopolamine-in-mice
#19
Hanjie Yu, Mengmeng Li, Xinbei Shen, Dan Lv, Xin Sun, Jinting Wang, Xinmei Gu, Jingning Hu, Chuang Wang
Background: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels (L-VDCC) were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-VDCC in the action of scopolamine...
August 25, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29020304/identification-of-a-targeted-and-testable-antiarrhythmic-therapy-for-long-qt-syndrome-type-2-using-a-patient-specific-cellular-model
#20
Ashish Mehta, Chrishan J A Ramachandra, Pritpal Singh, Anuja Chitre, Chong Hui Lua, Manuela Mura, Lia Crotti, Philip Wong, Peter J Schwartz, Massimiliano Gnecchi, Winston Shim
Aims: Loss-of-function mutations in the hERG gene causes long-QT syndrome type 2 (LQT2), a condition associated with reduced IKr current. Four different mutation classes define the molecular mechanisms impairing hERG. Among them, Class 2 mutations determine hERG trafficking defects. Lumacaftor (LUM) is a drug acting on channel trafficking already successfully tested for cystic fibrosis and its safety profile is well known. We hypothesize that LUM might rescue also hERG trafficking defects in LQT2 and exert anti-arrhythmic effects...
July 21, 2017: European Heart Journal
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