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https://www.readbyqxmd.com/read/29046002/-optimal-diagnostics-and-therapy-for-microvascular-angina-pectoris
#1
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/29045762/synthesis-determination-of-the-lipophilicity-anticonvulsant-activity-and-preliminary-safety-of-new-derivatives-of-n-4-arylpiperazin-1-yl-alkyl-pyrrolidine-2-5-dione
#2
Sabina Rybka, Jolanta Obniska, Paweł Żmudzki, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Elżbieta Pękala, Adrian Bryła, Anna Rapacz
A new series of derivatives of 1,3-substituted pyrrolidine-2,5-dione as potential anticonvulsant agents are described in this paper. Initial pharmacological screening for these compounds was performed using acute models of seizures (MES and scPTZ tests) in mice after intraperitoneal administration. A quantitative pharmacological research revealed that the most promising compound were N-[{4-(3-trifluoromethylphenyl)-piperazin-1-yl}-propyl]-3-benzhydryl-pyrrolidine-2,5-dione monohydrochloride (11) with ED50=75...
October 18, 2017: ChemMedChem
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
#3
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/29044608/nutrient-sensing-in-pancreatic-islets-lessons-from-congenital-hyperinsulinism-and-monogenic-diabetes
#4
REVIEW
Ming Lu, Changhong Li
Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM))...
October 16, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29044427/genomic-identification-expression-profiling-and-functional-characterization-of-catsper-channels-in-the-bovine
#5
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/29044210/calmodulin-confers-calcium-sensitivity-to-the-stability-of-the-distal-intracellular-assembly-domain-of-kv7-2-channels
#6
Alessandro Alaimo, Eider Nuñez, Paloma Aivar, Juncal Fernández-Orth, Carolina Gomis-Perez, Ganeko Bernardo-Seisdedos, Covadonga Malo, Alvaro Villarroel
Tetrameric coiled-coil structures are present in many ion channels, often adjacent to a calmodulin (CaM) binding site, although the relationship between the two is not completely understood. Here we examine the dynamic properties of the ABCD domain located in the intracellular C-terminus of tetrameric, voltage-dependent, potassium selective Kv7.2 channels. This domain encompasses the CaM binding site formed by helices A and B, followed by helix C, which is linked to the helix D coiled-coil. The data reveals that helix D stabilizes CaM binding, promoting trans-binding (CaM embracing neighboring subunits), and they suggest that the ABCD domain can be exchanged between subunits of the tetramer...
October 18, 2017: Scientific Reports
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/29042943/suxiao-jiuxin-pill-protects-cardiomyocytes-against-mitochondrial-injury-and-alters-gene-expression-during-ischemic-injury
#8
Xiaofen Ruan, Tiejun Chen, Xiaolong Wang, Yiping Li
Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting primarily of tetramethylpyrazine and borneol, has been reported to protect against ischemic heart disease. However, the effects of SX on mitochondrial injury and gene expression in various signaling pathways are unclear. The aim of the present study was to investigate the effects of SX on mitochondrial injury and to screen the expression of genes potentially altered by SX using a cell culture model of ischemic injury. Simulated ischemia was established by culturing HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h...
October 2017: Experimental and Therapeutic Medicine
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
#9
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/29042207/nimodipine-attenuates-tau-phosphorylation-at-ser396-via-mir-132-gsk-3%C3%AE-pathway-in-chronic-cerebral-hypoperfusion-rats
#10
Zihu Tan, Yan Chen, Wenting Xie, Xi Liu, Yuanyue Zhu, Yan Zhu
Chronic cerebral hypofusion (CCH) promotes hyperphosphorylation of tau proteins, a key neuropathological trait that reflects neurodegenerative disorders. Nimodipine, an L-type calcium channel antagonist, has been reported to show neuroprotective effects. In this study, we investigated the potential mechanism of nimodipine in tauopathies induced by CCH. MiR-132 is downregulated in tauopathies such as AD and directly targets tau mRNA to regulate its expression. Here, we report that CCH induced miR-132 deficiency and increased tau phosphorylation at Ser396 while tau expression was not influenced...
October 14, 2017: European Journal of Pharmacology
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
#11
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/29038542/store-operated-ca-2-entry-facilitates-the-lipopolysaccharide-induced-cyclooxygenase-2-expression-in-gastric-cancer-cells
#12
Jhen-Hong Wong, Kuo-Hao Ho, Sean Nam, Wen-Li Hsu, Chia-Hsien Lin, Che-Mai Chang, Jaw-Yuan Wang, Wei-Chiao Chang
Helicobacter pylori has been identified as one of the major causes of chronic gastritis, gastric and duodenal ulcers, and gastric cancer. Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria, and H. pylori LPS might play an exclusively important role in activating inflammatory pathways in monocytes and macrophages. To study the role of LPS in the underlying mechanism of inflammatory responses, we established an in vitro model using the human AGS gastric cancer cell line...
October 16, 2017: Scientific Reports
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
#13
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
#14
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/29038230/ghrelin-receptor-constitutive-activity-reduces-surface-expression-of-voltage-gated-calcium-channels-in-a-cav%C3%AE-dependent-manner
#15
Emilio R Mustafá, Eduardo J López Soto, Valentina Martínez Damonte, Silvia S Rodríguez, Diane Lipscombe, Jesica Raingo
Voltage gated calcium (CaV) channels couple membrane depolarization to calcium influx, triggering a range of calcium-dependent cellular processes. CaV channels are therefore critical in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of CaV channels. GPCR-dependent mechanisms that down regulate CaV channel expression levels are observed in many neurons but are, by comparison, less studied...
October 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29038219/the-l-type-voltage-gated-calcium-channel-cav1-2-mediates-fear-extinction-and-modulates-synaptic-tone-in-the-lateral-amygdala
#16
Stephanie J Temme, Geoffrey G Murphy
L-type voltage-gated calcium channels (LVGCCs) have been implicated in both the formation and the reduction of fear through Pavlovian fear conditioning and extinction. Despite the implication of LVGCCs in fear learning and extinction, studies of the individual LVGCC subtypes, CaV1.2 and CaV1.3, using transgenic mice have failed to find a role of either subtype in fear extinction. This discontinuity between the pharmacological studies of LVGCCs and the studies investigating individual subtype contributions could be due to the limited neuronal deletion pattern of the CaV1...
November 2017: Learning & Memory
https://www.readbyqxmd.com/read/29038048/the-influence-of-doca-salt-hypertension-and-chronic-administration-of-the-faah-inhibitor-urb597-on-kca2-3-kca3-1-edh-type-relaxation-in-rat-small-mesenteric-arteries
#17
Monika Kloza, Marta Baranowska-Kuczko, Barbara Malinowska, Olga Karpińska, Ewa Harasim-Symbor, Irena Kasacka, Hanna Kozłowska
The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (KCa2.3/KCa3.1-EDH) in rat small mesenteric arteries (sMAs). The EDH-type response was investigated, in endothelium-intact sMAs using a wire myograph, by examining acetylcholine-evoked vasorelaxation in the presence of N(ω)-nitro-L-arginine methyl ester and indomethacin (inhibitors of nitric oxide synthase and cyclooxygenase, respectively)...
October 13, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29037241/the-potassium-channel-kca3-1-constitutes-a-pharmacological-target-for-astrogliosis-associated-with-ischemia-stroke
#18
Mengni Yi, Tianjiao Wei, Yanxia Wang, Qin Lu, Gaoxian Chen, Xiaoling Gao, Herbert M Geller, Hongzhuan Chen, Zhihua Yu
BACKGROUND: Reactive astrogliosis is one of the significantly pathological features in ischemic stroke accompanied with changes in gene expression, morphology, and proliferation. KCa3.1 was involved in TGF-β-induced astrogliosis in vitro and also contributed to astrogliosis-mediated neuroinflammation in neurodegeneration disease. METHODS: Wild type mice and KCa3.1(-/-) mice were subjected to permanent middle cerebral artery occlusion (pMCAO) to evaluate the infarct areas by 2,3,5-triphenyltetrazolium hydrochloride staining and neurological deficit...
October 16, 2017: Journal of Neuroinflammation
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
#19
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/29033792/spontaneous-and-evoked-activity-from-murine-ventral-horn-cultures-on-microelectrode-arrays
#20
Bryan J Black, Rahul Atmaramani, Joseph J Pancrazio
Motor neurons are the site of action for several neurological disorders and paralytic toxins, with cell bodies located in the ventral horn (VH) of the spinal cord along with interneurons and support cells. Microelectrode arrays (MEAs) have emerged as a high content assay platform for mechanistic studies and drug discovery. Here, we explored the spontaneous and evoked electrical activity of VH cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs. Primary VH cultures from embryonic day 15-16 mice were characterized by expression of choline acetyltransferase (ChAT) by immunocytochemistry...
2017: Frontiers in Cellular Neuroscience
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