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https://www.readbyqxmd.com/read/28329545/darier-white-disease
#1
Mitalee P Christman, Evan Reider, Randie H Kim, Nooshin Brinster, Elisa Femia, Miriam Keltz Pomeranz
We present a 58-year-old woman with bipolardisorder and with a longstanding history of yellowbrown,hyperkeratotic papules in a seborrheicdistribution and nail changes. Her father andpaternal grandmother had similar eruptions and alsohad psychiatric disease. Histopathologic examinationshowed acantholysis and dyskeratosis, which wasconsistent with Darier-White disease. Darier-Whitedisease is a rare, hereditary disorder that is inheritedin an autosomal dominant manner and that usuallypresents in adolescence or early adulthood dueto mutations in the SERCA2 calcium pump...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28320043/effects-of-ranolazine-in-a-model-of-doxorubicin-induced-left-ventricle-diastolic-dysfunction
#2
Donato Cappetta, Grazia Esposito, Raffaele Coppini, Elena Piegari, Rosa Russo, Loreta Pia Ciuffreda, Alessia Rivellino, Lorenzo Santini, Concetta Rafaniello, Cristina Scavone, Francesco Rossi, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
BACKGROUND AND PURPOSE: Doxorubicin (DOXO) is a highly effective anticancer drug but its clinical application is impeded by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of DOXO cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent late cardiotoxicity is warranted. Increased DOXO-dependent reactive oxygen species may explain, in part, Ca(2+) and Na(+) overload that contributes to diastolic dysfunction and development of heart failure...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28284503/renal-denervation-regulates-the-atrial-arrhythmogenic-substrates-through-reverse-structural-remodeling-in-heart-failure-rabbit-model
#3
Shinya Yamada, Li-Wei Lo, Yu-Hui Chou, Wei-Lun Lin, Shih-Lin Chang, Yenn-Jiang Lin, Shih-Ann Chen
BACKGROUND: Heart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF. METHODS: Rabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN...
February 24, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28255076/beneficial-effect-of-renal-denervation-on-ventricular-premature-complex-induced-cardiomyopathy
#4
Shinya Yamada, Li-Wei Lo, Yu-Hui Chou, Wei-Lun Lin, Shih-Lin Chang, Yenn-Jiang Lin, Shin-Huei Liu, Wen-Han Cheng, Tsung-Ying Tsai, Shih-Ann Chen
BACKGROUND: Frequent ventricular premature complexes (VPCs) can lead to the development of dilated cardiomyopathy and sudden cardiac death. Renal artery sympathetic denervation (RDN) may protect the heart from remodeling. This study aimed to investigate the effect of frequent VPCs on structural and electrical properties and whether RDN can protect the heart from remodeling. METHODS AND RESULTS: Eighteen rabbits were randomized to control (n=6), VPC (n=6), and VPC-RDN (n=6) groups...
March 2, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28246293/a-whole-genome-rna-interference-screen-reveals-a-role-for-spry2-in-insulin-transcription-and-the-unfolded-protein-response
#5
Zachary Pappalardo, Deeksha G Chopra, Thomas G Hennings, Hunter Richards, Justin Choe, Katherine Yang, Luc Baeyens, Kenny Ang, Steven Chen, Michelle Arkin, Michael S German, Michael T McManus, Gregory M Ku
Insulin production by the pancreatic beta cell is required for normal glucose homeostasis. While key transcription factors that bind to the insulin promoter are known, relatively little is known about the upstream regulators of insulin transcription. Using a whole genome RNA interference screen, we uncovered 26 novel regulators of insulin transcription that regulate diverse processes including oxidative phosphorylation, vesicle traffic, and the unfolded protein response(UPR). We focused on Spry2 -- a gene implicated in human type 2 diabetes by genome wide association studies but without a clear connection to glucose homeostasis...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28238269/long-acting-pde5-inhibitor-tadalafil-prevents-early-doxorubicin-induced-left-ventricle-diastolic-dysfunction-in-juvenile-mice-potential-role-of-cytoskeletal-proteins
#6
Mohamed Nagiub, Scott Filippone, David Durrant, Anindita Das, Rakesh C Kukreja
The chemotherapeutic use of doxorubicin (Dox) is hindered due to the development of irreversible cardiotoxicity. Specifically, childhood cancer survivors are at greater risk of Dox-induced cardiovascular complications. Because of the potent cardioprotective effect of phosphodiesterase 5 (PDE5) inhibitors, we examined the effect of long-acting PDE5 inhibitor tadalafil (Tada) against Dox cardiotoxicity in juvenile mice. C57BL/6J mice (6 weeks old) were treated with Dox (20 mg/kg, i.v.) and (or) Tada (10 mg/kg daily for 14 days, p...
March 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28156030/er-to-golgi-blockade-of-nascent-desmosomal-cadherins-in-serca2-inhibited-keratinocytes-implications-for-darier-s-disease
#7
Ning Li, Moonhee Park, Shengxiang Xiao, Zhi Liu, Luis A Diaz
Darier's disease (DD) is an autosomal dominantly inherited skin disorder caused by mutations in sarco/endoplasmic reticulum Ca(2+) -ATPase 2 (SERCA2), a Ca(2+) pump that transports Ca(2+) from the cytosol to the endoplasmic reticulum (ER). Loss of desmosomes and keratinocyte cohesion is a characteristic feature of DD. Desmosomal cadherins (DC) are Ca(2+) -dependent transmembrane adhesion proteins of desmosomes, which are mislocalized in the lesional but not perilesional skin of DD. We show here that inhibition of SERCA2 by 2 distinct inhibitors results in accumulation of DC precursors in keratinocytes, indicating ER-to-Golgi transport of nascent DC is blocked...
February 3, 2017: Traffic
https://www.readbyqxmd.com/read/28150875/atp2a3-gene-as-an-important-player-for-resveratrol-anticancer-activity-in-breast-cancer-cells
#8
Eduardo Izquierdo-Torres, Gabriela Rodríguez, Iván Meneses-Morales, Angel Zarain-Herzberg
The Ca(2+) -ATPases from the Sarco/endoplasmic reticulum (SERCA) are fundamental for maintaining intracellular [Ca(2+) ] homeostasis by pumping Ca(2+) into the endoplasmic reticulum (ER) of eukaryotic cells. SERCA enzymes are encoded by three different genes (ATP2A1-3), whose expression occurs in a tissue and development stage-specific manner. It has been reported alterations in the expression of SERCA2 and SERCA3 pumps in different types of cancer: oral, lung, colon, stomach, central nervous system, thyroid, breast, and prostate...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28120514/ultraviolet-radiation-induced-down-regulation-of-serca2-mediates-activation-of-nlrp3-inflammasome-in-basal-cell-carcinoma
#9
Israr Ahmad, Kashiff M Muneer, Michelle E Chang, Hana M Nasr, Jacqueline M Clay, Conway C Huang, Nabiha Yusuf
Basal cell carcinomas (BCCs) account for majority of skin malignancies in the United States. The incidence of BCCs is strongly associated with exposure of ultraviolet (UV) radiation. Nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome plays an important role in innate immune responses. Different stimuli such as toxins, microorganisms, and particles released from injured cells activate the NLRP3 inflammasome. Activated NLRP3 results in activation of caspase-1, which cleaves pro-IL-1β to active IL-1β...
January 25, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28094886/the-parathyroid-hormone-family-member-tip39-interacts-with-sarco-endoplasmic-reticulum-ca-2-atpase-activity-by-influencing-calcium-homeostasis
#10
Emi Sato, Michael R Williams, James A Sanford, George L Sen, Takekuni Nakama, Shinichi Imafuku, Richard L Gallo
Darier disease (DD) is a genetic skin disease that is associated with mutations in the ATP2A2 gene encoding the type 2 sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA2). Mutations of this gene result in alterations of calcium homeostasis, abnormal epidermal adhesion and dyskeratosis. Silencing of ATP2A2 in monolayer cell culture of keratinocytes reduces desmoplakin expression at the borders of cells and impacts cell adhesion. Here, we report establishment of a three-dimensional (3D) epidermal model of DD, and use this model to evaluate peptide therapy with tuberoinfundibular peptide of 39 residues (TIP39) to normalize calcium transport...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28008204/novel-and-recurrent-atp2a2-mutations-in-japanese-patients-with-darier-s-disease
#11
Kana Noda, Takuya Takeichi, Yusuke Okuno, Hiromichi Takama, Shunsuke Miura, Shinji Kagami, Haruko Hino, Yuki Nakamura, Yumi Fujio, Izumi Konohana, Ayako Otani, Hideki Mukai, Kazumitsu Sugiura, Masashi Akiyama
Darier's disease (DD, keratosis follicularis: OMIM#124200) is an autosomal dominant skin disorder characterized by multiple dark brown keratotic plaques and warty papules covered by thick crusts. Most cases of DD are caused by mutations in ATP2A2, which is expressed in both the skin and the brain. ATP2A2 encodes the cardiac muscle SERCA2a protein and the ubiquitously expressed SERCA2b. SERCA2 plays an important role as a calcium pump. It is thought that a mutation in ATP2A2 causes dyskeratosis and abnormality of cell-cell adhesion...
December 2016: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/27931779/complement-and-sepsis-induced-heart-dysfunction
#12
Fatemeh Fattahi, Peter A Ward
It is well known that cardiac dysfunction develops during sepsis in both humans and in rodents (rats, mice). These defects appear to be reversible, since after "recovery" from sepsis, cardiac dysfunction disappears and the heart returns to its function that was present before the onset of sepsis. Our studies, using in vivo and in vitro models, have demonstrated that C5a and its receptors (C5aR1 and C5aR2) play key roles in cardiac dysfunction developing during sepsis. Use of a neutralizing antibody to C5a largely attenuates cardiac dysfunction and other adverse events developing during sepsis...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27872214/effects-of-prolonged-anoxia-on-electrical-activity-of-the-heart-in-crucian-carp-carassius-carassius
#13
Elisa Tikkanen, Jaakko Haverinen, Stuart Egginton, Minna Hassinen, Matti Vornanen
The effects of sustained anoxia on cardiac electrical excitability were examined in the anoxia-tolerant crucian carp (Carassius carassius). The electrocardiogram (ECG) and expression of excitation-contraction coupling genes were studied in fish acclimatised to normoxia in summer (+18°C) or winter (+2°C), and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained bradycardia from a heart rate of 10.3±0.77 beats min(-1) to 4.1±0.29 beats min(-1) (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when oxygen was restored...
February 1, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27856713/effect-of-increased-and-maintained-frequency-of-speed-endurance-training-on-performance-and-muscle-adaptations-in-runners
#14
Casper Skovgaard, Nicki Winfield Almquist, Jens Bangsbo
The aim of the study was, in runners accustomed to speed endurance training (SET), to examine the effect of increased and maintained frequency of SET on performance and muscular adaptations. After familiarization (FAM) to SET, 18 male (n = 14) and female (n = 4) runners (V̇o2max: 57.3 ± 3.4 ml/min; means ± SD) completed 20 sessions of maintained low-frequency (LF; every fourth day; n = 7) or high-frequency (HF; every second day; n = 11) SET. Before FAM as well as before and after an intervention period (INT), subjects completed a series of running tests and a biopsy from m...
January 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27856611/loss-of-akap150-promotes-pathological-remodelling-and-heart-failure-propensity-by-disrupting-calcium-cycling-and-contractile-reserve
#15
Lei Li, Jing Li, Benjamin M Drum, Yi Chen, Haifeng Yin, Xiaoyun Guo, Stephen W Luckey, Merle L Gilbert, G Stanley McKnight, John D Scott, L Fernando Santana, Qinghang Liu
AIMS: Impaired Ca(2 + )cycling and myocyte contractility are a hallmark of heart failure triggered by pathological stress such as hemodynamic overload. The A-Kinase anchoring protein AKAP150 has been shown to coordinate key aspects of adrenergic regulation of Ca(2+ )cycling and excitation-contraction in cardiomyocytes. However, the role of the AKAP150 signalling complexes in the pathogenesis of heart failure has not been investigated. METHODS AND RESULTS: Here we examined how AKAP150 signalling complexes impact Ca(2+ )cycling, myocyte contractility, and heart failure susceptibility following pathological stress...
February 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/27853260/the-synthetic-antimicrobial-peptide-19-2-5-attenuates-septic-cardiomyopathy-and-prevents-down-regulation-of-serca2-in-polymicrobial-sepsis
#16
Lukas Martin, Klemens Horst, Fausto Chiazza, Silvia Oggero, Massimo Collino, Klaus Brandenburg, Frank Hildebrand, Gernot Marx, Christoph Thiemermann, Tobias Schuerholz
An impairment of cardiac function is a key feature of the cardiovascular failure associated with sepsis. Although there is some evidence that suppression of sarcoplasmic reticulum Ca(2+)-ATP-ase (SERCA2) contributes to septic cardiomyopathy, it is not known whether prevention of the down-regulation of SERCA2 improves outcome in sepsis. Thus, we investigated whether the administration of the synthetic antimicrobial peptide Pep2.5 may attenuate the cardiac dysfunction in murine polymicrobial sepsis through regulating SERCA2 expression...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27737958/mechanical-stress-conditioning-and-electrical-stimulation-promote-contractility-and-force-maturation-of-induced-pluripotent-stem-cell-derived-human-cardiac-tissue
#17
Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUND: Tissue engineering enables the generation of functional human cardiac tissue with cells derived in vitro in combination with biocompatible materials. Human-induced pluripotent stem cell-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electric pacing on the maturation of human-induced pluripotent stem cell-derived cardiac tissues...
November 15, 2016: Circulation
https://www.readbyqxmd.com/read/27737323/thyroxine-increases-serca2-and-ryr2-gene-expression-in-heart-failure-rats-with-euthyroid-sick-syndrome
#18
Fábio V G Campanha, Denise Perone, Dijon H S de Campos, Renata de A M Luvizotto, Maria T De Síbio, Miriane de Oliveira, Regiane M C Olimpio, Fernanda C F Moretto, Carlos R Padovani, Gláucia M F S Mazeto, Antonio C Cicogna, Célia R Nogueira
Objective: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups...
November 2016: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27721754/exacerbation-of-darier-disease-under-interferon-%C3%AE-2a-therapy-with-clinical-signs-of-lichen-nitidus
#19
Ioannis Karagiannidis, Martina Brunner, Christos C Zouboulis
Darier disease/dyskeratosis follicularis is a genodermatosis characterized by brown, oily keratotic papules and plaques in the seborrheic areas of the face and chest. Responsible for the disease are mutations in the ATP2A2 gene, encoding SERCA2, a calcium pump of the sarco-/endoplasmic reticulum. Mechanical trauma, heat, humidity, ultraviolet B radiation, oral corticosteroids and lithium are known trigger factors of the disorder. We report on a 48-year-old German woman with a flare-up of Darier disease under interferon-α-2a (IFNα-2a) therapy with clinical signs of lichen nitidus...
May 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/27688314/genotype-dependent-and-independent-calcium-signaling-dysregulation-in-human-hypertrophic-cardiomyopathy
#20
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban, calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM samples compared with controls...
November 29, 2016: Circulation
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