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https://www.readbyqxmd.com/read/28937244/cardiac-at1-receptor-dependent-and-igf1-receptor-independent-signaling-is-activated-by-a-single-bout-of-resistance-exercise
#1
S Fs Melo, V G Barauna, T Fernandes, E C Carmo, C Ro Carvalho, E M Oliveira
AT1 receptor (AT1R) blockade prevents physiological cardiac hypertrophy induced by resistance training. Also, our group showed that a single bout of resistance exercise (RE) activates the AKT/mTOR which was also inhibited by AT1R blocker. Here, we investigated whether IGF1-receptor (IGF1-R) and MAPKs were also activated after a single bout of RE. Wistar rats were divided into Sedentary (SED); Sedentary treated with losartan (SED+LOS); Exercise (EX); and Exercise treated with losartan (EX+LOS). Cardiac tissue was obtained 5 and 30 minutes after 4 sets of 12 repetitions of squat exercise (80%1RM)...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28930945/effects-of-propranolol-and-clonidine-on-brain-edema-blood-brain-barrier-permeability-and-endothelial-glycocalyx-disruption-following-fluid-percussion-brain-injury-in-the-rat
#2
Gustav Folmer Genét, Peter Bentzer, Morten Bagge Hansen, Sisse Rye Ostrowski, Pär Ingemar Johansson
BACKGROUND: Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain-barrier permeability and glycocalyx disruption at 24 hours after trauma. METHODS: We subjected fifty-three adult male Sprague-Dawley rats to lateral fluid-percussion brain injury and randomized infusion with propranolol (n=16), propranolol+clonidine (n=16), vehicle (n=16) or sham (n=5) for 24 hours...
September 20, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28930747/quantification-of-bisoprolol-and-metoprolol-in-simultaneous-human-serum-and-cerebrospinal-fluid-samples
#3
Ali Sigaroudi, Martina Kinzig, Oliver Wahl, Christoph Stelzer, Michael Schroeter, Uwe Fuhr, Ulrike Holzgrabe, Fritz Sörgel
BACKGROUND: Bisoprolol and metoprolol are moderately lipophilic, beta(1)-selective betablockers reported to cause adverse effects in the central nervous system (CNS), such as sleep disturbance, suggesting that both drugs may reach relevant concentrations in the brain. CNS beta(2)-receptor blockade has been suspected to be related to such effects. The higher molecular size of bisoprolol (325 Dalton) and the higher beta(1)-selectivity compared to metoprolol (267 Dalton) would suggest a lower rate of CNS effects...
September 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28918310/effect-of-eplerenone-on-markers-of-bone-turnover-in-patients-with-primary-hyperparathyroidism-the-randomized-placebo-controlled-epath-trial
#4
Nicolas Verheyen, Martin R Grübler, Andreas Meinitzer, Christian Trummer, Verena Schwetz, Karin Amrein, Hans P Dimai, Winfried März, Cristiana Catena, Dirk von Lewinski, Jakob Voelkl, Ioana Alesutan, Astrid Fahrleitner-Pammer, Helmut Brussee, Stefan Pilz, Andreas Tomaschitz
Mineralocorticoid receptor (MR) antagonism may affect bone turnover via direct and indirect pathways involving parathyroid hormone, but randomized controlled trials are lacking. In a pre-specified analysis of the "Eplerenone in primary hyperparathyroidism" placebo-controlled, randomized trial (ISRCTN 33941607), effects of eight weeks MR-blockade with eplerenone on bone turnover markers in 97 patients with primary hyperparathyroidism were tested. Mean age was 67.5±9.5years, and 76 (78.4%) were females. In analysis of covariance with adjustment for baseline values, eplerenone had no significant effect on isoform 5b of the tartrate-resistant acid phosphatase (TRAP), beta-crosslaps, N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin and bone-specific alkaline phosphatase...
September 14, 2017: Bone
https://www.readbyqxmd.com/read/28901011/persistent-aberrant-cortical-phase-amplitude-coupling-following-seizure-treatment-in-absence-epilepsy-models
#5
Atul Maheshwari, Abraham Akbar, Mai Wang, Rachel Marks, Katherine Yu, Suhyeorn Park, Brett L Foster, Jeffrey L Noebels
In childhood absence epilepsy, cortical seizures are brief and intermittent; however there are extended periods without behavioural or electrographic ictal events. This genetic disorder is associated with variable degrees of cognitive dysfunction, but no consistent functional biomarkers that might provide insight into interictal cortical function have been described. Previous work in monogenic mouse models of absence epilepsy have shown that the interictal EEG displays augmented beta/gamma power in homozygous stargazer (stg/stg) mice bearing a presynaptic AMPA receptor defect, but not homozygous tottering (tg/tg) mice with a P/Q type calcium channel mutation...
September 12, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28873410/n-terminally-truncated-pom121c-inhibits-hiv-1-replication
#6
Hideki Saito, Hiroaki Takeuchi, Takao Masuda, Takeshi Noda, Shoji Yamaoka
Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA...
2017: PloS One
https://www.readbyqxmd.com/read/28861757/histamine-h3-inverse-agonist-bf-2649-or-antagonist-with-partial-h4-agonist-activity-clobenpropit-reduces-amyloid-beta-peptide-induced-brain-pathology-in-alzheimer-s-disease
#7
Ranjana Patnaik, Aruna Sharma, Stephen D Skaper, Dafin F Muresanu, José Vicente Lafuente, Rudy J Castellani, Ala Nozari, Hari S Sharma
Alzheimer's disease (AD) is one of the leading causes for disability and death affecting millions of people worldwide. Thus, novel therapeutic strategies are needed to reduce brain pathology associated with AD. In view of increasing awareness regarding involvement of histaminergic pathways in AD, we explored the role of one H3 receptor inverse agonist BF 2649 and one selective H3 receptor antagonist with partial H4 agonist activity in amyloid beta peptide (AβP) infusion-induced brain pathology in a rat model...
August 31, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28844949/role-of-membrane-gm1-on-early-neuronal-membrane-actions-of-a%C3%AE-during-onset-of-alzheimer-s-disease
#8
E J Fernández-Pérez, F J Sepúlveda, R Peoples, Luis G Aguayo
The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1 levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20μm, control=16.2±1.1 vs. D-PDMP =6...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28821664/differential-desensitization-observed-at-multiple-effectors-of-somatic-%C3%AE-opioid-receptors-underlies-sustained-agonist-mediated-inhibition-of-proopiomelanocortin-neuron-activity
#9
Philip D Fox, Shane T Hentges
Activation of somatic μ-opioid receptors (MORs) in hypothalamic proopiomelanocortin (POMC) neurons leads to the activation of G-protein-coupled inward rectifier potassium (GIRK) channels and hyperpolarization, but in response to continued signaling MORs undergo acute desensitization resulting in robust reduction in the peak GIRK current after minutes of agonist exposure. We hypothesized that the attenuation of the GIRK current would lead to a recovery of neuronal excitability whereby desensitization of the receptor would lead to a new steady state of POMC neuron activity reflecting the sustained GIRK current observed after the initial decline from peak with continued agonist exposure...
September 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28805209/neuropeptide-s-induces-acute-anxiolysis-by-phospholipase-c-dependent-signaling-within-the-medial-amygdala
#10
Thomas Grund, Inga D Neumann
Neuropeptide S (NPS) is an important anxiolytic substance of the brain. However, the signaling pathways downstream of NPS receptor (NPSR) activation, underlying the behavioral effect of NPS, remain largely unknown. Here, we show that bilateral microinfusion of NPS (0.2 nmol/0.5 μl) into the medial amygdala (MeA) of male adult Wistar rats reduced anxiety-related behavior on both, the elevated plus-maze and the open field. Moreover, as shown in amygdala tissue micropunches intracerebroventricular infusion of NPS (1 nmol/5 μl) I) evoked phosphorylation and synthesis of CaMKIIɑ in relation to reference protein beta-tubulin representing Ca(2+) influx, and II) induced phosphorylation of mitogen-activated protein kinase ERK1/2...
August 14, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#11
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28782691/first-case-of-autonomic-dysreflexia-following-elective-lower-thoracic-spinal-cord-transection-in-a-spina-bifida-adult
#12
Juanita Garces, Mansour Mathkour, Tyler Scullen, Lora Kahn, Erin Biro, Alex Pham, Olawale A R Sulaiman, Roger Smith, Cuong J Bui
BACKGROUND: Spinal cord transection is a radical but effective treatment for highly selective cases of symptomatic spinal retethering in paraplegic spina bifida patients. Autonomic dysreflexia (AD) is a potentially life-threatening syndrome involving a dysregulated sympathetic discharge reflex commonly seen following cervical and high thoracic spinal cord injury, leading to a disconnect between autonomic pathways above and below the lesion that can lead to severe complications including uncontrolled hypertension, bradycardia, stroke, and potentially death...
August 3, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28780660/update-on-valvular-heart-disease-in-pregnancy
#13
REVIEW
Lucy M Safi, Sarah V Tsiaras
Valvular heart disease in women of childbearing age poses an increased risk of adverse maternal and fetal outcomes, and management in pregnancy can be challenging. Ideally, patients with suspected valvular disease should have preconception counseling by a multidisciplinary team including cardiologists with expertise in pregnancy and a maternal-fetal medicine specialist. Preconception planning should include a cardiac assessment of maternal risk, determination of frequency of surveillance, and a cardiovascular management plan during delivery...
September 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28749946/genome-wide-association-analysis-identifies-genetic-correlates-of-immune-infiltrates-in-solid-tumors
#14
Nathan O Siemers, James L Holloway, Han Chang, Scott D Chasalow, Petra B Ross-MacDonald, Charles F Voliva, Joseph D Szustakowski
Therapeutic options for the treatment of an increasing variety of cancers have been expanded by the introduction of a new class of drugs, commonly referred to as checkpoint blocking agents, that target the host immune system to positively modulate anti-tumor immune response. Although efficacy of these agents has been linked to a pre-existing level of tumor immune infiltrate, it remains unclear why some patients exhibit deep and durable responses to these agents while others do not benefit. To examine the influence of tumor genetics on tumor immune state, we interrogated the relationship between somatic mutation and copy number alteration with infiltration levels of 7 immune cell types across 40 tumor cohorts in The Cancer Genome Atlas...
2017: PloS One
https://www.readbyqxmd.com/read/28729830/resting-state-fluctuations-of-eeg-sensorimotor-rhythm-reflect-bold-activities-in-the-pericentral-areas-a-simultaneous-eeg-fmri-study
#15
Shohei Tsuchimoto, Shuka Shibusawa, Nobuaki Mizuguchi, Kenji Kato, Hiroki Ebata, Meigen Liu, Takashi Hanakawa, Junichi Ushiba
Blockade of the scalp electroencephalographic (EEG) sensorimotor rhythm (SMR) is a well-known phenomenon following attempted or executed motor functions. Such a frequency-specific power attenuation of the SMR occurs in the alpha and beta frequency bands and is spatially registered at primary somatosensory and motor cortices. Here, we hypothesized that resting-state fluctuations of the SMR in the alpha and beta frequency bands also covary with resting-state sensorimotor cortical activity, without involving task-related neural dynamics...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28685225/phase-ii-trial-of-pazopanib-in-advanced-progressive-malignant-pheochromocytoma-and-paraganglioma
#16
Sina Jasim, Vera J Suman, Camilo Jimenez, Pamela Harris, Kostandinos Sideras, Jill K Burton, Francis Paul Worden, Richard J Auchus, Keith C Bible
INTRODUCTION: Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. OBJECTIVES: To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. PATIENTS AND METHODS: This multicenter Phase II trial (MC107C) enrolled individuals  ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1...
August 2017: Endocrine
https://www.readbyqxmd.com/read/28644179/improving-heart-failure-patient-outcomes-utilizing-guideline-directed-therapy
#17
Beth Towery Davidson, Terri Lynn Allison
Heart failure (HF) prevalence continues to rise and remains a significant burden to patients, caregivers, providers, and the healthcare system. Guideline-directed medical therapy with standard neurohormonal blockade has been the cornerstone of medical management for many years. Despite aggressive utilization of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists, HF hospitalizations and readmissions are common and residual mortality remains high...
July 21, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28641581/thyrotoxic-and-pheochromocytoma-multisystem-crisis-a-case-report
#18
Kodai Suzuki, Takahito Miyake, Hideshi Okada, Fuminori Yamaji, Yuichiro Kitagawa, Tetsuya Fukuta, Ryu Yasuda, Yoshihito Tanaka, Haruka Okamoto, Sho Nachi, Tomoaki Doi, Takahiro Yoshida, Keisuke Kumada, Shozo Yoshida, Hiroaki Ushikoshi, Izumi Toyoda, Shinji Ogura
BACKGROUND: Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. CASE PRESENTATION: A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming...
June 23, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28638574/thyrotoxic-periodic-paralysis-a-case-study-and-review-of-the-literature
#19
Marcelle Meseeha, Behnaz Parsamehr, Kerri Kissell, Maximos Attia
Acute hypokalemic paralysis is a rare cause of acute weakness. Morbidity and mortality associated with unrecognized disease can occur and include respiratory failure and possibly death. Common causes of hypokalemic paralysis include thyrotoxic periodic paralysis (TPP) which is a disorder most frequently seen in Asian males. TPP is characterized by sudden onset of hypokalemia and paralysis that primarily affects the lower extremities. Treatment of TPP includes replacing potassium rapidly, using nonselective beta-blockade and correcting the underlying hyperthyroidism as soon as possible...
March 2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/28630289/green-mamba-peptide-targets-type-2-vasopressin-receptor-against-polycystic-kidney-disease
#20
Justyna Ciolek, Helen Reinfrank, Loïc Quinton, Say Viengchareun, Enrico A Stura, Laura Vera, Sabrina Sigismeau, Bernard Mouillac, Hélène Orcel, Steve Peigneur, Jan Tytgat, Laura Droctové, Fabrice Beau, Jerome Nevoux, Marc Lombès, Gilles Mourier, Edwin De Pauw, Denis Servent, Christiane Mendre, Ralph Witzgall, Nicolas Gilles
Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure and death in children and adults. Lowering cAMP in cystic tissues through the inhibition of the type-2 vasopressin receptor (V2R) constitutes a validated strategy to reduce disease progression. We identified a peptide from green mamba venom that exhibits nanomolar affinity for the V2R without any activity on 155 other G-protein-coupled receptors or on 15 ionic channels. Mambaquaretin-1 is a full antagonist of the V2R activation pathways studied: cAMP production, beta-arrestin interaction, and MAP kinase activity...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
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