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https://www.readbyqxmd.com/read/28339909/il-17-and-cd40-ligand-synergistically-stimulate-the-chronicity-of-diabetic-nephropathy
#1
Huey-Liang Kuo, Chiu-Ching Huang, Tze-Yi Lin, Ching-Yuang Lin
Background.: Early stages of diabetic nephropathy (DN) are characterized by an influx of inflammatory cells. Interactions between infiltrating T cells and podocytes may play an important role in the ongoing inflammatory response and remodelling. The aim of this study was to explore the role of IL-17 and CD40 ligand (CD40L) in DN. Methods.: The study design involved a case series. Kidney biopsy samples of 69 patients with type 2 diabetes were assessed for the presence of CD4 +  IL-17 +  T cells...
March 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28337414/pheochromocytoma-with-negative-metanephrines-a-rarity-and-the-significance-of-dopamine-secreting-tumors
#2
Michael Bozin, Alastair Lamb, Lydia Johns Putra
We describe a case of a 25-year-old female with a dopamine secreting PPGL diagnosed retrospectively with biochemical analysis. This finding resulted in change in approach to investigation and management, given their important clinical implications. There are important differences in management of dopamine secreting PPGL compared to classical noradrenaline and adrenaline-secreting PPGL. This includes the risk of peri-operative cardiovascular collapse peri-operatively with alpha/beta blockade, risk of malignancy/recurrence, and associated genetic abnormalities...
May 2017: Urology Case Reports
https://www.readbyqxmd.com/read/28323959/insulin-and-glucagon-partners-for-life
#3
Jens Juul Holst, William Holland, Jesper Gromada, Young Lee, Roger H Unger, Hai Yan, Kyle W Sloop, Timothy J Kieffer, Nicolas Damond, Pedro L Herrera
In August 2016, several leaders in glucagon biology gathered for the European Association for the Study of Diabetes Hagedorn Workshop in Oxford, England. A key point of discussion focused around the need for basal insulin to allow for the therapeutic benefit of glucagon blockade in the treatment of diabetes. Among the most enlightening experimental results presented were findings from studies where glucagon receptor-deficient mice were administered streptozotocin to destroy pancreatic beta cells or had undergone diphtheria toxin-induced beta cell ablation...
January 31, 2017: Endocrinology
https://www.readbyqxmd.com/read/28292194/clinical-utility-of-sympathetic-blockade-in-cardiovascular-disease-management
#4
Chan Soon Park, Hae-Young Lee
A dysregulated sympathetic nervous system is a major factor in the development and progression of cardiovascular disease; thus, understanding the mechanism and function of the sympathetic nervous system and appropriately regulating sympathetic activity to treat various cardiovascular diseases are crucial. Areas covered: This review focused on previous studies in managing hypertension, atrial fibrillation, coronary artery disease, heart failure, and perioperative management with sympathetic blockade. We reviewed both pharmacological and non-pharmacological management...
March 15, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#5
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not appreciably established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28280600/structural-basis-of-a-novel-pd-l1-nanobody-for-immune-checkpoint-blockade
#6
Fei Zhang, Hudie Wei, Xiaoxiao Wang, Yu Bai, Pilin Wang, Jiawei Wu, Xiaoyong Jiang, Yugang Wang, Haiyan Cai, Ting Xu, Aiwu Zhou
The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28279368/imaging-guided-cardioprotective-treatment-in-a-community-elderly-population-of-stage-b-heart-failure
#7
Hong Yang, Kazuaki Negishi, Ying Wang, Mark Nolan, Thomas H Marwick
OBJECTIVES: The purpose of the study was to evaluate the benefit of care guided by the detection of stage B heart failure (SBHF) using advanced echocardiography for the reduction of new HF in the community. BACKGROUND: The detection of nonischemic SBHF has been facilitated by advanced echocardiographic imaging modalities. However, improved outcomes have not been proven as they are predicated on benefit of treatment. METHODS: Between September 13, 2013 and November 6, 2015, 618 asymptomatic community-based patients with HF risks (age 71 ± 5 years) were randomized to care guided by advanced echocardiography (myocardial deformation and detailed diastolic function) versus usual care...
March 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28265730/does-beta-blockade-reduce-the-risk-of-depression-in-patients-with-isolated-severe-extracranial-injuries
#8
Rebecka Ahl, Galinos Barmparas, Louis Riddez, Eric J Ley, Göran Wallin, Olle Ljungqvist, Shahin Mohseni
BACKGROUND: Approximately half of trauma patients develop post-traumatic depression. It is suggested that beta-blockade impairs trauma memory recollection, reducing depressive symptoms. This study investigates the effect of early beta-blockade on depression following severe traumatic injuries in patients without significant brain injury. METHODS: Patients were identified by retrospectively reviewing the trauma registry at an urban university hospital between 2007 and 2011...
March 6, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28261841/a-sensitive-quantitative-assay-for-the-determination-of-propafenone-and-two-metabolites-5-hydroxypropafenone-and-n-depropylpropafenone-in-human-k2edta-plasma-using-lc-ms-ms-with-esi-operated-in-a-positive-mode
#9
Harilal Patel, Ashok Ghoghari, Chandrakant Bhatt, Shaival Shah, Anilkumar Jha, Nirmal Desai, Nuggehally R Srinivas
Propafenone is a potent antiarrhythmic agent; clinically propafenone has been used for a number of cardiac arrhythmias because it possesses multiple modes of action, via beta adrenergic receptor blockade and calcium antagonistic activity. Propafenone (PPF) exhibits extensive saturable presystemic biotransformation (first pass effect) resulting into two active metabolites; 5- hydroxypropafenone (5-OH PPF) formed by CYP2D6 and N-depropylpropafenone (NDP) formed by both CYP3A4 and CYP1A2 enzymes. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of PPF, 5-OH PPF and NDP using turboion spray in a positive ion mode...
March 6, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28256104/haemodynamic-influences-of-bisoprolol-in-hypertensive-middle-aged%C3%A2-men-a%C3%A2-double-blind-randomized-placebo-controlled-cross-over-study
#10
Lauri Suojanen, Antti Haring, Antti Tikkakoski, Jenni K Koskela, Anna M Tahvanainen, Heini Huhtala, Mika Kähönen, Kalle Sipilä, Arttu Eräranta, Jukka T Mustonen, Kari Kivistö, Ilkka H Pörsti
Treatment with beta-blockers appears to show inferior reduction of central versus peripheral blood pressure. We aimed to examine simultaneous changes in central and peripheral blood pressure, vascular resistance, cardiac function and arterial stiffness during beta-blockade. Haemodynamics were investigated after 3 weeks of bisoprolol treatment (5 mg/d) in a double-blind, randomized, placebo-controlled cross-over trial in never-treated 16 Caucasian males with grade I-II primary hypertension using continuous tonometric pulse wave analysis and whole-body impedance cardiography...
March 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28244261/effect-of-beta-adrenergic-blockade-with-carvedilol-on-cachexia-in-severe-chronic-heart-failure-results-from-the-copernicus-trial
#11
Andrew L Clark, Andrew J S Coats, Henry Krum, Hugo A Katus, Paul Mohacsi, Damien Salekin, Melissa K Schultz, Milton Packer, Stefan D Anker
BACKGROUND: Cardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined. METHODS: We prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%...
February 27, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28215000/angiotensin-ii-receptor-blockers-attenuate-lipopolysaccharide-induced-memory-impairment-by-modulation-of-nf-%C3%AE%C2%BAb-mediated-bdnf-creb-expression-and-apoptosis-in-spontaneously-hypertensive-rats
#12
Ruby Goel, Shahnawaz Ali Bhat, Kashif Hanif, Chandishwar Nath, Rakesh Shukla
Clinical studies demonstrated a positive correlation between hypertension and cognitive decline. Beneficial effects of angiotensin II receptor blockers on cognitive functions have also been reported earlier; however, its role in chronic neuroinflammation-induced memory impairment in the hypertensive state is not well understood. Therefore, in the present study, we investigated the effect of angiotensin II receptor blockers on memory impairment induced by lipopolysaccharide (LPS) in spontaneously hypertensive rats (SHRs)...
February 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#13
David Acton, Gareth Brian Miles
Activation of N-methyl-D-aspartate receptors (NMDARs) requires the binding of a co-agonist, either D-serine or glycine, in addition to glutamate. Changes in occupancy of the co-agonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR co-agonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by D(-)-2-amino-5-phosphonopentanoic acid (D-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28197025/current-perioperative-management-of-pheochromocytomas
#14
REVIEW
Rashmi Ramachandran, Vimi Rewari
Neuroendocrine tumors which have the potential to secrete catecholamines are either associated with sympathetic adrenal (pheochromocytoma) or nonadrenal (paraganglioma) tissue. Surgical removal of these tumors is always indicated to cure and prevent cardiovascular and other organ system complications associated with catecholamine excess. Some of these tumors have malignant potential as well. The diagnosis, localization and anatomical delineation of these tumors involve measurement of catecholamines and their metabolic end products in plasma and urine, (123)I-metaiodobenzylguanidine scintigraphy, computed tomography, and/or magnetic resonance imaging...
January 2017: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/28188785/sortilin-related-receptor-1-interacts-with-amyloid-precursor-protein-and-is-activated-by-6-shogaol-leading-to-inhibition-of-the-amyloidogenic-pathway
#15
Ji-Young Na, Kibbeum Song, Ju-Woon Lee, Sokho Kim, Jungkee Kwon
Sortilin-related receptor 1 (SORL1) is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate amyloid beta (Aβ). Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, research regarding the activation of SORL1 has not yet been reported. Here, we aimed to investigate whether 6-shogaol contributes to the increases in SORL1 that are related to Alzheimer's disease (AD). To clarify the effect of 6-shogaol as a possible activator of SORL1, we used SORL1 siRNA as a blockade of SORL1 in hippocampal neuronal cells (HT22)...
February 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28187503/beneficial-and-harmful-effects-of-non-selective-beta-blockade-on-acute-kidney-injury-in-liver-transplant-candidates
#16
Sang Gyune Kim, Joseph J Larson, Ji Sung Lee, Therneau M Terry, W Ray Kim
Non-selective beta-blockers have played an important role in the prevention of portal hypertensive bleeding in cirrhotic patients. However, recent studies have suggested that non-selective beta-blockers may be harmful in some patients with end-stage liver disease. To evaluate the association between use of non-selective beta-blocker and the incidence of acute kidney injury (AKI). We conducted a nested case-control study in a cohort of liver transplant waitlist registrants. Each patient with AKI was matched to a control by the model for end-stage liver disease (MELD)-Na score, age, serum creatinine, and follow-up duration...
February 10, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28185035/anthracycline-chemotherapy-and-cardiotoxicity
#17
REVIEW
John V McGowan, Robin Chung, Angshuman Maulik, Izabela Piotrowska, J Malcolm Walker, Derek M Yellon
Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane...
February 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28161400/memory-b-cells-are-major-targets-for-effective-immunotherapy-in-relapsing-multiple-sclerosis
#18
REVIEW
David Baker, Monica Marta, Gareth Pryce, Gavin Giovannoni, Klaus Schmierer
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28160292/preoperative-%C3%AE-blockade-and-hypertension-in-the-first-hour-of-functional-endoscopic-sinus-surgery
#19
Samuel A Schechtman, Aileen P Wertz, Amy Shanks, Aleda Thompson, Kevin Tremper, Melissa A Pynnonen, David W Healy
OBJECTIVES/HYPOTHESIS: Local anesthetic with epinephrine is commonly injected into the nasal mucosa during functional endoscopic sinus surgery (FESS). Systemic absorption of epinephrine following local injection may occur, resulting in a mild sympathetic response. This study seeks to determine whether an exaggerated sympathetic response to epinephrine is demonstrated in patients undergoing FESS treated preoperatively with established pharmacologic beta (β) adrenoceptor blockade. STUDY DESIGN: A retrospective analysis of adult patients undergoing FESS at a tertiary care university hospital...
February 3, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28144388/hepatic-structural-enhancement-and-insulin-resistance-amelioration-due-to-at1-receptor-blockade
#20
EDITORIAL
Vanessa Souza-Mello
Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling...
January 18, 2017: World Journal of Hepatology
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