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Pharmacology and physiology

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https://www.readbyqxmd.com/read/29345363/effects-of-il-10-and-th-2-cytokines-on-human-m%C3%AF-phenotype-and-response-to-csf1r-inhibitor
#1
Leon P Pradel, Andreas Franke, Carola H Ries
Tumor-associated Mφs display a plastic phenotype that is regulated by the local tumor milieu. Gene expression analysis and functional characterization of Mφs exposed in vitro to individual cytokines aids to delineate the cross-talk between defined cytokines shaping the complex Mφ phenotype. Human monocyte-derived Mφs can be differentiated in vitro with the T helper cell type 2 response cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking antibody emactuzumab...
January 4, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29343521/t-type-ca2-channels-t-for-targetable
#2
REVIEW
Marta C Sallán, Anna Visa, Soni Shaikh, Mireia Nàger, Judit Herreros, Carles Cantí
In the past decade, T-type Ca2+ channels (TTCC) have been unveiled as key regulators of cancer cell biology and thus have been proposed as chemotherapeutic targets. Indeed, in vitro and in vivo studies indicate that TTCC pharmacologic blockers have a negative impact on the viability of cancer cells and reduce tumor size, respectively. Consequently mibefradil, a TTCC blocker approved in 1997 as an antihypertensive agent but withdrawn in 1998 because of drug-drug interactions, was granted 10 years later the orphan drug status by the FDA to investigate its efficacy against brain, ovary, and pancreatic cancer...
January 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29343276/the-antihyperlipidemic-effects-of-fullerenol-nanoparticles-via-adjusting-the-gut-microbiota-in-vivo
#3
Juan Li, Runhong Lei, Xin Li, Fengxia Xiong, Quanyang Zhang, Yue Zhou, Shengmei Yang, Yanan Chang, Kui Chen, Weihong Gu, Chongming Wu, Gengmei Xing
BACKGROUND: Nanoparticles (NPs) administered orally will meet the gut microbiota, but their impacts on microbiota homeostasis and the consequent physiological relevance remain largely unknown. Here, we describe the modulatory effects and the consequent pharmacological outputs of two orally administered fullerenols NPs (Fol1 C60(OH)7(O)8 and Fol113 C60(OH)11(O)6) on gut microbiota. RESULTS: Administration of Fol1 and Fol113 NPs for 4 weeks largely shifted the overall structure of gut microbiota in mice...
January 17, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29341808/development-of-an-open-access-web-based-interactive-tool-to-learn-autonomic-nervous-system-physiology-and-pharmacology
#4
Aydin Zahedivash, Michael W Lee
No abstract text is available yet for this article.
March 1, 2018: Advances in Physiology Education
https://www.readbyqxmd.com/read/29341179/better-characterization-of-vinflunine-pharmacokinetics-variability-and-exposure-toxicity-relationship-to-improve-its-use-analyses-from-18-trials
#5
A Schmitt, L Nguyen, G Zorza, P Ferré, A Pétain
AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29341031/getting-more-than-you-paid-for-unauthorized-natural-substances-in-herbal-food-supplements-on-eu-market
#6
Marijana Zovko Končić
As the population in the industrialized world develops preference for what is perceived as a natural and holistic way of disease treatment, the popularity and the number of food supplements on the market, including herbal ones, is experiencing an unprecedented rise. However, unlike herbal medicinal products, intended for treating or preventing disease, current legislation classifies food supplements as products intended for achieving nutritional or physiological effect and to supplement the normal diet. Accordingly, most food supplements are not to be associated with specific health claims...
January 16, 2018: Planta Medica
https://www.readbyqxmd.com/read/29338544/a-direct-comparison-between-norepinephrine-and-phenylephrine-for-augmenting-spinal-cord-perfusion-in-a-porcine-model-of-spinal-cord-injury
#7
Femke Streijger, Kitty So, Neda Manouchehri, Ana Gheorghe, Elena B Okon, Ryan M Chan, Benjamin Ng, Katelyn Shortt, Mypinder Singh Sekhon, Donald E Griesdale, Brian K Kwon
Current clinical guidelines recommend elevating the mean arterial blood pressure (MAP) to increase spinal cord perfusion in patients with acute spinal cord injury (SCI). This is typically achieved with vasopressors such as norepinephrine (NE) and phenylephrine (PE). These drugs differ in their pharmacologic properties and potentially have different effects on spinal cord blood flow (SCBF), oxygenation (PO2), and downstream metabolism after injury. Using a porcine model of thoracic SCI, we evaluated how these vasopressors influenced intraparenchymal SCBF, PaPO2, hydrostatic pressure, and metabolism within the spinal cord adjacent to the injury site...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29337857/low-molecular-weight-chitosan-insulin-complexes-solubilized-in-a-mixture-of-self-assembled-labrosol-and-plurol-oleaque-and-their-glucose-reduction-activity-in-rats
#8
Amani M Elsayed, Aseel H Khaled, Mayyas M Al Remawi, Nidal A Qinna, Hussam Abu Farsakh, Adnan A Badwan
Oral insulin delivery that better mimics physiological pathways is a necessity as it ensures patient comfort and compliance. A system which is based on a vehicle of nano order where positively charged chitosan interacts with negatively charged insulin and forms a polyelectrolyte complex (PEC) solubilizate, which is then solubilized into an oily phase of oleic acid, labrasol, and plurol oleaque-protects insulin against enzymatic gastrointestinal reduction. The use of an anionic fatty acid in the oily phase, such as oleic acid, is thought to allow an interaction with cationic chitosan, hence reducing particle size...
January 16, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29337842/perioperative-coagulation-management-in-liver-transplant-recipients
#9
Dmitri Bezinover, Daniel Dirkmann, James Findlay, Cosmin Guta, Matthias Hartmann, Ramona Nicolau-Raducu, Ahmed M Mukhtar, Marina Moguilevitch, Evan Pivalizza, David Rosenfeld, Fuat Saner, Christopher Wray, Gebhardt Wagener, James West
We review contemporary coagulation management for patients undergoing liver transplantation. A better understanding of the complex physiologic changes that occur in patients with end-stage liver disease has resulted in significant advances in anesthetic and coagulation management. A group of internationally recognized experts have critically evaluated current approaches for coagulopathy detection and management. Strategies for blood component and factor replacement have been evaluated and recommended therapies proposed...
January 15, 2018: Transplantation
https://www.readbyqxmd.com/read/29336812/enhancing-surgical-performance-by-adopting-expert-musicians-practice-and-performance-strategies
#10
Mei Rui, Jeffrey E Lee, Jean-Nicolas Vauthey, Claudius Conrad
BACKGROUND: Surgery is a performing art-each surgical procedure is a live performance that has immediate and irreversible consequences for both the performer and the audience. Surgeons operate with surgical instruments, whereas musicians perform with musical instruments. Both perform in high-stress, high-risk work environments, where small errors in motor performance or judgment can have immediate negative consequences. While there is abundant literature on musical performance and their impact on outcome, little similar research has been published in the field of surgery...
January 11, 2018: Surgery
https://www.readbyqxmd.com/read/29336473/usefulness-of-identifying-g-protein-coupled-receptor-dimers-for-diagnosis-and-therapy-of-neurodegenerative-diseases-and-of-gliomas
#11
REVIEW
Irene Reyes-Resina, David Aguinaga, José Luis Labandeira-García, José Luis Lanciego, Gemma Navarro, Rafael Franco
Immunochemical detection of G-protein-coupled receptors (GPCRs) in cells and tissues was a technical challenge for years. After the discovery of formation of GPCR dimers/trimers/tetramers in transfected cells, a most recent challenge has been to confirm receptor-receptor interactions in natural sources. The occurrence of dimers or higher order oligomers is important from a therapeutic point of view, mainly because their physiology/pharmacology is different from those of individual receptors. On the one hand, pathophysiological factors need to count more on GPCR dimers than on individual receptors...
January 16, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29336271/anti-inflammatory-drugs-and-herbs-with-special-emphasis-on-herbal-medicines-for-countering-inflammatory-diseases-and-disorders-a-review
#12
Mohd Iqbal Yatoo, Arumugam Gopalakrishnan, Archana Saxena, Oveas Rafiq Parray, Noore Alam Tufani, Sandip Chakraborty, Ruchi Tiwari, Kuldeep Dhama, Hafiz M N Iqbal
BACKGROUND: Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life-threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases. OBJECTIVE: To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects...
January 15, 2018: Recent Patents on Inflammation & Allergy Drug Discovery
https://www.readbyqxmd.com/read/29335833/regulation-of-bone-metabolism-by-micrornas
#13
REVIEW
Hanna Taipaleenmäki
PURPOSE OF REVIEW: The small non-coding microRNAs (miRNAs) have emerged as important post-transcriptional regulators of various physiological and pathological processes. The purpose of this article is to review the important recent advances on the role of miRNAs in bone remodeling and metabolic bone disorders. RECENT FINDINGS: In a physiological context, miRNAs regulate bone formation and bone resorption, thereby contributing to the maintenance of bone homeostasis...
January 15, 2018: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29335480/novel-analgesic-effects-of-melanin-concentrating-hormone-on-persistent-neuropathic-and-inflammatory-pain-in-mice
#14
Jae-Hwan Jang, Ji-Yeun Park, Ju-Young Oh, Sun-Jeong Bae, Hyunchul Jang, Songhee Jeon, Jongpil Kim, Hi-Joon Park
The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, indicating the involvements of many physiological functions, but the role in pain has yet to be determined. In this study, we found that pMCH-/- mice showed lower baseline pain thresholds to mechanical and thermal stimuli than did pMCH+/+ mice, and the time to reach the maximum hyperalgesic response was also significantly earlier in both inflammatory and neuropathic pain...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330456/20-hete-promotes-glucose-stimulated-insulin-secretion-in-an-autocrine-manner-through-ffar1
#15
Sorin Tunaru, Remy Bonnavion, Isabell Brandenburger, Jens Preussner, Dominique Thomas, Klaus Scholich, Stefan Offermanns
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330286/agonist-induced-cxcr4-and-cb2-heterodimerization-inhibits-g%C3%AE-13-rhoa-mediated-migration
#16
Kisha A Scarlett, ElShaddai Z White, Christopher J Coke, Jada R Carter, Latoya K Bryant, Cimona V Hinton
G-protein coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically non-functional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro. However, the reduced signaling entities responsible for the observed functional outputs remain elusive...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330132/an-overview-of-the-safety-pharmacology-society-strategic-plan
#17
M K Pugsley, S Authier, J E Koerner, W S Redfern, C G Markgraf, T Brabham, K Correll, M V Soloviev, A Botchway, M Engwall, M Traebert, J-P Valentin, T J Mow, A Greiter-Wilke, D J Leishman, H M Vargas
Safety Pharmacology studies are conducted to characterize the confidence by which biologically active new chemical entities (NCE) may be anticipated as safe. Non-clinical safety pharmacology studies aim to detect and characterize potentially undesirable pharmacodynamic activities using an array of in silico, in vitro and in vivo animal models. While a broad spectrum of methodological innovation and advancement of the science occurs within the Safety Pharmacology Society, the society also focuses on partnerships with health authorities and technology providers and facilitates interaction with organizations of common interest such as pharmacology, physiology, neuroscience, cardiology and toxicology...
January 9, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29329415/establishment-of-a-three-dimensional-model-to-study-human-uterine-angiogenesis
#18
Camille L Duran, Colette A Abbey, Kayla J Bayless
STUDY QUESTION: Can primary human uterine microvascular endothelial cells (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic responses when stimulated with proangiogenic factors, including sphingosine 1-phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), physiological levels of wall shear stress (WSS), human chorionic gonadotropin (hCG) and various combinations of estrogen and progesterone...
December 21, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29327758/a-computational-analysis-of-pro-angiogenic-therapies-for-peripheral-artery-disease
#19
Lindsay E Clegg, Feilim Mac Gabhann
Inducing therapeutic angiogenesis to effectively form hierarchical, non-leaky networks of perfused vessels in tissue engineering applications and ischemic disease remains an unmet challenge, despite extensive research and multiple clinical trials. Here, we use a previously-developed, multi-scale, computational systems pharmacology model of human peripheral artery disease to screen a diverse array of promising pro-angiogenic strategies, including gene therapy, biomaterials, and antibodies. Our previously-validated model explicitly accounts for VEGF immobilization, Neuropilin-1 binding, and weak activation of VEGF receptor 2 (VEGFR2) by the "VEGFxxxb" isoforms...
January 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29327527/role-and-relevance-of-blood-pressure-variability-in-hypertension-related-co-morbidities
#20
Ashok Kumar, B C Kalmath, Georgi Abraham, Johann Christopher, Pln Kaparthi, Louie Fischer, Neeta Deshpande, N K Mishra, Praveen Raj, Rajesh Javerani, Ramesh Goyal, Reefa Dsouza, Shashank R Joshi
Despite maintaining mean blood pressure at optimal levels, cardiovascular complications still occur in hypertensive patients. Blood pressure variability (BPV) has been implicated as a prominent factor responsible for incurring this additional risk. In this review we attempted to generate a consensus on the importance of BPV in the hypertension management and to evaluate different therapeutic options available to reduce BPV. Panel comprising of 11 leading experts from India in different areas of clinical practice (including nephrology, diabetes and endocrinology, cardiology, and critical care medicine) was convened...
December 2017: Journal of the Association of Physicians of India
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