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https://www.readbyqxmd.com/read/30537520/diabetes-induced-neuropathic-mechanical-hyperalgesia-depends-on-p2x4-receptor-activation-in-dorsal-root-ganglia
#1
Juliana Maia Teixeira, Gilson Gonçalves Dos Santos, Amanda Ferreira Neves, Maria Carolina Pedro Athie, Ivan José Magayewski Bonet, Catarine Massucato Nishijima, Felipe Hertzing Farias, Jozi Godoi Figueiredo, Victor Hernandez-Olmos, Samer Alshaibani, Cláudia Herrera Tambeli, Christa E Müller, Carlos Amílcar Parada
Peripheral diabetic neuropathy (PDN) manifests in 50-60% of type I and II diabetic patients and is the major cause of limb amputation. Adequate therapy for PDN is a current challenge. There are evidences that the activation of the P2X4 receptor (P2X4R) expressed on microglial cells of the central nervous system takes part in the development of neuropathic pain. However, there is an open question: Is P2X4R activation on dorsal root ganglia (DRG) involved in the development of neuropathic pain? To answer this question, this study verified the involvement of P2X4R expressed in DRG cells on diabetes-induced neuropathic mechanical hyperalgesia in rats...
December 8, 2018: Neuroscience
https://www.readbyqxmd.com/read/30537160/mitochondrial-function-modulates-touch-signalling-in-arabidopsis-thaliana
#2
Yue Xu, Oliver Berkowitz, Reena Narsai, Inge De Clercq, Michelle Hooi, Bulone Vincent, Frank Van Breusegem, James Whelan, Yan Wang
Plants respond to short- and long-term mechanical stimuli, via altered transcript abundance and growth respectively. Jasmonate, gibberellic acid and calcium have been implicated in mediating responses to mechanical stimuli. Previously it was shown that the transcript abundance for the outer mitochondrial membrane protein of 66 kDa (OM66), is induced several-fold after 30 min in response to touch. Thus, the impact of mitochondrial function on the response to mechanical stimulation by touch at 30 min was investigated...
December 8, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/30534379/pharmacological-profile-of-the-neuropeptide-s-receptor-dynamic-mass-redistribution-studies
#3
Chiara Ruzza, Federica Ferrari, Remo Guerrini, Erika Marzola, Delia Preti, Rainer K Reinscheid, Girolamo Calo
Neuropeptide S (NPS) is the endogenous ligand of the neuropeptide S receptor (NPSR). NPS modulates several biological functions including anxiety, wakefulness, pain, and drug abuse. The aim of this study was the investigation of the pharmacological profile of NPSR using the dynamic mass redistribution (DMR) assay. DMR is a label-free assay that offers a holistic view of cellular responses after receptor activation. HEK293 cells stably transfected with the murine NPSR (HEK293mNPSR ) have been used. To investigate the nature of the NPS-evoked DMR signaling, FR900359 (Gq inhibitor), pertussis toxin (Gi inhibitor), and rolipram (phosphodiesterase inhibitor) were used...
December 2018: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/30528320/iron-deficiency-anemia-associated-with-acid-modifying-medications-two-cases-and-literature-review
#4
REVIEW
Ramya Deepthi Vinnakota, Allan S Brett
Iron deficiency anemia is often listed among potential adverse effects of gastric acid-suppressive medications, given that gastric acidity promotes intestinal absorption of nonheme iron. Additionally, the antacid calcium carbonate can inhibit iron absorption. However, there is little direct clinical evidence that proton-pump inhibitors, histamine-2 receptor antagonists, or calcium carbonate cause iron deficiency anemia. Most case reports have had substantial limitations (e.g., minimal follow-up and presence of other causes of iron deficiency), and retrospective cohort studies have lacked sufficient patient-specific detail to make strong causal inferences...
November 1, 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/30528162/synthesis-and-sar-of-novel-capsazepine-analogs-with-significant-anti-cancer-effects-in-multiple-cancer-types
#5
Jorge De La Chapa, Matthew Valdez, Franscisco Ruiz, Keith Gonzales, Wes Mitchell, Stanton F McHardy, Matthew Hart, Srikanth R Polusani, Cara B Gonzales
We previously demonstrated that capsazepine (CPZ), a synthetic transient receptor potential Vanilloid subtype 1 (TRPV1) antagonist, has significant anti-cancer effects in vivo. The purpose of this study was to develop more potent analogs based upon CPZ pharmacophore and structure-activity relationships (SAR) across analogs. We generated 30 novel compounds and screened for their anti-proliferative effects in cultured HeLa cervical cancer cells. Cell viability assays identified multiple compounds with IC50s  < 15 μM and one compound, 29 with an IC50  < 5 μM; six fold more potent than CPZ...
November 29, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/30526214/new-insights-in-purinergic-therapy-novel-antagonists-for-uridine-5-triphosphate-activated-p2y-receptors-from-brazilian-flora
#6
Natiele Carla da Silva Ferreira, Rômulo José Soares-Bezerra, Rebeca Ferreira Couto da Silveira, Clayton Menezes da Silva, Carla Santos de Oliveira, Andrea Surrage Calheiros, Tânia Maria Alves, Carlos Leomar Zani, Luiz Anastacio Alves
P2Y2 and P2Y4 receptors are physiologically activated by uridine 5'-triphosphate (UTP) and are widely expressed in many cell types in humans. P2Y2 plays an important role in inflammation and proliferation of tumor cells, which could be attenuated with the use of antagonists. However, little is known about the physiological functions related to P2Y4, due to the lack of selective ligands for these receptors. This can be solved through the search for novel compounds with antagonistic activity. The aim of this study was to discover new potential antagonist candidates for P2Y2 and P2Y4 receptors from natural products...
December 8, 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/30525440/-hardwickiic-acid-and-hautriwaic-acid-induce-antinociception-via-blockade-of-tetrodotoxin-sensitive-voltage-dependent-sodium-channels
#7
Song Cai, Shreya Sai Bellampalli, Jie Yu, Wennan Li, Yingshi Ji, E M Kithsiri Wijeratne, Angie Dorame, Shizhen Luo, Zhiming Shan, May Khanna, Aubin Moutal, John M Streicher, A A Leslie Gunatilaka, Rajesh Khanna
For an affliction that debilitates an estimated 50 million of U.S. adults, the current chronic pain management approaches are inadequate. The Centers for Disease Control and Prevention have called for a minimization in opioid prescription and use for chronic pain conditions, and thus, it is imperative to discover alternative non-opioid based strategies. For the realization of this call, a library of natural products was screened in search of pharmacological inhibitors of both voltage-gated calcium channels and voltage-gated sodium channels, excellent targets due to their well-established roles in nociceptive pathways...
December 7, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30525213/calcium-sensing-receptor-mediates-interleukin-1%C3%AE-induced-collagen-expression-in-mouse-collecting-duct-cells
#8
Min Wu, Si-Si Wang, Jing-Yuan Cao, Tao-Tao Tang, Min Gao, Kun-Ling Ma, Bi-Cheng Liu
The mechanisms that underlie the profibrotic effect of interleukin (IL)-1β are complicated and not fully understood. Recent evidence has suggested the involvement of the calcium-sensing receptor (CaSR) in tubular injury. Therefore, the current study aimed to investigate whether CaSR mediates IL-1β-induced collagen expression in cultured mouse inner medullary collecting duct cells (mIMCD3) and to determine the possible downstream signaling effector. The results showed that IL-1β significantly upregulated the expression of type I and III collagens in a concentration- and time-dependent manner...
December 7, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30517088/ip3-mediated-calcium-signaling-is-involved-in-the-mechanism-of-fractalkine-induced-hyperalgesia-response
#9
Aitao Wang, Tingting Yang, Lingli Zhang, Lizhou Jia, Qingping Wu, Shanglong Yao, Jianjun Xu, Hongxin Yang
BACKGROUND Fractalkine is widely expressed throughout the brain and spinal cord, where it can exert effects on pain enhancement and hyperalgesia by activating microglia through CX3C chemokine receptor 1 (CX3CR1), which triggers the release of several pro-inflammatory cytokines in the spinal cord. Fractalkine has also been shown to increase cytosolic calcium ([Ca2+]i) in microglia. MATERIAL AND METHODS Based on the characteristics of CX3CR1, a G protein-coupled receptor, we explored the role of inositol 1,4,5-trisphosphate (IP3) signaling in fractalkine-induced inflammatory response in BV-2 cells in vitro...
December 5, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/30517040/ltd-at-mossy-fiber-synapses-onto-stratum-lucidum-interneurons-requires-trkb-and-retrograde-endocannabinoid-signaling
#10
Enhui Pan, Zirun Zhao, James O McNamara
Hippocampal mossy fiber axons simultaneously activate CA3 pyramidal cells and stratum lucidum interneurons (SLIN), the latter providing feedforward inhibition to control CA3 pyramidal cell excitability. Filopodial extensions of giant boutons of mossy fibers provide excitatory synaptic input to the SLIN. These filopodia undergo extraordinary structural plasticity causally linked to executing memory tasks, leading us to seek the mechanisms by which activity regulates these synapses. High frequency stimulation of the mossy fibers induces LTD of their calcium permeable-AMPA receptor synapses with SLINs; previous work localized site of induction to be postsynaptic and site of expression to be presynaptic...
December 5, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/30509118/managing-chronic-kidney-disease-in-diabetes-patients-with-the-latest-chemical-therapies
#11
Jingbo Hu, Yongzhong Du
During the years, while treatment strategy for diabetes mellitus has improved, the incidence of diabetes worldwide increases continuously. Chronic kidney disease (CKD) is one of the major diabetic microvascular complications, and a primary cause leading to end-stage renal disease (ESRD). The progression to ESRD, affected by hyperglycemia and hypertension, is characterized by microalbuminuria and macroalbuminuria. With advances in understanding the pathogenesis of CKD in diabetic patients, many novel therapeutic targets have been proposed, and the corresponding agents are being developed continually to prevent the progression of CKD...
December 3, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/30508566/developmental-perfluorooctane-sulfonate-exposure-inhibits-long-term-potentiation-by-affecting-ampa-receptor-trafficking
#12
Qian Zhang, Wei Liu, Huimin Zhao, Zhou Zhang, Hui Qin, Fang Luo, Qiao Niu
Both animal study and epidemiological survey revealed the associations between defects of cognitive function and the developmental exposure to perfluorooctane sulfonate (PFOS), while the mechanism is not well known. The SD rats were exposed PFOS at 1.7, 5 and 15 mg/L by drinking water from gestation to the adulthood of the pups for evaluating the effects of PFOS exposure on long-term potentiation (LTP) and the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors trafficking. Whole-life exposure of PFOS beginning in utero to adulthood significantly inhibited the induction and expression of LTP, and the input/output curve (I/O) and paired-pulse facilitation (PPF) were moderately suppressed, suggesting that PFOS might affect the synaptic transmission and plasticity both in pre- and post-synaptic cells...
November 30, 2018: Toxicology
https://www.readbyqxmd.com/read/30507840/ryanodine-receptor-to-mitochondrial-reactive-oxygen-species-pathway-plays-an-important-role-in-chronic-human-immunodeficiency-virus-gp120mn-induced-neuropathic-pain-in-rats
#13
Kohei Godai, Keiya Takahashi, Yuta Kashiwagi, Ching-Hang Liu, Hyun Yi, Shue Liu, Chuanhui Dong, David A Lubarsky, Shuanglin Hao
BACKGROUND: Chronic pain is one of the most common complaints in patients with human immunodeficiency virus (HIV)-associated sensory neuropathy. Ryanodine receptor (RyR) and mitochondrial oxidative stress are involved in neuropathic pain induced by nerve injury. Here, we investigated the role of RyR and mitochondrial superoxide in neuropathic pain induced by repeated intrathecal HIV glycoprotein 120 (gp120) injection. METHODS: Recombinant HIV glycoprotein gp120MN was intrathecally administered to induce neuropathic pain...
November 30, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/30507781/pioglitazone-a-ppar%C3%AE-agonist-reduces-cisplatin-evoked-neuropathic-pain-by-protecting-against-oxidative-stress
#14
Iryna A Khasabova, Sergey G Khasabov, Julie K Olson, Megan L Uhelski, Amy H Kim, Alejandra M Albino-Ramírez, Chad L Wagner, Virginia S Seybold, Donald A Simone
Painful peripheral neuropathy is a dose-limiting side effect of cisplatin treatment. Using a murine model of cisplatin-induced hyperalgesia, we determined whether a PPARγ synthetic agonist, pioglitazone, attenuated the development of neuropathic pain and identified underlying mechanisms. Cisplatin produced mechanical and cold hyperalgesia and decreased electrical thresholds of Aδ and C-fibers, which were attenuated by co-administration of pioglitazone (10 mg/kg, i.p.) with cisplatin. Anti-hyperalgesic effects of pioglitazone were blocked by the PPARγ antagonist T0070907 (10 mg/kg, i...
November 29, 2018: Pain
https://www.readbyqxmd.com/read/30503945/design-synthesis-and-evaluation-of-pentacycloundecane-and-hexacycloundecane-propargylamine-derivatives-as-multifunctional-neuroprotective-agents
#15
Frank T Zindo, Sarel F Malan, Sylvester I Omoruyi, Adaze B Enogieru, Okobi E Ekpo, Jacques Joubert
The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The MTT cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 μM...
November 22, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30498821/use-of-ace-inhibitors-and-quality-of-life-in-an-older-population
#16
A Laudisio, S Giovannini, P Finamore, A Gemma, R Bernabei, R A Incalzi, G Zuccalà
BACKGROUND: Improved ability to treat chronic diseases have increased the interest in measuring health-related quality of life (HRQoL) in older adults. Hypertension and heart failure have been associated with decreased HRQoL. HYPOTHESIS: The aim of this study was to assess the association between health-related quality of life and use of angiotensin converting enzyme inhibitors in unselected community-dwelling elderly. METHODS: We analyzed data of all 387 subjects aged 75+ living in a rural Italian town, without exclusion criteria...
2018: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/30498197/glutamatergic-and-dopaminergic-modulation-of-cortico-striatal-circuits-probed-by-dynamic-calcium-imaging-of-networks-reconstructed-in-microfluidic-chips
#17
Benjamin Lassus, Jérémie Naudé, Philippe Faure, Denis Guedin, Ysander Von Boxberg, Clotilde Mannoury la Cour, Mark J Millan, Jean-Michel Peyrin
Although the prefrontal cortex and basal ganglia are functionally interconnected by parallel loops, cellular substrates underlying their interaction remain poorly understood. One novel approach for addressing this issue is microfluidics, a methodology which recapitulates several intrinsic and synaptic properties of cortico-subcortical networks. We developed a microfluidic device where cortical neurons projected onto striatal neurons in a separate compartment. We exploited real-time (low-resolution/high-output) calcium imaging to register network dynamics and characterize the response to glutamatergic and dopaminergic agents...
November 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30497083/use-of-metformin-and-platelet-reactivity-in-diabetic-patients-treated-with-dual-antiplatelet-therapy
#18
Monica Verdoia, Patrizia Pergolini, Roberta Rolla, Claudia Ceccon, Marina Caputo, Gianluca Aimaretti, Harry Suryapranata, Giuseppe De Luca
BACKGROUND: Enhanced platelet reactivity represents one of the major determinants of cardiovascular risk among diabetic patients. The aim of the present study was to evaluate the impact of metformin use on platelet reactivity in diabetic patients receiving dual antiplatelet therapy (DAPT). METHODS: We included diabetic patients treated with DAPT after an acute coronary syndrome or percutaneous coronary intervention. Platelet reactivity was assessed at 30-90 days by Multiple-electrode aggregometry...
November 29, 2018: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/30496623/prevention-of-injury-induced-osteoarthritis-in-rodent-temporomandibular-joint-by-targeting-chondrocyte-casr
#19
Mian Zhang, Hongxu Yang, Xianghong Wan, Lei Lu, Jing Zhang, Hongyun Zhang, Tao Ye, Qian Liu, Mianjiao Xie, Shibin Yu, Shaoxiong Guo, Wenhan Chang, Meiqing Wang
Traumatic joint injuries produce osteoarthritic cartilage manifesting accelerated chondrocyte terminal differentiation and matrix degradation via unknown cellular and molecular mechanisms. Here we report the ability of biomechanical stress to increase expression of the calcium-sensing receptor (CaSR), a pivotal driver of chondrocyte terminal differentiation, in cultured chondrogenic cells subjected to fluid flow shear stress (FFSS) and in chondrocytes of rodent temporomandibular joint (TMJ) cartilage subjected to unilateral anterior cross-bite (UAC)...
November 29, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/30480757/acupuncture-for-hypertension
#20
REVIEW
Jie Yang, Jiao Chen, Mingxiao Yang, Siyi Yu, Li Ying, Guan J Liu, Yu-Lan Ren, James M Wright, Fan-Rong Liang
BACKGROUND: Elevated blood pressure (hypertension) affects about one billion people worldwide. It is important as it is a major risk factor for stroke and myocardial infarction. However, it remains a challenge for the medical profession as many people with hypertension have blood pressure (BP) that is not well controlled. According to Traditional Chinese Medicine theory, acupuncture has the potential to lower BP. OBJECTIVES: To assess the effectiveness and safety of acupuncture for lowering blood pressure in adults with primary hypertension...
November 14, 2018: Cochrane Database of Systematic Reviews
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