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https://www.readbyqxmd.com/read/29163050/mechanisms-of-cisplatin-induced-ototoxicity-and-otoprotection
#1
REVIEW
Sandeep Sheth, Debashree Mukherjea, Leonard P Rybak, Vickram Ramkumar
Evidence of significant hearing loss during the early days of use of cisplatin as a chemotherapeutic agent in cancer patients has stimulated research into the causes and treatment of this side effect. It has generally been accepted that hearing loss is produced by excessive generation of reactive oxygen species (ROS) in cell of the cochlea, which led to the development of various antioxidants as otoprotective agents. Later studies show that ROS could stimulate cochlear inflammation, suggesting the use of anti-inflammatory agents for treatment of hearing loss...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29159869/acute-intermittent-hypoxia-with-concurrent-hypercapnia-evokes-p2x-and-trpv1-receptor-dependent-sensory-long-term-facilitation-in-na%C3%A3-ve-carotid-bodies
#2
Arijit Roy, Melissa M J Farnham, Fatemeh Derakhshan, Paul M Pilowsky, Richard J A Wilson
Apneas constitute an acute existential threat to neonates and adults. In large part, this threat is detected by the carotid bodies, the primary peripheral chemoreceptors, and combatted by arousal and acute cardiorespiratory responses, including increased sympathetic output. Similar responses occur with repeated apneas but they continue beyond the last apnea and can persist for hours (i.e. ventilatory and sympathetic LTF). These long-term effects may be adaptive during acute episodic apnea, but may prolong hypertension causing chronic cardiovascular impairment...
November 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29159769/diversity-effect-of-capsaicin-on-different-types-of-skeletal-muscle
#3
Gan Zhou, Lina Wang, Yaqiong Xu, Kelin Yang, Lv Luo, Leshan Wang, Yongxiang Li, Jiawen Wang, Gang Shu, Songbo Wang, Ping Gao, Xiaotong Zhu, Qianyun Xi, Jiajie Sun, Yongliang Zhang, Qingyan Jiang
Capsaicin is a major pungent content in green and red peppers which are widely used as spice, and capsaicin may activate different receptors. To determine whether capsaicin has different effects on different types of skeletal muscle, we applied different concentrations (0, 0.01, and 0.02%) of capsaicin in the normal diet and conducted a four-week experiment on Sprague-Dawley rats. The fiber type composition, glucose metabolism enzyme activity, and different signaling molecules' expressions of receptors were detected...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29156899/modulating-the-endocannabinoid-pathway-as-treatment-for-peripheral-neuropathic-pain-a-selected-review-of-preclinical-studies
#4
Shannon O'Hearn, Patrick Diaz, Bo Angela Wan, Carlo DeAngelis, Nicholas Lao, Leila Malek, Edward Chow, Alexia Blake
Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon...
August 31, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29154859/expression-of-cgrp-neurotransmitter-and-vascular-genesis-marker-mrna-is-age-dependent-in-superior-cervical-ganglia-of-senescence-accelerated-prone-mice
#5
Kazuyuki Mitsuoka, Takeshi Kikutani, Yoko Miwa, Iwao Sato
Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released from the superior cervical ganglion (SCG) and causes head and neck pain. The morphological properties of human SCG neurons, including neurotransmitter content, are altered during aging. However, morphological changes in CGRP in the SCG during aging are not known. Therefore, we investigated CGRP and other markers in the SCG during aging in an aging model of senescence-accelerated prone mouse (SAMP8) and senescence-accelerated resistant mice (SAMR1) using real-time RT-PCR mRNA analyses and in situ hybridization...
November 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29149827/therapeutic-applications-of-capsaicin-in-upper-airways
#6
Carlo Cavaliere, Simonetta Masieri, Franco Cavaliere
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the substance responsible of the irritation caused by the contact of chili peppers with the skin or mucous membranes. This protoalkaloid acts by stimulating the transient receptor potential cation channel subfamily V member 1 (TRPV1), which is mainly expressed by nociceptive fibers of peripheral sensory neurons, but is also present in the central nervous system, and in some non-neuronal cells. Following the initial, intense neuronal excitation, a brief refractory period occurs...
November 17, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#7
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29140280/trpv3-channel-in-keratinocytes-in-scars-with-post-burn-pruritus
#8
Chun Wook Park, Hyun Ji Kim, Yong Won Choi, Bo Young Chung, So-Youn Woo, Dong-Keun Song, Hye One Kim
Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29138447/the-semaphorin-3a-inhibitor-sm-345431-preserves-corneal-nerve-and-epithelial-integrity-in-a-murine-dry-eye-model
#9
Risa Yamazaki, Katsuya Yamazoe, Satoru Yoshida, Shin Hatou, Emi Inagaki, Hideyuki Okano, Kazuo Tsubota, Shigeto Shimmura
Dry eye disease (DED) is a common disorder causing discomfort and ocular fatigue. Corneal nerves are compromised in DED, which may further cause loss of corneal sensation and decreased tear secretion. Semaphorin 3A (Sema3A) is expressed by the corneal epithelium under stress, and is known as an inhibitor of axonal regeneration. Using a murine dry eye model, we found that topical SM-345431, a selective Sema3A inhibitor, preserved corneal sensitivity (2.3 ± 0.3 mm versus 1.4 ± 0.1 mm in vehicle control, p = 0...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137713/trpv1-a-potential-therapeutic-target-in-type-2-diabetes-and-comorbidities
#10
REVIEW
Dorte X Gram, Jens J Holst, Arpad Szallasi
With an estimated 422 million affected patients worldwide in 2016, type 2 diabetes (T2D) has reached pandemic proportions and represents a major unmet medical need. T2D is a polygenic disease with a chronic, low-grade inflammatory component. Second-generation transient receptor potential vanilloid-1 (TRPV1) antagonists are potent anti-inflammatory agents with proven clinical safety. In rodent models of T2D, TRPV1 blockade was shown to halt disease progression and improve glucose metabolism. Thus, we propose that TRPV1 antagonists merit further study as novel therapeutic approaches to potentially treat T2D and its comorbidities...
November 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29134561/cannabinoid-receptor-type-1-agonist-acea-protects-neurons-from-death-and-attenuates-endoplasmic-reticulum-stress-related-apoptotic-pathway-signaling
#11
Talita A Vrechi, Fernanda Crunfli, Andressa P Costa, Andréa S Torrão
Neurodegeneration is the result of progressive destruction of neurons in the central nervous system, with unknown causes and pathological mechanisms not yet fully elucidated. Several factors contribute to neurodegenerative processes, including neuroinflammation, accumulation of neurotoxic factors, and misfolded proteins in the lumen of the endoplasmic reticulum (ER). Endocannabinoid signaling has been pointed out as an important modulatory system in several neurodegeneration-related processes, inhibiting the inflammatory response and increasing neuronal survival...
November 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29132924/impact-of-capsaicin-an-active-component-of-chili-pepper-on-pathogenic-chlamydial-growth-chlamydia-trachomatis-and-chlamydia-pneumoniae-in-immortal-human-epithelial-hela-cells
#12
Kazuya Yamakawa, Junji Matsuo, Torahiko Okubo, Shinji Nakamura, Hiroyuki Yamaguchi
Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide. Capsaicin, a component of chili pepper, which can stimulate actin remodeling via capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) and anti-inflammatory effects via PPARγ (peroxisome proliferator-activated receptor-γ) and LXRα (liver X receptor α), is a potential candidate to control chlamydial growth in host cells. We examined whether capsaicin could inhibit C. trachomatis growth in immortal human epithelial HeLa cells...
November 10, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29132095/inhibition-of-tnf-reduces-mechanical-orofacial-hyperalgesia-induced-by-complete-freund-s-adjuvant-by-a-trpv1-dependent-mechanism-in-mice
#13
Krzysztof Lis, Tomasz Grygorowicz, Agnieszka Cudna, David E Szymkowski, Ewa Bałkowiec-Iskra
BACKGROUND: Inflammation in the orofacial region results in pain and is associated with many pathological states, including migraine, neuralgias and temporomandibular disorder. Although extensively studied, the mechanisms responsible for these conditions are not known and effective treatments are lacking. We reported earlier that the proinflammatory cytokine tumor necrosis factor (TNF) plays an important role in regulation of trigeminal ganglion (TG) neuron function in vitro. In the present study we investigated the role of TNF in mechanical hypersensitivity in mice...
June 3, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29131694/role-of-neuron-glial-interaction-mediated-by-il-1%C3%AE-in-ectopic-tooth-pain
#14
H Komiya, K Shimizu, N Noma, Y Tsuboi, K Honda, K Kanno, K Ohara, M Shinoda, B Ogiso, K Iwata
Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1β (IL-1β) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation...
November 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29130364/fluorescent-labeling-and-2-photon-imaging-of-mouse-tooth-pulp-nociceptors
#15
A Kadala, P Sotelo-Hitschfeld, Z Ahmad, P Tripal, B Schmid, A Mueller, L Bernal, Z Winter, S Brauchi, U Lohbauer, K Messlinger, J K Lennerz, K Zimmermann
Retrograde fluorescent labeling of dental primary afferent neurons (DPANs) has been described in rats through crystalline fluorescent DiI, while in the mouse, this technique was achieved with only Fluoro-Gold, a neurotoxic fluorescent dye with membrane penetration characteristics superior to the carbocyanine dyes. We reevaluated this technique in the rat with the aim to transfer it to the mouse because comprehensive physiologic studies require access to the mouse as a model organism. Using conventional immunohistochemistry, we assessed in rats and mice the speed of axonal dye transport from the application site to the trigeminal ganglion, the numbers of stained DPANs, and the fluorescence intensity via 1) conventional crystalline DiI and 2) a novel DiI formulation with improved penetration properties and staining efficiency...
November 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29129206/differential-cytotoxicity-and-intracellular-calcium-signalling-following-activation-of-the-calcium-permeable-ion-channels-trpv1-and-trpa1
#16
Thomas Stueber, Mirjam J Eberhardt, Yaki Caspi, Shaya Lev, Alexander Binshtok, Andreas Leffler
Several members of the transient receptor channel (TRP) family can mediate a calcium-dependent cytotoxicity. In sensory neurons, vanilloids like capsaicin induce neurotoxicity by activating TRPV1. The closely related ion channel TRPA1 is also activated by irritants, but it is unclear if and how TRPA1 mediates cell death. In the present study we explored cytotoxicity and intracellular calcium signalling resulting from activation of TRPV1 and TRPA1, either heterologously expressed in HEK 293 cells or in native mouse dorsal root ganglion (DRG) neurons...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29125703/pharmacokinetics-and-safety-of-mavatrep-jnj-39439335-a-trpv1-antagonist-in-healthy-japanese-and-caucasian-men-a-double-blind-randomized-placebo-controlled-sequential-group-phase-1-study
#17
Prasarn Manitpisitkul, Kevin Shalayda, Lucille Russell, Panna Sanga, Bhavna Solanki, Joseph Caruso, Yuki Iwaki, John A Moyer
This single-center, double-blind, placebo-controlled, sequential-group phase 1 study evaluated the safety, tolerability, and pharmacokinetics (PK) of mavatrep (JNJ-39439335), a transient receptor potential vanilloid 1 antagonist, in healthy Japanese and caucasian subjects. In part 1, a single-ascending-dose study, 50 subjects (25 each healthy Japanese and caucasians) were enrolled and received a single oral dose of 10, 25, or 50 mg mavatrep. Caucasian subjects were matched to Japanese subjects with respect to age (±5 years) and body mass index (±5 kg/m(2) )...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29125700/bioavailability-and-pharmacokinetics-of-trpv1-antagonist-mavatrep-jnj-39439335-tablet-and-capsule-formulations-in-healthy-men-two-open-label-crossover-single-dose-phase-1-studies
#18
Prasarn Manitpisitkul, Kevin Shalayda, Lucille Russell, Panna Sanga, Yinka Williams, Bhavna Solanki, Joseph Caruso, John A Moyer
To improve room temperature stability and oral bioavailability of mavatrep (JNJ-39439335, a transient receptor potential vanilloid subtype-1 antagonist), various formulations were initially developed and evaluated in 2 phase 1 open-label, randomized, 3-way crossover studies in healthy participants. Study 1 evaluated 2 new overencapsulated tablet formulations (formulations B and C) relative to an overencapsulated early tablet formulation (formulation A), using mavatrep HCl salt form. Because these tablets were still not room-temperature stable, in study 2: two free-base solid dispersion amorphous formulations (formulations D and E) were evaluated relative to the best encapsulated formulation from study 1 (formulation C) and also food effect...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29121795/berberine-ameliorates-diabetic-neuropathy-trpv1-modulation-by-pkc-pathway
#19
Yan Zan, Cui-Xing Kuai, Zhi-Xia Qiu, Fang Huang
In recent years, berberine has increasingly become a topic of research as a treatment for diabetes due to its repair function, which recovers damaged pancreatic β cells. However, it is the complications of diabetes that seriously affect patients' life quality and longevity, among which diabetic neuropathy and the consequent acute pain are the most common. In this study, we established STZ-induced diabetic models to observe whether berberine, a main constitute of Coptis chinensis Franch which has shown good hypoglycemic effects, could relieve diabetes-induced pain and explored its possible mechanism in rats and mice...
November 9, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29121401/mp29-02-reduces-nasal-hyperreactivity-and-nasal-mediators-in-patients-with-house-dust-mite-allergic-rhinitis
#20
Inge Kortekaas Krohn, Ina Callebaut, Yeranddy A Alpizar, Brecht Steelant, Laura Van Gerven, Per Stahl Skov, Ahmad Kasran, Karel Talavera, Mira M Wouters, Jan L Ceuppens, Sven F Seys, Peter W Hellings
BACKGROUND: Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate (FP)) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. METHODS: A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR...
November 9, 2017: Allergy
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