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1.
Nat Commun ; 11(1): 4169, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820172

RESUMO

Sensing and responding to temperature is crucial in biology. The TRPV1 ion channel is a well-studied heat-sensing receptor that is also activated by vanilloid compounds, including capsaicin. Despite significant interest, the molecular underpinnings of thermosensing have remained elusive. The TRPV1 S1-S4 membrane domain couples chemical ligand binding to the pore domain during channel gating. Here we show that the S1-S4 domain also significantly contributes to thermosensing and couples to heat-activated gating. Evaluation of the isolated human TRPV1 S1-S4 domain by solution NMR, far-UV CD, and intrinsic fluorescence shows that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity. Further NMR characterization of the temperature-dependent conformational changes suggests the contribution of the S1-S4 domain to thermosensing shares features with known coupling mechanisms between this domain with ligand and pH activation. Taken together, this study shows that the TRPV1 S1-S4 domain contributes to TRPV1 temperature-dependent activation.


Assuntos
Temperatura Alta , Ativação do Canal Iônico/fisiologia , Canais de Cátion TRPV/metabolismo , Sensação Térmica/fisiologia , Sítios de Ligação/genética , Capsaicina/química , Capsaicina/metabolismo , Dicroísmo Circular , Humanos , Ativação do Canal Iônico/genética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Ligação Proteica , Domínios Proteicos , Canais de Cátion TRPV/química , Canais de Cátion TRPV/genética , Sensação Térmica/genética
2.
Toxicol Lett ; 332: 36-41, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32629075

RESUMO

The study examined the degradation of riot control agents (RCAs): 2-chloroacetophenone (CN), 2-chlorobenzalmalononitrile (CS), and capsaicin, using the Reactive Skin Decontamination Lotion Kit (RSDL®) lotion and evaluated the the direct liquid phase reactivity of the RSDL lotion component with each RCA. RSDL lotion was mixed with the selected RCAs at different molar ratios. Reactivity of the active ingredient potassium 2,3-butanedione monoximate (KBDO) with the RCA was observed for one hour. Samples of 10 µL were taken and quenched, analyzed for residual RCA using LC-MS. CN, was degraded at molar ratios of two and above in less than 2 min. At a molar ratio of 1:1 KBDO:CN, ∼90 % of CN was degraded within 2 min, the remaining 10 % residual CN was observed for one hour without any change. CS, degradation of more than 68 % of CS was achieved at 20:1 M ratio of KBDO:CS within 1 h of reaction time. For capsaicin, no degradation was observed regardless of the higher molar ratios of up to 20:1 and longer reaction times of up to one hour. This study provides evaluation of neutralizing action of the RSDL lotion without assessment of the physical removal component by the RSDL Kit.


Assuntos
Capsaicina/isolamento & purificação , Descontaminação/métodos , Irritantes/isolamento & purificação , Fármacos do Sistema Sensorial/isolamento & purificação , Pele/química , ômega-Cloroacetofenona/isolamento & purificação , Calibragem , Capsaicina/análise , Substâncias para a Guerra Química , Cromatografia Líquida de Alta Pressão , Humanos , Irritantes/análise , Fármacos do Sistema Sensorial/análise , ômega-Cloroacetofenona/análise
3.
J Smooth Muscle Res ; 56(0): 46-57, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581185

RESUMO

Oropharyngeal dysphagia (OD) is a common symptom in the older people, and may cause fatal complications such as aspiration pneumonia. However, there is no established treatment for OD. The relationship between the transient receptor potential vanilloid 1 (TRPV1) and substance P released by activated TRPV1 was recently demonstrated. Further, there are several reports showing that capsaicin, a specific agonist of TRPV1, can improve OD. Currently, the evaluation of swallowing is mainly performed by videofluoroscopic examination. However, there are no reports on the clinical application of ultrasonography using tissue Doppler imaging. In this review, we describe the pathophysiology and treatments for OD, introduce our novel US method to evaluate cervical esophageal motility, and then outline our clinical study examining the effects of capsaicin, a specific TRPV1 agonist, in older patients with OD.


Assuntos
Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/terapia , Ultrassonografia Doppler/métodos , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Motilidade Gastrointestinal , Humanos , Substância P , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/metabolismo
4.
J Vasc Res ; 57(4): 185-194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32526735

RESUMO

Information on the function of transient receptor potential vanilloid 1 (TRPV1) in arteriogenesis is limited. We aimed to verify whether TRPV1 is involved in collateral vessel growth in rat hind limbs and elucidate the possible subcellular action mechanisms. Adult Sprague Dawley rats were chosen to establish the hind limb ischemic model and treatment with capsaicin. Angiographies were performed, and tissue was isolated for immunohistochemistry. In vitro, rat aortic endothelial cells (RAECs) were treated with capsaicin and antagonist capsazepine. The RAEC proliferation was determined, and the protein and mRNA levels of Ca2+-dependent transcription factors were assessed. In vivo, the collateral vessels exhibited positive outward remodeling characterized by enhanced inflammatory cell/macrophage accumulation in the adventitia and activated cell proliferation in all layers of the vascular wall and elevated endothelial NO synthetase expression in the rats with hind limb ligation. In RAECs, TRPV1 activation-induced Ca2+-dependent transcriptional factors, nuclear factor of activated T cells 1, calsenilin and myocyte enhancer factor 2C increase, and augmented RAEC proliferation could be a subcellular mechanism for TRPV1 in endothelial cells and ultimately contribute to collateral vessel growth. TRPV1, a novel candidate, positively regulates arteriogenesis, meriting further studies to unravel the potential therapeutic target leading to improved collateral vessel growth for treating ischemic diseases.


Assuntos
Indutores da Angiogênese/farmacologia , Artérias/efeitos dos fármacos , Capsaicina/farmacologia , Circulação Colateral/efeitos dos fármacos , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Canais de Cátion TRPV/agonistas , Animais , Artérias/metabolismo , Artérias/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Membro Posterior , Isquemia/metabolismo , Isquemia/fisiopatologia , Proteínas Interatuantes com Canais de Kv/metabolismo , Fatores de Transcrição MEF2/metabolismo , Fatores de Transcrição NFATC/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Transdução de Sinais , Canais de Cátion TRPV/metabolismo
5.
Expert Opin Pharmacother ; 21(11): 1377-1387, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32511032

RESUMO

INTRODUCTION: Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED: The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION: Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Capsaicina/administração & dosagem , Capsaicina/uso terapêutico , Neuralgia/tratamento farmacológico , Administração Tópica , Analgésicos/efeitos adversos , Capsaicina/efeitos adversos , Análise Custo-Benefício , Prova Pericial , Humanos , Neuralgia/metabolismo , Pregabalina/administração & dosagem , Pregabalina/efeitos adversos , Pregabalina/uso terapêutico , Qualidade de Vida , Canais de Cátion TRPV/metabolismo , Adesivo Transdérmico
6.
Am J Physiol Cell Physiol ; 318(5): C969-C980, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32293931

RESUMO

The porcine lens response to a hyperosmotic stimulus involves an increase in the activity of an ion cotransporter sodium-potassium/two-chloride cotransporter 1 (NKCC1). Recent studies with agonists and antagonists pointed to a mechanism that appears to depend on activation of transient receptor potential vanilloid 1 (TRPV1) ion channels. Here, we compare responses in lenses and cultured lens epithelium obtained from TRPV1-/- and wild type (WT) mice. Hydrostatic pressure (HP) in lens surface cells was determined using a manometer-coupled microelectrode approach. The TRPV1 agonist capsaicin (100 nM) caused a transient HP increase in WT lenses that peaked after ∼30 min and then returned toward baseline. Capsaicin did not cause a detectable change of HP in TRPV1-/- lenses. The NKCC inhibitor bumetanide prevented the HP response to capsaicin in WT lenses. Potassium transport was examined by measuring Rb+ uptake. Capsaicin increased Rb+ uptake in cultured WT lens epithelial cells but not in TRPV1-/- cells. Bumetanide, A889425, and the Akt inhibitor Akti prevented the Rb+ uptake response to capsaicin. The bumetanide-sensitive (NKCC-dependent) component of Rb+ uptake more than doubled in response to capsaicin. Capsaicin also elicited rapid (<2 min) NKCC1 phosphorylation in WT but not TRPV1-/- cells. HP recovery was shown to be absent in TRPV1-/- lenses exposed to hyperosmotic solution. Bumetanide and Akti prevented HP recovery in WT lenses exposed to hyperosmotic solution. Taken together, responses to capsaicin and hyperosmotic solution point to a functional role for TRPV1 channels in mouse lens. Lack of NKCC1 phosphorylation and Rb+ uptake responses in TRPV1-/- mouse epithelium reinforces the notion that a hyperosmotic challenge causes TRPV1-dependent NKCC1 activation. The results are consistent with a role for the TRPV1-activated signaling pathway leading to NKCC1 stimulation in lens osmotic homeostasis.


Assuntos
Cristalino/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/genética , Canais de Cátion TRPV/genética , Animais , Bumetanida/farmacologia , Capsaicina/farmacologia , Linhagem Celular , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Humanos , Pressão Hidrostática/efeitos adversos , Cristalino/efeitos dos fármacos , Camundongos , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Suínos
7.
Am J Physiol Cell Physiol ; 318(5): C1018-C1029, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32293932

RESUMO

Autophagy is a highly conserved self-protection mechanism that plays a crucial role in cardiovascular diseases. Cardiomyocyte hypoxic injury promotes oxidative stress and pathological alterations in the heart, although the interplay between these effects remains elusive. The transient receptor potential vanilloid 1 (TRPV1) ion channel is a nonselective cation channel that is activated in response to a variety of exogenous and endogenous physical and chemical stimuli. Here, we investigated the effects and mechanisms of action of TRPV1 on autophagy in hypoxic cardiomyocytes. In this study, primary cardiomyocytes isolated from C57 mice were subjected to hypoxic stress, and their expression of TRPV1 and adenosine 5'-monophosphate-activated protein kinase (AMPK) was regulated. The autophagy flux was assessed by Western blotting and immunofluorescence staining, and the cell viability was determined through Cell counting kit-8 assay and Lactate dehydrogenase assays. In addition, the calcium influx after the upregulation of TRPV1 expression in cardiomyocytes was examined. The results showed that the number of autophagosomes in cardiomyocytes was higher under hypoxic stress and that the blockade of autophagy flux aggravated hypoxic damage to cardiomyocytes. Moreover, the expression of TRPV1 was induced under hypoxic stress, and its upregulation by capsaicin improved the autophagy flux and protected cardiomyocytes from hypoxic damage, whereas the silencing of TRPV1 significantly attenuated autophagy. Our observations also revealed that AMPK signaling was activated and involved in TRPV1-induced autophagy in cardiomyocytes under hypoxic stress. Overall, this study demonstrates that TRPV1 activation mitigates hypoxic injury in cardiomyocytes by improving autophagy flux through the AMPK signaling pathway and highlights TRPV1 as a novel therapeutic target for the treatment of hypoxic cardiac disease.


Assuntos
Autofagia/genética , Traumatismos Cardíacos/genética , Proteínas Quinases/genética , Canais de Cátion TRPV/genética , Animais , Cálcio/metabolismo , Capsaicina/farmacologia , Sobrevivência Celular/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Traumatismos Cardíacos/patologia , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Hipóxia/patologia , Camundongos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais/genética
8.
J Pharmacol Sci ; 143(1): 60-63, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151541

RESUMO

TRPV1 is phosphorylated and functionally upregulated by protein kinases, and negatively regulated by phosphatases including calcineurin. Since the clinical use of calcineurin-inhibiting immunosuppressants is commonly associated with chronic diarrhea, we examined if tacrolimus, a calcineurin inhibitor, promotes TRPV1-dependent colonic hypersensitivity in mice. Intracolonic administration of capsaicin, a TRPV1 agonist, caused referred hyperalgesia in the lower abdomen, an effect prevented by capsazepine, a TRPV1 blocker. Tacrolimus accelerated the intracolonic capsaicin-induced referred hyperalgesia. Similarly, intracolonic capsaicin caused spinal ERK phosphorylation, a marker for nociceptor excitation, an effect promoted by tacrolimus. Thus, tacrolimus may aggravate TRPV1-related colonic pain accompanying irritable bowel syndrome.


Assuntos
Inibidores de Calcineurina/efeitos adversos , Capsaicina/efeitos adversos , Colo , Hiperalgesia/induzido quimicamente , Imunossupressores/efeitos adversos , Tacrolimo/efeitos adversos , Animais , Hiperalgesia/genética , Síndrome do Intestino Irritável/induzido quimicamente , Camundongos , Canais de Cátion TRPV/agonistas
10.
Life Sci ; 249: 117472, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112870

RESUMO

Aim Determine changes in the expressions of the ion channel-TRPV1-and neuropeptides-NKA, NKB, calcitonin gene-related peptide (CGRP), and SP-in 14-, 21-, and 42-day-old rats after inhaling 1.5% and 2.6% sevoflurane. MAIN METHODS: A small in-house inhalation anesthesia chamber was designed to allow 14-, 21-, and 42-day-old rats inhale 1.5% and 2.6% sevoflurane, and rats in the control group inhaled carrier gas(1 L/min air +1 L/min O2). In addition, 14- and 21-day-old rats were pretreated with capsazepine, followed by inhalation of 1.5% and 2.6% sevoflurane or the carrier gas. The expression of TRPV1 in lung tissues was detected by Western blotting, whereas the expressions of NKA, NKB, CGRP, and SP in the trachea were detected by immunohistochemistry. KEY FINDINGS: After inhalation of 1.5% sevoflurane, the expression of TRPV1 in the lung tissues of 14- and 21-day-old rats was significantly increased compared with that in the control group, which was antagonized by capsazepine pretreatment. Moreover, inhalation of 1.5% sevoflurane markedly increased the expressions of NKA, NKB, CGRP, and SP in the trachea of 21-day-old rats and of NKB, CGRP, and SP in the trachea of 14-day-old rats. The expressions of these molecules were antagonized by capsazepine pretreatment. Conversely, inhalation of 2.6% sevoflurane decreased the expressions of NKA and NKB in the trachea of 42-day-old rats. SIGNIFICANCE: Sevoflurane did not upregulate the expression of TRPV1 in the airways of late-developing rats. This anesthetic may have a two-way effect on airways, resulting in considerable effects in pediatric clinical anesthesia management.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Sevoflurano/administração & dosagem , Canais de Cátion TRPV/metabolismo , Traqueia/metabolismo , Administração por Inalação , Fatores Etários , Animais , Gasometria , Peso Corporal/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Neurocinina A/metabolismo , Neurocinina B/metabolismo , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Substância P/metabolismo
11.
J Pharmacol Sci ; 143(1): 9-16, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32107104

RESUMO

This study investigated the long-term effects of dihydrocapsaicin (DHC)-induced angiogenesis and improved functional outcomes in cerebral ischemia and reperfusion (I/R) rats. Middle cerebral artery occlusion was induced in I/R rats for 2 h, followed by reperfusion. The animals were divided into three groups: sham, I/R + vehicle, and I/R + DHC (10 mg/kg body weight). Fourteen days after I/R injury, the DHC-treated I/R rats had decreased neurological deficit scores, infarct volume, and brain morphology changes. DHC-induced angiogenesis significantly increased the expression of angiogenic factor proteins, such as hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and matrix metalloprotease 9 (MMP-9), at 3 d and 14 d following I/R and also increased the expression of angiogenic inhibitors, such as angiopoietin 1 (Ang-1) and its receptor tyrosine kinase (Tie-2), at 14 d following reperfusion. DHC-mediated angiogenesis was confirmed by a significant increase in positive BrdU labeling that co-localized with the von Willebrand factor (an endothelial cell marker) at 14 d after I/R. Furthermore, rotarod and pole tests demonstrated that DHC promoted functional recovery when compared with the vehicle group. Thus, the results reveal that DHC mediates angiogenesis and functional recovery after an ischemic stroke.


Assuntos
Indutores da Angiogênese , Isquemia Encefálica/tratamento farmacológico , Capsaicina/análogos & derivados , Neovascularização Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/patologia , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Fisiológica/genética , Ratos Wistar , Traumatismo por Reperfusão/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Metabolism ; 105: 154182, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32061660

RESUMO

The impairment of podocyte protein filtration function caused by excessive mitochondrial calcium intake is a critical feature of diabetic nephropathy (DN). Ca2+ channel transient receptor potential cation channel subfamily V member 1 (TRPV1) has been reported to protect against ischemia-reperfusion induced acute renal injury, but there is no report about its role in DN. Here, we report that dietary capsaicin potently inhibits and reverses chronic renal structural and functional damages in db/db or streptozotocin (STZ)-induced diabetic mice in a TRPV1-dependent manner. Activation of TRPV1 by capsaicin alleviated hyperglycemia-induced mitochondrial dysfunction in podocytes, accompanied by reduced mitochondria-associated membranes (MAMs) formation and fewer Ca2+ transport from endoplasmic reticulum (ER) to mitochondria. Mechanistically, TRPV1-mediated transient Ca2+ influx activated 5' AMP-activated protein kinase (AMPK) that reduced the transcription of Fundc1, a key molecule participating in MAMs formation. Inhibition of AMPK or overexpression of Fundc1 obviously blocked the inhibitory effect of capsaicin on MAMs formation and functional decline in podocytes. These findings emphasize the critical role of mitochondrial Ca2+ homeostasis in the maintenance of normal renal function and suggest an effective intervention method to counteract DN.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Podócitos/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Canais de Cálcio/metabolismo , Capsaicina/uso terapêutico , Dieta , Inibidores Enzimáticos/farmacologia , Hiperglicemia/tratamento farmacológico , Hiperglicemia/microbiologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Membranas Mitocondriais/efeitos dos fármacos , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/biossíntese
13.
14.
Drugs Aging ; 37(2): 83-89, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31916230

RESUMO

The prevalence of neuropathic pain in the older population has been reported to be very high and is most commonly localized to a circumscribed area. Treatment failure is frequent in neuropathic pain and is accompanied by central side effects with recommended oral drugs acting on the central nervous system. A number of topical pharmaceuticals are available on prescription and also sold over the counter. This review in persons aged older than 60 years shows the efficacy of lidocaine 5% and capsaicin 8% for localized neuropathic pain while results with other pharmaceuticals are rather inconsistent. Local application of drugs has a very limited systemic effect and the pharmacological advantages of local over systemic treatment are particularly interesting in older persons who often have comorbidities and take multiple medications. However, more information is needed on the efficacy and safety of lidocaine 5% and capsaicin 8% in older old persons and on the long-term effects of these pharmaceuticals. These studies should also pave the way for research and development in the field of topical analgesics with a satisfactory level of evidence-based medicine.


Assuntos
Analgésicos/administração & dosagem , Capsaicina/administração & dosagem , Lidocaína/administração & dosagem , Neuralgia/tratamento farmacológico , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Analgésicos/uso terapêutico , Capsaicina/uso terapêutico , Humanos , Lidocaína/uso terapêutico , Pessoa de Meia-Idade
15.
Sci Total Environ ; 710: 136361, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31926417

RESUMO

Capsaicin, which inhibits the attachment and growth of fouling organisms, is a bioactive substance that is generally recognized as a highly active environmental algaecide agent. Its derivatives are simple in structure and have been proven to have low toxicity and be environmentally friendly. Six capsaicin derivatives were synthesized via Friedel-Crafts alkylation and characterized using melting point (MP) analysis, infrared (IR) spectroscopy, nuclear magnetic resonance (1H NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The inhibition effect and toxicity of these compounds towards Phaeodactylum tricornutum (P. tricornutum), Skeletonema costatum (S. costatum) and Chaetoceros curvisetus (C. curvisetus) were tested. The capsaicin derivatives all showed inhibitory effects. In particular, compound E with over 95% (3 mg·L-1) inhibition and intermediate toxicity was superior to the other compounds, reflecting an environmentally friendly effect. This finding indicates that capsaicin derivatives possess the potential to become environmentally friendly algaecide agents. The fouling resistance of capsaicin derivatives incorporated into the coatings as antifouling agents was measured in the marine environment. The results showed that capsaicin derivatives possess excellent fouling resistance, with only a small amount of algae and muck attached to the tested panel at 90 days. The above results provide a scientific basis for the application of capsaicin derivatives as environmentally friendly antifouling agents.


Assuntos
Capsaicina/metabolismo , Incrustação Biológica , Capsaicina/química , Diatomáceas
16.
Am J Respir Crit Care Med ; 201(9): 1068-1077, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31990201

RESUMO

Rationale: Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, although its association with severe asthma remains unknown.Objectives: To determine the clinical impact of C-CS on severe asthma.Methods: We prospectively enrolled 157 patients with asthma (including 122 patients with severe asthma who were in step 4 or 5 according to the Global Initiative for Asthma 2015 guidelines) between November 2016 and October 2019. A capsaicin cough challenge was performed along with spirometry and assessment of biomarkers. The concentration required to induce at least five coughs by capsaicin was adopted as an index of C-CS. An Asthma Control Test and comorbidities were also evaluated. Associations of biomarkers with four clinical features of severe asthma made by the European Respiratory Society/American Thoracic Society guidelines (poor control [Asthma Control Test < 20; n = 58], frequent exacerbations [≥2/yr; n = 28], admissions [≥1/yr; n = 17], and airflow limitation [FEV1% predicted < 80%; n = 30]) were assessed.Measurements and Main Results: Heightened C-CS was associated with poor asthma control, frequent exacerbations, and admissions, particularly in patients without atopy (n = 54). Meanwhile, C-CS was not related to airflow limitation. Multivariate regression analysis has revealed that heightened C-CS (at least five coughs by capsaicin ≤ 2.44 µM) was a significant risk for poor asthma control and frequent exacerbations. Regarding general factors and comorbidities, ex-smoking status, diabetes mellitus, and chronic rhinosinusitis were associated with clinical features of severe asthma (all P < 0.05).Conclusions: Heightened C-CS is a risk factor for severe asthma. The present study suggests the association of airway neuronal dysfunction with the pathophysiology of non-type 2 severe asthma.


Assuntos
Asma/tratamento farmacológico , Capsaicina/efeitos adversos , Capsaicina/uso terapêutico , Doença Crônica/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais
17.
J Oral Facial Pain Headache ; 34(2020): 92­107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31560736

RESUMO

AIMS: To assess the pain and/or unpleasantness and the somatosensory changes caused by two experimental models of trigeminal nerve damage (topical application of capsaicin and local anesthetics) in healthy participants using extensive evaluation tools. METHODS: This double-blinded, randomized, placebo-controlled, crossover study included 20 healthy adult participants who underwent three separate sessions of testing. In each session, the psychophysical quantitative sensory testing (QST) and the electrophysiologic electrically evoked trigeminal "nociceptive-specific" blink reflex (nBR) investigations were performed at baseline. Following a 15-minute topical application of 0.1% capsaicin, 5% EMLA, or Vaseline (placebo) agents, the maximum numeric rating scale pain and unpleasantness scores were recorded. Additionally, qualitative sensory testing and somatosensory mapping were performed. The QST and nBR investigations were repeated immediately after each application. Data were analyzed using repeated-measures analysis of variance. RESULTS: Capsaicin application was associated with significantly higher pain and unpleasantness scores when compared to EMLA and Vaseline (P < .001), with varied bidirectional somatosensory changes among the participants and significant loss of thermosensory function (P < .030). EMLA application induced loss of thermal and mechanical somatosensory function (P < .030) and a significant reduction in electrically evoked pain scores on nBR investigation (P < .001). No significant changes were seen in the electrophysiologic component of the nBR after any of the applications (P = .922). CONCLUSION: Topical capsaicin and EMLA application mimicked certain aspects of somatosensory changes seen in trigeminal nerve damage patients and may be used as surrogate models of such changes.


Assuntos
Anestesia Local , Dor , Traumatismos do Nervo Trigêmeo , Adulto , Capsaicina , Estudos Cross-Over , Método Duplo-Cego , Humanos , Nervo Trigêmeo
18.
Schmerz ; 34(1): 21-32, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31562537

RESUMO

BACKGROUND: Neuropathic pain consistently presents a significant therapeutic challenge. Topically applied analgesics have the advantage of showing low systemic side effects, but data on long-term effectiveness are lacking. Consequently, interviews were carried out with all patients being treated with topical analgesics in hospital. METHODS: Ethics 16-5690, German Clinical Trials Register (DRKS) 00011877. Between 2008 and 2017 a total of 265 patients were treated at least once with either capsaicin 8% (C), lidocaine 5% (L) and/or perineural botulinum toxin type A (B). From this sample, 205 patients (77%) were interviewed by telephone for feedback on pain reduction (first/last treatment: low/moderate/very good), the possible reduction of analgesic prescription and if applicable the reasons for discontinuation of use (time of interview C: 26 ± 19 months, L: 61 ± 23 months, B: 11 ± 6 months after start). Further pretreatment data and diagnoses were obtained from the in-house documentation system. Responders or long-term responders were defined as patients with at least one moderate pain reduction after the first or last treatment, as long as the effect was adequately maintained. RESULTS: In all treatment groups (56 ± 13 years, 62% male, C: 80, L: 84, B: 58 patients) patients with a long history of pain (C: 60 ± 73 months, L: 59 ± 66 months, B: 67 ± 71 months) and high pain intensity (numeric rating scale, NRS, C: 7 ± 2, L: 7 ± 2, B: 6 ± 2), were predominant. The highest primary and long-term responder rates were exhibited by L (57%/60%, B: 52%/37%, C: 23%/15%). With B, long-term responders were most frequently able to reduce analgesic use (74%, C: 58%, L: 38%). DISCUSSION: Despite the long duration of the disease, the most used off-label topical drugs L and B demonstrated a high primary response rate (in contrast to C), with most benefiting from long-term treatment.


Assuntos
Analgésicos , Toxinas Botulínicas Tipo A , Neuralgia , Administração Tópica , Analgésicos/administração & dosagem , Capsaicina , Feminino , Humanos , Lidocaína , Masculino , Neuralgia/tratamento farmacológico
19.
J Sci Food Agric ; 100(1): 129-138, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31452202

RESUMO

BACKGROUND: Capsaicin, as a major pungent ingredient of peppers, has many health benefits. However, the strong irritation effect of capsaicin inhibits its application in the food industry. Emulsions can be an effective approach to alleviate the irritation. RESULTS: In this study, we used tocopheryl polyethylene glycol 1000 succinate (TPGS) as an emulsifier to prepare capsaicin emulsions through high-pressure homogenization. Capsaicin emulsions with a particle size of about 100 nm, -36.4 mV zeta potential, and 91.9% encapsulation efficiency were prepared successfully and showed better environmental stability and higher antioxidant activity. Emulsions reduced the cumulative release of capsaicin and had no toxic effect on buffalo rat liver (BRL-3A) cells. Moreover, the gastrointestinal injury model of rats showed that emulsions reduced the strong irritation of capsaicin. CONCLUSION: This work provides a theoretical basis for the application of irritant ingredients in food industry. © 2019 Society of Chemical Industry.


Assuntos
Capsaicina/química , Capsaicina/metabolismo , Trato Gastrointestinal/metabolismo , Animais , Emulsificantes/química , Emulsões/química , Emulsões/metabolismo , Masculino , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Vitamina E/química
20.
Medicina (Kaunas) ; 55(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795171

RESUMO

Background and Objectives: Among HIV infection symptoms, sensory neuropathy (HIV-SN) remains a main cause of suffering, with incidence varying from 13-50%. So far, numerous pharmacological and non-pharmacological treatments have been tested, although few evidence-based analgesic options are available. We conducted an up-to-date systematic review and meta-analysis of the literature in order to evaluate the efficacy and safety of pharmacologic and non-pharmacologic treatments for pain control, in patients with HIV neuropathy. Materials and Methods: We searched MEDLINE, EMBASE, Scopus/Elsevier, The Cochrane Central Register of Controlled Trials (CENTRAL), USA Clinical Trials registry, and The International Web of Science up to April 2019. All randomized controlled trials evaluating efficacy and safety of non-pharmacologic and pharmacologic therapies were included. Efficacy was defined as pain reduction during the study period. Safety was estimated from adverse events. A meta-analysis was performed whenever possible. Results: 27 randomized controlled trials (RCTs) were included for analysis (7 evaluating non pharmacologic interventions, 20 pharmacologic therapies). Non-pharmacologic studies (n = 742) involved seven different therapeutic modalities. Only Acupuncture/Moxibustion showed pain reduction over placebo, Gracely Pain Scale Mean (SD): Acu/Moxa 0.85 (0.12), placebo 1.10 (0.09), p = 0.05. Pharmacologic studies, involving 2516 patients revealed efficacy for capsaicin 8% over placebo (mean difference -8.04 [95% CI: -14.92 -1.15], smoked cannabis (where pooling data for meta-analysis was not possible) and recombinant Nerve Growth Factor. Conclusion: Despite various modalities for pain control in HIV-SN, strongest evidence exists for capsaicin 8% and smoked cannabis, although of low methodological quality. Among non-pharmacologic modalities, only Acu/Moxa gave a marginal beneficial effect in one study, possibly limited by inherent methodological flaws.


Assuntos
Infecções por HIV/complicações , Neuralgia/terapia , Manejo da Dor/métodos , Terapia por Acupuntura/métodos , Analgésicos/uso terapêutico , Capsaicina/uso terapêutico , Humanos , Maconha Medicinal/uso terapêutico , Neuralgia/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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