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2.
J Vis Exp ; (159)2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32510505

RESUMO

The current animal models of osteoarthritis (OA) can be divided into spontaneous models and induced models, both of which aim to simulate the pathophysiological changes of human OA. However, as the main symptom in the late stage of OA, pain affects the patients' daily life, and there are not many available models. The mono-iodoacetate (MIA)-induced model is the most widely used OA pain model, mainly used in rodents. MIA is an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, which causes chondrocyte death, cartilage degeneration, osteophyte, and measurable changes in animal behavior. Besides, expression changes of matrix metalloproteinase (MMP) and pro-inflammatory cytokines (IL1 ß and TNF α) can be detected in the MIA-induced model. Those changes are consistent with OA pathophysiological conditions in humans, indicating that MIA can induce a measurable and successful OA pain model. This study aims to describe the methodology of intra-articular injection of MIA in rats and discuss the resulting pain-related behaviors and histopathological changes.


Assuntos
Modelos Animais de Doenças , Ácido Iodoacético/administração & dosagem , Ácido Iodoacético/farmacologia , Osteoartrite/complicações , Dor/induzido quimicamente , Animais , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Citocinas/metabolismo , Injeções Intra-Articulares , Masculino , Metaloproteinases da Matriz/metabolismo , Dor/complicações , Dor/patologia , Ratos
3.
Zhongguo Zhong Yao Za Zhi ; 45(4): 916-922, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237494

RESUMO

The aim was to observe the analgesic effect of Fengshi Qutong Capsules(FSQTC) on chronic inflammatory pain in mice, and investigate its effect on p-ERK/COX-2 signal molecular activity. A model of chronic inflammatory pain was induced in mice by complete Freund's adjuvant(CFA). The mice were divided into normal control group, model group, model+FSQTC 0.3, 0.6 and 1.2 g·kg~(-1 )groups, model+positive control drug ibuprofen(IBP, 0.34 mg·kg~(-1)·d~(-1)) group, and normal control+ FSQTC 1.2 g·kg~(-1)group. FSQTC or IBP was given once a day by oral administration. Standard Von Frey fiber was used to evaluate the mechanical pain threshold, and the acetone stimulation was used to induce inflammatory plantar and observe the cold pain reaction scores. The mechanical pain threshold and cold pain reaction scores were observed before administration and 1, 2, 3, 4, 6 h after administration on the first day, as well as 3 h after administration on the 3 rd to 7 th day. The protein levels of PGE_2, COXs-1,2 and p-ERK in the spinal cord of the inflammatory foot and lumbar 4-5 were detected by enzyme-linked immunosorbent assay, Western blot, immunohistochemistry and immunofluorescence. The results showed that the mechanical pain threshold of the model group decreased and the cold pain reaction score increased as compared with the normal group. FSQTC application could dose-dependently increase the mechanical pain threshold and decrease the cold pain reaction score. The effect lasted for 6 h, most significant at 3 h. The effect of ibuprofen was similar to that of the 0.6 g·kg~(-1) dose group. In addition, FSQTC could reduce the abnormally increased protein content of PGE_2, COX-2 and p-ERK in the inflammatory foot and/or spinal cord of the model group, and the effect was most significant in middle and high dose groups. However, it had no effect on COX-1 in the inflammatory foot and spinal cord of mice. The results suggest that FSQTC has ob-vious analgesic effect on chronic inflammatory pain in mice, which may be related to inhibition of p-ERK/COX-2 signaling pathway.


Assuntos
Analgésicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Cápsulas , Adjuvante de Freund , Inflamação/induzido quimicamente , Camundongos , Dor/induzido quimicamente , Ratos Sprague-Dawley
4.
J Neurosci ; 40(18): 3517-3532, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32245829

RESUMO

One of the first signs of viral infection is body-wide aches and pain. Although this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization is well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-ß) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double-stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.SIGNIFICANCE STATEMENT It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. Although specific mechanisms have been discovered for diverse bacterial and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type I interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity.


Assuntos
Viroses do Sistema Nervoso Central/metabolismo , Interferon Tipo I/toxicidade , Nociceptores/metabolismo , Limiar da Dor/fisiologia , Dor/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Animais , Células Cultivadas , Viroses do Sistema Nervoso Central/induzido quimicamente , Viroses do Sistema Nervoso Central/patologia , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Nociceptores/efeitos dos fármacos , Nociceptores/patologia , Dor/induzido quimicamente , Dor/patologia , Limiar da Dor/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia
5.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32201575

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a common cause of pain and poor quality of life for those undergoing treatment for cancer and those surviving cancer. Many advances have been made in the pre-clinical science; despite this, these findings have not been translated into novel preventative measures and treatments for CIPN. This review aims to give an update on the pre-clinical science, preventative measures, assessment and treatment of CIPN.


Assuntos
Antineoplásicos/efeitos adversos , Dor/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Humanos , Neoplasias/tratamento farmacológico , Paclitaxel/efeitos adversos , Qualidade de Vida
6.
Ann Pharmacother ; 54(9): 872-878, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32126800

RESUMO

Objective: To review phase II and III clinical trial data to evaluate the efficacy and safety of the halobetasol propionate/tazarotene (HP/TAZ) combination lotion (Duobrii), a medication approved by the Food and Drug Administration in April 2019 for adults with plaque psoriasis. Data Sources: A systematic search (January 2005 to July 2019) of MEDLINE (PubMed) and EMBASE databases was performed using the terms halobetasol, tazarotene, halobetasol/tazarotene, Duobrii, and IDP-118. Study Selection and Data Extraction: Relevant English-language articles reporting on phase II and phase III clinical trials were included. Data from the individual trials were extracted independently and then cross-checked to ensure accuracy. Data Synthesis: HP/TAZ was safe and efficacious compared with HP alone, TAZ alone, or vehicle. More patients achieved treatment success, described as a ≥2-grade improvement on Investigator Global Assessment Scale, over 8 weeks of treatment and at the 4-week follow-up after treatment cessation. The most common adverse events were dermatitis, pain, and pruritus, which occurred more often in the TAZ groups compared with the HP/TAZ cohorts. Relevance to Patient Care and Clinical Practice: The once-daily HP/TAZ combination lotion simplifies psoriasis treatment and may facilitate adherence, which may improve psoriasis outcomes. Conclusions: HP/TAZ combination lotion is efficacious and safe for plaque psoriasis treatment, with more patients achieving end points and fewer side effects than in HP, TAZ, or vehicle-treated controls. Drug synergy may play a role. Importantly, patient adherence to a once-daily combinational therapy is likely to contribute to efficacy.


Assuntos
Clobetasol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Ácidos Nicotínicos/uso terapêutico , Psoríase/tratamento farmacológico , Administração Cutânea , Adulto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Clobetasol/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Ácidos Nicotínicos/administração & dosagem , Ácidos Nicotínicos/efeitos adversos , Dor/induzido quimicamente , Prurido/induzido quimicamente , Índice de Gravidade de Doença , Creme para a Pele , Resultado do Tratamento , Estados Unidos
7.
Phytochemistry ; 171: 112234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901735

RESUMO

A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9ß-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.


Assuntos
Analgésicos/uso terapêutico , Diterpenos/uso terapêutico , Ericaceae/química , Glucosídeos/uso terapêutico , Dor/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Ácido Acético , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Glucosídeos/química , Glucosídeos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Estrutura Molecular , Dor/induzido quimicamente , Medição da Dor , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Relação Estrutura-Atividade
8.
Chem Biol Interact ; 317: 108941, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31926916

RESUMO

m-Trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2] is an organoselenium molecule that displays multiple pharmacological actions, including the antinociceptive effect. The current study investigated the (m-CF3-PhSe)2 restorative properties in models of acute and chronic inflammatory pain induced by complete Freund's adjuvant (CFA). Male adult Swiss mice received an intraplantar injection of CFA in the hindpaw and 24 h (acute) or 14 days (subchronic) later they were treated with a single or repeated (m-CF3-PhSe)2 schedule via intragastric route, respectively. The mechanical and thermal hypernociceptive behaviors were assessed by von Frey hair and hot plate tests. Samples of injected paw were collected to evaluate the tissue edema and myeloperoxidase (MPO) activity while cerebral contralateral cortex samples were used to determine the inflammatory proteins content (subchronic protocol). The acute (m-CF3-PhSe)2 administration (1 and 10 mg/kg) reduced the hypernociceptive behavior and both paw thickness and MPO activity induced by CFA injection. In the subchronic protocol, the repeated administration with a low effective dosage of (m-CF3-PhSe)2 reduced the mechanical and thermal hypernociception as well as restored the edema and MPO activity in paw samples. In addition, the repeated treatment schedule mitigated the increase in TNF-α, IL-1ß and COX-2 content in cerebral contralateral cortex induced by CFA injection. Collectively, these data showed that (m-CF3-PhSe)2 presents anti-inflammatory properties, which could be mediated by an interplay between peripheral and central mechanisms of action, reinforcing the potential biological properties of the compound.


Assuntos
Inflamação/induzido quimicamente , Compostos de Organossilício/farmacologia , Dor/induzido quimicamente , Dor/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Comportamento Animal/efeitos dos fármacos , Diclofenaco/administração & dosagem , Diclofenaco/farmacologia , Adjuvante de Freund/toxicidade , Inflamação/tratamento farmacológico , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Compostos de Organossilício/administração & dosagem , Medição da Dor , Sintase do Porfobilinogênio/metabolismo , Carbonilação Proteica , Compostos de Sulfidrila/metabolismo
10.
J Acupunct Meridian Stud ; 13(1): 19-24, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31743772

RESUMO

Melissa officinalis (MO) is one of the oldest herbal medicines commonly used in traditional medicine, which some studies have investigated for its analgesic effect. This study is an attempt to investigate the effects of intrathecal administration of Melissa officinalis on the pain induced by heat and formalin. In this experimental study, 70 male Wistar rats with an average weight of 270-320 g were randomly divided into five groups: control; sham that received 25 µl of saline through the spinal catheter; and three experimental groups that received 5, 10 or 20 mg/kg M. officinalis via the spinal catheter respectively. Five days after catheterization of the spinal cord from the lumbar region under anesthesia, the effects of Intrathecal administration of M. officinalis on heat- and formalin-induced pain were evaluated. Data were analyzed by using one-way ANOVA. Intrathecal injection of M. officinalis blocked heat-induced pain compared to sham group (p = 0.001). Maximum analgesia was observed 30 min after the injection. Furthermore, intrathecal administration of MO alleviated both acute (p = 0.007) and chronic (p = 0.001) phases of formalin-induced pain. Motor block was not observed in any of the above mentioned groups. The results showed that intrathecal administration of MO could significantly improve hot-water and formalin-induced pain in male Wistar rats.


Assuntos
Analgésicos/administração & dosagem , Melissa/química , Manejo da Dor , Extratos Vegetais/administração & dosagem , Animais , Formaldeído/efeitos adversos , Humanos , Injeções Espinhais , Masculino , Dor/induzido quimicamente , Ratos , Ratos Wistar
11.
Asia Pac J Clin Oncol ; 16(1): 80-85, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31774247

RESUMO

AIM: This study aimed to validate a simplified method of quantifying chemotherapy-induced peripheral neuropathy using the PainVision PS-2100® (PV) electrical perception system. METHODS: We assessed patients diagnosed with epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer and were about to undergo first-time paclitaxel and carboplatin chemotherapy. Peripheral neuropathy was assessed before and after chemotherapy administration in all patients according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE4.0), using a conventional assessment in combination with the PV system. The PV device comprises electrodes attached to the ulnar side of the forearm and the first joint of index fingers on both the left and right sides to measure the electrical perceptual threshold. The average of three threshold measurements was recorded for each patient. RESULTS: Thirty female patients (age 51.6 ± 12.2 [mean ± SD]) were included, and median number of chemotherapy drug treatments was 5 (first quartile: 4, second quartile: 5, and third quartile: 5). Twenty-seven patients (90%) reported posttreatment numbness; NCI-CTCAE4.0 perceptual anomaly grades were as follows: G1, 57 (40%); G2, 19 (13%); and G3, 7 (5%). A positive correlation was identified between right medial side PV threshold score and perceptual anomaly grade on measurements of the inner right-hand side only. CONCLUSION: Our preliminary results suggest that peripheral neuropathy may be quantified using PV. As CIPN often lowers QOL, it needs to be appropriately evaluated. Future studies with a larger patient cohort and methodological refinements to improve accuracy are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Dor/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Feminino , Humanos , Incidência , Japão/epidemiologia , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Dor/induzido quimicamente , Dor/epidemiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Projetos Piloto , Fatores de Risco , Pele/efeitos dos fármacos , Pele/patologia , Adulto Jovem
12.
J Photochem Photobiol B ; 202: 111700, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810039

RESUMO

Zinc oxide (ZnO), an inorganic metal oxide established in the form of nanoparticles, has considerable biological properties. The current research uses Selaginella convolute (S. convolute) leaf extract to establish ZnO NPs and to assess their use in pain management. S. Convolute leaf extract mediated ZnO NPs were characterized by modern techniques and instruments such as Fourier transforms infrared spectroscopy (FTIR), electron microscopy, X-ray diffraction (XRD), and Ultraviolet-vis-spectroscopy (UV-vis), energy dispersive X-ray spectroscopy (EDX), indicating the emergence of spherical NPs of which is around 40 nm. The FTIR spectrum also signified that S. convolute plant extract polyphenols acted as a capping ligand for the fabricated ZnO NPs. Possessed ZnO NPs have shown important characteristics of muscle relaxing and antinociceptive. A concentration dependent acetic acid induced writhing effect was noted for both S. convolute extract and ZnO NPs. S. convolute plant extract and ZnO NPs are found to exhibit highest muscle relaxation effect in both traction and chimney tests and no sedative effect was shown by both ZnO NPs and plant extract. The present results showed that the S. convolute leaves extract is a very effective green reducing agent for the preparation of ZnO NPs and the prepared NPs can be used in pain management in emerging nursing care in future.


Assuntos
Nanopartículas Metálicas/química , Selaginellaceae/química , Óxido de Zinco/química , Ácido Acético/toxicidade , Animais , Química Verde , Locomoção/efeitos dos fármacos , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Relaxamento Muscular/efeitos dos fármacos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Manejo da Dor , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Selaginellaceae/metabolismo
13.
J Photochem Photobiol B ; 202: 111674, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778953

RESUMO

The present work showed the preparation of gold (Au NPs) and silver nanoparticles (Ag NPs) using aqueous leaf extract of Clinacanthus nutans Lindau (C. Lindau). The prepared NPs were studied using various microscopic and spectroscopic techniques, which confirmed the formation of crystalline Ag NPs, Au NPs that are stabilized with C. Lindau extract polyphenols. The prepared Au NPs and Ag NPs are studied to assess their comparative analgesic and muscle relaxant activities conducted on BALB/c mice. The muscle relaxant studies displayed that Ag NPs were comparatively higher efficient than Au NPs and methanolic C. Lindau extract in traction examination. Additionally, the analgesic studies exhibited that Ag NPs, Au NPs showed maximum percentage reduction in acetic acid induced writhing at the concentrations of 50, 100 and 150 mg/kg body weight. Further, these results conclude that as prepared Au NPs and Ag NPs prepared from C. Lindau leaf extract demonstrated very good analgesic and muscle relaxant activities for the use of pain management in nursing care.


Assuntos
Acanthaceae/química , Analgésicos/síntese química , Ouro/química , Nanopartículas Metálicas/química , Prata/química , Acanthaceae/metabolismo , Ácido Acético/toxicidade , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Química Verde , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Relaxamento Muscular/efeitos dos fármacos , Cuidados de Enfermagem , Dor/induzido quimicamente , Dor/tratamento farmacológico , Manejo da Dor/métodos , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo
14.
J Photochem Photobiol B ; 202: 111668, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734435

RESUMO

Fraxinus rhynchophylla belongs to the family of Oleaceae and also called as Chinese ash wood possesses various pharmacological properties such as neuroprotective, antimicrobial, anti-inflammatory, etc. Therefore we synthesized ZnO nanoparticles using Fraxinus rhynchophylla wood extract as reducing and capping agent. The synthesized nanoparticles were characterized with the aid of UV-Spec, DLS, FT-IR and TEM analysis. Green synthesized ZnO nanoparticles were then assessed for anti-nociceptive property by using various nociception models such as thermal stress-induced, acetic acid, glutamate, capsaicin, and formalin-induced nociception. The sedative effect of synthesized ZnO nanoparticles was evaluated with an open field test. UV-Spectroscopic analysis confirms the formation of ZnO nanoparticles and the characterization studies DLS, FT-IR, and TEM analysis prove it has ideal nanoparticle can be used as a nano-drug. Results of both thermal stress-induced methods hot plate and tail immersion nociception test verified the synthesized ZnO nanoparticles are a potent antinociceptive drug. ZnO nanoparticles effectively reduced the abdominal writhes in acetic acid-induced nociception and it also significantly decreased the nociception activity in another glutamate, capsaicin, and formalin-induced nociception models. Open field experiment proved that synthesized ZnO nanoparticles are less sedative compared to the standard antinociceptive drug morphine. Overall our findings authentically confirm ZnO nanoparticles synthesized from Fraxinus rhynchophylla wood extract is a novel drug that persuasively reduces nociception in different nociceptive induced mice models and can be the best alternative for allopathic drugs which renders severe side effects.


Assuntos
Analgésicos/uso terapêutico , Fraxinus/química , Nanopartículas Metálicas/química , Dor/tratamento farmacológico , Óxido de Zinco/química , Analgésicos/síntese química , Analgésicos/química , Animais , Modelos Animais de Doenças , Formaldeído/toxicidade , Fraxinus/metabolismo , Química Verde , Temperatura Alta , Masculino , Nanopartículas Metálicas/uso terapêutico , Camundongos , Dor/induzido quimicamente , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química
15.
J Ethnopharmacol ; 247: 112265, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580941

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea cangaceira Pinto, Mansano & Azevedo (Fabaceae) is a Brazilian medicinal plant widely known as "Jatobá". In folk medicine, it is used to treat infections, respiratory problems, rheumatism, antitumoral, inflammation and pain, however, no activity has been scientifically validated. AIM OF THE STUDY: This study investigated chemical composition of essential oil from Hymenaea cangaceira (EOHc), antimicrobial, antinociceptive and antioxidant activities besides protection against DNA damage and hemolysis. MATERIAL AND METHODS: The essential oil was obtained by hydrodistillation, and characterized by GC-MS and GC-FID. The evaluation of antimicrobial activity was performed by microdilution method. The evaluation of the antioxidant activity was performed using the radicals DPPH, ABTS, O2- and OH-, and the protection of DNA damage using plasmid pBR322. Different experimental models were used to evaluate the antinociceptive effect (acetic acid and formalin), and evaluate the mechanisms of action involved with pharmacological antagonists (naloxone, atropine and gibenclamide) in mice. The essential oil was evaluated for hemolysis on human erythrocytes. RESULTS: The extraction of EOHc showed a yield of 0.18% on a dry basis, presenting high content of hydrocarbon sesquiterpenes (79.04%), high antioxidant activity and protect DNA from damage, besides presenting antifungal and antibacterial activity against Gram-positive and Gram-negative bacteria in vitro. It was found that the essential oil had no acute toxicity in mice up to 5000 mg/kg oral administration (o.a.), in addition to no hemolysis on human erythrocytes. The reduction of antinociceptive activity was 75%, with the opioid system as the mechanism of action. CONCLUSION: Our results validate the main activities by the traditional use attributed to H. cangaceira for antimicrobial and analgesic activity. In addition, the oil has a potent antioxidant activity, protecting the body against oxidative stress damage, adding new value to an endemic species not known to the industry.


Assuntos
Analgésicos/farmacologia , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Hymenaea/química , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Ácido Acético/toxicidade , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Brasil , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Etanol/química , Etnofarmacologia , Formaldeído/toxicidade , Humanos , Medicina Tradicional/métodos , Camundongos , Testes de Sensibilidade Microbiana , Nociceptividade/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/uso terapêutico , Dor/induzido quimicamente , Dor/diagnóstico , Dor/tratamento farmacológico , Medição da Dor , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Testes de Toxicidade Aguda
16.
Lancet Haematol ; 7(2): e112-e121, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866281

RESUMO

BACKGROUND: Chemoimmunotherapy is typically the standard of care for patients with Waldenström macroglobulinemia; however, infectious and hematologic toxic effects are problematic. Acalabrutinib is a selective, potent Bruton tyrosine-kinase inhibitor. The aim of this trial was to evaluate the activity and safety of acalabrutinib in patients with Waldenström macroglobulinemia. METHODS: This single-arm, multicentre, phase 2 trial was done in 19 European academic centres in France, Italy, Greece, the Netherlands, and the UK, and eight academic centres in the USA. Eligible patients were 18 years or older and had treatment naive (declined or not eligible for chemoimmunotherapy) or relapsed or refractory (at least one previous therapy) Waldenström macroglobulinemia that required treatment, an Eastern Cooperative Oncology Group performance status of 2 or less, and received no previous Bruton tyrosine-kinase inhibitor therapy. Patients received 100 mg oral acalabrutinib twice per day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response (at least a minor response) according to the 6th International Workshop for Waldenström Macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The primary outcome and safety were assessed in all patients who received at least one dose of treatment. This study is registered with ClinicalTrials.gov, number NCT02180724, and is ongoing, but no longer enrolling. FINDINGS: Between Sept 8, 2014, and Dec 24, 2015, 122 patients were assessed for eligibility, of which 106 (87%) patients were given acalabrutinib (14 were treatment naive and 92 had relapsed or refractory disease). With a median follow-up of 27·4 months (IQR 26·0-29·7), 13 (93% [95% CI 66-100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86-98]) of 92 relapsed or refractory patients per both the modified 3rd and 6th IWWM criteria. Seven (50%) of 14 treatment naive patients and 23 (25%) of 92 relapsed or refractory patients discontinued treatment on study. Grade 3-4 adverse events occurring in more than 5% of patients were neutropenia (17 [16%] of 106 patients) and pneumonia (7 [7%]). Grade 3-4 atrial fibrillation occurred in one (1%) patient and grade 3-4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7 [7%]), pneumonia (n=7 [7%]), pyrexia (n=4 [4%]), cellulitis (n=3 [3%]), fall (n=3 [3%]), and sepsis (n=3 [3%]). Pneumonia (n=5 [5%]) and lower respiratory tract infection (n=4 [4%]) were considered treatment related. One treatment-related death was reported (intracranial hematoma). INTERPRETATION: This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenström macroglobulinemia. Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. FUNDING: Acerta Pharma.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Benzamidas/efeitos adversos , Benzamidas/farmacologia , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Proteínas de Neoplasias/antagonistas & inibidores , Neutropenia/induzido quimicamente , Dor/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/efeitos adversos , Pirazinas/farmacologia , Qualidade de Vida , Recidiva , Infecções Respiratórias/etiologia , Terapia de Salvação , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/enzimologia , Macroglobulinemia de Waldenstrom/genética
17.
Cochrane Database Syst Rev ; 12: CD003006, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786810

RESUMO

BACKGROUND: Spinal anaesthesia has been implicated as one of the possible causes of neurological complications following surgical procedures. This painful condition, occurring during the immediate postoperative period, is termed transient neurological symptoms (TNS) and is typically observed after the use of spinal lidocaine. Alternatives to lidocaine that can provide high-quality anaesthesia without TNS development are needed. This review was originally published in 2005, and last updated in 2009. OBJECTIVES: To determine the frequency of TNS after spinal anaesthesia with lidocaine and compare it with other types of local anaesthetics by performing a meta-analysis for all pair-wise comparisons, and conducting network meta-analysis (NMA) to rank interventions. SEARCH METHODS: We searched CENTRAL, MEDLINE, Elsevier Embase, and LILACS on 25 November 2018. We searched clinical trial registries and handsearched the reference lists of trials and review articles. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing the frequency of TNS after spinal anaesthesia with lidocaine to other local anaesthetics. Studies had to have two or more arms that used distinct local anaesthetics (irrespective of the concentration and baricity of the solution) for spinal anaesthesia in preparation for surgery. We included adults who received spinal anaesthesia and considered all pregnant participants as a subgroup. The follow-up period for TNS was at least 24 hours. DATA COLLECTION AND ANALYSIS: Four review authors independently assessed studies for inclusion. Three review authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. We performed meta-analysis for all pair-wise comparisons of local anaesthetics, as well as NMA. We used an inverse variance weighting for summary statistics and a random-effects model as we expected methodological and clinical heterogeneity across the included studies resulting in varying effect sizes between studies of pair-wise comparisons. The NMA used all included studies based on a graph theoretical approach within a frequentist framework. Finally, we ranked the competing treatments by P scores. MAIN RESULTS: The analysis included 24 trials reporting on 2226 participants of whom 239 developed TNS. Two studies are awaiting classification and one is ongoing. Included studies mostly had unclear to high risk of bias. The NMA included 24 studies and eight different local anaesthetics; the number of pair-wise comparisons was 32 and the number of different pair-wise comparisons was 11. This analysis showed that, compared to lidocaine, the risk ratio (RR) of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine with RRs in the range of 0.10 to 0.23 while 2-chloroprocaine and mepivacaine did not differ in terms of RR of TNS development compared to lidocaine. Pair-wise meta-analysis showed that compared with lidocaine, most local anaesthetics were associated with a reduced risk of TNS development (except 2-chloroprocaine and mepivacaine) (bupivacaine: RR 0.16, 95% confidence interval (CI) 0.09 to 0.28; 12 studies; moderate-quality evidence; 2-chloroprocaine: RR 0.09, 95% CI 0.01 to 1.51; 2 studies; low-quality evidence; levobupivacaine: RR 0.13, 95% CI 0.02 to 0.69; 2 studies; low-quality evidence; mepivacaine: RR 1.01, 95% CI 0.18 to 5.82; 4 studies; very low-quality evidence; prilocaine: RR 0.18, 95% CI 0.07 to 0.49; 4 studies; moderate-quality evidence; procaine: RR 0.14, 95% CI 0.04 to 0.52; 2 studies; moderate-quality evidence; ropivacaine: RR 0.10, 95% CI 0.01 to 0.78; 2 studies; low-quality evidence). We were unable to perform any of our planned subgroup analyses due to the low number of TNS events. AUTHORS' CONCLUSIONS: Results from both NMA and pair-wise meta-analysis indicate that the risk of developing TNS after spinal anaesthesia is lower when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine are used compared to lidocaine. The use of 2-chloroprocaine and mepivacaine had a similar risk to lidocaine in terms of TNS development after spinal anaesthesia. Patients should be informed of TNS as a possible adverse effect of local anaesthesia with lidocaine and the choice of anaesthetic agent should be based on the specific clinical context and parameters such as the expected duration of the procedure and the quality of anaesthesia. Due to the very low- to moderate-quality evidence (GRADE), future research efforts in this field are required to assess alternatives to lidocaine that would be able to provide high-quality anaesthesia without TNS development. The two studies awaiting classification and one ongoing study may alter the conclusions of the review once assessed.


Assuntos
Anestesia Local/efeitos adversos , Raquianestesia/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Anestésicos Locais/efeitos adversos , Humanos , Lidocaína/efeitos adversos , Metanálise em Rede , Dor/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Integr Cancer Ther ; 18: 1534735419888584, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31868025

RESUMO

Background and Aims: In cancer patients, a common complication during chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). For this reason, we decided to conduct a phase II prospective study on 33 patients with multiple myeloma at first diagnosis, to evaluate whether a nutraceutical compound given for 6 months during bortezomib (BTZ) treatment succeeded in preventing the onset of neurotoxicity. Methods: Neurological evaluation, electroneurography, and functional and quality of life (QoL) scales were performed at baseline and after 6 months. We administered a tablet containing docosahexaenoic acid 400 mg, α-lipoic acid 600 mg, vitamin C 60 mg, and vitamin E 10 mg bid for 6 months. Results: Concerning the 25 patients who completed the study, at 6-month follow-up, 10 patients had no neurotoxicity (NCI-CTCAE [National Cancer Institute-Common Terminology Criteria for Adverse Events] = 0), while 13 progressed to NCI-CTCAE grade 1, 1 had NCI-CTCAE grade 1 with pain, and 1 experienced a NCI-CTCAE grade 2. Painful symptoms were reported only in 2 patients, and we observed stability on functional and QoL scales in all patients. None of the 25 patients stopped chemotherapy due to neurotoxicity. Conclusions: Our data seem to indicate that the co-administration of a neuroprotective agent during BTZ treatment can prevent the appearance/worsening of symptoms related to CIPN, avoiding the interruption of BTZ and maintaining valuable functional autonomy to allow normal daily activities. We believe that prevention remains the mainstay to preserve QoL in this particular patient population, and that future studies with a larger patient population are needed.


Assuntos
Bortezomib/efeitos adversos , Bortezomib/uso terapêutico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Síndromes Neurotóxicas/prevenção & controle , Ácido Tióctico/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Dor/induzido quimicamente , Estudos Prospectivos , Qualidade de Vida
19.
Molecules ; 24(24)2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31847360

RESUMO

Infusions of roots of Siolmatra brasiliensis (Cogn.) Baill, ("taiuiá", "cipó-tauá") are used for toothache pain and ulcers. We aimed to study the antinociceptive effects and identify the possible mechanism of action of this plant and its isolated substances (cayaponoside A1, cayaponoside B4, cayaponoside D, and siolmatroside I). Hydroethanol extract (HE), ethyl acetate fraction (EtOAc), and isolated saponins were evaluated in chemical and thermal models of pain in mice. Animals were orally pretreated and evaluated in the capsaicin- or glutamate-induced licking and in the hot plate tests. The antinociceptive mechanism of action was evaluated using the hot plate test with the following pretreatments: Atropine (cholinergic antagonist), naloxone (opioid antagonist), or L-NAME (nitric oxide synthase inhibitor). All extracts and isolated saponins increased the area under the curve in the hot plate test. Tested substances induced a higher effect than the morphine-treated group. Our data suggest that stems of S. brasiliensis and their isolated substances present antinociceptive effects. Cholinergic and opioidergic pathways seem to be involved in their mechanism of action. Taken together our data corroborate the traditional use of the plant and expands the information regarding its use.


Assuntos
Analgésicos/farmacologia , Cucurbitaceae/química , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Modelos Animais de Doenças , Extração Líquido-Líquido , Camundongos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Manejo da Dor , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Saponinas/administração & dosagem , Saponinas/química , Saponinas/isolamento & purificação , Solventes
20.
Pak J Pharm Sci ; 32(4(Supplementary)): 1879-1883, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31680087

RESUMO

Opioids and non-opioids have long been used as analgesic, anti-inflammatory and antipyretic. Long-term use of these drugs may lead to severe toxicities. Therefore natural remedies are now being explored to avoid risk of adverse effects associated with the use of these conventional medicines. Bioactive components from milk of different species have been identified as nutraceuticals, but no experimental or clinical study is conducted so far to explore the analgesic and anti-inflammatory potential of camel milk. In this study we evaluated camel milk for its possible analgesic and antiinflammatory activity. The anti-inflammatory effects of camel milk was studied in rats using paw edema method (induced by acetic acid) while tail-flick method was used to evaluate its analgesic effect in mice. Significantly increased tail-flick latency was shown after camel milk (33ml/kg) treatment when compared with acetylsalicylic acid at all time intervals. Anti-inflammatory activity of camel milk was significant (p<0.001) at 4th hour of treatment as shown by maximum percentage inhibition in edema volume (46.84%) in comparison to control. Results of our present study suggested possible use of camel milk as adjuvant therapy in treating various chronic pain and inflammatory ailments. Camel milk could further be investigated in future for recognition of biochemical constituents responsible for its antiinflammatory and pain relieving activities.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Camelus/metabolismo , Leite/metabolismo , Animais , Antipiréticos/farmacologia , Carragenina/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Febre/induzido quimicamente , Febre/tratamento farmacológico , Masculino , Camundongos , Modelos Animais , Dor/induzido quimicamente , Dor/tratamento farmacológico , Ratos
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