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1.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731872

RESUMO

Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.


Assuntos
Trifosfato de Adenosina , Adenilil Ciclases , Relaxamento Muscular , Músculo Liso , Testosterona , Traqueia , Uridina Trifosfato , Animais , Uridina Trifosfato/farmacologia , Uridina Trifosfato/metabolismo , Cobaias , Relaxamento Muscular/efeitos dos fármacos , Masculino , Trifosfato de Adenosina/metabolismo , Traqueia/metabolismo , Traqueia/efeitos dos fármacos , Testosterona/farmacologia , Testosterona/metabolismo , Adenilil Ciclases/metabolismo , Músculo Liso/metabolismo , Músculo Liso/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptores Purinérgicos P2/metabolismo
2.
J Physiol Sci ; 74(1): 26, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654149

RESUMO

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10-100 µM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 µM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 µM), and a P2Y receptor antagonist, cibacron blue F3GA (200 µM), inhibited the ATP (100 µM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 µM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 µM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 µM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.


Assuntos
Trifosfato de Adenosina , Esôfago , Canais KATP , Músculo Liso , Receptores Purinérgicos P2Y , Animais , Ratos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Músculo Liso/metabolismo , Masculino , Receptores Purinérgicos P2Y/metabolismo , Esôfago/efeitos dos fármacos , Esôfago/fisiologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Canais KATP/metabolismo , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Ratos Wistar , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Ratos Sprague-Dawley
3.
Medicine (Baltimore) ; 103(16): e37929, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640262

RESUMO

RATIONALE: Fibromyalgia (FM) is characterized by idiopathic persistent chronic pain in the ligaments or musculoskeletal system, and more than half of the patients with FM might have migraine headaches. Direct musculoskeletal intervention could be a non-pharmacological management to relieve symptoms. However, patients with severe FM often have intense pain from only a soft touch, thereby rendering musculoskeletal intervention challenging. PATIENT CONCERNS: A 47-year-old man had progressing intense pain, and this affected his everyday life. There were no abnormal physical findings on laboratory examination such as levels of complement, antinuclear antibodies, and C-reactive protein, which were within normal limits. Magnetic resonance imaging did not indicate abnormalities. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient satisfied the American College of Rheumatology criteria. Finally, we made a final diagnosis of fibromyalgia. The therapeutic intervention of Kanshoho, the unique muscle relaxation technique with low force, relieved his pain. LESSONS: If Kanshoho is carefully applied in a state of hospitalization under surveillance by an experienced physician, it could be a promising muscle relaxation method. Relaxing the trapezius muscle and reducing its intramuscular pressure might be key in treating patients with severe FM. However, it needs elucidation of its mechanism.


Assuntos
Dor Crônica , Fibromialgia , Masculino , Humanos , Pessoa de Meia-Idade , Fibromialgia/complicações , Fibromialgia/terapia , Fibromialgia/diagnóstico , Terapia de Relaxamento , Dor Crônica/diagnóstico , Ligamentos , Músculos , Relaxamento Muscular
4.
Am J Physiol Regul Integr Comp Physiol ; 326(5): R438-R447, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38525536

RESUMO

The force drop after transcranial magnetic stimulation (TMS) delivered to the motor cortex during voluntary muscle contractions could inform about muscle relaxation properties. Because of the physiological relation between skeletal muscle fiber-type distribution and size and muscle relaxation, TMS could be a noninvasive index of muscle relaxation in humans. By combining a noninvasive technique to record muscle relaxation in vivo (TMS) with the gold standard technique for muscle tissue sampling (muscle biopsy), we investigated the relation between TMS-induced muscle relaxation in unfatigued and fatigued states, and muscle fiber-type distribution and size. Sixteen participants (7F/9M) volunteered to participate. Maximal knee-extensor voluntary isometric contractions were performed with TMS before and after a 2-min sustained maximal voluntary isometric contraction. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Fiber type I distribution and relative cross-sectional area of fiber type I correlated with TMS-induced muscle relaxation at baseline (r = 0.67, adjusted P = 0.01; r = 0.74, adjusted P = 0.004, respectively) and normalized TMS-induced muscle relaxation as a percentage of baseline (r = 0.50, adjusted P = 0.049; r = 0.56, adjusted P = 0.031, respectively). The variance in the normalized peak relaxation rate at baseline (59.8%, P < 0.001) and in the fatigue resistance (23.0%, P = 0.035) were explained by the relative cross-sectional area of fiber type I to total fiber area. Fiber type I proportional area influences TMS-induced muscle relaxation, suggesting TMS as an alternative method to noninvasively inform about skeletal muscle relaxation properties.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. We showed that fiber type I proportional area influences the TMS-induced muscle relaxation, suggesting that TMS could be used for the noninvasive estimation of muscle relaxation in unfatigued and fatigued human muscles when the feasibility of more direct method to study relaxation properties (i.e., muscle biopsy) is restricted.


Assuntos
Músculo Esquelético , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Estimulação Elétrica/métodos , Músculo Esquelético/fisiologia , Relaxamento Muscular , Fadiga Muscular/fisiologia , Contração Muscular/fisiologia , Contração Isométrica/fisiologia , Fibras Musculares Esqueléticas , Eletromiografia/métodos
5.
Semin Oncol Nurs ; 40(2): 151620, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38494385

RESUMO

OBJECTIVES: This study aimed to evaluate the effect of progressive muscle relaxation exercises (PMRE) on sleep quality in patients undergoing chemotherapy treatment and experiencing disturbed sleep. METHODS: The prospective randomized controlled study was conducted between March and September 2022 with 69 patients (intervention group: 34 patients, control group: 35 patients) in a hospital chemotherapy unit. During the data collection process, the "Personal Information Form" and "Pittsburgh Sleep Quality Index (PSQI)" were utilized. Patients in the intervention group performed PMRE twice a day for 8 weeks. Patients in the control group received routine care at the clinic without additional intervention. For data analysis, Student's t-test, Mann-Whitney U test, Fisher's exact test, and chi-square test were used. RESULTS: The sociodemographic attributes of patients within both the intervention and control groups exhibited comparability. However, notable distinctions emerged in the PSQI Global sleep score and PSQI subdimension scores, encompassing sleep latency and duration, subjective sleep quality, habitual sleep efficiency, sleep disturbance, and daytime dysfunction between the two groups. The study found a notable difference in scores between the patients in the intervention group and those in the control group. The patients who received the intervention had significantly lower scores (P < .001). CONCLUSION: The study revealed that PMRE was beneficial in improving sleep quality in cancer patients undergoing chemotherapy who had poor sleep quality. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses may consider using PMRE to improve the sleep quality of cancer patients receiving chemotherapy.


Assuntos
Neoplasias , Qualidade do Sono , Humanos , Masculino , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Neoplasias/terapia , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Idoso , Relaxamento Muscular , Transtornos do Sono-Vigília/etiologia , Terapia de Relaxamento/métodos
6.
Naunyn Schmiedebergs Arch Pharmacol ; 397(6): 4419-4434, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38108836

RESUMO

Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (< 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of ß2-adrenergic receptors/AC/cAMP pathway.


Assuntos
Asma , Broncodilatadores , AMP Cíclico , Modelos Animais de Doenças , Inibidores da Fosfodiesterase 4 , Traqueia , Animais , Cobaias , Inibidores da Fosfodiesterase 4/farmacologia , Asma/tratamento farmacológico , Asma/fisiopatologia , Traqueia/efeitos dos fármacos , Masculino , Broncodilatadores/farmacologia , AMP Cíclico/metabolismo , Músculo Liso/efeitos dos fármacos , Ovalbumina , Relaxamento Muscular/efeitos dos fármacos , Aminofilina/farmacologia
7.
J Med Food ; 26(11): 820-830, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37902984

RESUMO

Rhus coriaria L. (Anacardiaceae), also known as Sumac, is commonly used as a spice, flavoring agent, and as a traditional medicinal herb. This includes also the traditional use for treating asthma, catarrh, and common colds. The accumulating evidence supports its cardioprotective, antidiabetic, neuroprotective, anticancer, gastroprotective, antibacterial, anti-inflammatory, antiviral, antioxidant, and respiratory effects. However, there are no previous studies that have shown its effects and mechanism in the airway smooth muscle tone, and therefore, the aim of our study was to investigate the in vitro pharmacological action of R. coriaria L. extract (RCE) on the rat isolated tracheal and bronchial preparations by exploring its relaxant activity and mechanism of action. The direct relaxant effect of RCE (0.1-0.7 mg/mL) was tested in the rat bronchi and trachea rings precontracted by carbachol (CCh). In addition, the pretreatment with RCE (1 mg/mL) was tested on the bronchial and tracheal reactivity induced by CCh, potassium chloride (KCl), or CaCl2. In addition, the cyclooxygenase inhibitor indomethacin and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME), respectively, were used for exploring the mechanisms of RCE-induced relaxation and reduction of reactivity. Our findings demonstrated that RCE induced a concentration-dependent relaxation and a significant reduction of reactivity, significantly reduced with either indomethacin or L-NAME. In addition, RCE decreased the responsiveness to KCl and affected the extracellular Ca2+-induced contraction in the tissues with added CCh or KCl in Ca2+-free Krebs-Henseleit solution. In summary, we have shown that RCE displayed relaxant activities in the in vitro airway smooth muscles, and the possible mechanisms seems to involve the prostaglandin, nitric oxide, and Ca2+ pathways. Taken together, our findings indicate the potential role of RCE in the treatment of respiratory diseases with limited airflow, or obstructive respiratory diseases, and could justify its traditional use in the respiratory diseases.


Assuntos
Asma , Rhus , Ratos , Animais , Rhus/metabolismo , Relaxamento Muscular , NG-Nitroarginina Metil Éster/farmacologia , Frutas/metabolismo , Músculo Liso , Etanol , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Indometacina/farmacologia
8.
Distúrb. comun ; 35(3): e57872, 25/10/2023.
Artigo em Inglês, Português | LILACS | ID: biblio-1517690

RESUMO

Objetivo: A pesquisa tem por objetivo verificar os limiares de repouso eletromiográfico dos músculos masseter e temporal em pacientes com disfunção temporomandibular (DTM) antes e após intervenção fonoaudiológica com e sem a utilização de bandagem elástica terapêutica. Métodos: A coleta contou com 14 participantes do sexo feminino, com idade entre 18 e 40 anos, com diagnóstico de DTM muscular ou mista. As pacientes foram divididas entre dois grupos classificados em: pacientes com bandagem associada à terapia tradicional (CB) e grupo de terapia tradicional (SB). As pacientes inicialmente foram avaliadas pelo exame de eletromiografia de superfície nas situações de contração voluntária máxima e repouso, e após quatro semanas de intervenção, foi realizada nova avaliação com os mesmos instrumentos. A análise dos dados ocorreu de forma quantitativa e qualitativa. Resultados:No grupo SB o músculo masseter direito apresentou aumento dos valores de repouso com significância, foi observado que o mesmo ocorreu para todos os músculos deste grupo, influenciando no equilíbrio da musculatura ipsilateral e contralateral, no entanto sem evidência estatística. O grupo CB não demonstrou valores estatísticos significativos, porém qualitativamente os valores de repouso muscular diminuíram e equilibraram-se de forma contralateral. Conclusão: Não foram observadas mudanças estatisticamente significantes nos limiares eletromiográficos durante repouso dos músculos masseter e temporal em ambos os grupos. Qualitativamente houve aumento dos valores eletromiográficos após terapia manual tradicional em todos os músculos do grupo SB. Com relação ao grupo CB, houve diminuição dos valores do repouso eletromiográfico após terapia, embora sem evidências estatísticas. (AU)


Purpose: Objective: The research aims to verify the electromyographic rest thresholds of the masseter and temporal muscles in patients with temporomandibular disorders (TMD) before and after speech therapy intervention with and without the use of therapeutic elastic bandage. Methods: The collection included 14 female participants, aged between 18 and 40 years, who had a diagnosis of muscular or mixed TMD. The patients were divided into two groups: with traditional therapy (CB) bandage and traditional therapy (SB) only group. The patients underwent initial evaluation, as well as surface electromyography in situations of maximum voluntary contraction and rest and at the end of the four weeks of intervention, a new evaluation was performed with the same instruments. Data analysis occurred quantitatively and qualitatively. Results: In the SB group, the right masseter muscle showed a significant increase in resting values. It was observed that the same occurred for all muscles in this group, influencing the balance of the ipsilateral and contralateral muscles, although without statistical evidence. The CB group did not show statistically significant values, but qualitatively the muscle rest values decreased and balanced in a contralateral way. Conclusion: No statistically significant changes were observed in the resting electromyographic thresholds of the masseter and temporalis muscles in both groups. Qualitatively, there was an increase in electromyographic values after traditional manual therapy in all muscles in the SB group. Regarding the CB group, there was a decrease in electromyographic resting values after therapy, although without statistical evidence. (AU)


Objetivo: La investigación tiene como objetivo verificar los umbrales electromiográficos de reposo de los músculos masetero y temporal en pacientes con trastornos temporomandibulares (TMD) antes y después de la terapia del habla con y sin el uso de venda elástica terapéutica. Métodos: La colección incluyó a 14 participantes mujeres, con edades entre 18 y 40 años, diagnosticadas con TTM muscular o mixta. Los pacientes fueron divididos en dos grupos clasificados en: pacientes con vendaje asociado a terapia tradicional (CB) y grupo de terapia tradicional (SB). Los pacientes fueron inicialmente evaluados mediante electromiografía de superficie en situaciones de máxima contracción voluntaria y reposo, luego de cuatro semanas de intervención se realizó una nueva evaluación con los mismos instrumentos. El análisis de datos se llevó a cabo cuantitativa y cualitativamente. Resultados: En el grupo SB, el músculo masetero derecho presentó un aumento significativo en los valores de reposo, se observó que lo mismo ocurrió para todos los músculos de este grupo, influyendo en el equilibrio de los músculos ipsilaterales y contralaterales, sin embargo, sin evidencia estadística. El grupo CB no mostró valores estadísticamente significativos, pero cualitativamente los valores de descanso muscular disminuyeron y se equilibraron contralateralmente. Conclusión: No se observaron cambios estadísticamente significativos en los umbrales electromiográficos en reposo de los músculos masetero y temporal en ambos grupos. Cualitativamente, hubo un aumento de los valores electromiográficos después de la terapia manual tradicional en todos los músculos del grupo SB. En cuanto al grupo CB, hubo una disminución de los valores electromiográficos de reposo después de la terapia, aunque sin evidencia estadística. (AU)


Assuntos
Humanos , Feminino , Adolescente , Adulto , Eletromiografia , Músculos da Mastigação , Relaxamento Muscular/fisiologia , Síndrome da Disfunção da Articulação Temporomandibular/terapia , Manipulações Musculoesqueléticas , Fita Atlética , Estudos Controlados Antes e Depois
9.
BMC Anesthesiol ; 23(1): 290, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626303

RESUMO

BACKGROUND: Partial neuromuscular blockade (NMB) has been applied for some surgeries to reduce bleeding and prevent patient movement for spinal surgery. Sugammadex selectively binds to rocuronium in the plasma and consequently lowers the rocuronium concentration at the neuromuscular junction. In this study, we aimed to observe whether the success rate of transcranial motor-evoked potential (TceMEP) can be increased by sugammadex compared with partial NMB during spinal surgery. METHODS: Patients who underwent elective spinal surgery with TceMEP monitoring were randomly assigned to the sugammadex group and control group. Rocuronium was continuously infused to maintain the train of four counts (TOFc) = 2. The sugammadex group discontinued rocuronium infusion at the time of TceMEP monitoring and was infused with 2 mg/kg sugammadex; the control group was infused with the same dose of saline. RESULTS: A total of 171 patients were included. The success rate of TceMEP monitoring in the sugammadex group was significantly higher than that in the control group. TceMEP amplitudes were greater in the sugammadex group than in the control group at 5 min, 10 min, and 20 min after the start of motor-evoked potential monitoring. The latencies of upper extremity TceMEPs monitoring showed no difference between groups. TOF ratios were greater in the sugammadex group at 5 min, 10 min, and 20 min after the start of motor-evoked potential monitoring. There were no adverse effects caused by sugammadex. CONCLUSIONS: Sugammadex can improve the success rate of motor-evoked potential monitoring compared with moderate neuromuscular blockade induced by continuous infusion of rocuronium in spinal surgery. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov.cn on 29/10/2020 (trial registration number: NCT04608682).


Assuntos
Potencial Evocado Motor , Doenças Neuromusculares , Humanos , Rocurônio , Sugammadex/farmacologia , Relaxamento Muscular
10.
Chem Biol Interact ; 382: 110630, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37442289

RESUMO

ß2-adrenoceptors agonists and phosphodiesterase (PDE) inhibitors are effective bronchodilators, due to their ability to increase intracellular cyclic AMP (cAMP) levels and induce airway smooth muscle (ASM) relaxation. We have shown that increment of intracellular cAMP induced by ß2-adrenoceptors agonist fenoterol is followed by efflux of cAMP, which is converted by ecto-PDE and ecto-5'-nucleotidases (ecto-5'NT) to adenosine, leading to ASM contraction. Here we evaluate whether other classical bronchodilators used to treat asthma and chronic obstructive pulmonary disease (COPD) could induce cAMP efflux and, as consequence, influence the ASM contractility. Our results showed that ß2-adrenoceptor agonists formoterol and PDE inhibitors IBMX, aminophylline and roflumilast induced cAMP efflux and a concentration-dependent relaxation of rat trachea precontracted with carbachol. Pretreatment of tracheas with MK-571 (MRP transporter inhibitor), AMP-CP (ecto-5'NT inhibitor) or CGS-15943 (nonselective adenosine receptor antagonist) potentiated the relaxation induced by ß2-adrenoceptor agonists but did not change the relaxation induced by PDE inhibitors. These data showed that all bronchodilators tested were able to induce cAMP efflux. However, only ß2-adrenoceptor-induced relaxation of tracheal smooth muscle was affected by cAMP efflux and extracellular cAMP-adenosine pathway.


Assuntos
Adenosina , AMP Cíclico , Ratos , Animais , AMP Cíclico/metabolismo , Adenosina/farmacologia , Fumarato de Formoterol/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Broncodilatadores/farmacologia , Relaxamento Muscular , Agonistas Adrenérgicos beta , Traqueia , Receptores Adrenérgicos
11.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982538

RESUMO

Salvia miltiorrhiza Bunge (Danshen) has been widely used to treat cancer and cardiovascular diseases in Chinese traditional medicine. Here, we found that Neoprzewaquinone A (NEO), an active component of S. miltiorrhiza, selectively inhibits PIM1. We showed that NEO potently inhibits PIM1 kinase at nanomolar concentrations and significantly suppresses the growth, migration, and Epithelial-Mesenchymal Transition (EMT) in the triple-negative breast cancer cell line, MDA-MB-231 in vitro. Molecular docking simulations revealed that NEO enters the PIM1 pocket, thereby triggering multiple interaction effects. Western blot analysis revealed that both NEO and SGI-1776 (a specific PIM1 inhibitor), inhibited ROCK2/STAT3 signaling in MDA-MB-231 cells, indicating that PIM1 kinase modulates cell migration and EMT via ROCK2 signaling. Recent studies indicated that ROCK2 plays a key role in smooth muscle contraction, and that ROCK2 inhibitors effectively control the symptoms of high intraocular pressure (IOP) in glaucoma patients. Here, we showed that NEO and SGI-1776 significantly reduce IOP in normal rabbits and relax pre-restrained thoracic aortic rings in rats. Taken together, our findings indicated that NEO inhibits TNBC cell migration and relaxes smooth muscles mainly by targeting PIM1 and inhibiting ROCK2/STAT3 signaling, and that PIM1 may be an effective target for IOP and other circulatory diseases.


Assuntos
Doenças Cardiovasculares , Neoplasias de Mama Triplo Negativas , Humanos , Ratos , Animais , Coelhos , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Relaxamento Muscular , Transição Epitelial-Mesenquimal , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Movimento Celular , Proliferação de Células , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Fator de Transcrição STAT3/metabolismo , Quinases Associadas a rho/metabolismo
12.
Am J Respir Cell Mol Biol ; 68(1): 39-48, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36227725

RESUMO

Bronchomotor tone modulated by airway smooth muscle shortening represents a key mechanism that increases airway resistance in asthma. Altered glucose metabolism in inflammatory and airway structural cells is associated with asthma. Although these observations suggest a causal link between glucose metabolism and airway hyperresponsiveness, the mechanisms are unclear. We hypothesized that glycolysis modulates excitation-contraction coupling in human airway smooth muscle (HASM) cells. Cultured HASM cells from human lung donors were subject to metabolic screenings using Seahorse XF cell assay. HASM cell monolayers were treated with vehicle or PFK15 (1-(Pyridin-4-yl)-3-(quinolin-2-yl)prop-2-en-1-one), an inhibitor of PFKFB3 (PFK-1,6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3) that generates an allosteric activator for glycolysis rate-limiting enzyme PFK1 (phosphofructokinase 1), for 5-240 minutes, and baseline and agonist-induced phosphorylation of MLC (myosin light chain), MYPT1 (myosin phosphatase regulatory subunit 1), Akt, RhoA, and cytosolic Ca2+ were determined. PFK15 effects on metabolic activity and contractile agonist-induced bronchoconstriction were determined in human precision-cut lung slices. Inhibition of glycolysis attenuated carbachol-induced excitation-contraction coupling in HASM cells. ATP production and bronchodilator-induced cAMP concentrations were also attenuated by glycolysis inhibition in HASM cells. In human small airways, glycolysis inhibition decreased mitochondrial respiration and ATP production and attenuated carbachol-induced bronchoconstriction. The findings suggest that energy depletion resulting from glycolysis inhibition is a novel strategy for ameliorating HASM cell shortening and bronchoprotection of human small airways.


Assuntos
Asma , Humanos , Carbacol/farmacologia , Asma/metabolismo , Pulmão/metabolismo , Miócitos de Músculo Liso/metabolismo , Contração Muscular , Relaxamento Muscular , Glicólise , Glucose/metabolismo , Trifosfato de Adenosina/metabolismo , Células Cultivadas
13.
Psicol. ciênc. prof ; 43: e252743, 2023.
Artigo em Português | LILACS, INDEXPSI | ID: biblio-1448951

RESUMO

O objetivo desta pesquisa é identificar e compreender fenomenologicamente, por meio de relato de Psicólogos de Esporte (PE) e de Coaches, em sua vivência prática, como ocorrem os processos reflexivos em sua atuação, conforme apreendidos a partir de relatos de experiências. O método de investigação escolhido foi a fenomenologia, pois oferece os recursos necessários para tal mergulho junto à experiência reflexiva. A amostra intencional foi delineada por PE e Coaches (profissionais de Educação Física que recorrem ao Coaching) em atividade em esportes de alto rendimento, que tenham atuado ou estejam atuando em modalidades esportivas coletivas e/ou individuais. Realizaram-se nove entrevistas (cinco com PE, quatro com Coaches). O acesso ao objeto desse estudo se deu por meio de entrevistas em profundidade e semiestruturadas, orientadas pela escuta suspensiva. As questões disparadoras foram formuladas com base no Procedimento Estruturado de Reflexão adaptado. Para análise das entrevistas, realizou-se uma síntese de cada relato, seguindo-se de cruzamento intencional. Como resultados, percebeu-se que PE e Coaches trazem algumas similaridades no que se refere aos modos de refletir sobre sua prática. No entanto, as experiências que eles fazem desses processos reflexivos é que podem tomar rumos distintos. Os(as) PE amparam-se na regulamentação da profissão e resguardam-se em seus apontamentos, trazendo suas experiências e reflexões sobre os processos vividos. Os(as) Coaches trazem em suas explanações um trabalho coerente, organizado e compatível com o método do Coaching. Problematizar os processos reflexivos desses profissionais permite diferenciar qualitativa e eticamente suas atuações, possibilitando o fomento multiprofissional no esporte.(AU)


The aim of this study consists in phenomenologically identifying and understanding, by the report of Sport Psychologists (SP) and coaches, in their practical experience, how would be the reflexive processes that take place in their performance, as learned from reports of their experiences. The research method chosen was phenomenology, since it offers the necessary resources for such a dive along with the reflective experience. The intentional sample was outlined by SP and coaches (Physical Education professionals who use coaching) active in high performance sports, who have or are working in collective and/or individual sports. Nine interviews were conducted (five with SP, four with coaches). Access to the object of this study took place by in-depth and semi-structured interviews, guided by suspensive listening. The triggering questions were formulated based on the adapted Structured Reflection Procedure. For the analysis of the interviews, a synthesis of each report was carried out, followed by the intentional crossing. As results, it was noticed that SP and coaches bring some similarities regarding the ways of reflecting on their practice. However, their experiences of these reflective processes are that they can take different directions. The SP are based on the regulation of the profession and guard themselves in their notes, bringing their experiences and reflections on the processes experienced. Coaches bring in their explanations a coherent, organized, and compatible work with the coaching method. Problematizing the reflective processes of these professionals allows to differentiate their actuation qualitatively and ethically, making the multiprofessional phenomenon in sport possible.(AU)


El objetivo de este estudio consiste en identificar y comprender fenomenológicamente, a partir de la experiencia práctica de psicólogos del deporte (PD) y coaches, cómo serían los procesos reflexivos que se llevan a cabo en su rendimiento, tal y como se desprende de los informes de experiencias. El método de investigación elegido fue la fenomenología, ya que ofrece los recursos necesarios junto con la experiencia. La muestra intencional fue delineada por PD y coaches (profesionales de la educación física que utilizan el coaching) activos en deportes de alto rendimiento, que tienen o están trabajando en deportes colectivos e/o individuales. Se realizaron nueve entrevistas (cinco con PD, cuatro con coaches). El acceso al objeto de este estudio fue entrevistas en profundidad y semiestructuradas, guiadas por escuchas suspensivas. Las preguntas se formularon desde el procedimiento de reflexión estructurado adaptado. Para el análisis de las entrevistas, se hizo una síntesis de cada informe, seguida del cruce intencional. Como resultados, se notó que los PD y coaches tienen algunas similitudes con respecto a las formas de reflexionar sobre su práctica. Sin embargo, las experiencias que hacen de estos procesos pueden tomar diferentes direcciones. Los(las) PD se basan en la regulación de la profesión y se protegen en sus notas, aportando sus experiencias y reflexiones sobre los procesos vividos. Los(las) coaches plantean en sus explicaciones un trabajo coherente, organizado y compatible con el método de Coaching. Problematizar los procesos reflexivos de estos profesionales permite diferenciar sus acciones de manera cualitativa y ética, además de posibilitar la promoción multiprofesional en el deporte.(AU)


Assuntos
Humanos , Masculino , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Psicologia do Esporte , Tutoria , Ansiedade , Avaliação de Processos e Resultados em Cuidados de Saúde , Satisfação Pessoal , Aptidão , Educação Física e Treinamento , Resistência Física , Disciplinas das Ciências Naturais , Jogos e Brinquedos , Competência Profissional , Psicologia , Desempenho Psicomotor , Qualidade da Assistência à Saúde , Qualidade de Vida , Recreação , Reabilitação , Corrida , Atenção , Ciência , Sono , Futebol , Controle Social Formal , Identificação Social , Justiça Social , Medicina Esportiva , Estresse Psicológico , Natação , Ensino , Terapêutica , Atletismo , Orientação Vocacional , Ferimentos e Lesões , Yoga , Ciências do Comportamento , Exercícios Respiratórios , Saúde , Saúde Mental , Aptidão Física , Inquéritos e Questionários , Reprodutibilidade dos Testes , Saúde Ocupacional , Caminhada , Autonomia Profissional , Guias como Assunto , Entrevista , Congressos como Assunto , Meditação , Vida , Disciplinas e Atividades Comportamentais , Senso de Humor e Humor , Academias de Ginástica , Gerenciamento da Prática Profissional , Síndromes da Dor Regional Complexa , Credenciamento , Intervenção em Crise , Terapias Mente-Corpo , Técnicas de Exercício e de Movimento , Melhoramento Biomédico , Depressão , Dieta , Dietética , Educação não Profissionalizante , Avaliação de Desempenho Profissional , Emprego , Ética Profissional , Fiscalização Sanitária , Capacitação Profissional , Desempenho Atlético , Treinamento Resistido , Resiliência Psicológica , Fenômenos Fisiológicos Musculoesqueléticos e Neurais , Comportamento Alimentar , Atletas , Fortalecimento Institucional , Ciências da Nutrição e do Esporte , Volta ao Esporte , Desempenho Profissional , Profissionalismo , Aptidão Cardiorrespiratória , Sucesso Acadêmico , Esportes Aquáticos , Engajamento no Trabalho , Psicologia Cognitiva , Ciência e Desenvolvimento , Treino Cognitivo , Bem-Estar Psicológico , Condições de Trabalho , Ginástica , Ocupações em Saúde , Promoção da Saúde , Anatomia , Descrição de Cargo , Jurisprudência , Liderança , Aprendizagem , Estilo de Vida , Memória , Métodos , Motivação , Atividade Motora , Destreza Motora , Movimento , Relaxamento Muscular , Músculos , Obesidade
14.
Psicol. ciênc. prof ; 43: e257372, 2023. tab, graf
Artigo em Inglês | LILACS, INDEXPSI | ID: biblio-1529207

RESUMO

Mindfulness has been defined as attention and awareness to the present with an attitude of openness, non-judgment, and acceptance. It is suggested that mindfulness can positively influence experiences in sports and physical activity, increasing adherence to these activities. This study aimed to examine new psychometric properties of the State Mindfulness Scale for Physical Activity (SMS-PA) using classical and modern testing theories among Brazilian sport and exercise practitioners. Two studies were conducted. In the first, with 617 Brazilian sports practitioners, confirmatory factor analysis supported the bifactor structure of the SMS-PA composed of two specific (mental and body mindfulness) and one general factor (state mindfulness), which did not vary among genders. The Rasch Rating Scale Model (RSM) supported essential one-dimensionality indicated by the general factor with good item fit statistics (infit/outfit 0.62-1.27). The model presented a good level of Rasch reliability (0.85), and the items difficulty estimation provided an understanding of the continuum represented by their content. In the second study, with 249 Brazilian exercise practitioners, the structural equation modeling showed that Body Mindfulness was associated with positive outcomes (positive affect and satisfaction with practice). The mediation analysis showed that people with higher levels of Body mindfulness tend to experience greater levels of Positive Affect and, consequently, greater Satisfaction with exercises. The results suggest that the Brazilian version of the SMS-PA is an appropriate measure of the state of mindfulness.(AU)


Mindfulness pode ser definido como atenção e consciência no momento presente com uma atitude de abertura, não julgamento e aceitação. A literatura sugere que o mindfulness pode influenciar positivamente experiências no esporte e atividade física e pode exercer um papel na adesão a essas atividades. Este estudo teve como objetivo investigar novas propriedades psicométricas da State Mindulness Sacale for Physical Activity (SMS-PA) utilizando as teorias clássicas e modernas dos testes em praticantes de exercício físico e esporte brasileiros. Dois estudos foram conduzidos. No primeiro, com 617 brasileiros praticantes de esporte, a Análise Fatorial Confirmatória (AFC) demonstrou adequação à estrutura bifatorial da SMS-PA composta por dois fatores específicos (mindfulness mental e físico) e um fator geral (estado de mindfulness), que apresentou invariância entre sexos. A Rasch Rating Scale Model (RSM) corroborou a unidimensionalidade essencial indicada pelo fator geral com bons índices de ajustes (infit/outfit 0.62 -1.27). O modelo apresentou bom nível de precisão Rasch (.85), e a estimação de dificuldade dos itens possibilitou compreensão do continuum representado pelo conteúdo dos itens. No segundo estudo, com 249 brasileiros praticantes de esporte, a Modelagem de Equações Estruturais demonstrou que o mindfulness físico esteve associado a afetos positivos e satisfação com a prática. A análise de mediação mostrou que pessoas com níveis altos de mindfulness físico tendem a apresentar níveis mais elevados de afeto positivo e, consequentemente, níveis mais elevados de satisfação com a prática. Os resultados sugerem que a versão brasileira do SMS-PA é uma medida apropriada do estado de mindfulness para atividades físicas.(AU)


La atención plena puede definirse como la atención y la conciencia en el momento presente con una actitud de apertura, no juicio y aceptación. La literatura sugiere que el mindfulness puede influir positivamente en las experiencias en el deporte y en la actividad física, además de desempeñar un papel en la adherencia a estas actividades. Este estudio tuvo como objetivo investigar nuevas propiedades psicométricas de la State Mindfulness Scale for Physical Activity (SMS-PA) utilizando las teorías clásicas y modernas de las pruebas en practicantes de ejercicio físico y de deporte en Brasil. Para ello, se realizaron dos estudios. En el primer, participaron 617 practicantes de deporte brasileños, y el análisis factorial confirmatorio (AFC) demostró adecuación en la estructura bifactorial de la SMS-PA, compuesta por dos factores específicos (mindfulness mental y físico) y un factor general (estado de mindfulness), que mostró invarianza entre sexos. El Rasch Rating Scale Model (RSM) corroboró la unidimensionalidad esencial indicada por el factor general con buenos índices de ajuste (infit/outfit 0,62-1,27). El modelo mostró un buen nivel de precisión de Rasch (.85), y la estimación de la dificultad de los ítems permitió comprender el continuo representado por el contenido de estos. En el segundo estudio, con 249 practicantes de deporte, el modelo de ecuaciones estructurales mostró que el mindfulness físico estaba asociado a resultados positivos (afecto positivo y satisfacción con la práctica). El análisis de mediación reveló que las personas con altos niveles de mindfulness físico tendían a tener mayores niveles de afecto positivo y, en consecuencia, mayores niveles de satisfacción con la práctica. Los resultados sugieren que la versión brasileña de la SMS-PA es una medida adecuada de mindfulness.(AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Psicometria , Exercício Físico , Estudos de Avaliação como Assunto , Atenção Plena , Psicologia do Esporte , Ansiedade , Jogos e Brinquedos , Fenômenos Psicológicos , Testes Psicológicos , Psicologia , Qualidade de Vida , Recreação , Padrões de Referência , Corrida , Atenção , Autoimagem , Futebol , Estresse Fisiológico , Natação , Temperança , Terapêutica , Pensamento , Ferimentos e Lesões , Luta Romana , Yoga , Exercícios Respiratórios , Adaptação Psicológica , Dopamina , Terapia Cognitivo-Comportamental , Saúde Mental , Reprodutibilidade dos Testes , Competência Mental , Cognição , Meditação , Disciplinas e Atividades Comportamentais , Senso de Humor e Humor , Afeto , Terapias Mente-Corpo , Papel Profissional , Autonomia Pessoal , Redução do Dano , Emoções , Prevenção de Doenças , Desempenho Atlético , Voleibol , Resiliência Psicológica , Comportamento Alimentar , Prazer , Comportamento Sedentário , Função Executiva , Atletas , Pandemias , Terapia de Aceitação e Compromisso , Psicologia do Desenvolvimento , Otimismo , Autocontrole , Estilo de Vida Saudável , Dieta Saudável , Tutoria , Capacitação de Professores , Envelhecimento Saudável , Liberdade , Mentalização , Regulação Emocional , Angústia Psicológica , Funcionamento Psicossocial , Intervenção Psicossocial , COVID-19 , Fatores Sociodemográficos , Terapias Energéticas , Ginástica , Hábitos , Felicidade , Promoção da Saúde , Cura Mental , Metabolismo , Motivação , Atividade Motora , Movimento , Relaxamento Muscular
15.
Psicol. ciênc. prof ; 43: e253333, 2023. tab, graf
Artigo em Português | LILACS, INDEXPSI | ID: biblio-1440788

RESUMO

Este discute a representatividade da disciplina Psicologia do Esporte nos cursos de Psicologia e Educação Física em instituições de ensino superior reconhecidas pelo MEC e situadas na região Sul do país. Foi realizado um estudo documental, com base nos currículos das Instituições. Os resultados revelaram que no Sul do Brasil 21,02% dos cursos de Psicologia, 41,96% dos cursos de bacharelado em Educação Física e apenas 14,83% dos cursos de licenciatura em Educação Física apresentam a disciplina Psicologia do Esporte em sua grade curricular. Observou-se que a disciplina é ofertada mais frequentemente em regime obrigatório nos cursos de bacharelado em Educação Física. Nos cursos de Psicologia, quando ofertada, costuma ser optativa. Os resultados evidenciam uma maior oferta da disciplina para os estudantes de Educação Física, em relação aos de Psicologia, o que pode estar relacionado ao próprio contexto de surgimento da disciplina e sua popularização no meio acadêmico. Para que esse panorama possa mudar e se possa oferecer uma formação adequada no curso de Psicologia para fomentar essa opção de carreira, há necessidade de se repensar o currículo e o próprio perfil do egresso, de forma a dar mais oportunidade aos estudantes para que conheçam as bases teóricas e os campos de aplicação da Psicologia do Esporte. Tal lacuna pode acarretar a fragilização da disseminação desse conhecimento aos estudantes de graduação e a consequente ocupação do mercado de trabalho.(AU)


This study discusses the representativeness of Sports Psychology in Psychology and Physical Education courses at higher education institutions from Southern Brazil. A documentary study was conducted based on the institutions' curricula. Results show that 21.02% of the Psychology major, 41.96% of the bachelor's in Physical Education, and only 14.83% of the license in Physical Education offer Sports Psychology in their curricula. Sports Psychology is most often offered as a compulsory subject in the bachelor's program in Physical Education, whereas Psychology courses offer it mainly as an elective. Physical Education students have greater contact with the discipline when compared with Psychology students, which may be explained by its context of development and popularization in the academic environment. To change this scenario and offer adequate education in the Psychology programs to foster this career option, institutions must rethink their curriculum and the graduate profile itself. This would give students better opportunity to get to know its theoretical bases and fields of application. Such a gap can hinder the dissemination of this knowledge to undergraduate students and the consequent labor market occupation.(AU)


El objetivo de este estudio es discutir la representatividad de la materia Psicología del Deporte en los cursos de Psicología y Educación Física en instituciones de educación superior de la región Sur de Brasil, reconocidas por el Ministerio de Educación (MEC). Se realizó un estudio documental, basado en los planes de estudio de las instituciones. Los resultados revelaron que, en el Sur de Brasil, el 21,02% de los cursos de Psicología, el 41,96% de los cursos de licenciatura en Educación Física y sólo el 14,83% de los cursos de profesorado en Educación tienen la materia Psicología del Deporte en sus planes de estudio. Se observó que la materia Psicología del Deporte se ofrece con mayor frecuencia como asignatura obligatoria en los cursos de licenciatura en Educación Física. Cuando se ofrece en los cursos de Psicología, es una materia optativa. Los resultados muestran una mayor oferta para los estudiantes de Educación Física en comparación con Psicología, lo que puede estar relacionado con el contexto del surgimiento de la Psicología del Deporte como materia y su popularización en el ámbito académico. Para que este escenario cambie y sea posible ofrecer una formación adecuada en el curso de Psicología con el fin de fomentar esta opción de carrera, es necesario repensar el plan de estudios y el perfil del egresado, así los estudiantes tendrán más oportunidades de conocer sus bases teóricas y sus campos de actuación. Tal brecha puede debilitar la difusión de este conocimiento a los estudiantes de grado y la consecuente ocupación en el mercado laboral.(AU)


Assuntos
Humanos , Masculino , Feminino , Educação Física e Treinamento , Psicologia , Currículo , Avaliação Educacional , Psicologia do Esporte , Ansiedade , Percepção , Apetite , Satisfação Pessoal , Personalidade , Aptidão , Fisiologia , Competência Profissional , Área de Atuação Profissional , Psicologia Educacional , Qualidade de Vida , Reabilitação , Atenção , Autoimagem , Programas de Autoavaliação , Futebol , Mudança Social , Controle Social Formal , Especialização , Esportes , Medicina Esportiva , Estresse Fisiológico , Estresse Psicológico , Atletismo , Orientação Vocacional , Ferimentos e Lesões , Ciclismo , Fenômenos Biomecânicos , Terapia Cognitivo-Comportamental , Saúde , Saúde Mental , Aptidão Física , Responsabilidade Legal , Caminhada , Terapia de Relaxamento , Desenvolvimento de Pessoal , Guias como Assunto , Pessoas com Deficiência , Cognição , Diversidade Cultural , Criatividade , Credenciamento , Características Culturais , Tomada de Decisões , Regulamentação Governamental , Depressão , Dieta , Educação , Emoções , Política de Inovação e Desenvolvimento , Política de Educação Superior , Organismos Nacionais de Educação Superior , Capacitação Profissional , Fadiga , Fadiga Mental , Ensaios de Triagem em Larga Escala , Comportamento Sedentário , Atletas , Resistência à Doença , Ciências da Nutrição e do Esporte , Autocontrole , Volta ao Esporte , Aptidão Cardiorrespiratória , Tutoria , Desempenho Acadêmico , Desempenho Físico Funcional , Esgotamento Psicológico , Derrota Social , Bem-Estar Psicológico , Dinâmica de Grupo , Síndrome do Sobretreinamento , Hábitos , Promoção da Saúde , Homeostase , Ergonomia , Jurisprudência , Liderança , Atividades de Lazer , Estilo de Vida , Memória , Motivação , Atividade Motora , Relaxamento Muscular , Tono Muscular , Neuroanatomia
16.
Int J Mol Sci ; 23(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36555750

RESUMO

It has been reported that adiponectin (ADPN) and resistin are co-secreted by white mouse adipocytes and exert similar inhibitory effects in the mouse gastric fundus, in which resistin was observed to increase neuronal nitric oxide synthase (nNOS) expression. On these grounds, the present work aimed to investigate whether the effects of the two adipokines on the neurally-induced relaxant responses potentiate each other and whether there is a possible correlation with changes in nNOS expression in preparations from the mouse gastric fundus. In carbachol (CCh)-precontracted strips, electrical field stimulation elicited nitrergic relaxant responses, whose amplitude was increased by ADPN or resistin, but no additional enhancements were observed in their concomitant presence. Western blot and immunofluorescence analyses revealed that ADPN, like resistin, was able to up-regulate nNOS expression and to increase the percentage of nNOS-positive neurons in the myenteric plexus: co-treatment with the two adipokines did not induce additional changes. The results indicate that the two adipokines modulate nitrergic neurotransmission, and both do so by up-regulating nNOS expression. Therefore, nNOS appears to be a shared target for the two adipokines' effects, which, rather than mutually reinforcing each other, may represent a dual physiological control mechanism to guarantee gastric fundus relaxation.


Assuntos
Fundo Gástrico , Contração Muscular , Camundongos , Animais , Contração Muscular/fisiologia , Relaxamento Muscular , Adiponectina/farmacologia , Óxido Nítrico Sintase Tipo I/metabolismo , Resistina/farmacologia , Óxido Nítrico/metabolismo
17.
BMJ Open ; 12(5): e056571, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501072

RESUMO

INTRODUCTION: Transcranial motor-evoked potentials (TceMEPs) is conventionally performed without neuromuscular blockade (NMB) because of its potential interference with neuromuscular junction and signal interpretation. Sugammadex is the first highly selective antagonist that binds to rocuronium and can rapidly and effectively reverse NMB. This study aims to evaluate the success rate of intraoperative muscle relax reversal by sugammadex on intraoperative TceMEP recording. METHODS AND ANALYSIS: We will conduct a single-centre randomised controlled study. In total, 162 patients undergoing thoracic or lumbar spinal surgery will be randomly divided into the sugammadex group or control group at a ratio of 1:1. Total intravenous anaesthesia by propofol and remifentanil will be performed in both groups. In the sugammadex group, patients will receive continuous infusion of rocuronium to produce a blockade maintained for at least two twitches in train-of-four, rocuronium infusion will be discontinued and 2 mg/kg sugammadex will be given while performing TceMEPs monitoring. In the control group, rocuronium infusion will be discontinued and the same volume of saline will be infused while performing TceMEPs monitoring. The primary aim of this study is to evaluate the success rate of TceMEPs recording between two groups. ETHICS AND DISSEMINATION: The approval for the study was certificated by the Ethical Committee of Beijing Tiantan Hospital, Capital Medical University on, 16 July 2021 (KY2021-082-02). The study was registered on clincaltrials.gov on 25 October 2020. Our study might guide neuromuscular blockade plans in TceMEPs monitoring undergoing spinal surgery. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conference. TRIAL REGISTRATION NUMBER: NCT04608682.


Assuntos
Androstanóis , gama-Ciclodextrinas , Potenciais Evocados , Humanos , Relaxamento Muscular , Ensaios Clínicos Controlados Aleatórios como Assunto , Rocurônio , Sugammadex
18.
Life Sci ; 296: 120432, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35219697

RESUMO

AIMS: Nitric oxide (NO) and hydrogen sulfide (H2S) are involved in nerve-mediated corpus cavernosum (CC) relaxation. Expression of phosphodiesterase type 5 (PDE5) and type 4 (PDE4), cyclic guanosine monophosphate (cGMP)- and cyclic adenosine monophosphate (cAMP)-specific, respectively, has been described and PDE5- and PDE4-inhibitors induce cavernous smooth muscle relaxation. Whereas the NO/cGMP signaling pathway is well established in penile erection, the cAMP-mediated mechanism is not fully elucidated. The aim of this study is to investigate the localization and the functional significance of PDE4 in rat CC tone regulation. MAIN METHODS: We performed immunohistochemistry for the detection of the PDE4A isoenzyme. Isometric tension recordings for roflumilast and tadalafil, PDE4 and PDE5 inhibitors, respectively, electrical field stimulation (EFS) and ß-adrenoceptor agonist isoproterenol and endogenous H2S production measurement. KEY FINDINGS: A marked PDE4A expression was detected mainly localized in the nerve cells of the cavernous smooth muscle. Furthermore, roflumilast and tadalafil exhibited strong corpus cavernous relaxations. Endogenous H2S production was decreased by NO and H2S synthase inhibitors and increased by roflumilast. Isoproterenol- and EFS-induced relaxations were increased by roflumilast. SIGNIFICANCE: These results indicate that PDE4A is mainly expressed within the nerves cells of the rat CC, where roflumilast induces a potent corpus cavernous relaxation per se and potentiates the response induced by ß-adrenoceptor activation. The fact that roflumilast enhances H2S production, as well as EFS-elicited responses suggests that PDE4 inhibitors modulate, in a positive feedback fashion, nerve-mediated relaxation induced by gasotransmitters, thus indicating a key role for neuronal PDE4 in penile erection.


Assuntos
Aminopiridinas/farmacologia , Benzamidas/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Gasotransmissores/metabolismo , Pênis/fisiologia , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Aminopiridinas/administração & dosagem , Animais , Benzamidas/administração & dosagem , Ciclopropanos/administração & dosagem , Ciclopropanos/farmacologia , Relação Dose-Resposta a Droga , Sulfeto de Hidrogênio/metabolismo , Masculino , Relaxamento Muscular/efeitos dos fármacos , Nitroarginina/farmacologia , Pênis/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiologia , Ratos Wistar , Tadalafila/farmacologia
19.
Am J Respir Cell Mol Biol ; 66(1): 96-106, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648729

RESUMO

In most living cells, the second-messenger roles for adenosine 3',5'-cyclic monophosphate (cAMP) are short-lived, confined to the intracellular space, and tightly controlled by the binary switch-like actions of Gαs (stimulatory G protein)-activated adenylyl cyclase (cAMP production) and cAMP-specific PDE (cAMP breakdown). Here, by using human airway smooth muscle (HASM) cells in culture as a model, we report that activation of the cell-surface ß2AR (ß2-adrenoceptor), a Gs-coupled GPCR (G protein-coupled receptor), evokes cAMP egress to the extracellular space. Increased extracellular cAMP levels ([cAMP]e) are long-lived in culture and are induced by receptor-dependent and receptor-independent mechanisms in such a way as to define a universal response class of increased intracellular cAMP levels ([cAMP]i). We find that HASM cells express multiple ATP-binding cassette (ABC) membrane transporters, with ABCC1 (ABC subfamily member C 1) being the most highly enriched transcript mapped to MRPs (multidrug resistance-associated proteins). We show that pharmacological inhibition or downregulation of ABCC1 with siRNA markedly reduces ß2AR-evoked cAMP release from HASM cells. Furthermore, inhibition of ABCC1 activity or expression decreases basal tone and increases ß-agonist-induced HASM cellular relaxation. These findings identify a previously unrecognized role for ABCC1 in the homeostatic regulation of [cAMP]i in HASM that may be conserved traits of the Gs-GPCRs (Gs-coupled family of GPCRs). Hence, the general features of this activation mechanism may uncover new disease-modifying targets in the treatment of airflow obstruction in asthma. Surprisingly, we find that serum cAMP levels are elevated in a small cohort of patients with asthma as compared with control subjects, which warrants further investigation.


Assuntos
AMP Cíclico/metabolismo , Pulmão/citologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Relaxamento Muscular/fisiologia , Miócitos de Músculo Liso/fisiologia , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Asma/sangue , Asma/fisiopatologia , Cromograninas/metabolismo , AMP Cíclico/sangue , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , RNA Interferente Pequeno/metabolismo
20.
Nitric Oxide ; 119: 19-28, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902580

RESUMO

In this study, we investigated the possible role of the l-cysteine/hydrogen sulfide pathway in ß3-adrenoceptors-mediated relaxation in isolated mouse gastric fundus tissue. l-cysteine (endogenous H2S; 10-6-10-2 M), sodium hydrogen sulfide (NaHS; exogenous H2S; 10-6-10-3 M), selective ß3-adrenoceptors agonist BRL 37344 (10-9-10-4 M) and non-selective ß-adrenoceptor agonist isoprenaline (10-9-10-4 M) produced concentration-dependent relaxation in mouse gastric fundus. The non-selective ß-adrenoceptors antagonist propranolol (10-6 M) inhibited the relaxant response to isoprenaline but not to BRL 37344. On the other hand, the selective ß3-adrenoceptors antagonist SR 59230A (10-5 M) inhibited the relaxant responses to BRL 37344. In addition, cystathionine-gamma-lyase (CSE) inhibitor D,L-propargylglycine (PAG, 10-2 M), cystathionine-beta-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10-2 M), and the combination of these inhibitors significantly reduced the relaxant responses induced by l-cysteine and BRL 37344. Pre-incubation of gastric fundal strips with propranolol (10-6 M) and SR 59230A (10-5 M) did not affect relaxations to l-cysteine and NaHS. Also, the existence of CSE, CBS, 3-mercaptopurivate sulfur transferase (3-MST) enzymes and ß3-adrenoceptors were detected in gastric fundal tissue. Furthermore, basal H2S release was detected in the measurements. H2S level increased in the presence of l-cysteine, NaHS, and BRL 37344. The increase in H2S level by l-cysteine and BRL 37344 decreased significantly with PAG and AOAA enzyme inhibitors. These results suggest that endogenous H2S is synthesized from l-cysteine at least by CBS and CSE enzymes. Also, ß3-adrenoceptors are found in the mouse stomach fundus and mediate BRL 37344-induced relaxations, and l-cysteine/hydrogen sulfide pathway plays a partial role in ß3-adrenoceptors-mediated relaxation in mouse gastric fundus tissue.


Assuntos
Cisteína/metabolismo , Fundo Gástrico/metabolismo , Sulfeto de Hidrogênio/metabolismo , Relaxamento Muscular/fisiologia , Receptores Adrenérgicos beta 3/metabolismo , Animais , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Etanolaminas/farmacologia , Fundo Gástrico/enzimologia , Isoproterenol/farmacologia , Masculino , Camundongos , Propanolaminas/farmacologia , Propranolol/farmacologia , Sulfurtransferases/metabolismo
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