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BACKGROUND: Drug-induced sleep endoscopy (DISE) is used for evaluating upper airway anatomy and determining airway obstruction patterns. It is typically performed with the patient in the supine position. Airway collapse severity is influenced by body position and level of consciousness; the resultant dynamic changes may vary across patients. In this study, we evaluated the severity of upper airway collapse through awake endoscopy and DISE and identified factors affecting the pattern of airway collapse severity. METHODS: This study included 66 patients with obstructive sleep apnea. The patients underwent type 1 polysomnography, tongue strength assessment, awake endoscopy in the sitting and supine positions, and DISE. Group-based trajectory modeling was performed to identify patients with different collapse severity patterns in different body positions and at different levels of consciousness. RESULTS: Patient with similar severity trajectory were assigned to the same group. Two different severity trajectories (group 1 and group 2) were identified at the tongue base level. Tongue depression strength varied significantly between groups 1 and 2 (47.00 vs. 35.00 kPa; P = .047). During awake endoscopy, collapse severity was significantly higher in group 2 than in group 1. Group 1 had lower rapid eye movement/nonrapid eye movement apnea-hypopnea index ratios and higher tongue depression strength than did group 2. CONCLUSION: In patients with obstructive sleep apnea, tongue strength may vary depending on body position. Our results should be interpreted with caution because of the limited sample size. Future studies should investigate the effect of oropharyngeal rehabilitation on tongue strength and collapse severity.
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OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder associated with dysfunction of oropharyngeal muscles to maintain upper airway patency during sleep. Oropharyngeal rehabilitation (OPR) was developed to restore, reconstruct, and reeducate oropharyngeal muscle function, but current protocols and effectiveness of OPR have been inconsistent. The purpose of this study was to review (1) indications of OPR, (2) protocols of OPR, and (3) effectiveness of OPR. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library and then conducted both meta-synthesis and meta-analysis according to the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). RESULTS: A total of eight studies with 203 patients were included. By means of meta-synthesis, the patients with middle age, BMI < 40 kg/m2, mild-to-moderate OSA, and non-severe upper airway anatomical abnormality were found to benefit from OPR. The protocol of OPR was summarized to be an anatomically based, multilevel approach, including the retropalatal, retroglossal, hypopharyngeal, TMJ, and facial levels. By using meta-analysis, overall outcomes were presented as apnea hypopnea index (AHI) with significant improvement from 25.2 ± 7.8/h to 16.1 ± 6.6/h (mean difference [MD] - 9.8 [95% CI - 11.0 to - 8.6], p < 0.0001); the lowest oxygen saturation (LSAT) improved from 80.2 ± 4.7 to 83.8 ± 2.9% (MD 3.0% [95% CI 2.0 to 4.0], p < 0.0001); Epworth sleepiness scale (ESS) improved from 11.8 ± 1.9 to 6.3 ± 1.6 (MD - 5.9 [95% CI - 7.5 to - 4.2], p < 0.001), neck circumference (NC) from 35.2 ± 1.1 to 34.7 ± 0.9 cm (MD - 0.6 [95% CI - 0.9 to - 0.2], p = 0.002), BMI from 24.8 ± 3.7 to 24.8 ± 4.1 kg/m2 (MD - 0.0; 95% CI - 0.5 to 0.5, p = 0.95). All outcomes except BMI demonstrated significant improvement from OPR. CONCLUSIONS: Meta-analysis of previous OPR reports shows an improvement in AHI of 39%, compared with the usual surgical definition of success at 50%. Only mild and moderate cases of OSA were referred for OPR in the prior studies. In order to improve outcomes with OPR, a comprehensive approach to rehabilitation should be emphasized.
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Orofaringe/fisiopatologia , Apneia Obstrutiva do Sono/reabilitação , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVES: Patients with obstructive sleep apnea (OSA) (an obstructed airway and intermittent hypoxia) negatively affect their respiratory muscles. We evaluated the effects of a 12-week threshold inspiratory muscle training (TIMT) program on OSA severity, daytime sleepiness, and pulmonary function in newly diagnosed OSA. METHODS: Sixteen patients with moderate-to-severe OSA were randomly assigned to a TIMT group and 6 to a control group. The home-based TIMT program was 30-45 min/day, 5 days/week, for 12 weeks using a TIMT training device. Their apnea-hypopnea index (AHI), Epworth sleepiness scale (ESS), and forced vital capacity (FVC) scores were evaluated pre- and post-treatment. Polysomnographic (PSG) analysis showed that 9 TIMT-group patients had positively responded (TIMT-responder group: post-treatment AHI < pre-treatment) and that 7 had not (TIMT non-responder group: post-treatment AHI > pre-treatment). RESULTS: Post-treatment AHI and ESS scores were significantly (both P < 0.05) lower 6% and 20.2%, respectively. A baseline AHI ≤ 29.0/h predicted TIMT-responder group patients (sensitivity 77.8%; specificity 85.7%). FVC was also significantly (P < 0.05) higher 7.2%. Baseline AHI and FEV6.0 were significant predictors of successful TIMT-responder group intervention. OSA severity and daytime sleepiness were also significantly attenuated. CONCLUSIONS: Home-based TIMT training is simple, efficacious, and cost-effective.
Assuntos
Exercícios Respiratórios/métodos , Inalação/fisiologia , Apneia Obstrutiva do Sono/terapia , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Distúrbios do Sono por Sonolência Excessiva/terapia , Seguimentos , Humanos , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Resultado do Tratamento , Capacidade Vital/fisiologiaRESUMO
BACKGROUND: Critically compromised by upper airway anatomical impaired properties, obstructive sleep apnea (OSA) can be categorized into different phenotypic traits, mainly including oropharyngeal muscle dysfunction. The upper airway muscle strength training was targeted on oropharyngeal muscle dysfunction by re-educating the oropharyngeal muscles to maintain the upper airway patency. OSA was characterized with multilevel collapsibility of the upper airway; however, the programs are still inconsistent and the effects are unknown. Therefore, the purpose of this study was to investigate the effects of a comprehensive physical therapy on OSA. METHODS: Fifteen subjects with newly diagnosed moderate or severe OSA (AHI ≥ 15) were randomized into intervention and control groups. The intervention group underwent a 12-week-intervention of hospital based physical therapy, while the control group was kept on waiting for 12 weeks. Polysomnography (PSG) data, oropharyngeal and respiratory muscle performance were measured before and after intervention. RESULTS: In intervention group (n = 8), AHI was significantly improved (from 46.96 ± 19.45 to 32.78 ± 10.78 events/h, p = 0.017); in control group (n = 7), AHI was significantly increased (from 35.77 ± 17.49 to 42.96 ± 17.32 events/h, p = 0.043). While the control group remained no change between pre- and post- intervention, the intervention group demonstrated that other PSG outcomes significantly improved, including arousal index (46.04 ± 18.9 versus 32.98 ± 8.35/h), mean SpO2 (92.88 ± 2.1 versus 94.13 ± 1.46%), and oxygen desaturation index (ODI) (31.13 ± 19.48 versus 20.57 ± 7.83/h). CONCLUSION: This comprehensive physical therapy can be prescribed for the significant clinical improvement on sleep apnea for the patients with moderate and severe OSA.
Assuntos
Treinamento Resistido , Apneia Obstrutiva do Sono , Humanos , Modalidades de Fisioterapia , Polissonografia , Apneia Obstrutiva do Sono/terapiaRESUMO
BACKGROUND: Studies have found that many chemotherapy drugs will produce multiple side effects and complications in cancer patients, especially in the case of the cardiovascular disease. This study was intended to investigate whether the exercise training intervention could improve the body composition and exercise responses of patients with head and neck (H&N) cancer who are receiving chemotherapy. METHODS: This is a randomized controlled trial. Eighty-four H&N patients were assigned to sedentary group or exercise group. The data were collected pretraining and posttraining, where the body composition, heart rate (HR), blood pressure (BP), rate-pressure product (RPP), and exercise capacity were measured. RESULTS: Our data reported that body weight and body mass index were decreased after 8 weeks of chemotherapy in the sedentary group but not in the exercise group. The decreased visceral fat and the increased skeletal muscle rate had been found in the exercise group after 8 weeks of training. In addition, in the exercise group, the HR, HR recovery, BP, BP recovery, RPP, and minutes walking distance were better than the sedentary group. Results from this study suggested exercise training significantly improved exercise responses and body composition. CONCLUSION: These findings suggested that exercise can help to promote cardiopulmonary fitness and exercise capacity for H&N cancer patients undergoing chemotherapy.
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Composição Corporal/fisiologia , Terapia por Exercício/métodos , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/terapia , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Aptidão Cardiorrespiratória/fisiologia , Exercício Físico , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologiaRESUMO
BACKGROUND: The objective of the experiment was to assess the antinociceptive effect of dibucaine, bupivacaine, and epinephrine. To assess the mechanism of action of the interaction between dibucaine and epinephrine, phentolamine, a nonselective α-adrenergic antagonist, was added to the mixture. METHODS: We assessed sensory blockade with these drugs by injecting 0.6 mL of drug-in-saline in the dorsal thoracolumbar area of rats; pinprick of the "wheal" formed by the injectate was the area targeted for stimulation to elicit a cutaneous trunci muscle reflex. The sensory block of dibucaine was compared with that of bupivacaine or epinephrine. Drug-drug interactions were analyzed by isobologram. Phentolamine was added to investigate the antinociceptive effect of dibucaine coinjected with epinephrine. RESULTS: We demonstrated that dibucaine, epinephrine, and bupivacaine produced dose-dependent skin antinociception. On the median effective dose (ED50) basis, the potency was higher for epinephrine (mean, 0.011 [95% confidence interval {CI}, 0.007-0.015] µmol) than for dibucaine (mean, 0.493 [95% CI, 0.435-0.560] µmol) (P < .01), while there were no significant differences between dibucaine and bupivacaine (mean, 0.450 [95% CI, 0.400-0.505] µmol). On the equipotent basis (75% effective dose, median effective dose, and 25% effective dose), sensory block duration provoked by epinephrine was greater (P < .01) than that provoked by dibucaine or bupivacaine. Coadministration of dibucaine with epinephrine produced a synergistic nociceptive block, whereas phentolamine blocked that synergistic block. CONCLUSIONS: The preclinical data indicated that there is no statistically significant difference between the potency and duration of dibucaine and bupivacaine in this model. Epinephrine synergistically enhances the effects of dibucaine, while phentolamine partially blocked those effects. α-Adrenergic receptors play an important role in controlling synergistic analgesic effect of dibucaine combined with epinephrine.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Analgésicos/farmacologia , Bupivacaína/farmacologia , Dibucaína/farmacologia , Epinefrina/farmacologia , Fentolamina/farmacologia , Pele/efeitos dos fármacos , Analgesia , Anestésicos Locais/farmacologia , Animais , Área Sob a Curva , Relação Dose-Resposta a Droga , Interações Medicamentosas , Sinergismo Farmacológico , Injeções Subcutâneas , Masculino , Dor/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
Galectin-3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin-3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1), a receptor for oxLDL uptake, contributes to oxLDL-induced endothelial dysfunction. Whether galectin-3 induces endothelial dysfunction through modulation of LOX-1-mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin-3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX-1. Incubation of HUVECs with galectin-3 increased the expression of LOX-1 in RNA and protein levels. In addition, the expression of LOX-1 induced by oxLDL was promoted by galectin-3. However, pretreatment of LOX-1 antibody reduced LOX-1 mRNA expression level in cells with oxLDL plus galectin-3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen-activated protein kinases followed by nuclear factor kappa B (NF-κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL-8 release were also aggravated in cells treated with galectin-3 combined with oxLDL. Compared to cells treated with galectin-3 plus oxLDL group. We found that LOX-1 antibody mitigated NADPH oxidase activity, p-38 up-regulation, NF-κB activation, and proinflammatory responses in cells treated with galectin-3 combined with oxLDL. We conclude that galectin-3 enhances endothelial LOX-1 expression and propose a new mechanism by which galectin-3 may promote endothelial dysfunction by inducing inflammation via LOX-1/ROS/p38/NF-κB-mediated signaling pathway.
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Aterosclerose/induzido quimicamente , Endotélio Vascular/efeitos dos fármacos , Galectina 3/farmacologia , Lipoproteínas LDL/toxicidade , Receptores Depuradores Classe E/fisiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Cultivadas , Sinergismo Farmacológico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: We evaluated the interaction of dopamine-proxymetacaine and dopamine- oxybuprocaine antinociception using isobolograms. METHODS: This experiment uses subcutaneous drug (proxymetacaine, oxybuprocaine, and dopamine) injections under the skin of the rat's back, thus simulating infiltration blocks. The dose-related antinociceptive curves of proxymetacaine and oxybuprocaine alone and in combination with dopamine were constructed, and then the antinociceptive interactions between the local anesthetic and dopamine were analyzed using isobolograms. RESULTS: Subcutaneous proxymetacaine, oxybuprocaine, and dopamine produced a sensory block to local skin pinpricks in a dose-dependent fashion. The rank order of potency was proxymetacaine (0.57 [0.52-0.63] µmol/kg) > oxybuprocaine (1.05 [0.96-1.15] µmol/kg) > dopamine (165 [154-177] µmol/kg; P < .01 for each comparison) based on the 50% effective dose values. On the equianesthetic basis (25% effective dose, 50% effective dose, and 75% effective dose), the nociceptive block duration of proxymetacaine or oxybuprocaine was shorter than that of dopamine (P < .01). Oxybuprocaine or proxymetacaine coinjected with dopamine elicited a synergistic antinociceptive effect and extended the duration of action. CONCLUSIONS: Oxybuprocaine and proxymetacaine had a higher potency and provoked a shorter duration of sensory block compared with dopamine. The use of dopamine increased the quality and duration of skin antinociception caused by oxybuprocaine and proxymetacaine.
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Anestesia Local/métodos , Anestésicos Locais/administração & dosagem , Dopamina/administração & dosagem , Medição da Dor/efeitos dos fármacos , Procaína/análogos & derivados , Propoxicaína/administração & dosagem , Administração Cutânea , Animais , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Masculino , Medição da Dor/métodos , Procaína/administração & dosagem , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Fatores de TempoRESUMO
BACKGROUND: Although there are several evidences that suggest efficacies of therapeutic ultrasound (TU) or treadmill exercise (TE) to alleviate nerve injury-associated pain, molecular mechanisms are less clear. We aimed to investigate the impact of TU and/or TE on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve and their roles of proinflammatory and anti-inflammatory cytokines. METHODS: Rats were randomly divided into (n = 10 per group) sham operation (sham), CCI procedure followed by false application of TU (CCI + TU0), CCI procedure followed by false application of TU and TE (CCI + TU0 + TE), CCI, and CCI procedure followed by TU alone (CCI + TU), TE alone (CCI + TE), or both TU and TE (CCI + TU + TE) groups. TU and TE were administered daily, starting on postoperative day 8 (POD 8) for 3 weeks. Mechanical and thermal hypersensitivity, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and IL-6 in the sciatic nerve were assessed on PODs 14 and 28. Data were analyzed by 1-way, 2-way, or 3-way analysis of variance of repeated measures or 1-way analysis of variance. RESULTS: After the interventions, there was statistical significance (all P ≤ .0001) between the groups for all outcome parameters, all in favor of the experimental group: 4.2 for mean mechanical withdrawal thresholds (95% confidence interval, 1.8-7.6) and 4.8 for mean thermal withdrawal latencies (95% confidence interval, 2.2-8.1). TU and/or TE provoked an increase in mechanical withdrawal thresholds and thermal withdrawal latencies in CCI rats. TU + TE was more effective to reverse pain hypersensitivity than having each treatment alone. On PODs 14 and 28, the CCI rats exhibited an upregulation of sciatic TNF-α and IL-6 expression, whereas TU or TE alone or TU + TE combination prevented the upregulation. TU and/or TE also showed the upregulation of less IL-10 expression in the sciatic nerve. CONCLUSIONS: We found that TU + TE is better than TU or TE alone for treating neuropathic pain. TU and/or TE for pain management may be straightly associated with less TNF-α and IL-6 expression and more IL-10 expression.
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Terapia por Exercício , Hiperalgesia/terapia , Mediadores da Inflamação/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Ciática/terapia , Fator de Necrose Tumoral alfa/metabolismo , Terapia por Ultrassom , Animais , Comportamento Animal , Terapia Combinada , Modelos Animais de Doenças , Regulação para Baixo , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Hiperalgesia/psicologia , Masculino , Medição da Dor , Limiar da Dor , Ratos Sprague-Dawley , Tempo de Reação , Ciática/metabolismo , Ciática/fisiopatologia , Ciática/psicologia , Fatores de Tempo , Regulação para CimaRESUMO
HHcy (hyperhomocysteinaemia) is one of the major risk factors for cardiovascular diseases. A high concentration of Hcy (homocysteine) induces endothelial dysfunction by activating endothelial oxidative stress. LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1) plays a vital role in regulating the progression of atherosclerotic lesions. LOX-1 activation causes endothelial apoptosis and inflammation. The mechanism is still unclear as to whether Hcy affects human endothelial LOX-1 expression. LOX-1 expression level was confirmed by Western blotting assay in Hcy-treated endothelial cells. L-Methionine was used for HHcy induction in animals. Our results suggested that Hcy increased PKCß (protein kinase Cß) activation to enhance the LOX-1 expression level. The up-regulation of PKCß phosphorylation subsequently causes ROS (reactive oxygen species) formation and SIRT1 (sirtuin 1) degradation through a proteasome-dependent mechanism, thereby mitigating the activity of SIRT1 by deacetylating HSF1 (heat-shock transcription factor 1). We also found that NOX2 is a key NAPDH oxidase isoform responsible for the Hcy-caused ROS formation. The overexpression of SIRT1 and HSF1 reduced the Hcy-induced LOX-1 activation. Silencing PKCß function also reduced LOX-1 activation and endothelial apoptosis caused by Hcy. Our hypothesis was supported by analysing the data from methionine-induced HHcy-affected animals. Our data indicate a new direction for LOX-1 regulation by the modulation of the PKCß/NAPDH oxidase/SIRT1/HSF1 mechanism. Our findings might provide a novel route for developing new therapeutic treatments for HHcy.
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Apoptose/fisiologia , Proteínas de Ligação a DNA/metabolismo , Células Endoteliais/metabolismo , Homocisteína/metabolismo , Proteína Quinase C beta/metabolismo , Receptores Depuradores Classe E/metabolismo , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Células Cultivadas , Ativação Enzimática , Fatores de Transcrição de Choque Térmico , Humanos , Hiper-Homocisteinemia/genética , Hiper-Homocisteinemia/metabolismo , Lipoproteínas LDL/metabolismo , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Depuradores Classe E/genética , Regulação para CimaRESUMO
BACKGROUND: Insulin therapy plays a critical role in managing type 1 diabetes mellitus, and exercise produces alterations in pain sensation. This experiment explored the effects of insulin therapy combined with treadmill training on diabetic neuropathic pain and on the expression of malondialdehyde (MDA) and cytokines. METHODS: Rats were given 4 weeks of insulin (100 IU/kg) therapy and treadmill training (30-60 min/d of training at 20-25 m/min) each day beginning on day 3 after streptozotocin (65 mg/kg, IV) injection and continuing until day 27. Sensitivity to heat and mechanical stimuli and the expression of interleukin (IL)-10, IL-6, tumor necrosis factor-α, and MDA in the sciatic nerve were estimated. RESULTS: We showed that 2 to 4 weeks of treadmill training, insulin treatment, or their combination increased both paw withdrawal thresholds and latencies compared with the same regimen in sedentary diabetic rats (all P < 0.0022). Treatment with insulin, but without treadmill training, had significant effects on glycemic control (P < 0.0001) and restored body weight (P < 0.0001) in the diabetic rats. The diabetic rats demonstrated the upregulation (all P < 0.009) of IL-6, MDA, and tumor necrosis factor-α in the sciatic nerve on days 14 and 28 after streptozotocin treatment, whereas in diabetic rats receiving insulin, treadmill training, or a combination (all P < 0.01), this upregulation was decreased. Insulin, treadmill training, or the combination increased IL-10 expression (all P < 0.0051) in all diabetic rats. CONCLUSIONS: Treadmill training combined with insulin therapy showed the best improvements in tactile allodynia and thermal hyperalgesia among our 3 treatment groups. The benefits of insulin intervention and treadmill training could be related to chronic inflammation (proinflammatory cytokines) and oxidative stress (MDA).
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Citocinas/metabolismo , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Neuropatias Diabéticas/prevenção & controle , Terapia por Exercício/métodos , Hiperalgesia/prevenção & controle , Hipoglicemiantes/farmacologia , Mediadores da Inflamação/metabolismo , Insulina/farmacologia , Nervo Isquiático/efeitos dos fármacos , Ciática/prevenção & controle , Animais , Terapia Combinada , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Malondialdeído/metabolismo , Limiar da Dor/efeitos dos fármacos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Corrida , Nervo Isquiático/metabolismo , Nervo Isquiático/fisiopatologia , Ciática/metabolismo , Ciática/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: Chronic neck pain (CNP) is a prevalent musculoskeletal condition including notable impairments in respiratory function. The diaphragm, serving dual roles in respiration and spinal stability, is intricately linked to the cervical spine through fascial, neurophysiological, and biomechanical connections. However, to date, none has investigated the diaphragm function in patients with CNP. OBJECTIVES: To investigate the diaphragm function, respiratory muscle strength, and pulmonary function in patients with CNP. In addition, their associations were also examined. DESIGN: A case-control study. METHODS: A total of 54 participants were recruited including 25 patients with CNP (CNP group) and 29 healthy adults (CON group). Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), and respiratory muscle strength represented by maximal inspiratory (MIP) and maximal expiratory pressure (MEP), as well as diaphragm function including ultrasonographic measures of mobility and thickness changes during maximal inspiration and expiration were assessed in all participants. Additionally, the intensity of pain and disability were evaluated using a Visual Analog Scale and Neck Disability Index only in patients with CNP. RESULTS: Significant reductions of the FVC, FEV1, MIP, and MEP were found in the CNP group compared to the CON group (p < 0.05). The diaphragm mobility and thickness changes were also significantly decreased in the CNP group than the CON group with medium effect sizes (p < 0.05). Only diaphragm thickness change was positively correlated with FVC, FEV1, and MEP in patients with CNP. Furthermore, MEP showed the strongest contribution to diaphragm thickness change based on the regression analysis. CONCLUSIONS: Impaired diaphragm function, respiratory muscle strength, and pulmonary function were observed in patients with CNP. Patients with smaller diaphragm thickness change had poorer pulmonary function and reduced maximal expiratory muscle strength. Diaphragm assessment and intervention may be considered in CNP management.
Assuntos
Diafragma , Cervicalgia , Ultrassonografia , Humanos , Cervicalgia/fisiopatologia , Cervicalgia/diagnóstico por imagem , Masculino , Feminino , Diafragma/fisiopatologia , Diafragma/diagnóstico por imagem , Estudos de Casos e Controles , Adulto , Pessoa de Meia-Idade , Dor Crônica/fisiopatologia , Dor Crônica/diagnóstico por imagem , Testes de Função Respiratória , Força Muscular/fisiologia , Capacidade VitalRESUMO
BACKGROUND: This study examined the cutaneous analgesic effects of lidocaine co-injected with guanfacine and its comparison with dexmedetomidine. METHODS: Cutaneous analgesic effects are quantified through the blocking effects of the cutaneous trunci muscle reflex against skin pinpricks in rats. The dose-response curves of guanfacine, dexmedetomidine, and lidocaine were constructed and drug-drug interactions were analyzed by the ED50 isobologram. RESULTS: Subcutaneous injections of guanfacine, dexmedetomidine, and lidocaine produced dose-dependently nociceptive/sensory blockade. On the ED50 (50% effective dose) basis, the potency rankings of the drug are dexmedetomidine (0.09 [0.08-0.11] µmol/kg) > guanfacine (3.98 [2.96-5.34] µmol/kg) > lidocaine (25.40 [23.51-27.44] µmol/kg) (p < 0.01). On their equipotent doses (ED25, ED50, and ED75), the duration of sensory blockade induced by guanfacine or dexmedetomidine was longer than lidocaine's (p < 0.01). Both guanfacine and dexmedetomidine showed synergistic effects with lidocaine. CONCLUSIONS: We showed that guanfacine elicits dose-dependent cutaneous analgesia when administered subcutaneously. Lidocaine is less potent than guanfacine or dexmedetomidine. Both guanfacine and dexmedetomidine enhance the potency and duration of lidocaine. Better synergistic responses we are getting with guanfacine plus lidocaine.
Assuntos
Anestésicos Locais , Dexmedetomidina , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Guanfacina , Lidocaína , Ratos Sprague-Dawley , Animais , Dexmedetomidina/farmacologia , Dexmedetomidina/administração & dosagem , Lidocaína/farmacologia , Lidocaína/administração & dosagem , Masculino , Guanfacina/farmacologia , Guanfacina/administração & dosagem , Anestésicos Locais/farmacologia , Anestésicos Locais/administração & dosagem , Ratos , Analgesia/métodos , Analgésicos não Narcóticos/farmacologia , Analgésicos não Narcóticos/administração & dosagem , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Quimioterapia CombinadaRESUMO
BACKGROUND: The underlying mechanism of exercise on the development of diabetes-associated neuropathic pain is not well understood. We investigated in rats whether exercise regulates the functional recovery and heat shock protein 72 (Hsp72), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression in streptozotocin (STZ)-induced diabetes. METHODS: Male Wistar rats were divided into 4 groups: normal sedentary rats, normal rats with exercise, sedentary STZ-diabetic (SS) rats, and STZ-diabetic rats with exercise. Diabetes was induced with STZ (65 mg/kg IV). The trained rats ran daily on a treadmill 30 to 60 min/d with an intensity of 20 to 25 m/min. We monitored thermal withdrawal latency and mechanical withdrawal threshold as well as Hsp72, TNF-α, and IL-6 expression in the spinal cord and peripheral nerves. RESULTS: Two weeks after STZ injection, sedentary rats exhibited a marked and sustained hypersensitivity to von Frey tactile and heat stimuli. In contrast, diabetic rats undergoing exercise demonstrated delayed progress of tactile and thermal hypersensitivity. Exercise significantly suppressed diabetes-induced blood glucose levels and body weight loss, although they were not restored to control levels. Compared with normal sedentary rats, SS rats displayed significantly higher TNF-α and IL-6 levels in the spinal cord and peripheral nerves. The STZ-diabetic rats with exercise group showed greater Hsp72 expression and similar TNF-α or IL-6 level compared with the SS group in the spinal cord and peripheral nerves on day 14 after STZ treatment. CONCLUSIONS: These results suggest that progressive exercise training markedly decreases diabetes-associated neuropathic pain, including thermal hyperalgesia and mechanical allodynia. In rats, this protective effect is related to the increase of Hsp72, but not TNF-α and IL-6, expression in the spinal cord and peripheral nerves of STZ-induced diabetes.
Assuntos
Neuropatias Diabéticas/complicações , Proteínas de Choque Térmico HSP72/biossíntese , Hiperalgesia/complicações , Condicionamento Físico Animal/fisiologia , Animais , Glicemia/metabolismo , Citocinas/biossíntese , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/complicações , Temperatura Alta , Interleucina-6/biossíntese , Masculino , Nervos Periféricos/metabolismo , Estimulação Física , Ratos , Ratos Wistar , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Redução de Peso/fisiologiaRESUMO
The study examined the effect of intrathecal injection of dopamine (serotonin) and/or lidocaine. Intrathecal injections of dopamine (serotonin or epinephrine), lidocaine, or their combination were carried out in male Sprague Dawley rats. Neurobehavioral examinations (motor and nociceptive reactions) were performed before and after spinal injection. Intrathecal serotonin (1.5 µmol), dopamine (2.5 µmol), epinephrine (1:40000), and lidocaine (0.75 µmol) produced 29%, 33%, 29%, and 54% nociceptive blockade, whereas serotonin (1.5 µmol), dopamine (2.5 µmol), or epinephrine (1:40000) produced a longer duration of nociceptive blockade than lidocaine (0.75 µmol) (P < 0.05). Serotonin (1.5 µmol), dopamine (1.25 and 2.5 µmol), or epinephrine (1:40000 and 1:80000) prolonged the duration and increased the potency of spinal motor and nociceptive blockades of lidocaine (50% effective dose, ED50) (P < 0.05). The motor and nociceptive blockades caused by lidocaine (ED50) plus dopamine (2.5 µmol) or lidocaine (ED50) plus epinephrine (1:40000) were more outstanding than lidocaine (ED50) plus serotonin (0.75 µmol) (P < 0.05). Our study provides evidence that intrathecal dopamine or serotonin produces spinal nociceptive blockade dose-dependently. Dopamine and serotonin are less potent than lidocaine in inducing spinal nociceptive blockade. When mixed with lidocaine solution, dopamine or serotonin improves spinal motor and nociceptive blockades. The motor and nociceptive blockade caused by lidocaine (ED50) plus dopamine (2.5 µmol) is similar to that caused by lidocaine (ED50) plus epinephrine (1:40000).
Assuntos
Dopamina , Nociceptividade , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Serotonina , Epinefrina/farmacologia , Lidocaína/farmacologiaRESUMO
BACKGROUND: This study aimed to assess the effectiveness of swimming exercise in alleviating mechanical hypersensitivity and peripheral nerve degeneration associated with a pre-clinical model of painful diabetic neuropathy (PDN). METHODS: This study is a pre-clinical study conducted using the streptozocin (STZ)-induced PDN rat model. Rats were randomly allocated to three groups: a vehicle group of non-diabetic rats (Vehicle, n = 9), a group of rats with PDN (PDN, n = 8), and a group of rats with PDN that performed a swimming exercise program (PDN-SW, n = 10). The swimming exercise program included daily 30-minute swimming exercise, 5 days per week for 4 weeks. Von Frey testing was used to monitor hindpaw mechanical sensitivity over 4 weeks. Assessment of cutaneous peripheral nerve fiber integrity was performed after the 4-week study period via immunohistochemistry for protein gene product 9.5-positive (PGP9.5+) intra-epidermal nerve fiber density (IENFD) in hind-paw skin biopsies by a blinded investigator. RESULTS: The results showed that swimming exercise mitigated but did not fully reverse mechanical hypersensitivity in rats with PDN. Immunohistochemical testing revealed that the rats in the PDN-SW group retained higher PGP9.5+ IENFD compared to the PDN group but did not reach normal levels of the Vehicle group. CONCLUSIONS: The results of this study indicate that swimming exercise can mitigate mechanical hypersensitivity and degeneration of peripheral nerve fibers in rats with experimental PDN.
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Diabetes Mellitus Experimental , Neuropatias Diabéticas , Ratos , Animais , Neuropatias Diabéticas/terapia , Neuropatias Diabéticas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Natação , Fibras Nervosas/metabolismo , Nervos Periféricos/metabolismoRESUMO
This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED50 ; median effective dose) was epinephrine [0.013 (0.012-0.014) µmol] > oxymetazoline [0.25 (0.22-0.28) µmol] > naphazoline [0.42 (0.34-0.53) µmol] = bupivacaine [0.43 (0.37-0.50) µmol] > xylometazoline [1.34 (1.25-1.45) µmol] > lidocaine [5.86 (5.11-6.72) µmol] > tetrahydrozoline [6.76 (6.21-7.36) µmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED25 , ED50 , and ED75 ). Co-administration of lidocaine (ED50 ) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.
Assuntos
Analgesia , Lidocaína , Ratos , Animais , Anestésicos Locais , Nafazolina/uso terapêutico , Oximetazolina/farmacologia , Oximetazolina/uso terapêutico , Ratos Sprague-Dawley , Dor/tratamento farmacológico , Bupivacaína/farmacologia , Analgésicos/farmacologia , Epinefrina/farmacologia , Epinefrina/uso terapêutico , Agonistas Adrenérgicos/farmacologia , Agonistas Adrenérgicos/uso terapêuticoRESUMO
BACKGROUND: Worldwide, 60% of people use social media. Excessive and/or addictive use of social media termed "problematic social media use", has been reported to negatively influence psychological and physiological health. Therefore, we proposed an illustrated model to investigate the associations between social media addiction, psychological distress and food addiction among Taiwanese university students. METHODS: A total of 598 participants (mean age = 22.8 years) completed an online survey comprising the Bergen Social Media Addiction Scale (BSMAS) assessing social media addiction, the Depression Anxiety and Stress Scale (DASS-21) assessing psychological distress, and the Yale Food Addiction Scale 2.0 (YFAS 2.0) assessing food addiction. RESULTS: Structural equation modeling showed the significant associations between BSMAS and DASS-21 (standardized coefficient [ß] = 0.45; p < 0.01) and between DASS-21 and YFAS 2.0 (ß = 0.43; p < 0.01). In addition, mediation effect with 100 bootstrapping samples showed the indirect effect of DASS-21 in the association between BSMAS and YFAS 2.0 CONCLUSIONS: The present study details the relationships between social media addiction and psychological distress as well as food addiction. The results suggest the need for interventions aimed at reducing these negative outcomes. Coping strategies for improving self-control or reducing weight-related stigma, such as food consumption monitoring or mindfulness, could be adopted for at-risk individuals to address these problems.
Social media addiction has been found to have psychological and physiological impacts on individuals' health. In order to better understand the role of social media addiction, the present study constructed a model to investigate the potential mechanism of social media addiction in affecting the individuals' food addiction level. The findings showed a clear pathway between social media addiction and food addiction with the involvement of psychological distress. Accordingly, we suggested that individuals with the potential risk of social media addiction should pay attention to their psychological status and food intake. The potential effect of weight-related stigmatization would also need to be considered, strategies such as mindfulness or food consumption monitoring would be beneficial to address the issues.
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Purpose: In this study, we described "PT for Sleep Apnea", a smartphone application for home-based physical therapy of patients with Obstructive Sleep Apnea (OSA). Methods: The application was created in a joint program between the University of Medicine and Pharmacy at Ho Chi Minh City (UMP), Vietnam, and National Cheng Kung University (NCKU), Taiwan. Exercises maneuvers were derived from the exercise program previously published by the partner group at National Cheng Kung University. They included exercises for upper airway and respiratory muscle training and general endurance training. Results: The application provides video and in-text tutorials for users to follow at home and a schedule function to assist the user in organizing the training program, which may improve the efficacy of home-based physical therapy in patients with Obstructive Sleep Apnea. Conclusion: In the future, our group plans to conduct a user study and randomized-controlled trials to investigate whether our application can benefit patients with OSA.
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BACKGROUND: The underlying mechanism of exercise on neuropathic pain is not well understood. We investigated whether physical exercise regulates the functional recovery and heat shock protein 72 (Hsp72), tumor necrosis factor-α (TNF-α), and interlukin-1ß (IL-1ß) expression after chronic constriction injury (CCI) of the sciatic nerve. METHODS: Male Sprague-Dawley rats were divided into 7 groups: control, sham operated (SO), SO with swimming or treadmill exercise (SOSE or SOTE), CCI, CCI with swimming or treadmill exercise (CCISE or CCITE). We recorded body weight, thermal withdrawal latency, and mechanical withdrawal threshold as well as Hsp72, TNF-α, and IL-1ß expression in sciatic nerve. RESULTS: The body weights in the control and SO groups were heavier than those in the SOSE, SOTE, CCI, CCISE, and CCITE groups. CCI rats with swimming or treadmill exercise showed significant increase in thermal withdrawal latency and mechanical withdrawal threshold when compared with CCI rats without exercise on day 21 after CCI. Both CCISE and CCITE groups demonstrated greater Hsp72 expression and lower TNF-α or IL-1ß level than did the CCI group in sciatic nerve on day 21 after CCI. CONCLUSIONS: These results suggest that progressive exercise training decreases peripheral neuropathic pain as well as TNF-α and IL-1ß overproduction and increases HSP72 expression after CCI of the sciatic nerve.