RESUMO
Objective: To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection. Methods: Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results: A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group (P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [OR, 2.667 (CI: 1.389-5.122); P=0.003], increased CK [OR, 2.544 (CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] (CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [OR, 0.424 (CI: 0.254-0.709); P=0.001]. Conclusion: Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.
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COVID-19 , Estado Terminal , Dispneia , Febre , Humanos , Fígado , Masculino , Dor , Estudos Retrospectivos , SARS-CoV-2RESUMO
ß-amyloid peptides (Aßs) can exert neurotoxic effects through induction of oxidative damage, whereas lipoic acid (LA), a powerful antioxidant, can alleviate oxidative damage. In this study, we explored the effect and mechanism of action of LA on beta-amyloid-intoxicated C6 glioma cells. Cells were randomly divided into three groups: control (vehicle), Aß, and LA + Aß. The LA + Aß group was treated with LA for 2 h, then both the Aß-only and the LA + Aß groups were incubated with 25 µM Aß for 24 h. Cell viability was measured by the MTT method. Mitochondrial reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the GSH to GSSG ratio calculated. Real-time polymerase chain reaction and western blot analyses were used to detect MnSOD mRNA and protein, respectively. Aß significantly inhibited C6 cell proliferation compared with the control group (P < 0.05). LA markedly increased cell viability compared with the Aß group (P < 0.05). The increased GSSH and decreased GSH mitochondrial accumulation induced by Aß was profoundly reversed by treatment with LA (P < 0.05). Aß significantly reduced MnSOD expression compared to controls (P < 0.05), whereas LA pretreatment increased MnSOD expression compared with the Aß-only group (P < 0.05); MnSOD protein levels showed similar patterns. These results suggest that LA might protect Aß-intoxicated C6 glioma cells by alleviating oxidative damage, providing a new treatment strategy for neurodegenerative diseases.
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Peptídeos beta-Amiloides/metabolismo , Antioxidantes/farmacologia , Glioma/metabolismo , Ácido Tióctico/farmacologia , Peptídeos beta-Amiloides/toxicidade , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Expressão Gênica , Glioma/genética , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxirredução/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
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COVID-19 , Transtornos do Olfato , Feminino , Humanos , Adolescente , SARS-CoV-2 , Olfato , COVID-19/complicações , Estudos Transversais , Vacinas contra COVID-19 , Incidência , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologia , PrognósticoRESUMO
Objective: By analyzing the expression of pepsin in nasopharyngeal carcinoma (NPC) tissues, to investigate the correlation between laryngeal reflux (LPR) and NPC, as well as the effect of LPR on the quality of life of patients with NPC after radiotherapy. Methods: A total of 133 patients with NPC who underwent radiotherapy at the Department of Otorhinolaryngology of the Affiliated Hospital of Guizhou Medical University and the Affiliated Cancer Hospital of Guizhou Medical University from 2005 to 2019 were enrolled consecutively, including 90 males and 43 females, aged (44.32±7.47) years old. At the same period, 58 patients with chronic nasopharyngitis who underwent nasopharyngeal biopsy were selected as the control group. Immunohistochemical method was used to detect the expression of pepsin in nasopharyngeal specimens of the two groups. In addition, 188 normal individuals were selected as the normal group in the same period. NPC patients before and within 6 months after radiotherapy were inverstigated by the General Information Questionnaire and the Quality of Life Scale, and the pepsin levels in saliva of NPC patients before and after radiotherapy and the individuals in normal group were measured. SPSS 21.0 software was used for statistical analysis. Results: Pepsin expression in 133 specimens of NPC patients was strongly positive in 24 cases (18.05%), positive in 21 cases (15.79%), weakly positive in 69 cases (51.88%), and negative in 19 cases (14.29%). The specimens of control group had 10 cases of weakly positive (17.24%), 48 cases of negative (82.76%), but no strong positive or positive pepsin expression. The rate of positive pepsin expression in the NPC group was higher than that in the control group, with a statistically significant (χ2=83.15, P<0.001). The pepsin content in the saliva of NPC patients after radiotherapy ((30.31±7.82) ng/ml) was higher than that before radiotherapy ((20.47±8.21) ng/ml) and the normal group (5.11±2.13) ng/ml), and the pepsin content in saliva before radiotherapy was higher than that in the normal group, and all differences were statistically significant (all P<0.05). After radiotherapy, the five functional domains of quality of life and overall quality of life of NPC patients decreased, while the related symptom scores increased (all P<0.05). Multiple linear regression analysis showed that pepsin content in saliva was the influential factor of five functional domains of quality of life, related symptoms and overall quality of life in NPC patients after radiotherapy (all P<0.05). Conclusion: The positive rate of pepsin expression in NPC tissues is high, and the pepsin in saliva before and after radiotherapy of NPC patients is significantly higher than that in normal, suggesting that LPR may be involved in the process of NPC and affect the quality of life after radiotherapy in NPC patients.
Assuntos
Neoplasias Nasofaríngeas , Pepsina A , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Pepsina A/análise , Qualidade de Vida , Saliva/químicaRESUMO
Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1ß and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.
Assuntos
Piroptose , Rinite Alérgica , Animais , Caspases/farmacologia , Caspases/uso terapêutico , Modelos Animais de Doenças , Humanos , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Inflamassomos/uso terapêutico , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ovalbumina , Rinite Alérgica/tratamento farmacológico , OlfatoRESUMO
Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t=-8.564, P<0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P<0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P>0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.
Assuntos
Pólipos Nasais , Rinite , Sinusite , Adulto , Calcifediol , Doença Crônica , Eosinófilos , Feminino , Humanos , Masculino , Seio Maxilar , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/diagnóstico , Rinite/complicações , Rinite/diagnóstico , Sinusite/complicações , Sinusite/diagnósticoRESUMO
OBJECTIVE: The purpose of this study was to uncover the correlations of expression levels of microRNA-429 (miRNA-429) and SOX2 with clinical parameters and prognosis of nasopharyngeal carcinoma. PATIENTS AND METHODS: Nasopharyngeal carcinoma patients (n=95) and nasopharyngitis patients (n=95) in the same period were enrolled. The relative levels of miRNA-429 and SOX2 in nasopharyngeal tissues collected from these patients were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Then, the potential correlation between miRNA-429 and SOX2 was analyzed by Pearson correlation test. Next, the influences of miRNA-429 and SOX2 levels on clinical parameters of nasopharyngeal carcinoma patients were assessed. At last, the factors influencing the prognosis of nasopharyngeal carcinoma were determined using the Cox regression model. RESULTS: It was found that downregulated miRNA-429 and upregulated SOX2 were observed in nasopharyngeal tissues collected from nasopharyngeal carcinoma patients. MiRNA-429 level was negatively correlated with that of SOX2 in nasopharyngeal carcinoma tissues. In addition, miRNA-429 and SOX2 levels were related to age, tumor differentiation, T stage, N stage, and clinical grade of nasopharyngeal carcinoma patients. Moreover, worse prognosis was seen in nasopharyngeal carcinoma patients expressing low level of miRNA-429 or high level of SOX2. Furthermore, Cox regression analysis showed that T3-T4 stage, moderate to high differentiation, and high level of SOX2 were risk factors, while high level of miRNA-429 was the protective factor for nasopharyngeal carcinoma. CONCLUSIONS: Downregulation of miRNA-429 and upregulation of SOX2 are unfavorable to the prognosis of nasopharyngeal carcinoma.
Assuntos
Regulação para Baixo , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Fatores de Transcrição SOXB1/metabolismo , Regulação para Cima , Adulto , Idoso , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Fatores de Transcrição SOXB1/genéticaRESUMO
OBJECTIVE: To elucidate the promotive role of TRPP2 in nasopharyngeal carcinoma (NPC) proliferation by targeting Skp2/c-Myc, thus accelerating the malignant progression. PATIENTS AND METHODS: TRPP2 levels in NPC patients with different T stages were detected. Correlation between TRPP2 level and clinical features of NPC patients was analyzed. Kaplan-Meier curves were depicted for assessing the prognostic value of TRPP2 in NPC. Subsequently, regulatory effects of TRPP2 on viability and 5-ethynyl-2'-deoxyuridine (EdU)-positive ratio were determined by cell counting kit-8 (CCK-8) and EdU assay, respectively. Relative levels of Skp2 and c-Myc in NPC cells transfected with si-TRPP2 were examined. At last, the involvement of c-Myc in TRPP2-regulated proliferative ability of NPC was evaluated by performing rescue experiments. RESULTS: TRPP2 was upregulated in NPC tissues. TRPP2 level was higher in NPC patients with T3+T4 than those with T1+T2. Worse survival was observed in NPC patients expressing high level of TRPP2. TRPP2 level was correlated to T stage, N stage, M stage, and locoregional failure of NPC patients. Knockdown of TRPP2 reduced viability and EdU-positive ratio in NPC cells. In addition, relative levels of Skp2 and c-Myc in NPC cells transfected with si-TRPP2 were downregulated. Overexpression of c-Myc could partially reverse the regulatory effects of TRPP2 on NPC proliferation. CONCLUSIONS: TRPP2 stimulates NPC cells to proliferate by upregulating expressions of Skp2/c-Myc, thus deteriorating the development of NPC.
Assuntos
Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Canais de Cátion TRPP/metabolismo , Regulação para Cima , Proliferação de Células , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Quinases Associadas a Fase S/genética , Canais de Cátion TRPP/genética , Células Tumorais CultivadasRESUMO
Objective: To evaluate the mental state and quality of life in patients with vasomotor rhinitis (VMR) before and after treatment, and to provide guidance for improving the overall health of VMR patients. Methods: Two hundred and twenty VMR patients (VMR group, 118 males, 102 females; aged from 18 to 72 years old), three hundred and twenty allergic rhinitis (AR) patients (AR group, 178 males, 142 females; aged from 18 to 79 years old) from January 2016 to September 2019 were selected in the otolaryngology clinic of Affiliated Hospital of Guizhou Medical University, four hundred and twenty-three healthy people (control group, 243 males, 180 females; aged from 19 to 70 years old) were selected in physical examination center at the same time by continuous enrollment method, symptom check list (SCL-90), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the mental state of VMR patients before and after treatment, and 12-item short form health survey version 2.0 (SF-12v2) was used to evaluate their quality of life, statistical data were collected and analyzed by ANOVA and t-test. Results: The scores of eight factors (physical function, role physical function, general health, vitality, role-emotional, mental health) of SF-12v2 in VMR patients before treatment were lower than that of posttreatment, that of AR patients and the control group, the differences were significant (all P<0.05), the scores of somatization, obsession, depression, anxiety and psychosis in SCL-90 in VMR patients before treatment were significantly higher than that of posttreatment, that of AR patients and the control group (all P<0.05), the SAS and SDS in VMR patients before treatment (51.28±16.32; 53.28±18.55) were significantly higher than that of posttreatment (38.53±13.21; 39.35±13.34), that of AR patients (42.23±14.32; 43.32±13.78) and the control group (29.78±10.07;33.46±10.55; t(SAS) were 9.007, 6.813 and 20.59; t(SDS) were 9.043, 7.154 and 17.260, all P<0.05). Conclusion: VMR patients generally suffer from psychological damage, which seriously affects the quality of life of the patients. On the basis of routine treatment, we should attach more importance to the negative psychology of VMR patients and intervene when necessary.
Assuntos
Rinite Alérgica , Rinite Vasomotora , Adolescente , Adulto , Idoso , Ansiedade/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Rinite Alérgica/psicologia , Rinite Vasomotora/psicologia , Rinite Vasomotora/terapia , Adulto JovemRESUMO
Objective:To investigate the efficacy of flupentixol melitracen on different stages of sudden deafness patients with anxiety and depression.Method:Totally one hundred and sixty-three sudden deafness patients with anxiety and depression were randomly divided into two groups: experimental group(81 cases) and control group (82 cases). All patients were given routine treatment for 2 weeks. The experimental group was given oral flupentixol melitracen (1 tablet/day)for a period of 3 months. The hearing, tinnitus effect and vertigo treatment course were observed and compared. Curing rate of tinnitus at 2 weeks, 3 months and 6 months after treatment, self-rating anxiety scale (SAS) and depressive state scale (self-rating depression scale, SDS) score were collected and compared.Result:Total efficiency of hearing and tinnitus of experimental group(86.42%,84.21%)were higher than that of the control group(67.07%,61.29%);the vertigo cured the average treatment time of experimental group days was less than that of the control groupdays,all the differences were statistically significant.After treatment,the average hearing threshold value of the two groups of patients were lower than that before treatment,the low frequency descent type, high-frequency descent type,flat down type and total deafness type thresholds of the experimental group were lower than of the control group,all the differences were statistically significant.The tinnitus cure rate of experiment group were higher than the control group at 3months and 6 months after treatment,the differences were statistically significant;and after 3months and 6 months treatment tinnitus cure rate higher of the experimental group than that of after 2 weeks the treatment,the difference was statistically significant.After 2 weeks,3 months and 6 months treatment,the SAS and SDS scores of two groups were lower than that before treatment.The SAS and SDS scores of the experimental group decreased after 2 weeks,3 months and 6 months treatment, and the difference was statistically significant at different time points,the SAS,SDS scores of experimental group after treatment were lower than the control group at the same time,the differences were statistically significant.Conclusion:For the sudden deafness patients with anxiety and depression , the combination of flupentixol melitracen on the basis of conventional therapy can improve the clinical efficacy, the patient's mental status and long-term therapeutic effect of tinnitus..
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Ansiedade/complicações , Depressão/complicações , Antagonistas de Dopamina/uso terapêutico , Flupentixol/uso terapêutico , Perda Auditiva Súbita/tratamento farmacológico , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Transtorno Depressivo , Perda Auditiva Súbita/complicações , Humanos , ZumbidoRESUMO
As a test of the origin of the melatonin-sensitivity rhythm recorded from SCN cells in brain slices from intact Syrian hamsters, hamsters were either pinealectomized to remove the influence of endogenous melatonin, or sham operated. Cells from sham-operated hamsters showed a trough in responsiveness during the projected night. Pinealectomy eliminated the daily rhythm of melatonin responsiveness, reduced the proportions of cells responding to melatonin, and raised response thresholds in those cells that did not meet the criterion for responsiveness. Pinealectomy also altered the firing-rate rhythm so that the morning peak in firing rate was not sustained and the nocturnal trough was attenuated, leading to a firing-rate rhythm with reduced amplitude compared to those recorded from sham-operated or intact animals. These results indicate a role for endogenous melatonin in regulating both melatonin sensitivity and the integrity of the SCN firing-rate rhythm, and they suggest why pinealectomy can disrupt circadian organization in some situations.
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Melatonina/fisiologia , Neurônios/fisiologia , Glândula Pineal/fisiologia , Núcleo Supraquiasmático/fisiologia , Animais , Ritmo Circadiano/fisiologia , Cricetinae , Eletrofisiologia , Masculino , Mesocricetus , Núcleo Supraquiasmático/citologiaRESUMO
Rhythms of spontaneous firing rate and of responsiveness to pressure ejection of melatonin were recorded from neurons in the Syrian hamster suprachiasmatic nuclei (SCN) in a slice preparation. In animals taken from light-dark cycles (LD 14:10), SCN cells had high firing rates during the projected day and lower rates during the projected night. The proportion of melatonin-suppressed cells (35% overall) was also high during the day and fell during the night, while melatonin activated approximately 23% of cells at all phases. To assess the source of the melatonin-responsiveness rhythm, hamsters were exposed for approximately 48 h to constant illumination (LL) to suppress melatonin secretion. LL exposure before slice preparation altered both firing-rate and melatonin-responsiveness rhythms. Firing rates failed to show a morning peak and remained at low levels, with no indication of daily rhythmicity. Melatonin responsiveness also failed to show the usual rhythm and even tended to rise at night. Overall melatonin responsiveness rose after LL exposure so that 50% of cells were suppressed and 21% activated. LL exposure also increased the proportions of cells which showed regular baseline firing rates. Control studies indicated that pressure artifacts did not account for either suppression or activation by melatonin, while the composition of the saline vehicle appeared to be responsible for the activations recorded. The results indicate that brief LL exposure alters SCN sensitivity to melatonin and SCN rhythmicity in Syrian hamsters, perhaps as a result of the loss of the daily melatonin secretion rhythm. Physiological melatonin patterns may have important effects on the rodent circadian pacemaker.
Assuntos
Melatonina/fisiologia , Neurônios/fisiologia , Núcleo Supraquiasmático/fisiologia , Animais , Ritmo Circadiano/fisiologia , Cricetinae , Eletrofisiologia , Técnicas In Vitro , Luz , Masculino , Mesocricetus , Neurônios/efeitos da radiação , Núcleo Supraquiasmático/citologiaRESUMO
The effects of serotonin (5-HT) receptor agonists and antagonists on the spontaneous discharge of suprachiasmatic nucleus (SCN) neurons were investigated using rat hypothalamic slice. It was found that: (1) the SCN neurons showed a persistent rhythm in the spontaneous discharge rate, which was higher during the light phase than during the dark phase; (2) the effects of 5-HT on SCN neurons was inhibitory in nature and the sensitivity of SCN neurons to 5-HT during the light phase was lower than that during the dark phase; (3) both 5-HT and 5-HT(1/7) receptor agonist, (+/-)-8-hydroxy-2-(DL-N-propylamino) tetralin hydrobromide, could inhibit the spontaneous discharge of SCN neurons. This inhibitory effect could be blocked by 5-HT(2/7) receptor antagonist ritanserin and putative 5-HT(7) receptor antagonists clozapine, but neither by selective 5-HT(2) receptor antagonist ketanserin, nor by 5-HT(1) receptor antagonist pindolol. It was suggested that the inhibitory effect of 5-HT on the spontaneous discharge of SCN neurons in rat hypothalamic slice is mediated by 5-HT(7) receptor subtype.
Assuntos
Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/farmacologia , Núcleo Supraquiasmático/efeitos dos fármacos , Animais , Ritmo Circadiano/fisiologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Wistar , Receptores de Serotonina/fisiologia , Núcleo Supraquiasmático/fisiologiaRESUMO
This study was undertaken to evaluate the analgesic effect of paraventricular nucleus (PVN) stimulation with tail stimulation-vocalization test. The mechanism of this analgesia was analysed with nuclear lesion and microinjection technique. The main results were as follows: (1) Electrical stimulation of the PVN could significantly enhance the pain threshold and increase the content of AVP in brainstem measured by radioimmunoassay. (2) Solitary tract nucleus (STN) lesion could eliminate the analgesic effect induced by PVN stimulation. (3) Intranuclear microinjection of AVP-antagonist and AVP-antiserum into the STN could block the analgesic effect of PVN stimulation. (4) Intranuclear microinjection of AVP into the STN could mimick the analgesic effect similar to that of PVN stimulation. These results suggest that electrical stimulation of the PVN could produce an analgesic effect. This effect might be mediated by the activation of VP-ergic neurons in PVN and upon releasing VP from the descending fibers, the activities of neurons in the STN are influenced.
Assuntos
Bulbo/fisiologia , Dor/fisiopatologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Vasopressinas/farmacologia , Animais , Estimulação Elétrica , Masculino , Microinjeções , Nociceptores/fisiologia , Ratos , Ratos Endogâmicos , Limiar SensorialRESUMO
Previous studies have demonstrated that locus coeruleus (LC)-noradrenergic neuronal system plays an important role in pain modulation and electroacupuncture (EA) analgesia. In the present experiment, the effect of LC stimulation and EA on nociceptive response of spinal dorsal horn neurons was investigated. The main results were: 1) LC stimulation and electroacupuncture produced a significant inhibitory effect on nociceptive response of dorsal horn neurons; 2) The inhibitory effect of LC stimulation was not affected by the lesion of nucleus raphe magnus or by the injection of naloxone; 3) These inhibitory effects of LC stimulation and electroacupuncture could be enhanced by alpha 2-agonist clonidine, and decreased slightly by alpha-antagonist phentolamine. These results suggest that the inhibitory effect of LC stimulation and electroacupuncture on the nociceptive response of dorsal horn neurons might be mediated by alpha 2-receptors.
Assuntos
Eletroacupuntura , Locus Cerúleo/fisiologia , Nociceptores/fisiologia , Medula Espinal/fisiologia , Animais , Clonidina/farmacologia , Feminino , Masculino , Naloxona/farmacologia , Neurônios Aferentes/fisiologia , Fentolamina/farmacologia , Núcleos da Rafe/fisiologia , Ratos , Ratos EndogâmicosRESUMO
Spontaneous firing of suprachiasmatic nucleus (SCN) neurons and the effect of melatonin (MEL) were examined in hypothalamic slices made from pinealectomized rats or from the rats exposed to constant light. The results are as follows. (1) Under normal light cycle (light dark=12 12), SCN neurons displayed a circadian rhythm in spontaneous discharges. A peak about 8.3 Hz was presented at CT (circadian time) 6 8 and a trough about 3.8 Hz at CT18 20. The circadian rhythm persisted after pinealectomy, but disappeared after constant light exposure. (2) The response of SCN neurons to MEL was mainly inhibitory. Under normal light exposure, the inhibitory proportion was higher during the subjective day with the largest proportion of about 42% at CT8 10, and was lower during the subjective night with the largest proportion of about 26% at CT22 24. Under both constant light exposure and pinealectomy, the circadian rhythm of the response of SCN neurons to MEL disappeared. (3) The inhibitory effect of MEL on spontaneous discharges of SCN neurons was blocked by ML-1 receptor antagonist luzindole, but not by ML-2 receptor antagonist prazosin. The above results suggest that pineal gland, as a regulator of the organization of circadian rhythm, regulates the circadian rhythm of SCN neurons at two responsive time windows (CT8 10 and CT22 24) through high affinity ML-1 receptors in SCN.
Assuntos
Ritmo Circadiano/efeitos dos fármacos , Hipotálamo/fisiologia , Melatonina/farmacologia , Núcleo Supraquiasmático/fisiologia , Animais , Eletrofisiologia , Masculino , Microeletrodos , Neurônios/fisiologia , Ratos , Ratos WistarRESUMO
The effects of hypothalamic arcuate nucleus (ARC) or anterior lobe of pituitary (AL) stimulation on the nociceptive responses of thalamic parafascicular (Pf) neurons were studied in rats with electrophysiological technique. The results showed that ARC stimulation could inhibit the nociceptive discharges of Pf neurons, namely, the immediate inhibition because of its very short latency and duration. AL stimulation could also inhibit the nociceptive discharges of Pf neurons, but this inhibition was a delayed one because of its longer latency and duration. Hypophysectomy diminished the immediate inhibition due to ARC stimulation, while ARC lesion diminished the delayed inhibition due to AL stimulation. Both kinds of inhibition were blocked by dexamethasone pretreatment. The above results suggest that neuroendocrine relationship between ARC and AL is involved in pain modulation.