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1.
Front Pharmacol ; 13: 861799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401205

RESUMO

Inflammatory bowel disease (IBD) results in chronic abdominal pain in patients due to the presence of inflammatory responses in the colon. Electroacupuncture (EA) is effective in alleviating visceral pain and colonic inflammation associated with IBD. Cannabinoid CB2 receptor agonists also reduce colonic inflammation in a mouse model of IBD. However, whether EA reduces visceral pain and colonic inflammation via the CB2 receptor remains unknown. Here, we determined the mechanism of the antinociceptive effect of EA in a mouse model of IBD induced by rectal perfusion of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS). EA or sham EA was performed at the bilateral Dachangshu (BL25) point for seven consecutive days. The von Frey and colorectal distension tests were performed to measure mechanical referred pain and visceral pain. Western blotting and immunohistochemistry assays were carried out to determine the expression of IL-1ß and iNOS and activation of macrophages in the colon tissues. We found that EA, but not sham EA, attenuated visceral hypersensitivity and promoted activation of CB2 receptors, which in turn inhibited macrophage activation and the expression of IL-1ß and iNOS. The effects of EA were blocked by AM630, a specific CB2 receptor antagonist, and by CB2 receptor knockout. Our findings suggest that EA attenuates mechanical allodynia and visceral hypersensitivity associated with IBD by activating CB2 receptors and subsequent inhibition of macrophage activation and expression of IL-1ß and iNOS.

2.
Fitoterapia ; 157: 105124, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35007685

RESUMO

Four new cytochalasans, arbuschalasins A-D (1-4), along with thirteen known analogues (5-17), were isolated from the solid rice medium of endophytic fungus Xylaria arbuscula. Arbuschalasins A-B feature a rare 5/6/6/6 fused ring system while arbuschalasin D was characterized as the first example of natural cytochalasans that possesses a 5/5/11 fused scaffold. The structures of 1-4 were assigned by spectroscopic data, with their absolute structures being determined by electronic circular dichroism (ECD) calculations. All of the isolates were evaluated against the human colorectal adenocarcinoma cell lines (HCT15). Compounds 6 and 7 showed significant inhibitory effects (IC50 values were 13.5 and 13.4 µM, respectively), being more active than those of the positive control, fluorouracil (103.1 µM).


Assuntos
Ascomicetos/química , Citocalasinas/isolamento & purificação , Rhizophoraceae/microbiologia , Linhagem Celular Tumoral , Sobrevivência Celular , Citocalasinas/química , Fermentação , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
3.
Artigo em Inglês | MEDLINE | ID: mdl-34925530

RESUMO

Sishen Pill (SSP) is a classical prescription of traditional Chinese medicine and often used to treat gastrointestinal diseases, including ulcerative colitis (UC). However, its mechanism is still unclear. We aimed to determine the mechanism of SSP in the treatment of UC by investigating if it maintains the integrity of the intestinal mucosal barrier via the Rho A/Rho kinase (ROCK) signaling pathway. Administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) successfully induced chronic UC in rats, while the treatment effect of SSP was evaluated by body weight change, colonic length, colonic weight, colonic weight index, histological injury score, and pathological injury score after colitis rats were treated for 7 days. TNF-α and IL-1ß levels were analyzed by ELISA, and the proteins of PI3K/Akt and RhoA/ROCK signaling pathway and junction proteins expression were measured by western blotting assay, and the distribution of Claudin 5 was shown by immunofluorescence. SSP significantly improved the clinical symptoms of colitis in rats and reduced the expression of p-RhoA, ROCK1, PI3K, and Akt in the colon mucosa, while it increased the expression of p-Rac and related proteins (Claudin-5, JAM1, VE-cadherin, and Connexin 43). In addition, SSP increased p-AMPKα and PTEN proteins expression, decreased Notch1 level, and hinted that activation of the PI3K/Akt signaling pathway was inhibited. In conclusion, SSP effectively treated chronic colitis induced by TNBS, which may have been achieved by inhibiting PI3K/Akt signal to suppress activation of the Rho/ROCK signaling pathway to finally maintain the integrity of the intestinal mucosal barrier.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34781405

RESUMO

BACKGROUND: Microvascular decompression (MVD) has become accepted as an effective therapeutic option for hemifacial spasm (HFS); however, the curative rate of MVD for HFS varies widely (50-98%) in different medical centers. This study could contribute to the improvement of the MVD procedure. METHODS: We retrospectively analyzed 32 patients in whom initial MVD failed in other hospitals and who underwent a second MVD at our center. The clinical characteristics, operative findings, outcome of the second MVD, and complications were recorded. RESULTS: There were 18 women and 14 men (56.3 and 43.7%, respectively). The left-to-right ratio was 19:13. The mean age of the patients was 59.8 years. We found an undiscovered conflict site located in zone 4 in 10 patients and in the root entry zone in 8 patients. The initial MVD failed in nine patients because of ignorance of the arterioles that originate from the anterior inferior cerebellar artery. There were no special findings in four patients. No Teflon felts were found in the whole surgical field in one patient. CONCLUSION: Omission of the offending vessel is the most common cause of an unsuccessful MVD. Intraoperative abnormal muscle response associated with the Z-L response is a good measure to correctly identify the involved arterioles.

5.
J Cardiothorac Surg ; 16(1): 96, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879210

RESUMO

PURPOSE: The present study aimed to explore the clinical characteristics of heparin-induced thrombocytopenia (HIT) after surgery for acute type A aortic dissection and perform a relevant prognostic analysis. METHODS: After continuous observation and analysis of 204 patients who underwent acute type A aortic dissection, we found that blood platelets decreased significantly after surgery and that these patients can be suspected to suffer HIT based on relevant 4Ts scores. For these suspected HIT patients, a latex particle-enhanced immunoturbidimetric assay was conducted to detect heparin-induced antibodies. Perioperative clinical data of patients in HIT and non-HIT groups were recorded as were blood platelet counts, HIT antibody test results, 4Ts scores, thromboembolic complications, clinical prognosis and outcomes. RESULTS: In the present study, 38 suspected HIT patients, 16 HIT patients and 188 non-HIT patients were selected in the clinical setting. Among them, HIT patients were found to have prolonged cardiopulmonary bypass time (223 min on average vs. 164 min) and delayed aortic cross-clamp time (128 min on average vs. 107 min), and these differences between HIT patients and non-HIT patients were significant (P < 0.05). Additionally, the HIT group required longer operation time and higher dose of heparin, but showing no statistical differences (P > 0.05). The transfusions of blood platelets in the HIT group and non-HIT group were 18.7 ± 5.0u and 15.6 ± 7.34 u, respectively. In the HIT group, the mechanic ventilation time and the length of ICU stay were longer comparing the non-HIT group(P < 0.05), though no significant differences in total length of stay or In-hospital mortality were observed (P > 0.05). The incidence of continuous renal replacement therapy in HIT group was higher than the non-HIT group (P < 0.05). Additionally,there were no significant differences in 24-h postoperative drainage or reoperation for bleeding in both group(P > 0.05). However, the HIT antibody titer in the HIT group was significantly higher than that in the Suspected HIT group (2.7 ± 0.8 U/mL vs. 0.3 ± 0.2 U/mL) (P < 0.05). Among patients diagnosed with HIT, the incidence of thromboembolism reached 31.5%.For example, two HIT patients newly developed thromboembolism in both lower extremities,and three patients experienced cerebral infarction. CONCLUSIONS: After surgery for acute type A aortic dissection, HIT patients developed postoperative complications, the duration of ventilatory support and length of ICU stay were extended, and the incidence of thromboembolism increased. HIT antibody detection and risk classification should be implemented for high-risk patients showing early clinical characteristics.


Assuntos
Aneurisma Dissecante/cirurgia , Anticoagulantes/efeitos adversos , Aneurisma Aórtico/cirurgia , Heparina/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Trombocitopenia/induzido quimicamente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Prognóstico , Estudos Prospectivos , Medição de Risco , Trombocitopenia/diagnóstico , Trombocitopenia/fisiopatologia , Trombocitopenia/prevenção & controle
6.
Neural Regen Res ; 16(10): 2078-2085, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33642397

RESUMO

Postmenopausal women with Alzheimer's disease (AD) exhibit dramatically reduced sensitivity to estrogen replacement therapy, which is though to be related to an estrogen receptor (ER)α/ERß ratio imbalance arising from a significantly decreased level of ERs of the brain. The aim of our study was to investigate whether valproic acid (VPA) can enhance the beneficial effects of estrogen on cognitive function through restoration of ERα and ERß expression in the brain. We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA (30 mg/kg, intraperitoneal injection, once daily), 17ß-estradiol (E2) (2.4 µg, intraperitoneal injection, once daily), liquiritigenin (LG) (50 µg/kg, intragastric infusion, once daily), VPA + E2, or VPA + LG for 4 successive weeks. Compared with treatment with a single drug, treatment with VPA + E2 or VPA + LG significantly increased the level of glycogen synthase kinase 3ß, increased the expression of estrogen receptor α, reduced the expression of small ubiquitin-like modifiers, and increased the level of estrogen receptor ß. This resulted in enhanced sensitivity to estrogen therapy, reduced amyloid ß aggregation, reduced abnormal phosphorylation of the tau protein, reduced neuronal loss, increased dendritic spine and postsynaptic density, and significantly alleviated memory loss and learning impairment in mice. This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee, China on March 6, 2013.

7.
World J Clin Cases ; 8(20): 5030-5035, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33195678

RESUMO

BACKGROUND: Posterior scleritis is a rare inflammatory ocular disease, characterized by severe and painful inflammation of the sclera. It is often misdiagnosed or underdiagnosed, due to its general and varying clinical presentation profile, which primarily involves pain and visual impairment but which can include eyelid edema, choroidal folds, serous retinal detachment, disc edema, hard exudates in fovea and subretinal mass. We report here a case of posterior scleritis, with symptoms of eye pain and red eye, initially misdiagnosed as acute conjunctivitis. CASE SUMMARY: A 56-year-old man presented to a local hospital with complaint of pain and redness in the right eye. The initial diagnosis was acute conjunctivitis and he was given antibiotic eyedrops. Upon week-long continuance of the symptoms despite treatment, he presented to our hospital. Initial examination revealed a shallow anterior chamber in the right eye and vision reduction to 0.6. Further testing by optical coherence tomography, ultrasound biomicroscopy, and fundus photography indicated diagnosis of posterior scleritis. The patient was given methylprednisolone (oral) on a tapered reduction schedule (starting with 70 mg/d). According to the peaks and troughs of symptoms, compound betamethasone injection was administered into the bulb, culminating in discontinuation of the oral corticosteroid. Subsequent optical coherence tomography showed the subretinal fluid near the optic disc to be completely absorbed after treatment. CONCLUSION: Posterior scleritis should be among the differential diagnosis of eye pain and redness, and diagnosis requires further ophthalmic accessory examination, such as by optical coherence tomography.

8.
Gene ; 669: 63-68, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-29800734

RESUMO

To explore the role of genetic factors in the pathogenesis of hypertension, our study investigated the gender-specific association between four polymorphisms in the Apelin/APJ gene and hypertension risk in southeastern Chinese population. All participants including 645 hypertensive patients and 362 normotensive controls were genotyped for 4 gene polymorphisms associated with hypertension susceptibility including Apelin (rs909656, rs5975126) and APJ (rs10501367, rs11544374). According to genotype analysis, for male subjects, the frequencies of genotypes (P = 0.046 and 0.046, respectively) of rs10501367 and rs11544374 revealed significant differences between the hypertension and control groups. Moreover, for female subjects, there was significant difference on the genotype distribution of rs11544374 between two groups (P = 0.046). The association of rs10501367 with hypertension was significant for males under additive models and recessive models, even after adjusting for age, BMI, fasting glucose and waistline. Besides, significant association was observed for rs11544374 in females under additive models. As for haplotype analysis, haplotype T-A (in order of rs10501367 and rs11544374) in APJ gene was marginally overrepresented in controls (17.9%) compared to patients with hypertension (11.6%) in males (P = 0.003). The mutation of polymorphism rs10501367 in APJ gene decreased risk of hypertension in Chinese males.


Assuntos
Receptores de Apelina/genética , Apelina/genética , Hipertensão/genética , Adulto , Idoso , Pressão Sanguínea/genética , Estudos de Casos e Controles , China , Feminino , Haplótipos , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Fatores Sexuais
9.
Int J Surg ; 54(Pt A): 201-205, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29678619

RESUMO

PURPOSE: To explore effect of goal-directed fluid therapy (GDFT) on early cognitive function in elderly patients with spinal stenosis. METHODS: 83 elderly patients with spinal stenosis were randomly classified into two groups: control group (n = 40) and GDFT group (n = 43). The Montreal Cognitive Assessment (MoCA) score, IL-6 and S100ß levels, hemodynamic parameters, cerebral oxygen saturation (rSO2), arterial lactic acid values, output of surgery, operation time and cases of hypotension, intraoperative complications within 7 days were recorded for all patients. RESULTS: The incidence of postoperative cognitive dysfunction (POCD) was about 21.67% in this study. The MoCA scores, inflammatory mediators, perfusion indexes (rSO2 and lactic acid)and intraoperative hemodynamics(HR, MAP, and CI)were not all the same at different time points (P < 0.05). The levels of inflammatory mediators (IL-6 and S100ß) in GDFT group were lower than those in the control group (P < 0.05). Total intake, amount of lactated Ringer's solution and cases of hypotension in GDFT group were significantly lower than control group (P < 0.05), but amount of voluven was higher than control group(P < 0.05). Compared with control group, the incidence of postoperative delirium, nausea and vomiting, and hypotension in GDFT group was lower (P < 0.05). CONCLUSIONS: GDFT can maintain the stability of perioperative hemodynamics in the prone position of elderly patients with spinal stenosis, improve the balance between perfusion of tissue and organ and supply and demand of oxygen, reduce the inflammatory response, and reduce the incidence of early POCD in this type of surgery.


Assuntos
Disfunção Cognitiva/terapia , Terapia Precoce Guiada por Metas/métodos , Hidratação/métodos , Complicações Pós-Operatórias/terapia , Estenose Espinal/psicologia , Idoso , Estudos de Casos e Controles , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Feminino , Hemodinâmica , Humanos , Derivados de Hidroxietil Amido/uso terapêutico , Soluções Isotônicas/uso terapêutico , Masculino , Complicações Pós-Operatórias/etiologia , Lactato de Ringer , Estenose Espinal/cirurgia , Resultado do Tratamento
10.
Pharm Res ; 27(9): 1977-86, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20625801

RESUMO

PURPOSE: Microparticles containing solid lipid nanoparticles (SLNs) are receiving increased attention as carriers for the lung delivery of the SLNs. Thus, we aim to prepare the hybrid microparticles and thoroughly evaluate their feasibility for the pulmonary drug delivery. METHODS: The microparticles were prepared by co-spray-drying the thymopentin (TP5)-loaded SLNs with bulking agents. Thereafter, we systematically estimated the potential of the microparticles as the carriers for the pulmonary delivery of the SLNs, including the investigations of their characteristics, aerodynamic properties, pharmacokinetics and pharmacodynamics. RESULTS: The spherical and hollow microparticles presented a size of 4.1 +/- 0.1 microm and a low tap density of 0.175 +/- 0.02 g/cm(3). In addition, the microparticles showed a high aerosolization efficiency (emitted dose of 98.0% +/- 1.23% and respirable fraction of 51.07% +/- 1.21%). Furthermore, the SLNs could be easily recovered from the microparticles without essential changes on their characteristics and the drug release behavior. The pharmacokinetic and pharmacodynamic studies suggested that, compared to i.v. TP5 solution, the bioavailability and therapeutic efficacy of TP5 were remarkably strengthened after the pulmonary administration of the microparticles. CONCLUSIONS: Taken together, we believe the microparticles were suitable for inhalation and possessed an ample potential for the pulmonary delivery of the SLNs.


Assuntos
Adjuvantes Imunológicos/farmacocinética , Portadores de Fármacos/química , Lipídeos/química , Pulmão/metabolismo , Nanopartículas/química , Timopentina/farmacocinética , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/uso terapêutico , Administração por Inalação , Animais , Relação CD4-CD8 , Estabilidade de Medicamentos , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/imunologia , Subpopulações de Linfócitos/citologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Microscopia Confocal , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Propriedades de Superfície , Timopentina/administração & dosagem , Timopentina/química , Timopentina/uso terapêutico
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