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1.
Ecotoxicol Environ Saf ; 241: 113773, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35753269

RESUMO

Rosmarinic acid (RA) is a natural polyphenol with various biological activities, such as anti-oxidative, anti-fibrotic, and hepatoprotective properties. The objective of this study was to investigate the protective effect of RA against acetaminophen (APAP)-induced hepatotoxicity (AILI) and explore the underlying mechanisms. Kunming mice were treated with RA (20, 40, or 80 mg/kg, i.g) for 7d, followed by an intraperitoneal injection of APAP (500 mg/kg). The liver injury was evaluated by serum biochemical and liver histopathological examinations. Human HepG2 cells were pre-treated with RA (20, 40, or 80 µmol/L) and then incubated with APAP (25 mmol/L) for 24 h. The MTT assay, wound healing assay, transwell migration assay, flow cytometry, and western blotting were employed to further evaluate RA's protective effects on AILI and explore the mechanisms. The results indicated that RA pre-treatment lowered the serum ALT and AST levels, ameliorated the histological damage to the liver, and reduced ROS generation and the production of IL-1ß and IL-18 in the liver tissues in APAP-treated mice. Moreover, pre-treatment with RA could promote the cell viability and migration ability and inhibit apoptosis in APAP-treated HepG2 cells. Mechanistically, RA could significantly suppress the APAP-induced activation of the NEK7-NLRP3 signaling pathway. Notably, depletion of Nrf2 by short hairpin RNA (shRNA) partly eliminated the protective effects of RA on AILI and the suppression of NEK7-NLRP3 signaling by RA. In summary, these results indicate that RA has a protective role against AILI through Nrf2-mediated inhibition of ROS production and suppression of the NEK7-NLRP3 pathway.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Cinamatos , Depsídeos , Acetaminofen/metabolismo , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cinamatos/metabolismo , Cinamatos/farmacologia , Depsídeos/metabolismo , Depsídeos/farmacologia , Humanos , Fígado , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Quinases Relacionadas a NIMA/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ácido Rosmarínico
2.
Exp Ther Med ; 19(5): 3177-3188, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32266013

RESUMO

The underlying mechanism of the myocardial protective effect of fisetin was studied in a rat ischemia/reperfusion injury model. Sprague-Dawley rats were randomly assigned to seven groups and pretreated with different solutions by gavage administration. A rat model of cardiac ischemia/reperfusion injury was established. Plasma levels of Von Willebrand factor (vWF) were determined by ELISA, flow cytometry was used to determine the level of cardiomyocyte apoptosis and 2,3,5-triphenyltetrazolium staining was used to determine the size of myocardial infarcts. Hematoxylin and eosin-stained sections of myocardial tissues were examined for pathological changes. Expressions of nuclear factor (NF)-κB and matrix metallopeptidase 9 (MMP-9) were measured by immunohistochemistry. Compared with the model group, rats pretreated with fisetin, quercetin and aspirin showed significant prolongation of clotting time, prothrombin time, thrombin time and activated partial thromboplastin time. Fisetin treatment better maintained the integrity of myocardial fibers and nuclear integrity, reduced the percentage of apoptotic myocardial cells, inhibited expression of NF-κB, decreased the loss of MMP-9 and reduced nuclear translocation of NF-kB. Rats pretreated with fisetin also demonstrated a significant decrease in plasma levels of vWF. In addition, the protective effect of fisetin on myocardial cells was found to be dose dependent.

3.
Postgrad Med J ; 95(1121): 162-168, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31109934

RESUMO

Elevated levels of proinflammatory markers are evident in patients with diabetic retinopathy (DR) and are associated with disease progression and prognosis. Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and acts as a local intensifying signal in the pathological processes associated with chronic eye inflammation. The aim of this systematic review and meta-analysis was to investigate the relationship between ICAM-1 level and DR. Online electronic databases were searched to retrieve all relevant articles published before December 2017. The standard mean difference (SMD) and their 95% CI were included and then pooled with a random effects model. Subgroup analysis and metaregression analysis were applied to explore the sources of heterogeneity, and publication bias was calculated to assess the quality of pooled studies. A total of 11 articles, containing 428 patients with DR and 789 healthy controls, were included in this meta-analysis. The results indicated a significant increase in ICAM-1 level in the DR group compared with the control group (SMD: 1.20, 95%CI 0.83 to 1.57, p<0.001). Subgroup analyses and metaregression analysis indicated that publication year, region, study method, diabetes mellitus type, Newcastle-Ottawa Scale and sample size were not the potential sources of heterogeneity. The results of this current meta-analysis indicated that the increased level of ICAM-1 generally exists in the patients with DR and it may associated with the severity of DR. However, large-scale and high-quality studies are required to confirm this finding in the future.


Assuntos
Retinopatia Diabética/sangue , Molécula 1 de Adesão Intercelular/sangue , Biomarcadores/sangue , Progressão da Doença , Humanos , Prognóstico
4.
Curr Eye Res ; 44(5): 564-574, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30644770

RESUMO

BACKGROUND: Interleukin-6 (IL-6) is produced by a variety of cells involved in inflammation and acts as local intensification signals in pathological processes associated with chronic eye inflammation. This meta-analysis was performed to provide a better understanding of the relationship between IL-6 and diabetic retinopathy. METHODS: The study was started with systematic search for literatures by using the PubMed, Web of Science and Embase online databases. The standard mean difference (SMD) and its 95% confidence intervals (CIs) were was included and then pooled with a random effects model. RESULTS: Thirty-one articles, containing1099 DR patients and 1010 controls, were included in this meta-analysis. The level of IL-6 in the DR group was found to be higher than that in the control group (SMD: 2.12, 95% CI: 1.53-2.70, p < 0.00001).Obvious heterogeneity existed between the studies (p < 0.00001, I2 = 96%). So a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the stability of the overall treatment effect was good. Subgroup analysis showed that the levels of IL-6 in case group were observed to be higher than those in the control group; and the IL-6 levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group. (SMD: 0.78, 95% CI: 0.26-1.31, p=  0.003) Conclusion: The results from this current meta-analysis indicated that increased level of IL-6 generally exist in DR patients. And it may associated with the severity of DR. However, large-scale and high-quality studies in future are required to confirm the present findings.


Assuntos
Retinopatia Diabética/metabolismo , Interleucina-6/fisiologia , Humanos
5.
Cancer Manag Res ; 11: 455-465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30655697

RESUMO

OBJECTIVE: NIMA-related kinase 2 (NEK2) has been reported to be overexpressed in various types of cancer and correlated with poor prognosis. The role(s) of NEK2 in cancer, however, is still uncertain. The aim of this study was to evaluate the prognostic value of NEK2 in human tumors. METHODS: A comprehensive literature search was performed for PubMed, Embase, Web of Science, and CNKI databases, and eligible studies were included based on the inclusion and exclusion criteria. A meta-analysis of the included studies was then carried out. RESULTS: Fifteen studies with 3,280 cancer patients were included in the present meta-analysis. All publications were of moderate to high quality, and had no significant heterogeneity (I 2=46%, P=0.03) or publication bias was discovered. The results showed that a high NEK2 level was associated with shorter overall survival (OS) in patients with various types of cancers (pooled HR=1.72, 95% CI 1.49-2.00, P<0.00001). However, the disease-free survival (DFS) had no significant association with NEK2 level (HR=1.13, 95% CI: 0.29-4.38, P=0.85). In the subgroup analyses, high NEK2 level was correlated with an increased risk of poor OS in patients with hepatocellular carcinoma (HR=1.62, 95% CI: 1.25-2.10, P=0.02) and lung cancer (HR=2.18, 95% CI: 1.40-3.38, P=0.0005). However, other factors, including sample size, follow-up period, HR estimation method, and country, also affect the association between NEK2 expression and OS. Analysis of clinicopathological parameters further showed that increased NEK2 level was correlated with younger age, male gender, better tumor differentiation, and lower number of tumor nodules. CONCLUSION: The results of this study indicated that increased expression of NEK2 was associated with unfavorable survival of cancer patients and that NEK2 could be used as a prognostic predictor for cancers.

6.
J Cell Physiol ; 234(2): 1758-1767, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30146678

RESUMO

Atherosclerosis is widely known to be a chronic inflammatory disease. C-reactive protein (CRP), an important inflammatory factor, plays an essential role in the pathogenesis of atherosclerosis. Nicotine, the main addictive component of cigarette, has been shown to induce the production of CRP. The aim of this study was to investigate the effect of rosmarinic acid (RA), a polyphenol with antiinflammatory activity, on nicotine-induced elevation of CRP in vascular smooth muscle cells (VSMCs). We found that pretreatment of VSMCs with RA attenuated nicotine-induced expression of CRP in a time- and dose-dependant manner. In addition, RA also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and reactive oxygen species (ROS) production resulting from nicotine treatment in VSMCs. To confirm these findings in vivo, we constructed a nicotine-induced atherosclerosis rat model. RA did not significantly reduce the serum nicotine level of the rats, whereas it significantly decreased the levels of serum lipids, including concentrations of cholesterol, triglycerides, and low-density lipoprotein cholesterol, and the serum level of CRP. RA also led to diminished nicotine-induced activation of NLRP3 inflammasome and elevation in the CRP level in the aortic tissue of the model rats. The results of this study suggested a protective role of RA in nicotine-induced atherosclerosis by inhibiting the ROS-NLRP3 inflammasome-CRP axial, and RA therefore represented a potential effective therapeutic approach to atherosclerosis, in particular for those who smoke.


Assuntos
Anti-Inflamatórios/farmacologia , Aterosclerose/prevenção & controle , Proteína C-Reativa/metabolismo , Cinamatos/farmacologia , Depsídeos/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamação/prevenção & controle , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Nicotina , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/imunologia , Aterosclerose/metabolismo , Proteína C-Reativa/imunologia , Células Cultivadas , Modelos Animais de Doenças , Inflamassomos/imunologia , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/metabolismo , Lipídeos/sangue , Masculino , Músculo Liso Vascular/imunologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ácido Rosmarínico
7.
Clin Chim Acta ; 485: 210-217, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29959897

RESUMO

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is produced by multinuclear giant cells and acts as local intensification signals in pathological processes associated with chronic eye inflammation. This meta-analysis was performed to provide a better understanding of the relationship between TNF-α and diabetic retinopathy (DR). METHOD: Online electric databases were searched to retrieve all relevant articles published before October 2017. The standard mean difference (SMD) and their 95% confidence intervals (CI) were included and then pooled with a random effects model. RESULTS: A total of 16 articles with 1286 participants were included in this meta-analysis. No difference in the level of TNF-α was found between DR patients and healthy controls (SMD = 0.39, 95% CI = -0.09 to 0.68, P = 0.01). Subgroup analysis showed that with respect to the level of TNF-α, the association was significant for studies conducted in Europe (SMD: 0.57, 95% CI: 0.11-1.02, P = 0.01), patients with type 1 DM (SMD: 1.06, 95% CI: 0.09-2.04, P = 0.03), studies based on serum samples (SMD: 0.57, 95% CI: 0.12-1.02, P = 0.01) and studies with a sample size >50 (SMD: 0.39, 95% CI: 0.03-0.75, P = 0.04). CONCLUSION: The results this meta-analysis indicated that the level of TNF-α in DR patients was significantly different from that in the healthy controls, so TNF-α represents a candidate biomarker for DR.


Assuntos
Retinopatia Diabética/sangue , Fator de Necrose Tumoral alfa/sangue , Biomarcadores/sangue , Humanos
8.
Int J Exp Pathol ; 97(2): 187-93, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27256579

RESUMO

The main vitamin K-deficient model, minidose warfarin, is different from the pathological mechanism of vitamin K deficiency, which is a shortage of vitamin K. The objective of this study was to establish a new method of vitamin K-deficient model combining a vitamin K-deficient diet with the intragastrical administration of gentamicin in rats. The clotting was assayed by an automated coagulation analyser. The plasma PIVKA-II was assayed by ELISA. The vitamin K status was detected by an HPLC-fluorescence system. In the diet- and gentamicin-induced vitamin K-deficient 14-day group, the rats had undetected vitamin K1 and vitamin K2 in the liver and a prolonged APTT. In the 21-day group, there was also a prolonged PT and a decrease of the FIX activities. In the 28-day group, the undetected vitamin K1 and vitamin K2, the prolonged PT and APTT, and the decrease of the FII, FVII, FIX, and FX activities prompted the suggestion that there were serious deficiencies of vitamin K and vitamin K-dependent coagulation in rats. It is suggested that the diet- and gentamicin-induced vitamin K-deficient 14-day or 21-day model can be used for studies related to the status of vitamin K. The vitamin K-deficient 28-day model can be applied to research involving both the status of vitamin K and of vitamin K-dependent coagulation. In conclusion, the combination of a vitamin K-deficient diet with the administration of gentamicin results in a useful model of vitamin K-deficieny.


Assuntos
Modelos Animais de Doenças , Deficiência de Vitamina K/etiologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Fatores de Coagulação Sanguínea/metabolismo , Testes de Coagulação Sanguínea/métodos , Dieta/efeitos adversos , Feminino , Gentamicinas , Fígado/metabolismo , Masculino , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos Sprague-Dawley , Vitamina K 1/metabolismo , Vitamina K 1/farmacologia , Vitamina K 2/metabolismo , Deficiência de Vitamina K/metabolismo
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(4): 427-33, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27241156

RESUMO

OBJECTIVE: To evaluate the anesthesia effect of etomidate and propofol on painless abortion surgery. 
 METHODS: After screening the Cochrane Library, Pubmed, China National Knowledge Infrastructure (CNKI), WANFANG, VIP database, the literatures regarding the anesthesia effect of etomidate and propofol on painless abortion surgery were collected from 1995 to 2014. The randomized controlled trials (RCTs) were selected, the quality evaluation was performed and the data was analyzed by using RevMan5.3 software.
 RESULTS: A total of 1 130 patients were included in 9 RCTs. The results of Meta analysis were as follows: the anesthesia induction time in the etomidate group was less than that in propofol group (MD=-0.14, 95% CI -0.24 to -0.04, P=0.004); there were more adverse reactions, such as myoclonus, nausea and vomiting, in the etomidate group compared with the propofol group (P<0.001); the incidence of pain in the etomidate group was less than that in the propofol group (P<0.001); there was no significant difference in the incidence of respiratory depression between the 2 groups (P>0.05); the surgery time, analgesia and duration from withdrawal to the wake-up was not significantly different between the 2 groups (P>0.05). 
 CONCLUSION: Etomidate had a shorter anesthesia induction time than propofol in the painless abortion surgery. The incidence of reverse reactions such as myoclonus, nausea and vomiting, was more common in application of etomidate, whereas the incidence of injection pain was more common in the use of propofol group. There was no significant difference in respiratory depression between the 2 drugs. The comprehensive efficacy of propofol is better than etomidate.


Assuntos
Aborto Induzido , Anestesia , Etomidato/uso terapêutico , Propofol/uso terapêutico , Anestésicos Intravenosos , China , Feminino , Humanos , Dor/prevenção & controle , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Chemotherapy ; 61(6): 323-30, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27144279

RESUMO

BACKGROUND: Tigecycline is an antibiotic agent with a broad spectrum, which has an antibacterial effect against many multidrug-resistant organisms. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is disputed. MATERIALS AND METHODS: In this report, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of tigecycline for the treatment of HAP. The primary outcome was the rate of clinical cure, and the secondary outcomes were mortality and adverse events (AEs). RESULTS: Four trials involving 1,234 patients were included. The standard-dose tigecycline and comparator groups did not differ significantly in their rates of clinical cure. However, high-dose tigecycline was more effective than standard-dose tigecycline or the comparators for the treatment of HAP. There was no significant difference in mortality between the standard-dose or high-dose regimen and the comparators. Although the safety profile of standard-dose tigecycline was similar to the comparators, the high-dose regimen exhibited more AEs compared with the other groups. CONCLUSION: High-dose tigecycline is efficient for the treatment of HAP but is associated with more AEs.


Assuntos
Antibacterianos/uso terapêutico , Minociclina/análogos & derivados , Pneumonia/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Bases de Dados Factuais , Feminino , Meia-Vida , Hospitais , Humanos , Masculino , Minociclina/efeitos adversos , Minociclina/farmacocinética , Minociclina/uso terapêutico , Razão de Chances , Pneumonia/mortalidade , Pneumonia/patologia , Tigeciclina
11.
Pharmazie ; 71(9): 491-498, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29441843

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of inhaled antibiotics for the treatment of non-cystic fibrosis bronchiectasis (NCFB). METHODS: Pubmed, Cochrane library, Embase, Elsevier, OVID, Springerlink, Web of knowledge and NEJM were searched for randomized controlled trials (RCTs) on inhaled antibiotics in treatment of NCFB from inception until April 2015. Meta-analysis was conducted to assess the efficacy and safety of inhaled antibiotics in the treatment of NCFB. RESULTS: Twelve RCTs involving 1154 participants were included. They showed that inhaled antibiotics were more effective in reduction of sputum bacterial density, eradication of P. aeruginosa, prolonged time to exacerbation and reduction of new pathogens emergence with no significant difference in adverse events compared with control groups. However, we did not find significant benefits of inhaled antibiotics in reducing the risk of acute exacerbation, improving health-related quality of life and reduction of P. aeruginosa resistance. Moreover, inhaled antibiotics exerted a statistically significant reduction in FEV1%. CONCLUSIONS: Inhaled antibiotics may be an alternative pathway to inhibit airway inflammation with no more adverse events in patients with NCFB.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bronquiectasia/tratamento farmacológico , Administração por Inalação , Fibrose Cística , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Hepat Mon ; 15(7): e29052, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26300933

RESUMO

CONTEXT: To systematically evaluate the effects of hepatoprotective agents, when delivered either alone or in combination with other antiviral or non-antiviral drugs in patients with hepatitis B and hepatic fibrosis. OBJECTIVES: The current randomized controlled clinical trials aimed to evaluate the efficacy of combinations of antiviral and non-antiviral hepatoprotective agents on indexes of liver function and liver fibrosis in patients with hepatitis B. DATA SOURCES: Published literatures in Chinese and English on hepatoprotective treatment strategies for chronic hepatitis B and liver fibrosis were searched in three databases and randomized controlled clinical trials were selected. STUDY SELECTION: Data were extracted according to a variety of inclusion and exclusion criteria. Meta-analysis was employed to analyze the data. RESULTS: A total of 22 randomized controlled trials encompassing 1,714 cases were considered in the meta-analysis. The obtained results indicated that the combination of antiviral drug and hepatoprotective agent was better than antiviral drug alone to improve liver function. Similarly, regarding liver fibrosis, using two different hepatoprotective agents was better than using one agent. The normalization rates of Aminotransferase (ALT) and total Bilirubin (TBil) were improved 25.7% by two hepatoprotective agents compared to the single agent. Acetylcysteine was superior to ursodeoxycholic acid or silibinin to reduce ALT. Ursodeoxycholic acid was superior to acetylcysteine or silibinin to reduce TBIL. CONCLUSIONS: Hepatoprotective agents combined with antiviral drugs can significantly improve liver function and liver fibrosis parameters in patients with hepatitis B.

13.
J Thromb Thrombolysis ; 33(1): 74-81, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22016106

RESUMO

Our previous study has shown that P1 polypeptide-loaded microbubbles (clot-targeted microbubbles, TMB) are effective for thrombolysis and recanalization in a 0.5 h cerebral thrombosis rabbit model when combined with low-frequency ultrasound (LFUS, 0.8 MHz). However, the thrombolytic effects of TMB combined with LFUS are still unclear in a 6 h cerebral thrombosis rabbit model, which closely resembles human embolic stroke. Aiming to extend the 3 h therapeutic window limitation of thrombolytic drugs, a 6 h cerebral thrombosis model of common carotid artery (CCA) occlusion was induced in rabbits, and thrombolysis using TMB by intra-arterial (IA) and intravenous (IV) application combined with LFUS was then compared to untargeted microbubbles (UTMB) and recombinant tissue plasminogen activator (rt-PA). The patency score and thrombolysis in brain ischemia (TIBI) in IA TMB combined with LFUS (IA TMB/LFUS) were significantly higher compared to the IA normal saline control with LFUS (IA SC/LFUS) (both P < 0.05) and IA UTMB plus LFUS (IA UTMB/LFUS) (both P < 0.05), respectively. The recanalization rate in the IA TMB/LFUS group (66.67%) was significantly higher compared to the IA SC/LFUS group (12.50%, P < 0.05). The patency score, TIBI and recanalization rate of IA TMB/LFUS were higher than in the IV TMB/LFUS group, but there was no significant difference between the two groups, which was similar to the infarction ratio. TMB/LFUS is an effective and safe therapy for thrombolysis in a 6 h cerebral thrombosis rabbit model, and the IA TMB/LFUS group was slightly better than the IV TMB/LFUS group.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Fibrinolíticos/administração & dosagem , Trombose Intracraniana/terapia , Microbolhas/uso terapêutico , Terapia Trombolítica/métodos , Terapia por Ultrassom/métodos , Animais , Terapia Combinada , Feminino , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/patologia , Masculino , Coelhos , Distribuição Aleatória , Ultrassonografia
14.
J Pharm Pharmacol ; 63(11): 1454-61, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21988426

RESUMO

OBJECTIVES: Hexapeptide is a novel synthetic oligopeptide with a structure similar to that of eptifibatide. This study was designed to investigate the anticoagulant, anti-aggregation, disaggregation and anti-thrombogenesis effects of hexapeptide. METHODS: The effects of antiplatelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin, and the effect of disaggregation of platelet aggregation induced by ADP were determined. The anticoagulation indexes were determined by different kits. KEY FINDINGS: Hexapeptide 1 × 10(-5) -1 × 10(-4) m could significantly prolong rabbit blood clotting time, thrombin time, prothrombin time and activated partial thromboplastin enzyme time, and reduce the length, wet weight, dry weight and the index of thrombus in a concentration-dependent manner. Hexapeptide 1 × 10(-4) m decreased platelet adhesion rate by 40.2%. The platelet aggregation inhibition of hexapeptide in dogs and humans was more obvious than in rabbits and rats. The aggregation inhibition rate of 1 × 10(-5) m hexapeptide in dogs, rabbits, rats and humans induced by ADP was 93.9 ± 1.3%, 66.2 ± 1.4%, 76.1 ± 3.2% and 99.8 ± 0.2%, respectively; the 50% inhibitory concentration (IC50) of hexapeptide was 7.24 × 10(-8), 3.24 × 10(-6), 6.61 × 10(-6) and 8.91 × 10(-8) m, respectively. For the aggregation inhibition rate of hexapeptide in dogs, rabbits and humans induced by AA, the IC50 was 1.29 × 10(-9), 1.32 × 10(-6) and 9.33 × 10(-8) m, respectively; the IC50 of aggregation inhibition rates induced by thrombin was 2.88 × 10(-6), >1 × 10(-5) and 4.17 × 10(-6) m, respectively. The disaggregation rate of 1 × 10(-4) m hexapeptide in dog induced by ADP was 68.8 ± 7.4%. CONCLUSIONS: Hexapeptide has anticoagulant, antiplatelet aggregation, disaggregation and antithrombotic effects in vitro.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Oligopeptídeos/farmacologia , Peptídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Animais , Cães , Eptifibatida , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Coelhos , Ratos , Ratos Sprague-Dawley , Tempo de Trombina
15.
J Pharm Pharmacol ; 61(11): 1499-504, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19903375

RESUMO

OBJECTIVES: The aim was to evaluate the adsorbing effect of montmorillonite on uric acid, promoting diffusion of uric acid from blood to intestine, preventing absorption of uric acid in intestine and reducing uric acid level in serum. METHODS: The adsorbing effect of montmorillonite on uric acid was observed in vitro. The intestine and blood vessel of rats were circularly perfused with intestinal perfusate and vascular perfusate, respectively. A model of hyperuricaemia in mice was prepared by intraperitoneal injection of hypoxanthine and potassium oteracil. The concentration of uric acid was determined by the method of urate oxidase and peroxide enzyme. KEY FINDINGS: The results showed that different concentrations of montmorillonite could adsorb uric acid in a concentration-dependent manner. The adsorbing effect was fast. The adsorptive rate was high in acid solution and was low in alkaline solution. When blood vessels were circularly perfused by vascular perfusate containing uric acid, the concentration of uric acid in vascular perfusate was decreased and the concentration of uric acid in intestinal perfusate was increased, suggesting that uric acid in blood vessels diffused into the intestine. When the intestine was perfused with intestinal perfusate containing uric acid, the uric acid concentration in vascular perfusate was increased, but the uric acid concentration of intestinal perfusate was decreased, suggesting that uric acid was absorbed in the intestine. The uric acid concentrations of intestinal perfusate and vascular perfusate in montmorillonite 0.5 and 1.0 g/kg groups were lower than the control group. Concentrations of uric acid in serum and urine in the montmorillonite 1 and 2 g/kg groups were lower compared with mice in the hyperuricaemic group. CONCLUSIONS: The results suggested that montmorillonite adsorbed uric acid and promoted diffusion of uric acid from blood vessels to intestine, prevented absorption of uric acid in intestine and decreased uric acid level in serum.


Assuntos
Bentonita/farmacologia , Hiperuricemia/prevenção & controle , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Ácido Úrico/metabolismo , Animais , Bentonita/química , Bentonita/uso terapêutico , Difusão/efeitos dos fármacos , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Hiperuricemia/metabolismo , Intestinos/irrigação sanguínea , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-Dawley , Ácido Úrico/química
16.
Zhong Yao Cai ; 32(2): 249-53, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19504973

RESUMO

OBJECTIVE: To study the effect of montmorillonite on promoting diffussion of urea from blood vessel to intestine and preventing absorption of urea in intestine. METHODS: Rat intestine tract and blood vessel were perfusated circularly with intestinal tract perfusate and blood vessel perfusate with or without urea 1 g/L, respectively. The concentration of urea in perfusates was measured by urease and glutamic dehydrogenase coupling method. RESULTS: The blood vessel was circularly perfusated with vascular perfusate containing urea and intestinal tract was circularly perfusated with intestinal perfusate without urea. The concentration of urea in vascular perfusate decreased gradually, and the concentration of urea in intestine perfusate increased slowly. When montmorillonite was added into the intestinal tract, the urea concentration in both intestinal tract perfusate and the vascular perfusate in montmorillonite 0.5 g/kg and 1.0 g/kg groups were significantly lower than that of control group (P < 0.05). The blood vessel was circularly perfusated with vascular perfusate without urea and intestinal tract was circularly perfusated with perfusate containing urea, the concentration of urea in intestine perfusate decreased little by little, and the concentration of urea in vascular perfusate increased slowly. After montmorillonite was administrated into the intestinal tract, the urea concentrations in both the vascular perfusate and intestinal tract perfusate in montmorillonite 0.5 g/kg and 1.0 g/kg were obviously lower than that of control group (P < 0.05). CONCLUSION: Montmorillonite promotes the diffusion of urea from blood vessel to intestine, and inhibits the absorption of urea in intestine.


Assuntos
Bentonita/farmacologia , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Ureia/farmacocinética , Adsorção , Animais , Difusão , Relação Dose-Resposta a Droga , Feminino , Perfusão , Ratos , Ratos Sprague-Dawley , Ureia/sangue
17.
J Pharm Pharmacol ; 61(4): 459-64, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19298692

RESUMO

OBJECTIVES: This study aims to evaluate the sorption by montmorillonite of creatinine and the accelerating effect of montmorillonite on creatinine excretion from the intestine. METHODS: The sorption of montmorillonite was observed in vitro. Also, rat intestinal tract and blood vessels were perfused circularly with perfusate with or without creatinine, respectively, to study the promotion of creatinine diffusion from the blood vessel to the intestine and the inhibition of creatinine absorption in the intestinal tract. The effect of decreasing the serum concentration of creatinine was studied in an acute hypercreatininaemia mouse model. The concentration of creatinine was determined by the basic picric acid method. KEY FINDINGS: Montmorillonite adsorbed creatinine markedly in the simulated intestinal solution in a concentration-dependent manner. The sorption-time curve of montmorillonite with creatinine showed that the sorption was fast. The adsorption rate reached a maximum in 10 min. The pH of the solution influenced the sorption, the rate of which was higher at a low pH than at a high pH. Creatinine could diffuse from the blood vessel to the intestine and was reabsorbed in the intestine. Montmorillonite promoted the diffusion and inhibited the absorption. Montmorillonite decreased the serum creatinine level of hypercreatininaemia mice prepared by injecting creatinine intraperitoneally. CONCLUSIONS: Montmorillonite adsorbs creatinine and accelerates its excretion from the intestine.


Assuntos
Bentonita/farmacologia , Creatinina/farmacocinética , Adsorção , Animais , Bentonita/administração & dosagem , Creatinina/administração & dosagem , Creatinina/sangue , Concentração de Íons de Hidrogênio , Absorção Intestinal/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
18.
Zhong Yao Cai ; 30(11): 1398-401, 2007 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-18323208

RESUMO

OBJECTIVE: To determine total tannins and gallic acid of the root of Euphorbia hyloomla. METHODS: With the gallic acid as reference, tannins and gallic acid of the root of Euphorbia hylonoma were determined by ultraviolet spectrophtometer and high performance liquid chromatography, respectively. RESULTS: The content of tannins of the root of Euphorbia hylonoma were determined by different extract methods, including extracted by water, 70% alcohol, acetone on supersound, the determination data were 4.375%, 7.240%, 3.958%, respectively. When used recirculation method by water, 70% alcohol, acetone, the determination data were the determination data are 3.773%, 2.503%, 1.59%, respectively. The content of gallic acid of the root was 0.047%. CONCLUSION: Content of total tannins by alcohol super sound is the highest comparing with other extract methods, this method can used in extract of total Tannins of the root of Euphorbia hylonoma.


Assuntos
Euphorbia/química , Ácido Gálico/análise , Plantas Medicinais/química , Taninos/análise , Acetona , Cromatografia Líquida de Alta Pressão , Etanol , Ácido Gálico/isolamento & purificação , Raízes de Plantas/química , Taninos/isolamento & purificação
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