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1.
BMC Infect Dis ; 19(1): 925, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666015

RESUMO

BACKGROUND: Ruili is a border city in southwest China along the heroin trafficking route. In recent decades, the city has witnessed increased in HIV transmission. The current study aims to explore the spatiotemporal trends in HIV prevalence identify and map the spatial variation and clustering of factors associated with HIV transmission through drug use and heterosexual contact transmissions at the village level from 1989 through 2016. METHODS: Geographic information system-based spatiotemporal analyses, including global and local spatial autocorrelation analyses and space-time scanning statistics, were applied to detect the location and extent of HIV/AIDS high-risk areas. RESULTS: Drug use and heterosexual contact were identified as the major transmission routes causing infection in Ruili. Results of global spatial analysis showed significant clustering throughout the city caused by transmission via drug use in the early phase of the epidemic and transmission via heterosexual contact in the late phase of the epidemic during the study period. Hotspots of transmission from drug use were randomly distributed throughout the city. However, the hotspots of transmission by heterosexual contact were located in the central area only around the Jiegao China-Myanmar land port. Space-time scanning showed that transmission from drug use clustered in the southwest area between 1989 and 1990, while transmission by heterosexual contact clustered in the central area between 2004 and 2014. CONCLUSIONS: Heterosexual contact has become the dominant mode of transmission. Interventions should focus on highly clustered area where is around the Jiegao land port.

2.
J Sep Sci ; 42(9): 1740-1749, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30805999

RESUMO

Notoginsenoside Fc, which is a protopanaxdiol-type saponin isolated from the leaves of Panax notoginseng, exhibits an exceptional antiplatelet aggregatory effect. To study the modulating effect of gastrointestinal contents on the metabolic profile and pharmacokinetics, pseudo germ-free rats were used to study the influence of the bacterial community structure on the metabolic profile. Glycosidase activities were measured using the spectrophotometric method. Biotransformations of notoginsenoside Fc in normal and pseudo germ-free rat intestinal microflora were systematically investigated using ultra high performance liquid chromatography with tandem quadrupole/time-of-flight mass spectrometry. Moreover, a liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of the notoginsenoside Fc prototype and its degradation products. Through an in vivo pharmacokinetic study, the pharmacokinetic characteristics were compared between normal rats and pseudo germ-free rats. During the in vitro biotransformation, seven deglycosylated products were detected and identified after incubation in the intestinal bacteria of normal rats. In pseudo germ-free rats, glycosidase activities were significantly decreased, and no obvious degradation occurred. In an in vivo study, the systemic exposure was significantly increased 40%, as evidenced by the area under the blood concentration-time curve from time zero to infinity value and half-life value, which were prolonged more in the pseudo germ-free group than in normal rats. The results demonstrate that patients who use intestinal bacteria-metabolized herbs, such as panax notoginseng, should understand the profile of intestinal bacteria to ensure therapeutic efficacy.


Assuntos
Bactérias/metabolismo , Medicamentos de Ervas Chinesas/química , Microbioma Gastrointestinal , Ginsenosídeos/química , Panax notoginseng/química , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Feminino , Ginsenosídeos/metabolismo , Ginsenosídeos/farmacocinética , Intestinos/microbiologia , Masculino , Metaboloma , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
3.
J Ginseng Res ; 42(3): 270-276, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29983608

RESUMO

Background: Notoginsenoside Ft1 is a promising potential candidate for cardiovascular and cancer disease therapy owing to its positive pharmacological activities. However, the yield of Ft1 is ultralow utilizing reported methods. Herein, an acid hydrolyzing strategy was implemented in the acquirement of rare notoginsenoside Ft1. Methods: Chemical profiles were identified by ultraperformance liquid chromatography coupled with quadruple-time-of-flight and electrospray ionization mass spectrometry (UPLC-Q/TOF-ESI-MS). The acid hydrolyzing dynamic changes of chemical compositions and the possible transformation pathways of saponins were monitored by ultrahigh-performance LC coupled with tandem MS (UHPLC-MS/MS). Results and conclusion: Notoginsenoside Ft1 was epimerized from notoginsenoside ST4, which was generated through cleaving the carbohydrate side chains at C-20 of notoginsenosides Fa and Fc, and vina-ginsenoside R7, and further converted to other compounds via hydroxylation at C-25 or hydrolysis of the carbohydrate side chains at C-3 under the acid conditions. High temperature contributed to the hydroxylation reaction at C-25 and 25% acetic acid concentration was conducive to the preparation of notoginsenoside Ft1. C-20 epimers of notoginsenoside Ft1 and ST4 were successfully separated utilizing solvent method of acetic acid solution. The theoretical preparation yield rate of notoginsenoside Ft1 was about 1.8%, which would be beneficial to further study on its bioactivities and clinical application.

5.
Circ Arrhythm Electrophysiol ; 11(6): e005739, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29884619

RESUMO

BACKGROUND: Ablation for atrial fibrillation (AF) is superior to medical therapy for rhythm control. We compared stroke and mortality among patients undergoing ablation for AF to matched controls in a large multiethnic population. METHODS: Using discharge and surgical records from California nonfederal hospitals, we identified patients who had ablation and principal diagnosis of AF with at least 1 prior hospitalization for AF. We excluded cases with valve disease, open maze, other arrhythmias, or implantable devices. Matched controls were selected based on years of AF diagnosis, age, sex, and being alive the same number of days from the initial AF encounter to the ablation date. Clinical outcomes, including mortality, ischemic stroke, or hemorrhagic stroke, were assessed using a weighted proportional hazard model, adjusting for demographics, prior admissions with AF before the ablation, calendar year, and presence of chronic comorbidities. RESULTS: There were 4169 ablation cases and 4169 weighted-matched controls; 39% percent of the ablation group was >65 years, 72% men, 84% white; mean follow-up was up to 3.6±0.9 years. In adjusted models, ablation was associated with significantly lower mortality (per patient-years) 0.9% versus 1.9%, hazard ratio=0.59 (P<0.0001; confidence interval: 0.45-0.77); ischemic stroke (>30 days post-ablation ≤5 years), 0.37% versus 0.59%, hazard ratio=0.68 (P=0.04; confidence interval: 0.47-0.97); hemorrhagic stroke 0.11% versus 0.35%, hazard ratio=0.36 (P=0.001; confidence interval: 0.20-0.64) compared with controls. CONCLUSIONS: In this large population-based study of hospitalized patients with nonvalvular AF, ablation was associated with lower mortality, ischemic stroke, and hemorrhagic stroke compared with controls.

6.
J Asian Nat Prod Res ; : 1-7, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29717884

RESUMO

Nigakialcohol A (1), as unusual cyclization ionone derivative, together with eight known ones (2-9), were isolated from the leaves of Picrasma quassioides (D. Don) Benn (Simaroubaceae). Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. Compound 2 showed a weak inhibitory effect on NO production at non-cytotoxic concentration (100 µM) with inhibitory rate of 59%, and thus it should be regarded as potential anti-inflammatory agents.

7.
Sci Rep ; 8(1): 3136, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29453340

RESUMO

Elevated nitrogen associated with global change is believed to promote the invasion of many vigorous exotic plants. However, it is unclear how a weak exotic plant will respond to elevated nitrogen in the future. In this study, the competitive outcome of a weak invasive plant (Galinsoga quadriradiata) and two non-invasive plants was detected. The plants were subjected to 3 types of culture (mixed, monoculture or one-plant), 2 levels of nitrogen (ambient or elevated at a rate of 2 g m-2 yr-1) and 2 levels of light (65% shade or full sunlight). The results showed that elevated nitrogen significantly promoted the growth of both the weak invader and the non-invasive plants in one-plant pots; however, growth promotion was not observed for the non-invasive species in the mixed culture pots. The presence of G. quadriradiata significantly inhibited the growth of the non-invasive plants, and a decreased negative species interaction was detected as a result of elevated nitrogen. Our results suggest that competitive interactions between G. quadriradiata and the non-invasive plants were altered by elevated nitrogen. It provides exceptional evidence that an initially weak invasive plant can become an aggressive invader through elevated nitrogen deposition.

8.
Am J Med ; 131(2): 141-143, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29079399
9.
J Atr Fibrillation ; 10(1): 1599, 2017 Jun-Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29250223

RESUMO

Background: Catheter ablation (ABL) for non-valvular AF (NVAF) is recommended for symptomatic patients refractory to medical therapy and its success is related to the duration of the arrhythmia prior to intervention.Our aim was to assess the early utilization and the factors that prompted ABL in patients hospitalized for new onset NVAF. Methods: Using de-identified administrative discharge records for hospitalizations and emergency department (ED) visits, we determined the patients who had a first-time (since 1991) health record diagnosis of AF between2005 - 2011. We linked ambulatory surgery encounters for ABL based on ICD 9 code occurring within two years of initial hospitalization. After excluding other cardiac arrhythmias, atrio-ventricular nodal ablation or pacemaker/defibrillator placement and cardiac valve disease, bivariate comparisons were made with those who did not undergo ABL. Results: During the study period,3,440 of 424,592 patients (0.81%) hospitalized for new onset NVAF underwent ABL. Parameters significantly (p<0.001) associated with ABL compared tonon-ABL patientsincluded: principal diagnosis of AF (55% vs 25%), age 35-64 yrs (46.1% vs. 22.4%), male (58.9% vs. 48.2%), private insurance (46.6% vs. 21.1%), Caucasian (81.0% vs.71.6%), lower frequency of ED visit < 6 months before index AF hospitalization (10.7% vs. 15.9%), lower severityofillness at time of AF diagnosis (16.5% vs. 35.6%) anda lower prevalence ofmajor comorbidities (p< 0.001). Conclusions: Ablation has low utilization for treatment of new onset NVAF within two years of diagnosis. Earlier utilization of ABL may reduce health care burden related to NVAF and requires further evaluation.

10.
J Atr Fibrillation ; 10(2): 1658, 2017 Aug-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29250237

RESUMO

We report a case with complete atrioventricular block (AVB) present both during sinus rhythm and with atrial fibrillation (AF). He had declined pacemaker placement and opted for ablation for the symptomatic AF. He underwent staged hybrid approach with video-assisted thoracoscopic surgical maze (VATS) followed by endocardial ablation. VATS included ganglionic plexi cauterization. One month after the endocardial procedure, he had complete resolution of AF and AVB and remains so at 18 months follow up. We discuss possible abolition of vagal input for this improvement in AV conduction.

11.
J Exp Bot ; 66(20): 6259-71, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26163698

RESUMO

A lignan, lariciresinol, is an important efficacious compound for the antiviral effect of Isatis indigotica, a widely used herb for the treatment of colds, fever, and influenza. Although some rate-limiting steps of the lariciresinol biosynthetic pathway are well known, the specific roles of gene family members in I. indigotica in regulating lariciresinol production are poorly understood. In the present study, a correlation analysis between the RNA sequencing (RNA-Seq) expression profile and lignan content by using I. indigotica hairy roots treated with methyl jamonate (0.5 µM) at different time points as a source implicated that I. indigotica pinoresinol/lariciresinol reductase 1 (IiPLR1), but not IiPLR2 or IiPLR3, contributed greatly to lariciresinol accumulation. Gene silencing by RNA interference (RNAi) demonstrated that IiPLR1 indeed influenced lariciresinol biosynthesis, whereas suppression of IiPLR2 or IiPLR3 did not change lariciresinol abundance significantly. IiPLR1 was thus further characterized; IiPLR1 was constitutively expressed in roots, stems, leaves, and flowers of I. indigotica, with the highest expression in roots, and it responds to different stress treatments to various degrees. Recombinant IiPLR1 reduces both (±)-pinoresinol and (±)-lariciresinol efficiently, with comparative K cat/K m values. Furthermore, overexpression of IiPLR1 significantly enhanced lariciresinol accumulation in I. indigotica hairy roots, and the best line (ovx-2) produced 353.9 µg g(-1) lariciresinol, which was ~6.3-fold more than the wild type. This study sheds light on how to increase desired metabolites effectively by more accurate or appropriate genetic engineering strategies, and also provides an effective approach for the large-scale commercial production of pharmaceutically valuable lariciresinol by using hairy root culture systems as bioreactors.


Assuntos
Furanos/metabolismo , Isatis/genética , Lignanas/metabolismo , Proteínas de Plantas/genética , Transcriptoma , Isatis/metabolismo , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/metabolismo , Análise de Sequência de DNA
12.
PLoS One ; 10(2): e0116922, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25658100

RESUMO

Alpha-glucosidase inhibitors currently form an important basis for developing novel drugs for diabetes treatment. In our preliminary tests, the ethyl acetate fraction of Phlomis tuberosa extracts showed significant α-glucosidase inhibitory activity (IC50 = 100 µg/mL). In the present study, a combined method using Sepbox chromatography and thin-layer chromatography (TLC) bioautography was developed to probe α-glucosidase inhibitors further. The ethyl acetate fraction of P. tuberosa extracts was separated into 150 individual subfractions within 20 h using Sepbox chromatography. Then, under the guidance of TLC bioautography, 20 compounds were successfully isolated from these fractions, including four new diterpenoids [14-hydroxyabieta-8,11,13-triene-11-carbaldehyde-18-oic-12-carboxy-13-(1-hydroxy-1-methylethyl)-lactone (1), 14-hydroxyabieta-8,11,13-triene-17-oic-12-carboxy-13-(1-hydroxy-1-methylethyl)-lactone (2), 14,16-dihydroxyabieta-8,11,13-triene-15,17-dioic acid (3), and phlomisol (15,16-eposy-8,13(16),14-labdatrien-19-ol) (4)], and 16 known compounds. Activity estimation indicated that 15 compounds showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 0.067-1.203 mM) than the positive control, acarbose (IC50 = 3.72 ± 0.113 mM). This is the first report of separation of α-glucosidase inhibitors from P. tuberosa.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Phlomis/química , alfa-Glucosidases/química , Cromatografia em Camada Delgada
13.
Pharm Res ; 32(3): 1128-40, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25319098

RESUMO

PURPOSE: Since the vitamin D receptor (VDR) was found to up-regulate cerebral P-glycoprotein expression in vitro and in mice, we extend our findings to rats by assessing the effect of rat Vdr activation on brain efflux of quinidine, a P-gp substrate that is eliminated primarily by cytochrome P450 3a. METHODS: We treated rats with vehicle or the active VDR ligand, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] (4.8 or 6.4 nmol/kg i.p. every 2nd day × 4) and examined P-gp expression and cerebral quinidine disposition via microdialysis in control and treatment studies conducted longitudinally in the same rat. RESULTS: The 6.4 nmol/kg 1,25(OH)2D3 dose increased cerebral P-gp expression 1.75-fold whereas hepatic Cyp3a remained unchanged. Although there was no change in systemic clearance elicited by 1,25(OH)2D3, brain extracellular fluid quinidine concentrations were lower in treated rats. We noted that insertion of indwelling catheters increased plasma protein binding of quinidine and serial sampling decreased the blood:plasma concentration ratio, factors that alter distribution ratios in microdialysis studies. After appropriate correction, KECF/P,uu and KECF/B,uu, or ratios of quinidine unbound concentrations in brain extracellular fluid to plasma or blood at steady-state, were more than halved. CONCLUSION: We demonstrate that VDR activation increases cerebral P-gp expression and delimits brain penetration of P-gp substrates.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Calcitriol/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Microdiálise , Quinidina/metabolismo , Receptores de Calcitriol/agonistas , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Estado de Consciência , Citocromo P-450 CYP3A/metabolismo , Relação Dose-Resposta a Droga , Masculino , Microssomos Hepáticos/enzimologia , Ligação Proteica , Quinidina/sangue , Ratos Sprague-Dawley , Receptores de Calcitriol/metabolismo , Regulação para Cima
14.
Heart Rhythm ; 11(11): 1898-903, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25048442

RESUMO

BACKGROUND: Ablation (ABL) is a second-line therapy for the management of atrial fibrillation (AF). Single-center studies have demonstrated the safety and efficacy of ABL; however, the low event rates render it difficult to assess predictors of major adverse events. OBJECTIVE: The purpose of this study was to determine the population-based incidence of data and risk factors for both stroke <30 days and death after AF ABL. METHODS: Patients (n = 6207) identified as having undergone AF ABL between 2005 and 2009 by the California Ambulatory Surgery Database in 97 nonfederal hospitals in California were linked to the California Patient Discharge Database and to a master death registry. Data from these patients were analyzed for primary outcomes of 30-day death and ischemic stroke. Independent risk factors for these end-points were determined. RESULTS: Mean patient age was 61.9 years, and the majority of the patients were men. Thirty-day mortality and stroke after ABL were 0.39% and 0.61%, respectively. Independent predictors of death were age ≥80 years (odds ratio [OR] 8.2, 95% confidence interval [CI] 1.5-43) and heart failure (OR 9.2, 95% CI 3.0-28). Prior stroke/transient ischemic attack/stroke was the only independent predictor for stroke (OR 6.3, 95% CI 3-13). CONCLUSION: In our large population-based study, we found higher procedure-related mortality but comparable stroke rate after AF ABL than previously reported. Age ≥80 years and heart failure was each independently associated with >8-fold increase in odds of death. The only significant predictor of stroke was prior stroke/transient ischemic attack. These findings may aid in patient selection for AF ABL.


Assuntos
Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Fibrilação Atrial/cirurgia , Ablação por Cateter , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Comorbidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
15.
J Nat Prod ; 77(7): 1594-600, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24955889

RESUMO

Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17ß-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-ß-D-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 µM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 µM.


Assuntos
Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Acarbose/farmacologia , Apigenina/química , Apigenina/farmacologia , Diterpenos/química , Diterpenos de Abietano/química , Diterpenos de Abietano/farmacologia , Flavonoides/química , Glucosídeos/química , Inibidores de Glicosídeo Hidrolases , Luteolina/química , Luteolina/farmacologia , Estrutura Molecular , PPAR gama/agonistas , Componentes Aéreos da Planta/química , Scoparia
16.
Phytochemistry ; 103: 196-202, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24726372

RESUMO

Abietane derivatives, bungnates A, B, 15-dehydrocyrtophyllone A and 15-dehydro-17-hydroxycyrtophyllone A, and two phenylethanoid glycosides, bunginoside A and 3″,4″-di-O-acetylmartynoside, together with nine known abietane derivatives and fourteen known phenylethanoid glycosides, were isolated from dried roots of Clerodendrum bungei. Their structures were determined on the basis of detailed spectroscopic analyses and acidic hydrolysis. The absolute configuration of bunginoside A was established from analysis of CD data. Selected compounds were evaluated for inhibitory effects against angiotensin converting enzyme (ACE) and α-glucosidase. 15-Dehydrocyrtophyllone A showed an ACE inhibitory effect, and verbascoside, leucosceptoside A and isoacteoside exhibited strong inhibitory capacity against α-glucosidase.


Assuntos
Clerodendrum/química , Diterpenos/química , Diterpenos/farmacologia , Glicosídeos/química , Peptidil Dipeptidase A/metabolismo , Raízes de Plantas/química , alfa-Glucosidases/metabolismo , Ativação Enzimática/efeitos dos fármacos
17.
Zhong Yao Cai ; 37(9): 1590-3, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25857158

RESUMO

OBJECTIVE: To investigate the chemical constituents of the leaves of Clerodendrum trichotomum. METHODS: The chemical constituents of petroleum ether extract of the leaves of Clerodendrum trichotomum were isolated and purified by various chromatographic techniques, such as silica gel, ODS, Sephadex LH-20, semi-preparative HPLC and recrystallization. The structures of these isolated compounds were identified by spectroscopic analysis (1 H-NMR,13 C-NMR,2D-NMR and MS). RESULTS: Ten compounds were isolated and identified from petroleum ether extract, containing four triterpenes, lupeol(1), friedelin(2), betulinic acid(3) and taraxerol(4); four sterols, 22-dehydroclerosterol(5), clerosterol(6), stigmasterol(7) and sitosterol(8); one diterpenoid, transphytol(9), and one alkaloid, 1H-indole-3-carboxylic acid(10). CONCLUSION: Compound 10 is obtained from the genus Clerodendrum for the first time, and seven compounds (1,3-4, and 7-10) are firstly isolated from this plant.


Assuntos
Clerodendrum , Indóis , Ácido Oleanólico/análogos & derivados , Triterpenos Pentacíclicos , Folhas de Planta , Sitosteroides , Esteróis , Estigmasterol , Triterpenos
18.
Zhonghua Liu Xing Bing Xue Za Zhi ; 34(6): 552-6, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24125601

RESUMO

OBJECTIVE: To determine the incidence and risk factors of HCV infection among heroin addicts who were receiving methadone maintenance treatment(MMT)in Dehong prefecture, Yunnan province. METHODS: All heroin addicts who were HCV negative at the initiation of MMT in June 2005 through March 2012, in Dehong prefecture, were included in this cohort analysis. HCV incidence was calculated and related risk factors determined by using Cox proportional hazard regression model. RESULTS: A total of 2390 MMT clinic attendants were qualified for this cohort study by March 2012. 731(30.6%) of them had never received any follow-up HCV testing so were recognized as loss to follow-up. The other 1659 (69.4%) participants had received at least one follow-up HCV testing and were observed for a total of 3509.12 person-years(py). During this period 99 new HCV infections or HCV sero-converters were identified. The overall HCV incidence was 2.82/100 py and was 3.62/100 py for 2006, 5.36/100 py for 2007, 6.71/100 py for 2008, 2.56/100 py for 2009, 1.90/100 py for 2010, and 0.44/100 py for 2011, respectively. Results from multiple regression analysis, using Cox proportional hazard model, indicated that after controlling for confounding variables, those who were unemployed, being injecting drug users(IDUs)or HIV positive at entry into the MMT program were more likely to be newly infected with HCV or HCV sero-converted during the follow-up period than those who were peasants, non-IDUs or HIV negative at entry into the MMT program(HR = 2.02, 95% CI:1.18-3.48; HR = 9.05, 95% CI:5.49-14.93; HR = 2.12, 95% CI: 1.37-3.56), respectively. CONCLUSION: The incidence of HCV infection among MMT clinic attendants was decreasing since 2009 in Dehong prefecture. Those who were unemployed, injecting drug users and HIV positive were at higher risk of HCV infection.


Assuntos
Hepatite C/epidemiologia , Metadona/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Usuários de Drogas , Feminino , Humanos , Incidência , Masculino , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/virologia
19.
J Neurochem ; 127(3): 342-52, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23777437

RESUMO

Intracerebral microdialysis was utilized to investigate the effect of P-glycoprotein (a drug efflux transporter) induction at the mouse blood-brain barrier (BBB) on brain extracellular fluid concentrations of quinidine, an established substrate of P-glycoprotein. Induction was achieved by treating male CD-1 mice for 3 days with 5 mg/kg/day dexamethasone (DEX), a ligand of the nuclear receptor, pregnane X receptor, and a P-glycoprotein inducer. Tandem liquid chromatography mass spectrometric method was used to quantify analytes in dialysate, blood and plasma. P-glycoprotein, pregnane X receptor and Cyp3a11 (metabolizing enzyme for quinidine) protein expression in capillaries and brain homogenates was measured by immunoblot analysis. Following quinidine i.v. administration, the average ratio of unbound quinidine concentrations in brain extracellular fluid (determined from dialysate samples) to plasma at steady state (375-495 min) or Kp, uu, ECF /Plasma in the DEX-treated animals was 2.5-fold lower compared with vehicle-treated animals. In DEX-treated animals, P-glycoprotein expression in brain capillaries was 1.5-fold higher compared with vehicle-treated animals while Cyp3a11 expression in brain capillaries was not significantly different between the two groups. These data demonstrate that P-gp induction mediated by DEX at the BBB can significantly reduce quinidine brain extracellular fluid concentrations by decreasing its brain permeability and further suggest that drug-drug interactions as a result of P-gp induction at the BBB are possible. Applying microdialysis, distribution of quinidine, a P-gp substrate, in mouse brain extracellular fluid (ECF) was investigated following ligand-mediated P-glycoprotein (P-gp) induction at the blood-brain barrier (BBB). We demonstrated that a PXR agonist (dexamethasone) significantly up-regulated P-gp in brain capillaries and reduced quinidine brain ECF concentrations. Our data suggest that drug-drug interactions as a result of P-gp induction at the BBB are possible.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Barreira Hematoencefálica/metabolismo , Animais , Western Blotting , Capilares/metabolismo , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A/metabolismo , Interpretação Estatística de Dados , Densitometria , Dexametasona/farmacologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Microdiálise , Receptor de Pregnano X , Quinidina/sangue , Quinidina/metabolismo , Receptores de Esteroides/metabolismo , Espectrometria de Massas em Tandem
20.
Drug Metab Dispos ; 41(7): 1398-403, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23628674

RESUMO

Wuzhi capsule (WZC) is a preparation of an ethanol herbal extract of Schisandra sphenanthera (Nan-Wuweizi), with its main active ingredients that include schisandrin, schizandrol B, schisantherin A, schisanhenol, and deoxyschizandrin. WZC and tacrolimus are often coadministered for the treatment of drug-induced hepatitis in organ transplant recipients in China. Recently, it was reported that WZC could significantly increase the blood concentration of tacrolimus. The purpose of this study was to investigate whether and how WZC affects the pharmacokinetics of tacrolimus in rats. Liquid chromatography-tandem mass spectrometry method was used to determine the plasma concentration of tacrolimus. The results showed that WZC increased the mean plasma concentration of tacrolimus. Compared with administration of tacrolimus alone [maximum plasma concentration (C(max)), 18.87 ± 10.29 ng/ml; area under the plasma concentration-time curve from time zero to last sampling time (AUC(0→t)), 40.98 ± 37.07 ng h/ml], a single intragastric administered dose of WZC increased the pharmacokinetic parameters of tacrolimus (C(max), 59.42 ± 30.32 ng/ml; AUC(0→t), 239.71 ± 28.86 ng h/ml) by 5-fold in rat plasma. After pretreatment with WZC for 12 days, there were still significant increases in AUC(0→t) (from 40.98 ± 37.07 to 89.21 ± 26.39 ng h/ml; P < 0.05) and C(max) (from 18.87 ± 10.29 to 43.16 ± 10.61 ng/ml; P < 0.05) of tacrolimus, compared with oral of tacrolimus alone, suggesting that WZC increased the exposure of tacrolimus by one or more mechanisms. The increase in tacrolimus C(max) by WZC was dose-dependent. The effect of WZC on tacrolimus AUC(0→t) also increased with dose, with a maximal effect observed at 450 mg/kg (825.34 ng h/ml). No further increases in tacrolimus AUC(0→t) were observed at WZC dose above 450 mg/kg. It is suggested that, because of the effect of WZC on the pharmacokinetics of tacrolimus, the herb-drug interaction between WZC and tacrolimus should be taken into consideration in clinical practice.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Interações Ervas-Drogas , Imunossupressores/farmacocinética , Medicina Tradicional Chinesa , Tacrolimo/farmacocinética , Animais , Cápsulas , Inibidores do Citocromo P-450 CYP3A , Masculino , Ratos , Ratos Sprague-Dawley
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