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1.
Front Pharmacol ; 13: 932686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928262

RESUMO

Objective: We aimed to establish a population pharmacokinetic (PPK) model for isoniazid (INH) and its major metabolite Acetylisoniazid (AcINH) in healthy Chinese participants and tuberculosis patients and assess the role of the NAT2 genotype on the transformation of INH to AcINH. We also sought to estimate the INH exposure that would achieve a 90% effective concentration (EC90) efficiency for patients with various NAT2 genotypes. Method: A total of 45 healthy participants and 157 tuberculosis patients were recruited. For healthy subjects, blood samples were collected 0-14 h after administration of 300 mg or 320 mg of the oral dose of INH; for tuberculosis patients who received at least seven days therapy with INH, blood samples were collected two and/or six hours after administration. The plasma concentration of INH and AcINH was determined by the reverse-phase HPLC method. NAT2 genotypes were determined by allele-specific amplification. The integrated PPK model of INH and AcINH was established through nonlinear mixed-effect modeling (NONMEM). The effect of NAT2 genotype and other covariates on INH and AcINH disposition was evaluated. Monte Carlo simulation was performed for estimating EC90 of INH in patients with various NAT2 genotypes. Results: The estimated absorption rate constant (Ka), oral clearance (CL/F), and apparent volume of distribution (V2/F) for INH were 3.94 ± 0.44 h-1, 18.2 ± 2.45 L⋅h-1, and 56.8 ± 5.53 L, respectively. The constant of clearance (K30) and the volume of distribution (V3/F) of AcINH were 0.33 ± 0.11 h-1 and 25.7 ± 1.30 L, respectively. The fraction of AcINH formation (FM) was 0.81 ± 0.076. NAT2 genotypes had different effects on the CL/F and FM. In subjects with only one copy of NAT2 *5, *6, and *7 alleles, the CL/F values were approximately 46.3%, 54.9%, and 74.8% of *4/*4 subjects, respectively. The FM values were approximately 48.7%, 63.8%, and 86.9% of *4/*4 subjects, respectively. The probability of target attainment of INH EC90 in patients with various NAT2 genotypes was different. Conclusion: The integrated parent-metabolite PPK model accurately characterized the disposition of INH and AcINH in the Chinese population sampled, which may be useful in the individualized therapy of INH.

2.
Biomed Environ Sci ; 34(10): 761-772, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34782043

RESUMO

OBJECTIVE: This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease (CKD) in Shanghai community residents. METHODS: We used data from a cohort study of community residents who participated in three examinations in 2008, 2009, and 2013, respectively. Fasting plasma glucose (FPG) level, blood pressure (BP), and lipid levels were determined in 2,109 participants at all three visits, and CKD was evaluated between the second and the third visits. Visit-to-visit variabilities in metabolic factors were described by coefficients of variation (CV) at three visits. A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV. CKD was defined as the estimated glomerular filtration rate < 60 mL/min per 1.73 m 2 or urinary albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS: A total of 200 (9.5%) participants had CKD at the third visit. Compared with the lowest quartile of CV, the highest quartile was associated with a 70% increased risk of CKD for FPG [odds ratio, OR = 1.70; 95% confidence interval ( CI) 1.06-2.72], 62% for systolic BP ( OR = 1.62, 95% CI 1.04-2.50), and 85% for low-density lipoprotein cholesterol ( OR = 1.85, 95% CI 1.23-2.80). Furthermore, the risk of CKD increased significantly with an increasing variability score. Compared with participants with score 0, participants with scores of 1, 2, and 3 were associated with 58% ( OR = 1.58, 95% CI 1.08-2.32), 121% ( OR = 2.21, 95% CI 1.40-3.49), and 548% ( OR = 6.48, 95% CI 3.18-13.21) higher risks of CKD, respectively. CONCLUSION: The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.


Assuntos
Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia
3.
BMC Vet Res ; 16(1): 473, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272251

RESUMO

BACKGROUND: Fasciola hepatica is an important zoonotic parasite that causes fasciolosis in a broad range of animals. No information is available about the prevalence of F. hepatica in Père David's deer (Elaphurus davidianus), an endangered species in the world. Therefore, the purpose of the study was to evaluate the prevalence of fasciolosis in Père David's deer in the Dafeng Elk National Natural Reserve, Jiangsu province, China. RESULTS: In this study, 142 fecal samples from Père David's deer were analyzed for F. hepatica by microscopy and nest-PCR. Only one sample was positive for F. hepatica according to microscopy examination, while 18 of 142 (12.68, 95%CI: 2.841-22.45%) samples were positive for F. hepatica according to nest-PCR results. CONCLUSIONS: This is the first report of prevalence of F. hepatica in Père David's deer. The prevalence data indicated that F. hepatica was also present in this endangered animal, which may cause a potential threat to this precious species.


Assuntos
Cervos , Fasciola hepatica/isolamento & purificação , Fasciolíase/veterinária , Animais , China/epidemiologia , Espécies em Perigo de Extinção , Fasciolíase/epidemiologia , Fezes/parasitologia , Reação em Cadeia da Polimerase/veterinária , Prevalência
4.
Gastroenterol Res Pract ; 2020: 3467419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655630

RESUMO

OBJECTIVES: The aims of this study were to evaluate the C-reactive protein/albumin ratio (CRP/ALB), inflammatory markers, and parameters from the complete blood count (CBC) in patients with inflammatory bowel disease (IBD) and their associations with disease activity. METHODS: A total of 876 IBD patients, composed of 275 patients with ulcerative colitis (UC) and 601 patients with Crohn's disease (CD), were included in this retrospective study, and the serum C-reactive protein (CRP), albumin (ALB), erythrocyte sedimentation rate (ESR), and CBC parameters were measured. To explore the disease activity, the Mayo score and Crohn disease activity index were used to assess UC and CD patients, respectively. RESULTS: The CRP/ALB ratio, CRP, ESR, platelet to lymphocyte ratio (PLR), red blood cell distribution width (RDW), and neutrophil to lymphocyte ratio (NLR) levels in active IBD patients were significantly higher than those in inactive IBD patients, whereas ALB and lymphocyte to monocyte ratio (LMR) levels were significantly decreased (P < 0.001). The receiver operating characteristic analysis showed that the optimum cut-off values of the CRP/ALB ratio for active UC and CD were 0.18 and 0.43, with sensitivities of 67.8% and 75.8% and specificities of 86.7% and 92.0%, respectively. Multivariable logistic analysis revealed that after adjusting for these inflammatory markers (ESR, NLR, PLR, and LMR), the CRP/ALB ratio was a statistically significant parameter capable of differentiating the disease activity of UC and CD. CONCLUSIONS: This study indicated that the CRP/ALB ratio was closely related to the IBD disease activity. Compared with CBC parameters, the CRP/ALB ratio had a higher discriminative capacity for active IBD.

5.
J Food Sci ; 85(4): 1285-1291, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32157685

RESUMO

Green tea is widely consumed as a beverage and/or dietary supplement worldwide, resulting in the difficulty to avoid the comedication with ticagrelor for acute coronary syndrome (ACS) patients receiving antiplatelet therapy. This study was designed to investigate the effect of the most abundant content in green tea, tea polyphenols on the oral and intravenous pharmacokinetics of ticagrelor in rats and its in vitro metabolism. Rats were orally treated with either saline or tea polyphenol extracts (TPEs) dissolved in saline once daily for 6 consecutive days. On day 6, after the last dose of saline or TPE, ticagrelor was given to the rats orally or intravenously. Plasma samples were collected for pharmacokinetic analysis. Human liver and intestinal microsomes were then used to investigate the inhibition by TPE, as well as its major constituents on the metabolism of ticagrelor to its two metabolites, AR-C124910XX and AR-C133913XX. Apparent kinetic constants and inhibition potency (IC50 ) for each metabolic pathway of each compound were estimated. Oral study indicated that exposure of ticagrelor and AR-C124910XX was significantly decreased after TPE administration, while no significant differences were observed in pharmacokinetic parameters after intravenous administration of ticagrelor. TPE effectively inhibited the metabolism of ticagrelor in vitro, with epigallocatechin-3-gallate as the major constituent responsible for the observed inhibitory effects in human liver microsomes and intestinal microsomes (IC50 = 4.23 ± 0.18 µM). Caution should be taken for ACS patients receiving ticagrelor therapy with daily drinking of green tea. PRACTICAL APPLICATION: Potential interactions between tea polyphenols and ticagrelor were revealed for the first time. Results can provide suggestions for clinicians to optimize the dosing of ticagrelor while they are in the face of ACS patients receiving ticagrelor therapy, who also take green tea or its related products in their daily life.


Assuntos
Microssomos Hepáticos/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacocinética , Polifenóis/farmacocinética , Chá/química , Ticagrelor/farmacocinética , Adenosina/análogos & derivados , Administração Intravenosa , Administração Oral , Animais , Catequina/análogos & derivados , Masculino , Microssomos Hepáticos/metabolismo , Inibidores da Agregação Plaquetária/administração & dosagem , Polifenóis/administração & dosagem , Polifenóis/química , Ratos , Ticagrelor/administração & dosagem , Ticagrelor/metabolismo
6.
Acta Pharmacol Sin ; 39(9): 1522-1532, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29644999

RESUMO

Liver metabolism is commonly considered the major determinant in drug discovery and development. Many in vitro drug metabolic studies have been developed and applied to understand biotransformation. However, these methods have disadvantages, resulting in inconsistencies between in vivo and in vitro experiments. A major factor is that they are static systems that do not consider the transport process in the liver. Here we developed an in vitro dynamic metabolic system (Bio-PK metabolic system) to mimic the human pharmacokinetics of tolbutamide. Human liver microsomes (HLMs) encapsulated in a F127'-Acr-Bis hydrogel (FAB hydrogel) were placed in the incubation system. A microdialysis sampling technique was used to monitor the metabolic behavior of tolbutamide in hydrogels. The measured results in the system were used to fit the in vitro intrinsic clearance of tolbutamide with a mathematical model. Then, a PBPK model that integrated the corresponding in vitro intrinsic clearance was developed to verify the system. Compared to the traditional incubation method, reasonable PK profiles and the in vivo clearance of tolbutamide could be predicted by integrating the intrinsic clearance of tolbutamide obtained from the Bio-PK metabolic system into the PBPK model. The predicted maximum concentration (Cmax), area under the concentration-time curve (AUC), time to reach the maximum plasma concentration (Tmax) and in vivo clearance were consistent with the clinically observed data. This novel in vitro dynamic metabolic system can compensate for some limitations of traditional incubation methods; it may provide a new method for screening compounds and predicting pharmacokinetics in the early stages, supporting the development of compounds.


Assuntos
Microssomos Hepáticos/metabolismo , Tolbutamida/farmacocinética , Difusão , Feminino , Humanos , Hidrogéis/síntese química , Hidrogéis/química , Masculino , Microdiálise/métodos , Modelos Teóricos , Poloxâmero/síntese química , Poloxâmero/química , Tolbutamida/metabolismo
7.
Asian Pac J Cancer Prev ; 17(8): 3917-21, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27644639

RESUMO

BACKGROUND: Any association between calcium channel blockers (CCBs) and survival in cancer patients remains unclear and the results of related studies are conflicting. The objective of the study was to investigate the association between calcium channel blocker (CCB) use and survival in cancer patients. MATERIALS AND METHODS: We searched PubMed, EMBASE, Web of Science and Cochrane Library for studies published before January 2016 with terms related to CCBs and survival in cancer patients. The information was reviewed and extracted by two evaluators independently. Data from publications were extracted and used to calculate hazard ratios (HRs) for overall survival (OS). Statistical analysis was performed by using Review Manager 5.3. RESULTS: There were 11 studies included in our meta-analysis. Analysis of all showed that CCBs use was not associated with survival in cancer patients (HR=1.07; 95% CI: 0.91-1.25; P=0.42). No association between CCB use and overall survival in cancer patients existed, whether in Asian (HR=1.18, 95% CI: 0.72-1.93; P=0.52) or Caucasian populations (HR=1.03, 95% CI: 0.89-1.20; P=0.66). CONCLUSIONS: There is no evidence that CCB use is associated with a better or worse survival in cancer patients.


Assuntos
Bloqueadores dos Canais de Cálcio/efeitos adversos , Neoplasias/mortalidade , Idoso , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Estudos Observacionais como Assunto
8.
Acta Pharmacol Sin ; 36(5): 614-26, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25864651

RESUMO

AIM: Blockade of EGFR by EGFR tyrosine kinase inhibitors such as erlotinib is insufficient for effective treatment of human pancreatic cancer due to independent activation of the Akt pathway, while amiloride, a potassium-sparing diuretic, has been found as a potential Akt inhibitor. The aim of this study was to investigate the anticancer effects of combined amiloride with erlotinib against human pancreatic cancer cells in vitro. METHODS: Cell proliferation, colony formation, cell cycle and apoptosis were analyzed in 4 human pancreatic cancer cell lines Bxpc-3, PANC-1, Aspc-1 and CFPAC-1 treated with erlotinib or amiloride alone, or in their combination. The synergistic analysis for the effects of combinations of amiloride and erlotinib was performed using Chou-Talalay's combination index isobolographic method. RESULTS: Amiloride (10, 30, and 100 µmol/L) concentration-dependently potentiated erlotinib-induced inhibition of cell proliferation and colony formation in the 4 pancreatic cancer cell lines. Isobolographic analysis confirmed that combinations of amiloride and erlotinib produced synergistic cytotoxic effects. Amiloride significantly potentiated erlotinib-induced G0/G1 cell-cycle arrest and apoptosis in Bxpc-3 and PANC-1 cells. Amiloride inhibited EGF-stimulated phorsphorylation of AKT, and significantly enhanced erlotinib-induced downregulation of phorsphorylation of EGFR, AKT, PI3K P85 and GSK 3ß in Bxpc-3 and PANC-1 cells. CONCLUSION: Amiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through inhibition of the PI3K/AKT signaling pathway. Treatment of pancreatic cancer patients with combination of erlotinib and amiloride merits further investigation.


Assuntos
Amilorida/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cloridrato de Erlotinib/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Fatores de Tempo
9.
J Hepatol ; 59(4): 738-45, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23747755

RESUMO

BACKGROUND & AIMS: Proliferation of liver progenitor cells (LPCs) is associated with inflammation and fibrosis in chronic liver diseases. However, how inflammation and fibrosis affect LPCs remains obscure. METHODS: We examined the role of interferon (IFN)-γ, an important pro-inflammatory and anti-fibrotic cytokine, in LPC expansion in HBV-infected patients and in mice challenged with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)- or choline-deficient, ethionine-supplemented (CDE) diet as well as in primary LPCs and LPC cell line. RESULTS: The CK19 staining scores correlated with inflammation and fibrosis grades in the livers from 110 HBV-infected patients. Nine-month IFN-γ treatment decreased LPC numbers, inflammation, and fibrosis in these HBV-infected patients. Similarly, a two-week IFN-γ treatment also decreased LPC activation in DDC-treated mice. Disruption of IFN-γ or its signaling components (e.g., IFNGR, STAT1, and IRF-1) increased LPC proliferation and liver fibrosis in DDC-fed mice. In contrast, deletion of IFN-γ did not increase, but rather slightly reduced LPC proliferation in CDE-fed mice. In vitro, IFN-γ attenuated proliferation of the LPC cell line BMOL and of primary LPCs from wild type mice, but not STAT1(-/-) or IRF-1(-/-) mice. Furthermore, co-culture assays suggest that IFN-γ can indirectly promote LPC proliferation via the activation of macrophages but attenuate it via the inhibition of hepatic stellate cells. CONCLUSIONS: IFN-γ inhibits LPC expansion via the direct inhibition of LPC proliferation and indirect attenuation of liver fibrosis in the DDC model, but it may also enhance LPC expansion via the promotion of inflammation in the CDE model; thereby playing dual roles in regulating LPC proliferation in vivo.


Assuntos
Células-Tronco Adultas/citologia , Hepatite B Crônica/patologia , Hepatócitos/citologia , Interferon gama/fisiologia , Células-Tronco Adultas/efeitos dos fármacos , Células-Tronco Adultas/fisiologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Células Estreladas do Fígado/fisiologia , Hepatite B Crônica/fisiopatologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/fisiologia , Humanos , Interferon gama/deficiência , Interferon gama/farmacologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Cirrose Hepática/prevenção & controle , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Piridinas/administração & dosagem , Piridinas/toxicidade , Transdução de Sinais/efeitos dos fármacos
10.
Artigo em Chinês | MEDLINE | ID: mdl-24809185

RESUMO

OBJECTIVE: To study the expression of Smads proteins involved in TGF-beta1 signal transduction during the process of liver fibrosis in BALB/c mice infected with Schistosoma japonicum. METHODS: Thirty-four BALB/c mice were each infected with (20 +/- 1) S. japonicum cercariae. The mice were sacrificed at 8, 12, 16 and 24 weeks postinfection. Ten healthy BALB/c mice served as normal control group. The liver tissues were fixed in 10% formaldehyde for histology and immunohistochemistry assay. The single-egg granuloma area was measured in hematoxylin-eosin stain section. The degree of liver fibrosis was determined by Sirius red staining. Immunohistochemistry was used to observe the expression of Smad protein. RESULTS: The area of single-egg granuloma peaked at 8th week post-infection [(533 +/- 1.03) mm2], and with time passing, the area diminished, and the area of granuloma reduced to (2.94 +/- 1.69) mm2 at 24 weeks post-infection. The difference was significant among the 4 periods after infection in single-egg granuloma area (P < 0.05). Collagen fibers appeared around granulomas at 8 weeks (2.03 +/- 0.52) and increased gradually. At 24 weeks post-infection, the degree of liver fibrosis reached a peak (6.90 +/- 1.57), and the liver fibrosis degree was significantly different among infection groups (P < 0.05). Immunohistochemistry showed low expression level of Smad2/3 and Smad7 and inconspicuous level of Smad4 in livers of the normal mice. The expression of Smad2/3 was found mostly in the cytoplasm and nucleus of cells around granulomas at 8th week post-infection, and the positive area of Smad2/3 was (7.24 +/- 1.64)% by semi-quantity. At 12 weeks post-infection, the Smad2/3 protein expression level around granulomas and liver sinus reached the peak [(10.01 +/- l.07)%], and there was significant difference between infection groups and the control [(2.13 +/- 0.32)%]. A significant difference in the Smad2/3 protein expression level was found between 12 weeks post-infection group and 8 weeks or 16 weeks post-infection groups. The expression level of Smad4 was (8.81 +/- 1.13)% at 8th week post-infection, higher than that in the control [(4.83 +/- 1.15)%] (P < 0.05). There was no difference among the infected mice at different periods in the level of Smad4 (P > 0.05). After 8 weeks post infection, Smad7 protein sparsely appeared around the granuloma [(4.15 +/- 1.26)%] while it disappeared around liver sinus. At 12 weeks post-infection, the level of Smad7 protein was higher [(6.34 +/- 1.5)%], but with prolonged infection time, no significant difference was revealed (P > 0.05). The level of Smad7 in infected mice was higher than that in the control (P < 0.05). CONCLUSION: Resylts show high expression for Smad2/3 and Smad7 and low expression level of Smad4 during the process of liver fibrosis in BALB/c mice infected with Schistosoma japonicum.


Assuntos
Cirrose Hepática/parasitologia , Fígado/patologia , Esquistossomose Japônica/patologia , Proteínas Smad/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Granuloma/parasitologia , Granuloma/patologia , Fígado/metabolismo , Fígado/parasitologia , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óvulo , Schistosoma japonicum , Esquistossomose Japônica/metabolismo , Transdução de Sinais
11.
Acta Pharmacol Sin ; 33(6): 839-44, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22543704

RESUMO

AIM: To study the distribution, metabolism and excretion of S-propargyl-cysteine (SPRC), a novel hydrogen sulfide (H2S) donor, after oral administration in rats. METHODS: Adult Sprague-Dawley rats were used. The tissue distribution of [(35)S] SPRC-derived radioactivity was measured using a liquid scintillation counter. The plasma protein binding of SPRC was examined using 96-well equilibrium dialysis. The excretion of SPRC in urine, bile and feces was analyzed using the LC-MS/MS method. The major metabolites in rat biomatrices were identified using MRM information-dependent, acquisition-enhanced product ion (MRM-IDA-EPI) scans on API 4000QTrap system. RESULTS: After oral administration of [(35)S]-SPRC at a dose of 75 mg/kg, [(35)S] SPRC-derived radioactivity displayed broad biological distribution in various tissues of rats, including its target organs (heart and brain) with the highest in kidney. On the other hand, the binding of SPRC to human, rat and dog plasma protein was low. Only 2.18% ± 0.61% and 0.77% ± 0.61% of the total SPRC administered was excreted unchanged in the bile and urine. However, neither intact SPRC nor its metabolites were detected in rat feces. The major metabolic pathway in vivo (rat bile, urine, and plasma) was N-acetylation. CONCLUSION: The preliminary results suggest that SPRC possesses acceptable pharmacokinetic properties in rats.


Assuntos
Cisteína/análogos & derivados , Sulfeto de Hidrogênio/metabolismo , Animais , Bile/metabolismo , Proteínas Sanguíneas/metabolismo , Cisteína/metabolismo , Cisteína/farmacocinética , Cisteína/farmacologia , Cães , Fezes/química , Feminino , Humanos , Masculino , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
12.
Clin Chim Acta ; 412(23-24): 2237-40, 2011 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-21884687

RESUMO

BACKGROUND: The CDA 79A>C (K27Q, rs2072671) functional SNP has recently shown a crucial role in the pharmacogenetics of cytidine-based anticancer drugs widely administered to different subsets of patients. Current gold standard in screening for the CDA rs2072671 is the sequence-based genotyping method. Here we developed a novel, rapid Allele-Specific PCR method for CDA rs2072671 genotyping. METHODS: DNA was extracted from 324 healthy individuals from two different populations (Italian and Han Chinese). CDA rs2072671 genotyping was performed by Allele-Specific PCR. Sequencing was performed to validate the test results. Results obtained from population screening were compared to that already available in HapMap and in the literature. RESULTS: Samples analyzed were successfully genotyped and the results were confirmed by sequencing. Genotype distribution does not differ significantly from that previously reported for each relative ethnic group. Also, the world-wide distribution of the CDA rs2072671 SNP is reported. A striking difference is present among the main ethnicities (p=1.715×10(-77)), with CDA*27Q allele showing the lowest frequency in African group (9.7%) and the highest in Caucasians (35.9%). CONCLUSION: This Allele-Specific PCR method is a useful tool in pharmacogenetics research and a valid and reliable alternative for CDA rs2072671 screening where sequencing or Real-Time PCR is not available.


Assuntos
Alelos , Farmacogenética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Primers do DNA , Genótipo , Humanos
13.
Hepatobiliary Pancreat Dis Int ; 10(2): 151-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21459721

RESUMO

BACKGROUND: The first priority in treating fibrosis is to eliminate the causes that result in liver injury, e.g., hepatitis B and C virus. However, in many liver diseases the cause is either unknown or untreatable. The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma (IFN-gamma) treatment in patients chronically infected with hepatitis B virus. METHODS: A total of 42 patients, 30 treated with IFN-gamma and 12 controls, were enrolled from an original clinical trial (Clin Gastroenterol Hepatol 2005;3:819.). Three serial liver biopsies that were obtained at the initiation and end of IFN-gamma treatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system. RESULTS: Twenty-five out of 30 IFN-gamma-treated patients were followed up until 4 to 6 years after the treatment was stopped. However, all controls were excluded from follow-up due to death, loss and elevated virus level within 2 years. Twenty-five IFN-gamma-treated patients had stable serum liver function and liver fibrosis indices without any further anti-viral or anti-fibrotic treatment. Improved inflammatory and fibrotic scores were found after nine months of IFN-gamma treatment according to the modified Chevallier scoring system (inflammation: 11.8+/-6.5 at the beginning of IFN-gamma treatment vs. 9.2+/-4.1 after 9 months, P<0.05; fibrosis: 15.0+/-7.3 at baseline vs. 12.6+/-6.8 after 9 months, P<0.05). Among them, 14 patients accepted a third serial liver biopsy 4 to 6 years after treatment discontinuation, and the fibrotic score was increased (14.2+/-8.3 vs. 11.9+/-7.6 after 9 months, P<0.05). CONCLUSIONS: Nine-month IFN-gamma treatment significantly improves the fibrosis score in patients with chronic HBV infection. The majority of patients demonstrate stable serum biochemical indices and quality of life. However, they do not show a long-term benefit according to histological criteria. Given the limited sample size, long-term IFN-gamma treatment regimens should be assessed in further clinical trials.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon gama/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Adulto , Feminino , Hepatite B Crônica/patologia , Hepatite B Crônica/fisiopatologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes
14.
Zhonghua Gan Zang Bing Za Zhi ; 18(5): 346-52, 2010 May.
Artigo em Chinês | MEDLINE | ID: mdl-20509999

RESUMO

OBJECTIVE: To identify the active material of anti-hepatic fibrosis from Amydae Carapax. METHODS: Membrane separation technology was adopted to screen active fraction in Amydae Carapax, and the active components were isolated from the active fraction using gel chromatography and high performance liquid chromatography. The purified active components in Amydae Carapax were further analyzed using 4700 series time-of-flight mass spectrometer. RESULTS: Proteins and peptides of Amydae Carapax with molecular weight less than 6000 were proved to have biological activity. 8 components (Bj1-Bj8) were isolated from the active fraction. Bj4, Bj6 and Bj7 were screened as active components. Bj7 was further purified, resulting in 7 components (Bj701-Bj707). Bj704 and Bj707 showed significant biological activity. Mass spectrometry showed three molecular ion peaks with highest abundance, i.e. m/e 526, 542 and 572, i.e. m/e 526, 542 and 572, in Bj707 -A The amino acid sequences of above three peptide compounds were NDDY (Asn-Asp-Asp-Tyr), NPNPT (Asn-Pro-Asn-Pro-Thr), and HGRFG (His-Gly-Arg-Phe-Gly), respectively. And M572 was the most abandunt components. CONCLUSION: Three active peptide compounds of anti-hepatic fibrosis of Amydae Carapax were identified.


Assuntos
Cirrose Hepática , Medicina Tradicional Chinesa , Extratos de Tecidos/isolamento & purificação , Extratos de Tecidos/farmacologia , Animais , Linhagem Celular , Humanos
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(4): 878-82, 2009 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-19626863

RESUMO

The emission spectra of pure oxygen in dielectric barrier discharge at atmospheric pressure were observed. Comparison between experimental and fitting spectra of oxygen A band (b 1Sigmag(+) --> X 3Sigmag(-)) (0, 0) was used to determine the gas temperature, and the electronic temperature was calculated from O I lines. The causation of oxygen A band in atmospheric dielectric barrier discharge was discussed by means of analysis of producing and quenching approaches. The result showed that the electronic temperature, (11,800+/-400) K, was much higher than the gas temperature, (650+/-20) K. The emission from a 1Deltag or A 3Sigmau(+) was not been observed, but atmospheric band with its resoluble rotational structure was measured.

18.
Sci Total Environ ; 407(7): 2411-9, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19138789

RESUMO

Desert mosses are components of biological soil crusts (BSCs) and their ecological functions make assessment and protection of these mosses a high-ranking management priority in desert regions. Drying is thought to be useful for desert mosses surviving heat shock. In this study, we investigated the role of drying by monitoring the responses of physiological characters and asexual reproduction in the typical desert moss Syntrichia caninervis. Heat significantly decreased chlorophyll content and weakened rapid recovery of photochemical activity, and increased carotenoid content and membrane permeability. Lethal temperatures significantly destroyed shoot regeneration potential. In comparison with heat alone, drying significantly increased protonema emergence time and depressed protonema emergence area. Drying combined with heat accelerated water loss, followed by a decrease of photosynthetic activity. Drying had different influences on membrane permeability at different temperatures. When moss leaves were subjected to a combined stress of drying and heat shock, photosynthesis was maintained mainly due to the effects of drying on physiological activity although the cellular morphological integrity was affected. Drying caused opposing effects on moss physiological and reproductive characteristics. On the one hand, drying caused a positive synergistic effect with heat shock when the temperature was below 40 degrees C. On the other hand, drying showed antagonism with heat shock when the moss was subjected to temperatures higher than 40 degrees C. These findings may help in understanding the survival mechanism of dessert mosses under heat shock stress which will be helpful for the artificial reconstruction of BSCs.


Assuntos
Bryopsida/fisiologia , Dessecação , Temperatura Alta , Estresse Fisiológico , Bryopsida/metabolismo , Bryopsida/ultraestrutura , Membrana Celular/fisiologia , Permeabilidade da Membrana Celular , Clorofila/metabolismo , Cinética , Microscopia Eletrônica de Transmissão , Fotossíntese , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/ultraestrutura , Brotos de Planta/metabolismo , Brotos de Planta/fisiologia , Brotos de Planta/ultraestrutura , Regeneração
19.
J Hazard Mater ; 163(2-3): 538-43, 2009 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-18725176

RESUMO

The investigations for selective adsorption of dibenzothiophene (DBT) over Ce/Ni-loaded Y zeolites with the emphasis on the effect of Ce as a cocation in the Ni-loaded Y zeolite are carried out in an attempt to produce more effective adsorbents for the desulfurization from transportation fuels. The promotional effects of Ce and coexisting toluene in the model fuel as well as contact time and adsorbent dose on the adsorptive performance were examined. The sulfur uptake strongly depends on the amount of Ce in the zeolite structure. The sorption data is varied according to both Langmuir and Freundlich isotherm models. The maximum sorption capacity by theoretically calculation is 22.2mg/g at 25 degrees C. The Langmuir constants b=5.82 mL/mg and the Freundlich constants K=1.042 L/mg and 1/n=0.4 are evaluated. Ni/Ce-loaded Y zeolites (NiCeY) and NiY, CeY, NaY zeolites were used as adsorbents for the removal of DBT from model fuel containing 500 mg/L sulfur with 5 vol% of toluene by a batch method under ambient conditions. NiCeY exhibits higher adsorptive selectivity for DBT than NiY and CeY, indicating that NiCeY is a more effective adsorbent to remove sulfur compounds from transportation fuels.


Assuntos
Combustíveis Fósseis , Tiofenos/isolamento & purificação , Adsorção , Cério , Poluentes Ambientais/isolamento & purificação , Níquel , Zeolitas
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