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1.
Biomed Res Int ; 2018: 4969385, 2018.
Article in English | MEDLINE | ID: mdl-29955603

ABSTRACT

AIM: To investigate the genetic contribution of adenosine A3 receptor (ADORA3) gene polymorphisms in the pathogenesis of chronic heart failure (CHF). METHODS: Firstly, a case-control study was performed to investigate the association of ADORA3 polymorphisms with CHF risk. Three hundred northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls were included. Four polymorphisms were genotyped. This case-control study was also replicated in 304 CHF patients and 402 controls from southern China. Finally, the functional variability of positive polymorphism was analyzed using luciferase reporter assay and real-time PCR. RESULTS: Overall, the rs1544223 was significantly associated with CHF risk under the dominant model (P = 0.046, OR = 1.662, 95% CI = 1.009-2.738). But it did not affect disease severity. These results were also consistent in replicated population. In addition, the transcriptional activity for promoter with the A allele was lower than that with the G allele (n = 3, 4.501 ± 0.308 versus 0.571 ± 0.114, P < 0.01) and ADORA3 mRNA levels were significantly higher in GG homozygotes than subjects carrying GA (n = 6, 0.058 ± 0.01 versus 0.143 ± 0.068, P = 0.004) or AA genotypes (n = 6, 0.065 ± 0.01 versus 0.143 ± 0.068, P = 0.008). CONCLUSIONS: Should the findings be validated by further studies with larger patient samples and in different ethnicities, they may provide novel insight into the pathogenesis of CHF.


Subject(s)
Genetic Predisposition to Disease , Heart Failure/genetics , Polymorphism, Single Nucleotide , Receptor, Adenosine A3/genetics , Aged , Asian People , Case-Control Studies , China , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Transcription, Genetic
2.
Acta Pharmacol Sin ; 39(9): 1533-1543, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29849129

ABSTRACT

Caspofungin is an echinocandin antifungal agent licensed as a first-line therapy for invasive candidiasis in patients with moderate to severe illness or recent exposure to azoles. In this study we developed a whole-body physiology-based pharmacokinetics (WB-PBPK) model to predict the pharmacokinetics (PK) of caspofungin, and combined with Monte Carlo simulation (MCS) to optimize clinical dosage regimens of caspofungin in different kinds of patients. A WB-PBPK model of caspofungin was built and validated with raw data from 4 previous trials of general patients, intensive care unit (ICU) patients with Child-Pugh B, ICU patients on continuous renal replacement therapy, mild and moderate hepatic insuffciency (HI) patients. MCS was used to optimize clinical dosage regimens of caspofungin in these patients. A cumulative fraction of response (CFR) value of ≥90% was considered to be the minimum for achieving optimal empirical therapy. The simulated results of the WB-PBPK model were in good agreement with observed values of all trials. For general and ICU patients with caspofungin 70/50 mg, AUC and Cmax were decreased with the increase of body weight (BW) and showed great variation. MCS showed all general patients achieved CFR≥90% regardless of BW. But not all ICU patients with higher BW (≥70 kg) could achieve CFR≥90%. Compared with standard dosage regimens in general patients, caspofungin 70/35 mg in ICU patients with Child-Pugh B achieved significantly decreased AUC and Cmax, but obtained similar AUC and Cmax in moderate HI patients with Child-Pugh B. The WB-PBPK model of caspofungin is able to predict PK of all populations correctly. The combined WB-PBPK model with MCS can successfully optimize clinical dosage regimens of caspofungin in all patient populations.


Subject(s)
Antifungal Agents/pharmacokinetics , Caspofungin/pharmacokinetics , Models, Biological , Adult , Antifungal Agents/administration & dosage , Caspofungin/administration & dosage , Hepatic Insufficiency/metabolism , Humans , Intensive Care Units , Male , Monte Carlo Method , Young Adult
3.
Heart Lung ; 45(4): 363-71, 2016.
Article in English | MEDLINE | ID: mdl-27377334

ABSTRACT

OBJECTIVES: This meta-analysis summarized the risks that reintubation impose on ventilator-associated pneumonia (VAP) and mortality. BACKGROUND: Extubation failure increases the probability of poor clinical outcomes pertaining to mechanical ventilation. METHODS: Literature published during a 15-year period was retrieved from PubMed, Web of Knowledge databases, the Embase (Excerpa Medica database), and the Cochrane Library. Data involving reintubation, VAP, and mortality were extracted for a meta-analysis. RESULTS: Forty-one studies involving 29,923 patients were enrolled for the analysis. The summary odds ratio (OR) between VAP and reintubation was 7.57 (95% confidence interval [CI] = 3.63-15.81). The merged ORs for mortality in hospital and intensive care unit were 3.33 (95% CI = 2.02-5.49) and 7.50 (95% CI = 4.60-12.21), respectively. CONCLUSIONS: Reintubation can represent a threat to survival and increase the risk of VAP. The risk of mortality after reintubation differs between planned and unplanned extubation. Extubation failure is associated with a higher risk of VAP in the cardiac surgery population than in the general population.


Subject(s)
Intensive Care Units , Intubation, Intratracheal/methods , Pneumonia, Ventilator-Associated/mortality , Postoperative Complications , Respiration, Artificial , Airway Extubation/methods , Cardiac Surgical Procedures , Global Health , Humans , Odds Ratio , Pneumonia, Ventilator-Associated/therapy , Risk Factors , Survival Rate/trends
4.
Onco Targets Ther ; 8: 3277-87, 2015.
Article in English | MEDLINE | ID: mdl-26609240

ABSTRACT

BACKGROUND: Associations between Arg399Gln single-nucleotide polymorphism (SNP) in the XRCC1 gene and leukemia susceptibility have been studied extensively, however, the results are inconsistent. The aim of this study was to determine these associations using meta-analytical methods. METHODS: A meta-analysis was performed to examine the associations between XRCC1 Arg399-Gln SNP and leukemia risk. A literature search of PubMed and Web of Science databases was conducted to identify relevant studies published up to March 10, 2015. The references of the retrieved articles were also screened. All the statistical analyses were conducted using Review Manager software. RESULTS: The XRCC1 Arg399Gln SNP was found to be associated with increased childhood risk of acute lymphoblastic leukemia among Asians under the dominant (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.50-2.97, P<0.0001), allele contrast (OR 1.72, 95% CI 1.33-2.23, P<0.0001), and homozygote contrast (OR 2.34, 95% CI 1.25-4.36, P=0.008) models. However, no association was found in Caucasians between the SNP and risk of either chronic myeloid leukemia or chronic lymphocytic leukemia under any contrast model. CONCLUSION: The findings of the current meta-analysis indicate that the XRCC1 Arg399Gln SNP is a risk factor for childhood lymphoblastic leukemia in Asians.

5.
Onco Targets Ther ; 8: 2883-902, 2015.
Article in English | MEDLINE | ID: mdl-26491362

ABSTRACT

The associations between CYP1A1 polymorphisms and risk of leukemia have been studied extensively, but the results have been inconsistent. Therefore, in this study, we performed a meta-analysis to clarify associations of three CYP1A1 polymorphisms (T3801C, A2455G, and C4887A) with the risks of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Medline, EMBASE, and China National Knowledge Infrastructure databases were searched to collect relevant studies published up to April 20, 2015. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated to quantify the associations. Overall, 26 publications were included. Finally, T3801C was associated with an increased risk of AML in Asians under the dominant model. For A2455G, the risk of ALL was increased among Caucasians in the recessive model and the allele-contrast model; A2455G was also associated with an increased risk of CML among Caucasians under the recessive model, dominant model, and allele-contrast model. For C4887A, few of the included studies produced data. In conclusion, the results suggest that Asians carrying the T3801C C allele might have an increased risk of AML and that Caucasians with the A2455G GG genotype might have an increased risk of ALL. Further investigations are needed to confirm these associations.

6.
Onco Targets Ther ; 8: 2443-51, 2015.
Article in English | MEDLINE | ID: mdl-26388693

ABSTRACT

Acute lymphoblastic leukemia (ALL) has been studied intensively for decades, but the details of its etiology and underlying mechanisms have yet to be fully elucidated. It is now generally acknowledged that genetic factors contribute greatly to the development of this disease. The gene encoding CCAAT/enhancer-binding protein ε (CEBPE) is involved in the development of leukemia, and in particular the rs2239633 single nucleotide polymorphism (SNP) of CEBPE. The association between rs2239633 and risk of ALL has been well studied, but remains unclear. Therefore, a meta-analysis was performed in this study to establish a more precise estimation of that relationship. A comprehensive literature search of the PubMed electronic database was conducted, and relevant studies published up to February 20, 2015 were selected for analysis. The references of the retrieved articles were also screened. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated using Review Manager (version 5.2) to estimate the association strength. Finally, eleven studies were included in the meta-analysis. The pooled analyses revealed that rs2239633 was associated with an increased risk of childhood ALL in Caucasians under any contrast models (P<0.01). However, this SNP did not affect the risk of ALL in adulthood among Caucasians, or in childhood among East Asians. In conclusion, these findings confirm that the CEBPE rs2239633 SNP could be considered a good marker of pediatric ALL risk in Caucasians, but not in East Asians; it is not a good marker of adult ALL risk in Caucasians.

7.
Int J Mol Sci ; 16(2): 2732-46, 2015 Jan 26.
Article in English | MEDLINE | ID: mdl-25629231

ABSTRACT

The causes of chronic heart failure (CHF) and its progression are likely to be due to complex genetic factors. Adenosine receptors A2A and A2B (ADORA2A and ADORA2B, respectively) play an important role in cardio-protection. Therefore, polymorphisms in the genes encoding those receptors may affect the risk and severity of CHF. This study was a case-control comparative investigation of 300 northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls. Four common single-nucleotide polymorphisms (SNPs) of ADORA2A (rs2236625, rs2236624, rs4822489, and rs5751876) and one SNP of ADORA2B (rs7208480) were genotyped and an association between SNPs and clinical outcomes was evaluated. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. The rs4822489 was significantly associated with the severity of CHF after adjustment for traditional cardiovascular risk factors (p = 0.040, OR = 1.912, 95% CI = 1.029-3.550). However, the five SNPs as well as the haplotypes were not found to be associated with CHF susceptibility. The findings of this study suggest that rs4822489 may contribute to the severity of CHF in the northern Chinese. However, further studies performed in larger populations and aimed at better defining the role of this gene are required.


Subject(s)
Heart Failure/genetics , Receptor, Adenosine A2A/genetics , Receptor, Adenosine A2B/genetics , Aged , Asian People/genetics , Case-Control Studies , China , Chronic Disease , Disease Susceptibility , Female , Gene Frequency , Genotype , Haplotypes , Heart Failure/pathology , Humans , Linkage Disequilibrium , Logistic Models , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide , Risk Factors , Severity of Illness Index
8.
Int J Mol Sci ; 15(9): 15259-71, 2014 Aug 28.
Article in English | MEDLINE | ID: mdl-25170811

ABSTRACT

Adenosine (Ado) is an important cardioprotective agent. Since endogenous Ado levels are affected by the enzyme Ado deaminase (ADA), polymorphisms within the ADA gene may exert some effect on chronic heart failure (CHF). This study applied a case-control investigation to 300 northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls in which nine single-nucleotide polymorphisms (SNPs) of ADA were genotyped and association analyses were performed. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the association. Overall, rs452159 polymorphism in ADA gene was significantly associated with susceptibility to CHF under the dominant model (p = 0.013, OR = 1.537, 95% CI = 1.10-2.16), after adjustment for age, sex, and traditional cardiovascular risk factors. No difference in genotype distribution and allele frequency for the rs452159 according to the functional New York Heart Association class was found. Furthermore, the values of left ventricular ejection fraction, left-ventricle end-diastolic diameter or left-ventricle end-systolic diameter did not differ significantly among the different rs452159 genotype CHF patients. Although further studies with larger cohorts and other ethnicities are required to validate the conclusions, the findings of this study potentially provide novel insight into the pathogenesis of CHF.


Subject(s)
Adenosine Deaminase/genetics , Heart Failure/genetics , Polymorphism, Single Nucleotide , Aged , Case-Control Studies , China , Female , Humans , Male , Middle Aged
9.
Fitoterapia ; 84: 237-41, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23262269

ABSTRACT

Two new trisaccharide intermediates of phenylethanoid glycosides, peiioside A(1)/A(2) (1a/1b) and peiioside B (2), were isolated from the n-BuOH fraction of MeOH extract of the stems of Callicarpa peii H.T. Chang, together with five biogenetic relevant known compounds 3-7. The structures of compounds 1 and 2 were elucidated by extensive spectroscopic methods (especially 2D-NMR techniques) and acid-catalyzed hydrolysis as O-α-l-rhamnopyranosyl-(1″→3')-O-[ß-d-apiofuranosyl-(1‴→6')] -4'-O-[(E)-caffeoyl]-d-glucopyranoside] (1a/1b), 3,4-dihydroxy-ß-phenylethoxy-O-[ß-d-apiofuranosyl-(1‴→6')-α-l-rhamnopyranosyl-(1″→3')-O-ß-d-glucopyranoside] (2), respectively. On the basis of the isolated compounds, a presumable biogenetic pathway of the biologically interesting phenylethanoid glycosides about forsythoside B (3) and acteoside (4) isolated from this species was proposed. Isolation of five related intermediates (1-2, 5-7) provided further support for the biogenetic path. This is the first report about phytochemical research on C. peii and the biogenetic hypothesis of forsythoside B and acteoside.


Subject(s)
Callicarpa/chemistry , Glycosides/chemistry , Glycosides/pharmacology , Hemostatics/chemistry , Hemostatics/pharmacology , Animals , Molecular Structure
10.
J Pharm Anal ; 3(1): 61-65, 2013 Feb.
Article in English | MEDLINE | ID: mdl-29403797

ABSTRACT

Two phenylethanoid glycosides, acteoside and forsythoside B, were first isolated from the traditional Chinese herb Callicarpa peii H.T. Chang. The interaction between the two phenylethanoid glycosides and bovine serum albumin (BSA) was investigated by fluorescence, UV-vis absorbance and circular dichroism (CD). The results showed that the quenching mechanism in the drug-BSA binary systems was a combination of static quenching and non-radiative energy transfer. Displacement experiments confirmed that the drug bound to the site I of BSA. UV-vis and CD measurements indicated that the binding of the drug to BSA induced conformational changes in BSA.

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