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1.
Chen CH Lu ML Kuo PH Chen PY Chiu CC Kao CF Huang MC 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):239-245
Objective
Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.Methods
Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.Results
In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR = 2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.Conclusions
We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients. 相似文献2.
Introduction
Growing studies have revealed the underlying association between eNOS 894 G/T (rs1799983) polymorphism and coronary heart disease (CHD) among Asia population. Results from these studies remained conflicting. We conducted this meta-analysis to estimate the overall CHD risk of eNOS 894 G/T polymorphism regarding Asia population.Materials and methods
Up to October 2011, databases including PubMed, Embase and CNKI (China National Knowledge Infrastructure) were searched to access the relevant genetic association studies. Summary odds ratios and corresponding 95% confidence intervals (CIs) for eNOS 894 G/T polymorphism and CHD risk were estimated using fixed or random-effects models when appropriate.Results
18 case-control studies with 2,994 cases and 3,130 controls were available for this study, including 13 studies of East-Asia descendents, 5 studies of Non East-Asian descendents. The mean T allele frequency was 0.111 in the East-Asia population and 0.147 in the Non East-Asia population, respectively. The summary OR for CHD associated with the T allele was 1.52 (95% confidence intervals (95%CI), 1.37-1.69) by random effects model. Similarly, significantly increased risks were observed in the East-Asia population (OR = 1.54; 95%CI = 1.35-1.76) and in the Non East-Asia population (OR = 1.48; 95%CI = 1.24-1.77), respectively.Conclusions
This meta-analysis indicated that eNOS 894 G/T polymorphism may play an important role in CHD development among Asia population. 相似文献3.
Lazary J Viczena V Dome P Chase D Juhasz G Bagdy G 《Progress in neuro-psychopharmacology & biological psychiatry》2012,36(1):155-160
Objectives
Hopelessness is one of the strongest risk factors for suicidal behavior but relevant genetic studies are poorly available. Tryptophan hydroxylase (TPH) is widely considered to be a good candidate for genetic association studies on depression and suicide, however, investigations on these complex, multifactorial phenotypes have resulted in conflicting data. We hypothesized that hopelessness could be a mediating phenotype between TPH2 gene, depression and suicidal behavior.Methods
Depressive phenotype and suicidal risk were investigated of 760 individuals from general population by Zung Self Rating Depression Scale (ZDS), Beck's Hopelessness Scale (BHS) and a detailed background questionnaire. All participants' DNA samples were genotyped for 7 tag SNPs in TPH2 gene. Generalized linear models were performed for single marker association studies and p-values were corrected by Bonferroni criteria. In haplotype analyses score tests were used and permutated p-values were computed.Results
Four SNPs of TPH2 gene showed association with hopelessness but only rs6582078 had a significant effect on the BHS scores after Bonferroni's correction; GG individuals had significantly higher BHS scores, while GT and TT had intermediate and lower BHS scores respectively (p = 0.0047). Compared with other genotypes, homozygous GG individuals also had almost three times greater estimated suicidal risk, as did carriers of the AA genotype of rs6582078 (OR = 2.87; p = 0.005) and also of rs1352250 (OR = 2.86; p = 0.006). A risk and a protective haplotype of TPH2 gene were also identified in association with hopelessness. ZDS scores have not shown any association with TPH2 gene.Conclusions
We found that hopelessness, with its allied increased suicidal risk was strongly associated with TPH2 gene variants in multiple tests. These findings suggest that TPH2 gene confers risk for suicidal behavior while hopelessness can be a potential endophenotype for suicidal vulnerability. 相似文献4.
Introduction
Toll like receptor 4 (TLR4) expression was found to increase markedly in human atherosclerotic lesions, notably on macrophages and endothelial cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor activity and a subsequently diminished inflammatory response, and may subsequently reduce atherosclerosis (AS) risk. However, the results of molecular epidemiological studies remained inconsistent.Materials and methods
The PubMed, CNKI databases were searched for all articles available. The OR corresponding to the 95% confidence interval (95% CI) was used to assess the association between TLR4 Asp299Gly polymorphism and risk of AS.Results
15 case-control studies with 9,989 cases and 6,746 controls were available for this analysis. For control subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from 0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with significantly risk of AS (OR = 1.02, 95% CI = 0.83 - 1.26 for G versus A and OR = 0.96, 95% CI = 0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model.Conclusion
These findings indicated that TLR4 Asp299Gly polymorphism may not play a role in AS development. 相似文献5.
de Oliveira GN Kummer A Salgado JV Filho GM David AS Teixeira AL 《Epilepsy & behavior : E&B》2011,22(4):745-749
Objective
The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE).Methods
Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale.Results
A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P = 0.012), current major depression (P = 0.001), and motor impulsivity (P = 0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR = 12.82, 95% CI = 2.58-63.76, P = 0.002) and motor impulsivity (OR = 1.21, 95% CI = 1.06-1.38, P = 0.005) to suicide risk.Conclusion
Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk. 相似文献6.
Purpose
Several studies have reported apparently conflicting findings for the effects of tumor necrosis factor-alpha (TNF-α) G-308A polymorphism on coronary heart disease (CHD) susceptibility. We undertook a systematic review and meta-analysis to investigate the association between this gene variant and CHD predisposition.Methods
We systematically searched electronic databases (Medline, EMbase, Chinese BioMedical, BIOSIS, Global Health, PsycINFO, Allied and Complementary Medicine Database, Cochrane Library, HuGE Navigator, and British Nursing) for relevant studies published between 1947 and October, 2010. Summarized estimation of odds ratio (OR) and 95% confidence interval (CI) were calculated. Publication bias and heterogeneity among studies were explored.Results
We identified 24 studies providing data for 9 921 cases and 7 944 controls. Pooled analysis based on ORs adjusted by CHD risk factors showed that carrying the TNF-α gene A variant conferred a 1.5-fold increased risk of developing CHD (AG + AA vs. GG, OR = 1.50, 95% CI: 1.23-1.77) in Caucasian population. No significant association between the gene polymorphism and CHD risk could be found in other ethnic groups.Conclusions
It is probable that carrying the A variant is associated with CHD risk in Caucasians but not in Asians, Indians, or Africans. Further studies are merited to assess the association in greater details, especially in Asians, Indians and Africans. 相似文献7.
G Lian Y Yan L Jianxiong X Juanjuan C Qing W Guangliang S Li 《Thrombosis research》2012,130(3):e95-e102
Background
In 2009, a GWAS has confirmed that rs11833579 and rs12425791 near the NINJ2 gene could increase the stroke and ischemic stroke (IS) risk. Recently, several studies have been implemented to assess the relationship between the two SNPs and ischemic stroke risk in Asian. However, the results were poorly consistent. To study the association between the both polymorphisms and the risk of ischemic stroke, we performed a meta-analysis.Methods
We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of association. The heterogeneity was checked by Q test and the inconsistency index (I2). Begg's test and Egger's test were used to assess the possible publication bias.Results
Our study included 6 articles, contained 9 independent case-control studies, involved a total of 9,142 cases and 10,652 controls about rs11833579, 10,165 cases and 11,592 controls about rs12425791. There was a significant association between rs12425791 and IS risk with dominant genetic model (OR = 1.087, 95%CI = 1.021-1.158, I2 = 34.6%, P = 0.152), but not with recessive genetic model and allele A vs. allele G. For rs11833579, we failed to verify it relate with IS risk under allele A vs. allele G, dominant and recessive genetic model.Conclusions
This meta-analysis suggest that rs12425791 is relative to ischemic stroke risk under dominant model in Asian population, but not for rs11833579. 相似文献8.
Otowa T Kawamura Y Sugaya N Yoshida E Shimada T Liu X Tochigi M Umekage T Miyagawa T Nishida N Kaiya H Okazaki Y Tokunaga K Sasaki T 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(2):545-549
Background
Panic disorder (PD) is a severe and chronic psychiatric disorder with genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B) gene has been reported to be associated with several psychiatric disorders. Several studies indicated that PDE4B may be involved in the regulation of anxiety and depression. Therefore, we investigate the association of PDE4B with PD in the Japanese population.Methods
We genotyped 14 single nucleotide polymorphisms (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162 males and 245 females). Differences in the genotype, allele and haplotype frequencies between the two groups were compared.Results
We found a significant association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A, permutation P = 0.031, OR = 1.81, 95% CI = 1.30-2.51). Sex-specific analyses demonstrated that PDE4B was associated with PD in females in the allele/genotype and haplotype analyses (rs10454453, allele P = 0.042, genotype P = 0.0034; haplotype C-T-T-A, permutation P = 0.028).Conclusion
Our results suggest that PDE4B may play a role in the pathophysiology of PD in the Japanese population. Replication studies using larger samples will be needed for more reliable conclusions. 相似文献9.
Chen Q Cai ZJ Mao PX Zhai YM Mitchell PB Tang YL 《Journal of psychiatric research》2008,43(2):124-128
Background
While most of the second generation antipsychotic agents are associated with abnormal glucose metabolism, previous studies have shown that risperidone has relatively little effect upon blood glucose levels. This study aimed to explore the effect of risperidone on the glucose-regulating mechanism of patients with schizophrenia by using the oral glucose tolerance test (OGTT), measuring insulin and C-peptide levels.Methods
Thirty inpatients with schizophrenia taking risperidone were studied. All the patients were given a simplified OGTT at baseline and six weeks after treatment. Plasma glucose, insulin, and C-peptide concentrations were measured at fasting, then 1 and 2 h after OGTT respectively. Other data, including demographic characteristics and plasma drug concentrations, were also recorded.Results
(1) There was no significant increase in the proportion of patients demonstrating abnormal plasma glucose levels compared with baseline (p = 1.000, McNemar test); (2) risperidone was associated with elevated insulin concentrations (p = 0.013), C-peptide levels (p = 0.020), insulin/glucose ratio (p = 0.020) and BMI (p < 0.01); (3) no sex differences in glucose-related measures were observed.Conclusion
Risperidone treatment may be associated with alterations in glucose-regulating mechanisms in patients with schizophrenia. 相似文献10.
LL Gong JH Peng FF Han J Zhu LH Fang YH Wang GH Du HY Wang LH Liu 《Thrombosis research》2012,130(3):e43-e51
Introduction
To investigate whether t-PA Alu repeat insertion/deletion (I/D) and PAI-1 4 G/5 G genetic variations are associated with the risk of MI.Methods
We conducted a meta-analysis to assess the association between the t-PA I/D and PAI-1 4 G/5 G polymorphisms and risk of MI. We also performed subgroup analyses based on ethnicity (Caucasian, Asian, and African), gender and age. Forty one eligible studies including 12,461 cases and 14,993 controls were identified to evaluate the impact of PAI-1 4 G/5 G polymorphism on MI. Seven studies investigated the relationship between t-PA I/D and MI.Results
This meta-analysis revealed that the PAI-1 4 G allele (4 G/4 G and 4 G/5 G genotype) was associated with an increased risk of MI compared with the 5 G allele in the overall population (OR = 1.094, 95% CI = 1.021 - 1.172, p = 0.011). The relative risks of MI for 4 G/4 G genotype was increased when compared to 5 G/5 G genotype and 5 G allele, with odds ratio at 1.157 (95% CI 1.015 - 1.320, p = 0.029) and 1.126 (95% CI = 1.015 - 1.249, p = 0.025). However, the results show that the 4 G/5 G polymorphism risk for MI was not associated with ethnicity stratification as Caucasian, Asian or African population. No substantial differences in the genotype distributions were observed in the MI group and control group along the lines of gender and age. After multivariable analysis t-PA I/D polymorphism showed no consistent association with MI.Conclusions
This study suggests that the 4 G/5 G polymorphism of PAI-1 may be a risk factor for MI in overall populations. 相似文献11.
Nan Li 《Brain research bulletin》2010,81(1):38-42
Background
The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites. However, little is known about whether this association could also occur in Han Chinese.Method
A total of 371 patients with IS and unrelated healthy controls were recruited and the SNPs of the PDE4D (83T/C), (87T/C), IL-1 (−889C/T) and IL-1 (−511C/T) were characterized, respectively, by polymerase chain reactions-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequencies of these SNPs in this population were statistically analyzed.Results
The genotype and allele frequencies of the PDE4D (87T/C) and IL-1 (−511C/T) were similar between IS patients and controls. In contrast, the frequencies of CC genotype and C allele of the PDE4D (83T/C) and the T allele frequency of IL-1 (−889C/T) in IS patients were significantly higher than that in healthy controls (p = 0.001, p = 0.003 and p = 0.02, respectively), independent of the conventional risk factors. The values of odds ratio (OR) reached at OR = 1.603; 95%CI = 1.032-2.489; p = 0.036 for the CC genotype of the PDE4D (83T/C) and OR = 1.913; 95%CI = 1.621-2.375; p = 0.034 for the TT genotype of the IL-1 (−889C/T), respectively.Conclusions
the SNPs of the PDE4D (83T/C) and IL-1 (−889C/T) were associated with increased risk for the development of IS in Northern Han Chinese. 相似文献12.
Dragoni F Chiarotti F Rosano G Simioni P Tormene D Mazzucconi MG Cafolla A Avvisati G 《Thrombosis research》2011,127(2):85-90
Introduction
Despite extensive clinical and laboratory investigations, the etiology of ischemic stroke remains unknown in approximately one third of patients.Materials and Methods
Thirty-four consecutive patients less than 40 years old (Males 13, Females 21, mean age 26.6 years, range 2-39) with documented ischemic stroke underwent, one year after the acute event, laboratory evaluation of antithrombin, protein C, free and total protein S, activated protein C resistance, fibrinogen, factor VII:C, homocysteine levels and antiphospholipid antibodies (APA). Moreover, prevalence of F5 R506Q, F2 G2021A and homozygosis for thermolabile variant C677T of the methylenetetrahydrofolate reductase (MTHFR) were also evaluated and compared to the results obtained in 120 normal controls.Results
Antithrombin and protein C levels resulted normal in all cases. One patient (2.9%) showed free protein S deficiency and 3 patients (8.8%) had activated protein C resistance. Homocysteine levels above 15 μmol/L were found in one patient (2.9%). APA were found in 21 patients (61.7%) and in only 2 out of 120 (1.66%) controls (OR = 95.31; 95% C.I.: 18.22-667.81). The multivariate analysis selected that the presence of APA was significantly associated with an increased risk of stroke (OR = 156.60; 95% C.I.: 25.99-943.47) in this cohort of patients. The combination between APA and cardiovascular risk factors determined a risk of 29-fold (OR = 29.31; 95% CI: 3.28-261.69).Discussion
Our data suggest that the presence of APA is associated with an increased risk of idiopathic ischemic stroke in young patients. Furthermore, also the combination of APA and cardiovascular risk factors is significantly associated with development of idiopathic ischemic stroke. 相似文献13.
Hsiang-Yi Tsai Kao Chin Chen Yen Kuang Yang Po See Chen Tzung Lieh Yeh Nan Tsing ChiuI Hui Lee 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):107-110
Background
In addition to the serotonergic system, the central dopaminergic system has been reported to be correlated with seasonality. The aim of this study was to explore the difference in striatal dopamine D2/D3 receptor availability between healthy volunteers who had a high-sunshine exposure and those who had a low exposure.Methods
Sixty-eight participants were enrolled, and those in the upper and lower quartiles in terms of sunshine exposure were categorized into high- (n = 17) and low-sunshine-exposure (n = 18) subgroups. Single photon emission computed tomography with [123I] iodo-benzamide was used to measure striatal dopamine D2/D3 receptor availability.Results
Striatal dopamine D2/D3 receptor availability was significantly greater in the subjects with high-sunshine exposure than in those with low-sunshine exposure (F = 7.97, p = 0.01) after controlling for age, sex, and smoking status.Limitations
Different subjects were examined at different time points in our study. In addition, the sex and tobacco use distributions differed between groups.Conclusion
The central dopaminergic system may play a role in the neurobiological characteristics of sunshine-exposure variation. 相似文献14.
Introduction
Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.Materials and methods
We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.Results
Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).Conclusion
Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE. 相似文献15.
Abbott C Juárez M White T Gollub RL Pearlson GD Bustillo J Lauriello J Ho B Bockholt HJ Clark VP Magnotta V Calhoun VD 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(2):473-482
Background
The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.Methods
Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.Results
Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = − 0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t77 = 2.01, P = 0.048).Conclusion
The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia. 相似文献16.
Introduction
Several inflammatory markers have been shown to be independent predictors for both the development of clinically significant atherosclerosis and for adverse outcome in patients with symptomatic coronary artery disease (CAD). We investigated the prognostic role of eosinophil count in low to intermediate risk patients with CAD.Methods
We studied 909 patients admitted for elective or urgent percutaneous coronary intervention (PCI) from April 2002 to December 2004, and measured pre-procedural total and differential white blood cell (WBC) counts. Inter-tertile WBC differences in short (6 months) and long term (up to 74 months) mortality were analysed after adjusting for differences in baseline characteristics.Results
Over a median period of 54 months (inter-quartile range 47-65), a total of 138 deaths (15.2%) occurred, of which 24 were in the first 6 months of follow-up. Cox regression analysis showed that high pre-procedural eosinophil count (top tertile) was associated with improved outcome within the first 6 months (OR = 0.23 [0.06-0.84]; p = 0.03) but after this period there was an increased risk of mortality (OR = 2.21, [1.26-3.88]; p = 0.006).Conclusions
Eosinophil count is a novel biomarker for risk stratification of CAD patients, which was associated initially with reduced mortality, but after 6 months with increased mortality. 相似文献17.
18.
Introduction
Plasma serine protease thrombin plays a key role in coagulation, haemostasis and thromboembolic diseases. Direct thrombin inhibitors could be beneficial for future anticoagulant therapy. We have synthesized and studied liporetro-D-peptides - efficient thrombin inhibitors resistant to enzymatic degradation.Materials and Methods
Compounds X-D-Arg-D-Phe-OMe, where X = residue of lauric or myristic acid or 9-fluorenylmethoxycarbonyl, have been synthesized by conventional peptide synthesis in solution and their comparative inhibitory analysis in relation to thrombin, factor X, plasmin and trypsin has been conducted.Results
Modification of the synthetic liporetro-D-peptides with the myristic acid residue was the most successful one. This modification has dramatically increased the inhibition efficacy (Ki = 0,17 μM) and selectivity toward the chosen target enzyme, thrombin, in comparison to factor X, plasmin and trypsin (more than 600, 900, and 5000-fold, respectively).Conclusions
Our findings establish an important role of the fatty moiety in the structure of peptide inhibitors with regards to their potency and selectivity toward thrombin. 相似文献19.
Campbell EC DeJesus M Herman BK Cuffel BJ Sanders KN Dodge W Dhopesh V Caroff SN 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):246-251
Background
Evidence on antipsychotic prescribing decisions is limited. This pilot study quantified factors considered in choosing an antipsychotic and evaluated the influence of metabolic status on treatment decisions.Methods
Prescribing decisions by 4 psychiatrists were examined based on 80 adult patients initiated on antipsychotic medication diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder by DSM-IV criteria, who were admitted to an acute inpatient psychiatric program of an urban Veterans Affairs Medical Center. The primary analysis examined the association between antipsychotic treatment choice and predictions of symptom control and metabolic risk. Secondary analyses included comparison of the chosen and next best treatments in predicted symptom control and metabolic risk, the frequency of reasons cited for drug choice, and the association between treatment choice and patients' baseline metabolic parameters. Mean differences and odds-ratios (OR) with 95% confidence intervals were used to compare relationships between treatment choice, ratings of risk and metabolic data.Results
Antipsychotic choice correlated significantly with ratings of predicted symptom control (OR = .92, p = 0.02) and metabolic risk (OR = .88, p = 0.01). Mean differences between the chosen and next best drugs were significant but small in predicted symptom control (F = 2.81, df = 3, 76; p < 0.05) compared with larger differences in anticipated metabolic risk (F = 14.80, df = 3, 76; p = 0.0001). Nevertheless, among 24 identified reasons influencing drug selection, anticipated metabolic risk of chosen antipsychotics was cited less often than efficacy measures. In contrast to psychiatrists' expectations of metabolic risk with selected treatments, we found that patients' actual baseline BMI, fasting glucose, blood pressure, and Framingham risk levels did not necessarily predict antipsychotic treatment choice independent of other factors.Conclusion
In the context of an acute psychiatric hospitalization, pilot data suggest that predictions of symptom control and metabolic risk correlated significantly with antipsychotic choice, but study psychiatrists were willing to assume relative degrees of metabolic risk in favor of effective symptom control. However, prescribing decisions were influenced by numerous patient and treatment factors. These findings support the potential utility of the ATCQ questionnaire in quantifying antipsychotic prescribing decisions. Further validation studies of the ATCQ questionnaire could enhance translation of research findings and application of treatment guidelines. 相似文献20.