Search

We compared midterm prognostic predictors of peripheral artery disease (PAD) with or without diabetes mellitus (DM) presenting with critical lower limb ischemia (CLI). A total of 172 patients with PAD (109 DM; 63 non-DM) were enrolled. The major adverse events (MAEs) were death or amputation. The diabetic group had a higher MAE rate (39% vs 22%, P = .042) with a mean follow-up duration of 30 ± 19 months. In a multivariate binary logistic regression analysis, revascularization (odds ratio = 0.289, P = .006) and higher serum cholesterol (odds ratio=0.988, P = .027) predicted a lower MAE rate in the DM group. In contrast, the presence of severe chronic kidney disease (stage 4 or 5, odds ratio = 5.238, P = .025) was a positive predictor of MAEs in the nondiabetic group. In conclusion, the prognostic predictors of MAE in diabetic and nondiabetic patients with PAD and CLI were different.

Caveolin-1 (CAV-1) participates in regulating vesicular transport, signal transduction, tumor progression, and cholesterol homeostasis. In the present study, we tested the hypothesis that CAV-1 improves dyslipidemia, inhibits cyclophilin A (CypA)- mediated ROS production, prevents mitochondrial compensatory action and attenuates oxidative stress responses in cholesterol-induced hypercholesterolemia. To determine the role of CAV-1 in mediating oxidative and antioxidative as well as cholesterol homeostasis, hypercholesterolemic rabbits were intravenously administered antenapedia-CAV-1 (AP-CAV-1) peptide for 2 wk. AP-CAV-1 enhanced CAV-1 expression by ˃15%, inhibited CypA expression by ˃50% (P < 0.05) and significantly improved dyslipidemia, thus reducing neutral lipid peroxidation. Moreover, CAV-1 attenuated hypercholesterolemia-induced changes in mitochondrial morphology and biogenesis and preserved mitochondrial respiratory function. In addition, CAV-1 protected against hypercholesterol-induced oxidative stress responses by reducing the degree of oxidative damage and enhancing the expression of antioxidant enzymes. CAV-1 treatment significantly suppressed apoptotic cell death, as evidenced by the reduction in the number of terminal deoxynucleotidyl transferase dUTP nick end-labeling-positive cells. We concluded that CAV-1 plays a critical role in inhibiting CypA-mediated ROS production, improving dyslipidemia, maintaining mitochondrial function, and suppressing oxidative stress responses that are vital for cell survival in hypercholesterol-affected renal organs.

Background Transcatheter device closure of postmyocardial infarction ventricular septal defect (PMIVSD) is less invasive than surgical repair. However, its feasibility, timing, outcome, and prognostic factors remain unclear. Methods This was a multicenter, retrospective cohort study. Between February 2012 and July 2015, a total of 10 (8 male and 2 female) patients with PMIVSD undergoing attempted device closure were enrolled retrospectively. The procedures were performed under general anesthesia with fluoroscopic and transesophageal echocardiographic guidance. Results The patients enrolled in the study were in the age range 50–85 years (median age of 76.5 years). The interval from infarction to device closure ranged from 6–147 days, with the median of 12 days. A total of 13 devices were implanted in 10 patients. There were five Amplatzer muscular ventricular septal defect occluders, four Amplatzer septal occluders, three Amplatzer PMIVSD occluders and one Amplatzer vascular plug II. Complications included transient ventricular tachycardia in three patients, device embolization in one patient, and tracheal bleeding in one patient. No procedure-related death, stroke, or cardiac tamponade was noted. During follow-up, two patients died of heart failure and two patients died of sepsis. Overall, subjects with age ≥ 80 years, systolic blood pressure ≤ 90 mmHg, and procedure time ≥180 minutes were significant predictor factors for mortality. All patients with the interval of infarction to device closure >12 days survived. Conclusion Our findings indicate that transcatheter device closure of PMIVSD is technically feasible, safe, and effective to reduce the shunt. The crucial prognostic factors were ascertained to be age ≥ 80 years, systolic blood pressure ≤ 90 mmHg, and procedure time ≥180 minutes.

Stem cell transplantation may repair the infarcted heart. Despite the encouraging preliminary results, an optimal cell type used and low retention of the transplanted cells remain to be overcome. In this study, a multiwelled methylcellulose hydrogel system was used to cultivate human amniotic-fluid stem cells (hAFSCs) to form spherically symmetric cell bodies for cellular cardiomyoplasty. The grown hAFSC bodies enriched with extracellular matrices (ECM) were xenogenically transplanted in the peri-infarct area of an immune-suppressed rat, via direct intramyocardial injection. Results of bioluminescence imaging and real-time PCR revealed that hAFSC bodies could considerably enhance cell retention and engraftment in short-term and long-term observations, when compared with dissociated hAFSCs. Echocardiography and magnetic resonance imaging showed that the enhanced cell engraftment in the hAFSC-body group could significantly attenuate the progression of heart failure, improve the global function, and increase the regional wall motion. At the infarct, expressions of HGF, bFGF and VEGF were significantly up-regulated, an indication of the significantly increased vessel densities in the hearts treated with hAFSC bodies. The injected hAFSC bodies could undergo differentiation into angiogenic and cardiomyogenic lineages and contribute to functional benefits by direct regeneration. The aforementioned results demonstrate that hAFSC bodies can attenuate cell loss after intramuscular injection by providing an adequate physical size and offering an enriched ECM environment to retain the transplanted cells in the myocardium, thus improving heart function.

Background Percutaneous transvenous mitral commissurotomy (PTMC) is an effective treatment for mitral stenosis, but transseptal puncture carries a certain risk of complications. Our previous report has shown the effectiveness of phase-array intracardiac echocardiography (ICE)-guided transseptal puncture in patients with dilated left atrium undergoing PTMC. However, there are few reports comparing the new-generation mechanical versus phase-array ICE-guided transseptal puncture in PTMC. Methods Between March 2007 and March 2008, 6 consecutive patients with symptomatic mitral stenosis with dilated left atrium (range, 4.1–6.1 cm) underwent transseptal puncture by mechanical ICE guidance in PTMC by the same experienced operator. The procedural, echocardiographic and clinical results were retrospectively retrieved and analyzed. In addition, phase-array ICE-guided transseptal cases ( n = 7), which included consecutive cases from May to December 2008, were compared. Results All 6 patients could have fossa ovalis visualized by ICE, and none of them had false transseptal puncture. Mechanical ICE provided a panoramic wider view of the interatrium septum, and offered better knowledge of the needle's geographic contact to the fossa ovalis than did the phase-array system. The fluoroscopic time of PTMC in the mechanical ICE-guided group (37 ± 9 minutes, n = 6) was similar ( p = 0.465) to that of phase-array guidance (31 ± 15 minutes, n = 7). Conclusion Mechanical ICE is effective in guiding transseptal puncture in PTMC.

Background: Several studies have suggested that the serotonin receptor 1B gene (5HT1B) may be important in the pathogenesis of alcohol dependence (alcoholism; ALC; AD). We examined whether 5HT1B gene A-161T polymorphisms (rs130058) are a susceptibility factor for total AD and subgroups of AD. We further explored correlation of this 5HT1B gene variant between anxiety–depression alcoholism (ANX/DEP ALC) and antisocial alcoholism (antisocial ALC) subgroups because of the high comorbidity of anxiety–depression, antisocial personality disorder, and AD. Methods: We recruited 522 Han Chinese in Taiwan for this study: 322 AD patients and 200 controls. The patient group was recruited primarily from medical teaching hospitals; patients with antisocial alcoholism were recruited from Taiwanese prisons. Individuals with AD were classified into 3 homogeneous clinical subgroups—pure alcoholism (pure ALC), ANX/DEP ALC, and antisocial ALC—using DSM-IV diagnosis. The 5HT1B gene A-161T polymorphism was determined using PCR–RFLP. Results: No significant differences in genotypic and allelic frequencies were found between controls and the total AD group or between controls and the 3 AD subgroups. However, there were significant differences in the 5HT1B gene A-161T polymorphism at both the genotype and allelic levels between the ANX/DEP ALC and antisocial ALC subgroups. Conclusions: This study suggests that the 5HT1B gene A-161T polymorphism alone is not a risk factor for increasing susceptibility to either AD or its subtypes. However, 5HT1B gene A-161T polymorphisms might be one of the common genetic factors between the ANX/DEP ALC and antisocial ALC subgroups.

Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extracellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation.

It has been proposed that an MAOA abnormality may be an important factor in the development of major depressive disorder (MDD). Various polymorphisms of the MAOA gene have been investigated for possible associations with mood disorders, but results have been inconsistent. The goal of the present study was to investigate whether polymorphisms of the MAOA gene are associated with MDD or alternatively with different clinical subgroups of MDD. A total of 590 Han Chinese subjects in Taiwan (312 controls and 278 MDD patients) were recruited. Among the males, there were no associations with MAOA polymorphisms. Among the females, an association was found between MAOA polymorphisms and severe MDD (P=0.041 for uVNTR and 0.017 for EcoRV (rs1137070), respectively). However, in analyses of haplotype frequencies and multiple logistic regression, MAOA polymorphisms were not associated with either MDD or its subgroups. The results suggest that MAOA polymorphisms do not play a major role in the pathogenesis of MDD or its subgroups. However, a potential role for a minor association with some specific subgroups and with different ethnic samples needs to be explored further.

Aims To provide the basis for uniform cardiac tissue regeneration, a spatially uniform distribution of adhered cells within a scaffold is a prerequisite. To achieve this goal, a bioengineered tissue graft consisting of a porous tissue scaffold sandwiched with multilayered sheets of mesenchymal stromal cells was developed. Methods and results This tissue graft (sandwiched patch) was used to replace the infarcted wall in a syngeneic Lewis rat model with an experimentally chronic myocardial infarction (MI). There were four treatment groups ( n ≥ 10): sham, MI, empty patch, and sandwiched patch. After a 7 day culture of the sandwiched patch, a tissue graft with relatively uniform cell concentrations was obtained. The cells were viable and tightly adhered to the tissue scaffold, as the endogenous extracellular matrix inherent with multilayered cell sheets can act as an adhesive agent for cell attachment and retention. At retrieval, the area of the empty patch was relatively enlarged, suggesting reduced structural support, while that of the sandwiched patch remained about the same ( P = 0.56). In the immunofluorescent staining, host cells together with neo-microvessels were clearly observed in the empty patch; however, there were still a large number of unfilled pores within the patch. In the sandwiched patch, besides host cells, originally seeded cells were populated within the entire patch. No apparent evidence of apoptotic cell death was found in both studied patches. Thus, the sandwiched-patch-treated hearts demonstrated a better heart function to the empty-patch-treated hearts ( P < 0.05). Conclusion The results demonstrated that this novel bioengineered tissue graft can serve as a useful cardiac patch to restore the dilated left ventricle and stabilize heart functions after MI.

Monoamine oxidase A (MAOA) abnormality has been suggested as a crucial factor in the pathogenesis of mood disorder, because MAOA is associated with the metabolism of monoamines such as serotonin and norepinephrine. Various MAOA gene polymorphisms have been investigated for possible associations with bipolar disorder (BD), but the results are controversial. Our goal was to investigate whether MAOA gene polymorphisms, especially the promoter uVNTR polymorphism and the EcoRV polymorphism, are associated either with BD or with different clinical subtypes of BD. A total of 714 Han Chinese subjects in Taiwan (305 controls and 409 BD patients) were recruited for study. All subjects were interviewed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime; BD was diagnosed according to DSM-IV criteria. Genotyping for MAOA polymorphisms was performed using PCR and restriction fragment length polymorphism. The MAOA promoter polymorphisms uVNTR and EcoRV were not associated with BD or any of its subtypes, in either the frequencies of alleles or genotypes. In multiple logistic regression and haplotype frequency analysis, we confirmed these negative results in both females and males. Our results suggest that MAOA polymorphisms do not play a major role in pathogenesis of BD or its clinical subtypes in Han Chinese.

OBJECTIVE: Asian populations may differ from other races in response to antipsychotics. Studies of aripiprazole in Asian populations are scarce. This study aimed to investigate the efficacy, safety, and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder. METHOD: This 4-week, double-blind, randomized, parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005. A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomly assigned (with a randomization ratio of 3:2) to 15 mg/day of aripiprazole (N = 49) or 6 mg/day of risperidone (N = 34). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were assessed as measures of safety and tolerability. RESULTS: Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total, PANSS positive, PANSS negative, and CGI-S scores at study endpoint (all p < .001). Significant improvement was noted in the first week of treatment for both treatment groups. There were no significant differences in efficacy measures between treatment groups. Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale (p < .005) and less serum prolactin level elevation (p < .001) than risperidone. Both groups showed mild weight gain. No patients showed clinically significant QTc interval prolongation in this study. CONCLUSION: Compared with risperidone 6 mg/day, aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia. In this group of Chinese patients, the overall response to aripiprazole did not differ from that of white patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00283179.

Many studies have indicated that the norepinephrine transporter (NET) may play an important role in the mechanisms underlying affective disorders. Thus, the genes of the NET (SLC6A2) are good candidates for research on bipolar disorder (BPD). This study examined whether the NET gene is a susceptibility factor for the BPD in Han Chinese. A promoter -182 T/C polymorphism (rs 2242446) and the exonic polymorphism 1287 G/A (rs 5569) of the NET gene were analysed using a polymerase chain reaction (PCR)-based method in 261 BPD patients and 245 unrelated, age- and gender-matched controls. Furthermore, to reduce the clinical heterogeneity, we also carried out analysis in clinical subgroups of bipolar patients defined according to type I and type II BPD, presence or absence of family history of major affective disorders and the age at onset of BPD. No significant difference was found between either bipolar patients or its more homogeneous subgroups and healthy controls in the genotype and allele frequencies for the investigated NET polymorphisms. Our results suggest that the investigated polymorphisms of NET are not major risk factors responsible for predisposition to BPD or its clinical subtypes in Han Chinese. However, replication studies with larger different ethnic samples are needed.

Both monoamine oxidase A (MAOA) and dopamine D2 receptor (DRD2) genes have been considered as candidate genes for antisocial personality disorder with alcoholism (Antisocial ALC) [Parsian, A., 1999. Sequence analysis of exon 8 of MAO-A gene in alcoholics with antisocial personality and normal controls. Genomics. 45, 290–295.; Samochowiec, J., Lesch, K.P., Rottmann, M., Smolka, M., Syagailo, Y.V., Okladnova, O., Rommelspacher, H., Winterer, G., Schmidt, L.G., Sander, T., 1999. Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatry. Res. 86, 67–72.; Schmidt, L.vG., Sander, T., Kuhn, S., Smolka, M., Rommelspacher, H., Samochowiec, J., Lesch, K.P., 2000. Different allele distribution of a regulatory MAO-A gene promotor polymorphism in antisocial and anxious-depressive alcoholics. J. Neural .Transm. 107, 681–689.]. However, the association between alcoholism and MAOA or DRD2 gene has not been universally accepted [Lee, J.F., Lu, R.B., Ko, H.C., Chang, F.M., Yin, S.J., Pakstis, A.J., Kidd, K.K., 1999. No association between DRD2 locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population. Alcohol. Clin. Exp. Res. 23, 592–599.; Lu, R.B., Lin, W.W., Lee, J.F., Ko, H.C., Shih, J.C., 2003. Neither antisocial personality disorder nor antisocial alcoholism association with MAOA gene among Han Chinese males in Taiwan. Alcohol. Clin. Exp. Res. 27, 889–893.]. Since dopamine is metabolized to 3,4-dihydroxyphenyl-acetaldehyde (DOPAL) via monoamine oxidase (MAO) [Westerink, B.H., de Vries, J.B., 1985. On the origin of dopamine and its metabolite in predominantly noradrenergic innervated brain areas. Brain. Res. 330, 164–166.], the interaction between MAOA and DRD2 genes might be related to Antisocial ALC. The present study aimed to determine whether Antisocial ALC might be associated with the possible interactions of DRD2 gene with MAOA gene. Of the 231 Han Chinese subjects who were recruited for the study, 73 participants were diagnosed with Antisocial ALC and 158 subjects were diagnosed with antisocial personality disorder without alcoholism (Antisocial Non-ALC). The DRD2 TaqI A and MAOA-uVNTR (variable number of tandem repeat located upstream) polymorphisms were not found to be associated with Antisocial ALC. However, an association between DRD2 TaqI A polymorphisms and Antisocial ALC was shown only after stratification for the MAOA-uVNTR 4-repeat polymorphism. Additionally, after multiple logistic regressions, we found that, under stratification of MAOA-uVNTR 4-repeat polymorphism and in comparison with the DRD2 A1/A1 genotype as a reference group, the DRD2 A1/A2 genotype has a possible protective effect against alcoholism in individuals with antisocial personality disorder (ASPD). We concluded that the possible interactions between MAOA-uVNTR polymorphism and DRD2 TaqI A polymorphism might be related to Antisocial ALC among Han Chinese men in Taiwan.

Hypereosinophilic syndrome (HES) describes a disorder characterized by persistent peripheral blood eosinophilia with evidence of multiple target organs damage caused by eosinophilia. HES most commonly involves the heart, and cardiac involvement typically presents in the form of endomyocarditis or myocarditis with apical mural thrombus formation. We present a case with atypical cardiac presentation with massive intracardiac fragile thrombi, causing peripheral emboli and strokes. HES can present as floating thrombi with thin attachment to the left ventricle, and clinicians should also be vigilant of thromboembolic complications and initiate early therapy to prevent or reduce the potential complications of HES.

Rationale: In atherosclerotic lesions, synthetic smooth muscle cells (sSMCs) induce aberrant microRNA (miR) profiles in endothelial cells (ECs) under flow stagnation. Increase in shear stress induces favorable miR modulation to mitigate sSMC-induced inflammation. Objective: To address the role of miRs in sSMC-induced EC inflammation and its inhibition by shear stress. Methods and Results: Coculturing ECs with sSMCs under static condition causes initial increases of 4 anti-inflammatory miRs (146a/708/451/98) in ECs followed by decreases below basal levels at 7 days; the increases for miR-146a/708 peaked at 24 hours and those for miR-451/98 lasted for only 6 to 12 hours. Shear stress (12 dynes/cm 2 ) to cocultured ECs for 24 hours augments these 4 miR expressions. In vivo, these 4 miRs are highly expressed in neointimal ECs in injured arteries under physiological levels of flow, but not expressed under flow stagnation. MiR-146a, miR-708, miR-451, and miR-98 target interleukin-1 receptor–associated kinase, inhibitor of nuclear factor–κB kinase subunit-γ, interleukin-6 receptor, and conserved helix-loop-helix ubiquitous kinase, respectively, to inhibit nuclear factor–κB signaling, which exerts negative feedback control on the biogenesis of these miRs. Nuclear factor-E2–related factor (Nrf)-2 is critical for shear-induction of miR-146a in cocultured ECs. Silencing either Nrf-2 or miR-146a led to increased neointima formation of injured rat carotid artery under physiological levels of flow. Overexpressing miR-146a inhibits neointima formation of rat or mouse carotid artery induced by injury or flow cessation. Conclusions: Nrf-2–mediated miR-146a expression is augmented by atheroprotective shear stress in ECs adjacent to sSMCs to inhibit neointima formation of injured arteries.

Pulmonary arterial hypertension (PAH) is a rare disease but with significant morbidity and high mortality. There is no specific way to diagnose PAH. Thus, an easy used with good sensitivity and specificity biomarker of PAH is highly desirable to aid in the screening, diagnosis, and follow-up. Caveolin-1 (Cav1) is the structural protein of caveolae and is highly expressed in type I pneumocytes. Lungs tissues from idiopathic PAH (IPAH) patients showed decreased expression of Cav1 in vascular endothelial cells. Therefore, we developed a direct sandwich immunoassay for the determination of Cav1 in IAPH patient’s serum. The result disclosed serum Cav1 level was significantly lower in IPAH than control groups. Using serum Cav1, 17.17 pg/mL as a cutoff value, the sensitivity was 0.59 and the specificity was 1.0. There were two major findings in our results. First, serum Cav1 might be a novel biomarker in the diagnosis of IPAH with fare sensitivity and good specificity. Second, Cav1 might be used to make differential diagnosis between COPD-PH and IPAH group.

Background: Thomasson et al., (1991) suggested that the genetic variation at ADH1B and ALDH2 influences the risk of alcoholism. The ADH1B*2 and ALDH2*2 alleles had been thought to be protective against alcoholism. Recent studies have suggested that either physiological tolerance of blood acetaldehyde, or innate insensitivity to it, or both may play a crucial role in keeping alcoholism from developing by protecting against adverse reactions. ALDH inactive form resulting from ALDH2*2, which slows the elimination of acetaldehyde and the more active isozymes produced by ADH1B*2, could generate higher acetaldehyde levels and thus deter heavy drinking (Thomasson et al., 1991). The genotype frequency of ADH1B*2/*2 and ALDH2*(1/*2 or 2/*2), which are regarded protective against drinking behavior, is about 70% and 50%, respectively, among the Han Chinese population in Taiwan (Chen et al., 1999a). Most previous studies, however, have failed to separate the effects of antisocial personality disorder from those of alcoholism because of their high comorbidity. To understand the relationship among alcoholism, antisocial personality disorder, and the protective effects of ADH and ALDH, it is necessary to recruit individuals with antisocial personality disorder but without alcoholism. This study was designed to stratify subjects by various ADH1B and ALDH2 genotypes for a more effective association study. The strata were: antisocial alcoholics, antisocial non-alcoholics, community alcoholics, and normal controls. Methods: We recruited 579 Han Chinese individuals in Taiwan, intending to examine the alcoholism-protection effects of different ADH1B and ALDH2 genotypes with or without antisocial personality disorder. Results: We found no difference of ADH1B*2 allele frequency between the subjects of antisocial alcoholism and subjects of antisocial non-alcoholism, but we found significant difference of ALDH2*2 allele between these two groups. Conclusions: We concluded that there is no alcoholism-protection effect of ADH1B*2 allele in antisocial alcoholics among Han Chinese in Taiwan.

Background: The role of the dopamine D2 receptor (DRD2) gene in the development of alcohol abuse or dependence is controversial. The controversy is due in part to the disparate definitions pertaining to the control groups used and to the definitions of subtypes in alcohol dependence. In the Han Chinese population, the alcohol dehydrogenase 1B*2/*2 (ADH1B*2/*2) genotype and the aldehyde dehydrogenase 2*2 (ALDH2*2) allele have been considered as protective factors against alcohol abuse or dependence. Moreover, the ADH1B and ALDH2 genes might be involved in dopamine metabolism. We hypothesized that the ADH1B and ALDH2 genes might interact with the DRD2 gene and that the association between the DRD2 gene and alcohol dependence might be affected by different ADH1B and ALDH2 genotypes. This study examined whether the DRD2 gene is associated with specific subtypes of alcohol dependence and evaluated the relationship between the DRD2 gene and alcohol-metabolizing genes in a specific subtype of alcohol dependence. Methods: Of the 465 Han Chinese subjects who were recruited for the study, 71 were classified with pure alcohol dependence, 113 with both alcohol dependence and anxiety-depression (ANX/DEP ALC), and 129 with anxiety-depression but without alcohol dependence (ANX/DEP). The remaining 152 subjects were supernormal controls. All subjects were interviewed with the Chinese version of the modified Schedule of Affective Disorders and Schizophrenia-Lifetime; all alcohol dependence, anxiety, and major depressive diagnoses were made according to DSM-IV criteria. Results: The DRD2 gene was not found to be associated with pure alcohol dependence or ANX/DEP, but was found to be associated with ANX/DEP ALC. Furthermore, the association between the DRD2 gene and ANX/DEP ALC was shown to be under the control of the ALDH2*1/*1 and ADH1B*1/*2 genotypes. Conclusions: ANX/DEP ALC is a specific subtype of alcohol dependence. Because ANX/DEP ALC was associated with the DRD2 gene only under the stratification of ADH1B*1/*2 or ALDH2*1/*1, the DRD2 gene might interact with the ADH1B gene and the ALDH2 gene, respectively, in the development of ANX/DEP ALC in the Taiwan Han Chinese population.

A positive association of MAOA polymorphisms with alcoholism has been demonstrated in certain recent studies, however, this association is not universally supported. The haplotype status of the MAOA gene polymorphisms could provide more information than alleles at a single site alone tested for an association with a complex, heterogeous disorder. This study examines whether there is an association between alcoholism and either a variable number of tandem repeat located upstream of the MAOA gene or an EcoRV functional polymorphism of the MAOA gene. These are analyzed both individually and as haplotypes. The study consisted of 214 subjects meeting DSM-IV criteria for alcoholism from northern Taiwan and 77 control individuals without history of alcoholism from Taipei. All of the subjects were Chinese Han males. For the two polymorphic sites, significant linkage disequilibrium occurred. No significant intergroup difference was observed between the two subject groups with respect to the allele frequencies for the two polymorphisms at the MAO locus tested both individually and as haplotypes. This finding suggests that no association exists between genetic variation at the MAOA locus and alcoholism in Chinese Han males.

Background The DEP domain is a globular domain containing approximately 90 amino acids, which was first discovered in 3 proteins: Drosophila disheveled, Caenorhabditis elegans EGL-10, and mammalian Pleckstrin; hence the term, DEP. DEPDC1B is categorized as a potential Rho GTPase-activating protein. The function of the DEP domain in signal transduction pathways is not fully understood. The DEPDC1B protein exhibits the characteristic features of a signaling protein, and contains 2 conserved domains (DEP and RhoGAP) that are involved in Rho GTPase signaling. Small GTPases, such as Rac, CDC42, and Rho, regulate a multitude of cell events, including cell motility, growth, differentiation, cytoskeletal reorganization and cell cycle progression. Results In this study, we found that it was a guanine nucleotide exchange factor and induced both cell migration in a cultured embryonic fibroblast cell line and cell invasion in cancer cell lines; moreover, it was observed to promote anchorage-independent growth in oral cancer cells. We also demonstrated that DEPDC1B plays a role in regulating Rac1 translocated onto cell membranes, suggesting that DEPDC1B exerts a biological function by regulating Rac1. We examined oral cancer tissue; 6 out of 7 oral cancer tissue test samples overexpressed DEPDC1B proteins, compared with normal adjacent tissue. Conclusions DEPDC1B was a guanine nucleotide exchange factor and induced both cell migration in a cultured embryonic fibroblast cell line and cell invasion in cancer cell lines; moreover, it was observed to promote anchorage-independent growth in oral cancer cells. We also demonstrated that DEPDC1B exerts a biological function by regulating Rac1. We found that oral cancer samples overexpressed DEPDC1B proteins, compared with normal adjacent tissue. Suggest that DEPDC1B plays a role in the development of oral cancer. We revealed that proliferation was linked to a novel DEPDC1B-Rac1-ERK1/2 signaling axis in oral cancer cell lines.

This aim of this study was to correlate heart rate variability (HRV) parameters to pulmonary arterial pressure (PAP) in patients with purely idiopathic pulmonary arterial hypertension (IPAH).HRV is decreased in patients with PAH. Whether HRV indices can be used to assess PAP in IPAH patients remains unclear.HRV parameters obtained by 24-h ECG were evaluated in 26 IPAH patients and 51 controls.Time-domain HRV parameters (SDNN, p 0.0001; SDANN, p 0.0001; RMSSD, p = 0.006) were lower in IPAH patients. Frequency-domain indices (high-frequency power, HFP, p = 0.001; low-frequency power, LFP, p = 0.003; total power, TP, p = 0.001) were also decreased in IPAH patients. In IPAH patients, RMSSD (p = 0.001), HFP (p = 0.015), and LFP (p = 0.027) were significantly correlated with PAP. IPAH patients had longer QTc intervals (p 0.0001) and more premature ventricular contractions (p 0.0001) than controls.IPAH is associated with autonomic dysfunction. RMSSD, HFP, and LFP may be used as a supplemental tool to assess PAP in IPAH patients. IPAH patients with autonomic dysfunction are at high risk for ventricular arrhythmia.

We surveyed Delta1-pyrroline 5-carboxylate dehydrogenase genes from four patients with hyperprolinemia type II using RT-PCR amplification, genomic PCR amplification and direct sequencing. We found four mutant alleles, two with frameshift mutations [A7fs(-1) and G521fs(+1)] and two with missense mutations (S352L and P16L). To test the functional consequences of three of these, we expressed them in a P5CDh-deficient strain of Saccharomyces cerevisiae . In contrast to wild-type human P5CDh, yeast expressing S352L and G521fs(+1) failed to grow on proline and had no detectable P5CDh activity. The P16L allele, however, produced fully functional P5CDh and subsequent analysis suggests that it is polymorphic in the relevant (Spanish) population. Interestingly, the G521fs(+1) allele segregates in the large Irish Traveller pedigree used to define the HPII phenotype. To our knowledge, this is the first description of the molecular basis for this inborn error.

Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for cellular cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell-extracellular matrix (ECM) interactions and cell-cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI.

Previous studies on acetaldehyde dehydrogenase 2 (ALDH2) focused on drinking behavior or alcoholism because the ALDH2*2 allele protects against the risk of developing alcoholism. The mechanism provides that the ALDH2 gene's protective effect is also involved in dopamine metabolism. The interaction of the ALDH2 gene with neurotransmitters, such as dopamine, is suggested to be related to alcoholism. Because alcoholism is often co-morbid with antisocial personality disorder (ASPD), previous association studies on antisocial alcoholism cannot differentiate whether those genes relate to ASPD with alcoholism or ASPD only. This study examined the influence of the interaction effect of the ALDH2*1*1, *1*2 or *2*2 polymorphisms with the dopamine 2 receptor (DRD2) Taq I polymorphism on ASPD. Our 541 Han Chinese male participants were classified into three groups: antisocial alcoholism (ASPD co-morbid with alcohol dependence, antisocial ALC; n = 133), ASPD without alcoholism (ASPD not co-morbid with alcohol dependence, antisocial non-ALC; n = 164) and community controls (healthy volunteers from the community; n = 244). Compared with healthy controls, individuals with the DRD2 A1/A1 and the ALDH2*1/*1 genotypes were at a 5.39 times greater risk for antisocial non-ALC than were those with other genotypes. Our results suggest that the DRD2/ANKK1 and ALDH2 genes interacted in the antisocial non-ALC group; a connection neglected in previous studies caused by not separating antisocial ALC from ASPD. Our study made this distinction and showed that these two genes may be associated ASPD without co-morbid alcoholism.

Much evidence suggests that dysfunction of dopamine transporter-mediated dopamine transmission may be involved in the pathophysiology of substance abuse and dependence. The aim of this study was to examine whether the dopamine transporter gene (DAT1; SLC6A3) is associated with the development of heroin dependence (HD) and whether DAT1 influences personality traits in patients with HD. Polymorphisms of DAT1 were analyzed in a case-control study of 1046 Han Chinese (615 patients and 431 controls). All participants were screened using a Chinese version of the modified Schedule of Affective Disorder and Schizophrenia-Lifetime and all patients met the criteria for HD. Furthermore, a Chinese version of the Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits in the patient group and examine the association between their personality traits and DAT1 polymorphisms. Of the patient group, 271 completed the TPQ. No statistically significant differences in allele or genotype frequencies of all investigated variants between HD patients and controls were observed. In haplotype analyses, four haplotype blocks of DAT1 were not associated with the development of HD. These DAT1 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. This study suggests that the DAT1 gene may not contribute to the risk of HD and specific personality traits in HD among the Han Chinese population.

Transcatheter closure of a secundum defect using a septal occluder is a safe and effective procedure based on long-term follow-up, but no clinical studies have examined immediate hemodynamic changes. We evaluated pulmonary venous flow velocity pattern before and immediately after deployment of the Amplatzer septal occluder for closure of atrial septal defect. From May 2003 to January 2005, 48 patients with secundum atrial septal defect received transcatheter closure with complete occlusion. Patients were divided into two groups according to age: pediatric group, under 16 years (n = 30, age 7.3 +/- 3.2 years), and adult group, 16 years or older (n = 18, age 30.1 +/- 11.4 years). Pulmonary venous flow pattern was recorded by transesophageal echocardiography before and immediately after occluder deployment. Immediately after deployment in both patient groups, pulmonary vein systolic (S) and diastolic (D) wave velocity decreased, but atrial reversal (AR) wave velocity increased. In the pediatric group, S-wave was 56.1 +/- 17.1 versus 35.5 +/- 11.3 cm/sec (P < 0.001); D-wave was 57.6 +/- 12.5 versus 42.9 +/- 11.8 cm/sec (P < 0.001); and AR wave velocity was 12.2 +/- 3.8 versus 15.5 +/- 4.1 cm/sec (P < 0.001). In the adult group, S-wave was 48.4 +/- 13.7 versus 32.7 +/- 10.3 cm/sec (P < 0.001); D-wave was 51.9 +/- 11.7 versus 38.0 +/- 8.5 m/sec (P < 0.001); and AR wave velocity was 12.1 +/- 4.1 versus 16.2 +/- 4.9 cm/sec (P < 0.001). Comparison of pulmonary venous flow before and immediately after deployment of the Amplatzer septal occluder provides an excellent model to evaluate the influence of an atrial communication on pulmonary venous flow. Pulmonary venous forward flow decreases following atrial septal defect (ASD) closure.

Growing three-dimensional scaffolds that contain more than a few layers of seeded cells is crucial for the creation of thick and viable cardiac tissues. To achieve this goal, a bioengineered cardiac patch (the MSC patch) composed of a sliced porous biological scaffold inserted with multilayered mesenchymal stem cells (MSCs) was developed for myocardial repair in a syngeneic rat model. After culture, sliced layers of the scaffold were stuck together and seeded MSCs were redistributed throughout the scaffold. Immunofluorescence analyses indicated that cells were viable and tightly adhered to a robust fibronectin meshwork within the scaffold. Results of echocardiography and heart catheterization revealed that the MSC-patch group had a superior heart function to the infarct group. Cells together with neo-muscle fibers and neo-microvessels were clearly observed in the entire MSC patch to fill its original pores, indicating that the implanted patch became well integrated into the host. The thickness of the retrieved MSC patch increased significantly as compared to that before implantation. When compared with the infarct group, expressions of angiogenic cytokines (bFGF, vWF and PDGF-B) and cardioprotective factors (IGF-1 and HGF) were significantly increased in the MSC-patch group. The aforementioned results indicated that transplantation of the MSC patch could restore the dilated LV and preserve cardiac functions after infarction.

Aims Cell transplantation is a promising approach for patients with myocardial infarction. However, following injection, retention of the transplanted cells in the injected area remains a central issue, which can be deleterious to cell transplantation therapy. We hypothesized that the use of cell sheet fragments, with the preservation of extracellular matrix (ECM), may significantly increase cell retention and thus improve cell therapy. Methods and results Mesenchymal stem cell (MSC) sheet fragments with ECM were fabricated. Experimental myocardial infarction was created in male syngeneic Lewis rats. Thirty minutes after myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n ≥ 10): sham; phosphate buffered saline; dissociated MSCs; and MSC sheet fragments. Echocardiography and pressure measurements were assessed postoperatively. At retrieval, the hearts were fixed for histological evaluation. After injection, the MSC sheet fragments remained intact, while the complete cell sheets were torn into pieces. The results obtained in the echocardiography and pressure measurements revealed a superior heart function in the MSC sheet fragment group compared with the dissociated MSC group ( P < 0.05). The MSC sheet fragments were able to conform and align their inherent ECM along the interstices of the muscular tissues at the injection sites, while only a few cells were identified in the dissociated MSC group at 12 weeks postoperatively. Additionally, transplantation of the MSC sheet fragments stimulated a significant increase in vascular density ( P < 0.05) and enhanced the graft/host cell connection. Conclusion The MSC sheet fragments may serve as a cell delivery vehicle by providing a favourable ECM environment to retain the transplanted cells and improve the efficacy of therapeutic cell transplantation.

Several studies have suggested that the norepinephrine transporter (NET) may play an important role in the pathogenesis of alcohol dependence. Additional studies have shown that the polymorphisms of T-182C (rs2242446) and G1287A (rs5569) in NET gene (hSLC6A2) may affect the NET function. Therefore, in this study, we examined whether these hSLC6A2 gene polymorphisms are a susceptibility factor for alcohol dependence or its clinical subgroup(s). A total of 690 Han Chinese subjects (408 alcohol dependent patients and 282 controls) in Taiwan were recruited for this study. Individuals with alcohol dependence were classified into several clinical subgroups to reduce the clinical heterogeneity. All subjects were interviewed with identical methods, and the mental disorders were diagnosed according to DSM-IV criteria. The polymorphisms of T-182C and G1287A in hSLC6A2 gene were analyzed by using a standard method. No significant differences in genotype and allele frequencies of hSLC6A2 polymorphisms were found between controls and total alcohol dependence or between more homogeneous subgroups with alcohol dependence and controls. This study suggests that the polymorphisms of T-182C and G1287A in hSLC6A2 gene are not major risk factors in increasing susceptibility to either alcohol dependence or its clinical subtypes.

Background Cloninger [Cloninger CR. 1987. Neurogenetic adaptive mechanisms in alcoholism. Science 236: 410–416.] had proposed a psychobiological model suggesting that three main personality dimensions distinguish the alcoholism into two subtypes (type I and type II). However, the classification was equivocal for clinical diagnosis. Recently, anxiety–depressive alcohol dependence (ANX/DEP ALC) has been posited as a genetically specific subtype of alcoholism. Its clinical characteristics were similar to individuals with type I alcoholism [Cloninger, C.R. 1987. Neurogenetic adaptive mechanisms in alcoholism. Science 236: 410–6.] such as having a high comorbidity with mood disorder, late-onset and more anxious/depressed traits. We attempted to investigate whether the dopamine D2 receptor ( DRD2 ) and the serotonin transporter promoter region ( 5-HTTLPR ) genes were involved in Novelty Seeking (NS) and Harm Avoidance (HA) of ANX/DEP ALC. Methods We recruited 46 pure alcohol dependents (Pure ALC) and 87 anxiety–depression alcohol dependents (ANX/DEP ALC). All participants were diagnosed by DSM-IV criteria, genotyped by the PCR method and assessed with Tridimensional Personality Questionnaire (TPQ). Results Both NS and HA were high in ANX/DEP ALC ( p = 0.021; p = 0.001, respectively). The association between NS and ANX/DEP ALC only existed in subjects with DRD2 Taq I A1 + allele ( A1/A1 or A1/A2 genotypes) ( p = 0.004) and in those with S/S genotype of 5-HTTLPR ( p = 0.005). With the stratification of DRD2 Taq I A1 + allele, high NS of ANX/DEP ALC existed only in carriers of 5-HTTLPR S/S genotype ( p = 0.001). Moreover, ANX/DEP ALC was related to high HA only in samples carrying 5-HTTLPR S/L or L/L genotype ( p = 0.02). Conclusions These findings provided the empirical genetic characterization of the specific personality traits in ANX/DEP ALC among Han Chinese population in Taiwan.

Interruption of the aortic arch is a rare and usually lethal congenital anomaly that is often associated with multiple cardiac malformations. Most neonates with aortic arch interruption perish once the ductus arteriosus closes after birth. However, sporadic cases have been reported to survive into adulthood uneventfully. Here, we report a 19-year-old male with a 3-month history of exertional dyspnea. A series of cardiovascular studies confirmed the presence of aortic arch interruption in conjunction with sinus venosus atrial septal defect and partial anomalous pulmonary venous connection. To the best of our knowledge, such an association has not been previously reported in adults.

Angiogenic therapies may need to select a stable agent to be delivered. In the study, a nonpeptide angiogenic agent, ginsenoside Rg(1) (Rg(1)), was encapsulated in the gelatin microspheres (MSs) crosslinked with genipin and intramuscularly injected into a rat model with infarcted myocardium. bFGF was used as a control. After swelling in an aqueous environment, the MSs without crosslinking became collapsed and stuck together. For those crosslinked, the swollen MSs appeared to be more stable with an increasing the degree of crosslinking. After it was released from MSs in vitro, the remaining activity of bFGF on HUVEC proliferation reduced significantly, while that of Rg(1) remained constant. An inspection of the retrieved hearts revealed a large aneurysmal left ventricle (LV) with a thinned myocardium and a significant myocardial fibrosis for that treated with the Empty MSs (without drug encapsulation). However, those receiving the MSs encapsulated with bFGF or Rg(1) attenuated the enlargement of the LV cavity and the development of myocardial fibrosis. The densities of microvessels found in the border zones of the infarct treated with the bFGF or Rg(1) MSs were significantly greater than that treated with the Empty MSs. These results indicated that Rg(1), a stable angiogenic agent, successfully enhanced the myocardial perfusion and preserved the infarcted LV function.

Context The ALDH2*2 allele has been shown to be a protective factor against alcoholism in a normal population owing in part to the elevated blood level of acetaldehyde and its accompanying physiological discomforts after drinking alcohol. Despite the well-established link between the ALDH2*2 allele and the physiological discomforts after drinking, very little is known regarding the psychological expectancies of drinking among persons with alcoholism with different ALDH genotypes. Objectives To determine whether there are differences in craving, alcohol consumption, and alcohol outcome expectancies between persons with alcoholism who have the ALDH2*1/*2 genotype and persons with alcoholism who have the ALDH2*1/*1 genotype. Design Cross-sectional survey. Setting Six outpatient alcohol treatment facilities in Taiwan. Participants Ninety-eight persons with alcoholism who met the DSM-IV criteria for current alcohol dependence. Main Outcome Measures Alcohol Craving Scale, Form 90, and Alcohol Expectancies Scale scores. Results Overall, the ALDH2*1/*2 group had lower negative alcohol outcome expectancies (F 4,93 = 2.43, P ≤.05, η p 2 = 0.10). Specifically, they had fewer expected negative outcomes in the social or interpersonal domain ( P P ≤.005) than did the ALDH2*1/*1 group. Moreover, the ALDH2*1/*2 group had higher positive alcohol outcome expectancies (F 7,90 = 2.36, P p 2 = 0.16), and they had more expected positive outcomes in the relaxation and tension reduction domain ( P P = .61) or consumption ( P = .11). Conclusions Although the ALDH2*2 allele has been associated with negative physiological responses in normal samples in past research, the psychological expectancies of drinking are more positive and less negative for persons with alcoholism who have the ALDH2*1/*2 genotype. A role of acetaldehyde is implied in these effects, which seem to override the usual discomfort effects associated with protection against alcohol drinking. Future studies are needed to assess alcohol outcome expectancies at different phases of alcohol dependence and to evaluate the concurrent relationships of blood levels of acetaldehyde with physiological and psychological outcomes among persons with alcoholism who have different ALDH genotypes.

Background: Epidemiological evidence suggests that heavy alcohol consumption increases the risk for either stroke or liver disease. The goal of this study was to determine whether heavy drinkers with mild liver disorder (MLD) are at risk of hemorrhagic stroke. Methods:All of the 524 patients recruited were males with a first-ever acute stroke and were consecutively admitted to the Tri-Service General Hospital between January 2000 and December 2001. The risk factors, liver function, stroke subtypes, and hemostatic factors were assessed among 68 patients defined as heavy drinker stroke (HDS) and 456 patients as nonheavy drinker stroke (NHDS). Results: HDS patients had a significantly higher incidence of hemorrhagic stroke than NHDS patients. HDS patients were also associated with significantly higher occurrence of cigarette smoking, hyperuricemia, liver dysfunction, and significantly lower platelet counts. HDS patients with MLD were more likely to have hemorrhagic stroke (76.5%) than HDS patients without MLD (33.3%) and NHDS patients with (40.3%) or without (26.7%) MLD. HDS patients with MLD also exhibited a significantly higher glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio (2.0 ± 1.2) and lower platelet number (185,000 ± 85,000 per µl) when compared with HDS patients without MLD (1.4 ± 0.5; 206,000 ± 59,000 per µl) and NHDS patients with (1.1 ± 1.0; 256,000 ± 97,000 per µl) or without (1.4 ± 0.7; 216,000 ± 68,000 per µl) MLD. Conclusions: HDS patients with MLD are at higher risk for hemorrhagic stroke in part due to the changes in hemostatic factors, although other factors may also contribute to hemorrhagic stroke.

The Amplatzer Septal Occluder (ASO) is the first and only device to receive full approval for clinical use in patients with secundum atrial septal defect (ASD) from the United States Food and Drug Administration. This study reports the device's initial results in Taichung Veterans General Hospital, a tertiary medical center in central Taiwan. Between October 2001 and December 2004, 39 consecutive patients (31 females, 8 males) with secundum ASD underwent attempt at transcatheter closure using the ASO under general anesthesia and transesophageal echocardiographic guidance. Six patients were excluded due to deficient rims (2 patients), multiple ASDs (1 patient), too large a defect (1 patient), too small a defect (1 patient) and 1 patient with associated atrial flutter. A total of 33 patients (26 females, 7 males) underwent the device closure procedure. The median age was 10.6 years (range 3.1-57.5 years) and median weight was 42 kg (range 13.5-73 kg). The median Qp/Qs ratio was 2.12 (range 1.02-5.52). The median balloon stretched diameter of the defect by sizing plate was 16 mm (range 5-37 mm). A total of 33 devices (median size 17 mm, range 7-38 mm) were implanted in 33 patients. The median fluoroscopy time was 10.1 minutes (range 5.9-29 minutes) and the median procedure time was 55 minutes (range 30-105 minutes). Complications included asymptomatic device embolization to the right ventricle in 1 patient (surgical removal) and transient complete atrioventricular block in 1 patient. Follow-up echocardiography at 10 minutes, 24 hours, 1 month, 6 months, 1 year and 2 years after the procedure showed complete closure rates of 76% (25/33), 91% (30/33), 100% (32/32), 100% (22/22), 100% (22/22), and 100% (9/9), respectively. In conclusion, transcatheter closure of secundum ASD using the Amplatzer Septal Occluder is safe and effective, with a very low complication rate.

Background Clinical trials on contrast-induced nephropathy (CIN) prevention with different approaches generated various results. In this study, we investigated whether intravenous aminophylline preceding percutaneous transluminal renal artery stenting (PTRS) might provide better renal protection. Methods Patients with severe atherosclerotic renal artery stenosis and undergoing PTRS were prospectively studied. Intravenous aminophylline 250 mg was administered 30 min before PTRS. Results The aminophylline group included 15 patients (mean age, 68±4 years) and the case-matched control group consisted of another 15 patients (mean age, 71±2 years). After a mean follow-up of 5–6 months, both groups showed similar serum creatinine (1.7±0.2 vs. 1.6±0.1 mg/dl, P =NS), BUN (20.0±3.0 vs. 24.0±3.0 mg/dl, P =NS), fall in systolic (−15±13 vs. −11±3 mm Hg, P =NS) and diastolic BP (−2±4 vs. −6±5 mm Hg, P =NS). The incidence of post-operative renal deterioration was 6.7% in the study group and none in the control group. Conclusion Pre-treatment intravenous aminophylline provides no additional renal protective effect in delicately practiced PTRS.

Background: Recent studies on the genetics of alcoholism have suggested an association between antisocial alcoholism and the MAO-A gene. However, previous studies have failed to include subjects with antisocial personality disorder without alcoholism even though there is a high comorbidity between antisocial personality disorder and alcoholism. Consequently, the finding of an association between the MAO-A gene and alcoholism or antisocial personality disorder seems tenuous. In Taiwan, about 70% of the Han Chinese population have the ADH2*2 allele and 50% show ALDH2*1/*2 or ALDH2*2/*2 genotypes, which offer protection against drinking behavior and the risk of developing alcoholism. Thus, it is possible to recruit individuals with antisocial personality disorder but without alcoholism in Taiwan. Therefore, association studies of alcoholism or antisocial personality disorder in Chinese may be more reliable if pure antisocial alcoholics, pure antisocial personality disorders, and normal controls as MAO-A gene are examined. Methods: In this study, the associations among antisocial alcoholism, antisocial personality disorder, and the uVNTR and Eco RV polymorphisms of the MAO-A gene, both individually and as a haplotype, were investigated among male adults recruited from jails in Taipei. A total of 129 Chinese Han males were studied, including 41 with antisocial personality disorder with alcoholism, 50 with antisocial personality disorder but without alcoholism, and 38 without either disorder as a jail control group. The diagnoses of alcohol dependence and antisocial personality disorder were made according to DSM-IV criteria. In addition, 77 normal controls were collected from the community. Results: Strong linkage disequilibrium was found for the uVNTR and Eco RV variants of MAO-A gene in each study group. Conclusions: No significant association was observed between these two polymorphisms and antisocial personality disorder with alcoholism, either individually or for the haplotype, or for antisocial personality disorder without alcoholism. Thus, neither antisocial alcoholism nor antisocial personality disorder was associated with the genetic variants of MAO-A gene.

Background : Cardiogenic shock complicating acute coronary syndrome (ACS) implies grim prognosis with conventional management. Previous studies of coronary intervention yielded controversial results and were rarely analyzed chronologically. This study was to determine the impact of percutaneous coronary revascularization on outcome by studying two time periods 5 years apart in which the revascularization was more frequent and techniques more refined in the later period. Methods and materials : All patients admitted to the intensive or coronary care unit for ACS in two 1.5-year study periods (Period I: Jan 1994–Jun 1995, Period II: Oct 1999–Apr 2000) were retrospectively screened. Patients who met strict criteria of cardiogenic shock within 24 h of ACS were enrolled. The demographics, management and in-hospital/3-month outcomes were analyzed. Results : Thirty-seven patients (33M/4F, aged 65±8 years) were enrolled in Period I and 32 patients (25M/7F, aged 68±13 years) in Period II. The incidence of cardiogenic shock was 11.8 and 9.3%, respectively. The demographics were similar except patients in Period II were older. Significantly more coronary angiography and interventions were done in the later period. The in-hospital (68 vs. 44%, P =0.047) and 3-month mortalities (70 vs. 44%, P =0.03) were significantly reduced in Period II. The in-hospital survivors in two study periods differed only in use of coronary angiography (94 vs. 50%, P =0.005) and interventions (83 vs. 33%, P =0.005) but not others. Conclusions : Percutaneous coronary revascularization does improve the clinical outcome of cardiogenic shock when analyzed chronologically. This treatment is warranted in every such patient in the interventional era.

Caveolins are an essential component of cholesterol-rich invaginations of the plasma membrane known as caveolae. These flask-shaped, invaginated structures participate in a number of important cellular processes, including vesicular transport, cholesterol homeostasis, and signal transduction. We investigated the effects of CAV-1 on mitochondrial biogenesis and antioxidant enzymes in hypercholesterolemia-affected target organs. A total of eighteen male New Zealand white rabbits were divided into three groups: a normal-diet group, an untreated hypercholesterolemia-induced group, and a hypercholesterolemia-induced group that received intravenous administration of antennapedia-CAV-1 (AP-CAV-1) peptide every 2 days for 2 weeks. Serum biochemistry, CAV-1 distribution, neutral lipid distribution, mitochondrial morphology, biogenesis-mediated protein content, oxidative stress balance, antioxidant enzyme levels, and apoptotic cell death of liver tissue were analysed. Hepatic and circulating cholesterol and low-density lipoprotein cholesterol (LDL-C) levels differed significantly between the three groups (P

Delta 1-pyrroline-5-carboxylate dehydrogenase (P5CDh; EC 1.5.1.12), a mitochondrial matrix NAD(+)-dependent dehydrogenase, catalyzes the second step of the proline degradation pathway. Deficiency of this enzyme is associated with type II hyperprolinemia (HPII), an autosomal recessive disorder characterized by accumulation of delta 1-pyrroline-5-carboxylate (P5C) and proline. As an initial step in understanding the biochemistry of human P5CDh and molecular basis of HPII, we utilized published peptide sequence data and degenerate primer polymerase chain reaction to clone two full-length human P5CDh cDNAs, differing in length by 1 kilobase pair (kb). Both cDNAs have the identical 1689-base pair open reading frame encoding a protein of 563 residues with a predicted molecular mass of 62 kDa. The long cDNA contains an additional 1-kb insert in the 3'-untranslated region that appears to be an alternatively spliced intron. The conceptual translation of human P5CDh has 89% sequence identity with the published human P5CDh peptide sequences and 42 and 26% identity with Saccharomyces cerevisiae and Escherichia coli P5CDhs, respectively, as well as homology to several other aldehyde dehydrogenases. Both P5CDh cDNA clones detect a single 3.2-kb transcript on Northern blots of multiple human tissues, indicating the long cDNA containing the 3'-untranslated intron represents the predominant transcript. The P5CDh structural gene appears to be single copy with a size of about 20 kb localized to chromosome 1. To confirm the identity of the putative P5CDh cDNAs, we expressed them in a P5CDh-deficient strain of S. cerevisiae. Both conferred measurable P5CDh activity and the ability to grow on proline as a sole nitrogen source.

Background: Premature coronary artery disease (CAD) is a special entity with a strong link to familial hypercholesterolemia, family history of premature CAD, or multiple coexistent atherosclerotic risk factors. Drug-eluting stenting (DES), including paclitaxel-eluting stenting (PES) and sirolimus-eluting stenting (SES), has been proven to have a lower restenotic rate. However, to date, few studies have investigated the clinical and angiographic results of DES in premature CAD patients. Methods: Between February 2004 and October 2005, premature CAD patients, defined as those younger than 50 years of age, who were treated with DES in our medical center were all retrospectively enrolled. Their baseline clinical characteristics, clinical outcome and angiographic follow-up results were analyzed. Results: A total of 26 patients (M/F: 23/3) were enrolled, with a mean age of 44 ± 6 years (range, 24–50 years). Conventional atherosclerotic risk factors were prevalent in this study group, including diabetes mellitus (35%), hypertension (35%), hyperlipidemia (54%) and smoking (73%). Moreover, there was 1 homozygous and 1 heterozygous familial hypercholesterolemia case in our study group. In terms of angiographic results, there were 40 target lesions in 34 target vessels. Forty DES (39 PES, 1 SES) were implanted with a median stent diameter of 3 mm and median length of 24 mm. The clinical follow-up was counted up to May 2006, with a mean follow-up duration of 540 ± 168 days; 11 (42%) patients had a second angiogram during the follow-up period (200 ± 98 days after DES). None of the patients had target lesion revascularization (TLR). In addition, there was no difference in TLR or stent thrombosis between patients with or without acute coronary syndrome. Conclusion: Based on our single-center experience, DES had good short-term follow-up results for a premature CAD group with diverse and multiple atherosclerotic risk factors. [J Chin Med Assoc 2008;71(7):342–346]