Effect of cholinergic pathway disruption on cortical and subcortical volumes in subcortical vascular cognitive impairment.

BACKGROUND AND PURPOSE: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor to subcortical vascular cognitive impairment (scVCI). We aimed to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI. METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (>2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores was obtained using multiple linear regression. RESULTS: In total, 80 patients were enrolled. The mean age was 78.4 ± 6.5 years, median Mini-Mental State Examination score was 17 (interquartile range, 13-20) and median CHIPS score was 11 (interquartile range, 7-17). CHIPS scores were positively correlated with subcortical volumes of the putamen (r' = 0.46, P = 0.002) and pallidum (r' = 0.45, P = 0.002), and were negatively associated with inferior temporal (r' = -0.35, P = 0.002) and medial orbitofrontal (r' = -0.32, P = 0.002) cortical thickness. CONCLUSION: Our study suggested that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons.

Pooled cohort risk equation and subclinical cerebrovascular diseases.

BACKGROUND AND PURPOSE: In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) introduced a novel pooled cohort risk (PCR) model for atherosclerotic cardiovascular disease. In this study, we evaluated the relationship between the PCR score and cerebral large- and small-vessel diseases (cLVD and cSVD) in a healthy population, METHODS: We assessed consecutive health check-up volunteers from 2006 to 2013. We calculated the estimated 10-year atherosclerotic cardiovascular disease risk as the PCR score based on the 2013 ACC/AHA guidelines. We evaluated both cSVD/cLVD, including the prevalence of cLVD, lacunes and cerebral microbleed (CMB), and the volume of white matter hyperintensity (WMH). In addition to PCR score, the risk factors that were associated with outcome variables at P < 0.10 in univariate analysis were included for further multivariable linear or regression analyses. RESULTS: A total of 2720 participants were evaluated (mean age, 57 years, male sex, 54%). In multivariable analysis, PCR score was associated with WMH volume [ß = 0.361; 95% confidence interval (CI), 0.320-0.402, P < 0.001], cLVD [adjusted odds ratio (aOR), 1.66; 95% CI, 1.29-2.16, P < 0.001], lacunes (aOR, 1.80; 95% CI, 1.52-2.14, P < 0.001) and CMBs (aOR, 1.75; 95% CI, 1.40-2.19, P < 0.001). Furthermore, PCR score also showed dose-response tendencies according to the burden of cLVD, WMH, lacunes and CMB. CONCLUSIONS: A higher PCR score based on the ACC/AHA guidelines is closely associated with a higher prevalence and burden of cLVD and cSVD.

Left ventricular ejection fraction is associated with small vessel disease in ischaemic stroke patients.

BACKGROUND AND PURPOSE: The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients. METHODS: Consecutive first-ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid-attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose-response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated. RESULTS: A total of 841 patients were included [median WMH volume 2.98 (1.22-10.50) ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF (B = -0.052, P < 0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR) 0.978, P = 0.012], CMBs (aOR = 0.96, P < 0.001) and moderate to severe EPVSs (aOR = 0.94, P < 0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes (P = 0.026), CMBs (P < 0.001) and EPVSs (P = 0.002). The total cSVD score also showed a negative association with LVEF in a dose-response manner (P < 0.001). CONCLUSIONS: The burden of cSVD is negatively correlated with the LVEF in a dose-response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.

Favorable impact of non-alcoholic fatty liver disease on the cerebral white matter hyperintensity in a neurologically healthy population.

BACKGROUND AND PURPOSE: Although non-alcoholic fatty liver disease (NAFLD) shares common cardiovascular risk factors with cerebral white matter hyperintensity (WMH), few studies have reported the association between NAFLD and WMH. The association between the presence of NAFLD with its severity and the volume of WMH was investigated. METHODS: This cross-sectional study was conducted for 2460 subjects who voluntarily participated in health screening check-ups including brain magnetic resonance imaging and liver ultrasonography at the Health Promotion Center at Seoul National University Hospital from 2009 to 2013. Ultrasonography was used to detect the presence and severity of NAFLD combined with the NAFLD fibrosis score and the FIB-4 index. The volume of WMH was measured using a semi-automated quantification method by a trained neurologist. RESULTS: The prevalence of NAFLD was 36.5%, and the median volume of WMH in all the subjects was 1.1 ml (interquartile range 0.2-2.7 ml). The presence of NAFLD was associated with a smaller volume of WMH [ß (standard error, SE) -0.051 (0.046); P = 0.012]. Moderate to severe NAFLD was associated with a smaller volume of WMH than was non-NAFLD [ß (SE) -0.067 (0.061); P = 0.002]. The negative correlation observed between NAFLD severity and WMH volume was persistent only in those with low FIB-4 index and low NAFLD fibrosis scores, whereas there was a positive association in those with high FIB-4 index and NAFLD fibrosis scores. CONCLUSIONS: Non-alcoholic fatty liver disease, and its severity, showed a favorable association with WMH volume. However, its causality and mechanism should be evaluated in further relevantly designed studies.

Clinical relevance of abnormal neuroimaging findings and long-term risk of stroke recurrence.

BACKGROUND AND PURPOSE: Previous studies have revealed that the predictors of short- and long-term stroke recurrence are different. We designed a comprehensive stroke recurrence (CSR) model, composed of demographic, clinical and radiological findings, to predict long-term ischaemic stroke recurrences. METHODS: We retrospectively collected the derivation cohort from consecutive patients with first-ever ischaemic stroke within 7 days of symptom onset. Univariate and multivariable Cox regression analysis were used to evaluate the association between 2-year recurrence and demographic, clinical and neuroradiological factors. The CSR score was calculated by adding the integer value of independent predictors that was derived from the ß-coefficient in the multivariable analysis. To qualify the model, we analyzed the receiver operating characteristics curve. We assessed internal validation with bootstrap methods and assessed external validation with another independent cohort. RESULTS: A total of 958 patients were enrolled, and 63 patients had recurrent strokes during the follow-up periods. The rate of stroke recurrence was 7.0% at 2 years. In the multivariable analysis, multiple stage lesions, isolated cortical lesions on diffusion-weighted imaging, severe white matter hyperintensities, multiple lacunar infarctions and relevant arterial stenosis were independently associated with stroke recurrence. The CSR model showed good discrimination [area under the curve (AUC), 0.81 (0.74-0.88)], which was consistent with internal [AUC, 0.75 (0.66-0.85)] and external [AUC, 0.80 (0.69-0.90)] validation. CONCLUSIONS: Abnormal neuroimaging findings, rather than cardiovascular risk factors, are predictive of long-term ischaemic stroke recurrence. Causative mechanism of stroke and underlying hostile brain milieu seem to be associated with long-term stroke recurrence.

Distal hyperintense vessel sign is associated with neurological deterioration in acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to evaluate the relationship between distal hyperintense vessel sign (HVS) and early neurological deterioration (END) in acute ischaemic stroke with large vessel steno-occlusion. METHODS: Acute ischaemic stroke patients with symptomatic severe steno-occlusion in the middle cerebral artery or internal carotid artery were recruited within 24 h from symptom onset. Stroke outcomes were evaluated using the National Institutes of Health Stroke Scale (NIHSS) score at the time of admission and at 72 h and 7 days. END was defined as an increment of ≥1 in the motor NIHSS score or ≥2 in the total NIHSS score. Distal HVS was defined as hyperintensity on fluid-attenuated inversion recovery image, located distal to the Sylvian fissure. The extent of distal HVS was divided into absent, subtle and prominent. RESULTS: Amongst a total of 325 participants, END was found in 103 (32%) patients. END was associated with age, atrial fibrillation, initial NIHSS score, initial infarct volume, severe leukoaraiosis, hemorrhagic infarction and distal HVS. In multivariate analysis, distal HVS remained an independent predictor of END [adjusted odds ratio (aOR) 2.86, 95% confidence interval (CI) 1.65-4.97, P < 0.001]. Initial infarct volume (aOR = 1.01, 95% CI 1.01-1.02, P < 0.001) and severe leukoaraiosis (aOR = 3.16, 95% CI 1.77-5.65, P < 0.001) were also associated with END, independently of distal HVS. In the analysis of the burden of distal HVS and stroke outcomes, prominent distal HVS was associated with stroke severity and infarct volume in a dose-response manner. CONCLUSIONS: Distal HVS is associated with END in acute ischaemic stroke patients with large vessel steno-occlusion.

Sex-dependent effects of uric acid on cerebral microbleed: a cross-sectional study in the general population.

BACKGROUND AND PURPOSE: Elevated serum uric acid (UA) is known to be associated with stroke. However, there is little information on the association between serum UA levels and cerebral microbleed (CMB), a precursor of stroke. Therefore, we investigated the association between UA and CMB in a general population taking into consideration sex-related differences. METHODS: The subjects in this cross-sectional study consisted of 2686 individuals of 40-79 years of age (1403 men and 1283 women) who underwent regular health screenings, including brain magnetic resonance imaging, at Seoul National University Hospital Health Promotion Center. Subjects were categorized into three groups according to tertiles of UA levels by sex. The presence and location of CMB were assessed by gradient-recalled echo magnetic resonance imaging. RESULTS: The prevalence of CMB was 3.8%. In multivariate logistic regression analysis by sex, the highest tertile of UA in male subjects was independently associated with the presence of CMB compared with the lowest tertile of UA (adjusted odds ratio, 2.46; P = 0.013). Meanwhile, the highest tertile of UA in female subjects was inversely associated with CMB compared with the lowest tertile of UA (adjusted odds ratio, 0.39; P = 0.040). CONCLUSIONS: High serum UA value was associated with higher prevalence of CMB in male, but lower prevalence of CMB in female subjects.

Association of intracranial atherosclerotic stenosis with severity of white matter hyperintensities.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) have been linked to small-vessel disease, but the precise pathogenesis underlying WMHs remains unclear. Studies about an association of WMHs with extracranial atherosclerotic stenosis (ECAS) showed conflicting results and the relationship of WMHs with intracranial atherosclerotic stenosis (ICAS) is uncertain. METHODS: A cross-sectional study of 679 consecutive Korean patients with acute ischaemic stroke (mean age 67.8 ± 12.6; 395 males) who underwent brain MRI/MR angiography was conducted. Severity of deep WMHs (d-WMHs, n = 560) and periventricular WMHs (p-WMHs, n = 590) was rated separately and compared across three groups: ICAS (n = 318), ECAS (n = 71) and no cerebral atherosclerotic stenosis (NCAS) (n = 290). RESULTS: The ICAS group showed a higher d-WMH/p-WMH score (1.62 ± 0.85/1.65 ± 0.79) than both the ECAS (1.25 ± 0.87/1.23 ± 0.78) and NCAS (1.19 ± 0.92/1.24 ± 0.81) groups (P < 0.001 for all). Patients with a greater number of ICAS were more likely to have higher scores of d-WMH/p-WMH (P < 0.001 for all). Patients with higher scores of d-WMH/p-WMH had a higher incidence of ICAS (P < 0.001 for all), but not of ECAS or NCAS. In multivariable analysis, a dose-response relationship was observed between the extent of ICAS versus WMHs. Compared with one ICAS lesion, for d-WMHs the odds ratio (OR) = 2.61 [95% confidence interval (CI) 0.95-7.20] for two ICAS lesions and OR = 3.37 (1.10-10.32) for ≥3 ICAS lesions; whilst for p-WMHs (score ≥2) OR = 1.70 (95% CI 0.96-2.98) for two ICAS lesions and OR = 2.02 (1.15-3.55) for ≥3 ICAS lesions. CONCLUSION: ICAS is independently associated with progressively greater WMH burden. The association of ICAS with WMH severity appears to be stronger than that of ECAS/NCAS in the Korean (Asian) stroke population.

Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial.

BACKGROUND AND PURPOSE: We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%). RESULTS: The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058). CONCLUSIONS: In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.

Cell volume regulated transporters of compatible osmolytes.

Virtually all cells respond to hypertonicity by accumulating certain small organic solutes (compatible osmolytes) that, in contrast to intracellular ions, do not perturb macromolecular function. Several important compatible osmolytes are accumulated by coupled transport. Transcription of genes encoding these cotransporters is increased by hypertonicity and a tonicity-responsive enhancer element has been identified. When cells return to an iso-osmotic environment, osmolytes are rapidly lost through a pathway that current evidence indicates may be a volume-sensitive chloride channel.

Pathotypes and genetic relationship of worldwide collections of Elsinoë spp. causing scab diseases of citrus.

Two scab diseases are recognized currently on citrus: citrus scab, caused by Elsinoë fawcettii, and sweet orange scab, caused by E. australis. Because the two species cannot be reliably distinguished by morphological or cultural characteristics, host range and molecular methods must be used to identify isolates. Four pathotypes of E. fawcettii and two of E. australis have been described to date based on host range. The host specificity and genetic relationships among 76 isolates from Argentina, Australia, Brazil, Korea, New Zealand, and the United States were investigated. Based on pathogenicity tests on eight differential hosts, 61 isolates were identified as E. fawcettii and 15 as E. australis. Of 61 isolates of E. fawcettii, 24 isolates were identified as the Florida broad host range (FBHR) pathotype, 7 as the Florida narrow host range (FNHR) pathotype, 10 as the Tryon's pathotype, and 3 as the "Lemon" pathotype. Two new pathotypes, the "Jingeul" and the satsuma, rough lemon, grape-fruit, clementine (SRGC), are described, and four isolates did not fit into any of the known pathotypes of E. fawcettii. Of the 15 isolates of E. australis from Argentina and Brazil, 9 belonged to the sweet orange pathotype and 6 from Korea to the natsudaidai pathotype. E. fawcettii and E. australis were clearly distinguishable among groups by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) assays and the E. fawcettii group was divided into three subgroups, A-1, A-2, and A-3. The A-1 group was composed of the FBHR, FNHR, and SRGC pathotypes; some Lemon pathotypes; and the uncertain isolates. The A-2 subgroup included all of the Tryon's pathotype isolates and one of the three Lemon pathotype isolates and the A-3 group contained the Jingeul pathotype isolates. E. australis was differentiated into two groups: B-1, the natsudaidai pathotype isolates, and B-2, the sweet orange pathotype isolates. Isolates of E. fawcettii and E. australis were clearly distinguishable by sequence analysis of the internal transcribed spacer (ITS) region and the translation elongation factor 1 alpha (TEF) gene. There were also fixed nucleotide differences in the ITS and TEF genes that distinguished subgroups separated by RAPD-PCR within species. We confirmed two species of Elsinoë, two pathotypes of E. australis, and at least six pathotypes of E. fawcettii and described their distribution in the countries included in this study.

Acute myocardial infarction due to sinus of Valsalva aneurysm in a patient with Behçet's disease.

Cardiovascular manifestations have been reported in 7-38% of patients with Behçet's disease (BD), and mortality occurs in up to 20% of those with marked vascular involvement. Sporadic cases of endocarditis, myocarditis, pericarditis, acute myocardial infarction, aortic aneurysm, ventricular thrombosis, congestive cardiomyopathy, and valvular dysfunction have been reported. Here we report a case of acute myocardial infarction that resulted from the compression of coronary arteries by a sinus of Valsalva aneurysm in a patient with BD.

Pretransplantation Cystatin C, but not Creatinine, Predicts 30-day Cardiovascular Events and Mortality in Liver Transplant Recipients With Normal Serum Creatinine Levels.

BACKGROUND: The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels. PATIENTS AND METHODS: Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I >0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events. RESULTS: The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (<0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment). CONCLUSIONS: Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine.

Diabetes With or Without Hypertension Does Not Affect Graft Survival and All-cause Mortality After Liver Transplant: A Propensity Score Matching Analysis.

BACKGROUND: Many studies have reported the negative influence of diabetes and hypertension on morbidity and mortality in the general population. In liver transplantation (LT) recipients, prevalence of nonalcoholic fatty liver disease and metabolic syndrome is increasing. Hence, concerns over the negative influence of metabolic syndrome, including diabetes and hypertension, are growing. However, there have been few studies about the outcomes of LT recipients with diabetes with/without hypertension. We aimed to evaluate the impact of diabetes with/without hypertension on the outcomes of LT. METHODS: Between May 2010 and October 2015, 814 LT recipients (median age, 51 [46-55] years; median MELD score, 13 [9-18]), without overt cardiovascular disease were retrospectively evaluated. To rigorously adjust for clinically confounding factors, a 1:2 propensity score matching analysis was performed. Kaplan-Meier survival curves and Cox proportional hazard regression analysis were performed to examine the association between diabetes with/without hypertension and all-cause mortality or graft survival rate. RESULTS: There were 77 (9.5%) graft failures and 71 (8.7%) deaths during a median follow-up of 2.4 years. After 1:2 matching of 173 (21.3%) diabetic patients, no significant differences were evident in graft survival rate (log-rank test, P = .46; and hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.55-2.06; P = .865) and all-cause mortality (log-rank test, P = .59; and HR, 1.06; 95% CI, 0.55-2.06; P = .727). Separate 1:2 matching was applied to a subgroup of 43 (5.3%) patients with diabetes and hypertension. This matching also showed no difference in graft survival rate (log-rank test, P = .45; and HR, 1.35; 95% CI, 0.43-4.27; P = .613) and all-cause mortality (log-rank test, P = .25; and HR, 1.87; 95% CI, 0.54-6.50; P = .325). CONCLUSION: Diabetes with/without hypertension does not have an impact on graft survival rate or all-cause mortality in LT recipients.

Brief Episodes of Newly Developed Intraoperative Atrial Fibrillation Predicts Worse Outcomes in Adult Liver Transplantation.

BACKGROUND: Although patients undergoing liver transplantation (LT) are frequently exposed to predisposing factors of atrial fibrillation (AF) such as autonomic imbalance, surgical stress, and elevated catecholamine levels, the occurrence of intraoperative AF (IOAF) has not been fully examined in LT candidates. METHODS: Data from 1059 patients who underwent adult LT from 2006 to 2010 were analyzed. Among patients with preoperative normal sinus rhythm, the incidence, prognosis, and detailed characteristics of newly developed IOAF were assessed. Their risk factors and clinical implication, including hepatic graft survival and mortality, were also examined. RESULTS: Thirteen (1.2%) cases of AF newly developed intraoperatively. A higher Model for End-Stage Liver Disease score (adjusted odds ratio, 1.077 [95% confidence interval, 1.015-1.143]; P = .015) and fulminant hepatic failure (adjusted odds ratio, 6.844 [95% CI, 1.944-24.096]; P = .003) were associated with its occurrence. Eight cases of newly developed AF occurred immediately after hepatic graft reperfusion; the other 3 cases occurred during the pre-anhepatic or anhepatic phase. The majority of patients (9 cases) experienced only brief episodes of AF lasting <1 hour. Despite all patients with newly developed AF eventually converting to sinus rhythm within 1 week after surgery, the episode of IOAF was independently associated with mortality (adjusted hazard ratio, 5.097 [95% confidence interval, 2.189-11.868]; P < .001) after adjustment for Model for End-Stage Liver Disease score. CONCLUSIONS: For LT recipients, even a brief episode of newly developed IOAF seems to be an important prognosticator, regardless of AF duration.

Prevalence of Antiphospholipid Antibody Positivity and Association of Pretransplant Lupus Anticoagulant Positivity With Early Allograft Dysfunction in Liver Transplantation.

BACKGROUND: Antiphospholipid antibodies (aPL), including anticardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2GPI), and lupus anticoagulant (LA) antibodies, are frequently found in liver cirrhosis and associated with splanchnic vein thrombosis. Although the risk factors of early allograft dysfunction (EAD) are known, the association between EAD and aPL has been poorly investigated. We hypothesized that LA, potent aPL with thrombotic potential, may be associated with EAD development after living donor liver transplantation (LDLT). METHODS: Data of 719 patients who underwent LDLT from February 2014 to June 2016 at our center were retrospectively collected and analyzed. Patients were divided into 2 groups according to the positivity of LA screening test (LA group [n = 148] vs no-LA group [n = 571]). Risk factors for EAD were investigated using multivariable regression analysis and inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: The prevalence of LA screening positivity, confirmatory test positivity, and EAD was 20.6%, 1.1%, and 11.3%, respectively. aCL positivity rate was 7.5% and anti-ß2GPI positivity rate was 7.0%. The EAD prevalence in LA and no-LA group was 25.7% and 7.5%, respectively. However, multivariable and IPTW analyses showed no association between EAD and LA screening positivity (P = .263 and P = .825, respectively), although a significant association was found in univariate analysis (odds ratio, 4.242; P < .001). Model for End-stage Liver Disease score, operation time, and C-reactive protein level remained significant after multivariable analysis. CONCLUSION: A positive LA screening test result was associated with EAD only in the univariate analysis. Inflammation, based on C-reactive protein level, was more important for EAD development.

Taurine behaves as an osmolyte in Madin-Darby canine kidney cells. Protection by polarized, regulated transport of taurine.

Using a clonal growth assay, we demonstrated that taurine, a nonperturbing osmolyte accumulated in kidney medulla, brain, and some other tissues of hypertonic experimental animals can function as a nonperturbing osmolyte in Madin-Darby canine kidney (MDCK) cells. The taurine content of hypertonic MDCK cells is twice that of isotonic MDCK cells (isotonic 160 nmol/mg protein; hypertonic 320 nmol/mg protein). Therefore we studied taurine transport in MDCK cells grown on porous supports and then studied the effect of hypertonicity which is known to elicit increased uptake of some other nonperturbing osmolytes by MDCK cells. Basal uptake exceeded apical uptake, with Km and Vmax of 56 microM and 933 pmol/min.mg protein on the basal surface and 10 microM and 50 pmol/min.mg protein on the apical surface. On both surfaces, virtually all taurine uptake was Na+ and Cl- dependent. 24 h after cells were shifted to hypertonic medium (500 mosmol/kg), taurine uptake doubled on the basolateral surface without change on the apical surface. The response to hypertonicity was the result of an increase in Vmax without change in Km. There was no change in taurine efflux when cells were shifted from isotonic to hypertonic medium. When cells adapted to hypertonic medium were shifted to isotonic medium, a large transient basolateral efflux of taurine occurred within 10 min. We conclude that taurine can function as a nonperturbing osmolyte in MDCK cells and that tonicity-regulated taurine transport is a basolateral function in MDCK cells.

Medium tonicity regulates expression of the Na(+)- and Cl(-)-dependent betaine transporter in Madin-Darby canine kidney cells by increasing transcription of the transporter gene.

Betaine is one of the major compatible osmolytes accumulated by kidney derived Madin-Darby canine kidney cells cultured in hypertonic medium. Betaine is accumulated by Na(+)- and Cl(-)-dependent uptake from the medium. To gain insight into the mechanism by which hypertonicity evokes an increase in the Vmax of the betaine transporter in Madin-Darby canine kidney cells, we measured the relative abundance of mRNA for the transporter in cells shifted to a hypertonic medium and found parallel increases in mRNA abundance and cotransporter activity. The increase in mRNA levels preceded the increase in transporter activity slightly. Transcription of the gene for the transporter rose rapidly and to the same relative extent as mRNA abundance in cells shifted to hypertonic medium, indicating that transcription of the gene for the cotransporter plays a major role in regulating the accumulation of betaine in response to hypertonicity.

Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia.

Coronary arteries contain a network of vasa vasorum in the adventitia. The three-dimensional anatomy of the vasa vasorum in early coronary atherosclerosis is unknown. This study was designed to visualize and quantitate the three-dimensional spatial pattern of vasa vasorum in normal and experimental hypercholesterolemic porcine coronary arteries, using a novel computed tomography technique. Animals were killed after being fed either a high cholesterol diet (n = 4) or a control diet (n = 4) for 12 wk. The proximal left anterior descending coronary artery was removed from the heart, scanned, and reconstructed, and quantitation of vasa vasorum density was performed. Two different types of vasa vasorum were defined: first-order vasa vasorum ran longitudinally parallel to the vessel and second-order originated from first-order vasa circumferentially around the vessel wall. Compared with controls in hypercholesterolemic coronary arteries, there was a significant increase in the area of the vessel wall (3.86+/-0.22 vs. 8.07+/-0.45 mm2, respectively, P < 0.01) and in the density of vasa vasorum (1. 84+/-0.05/mm2 vs. 4.73+/-0.24/mm2; respectively, P = 0.0001). This occurred especially by an increase of second-order vasa vasorum and disorientation of normal vasa vasorum spatial pattern. This study suggests that adventitial neovascularization of vasa vasorum occurs in experimental hypercholesterolemic coronary arteries and may be a part of the early atherosclerotic remodeling process.

Metabolic syndrome is more associated with intracranial atherosclerosis than extracranial atherosclerosis.

To elucidate the relationship between metabolic syndrome (MetS) and cerebrovascular stenosis, we performed comparative studies of MetS and its components between ischemic stroke patients with intra- and extracranial atherostenosis. We evaluated 378 acute ischemic stroke patients who underwent brain magnetic resonance (MR) imaging and MR angiography. Stenosis was diagnosed in cases showing a degree of luminal narrowing of > or = 50%. The stroke subtypes were categorized as large artery atherosclerosis (LAA), small artery occlusion (SAO), cardioembolism (CE), and stroke of undetermined etiology (SUE). MetS was defined using the criteria of the Adult Treatment Panel III. The mean carotid intimal medial thickness values showed increased tendency as the number of MetS components increased (P < 0.001). Regardless of stroke subtype, the MetS (+) group showed an increasing tendency toward stenosis (LAA, SAO, all P < 0.001; CE, P = 0.001; SUE, P = 0.077). MetS was independently associated with intracranial atherosclerosis (odds ratio, 3.58; 95% CI, 2.28-5.63), which was prominent with more severe MetS components after adjustment for other risk factors (P < 0.001). Amongst the component conditions, elevated blood pressure, increased blood glucose/hyperglycemia, and abdominal obesity were dominantly associated with stenosis (all P < 0.001). Modifications of the individual MetS components need to be considered for stroke prevention because of intracranial atherogenic progression.