An enhanced model for environmental dry eye: Exploring pathological features and underlying factors.

This study aimed to develop an enhanced environmental dry eye (EDE) model that accurately reproduces the etiology of prolonged visual fatigue and investigates the underlying pathological features. A total of 40 adult SPF-grade Wistar rats were randomly assigned to control (n = 20) and model (n = 20) groups. Rats in the control group were maintained under normal conditions, while rats in the model group were exposed to a controlled frontal airflow of 2-4 m/s from a fan for 7.5 h daily while placed on a suspended cylindrical wire mesh frame. Various assessments were performed at different time points during the 14-day experiment, including blink frequency, tear secretion (phenol red thread test), tear film breakup time (BUT), fluorescein staining (FL), corneal epithelial status (light microscopy), ultrastructure of corneal epithelial cells (electron microscopy), and expression levels of inflammatory cytokines (IL-1ß, TNF-α) in tears (enzyme-linked immunosorbent assay). Additionally, mRNA and protein expression levels of MMP-9, IL1ß, IL6, TNF-α, IFN-γ, and caspase-3 in corneal tissues were quantified (real-time quantitative PCR and Western blotting). Compared to the control group, the model group rats exhibited significant decreases in blink frequency (P < 0.001), tear secretion (Schirmer I test) values (P < 0.001), and tear film breakup time levels (P < 0.001). There was also a significant increase in fluorescein staining scores (P < 0.001) in the model group. Histological examination revealed distinct differences of the corneal epithelium between groups. The corneal epithelium of the model group appeared thicker, with disorganized cell arrangement in the superficial and basal layers, partial defects or detachment of superficial epithelial cells, and a rough, uneven surface. Scanning electron microscopy observations showed a rough corneal epithelial surface with numerous cracks and scattered vesicular-like structures in the model group. Furthermore, the model group rats exhibited a significant increase in expression of IL-1ß and TNF-α in tears (P < 0.001), and upregulated expression levels of MMP-9, TNF-α, IL-1ß, caspase-3, IL-6, and IFN-γ at both the mRNA and protein levels in corneal tissues (P < 0.001). In conclusion, the modified "wire-meshing cylindrical board" model effectively overcomes the limitations of the traditional "jogging board " dry eye model and successfully simulates the etiology of prolonged visual fatigue. This innovative EDE model demonstrates a high degree of relevance to dry eye conditions resulting from prolonged visual tasks, with a high success rate of model induction. Moreover, it proves to be a simple, practical, and easily replicable model, making it highly suitable for further studies on prolonged visual fatigue and facilitating its widespread adoption in research and clinical applications.

Utilization of Amplitude-Integrated Electroencephalography to Predict Neurologic Function after Resuscitation in Adults with Cardiogenic Cardiac Arrest.

BACKGROUND: Amplitude-integrated electroencephalography (aEEG) has been used as a tool to recognize brain activity in children with hypoxic encephalopathy. OBJECTIVES: To assess the prognostic value of aEEG during the post-resuscitation period of adult cardiogenic cardiac arrest, comatose survivors were monitored within 24 h of a return of spontaneous circulation using aEEG. METHODS: Forty-two consecutive patients experiencing cardiac arrest were retrospectively enrolled, and a return of spontaneous circulation was achieved in all cases. These patients were admitted to the Coronary Intensive Care Unit due to cardiogenic cardiac arrest. The primary outcome was the best neurologic outcome within 6 months after resuscitation, and the registered patients were divided into two groups based on the Cerebral Performance Category (CPC) scale (CPC 1-2, good neurologic function group; CPC 3-5, poor neurologic function group). All patients received an aEEG examination within 24 h after a return of spontaneous circulation, and the parameters and patterns of aEEG recordings were compared. RESULTS: Nineteen patients were in the good neurologic function group, and 23 were in the poor group. The four voltage parameters (minimum, maximum, span, average) of the aEEG recordings in the good neurologic function groups were significantly higher than in the poor group. Moreover, the continuous pattern, but not the status epilepticus or burst suppression patterns, could predict mid-term good neurologic function. CONCLUSIONS: aEEG can be used to predict neurologic outcomes based on the recordings' parameters and patterns in unconscious adults who have experienced a cardiac collapse, resuscitation, and return of spontaneous circulation.

Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease.

BACKGROUND: This study examines the predictive value of a novel systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients. METHODS: A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long-term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure. RESULTS: An optimal SII cut-off point of 694.3 × 109 was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43-2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09-1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28-2.99), MACE (HR: 1.65; 95% CI: 1.36-2.01) and total major events (HR: 1.53; 95% CI: 1.32-1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C-index (P < .001) and reclassification risk categories by significant NRI (P < .05) and IDI (P < .05). CONCLUSIONS: SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention.

The impact of successful revascularization of coronary chronic total occlusions on long-term clinical outcomes in patients with non-ST-segment elevation myocardial infarction.

OBJECTIVES: The purpose of this study was to assess the long-term clinical impact of revascularization of coronary concomitant coronary chronic total occlusion (CTO) in patients with Non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: CTO is associated with poorer prognosis in patients with NSTEMI. The evidence of revascularization of CTO in patients with NSTEMI is still conflicting. METHODS: Consecutive patients with NSTEMI and CTO who underwent percutaneous coronary intervention (PCI) within 72 h of admission from 2006 to 2015 were retrospectively recruited and analyzed. A total of 967 patients underwent PCI for NSTEMI. Among them, 106 (11%) patients had concomitant CTO and were recruited for analysis. CTO lesions were revascularized successfully in 67 (63.2%) patients (successful CTO PCI group), while the CTO in the remaining 39 patients were either not attempted or failed (No/failed CTO PCI group). RESULTS: The 30-day cardiac death and major adverse cardiac events (MACE) were significantly lower in the successful CTO PCI group (both cardiac death and MACE were 3% vs 30%, P < 0.001, respectively). A landmark analysis set at 30th day for 30-day survivals was performed. After a mean of 2.5-year follow-up, the long-term cardiac death was still significantly lower (16.9% vs 42.3%, P < 0.001), whereas the MACE showed a trend toward lower incidence (26.2% vs 40.7%, P = 0.051) in the successful CTO PCI group. In multivariate Cox regression analysis, successful revascularization of CTO is an independent protective predictor for long-term cardiac death (HR 0.310, 95% CI, 0.109-0.881, P = 0.028) in all population and in propensity-score matched cohort (P = 0.007). CONCLUSIONS: Successful revascularization of CTO was associated with reduced risk of long-term cardiac death in patients with NSTEMI and concomitant CTO.

Sex and age differences of major cardiovascular events in patients after percutaneous coronary intervention.

BACKGROUND: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure. METHODS: Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events). RESULTS: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category. CONCLUSION: Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.

Effect of invasive strategy on different genders of Chinese patients with non-ST-elevation myocardial infarction.

OBJECTIVES: The aim of this study was to determine the impact of in-hospital revascularization on different genders and to compare the gender difference in short- and long-term prognosis of Chinese patients with non-ST-elevation myocardial infarction (NSTEMI). BACKGROUND: The benefit of invasive strategy between the genders of Asian ethnic populations with NSTEMI remains unclear. METHODS: A total of 343 consecutive NSTEMI patients were enrolled, 104 (30%) of them were women. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary end point was all-cause death. The secondary end point was the combined occurrence of death or myocardial (re-)infarction (MI). RESULTS: The adjusted in-hospital and long-term clinical outcomes were similar between men and women. However, in-hospital revascularization significantly reduced long-term mortality and composite endpoint in men (P < 0.001), but not in women. After risk stratification by GRACE score, there was favorable effect of invasive strategy in high-risk women. In a multivariate Cox regression analysis, GRACE score (hazard ratio; HR, 1.017; P < 0.001) and in-hospital revascularization (HR, 0.516; P = 0.008) were the independent predictors of death or MI in men. However, only GRACE score was the independent predictor of composite endpoint in women (HR, 1.012; P = 0.004). CONCLUSIONS: In Asian ethnic patients with NSTEMI, the in-hospital and long-term prognosis were similar between men and women. In-hospital revascularization has a benefit in men and high-risk women for reducing the all-cause death at 1 and 3 years. Our data provide evidence supporting the guideline recommendation for an invasive strategy in high-risk women.

[Effect of acupuncture on dry eye and tear inflammatory factors].

OBJECTIVE: On the basis of sodium hyaluronate eye drops, to observe the clinical efficacy of acupuncture on dry eye and explore the effect mechanism of ocular surface protection. METHODS: A total of 80 patients with dry eye were randomly divided into an observation group and a control group, 40 cases in each group. The control group was treated with routine cleaning of eyelid margin, hot compress of eyes with warm towel, and external application of sodium hyaluronate eye drops for 5 weeks. On the basis of the treatment as the control group, the observation group was treated with acupuncture at Jingming (BL 1), Cuanzhu (BL 2), Chengqi (ST 1), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6), etc., once a day, 6 times a week for 5 weeks (30 times totally). Before and after treatment, SchirmerⅠtest (SⅠT), breaking up time (BUT), corneal fluorescent (FL) score, ocular surface disease index (OSDI) score, and the contents of IL-6 and TNF-α in tears were evaluated and the therapeutic effect was compared between the two groups. RESULTS: Compared with before treatment, SⅠT and BUT after treatment in the observation group were prolonged (P<0.05), the scores of FL and OSDI and the contents of IL-6 and TNF-α in tears were decreased (P<0.05). After treatment, SⅠT and BUT in the observation group were longer than the control group (P<0.05), and the scores of FL and OSDI and the contents of IL-6 and TNF-α in tears in the observation group were lower than the control group (P<0.05). The total effective rate in the observation group was 87.5% (35/40), which was higher than 45.0% (18/40) in the control group (P<0.05). CONCLUSION: On the basis of sodium hyaluronate eye drops, acupuncture could improve the clinical symptoms of dry eye, promote the secretion of tears, prolong the tear film breaking up time, and reduce corneal damage, and effect mechanism may be related to the reduction of inflammatory response.

Association between visit-to-visit blood pressure variability and adverse events in coronary artery disease patients after coronary intervention.

Blood pressure variability (BPV) is independently associated with higher cardiovascular risks. However, whether BPV is associated with poor outcomes for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remained undetermined. We aimed to investigate the relationship between BPV and the outcomes of CAD patients undergoing PCI. Two thousand seven hundred and sixty-two CAD patients (1938 males, mean age 69.6 ± 12.9) who received PCI at Taipei Veterans General Hospital from 2006 to 2015 with multiple blood pressure measurements before and after the index PCI were enrolled. We calculated the standard deviation of systolic blood pressure, diastolic blood pressure, and pulse pressure as parameters of BPV. The primary endpoint was the composite of major adverse cardiovascular events [MACE comprising of cardiovascular death, nonfatal myocardial infarction (MI), and non-fatal stroke] and heart failure hospitalization (HHF). The key secondary endpoint was MACE. Both pre-PCI and post-PCI BPV were associated with CV events even after adjusting for co-morbidities and mean blood pressure. In Cox analysis, for every 1 mmHg increase in systolic BPV, the hazard ratio for the MACE + HHF, MACE, HHF, and cardiovascular death was 1.04 (95%CI: 1.03-1.05), 1.04 (95%CI: 1.02-1.05), 1.05 (95%CI: 1.04-1.06), and 1.06 (95%CI: 1.03-1.09), respectively. The association between BPV and cardiovascular risk is independent of blood pressure control status. The prognostic value of BPV was superior to mean blood pressure in both pre-PCI and post-PCI period. BPV is independently associated with cardiovascular events after PCI and has a better prognostic value than mean blood pressure suggesting the importance of maintaining stable blood pressure for CAD patients.

Haptoglobin phenotypes and plasma haptoglobin levels in patients with abdominal aortic aneurysm.

OBJECTIVE: Inflammation is associated with the disruption of the aortic media and appears to play a fundamental role in the progression and development of abdominal aortic aneurysm (AAA). Haptoglobin (Hp) is a genetically determined acute phase protein, the synthesis of which is increased during inflammation. This study was designed to investigate both phenotype and plasma levels of Hp in patients with AAA. METHODS: Patients with documented AAA who were admitted for elective open repair operation or endograft stent implantation, and non-AAA subjects admitted for coronary arteriography, but found to have normal or insignificant coronary artery disease, were included in the study. Plasma Hp levels were determined using a standard specific enzyme-linked immunosorbent assay, while Hp phenotype was determined by native polyacrylamide gel electrophoresis. Total cholesterol, high density lipoprotein, low density lipoprotein, and triglyceride levels were analyzed enzymatically, and C-reactive protein was analyzed by immunochemistry. RESULTS: Forty-five patients with AAA and 49 non-AAA subjects were included. The Hp 2-2 phenotype was more predominant in AAA patients compared with non-AAA subjects, but this difference was not significant (67% vs 47%; P = .141), while plasma Hp concentrations were significantly higher in AAA patients (237 ± 144 vs 163 ± 86 ng/mL; P = .024). Further analysis revealed that plasma Hp concentrations were significantly higher in AAA patients with the 2-2 phenotype compared with corresponding non-AAA subjects (238 ± 144 vs 163 ± 86 ng/mL;P = .024). CONCLUSIONS: Our findings suggest that plasma Hp concentrations are elevated in patients with AAA, particularly those with the Hp 2-2 phenotype.

Human haptoglobin phenotypes and concentration determination by nanogold-enhanced electrochemical impedance spectroscopy.

Haptoglobin (Hp) is an acute phase protein that binds free hemoglobin (Hb), preventing Hb-induced oxidative damage in the vascular system. There are three phenotypes in human Hp, whose heterogeneous polymorphic structures and varying concentrations in plasma have been attributed to the cause of diseases and outcome of clinical treatments. Different phenotypes of Hp may be composed of the same subunits but different copy numbers, rendering their determination difficult by a single procedure. In this study, we have developed a simple, fast, reliable and sensitive method, using label-free nanogold-modified bioprobes coupled with self-development electrochemical impedance spectroscopy (EIS). By this method, probe surface charge transfer resistance is detected. The relative charge transfer resistance ratios for Hp 1-1, Hp 2-1 and Hp 2-2 were characterized. We were able to determine protein size difference within 3 nm, and the linear region of the calibration curve for Hp levels in the range of 90 pg ml(-1) and 90 µg ml(-1) (∼1 fM to 1 pM). We surmise that similar approaches can be used to investigate protein polymorphism and altered protein-protein interaction associated with diseases.

Association of apolipoprotein J polymorphism 1598delT with coronary artery disease and lipoprotein levels.

OBJECTIVES: To investigate a polymorphism of the apolipoprotein J (APOJ) gene in relation to coronary artery disease (CAD) and lipid variables in a Chinese male population of genetically unrelated individuals. METHODS: In this study, we recruited 126 control male subjects and 237 CAD male patients. CAD was defined as a fixed stenotic lesion with luminal narrowing ≥50% in at least one of the major or minor coronary arteries. In cases with documented myocardial infarction, only those rated as fully recovered for more than 3 months were enrolled. Patients with acute or chronic infectious diseases and those with malignancies were excluded. All subjects with a fasting serum triglyceride level higher than 300 mg/dl were likewise excluded. RESULTS: We identified a single nucleotide polymorphism, 1598delT, and showed its association with CAD. Subjects with the I/I genotype showed a significantly higher CAD risk compared to those with the D/D genotype (OR 2.34, 95% CI 1.11-4.94, p = 0.026). Patients with the I/I genotype also had abnormal levels of high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol associated with CAD. CONCLUSIONS: Our data indicated that the APOJ single nucleotide polymorphism (1598delT) is associated with risk factors for CAD in a Chinese population.

Association between phosphate and long-term outcome in CAD patients underwent coronary intervention.

Phosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization (HHF). The key secondary outcome was MACE. There was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1 mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE + HHF (HR: 1.12, 95% CI: 1.05-1.21): CV death (HR: 1.37, 95% CI: 1.22-1.55) and HHF (HR: 1.12, 95% CI: 1.02-1.23). Subgroup analyses showed more prominent association between phosphate and MACE + HHF in male, age > 65, bare-metal stents (BMSs), LVEF < 50%, eGFR < 60, LDL > 70 mg/dL, and emergent PCI. Phosphate has a significant association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function.

Optimal blood pressure for patients with end-stage renal disease following coronary interventions.

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end-stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m2 ) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy-five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17-3.46, p = .008) than those with systolic BP 140-149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27-1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15-4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg. A J-shaped association between systolic (140-149 mm Hg) and diastolic (80-89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non-Western population.

Computer-Assisted Quantitative Analysis of Drug-Induced Sleep Endoscopy for Obstructive Sleep Apnea/Hypopnea Syndrome.

OBJECTIVES: To use computer-assisted quantitative measurements of upper airway changes during drug-induced sleep endoscopy (DISE) and to correlate these parameters with disease severities and physiologic changes in patients with obstructive sleep apnea/hypopnea syndrome (OSA). DESIGN: A retrospective study. SETTING: Tertiary academic medical center. PATIENTS AND METHODS: A total of 170 patients who failed continuous positive airway pressure therapy and then underwent upper airway surgery were enrolled. All patients received polysomnography and DISE preoperatively. We used ImageJ 1.48v to obtain maximal and minimal measurements, including cross-sectional areas and anterior-posterior and lateral diameters at 4 anatomic levels (retropalatal, oropharyngeal, retroglossal, and retroepiglottic) under DISE, and then computed the percentage changes. We analyzed the clinical values of DISE changes by computer-assisted analysis in patients with OSA and any correlations between these changes and polysomnography parameters. RESULTS: The percentage changes of upper airway showed significant collapses at all 4 anatomic levels (all P < .0001). We also found that the changes at retropalatal levels were significantly greater and that retroglossal levels were significantly smaller, while the changes of anterior-posterior diameters at retroglossal levels showed a significant positive association with apnea-hypopnea index and desaturation index. However, there were no statistically significant correlations between upper airway changes and obesity. CONCLUSION: Computer-assisted quantitative analysis could evaluate upper airway changes of OSA in an objective way and may help identify the sites of obstruction during DISE more accurately. Upper airway showed multilevel collapse with independent significant changes in patients with OSA, with the retropalatal and retroglossal levels playing important roles in particular.

Association between Preoperative Nutritional Status and Clinical Outcomes of Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Malnutrition is associated with poor outcomes in patients with cancer, heart failure and chronic kidney disease. This study aimed to investigate the predictive value of the Controlling Nutritional Status (CONUT) score in coronary artery disease (CAD) patients. METHODS: We recruited a cohort of 3118 patients with CAD undergoing percutaneous coronary intervention (PCI) from 2005 to 2015. Nutritional status was evaluated using the CONUT score, with higher scores reflecting worse nutritional status. RESULTS: After adjustment for comorbidities and medication, an increased CONUT score was independently associated with a higher risk of acute myocardial infarction (AMI) (HR: 1.13; 95% CI: 1.03-1.24), cardiovascular (CV) death (HR: 1.18; 95% CI: 1.07-1.30), congestive heart failure (CHF) (HR: 1.11; 95% CI: 1.04-1.18), a major adverse cardiovascular event (MACE) (HR: 1.14; 95% CI: 1.07-1.22), and total CV events (HR: 1.11; 95% CI: 1.07-1.15). The subgroup analyses demonstrated that the association of the CONUT score existed independently of other established cardiovascular risk factors. In addition, CONUT significantly improved risk stratification for myocardial infarction (MI), cardiac death, CHF, MACEs and total CV events compared to conventional risk factors in CAD patients by the significant increase in the C-index (p < 0.05) and reclassification risk categories in cardiac death and MACEs. Conclusions The CONUT score improved the risk prediction of adverse events compared to traditional risk factors in CAD patients after percutaneous coronary intervention (PCI).

Association of variability in uric acid and future clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. METHODS: We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. RESULTS: During an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78-3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53-3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52-16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32-5.05), and total major CV events (HR: 2.72, 95% CI: 2.09-3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36-1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38-1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13-1.82), CV death (HR: 1.77, 95% CI: 1.50-2.11), HF (HR: 1.43, 95% CI: 1.29-1.58), and total major CV events (HR: 1.46, 95% CI: 1.34-1.58). CONCLUSIONS: High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI).

Plasma haptoglobin level can augment NT-proBNP to predict poor outcome in patients with severe acute decompensated heart failure.

To evaluate the use of plasma haptoglobin (Hp) levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in predicting survival in patients with severe acute decompensated heart failure (AHF). Management of AHF is challenging. Identifying markers associated with patient prognosis in this disease is clinically important. In this prospective observational study, plasma Hp and NT-proBNP levels were measured. Receiver operating characteristic (ROC) curves were used to identify cut-offs of Hp and NT-proBNP with the greatest specificity and sensitivity for predicting overall survival and cardiovascular-related survival. The cut-off values were tested in patients with AHF (n=41). The cut-off value with the greatest specificity and sensitivity with respect to overall survival and for cardiovascular-related survival for Hp was 177. 1 ng/mL for both outcomes and for NT-proBNP was 34 246.0 pg/mL and 11 848.5 ng/mL, respectively. Using these cut-off values, this study found that patients with lower baseline Hp levels (<177. 1 ng/mL) or higher baseline NT-proBNP (≥34 246 pg/mL) were more likely to have shorter overall survival. Similarly, patients with <177. 1 ng/mL of Hp and ≥11 848.5 pg/mL of NT-proBNP had the highest risk of death related to cardiovascular disease. Our findings indicate that Hp and NT-proBNP using specific cut-off values for AHF can be used to determine risk of survival in these patients.

2,3,7,8-Tetrachlorodibenzo-p-dioxin modulates the induction of DNA strand breaks and poly(ADP-ribose) polymerase-1 activation by 17beta-estradiol in human breast carcinoma cells through alteration of CYP1A1 and CYP1B1 expression.

The primary purpose of this research is to investigate the effects of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) pretreatment and estrogen receptors-alpha (ER alpha) status on the induction of DNA damage by 17beta-estradiol (E 2) in human ER alpha(+)/MCF-7 and ER alpha(-)/MDA-MB-231 breast cancer cells. Results indicated that E 2 (0.1-100 nM) alone induced significant increases in cytotoxic response, reactive oxygen species (ROS) generation, and glutathione depletion in MDA-MB-231 cells but not in MCF-7 cells. At noncytotoxic concentrations, E 2 induced dose-related reduction in intracellular NAD(P)H in MDA-MB-231 cells through decreases in intracellular NAD (+) mediated by poly(ADP-ribose) polymerase-1 (PARP-1) activation as determined by detection of the presence of polymers of ADP-ribose-modified PARP-1 using Western blotting. Further investigation using the single-cell gel electrophoresis (Comet) assay confirmed that the PARP-1 activation induced by estrogen in MDA-MB-231 was due to increases in the number of DNA strand breaks. This evidence indicates that E 2 induces decreases in intracellular NAD(P)H and NAD (+) in MDA-MB-231 cells through PARP-1 activation mediated by the formation of DNA strand breaks. Further investigation indicated that the cytotoxic and DNA-damaging effects induced by E 2 in MDA-MB-231 cells were completely blocked by pretreatment of TCDD (10 nM for 72 h). In contrast, with TCDD pretreatment, significant increases in cytotoxic response, ROS generation, glutathione (GSH) depletion, DNA strand breaks, and PARP-1 activation were detected in MCF-7 cells exposed to E 2. We demonstrated that TCDD modulated the differential induction of DNA damage by estrogen in MDA-MB-231 and MCF-7 cells primarily through the inducibility of cytochrome P450 1A1 and 1B1 expression. Overall, this evidence suggests that TCDD is capable of inducing imbalances in the expression of enzymes responsible for the bioactivation of estrogen leading to the subsequent accumulation of DNA damage and initiation of DNA repair in MDA-MB-231 and MCF-7 cells. Furthermore, we confirmed that ER alpha plays a protective role in modulating the induction of DNA damage by E 2 in human breast cancer cells.

Immunochemical property of human haptoglobin phenotypes: determination of plasma haptoglobin using type-matched standards.

OBJECTIVES: Haptoglobin (Hp) phenotypes 1-1, 2-1, and 2-2 are associated with inflammatory diseases. Since their biochemical structures are rather heterogeneous, it is necessary to accurately determine the plasma Hp levels. DESIGN AND METHODS: Immunodiffusion, immunoturbidimetric, and noncompetitive ELISA were conducted to determine the differences in immunoreactivity among Hp phenotypes and to verify that such difference may significantly affect the outcome of Hp determinations. A novel ELISA using phenotype-matched calibrators was performed to compared with a commercial GenWay ELISA kit using a single calibrator in normal healthy males. RESULTS: In immunodiffusion and immunoturbidimetric assays, the immunoreactivity of Hp 1-1 was markedly higher than 2-1 and 2-2, while an opposite result was observed using an ELISA. The latter was primarily due to the repeated antigenic epitopes in polymeric 2-1 and 2-2. Thus, Hp levels could be significantly over- or underestimated depending on the method. An accurate ELISA could be achieved when using each type-specific Hp calibrator matched to each type subject. We show the mean levels of Hp 1-1 subjects (n=16; 184+/-42 mg/dL) to be significantly and differentially greater than 2-1 (n=28; 153+/-55 mg/dL) (p<0.05) and 2-2 (n=24; 93+/-54 mg/dL) (p<0.01) subjects. CONCLUSIONS: Due to the diverse immunochemical structure among the Hp types, phenotyping should be performed in all the patients and a type-matched Hp calibrator should be used in clinical Hp determination.

Gel electrophoresis of polyphenol oxidase with instant identification by in situ blotting.

Polyphenol oxidase (PPO) or tyrosinase is an important and ubiquitous enzyme responsible for browning in plants and melanization in animals. The molecular size of the plant PPO is varied among the species and its activity can be enhanced by a variety of anionic detergents. In the present study, we developed a simple method for the first-step identification of PPO in fruit and vegetable extracts. First, 3mm chromatographic paper was immersed in 0.5% (w/v) catechol solution as an immobilized PPO substrate. After running the extract with 10% sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), one side of the glass plate was removed. The plate was immediately laid on top of the dried catechol-paper. A dark-brown band corresponding to PPO was visualized within 1 min and was further confirmed by a conventional Western blot using an antibody prepared against mushroom PPO. It also reveals that some vegetation (such as tomato, radish, and oriental melon) with low or no detectable activity in a conventional enzyme assay actually possessed marked levels of PPO activity when assessed by PAGE-blot. We propose that an inhibitor is associated with PPO in some plants; the inhibitor, however, is dissociated during the electrophoresis. Therefore, in addition to identify the molecular form of PPO, the present technique may explore the existence of PPO inhibitor(s) in plants. The detail of the method with respect to its relevance for searching a natural PPO inhibitor is described and discussed.