Cholesterol esters regulate apoB48 secretion in CaCo2 cells

In this study, we investigated the effect of atorvastatin, an HMG-CoA reductase inhibitor and CL277082, an ACAT inhibitor, on apolipoprotein B48 synthesis, degradation and secretion in transformed human intestinal enterocytes (CaCo2 cells). Cells were incubated with atorvastatin or CL277082 in the absence or presence of sterol containing media and pulsed with [S35]-methionine and chased with unlabelled methionine. Concomitantly, the effect of atorvastatin and CL277082 on the relative amount of apoB48 protein in cells and media was also quantified by western blotting using an apoB antibody and enhanced chemiluminescence. Suppression of cholesterol synthesis with atorvastatin did not attenuate the production or secretion of apoB48 from CaCo2 cells under basal conditions. On the other hand, suppression of cholesterol biosynthesis with atorvastatin under stimulatory conditions accelerated the degradation of apoB48 in cells without affecting its synthesis or secretion. There was no effect of exogenous sterols on apoB48 secretion. Taken together, neither endogenous nor exogenous cholesterol appears to acutely modulate apoB48 secretion from intestinal cells. In contrast, inhibition of cholesterol esterification with ACAT inhibitor significantly attenuated apoB48 secretion under basal and stimulatory conditions by a mechanism which enhanced apoB48 degradation. Collectively, our results suggest that in CaCo2 cells, newly synthesized cholesterol ester may be an immediate regulator apoB48 secretion.     

Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver.

Apolipoprotein-B 48 (apoB 48) and apoB 100 expression and the editing of apoB mRNA have previously been shown to be hormonally regulated in rat liver. We have investigated the effects of hypophysectomy and replacement therapy with T4, cortisol (C), and GH in vivo on the proportion of edited apoB mRNA in rat liver and cultured rat hepatocytes as well as the synthesis and secretion of apoB 48 and apoB 100 in cultured rat hepatocytes. Hypophysectomy decreased the proportion of edited apoB mRNA in intact liver from 62% in normal rats to 29% in hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C did not influence the proportion of edited apoB mRNA, whereas treatment with GH, either alone or together with T4 and C, increased the proportion of edited apoB mRNA to the levels observed in normal rats. In cultured hepatocytes isolated from normal rats, the proportion of apoB 48 (percentage of total labeled apoB) was 78% and decreased to 40% in cells isolated from hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C had no effect on the proportion of apoB 48 present in isolated cells, whereas it increased to 60% after treatment with GH together with T4 and C. The proportion of apoB 48 in the medium was affected by hypophysectomy and the various hormonal treatments in a similar way to that observed in the cells. Results from in vivo labeling experiments suggested that GH alone had the capacity to increase the percentage of apoB 48 in hypophysectomized rats. On the contrary, T4 and C was needed, in addition to GH, to increase the proportion of apoB 48 in isolated hepatocytes from hypophysectomized rats. Our results suggest that this discrepancy is due to a difference between the effect of GH alone on apoB mRNA editing in the intact liver and that in isolated hepatocytes. The total secretion of apoB into the cell culture medium was not affected by hypophysectomy and hormonal treatments of the rats. In conclusion, these results indicate that GH is involved in the regulation of editing of apoB mRNA and the proportion of apoB 48 synthesized and secreted in rat liver. Thus, our observations emphasize the importance of GH as a regulator of lipoprotein metabolism.     

Cardiac computed tomography of an asymptomatic 48‐year‐old woman with ALCAPA syndrome

Untreated ALCAPA cases most often die in infancy. Adults with untreated ALCAPA commonly present with mitral regurgitation, severe left ventricular dysfunction, and sometimes myocardial infarction. Herein, we present an asymptomatic adult female with ALCAPA recognized through cardiac computed tomography (CT). In ALCAPA, like other coronary anomalies, cardiac CT is often instrumental in providing unique noninvasive and clinically relevant evaluation. Herein, we present an atypical presentation of an asymptomatic middle‐aged adult female with ALCAPA.     

Temporal discrepancies in the association between the apoB/apoA‐I ratio and mortality in incident dialysis patients

Background. In the general population, a high apoB/apoA‐I ratio is a strong risk factor for cardiovascular disease and mortality. However, whether this is the case in chronic kidney disease (CKD) patients is currently unknown. Study design. The apoB/apoA‐I ratio was evaluated in 391 incident CKD stage 5 patients examined close to dialysis initiation, and again after 1 year of dialysis in a subgroup of 182 patients, subsequently followed for up to 3 years. Results. Baseline values of the apoB/apoA‐I ratio as well as changes in the ratio during the first year of dialysis correlated with body mass index (BMI) and fat mass. The baseline apoB/apoA‐I ratio showed no association with 4‐year mortality. However, after adjustment for confounders, a high apoB/apoA‐I ratio (>0.9) predicted short‐term (first year) survival [hazard ratio (HR): 0.35; 95% confidence interval (CI): 0.13–0.85)] and long‐term (next 3 years) mortality (HR: 1.72; 95% CI: 1.01–2.96). An increase in the apoB/apoA‐I ratio during the first year of dialysis was linked to a survival advantage thereafter (HR: 0.48; 95% CI: 0.22–0.98). However, this association lost its significance (HR: 0.62; 95% CI: 0.26–1.36) after adjustment for indices of protein‐energy wasting. Conclusions. A high apoB/apoA‐I ratio and an increase in this ratio during the first year on dialysis were associated with short‐term survival advantage in CKD patients. This paradoxical relationship represents an example of the so‐called reverse epidemiology phenomenon in CKD patients and suggests that the apoB/apoA‐I ratio should always be interpreted with caution in this patient population.     

Repeatability of Sleep Apnea Detection in 48‐Hour Holter ECG Monitoring

Background: There is a significant relationship between obstructive sleep apnea (OSA) and cardiovascular diseases. Reliability of new methods evaluating apnea in Holter ECG monitoring is still the matter of investigators’ studies. Methods: In 48‐hour Holter ECG monitoring recordings of 63 patients, we assessed repeatability, comparing the results from both sleep periods. Results: We found good repeatability in evaluation of apnea‐hypopnea index value. There was moderate agreement in three categories, that is, normal or bordeline or apneic assignment. Assignment to “healthy” (normal and borderline) or apneic subgroup during consecutive sleep periods showed high repeatability. Conclusions: Holter ECG monitoring is a repetitive method of preliminary diagnosis in patients evaluated for sleep apnea syndrome. Ann Noninvasive Electrocardiol 2010;15(3):218–222     

Impact of Occluded Culprit Arteries on Long‐Term Clinical Outcome in Patients with Non‐ST‐Elevation Myocardial Infarction: 48‐Month Follow‐Up Results in the COREA‐AMI Registry

Background

The prognostic impact of occluded culprit arteries in non‐ST‐elevation myocardial infarction (NSTEMI) patients beyond 12 months has not been investigated.

Objectives

The impact of occluded culprit arteries on a composite of cardiac death (CD), recurrent nonfatal MI (RMI), and target vessel revascularization (TVR) in patients who presented with NSTEMI was investigated during a 48‐month follow‐up using propensity‐score (PS) matching.

Methods

A total of 2,878 NSTEMI patients in the COREA‐AMI (COnvergent REgistry of cAtholic and chonnAm university for Acute MI) Registry were classified according to the angiographic flow of culprit arteries (occlusion [OC], n = 1,070; nonocclusion, n = 1,808). After PS matching, the incidence of the primary end‐point, a composite of CD, RMI, and TVR was compared.

Results

The median follow‐up duration was 47.3 months (IQR 32.7–66.2). In the PS‐matched population, the 48‐month cumulative rates of the primary end‐point (27.5% vs. 17.9%, P < 0.001) and each event were higher in the OC group (CD: 9.0% vs. 5.4%, RMI: 16.3% vs. 9.4%, TVR: 10.5% vs. 5.6%, respectively, P < 0.05). In multivariate Cox regression analysis, occluded culprit arteries showed the significant statistical impact on the primary end‐point (HR 1.689 [1.385–2.059], P < 0.001) and each event (CD: 1.736 [1.218–2.475], RMI: 1.918 [1.468–2.505], TVR: 2.042 [1.453–2.869], respectively, P < 0.05). Furthermore, in the 12‐month landmark analysis, occluded culprit arteries were still associated with higher risk of primary end‐point beyond 12 months (P < 0.001).

Conclusions

Occluded culprit arteries were independently associated with the higher risk of CD, RMI, and TVR in NSTEMI patients during the 48‐month follow‐up. (J Interven Cardiol 2014;27:12–20)

     

Comparison of 48‐week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta‐analysis

Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first‐line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta‐analysis of randomized trials. The secondary aim was to additionally include propensity‐matched cohort studies in a conventional meta‐analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English‐language randomized and propensity‐matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48 weeks. We excluded patients who had co‐infection or significant prior treatment with antivirals. 13 517 participants from 16 studies (11 RCTs, n = 2675; five propensity‐matched cohort studies, n = 10 842) were included. Virological response at 48 weeks was higher in patients receiving TDF compared to ETV using both the network meta‐analytic approach (OR 1.69, P < .001) and the conventional meta‐analysis including propensity‐matched cohort studies (OR 1.40, P < .001). On subgroup analysis, this difference was only significant in HBeAg‐positive patients (OR 1.81, P = .037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P = .07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48 weeks in treatment‐naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.     

Evaluation of Patients with Palpitations: Cardiac Event Recorder Versus 48‐hour Holter Monitoring

Objectives: (1) To compare a diagnostic yield of cardiac event recorders with that of 48‐hour Holler monitoring, (2) to determine the etiologies of palpitations, and (3) to assess an optimal duration of using an event recorder by a patient. Background: Palpitation is a common symptom which accounts for 16% of total complaints reported by patients in general medical settings. An ambulatory Holter ECG monitoring or an event recorder can be used to establish the cause of palpitations. Methods: (1)The study group consisted of 33 consecutive patients (24 females, 9 males, mean age 50 ± 32 years) with undiagnosed attacks of palpitations, occurring at least once per month. Each patient was randomly allocated to use either an event monitor or 48‐hour Holler monitoring. The patient kept the event monitor for 4 weeks. After the first monitor was returned, the patient was given the other device. Results: Holter monitoring determined the etiology of palpitations in 11 (33%) patients, and the event recorder in 21 (64%) patients (P = 0.0138). In the whole study group, the etiology of palpitations was disclosed in 23 (70%) patients. The diagnosis was possible using Holler ECG monitoring in only 2 (9%) patients, whereas the event recorder revealed the underlying mechanism of palpitations in 12 (52%) patients (P = 0.0007). In nine (39%) patients both methods were able to disclose the eliology of palpitations. The findings of 117 recordings obtained using an event recorder during palpitations were atrial fibrillation in 10 (9%), narrow QRS tachycardia in 4 (3%), frequent supraventricular eclopy in 17 (15%), frequent ventricular eclopy in 6 (5%), and episodes of palpitations sinus rhythm were recorded in the remaining 80 (68%). Of patients who experienced episodes of palpitations while using an event recorder, the earliest recording was obtained on the first day of the study, and the latest on the 18 day of using the event recorder. Conclusions: (1) The cardiac event recorders yield more diagnoses than 48‐hour Holter monitoring in patients with palpitations occurring at least once per month, (2) in this group of patients the event recorder provided a diagnostic ECG recording during the first 18 days of using the device, and (3) in the majority (57%) of patients a normal sinus rhythm was recorded during episodes of palpitations. A.N.E. 2000;5(4):315–321     

载脂蛋白B对急性脑梗塞患者的影响

目的 探讨急性脑梗塞时载脂蛋白Ｂ与病情严重程度的预后关系。方法 对住院的急性脑梗塞患者３８７例进行分析，其中按脑梗塞严重程度分轻、中、重三组，而对血脂和ａｐｏＡ１ａｐｏＢ的含量进行分组对０；按入院时ａｐｏＢ高低分甲乙、丙三组进行分析。结果急性脑梗塞患者中有高血压病、冠心我者占７５．１９％，ＡＴＧ和ａｐｏＢ水平在重型脑梗塞患者中明显高于中型、轻型两者比较有显著性差异（Ｐ〈０．０１）；入院时ａｐｏＢ     

A 48‐week,randomized, double‐blind,double‐observer,placebo‐controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: Results of the METGO study

Objective

To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX).

Methods

A randomized, double‐blind, double‐observer, placebo‐controlled multicenter trial of 48 weeks was conducted. Sixty‐five RA patients who had a suboptimal response to ≥12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent‐to‐treat strategy.

Results

Sixty‐one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (χ² = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty‐six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost‐effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy.

Conclusion

In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold–related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.