Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients

Background. Cyclooxygenase-2 (COX-2) enzyme over expression is reported in many human HCC cell line studies and is linked to tumor cell resistance to chemotherapy-induced apoptosis. We hypothesized that adding a COX-2 inhibitor would improve the therapeutic benefits in patients with HCC. COX-2 is often increased and involved in drug resistance and poor prognosis.Method. Between January 2001 and December 2007, 15 patients with MDR-positive-HCC from 34 HCC patients based on tissue and serum liver of glypican-3 and fitting the preset eligibility criteria, were treated with a combination regimen with intravenous infusion of (5-FU) 750 mg once per week, 100mg/day cyclophosphamide (Endoxan) and 400 mg/day celecoxib taken orally in divided doses, while the rest of the patients received only 5-FU and Endoxan. Twenty-one patients (62%) had liver disease associated with hepatitis C virus (HCV) and 5 patients with hepatitis B virus (62%). Results. We found that celecoxib reduced P-glycoprotein with activation of caspase-3 and marked regression of tumor sizes. Sera angiogenic factors (VEGF &amp; bFGF) levels measurement in HCC patients indicated that, the sera levels of both angiogenic factors were reduced significantly (p < 0.05) after treatment. Based on the tumor markers AFP &amp; Glypican-3, 11 of the patients had a PR (11/15), including 3 patients who had normalization of AFP, and four patients had CR (4/15).Conclusions. These data suggest that the combination of 5-FU, Endoxan and Celecoxib is highly effective palliative regimen for patients with HCC with good performance status (score ≤ 3). The study suggests a framework for Celecoxib-based combination treatment of HCC

Alteration of AP-endonuclease1 expression in curcumin-treated fibrotic rats

Background. Apurinic/apyrimidinic endonuclease1/ redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA base excision repair and redox regulation of many transcription factors. It is an important pro-survival protein activated in response to oxidative stress. Increased level of this essential redox sensi¬tive protein correlates closely with cellular survival against oxidative insults. Curcumin (diferuloylmethane) a naturally occurring compound derived from turmeric has attracted interest because of its anti-inflamma¬tory, anti-oxidative, and chemopreventive activities.Material and methods. The current study evaluates the in vivo role of curcumin in protecting and treating liver injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats. It also addresses the possible involvement of the multifunctional protein APE1 in hepatoprotection. Analysis of APE1 expression was performed at mRNA and protein levels by reverse trans¬criptase (RT)-PCR and western blotting respectively. Profile of HSCs-activation related genes were assayed by RT-PCR and pro-inflammatory cytokines levels were determined by enzyme-linked immune assays.Results. Here we show that oral administration of curcumin was accompanied by a robust increase in APE1 protein and mRNA levels, and improved the histological architecture of rat liver. In addition, curcumin attenuated oxidative stress by increasing the content of hepatic glutathione within normal values, leading to the re¬duction in the level of lipid hydroperoxide. Curcumin remarkably suppressed inflammation by reducing le¬vels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-kB) and interleukin-6 (IL-6). It also inhibited hepatic stellate cells (HSCs) activation by elevating the level of PPARγ and reducing the abundance of transforming growth factor-β (TGF-β). We found that oral adminis¬tration of curcumin at 200 mg/kg dose not only protected against CCl4-induced hepatic injury, but also re¬sulted in more than two-fold induction of APE1 protein expression in CCl4-induced rat group.Conclusions. It can be concluded that curcumin reduced markers of liver damage in rats treated with CCl4, with conco¬mitant elevation in APE1 protein level indicating a possible protective effect with unknown mechanism. The induction of DNA repair enzymes may be an important and novel strategy for hepatic protection against oxidative injury

Prevalence, Management, and Outcome of Atrial Fibrillation and Other Supraventricular Arrhythmias in COVID-19 Patients

COVID-19 mainly affects the respiratory system but has been correlated with cardiovascular manifestations such as myocarditis, heart failure, acute coronary syndromes, and arrhythmias. Cardiac arrhythmias are the second most frequent complication affecting about 30% of patients. Several mechanisms may lead to an increased risk of cardiac arrhythmias during COVID-19 infection, ranging from direct myocardial damage to extracardiac involvement. The aim of this review is to describe the role of COVID-19 in the pathogenesis of cardiac arrhythmias and provide a comprehensive guidance for their monitoring and management

Catheter ablation of life-threatening ventricular arrhythmias in athletes

A recent surveillance analysis indicates that cardiac arrest/death occurs in ≈1:50,000 professional or semi-professional athletes, and the most common cause is attributable to life-threaten-ing ventricular arrhythmias (VAs). It is critically important to diagnose any inherited/acquired cardiac disease, including coronary artery disease, since it frequently represents the arrhythmogenic substrate in a substantial part of the athletes presenting with major VAs. New insights indicate that athletes develop a specific electro-anatomical remodeling, with peculiar anatomic distribution and VAs patterns. However, because of the scarcity of clinical data concerning the natural history of VAs in sports performers, there are no dedicated recommendations for VA ablation. The treatment remains at the mercy of several individual factors, including the type of VA, the athlete’s age, and the operator’s expertise. With the present review, we aimed to illustrate the prevalence, electrocar-diographic (ECG) features, and imaging correlations of the most common VAs in athletes, focusing on etiology, outcomes, and sports eligibility after catheter ablation

Clinical presentation, diagnosis, and treatment of atrioesophageal fistula resulting from atrial fibrillation ablation

Background: Atrioesophageal fistula (AEF) is a worrisome complication of atrial fibrillation (AF) ablation. Its clinical manifestations and time course are unpredictable and may contribute to diagnostic and treatment delays. We conducted a systematic review of all available cases of AEF, aiming at characterizing clinical presentation, time course, diagnostic pitfalls, and outcomes. Methods: The digital search retrieved 150 studies containing 257 cases, 238 (92.6%) of which with a confirmed diagnosis of AEF and 19 (7.4%) of pericardioesophageal fistula. Results: The median time from ablation to symptom onset was 21 days (interquartile range [IQR]: 11–28). Neurological abnormalities were documented in 75% of patients. Compared to patients seen by a specialist, those evaluated at a walk-in clinic or community hospital had a significantly greater delay between symptom onset and hospital admission (median: 2.5 day [IQR: 1–8] vs. 1 day [IQR: 1–5); p =.03). Overall, 198 patients underwent a chest scan (computed tomography [CT]: 192 patients and magnetic resonance imaging [MRI]: 6 patients), 48 (24.2%; 46 CT and 2 MRI) of whom had normal/unremarkable findings. Time from hospital admission to diagnostic confirmation was significantly longer in patients with a first normal/unremarkable chest scan (p &lt;.001). Overall mortality rate was 59.3% and 26.0% survivors had residual neurological deficits at the time of discharge. Conclusions: Since healthcare professionals of any specialty might be involved in treating AEF patients, awareness of the clinical manifestations, diagnostic pitfalls, and time course, as well as an early contact with the treating electrophysiologist for a coordinated interdisciplinary medical effort, are pivotal to prevent diagnostic delays and reduce mortality