Targeting AngII/AT1R signaling pathway by perindopril inhibits ongoing liver fibrosis in rat

The renin–angiotensin system (RAS) has a substantial role in liver fibrosis, cirrhosis, and portal hypertension. Hence, targeting RAS through angiotensin‐converting enzyme (ACE) inhibitors can mend hepatic fibrosis; the current study was designed to examine the potential fibrosis inhibition activity of perindopril using a rat model of liver fibrosis induced by thioacetamide (TAA). Four groups of rats were used throughout this study, Group I (control group); rats received the vehicle. TAA was used for inducing liver fibrosis in rats by intraperitoneal injection of 200‐mg/kg body weight twice a week for 6 weeks. Group II served as (TAA group). Rats of Groups III and IV were given perindopril at doses of 2 and 8 mg/kg 2 weeks after TAA administration and continued concomitantly with TAA till the end of the experiment. Injection of TAA resulted in a significant increase in aminotransferases' activities and bilirubin with a significant decrease in serum albumin and total protein and a significant decrease in hepatic content of GSH and SOD. Additionally, TAA injection raised the hepatic content of TGF‐β1, α‐SMA, TNF‐α, and level of MDA. Histological and immunohistochemical data presented marked fibrosis in liver sections of TAA‐administrated rats with increased collagen deposition, elevated METAVIR scoring, and increased expression of α‐SMA, caspase‐3, and AT1R. Oral dosing of perindopril for 4 weeks concomitant with TAA could mend the altered parameters near to normal values and abolished the ongoing fibrosis extension. In conclusion, these results demonstrated that perindopril, as ACE inhibitor, could grant a superior remedial nominee in preventing liver fibrosis progression through targeting angiotensin II formation.     

Beneficial use of ultrasound irradiation in synthesis of beta–clinoptilolite composite used in heavy oil upgrading process

A novel beta–clinoptilolite composite was prepared from beta zeolite and alkaline treated clinoptilolite by employing conventional and sonicated mixing procedures. Parent and prepared catalysts were characterized by XRD, FE-SEM, N₂ adsorption–desorption and NH₃-TPD analyses. Prepared composite of beta zeolite and treated clinoptilolite exhibited improved structural properties especially upon sonicated mixing procedure. Employing ultrasound irradiation notably improved beta distribution in the composite and increased mesoporous volume and specific surface area from 0.245 cm³ g⁻¹ and 171.3 m² g⁻¹ in conventionally mixed composite to 0.353 cm³ g⁻¹ and 232.9 m² g⁻¹ in sonicated sample. Catalytic performance of prepared composite was evaluated in heavy oil upgrading process in a continuous fixed bed apparatus. Liquid product was specified by conducting SIMDIS-GC and GC/MS analyses. Spent catalysts were characterized by TGA, FTIR and XRD. Beta–clinoptilolite composite containing only 30 wt% of beta zeolite, exhibited similar performance to beta zeolite catalyst by resulting 75.3% viscosity reduction while producing lower amount of coke. Amount of light hydrocarbons produced over beta–clinoptilolite composite was 33.51 wt% while beta zeolite catalyst produced 35.58 wt% light hydrocarbons in upgrading process. Ultrasound irradiated composite showed more stable structure in catalytic cracking procedure compared to conventionally mixed composite. After 5 h time on stream, relative crystallinity of clinoptilolite phase in the conventionally mixed composite was reduced by 34.5% while sonicated sample remarkably preserved its structure during the reaction and only 1% reduction occurred for this sample.

Beta–clinoptilolite composite synthesized in the presence of ultrasound irradiation exhibited high stability in heavy oil upgrading process while producing equal amount of light fuels and lower amount of coke compared to beta zeolite catalyst.     

The use of AIR-Q as conduit for fiberoptic endotracheal intubation in adult paralyzed patients

BackgroundThe AIR-Q Laryngeal Mask (Cookgas LLC; distributed by Mercury Medical) is a supraglottic device present in the market since 2004. It has different sizes for pediatric and adult use. This device proved to be of utmost importance in the management of difficult airway [1]. The study evaluates the different adult sizes of the Air Q when used for intubation regarding the ease of insertion, the laryngeal view grade, their efficacy as conduit for standard cuffed endotracheal tubes using fiberoptic bronchoscope. The study also records the time of intubation, the ease and time of removal of the AIRQ over a removal stylet without dislodgement of the tube from trachea. Any complications related to the use of AIRQ were also recorded such as laryngeal oedema, blood streaked mucous, trauma to the airway, laryngeal spasm or aspiration.MethodsSixty adult patients aged 20–50 years, ASA I, II undergoing elective surgeries requiring general anesthesia, were enrolled in the study. The patients were divided into 2 equal groups according to their body weight. The body weight of the first group ranged from 50 to 70 kg and used the Air Q 3.5 for intubation with an endotracheal tube (ETT) 7 mm ID, while the body weight of the second group ranges from 70 to 100 kg and used the Air Q 4.5 for intubation with a tube 7.5 mm ID. The number of attempts of insertion, the seal pressure, the laryngeal view grade, the time and the number of attempts of intubation, time of removal of the AIRQ over the tube without dislodgement, and any complications related to the use of AIRQ were recorded such as laryngeal oedema, blood streaked mucous, trauma to the airway, laryngeal spasm or aspiration.ResultsThe insertion and removal of the AIRQ were easy and successful in all patients of both groups. The endotracheal intubation by fiberoptic bronchoscope through the Air Q was successful and easy in both groups. Grade 5 laryngeal view was seen with AIRQ 4.5 in some patients with higher body weight.ConclusionThe insertion of AIRQ in adult patients is easy and provides an effective conduit for the standard cuffed endotracheal tubes using fiberoptic bronchoscope. The removal of the AIRQ over the removal stylet is easy without dislodgement of the tube. Because of higher incidence of down folding of the epiglottis in some obese patients, they are better intubated under direct vision with the use of fiberoptic bronchoscope.     

Heme oxygenase-1 mRNA expression in egyptian patients with chronic liver disease

Background

Chronic liver disease (CLD) is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1).

Objectives

This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers.

Patients and Methods

Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA), and erythrocyte-reduced glutathione (GSH) were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis) and 15 healthy controls.

Results

HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients.

Conclusions

HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD.     

Update on the management of ulcerative colitis

The present treatment goals for inflammatory bowel diseases (IBD) especially ulcerative colitis (UC) include rapid induction of clinical remission, steroid-free maintenance of clinical remission, mucosal healing and improvement of quality of life in UC patients. Immunomodulators have been reserved for steroid- dependent or steroid- refractory UC patients. Among these agents, azathioprine/6-mercaptopurine should be used for maintenance of remission in quiescent UC. Calcineurin inhibitors can be prescribed as a short-term rescue therapy in steroid- refractory UC patients, but the long term efficacy of these agents remains unclear. According to retrospective studies, methotraxate is not recommended for inducing and maintaining remission in UC. Novel biological therapies targeting different specific immunological pathways continue to be developed and introduced for a variety of clinical scenarios in IBD. Infliximab is currently used for induction and maintenance therapy in patients who have moderately to severely active UC with an inadequate response to conventional agents such as aminosalicylates, corticosteroids, or immunomodulators. Other anti-TNF agents and biologic therapies are undergoing evaluation in clinical trials for their efficacy in IBD. Most patients who start biologics should continue treatment for the foreseeable future and potential consequences of discontinuation should be discussed with individual patients. Currently, data do not exist to administer biologics as first-line therapy in UC. Emerging data suggest that biologics may have the potential to prevent complications and limit disease progression. If such benefits are proven, biologics may be used in the future to modulate subclinical inflammation and to prevent the development of clinical disease.     

Cardiac surgery in patients on chronic hemodialysis: short and long-term survival

OBJECTIVE: Open-heart surgery carries a high risk for hemodialysis patients. This study focuses on the short and long-term outcomes of hemodialysis patients undergoing heart surgery. DESIGN: The study was carried out as a retrospective analysis in the Department of Cardiothoracic Surgery in a large university-affiliated hospital. PATIENTS: 115 hemodialysis patients underwent cardiac surgery in our department between 1 July 1996 and 31 July 2006. 67.5 % (77 patients) underwent isolated coronary artery bypass grafting (CABG), 13.2 % (15 patients) underwent isolated aortic valve replacement (AVR) and 20.2 % (23 patients) underwent mitral valve surgery or combined valve and coronary artery bypass grafting or multiple valve surgery. METHODS: The relationship between several variables (age, sex, hypertension, diabetes, and previous myocardial infarction, type of disease, preoperative ejection fraction, and congestive heart failure) and operative (30 days) mortality and late survival was analyzed. RESULTS: The overall 30-day mortality was 18.3 % (21 patients). It was 13 % (10/77 patients) for the isolated CABG group and 13.3 % (2/15) for the isolated AVR group. Patients undergoing combined valve and coronary surgery or multiple valve surgery had a higher perioperative mortality of 39.1 % (9/23) compared to the isolated CABG and isolated AVR patients. Perioperative death was also higher in patients with moderate and severe LV dysfunction, and in patients with diabetes. The duration of dialysis periods was not related to perioperative death. Mean follow-up was 26.4 +/- 29.7 months (0.1 to 104 months). Actuarial survival at 1 year and 5 years was 76 % and 55 % for isolated CABG, 59 % and 21 % for isolated AVR, and 44 % and 33 % for all other cases, respectively (log rank P = 0.001). CONCLUSION: Patients on dialysis have a high risk of perioperative mortality and poor long-term survival rates. Mortality is higher and survival is worse after combined CABG and valve-related procedures or multiple valve surgery than after isolated CABG and AVR.     

Randomized controlled trial comparing the Franseen needle with the Fork-tip needle for EUS-guided fine-needle biopsy

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Cyclooxygenase-2 inhibition augments the hepatic antitumor effect of oral Salmonella typhimurium in a model of mouse metastatic colon cancer

INTRODUCTION: Oral inoculation with a nontoxic, attenuated strain of Salmonella typhimurium reduces tumor burden and improves survival in a mouse model of metastatic colon cancer. These effects are likely mediated by S. typhimurium-induced increases in hepatic natural killer leukocytes. Cyclooxygenase-2 inhibitors may mediate antitumor effects through antiangiogenic, immune, or proapoptotic pathways. We hypothesized that cyclooxygenase-2 inhibitors would act synergistically with S. typhimurium, resulting in additional antitumor effects. METHODS: Four groups of mice were studied: control, S. typhimurium alone, cyclooxygenase-2 inhibitor alone, and S. typhimurium plus cyclooxygenase-2 inhibitor. Mice were given normal drinking water (control, S. typhimurium alone) or water with 1,600 parts per million cyclooxygenase-2 inhibitor (cyclooxygenase-2 inhibitor alone, and S. typhimurium plus cyclooxygenase-2 inhibitor) and orally inoculated with saline (control, cyclooxygenase-2 inhibitor alone) or 109 S. typhimurium (S. typhimurium alone, S. typhimurium plus cyclooxygenase-2 inhibitor). Twenty-four hours later, all mice underwent laparotomy, and 5 × 104 MCA38 murine adenocarcinoma cells were injected into the spleen. On Day 14, hepatic tumor number and tumor volume was quantitated and hepatic leukocytes were analyzed by flow cytometry. RESULTS: Compared with control mice orally inoculated with saline, S. typhimurium-treated mice had fewer and smaller tumors; mice treated with cyclooxygenase-2 inhibitor alone had tumor burden similar to control mice, and mice treated with S. typhimurium plus cyclooxygenase-2 inhibitor had fewer and smaller tumors compared with all other groups. Increased liver natural killer cells and decreased CD4+ and CD8+ T cells were observed in both S. typhimurium-treated groups. No alterations in hepatic leukocyte phenotype were observed in mice receiving cyclooxygenase-2 inhibitor alone. CONCLUSION: Oral cyclooxygenase-2 inhibitor appeared to act synergistically with S. typhimurium to reduce tumor burden. This combination therapy may have clinical application in the treatment or prevention of hepatic metastases associated with colorectal cancer.