The anti-inflammatory and antioxidant effects of thymoquinone on ceruleine induced acute pancreatitis in rats.

INTRODUCTION: The aim of this study is to investigate the potential antioxidant and anti-inflammatory effects of thymoquinone (TQ) on ceruleine induced acute pancreatitis. MATERIAL AND METHODS: A total of 14 male Wistar albino rats were divided into 2 groups as follows: (1) normal saline-treated group and (2) thymoquinone- treated groups. For achieving acute pancreatitis, intraperitoneal (IP) cerulein, a stable cholecystokinin (CCK) analogue, was applied in a 50 mcg/kg dose 2 times in one-hour interval in total. One hour after last ceruleine injection, IP 2 ml/kg isotonic saline solution was applied to the saline group and IP 5 mg/kg TQ was applied. The rats were sacrificed by decapitation 12 h after the last injection of last medication. Blood samples were taken, and serum interleukin-1ß (IL-1ß), amylase, lipase pancreatic, total antioxidant capacity (TAC), total oxidant status (TOS), and pancreatic Schoenberg scores were determined. Oxidative stress index (OSI) was calculated for each group. Results are given as mean ± SD. A value of p < 0.05 was accepted as statistically significant. SPSS for Windows v15.0 was used for statistical analyses. RESULTS: The increased serum amylase, lipase levels and histopathological scoring of pancreatic tissue showed that acute pancreatitis was present in both groups. Furthermore, serum IL-1ß level was significantly reduced in TQ administered group (p < 0.05). Although serum TAC level was high and TOS level was low, those changes were not statistically significant. Nevertheless, OSI index, which was driven from TOS/TAC, was significantly low in TQ groups (p < 0.05). Although TQ partially ameliorated the acute pancreatitis in terms of histopathological evaluations, the main effect of it was brought about by reducing the hemorrhage in acute pancreatitis (p < 0.05). CONCLUSION: In this study, it was shown that TQ can reduce the inflammation and has a positive effect on the oxidative status of organism in inflammatory cases such as acute pancreatitis. This is consistent with partial amelioration of acute pancreatitis in rats given TQ (Tab. 2, Fig. 4, Ref. 31).

Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B.

BACKGROUND: Results are conflicting with respect to the renal effects of anti-viral agents used for hepatitis B virus infection. AIM: To compare short and long-term renal effects in real-life settings and to determine risk factors for renal impairment during treatment. METHODS: 2221 treatment-naïve patients were enrolled. Among these, 895 (302 lamivudine, 27 telbivudine, 282 entecavir, 273 tenofovir and 11 adefovir initiated patients) had 'repeated measures' of creatinine (baseline, 1st, 6th, 12th and 24th month of treatment). Telbivudine and adefovir groups were excluded from further analysis because of the low number of patients. We calculated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula at each time point. Hypophosphataemia was also recorded. Risk factors for renal impairment were analysed. RESULTS: Tenofovir caused a decline in GFR at each time point when compared to baseline levels. However, lamivudine and entecavir did not change GFR. GFR-shifting from ≥90 to 60-89 mL/min/1.73 m(2) was comparable among groups. The proportion of patients whose baseline creatinine increased more than 25% was comparable among all anti-virals. GFR showed a decline in patients who switched from entecavir to tenofovir. One patient with compensated cirrhosis needed to change from tenofovir because of renal safety. Seven and three patients developed transient hypophosphataemia in the tenofovir and lamivudine groups, respectively. CONCLUSIONS: Although tenofovir caused a decline in GFR, differences between the anti-viral agents do not appear to be so impressive. In patients with and without renal risk factors at baseline, there is no impact of anti-virals, including tenofovir.

Metallic stent in the endoscopic treatment of pancreatic fluid collections.

BACKGROUND AND AIMS: The endoscopic treatment of pancreatic fluid collections (PFCs) has become the preferred first-line approach. Fully covered self-expandable metal stents (FCSEMS) were considered as an alternative to multiple double pigtail stents. The aim of this study was to evaluate the results of the endosonography guided drainage (EUS-GD) of PFCs with FCEMS. MATERIALS AND METHODS: A total of 33 consecutive patients were included. Cystogastrostomy and cystoduodenostomy were created with a linear echoendoscope under endosonographic and fluoroscopic control. Procedures were performed in a standard way of, puncture with a 19 gauge needle, bougie dilation and insertion of FCSEMS. RESULTS: A total of 33 patients (mean age 52 years, 21 men, range: 18-77 years), were included. PFCs were 22 non-infected symptomatic pseudocyst and 11 walled-off necrosis or abscess. EUS-GD was successful in 30 (90.9%) patients. Stent insertion failed in one patient. Two patients needed surgery. Complications were observed in 8 (25%) patients (stent dislocation in 3, perforation in 2, bleeding in 2 and pneumoperitoneum in 1 patient). Procedure related mortality was not seen. The mean cyst size was 11.3 cm (5-22). FCSEMS were successful in the treatment of pseudocysts (after 1 month mean cyst size is 6.2 cm, range: 0-15 cm, with 54.8% decrement rate). During a mean follow-up of 15 months complete resolution was 66.6% (20 patients) and recurrence due to stent malfunction was 10%. All these cases were submitted to a new session of endoscopic drainage. CONCLUSIONS: EUS-GD, FCSEMS insertion provides an effective, minimally invasive, and safe approach in the management of PFCs.

Endothelial dysfunction in Turkish patients with non-alcoholic fatty liver disease.

BACKGROUND: The components of the metabolic syndrome are closely related with endothelial dysfunction, which is a pathophysiological issue of cardiovascular diseases. Non-alcoholic fatty liver disease (NAFLD) is considered as one of the components of the metabolic syndrome. The aim of this study was to evaluate the endothelial-dependent dilatation (EDD) and endothelial-independent dilatation (EID) of the brachial artery in NAFLD. METHODS: Fifteen non-alcoholic steatohepatitis (NASH), 17 patients with simple steatosis and 16 healthy subjects formed the study group. Non-alcoholic fatty liver disease group was composed of patients admitted to the gastroenterology outpatient clinic because of increased liver enzymes. Endothelial functions of the brachial artery were evaluated by vascular ultrasound. EDD was assessed by establishing reactive hyperaemia, and EID was determined by using sublingual nitrate. RESULTS: No statistical difference for the basal diameter of brachial artery was found between the groups (P = 0.49). The values for EDD and EID were significantly different across all three groups (P < 0.0001 and P < 0.0001, respectively). EDD and EID were significantly lower in NASH compared with simple steatosis (P = 0.01 and P < 0.01, respectively). However, there was no statistical significance for EDD and EID in simple steatosis groups compared with controls (P = 0.58 and P = 0.98, respectively). CONCLUSIONS: Our study showed that patients with NASH had significantly worse endothelial dysfunction compared with patients with simple steatosis and healthy subjects. The treatment strategies with ameliorative effects for endothelial dysfunction might be effective for delaying the development of cardiovascular complications in NAFLD.

Molecular analysis and long-term clinical evaluation of three siblings with Alström syndrome.

Alström syndrome is a rare, autosomal recessive disorder characterized by a wide spectrum of clinical features including early-onset retinal degeneration leading to blindness, sensorineural hearing loss, short stature, obesity, type 2 diabetes, hyperlipidemia and dilated cardiomyopathy. Renal, hepatic and pulmonary dysfunction may occur in the later phases of the disease. The three affected sisters, from a consanguineous Turkish family, with the characteristic features of Alström syndrome, were clinically diagnosed in 1987 and followed for 20 years. DNA sequence analysis of ALMS1, the causative gene in Alström syndrome, identified a novel homozygous disease-causing mutation, c.8164C>T, resulting in a premature termination codon in exon 10 in each of the three affected sisters. Furthermore, we describe the longitudinal disease progression in this family and report new clinical findings likely associated with Alström syndrome, such as pes planus and hyperthyroidism.

Endothelial dysfunction in renal transplant patients is closely related to serum cyclosporine levels.

BACKGROUND: Cyclosporine (CsA), one of the standard agents used in renal transplant recipients, has been considered to cause endothelial dysfunction and to contribute to arterial complications posttransplant. Since concentration-dependent effects of CsA on endothelial functions in humans have not been examined, this study was performed to investigate this relationship. METHODS: Fifteen renal transplant patient and 20 healthy subjects (controls) were evaluated for brachial artery endothelial function using high-resolution vascular ultrasound just before the CsA dosage (baseline) and at the second hour after the administration. Endothelium-dependent and -independent vasodilatations (EDD and EID, respectively) were assessed by establishing of the responses to reactive hyperemia and by using sublingual nitroglycerine, respectively. CsA levels were assessed at baseline and at second hour, times when performing brachial artery measurements. RESULTS: There were no significant differences between recipients and controls with respect to atherosclerosis risk factors. Mean EDD of recipients at baseline times were significantly less than those in controls (9.1% +/- 5.5% vs 15.2% +/- 7.2%, respectively; P < .001). CsA levels at trough and at second hour were 153.9 +/- 74.8 ng/mL and 646.8 +/- 163.2 ng/mL, respectively (P < .0001). Recipient, EDD at second hour was significantly reduced compared to baseline values (5.3% +/- 3.6% vs 9.1% +/- 5.5% respectively; P = .014) while changes in EID and in the diameter of the brachial artery between baseline and second hour were insignificant. CONCLUSION: Endothelial dysfunction evaluated by brachial ultrasound in renal transplant recipients is closely related to CsA levels. It is more pronounced at 2 hours after CsA dosage, at the time of peak drug levels.

Does the endothelial function change in renal transplant patients with longer duration of exposure and with higher cumulative doses of cyclosporine?

OBJECTIVE: Administration of cyclosporine (CsA) is one potential cause of endothelial dysfunction in renal transplant patients. We sought to investigate endothelial functional changes with respect to the cumulative dose and duration of exposure to CsA. METHODS: Sixty-six renal recipients and 25 healthy controls were included in the study. The recipients were classified according to their time of CsA exposure: group 1 (0 to 36 months); group 2 (36 to 72 months); and group 3 (over 72 months). Endothelial function of the brachial artery was evaluated using high-resolution vascular ultrasound. Endothelium-dependent and -independent vasodilatation (EDD and EID, respectively) were assessed by assessing the responses to reactive hyperemia and using sublingual isosorbide dinitrate (ISDN), respectively. RESULTS: There were no statistically significant differences between the groups with regard to their demographic, clinical, and most biochemical characteristics. Baseline measurements of the diameter of the brachial artery were similar in all groups. The values of mean brachial artery EDD and EID responses in groups 1, 2, and 3 were less than those in the control group (P < .05, P < .05, and P < .05, respectively). Mean brachial artery EDD and EID in group 1 were significantly impaired compared to groups 2 and 3 (for EDD: P < .05 and P < .05, respectively; for EID: P < .05 and P < .05, respectively). In contrast there was no difference between groups 2 and 3 with respect to these parameters. There were mild to moderate positive correlations between the cumulative doses of CsA and EDD and EID (r = .26 and r = .52, P < .05, respectively). CONCLUSION: Endothelial dysfunction was more prominent in the first 36-month period than later despite the longer exposure to and higher cumulative doses of CsA. This finding may reflect an extended effect of the uremic state on endothelial function or more intense doses of CsA in early posttransplant period.

Is there a relation between duration of cyclosporine usage and right and left ventricular function in renal transplant patients? Tissue Doppler Echocardiography study.

BACKGROUND: Our aim was to investigate the effect of cyclosporine (CsA), which is commonly used in renal transplant patients and causes myocardial fibrosis and elevated arterial tension, on cardiac function. METHODS: Sixty-six renal transplant patients (RTPs) and 25 healthy controls were included in the study. Renal transplantation patients were divided according to time of CsA exposure: group 1 (0 to 36 months); group 2 (36 to 72 months) and group 3 (> 72 months). Systolic peak velocity (Sm, mitral; St, tricuspid) and mitral early (e)/late (a) (Me/a) and tricuspid e/a (Te/a) waves of the right and the left ventricles were measured by pulse-wave (PW) Doppler used for tissue Doppler imaging of both ventricles as well as the ventricle free wall near to the lateral tricuspid and the posterior mitral leaflets. The measurements included conventional diastolic early (E) and late (A) waves and deceleration time (DT) of the E wave, isovolumetric relaxation time (IVRT) of both ventricles, as well as left ventricular systolic ejection fraction (EF). RESULTS: There were no statistically significant differences between the groups with regard to demographic, clinical, and most biochemical characteristics. Left ventricular EF was normal in all groups; there were no statistically significant differences. IVRT and DT of left ventricle and right ventricle DT values were similar among RTPs. On the other hand, values were found to be increased in RTP groups compared with the control group. E/A ratio, Me/a Te/a of both ventricles were similar among RTPs. However, these values were found to be decreased in RTP groups compared with the control group. CONCLUSIONS: Although left ventricular systolic functions were normal in all groups, there were statistically significant impairments of biventricular diastolic function parameters among renal transplant recipients compared with the control group.