Effects of Storage Temperature and Time on Stability of Serum Tacrolimus and Cyclosporine A Levels in Whole Blood by LC-MS/MS.

Tacrolimus and cyclosporine A are immunosuppressant drugs with narrow therapeutic windows. The aim of this study was to investigate the stability of tacrolimus and cyclosporin A levels in whole blood samples under different storage conditions. Whole blood samples were obtained from 15 patients receiving tacrolimus and 15 patients receiving cyclosporine A. Samples were immediately analyzed and then stored at different conditions (room temperature (24°C-26°C) for 24 hours, +4°C for 24 and 48 hours, and -20°C for one month) and then analyzed again. For tacrolimus, there was a significant difference between samples analyzed immediately and those kept 24 hours at room temperature (P = 0.005) (percent change 32.89%). However, there were no significant differences between the other groups. For cyclosporine A, there was a significant difference between samples analyzed immediately and those kept 24 hours (P = 0.003) (percent change 19.47%) and 48 hours (P = 0.002) (percent change 15.38%) at +4°C and those kept 24 hours at room temperature (P = 0.011) (percent change 9.71%). Samples of tacrolimus should be analyzed immediately or stored at either +4°C or -20°C, while samples of cyclosporine A should be analyzed immediately or stored at -20°C.

The effects of ellagic acid on the liver and remote organs' oxidative stress and structure after hepatic ischemia reperfusion injury caused by pringle maneuver in rats.

INTRODUCTION: We aimed to investigate the possible protective effects of ellagic acid (EA) on the liver and remote organs against the hepatic ischemia-reperfusion injury. METHODS: Forty Wistar-Albino rats were divided into four groups each containing 10 rats. Group I with laparotomy only, Group II with laparatomy and ellagic acid application, Group III with hepatic ischemia-reperfusion and Group IV with hepatic ischemia-reperfusion and ellagic acid application. Hepatic ischemia was induced by pringle's manoeuvre for 30 minutes followed by 30 minutes reperfusion period. After induction of ischemia, EA was applied via oral gavage at a dose of 85 mg/kg. Blood samples were taken from the animals for biochemical analysis at 60th minute of the experiment in all groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical analyses and histopathological examinations. RESULTS: The administration of EA reduced serum malonyldialdehid levels (p<0.05) and liver's oxidative stress index compared with the non-use EA groups (p0.05). The use of EA did not exert significant protective effects against the effects of liver ischemia-reperfusion injury on the kidney and lung. CONCLUSION: In our experiments ellagic acid reduced the liver oxidative stress induced by ischemia-reperfusion injury. However, no significant histological improvement was found with EA. There were no significant protective effects on the remote organ injuries induced by ischemia-reperfusion (Tab. 3, Fig. 7, Ref. 37).

Effects of exercise and caffeic acid phenethyl ester after chronic exercise rat model.

In order to understand whether exercise and caffeic acid phenethyl ester (CAPE) has an effect on obesity and weight control, we investigated the effects of CAPE, and exercise on lipid parameters (triglyceride, total cholesterol, HDL-C, LDL-C), and adipokine substances such as leptin and resistin in rats. 40 male rat were randomly assigned into 4 groups. It was determined that CAPE does not have any significant effect on these parameters but that lipid parameters and leptin values in exercise groups decreased considerably, while no significant change occurred in resistin levels. In order to understand whether diet has an effect on exercise, body weights of all animal groups in pre and post-exercise were compared. A significant weight gain was observed (p = 0.005) in all groups. This study concluded that exercise has a considerable effect on leptin and lipid parameters; however, exercise alone was not sufficient for weight control and could be effective in weight control only when accompanied by a restricted diet. Key pointsCaffeic acid phenethyl ester is not effective on weight control, lipid parameters, and adipokine substances such as leptin and resistin.Exercise can be effective in weight control only when accompanied by a restricted diet.

Antifibrotic effects of aldosterone receptor blocker (spironolactone) in patients with chronic kidney disease.

AIMS: Proteinuria and transforming growth factor beta (TGF-beta) are parameters that can lead to glomerulosclerosis and tubulointerstitial fibrosis. All components of the renin-angiotensin-aldosterone system (RAAS) activate the TGF-beta. Aldosterone may not be inhibited with angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) due to aldosterone escape. We aimed to evaluate the effect of spironolactone on parameters leading to fibrosis. METHODS: This prospective study included 30 non-diabetic chronic kidney disease (CKD) patients treated with ACEIs and/or ARBs. The patients were divided into two groups that are similar in terms of demographic parameters. 25 mg of spironolactone was added to group 1 (n = 15) for six months, though it was not administered to group 2 (n = 15). Creatinine (U-Cr), protein (U-Prot), and TGF-beta1 (U- TGF-beta1) were measured in spot urine sample in the beginning of study and six months later. RESULTS: Twenty-four patients completed the study. There were no significant changes in mean blood pressure, glomerular filtration rate, creatinine, albumin, and plasma aldosterone concentrations during the observation period in either group. U-Prot/U-Cr (mg/mg Cr) was reduced from 2.43 +/- 4.85 at baseline to 1.66 +/- 3.51 at sixth month (p = 0.003) in group 1. In addition, U-TGF-beta1/U-Cr (ng/mg Cr) was also reduced from 22.50 +/- 6.65 at baseline to 17.78 +/- 10.94 at sixth month (p = 0.041) in the same group. U-TGF-beta1/U-Cr and U-Prot/U-Cr ratios after the sixth month were not found significant compared with baseline values in group 2. CONCLUSION: Spironolactone reduced both proteinuria and urinary TGF-beta1 excretion in CKD patients. We consider that spironolactone would be beneficial to prevent progression of renal fibrosis in CKD.