Diabetic Encephalopathy Affecting Mitochondria and Axonal Transport Proteins.

INTRODUCTION: Diabetic encephalopathy is described as any cognitive and memory impairments associated with hippocampal degenerative changes, including the neurodegenerative process and decreased number of living cells. Mitochondrial diabetes (MD) appears following activation of mutant mitochondrial DNA and is a combination of diabetes and cognitive deficit. In this research, we showed the correlation of diabetic encephalopathy, dysfunctional mitochondria, and changes in the expression of axonal transport proteins (KIF5b, Dynein). METHODS: Twenty-four male Wistar rats were divided into three groups: (n=8 in each group):1. Control + saline; 2. Diabetic, and 3. Diabetic + insulin. Before starting the experiments, the animals with blood sugar lower than 150 mg/dL entered the study. Diabetes induction was carried out by Intraperitoneal (IP) Streptozotocin (STZ) administration. Fasting Blood Sugar (FBS) and body weight was checked after the first week and at the end of the eighth week. Then, behavioral studies (elevated plus maze, Y-maze, and passive avoidance learning) were performed. After behavioral studies, blood samples were taken to measure serum insulin level and HgbA1c. Next, fresh hippocampal tissue was collected. Gene expression of motor proteins was assessed by real-time PCR and mitochondrial membrane potential by rhodamine123. RESULTS: Our results showed the impairment of HgbA1c, serum insulin, FBS, and weight in the diabetic group (P<0.05). Behavioral tests revealed different degrees of impairment in diabetic rats (P<0.05). KIF5b mRNA expression increased in the hippocampus (P<0.05) with no change in dynein gene expression. These changes were associated with abnormal mitochondrial membrane potential (P<0.05). CONCLUSION: KIF5b mRNA up-regulation in hippocampal neurons of STZ-diabetic rats is a factor that can be involved in abnormal axonal transport and decreased MMP, leading to impairment of mitochondrial function. These manifestations showed mitochondrial dysfunction in diabetes and resulted in abnormal behavioral tests and diabetic encephalopathy.

Ibuprofen Protection Against Restrained Chronic Stress-induced Depression in Male Rats.

INTRODUCTION: Stress predisposes organisms to depression and cognitive impairments, and seems to interact with metabolic homeostasis. The inflammatory response and the upregulation of proinflammatory cytokines are some of the consequences related to chronic stress. In this study, we investigated the preventive effect of chronic administration of ibuprofen, as an inhibitor of cyclooxygenases, on the cognitive and behavioral alterations and the weight gain reduction induced by simultaneous chronic restraint stress in rats. MATERIALS AND METHODS: Male Wistar rats were subjected to chronic restraint stress and injected daily with the variable doses of ibuprofen or vehicle, for 21 consecutive days. Then, all animals were tested with the forced swim test and passive avoidance conditioning. Also, the weight of the animals was recorded before and after the interventions. Ultimately, plasma interleukin 6 (IL-6) levels were measured. RESULTS: Chronic stress increased depressive-like behaviors, impaired learning, and disrupted the normal weight gain. However, the animals that received the highest dose of ibuprofen showed less depressive-like behaviors, a better avoidance memory, and a higher weight gain. However, the level of plasma IL-6 did not differ significantly between the study groups. CONCLUSION: The administration of ibuprofen prevents the cognitive and behavioral consequences of chronic stress. During the recovery, the plasma levels of IL-6 were not elevated by stress, and the IL-6 levels did not predict the behavioral performance of the stressed animals. The exact mechanisms of the protective effects of ibuprofen against chronic stress need to be further investigated.

Atorvastatin and prevention of contrast induced nephropathy following coronary angiography.

BACKGROUND: Contrast induced nephropathy (CIN) is one of the most common complications after radiographic procedures using intravascular radiocontrast media. The aim of the current study was to assess the effect of atorvastatin on prevention of CIN in patients undergoing coronary angiography. MATERIALS AND METHODS: In a clinical trial study, 200 patients referred for angiography were randomly divided into two groups of using 80 mg atorvastatin and placebo before the procedure. Furthermore, 100 patients who were under chronic treatment of statins were included as the third group. Serum creatinine (Scr) levels before and after the procedure were evaluated and incidence of CIN (post-procedural Scr of >0.5 mg/dl or >25% from baseline) was assessed. RESULTS: Mean age of the participants was 60.06 ± 0.69 years and 276 (92%) were male. There were no significant differences between group with respect to age and gender. In pre-operation atorvastatin, placebo and long term statin groups, the incidence of CIN was 1%, 2% and 1%, and mean changes of Glomerular filtration rate (GFR) was 3.68 ± 1.32, -0.77 ± 1.21 and 1.37 ± 0.86; and mean changes of creatinine (Cr) was -0.05 ± 0.02, 0.02 ± 0.02 and -0.01 ± 0.01 respectively. (P = 0.776, 0.026 and 0.041 respectively). In pre-operation atorvastatin group, Cr decreased, and GFR increased significantly (P = 0.019 and 0.007 respectively). CONCLUSION: pre-operation short term high dose atorvastatin use was associated with a significant decrease in serum Cr level and increase in GFR after angiography.

The relation between body iron store and ferritin, and coronary artery disease.

BACKGROUND: Iron is essential for many physiological processes; whereas, iron overload has been known as a risk factor in progression of atherosclerosis. The aim of this study was to investigate the importance of serum ferritin levels, which are known as an indicator of body iron stored in the incidence of coronary artery disease (CAD). METHODS: In a case-control study, we evaluated 432 eligible men who underwent coronary angiography at Chamran Cardiology Hospital, Isfahan, Iran. They were separated into two groups of case (with CAD) and control (without CAD). All subjects had given written informed consents. Then, the blood samples were taken after 12-14 hours of fast by a biologist for measuring cardiovascular risk factors and body iron stores, including serum ferritin, serum iron, and total iron binding capacity (TIBC). For statistical analyses, chi-square test, Student's t-test, one-way ANOVA, and the logistic regression were used. RESULTS: In the present study, 212 participants with CAD in the case group and 220 participants free of CAD in the control group were included in the analysis. At baseline, there were significant differences in serum ferritin (P < 0.001) and other cardiovascular risk factors between the two groups. Moreover, when other risk factors of CVD were included in the model, serum ferritin [Odd Ratio (OR) = 1.006, 95% confidence interval of 95% (95% CI) 1.00-1.01, P = 0.045] and serum ferritin ≥ 200 (OR = 4.49, 95% CI 1.72-11.70, P < 0.001) were associated with CAD. CONCLUSION: High iron store, as assessed by serum ferritin, was associated with the increased risk of CAD. Furthermore, it was a strong and independent risk factor in the incident of atherosclerosis in the Iranian male population.