Diabetic Neuropathy and Treatment Strategy – New Challenges and Applications

Smart drug delivery systems are very popular drug delivery systems for treatment to common disease such as gene therapy, heart disease, cancer therapy, and neuropathy. Neuropathy is the most common chronic complication of diabetes that is associated with especially loss of peripheral nerve fibers. Hyperglycemia, insulin deficiency and dyslipidemia largely affect the development and progression of diabetic neuropathy. Several metabolic disruptions including altered protein kinase C, elevated polyol pathway activity, oxidative stress, the formation of advanced glycation and lipoxidation end products, and various pro-inflammatory changes directly affect neural tissue and cause neurodegenerative changes in diabetes. The therapeutic interventions of these metabolic pathways have a limited success to relieve the symptoms of diabetic neuropathy. This review emphasizes on the pathogenesis of neurovascular changes, presently available therapeutic approaches future directions for the management of diabetic neuropathy and related new drug delivery systems

Influence of walnut on hepatic ischemia-reperfusion injury in streptozotocin-induced diabetic rats

Nutritional benefits of walnut are well known; however, currently, there is no research showing that walnut can be used as an antioxidant in people with diabetes mellitus (DM). Therefore, the objective of this study was to investigate the protective effects of walnut against oxidative stress in hepatic ischemia-reperfusion (I/R) injury in streptozotocin (STZ) induced diabetic rats. Animals were divided into four-groups (Control, DM, DM+I/R, DM+I/R+Walnut; n=6 each). STZ treatment and I/R procedures were not performed in the control group, other groups were first administered 60-mg/kg STZ intraperitoneally. After 48-h, animals were considered as DM. After four-weeks, DM groups were subjected to 30 min of hepatic-ischemia followed by 45-min reperfusion. DM+I/R+Walnut group was fed pellet-feed mixed with walnut (2 g/100 g/day) until I/R. Other groups were fed only with pellet-feed. At the experimental end, animals decapacitated, blood samples collected to determine serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, malondialdehyde (MDA). Liver samples were collected for histological examinations. Forty-eight-hours after STZ, animals showed significant weight-loss compared to age-matched controls, blood glucose levels were increased (P< 0.05). Four-weeks post-STZ, blood glucose also increased significantly. TNF-α, IL-6, MDA substantially increased in the DM+/I/R group (P< 0.01), whereas in DM+I/R+Walnut group this increase was lesser (P< 0.05). Aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) levels were lower in DM+/I/R+Walnut vs. DM+I/R groups; but higher than DM/control groups (P< 0.05). Positive-correlation observed between TNF-α and IL-6 (Spearman r:0.793; P< 0.001), and moderately-positive-correlation between IL-6 and LDH (Spearman r:0.429; P< 0.05). Histopathology revealed disordered hepatic lobules, swelling cells, vacuoles in liver specimens visible in the DM+I/R group, implicating hepatic I/R injury, which improved in DM+I/R+Walnut specimens. We conclude that in diabetic rats, hepatic I/R injury is associated with augmented inflammatory response and oxidative stress, while walnut pre-treatment significantly decreased these responses

Influence of walnut on hepatic ischemia-reperfusion injury in streptozotocin-induced diabetic rats

13-20Nutritional benefits of walnut are well known; however, currently, there is no research showing that walnut can be used as an antioxidant in people with diabetes mellitus (DM). Therefore, the objective of this study was to investigate the protective effects of walnut against oxidative stress in hepatic ischemia-reperfusion (I/R) injury in streptozotocin (STZ) induced diabetic rats. Animals were divided into four-groups (Control, DM, DM+I/R, DM+I/R+Walnut; n=6 each). STZ treatment and I/R procedures were not performed in the control group, other groups were first administered 60-mg/kg STZ intraperitoneally. After 48-h, animals were considered as DM. After four-weeks, DM groups were subjected to 30 min of hepatic-ischemia followed by 45-min reperfusion. DM+I/R+Walnut group was fed pellet-feed mixed with walnut  (2 g/100 g/day) until I/R. Other groups were fed only with pellet-feed. At the experimental end, animals decapacitated, blood samples collected to determine serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, malondialdehyde (MDA). Liver samples were collected for histological examinations. Forty-eight-hours after STZ, animals showed significant weight-loss compared to age-matched controls, blood glucose levels were increased (P0.05). Four-weeks post-STZ, blood glucose also increased significantly. TNF-α, IL-6, MDA substantially increased in the DM+/I/R group (P0.01), whereas in DM+I/R+Walnut group this increase was lesser (P0.05). Aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) levels were lower in DM+/I/R+Walnut vs. DM+I/R groups; but higher than DM/control groups (P0.05). Positive-correlation observed between TNF-α and IL-6 (Spearman r:0.793; P0.001), and moderately-positive-correlation between IL-6 and LDH (Spearman r:0.429; P0.05). Histopathology revealed disordered hepatic lobules, swelling cells, vacuoles in liver specimens visible in the DM+I/R group, implicating hepatic I/R injury, which improved in DM+I/R+Walnut specimens. We conclude that in diabetic rats, hepatic I/R injury is associated with augmented inflammatory response and oxidative stress, while walnut pre-treatment significantly decreased these responses

Protective effect of famotidine, omeprazole, and melatonin against acetylsalicylic acid-induced gastric damage in rats

It has been reported that both omeprazole and famotidine have a protective effect against gastric mucosal damage induced by acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs. Since active oxygen species and lipid peroxidation were reported to play a role in the pathogenesis induced by ASA, we aimed to study if omeprazole and famotidine have any antioxidant effect by comparing their protective effect with that of melatonin, an effective antioxidant and free radical scavenger. Mucosal damage was evaluated by macroscopic examination, histological analysis and by measurement of lipid peroxidation (LPO), glutathione (GSH), and myeloperoxidase (MPO) activity. Omeprazole (20 micromol/kg per os), famotidine (3 mg/kg per os), and melatonin (10 mg/kg intraperitoneally) significantly prevented gastric ulcerogenesis induced by ASA (200 mg/kg per os) and decreased the ulcer index. Gastric LPO and MPO activity that were increased significantly by ASA were decreased after treatment with omeprazole, famotidine, and melatonin. ASA treatment decreased significantly the gastric GSH levels, and pretreatment with omeprazole, famotidine, or melatonin increased it significantly. Famotidine and omeprazole decreased the gastric acidity, which was increased by ASA, whereas melatonin had no effect on this parameter. These findings suggest that active oxygene species and LPO have an important role in the pathogenesis of gastric mucosal damage induced by ASA and that both famotidine and omeprazole may be protective against this damage, although they were not as efficient as melatonin as an antioxidant. On the other hand, the antisecretory effect of omeprazole and famotidine may also be contributing to their antiulcer effect

VASPIN, ADIPONECTIN AND LEPTIN LEVELS IN TYPE 1 DIABETIC RATS INDUCED BY STREPTOZOTOCIN

Background. Adiponectin, vaspin and leptin are only a few of these numerous adipocytokines. Little is known about the behavior of adipocytokines and how adipose tissue metabolism is affected in this Type 1 DM model. In this study we investigated the serum levels of adiponectin, leptin, vaspin in streptozotocin(STZ) induced diabetic rats. Material and methods. Twelve Sprague Dawley albino rats were included in the study. The animals were divided into two groups. The first group was diabetic (D) (n: 6) and 60mg / kg STZ was administered intraperitoneally (i.p.) to these rats. The second group was the non-diabetic control (ND) group (n: 6). All the animals were euthanized by cervical dislocation. Quantification of vaspin, Adiponectin, leptin in serum was performed using the ELISA kit. Results. Adiponectin, vaspin levels of diabetic group were found to be statistically lower than of control group (p<0.05). Leptin levels were significantly higher in the diabetic group (P<0.05). Conclusion. There is a need for new researches that can explain the relationship between Vaspin, Leptin and Adiponectin and Type 1 diabetes. New studies in this area will open new horizons for the identification of new biomarkers in the diagnosis and treatment of Type 1 diabetes

Evaluation of the design and methodology of applications to the local ethics committee

Objectives: Proposals for scientific studies must have an original hypothesis and the appropriate design and methodology to test the premise. Methods: This study is an evaluation of the suitability of applications submitted to a local ethics committee (EC) and the rate of publication of that research. Results: A total of 899 files submitted for EC approval were retrospectively assessed. The EC found that the description of the methods in 44% of the applications was inaccurate, and that this type of error was most often seen in submissions from the surgical branch. In all, 52% of the applications for which we were informed about their final status were not published. Conclusion: The results suggest that improved training in epidemiology is required to reduce the number of application errors and that new regulations could help to motivate healthcare personnel to conduct scientific research and publish their findings. Keywords: Case-control study; epidemiology; ethics committees; interventional studies; research misconduct; thesis studie

Sıçanlarda etilen glikol kaynaklı böbrek taşı hastalığında Scolymus hispanicus L.'nin (sevketibostan) doza bağlı etkisi

Kidney stone, also known as calcium oxalate nephrolithiasis, is one of the most common diseases worldwide. Calculi usually forms when urine becomes supersaturated with particular calcium salts such as calcium oxalate. In the present study, we investigated the ameliorative potential of the root extract of the Common golden thistle, Scolymus hispanicus L. (SH) on rats with ethylene glycol (EG) induced kidney stone disease. Sprague-Dawley rats, each weighing 250-300 g, were divided into three groups (n=6 per group): (i) Control (C); (ii) EG; and (iii) EG+SH. To induce nephrolithiasis, the rats received 1% of EG with drinking water, while the C group received normal drinking water during the study. SH extract 2 g/kg was added to the treatment from the 4th week onwards in EG+SH group. At the end of each experiment, rats were decapacitated and serum levels of calcium, magnesium, phosphorus, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were assessed in all groups at 0, 4, and 8 weeks. Oxalic acid and creatininelevels were measured in urine samples collected at 24 h in metabolic cages. Renal tissues were evaluated histopathologically at the end of the experiment. After 8 weeks, serum creatinine levels were found decreased in the SH group while increased in the EG group. Serum magnesium and AST levels were also found decreased in the EG group, however, SH treatment reversed these values. The SH treatment also increased urinary oxalic acid levels. When the kidney tissue of EG group was examined, there was a high level of crystal/stone, especially in the renal cortex. In kidney tissues of the SH group, only small amounts of crystal/stone were observed. Our experimental findings have demonstrated the ameliorative potential of the aqueous extracts of S. hispanicus roots and shells on EG-induced in the kidney stones in rats. Isolation of active compounds of SH would be desirable to understand the biochemical mechanism behind the process better