Utility of urinary progranulin in patients with type 2 diabetic nephropathy and its correlation with renal function

International Journal of Diabetes in Developing Countries - Urinary progranulin is an inflammatory marker that may indicate renal damage at an early stage of diabetic nephropathy. To determine...     

Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy

Aims

Diabetic Retinopathy (DR) is the leading cause of vision loss in the working age population. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), are molecules involved in extracellular tissue matrix remodelling. They are implicated in the loss of retinal tissue integrity, a major cause of DR, that leads to retinal tissue degradation and apoptosis. This study is therefore, conducted to compare the serum levels of MMP-9 and TIMP-1 in T2DM patients without and with retinopathy, and to evaluate their association with the severity of DR.

Evaluation of the antipsoriatic activity of Aloe vera leaf extract using a mouse tail model of psoriasis

Aloe vera gel is used traditionally for the treatment of skin diseases, including psoriasis. An ethanolic extract of the gel was assessed for antipsoriatic activity using a mouse tail model of psoriasis. The extract produced a significant differentiation in the epidermis, as seen from its degree of orthokeratosis (85.07 ± 3.36%) when compared with the negative control (17.30 ± 4.09%). This was equivalent to the effect of the standard positive control, tazarotene (0.1%) gel, which showed a 90.03 ± 2.00% degree of orthokeratosis. The ethanolic extract of Aloe vera leaf gel also produced a significant increase in relative epidermal thickness when compared with the control group, whereas the standard tazarotene showed no change. Taken together, the extract showed an overall antipsoriatic activity of 81.95%, compared with 87.94 for tazarotene, in the mouse tail model for psoriasis.     

Antidiabetic activity of ethanolic extract of tubers of Dioscorea alata in alloxan induced diabetic rats

Objective:

To evaluate the antidiabetic activity of ethanolic extract of Dioscorea alata in glucose loaded and alloxan induced diabetic rats.

Materials and Methods:

The authenticated tubers of D. alata (DA) (JSSCPDP/2008/157) were collected from Dharmapuri, Tamil Nadu. The ethanol extract was tested for hypoglycemic activity in normal rats. In oral glucose tolerance test, glucose (3 g/kg, p.o.) was administered to non diabetic control, metformin (250 mg/kg, p.o.) and DA extract (100 and 200 mg/kg, p.o.) to treat treated rats. Diabetes mellitus was induced by alloxan monohydrate (120 mg/kg, i.p.) in physiological saline after overnight fasting for 18 hours. DA extract (100 and 200 mg/kg, p.o.) and standard drug metformin (250 mg/kg, p.o.) were administered to diabetic rats for 21 days. Fasting blood glucose level and changes in body weight were measured on days 0, 7, 14, and 21. At the end of 21^st day, serum lipid profile, total protein, albumin, and creatinine were assessed.

Results:

In glucose loaded normal rats, the treatment with the extract of DA had shown a highly significant reduction (P < 0.001) in blood glucose levels at the doses of 100 and 200 mg/kg, respectively. The extract did not produce hypoglycemic activity at both the dose levels in normal, fasted rats. In alloxan induced diabetic rats, the body weight of the DA extract treated animals had shown a significant increase (P < 0.001) after 21 days treatment. The blood glucose level was reduced significantly by 47.48% and 52.09% after 21 days treatment at dose levels 100 and 200 mg/kg, respectively. Serum lipid levels, total protein, albumin, and creatinine were reversed toward near normal in treated rats as compared to diabetic control.

Conclusion:

The results indicate that ethanol extract of DA tubers possesses significant antidiabetic activity.     

Utility of urinary biomarkers as a diagnostic tool for early diabetic nephropathy in patients with type 2 diabetes mellitus

Introduction

Renal tubulo-interstitial damage has an important role in the pathogenesis of early diabetic nephropathy. Urinary biomarkers can help in the detection of early nephropathy in type 2 diabetic patients. The aim of this study was to estimate the levels of urinary neutrophil gelatinase associated lipocalin (NGAL) and cystatin-C in type 2 diabetic patients with early diabetic nephropathy & to compare them with diabetic patients without nephropathy and to correlate urinary NGAL and cystatin-C levels with microalbuminuria in them.

Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models

Glycogen Synthase Kinase 3beta is one of the important targets in the treatment of type II diabetes and Alzheimer's disease. Currently this target is in pursuit for type II diabetes and a few GSK-3beta inhibitors have been now advanced to Phases I and II of clinical trials. The best validated HypoGen model consists of four pharmacophore features; 1) two hydrogen bond acceptors, 2) one hydrogen bond donor and 3) one hydrophobic. This pharmacophore model correlates well with the docking model, one hydrogen bond acceptor is necessary for the H-bond interaction with VAL135, and second hydrogen bond acceptor is important for the H-bond interactions with ARG141 and the hydrophobic feature may be required for the weak H-bond interactions with ASP133. The comparative model was developed from analogue and structure-based models like Catalyst, Glide SP & XP, Gold Fitness & ChemScore and Ligand Fit using multiple linear regression analysis. A virtual library of 10,000 molecules was generated employing fragment and knowledge-based approach and the comparative model was used to predict the activities of these molecules. The H-bond with ARG141 appears to be unique to GSK-3beta and explains the high GSK-3beta selectivity observed for 1H-Quinazolin-4-ones and Benzo[e][1,3]oxazin-4-ones. This understanding of protein-ligand interactions and molecular recognition increases the rapid development of potent and selective inhibitors, and also helps to eliminate the increase in number of false positives and negatives.     

Nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and its association with cardiovascular disease

Introduction

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver disease that ranges from hepatic steatosis to non-alcoholic steatohepatitis. Obesity and diabetes mellitus are the prime risk factors for NAFLD. The aim of this study was to find out the prevalence of NAFLD among patients with type 2 diabetes mellitus and to detect the association of NAFLD with cardiovascular disease in them.

Anti-oxidant,anti-inflammatory and anti-cholinergic action of Adhatoda vasica Nees contributes to amelioration of diabetic encephalopathy in rats: Behavioral and biochemical evidences

‘Diabetic encephalopathy’ refers to diabetes associated cognitive decline (DACD), which involves oxidative-nitrosative stress, inflammation and cholinergic dysfunction. Current study was designed to investigate the effect of Adhatoda vasica, a known anti-inflammatory, antioxidant, anti-cholinesterase and anti-hyperglycemic plant, on diabetic encephalopathy. Streptozotocin (STZ)-induced diabetic Wistar rats were treated with Adhatoda vasica leaves ethanolic extract (AVEE) for 6 weeks at 100, 200 and 400 mg/kg/day dose. During fifth week of treatment, learning and memory was investigated in single Y-maze and passive avoidance test. At the end of the study biochemical parameters like acetylcholinesterase (AchE) activity, nitrite levels, tumor necrosis factor-alpha (TNF-α) and oxidative stress was measured from cerebral cortex and hippocampus regions of brain. AchE activity was found increased by 70 % in the cerebral cortex of diabetic rat brain. Lipid peroxidation (LPO) levels were increased by 100 % and 94 % in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels, enzymatic activities of superoxide dismutase and catalase were found decreased in cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in both regions of diabetic brain were increased by 170 % and 137 % respectively. TNF-α, a pro-inflammatory cytokine, was found significantly increased in diabetic rats. Conversely, animal groups treated with AVEE significantly attenuated these behavioral and biochemical abnormalities. The results suggest a protective role of Adhatoda vasica Nees against diabetic encephalopathy, which may be sum of its anti-oxidant, anti-cholinesterase, anti-inflammatory and glucose lowering action.