Effects and association of pro-oxidants with magnesium in patients with diabetic nephropathy.

Diabetic nephropathy (DN) is the most common microvascular complication observed in patients with type-2 diabetes mellitus. Furthermore, magnesium (Mg) deficiency is a common problem in diabetic patients. In this study, we estimated the levels of Mg, which is an important trace element and pro-oxidant marker, and then evaluated the association between serum Mg and pro-oxidants in patients with DN. In the present study, 200 patients were enrolled and were divided into two groups. The control and DN groups consisted of 100 healthy individuals and 100 patients with DN, respectively. Serum Mg, total anti-oxidant capacity (TAC), and superoxide dismutase (SOD) levels were estimated using the Calmagite, Koracevic, and Marklund and Marklund methods, respectively. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated using the Tietze F and Jean CD method, respectively. Mg levels were found to be significantly decreased in the DN group in comparison to the control group. Anti-oxidant markers were statistically significantly reduced (P <0.001), whereas MDA levels were statistically significantly elevated (P <0.001) in the DN group compared to the control group. There was a significant positive association of Mg with TAC, SOD, and GSH. A statistically significant negative association of Mg with MDA (r = -0.302, P <0.001, n = 100) was also observed. An apparent relationship was observed between hypomagnesemia and oxidative stress in patients with DN. Lower levels of Mg and oxidative stress were also strongly linked.

Association of Dyslipidemia, Increased Insulin Resistance, and Serum CA 15-3 with Increased Risk of Breast Cancer in Urban Areas of North and Central India.

OBJECTIVE: This study aims to determine the association of dyslipidemia and increased insulin resistance (IR) with increased breast cancer (BC) risk. MATERIALS AND METHODS: The study group comprised 110 premenopausal and 143 postmenopausal, untreated female BC patients in the age range of 29-72 years. Control group consisted of 117 premenopausal and 141 postmenopausal healthy females in the age range of 23-75. Approximately 8-ml blood samples were drawn to measure various biochemical parameters. Serum glucose, total cholesterol, triglyceride (TG), and high-density lipoprotein-cholesterol were measured. Very low-density lipoprotein-cholesterol (VLDL-C) and LDL-C were calculated using Friedewald's formula. Serum insulin and serum CA 15-3 were estimated by immune enzymatic assay. IR was assessed using homeostasis model assessment IR index (HOMA-IR). RESULTS: Clinical variables in the case and control groups were compared using the unpaired Student's t-test. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by binary logistic regression analysis. Pearson's correlation analysis was used to determine the association between CA 15-3 and variables of interest. Total cholesterol, TG, LDL, VLDL, serum glucose, serum insulin, HOMA-IR, and serum CA 15-3 were significantly higher (P < 0.001) in BC patients compared to those in controls. Significant adjusted ORs with 95% CI were found to be fasting glucose, total cholesterol, and TGs. We also found a significant positive correlation between total cholesterol, TG, LDL, serum glucose, serum insulin, HOMA-IR, and serum CA 15-3. CONCLUSION: This study confirms the association between dyslipidemia, IR, and increased BC risk.

Modulation of neuro-inflammatory condition, acetylcholinesterase and antioxidant levels by genistein attenuates diabetes associated cognitive decline in mice.

The association of diabetes and cognitive decline may indicate that high sugar level might be a risk factor for Alzheimer's disease. A collective term 'diabetes associated cognitive decline' (DACD) has been coined for the patients with type 2 diabetes mellitus showing decline in their cognitive function, especially weak episodic memory, cognitive inflexibility and poor psychomotor performance leading towards Alzheimer's disease. However, at present, no specific treatment exists for the prevention and/or treatment of DACD. Genistein, an isoflavone phytoestrogen, reveals neuroprotective effects in many experimental murine models, though its role on DACD with probable mechanistic approach has still been scope for research. The motive behind the present study is to investigate the outcome of genistein treatment against DACD in streptozotocin-induced diabetic mice with Morris water maze paradigm followed by open field trial to rule out the possibility of impairment in locomotor performance. Chronic (30 days) genistein treatment (2.5, 5.0 and 10.0 mg/kg, i.p. once daily) in diabetic mice significantly lowered hyperglycemia, recovered cognitive performance by affecting acetylcholinesterase activity and oxidative stress and ameliorated neuro-inflammatory condition by varying TNF-α, IL-1ß and nitrite levels as impaired in diabetic mice. Thirty days treatment with vitamin C or metformin also improved diabetes-induced memory impairment and significantly dragged these biochemical parameters towards respective controls. Locomotor performance was not influenced by diabetic condition or any associated treatment. It is concluded that genistein supplementation might be a prospective therapeutic approach for the treatment and/or avoidance of diabetic linked learning and memory dysfunction.

Inhibition of DPP-4 Activity and Neuronal Atrophy with Genistein Attenuates Neurological Deficits Induced by Transient Global Cerebral Ischemia and Reperfusion in Streptozotocin-Induced Diabetic Mice.

Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury. Effect of genistein (2.5, 5.0, and 10.0 mg/kg, i.p., o.d.) treatment on ischemia-reperfusion-induced neuronal injury in diabetic mice was evaluated in terms of cerebral infarct size, oxidative damage, mitochondrial activity in terms of neuronal apoptosis and cellular viability, dipeptidyl peptidase-4 activity and active glucagon-like peptide-1 concentration, and neurological functions measured as short-term memory and motor performance. Genistein administration following transient cerebral ischemia significantly (p ˂ 0.0001) counteracted cognitive impairment and re-established (p ˂ 0.001) motor performance in diabetic mice. Ischemia-reperfusion increased the infarct size, genistein administration prevented the increase in cerebral infarct size (p ˂ 0.0001) and significantly suppressed (p ˂ 0.001) the increase in cerebral oxidative stress in transient cerebral ischemia-reperfusion subjected diabetic mice. Genistein treatment significantly (p ˂ 0.001) reduced neuronal apoptosis and increased cellular viability (p ˂ 0.0001), almost completely suppressed (p ˂ 0.0001) the circulating dipeptidyl peptidase-4 activity, and enhanced (p ˂ 0.0001) glucagon-like peptide-1 concentration in diabetic mice with cerebral ischemia-reperfusion. This study suggests that genistein has potent neuroprotective activity against global cerebral ischemia-reperfusion-induced neuronal injury and consequent neurological deficits in streptozotocin-induced diabetic mice.

Role of adiponectin in mediating the association of osteocalcin with insulin resistance and type 2 diabetes: a cross sectional study in pre- and post-menopausal women.

OBJECTIVE: To analyse the association of osteocalcin with insulin resistance and type 2 diabetes and assess the role of adiponectin in these relationships. METHODS: This study comprised 98 newly diagnosed type 2 diabetic women (51 pre-menopausal and 47 post-menopausal) and 102 age and BMI matched controls (53 pre-menopausal and 49 post-menopausal). Insulin resistance was calculated by homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS: Osteocalcin was significantly positively correlated with adiponectin in both pre-menopausal (p = 0.0026) and post-menopausal diabetic women (p = 0.0357). Significant negative association between osteocalcin and HOMA-IR was observed only in pre-menopausal diabetic women (p = 0.0019), but the association was partially reduced (p = 0.0219) after additional adjustment for adiponectin. Adiponectin slightly attenuated the inverse association between osteocalcin and presence of type 2 diabetes in both pre- and post-menopausal women. CONCLUSION: The protective action of osteocalcin against the development of insulin resistance and type 2 diabetes in women may be partially mediated through up-regulation of adiponectin secretion.

Attenuation of serum ferritin and iron burden by intake of antioxidants in beta thalassemia major.

It has been anticipated that iron and ferritin burden in patients with beta thalassemia major is associated with enhanced free radical formation and blemished antioxidant defense system. The goal of study was to scrutinize impact of serum iron, total iron binding capacity (TIBC), ferritin and erythrocyte catalase in patients with beta thalassemia major. 140 beta thalassemia major patients were studied before and after supplementation of antioxidants for one month, and status was compared with 140 age and sex matched healthy controls. A significant elevation was found in the levels of serum iron and ferritin (P < 0.001) with concomitant decrease in erythrocyte catalase (P < 0.001) in patients when compared with controls. After one month supplementation of antioxidants, catalase was elevated significantly (P < 0.001) and marginal rise in serum TIBC concentration increased marginally while iron and ferritin were decreased marginally (P > 0.05) when compared with controls and baselines values. Beta thalassemia major children receive multiple blood transfusions, and are at risk of secondary iron overload induced oxidative stress. These effects may be help to minimize with supplementation of antioxidants.

Relationship of serum osteocalcin levels with blood glucose, insulin resistance and lipid profile in central Indian men with type 2 diabetes.

OBJECTIVE: To assess the relationship of serum osteocalcin levels with blood glucose, insulin resistance and lipid profile in central Indian men with type 2 diabetes. METHODS: Anthropometric and biochemical parameters were measured in 56 newly diagnosed type 2 diabetic men and in 56 age and body mass index (BMI) matched controls. Insulin resistance was calculated by homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: After adjustment for age and BMI, osteocalcin levels were negatively correlated with fasting plasma glucose (p = 0.0004), fasting insulin (p = 0.0311), HOMA-IR (p = 0.0023), and triglycerides (p = 0.0095), and positively correlated with high density lipoprotein (HDL)-cholesterol (p = 0.0042) in type 2 diabetic patients. In multivariate logistic regression analyses that adjusted for age, BMI, waist circumference and waist-to-hip ratio, osteocalcin was inversely associated with the presence of type 2 diabetes (p < 0.0001). CONCLUSION: Osteocalcin may play a protective role in the pathogenesis of type 2 diabetes, not only through direct involvement in glucose homeostasis, but also through improving lipid profile.

Comparative analysis of lycopene in oxidative stress.

OBJECTIVE: Lycopene is a phytochemical, found in tomatoes having singlet oxygen quenching ability higher than other antioxidants, participates in most of chemical reactions to protect critical cellular biomolecules. Present study is to analyze effect of tomato's lycopene, synthetic lycopene, its placebo form in patients of OS. METHODS: Study includes 45 patients having oxidative stress, age 40-60 years and 30 age and sex matched healthy control. Blood samples were collected at the enrollment, end of 2 weeks of lycopene restricted diet and after 10 weeks of lycopene supplementation. Oxidative stress biomarkers MDA, SOD, GPX, GR, GSH, Catalase, vitamin C and E were measured. RESULTS: Results of study revealed decreased lipid peroxidation and OS after various forms of lycopene supplementation but comparative analysis showed significant increase in OS biomarkers except MDA in patients receiving synthetic lycopene as compare to natural and placebo form. CONCLUSION: Dietary intake of tomato lycopene is beneficial to fight against OS but in the synthetic form it is more bioavailable and more effective against OS.

Prematurity and related biochemical outcomes: study of bone mineralization and renal function parameters in preterm infants.

Preterm is defined as a baby with a gestation of less than 37 completed weeks. In this study, serum calcium, phosphorus, ALP, creatinine, and electrolytes were measured in preterm babies. The present study comprised of 75 preterm babies of which 25 were of 28-30 weeks, 25 were of 30-32 weeks, and remaining 25 were of 34-36 weeks (controls) of gestational age. Serum calcium and phosphorus levels were found to be significantly decreased, and serum ALP, creatinine, and electrolytes were found to be significantly increased (P < 0.001) at 28-30 weeks as compared to controls, but serum calcium and phosphorous levels were found to be insignificantly decreased, whereas serum ALP activities were found to be insignificantly increased at 28-30 weeks as compared to 30-32 weeks of gestational age in preterm babies. It can be concluded that high serum ALP activity and low serum calcium and phosphorus levels are associated with preterm babies. A significant difference in the mean values of these renal function parameters was also obtained, except for serum sodium and potassium.

Comparative study of nitro blue tetrazolium (NBT) reduction method for estimation of glycated haemoglobin with glycated HbA1c estimated on DCA2000+analyzer (immunoagglutination inhibition).

Glycated haemoglobin is a diagnostic tool, used for the monitoring of the glycemic status among diabetic patients. The present study is designed to compare and correlate modified NBT reduction method for the estimation of Glycated protein (Glycated Haemoglobin) with HbA1C estimated on DCA+2000Analyzer. Glycated protein reduces Nitro Blue Tetrazolium (NBT) reagent in alkaline medium to tetrazinolyl radical NBT+ which is disproportional to yield a highly colored formazan dye (MF+) (monoformazen), absorbance of colored compound was measured which gives the concentration of glycated proteins present in the sample. Heme free globin (glycated hemoglobin) was extracted out and dissolved immediately in 1 ml normal saline. Dissolved globin was treated with modified NBT reagent, absorbance of color developed was recorded in milli delta A/min. The results of modified NBT were then compared with HbA1c estimated by immunoagglutination inhibition method. Correlation coefficient between Glycated hemoglobin and HbAlc was found to be r=0.926 using Schimadzu CL-750 spectrophotometer and r=0.902 using colorimeter. Results of this study were found to be statistically significant p < 0.001. Thus the present study concludes that Glycated hemoglobin testing by modified NBT reduction method is as sensitive as HbAlc estimated by DCA2000+Analyzer (immunoagglutination inhibition). Hence it could be used for routine monitoring of blood glucose control level in diabetic subjects.

Oxidized LDL and paraoxanase status in ischemic stroke patients.

Stroke is the leading cause of mortality and long term disability among adults in industrialized countries. Oxidative stress is an independent risk actor by inducing production of oxygen free radicals in ischemic stroke. Because a relationship may be associated between ox-ldl and paraoxanase, the aim of this study was to investigate the association between ox-ldl and paraoxanase in ischemic stroke patients by determining whether ox-ldl is a useful marker for monitoring oxidative stress in ischemic stroke patients. Our study included 100 patients of ischemic stroke and 100 controls. Compared with controls ox-ldl was significantly raised in stroke patients and Paraoxanase activity was low. Our findings suggest that there is a significant association between raised plasma ox-ldl and decrease activity of Paraoxanase with age indicating that plasma ox-ldl may reflect oxidative stress in ischemic stroke patients.

Comparative study of NBT reduction method for estimation of glycated protein (serum fructoseamine) with glycated HbA1c estimated on DCA 2000+Analyzer (immunoagglutination inhibition).

Glycated protein estimation is a diagnostic tool, used for the long term and short term monitoring of the glycemic status of diabetic patients. The present study is designed to compare and correlate modified NBT reduction method for the estimation of Glycated protein (serum fructosamine) with HbAlc estimated on DCA+2000 Analyzer. Glycated protein (serum fructosamine) reduces Nitro Blue Tetrazolium (NBT) reagent in alkaline medium to tetrazinolyl radical NBT+ which forms a highly colored monoformazen compound, absorbance of which is directly proportional to the concentration of glycated protein (serum fructosamine) present in the sample and is recorded as delta A/min. The results of modified NBT were then compared with HbA1c estimated by immunoagglutination inhibition method. Correlation coefficient between HbAlc with serum fructosamine was found to be r = 0.739 using Schimadzu CL-750 spectrophotometer and r = 0.731 using colorimeter. Results of this study were found to be statistically significant P < 0.001. Hence this method could be used for routine monitoring of blood glucose control in diabetics as HbA1c estimation.

Association between paraoxonase activity and lipid levels in patients with premature coronary artery disease.

BACKGROUND: South Asians, especially Indians show increased risk for atherosclerosis and have the higher mortality rates due to coronary artery disease. The increasing incidence of coronary artery disease in young patients is possibly due to industrialization, stress of life, less exercise and increasing incidence of smoking and other factors. We attempted to determine an independent association of paraoxonase with coronary artery disease in young patients. METHOD: The lipid profile and serum paraoxonase were investigated in 120 angiographically-proven premature coronary artery disease patients (99 males and 21 females, all <45 years) with diabetes mellitus, smoking, hyperlipidemia, obesity, hypertension along with 50 (41 male and 9 female) normal subjects and compared. RESULTS: A significant increase was observed in the concentrations of total cholesterol, triglycerides and LDL cholesterol in premature coronary artery disease patients. The activities of paraoxonase and HDL cholesterol concentrations decreased in coronary artery disease patients compared to control subjects. CONCLUSION: A paraoxonase was an independent (p<0.001, OR 14.9 and 95% CI 5.6-35.9) risk factor for premature coronary artery disease patients along with lipid profiles. Paraoxonase activity should be evaluated in all coronary artery disease patients in the absence of traditional risk factors.

Cystatin C-A novel marker of glomerular filtration rate: A review.

Glomerular filtration rate is routinely assessed by measuring the serum markers such as urea nitrogen and serum creatinine. Although these markers are widely used to assess renal function but they do not perform optimally in certain clinical settings. There is thus a practical need for an easily automated alternative to plasma creatine, which would be more specific, sensitive and reliable from the analytical and clinical view point. Compared with the above endogenous markers, and time consuming laborious tests, Cystatin C facilitates the recognition of abnormal renal function in children, as its reference range is constant beyond the 1(st) year of life. This review mainly focuses on the diagnostic performance of Cystatin C against other renal markers in the pediatric population and in specific subpopulations of patients.