The importance of the enzyme Gamma-glutamyltransferase in the pathogenic cluster in type2 diabetic patient.

Introduction. Gamma-glutamyltransferase (GGT) is a liver enzyme involved in inflammation and oxidative stress. It is already known that MCP-1 (Monocyte Chemoattractant Protein-1) and TNF-α (tumour necrosis factor) as inflammatory markers, ICAM-1 (Intercellular Adhesion Molecule-1) as an endothelial dysfunctional marker, and glutathione, as an antioxidant, have abnormal levels in type 2 diabetic patients. The aim of this study was to evaluate the specific biological picture of type 2 diabetic patients that also associate higher GGT activity. Methods. Eighty-five type 2 diabetes, aged 40-70 years with a duration of diabetes less than 6 years without infections, epilepsy, chronic liver or cardiac diseases, without alcohol consumption (>20 g/day) were divided in two subgroups, those with normal and those with high abnormal GGT. Results. The diabetic patients with high GGT (n=31) had dysglycaemia, dyslipidemia, higher inflammatory markers (CRP, TNF-α, MCP-1) and endothelial dysfunction (high leptin and sICAM). sICAM, serum MCP-1 and TNF-α levels had significant correlations with GGT activity (r= 0.38, r=0.30 and 0.26 respectively, p<0.05). Conclusion. This study underlines that in non-alcoholic diabetic patients, with a duration of the metabolic disease less than 6 years, sICAM, serum MCP-1 and TNF-α might play an important role in dysmetabolism, and higher level for GGT represents the "red flag" for this condition.

Prediabetes and cardiovascular risk alert programs - useful tools for preventing diabetes mellitus and cardiovascular events in primary medicine.

We propose alert programs, made in Excel using VBA, for general practitioners, in order not to miss the diagnosis of prediabetes and cardiovascular risk factors for their patients and to improve their management.

Erythrocyte membrane stability to hydrogen peroxide is decreased in Alzheimer disease.

The brain and erythrocytes have similar susceptibility toward free radicals. Therefore, erythrocyte abnormalities might indicate the progression of the oxidative damage in Alzheimer disease (AD). The aim of this study was to investigate erythrocyte membrane stability and plasma antioxidant status in AD. Fasting blood samples (from 17 patients with AD and 14 healthy controls) were obtained and erythrocyte membrane stability against hydrogen peroxide and 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH), serum Trolox equivalent antioxidant capacity (TEAC), residual antioxidant activity or gap (GAP), erythrocyte catalase activity (CAT), erythrocyte superoxide dismutase (SOD) activity, erythrocyte nonproteic thiols, and total plasma thiols were determined. A significant decrease in erythrocyte membrane stability to hydrogen peroxide was found in AD patients when compared with controls (P<0.05). On the contrary, CAT activity (P<0.0001) and total plasma thiols (P<0.05) were increased in patients with AD compared with controls. Our results indicate that the most satisfactory measurement of the oxidative stress level in the blood of patients with AD is the erythrocyte membrane stability to hydrogen peroxide. Reduced erythrocyte membrane stability may be further evaluated as a potential peripheral marker for oxidative damage in AD.

Effect of diet and omega-3 fatty acids in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis to steatohepatitis (NASH) and cirrhosis. The aim of this study is to test beneficial effects of omega-3 fatty acids (DHA 130 mg, EPA 25 mg) treatment in NAFLD, in a mouse model of non-alcoholic fatty liver disease. As pretreatment, 50 mice were fed for one month with a high-fat diet to induce NAFLD. Then, the mice were divided in different groups according to diet (normo- or hypercaloric), with and without treatment with omega-3 fatty acids, for another month, forming the post-treatment group. The liver and blood samples were collected for biochemical and histopathological analysis. Biochemical parameters including: glycemia, total cholesterol, triglycerides, uric acid, albumin, total plasma antioxidant capacity (TEAC) was measured in serum. Glutathione (GSH), total thiols and malonyldialdehyde (MDA) were determined in mouse liver homogenates. Mice from post-treatment group, on hypercaloric diet with or without omega-3 fatty acids treatment, had medium hepatopathy (granular and vacuolar degeneration of the hepatocytes) and hypertriglyceridemia. Omega-3 fatty acid treatment lowered the rise of triglycerides (p<0.03), glycemia (p<0.01) and cholesterol (p<0.02) in serum and MDA level of the liver (p<0.05). Mice from post-treatment group, on normocaloric diet with or without omega-3 fatty acid had different histopathological and biochemical results. Those with normocaloric/normolipidic diet and omega-3 fatty acids treatment had reversed liver histopathological results from NASH to normal aspect and had the best metabolic parameters results. In conclusion, omega-3 fatty acids treatment associated with a normocaloric/normolipidic diet has hepatoprotective action in nonalcoholic fatty liver disease.

Systemic redox modifications in senile cataract.

UNLABELLED: Recent studies on cataract formation focus on a primary role of systemic oxidative stress, generated outside the lens. Plasma inflammatory markers are associated with senile cataract. OBJECTIVE: The aim of this study was to find correlations between blood oxidative stress markers and some inflammatory plasma markers in cataractous patients. DESIGN AND METHODS: The blood samples were collected from 38 patients (aged 50 to 80). Patients were subdivided according to two criteria. Considering age criteria, presenile and senile cataract groups were formed. According to the absence or presence of other ocular comorbidities (age-related macular degeneration, glaucoma), pure cataract and nonpure cataract groups were constituted. Fifteen age and sex matched healthy subjects were selected for the control group. RESULTS: In our study, for all groups of patients, the measured markers of oxidative stress were modified vs. control values. Plasma antioxidant capacity, plasma antioxidant "gap", cholesterol and albumin/globulin levels were significantly decreased while RBC SOD activity, RBC catalase activity and plasma ceruloplasmin were significantly increased. Inflammatory markers, ceruloplasmin and albumin/globulins were correlated with different parameters of oxidative stress. CONCLUSION: The blood redox values and the level of some inflammatory markers demonstrate that senile cataract is a systemic disease with an inflammatory component.

Protection of erythrocyte membrane against oxidative damage by geriforte in healthy human subjects.

The influence of Geriforte, an Ayurvedic natural supplement, on the antioxidant defense systems in human erythrocytes and plasma was investigated in an open human clinical study. The ability of Geriforte to inhibit the azo-bis 2-amidinopropane dihydrochloride (AAPH) dependent lysis of erythrocytes was also evaluated. Geriforte supplementation increased the activity of erythrocyte catalase (265.745 +/- 15.768 vs. 352,329 +/- 18.480 K/g Hb/mL, p < 0.01) and reduced the free radical mediated cytotoxicity induced by azo-bis 2-amidinopropane dihydrochloride (AAPH), which was measured by erythrocyte membrane stability assay (0.0439 +/- 0.0069 vs. 0.1291 +/- 0.0396 C50- AAPH (mM), p < 0.05). The intervention did not change significantly the activity of erythrocyte superoxide dismutase and the plasma levels of antioxidant agents. The results indicate that Geriforte possesses cytoprotective properties on erythrocytes against oxidative challenge and specific antioxidant activity, which involves mainly the intracellular protective systems and the membranes.

Diabetic foot patients with and without retinopathy and plasma oxidative stress.

OBJECTIVE: The first aim of this study was to evaluate some plasma oxidative stress markers in diabetic patients (type2 diabetes mellitus) with peripheral arteriopathy. Secondly, these patients were divided into two groups considering the presence or absence of retinopathy. The differences in the levels of the oxidative stress parameters could be important to select patients prone to develop multiple vascular complications, including retinopathy. PATIENTS AND METHODS: Forty hospitalized type II diabetic patients, aged between 40 and 70, with stage III or IV foot ulceration according to the Wagner classification, had an ophthalmologic evaluation for retinopathy. Among them, 23 were with retinopathy with different grades of severity and 17 were without retinopathy. Twenty healthy subjects served as a control group. Fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, total serum proteins, serum uric acid and plasma ceruloplasmin levels were determined and compared. RESULTS: Plasma levels for fasting glucose, glycosylated hemoglobin, ceruloplasmin and serum concentrations for fructosamine and uric acid were significantly increased in diabetic foot patients vs. control subjects. Comparing the two groups of patients, with and without retinopathy, the concentrations of ceruloplasmin and uric acid were significantly increased in diabetic patients with retinal disease. In diabetic patients with retinopathy, positive correlations were calculated between glycated hemoglobin and fructosamine concentrations and between glycated hemoglobin and ceruloplasmin. CONCLUSION: Diabetic foot patients with retinopathy have increased plasma levels of uric acid and ceruloplasmin. These plasma compounds could be important in the pathogenesis of retinal disease. Two aspects should be considered when these high values are analysed. First, these antioxidant compounds may become prooxidant in diabetic vascular environment. Secondly, it is not known whether these modified plasma oxidative stress parameters are cause or effect in diabetic complication development.

Plasma redox status and premature onset of senile cataract.

UNLABELLED: Dysfunction of the lens due to opacification is called cataract. Senile cataract is associated with old age. It is estimated that the need for cataract extractions would be diminished by half if onset of cataract would be delayed by only ten years. It thus appears crucial to have a better characterization of the etiology of cataract to detect modifiable factors. It seems that oxidative stress may play an important role in cataractogenesis. Also, it was demonstrated that some plasma constituents correlate with human cataract location. OBJECTIVE: We supposed that in senile cataract the oxidative insult may be systemic and not only at the lens level. The aim of our study was to evaluate the blood redox status in cataractous patients aged between 50-65. DESIGN AND METHODS: The blood samples were collected from 15 patients with pure nuclear cataract and/or posterior subcapsular cataract, without metabolic or somatic diseases and from 15 age and sex matched controls. Carbonyl content of plasma proteins was evaluated with 2,4-dinitro-phenyl-hydrazine method. The a-oxoaldehydes were measured in the presence of Girard T reactive. The lipid peroxides concentration was assessed measuring malondialdehyde concentration using thiobarbituric acid. For the other plasma parameters we used kits. RESULTS: The levels of plasma protein carbonyls and malondialdehyde were significantly increased in the cataract group. The plasma levels of: total proteins, globulins, total thiols, fasting glucose, triglycerides and alpha-oxoaldehydes were not modified comparing the groups. Plasma concentrations of albumin and cholesterol were significantly decreased. CONCLUSION: The study underlies the presence of an increased plasma oxidative stress in cataractous patients. The abnormal oxidative stress parameters are linked to the premature development of senile cataract. Preventive therapy in order to delay the onset of senile cataract requires more research work on plasma oxidative stress markers.

[Risk factors in cataract]. / Factorii de risc in cataracta.

Cataract is one of the major causes of blindness throughout the world. Considerable effort to elucidate risk factors for cataract has been undertaken in hopes that simple, preventive strategies may be implemented to avoid or delay the progression of lens opacification. Advanced age, female gender, poor education, lower socioeconomic status, high or low body mass index and heavy alcohol consumption are some risk factors for senile cataract. Smoking appears to provide an oxidative challenge associated with depletion of antioxidants as well as with enhanced risk for cataract formation. Multiple drugs are responsive in iatrogenic cataract. Nonsteroidal anti-inflammatory drugs (NSAIDs) and pyruvate may have protective effects for senile cataract. Randomized clinical trials should be encouraged to find medical therapeutic ways to delay the cataract development.

[Blood constituents and senile cataract]. / Diversi compusi plasmatici si cataracta senila.

In cataractous older age group subjects, different blood constituents have the mean concentrations and standard deviations within normal limits but, of course, differing significantly from the corresponding means in the control population. Various morphological types of senile cataract have different risk factors. The mechanisms underlying the associations between different blood constituents with different patterns of lens opacification remain to be elucidated.

Oxidative stress parameters in hemodialysis patients with or without diabetes.

Oxidative stress (imbalance of antioxidant and prooxidants in favour of the later) is considered to be a feature of diabetes and chronic renal failure. Carbonyl stress defined as accumulation of reactive carbonyl compounds due to excess production or disturbed clearance from the body is thought to amplify oxidative stress in these conditions. The accumulation of carbonyl compounds can be also a consequence of oxidative stress. A vicious cycle can thus be formed. We have studied the association between carbonyl stress markers (dicarbonyl compounds, Amadori products) and oxidative stress markers (total plasmatic thiols and malondialdehyde level) in hemodialysed patients with or without diabetes taking into account the levels of possible excess substrates (glucose and triglycerides). We have concluded that hemodialysed diabetes patients are more susceptible to oxidative stress than hemodialysed patients without diabetes.

Free radical activity in obese patients with type 2 diabetes mellitus.

UNLABELLED: Oxidative stress plays critical roles in the pathogenesis of various diseases. The aim of the present study was to investigate the relationship between oxidative stress, measured by plasma dicarbonyls and plasma antioxidant defence, measured by reduced glutathione (G-SH) in the whole blood, protein thiols in the plasma and erythrocyte superoxide dismutase activity in obese and obese with type-2 diabetes mellitus subjects, clinically free of complications. Twenty obese patients with type-2 diabetes mellitus and twenty nondiabetic obese patients were examined and compared with twenty healthy controls (matched for age and sex against the obese patients with or without diabetes). RESULTS: Obese patients and obese diabetic patients had lower blood glutathione than control subjects (p<0.02 and respectively p<0.04) and higher plasma MDA, an end product of lipid peroxidation (p<0.004 and respectively p<0.01). There was a significant difference between plasma MDA from obese and obese diabetic subjects (p<0.05). Plasma thiols (expressed as micromol/mg protein) did not differ between the three groups. Plasma dicarbonyls concentrations were significantly increased in obese (p<0.043) and obese diabetic patients (p<0.047) and SOD activity (U/g Hb) was significantly decreased in obese (p<0.0 ) and obese diabetic patients (p<0.05) compared to controls. Analysing the results of our study, which show that most of the markers of oxidative stress are modified in the same way in obesity and obesity with diabetes mellitus type 2, we suppose that obesity leads to oxidative stress which can contribute to obesity-associated diseases such as diabetes mellitus.

A comparative oxidative stress study--obesity with and without diabetes mellitus.

Oxidative stress and inflammation are involved in the initiation and progression of obesity and diabetes mellitus. The aim of our study was to find out some markers of oxidative stress in twenty obese patients with type 2 diabetes mellitus (group D) and twenty age-matched obese subjects (group O) and compare the results with the control values from twenty matched healthiy subjects (group H). Spectrophotometric methods were used. For the following plasma parameters: ceruloplasmin, d-ROM (determinable Reactive Oxygen Metabolites), alpha-dicarbonyls, the values were modified in the same way for the groups of patients versus healthy subjects. The patients had higher alpha-dicarbonyls levels than the controls (for D versus H, p<0.047 and for O versus H, p<0.043). There were not significant differences for plasma ceruloplasmin and d-ROM levels. Comparing group O versus D, all the above parameters had very close values. The antioxidant capacity (AC) was higher in group O versus group H (p<0.001) and higher in group O versus D (p<0.02). The high AC for obese patients may be due to hyperuricemia. A negative correlation between AC and d-ROM concentrations and a positive correlation between ceruloplasmin and AC levels was observed for group D. Our data underline that in type 2 diabetes mellitus and obesity, the plasma markers of oxidative stress are modified in the same way. Oxidative stress may be a "connector" between these two diseases. Probably body fat reduction (for obese individuals) diminishes oxidant formation and, in its turn, the incidence of obesity related diseases, such as diabetes mellitus.