Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients.

AIMS/HYPOTHESIS: This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes. METHODS: The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA(1c), malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile. RESULTS: Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 microg/min) and 62 with microalbuminuria (AER > or =20 microg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean +/- SD): fasting plasma glucose 9.41 +/- 2.88 vs 8.19 +/- 1.93 mmol/l, p < 0.05; HbA(1c) 7.97 +/- 1.51 vs 7.39 +/- 1.03%, p < 0.05; MDA 1.18 +/- 0.35 vs 1.02 +/- 0.29 micromol/l, p < 0.05; pentosidine 98.5 +/- 24.6 vs 82.9 +/- 20.9 pmol/ml, p < 0.005; and AGE 13.2 +/- 4.8 vs 10.6 +/- 3.8 microg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA(1c) r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = -0.55, p < 0.001; TRAP r = -0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA(1c) and MDA, but not pentosidine or AGE. CONCLUSIONS/INTERPRETATION: Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.

Desaturase activities and metabolic control in type 2 diabetes.

The aim of this study was to elucidate the effects of a poor glycemic control on fatty acid composition and desaturase activities in type 2 diabetic patients. Plasma phospholipid fatty acid composition and desaturase activities (estimated from fatty acid product to precursor ratios) were measured in 30 type 2 diabetic patients during poor metabolic control and after achieving a good metabolic control. Significant changes were recorded in the percentages of palmitic, stearic, dihomo-gamma-linolenic, docosatetraenoic and docosapentaenoic acid. The delta-5 desaturase activity was significantly higher with poor than with good metabolic control. The changes identified in plasma phospholipid fatty acid composition and the desaturase activity in type 2 diabetic patients go in the opposite direction to those described in similar conditions in type 1 diabetic patients and may be relevant to a better understanding of the role of metabolic control in the progression of chronic complications in type 2 diabetic patients.

Radiative mechanism and surface modification of four visible deep level defect states in ZnO nanorods.

Visible luminescence from ZnO nanorods (NRs) is attracting large scientific interest for light emission and sensing applications. We study visible luminescent defects in ZnO NRs as a function of post growth thermal treatments, and find four distinct visible deep level defect states (VDLSs): blue (2.52 eV), green (2.23 eV), orange (2.03 eV), and red (1.92 eV). Photoluminescence (PL) studies reveal a distinct modification in the UV (3.25 eV) emission intensity and a shift in the visible spectra after annealing. Annealing at 600 °C in Ar (Ar600) and O2 (O600) causes a blue and red-shift in the visible emission band, respectively. All samples demonstrate orange emission from the core of the NR, with an additional surface related green, blue, and red emission in the As-Prep, Ar600, and O600 samples, respectively. From PL excitation (PLE) measurements we determine the onset energy for population of the various VDLSs, and relate it to the presence of an Urbach tail below the conduction band due to a presence of ionized Zni or Zni complexes. We measured an onset energy of 3.25 eV for the as prepared sample. The onset energy red-shifts in the annealed samples by about 0.05 to 0.1 eV indicating a change in the defect structure, which we relate to the shift in the visible emission. We then used X-ray photoemission spectroscopy (XPS), and elastic recoil detection analysis (ERDA) to understand changes in the surface structure, and H content, respectively. The results of the XPS and ERDA analysis explain how the chemical states are modified due to annealing. We summarize our results by correlating our VDLSs with specific intrinsic defect states to build a model for PL emission in ZnO NRs. These results are important for understanding how to control defect related visible emission for sensing and electroluminescence applications.

Advanced glycation end products/peptides: an in vivo investigation.

Advanced glycation end products/peptides (AGE/peptides) originate by in vivo enzymatic digestion of nonenzymatically glycated proteins, which are produced by reaction of glucose with primary amino groups present in the protein chain following the Maillard pattern. AGE/peptides are highly reactive species and can interact with tissue and circulating proteins, leading to tissue modification and impaired protein functionality. Serum levels of AGE/peptides are reported to be particularly high in diabetes (in terms of higher production) or in end-stage renal disease (in terms of accumulation). For these reasons, their structural identification is of high interest, giving information on their relationship with the pathological state and allowing the design of possible therapeutic interventions. We report here some preliminary results obtained by liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) and matrix-assisted laser desorption ionization MS (MALDI-MS) investigations carried out on the low-molecular-weight serum peptide fraction from 10 healthy subjects, 10 patients with poorly controlled diabetes, and 10 patients with end-stage nephropathy.

Evaluation of glyoxal and methylglyoxal levels in uremic patients under peritoneal dialysis.

Advanced glycation end products (AGEs) accumulate in serum and tissues of patients with chronic renal failure, even in the absence of diabetes, and a different clearance of these species has been observed by hemodialysis and peritoneal dialysis (CAPD). Furthermore, it has been shown that not only AGE but also 1,2-dicarbonyl compounds are formed during heat sterilization of glucose-based peritoneal dialysis fluids. Therefore, we investigated the level of some AGEs (pentosidine and free pentosidine) and dicarbonyl compounds (glyoxal and methylglyoxal) in end-stage renal disease patients subjected to peritoneal dialysis. Samples (20 from healthy subjects, 16 from uremic patients before and after 12 h of peritoneal dialysis) were analyzed, and the plasma and dialysate levels of glyoxal, methylglyoxal, pentosidine, and free pentosidine were determined. In plasma of uremic patients, mean values of pentosidine showed a small decrease after dialysis and were always higher than those of healthy control subjects. An analogous trend was observed for free pentosidine. In the case of peritoneal dialysate, no pentosidine and free pentosidine were found at time zero, whereas both compounds were detected after 12 h of dialysis. Glyoxal and methylglyoxal mean levels showed a decrease in plasma after dialysis even if their values were always higher than those of healthy control subjects. Surprisingly, an analogous trend was observed also in dialysate. These results might indicate that glyoxal and methylglyoxal already present in the dialysis fluid react with the peritoneal matrix proteins, accounting for the gradual loss of peritoneal membrane function that is often observed in patients subjected to CAPD for a long time.

The effects of psyllium on lipoproteins in type II diabetic patients.

We examined the effects of 2 months of psyllium treatment in optimizing metabolic control and lipoprotein profile, and its postprandial effects on lipids in type II diabetes. We recruited 40 type II diabetic patients who were on sulfonylureas and a controlled diet, sequentially assigning them to psyllium treatment (G1) or to a control group (G2) treated with dietary measures alone. After 2 months of treatment, body mass index, waist circumference, HbA1c (hemoglobin A1c) and fasting plasma glucose levels had significantly decreased in both groups. There were no postprandial differences in the lipoprotein profile between the two groups. Triglycerides were significantly lower in G1, but not in G2. Our study contributes toward elucidating the effects of psyllium on serum lipids, and suggests that psyllium treatment may help in reducing triglycerides (a known risk factor for cardiovascular disease) in type II diabetic patients.

Pentosidine plasma levels and relation with metabolic control in diabetic patients.

Levels of plasma pentosidine, a well-known AGE, were measured in type 2 diabetic patients in varying states of metabolic control to verify possible relationships between this parameter and traditional metabolic control parameters such as HbA1c and plasma glucose levels. At baseline, mean values of fasting plasma glucose, HbA1c and pentosidine were significantly higher in diabetic patients than those of controls, confirming patients' poor glycemic control. After ten months, patients with good metabolic control achieved showed near-normal HbA1c levels and reduced but not normalized pentosidine levels. Significant differences were found in the mean percentage decrease in the parameters. Regarding linear correlation, HbA1c levels only showed a positive relationship with plasma glucose values at baseline. Patients affected by chronic complications showed higher levels of pentosidine than those without complications. Thus, pentosidine plasma levels may be used to evaluate very long-term metabolic control in diabetic patients. In addition, a period of ten months of acceptable metabolic control is not enough to normalize pentosidine levels in diabetics, thus emphasizing the need for a longer period of improved metabolic control to reduce both this parameter and the burden of chronic diabetic complications.

A matrix-assisted laser desorption/ionization mass spectrometry study of the non-enzymatic glycation products of human globins in diabetes.

The molecular species present in globins from healthy and diabetic subjects with and without chronic complications have been analyzed by matrix-assisted laser desorption/ionization mass spectrometry. The technique demonstrated the presence of glycated and glyco-oxidated species of both alpha- and beta-globins. Their abundances show a good linear relationship with respect to HbA1c values and with the mean daily plasma glucose levels over the 6 weeks preceding the investigation. Interestingly, slightly different behaviour is observed in the data from patients with and without chronic complications; the plots of HbA1c vs. the abundance of glycated and glyco-oxidated species show different slopes and different intercepts with the y-axis. To investigate this aspect the mean abundances of glyco-oxidated species from healthy subjects and from diabetic patients with and without complications were calculated. Higher values were found for the two last sets of samples, but no significant difference was found between them. These data could indicate different individual proclivities to oxidation and/or different oxidation kinetics related to behavioural and environmental factors.

[Collagenous colitis. Morphologic and immunohistochemical study]. / Colite collagena. Studio morfologico ed immunoistochimico.

Collagenous colitis is a clinico-pathological entity characterized by chronic diarrhoeas and deposition of collagen beneath the epithelium surface of large bowel. We revised 265 endoscopy biopsy specimens of the large bowel from 198 consecutive patients with "aspecific chronic colitis". Morphometric study showed that were not significant differences among various tracts in the same patients regarding to the thickness of basament membrane. It was more than 11.9 +/- 0.49 mu only in 13 pts (6.6%), while it was 3.96 +/- 1.4 mu in the others. Immunohistochemistry study confirmed the normality of subepithelial basement membrane and the below deposition of the large quantity of collagen IV.

[Effects of hypoxia on the production of angiotensin converting enzyme in decompensated liver cirrhosis]. / Effetti dell'ipossia sulla produzione dell'enzima di conversione dell'angiotensina nella cirrosi epatica scompensata.

The high angiotensin-converting activity, in 13 of the 17 patients afflicted with hepatic cirrhosis, has been put in relation to the hypoxia influence. The insufficient cession of O2 seems to stimulate the enzyme activity, especially for the patients who simultaneously present low values of blood pseudo-cholinesterase. The AA think that this behaviour is to be ascribed to a deficiency of the hepatic proteic synthesis of vasoactive substances, such as the angiotensins.

The complexity of non-enzymatic glycation product sets of human globins.

AIMS/HYPOTHESIS: Recently an individual variability in the relationships between mean blood glucose levels and HbA1c has been observed among diabetic patients. The aim of this study was to provide an accurate description and evaluation of glycated and glyco-oxidated globins from diabetic subjects and their relationship with HbA1c and plasma glucose values. METHODS: We studied 20 type 2 diabetic and 10 healthy subjects. Plasma samples were analysed by matrix-assisted laser desorption ionisation mass spectrometry. RESULTS: The presence of glycated and glyco-oxidated species of both alpha and beta globin was demonstrated. Values for these showed a good linear relationship with HbA1c values and the mean daily plasma glucose values for the 6 weeks preceding the investigation. Trends differed according to whether patients had chronic complications or not, differences being seen in the slopes of the plots relating HbA1c to the abundance of glycated and glyco-oxidated species. CONCLUSIONS/INTERPRETATION: The data obtained are consistent with the concept that individuals have a different individual proclivity for oxidation and/or that different oxidation kinetics are related to behavioural and environmental factors. Our data are thus relevant to the analysis of phenotype differences in diabetic patients.