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Biomedical subjects

D Fedele

Publications and source records attributed to D Fedele.

At least 73 records · Page 4Linked to original sources

[Oxidative stress and diabetes: role in the development of chronic complications].

"Oxidative stress" resulting both from over-production of reactive oxygen radicals and decreased efficiency of antioxidant defenses is now considered a factor contributing to the determination of chronic diabetic complications. The strict relations between the known pathogenetic factors involved in the development of these complications (non enzymatic protein glycation, activation of polyol pathway, lipidic changes, haematostatic abnormalities) and oxidative stress are examined in the light of the most recent research studies. The latest therapeutical approaches aiming at an increase in antioxidant defenses, and a reduction of oxidant are reported.

Alcohols↗

Use of premixed insulin among the elderly. Reduction of errors in patient preparation of mixtures.

OBJECTIVE: To evaluate the accuracy of elderly patients in their mixing of regular and intermediate insulins, to assess the safety and efficacy of premixed insulins compared with extemporarily mixed insulins, and to determine patients' preferences. RESEARCH DESIGN AND METHODS: We conducted a crossover multicenter study of 5 mo duration. Premixed insulins and patient-mixed, human biosynthetic (rDNA) insulins were used among 64 insulin-treated patients with NIDDM. After a 4-wk run-in period, eligible patients were randomly assigned to treatment 1 (extemporarily mixed insulins) or treatment 2 (premixed insulins) for 8 wk. After that period, the two treatments were crossed for an additional 8-wk period. A blood glucose profile was recorded monthly and HbA1c was measured at the beginning and at the end of each treatment period. An in vitro skills test was performed to assess the accuracy and reproducibility of the patient preparation of insulin doses, and a questionnaire was used to determine their personal preferences for premixed versus extemporarily mixed insulin. RESULTS: In our study, the quality of the metabolic control was the same whether patients used self-mixed or premixed insulin. The differences in blood glucose profiles and HbA1c were negligible between type and periods of treatment. The overall number of hypoglycemic episodes increased during the trial in both groups, but the difference between treatments was not significant. The in vitro skills test, however, indicated that the accuracy in the preparation of insulin doses was significantly higher when patients aspirated from one vial compared with preparation from two vials (P < 0.001). The CVs were 3.7% when drawing up a single dose and 5.0% when preparing a mixture, but the ranges were rather elevated (0.1-20.7 and 0.6-35.8%, respectively). Forty-two patients described the preparation of their daily insulin dose as very easy and 21 described it as easy when using premixed insulins versus 11 and 43, respectively, when using extemporarily mixed insulins (P < 0.001). CONCLUSIONS: While the quality of the metabolic control was the same whether patients used self-mixed or premixed insulin, the in vitro skills test indicated that insulin preparation by elderly patients is highly inaccurate. In some patients, a modification of the contents of the insulin is likely to occur in a few days. The use of premixed insulins should lessen the errors that occur in mixing insulins and from the contamination of the second insulin vial. Draw-up errors could partially account for the lack of improvement of glucose control during the period when patients received premixed insulins. A longer observation period probably is needed to assess appreciable changes in the quality of diabetes control.

Aged↗

Mass spectrometry in the study of advanced glycation processes, responsible for long-term diabetes complications.

Mass spectrometry has been usefully employed in the study of the products arising from in vitro and in vivo glycation of proteins. In particular, daughter-ion spectroscopy has led to an easy detection of 2-(2-furoyl)4-(5)2(furanyl)1-H-imidazole in HCl-hydrolysed glycated albumen and polylysine and the method has allowed us to exclude the presence of the same molecule in in vivo glycated proteins. Parent-ion spectroscopy has been successfully employed in the identification of furoyl-containing compounds, which are possibly responsible for the results obtained with other analytical approaches.

Albumins↗

Investigation of products arising from enzymatic digestion of advanced glycated albumin by high-performance liquid chromatography/mass spectrometry.

The structural investigation of the products arising from 28 days incubation of albumin with high glucose concentration and further enzymatic hydrolysis has been carried out by means of high-performance liquid chromatography/mass spectrometry (HPLC/MS) under plasmaspray conditions. By this approach many different compounds have been detected, and for most of them, possible structures have been proposed on the basis of literature data and molecular weight assignments.

Animals↗

The epidemiology and prevalence of diabetic retinopathy in the Veneto region of north east Italy. Veneto Group for Diabetic Retinopathy.

The prevalence of diabetic retinopathy and its relationship to a number of risk factors were examined in a population-based study in the Veneto region of North East Italy. Of 1321 diabetic patients selected, 98% attended for examination. Prevalence of diabetic retinopathy was 26.2% (24.4% background and 1.8% proliferative). The prevalence of retinopathy was significantly related (p less than 0.01) to the duration of diabetes (17.3% for less than 5 years; 60.8% for greater than 20 years). Proliferative retinopathy was much more prevalent after 20 years of diabetes. After 10 years most proliferative retinopathy was found in Type 1 diabetic patients, but before 10 years from diagnosis it was most prevalent in Type 2 diabetes. The prevalence of retinopathy was significantly related (p less than 0.001) to the type of diabetes and was found predominantly in Type 1 (46.2%) and insulin-treated Type 2 (45.9%) subjects and to a lesser degree in non-insulin-treated patients (24.6%). The prevalence of retinopathy was significantly related to both fasting and post-prandial blood glucose levels (p less than 0.001), blood urea nitrogen (p less than 0.05), and systolic (p less than 0.001) and diastolic (p less than 0.01) blood pressure. No significant differences were found in the prevalence of total or proliferative retinopathy between males and females. No significant relationships were found with family history of diabetes, alcohol intake, smoking habits, cholesterol, triglycerides, and serum uric acid.

Blood Glucose↗

Identification of furoyl-containing advanced glycation products in collagen samples from diabetic and healthy rats.

The compounds resulting from the reaction of glucose with proteins (advanced glycation products) can be important markers of chronic diabetic complications. To test the possible diagnostic value of advanced glycation products containing the furoyl moiety, collagen samples from diabetic and healthy rats were analyzed by parent ion spectroscopy. In our study, we compared normal collagen, diabetic collagen and normal collagen incubated with different glucose concentrations and we employed different hydrolysis procedures (HCl and proteinase). Mass spectroscopic measurements performed on hydrolyzed samples showed that either different samples or different hydrolysis procedures produce a similar set of furoyl-containing compounds. 2-(2-Furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI) which has been reported to be one of the advanced glycation products, was never found in any of the samples examined. Hence neither FFI nor furoyl-containing molecules can be considered markers of advanced glycation processes.

Animals↗

Cough test to assess cardiovascular autonomic reflexes in diabetes.

Coughing induces cardioacceleratory responses under cholinergic control. The Cough Test (CT), a standardized test that uses a series of coughs with electrocardiographic monitoring, was used to assess the functional integrity of cardiovascular autonomic nerves. In 224 control subjects and 235 diabetic patients, heart-rate (HR) responses were compared with four established tests: lying to standing (LS), standing to lying (SL), deep breathing (DB), and Valsalva maneuver (VM). In control subjects, HR responses declined significantly with age in a curvilinear pattern. Log-transformed indices were used to estimate percentiles. The CT-HR responses were reproducible and significantly associated with other HR-response tests. Sixty-nine (29%) diabetic patients had an abnormal value less than or equal to 1st percentile, whereas only 2 control subjects had such an abnormality. Among diabetic patients, age and duration of diabetes exerted a significant negative influence. With the use of the criteria of two abnormal or one abnormal and two borderline tests (among CT, LS, SL, DB, or VM) as a minimal criteria for cardiovascular autonomic neuropathy, CT and LS had the least overlap between the control and diabetic populations and were significantly better than SL or VM (P less than 0.005 for CT, P less than 0.01 for LS). They were not different from DB. We found the CT to be simple to perform, reproducible, and useful for the assessment of cardiovascular autonomic reflexes.

Adult↗

Absence of brown product FFI in nondiabetic and diabetic rat collagen.

Accumulation of brown products in long-lived proteins might be an important factor in determining long-term diabetic complications. Fluorescent chromophore 2-(2-furoyl)-4-(5)-(2-furanyl)-1H-imidazole (FFI), isolated from hydrolyzed brown products synthesized in vitro, was proposed as a specific brown product responsible for functional and structural changes in long-lived proteins. In this study, an attempt was made to demonstrate by means of collision spectroscopy the presence of FFI in collagen samples taken from diabetic rats. Diabetic rat collagen samples showed mean values of absorbance per milligram of 4-hydroxy-L-proline significantly higher than those observed in nondiabetic rats, suggesting higher FFI levels. Surprisingly, all collagen samples from diabetic and nondiabetic rats gave collision spectra in which no peak diagnostic of FFI presence was observed. These data suggest that the absorbance level observed in diabetic rats is not due to the presence of FFI but to structurally related compounds, which are being investigated by means of mass spectrometry.

Animals↗

Fructosamine assay: an index of medium-term metabolic control parameters in diabetic disease.

The fructosamine levels and some metabolic control parameters were evaluated in 120 diabetics and in 60 controls. Higher levels of fructosamine were found in diabetics compared to normals (3.22 +/- 0.06 vs. 1.82 +/- 0.05 mmol/l; P less than 0.001). Positive correlations were found between fructosamine and metabolic control parameters in diabetic subjects. Moreover, non-insulin-dependent diabetic subjects had better correlations. The study of fructosamine variation in relation to plasma glucose change showed that fructosamine levels were modified after at least 2 weeks of good metabolic control. In conclusion, the fructosamine assay could be a useful method for medium-term metabolic control evaluation.

Adolescent↗

Collisional spectroscopy as a screening procedure for the determination of 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole from acid hydrolysis of B-poly(L-lysine) and B-albumin.

The direct determination of 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), present in the acid hydrolysis products of B-poly(L-lysine) and B-albumin and which appears to be a key intermediate in the physicochemical changes occurring during the incubation of protein with glucose, has been carried out by collisional spectroscopy, using a commercial double-focusing, reverse-geometry mass spectrometer and without any sample derivatization and chromatographic separation procedures.

Albumins↗

Prolonged QT period in diabetic autonomic neuropathy: a possible role in sudden cardiac death?

Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval. The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy.

Adult↗

Reduced in vivo biological activity of in vitro glycosylated insulin.

We evaluated the in vivo biological activity of in vitro extensively glycosylated insulin (GI) with the euglycemic-hyperinsulinemic glucose-clamp technique in postabsorptive nondiabetic subjects. Insulin-mediated glucose disposal was approximately 30% lower (P less than .03) with GI (9.2 +/- 1.2 mg.kg-1.min-1, mean +/- SE) than with the nonglycosylated hormone (12.6 +/- 0.7 mg.kg-1.min-1) at comparable plasma insulin concentrations (approximately 90 microU/ml). Binding of GI to a specific receptor on circulating cells (erythrocytes and monocytes) was normal. We conclude that in vitro extensive glycosylation of insulin reduces its biological activity in vivo, as reflected by insulin-mediated glucose disposal, probably at a postreceptor level.

Adult↗

Autonomic mechanisms in the heart rate response to coughing.

To differentiate between the possible reflex and mechanical components in the heart rate response to cough, eight healthy subjects performed a standardized cough test before and after pharmacological autonomic blockade; to test the clinical usefulness of the cough manoeuvre two groups of diabetic patients (without and with autonomic neuropathy) were compared with a group of age-matched normal subjects. Because of the use of abdominal and expiratory muscles during cough, the cardioacceleratory response was compared with that induced by an intense contraction of the arm muscles (handgrip). The cardioacceleratory response was completely abolished by atropine while propranolol failed to affect it. The diabetic patients with autonomic neuropathy showed a response similar to that after cholinergic blockade. The response was similar to that induced by muscular contraction for 4 s, after which it differed showing a continued cardioacceleration. The patterns of recovery were not different. The cough-induced cardioacceleration is essentially reflex in nature and under cholinergic control; initially the mechanism may be partially related to the intense contraction of abdominal and expiratory muscles; later, the arterial hypotension related to the cough may contribute to the more sustained shortening of the R-R interval. The cough test may be useful for the evaluation of cardiac parasympathetic integrity.

Adult↗

Improvement of cardiovascular autonomic reflexes after amelioration of metabolic control in insulin-dependent diabetic subjects with severe autonomic neuropathy.

To evaluate the influence of good metabolic equilibrium on Diabetic Autonomic Neuropathy (DAN), cardiovascular autonomic reflexes were monitored in 9 male insulin-dependent diabetic patients with DAN, treated with Continuous Subcutaneous Insulin Infusion (CSII) by pump: 9 for 10 days, 4 for 1 year and 2 for 20 months. Autonomic neuropathy was assessed evaluating 5 cardiovascular autonomic tests: Valsalva Manoeuvre (VR), Deep Breathing (DB), Lying-to-Standing (L-S), Sustained Handgrip (SHG), and Postural Hypotension (PH). Metabolic control was assessed evaluating the mean daily plasma glucose, glucosuria and glycosylated hemoglobin. Ten days of CSII treatment induced a normalization of glucose balance and a slight but significant improvement in some parasympathetic cardiovascular tests (VR: from 1.09 +/- 0.01 to 1.13 +/- 0.02; P less than 0.05). After 4-8 months of CSII treatment a significant improvement in VR (P less than 0.05); DB (P less than 0.01) and L-S (P less than 0.05) was recorded. The long-term treatment with CSII did not seem to induce a further amelioration in cardiovascular autonomic reflexes. These results show that the slight improvement induced by good metabolic balance in the cardiovascular autonomic response could be related to functional-metabolic rather than structural changes in the nerves.

Adult↗

Sensory, motor, and autonomic neuropathy in patients with multiple symmetric lipomatosis.

Clinical evaluation of 33 male patients affected by multiple symmetric lipomatosis has revealed a previously unreported high prevalence of somatic and autonomic neuropathies. In 84% of the patients, clinical examination revealed signs or symptoms of neural disturbances, ranging from a vibratory sensory loss to severely incapacitating trophic ulcers or Charcot's arthropathy. Electrodiagnostic investigations demonstrated a significant reduction of motor and sensory conduction velocity in the peroneal and sural nerves. Morphometric studies of nerve and muscle biopsies from five patients with multiple symmetric lipomatosis revealed a significant reduction in myelinated fiber density (4435 +/- 593 fibers/mm2 in MSL vs 7660 +/- 800 in controls; p less than 0.05), a selective reduction in the large fibers of 7 to 10 micron in diameter, and signs of chronic denervation-reinnervation processes. Bedside tests for autonomic neuropathy were abnormal in 15 of 20 patients studied. Metabolic studies in these patients confirmed a significant increase in plasma high-density lipoprotein fractions consistent with the diagnosis of hyperalphalipoproteinemia, and a significant reduction in plasma low-density lipoprotein fractions (hypobetalipoproteinemia) associated with a marked enhancement of lipoprotein lipase activity in adipose tissue. Thus, a metabolic factor has to be considered in the pathogenesis of MSL neuropathy.

Adult↗

Evidence of early impairment of parasympathetic reflexes in insulin dependent diabetics without autonomic symptoms.

Cardiovascular (CV) autonomic functions were assessed in 50 insulin-dependent diabetic patients and in 30 controls using a battery of autonomic tests: Valsalva Manoeuvre (VR), Deep Breathing (DB), Lying-to-Standing (LS), Sustained Handgrip (SHG) and Postural Hypotension (PH). The results were compared with those obtained from a study of cardiac resting adjustment to different static postures (quiet lying and standing). 10 diabetics with abnormal responses to the majority of tests were considered affected by Diabetic Autonomic Neuropathy (DAN); 15 with some abnormal of borderline responses were defined much less than Borderlines much greater than. The remaining 25 diabetics, while displaying lower values than the controls in parasympathetic tests, had much less than normal much greater than autonomic responses. The VR mean (+/- SD) value was 1.71 +/- 31 in much less than normal much greater than diabetics and 2.01 +/- 0.29 in controls (p less than 0.001); the DB mean value was 20.6 +/- 87 and 28 +/- 8.13 (p less than 0.001), and the LS mean value 1.16 +/- 0.12 and 1.33 +/- 0.18 (p less than 0.001) respectively. No significant differences were found in the sympathetic tests (SHG, PH). However Heart Rate (HR) adjustment of diabetics with normal CV responses to immobile standing (RR mean 783 +/- 136 ms) and lying (RR mean increment of 25 +/- 11%; p less than 0.001) was similar to that of controls who had a resting HR standing (RR mean 749 +/- 104 ms) and lying (RR mean 884 +/- 116 ms) with a mean increment of 20.2 +/- 10.9% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗