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Biomedical subjects

M Borra

Publications and source records attributed to M Borra.

14 recordsLinked to original sources

Variability among polysulphone calibration curves.

Within an epidemiological study regarding the correlation between skin pathologies and personal ultraviolet (UV) exposure due to solar radiation, 14 field campaigns using polysulphone (PS) dosemeters were carried out at three different Italian sites (urban, semi-rural and rural) in every season of the year. A polysulphone calibration curve for each field experiment was obtained by measuring the ambient UV dose under almost clear sky conditions and the corresponding change in the PS film absorbance, prior and post exposure. Ambient UV doses were measured by well-calibrated broad-band radiometers and by electronic dosemeters. The dose-response relation was represented by the typical best fit to a third-degree polynomial and it was parameterized by a coefficient multiplying a cubic polynomial function. It was observed that the fit curves differed from each other in the coefficient only. It was assessed that the multiplying coefficient was affected by the solar UV spectrum at the Earth's surface whilst the polynomial factor depended on the photoinduced reaction of the polysulphone film. The mismatch between the polysulphone spectral curve and the CIE erythemal action spectrum was responsible for the variability among polysulphone calibration curves. The variability of the coefficient was related to the total ozone amount and the solar zenith angle. A mathematical explanation of such a parameterization was also discussed.

Biocompatible Materials↗

Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population-based cohort.

OBJECTIVE: To evaluate the prevalence of prolonged QT interval and dispersion in a population-based cohort of type 2 diabetic patients and their relationship with clinical and metabolic variables. DESIGN: Cross-sectional population-based cohort. SETTING: Diabetes clinics and general practitioners in Casale Monferrato (Northern Italy). SUBJECTS: A total of 1357 patients with known type 2 diabetes (70% of the cohort). MAIN OUTCOMES MEASURES: Albumin excretion rate and coronary heart disease (CHD); a standard supine 12-lead electrocardiogram (ECG) was recorded and coded according to the Minnesota code criteria. QT interval corrected for heart rate (QTc) > 0.44 s and QTc dispersion > 0.080 s were considered abnormally prolonged. RESULTS: Prevalence of increased QTc duration and QTc dispersion were 25.8% (95% CI 23.5-28.3) and 33.1% (95% CI 30.6-35.7), with no sex differences. No metabolic differences were found, apart from fibrinogen and creatinine levels, which were higher in patients with increased QTc dispersion. Patients with CHD had higher mean adjusted values of QTc and QTc dispersion, whereas no association was found with albumin excretion rate (AER) and diabetes treatment. QTc duration and QTc dispersion were significantly correlated (0.17, P < 0.001). In multiple regression analysis, only CHD was independently associated with QTc, after adjustment for age and sex (beta=0.010, P < 0.001, R2=2.5%); as regards QTc dispersion, a similar association with CHD was found (beta=0.20, P < 0.001, R2=4.8%). CONCLUSIONS: This population-based study shows a considerably high prevalence of increased QTc and QTc dispersion in type 2 diabetic patients and their association with CHD. These findings have both epidemiological and clinical relevance, as they might be implicated in the excess mortality risk of type 2 diabetic patients.

Aged↗

Advanced technology for extracorporeal liver support system devices.

Acute Liver Failure (ALF) still presents high mortality rates, and liver transplant is the only treatment with proven efficacy. However transplant is not always possible and systems for Extracorporeal Liver Support (ELS) are being developed which can treat patients with ALF, for whom a transplant is not available, or is delayed. They can also treat patients with chronic liver disease who develop ALF. There are two types of ELS: artificial systems (hemoperfusion, plasmaperfusion, therapeutic plasma exchange, continuous hemodialysis and high volume continuous hemofiltration) and bioartificial systems. These are based on a biological component (animal or human hepatocytes) inserted into a bioreactor, whose main function is to perform the metabolic activity and synthesis that the liver can no longer perform. The results obtained in clinical trials have so far shown that the best results in terms of compensating for lost metabolic function and detoxification are obtained inserting artificial components in the bioartificial circuit.

Extracorporeal Circulation↗

Dynamics of tearing modes during strong electron cyclotron heating on the FTU tokamak.

The localized electron cyclotron resonance heating power that can suppress sawteeth reconnection often drives m = 2 tearing modes in a tokamak operating at constant current. The dynamics of mode onset and coupled mode evolution is described in detail and compared with a nonlinear theoretical model that identifies the effects of mode coupling, finite inertia of the rotating islands, and wall braking.

Journal Article↗

Characterization of ADP-glucose pyrophosphorylase from Rhodobacter sphaeroides 2.4.1: evidence for the involvement of arginine in allosteric regulation.

ADP-glucose pyrophosphorylase (ADPGlc PPase, EC 2.7.7.27) from Rhodobacter sphaeroides 2.4.1 has been purified to near homogeneity. The enzyme reacted in Western blots to polyclonal antibodies raised against other bacterial ADPGlc PPases. The purified enzyme was found to be activated by fructose 6-phosphate, fructose 1,6-bisphosphate, and pyruvate and inhibited by phosphate, phosphoenolpyruvate, ADP, and pyridoxal phosphate. Kinetic studies indicate that AMP, while having little effect on kinetic parameters at pH 8 in the absence of effectors, is a specific ligand for an allosteric site(s). Treatment of the purified enzyme with the arginyl reagents 2,3-butanedione and phenylglyoxal resulted in desensitization of the enzyme to both activation and inhibition by metabolites. Phosphate, fructose 6-phosphate, and AMP were found to protect the enzyme against allosteric desensitization supportive of these metabolites interacting at common site(s) or with a common enzyme form. As a first step in cloning the gene coding for this enzyme, a polymerase chain reaction fragment was generated from genomic DNA using primers based on amino terminal sequencing data and a highly conserved region in known ADPGlc PPases. The sequence of this fragment and position of amino terminal arginines in comparison to other known ADPGlc PPases is discussed in relation to the kinetic and chemical modification data.

Allosteric Regulation↗

The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group.

The prevalence of QT interval prolongation is higher in people with diabetes and its complications. Sudden death has been reported as a common cause of death in insulin-dependent diabetic patients affected by autonomic neuropathy. It has been postulated that QT prolongation predisposes to cardiac arrhythmias and sudden death. In this analysis the prevalence of QT interval prolongation and its relation with diabetic complications were evaluated in the EURODIAB IDDM Complications Study (3250 insulin-dependent diabetic patients attending 31 centres in 16 European countries). Five consecutive RR and QT intervals were measured with a ruler on the V5 lead of the resting ECG tracing and the QT interval corrected for the previous cardiac cycle length was calculated according to the Bazett's formula. The prevalence of an abnormally prolonged corrected QT was 16% in the whole population, 11% in males and 21 % in females (p < 0.001). The mean corrected QT was 0.412 s in males and 0.422 s in females (p < 0.001). Corrected QT duration was independently associated with age, HbA1c and blood pressure. Corrected QT was also correlated with ischaemic heart disease and nephropathy but this relation appeared to be stronger in males than in females. Male patients with neuropathy or impaired heart rate variability or both showed a higher mean adjusted corrected QT compared with male patients without this complication. The relation between corrected QT prolongation and autonomic neuropathy was not observed among females. In conclusion we have shown that corrected QT in insulin-dependent diabetic female patients is longer than in male patients, even in the absence of diabetic complications known to increase the risk of corrected QT prolongation.

Adult↗

Cardiovascular risk profile of type 2 diabetic patients cared for by general practitioners or at a diabetes clinic: a population-based study.

The aims of this study were to compare the cardiovascular risk profiles of patients with type 2 diabetes mellitus cared for by general practitioners and those regularly attending a diabetes center. Out of an Italian population-based cohort of 1967 diabetic patients, 1574 (80%) were investigated. Patients exclusively cared for by general practitioners (23.8%) were older and showed lower prevalence of hypertension (79.0% vs 85.9%, P < 0.001), poor blood glucose control (HbA1c >8.0, 33.4% vs 47.9%, P < 0.001) and coronary heart disease (18.1% vs 22.3%, P = 0.003), and lower plasma fibrinogen (3.5 +/- 0.8 vs 3.7 +/- 0.9 g/L, P < 0.001). In logistic regression analysis, they had significantly lower ORs for HbA1c >8.8% (OR 0.67, 95% CI 0.45-0.99), hypertension (OR 0.53, 95% CI 0.36-0.78), fibrinogen >4.1 g/L (OR 0.50, 95% CI 0.32-0.77), smoking (OR 0.60, 95% Cl 0.36-1.00), and coronary heart disease (OR 0.65, 95% CI 0.45-0.93), after adjustment for age, sex, duration of diabetes, BMI, and antidiabetic treatment. Patients regularly cared for at a diabetes clinic had a higher cardiovascular risk profile, suggesting selective referral to the clinics of patients with more difficult management and/or severity of the disease. These findings have implications in the interpretation of morbidity and mortality clinic-based studies.

Aged↗

Clinical, immunological, and genetic heterogeneity of diabetes in an Italian population-based cohort of lean newly diagnosed patients aged 30-54 years. Piedmont Study Group for Diabetes Epidemiology.

OBJECTIVE: In lean diabetic patients, the presentation of the disease does not allow one to easily distinguish between type 1 and type 2. Aims of this study were to describe clinical, immunological, and genetic features of lean newly diagnosed diabetic patients. RESEARCH DESIGN AND METHODS: A population-based cohort of 130 lean (BMI < 25 kg/m2) newly diagnosed patients, aged 30-54 years, was identified among residents of the province of Turin. Islet cell antibodies (ICAs), anti-GAD, fasting and glucagon-stimulated C-peptide values, and HLA DQA1-DQB1 susceptibility genotypes were assessed within 2 months of the diagnosis. RESULTS: A total of 45 (34.6%) and 29 (22.3%) patients were, respectively, ICA+ and anti-GAD+, with 15 (11.5%) having both antibodies. In 59 patients, ICAs and/or anti-GAD antibodies were detected, giving a high prevalence of autoimmunity (45.4%, 95% Cl 36.8-54.0); relative to patients without markers (n = 71), they were younger (40.8 +/- 7.5 vs. 45.0 +/- 6.5 years, P < 0.001) and showed lower values of fasting C-peptide (0.56 +/- 0.33 vs. 0.79 +/- 0.41 nmol/l, P < 0.001) and stimulated C-peptide (1.03 +/- 0.56 vs. 1.42 +/- 0.69 nmol/l, P < 0.001). The lowest stimulated C-peptide values were found in patients with both ICA and anti-GAD antibodies. Frequencies of adult-onset type 1 and type 2 diabetes were, respectively, 49.2 and 50.8%. Clinical and genetic features were not useful in the classification of patients. CONCLUSIONS: Almost 50% of lean young and middle-aged patients were ICA+ and/or anti-GAD+, suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.

Adult↗

Glycaemic control and cardiovascular risk factors in type 2 diabetes: a population-based study.

The objective of this study was to estimate the prevalence of poor glycaemic control and cardiovascular risk factors in an Italian population-based cohort of subjects with Type 2 diabetes mellitus (DM). Out of a cohort of 1967 subjects (estimated completeness of ascertainment 80%), 1574 (80%) were investigated, and adherence to targets for control of the European NIDDM Policy Group assessed. Prevalence of poor glycemic control (HbA1c > = 8) was 47.7%. Obesity was present in 23.4% of the cohort, hypertension in 83.4%, hypertriglyceridaemia (>2.26 mM) in 19.3%, hypercholesterolaemia (>6.46 mM) in 25.5%, and low HDL-cholesterol (<0.90 mM in men and <1.03 mM in women) in 13.7%. Only 153 (9.7%) subjects were free from other disorders. Subjects were treated as follows: 26.2% exclusively by general practitioners; 13.3%, 69.9%, 10.9%, and 5.9% with diet, oral hypoglycaemic drugs, insulin, and both, respectively. Multiple linear regression analysis showed associations between HbA1c and fibrinogen (p < 0.001), total cholesterol (p = 0.006), and triglycerides (p = 0.04), independent of age, sex, duration of diabetes, and antidiabetic treatment. Neither BMI nor blood pressure were associated with HbA1c. In conclusion, this Italian population-based cohort of subjects with Type 2 DM showed a high prevalence of poor glycaemic control, high consumption of oral hypoglycaemic drugs, and an independent association between glycaemic control and cardiovascular risk factors (fibrinogen, total cholesterol, and triglycerides). The presence of obesity or hypertension was not significantly associated with glycaemic control.

Blood Glucose↗

Association of fibrinogen with glycemic control and albumin excretion rate in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: The high prevalence of classic cardiac risk factors in patients with non-insulin-dependent diabetes mellitus does not explain the increased cardiovascular-related morbidity and mortality in these patients. Fibrinogen may have a role in this excess risk. OBJECTIVE: To evaluate the following in patients with non-insulin-dependent diabetes mellitus: 1) the distribution of plasma fibrinogen levels and the prevalence of hyperfibrinogenemia and 2) the association of fibrinogen level with hemoglobin A1c value and albumin excretion rate. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rural area in northern Italy. PATIENTS: 1574 patients with non-insulin-dependent diabetes mellitus who represented 81% of the initial cohort of 1967 patients. MEASUREMENTS: Albumin excretion rate was measured in urine samples obtained during an overnight collection. Venous blood samples were collected while patients fasted. RESULTS: Fibrinogen levels were available for 1525 of the 1574 patients who were examined (669 men and 856 women). The mean age (+/- SD) was 67.3 +/- 10.3 years for men and 70.7 +/- 10.7 years for women. The mean plasma fibrinogen level (+/- SD) was 3.6 +/- 0.9 g/L; levels slightly differed between men and women. In 50.3% of patients, plasma fibrinogen level exceeded 3.5 g/L. In men, fibrinogen level increased with age (P < 0.001). In both men and women, fibrinogen level adjusted for age and sex was significantly and linearly related to hemoglobin A1c value (P < 0.001) and albumin excretion rate (P < 0.001). In a multiple regression analysis, hemoglobin A1c value (b = 0.06; P < 0.001) and albumin excretion rate (b = 0.09; P = 0.005) were associated with fibrinogen level independent of other cardiovascular risk factors (sex, age, hypertensive status, total cholesterol level, smoking habit, and body mass index). CONCLUSIONS: Patients with non-insulin-dependent diabetes mellitus had a high prevalence of hyperfibrinogenemia. Fibrinogen level was independently associated with hemoglobin A1c value and albumin excretion rate, which suggests that fibrinogen may be involved in the increased cardiovascular risk of patients with diabetes mellitus.

Adult↗

Prevalence and risk factors for micro- and macroalbuminuria in an Italian population-based cohort of NIDDM subjects.

OBJECTIVE: To determine the prevalence of micro- and macroalbuminuria in NIDDM and their relationship with some known and putative risk factors. RESEARCH DESIGN AND METHODS: Out of a population-based cohort of 1,967 NIDDM subjects, 1,574 were investigated (80%). Albumin excretion rate (AER) was evaluated on an overnight urine collection, and plasma and urine determinations were centralized. RESULTS: The prevalences of microalbuminuria (AER 20-200 micrograms/min), macroalbuminuria (AER > 200 micrograms/min), and hypertension were 32.1% (95% CI 29.8-34.4), 17.6% (15.7-19.5), and 67% (64.6-69.3), respectively. Apart from prevalence of hypertension, which after adjustment for age, BMI, and duration of diabetes was 2.3 times higher in women, rates were higher in men (odds ratio [OR] 1.31, 95% CI 1.04-1.66 for microalbuminuria and OR 1.63, 1.22-2.17 for macroalbuminuria). In comparison with normoalbuminuric subjects, both micro- and macroalbuminuric diabetic subjects had significantly longer duration of diabetes, higher levels of systolic blood pressure, fasting plasma glucose, HbA1c, triglycerides, and uric acid; in macroalbuminuric subjects only, levels of apolipoprotein B and HDL cholesterol were, respectively, higher and lower than in normo- and microalbuminuric subjects. In logistic regression, variables independently related to both micro- and macroalbuminuria were age, HbA1c, cigarette smoking habits, plasma uric acid, and diastolic blood pressure, after adjustment for plasma creatinine and diabetic treatment. In addition, duration of diabetes and HDL cholesterol levels were associated with macroalbuminuria. CONCLUSIONS: This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.

Aged↗

Does abnormal QT interval prolongation reflect autonomic dysfunction in diabetic patients? QTc interval measure versus standardized tests in diabetic autonomic neuropathy.

The question as to whether the QTc interval correlates with five cardiovascular tests (deep breathing test, 30/15 ratio test, lying to standing test, cough test, and postural blood pressure test) for the diagnosis of diabetic autonomic neuropathy (DAN) was investigated in 168 (38 Type 1, 130 Type 2) consecutive outpatients (mean age 54.9 +/- 11.2 years). QT interval was measured on an ECG recorded at rest and QTc calculated according to Bazett's formula. The percentage of patients with a QTc greater than 0.440 s was: absent DAN = 11% (n = 7), probable DAN = 7% (n = 4), definite DAN = 23% (n = 12) (p < 0.05), and the mean (+/- SD) QTc values were 0.403 +/- 0.028 s, 0.405 +/- 0.023 s, and 0.421 +/- 0.026 s, respectively. A significant correlation between QTc duration and DAN score of autonomic cardiovascular test results (r = 0.34, p < 0.0001) was observed. The calculated specificity, sensitivity, positive and negative predictive values were 89%, 15%, 70% and 37%, respectively. In conclusion, QTc can be considered as an additional specific test in the assessment of diabetic autonomic neuropathy, but cannot replace the standard battery of cardiovascular tests.

Analysis of Variance↗

Hyperfibrinogenemia and metabolic syndrome in type 2 diabetes: a population-based study.

BACKGROUND: It has been hypothesized that fibrinogen clusters with several components of the metabolic syndrome, thus increasing its cardiovascular risk. The aims of the present study were to assess in a large population-based cohort of patients with type 2 diabetes (1) variables associated with fibrinogen and (2) the relationship between hyperfibrinogenemia, a number of components of the metabolic syndrome, and coronary heart disease (CHD). METHODS: We identified a cross-sectional, population-based cohort of 1574 patients with type 2 diabetes using multiple sources of ascertainment. Components of the metabolic syndrome were hypertension (systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg and/or treatment with antihypertensive drugs), dyslipidemia (tryglicerides >2.82 mmol/l and/or HDL-cholesterol <1.03 mmol/l), hyperuricemia (uric acid >416 micromol/l) and increased albumin excretion rate (AER > or = 20 microg/min). RESULTS: Fibrinogen increases with age, HbA(1c), smoking, hypertension and a number of components of the metabolic syndrome, even after adjustment for confounders. Prevalence of CHD increases linearly across quartiles of fibrinogen (from 26.1 to 40.6%, p=0.046). However, in logistic regression, after adjustment for both confounders and known risk factors for CHD, the role of fibrinogen is no more significant, whereas ORs for HbA(1c) between 6.8 and 8.8% and >8.8% vs values <6.8% are, respectively, 1.91 (95% CI 1.36-2.69) and 1.56 (1.07-2.27). CONCLUSIONS: This population-based study shows that fibrinogen increases with age, HbA(1c), smoking, hypertension and a number of components of the metabolic syndrome, independent of major confounders. We also found that poor blood glucose control was associated with CHD.

Aged↗

[In vitro experimentation of a new model of radial flow bioreactor containing isolated hepatocytes].

Hepatocyte based artificial liver support systems are under investigation to support acute liver failure patients. The main purpose of such systems is to serve as a bridge to liver transplantation, or to promote spontaneous liver recovery. Limitation in mass-transfer capacity makes hollow-fiber bioreactors unsuited for long-term functioning of hybrid devices. We developed a novel radial-flow bioreactor in which the fluid perfuses the module from the center to the periphery, after having diffused through a space occupied by a three-dimensional structure filled with the hepatocytes. Five grams of freshly isolated porcine hepatocytes were seeded into uncoated, woven-non woven, hydrophilic polyester fabric, overlaid by two polyethersulfone membranes. Liver cells were perfused with 37 degrees C-warm, oxygenated, serum-free tissue culture medium, in which NH4Cl and Lidocaine were added at the final concentration of 1 mM and 60 micrograms/ml, respectively. Ammonium chloride removal, urea synthesis, monoethylglycinexylide (MEGX), pO2, pCO2, and pH were measured throughout the 14 day duration of the study. In a separate set of experiments, a scaled-up version of the radial flow bioreactor containing 150 grams of cells was perfused for 7 h with recirculating human plasma and MEGX production was monitored. During the 2 weeks of the study, an increasing production of urea was paralleled by constant ammonium removal. MEGX concentration after Lidocaine addition increased throughout the 14 days of perfusion with tissue culture medium, as well as after 7 hour perfusion with human plasma. Under transmission and scanning electron microscopy cells appeared attached to the polyester and one to each other, displaying ultrastructural features typical of functioning hepatocytes. Our study showed that liver cells were metabolically active when perfused into the radial-flow bioreactor. This configuration allowed close contact between media, or plasma, and cells at a physiological flow rate, by equalizing the concentration of the perfusing components, including O2, throughout the module. Our results suggest a potential use of this system for temporary extracorporeal liver support in acute hepatic failure patients.

Animals↗