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Biomedical subjects

F Franconi

Publications and source records attributed to F Franconi.

At least 73 records · Page 4Linked to original sources

Glutathione, glutathione utilizing enzymes and thioltransferase in platelets of insulin-dependent diabetic patients: relation with platelet aggregation and with microangiopatic complications.

Reduced glutathione (GSH) and activity of GSH related enzymes play a key role in defence against oxygen free radicals, whose production is, as known, raised in patients affected by diabetes mellitus, and at the same time they may contribute to the process of platelet aggregation. The purpose of this study was to evaluate GSH levels and activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-Red), glutathione transferase (GSH-Tr), glucose-6-phosphate-dehydrogenase (G6PDH), and thioltransferase (TT) in platelets of insulin-dependent diabetic patients in fair metabolic control (mean glycated haemoglobin: 6.5%), as related to presence of retinopathy, neuropathy or nephropathy and to platelet aggregation by arachidonic acid (AA) in vitro. Mean effective dose (ED50) of AA was on average significantly lower in the group of insulin-dependent diabetic patients (0.41 +/- 0.02 mM (SEM), n = 46) as compared with that of control subjects strictly matched for age, sex and weight (0.77 +/- 0.02, n = 51; P = 0.0001). Mean platelet GSH as well as the activity of GSH related enzymes expressed as geometric mean (95% confidence intervals) were similar in diabetic patients and in controls, except for GSSG-Red whose activity was significantly higher in diabetic subjects (28.5 (14.4-57.5) mU 10(-9) platelets vs. 20.3 (8.7-56) mU 10(-9) platelets; P = 0.01). In the diabetic group TT was reduced when compared with healthy controls (3.8 (0.9-12.2) mU 10(-9) platelets vs. 6 (1.6-26.1) mU 10(-9) platelets; P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

T1 mapping from spin echo and stimulated echoes.

We present an imaging method to obtain a map of the spin-lattice relaxation time. Images were acquired with the same spatial resolution and in the same time as for a regular spin-echo acquisition. The sequence was based on the simultaneous acquisition of a spin echo and several stimulated echoes with the same intensity except for T1 weighting which increases with the interval between the excitation pulse and the readout pulse. T1 values obtained on phantoms were compared to those from the inversion-recovery method and show the accuracy (2%) and the precision (5%) of the method. T1 images of the brain of a healthy volunteer are presented and demonstrate the ability of the method to obtain T1 mapping in vivo in 12 min and without susceptibility artifacts. In vivo and in vitro results were compared to those obtained by a TOMROP sequence in the same acquisition time.

Biophysical Phenomena↗

Cytotoxicity of lazaroid U-75412E in human epithelial cell line (Wish).

The 21-aminosteroids (or lazaroids) are a recently synthesized class of compounds demonstrated to protect tissue against damage induced by trauma and/or ischemia. Currently, very little is known about the biological effects of lazaroids. In this work the action of lazaroid U-75412E on a human epithelial cell line (Wish) was evaluated. The data obtained showed an inhibition of cell growth and a dose- and time-dependent decrease of cell viability. Furthermore, a dose- and time-dependent increase of cells in the G2/M phase with the appearance of apoptotic cells was observed by flow cytometric analysis. Nuclear fragmentation was also evident. Lactate dehydrogenase release and scanning electron microscopy experiments suggested that plasma membrane integrity was altered by this compound. The immunofluorescence technique and transmission electron microscopy images also showed intracellular damage, such as alteration of microtubular arrangement, mitochondrial swelling and the presence of vacuoles. This study demonstrated that 1 microM U-75412E was unable to modify these parameters, while higher concentrations (6-75 microM) had a cytotoxic effect on Wish cells.

Antioxidants↗

Acquisition of spin echo and stimulated echo by a single sequence: application to MRI of diffusion.

A new method is described to measure the restricted diffusion coefficient with magnetic resonance imaging. The two images necessary to calculate the diffusion image are obtained with a simultaneous acquisition of a spin-echo and a stimulated echo, and so, in half the time needed by usual spin-echo or stimulated echo method. A different diffusion contrast is created on each echo. A map of an estimate of the diffusion coefficient and an estimation of T1 value are obtained with only one experiment. The accuracy of the method has been evaluated on phantom and results are in agreement with values found in previous papers and with measurements performed with a usual spin-echo method. Furthermore, in vivo measurements have shown that this method can be used without electrocardiogram triggering.

Brain↗

Renal excretion of ascorbic acid in insulin dependent diabetes mellitus.

Serum ascorbic acid (AA) is reduced in diabetic patients. Aim of this study was 1) to verify whether such a decrease might be due to an altered urinary excretion of AA, and 2) whether this latter was modified in presence of early diabetic nephropathy with microalbuminuria (albumin excretion rate [AER] > 20 micrograms/min) in a group of 21 patients affected by insulin-dependent (type 1) diabetes mellitus (IDDM) as compared with 13 healthy controls matched for sex, age, dietary AA intake, and creatinine clearance per 1.73 m2 (CCl). Mean serum AA (+/- SD) was lower in diabetics (40.3 +/- 14 microM/l) than in controls (85.1 +/- 23.5 microM/l; p = 0.0001) and there was no difference between serum AA of patients with or without microalbuminuria. Urinary excretion of AA to creatinine x 100 (UAA/Cr) was higher in micro- (n = 6; 4.6 +/- 1.7) as compared to normoalbuminurics (n = 15; 1.6 +/- 0.9) or controls (1.5 +/- 1.2; p = 0.0001). For values exceeding renal threshold of tubular AA reabsorption (39 microM) the regression line of serum AA to UAA/Cr was significantly (p = 0.001) steeper in diabetics than in controls, suggesting an impaired tubular reabsorption of filtered AA in IDDM. The ratio of AA clearance to CCl was moreover related to AER (r = 0.48; p = 0.03) and to blood glucose (r = 0.51; p = 0.01), being unrelated to uric acid clearance, glycosuria and to urinary excretion of both alanine aminopeptidase and N-acetyl-beta-glucosaminidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Radiofrequency map of an NMR coil by imaging.

We propose a new imaging method to obtain a map of the radiofrequency (RF) field amplitude over a sample. The sequence contains three RF pulses (alpha, 2 alpha, and alpha) and produces two images by a classical spin echo and a stimulated echo. A third image is computed and gives the distribution of the flip angle alpha, and so the RF amplitude, over the sample. The accuracy of the flip angle determination is verified on an homogeneous sample and results show a good correlation between experimental and theoretical flip angles in the range of 50 degrees to 130 degrees. Experiments with a surface coil and a resonator show the method is available in an inhomogeneous RF field. Images obtained on the calf of a volunteer confirms the independence of the computed RF distribution from proton density, T1, or T2 contrast.

Humans↗

Enhancement of the antitrichomonal activity of 5-nitroimidazole derivatives by hydrogen peroxide.

The in vitro sensitivity of nine Trichomonas vaginalis isolates to commonly employed 5-nitroimidazoles (metronidazole, nimorazole, ornidazole and tinidazole) was evaluated in absence and in presence of sub-inhibitory concentrations of hydrogen peroxide (H2O2). Co-incubation with H2O2 and 5-nitroimidazole compounds decreased the MIC values of the strains exhibiting cross-resistance to these drugs. It was suggested that H2O2 produced in the inflammatory process during trichomonal infection could enhance the therapeutic effect of 5-nitroimidazole drugs.

Animals↗

Release of cytochromes from hypoxic and reoxygenated guinea pig heart.

Isolated, perfused hearts from guinea pigs were subjected to hypoxia for 30 minutes followed by reoxygenation for 30 minutes. Cellular damage was assessed by measuring the release of the cytoplasmic enzyme lactate dehydrogenase and the mitochondrial markers cytochrome c and cytochrome oxidase. The release of the enzymes was correlated with electron microscopy. Hypoxia induced an increase in the release of lactate dehydrogenase and cytochrome c. During reoxygenation, the release of lactate dehydrogenase was exacerbated while that of cytochrome c decreased, suggesting a partial recovery of the mitochondria. Cytochrome oxidase was not detectable in the extracellular space during hypoxia or reoxygenation. It is suggested that cytochrome c is a specific marker for damage to mitochondria caused by hypoxia and its loss may affect respiratory chain function.

Animals↗

Plasma retinol and alpha-tocopherol concentrations in insulin-dependent diabetes mellitus: their relationship to microvascular complications.

Plasma alpha-tocopherol and retinol, both assayed by an HPLC method, have been evaluated in a group of 60 patients affected by insulin-dependent (type 1) diabetes mellitus, stratified according to the presence of retinopathy and nephropathy diagnosed by an urinary albumin excretion rate ranging between 20 and 200 micrograms/min (microalbuminaria) or > 200 micrograms/min (macroalbuminuria), all of whom were compared with 26 healthy controls strictly matched for age and sex. Plasma lipids and age were positively correlated with plasma retinol and alpha-tocopherol in both diabetic and control subjects. Either plasma retinol or its ratio to cholesterol were significantly and independently reduced in the younger subset of diabetics, as compared to controls, independently from other confounding variables, while plasma alpha-tocopherol was unchanged in diabetic subjects and in healthy controls. Retinopathy was not associated with altered levels of both plasma alpha-tocopherol or retinol. The presence of increased urinary albumin excretion was associated with higher plasma levels of alpha-tocopherol and, only for macroalbuminuria, of retinol. However, after processing the data by a multivariate model, nephropathy was characterized by an increase only in plasma alpha-tocopherol. In conclusion, according to our findings, plasma retinol is significantly decreased in younger insulin-dependent diabetic patients while alpha-tocopherol is significantly altered in diabetic patients with nephropathy.

Adolescent↗

Taurine antagonizes the increase in intracellular calcium concentration induced by alpha-adrenergic stimulation in freshly isolated guinea-pig cardiomyocytes.

The effect of taurine on phenylephrine alpha-adrenergic action was studied in freshly-isolated guinea-pig ventricular myocytes. Intracellular calcium concentration was measured at nearly physiological extracellular CaCl2 in both cell suspension using quin-2 (mean intracellular calcium concentration 154.0 +/- 8.0 nM, n = 24), and single myocyte with fura-2 (mean intracellular calcium concentration 159.0 +/- 20.0 nM, n = 23). Phenylephrine increased intracellular calcium concentration in both preparations. In cell suspensions in the presence of 10(-6) M propranolol and at 2.2 mM extracellular calcium concentration, phenylephrine dose-dependently (3 x 10(-7)-10(-5) M) increased intracellular calcium concentration, its effect being abolished in the presence of phentolamine. Taurine 20 mM in the incubation fluid increased taurine content in the cells from 110 +/- 7 nmol/mg to 317 +/- 49 nmol/mg of total proteins. In the range 0.5-20 mM, taurine concentration-dependently reduced the phenylephrine-induced intracellular calcium increase in cell suspensions and 20 mM taurine decreased the effect of 10(-5) M phenylephrine (measured in the presence of 10(-6) M propranolol) by about 80%. Beta-Alanine (20 mM) did not modify the phenylephrine effect. Our data show that the "protective" effect of taurine in in vitro cardiac preparations and in cardiomyocyte isolation procedures is due to its effect on cardiomyocyte intracellular calcium ion concentration, and that taurine specifically antagonizes alpha-adrenoceptor activation.

Animals↗

Do ethoxy radicals reduce 3H-nitrendipine binding in rat cardiac membranes?

The incubation of xanthine-oxidase (XOD) with rat cardiac membranes induced the formation of free radicals; they were identified by electron spin resonance spectroscopy (ESR) studies using 0.1 M 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) for spin-trapping. The following DMPO adducts were measured: DMPO-OH, which was produced during the first minute of incubation, DMPO-R radicals, which were present after 4 min of incubation and where the signal intensity remained constant for at least 20 min. The binding studies performed after 15 min incubation showed that XOD (1-50 mU) dose dependently reduced 3H-nitrendipine binding. This reduction was caused by a decrease in the density of binding sites while the affinity remained unchanged. These results suggest that ethoxy radical formation may be an important step in the regulation of L type calcium channels.

Animals↗

Erythrocyte spermidine levels in IDDM patients.

OBJECTIVES: To evaluate whether erythrocyte levels of polyamines spermidine and spermine (expressed in nmol/ml packed erythrocytes [PRBCs]) are modified in insulin-dependent diabetes mellitus (IDDM) and are associated with the presence of retinopathy or nephropathy. RESEARCH DESIGN AND METHODS: We studied erythrocyte spermidine and spermine levels in 38 IDDM patients with or without persistent microalbuminuria (urinary albumin excretion rate [AER] between 20 and 200 micrograms/min), macroalbuminuria (AER greater than 200 micrograms/min), or retinopathy compared with 60 sex- and age-matched control subjects. RESULTS: Mean +/- SD erythrocyte spermine content was similar in both diabetic (9.7 +/- 5.5 nmol/ml PRBCs) and control (8.8 +/- 3.5 nmol/ml PRBCs) subjects, whereas spermidine was higher in diabetic (19.1 +/- 7.2 nmol/ml PRBCs) than in control (14.5 +/- 4 nmol/ml PRBCs, P = 0.0007) subjects. Moreover, spermidine was significantly higher in the groups with microalbuminuria (n = 11, 22.5 +/- 9.2 nmol/ml PRBCs) and macroalbuminuria (n = 4, 22.2 +/- 5.7 nmol/ml PRBCs) than in both normoalbuminuric (n = 23, 16.9 +/- 5.6 nmol/ml PRBCs) and control (F = 9.78, P = 0.0001) subjects, and correlated with log AER (r = 0.41, P = 0.009). Similarly, proliferative retinopathy was associated with a significant increase in spermidine (n = 5, 20 +/- 7 nmol/ml PRBCs compared with control subjects [P = 0.0009]). CONCLUSIONS: Our data suggest that erythrocyte spermidine content is increased in IDDM patients associated with both diabetic nephropathy and advanced retinopathy.

Adult↗

Immunoquantitation of cytochrome C in cardiac perfusate.

An indirect three step ELISA has been assessed in order to detect the possible release of cytochrome c, a mitochondrial protein, from isolated and perfused guinea-pig heart. The ELISA described in this study is sufficiently sensitive and accurate to measure extracellular cytochrome c.

Animals↗

Cingulin, a specific protein component of tight junctions, is expressed in normal and neoplastic human epithelial tissues.

Cingulin is a 140-kd protein localized on the cytoplasmic face of avian tight junctions. The expression of cingulin in human normal and neoplastic colonic tissue has been investigated with an antiserum against chicken cingulin. Human cingulin shares its apparent molecular mass and localization with avian cingulin. In normal colonic epithelium, villous adenomas, and differentiated adenocarcinomas, cingulin staining is observed in the junctional region of the polarized cells lining the surface, the crypts, and the glandular lumina. In poorly differentiated adenocarcinomas, labeling also is observed at the interface between cancer tissue and stroma, or in clumps of malignant cells, forming a pattern that highlights the presence of small, compressed lumina. The cingulin content of four adenocarcinomas, estimated by immunoblotting and densitometry, was higher than that of the normal tissue (150% to 230%). Cingulin was detected in a metastasis from a colon adenocarcinoma but not in nonepithelial tissues and neoplasias, suggesting that cingulin may be a useful marker in the characterization of colonic and probably other epithelial neoplasias.

Adenocarcinoma↗