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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 163 records · Page 9Linked to original sources

Glutathione kinetics in normal man and in patients with liver cirrhosis.

BACKGROUND/AIMS: The dynamics of glutathione in plasma has always been studied by bolus injections. Data are available suggesting that the low plasma levels of cirrhosis are due to decreased production in glutathione-producing tissues, mainly the liver. We aimed to measure the kinetics of glutathione during controlled steady-state conditions, and to determine the reasons for its reduced plasma levels in advanced cirrhosis. METHODS: The plasma clearance of glutathione was measured in six control subjects and in ten patients with cirrhosis during a 2-step infusion study, producing steady-state levels approximately 5 and 10 times basal values. The plasma disappearance curve after infusion stop was used to determine the apparent volume of distribution and half-life of glutathione, and the estimated basal appearance rate. RESULTS: The clearance of glutathione did not reject 1st-order kinetics, i.e., it was concentration-independent, and was nearly doubled in cirrhosis. The half-life of exogenous glutathione was not different, whereas the volume of distribution was larger in cirrhosis, in the same range as extracellular water. The endogenous basal appearance rate of glutathione was reduced by 50%, and correlated with liver function, measured by routine and dynamic tests. CONCLUSIONS: The data confirm that the primary defect responsible for reduced glutathione in liver disease is a reduced production, possibly related to hepatocyte dysfunction and a block along the pathway of methionine metabolism.

Adult↗

Clinical implications of GBV-C/HGV infection in patients with "HCV-related" chronic hepatitis.

BACKGROUND/AIMS: To evaluate the clinical, biochemical and histological implications of a concomitant HGV infection in "HCV-related" chronic liver disease. METHODS: Eighty-three HCV-RNA positive patients with chronic liver disease were tested for GBV-C/HGV coinfection by heminested PCR. RESULTS: Twenty-two (26.5%) patients were found to be positive for GBV-C/HGV RNA. GBV-C/HGV+ patients differed significantly from GBV-C/HGV- ones for younger age, higher frequency of history of drug addiction, which in turn might favor coinfection with interferon-sensitive HCV genotypes (3a), and increased probability of long-term response to interferon. GBV-C/HGV infection appears to have no responsibility for specific aspects of HCV infection such as biochemical or histological cholestatic features, lymphoid follicles, symptomatic cryoglobulinemia or presence of serum autoantibodies, including LKM1. It does not worsen the HCV-related disease (ALT levels and histological activity) and does not significantly interfere with HCV infection, as explored by the number of hepatocytes positive for HCV antigens. The amount of steatosis (mean score) was shown to be higher in GBV-C/HGV+ patients. A virological follow up was performed in 17 interferon-treated GBV-C/HGV+ patients On the whole, GBV-C/HGV seems to be as sensitive to IFN treatment as HCV, but recurrence after withdrawal is more frequent. In spite of this, ALT levels often remain normal after treatment withdrawal. CONCLUSIONS: The present data suggest that GBV-C/HGV infection, apart from more marked liver steatosis, does not modify the overall picture of chronic hepatitis due to HCV infection.

Adolescent↗

Nonacidotic proximal tubulopathy transmitted as autosomal dominant trait.

The family of a patient with a nonacidotic and hypercalciuric proximal tubulopathy was studied. The proband showed glycosuria, aminoaciduria, tubular proteinuria, renal hypophosphatemia, and urate tubular hyporeabsorption without bicarbonate loss. He also presented increased urine calcium excretion, plasma 1,25-dihydroxyvitamin D, and enteral calcium absorption. Clinical consequences of the tubulopathy were osteopenia and calcium kidney stones. Fifteen of the proband's relatives were studied; six of them had renal hypophosphatemia, 10 presented hypercalciuria, and three showed both hypercalciuria and hypophosphatemia. No other reabsorption defects were observed. High plasma levels of 1,25-dihydroxyvitamin D were found in 13 family members; their values correlated positively with calcium excretion and negatively with tubular phosphate reabsorption. None produced stones or had reduced mineral bone density. Hypophosphatemia and hypercalciuria occurred in the two generations studied; their transmission was independent of gender, and male-to-male transmission occurred for both defects. Our findings suggest that a genetic alteration of proximal tubular function could cause multiple reabsorption defects in the proband or renal phosphate leakage in the proband's relatives. The genotypic alteration causing the proximal dysfunctions may be monogenic, with an autosomal dominant pattern of inheritance and variable expressivity. Increased calcium excretion may be due to the proximal tubular alteration; alternatively, it may be the result of a genetic background predisposing to idiopathic hypercalciuria. Phosphate and calcium loss could stimulate 1,25-dihydroxyvitamin D synthesis in proximal tubular cells.

Absorption↗

Effect of lactulose on carbohydrate metabolism and diabetes mellitus.

BACKGROUND: Unabsorbable disaccharides, by reducing transit time and possibly glucose absorption, are expected to affect carbohydrate metabolism. AIM: To test the effects of a preparation containing fibre and lactulose in the form of biscuits on glucose and insulin levels in obesity. METHODS: In 10 obese patients glucose and insulin were measured in the fasting state and in response to a meal during two consecutive days on a strictly controlled diet; on one day a total of 11 biscuits (10 g dietary fibre, 2 g raw fibre +8.2 g lactulose) were randomly substituted for an equicaloric part of a diet. RESULTS: Glucose and insulin in response to breakfast and to lunch were blunted by dietary fibre and lactulose, without any trend towards post-meal hypoglycaemia. Average day-time glucose decreased by 0.53 +/- SD 0.28 mmol/L, and insulin by 74.6 +/- 45.2 pmol/L. Plasma amino acids were higher during supplementation, ruling out malabsorption as a cause of glucose flattening. CONCLUSION: Because of the rationale of the preparation, good compliance of patients, and significant results in short-term experiments, the association of fibre and lactulose deserves more careful evaluation in long-term clinical studies.

Blood Glucose↗

Genetics of renal mechanisms of primary hypertension: the role of adducin.

PURPOSE: To summarize data concerning the identification of adducin as a 'candidate' gene in the Milan hypertensive strain of rats (MHS), a genetic model of essential hypertension, and in human essential hypertension. RESULTS: The sequence of events from renal function to cell membrane ion transports and finally to the molecular defect has been established in MHS rats. This led to the identification of polymorphisms in the cytoskeletal protein adducin. These polymorphisms are involved in blood pressure regulation in these rats. A linkage and an association study on Caucasian populations support the involvement of adducin in human hypertension also. A polymorphism of alpha-adducin gene is significantly associated with human hypertension. In particular, both in humans and in rats, adducin polymorphisms affect kidney function by modulating the overall capacity of tubular epithelial cells to transport ions. CONCLUSIONS: Adducin polymorphisms account for only a portion of hypertension both in humans and rats. Therefore additive or epistatic interactions with other genes involved in renal sodium handling need to be studied.

Animals↗

Erythrocyte calpain activity and left ventricular mass in essential hypertension.

BACKGROUND: Calpains are cytoplasmic proteases widely distributed among eucaryotic cells. Low levels of calpain activity were found in hypertrophic hearts from hypertensive rats, but its role in hypertrophic hearts from human hypertensives is unknown. Therefore, calpain activity was investigated in erythrocytes from essential hypertensive patients in relation to their left ventricular mass. OBJECTIVE: To study the role of calpain activity in the development of left ventricular hypertrophy (LVH) in human essential hypertension. METHODS: A total of 115 hypertensives (72 untreated and 43 with treatment interrupted for at least 4 months) were included in the study. Calpain I activity was measured in human erythrocytes and LVH was measured as left ventricular mass index (LVMI) by M-mode echocardiography. RESULTS: Values are given as mean+/-SEM. The hypertensives (97 men and 18 women) were 43.5+/-0.9 years old with mild to moderate levels of hypertension (systolic/diastolic blood pressure of 147.9+/-1.4/98.7+/-0.9 mmHg) and relatively recent LVH onset (3.5+/-0.5 years). An inverse relation between LVMI and erythrocytic calpain activity was present in all (P = 0.0023, R2 = 7.9%). This relation was still present considering only untreated hypertensives (P = 0.008; R2 = 9.7%), but was lost in the 43 previously treated hypertensives. Moreover, in the untreated hypertensives, after excluding the possible confounding effects of sex, age, body mass index, blood pressure and duration of hypertension, a stepwise regression showed that only two variables remained significantly related to LVMI: calpain (F = 6.23) and mean arterial pressure (F = 4.689). No relations were found between LVMI and calpastatin activity either in the whole population, or in treated or untreated hypertensives. CONCLUSIONS: If we assume that the level of erythrocyte calpain activity mirrors the level in cardiomyocytes, these data seem to suggest that increased protein degradation by calpain may prevent the development of LVH in hypertensive patients. This effect is independent of the duration and severity of hypertension.

Adult↗

Renal artery stenosis: evaluation with breath-hold, three-dimensional, dynamic, gadolinium-enhanced versus three-dimensional, phase-contrast MR angiography.

PURPOSE: To compare breath-hold, three-dimensional, gadolinium-enhanced magnetic resonance (MR) angiography with three-dimensional, phase-contrast MR angiography in the evaluation of renal artery stenosis. MATERIALS AND METHODS: Fifty-five consecutive adult patients with clinical suspicion of renovascular disease were prospectively examined with three-dimensional, phase-contrast MR angiography and breath-hold, three-dimensional MR angiography with injection of a standard dose of gadopentetate dimeglumine to evaluate the number of renal arteries and the presence and degree of stenosis. The standard of reference was intraarterial digital subtraction angiography. RESULTS: Gadolinium-enhanced MR angiography depicted all 105 main renal arteries, whereas phase-contrast MR angiography depicted 104. The number of accessory renal arteries depicted was significantly higher with gadolinium-enhanced (17 of 18) than with phase-contrast (11 of 18) studies (P = .04). Both techniques depicted 27 of the 29 stenoses (sensitivity, 93%; P > .05). Sensitivities, specificities, and accuracies in the diagnosis of hemodynamically significant stenosis (> 50% narrowing) were, respectively, 94%, 96%, and 96% for phase-contrast and 100%, 97%, and 98% for gadolinium-enhanced MR angiography (P > .05). CONCLUSION: Gadolinium-enhanced MR angiography is superior to phase-contrast MR angiography in accessory renal artery depiction. No statistically significant difference in the assessment of stenosis has been found between the two techniques.

Aged↗

Uncertainty in liver function assessment on the basis of single-point galactose concentration.

The uncertainty in liver function assessment based on single-sample galactose levels after galactose injection, in comparison to the standard procedure using the galactose elimination capacity (GEC), was assessed in 905 tests performed in a wide range of liver functions. The 45-min galactose levels significantly correlated with GEC, the correlation being better in subjects with a good liver function. In cirrhosis, the prediction using the 60-min galactose value was better than when the 45-min value was used. In the whole series, the 95% confidence interval of GEC predicted by 45-min galactose was as large as +/- 1.55mg x kg(-1) x min(-1) as absolute value, corresponding to a range from -41 to +47% of measured GEC. In cirrhosis, the 95% confidence interval was +/- 1.42 mg x kg(-1) x min(-1) and between -40 and +46% of measured GEC. The 60-min values were more predictive, but in Child class C patients the average error was 0.42 mg x kg(-1) x min(-1) (95% confidence interval -0.64 to +1.49, corresponding to -39 to +76% of measured GEC). The uncertainty was maintained within +/- 10% of measured values only in 50% of the tests. We conclude that the single-point galactose test introduces a considerable error, mainly in patients with more advanced liver disease, which may bias the decision-making process.

Analysis of Variance↗

Ouabain-like factor quantification in mammalian tissues and plasma: comparison of two independent assays.

The resolution of controversies that concern the detectability of an endogenous ouabain-like factor (OLF) in mammalian tissues and plasma was approached by the application of a standardized method for its extraction and quantification. Two independent assays were used to quantify the OLF: (1) a radioimmunoassay, which used a polyclonal anti-ouabain antiserum, and (2) a radioenzymatic assay based on the inhibition of dog kidney Na+,K+-ATPase. Plasma and tissues were obtained from the Milan hypertensive strain (MHS) and the Milan normotensive strain (MNS) of rats and from healthy human volunteers. Results indicate that (1) a single high-performance liquid chromatography (HPLC) fraction identical to that of ouabain was identified by both assay methods in the rat hypothalamus and hypophysis and in both rat and human plasma; (2) dilution curves of OLF and standard ouabain were parallel and with a similar Kd, both in radioimmunoassay (3 nmol/L) and ATPase assay (14 nmol/L); (3) after HPLC, OLF was similarly quantified by the two methods in the hypothalamus, hypophysis, adrenals, and plasma of rats and in human plasma; (4) OLF was present in larger amounts in the hypothalamus, hypophysis, and plasma of MHS rats than that of MNS rats; (5) the HPLC fraction of human plasma was quantified similarly by both assays (range, 60 to 150 pmol/L); (6) recovery of standard ouabain in pre-HPLC plasma extracts was approximately 90%; and (7) pre-HPLC OLF concentrations in human plasma ranged between 0.05 and 0.75 nmol/L. Rat cerebral tissues and both rat and human plasma contained measurable amounts of OLF, which were quantified similarly by radioimmunoassay and ATPase assay, both before and after HPLC fractionation. The increased MHS tissue and plasma levels of OLF are in keeping with the pathogenetic role of this factor in MHS hypertension.

Adrenal Glands↗

[Mechanical endarterectomy: review of the literature and description of an original device].

The Authors, after a Literature review on endovascular invasive procedures used for inferior limbs obstructive arteriopathy, describe the use of a new device for mechanical endarterectomy. Through the latest acquired experience the importance of dissecting progressively the single layers of the atheroma plaque without arriving to a complete denudation of the arterial wall, so avoiding the risk of myointimal hyperplasia reactions, is outlined. The possibility of using endoarterial stents in case of more indaginous recanalization is also stressed.

Angioplasty, Balloon↗