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S Bonato

Publications and source records attributed to S Bonato.

6 recordsLinked to original sources

Nuclear reprogramming and adult stem cell potential.

Cell-based therapy may represent a new strategy to treat a vast array of clinical disorders including neurodegenerative diseases. Recent observations indicate that adult somatic stem cells have the capacity to contribute to the regeneration of different tissues, suggesting that differentiative restrictions are not completely irreversible and can be reprogrammed. Cell fusion might account for some changed phenotype of adult cells but it seems to be biologically irrelevant for its extreme rarity. Other experimental evidences are compatible with the hypothesis of wide multipotency of well-defined stem cell populations, but also with transdifferentiation and/or dedifferentiation. Further studies on nuclear reprogramming mechanisms are necessary to fulfil the promise for developing autologous cellular therapies.

Adult↗

A CAV3 microdeletion differentially affects skeletal muscle and myocardium.

BACKGROUND: Caveolin-3 is the muscle-specific protein product of the caveolin gene family and an integral membrane component of caveolae. Mutations in the gene encoding caveolin-3 (CAV3) underlie four distinct disorders of skeletal muscle: the autosomal dominant form of limb-girdle muscular dystrophy type 1C (LGMD-1C), rippling muscle disease (RMD), sporadic and familial forms of hyperCKemia, and distal myopathy. OBJECTIVE: To characterize a multigenerational Italian family affected by an autosomal dominant myopathic disorder and to assess the expression of caveolin-3, dystrophin, dystrophin-associated glycoproteins, and neuronal nitric oxide synthase in the myocardium of an affected patient. METHODS: Clinical analysis involved 15 family members. Skeletal muscle expression of sarcolemmal proteins was evaluated by immunohistochemistry and western blot analysis in three affected individuals. Caveolar structures were analyzed through electron microscopy in muscle biopsies and in one heart biopsy. RESULTS: CAV3 genetic analysis showed a heterozygous 3-bp microdeletion (328-330del) in affected individuals, resulting in the loss of a phenylalanine (Phe97del) in the transmembrane domain. In the skeletal muscle, the mutation was associated with severe caveolin-3 deficiency and caveolar disorganization, whereas the expression of the other analyzed muscle proteins was unaltered. Remarkably, caveolin-3 was expressed in myocardium at a level corresponding to about 60% of that of control individuals and was correctly localized at the myocardial cell membranes, with preservation of cardiac myofiber caveolar structures. Clinical analysis revealed the concomitant presence in this family of the following phenotypes: RMD, LGMD, and hyperCKemia. CONCLUSIONS: Intrafamilial phenotypic heterogeneity is associated with caveolin-3 Phe97 microdeletion. The molecular network interacting with caveolin-3 in skeletal muscle and heart may differ.

Adult↗

Cognitive assessment in primary biliary cirrhosis: a case-control study.

OBJECTIVES: Primary biliary cirrhosis (PBC) patients frequently complain of fatigue and loss of memory. The aim of this study was to evaluate the mental performance and the neuropsychological assessment in patients with PBC. METHODS: A case-control study was performed that included 36 PBC patients (34 female, two male, mean age 55 yrs, 11 with stage II, 16 with stage III, and nine with stage IV disease) and 36 sex and age-matched controls with rheumatoid arthritis. A preliminary routine neurological examination failed to show any abnormality in each patient, including signs of encephalopathy. A battery of neuropsychological tests was administered to each subject, including: the Global Deterioration Scale; the Mini Mental State Examination; Buschke test; Gatterer's test; the Wechsler Memory Scale; the Blessed-Roth memory test; and the Clifton Assessment Schedule. RESULTS: The overall score for each test was not statistically different in PBC patients compared with rheumatoid arthritis patients, except for the Global Deterioration Scale and the Clifton Assessment Schedule; the performance was significantly poorer for these measures in PBC patients compared with rheumatoid arthritis patients. In both groups no correlation was found between the score of each test and age and/or duration of the disease. However, in the PBC group the score of BR was negatively correlated with the histological stage (p < 0.0025). CONCLUSION: The global mental status is not altered in PBC, but early changes in orientation and in personal memory are present in cirrhotic stage.

Adult↗

Concentrated ascitic fluid reinfusion after cascade filtration in tense ascites.

A new method for concentrated ascitic fluid reinfusion using a double ultrafiltration device is reported as 22 procedures in 20 cirrhotic patients (6 females, 14 males; median age 55 years, range 33-69) with tense, refractory ascites. Eight of the 20 patients had elevated creatinine levels. The mean time for each procedure was 189 +/- 82 min, during which a mean of 7.7 liters (1.3-13.3) of ultrafiltered ascitic fluid was removed and 613 ml (140-1700) of concentrated ascitic fluid rich in albumin (mean: 60 g, range 14-175) was reinfused. The procedure resulted in a mean weight loss of 8.1 kg (2.2-14.0) and a mean increase of 163 ml in urine output (24 hr). A reduction in the serum creatinine level (P < 0.05) and an increase in the plasma atrial natriuretic factor level (P < 0.02) 24 hr after reinfusion, while no changes in serum albumin, plasma and urinary electrolytes, plasma renin activity, aldosterone, and antidiuretic hormone levels were noted. Although minor evidence for a disturbance in coagulation was observed, there were no episodes of clinical bleeding. Four patients (20%) had transient chills or fever. Based upon this experience, it can be concluded that reinfusion of cascade filtered and concentrated ascitic fluid is a rapid, safe, and effective treatment for patients with tense ascites; it appears to have less side effects than more traditional methods and importantly does not require administration of heterologous plasma derivatives.

Adult↗

Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content.

In order to clarify debated issues of the medical treatment of ascites in cirrhosis--the usefulness of a low sodium diet and washout period preceding diuretic administration, maximal dosage of antimineralocorticoid to be reached before the addition of a loop diuretic, identifications of factors influencing treatment efficacy--115 hospitalized patients with non-azotemic cirrhosis and ascites were recruited and randomized to receive a diet providing either 40 or 120 mmol of sodium daily. After a washout period from the outpatient diuretic regimen for 7 days (Step 1), increasing dosages of K-canrenoate (200 mg/day every 4th day up to 600 mg) were administered to patients not undergoing spontaneous diuresis (Step 2). Upon the failure of Step 2, K-canrenoate (400 mg/day) and furosemide at increasing dosage (25-50-100 mg every other day) were given (Step 3). Nine percent of patients underwent spontaneous diuresis, and 77% developed a negative sodium balance by the end of Step 2 (69% with a dosage of K-canrenoate < or = 400 mg/day) and 93% by the end of Step 3. Two patients were withdrawn from the protocol due to diuretic side-effects. Univariate analysis showed that the type of diet did not influence the response to treatment. The washout period led to a significant increase in endogenous creatinine clearance; natremia significantly rose in hyponatremic patients. Multivariate analysis showed that creatinine clearance and plasma aldosterone were independent predictive factors of the response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗