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  • 1
    ISSN: 1432-1912
    Keywords: Skeletal muscle ; Chloride channel conductance ; Taurine binding site ; Taurine analogues ; Structure-activity relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rat skeletal muscle, taurine was proposed to interact with a low affinity binding site on sarcolemmal phospholipids near chloride channel, increasing chloride conductance (GCI). In an attempt to evaluate the structure-activity relationship between taurine and its binding site, a series of N-azacycloalkenyl analogues of taurine (A: N-(1′aza-cyclopenten-2′yl)-2-aminoethane sulfonic acid; B: N-(1′-aza-cyclopenten-2′-yl)-2-aminoethane sulfonic acid; C: N-(1′aza-cyclopenten-2′-yl)-3-amino-propane sulfonic acid; D: N-(1′aza-cyclopenten-2′-yl)-3-aminopropane sulfonic acid) have been synthetized and tested in vitro on rat extensor digitorum longus (EDL) muscle. In spite of the presence of a bulky and lipophilic 5 or 7 membered heterocycle linked to the taurine amino group, analogues A and B determined an increase of GCI, although less potently than taurine. Also 3-aminopropane sulfonic acid (homotaurine), tested in comparison, showed less activity in increasing GCI with respect to taurine, probably for the increased distance between charged groups. Taurine analogues C and D, which differ from compounds A and B for an additional methylene group, showed much lower activity in increasing GCI. It has been reported that guanidinoethane sulfonate (GES) displaces taurine from the low affinity site on sarcolemma by only 7%. This compound, characterized by lower charge density on the guanidinium cationic head, applied in vitro on EDL muscle, show reduced taurine-like activity in increasing GCl. Our results support the hypothesis that the effect of taurine on muscle GCI is due to a specific binding on a low affinity site on sarcolemma and that charge delocalization reduces the binding probability more than the substitution of the primary amino group or the increased distance between charged groups.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2277
    Keywords: Key words Pediatric heart transplantation ; Long-term follow up ; Pediatric myocarditis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From November 1985 to 31 July 1997, 65 pediatric patients underwent heart transplantation at Bambino Gesù Hospital in Rome. Two of them underwent retransplantation, both 6 years after the first transplant. The 67 transplant patients had a mean age of 59 months; 11 were under 1 year of age. Their indications for transplantation were cardiomyopathies (38), lymphocytic myocarditis (8), and congenital heart diseases (19). Two patients of the first group successfully received a combined heart and kidney transplant. The 1-, 5-, and 11-year actuarial survival rates for the 65 patients who underwent heart transplantation were 68 %, 62 %, and 42 %, respectively. In the 1st postoperative year in patients who had had cardiomyopathy, a total of 50 episodes of acute rejection (AR), with one death, occurred (mean 1.7 AR/patient per year ± 1.5) and, in patients who had had congenital heart diseases, 19 ARs (one death) occurred with a mean of 1.58 AR/patient per year ± 1.4. The incidence of AR was significantly higher in patients who had had myocarditis with a total of 26 episodes (mean 3.7 AR/patient per year ± 2) and one death. Rehabilitation of heart transplanted children and infants was complete (NYHA class 1) in 52 % of patients of this series. We conclude that heart transplantation may give a good intermediate and long-term survival in selected patients; the extension of indications to desperately ill patients, or patients with systemic diseases or complex congenital heart diseases may bring less encouraging results, but should not be definitely excluded. Scarcity of donors remains the main limit, being still the first cause of death for patients on our waiting list. Our limited experience seems to suggest that, as described in adults, the cellular amplification of the immune response might affect the post-heart transplant follow up of pediatric patients with myocarditis resulting in a poor outcome for this population.
    Type of Medium: Electronic Resource
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