Einfluss von zyklischer Dehnung auf die Matrixsynthese von humanen Patellarsehnenzellen

Die Bedeutung von Mobilisation und Belastung für die Band- und Sehnenheilung ist heute allgemein anerkannt. Die lokale Deformation von Zellen ist dabei der zentrale Stimulus für die zellul?re Antwort. über den Einfluss von zyklischer Dehnung auf zellul?rer und molekularer Ebene ist bisher jedoch wenig bekannt. Der Einfluss kurzzeitiger zyklischer Dehnung auf die Synthese von Kollagen Typ I und III sowie von Fibronektin wurde daher in humanen Fibroblasten aus der Patellarsehne untersucht. Die Fibroblasten wurden aus Gewebeproben von 5 Donoren (mittleres Alter 29,2 Jahre) kultiviert. Zellen der 3. Passage wurden auf Silikonschalen für 30 bzw. 60 min zyklisch gedehnt (Dehnung 5%, Frequenz 1 Hz).     

Total gastric transposition: an alternative to esophageal replacement in children

Total gastric transposition was performed in 21 children as an alternative procedure for esophageal replacement. The age at the operation ranged from 15 months to 11 years. Half of the children were less than 2 years old. Fifteen patients had esophageal atresia. The stomach was passed toward the neck either through the esophageal bed (6 cases, with concomitant blunt esophagectomy without thoracotomy) or the retrosternal route (15 cases). There was one death in the early postoperative period secondary to an anastomotic leak and acute mediastinitis in a case of pharyngogastric anastomosis. Three other patients developed cervical leak with spontaneous closure but this ultimately led to a late anastomotic stricture (more than 6 months) requiring endoscopic dilatation. Only one child needed more than three attempts of endoscopic dilatation. None of these patients required surgical revision. The mean follow-up was 60 months (range, 10 to 122 months). Despite bulky atonic intrathoracic stomach occurring in some children, only two patients developed regurgitation and symptoms of poor gastric emptying. There were neither early nor late respiratory problems. Excellent and good functional outcome were achieved in 85% and 15% of the patients, respectively. Two patients have not undergone a weight catch-up phase. The majority of the children have been between the 20th and 80th percentile for weight. Five children remain below the 20th and two below the 5th percentile. The remarkably low morbidity and mortality combined with satisfactory functional results indicate that the total gastric transposition is a safe and easy alternative surgical procedure for esophageal replacement in children.     

Effect of the glucocorticoid receptor antagonist RU 38486 on muscle protein breakdown in sepsis

The role of glucocorticoids in muscle catabolism during sepsis was tested with the glucocorticoid receptor antagonist RU 38486. Sepsis was induced in male Sprague-Dawley rats (40 to 60 gm) by cecal ligation and puncture (CLP). Other animals underwent sham operation. Two hours before CLP or sham operation, rats received RU 38486 (5 mg/kg) or a corresponding volume of vehicle by gavage. Sixteen hours after CLP or sham operation, protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus muscles. Total and myofibrillar protein breakdown rates were determined by measuring net release of tyrosine and 3-methylhistidine, respectively. The protein synthesis rate was approximately 30% lower in rats with sepsis than in sham operated rats and was not affected by treatment with RU 38486. The total protein breakdown rate was increased by approximately 70% and myofibrillar protein degradation was increased more than fivefold in muscle from rats with sepsis. Treatment with RU 38486 resulted in a 28% reduction of total and a 44% reduction of myofibrillar protein breakdown in rats with sepsis but did not affect proteolysis in muscle from sham-operated animals. The results support a role of glucocorticoids in accelerated muscle proteolysis during sepsis. It is not clear whether glucocorticoids are the only required mediator or they interact with other substances to induce muscle protein breakdown during sepsis.     

Stereoselective disposition of flecainide in relation to the sparteine/debrisoquine metaboliser phenotype.

1. The disposition of the enantiomers of the antiarrhythmic drug flecainide has been studied in five extensive (EM) and five poor (PM) metabolisers of sparteine/debrisoquine after administration of 50 mg of racemic flecainide acetate under conditions of high urinary flow rate and acidic urinary pH. 2. In the EM subjects there were no significant differences in the oral clearance, half-life or urinary excretion of (+)-S- and (-)-R-flecainide. 3. In the PM subjects differences in the pharmacokinetics of S- and R-flecainide were observed. The oral clearance of R-flecainide (467 +/- 109 ml min-1) was less (P less than 0.03) than that of the S-enantiomer (620 +/- 172 ml min-1). The half-life of R-flecainide (12.9 h) was longer (P less than 0.03) than that of S-flecainide (9.8 h). The renal clearance of the two enantiomers was, however, comparable and similar to that observed in the EM subjects. The urinary recovery of R-flecainide (15.6 +/- 3.7 mg) was greater (P less than 0.03) than that of the S-enantiomer (12.0 +/- 3.7 mg). The enantioselective disposition observed in PMs is therefore due to greater impairment in the metabolism of R- than S-flecainide. 4. The urinary recoveries of two major metabolites of flecainide, meta-O-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of flecainide (MODLF) were lower (P less than 0.05) in PMs, 12.0% +/- 3.1% and 8.2% +/- 3.2% of the dose administered, respectively, than in EMs of 17.7% +/- 3.3% and 16.5% +/- 3.3%, respectively. 5. One PM subject had a greatly diminished flecainide metabolic capacity and a rare genotype, as assigned by Xbal RFLP analysis.     

Influence of triethyl lead on neurofilaments in vivo and in vitro

The influence of triethyl lead chloride (TriEL) on the organization of neurofilaments in vivo was studied by indirect immunofluorescence microscopy employing mouse neuroblastoma cells (Neuro-2a). TriEL induces perinuclear coil formation of neurofilaments in those cells. The rearrangements observed are not correlated with significant changes of the microtubular system. Cells in which the microtubular network was stabilized by Taxol treatment prior to incubation with TriEL even show the rearrangement of the neurofilaments. The effect of TriEL is reversible. In vitro, the effect of TriEL on isolated neurofilaments and on filament formation as well as on the structure of preformed filaments was investigated by electron microscopy. If isolated neurofilaments from porcine spinal cord are incubated in the presence of TriEL, they show constrictions and bulges. Additionally, many fragments are seen. If preformed filaments are treated with TriEL, unraveling of fibers into protofilamentous strands is observed. The assembly of neurofilaments in vitro is disturbed in the presence of TriEL. The interaction of TriEL with neurofilaments in vivo is likely to be at least partly responsible for the neurotoxicity of TriEL.     

Localization and retention of mycobacterial antigen in lymph nodes of leprosy patients.

Although leprosy, a chronic disease caused by M. leprae, primarily affects skin and peripheral nerves, pathological changes and granulomas have been observed in lymph nodes which are: (a) present in tuberculoid lymph nodes in the absence of acid-fact bacilli and (b) persistent in lepromatous patients even after prolonged treatment. We detected substantial amounts of mycobacterial antigen in 16 leprous lymph nodes using anti-BCG by the peroxidase anti-peroxidase method. The load and distribution of antigen varied along the spectrum and with the duration of treatment. Tuberculoid and long-term treated lepromatous lymph nodes had a similar distribution of antigen in clusters of cells giving a ''speckled'' appearance. The untreated lepromatous had a ''diffuse'' staining of antigen in foamy histiocytes whereas lepromatous lesions with a lower bacillary load had a mixed pattern of ''diffuse'' and ''speckled''. Antigen was also detected in a number of plasma cells along the spectrum but predominantly in lepromatous lymph nodes. Our observations indicate that: (a) antigen exists in lymph nodes despite prolonged chemotherapy which may be responsible for the persistent granuloma and (b) antigen is not confined to any particular anatomical compartment of the lymph node.