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  • Key words: Ion transport — Cotransport — Erythrocytes — Ionic strength — Intracellular pH  (1)
  • Podospora anserina  (1)
  • Prophylaxe  (1)
  • 2000-2004  (3)
  • 1915-1919
  • 1
    ISSN: 1439-099X
    Keywords: Schlüsselwörter: Strahlentherapie ; Diarrhö ; Prophylaxe ; Smektit ; Key Words: Radiotherapy ; Diarrhea ; Prophylaxis ; Smectite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Purpose: Diarrhea and abdominal pain are well-known side effects abdominal or pelvic of radiation therapy that may lead to interruption of treatment in serious cases. In recent trials the silicate smectite has proven a promising drug in the prophylaxis if these adverse events. The presented trial aimed at the verification of earlier studies and the evaluation of a dose-effect relationship. Patients and Methods: Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (= Colina®) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2 × 6 g smectite daily and 91 patients received 2 × 6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (≥ 3 pappy stools). Results: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume ≤ 837.5 ml, the other with a small bowel volume 〉 837,5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. Conclusion: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis.
    Notes: Hintergrund und Ziel: Strahlentherapieinduzierte Diarrhöen und Schmerzen sind bekannte Nebenwirkungen der Becken- und Abdominalbestrahlung und können in schwerwiegenden Fällen zur Unterbrechung der Strahlenbehandlung führen. Das Schichtsilikat Smektit hat sich in den ersten Anwendungsstudien als ein vielversprechendes Therapeutikum zur Prophylaxe dieser Nebenwirkungen erwiesen. Die vorliegende Untersuchung diente der Verifizierung bekannter Studienresultate und der Erarbeitung einer Dosis-Wirkungs-Beziehung. Patienten und Methoden: Zwischen April 1994 und Mai 1995 wurde bei 176 Patienten mit Becken- bzw. Abdominalbestrahlung die prophylaktische Wirkung von Smektit (Handelsname: Colina®) bezüglich radiogener Diarrhöen in einer doppelblinden, randomisierten und plazebokontrollierten Studie untersucht. Während des gesamten Zeitraums der Strahlentherapie erhielten 85 Patienten täglich 2mal 6 g Smektit und 91 Patienten täglich 2mal 6 g von identisch aussehender Plazebosubstanz. Das Hauptzielkriterium der Auswertung war der Zeitraum bis zum Auftreten einer bestrahlungsinduzierten Diarrhö (definiert als ≥ 3 breiige Stühle). Ergebnisse: Alle 176 Patienten wurden in der Intent-to-treat-Analyse ausgewertet. In der Gesamtgruppe zeigten sich keine signifikanten Unterschiede zwischen der prophylaktischen Wirkung von Smektit und Plazebo. Eine explorative Post-hoc-Analyse mit Teilung des Gesamtkollektivs in Subgruppen mit einem bestrahlten Dünndarmvolumen ≤ 837,5 ml bzw. 〉 837,5 ml (Median) deutet im Kollektiv ≤ 837,5 ml an, dass bei gegebener Dosierung ein Vorteil für Smektit gegenüber Plazebo (32 versus 18 Kalendertage bis zum ersten Auftreten einer Diarrhö) besteht; dieser Vorteil ist jedoch statistisch nicht signifikant. Schlussfolgerung: Durch den prophylaktischen Einsatz eines Smektitpräparates als Antidiarrhoikum während einer Bestrahlung des Becken- und Abdominalbereiches kann die Entstehung einer bestrahlungsinduzierten Diarrhö verzögert werden, eine statistische Signifikanz konnte jedoch sowohl im Gesamtkollektiv als auch in einer Post-hoc-Subgruppenanalyse nicht nachgewiesen werden.
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  • 2
    ISSN: 1432-1424
    Keywords: Key words: Ion transport — Cotransport — Erythrocytes — Ionic strength — Intracellular pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract. The change of intracellular pH of erythrocytes under different experimental conditions was investigated using the pH-sensitive fluorescent dye BCECF and correlated with (ouabain + bumetanide + EGTA)-insensitive K+ efflux and Cl− loss. When human erythrocytes were suspended in a physiological NaCl solution (pH o = 7.4), the measured pH i was 7.19 ± 0.04 and remained constant for 30 min. When erythrocytes were transferred into a low ionic strength (LIS) solution, an immediate alkalinization increased the pH i to 7.70 ± 0.15, which was followed by a slower cell acidification. The alkalinization of cells in LIS media was ascribed to a band 3 mediated effect since a rapid loss of approximately 80% of intracellular Cl− content was observed, which was sensitive to known anion transport inhibitors. In the case of cellular acidification, a comparison of the calculated H+ influx with the measured unidirectional K+ efflux at different extracellular ionic strengths showed a correlation with a nearly 1:1 stoichiometry. Both fluxes were enhanced by decreasing the ionic strength of the solution resulting in a H+ influx and a K+ efflux in LIS solution of 108.2 ± 20.4 mmol (l cells hr)−1 and 98.7 ± 19.3 mmol (l cells hr)−1, respectively. For bovine and porcine erythrocytes, in LIS media, H+ influx and K+ efflux were of comparable magnitude, but only about 10% of the fluxes observed in human erythrocytes under LIS conditions. Quinacrine, a known inhibitor of the mitochondrial K+(Na+)/H+ exchanger, inhibited the K+ efflux in LIS solution by about 80%. Our results provide evidence for the existence of a K+(Na+)/H+ exchanger in the human erythrocyte membrane.
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  • 3
    ISSN: 1617-4623
    Keywords: Key words Filamentous fungi ; DNA transposon ; Fot1-like element ; Podospora anserina ; Repeat-induced point mutation (RIP)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A degenerate DNA transposon, Pat, was identified in the genomes of various wild-type strains of the filamentous fungus Podospora anserina. In these strains, the number (approximately 20–25 copies per genome) and location of Pat sequences appear to be conserved. Two copies of Pat, one complete and one partial, were cloned and characterized. The sequence of the complete element is 1856 bp long and contains imperfect inverted terminal repeats (ITRs) of 53 bp. The target site duplication comprises the sequence TA. The amino acid sequence derived from one reading frame of Pat shows significant homology to members of the Fot1 family of transposons. However, this reading frame is interrupted by numerous stop codons. Since no transcripts of Pat were identified in different P. anserina strains grown under standard conditions and under increased stress, we conclude that none of the copies of Pat is active in the strains analyzed, under the environmental conditions investigated. Comparison of the sequences of the two cloned Pat sequences revealed 89% (589/747 nucleotides) identity. Most of the differences (82%, 129/158) can be attributed to transitions preferentially at CpA:TpG and CpT:ApG dinucleotides. The dinucleotide ratios in Pat are similar to those in a Neurospora crassa transposon which was subject to repeat-induced mutation (RIP), but differ significantly from those found in single-copy genes of P. anserina and in fungal DNA transposons not modified by this mechanism. Molecular analysis of the progeny of a cross between the wild-type strain and a transgenic strain in which a nuclear gene was duplicated by transformation yielded the first clear evidence that a RIP-like process is active in P. anserina.
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