Enterale Resorptionsvorgänge und ihre Beeinflussung

Ohne ZusammenfassungMit 4 Textabbildungen     

Multiple sclerosis as a model to investigate SARS‐CoV‐2 effect on brain atrophy

IntroductionData on structural brain changes after infection with SARS‐CoV‐2 is sparse. We postulate multiple sclerosis as a model to study the effects of SARS‐CoV‐2 on brain atrophy due to the unique availability of longitudinal imaging data in this patient group, enabling assessment of intraindividual brain atrophy rates.MethodsGlobal and regional cortical gray matter volumes were derived from structural MRIs using FreeSurfer. A linear model was fitted to the measures of the matching pre‐SARS‐CoV‐2 images with age as an explanatory variable. The residuals were used to determine whether the post‐SARS‐CoV‐2 volumes differed significantly from the baseline.ResultsFourteen RRMS patients with a total of 113 longitudinal magnetic resonance images were retrospectively analyzed. We found no acceleration of brain atrophy after infection with SARS‐CoV‐2 for global gray matter volume (p = 0.17). However, on the regional level, parahippocampal gyri showed a tendency toward volume reduction (p = 0.0076), suggesting accelerated atrophy during or after infection.ConclusionsOur results illustrate the opportunity of using longitudinal MRIs from existing MS registries to study brain changes associated with SARS‐CoV‐2 infections. We would like to address the global MS community with a call for action to use the available cohorts, reproduce the proposed analysis, and pool the results.     

Induction of apoptosis by 2-chloro-2'deoxyadenosine (2-CdA) alone and in combination with other cytotoxic drugs: synergistic effects on normal and neoplastic lymphocytes by addition of doxorubicin and mitoxantrone

2-CdA is active as a single agent in the treatment of low-grade lymphomas. We analyzed the induction of apoptosis by 2-CdA alone (n=5) and in combination with other drugs in peripheral lymphocytes from 25 patients with leukemic low-grade lymphomas and from 25 healthy volunteers. 2-CdA was tested in 4 escalating concentrations (0.05 microg/ml to 0.4 microg/ml). Linear regressions showed a dose dependent apoptosis rate of 0.29 x microg 2-CdA/ml + 0.11 (r2=0.88, p=0.006) in normal cells and 0.41 x microg 2-CdA/ml + 0.15 (r2=0.88, p=0.005) in leukemic cells. Intracellular metabolization of 2-CdA into 2-CdA-5'mono-, -di- and the active metabolite -triphosphate was analyzed by HPLC and paralleled the dose dependent increase of apoptosis. The combination of 2-CdA with doxorubicin or mitoxantrone had a synergistic effect on the induction of apoptosis (p<0.001) in both normal and neoplastic lymphocytes, whereas 2-CdA plus etoposide or cytosine arabinoside were only additive. Due to the flat slope of the dose response of 2-CdA concentration on apoptosis we assume that higher in vivo dosages of 2-CdA in the treatment of low-grade lymphomas may not result in a higher clinical efficacy. The synergistic lymphocytotoxic effect of 2-CdA combined with doxorubicin or mitoxantrone may be relevant for new treatment approaches.     

Ausscheidung freien und konjugierten Sulfates bei Ratte und Menschen nach Verabreichung von N-Acetyl-p-Aminophenol

Zusammenfassung Bei der Ratte nimmt nach i.p. Verabreichung von 200 mg/kg N-Acetyl-p-aminophenol (NAPAP) die Ausscheidung des freien Sulfates im Urin um ca. 90% des Kontrollwertes ab. Demnach ist die Konjugation mit Schwefelsäure bei der Ratte — gemessen an der Ausscheidung von NAPAP-sulfat — durch die verfügbare Menge an anorganischem Sulfat limitiert. Durch Zulage von Natriumsulfat bzw. Natriumthiosulfat wird die Sulfat-Konjugation bis zu 100% erhöht und damit die Elimination des NAPAP insgesamt beträchtlich gesteigert. Nach Phenobarbital-Vorbehandlung und gleichzeitiger Sulfatzulage tritt eine induktiv bedingte Mehrausscheidung an NAPAP-sulfat auf.Auch beim Menschen wird nach Gabe von 2 g N-Acetyl-p-aminophenol bis zu 50% weniger freies Sulfat ausgeschieden. Außerdem wird nach dieser NAPAP-Dosis die Ausscheidung physiologischer Sulfat-Konjugate eingeschränkt.Über einen Teil der Ergebnisse wurde auf der 7. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft in Mainz, 24. – 27. April 1966, berichtet: Büch, H., Ch. Eschrich u. K. Pfleger: Zur Frage der Induzierbarkeit der Sulfurylierung des N-Acetyl-p-aminophenols (NAPAP). Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 255, 6 (1966).     

Zur Hemmung der L-Glutaminsäure-und L-Dopadecarboxylase durch D-Cycloserin und andere Isoxazolidone

Summary 1. D-Cycloserine, an antibiotic produced by different strains of Streptomyces, to which frequent side effects on the central nervous system—particularly seizures and psychotic reactions—are attributed, inhibits the pyridoxal-5-phosphate dependent enzymes L-glutamic acid- and L-dopadecarboxylase in vitro. Additional data for some structurally related isoxazolidones are presented, among which 2,5-bis-(aminoxy-methyl)-1,4-dioxopiperazine, a spontaneous degradation product of D-cycloserine, was the most active compound.2. It can be demonstrated by kinetic analysis, that the inhibition of the L-dopadecarboxylase is due to competition of the coenzymatically inactive (pyridoxalphosphate-cycloserine)-complex with the free pyridoxal-5-phosphate for the apoenzyme thus diminishing the formation of the active holoenzyme. Numerical figures for the different equilibria-constants are given.3. The implications of these findings for the central nervous toxicity of D-cycloserine are discussed.

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Herrn Prof. Dr. P. Holtz zum 60. Geburtstag gewidmet.     

Gegenüberstellung von blockierenden und deblockierenden Substanzen am Zwerchfellphrenicuspräparat der Ratte

Zusammenfassung Die durch depolarisierende Stoffe unterbrochene neuromuskuläre Überleitung läßt sich mit Calcium, Chinidin und Coffein wiederherstellen. Diese Stoffe bilden mit Adrenalin als Antagonisten der Depolarisatoren eine Gruppe.Mit 7 Textabbildungen.