The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson’s disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells.     

Application of Teleonic Principles in the Search for Systemic Causes of Accidents in Anesthesia

Safety of patients in anesthesia has always been one of the major concerns of the anesthetist. It is clear from studies of safety in general that many accidents and critical incidents occur as the result of latent systemic failures to which a great number of factors contribute (Reason, 1990). An ideal way to approach this problem would be within a systemic framework, such as teleonics, developed by Járos and his co-workers (Cloete, 1999; Járos and Cloete, 1987, 1993). In this framework the events and procedures in anesthesia are considered to be part of a very complex network of process systems (teleons). It is postulated that teleonic uncertainty (telentropy) in this complex network is a factor that might lead to accidents. In a previous paper presented to the World Congress at Toronto in 2000, the principles of teleonics were described in a mathematico symbolic way (Horváth et al., 2000). This paper contains selected examples of application of these principles to the identification of possible systemic causes of accidents in anesthesia.     

Effects of butyrate and insulin and their interaction on the DNA synthesis of rumen epithelial cells in culture

Summary Rumen epithelial cells (REC) were incubated in the presence of various concentrations of butyrate or insulin or with both of them, to obtain information on their effect on the DNA synthesis of cultured cells. The 24-h values of³H-thymidine incorporation into cellular DNA were measured in the presence of butyrate, insulin or butyrate plus insulin. While butyrate reduced DNA synthesis, insulin produced an increase over the control. Combined butyrate plus insulin treatment influenced the incorporation of label in accordance with the relative proportion of these two substances.     

Aging alters resynchronization of the circadian system in rats after a shift of the light-dark cycle

Four days following an 8-h advance of the light-dark cycle, the circadian rhythms in the pineal N-acetyltransferase activity and melatonin content reappeared in 7-week-old rats, but were still abolished in 24-month-old animals.     

Thyroid-catecholamines interrelationships in free fatty acids release from adipose tissue

Zusammenfassung Die Abgabe freier Fettsäuren aus dem mesenterialen Fettgewebe kann durch Phentolamin nicht nur bei hyperthyroeten, sondern auch bei euthyreoten Ratten blockiert werden. Die erhöhte Freisetzung bei Hyperthyreose lässt sich wahrscheinlich durch eine gesteigerte Katecholaminaktivität erklären.     

On the mechanism of increasing the tuberculostatic activity of isoniazid in the presence of 4-aminobenzoic acid

Zusammenfassung 4-Acetaminobenzoesäure hatin vitro im Unterschied zu 4-Aminobenzoesäure, keinen günstigen Einfluss auf die antituberkulotische Wirkung von Isoniazid. Bei den StämmenMycobacterium 607 und H37Rv wurde jedoch chromatographisch keine Bildung acetylierter 4-Aminobenzoesäure nachgewiesen.