Regionális hátránykompenzáció a közművelődésben megvalósuló kulturális tanulás segítségével

A hazai közművelődésben megvalósuló kulturális tanulás magába foglalja mindazokata nem formális, illetve informális tanulási eseményeket, amelyek részben asaját, részben a partneri kezdeményezések révén az egyes közművelődésiintézményekben létrejönnek (vö. Juhász–Szabó 2016; Kozma et al.2015 ). Ezek a tanulási alkalmak aktív (rendszeres és nem rendszeresművelődési formák szervezői, szolgáltatói, résztvevői), illetve passzív (külsőszervek tevékenységei, alapterületből kizárólagossággal átengedett területi,terembérlési, helyszínbiztosítási) formában valósulnak meg a helyi közösségekigényeinek, szükségleteinek figyelembevételével. A területspecifikus igényekreés adottságokra építő közművelődésben megvalósuló kulturális tanuláshátránykompenzáló, esélyteremtő funkciói empirikus vizsgálatunk alapjánbeazonosíthatók. A lokalitást célzó, a helyi művelődő közösségeket központbahelyező szakmai szemlélet a vizsgálati eredmények tükrében a közművelődéscsúcsintézményeiben ( N = 197) még további fejlesztésikezdeményezéseket igényel, de regionálisan már eredménnyel mérhető

Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure

Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure.BackgroundThe p21 protein is found in the nucleus of most cells where it modulates cell cycle activity. At low levels, p21 stabilizes interactions between D cyclins and their cyclin-dependent kinases (cdks), but at high levels after induction by several different stress pathways, it causes cell cycle arrest. The p21 mRNA is induced in murine kidney after several types of acute renal failure, including cisplatin administration, ischemia-reperfusion, and ureteral obstruction. We reported that after cisplatin injection, mice with a p21 gene deletion developed much more severe renal damage than wild-type mice. To dissociate the effects of cisplatin-induced DNA damage and subsequent initiation of DNA damage-dependent cell death pathways from effects of acute renal failure, we have now examined mice after ischemia-reperfusion, a model of renal failure not associated with genotoxin-induced DNA damage early after the injury.MethodsWild-type and p21(-/-) mice were made ischemic by clamping both renal hila for 30 or 50 minutes. At various times after reflow, mortality and parameters of renal function and morphology were quantified. Also, the nuclear proteins p21 and proliferating cell nuclear antigen (PCNA) were localized in kidney sections by immunohistochemistry.ResultsKidney function was more impaired and mortality increased significantly in p21(-/-) mice as compared with p21(+/+) mice. We found more cell cycle activity, indicated by increased number of mitotic cells and nuclear PCNA-positive cells, in kidney of p21(-/-) mice.ConclusionsIn this study, p21(-/-) mice were more susceptible to ischemia-induced acute renal failure, with similarly elevated levels of parameters of cell cycle activity. We propose that the increased and inappropriate cell cycle activity in kidney cells is responsible for the increased kidney impairment and mortality

Alteration of renal respiratory Complex-III during experimental type-1 diabetes

<p>Abstract</p> <p>Background</p> <p>Diabetes has become the single most common cause for end-stage renal disease in the United States. It has been established that mitochondrial damage occurs during diabetes; however, little is known about what initiates mitochondrial injury and oxidant production during the early stages of diabetes. Inactivation of mitochondrial respiratory complexes or alteration of their critical subunits can lead to generation of mitochondrial oxidants, mitochondrial damage, and organ injury. Thus, one goal of this study was to determine the status of mitochondrial respiratory complexes in the rat kidney during the early stages of diabetes (5-weeks post streptozotocin injection).</p> <p>Methods</p> <p>Mitochondrial complex activity assays, blue native gel electrophoresis (BN-PAGE), Complex III immunoprecipitation, and an ATP assay were performed to examine the effects of diabetes on the status of respiratory complexes and energy levels in renal mitochondria. Creatinine clearance and urine albumin excretion were measured to assess the status of renal function in our model.</p> <p>Results</p> <p>Interestingly, of all four respiratory complexes only cytochrome c reductase (Complex-III) activity was significantly decreased, whereas two Complex III subunits, Core 2 protein and Rieske protein, were up regulated in the diabetic renal mitochondria. The BN-PAGE data suggested that Complex III failed to assemble correctly, which could also explain the compensatory upregulation of specific Complex III subunits. In addition, the renal F₀F₁-ATPase activity and ATP levels were increased during diabetes.</p> <p>Conclusion</p> <p>In summary, these findings show for the first time that early (and selective) inactivation of Complex-III may contribute to the mitochondrial oxidant production which occurs in the early stages of diabetes.</p

γ-Tocotrienol Protects against Mitochondrial Dysfunction, Energy Deficits, Morphological Damage, and Decreases in Renal Functions after Renal Ischemia

Ischemia-induced mitochondrial dysfunction and ATP depletion in the kidney result in disruption of primary functions and acute injury of the kidney. This study tested whether γ-tocotrienol (GTT), a member of the vitamin E family, protects mitochondrial function, reduces ATP deficits, and improves renal functions and survival after ischemia/reperfusion injury. Vehicle or GTT (200 mg/kg) were administered to mice 12 h before bilateral kidney ischemia, and endpoints were assessed at different timepoints of reperfusion. GTT treatment reduced decreases in state 3 respiration and accelerated recovery of this function after ischemia. GTT prevented decreases in activities of complexes I and III of the respiratory chain, and blocked ischemia-induced decreases in F0F1-ATPase activity and ATP content in renal cortical tissue. GTT improved renal morphology at 72 h after ischemia, reduced numbers of necrotic proximal tubular and inflammatory cells, and enhanced tubular regeneration. GTT treatment ameliorated increases in plasma creatinine levels and accelerated recovery of creatinine levels after ischemia. Lastly, 89% of mice receiving GTT and 70% of those receiving vehicle survived ischemia. Conclusions: Our data show novel observations that GTT administration improves mitochondrial respiration, prevents ATP deficits, promotes tubular regeneration, ameliorates decreases in renal functions, and increases survival after acute kidney injury in mice

Cytoplasmic initiation of cisplatin cytotoxicity

The mechanism of action of cisplatin as a chemotherapeutic agent has been attributed to DNA binding, while its mechanism of action as a nephrotoxin is unresolved. Only ∼1% of intracellular cisplatin interacts with DNA, primarily forming intrastrand cross-linked adducts, and many studies have implicated both nuclear and cytoplasmic causes of cisplatin-induced death in cultured cells. We have demonstrated that cisplatin cytotoxicity depends on cdk2 activity, which is at least partly through the cdk2-E2F1 pathway. The mechanism of the dependency on cdk2, and whether cdk2 activation of E2F1 represents the only cell death pathway involved, is still unclear. Our previous work showed that deletion of the nuclear localization signal from p21WAF1/CIP1, a cdk2 inhibitor, did not alter its protective action against cisplatin cytotoxicity. Active cdk2-cyclin complexes are localized in both the nucleus and cytoplasm, and it was reported that cdk2 translocated to the cytoplasm after an apoptotic stimulus. Herein, we show that cisplatin caused cell death in enucleated mouse kidney proximal tubule cells (TKPTS), which was prevented by cdk2 inhibition. Also, we localized cytoplasmic cdk2 to both the endoplasmic reticulum (ER) and Golgi compartments, and ER stress was blocked by specific cdk2 inhibition. We conclude that cisplatin can induce nuclear independent apoptosis, cisplatin cytotoxicity can be initiated by cytoplasmic events, and cytoplasmic cdk2 plays an important role in apoptosis signaling

Cell cycle regulation: Repair and regeneration in acute renal failure

Cell cyle regulation: Repair and regeneration in acute renal failure. Research into mechanisms of acute renal failure has begun to reveal molecular targets for possible therapeutic intervention. Much useful knowledge into the causes and prevention of this syndrome has been gained by the study of animal models. Most recently, investigation of the effects on acute renal failure of selected gene knock-outs in mice has contributed to our recognition of many previously unappreciated molecular pathways. Particularly, experiments have revealed the protective nature of two highly induced genes whose functions are to inhibit and control the cell cycle after acute renal failure. By use of these models we have started to understand the role of increased cell cycle activity after renal stress, and the role of proteins induced by these stresses that limit this proliferation

Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite

Due to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescence spectroscopic measurements gave 1.9 × 105 M−1 and 1.0 × 104 M−1 as the association constants of the protonated metronidazole inclusion in CB7 and SCX4, whereas the unprotonated guests had values more than one order of magnitude lower, respectively. The preferential binding of the protonated metronidazole resulted in 1.91 pH unit pKa diminution upon encapsulation in CB7, but the complexation with SCX4 led to a pKa decrease of only 0.82 pH unit. The produced protonated metronidazole–SCX4 complex induced nanoparticle formation with protonated chitosan by supramolecular crosslinking of the polysaccharide chains. The properties of the aqueous nanoparticle solutions and the micron-sized solid composite produced therefrom by nano spray drying were unraveled. The results of the present work may find application in the rational design of tailor-made self-assembled drug carrier systems