Real-time Base Excision Repair Assay to Measure the Activity of the 8-oxoguanine DNA Glycosylase 1 in Isolated Mitochondria of Human Skin Fibroblasts.

7,8-dihydro-8-oxoguanine (8-oxoG) is one of the most common and mutagenic oxidative DNA damages induced by reactive oxygen species (ROS). Since ROS is mainly produced in the inner membranes of the mitochondria, these organelles and especially the mitochondrial DNA (mtDNA) contained therein are particularly affected by this damage. Insufficient elimination of 8-oxoG can lead to mutations and thus to severe mitochondrial dysfunctions.

Plasmapheresis for Rescue in Severe Encephalopathy and Multiorgan Failure from Fulminant Influenza (H3N2) Infection.

We are presenting a case of 4-years-old previously healthy male with coma, severe acute hepatitis and multiorgan failure in presence of Influenza infection. Literature review highlighted an immune-mediated pathophysiology for such presentations so the child underwent a trial of plasmapheresis which resulted in a rapid clinical improvement and child was discharge in his baseline neurologic status by day 14.

The activity of the DNA repair enzyme hOGG1 can be directly modulated by ubiquinol.

The DNA of human cells suffers about 1.000-100.000 oxidative lesions per day.

A New Efficient Method for Measuring Oxygen Consumption Rate Directly in Human Epidermal Biopsies.

Skin cells are constantly exposed to environmental influences such as air pollution, chemicals, pathogens and UV radiation. UV radiation can damage different biological structures, but most importantly cellular DNA. Mitochondria contain their own genome and accumulate UV-induced DNA mutations to a large extent.

Age-Dependent Loss of Mitochondrial Function in Epithelial Tissue Can Be Reversed by Coenzyme Q.

The process of aging is characterized by the increase of age-associated disorders as well as severe diseases. Due to their role in the oxidative phosphorylation and thus the production of ATP which is crucial for many cellular processes, one reason for this could be found in the mitochondria. The accumulation of reactive oxygen species damaged mitochondrial DNA and proteins can induce mitochondrial dysfunction within the electron transport chain.

PARP1 protects from benzo[a]pyrene diol epoxide-induced replication stress and mutagenicity.

Poly(ADP-ribosyl)ation (PARylation) is a complex and reversible posttranslational modification catalyzed by poly(ADP-ribose)polymerases (PARPs), which orchestrates protein function and subcellular localization. The function of PARP1 in genotoxic stress response upon induction of oxidative DNA lesions and strand breaks is firmly established, but its role in the response to chemical-induced, bulky DNA adducts is understood incompletely. To address the role of PARP1 in the response to bulky DNA adducts, we treated human cancer cells with benzo[a]pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE), which represents the active metabolite of the environmental carcinogen benzo[a]pyrene [B(a)P], in nanomolar to low micromolar concentrations.

Fluid Overload and Kidney Injury Score: A Multidimensional Real-Time Assessment of Renal Disease Burden in the Critically Ill Patient.

Objective: Interruptive acute kidney injury alerts are reported to decrease acute kidney injury-related mortality in adults. Critically ill children have multiple acute kidney injury risk factors; although recognition has improved due to standardized definitions, subtle changes in serum creatinine make acute kidney injury recognition challenging. Age and body habitus variability prevent a uniform maximum threshold of creatinine.

Accelerated Regeneration of ATP Level after Irradiation in Human Skin Fibroblasts by Coenzyme Q10.

Human skin is exposed to a number of harmful agents of which the ultraviolet (UV) component of solar radiation is most important. UV-induced damages include direct DNA lesions as well as oxidative damage in DNA, proteins and lipids caused by reactive oxygen species (ROS). Being the main site of ROS generation in the cell, mitochondria are particularly affected by photostress.

Influence of calorie reduction on DNA repair capacity of human peripheral blood mononuclear cells.

Caloric restrictive feeding prolongs the lifespan of a variety of model organisms like rodents and invertebrates. It has been shown that caloric restriction reduces age-related as well as overall-mortality, reduces oxidative stress and influences DNA repair ability positively. There are numerous studies underlining this, but fewer studies involving humans exist.

Acute Kidney Injury in Pediatric Heart Failure.

Acute kidney injury (AKI) is very common in pediatric medical and surgical cardiac patients. Not only is it an independent risk factor for increased morbidity and mortality in the short run, but repeated episodes of AKI lead to chronic kidney disease (CKD) especially in the most vulnerable hosts with multiple risk factors, such as heart transplant recipients. The cardiorenal syndrome, a term coined to emphasize the bidirectional nature of simultaneous or sequential cardiac-renal dysfunction both in acute and chronic settings, has been recently described in adults but scarcely reported in children.

Disruption of the GABA shunt affects mitochondrial respiration and virulence in the cereal pathogen Fusarium graminearum.

The cereal pathogen Fusarium graminearum threatens food and feed production worldwide. It reduces the yield and poisons the remaining kernels with mycotoxins, notably deoxynivalenol (DON). We analyzed the importance of gamma-aminobutanoic acid (GABA) metabolism for the life cycle of this fungal pathogen.

Poly(ADP-ribose)-mediated interplay of XPA and PARP1 leads to reciprocal regulation of protein function.

Poly(ADP-ribose) (PAR) is a complex and reversible post-translational modification that controls protein function and localization through covalent modification of, or noncovalent binding to target proteins. Previously, we and others characterized the noncovalent, high-affinity binding of the key nucleotide excision repair (NER) protein XPA to PAR. In the present study, we address the functional relevance of this interaction.

Shortwave UV-induced damage as part of the solar damage spectrum is not a major contributor to mitochondrial dysfunction.

Because of the absence of a nucleotide excision repair in mitochondria, ultraviolet (UV)-induced bulky mitochondrial DNA (mtDNA) lesions persist for several days before they would eventually be removed by mitophagy. Long persistence of this damage might disturb mitochondrial functions, thereby contributing to skin ageing. In this study, we examined the influence of shortwave UV-induced damage on mitochondrial parameters in normal human skin fibroblasts.

Mitochondrial DNA copy number - but not a mitochondrial tandem CC to TT transition - is increased in sun-exposed skin.

Mitochondrial DNA (mtDNA) mutations are causatively associated with photo-ageing and are used as biomarkers of UV exposure. The most prominent mitochondrial mutation is the common deletion (CD), which is induced in many tissues by oxidative stress. More photo-specific mutations might be CC to TT tandem transitions which arise from UV-induced cyclobutane pyrimidine dimers.

A modified fluorimetric host cell reactivation assay to determine the repair capacity of primary keratinocytes, melanocytes and fibroblasts.

Background: The Host Cell Reactivation Assay (HCRA) is widely used to identify circumstances and substances affecting the repair capacity of cells, however, it is restricted by the transfection procedure used and the sensitivity of the detection method. Primary skin cells are particularly difficult to transfect, and therefore sensitive methods are needed to detect any variations due to the cell-type or inter-individual differences or changes induced by diverse substances.A sensitive and repeatable method to detect the repair capacity of skin cells would be useful in two different aspects: On the one hand, to identify substances influencing the repair capacity in a positive manner (these substances could be promising ingredients for cosmetic products) and on the other hand, to exclude the negative effects of substances on the repair capacity (this could serve as one step further towards replacing or at least reducing animal testing).