Oxidized proportion of muscle coenzyme Q10 increases with age in healthy children.

BACKGROUND: Coenzyme Q10 (CoQ10) is synthesized in most human tissues, with high concentration in the skeletal muscle. CoQ10 functions in the mitochondrial respiratory chain and serves as a potent liphophilic antioxidant in membranes. CoQ10 deficiency impairs mitochondrial ATP synthesis and increases oxidative stress. It has been suggested that plasma CoQ10 status is not a robust proxy for the diagnosis of CoQ10 deficiency. METHODS: We determined the concentration and redox-status of CoQ10 in plasma and muscle tissue from 140 healthy children (0.8-15.3 y) by high-performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: There was no correlation between CoQ10 concentration or redox status between plasma and muscle tissue. Lipid-related CoQ10 plasma concentrations showed a negative correlation with age (Spearman's, P ≤ 0.02), but there was no significant age-related correlation for muscle concentration. In muscle tissue, we found a distinct shift in the redox status in favor of the oxidized proportion with increasing age (Spearman's, P ≤ 0.00001). Reference values for muscle CoQ10 concentration (40.5 ± 12.2 pmol/mg wet tissue) and CoQ10 redox status (46.8 ± 6.8% oxidized within total) were established for healthy children. CONCLUSION: The age-related redox shift in muscle tissue suggests changes in antioxidative defense during childhood. The reference values established here provide a necessary prerequisite for diagnosing early CoQ10 deficiency.

[Classification of cell-based medicinal products and legal implications: An overview and an update]. / Klassifizierung von zellbasierten Arzneimitteln und rechtliche Implikationen : Eine Übersicht und ein Update.

In general, cell-based medicinal products do not represent a uniform class of medicinal products, but instead comprise medicinal products with diverse regulatory classification as advanced-therapy medicinal products (ATMP), medicinal products (MP), tissue preparations, or blood products. Due to the legal and scientific consequences of the development and approval of MPs, classification should be clarified as early as possible. This paper describes the legal situation in Germany and highlights specific criteria and concepts for classification, with a focus on, but not limited to, ATMPs and non-ATMPs. Depending on the stage of product development and the specific application submitted to a competent authority, legally binding classification is done by the German Länder Authorities, Paul-Ehrlich-Institut, or European Medicines Agency. On request by the applicants, the Committee for Advanced Therapies may issue scientific recommendations for classification.

Safety assessment of biolistic DNA vaccination.

DNA-based vector systems have been widely studied as new modalities for the prevention and treatment of human diseases. As for all other medicinal products, safety is an important aspect in the evaluation of such products. In this chapter we reflect on the basic safety issues which have been raised with respect to preventive and therapeutic DNA vaccines, including insertional mutagenesis in case of chromosomal integration, possible formation of anti-DNA antibodies, induction of autoimmune responses and/or immunological tolerance. In addition, local reactions at the site of administration and adverse effects resulting from plasmid DNA spread to nontarget tissues are discussed. Most importantly, however, the benefit-risk profile of a medicinal product is crucial for a decision on providing marketing authorization or not. A product has an acceptable benefit-risk profile if the benefits of the product outweigh its risks for the treated patient.

Developmental expression of HERV-R (ERV3) and HERV-K in human tissue.

The human endogenous retroviruses (HERVs), ERV3 (HERV-R) and HERV-K, are both known to be transcriptionally active in human placenta. In the case of ERV3 there is also indirect evidence for its participation in cellular differentiation. In this study we examined the expression of ERV3 (HERV-R) and HERV-K in human normal fetal tissues by in situ hybridization. The highest level of ERV3 env expression was detected in primitive adrenal cortex. Elevated levels of expression were also found in the following developing tissues: kidneys (tubules), tongue, heart, liver, and central nervous system. Tissue-specific expression was found for HERV-K rec (former cORF) but not for pol/int transcripts. The highest rec expression was found in placenta and levels slightly higher than sense control were found in the rest of the tissues examined. Pol/Int was not possible to quantitate. It appears that ERV3 is expressed in an organ-specific way during embryogenesis and might suggest a possible role in the development and differentiation of human tissues.