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Traditional Chinese Medicine (TCM) consists of a plethora of therapeutic approaches aiming to both characterize and treat diseases. Its utilization has gained significant popularity in the western world and is even backed by the World Health Organization's decision to include TCM diagnostic patterns into the new revision of the International Classification of Diseases code, the global standard for diagnostic health information. As these developments and potentially far-reaching decisions can affect modern healthcare systems and daily clinical work as well as wildlife conservation, its underlying factual basis must be critically examined. This article therefore provides an overview of the evidence underlying the basic TCM concepts, such as Qi, meridians, acupuncture, pulse and tongue diagnostics as well as traditional herbal treatments. Moreover, it discusses whether scientific literature on TCM reflects the current standard for evidence-based research, as described in good scientific practice and good clinical practice guidelines. Importantly, misinformation regarding the therapeutic efficacy of animal-derived substances has lead and currently leads to problems with wildlife preservation and animal ethics. Nevertheless, the (re-)discovery of artemisinin more than 50 years ago introduced a novel development in TCM: the commingling of Eastern and Western medicine, the appreciation of both systems. The need for more rigorous approaches, fulfilment of and agreement to current guidelines to achieve highquality research are of utmost relevance. Thereby, ancient knowledge of herbal species and concoctions may serve as a possible treasure box rather than Pandora's box.
Ascorbic acid (AA; or vitamin C) is an important physiological antioxidant and radical scavenger. Some mammalian species, including homo sapiens, have lost the ability to synthetize AA and depend on its nutritional uptake. Erythrocytes from AA-auxotroph mammals express high amounts of the glucose transporter GLUT1. This isoform enables rapid uptake of glucose as well as dehydroascorbate (DHA), the fully oxidized form of AA. Here, we explored the effects of DHA uptake on the redox metabolism of human erythrocytes. DHA uptake enhanced plasma membrane electron transport (PMET) activity. This process is mediated by DCytb, a membrane bound cytochrome catalyzing extracellular reduction of Fe3+ and ascorbate free radical (AFR), the first oxidized form of AA. DHA uptake also decreased cellular radical oxygen species (ROS) levels. Both effects were massively enhanced in the presence of physiological glucose concentrations. Reduction of DHA to AA largely depleted intracellular glutathione (GSH) and induced the efflux of its oxidized form, GSSG. GSSG efflux could be inhibited by MK-571 (IC50 = 5 μM), indicating involvement of multidrug resistance associated protein (MRP1/4). DHA-dependent GSH depletion and GSSG efflux were completely rescued in the presence of 5 mM glucose and, partially, by 2-deoxy-glucose (2-DG), respectively. These findings indicate that human erythrocytes are physiologically adapted to recycle AA both intracellularly via GLUT1-mediated DHA uptake and reduction and extracellularly via DCytb-mediated AFR reduction. We discuss the possibility that this improved erythrocyte-mediated AA recycling was a prerequisite for the emergence of AA auxotrophy which independently occurred at least twice during mammalian evolution.
Original Clinical Science-General Background. Pretransplant kidney graft biopsies have been suggested for organ quality assessment. Data on the association between donor proteinuria and organ quality of deceased donors are not available. Methods. In this prospective study, we analyzed 147 pretransplant kidney biopsies from 88 deceased adult donors procured and transplanted consecutively at the Medical University Vienna between July 2017 and May 2020. Lesions in each renal compartment were scored from 0 to 5 with each ascending score representing a 20% increase in organ damage. A chronic lesions score was calculated including glomerulosclerosis, intima fibrosis, hyalinosis, interstitial fibrosis, and tubular atrophy. Results. The median chronic lesion score was 2 (interquartile range [IQR] 1-4) and the median donor urinary protein to creatinine ratio (UPCR) was 382 mg/dL (IQR 222-703). There was a positive correlation between UPCR and number of chronic lesions (β 0.15, 95% confidence interval, 0.03-0.28; P = 0.019). Biopsies with 2 or more lesions had a median UPCR of 486 mg/dL (IQR 251-717) compared with 274 mg/dL (IQR 211-556; P = 0.016) in biopsies with <2 lesions. The risk for detection of 2 or more lesions rose by 18% for every log increase in UPCR (risk ratio 1.18, 95% confidence interval, 1.03-1.25; P = 0.017). Multivariable and sensitivity analysis revealed an independent and robust association between chronic lesions and UPCR. Conclusions. Donor UPCR is associated with chronic lesions in pretransplant deceased donor kidney graft biopsies. This finding justifies further investigation of donor proteinuria for the assessment of organ quality and outcome. (Transplantation 2022;106: 2044-2051.
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