Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation.

Aristolochic acid contamination in herbal remedies leads to interstitial fibrosis, tubular atrophy, and renal failure in humans. To study the cellular mechanisms contributing to the pathophysiology of this renal disease, we studied Wistar rats treated with aristolochic acid and measured tubular and interstitial cell proliferation, epithelial/mesenchymal cell marker expression, tubular membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin concomitant with vimentin expression, basement membrane denudation with active caspase-3 expression, and mitochondrial injury within tubular cells were evident within 5 days of administration of the toxin. During the chronic phase, interstitial mesenchymal cells accumulated in areas of collagen deposits. Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule atrophy with a near absence of dedifferentiated cell transmembrane migration. We suggest that resident fibroblast activation plays a critical role in the process of renal fibrosis during aristolochic acid toxicity.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Clinical significance of blood-device interaction in hemodialysis

The syndrome of dialysis-associated leukopenia and complement activation by cellulosic membranes, including the so-called "first use syndrome", is reviewed and the pathophysiology of these phenomena is discussed. Subsequently the clinical side effects of hemodialysis, including dialysis-associated hypoxemia, are discussed. The hypoxemia, according to the authors, is mainly related to the loss of carbon dioxide through the dialyser. A minor role may be played by complement activation causing temporary sequestration of leukocytes in the pulmonary capillaries with (asymptomatic) peripheral leukopenia on the one hand and plugging of the pulmonary capillary bed with transient pulmonary hypertension and hypoxemia on the other. The question of dialysis-associated eosinophilia and ethylene oxide hypersensitivity is addressed as also contributing to the first use syndrome. The effects of interleukin release from monocytes and of contamination of the dialysis fluid are briefly discussed. The rare syndrome of silicone rubber spallation with hepato-and splenomegaly is also mentioned and finally the pathogenesis and symptomatology of the beta 2 microglobulin amyloidosis syndrome in long-term dialysis patients is presented.Journal ArticleReviewinfo:eu-repo/semantics/publishe

厚朴及其成分的生物活性和毒性

Traditional Chinese herbal drugs have been used for thousands of years in Chinese pharmacopoeia. The bark of Magnolia officinalis Rehder & E. Wilson, known under the pinyin name “Houpo”, has been traditionally used in Chinese and Japanese medicines for the treatment of anxiety, asthma, depression, gastrointestinal disorders, headache, and more. Moreover, Magnolia bark extract is a major constituent of currently marketed dietary supplements and cosmetic products. Much pharmacological activity has been reported for this herb and its major compounds, notably antioxidant, anti-inflammatory, antibiotic and antispasmodic effects. However, the mechanisms underlying this have not been elucidated and only a very few clinical trials have been published. In vitro and in vivo toxicity studies have also been published and indicate some intriguing features. The present review aims to summarize the literature on M. officinalis bark composition, utilisation, pharmacology, and safety