Easy Access to Arylboron Dichloride from Aryboronic Acid with Tetrachlorosilane

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The bioactivation of potential anti-melanoma phenolic agents in isolated rat hepatocytes

grantor: University of TorontoPrevious studies in our laboratory showed that the antimelanoma agent 4-hydroxyanisole was O-demethylated to hydroquinone, a cytotoxic metabolite, by hepatocytes via CYP2E1 and CYP1A. The cytotoxicity of 4-hydroxyanisole was attributed to benzoquinone, the autoxidation product of hydroquinone. In the following 3-hydroxyanisole was found to be more hepatotoxic than 4-hydroxyanisole both in vitro and in vivo even though resorcinol, the O-demethylated metabolite, cannot form a quinone. However, we found that CYP2E1 catalyzed the ring hydroxylation of 3-hydroxyanisole to form 4-methoxycatechol, which subsequently autoxidized to the cytotoxic o-quinone. The thiol reductant dithiothreitol and reactive oxygen species scavengers prevented 3-hydroxyanisole and catechol cytotoxicity but not 4-hydroxyanisole or hydroquinone-induced cytotoxicity. Thus, 4-hydroxyanisole toxicity appears to involve primarily protein alkylation while 3-hydroxyanisole cytotoxicity may be due to oxidative stress as a result of reductive oxygen activation. Cu\sp{2+} and peroxidase could also catalyze 3- and 4-hydroxyanisole bioactivation via a one electron oxidation to form quinones and phenoxyl radicals, respectively.M.Sc

Central and Peripheral Mechanism of Acupuncture Analgesia on Visceral Pain: A Systematic Review

Background/Aims. Despite the wide use of acupuncture for the management of visceral pain and the growing interest in the pathophysiology of visceral pain, there is no conclusive elucidation of the mechanisms behind the effects of acupuncture on visceral pain. This systematic review aims to provide an integrative understanding of the treatment mechanism of acupuncture for visceral pain. Methods. Electronic and hand searches were conducted to identify studies that involved visceral pain and acupuncture. Results. We retrieved 192 articles, out of which 46 studies were included in our review. The results of our review demonstrated that visceral pain behaviors were significantly alleviated in response to acupuncture treatment in groups treated with this intervention compared to in sham acupuncture or no-treatment groups. Changes in the concentrations of β-endorphin, epinephrine, cortisol, and prostaglandin E2 in plasma, the levels of c-Fos, substance P, corticotropin-releasing hormone, P2X3, acetylcholinesterase (AchE), N-methyl-D-aspartate (NMDA) receptors, and serotonin in the gut/spinal cord, and the neuronal activity of the thalamus were associated with acupuncture treatment in visceral pain. Conclusions. Acupuncture reduced visceral pain behavior and induced significant changes in neuronal activity as well as in the levels of pain/inflammation-related cytokines and neurotransmitters in the brain-gut axis. Further researches on the thalamus and on a standard animal model are warranted to improve our knowledge on the mechanism of acupuncture that facilitates visceral pain modulation

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Document(en) uit de collectie Chemische ProcestechnologieDelftChemTechApplied Science

Pharmacopuncture for Cancer Care: A Systematic Review

Background. Pharmacopuncture, injection to acupoints with pharmacological medication or herbal medicine, is a new acupuncture therapy widely available in Korea and China for cancer-related symptoms. However, the evidence is yet to be clear. Objective. To determine pharmacopuncture’s effectiveness on cancer-related symptoms. Methods. Eleven databases were searched for randomized controlled trials of pharmacopuncture in cancer patients. The Cochrane risk of bias (ROB) assessment tool was used for quality assessment. Results. Twenty-two studies involving 2,459 patients were included. Five trials of chemotherapy-induced nausea and vomiting (CINV) underwent meta-analysis. Pharmacopuncture significantly relieved severity of CINV compared with control group (3 trials, risk ratio (RR) 1.28, 95% confidence interval (CI) = 1.14–1.44). The frequency of CINV was also significantly reduced with pharmacopuncture (2 trials, RR 2.47, 95% CI = 2.12–2.89). Seventeen trials studied various symptoms, and in most studies, pharmacopuncture significantly relieved pain, ileus, hiccup, fever, and gastrointestinal symptoms and improved quality of life in various cancer patients. ROB was generally high. Conclusion. It may be suggested with caution that pharmacopuncture may help various symptom relief in cancer patients, but it is hard to draw a firm conclusion due to clinical heterogeneity and high ROB of the included studies, hence warranting further investigation