Polyphenols, a group of complex naturally occurring compounds, are widely distributed throughout the plant kingdom and thus are readily consumed by humans.1,2) As members of the polyphenol family, dietary anthraquinones have received much attention as potential protectors against a variety of human diseases, in particular cardiovascular disease and cancer.3,4) Emodin (1,3,8-trihydroxy-6-methylanthraquinone), the active components of many herbal laxatives such as aloe, senna, cascara sagrada, and rhubarb, belongs to the anthraquinone family. 5,6) Intestinal absorption is a prerequisite for a possible causal relationship between emodin intake and its proposed chemopreventive action. However, our limited knowledge of how emodin is absorbed and metabolized has hampered our understanding of its effect in the body. In addition, some similar compounds have poor bioavailability due to weak absorption and significant degradation by enzymes. 7) Furthermore, to date, information on in vivo absorption and metabolism of emodin is scarce-there are no reports of evidence of extensive first-pass metabolism of emodin in the gut-and thus intestinal handling of emodin requires further investigation to appraise its beneficial action in vivo.To address this issue, we evaluated the contribution of the small intestine to the absorption and first-pass metabolism of emodin using an isolated rat small intestine perfusion model. This model facilitates direct investigation of luminal disappearance and venous appearance of administered emodin and analyses the metabolites in both perfusate and mesenteric blood, thereby allowing the direct estimation of intestinal absorption and first-pass metabolism of this drug. 8,9) MATERIALS AND METHODS Reagents and ChemicalsEmodin and chrysophanol was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China) at the highest purity available (98%, as determined by HPLC). Emodin was dissolved in DMSO (0.1% v/v final concentration) because it is hydrophobic and poorly soluble in water. b-Glucuronidase (catalog no. G-0251) and sulfatase (catalog no. S-9754) were purchased from Sigma. All chemicals and reagents used were of analytical grade or HPLC grade.Animals Male Sprague-Dawley rats (70-110 d old) weighing between 270 and 320 g were obtained from the experimental animal center of the Fourth Military Medical University, Xi'an, China. The rats were fasted overnight with free access to water before the day of the experiment.Animal Surgery The rats were anesthetized with an intra-abdominal injection of a mixture containing 40 mg/kg phenobarbital sodium. The animals were then heparinized (90 U/kg Ϫ1 ) via the vena caudalis. During surgery, the body temperature was maintained at 37°C by a heating lamp.The small intestine was prepared as described. [10][11][12] Figure 1 schematically illustrates the vascular-luminal perfused rat intestine preparation. Briefly, the small intestine was exposed by midline incision, and a 7-to 11-cm-long segment of the intestin...
Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A4 which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE). CBZE is an active and toxicity metabolite, and it is a substrate of MRP-2. Using CBZ for a long time can cause hepatic injury. Sophora flavescens (SF) is a medicinal herb used for the protected hepatic injury. This study investigated the acute and chronic effects of SF on the pharmacokinetics of CBZ in rats. The concentrations of CBZ and CBZE in plasma and tissues were determined by HPLC method. The results showed that SF which significantly decreased the AUC0-t of CBZ, increased CBZE conversely. Tissue analysis showed that the concentrations of CBZ and CBZE in brain and liver were decreased by SF. In addition, the distribution of CBZE in kidney was reduced significantly, which influenced the CBZE excretion and increased the drug toxic potentially. Results in the current study suggest that patients using CBZ might be cautioned in the use of SF extract or Sophora-derived products. Meanwhile, patients receiving drugs which are substrates of CYP 3A4 and/or MRP-2 should be advised of the potential herb-drug interaction to reduce the risk of therapeutic failure or increased toxicity of conventional drug therapy.
The majority of digital sensors rely on von Neumann architecture microprocessors to process sampled data. When the sampled data require complex computation for 24×7, the processing element will a consume significant amount of energy and computation resources. Several new sensing algorithms use deep neural network algorithms and consume even more computation resources. High resource consumption prevents such systems for 24×7 deployment although they can deliver impressive results. This work adopts a Computing-In-Memory (CIM) device, which integrates a storage and analog processing unit to eliminate data movement, to process sampled data. This work designs and evaluates the CIM-based sensing framework for human pose recognition. The framework consists of uncertainty-aware training, activation function design, and CIM error model collection. The evaluation results show that the framework can improve the detection accuracy of three poses classification on CIM devices using binary weights from 33.3% to 91.5% while that on ideal CIM is 92.1%. Although on digital systems the accuracy is 98.7% with binary weight and 99.5% with floating weight, the energy consumption of executing 1 convolution layer on a CIM device is only 30,000 to 50,000 times less than the digital sensing system. Such a design can significantly reduce power consumption and enables battery-powered always-on sensors.
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