ABSTRACT:Blood-based vascular perfusion of isolated segments of human jejunum was developed as a tool for drug absorption studies before clinical trials. Acceptance criteria for viable human gut preparations included stable blood flow, arterial pressure, glucose utilization, active peristalsis, oxygen uptake, less than 3% absorption of a 70,000 mol. wt. dextran, and a ratio of first-order absorption rate constants (k a ) of antipyrine to terbutaline of >1.4. Mannitol absorption was less than that of antipyrine but larger than that of terbutaline and could not be used as a negative control in absorption studies with human intestine. In separate perfusions (n ‫؍‬ 3) a cassette of nine drugs was administered into the gut lumen, and the net absorption of each drug into the circulation was measured over 75 min. Using the mean values of k a , the test compounds could be ranked into four groups: group 1: sulfasalazine and furosemide, k a ‫؍‬ 3.9 to 4.0 ؋ 10 ؊3 min ؊1 ; group 2: cimetidine, timolol, nadolol, and ranitidine, k a ‫؍‬ 6.4 to 8.3 ؋ 10 ؊3 min ؊1; group 3: atenolol and metoprolol, k a ‫؍‬ 9.6 ؋ 10 ؊3 min ؊1 ; and group 4: theophylline, k a ‫؍‬ 17.5 ؋ 10 ؊3 min ؊1. The rationale for evaluating yet another oral absorption system was as follows: first, a human gut segment with an intact vascular system is the closest system available to a clinical trial without performing one; and second, the data generated would be a direct measure of net drug transport from the gut lumen into the vascular circulation under near physiological conditions, which is not possible in models lacking a blood supply.In drug development programs, knowledge of the range of oral absorption from gut lumen into blood in human subjects can be one of the key factors in drug candidate selection. Consequently, considerable resources and ingenuity have been applied to the development and validation of preclinical models, which are then claimed to predict oral absorption in vivo in human subjects. These diverse models span a broad range of biological complexity from isolated cells in culture (Arturrsson and Karlsson, 1991;Hilgendorf et al., 2000), mucosal sheets (Jezyk et al., 1992), everted gut sacs (Barthe et al., 1998), in situ lumen perfusion of animal intestine (Cao et al., 2006;Castella et al., 2006; Zakeri-Milania et al., 2007), and vascular perfused animal intestine (Roy et al., 1991) to whole animal absorption studies in vivo. Invariably, these model systems are validated by a quantitative comparison against standard human absorption data in vivo, such as percent fraction of dose absorbed (FA) obtained from oral versus intravenous pharmacokinetics in vivo or disappearance of native drug from the gut lumen in vivo (Lennernäs, 1998(Lennernäs, , 2007. However, the percent FA for a single compound, even in the same subject, is not a unique number because absorption is known to be affected by a variety of host factors including absorptive surface area, local pH, food effects, blood flow, intestinal transporter, and enzyme compliment. These an...

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The scientific community is looking for efficient solutions to improve the quality of life in large cities because of traffic congestion, driving experience, air pollution, and energy consumption. This surge exceeds the capacity of existing transit infrastructure and parking facilities. Intelligent Parking Systems (SPS) that can accommodate short-term parking demand are a must-have for smart city development. SPS are designed to count the number of parked automobiles and identify available parking spaces. In this paper, we present a novel SPS based on real-time computer vision techniques. The proposed system provides features including: vacant parking space recognition, inappropriate parking detection, forecast of available parking spaces, and directed indicators toward various sorts of parking spaces (vacant, occupied, reserved and handicapped). Our system leverages existing video surveillance systems to capture, process image sequences, train computer models to understand and interpret the visual world, and provide guidance and information to the drivers.