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Safety Pharmacology and the GI Tract
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
The guidelines suggest evaluation on gastric secretion, gastrointestinal mucosal injury potential, bile secretion, and intestinal transit time. The investigator has discretion on which testing shall be used depending on the class of pharmacological agent being developed. The tests recommended, but not required, to provide important information on safety and potential side effects, including gastric ulcerogenicity (rat), gastric acid secretion, (rat), gastric emptying (rat), fecal pellet output (mice or rats), emesis (ferret), intestinal transit (mice or rats), and biliary secretion (rat), pancreatic secretion (rat). This chapter will not consider in vitro organ bath systems since they do not appear to offer useful additional information in most cases.
Effects of COX inhibitors on responsiveness of the tracheal tract to acetylcholine and histamine and their relationship with LTC4 and PGE2 levels of bronchoalveolar lavage fluid in allergic Guinea pigs
Published in Toxicology Mechanisms and Methods, 2020
Ali Rassouli, Hossein Keshavraz Tarikhi, Goudarz Sadeghi Sadeghi, Hadi Tabarraei, Farhang Sasani, Sepideh Ghaffari, Mohammad Amin Fayaz, A. Wallace Hayes
On day 19, twenty-four h after being challenged with ovalbumin, guinea pigs were euthanized with an i.p injection of thiopental sodium (100 mg/kg) (ACLAM Task Force 2006) Immediately after death, the trachea was exposed and cut from the larynx by a longitudinal incision on the neck. Five mL of Krebs’ solution was infused three times into the lungs using an endotracheal tube at 37 °C and after one min the liquid was collected and centrifuged. The supernatant fraction was used for total protein and the remained liquid was kept at −70 °C for PGE2 and LTC4 measurements. The sediment after centrifugation was used for evaluation of inflammatory cells. The trachea from each guinea pig was cut into three sections each consisting of four cartilage rings. These sections were placed in an organ bath with warm water.
Intact coronary and myocardial functions after 24 hours of non-ischemic heart preservation
Published in Scandinavian Cardiovascular Journal, 2020
Guangqi Qin, Björn Wohlfart, Long Zuo, Jingfeng Hu, Trygve Sjöberg, Stig Steen
The same type of organ bath as described above was used. Preformed loops of thread were tied at either side of the trabecula and these were used to mount the preparation in the organ bath between two metal holders, one connected to a force transducer (Figure 1). After mounting, there was a run-in period of 30–45 min with electric stimulation to obtain an equilibration in force development. The signals from stimulation and force were continuously stored on computer (AD instruments Ltd, Oxford, United Kingdom). The optimum muscle length for force production was established in each preparation by stretching the muscle in small steps and monitoring the force (Frank-Starling law). At optimal muscle tension the size of the trabecula was measured using the stereo microscope (Zeiss) at 10 × magnification. The size did not differ between the groups. The preparations had a mean length of 3.8 ± 1.2 (SD) mm and a diameter of 0.59 ± 0.17 (SD) mm. The diameters were used to measure force production in units of mN/mm2. Stimulation took place by means of a pair of electrodes placed under the muscle. The stimulus pulse was 5 ms in duration and with amplitude of 150% of the threshold value. Measurements were made at 60/min. A typical force recording is shown in Figure 1.
Inducing intravesical hyperthermia of the ex-vivo porcine bladder wall: radiofrequency-induction versus recirculation using a custom-made device
Published in International Journal of Hyperthermia, 2018
F. J. P. van Valenberg, J. A. Witjes, B. Aklan, S. F. de Jong, H. Zegers, E. Oosterwijk
Bladders were taken from 12 female pigs weighing 80–100 kg from a commercial slaughterhouse within 3 h of sacrifice. They were placed in a temperature-controlled 0.9% NaCl bath to simulate body temperature and heat dissipation (flow organ bath 2.0 L/min, volume 10 L). The temperature of the organ bath was kept constant at 37 °C to mimic that of humans. A three-way 20-French catheter containing three mucosal and two urethral thermocouples (TCs) and a 915 MHz RF antenna was placed intravesically. Additional TCs were surgically placed at different tissue levels (Figure 1). A solution of 50 mL of NaCl 0.9% was used intravesically.