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A wireless multisensor telemetry capsule for monitoring gastrointestinal function in the dog
e58
Abstracts
Gastro-intestinal (GI) side effects are common in clinical trials. Since studies on GI function are not core battery studies (ICHS7A), preclinical testing is rarely done. Effects on GI function using barium sulfate in the rat can detect upper GI effects but only single time points p.a. can be tested. We have tested a prototype, telemetry-based system for monitoring total GI transit time in the conscious, unrestrained dog. Two female beagle dogs were instrumented with a prototype GItelemetry total implant system (ITS). Twelve magnetic sensors were sutured on the gut wall from esophagus to rectum. After recovery, the dogs received orally a small magnet to assess GI-transit time. NOTOCORD HEM 4.2 software was used for data acquisition and Microsoft EXCEL was used for data analysis. Effects of feeding status on GI transit were determined. Five different magnet types were used to assess signal strength/noise ratios. A barium sulfate meal together with a magnet was used to compare techniques. The implant and oral application of the magnet were well tolerated. The GI-emptying time was 10 ± 2 h when the dogs were fasted but was delayed (up to 24 h) when given a high caloric meal. The intestinal transit time was 6–8 h, independent of feeding. This was the same as after receiving a barium sulfate meal. The average transit times seen are comparable to published data for the dog using other approaches. This new GI telemetry system is a novel method for assessing GI function in the dog or potentially other species (e.g. primate). Further evaluation will be performed using compounds known to accelerate or delay the GI-transit time. doi:10.1016/j.vascn.2011.03.199
Poster No: 195 A wireless multisensor telemetry capsule for monitoring gastrointestinal function in the dog Stephane P. Milano a, Stephane Baudet a, Estelle Chalencon a, Philippe Lege a, Celine Dupuis a, Jack Semler b, Bemina Rhode b a b
RICERCA BIOSCIENCES, France SMARTPILL CORPORATION, USA
Alterations in gastrointestinal (GI) function are common side effects of many drugs, not limited to those administered orally. Preclinically, GI disturbances such as intestinal/colonic motility, gastric emptying/secretion are generally assessed in a number of usually rodent systems, to provide a safety pharmacology evaluation. In these models, measurements are usually performed in the context of a non-caloric meal, use large cohorts of animals and require terminal sacrifice. SmartPill® is an ingestible, wireless motility capsule which provides ambulatory testing for GI pressure, temperature, luminal pH, gastric emptying time and intestine transit time. This device, although extensively tested in humans, has not been fully evaluated in dogs. The objective of this study was to assess the feasibility of measuring GI transit time and gastric pH in dogs in safety pharmacology studies. Four female beagle dogs were used. Following overnight fasting, animals were fed with 100 g of canned food. The SmartPill® was administered immediately following food consumption. Dogs were equipped with pocketed jackets to hold the data receiver, and animals were returned to their pens. Dogs were monitored until the capsule was expelled in the feces. In order to evaluate the ability of the SmartPill® to reliably detect GI effects of drugs, animals were treated with a pro-kinetic (erythromycin), an anti-kinetic (morphine) and an anti-acid (pantoprazole).
Our results show that the SmartPill® technology is a novel, noninvasive method for assessing several aspects of GI function in the dog. doi:10.1016/j.vascn.2011.03.200
Poster No: 196 An evaluation of staining procedures for cytocochleogram analysis of middle ear organ of corti surface preparations Rachel L. Tapp, Matthew M. Abernathy, Joshua D. Yoder, Andrea A. Koch, Stephanie M. Tack, Richard N. Voci, Brett L. Toman, Phaedra I. Cole, Derek J. Gregorich, David V. Gauvin, Theodore J. Baird Safety Pharmacology and Neurobehavioral Sciences, MPI Research, Mattawan, MI, USA Cytocochleogram analysis including middle ear hair cell counts is a vital endpoint for ototoxicity evaluation of select new potential therapeutics. During a validation of histological procedures to microdissect and stain the organ of corti, we evaluated exposure duration of the fixatives and stains that provided the best slides towards quantitative assessment of inner and outer hair cells. Optimization of the staining procedures was conducted to provide the best stereocillia resolution and to reduce the photobleaching that occurs with the fluorescent stains that are typically utilized. The procedures included 4 staining conditions following a standard fixative. Exposure times for Triton-X100 and Phalloidin were varied for these condition tests, and two middle ear tissues were tested for each set of conditions. The tissues from the test conditions were mounted, stained, and reviewed by a cytocochleogram analyst to determine which staining procedure provided for the optimal tissue evaluation. It was determined that the optimal staining procedure for the tissues for cytocochleogram analysis was 45 min for Triton-X100 and 90 min for Phalloidin, resulting in reduced photobleaching and increased cellular definition which allowed the most accurate hair cell counts. doi:10.1016/j.vascn.2011.03.201
Poster No: 197 A novel algorithm for quantifying multiunit peripheral nerve activity Marina V. Brockway a, Pilar Guzman b, Marcos Kuroki b, John W. Osborn b a
VivaQuant, LLC/ University of Minnesota, St Paul, MN, United States University of Minnesota Dept. of Integrative Biology and Physiology, Minneapolis, MN, United States
b
Although methods for long-term recording of peripheral nerve activity (PNA) in conscious animals have become available, the poor signal-to-noise ratio (SNR) that is characteristic of PNA recordings has limited the use of PNA preparations in understanding the role of neural control of physiological function. A novel software algorithm Multi-Domain Signal Processing (MDSP) for analysis, de-noising, and quantification of PNA has been developed. The MDSP technique removes noise and artifact from PNA recordings including myoelectric artifacts, thermal, electrical and other noises while preserving information regarding the underlying PNA. In addition to de-noising, the technique includes a rigorous computation of integrated PNA that more accurately reflects neural spike activity and avoids the time lag
Abstracts
Gastro-intestinal (GI) side effects are common in clinical trials. Since studies on GI function are not core battery studies (ICHS7A), preclinical testing is rarely done. Effects on GI function using barium sulfate in the rat can detect upper GI effects but only single time points p.a. can be tested. We have tested a prototype, telemetry-based system for monitoring total GI transit time in the conscious, unrestrained dog. Two female beagle dogs were instrumented with a prototype GItelemetry total implant system (ITS). Twelve magnetic sensors were sutured on the gut wall from esophagus to rectum. After recovery, the dogs received orally a small magnet to assess GI-transit time. NOTOCORD HEM 4.2 software was used for data acquisition and Microsoft EXCEL was used for data analysis. Effects of feeding status on GI transit were determined. Five different magnet types were used to assess signal strength/noise ratios. A barium sulfate meal together with a magnet was used to compare techniques. The implant and oral application of the magnet were well tolerated. The GI-emptying time was 10 ± 2 h when the dogs were fasted but was delayed (up to 24 h) when given a high caloric meal. The intestinal transit time was 6–8 h, independent of feeding. This was the same as after receiving a barium sulfate meal. The average transit times seen are comparable to published data for the dog using other approaches. This new GI telemetry system is a novel method for assessing GI function in the dog or potentially other species (e.g. primate). Further evaluation will be performed using compounds known to accelerate or delay the GI-transit time. doi:10.1016/j.vascn.2011.03.199
Poster No: 195 A wireless multisensor telemetry capsule for monitoring gastrointestinal function in the dog Stephane P. Milano a, Stephane Baudet a, Estelle Chalencon a, Philippe Lege a, Celine Dupuis a, Jack Semler b, Bemina Rhode b a b
RICERCA BIOSCIENCES, France SMARTPILL CORPORATION, USA
Alterations in gastrointestinal (GI) function are common side effects of many drugs, not limited to those administered orally. Preclinically, GI disturbances such as intestinal/colonic motility, gastric emptying/secretion are generally assessed in a number of usually rodent systems, to provide a safety pharmacology evaluation. In these models, measurements are usually performed in the context of a non-caloric meal, use large cohorts of animals and require terminal sacrifice. SmartPill® is an ingestible, wireless motility capsule which provides ambulatory testing for GI pressure, temperature, luminal pH, gastric emptying time and intestine transit time. This device, although extensively tested in humans, has not been fully evaluated in dogs. The objective of this study was to assess the feasibility of measuring GI transit time and gastric pH in dogs in safety pharmacology studies. Four female beagle dogs were used. Following overnight fasting, animals were fed with 100 g of canned food. The SmartPill® was administered immediately following food consumption. Dogs were equipped with pocketed jackets to hold the data receiver, and animals were returned to their pens. Dogs were monitored until the capsule was expelled in the feces. In order to evaluate the ability of the SmartPill® to reliably detect GI effects of drugs, animals were treated with a pro-kinetic (erythromycin), an anti-kinetic (morphine) and an anti-acid (pantoprazole).
Our results show that the SmartPill® technology is a novel, noninvasive method for assessing several aspects of GI function in the dog. doi:10.1016/j.vascn.2011.03.200
Poster No: 196 An evaluation of staining procedures for cytocochleogram analysis of middle ear organ of corti surface preparations Rachel L. Tapp, Matthew M. Abernathy, Joshua D. Yoder, Andrea A. Koch, Stephanie M. Tack, Richard N. Voci, Brett L. Toman, Phaedra I. Cole, Derek J. Gregorich, David V. Gauvin, Theodore J. Baird Safety Pharmacology and Neurobehavioral Sciences, MPI Research, Mattawan, MI, USA Cytocochleogram analysis including middle ear hair cell counts is a vital endpoint for ototoxicity evaluation of select new potential therapeutics. During a validation of histological procedures to microdissect and stain the organ of corti, we evaluated exposure duration of the fixatives and stains that provided the best slides towards quantitative assessment of inner and outer hair cells. Optimization of the staining procedures was conducted to provide the best stereocillia resolution and to reduce the photobleaching that occurs with the fluorescent stains that are typically utilized. The procedures included 4 staining conditions following a standard fixative. Exposure times for Triton-X100 and Phalloidin were varied for these condition tests, and two middle ear tissues were tested for each set of conditions. The tissues from the test conditions were mounted, stained, and reviewed by a cytocochleogram analyst to determine which staining procedure provided for the optimal tissue evaluation. It was determined that the optimal staining procedure for the tissues for cytocochleogram analysis was 45 min for Triton-X100 and 90 min for Phalloidin, resulting in reduced photobleaching and increased cellular definition which allowed the most accurate hair cell counts. doi:10.1016/j.vascn.2011.03.201
Poster No: 197 A novel algorithm for quantifying multiunit peripheral nerve activity Marina V. Brockway a, Pilar Guzman b, Marcos Kuroki b, John W. Osborn b a
VivaQuant, LLC/ University of Minnesota, St Paul, MN, United States University of Minnesota Dept. of Integrative Biology and Physiology, Minneapolis, MN, United States
b
Although methods for long-term recording of peripheral nerve activity (PNA) in conscious animals have become available, the poor signal-to-noise ratio (SNR) that is characteristic of PNA recordings has limited the use of PNA preparations in understanding the role of neural control of physiological function. A novel software algorithm Multi-Domain Signal Processing (MDSP) for analysis, de-noising, and quantification of PNA has been developed. The MDSP technique removes noise and artifact from PNA recordings including myoelectric artifacts, thermal, electrical and other noises while preserving information regarding the underlying PNA. In addition to de-noising, the technique includes a rigorous computation of integrated PNA that more accurately reflects neural spike activity and avoids the time lag