ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Eval... more ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Evaluation Program (PEP), which focuses on microbial monitoring by and for laboratory animal diagnostic laboratories, and the Genetic Reference Monitoring Program (GENRef), which provides assay-ready reference DNA for genetic testing of mouse strains. Since 2008, PEP has grown to become a truly international program with participating laboratories in 5 continents. Launched in 2016, GENRef currently distributes DNA from 12 common inbred mouse strains for use in genetic monitoring of locally inbred colonies as well as for genetic testing of stocks, particularly genetically engineered stocks, of uncertain origins. GENRef has the capacity to include additional strains as well as additional species. PEP and GENRef provide the reagents at cost, as a resource to the international scientific community, in the interest of improving research quality in an environment of growing concern for research qu...
G A A b st ra ct s showed a 2-fold (p<0.05) increase in Brain-derived neurotrophic factor (BDN... more G A A b st ra ct s showed a 2-fold (p<0.05) increase in Brain-derived neurotrophic factor (BDNF) mRNA and a 50% decrease in the mRNA of Kv1.1 channels, compared with controls. BDNF protein was increased 50% (p<0.05) in the thoracic spinal cord. Intrathecal administration of Kv1.1 siRNA in naive rats significantly increased sensitivity to gastric distention, suggesting that the suppression of Kv1.1 contributes to GHS. Intrathecal treatment with a BDNF antagonist, trkB-Fc, significantly reduced gastric hypersensitivity in FD rats. Nerve growth factor (NGF) protein expression was 75% (p<0.05) greater in fundic muscularis externa of FD rats. Systemic treatment with an NGF antibody significantly attenuated gastric hypersensitivity. The plasma concentration of norepinephrine was significantly greater in FD rats, compared with control rats. Treatment of fundic muscularis externa In Vitro with norepinephrine produced a 50% (p<0.05) increase in NGF expression. Sodium butyrate, a histone deacetylase inhibitor, treatment in sensitized FD rats significantly reduced both gastric hypersensitivity and NGF expression in the fundus. Conclusions: Neonatal inflammatory insult induces persistent gastric hypersensitivity in adulthood. A persistent increase in plasma norepinephrine mediates GHS by elevating NGF in muscularis externa, which suppresses Kv1.1 channels in DRGs and enhances BDNF in DRGs and thoracic spinal cord. The normalization of gastric hypersensitivity by sodium butyrate suggests epigenetic dysregulation of genes.
Globalization of science and ethical values have led to implementation of regulations on protecti... more Globalization of science and ethical values have led to implementation of regulations on protection of animals used for scientific purposes worldwide, based on the principles of replacement (to avoid or replace the use of animals), reduction (to minimize the number of animals used), and refinement (to minimize animal suffering and increase animal well-being). However, while regulations in individual countries are generally based on these principles, there are variations in the way they are practically applied. For this reason, international and global organizations have developed guiding principles to harmonize animal care and use and have issued recommendations, which can be similarly applied irrespective of the regulatory framework operating in a particular country. This introductory chapter describes the principles underlying current animal research legislation and summarizes the efforts made by global organizations and professional associations to harmonize their implementation.
He was a specialist in pathology and radiobiology and an important influence in the development o... more He was a specialist in pathology and radiobiology and an important influence in the development of laboratory animal science in Belgium and in the early years of the International Council for Laboratory Animal Science (ICLAS). Married and a father of three children, Jean-ReneḾ aisin obtained his medical degree in 1954, becoming a specialist in pathology in 1959 and in radiobiology in 1961. He worked at the Center for Nuclear Energy Studies in Mol (CEN-SCK), where he was the Head of the Department of Radiobiology. In 1981, he became Professeur Extraordinaire at the Universite´Catholique de Louvain (UCL) and Professor Emeritus in 1993. After his period as emeritus professor, he was Vice-Chair of the Belgian Deontological Committee on the use of Laboratory Animals at the Ministry of Public Health, and chairman of the working group ''Science and Technology'' of the same Committee. Jean-Rene´Maisin was also a founding member and President of the Belgian Council for Laboratory
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1995
Infusion of lipids into the ileum delays gastric emptying and intestinal transit time in some spe... more Infusion of lipids into the ileum delays gastric emptying and intestinal transit time in some species. The aim of this study was to characterize the actions of intraluminal lipid infusion on gastrointestinal electrical activity in chickens. Animals were prepared for electromyography with chronic electrodes in stomach, duodenum, and small intestine. Two catheters were chronically placed in the esophagus and ileum to infuse equimolar doses of either oleic acid (OA) or triolein (TO). Both OA and TO, esophageally infused, inhibited the frequency of the gastroduodenal cycle and increased the frequency of antiperistaltic spike bursts in the duodenum. Ileal infusion of OA, but not of TO, produced the same effects. Both esophageal and ileal OA infusion increased the duration of the migrating myoelectric complex (MMC) and decreased the speed of propagation of phase III. In conclusion, intraluminal infusion of lipids modulates gastrointestinal motility by decreasing the frequency of the gastr...
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1993
Our objective was to study the mechanism of action of cholecystokinin (CCK) on the motility of th... more Our objective was to study the mechanism of action of cholecystokinin (CCK) on the motility of the gastroduodenal area. Chickens were implanted with five electrodes for electromyography in the stomach and duodenum. The effects of CCK (10(-9) mol.kg-1.10 min-1) were studied against the presence of several antagonists and in vagotomized animals. CCK caused inhibition of gastric motility and duodenal hyperactivity. Vagotomy blocked CCK responses in the stomach but not in the duodenum. Hexamethonium partially blocked gastric inhibition induced by CCK. NG-nitro-L-arginine methyl ester blocked the inhibitory response to CCK in the stomach but did not modify duodenum response. L-Arginine did not modify CCK actions. Opioid antagonists naloxone and naltrindole and adrenergic antagonists phentolamine and propranolol did not modify CCK response. Atropine did not modify duodenal response to CCK. Sodium nitroprusside (10(-8)-10(-6) mol/kg) inhibited gastroduodenal activity in a dose-related mann...
Clinics and Research in Hepatology and Gastroenterology, 2019
Introduction: Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver disea... more Introduction: Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver diseases. We administered Ketotifen, a mast cell stabilizer, and measured the mast cells in the splanchnic organs of cholestatic rats. Material and Methods: These groups were studied: sham-operated rats (S; n = 15), untreated microsurgical cholestasic rats (C; n = 20) and rats treated with Ketotifen: early (SK-e; n = 20 and CKe; n = 18), and late (SK-l; n = 15 and CK-l; n = 14). Results: The cholestatic rats showed systemic and splanchnic impairments, such as ascites, portal hypertension, and biliary proliferation and fibrosis. The rats also showed a splanchnic increase of TNF-␣, IL-1 and MCP-1, and a reduction of IL-4, IL-10 and antioxidants. An increase of VEGF in the ileum and mesenteric lymphatic complex was associated with a liver reduction of TGF-1. Ketotifen reduces the degree of hepatic insufficiency and the splanchnic inflammatory mediators, as well as VEGF and TGF-ß1 levels. Ketotifen also reduces the connective tissue
Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2018
The inflammatory response expressed after wound healing would be the recapitulation of systemic e... more The inflammatory response expressed after wound healing would be the recapitulation of systemic extra-embryonic functions, which would focus on the interstitium of the injured tissue. In the injured tissue, mast cells, provided for a great functional heterogeneity, could play the leading role in the re-expression of extra-embryonic functions, i.e., coelomic-amniotic and trophoblastic-vitelline. Moreover, mast cells would favor the production of a gastrulation-like process, which in certain tissues and organs would induce the regeneration of the injured tissue. Therefore, the engraftment of mesenchymal stem cells and mast cells, both with an extra-embryonic regenerative phenotype, would achieve a blastema, from the repaired and regenerated injured tissue, rather than by fibrosis, which is commonly made through wound-healing.
Cholecystokinin (CCK) regulates intestinal motility after being released by several luminal nutri... more Cholecystokinin (CCK) regulates intestinal motility after being released by several luminal nutrients. However the mechanism of action of CCK is still not well known. The aim of our study was to establish the mechanism of action of CCK in the rat intestine using an in vivo model and focusing on the nervous pathways involved in the response as well as type of receptors. Anesthetized rats were prepared with two strain-gauges, in duodenum and jejunum, to record circular muscle motor activity. A group of animals was also prepared with a catheter to infuse capsaicin inside the duodenum. Responses to CCK-octapeptide (CCK-8) as well as to CCK agonists were studied. CCK-8 was also infused after CCK antagonists, atropine, hexamethonium or L-nitroarginine. Results show that duodenal response to CCK-8 is excitatory although inhibitory responses can be induced by gastrin. In the jejunum, CCK-8 induces an inhibitory response that is mediated by both CCK-A and-B receptors. Excitatory responses to CCK-8 are due to stimulation of preganglionic receptors while inhibitory responses are NO mediated through stimulation of postganglionic CCK-B receptors. Capsaicin locally applied in duodenal mucosa significantly decreased CCK-8 response, whereas mucosal exposure to lidocaine completely blocked CCK-8 response. In conclusion our results show that CCK response varies along the intestine according to the predominance of excitatory or inhibitory efferent innervation. Moreover, CCK-8 actions are mediated through both extrinsic and intrinsic afferent fibres.
AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. ... more AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. METHODS: The concentrations of free fatty acids, diacylglycerol, triglycerides, and phospholipids were assayed by using D-[U-14 C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry, in liver samples of Wistar rats with partial portal vein ligation at short-(1 mo) and long-term (1 year) (i.e. portal hypertensive rats) and the control rats. RESULTS: In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 ± 0.50 vs 4.70 ± 0.44 nCi/g protein; P < 0.01) and was associated with an increased synthesis of free fatty acids (2.08 ± 0.14 vs 3.36 ± 0.33 nCi/g protein; P < 0.05), diacylglycerol (1.93 ± 0.2 vs 2.26 ± 0.28 nCi/g protein), triglycerides (2.40 ± 0.30 vs 4.49 ± 0.15 nCi/g protein) and cholesterol (24.28 ± 2.12 vs 57.66 ± 3.26 mg/g protein; P < 0.01). CONCLUSION: Prehepatic portal hypertension in rats impairs the liver lipid metabolism. This impairment consists in an increase in lipid deposits (triglycerides, diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis.
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2015
Stabilization of mast cell (MC) degranulation has been proposed to prevent postoperative ileus (P... more Stabilization of mast cell (MC) degranulation has been proposed to prevent postoperative ileus (POI). Nerve growth factor (NGF) mediates MC degranulation. The aim of the study was to evaluate whether NGF receptor antagonist K252a acts as a MC stabilizer in vitro and in vivo model of POI. Peritoneal mast cells (PMCs) were obtained from Sprague-Dawley rats and were incubated with K252a and exposed to NGF or Compound 48/80 (C48/80). MC degranulation was assessed by β-hexosaminidase assay. POI was induced in rats by intestinal manipulation (IM). Rats were pretreated with K252a (100 μg/kg sc) 20 min prior to POI induction. At 20 min after IM, release of rat mast cell protease 6 (RMCP-6) was evaluated in peritoneal lavage. At 24 h, intestinal transit (IT) and gastric emptying (GE) were evaluated. Ileal inflammation was assessed by myeloperoxidase (MPO) activity, expression of IL-6, NGF, TrkA, RMCP-2 and 6, and MC density within the full-thickness ileum. C48/80 and NGF evoked degranulation...
ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Eval... more ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Evaluation Program (PEP), which focuses on microbial monitoring by and for laboratory animal diagnostic laboratories, and the Genetic Reference Monitoring Program (GENRef), which provides assay-ready reference DNA for genetic testing of mouse strains. Since 2008, PEP has grown to become a truly international program with participating laboratories in 5 continents. Launched in 2016, GENRef currently distributes DNA from 12 common inbred mouse strains for use in genetic monitoring of locally inbred colonies as well as for genetic testing of stocks, particularly genetically engineered stocks, of uncertain origins. GENRef has the capacity to include additional strains as well as additional species. PEP and GENRef provide the reagents at cost, as a resource to the international scientific community, in the interest of improving research quality in an environment of growing concern for research qu...
G A A b st ra ct s showed a 2-fold (p<0.05) increase in Brain-derived neurotrophic factor (BDN... more G A A b st ra ct s showed a 2-fold (p<0.05) increase in Brain-derived neurotrophic factor (BDNF) mRNA and a 50% decrease in the mRNA of Kv1.1 channels, compared with controls. BDNF protein was increased 50% (p<0.05) in the thoracic spinal cord. Intrathecal administration of Kv1.1 siRNA in naive rats significantly increased sensitivity to gastric distention, suggesting that the suppression of Kv1.1 contributes to GHS. Intrathecal treatment with a BDNF antagonist, trkB-Fc, significantly reduced gastric hypersensitivity in FD rats. Nerve growth factor (NGF) protein expression was 75% (p<0.05) greater in fundic muscularis externa of FD rats. Systemic treatment with an NGF antibody significantly attenuated gastric hypersensitivity. The plasma concentration of norepinephrine was significantly greater in FD rats, compared with control rats. Treatment of fundic muscularis externa In Vitro with norepinephrine produced a 50% (p<0.05) increase in NGF expression. Sodium butyrate, a histone deacetylase inhibitor, treatment in sensitized FD rats significantly reduced both gastric hypersensitivity and NGF expression in the fundus. Conclusions: Neonatal inflammatory insult induces persistent gastric hypersensitivity in adulthood. A persistent increase in plasma norepinephrine mediates GHS by elevating NGF in muscularis externa, which suppresses Kv1.1 channels in DRGs and enhances BDNF in DRGs and thoracic spinal cord. The normalization of gastric hypersensitivity by sodium butyrate suggests epigenetic dysregulation of genes.
Globalization of science and ethical values have led to implementation of regulations on protecti... more Globalization of science and ethical values have led to implementation of regulations on protection of animals used for scientific purposes worldwide, based on the principles of replacement (to avoid or replace the use of animals), reduction (to minimize the number of animals used), and refinement (to minimize animal suffering and increase animal well-being). However, while regulations in individual countries are generally based on these principles, there are variations in the way they are practically applied. For this reason, international and global organizations have developed guiding principles to harmonize animal care and use and have issued recommendations, which can be similarly applied irrespective of the regulatory framework operating in a particular country. This introductory chapter describes the principles underlying current animal research legislation and summarizes the efforts made by global organizations and professional associations to harmonize their implementation.
He was a specialist in pathology and radiobiology and an important influence in the development o... more He was a specialist in pathology and radiobiology and an important influence in the development of laboratory animal science in Belgium and in the early years of the International Council for Laboratory Animal Science (ICLAS). Married and a father of three children, Jean-ReneḾ aisin obtained his medical degree in 1954, becoming a specialist in pathology in 1959 and in radiobiology in 1961. He worked at the Center for Nuclear Energy Studies in Mol (CEN-SCK), where he was the Head of the Department of Radiobiology. In 1981, he became Professeur Extraordinaire at the Universite´Catholique de Louvain (UCL) and Professor Emeritus in 1993. After his period as emeritus professor, he was Vice-Chair of the Belgian Deontological Committee on the use of Laboratory Animals at the Ministry of Public Health, and chairman of the working group ''Science and Technology'' of the same Committee. Jean-Rene´Maisin was also a founding member and President of the Belgian Council for Laboratory
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1995
Infusion of lipids into the ileum delays gastric emptying and intestinal transit time in some spe... more Infusion of lipids into the ileum delays gastric emptying and intestinal transit time in some species. The aim of this study was to characterize the actions of intraluminal lipid infusion on gastrointestinal electrical activity in chickens. Animals were prepared for electromyography with chronic electrodes in stomach, duodenum, and small intestine. Two catheters were chronically placed in the esophagus and ileum to infuse equimolar doses of either oleic acid (OA) or triolein (TO). Both OA and TO, esophageally infused, inhibited the frequency of the gastroduodenal cycle and increased the frequency of antiperistaltic spike bursts in the duodenum. Ileal infusion of OA, but not of TO, produced the same effects. Both esophageal and ileal OA infusion increased the duration of the migrating myoelectric complex (MMC) and decreased the speed of propagation of phase III. In conclusion, intraluminal infusion of lipids modulates gastrointestinal motility by decreasing the frequency of the gastr...
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1993
Our objective was to study the mechanism of action of cholecystokinin (CCK) on the motility of th... more Our objective was to study the mechanism of action of cholecystokinin (CCK) on the motility of the gastroduodenal area. Chickens were implanted with five electrodes for electromyography in the stomach and duodenum. The effects of CCK (10(-9) mol.kg-1.10 min-1) were studied against the presence of several antagonists and in vagotomized animals. CCK caused inhibition of gastric motility and duodenal hyperactivity. Vagotomy blocked CCK responses in the stomach but not in the duodenum. Hexamethonium partially blocked gastric inhibition induced by CCK. NG-nitro-L-arginine methyl ester blocked the inhibitory response to CCK in the stomach but did not modify duodenum response. L-Arginine did not modify CCK actions. Opioid antagonists naloxone and naltrindole and adrenergic antagonists phentolamine and propranolol did not modify CCK response. Atropine did not modify duodenal response to CCK. Sodium nitroprusside (10(-8)-10(-6) mol/kg) inhibited gastroduodenal activity in a dose-related mann...
Clinics and Research in Hepatology and Gastroenterology, 2019
Introduction: Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver disea... more Introduction: Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver diseases. We administered Ketotifen, a mast cell stabilizer, and measured the mast cells in the splanchnic organs of cholestatic rats. Material and Methods: These groups were studied: sham-operated rats (S; n = 15), untreated microsurgical cholestasic rats (C; n = 20) and rats treated with Ketotifen: early (SK-e; n = 20 and CKe; n = 18), and late (SK-l; n = 15 and CK-l; n = 14). Results: The cholestatic rats showed systemic and splanchnic impairments, such as ascites, portal hypertension, and biliary proliferation and fibrosis. The rats also showed a splanchnic increase of TNF-␣, IL-1 and MCP-1, and a reduction of IL-4, IL-10 and antioxidants. An increase of VEGF in the ileum and mesenteric lymphatic complex was associated with a liver reduction of TGF-1. Ketotifen reduces the degree of hepatic insufficiency and the splanchnic inflammatory mediators, as well as VEGF and TGF-ß1 levels. Ketotifen also reduces the connective tissue
Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2018
The inflammatory response expressed after wound healing would be the recapitulation of systemic e... more The inflammatory response expressed after wound healing would be the recapitulation of systemic extra-embryonic functions, which would focus on the interstitium of the injured tissue. In the injured tissue, mast cells, provided for a great functional heterogeneity, could play the leading role in the re-expression of extra-embryonic functions, i.e., coelomic-amniotic and trophoblastic-vitelline. Moreover, mast cells would favor the production of a gastrulation-like process, which in certain tissues and organs would induce the regeneration of the injured tissue. Therefore, the engraftment of mesenchymal stem cells and mast cells, both with an extra-embryonic regenerative phenotype, would achieve a blastema, from the repaired and regenerated injured tissue, rather than by fibrosis, which is commonly made through wound-healing.
Cholecystokinin (CCK) regulates intestinal motility after being released by several luminal nutri... more Cholecystokinin (CCK) regulates intestinal motility after being released by several luminal nutrients. However the mechanism of action of CCK is still not well known. The aim of our study was to establish the mechanism of action of CCK in the rat intestine using an in vivo model and focusing on the nervous pathways involved in the response as well as type of receptors. Anesthetized rats were prepared with two strain-gauges, in duodenum and jejunum, to record circular muscle motor activity. A group of animals was also prepared with a catheter to infuse capsaicin inside the duodenum. Responses to CCK-octapeptide (CCK-8) as well as to CCK agonists were studied. CCK-8 was also infused after CCK antagonists, atropine, hexamethonium or L-nitroarginine. Results show that duodenal response to CCK-8 is excitatory although inhibitory responses can be induced by gastrin. In the jejunum, CCK-8 induces an inhibitory response that is mediated by both CCK-A and-B receptors. Excitatory responses to CCK-8 are due to stimulation of preganglionic receptors while inhibitory responses are NO mediated through stimulation of postganglionic CCK-B receptors. Capsaicin locally applied in duodenal mucosa significantly decreased CCK-8 response, whereas mucosal exposure to lidocaine completely blocked CCK-8 response. In conclusion our results show that CCK response varies along the intestine according to the predominance of excitatory or inhibitory efferent innervation. Moreover, CCK-8 actions are mediated through both extrinsic and intrinsic afferent fibres.
AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. ... more AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. METHODS: The concentrations of free fatty acids, diacylglycerol, triglycerides, and phospholipids were assayed by using D-[U-14 C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry, in liver samples of Wistar rats with partial portal vein ligation at short-(1 mo) and long-term (1 year) (i.e. portal hypertensive rats) and the control rats. RESULTS: In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 ± 0.50 vs 4.70 ± 0.44 nCi/g protein; P < 0.01) and was associated with an increased synthesis of free fatty acids (2.08 ± 0.14 vs 3.36 ± 0.33 nCi/g protein; P < 0.05), diacylglycerol (1.93 ± 0.2 vs 2.26 ± 0.28 nCi/g protein), triglycerides (2.40 ± 0.30 vs 4.49 ± 0.15 nCi/g protein) and cholesterol (24.28 ± 2.12 vs 57.66 ± 3.26 mg/g protein; P < 0.01). CONCLUSION: Prehepatic portal hypertension in rats impairs the liver lipid metabolism. This impairment consists in an increase in lipid deposits (triglycerides, diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis.
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2015
Stabilization of mast cell (MC) degranulation has been proposed to prevent postoperative ileus (P... more Stabilization of mast cell (MC) degranulation has been proposed to prevent postoperative ileus (POI). Nerve growth factor (NGF) mediates MC degranulation. The aim of the study was to evaluate whether NGF receptor antagonist K252a acts as a MC stabilizer in vitro and in vivo model of POI. Peritoneal mast cells (PMCs) were obtained from Sprague-Dawley rats and were incubated with K252a and exposed to NGF or Compound 48/80 (C48/80). MC degranulation was assessed by β-hexosaminidase assay. POI was induced in rats by intestinal manipulation (IM). Rats were pretreated with K252a (100 μg/kg sc) 20 min prior to POI induction. At 20 min after IM, release of rat mast cell protease 6 (RMCP-6) was evaluated in peritoneal lavage. At 24 h, intestinal transit (IT) and gastric emptying (GE) were evaluated. Ileal inflammation was assessed by myeloperoxidase (MPO) activity, expression of IL-6, NGF, TrkA, RMCP-2 and 6, and MC density within the full-thickness ileum. C48/80 and NGF evoked degranulation...
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