Surgery – Means for introducing or removing material from body for... – Treating material introduced into or removed from body...
Reexamination Certificate
2001-07-31
2003-03-25
Falk, Anne-Marie (Department: 1632)
Surgery
Means for introducing or removing material from body for...
Treating material introduced into or removed from body...
C800S008000
Reexamination Certificate
active
06537267
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the modification of laboratory animals for use in clinical studies and more specifically, to chronic catheterization of bile ducts of rats.
Tumor necrosis factor-&agr; (TNF&agr;) is believed to be the primary mediator of endotoxin-induced hepatocellular dysfunction. This dysfunction results in decreased bile formation, a condition known as cholestasis. It has been shown that the endotoxin-induced TNF&agr; response is dramatically attenuated by the surgical and nonsurgical stress associated with experimental protocols. In general, this condition, and others, can be evaluated in clinical studies by the use of chronically catheterized rats. Such rats have ligated common bile ducts, and a catheter connecting the bile duct to either a distal part of the bile duct or the intestine. In this use of such chronically catheterized rats, the bile duct will block or harbor bacterial colonies which adversely affect the study.
SUMMARY OF THE INVENTION
In the method of the subject invention, the common bile duct of a laboratory animal is cannulated but not ligated. The bile duct is left intact. Bile is siphoned by gravity from the catheter. In this manner, 100% of the bile is collected. The presence of the catheter does not alter hepatic function with respect to bile flow, bile acid flux, maximal indocyanine green biliary excretion, biliary gamma GT, or drug metabolism.
REFERENCES:
Beno et al., Endotoxin-induced reduction in biliary indocyanine green excretion rate in a chronically catheterized rat model, 2001, AM. J. Physiol. Gestrointest. Liver Physiol., vol. 280, pp. G858-G865.*
Lebrec et al., Hepatic vein catheterization in the rat, 1980, Pfluggers Arch., vol. 387, pp. 67-68.*
Kanz et al., Biliary function studies during multiple time periods in freely moving rats, a useful system and set of marker solutes, 1992, JPM, vol. 27, pp. 7-15.*
Beno, et al.; “Staphylococcal exterotoxin B potentiates LPS-induced hepatic dysfunction in chronically catheterized rats”;Am J. Physiol Gastrointest Liver Physio(280:G866-G872,2001).
Beno, et al.; “Endotoxin-induced reduction in biliary indocyanine green excretion rate in a chronically catheterized rat model”;Am J. Physiol Gastrointest Liver Physiol(280:G858-G865,2001).
Heitmeyer, et al.; “Improved Method for Bile Collection in Unrestrained Conscious Rats”;Laboratory Animal Science; vol. 42, No. 3, Jun. 1992.
Rolf, et al.; “Chronic Bile Duct Cannulation in Laboratory Rats”;Laboratory Animal Science; vol. 41, Jun. 1991.
Rath, et al.; “A new method of bile duct cannulation allowing bile collection and re-infusion in the conscious rat”.
Wang, et al.; “A Comparison of Two Surgical Techniques for Preparation of Rats with Chronic Bile Duet Cannulae for the Investigation of Enterohepatic Circulation”;Laboratory Animal Science; vol. 44, No. 5, Jun. 1994.
Kan, et al.; “Biliary Function Studies During Multiple Time Periods in Freely Moving Rats A Useful System and Set of Marker Solutes”;Journal of Pharmacological Methods 27; 7-15 (1992) Elsevier Science Publishing Co., Inc.
Epstein, et al.; “A Model for Biliary and Vascular Access in the Unanesthetized, Unrestrained Rat”;Physiology & Behavior; vol. 48. pp-539-542; Pergamon Press 1990.
Balabaud, et al.; “Bile Collection in Free Moving Rats”;Laboratory Animal Science; © 1981 by the American Associaton for Laboratory Animal Science.
Enderlin,et al. “Technical Notes, Long Term Bile Collection in the Rat”;Laboratory animal Science; © 1977 by the American Associaton for Laboratory Animal Science; vol. 27.
Knapp,et al. “An Improved Technic for the Collection of Bile in the Unanesthetized Rat”;Laboratory animal Science; © 1971 by the American Association for Laboratory Animal Science; vol. 21, No. 3.
Xu, et al.; “Simultaneous Sampling of Blood, Bile, and Urine in Rats for Pharmacokinetic Studies”;Journal of Pharmacological Methods; 24, 203-208; © 1990; Elsevier Science Publishing Co., Inc.
Falk Anne-Marie
Qian Celine
Rush-Presbyterian St. Luke's Medical Center
Welsh & Katz Ltd.
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