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Volume 115, Issue 1, Pages 67-74 (July 1998)
The effect of tacrolimus (FK506) on intestinal barrier function and cellular energy production in humans Simon M. Gabe*,‡, Ingvar Bjarnason§, Zahra Tolou–Ghamari‡, J.Michael Tredger‡, Philip G. Johnson∥, G.Robin Barclay¶, Roger Williams#, David B.A. Silk* Gastroenterology Volume 115, Issue 1, Pages (July 1998) DOI: /S (98)70366-X Copyright © 1998 American Gastroenterological Association Terms and Conditions
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Fig. 1 (A) Resting energy expenditure in the patient groups studied. The resting energy expenditure was determined by indirect calorimetry over a 20-minute period in the nonfasting state. ★, Significant difference compared with control 1 and control 2 (P = and P = 0.02, respectively; Mann–Whitney U test). (B) [13C]KICA decarboxylation in the patient groups studied. [13C]KICA decarboxylation was determined by measuring 13CO2 excretion in the breath over a 2-hour period after ingestion of [13C]KICA. Tacrolimus, patients after orthotopic liver transplantation on tacrolimus; Control 1, healthy control subjects; Control 2, patients after orthotopic liver transplantation off all immunosuppression. Straight bars represent median values. There is no significant difference in the median [13C]KICA decarboxylation between groups, although the range of [13C]KICA decarboxylation is wider in the tacrolimus group. (C) Correlation between [13C]KICA decarboxylation and resting energy expenditure in all patients studied with 95% confidence bands applied. A significant direct correlation is shown (r = 0.48, P < 0.005). Gastroenterology , 67-74DOI: ( /S (98)70366-X) Copyright © 1998 American Gastroenterological Association Terms and Conditions
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Fig. 1 (A) Resting energy expenditure in the patient groups studied. The resting energy expenditure was determined by indirect calorimetry over a 20-minute period in the nonfasting state. ★, Significant difference compared with control 1 and control 2 (P = and P = 0.02, respectively; Mann–Whitney U test). (B) [13C]KICA decarboxylation in the patient groups studied. [13C]KICA decarboxylation was determined by measuring 13CO2 excretion in the breath over a 2-hour period after ingestion of [13C]KICA. Tacrolimus, patients after orthotopic liver transplantation on tacrolimus; Control 1, healthy control subjects; Control 2, patients after orthotopic liver transplantation off all immunosuppression. Straight bars represent median values. There is no significant difference in the median [13C]KICA decarboxylation between groups, although the range of [13C]KICA decarboxylation is wider in the tacrolimus group. (C) Correlation between [13C]KICA decarboxylation and resting energy expenditure in all patients studied with 95% confidence bands applied. A significant direct correlation is shown (r = 0.48, P < 0.005). Gastroenterology , 67-74DOI: ( /S (98)70366-X) Copyright © 1998 American Gastroenterological Association Terms and Conditions
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Fig. 1 (A) Resting energy expenditure in the patient groups studied. The resting energy expenditure was determined by indirect calorimetry over a 20-minute period in the nonfasting state. ★, Significant difference compared with control 1 and control 2 (P = and P = 0.02, respectively; Mann–Whitney U test). (B) [13C]KICA decarboxylation in the patient groups studied. [13C]KICA decarboxylation was determined by measuring 13CO2 excretion in the breath over a 2-hour period after ingestion of [13C]KICA. Tacrolimus, patients after orthotopic liver transplantation on tacrolimus; Control 1, healthy control subjects; Control 2, patients after orthotopic liver transplantation off all immunosuppression. Straight bars represent median values. There is no significant difference in the median [13C]KICA decarboxylation between groups, although the range of [13C]KICA decarboxylation is wider in the tacrolimus group. (C) Correlation between [13C]KICA decarboxylation and resting energy expenditure in all patients studied with 95% confidence bands applied. A significant direct correlation is shown (r = 0.48, P < 0.005). Gastroenterology , 67-74DOI: ( /S (98)70366-X) Copyright © 1998 American Gastroenterological Association Terms and Conditions
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Fig. 2 Correlation between tacrolimus exposure and [13C]KICA decarboxylation with 95% confidence bands applied. Tacrolimus exposure (area under the concentration–time curve) and [13C]KICA decarboxylation were determined over 2 hours as described in the text. A significant inverse correlation is shown by linear regression analysis (r = −0.71, P < 0.001). Gastroenterology , 67-74DOI: ( /S (98)70366-X) Copyright © 1998 American Gastroenterological Association Terms and Conditions
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Fig. 3 (A) Correlation between tacrolimus exposure and the resting energy expenditure with 95% confidence bands applied. The resting energy expenditure was determined by indirect calorimetry at the midpoint of a 5-hour period of tacrolimus exposure. A significant inverse correlation is shown by linear regression analysis (r = −0.49, P < 0.02). (B) Correlation between the respiratory quotient and tacrolimus exposure with 95% confidence bands applied. The respiratory quotient was determined by indirect calorimetry at the midpoint of a 5-hour period of tacrolimus exposure. Linear regression analysis shows a significant inverse correlation (r = −0.56, P = 0.007). Gastroenterology , 67-74DOI: ( /S (98)70366-X) Copyright © 1998 American Gastroenterological Association Terms and Conditions
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Fig. 4 Intestinal permeability in the patient groups studied. Intestinal permeability was assessed by the 5-hour urinary excretion ratio of lactulose to L-rhamnose. Tacrolimus, patients after orthotopic liver transplantation on tacrolimus; Control 1, healthy control subjects; Control 2, patients after orthotopic liver transplantation not receiving any immunosuppression. Straight bars represent median values. Gastroenterology , 67-74DOI: ( /S (98)70366-X) Copyright © 1998 American Gastroenterological Association Terms and Conditions
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Fig. 5 Correlation between the intestinal absorptive capacity and tacrolimus exposure with 95% confidence bands applied. Intestinal absorptive capacity was determined by the 5-hour urinary excretion ratio of D-xylose to 3-o-methyl-D-glucose, and tacrolimus exposure was calculated over a 5-hour period. Linear regression analysis shows a significant inverse correlation (r = −0.57, P = 0.004). Gastroenterology , 67-74DOI: ( /S (98)70366-X) Copyright © 1998 American Gastroenterological Association Terms and Conditions
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