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ABSTRACT: Demand for bariatric surgery has risen exponentially and bariatric patients often have multiple indications for post-operative pharmacotherapy. The purpose of this study was to systematically review the published literature examining the effect of bariatric surgery on drug absorption. Studies were sought through searches of MEDLINE, EMBASE, the Cochrane Controlled Trials Registry and hand searches of reference lists. Two reviewers independently assessed studies for inclusion. Twenty-six studies (15 case reports/case series evaluating 12 different agents and 11 non-randomized controlled studies examining 15 different agents) were found. Evidence for diminished drug absorption was found in 15/22 studies involving jejunoileal bypass, 1/3 studies of gastric bypass/gastroplasty and 0/1 studies examining biliopancreatic diversion. The effect of bariatric surgery on drug absorption appears drug-specific. Drugs that are intrinsically poorly absorbed, highly lipophilic and/or undergo enterohepatic recirculation exhibited the greatest potential for malabsorption. The most consistent evidence for diminished absorption was found for cyclosporine, thyroxine, phenytoin and rifampin. Reduced drug absorption may occur post-bariatric surgery and this effect appears drug-specific. Individual dose-adjustment and therapeutic monitoring may be required. Rigorously conducted controlled studies are needed to evaluate the effect of modern bariatric procedures on drug absorption.
Obesity Reviews 07/2009; 11(1):41-50. · 7.04 Impact Factor
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ABSTRACT: Peptides containing the unphysiological amino acid 5-oxaproline (Opr) in the sequence R1-Xaa-Opr-Gly-OR2 were found to inactivate prolyl 4-hydroxylase from chick and human origins. Of the substances investigated, compounds with aromatic substituents R1 and R2 were particularly effective when compared with those with an aliphatic group or without a C-terminal blocking group. Both affinity of the individual peptides for the enzyme and partition ratio contributed to the differences in efficiency. Benzylcarbonyl-Phe-Opr-Gly-benzyl ester was the most effective substance tested, its concentration giving 50% inactivation in 1 h being 0.8 microM. Inactivation was only observed in the presence of 2-oxoglutarate and Fe2+. The Opr peptides enhanced the decarboxylation of 2-oxoglutarate by prolyl 4-hydroxylase, the Vmax values obtained with the individual peptides being positively correlated with their inactivating efficiency. Inactivation was prevented by high concentrations of peptide substrate and ascorbate. Lineweaver-Burk kinetics experiments suggested noncompetitive inhibition with respect to peptide substrate and ascorbate. Lysyl hydroxylase was not affected by Opr peptides in concentrations of up to 1.5 mM in either the presence or absence of prolyl 4-hydroxylase. The results suggest that the oxaproline compounds are specific syncatalytic inactivators of prolyl 4-hydroxylase.
Journal of Biological Chemistry 01/1989; 263(36):19498-504. · 4.77 Impact Factor
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ABSTRACT: The serum concentrations of collagen type IV,7S, collagen type IV,nc1, and aminoterminal type III procollagen peptide immunoreactive components were measured by means of specific radioimmunoassays during development of granulation tissue in rats. The results were compared with tissue deposition of basement membranes and interstitial collagens in the granulation as measured morphometrically. A parallel sequential pattern in tissue deposition of collagen types III and IV, and serum increase of collagen types III- and IV-related fragments, was observed. Serum collagen type IV was less sensitive as a marker for development of granulation tissue than the serum procollagen type III N-peptide. This was in accordance with a low collagen type IV/interstitial collagen ratio in the granulation tissue. However, a cross-sectional study showed that serum collagens types IV,7S and IV,nc1 may be useful as early quantitative indicators of granulation tissue formation. Simultaneously, measurement of collagen type IV- and procollagen type III N-peptide-related antigens in serum provides a differentiated reflection of the dynamic matrix processes in developing granulation tissue.
European Journal of Clinical Investigation 09/1988; 18(4):352-9. · 3.02 Impact Factor
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ABSTRACT: Sera from patients with progressive systemic sclerosis (PSS) were studied using immuno-assays for laminin P1 fragment and the carboxyterminal NC1 domain from type IV collagen. Compared to healthy controls, patients with PSS showed elevated serum levels of both fragments derived from basement membrane proteins. However, there was no difference when patients with and without Raynaud's phenomenon were compared and no correlation could be established with the activity of the disease or clinically defined types of scleroderma. Our data indicate that the metabolism of basement membrane proteins is involved in the course of scleroderma; however, it remains questionable whether these assays could become useful as diagnostic or prognostic tools.
The Journal of Rheumatology 07/1988; 15(6):969-72. · 3.69 Impact Factor
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ABSTRACT: Dimethylnitrosamine (DMN)-induced liver fibrosis was used as an experimental model to study the relationship between serum concentrations of the N-terminal propeptide of type III procollagen [S-Pro(III)-N-P] and the N-terminal (S-7S) and C-terminal (S-NC1) domains of type IV collagen and hepatic concentrations of type III and IV collagen mRNAs. Increases in S-Pro(III)-N-P, and especially in the two type IV collagen-related antigens, were found to be early events in the formation of DMN-induced hepatic fibrosis. The mean concentration of S-Pro(III)-N-P was 120% of the control mean on day 7 of DMN treatment, 230% on day 14 and 250% on day 21. The corresponding values for S-7S were 260, 950 and 1100% and, for S-NC1, 310, 820 and 1000%. All these changes were very similar to those found in the hepatic concentrations of the respective mRNAs. These data support a previous suggestion that an enhanced production of basement-membrane (type IV) collagen is an early event in the development of the DMN-induced hepatic fibrosis. The results also indicate that S-7S and S-NC1 are very sensitive indicators of changes in type IV collagen metabolism. Data obtained in gel-filtration experiments for these three serum antigens were consistent with the suggestion that all three antigens are mainly derived from the synthesis of the respective collagens.
Biochemical Journal 03/1988; 249(3):753-7. · 4.90 Impact Factor
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ABSTRACT: The serum concentration of 7S collagen was measured radioimmunologically as a marker of basement membrane type IV collagen synthesis in diabetic and nondiabetic rats with Goldblatt hypertension. In non-diabetic rats the 7S collagen level was significantly raised after induction of hypertension (51%; p less than 0.001), and showed a positive correlation with relative heart weight as an integral parameter of hypertension (r = 0.63; p less than 0.01). In diabetic rats, which displayed a 7S collagen concentration roughly 2.5 times as high as the metabolically normal animals, the 7S collagen level was 27% higher in the hypertensive animals (p less than 0.01). There was no correlation with blood pressure or heart weight, but only a positive correlation with blood glucose (r = 0.51; p less than 0.05). The results indicate that haemodynamic alterations may alter basement membrane collagen metabolism. However, type IV collagen metabolism in diabetes is influenced to a greater extent by metabolic than by haemodynamic factors.
Diabetologia 06/1987; 30(5):344-7. · 6.81 Impact Factor
