The Comparative Absorption of Creatinine from «Gitter» Tablets and Control Tablets.

Lundholm, Lennart; Svedmyr, N

doi:10.1111/j.1600-0773.1963.tb01720.x

Cited by 7 publications

(4 citation statements)

References 3 publications

(1 reference statement)

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“…size, charge distribution, shape) may affect the rate of paracellular absorption of a given probe, creatinine absorption seems a reasonable surrogate for paracellular proline absorption. As such, our creatinine absorption data, along with previous reports (Dominguez and Pomerene, 1945;Lundholm and Svedmyr, 1963;Pappenheimer, 1990;Turner et al, 2000), demonstrate that the paracellular route of absorption is important for proline across many mammals including humans. Moreover, several amino acids are of similar size or smaller than proline (and have more linear structures), implying that much amino acid absorption may occur via the tight junctions.…”

Section: Whole Animal Paracellular Nutrient Absorptionmentioning

confidence: 71%

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Price

Rott

Caviedes‐Vidal

et al. 2014

Journal of Experimental Biology

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Flying vertebrates have been hypothesized to rely heavily on paracellular absorption of nutrients to compensate for having smaller intestines than non-flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In intact animals, the fractional absorption of orally dosed L-arabinose (M r 150) was 82% in M. lucifugus, which was more than twice that of the rodents. Absorption of creatinine (M r 113) was greater than 50% for all species and did not differ between M. lucifugus and the rodents. We also conducted intestinal luminal perfusions on anesthetized animals. Absorption of L-arabinose per nominal surface area in M. lucifugus was nearly double that of the rodents, while absorption of creatinine was not different among species. Using an everted sleeve preparation, we demonstrated that high concentrations of L-arabinose and creatinine did not inhibit their own uptake, validating their use as passive, paracellular probes. Histological measurements indicated that M. lucifugus has more cells, and presumably more tight junctions, per nominal surface area than P. leucopus. This seems unlikely to explain entirely the higher absorption of L-arabinose in M. lucifugus during perfusions, because L-arabinose absorption normalized to the number of enterocytes was still double that of P. leucopus. As an alternative, we investigated tight junction gene expression. M. lucifugus had higher expression of claudin-1 and claudin-15, and lower expression of claudin-2 relative to P. leucopus. Expression of claudin-7 and occludin did not differ among species. Taken together, our results support the hypothesis that bats have evolved higher paracellular nutrient absorption than non-flying animals, and that this phenomenon might be driven by both histological characteristics and differences in tight junction gene expression.

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Section: Whole Animal Paracellular Nutrient Absorptionmentioning

confidence: 71%

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Price

Rott

Caviedes‐Vidal

et al. 2014

Journal of Experimental Biology

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“…Pharmacokinetic model parameters for these perpetrators are listed in Table S3. Substantial overall underprediction of the magnitude of interactions for both the uptake and bidirectional OCT2 Figure 3 Creatinine kinetics in plasma simulated using one-compartment model following oral administration of either a cooked meat meal estimated to contain (a) 340 mg creatinine 45 or (b) a 3 g creatinine tablet 46 and compared with observed creatinine concentration data.…”

Section: Refinement Of the Model Using Creatininetrimethoprim Interacmentioning

confidence: 99%

A Novel Physiologically Based Model of Creatinine Renal Disposition to Integrate Current Knowledge of Systems Parameters and Clinical Observations

Scotcher

Arya

Yang

et al. 2020

CPT Pharmacom & Syst Pharma

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Creatinine is the most common clinical biomarker of renal function. As a substrate for renal transporters, its secretion is susceptible to inhibition by drugs, resulting in transient increase in serum creatinine and false impression of damage to kidney. Novel physiologically based models for creatinine were developed here and (dis)qualified in a stepwise manner until consistency with clinical data. Data from a matrix of studies were integrated, including systems data (common to all models), proteomics‐informed in vitro–in vivo extrapolation of all relevant transporter clearances, exogenous administration of creatinine (to estimate endogenous synthesis rate), and inhibition of different renal transporters (11 perpetrator drugs considered for qualification during creatinine model development and verification on independent data sets). The proteomics‐informed bottom‐up approach resulted in the underprediction of creatinine renal secretion. Subsequently, creatinine‐trimethoprim clinical data were used to inform key model parameters in a reverse translation manner, highlighting best practices and challenges for middle‐out optimization of mechanistic models.

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“…This may make functional sense, because the amino acid products of protein digestion tend to have smaller molecular masses and radii than the monosaccharide products of carbohydrate digestion. Studies in bats and rodents have shown that smaller paracellular probes (such as creatinine, which models the paracellular absorption of amino acids) are absorbed to a much greater extent than larger, glucose‐sized paracellular probes (Dominguez & Pomerene, ; Lundholm & Svedmyr, ; Pappenheimer, ; Price et al, ; Price et al, ; Turner, Cohen, Mrsny, & Madara, ). It is plausible that there has been less natural selection for high SEF and paracellular permeability in carnivores and insectivores compared to herbivores and omnivores.…”

Section: Discussionmentioning

confidence: 99%

Morphological bases for intestinal paracellular absorption in bats and rodents

Brun

Marinone

Price

et al. 2019

Journal of Morphology

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Flying mammals present unique intestinal adaptations, such as lower intestinal surface area than nonflying mammals, and they compensate for this with higher paracellular absorption of glucose. There is no consensus about the mechanistic bases for this physiological phenomenon. The surface area of the small intestine is a key determinant of the absorptive capacity by both the transcellular and the paracellular pathways; thus, information about intestinal surface area and microanatomical structure can help explain differences among species in absorptive capacity. In order to elucidate a possible mechanism for the high paracellular nutrient absorption in bats, we performed a comparative analysis of intestinal villi architecture and enterocyte size and number in microchiropterans and rodents.We collected data from intestines of six bat species and five rodent species using hematoxylin and eosin staining and histological measurements. For the analysis we added measurements from published studies employing similar methodology, making in total a comparison of nine species each of rodents and bats. Bats presented shorter intestines than rodents. After correction for body size differences, bats had~41% less nominal surface area (NSA) than rodents. Villous enhancement of surface area (SEF) was~64% greater in bats than in rodents, mainly because of longer villi and a greater density of villi in bat intestines. Both taxa exhibited similar enterocyte diameter. Bats exceeded rodents by~103% in enterocyte density per cm 2 NSA, but they do not significantly differ in total number of enterocytes per whole animal. In addition, there is a correlation between SEF and clearance per cm 2 NSA of L-arabinose, a nonactively transported paracellular probe. We infer that an increased enterocyte density per cm 2 NSA corresponds to increased density of tight junctions per cm 2 NSA, which provides a partial mechanistic explanation for understanding the high paracellular absorption observed in bats compared to nonflying mammals. K E Y W O R D Sbats, enterocytes, nutrient absorption, rodents, small intestine surface area

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The Comparative Absorption of Creatinine from «Gitter» Tablets and Control Tablets.

Cited by 7 publications

References 3 publications

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

A Novel Physiologically Based Model of Creatinine Renal Disposition to Integrate Current Knowledge of Systems Parameters and Clinical Observations

Morphological bases for intestinal paracellular absorption in bats and rodents

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