Intestinal Absorption of Cystine and Cysteine in Normal Human Subjects and Patients with Cystinuria

1974 ◽  
Vol 47 (4) ◽  
pp. 393-397 ◽  
Author(s):  
D. B. A. Silk ◽  
D. Perrett ◽  
A. D. Stephens ◽  
M. L. Clark ◽  
E. F. Scowen

1. An intestinal perfusion technique has been used to study absorption in vivo of l-cystine and l-cysteine in six normal human subjects and three patients with homozygous cystinuria. 2. No significant absorption of l-cystine was detected during perfusion of the cystinuric patients, whereas l-cysteine absorption was normal. These results imply that l-cystine and l-cysteine are normally absorbed by different transport processes. 3. No significant reduction of l-cystine to l-cysteine occurred in the gut lumen during the perfusion experiments. No more oxidation of l-cysteine to l-cystine occurred in the gut lumen during the perfusion experiments than in the test solutions which were simultaneously incubated in vitro.

1987 ◽  
Vol 57 (2) ◽  
pp. 195-199 ◽  
Author(s):  
Dharmaraj H. Patil ◽  
George K. Grimble ◽  
David B. A. Silk

1. In the first part of the study, the absorption of lactitol, a new disaccharide analogue of lactose, was studied using an in vivo jejunal perfusion technique in man. Intestinal uptake of lactitol from isotonic solutions containing 10, 30, 60, and 100 mmol lactitol/l was insignificant.2. In the second part of the study the laxative threshold of lactitol was determined and compared with that of sorbitol in a double-blind, randomized, cross-over study on twenty-one normal subjects. Laxative threshold was considered to be either the maximum dose tolerated without unacceptable diarrhoea or gastrointestinal side effects, or when the maximum dose in the study was reached. Increasing amounts of lactitol, sorbitol or placebo were administered in two divided doses each day until subjects developed diarrhoea or severe gastrointestinal side effects. The laxative threshold of lactitol (74 (SE 5) g/d) was similar to that of sorbitol (71 (SE 5) g/d).3. These findings indicate that lactitol is not absorbed by the human small intestine. Although diarrhoea or other gastrointestinal side effects occurred as the dose was increased, 40 g lactitol/d was well tolerated.


1958 ◽  
Vol 108 (6) ◽  
pp. 945-956 ◽  
Author(s):  
Theodore T. Puck ◽  
Steven J. Cieciura ◽  
Arthur Robinson

A methodology designed to eliminate mitotic inhibitor action and involving use of pretested fetal calf serum and careful pH and temperature control has been described by which cells from normal human and animal tissue can be maintained in active growth for long periods in vitro without development of aneuploidy. By means of this procedure, it is possible reliably to establish cell cultures from minute skin biopsies which can be taken from any individual. Clones of mammalian cells with chromosomal markers have been isolated by this means from x-irradiated non-irradiated cell cultures. Application of these techniques to chromosome delineation in large numbers of human subjects; determination of chromosomal sex in patients; spontaneuos and induced genetic changes in somatic mammalian cells in vivo and in vitro; comparison of metabolic differences between normal and cancerous cells and other problems have been indicated.


2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Namrata Singh ◽  
A. Bhatnagar

Purpose. The aim of this work was to develop specific radiopharmaceutical and to evaluate its efficacy in human to detect and locate the tubercular lesion.Materials and Methods.99mTc-Ethambutol (EMB) was produced by direct labeling method.In vitro and in vivobiological studies and animal experiments were done. Phase I Clinical trial was performed. As per plan, 2 normal human subjects for biodistribution studies and fourteen patients (8 males and 6 females; age range of 25–50, with one patient aged 12 years as an exception) were chosen for clinical trial. Whole body scan and spots were acquired at 1 hour and 4 hour. Angiography, blood pool, and 24-hours spot images of the infected areas were also acquired.Result. Radiolabeling yielded>85%of labeled complex.In vitro and in vivobiological studies and animal experiments indicated99mTc-EMB as a specific tuberculosis imaging agent. The biodistribution study in normal human subjects suggested stability of99mTc-EMB, with main excretory pathways being renal and hepatobiliary, which appeared to be similar to the known behavior of unlabeled EMB. No adverse reactions were observed.99mTc-EMB got localized in pulmonary and bone tubercular lesions. Scintigrams of99mTc-EMB and99mTc-Ciprofloxacin were compared at different time intervals.Conclusion. The present study states that developed99mTc-EMB has high potential to qualify as a specific tuberculosis imaging radiopharmaceutical and is safe for human use.


1992 ◽  
Vol 67 (01) ◽  
pp. 060-062 ◽  
Author(s):  
J Harsfalvi ◽  
E Tarcsa ◽  
M Udvardy ◽  
G Zajka ◽  
T Szarvas ◽  
...  

Summaryɛ(γ-glutamyl)lysine isodipeptide has been detected in normal human plasma by a sensitive HPLC technique in a concentration of 1.9-3.6 μmol/1. Incubation of in vitro clotted plasma at 37° C for 12 h resulted in an increased amount of isodipeptide, and there was no further significant change when streptokinase was also present. Increased in vivo isodipeptide concentrations were also observed in hypercoagulable states and during fibrinolytic therapy.


1972 ◽  
Vol 68 (2_Supplb) ◽  
pp. S285-S309 ◽  
Author(s):  
Kurt Ahrén ◽  
Per Olof Janson ◽  
Gunnar Selstam

ABSTRACT This paper discusses in vivo and in vitro ovarian perfusion systems described so far in the literature. The interest is not focussed primarily on the results of these studies but rather on the advantages and disadvantages of the techniques and methods used. Another part of the paper summarizes the points which are most important, in our opinion, to take into consideration when developing an in vitro perfusion technique of the ovary. The last part of the paper gives a description of and some preliminary results from an in vitro perfusion system of the rabbit ovary which is under development in this laboratory.


2018 ◽  
Vol 15 (9) ◽  
pp. 1305-1311 ◽  
Author(s):  
Giovanni Monastra ◽  
Yula Sambuy ◽  
Simonetta Ferruzza ◽  
Daniela Ferrari ◽  
Giulia Ranaldi

2019 ◽  
Vol 18 (26) ◽  
pp. 2209-2229 ◽  
Author(s):  
Hai Pham-The ◽  
Miguel Á. Cabrera-Pérez ◽  
Nguyen-Hai Nam ◽  
Juan A. Castillo-Garit ◽  
Bakhtiyor Rasulev ◽  
...  

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.


2009 ◽  
Vol 37 (6) ◽  
pp. 1207-1213 ◽  
Author(s):  
Yan Qiu ◽  
Coralie Hoareau-Aveilla ◽  
Sebastian Oltean ◽  
Steven J. Harper ◽  
David O. Bates

Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys–Drash syndrome and pre-eclampsia). Administration of recombinant VEGF165b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing factors and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGFxxxb isoforms to the pro-angiogenic VEGFxxx isoforms, including SRp55 (serine/arginine protein 55), ASF/SF2 (alternative splicing factor/splicing factor 2) and SRPK (serine arginine domain protein kinase), and inhibitors of these molecules can inhibit angiogenesis in the eye, and splice site selection in cancer cells, opening up the possibility of using splicing factor inhibitors as novel anti-angiogenic therapeutics. Endogenous anti-angiogenic VEGFxxxb isoforms are cytoprotective for endothelial, epithelial and neuronal cells in vitro and in vivo, suggesting both an improved safety profile and an explanation for unpredicted anti-VEGF side effects. In summary, C-terminal distal splicing is a key component of VEGF biology, overlooked by the vast majority of publications in the field, and these findings require a radical revision of our understanding of VEGF biology in normal human physiology.


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