Intraluminal metabolism

Fig. 2.4 Renal elimination processes of peptides and proteins Glomerular filtration followed by either (a) intraluminal metabolism or (b) tubular reabsorption with intracellular lysosomal metabolism, and (c) peritubular extraction with intracellular lysosomal metabolism (modified from [76]).

The second mechanism entails glomerular filtration followed by intraluminal metabolism, predominantly by exopeptidases in the luminal bmsh border membrane of the proximal tubules. The resulting peptide fragments and amino acids... 

After glomerular filtration, small linear peptides undergo intraluminal metabolism, predominantly by exopeptidases in the luminal brush border membrane of the proximal tubules. The resulting amino acids are transcellularly transported back into the systemic circulation [28, 43]. Larger peptides and proteins are actively reabsorbed in the proximal tubules via endocytosis. This cellular uptake is followed by addition of lysosomes... 

There is significant controversy over the role of loop diuretics in the treatment of ARE Theoretical benefits in hastening recovery of renal function include decreased metabolic oxygen requirements of the kidney, increased resistance to ischemia, increased urine flow rates that reduce intraluminal obstruction and filtrate backleak, and renal vasodilation.6 Theoretically, these effects could lead to increased urine output, decreased need for dialysis, improved renal recovery, and ultimately, increased survival. However, there are conflicting... 

The Inter-Relationship between LETT, Colonic Anaerobic Bacteriology, Bile-Acid-Metabolising Enzymes, Intraluminal pH and DCA Metabolism... 

Albendazole selectively blocks glucose uptake and depletes glycogen stores. ATP formation is thus inhibited. It should be administered on an empty stomach for intraluminal parasites and with a fatty meal for tissue parasites. It is metabolized to an active sulfoxide metabolite resulting in very low Albendazole blood levels. Albendazole sulfoxide is excreted in the urine with an elimination half-life of about 8 h. Used for 1-3 days in doses recommended for intestinal worms the incidence of adverse effects is similar in treatment and control groups. Hepato-toxicity may occur, especially after the higher doses that are needed for hydatid disease. Also alopecia has been reported. 

Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids. Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention. Lactulose is also used in the treatment of hepatic encephalopathy. 

Glaeser H, Drescher S, Hofmann U, et al. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans. Clin Pharmacol Ther 2004 76(3) 230-238. 

Belayev L, Zhao W, Busto R, Ginsbeig MD (1997) Tiansient middle cerebral artery occlusion by intraluminal suture I. Three-dimensiontil autoradiographic image-analysis of local cerebral glucose metabolism-blood flow interrelationships during ischemia and early recirculation. J Cereb Blood Flow Metab 17 1266-1280... 

In 1982 selective retention of phenolic PCB metabolites was first observed in the intraluminal uterine fluid of pregnant mice after administration of CB-31, using whole body autoradiography and subsequent chemical analysis [36]. Administration of CB-77 to pregnant mice resulted in a dramatic accumulation of a phenolic metabolite in fetal soft tissue [191]. The retained metabolite was shown to be 4-OH-3,3, 4, 5-tetraCB and localized in the blood in both the fetus and in adult mice [73], A metabolism study of the structurally related CB-105 in mice showed significant retention of the para-substituted hydroxylated metabolite 4-OH-CB-107 in blood [71]. The 4-OH-CB 107 was also shown to be retained in blood from rats administered Aroclor 1254 [39], and was observed at high levels in blood and brain tissue from rat fetuses exposed in utero [192],... 

Kinetics of Bile Acid Metabolism. Using an isotope dilution technique, the bile acid pool in normal adults has been found to average from 2 to 4g. Steady state is reached when hepatic synthesis and fecal loss are in balance. In health, the magnitude of each process is 0.3 to 0.8g/day. There are usually 4 to 10 enterohepatic cycles per day. Because of this recycling mechanism, the jejunal concentration of bile acids is maintained at -5 to lOmmol/L during the postprandial state, much higher than the critical micellar concentration of 2mmol/L. Between meals, with decreased entry of bile acids into the intestine, the intraluminal concentration... 

Other approaches to the prevention of traveler s diarrhea are the use of lactobacillus preparations or bismuth subsalicylate. Lactobacilli are bacteria that metabolize dietary carbohydrate to lactic acid and other organic acids, reducing the intraluminal pH and inhibiting the growth of enteropathogens. 

Similar to artificial kidneys, hoUow-fiber-based artificial liver devices can be developed by culturing living animal or human hepatocytes inside the hollow fibers and circulating the patient s blood in the extracapillary space. Toxic components in the blood that generally diffuse through the hollow fiber membrane are metabolized by the entrapped hepatocytes, and will then either diffuse back into the bloodstream or be washed out by the intraluminal stream. 

In the case of human exposure to ethylene glycol, oxalic acid was found to be the end-product of metabolism. It precipitated to crystals of calcium oxalate monohydrate in the tubular lumen, causing acute kidney injmy with extensive intracellular intraluminal crystal depositions, and subsequently acute oxalate nephropathy. ... 

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