Evidence for size and charge permselectivity of rat ascending colon. Effects of ricinoleate and bile salts on oxalic acid and neutral sugar transport.

We have measured unidirectional transmural fluxes of oxalate and neutral sugars across rat ascending colon in vitro, under short-circuit conditions, to characterize permeability barriers selective for size and charge. Ionic oxalate appears to be transported preferentially to sodium oxalate. Mucosal addition of taurocholate (1 mM), deoxycholate (1 mM), or ricinoleate (1 mM) increased bidirectional oxalate fluxes, and the ricinoleate effects were independent of medium calcium. Bidirectional fluxes of uncharged sugar molecules fell sharply at molecular weights above 76 (molecular radius above 3 A), and oxalate transport was retarded relative to that of uncharged molecules of similar size, suggesting that there is both size and charge permselectivity. Ricinoleate increased fluxes of all neutral molecules tested but changed neither the exclusion limits nor the cation selectivity of the epithelium. Bile salts and ricinoleate increase oxalate transport, probably by making more channels available, but do not alter size and charge selectivity.

Endocrine abnormalities associated with chronic renal failure.

It is evident that chronic renal failure has far-reaching metabolic consequences because endocrine aberrations are common. Uremia may alter endocrine function through its effect on the hypothalamopituitary axis, the individual end organs, and the peripheral metabolism of various hormones. Deficiency of some hormones and excess of others coexist in patients with renal failure. Since the physiologic effects of many of these abnormalities are still not well defined, no treatment is necessary with the exception of true deficiency states such as testosterone deficiency. In the latter instance, exogenous hormonal supplementation is recommended.

Charcoal hemoperfusion for treatment of ethchlorvynol overdose.

Charcoal hemoperfusion is commonly employed to treat overdose of a number of drugs. There are varying reports of its efficacy in the treatment of ethchlorvynol overdose. Herein is reported a case of ethchlorvynol overdose successfully treated with charcoal hemoperfusion within 5 h of ingestion of 12.5 g of the drug. The patient was deeply comatose at that time but recovered consciousness at the end of 4 h of hemoperfusion. Ethchlorvynol clearance over the charcoal varied from 118 to 147 ml/min. There were no bleeding complications. Prompt charcoal hemoperfusion may be an effective mode of treatment in cases of ethchlorvynol intoxication.

Kinetic characteristics of calcium absorption and secretion by rat colon.

The kinetic characteristics of calcium active transport in rat descending colon were determined by measuring unidirectional transmural calcium fluxes in vitro. The absorptive flux from mucosa to serosa (Jm leads to s) was saturable, with a calculated affinity (Kt) of calcium for the transport system of 1.6 mM and a maximal transport capacity (Vmax) of 133 nmol.cm-2.h-1. The administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] increased Jm leads to s by increasing Vmax to 236 nmol.cm-2.h-1 without changing Kt (1.8 mM). The secretory flux from serosa to mucosa (Js leads to m) was not saturable and was not increased by 1,25(OH)2D3. Mannitol, a marker of transepithelial extracellular flux, underwent net absorption in the absence of electrochemical gradients, and its Jm leads to s and Js leads to m were not altered by 1,25(OH)2D3 administration. Addition of 11 mM D-glucose to the bathing medium consistently increased calcium Js leads to m and mannitol Jm leads to s and Js leads to m. Glucose reduced net calcium absorption except when sodium was removed from the medium. Calcium Js leads to m varied linearly with mannitol Js leads to m over the range of medium calcium from 0.125 to 5.0 mM. The behavior of calcium absorption by descending colon is compatible with a carrier-mediated, active-transport mechanism, whereas calcium secretion occurs by a nonsaturable process via a predominately paracellular pathway.

Effects of diet calcium and 1,25-dihydroxyvitamin D3 on colon calcium active transport.

Unidirectional fluxes of calcium were studied in the absence of electrochemical gradients across rat descending colon segments in vitro. Dietary calcium restriction and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]enhanced absorption by increasing the mucosal-to-serosal fluxes, whereas secretory (serosal-to-mucosal) fluxes were unchanged. Low-calcium diet also stimulated calcium uptake by everted gut sac segments of ascending as well as descending colon, whereas transverse colon was unresponsive. These results show that the colon is a target organ for 1,25-(OH)2D3 and demonstrate the participation of colon in the intestinal adaptation to calcium deprivation.

Effects of chlorothiazide on 1,25-dihydroxyvitamin D3, parathyroid hormone, and intestinal calcium absorption in the rat.

Previous studies have shown that thiazide diuretic agents reverse secondary hyperparathyroidism and reduce circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and intestinal calcium absorption rates in patients with idiopathic hypercalciuria of the renal-leak variety. We have investigated whether thiazides can reverse the secondary increase in serum parathyroid hormone (PTH) and 1,25(OH)2D3 levels or intestinal calcium absorption induced by feeding rats a diet low in calcium (LCD, 0.02% calcium) but adequate in phosphorus and vitamin D. We found that LCD increased circulating immunoreactive PTH [chow vs. LCD, 0.52 +/- 0.06 vs. 1.06 +2- 0.1 (SE) ng/ml, P less than 0.001], 1,25(OH)2D3 (chow vs. LCD, 101 +/- 15 vs. 325 +/- 38 pg/ml, P less than 0.001), calcium uptake by everted gut sacs from duodenum, ileum, and descending colon, and net calcium absorption by descending colon studied in Ussing chambers in vitro. Chlorothiazide (CTZ) prevented the increase in PTH during LCD (chow + CTZ vs. LCD + CTZ, 0.69 +/- 0.07 vs. 0.73 +/- 0.06, NS) but not the increase in 1,25(OH)2D3 (chow + CTZ vs. LCD + CTZ, 88 +/- 10 vs. 277 +/- 31, P less than 0.002) or intestinal calcium transport. The drug caused no change in serum 1,25(OH)2D3 or intestinal calcium absorption in rats fed normal chow. In rats given exogenous 1,25(OH)2D3 to stimulate intestinal calcium absorption, CTZ reduced urine calcium excretion greatly but did not alter intestinal calcium absorption.