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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.

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.

Forty patients with serum antibody against herpes simplex virus (HSV) were enrolled in a randomized, placebo-controlled, double-blind investigation of acyclovir given orally in a low dosage as prophylaxis against recurrent HSV infection after renal transplantation. During 30 postoperative days of medication, 14 of 21 placebo-treated and one of 19 acyclovir-treated patient(s) developed reactivation of HSV infection. Eleven of the former, but not the latter, had herpetic lesions. The protection against active infection with HSV during the period of prophylaxis with acyclovir is statistically highly significant. From 30 to 90 days after transplantation when no antiviral medicine was given, 60% (3/5) of the remaining placebo recipients and 44% (7/16) of the acyclovir patients developed active HSV infections. Herpetic lesions occurred in two of three and two of seven of infected people in the respective groups. No adverse effects of the drug were observed. The results show that HSV infections in immunosuppressed renal allograft recipients can be safely prevented, deferred, and ameliorated by an initial period of prophylaxis with a low dose of oral acyclovir.

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SUMMARY The efficacy and toxicity of ganciclovir given by intravenous or intravenous plus intravitreal injection were studied in nine patients with cytomegalovirus (CMV) retinitis; seven with AIDS and two with drug induced immunodeficiency. Five patients had retinitis with macular involvement in six sighted eyes; six patients had only peripheral retinitis in seven eyes. In two patients (two eyes) with macular involvement intravenous plus intravitreal injection of ganciclovir preserved sight; intravenous infusion alone did not in four eyes of three other patients. In seven eyes (six patients) with peripheral retinitis vision was retained regardless of the route of ganciclovir treatment. Following intravenous ganciclovir drug levels in the vitreous fluid were 1A4-2-2 mmol/l, that is, 44 and 65% of the concomitant serum concentration. Clinically and at necropsy three eyes showed no evidence of toxicity from intravitreal injection of ganciclovir. All of five patients with AIDS who received intravenous ganciclovir for more than one week developed leucopenia. CMV retinitis of the macula may be benefited with minimal drug toxicity by intravitreal injection of ganciclovir. Treatment of peripheral CMV retinitis in patients with AIDS may be optional.Necrotising retinitis caused by cytomegalovirus (CMV) is one of the serious manifestations of immune deficiency states.'2 It has the potential for producing blindness and seriously depreciating the quality of life. In patients immunosuppressed by medication CMV retinitis can be controlled by withdrawal of the immunosuppressive drugs. In patients with the acquired immune deficiency syndrome (AIDS) the irreversibility of the immune suppression makes progression of CMV retinitis the expected course. The increasing prevalence of AIDS and of chemotherapy causing immunosuppression has increased the occurrence of CMV retinitis and emphasised the need for effective treatment.34The most effective antiviral drug for the treatment of CMV infections is 9-(1,3 dihydroxy 2-propoxymethyl) guanine (ganciclovir).'" Its use Correspondence to

A bbstract. 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.

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.