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Biomedical subjects

M J Favus

Publications and source records attributed to M J Favus.

At least 73 records · Page 4Linked to original sources
PubMed1984

Mechanism of chronic hypocalciuria with chlorthalidone: reduced calcium absorption.

Chlorthalidone, like other benzothiadiazides, lowers urine calcium excretion chronically. If intestinal calcium absorption did not fall or bone accretion did not increase, serum calcium and the filtered load of calcium would increase and urine calcium would return to pretreatment levels. To determine whether overall intestinal calcium absorption fell, we fed chlorthalidone (5 mg X kg body wt-1 X 24 h-1) to 10 adult male rats eating 15 g/day of a 0.6% calcium diet. Compared with 10 control rats, chlorthalidone reduced urine calcium [2.1 +/- 0.1 (SE) vs. 5.8 +/- 0.5 mg/6 days; P less than 0.001]. Fecal calcium rose (307 +/- 9 vs. 257 +/- 12; P less than 0.005) because percent intestinal calcium absorption fell (41 +/- 2 vs. 52 +/- 2; P less than 0.002). Twenty other rats given the same diet were injected subcutaneously with 1,25(OH)2D3 (50 ng/day). In these rats, chlorthalidone reduced urine calcium (23 +/- 3 vs. 59 +/- 3; P less than 0.001) and percent intestinal calcium absorption (60 +/- 1 vs. 66 +/- 1; P less than 0.01). With or without 1,25(OH)2D3, chronic administration of chlorthalidone reduces intestinal calcium absorption, and this reduction seems to be the mechanism that permits urine calcium excretion to remain low.

Animals↗
PubMed1984

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.

Animals↗
PubMed1983

Effects of trifluoperazine, ouabain, and ethacrynic acid on intestinal calcium transport.

Bidirectional steady-state calcium fluxes were measured in vitro under short-circuited conditions in segments of rat duodenum and descending colon. The calcium-activated ATPase (Ca-ATPase) inhibitor trifluoperazine (TFP, 0.1 mM) reduced net calcium absorption in both tissues by decreasing the absorptive flux from mucosa to serosa (Jm leads to s) without consistently altering the secretory flux from serosa to mucosa. 1,25-Dihydroxyvitamin D3 administration (50 ng/day for 4 days) increased net calcium absorption by increasing Jm leads to s, and TFP reduced Jm leads to s to the same extent across tissues from vehicle- or 1,25-dihydroxyvitamin D3-treated animals. Na-K-ATPase inhibitors ouabain and ethacrynic acid both reduced short-circuit current without affecting calcium fluxes. These data suggest that Ca-ATPase, located in the basolateral membrane of intestinal epithelial cells, plays a role in the transepithelial transport of calcium. More general effects of TFP on intestinal epithelium may also contribute to the reduction in calcium fluxes. Duodenal and descending colon calcium transport appears independent of transcellular sodium transport mediated by Na-K-ATPase.

Animals↗
PubMed1982

Effects of low-calcium diet on urine calcium excretion, parathyroid function and serum 1,25(OH)2D3 levels in patients with idiopathic hypercalciuria and in normal subjects.

We have used a low-calcium diet providing only 2 mg/kg (body weight) per 24 hours of calcium to distinguish between "renal" and "absorptive" idiopathic hypercalciuria. Sixteen of 27 hypercalciuric subjects excreted calcium in excess of intake during days seven, eight and nine of he diet, suggesting some element of renal hypercalciuria; however, all patients had low or normal serum PTH and urine cAMP levels. In general, fasting urine calcium was elevated in these 16 subjects and normal in the remaining 11, who conserved calcium more normally. SErum 1,25(OH)2D3 levels were the same in patients and normal subjects, even though PTH levels of the patients were below those of he normal subjects. Urine magnesium excretion and phosphorus excretion were both increased in the patients who excreted calcium in excess of intake. Our findings suggest that renal and absorptive hypercalciuria may not be distinct entities but rather the two extremes of a continuum of behavior. A uniform elevation of intestinal calcium absorption and a variable defect of renal calcium reabsorption could explain our results far better than the hypothesis of distinct absorptive and renal forms of hypercalciuria.

Calcitriol↗
PubMed1982

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.

Administration, Oral↗
PubMed1982

Effects of metabolic acidosis on PTH and 1,25(OH)2D3 response to low calcium diet.

To study the effects of chronic metabolic acidosis on the metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] rats were given either a low calcium diet (LCD) (0.002% calcium) or chow (1.2% calcium); ammonium chloride (NH4Cl) was added (1 or 1.5%) to the drinking water of some rats eating LCD or chow while others served as nonacidotic controls. LCD increased circulating 1,25(OH)2D3 levels from 46 +/- 14 to 204 +/- 24 pg/ml (P less than 0.001) in the absence of NH4Cl; 1.5% NH4Cl prevented the increase in 1,25(OH)2D3 (25 +/- 6 vs. 27 +/- 8 pg/ml (P, NS) but 1% NH4Cl did not (50 +/- 12 vs. 161 +/- 23 pg/ml; P less than 0.001). Acidosis suppressed neither serum immunoreactive parathyroid hormone (PTH) nor urine cAMP response to LCD. Although total serum calcium and phosphorus showed no regular changes with NH4Cl, acidosis raised blood ionized calcium in rats fed either chow or LCD, and serum 1,25(OH)2D3 levels were inversely correlated with ionized calcium (r = 0.714; P less than 0.001) during LCD. Chronic NH4Cl acidosis prevented serum 1,25(OH)2D3 from rising during LCD, independent of changes in PTH secretion, cAMP generation, or serum phosphorus. The absence of a 1,25(OH)2D3 response may be due to increased ionized calcium produced by acidosis.

Acidosis↗
PubMed1982

Scintigraphic thyroid abnormalities after radiation. A controlled study with 99mTc pertechnetate scanning.

We did 99mTc-pertechnetate thyroid scintigraphy on 99 subjects with no history of therapeutic irradiation to the head or neck. They were compared with 198 irradiated patients selected from a group of over 1700 who were evaluated because of radiation treatment for benign head and neck conditions during childhood. The two groups were similar with respect to age and sex distribution. There were significantly more abnormal scintigrams in the irradiated group (55 of 198 patients versus one of 99 controls). Even after patients and controls with palpable nodules were excluded from the analysis there were still more abnormal scintigrams in the irradiated group (16 of 150 irradiated versus one of 97 control subjects). We conclude that thyroid nodules, including the smaller, nonpalpable nodules discovered by scintigraphy, are related to previous radiation therapy. For persons at substantial risk, such as those who received high-dose treatment (greater than 700 R) during childhood, the data support the use of screening scintigraphy, even with normal findings on palpation.

Adult↗
PubMed1981

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.

Animals↗
PubMed1981

Effects of somatostatin on intestinal calcium transport in the rat.

The addition of somatostatin (SRIF) to rat descending colon in vitro increased the calcium secretory flux from serosa to mucosa (Js leads to m) and reduced tissue short-circuit current (Isc) but did not alter the absorptive flux from mucosa to serosa (Js leads to m). Js leads to m increased by 37% at 10(-9) M SRIF and by 48% at 10(-6) M. The response to SRIF was not altered by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and SRIF did not interfere with stimulation of calcium Jm leads to s by 1,25(OH)2D3. Removal of sodium from the buffer abolished the stimulation of Js leads to m by SRIF without reducing basal Js leads to m. Secretory fluxes of mannitol and calcium were strongly correlated in the presence and absence of SRIF, suggesting that SRIF stimulates a paracellular transepithelial pathway for calcium. In the duodenum, SRIF altered neither calcium Js leads to m nor Isc. In the ileum, calcium Js leads to m increased and Isc decreased, as in the colon, but only by 28 and 12%, respectively. The maximal change in calcium Js leads to m caused by SRIF in these three intestinal segments was negatively correlated with the tissue concentration of immunoreactive SRIF. These results suggest that intestinal calcium secretion could, in part, be regulated by intestinal SRIF.

Animals↗
PubMed1980

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.

Animals↗