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S J Whiting

Publications and source records attributed to S J Whiting.

35 records · Page 2Linked to original sources

Effect of diets high in sodium and potassium on the magnitude of theophylline-induced hypercalciuria in the rat.

The effects of dietary sodium and potassium, given as salts of chloride or bicarbonate, on theophylline-induced hypercalciuria in the rat were investigated. In experiment 1, rats fed diets containing 0.3 mmol/g diet NaCl, KCl, NaHCO3, or KHCO3 exhibited a calciuria of NaCl > KCl > controls = NaHCO3 = KHCO3. This study indicated that cation effects were dependent on the accompanying anion, however the dose of added salt was inadequate to produce a consistent, significant salt effect. A second experiment was run in which animals were given salts at 0.4 mmol/g diet; the salt-induced pattern of calciuria was similar. After one week of salt pretreatment, rats were given diets containing theophylline (7.72 mumol/g diet), which induced calciuria all groups regardless of salt pretreatment. Urinary volume and urinary phosphate changes were parallel to each other and not to the changes in urinary calcium induced by salt or theophylline. Changes in urinary excretion of prostaglandin E2 were directly proportional to changes in urinary calcium. In the rat, pretreatment with sodium bicarbonate or sodium chloride reduces the extent of theophylline-induced diuresis, but does not reduce theophylline-induced hypercalciuria. Further, potassium chloride increases and potassium bicarbonate does not reduce urinary calcium excretion. Theophylline-induced calciuria is correlated with prostaglandin E2 excretion rates.

Animals↗

Comparison of in vitro and in vivo tests for determination of availability of calcium from calcium carbonate tablets.

In vitro tests of calcium (Ca) availability and the oral Ca load test were conducted on eight brands of calcium carbonate (CaCO3) tablets (products A-H) each providing 500 mg Ca. Data were collected over three experiments with nine to 11 healthy premenopausal women testing two to four products. Subjects followed a low Ca diet (less than 10 mmol/day). On test mornings, fasting subjects collected baseline urine for 2 hours (-2 to 0 hours), then ingested the tablet with water. Urine was collected from 0 to 2 hours and 2 to 4 hours; for products E-H, urine was collected for an additional 2 hours (4 to 6 hours). Blood was sampled at hours 0, 4 and 6 during testing of products E and F. Three in vitro tests were run: the United States Pharmacopeia (USP) dissolution test, USP disintegration test, and a disintegration test using vinegar. Ca excretion rose significantly at hours 2 to 4 (p less than 0.05) compared to baseline for seven products. Ca excretion either fell or remained constant between hours 4 and 6. Serum Ca rose and serum parathyroid hormone fell at hour 4, compared to fasting values, suggesting that 4 hours represents peak response time. In vivo availability, measured as the incremental increase in Ca excretion (mmol/mmol creatinine) in hours 2 to 4 compared to baseline, did not correlate significantly with results of the USP dissolution test but did with results of either the USP disintegration test or the vinegar test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro and in vivo assessment of the bioavailability of potassium from a potassium tartrate tablet.

The bioavailability of potassium from orally administered potassium tartrate was evaluated in 20 normal subjects under metabolic balance conditions. Subjects were given 34 mmol potassium (5 tablets of Cal-K) as a divided dose on each of 2 consecutive days. Urinary excretion of potassium, as determined from 24-h urinary collections on the 3 days preceding dosage totalled 192.6 +/- 50.9 mmol (mean +/- S.D., n = 20). It increased significantly (p less than 0.05) to 258.7 +/- 54.2 mmol for the 2 days of dosage and the following day. The difference of 66.1 mmol representing absorbed potassium was close to the 68 mmol potassium given and indicated a bioavailability of potassium in excess of 97 per cent; after correction for creatinine excretion, potassium recovery rose to 99.9 per cent. The dissolution characteristics of the Cal-K tablets were also determined. After dissolution in simulated gastric juice (pH 1.2), 84.4 +/- 10.6 per cent (mean +/- S.D., 6 experiments) was dissolved; after adjustment to pH 7.3, dissolved potassium increased to 91.3 +/- 8.5 per cent. No precipitation or residue formed as a result of the pH change. Both sets of results indicate that potassium from these potassium tartrate tablets is in a highly bioavailable form.

Adult↗

Increased serum sulfate after protein loading in adult humans.

To determine the effects of a protein loading on sulfate metabolism in humans, we monitored serum sulfate concentrations in 12 fasting adult volunteers fed a high-protein meal of egg white and an isocaloric low-protein meal. With each subject serving as his or her own control, we found that mean serum sulfate rose only slightly with the low-protein meal but was significantly higher with high-protein loading at 3 and 3.5 h. The median of the peak sulfate concentration was 57% greater than baseline with the high-protein meal versus 11% with no loading. Since changes in serum sulfate have been shown to influence the rate of sulfation for a variety of different acceptor molecules, these observations indicate a means by which protein feeding may simultaneously influence diverse metabolic pathways.

Adult↗

Effect of prostaglandin inhibition on caffeine-induced hypercalciuria in healthy women.

Caffeine ingestion increases urinary calcium excretion. The mechanism is not known, but prostaglandin synthesis has been implicated. We hypothesized that administration of a prostaglandin inhibitor such as acetylsalicylic acid (aspirin) along with caffeine would prevent caffeine-induced hypercalciuria. We measured 3-hour excretion in fasting subjects who each randomly ingested four treatments on nonconcurrent mornings: no drug, caffeine (5 mg/kg body weight), acetylsalicylic acid (650 mg), or caffeine plus acetylsalicylic acid. In experiment 1, nine healthy premenopausal female subjects were studied; each treatment was taken with 200 ml of orange juice. Water was provided hourly to encourage urine flow. Urinary calcium excretion rose with caffeine treatment; mean 3-hour calcium (mmol/mmol creatinine) was 0.49 +/- 0.07 compared with 0.23 +/- 0.04 during the no-drug treatment. Acetylsalicylic acid caused a significant reduction in urinary calcium to 0.13 +/- 0.08; when it was combined with caffeine, caffeine-induced calcium excretion fell significantly to 0.35 +/- 0.08. Sodium excretion tended to reflect calcium excretion. Urinary prostaglandin E(2) fell significantly with acetylsalicylic acid, with and without caffeine. There were no significant changes in creatinine, water, or potassium excretion. Experiment 2 was similar, except that water was substituted for orange juice to test the possibility that acetylsalicylic acid affected elevated but not basal calcium excretion. Similar and even more pronounced results were obtained, with caffeine causing a threefold increase in urinary calcium, acetylsalicylic acid causing a decrease by half, and the combined drug treatment being greater than no drug but less than caffeine alone. Urinary phosphorus rose significantly with caffeine alone. Prostaglandin synthesis may not be directly involved in caffeine-induced hypercalciuria, as the magnitude of the caffeine-induced increase was similar when treatments given the acetylsalicylic acid were compared with those without a prostaglandin synthesis inhibitor.

Journal Article↗

The effect of adenosine and adenosine analogues on methylxanthine-induced hypercalciuria in the rat.

The chronic effects of dietary caffeine, theophylline, and theobromine on urinary calcium excretion were investigated in the adult male rat. The effect of acutely administered adenosine and adenosine analogues on methylxanthine-induced hypercalciuria was concurrently investigated. When rats were fed equimolar amounts of theobromine, caffeine, and theophylline, it was found that urinary calcium excretion increased; on day 7 values were increased over controls (p less than 0.05) by 54, 146, and 208%, respectively. On day 20, an injection of adenosine reduced calcium excretion in methylxanthine-treated rats to levels not different from control values. In another series of experiments, theophylline was fed to a group of rats to establish hypercalciuria. Three adenosine analogues N6-(L-2-phenylisopropyl)adenosine (R-PIA), N6-(D-2-phenylisopropyl)adenosine (S-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA) with different adenosine receptor specificities (A2,A1, and weakly A2, respectively) were administered to different groups of theophylline-fed and control rats, and their calcium excretions were measured. It was found that the order of efficacy of the analogues in reducing calcium excretion was NECA greater than R-PIA greater than S-PIA, which is consistent with the receptor being A2. A proportion of the methylxanthine-induced hypercalciuria may be due to adenosine antagonism.

Adenosine↗

Effect of dietary caffeine and theophylline on urinary calcium excretion in the adult rat.

The chronic effects of dietary caffeine or theophylline on urinary calcium excretion were investigated in the adult male rat. When caffeine was added at two concentrations, 0.75 and 1.50 g/kg diet, 24-h urinary calcium excretion rose 300 and 450% on d 7, and 200 and 330% on d 14, respectively. There were no changes in the 24-h urinary excretion of phosphate, sulfate, sodium and cAMP nor did urine volume change. The high dose of caffeine was compared to an equimolar dose of theophylline (1.39 g/kg diet) in both Wistar and Sprague-Dawley rats. Urinary calcium excretion in theophylline-treated rats was significantly greater than in caffeine-treated rats on all sampling days and in both strains of rat; the calciuric effect lasted at least 22 d. When rats were given indomethacin (3.3 mg/kg diet) the calciuria induced by caffeine and theophylline was abolished, and sodium excretion in all groups was reduced by 35-50%, but urine volume was unchanged. The calciuria of methylxanthine feeding may result from a prostaglandin-mediated process distinct from diuresis.

Animals↗

The comparative effects of feeding ammonium carbonate, ammonium sulfate, and ammonium chloride on urinary calcium excretion in the rat.

When either sulfate or chloride is added to the diet, the resulting acid load causes a rise in urinary calcium excretion. There is, however, the possibility that sulfate, which has been shown to complex renal tubular calcium, will further decrease renal calcium reabsorption and thus produce a greater calciuria than chloride. Because addition of a fixed cation (e.g., sodium) to the diet may also stimulate calciuresis, experiments were conducted using metabolizable ammonium to minimize cation effects. Ammonium salts of sulfate, chloride, and carbonate (control) were added to the diets of male rats at 0.3 mequiv./g weight of diet. Twenty-four hour excretion rates of calcium, sulfate, chloride, and net acid were measured at various intervals up to 1 month. As expected, the chloride and sulfate diets were both associated with significantly elevated urine calcium and net acid excretion as compared with controls. However, those fed sulfate exhibited significantly less calcium and acid excretion and absorbed a smaller proportion of the anion load than those given chloride. In a second experiment, the amounts of supplemental sulfate and chloride were adjusted so that total absorptions were similar. At 2 weeks, both calcium and acid excretions in the fixed anion groups were no longer significantly different. Thus, in chronic feeding trials, there appears to be no measurable difference in the calciuretic properties of sulfate and chloride anions.

Ammonium Chloride↗

Effect of dietary anion composition on acid-induced hypercalciuria in the adult rat.

The effects of replacing dietary carbonate (0.3 meq/g diet) by sulfate (SO4) or chloride (Cl) on urinary calcium (Ca) excretion were investigated in the adult male rat. When anion substitutions were made by manipulating Ca and Mg salts, urinary Ca excretion was significantly higher in the SO4 and Cl groups, the Cl-induced calciuria being twice that of the SO4 group. Replacement of carbonate by chloride was associated with higher net acid excretion. Replacement by SO4 promoted an equivalent excretion of acid, if apparent absorption of anion is taken into account. When substitutions were made by manipulating magnesium, sodium and potassium but not Ca salts, urinary Ca excretion and net acid excretion were higher in both fixed anion groups. In this second study, absorption of anion in the Cl and SO4 groups was not different (54 and 59%, respectively). Feeding either Cl or SO4 raises urinary Ca to a similar extent when equivalent changes in acid-base balance are induced. The excessive calciuria, ascribed by others to the formation of CaSO4 complexes in the urine, is not manifest when net acid excretion is significantly increased.

Animals↗

Electrolyte handling by the superficial nephron of the rabbit.

A micropuncture study of the rabbit was performed to evaluate the function of the superficial nephron. The mean glomerular filtration rate of the left micropunctured kidney was 4.0 +/- 0.8 ml/min. The concentration profile of electrolytes within the proximal tubule was similar to that of species previously investigated except for potassium. The mean tubular fluid (TF)-ultrafilterable (UF) concentration ratios were as follows: sodium, 1.01 +/- 0.03; chloride, 1.14 +/- 0.04; calcium, 1.12 +/- 0.04; magnesium, 1.47 +/- 0.08; and phosphate, 0.94 +/- 0.09, with a mean TF-plasma (P) inulin concentration ratio of 1.78 +/- 0.14 (n = 32). The TF/UF potassium value significantly increased in association with TF/P inulin to a mean value of 1.26 +/- 0.06. Accordingly, 29% of the filtered potassium was reabsorbed in the superficial proximal tubule compared with 43% of the filtered sodium. The loop of Henle reabsorbed 55-60% of the filtered sodium, chloride, and calcium, whereas considerably less magnesium (33%) was reabsorbed. Segments beyond the distal tubule collection site reabsorbed little of the delivered magnesium, which supports the notion that the loop of Henle is the principal segment accounting for adjustments in magnesium balance. These studies indicate that the superficial nephron of the rabbit performs similar to other species reported, except potassium reabsorption is significantly less in the proximal convoluted tubule.

Animals↗

Effects of intraluminal pH and dietary phosphate on phosphate transport in the proximal convoluted tubule.

The proximal tubule cell adjusts its phosphate absorption appropriately to meet the needs of the organism. Studies were performed to characterize some of the cellular changes involved with dietary phosphate adaptation. First, early proximal convoluted tubules were perfused with equilibrium Ringer solutions buffered to pH 7.65 or 6.5. Saturation kinetics for phosphate transport were determined at each pH value. Rats maintained on a diet of normal phosphate composition demonstrated the apparent Jmax and Km parameters about twofold greater with intraluminal pH 7.65 vs. pH 6.5. The Jmax values increased to 53.47 +/- 3.71 and 42.73 +/- 5.48 pmol X min-1 X mm-1, respectively, when the rats were placed on a phosphate-restricted diet for 5 days. By contrast, adaptation to a high dietary phosphate content resulted in diminished phosphate absorption, 8.53 +/- 1.80 and 12.87 +/- 1.61 pmol X min-1 X mm-1, for the respective pH 7.65 and 6.5 values. Second, the effect of peritubule phosphate concentration was evaluated at constant intraluminal phosphate concentrations. Unidirectional lumen-to-blood phosphate efflux was inhibited at all plasma phosphate concentrations in animals maintained on normal dietary phosphate. By contrast, rats adapted to a low phosphate diet exhibited an increase in phosphate absorption: pH 7.65, 86.21 +/- 2.63, and pH 6.5, 140.84 +/- 86.76 pmol X min-1 X mm-1 when plasma concentrations were elevated two- or three-fold from 2.4 to 6.4 mM. This was attributed to enhanced phosphate exchange on the basolateral membrane. Further hyperphosphatemic levels, above 6.4 mM, inhibited phosphate absorption. These data suggest that net phosphate absorption is determined, in part, by factors other than sodium-dependent uptake of phosphate by the brush border membrane including intracellular pH and peritubular phosphate that act in concert to control renal phosphate absorption.

Absorption↗

Effects of dietary calcium on renal calcium, magnesium and phosphate excretion by the rabbit.

The renal handling of calcium, phosphate and magnesium was evaluated in rabbits fed diets varying in calcium content. Rabbits fed a low calcium diet (0.29%) exhibited a significant decrease in 24-hour excretion of calcium and in plasma calcium, and a significant increase in 24-hour excretion of phosphate, compared with rabbits fed a normal calcium diet (0.61%). Rabbits fed a high-calcium diet (1.89%) excreted significantly more calcium and less phosphate than the group fed normal dietary calcium. When measured under acute clearance conditions, the fractional excretion of calcium averaged 1-2% in rabbits fed either the low- or normal-calcium diets and increased to 6% in rabbits fed the high-calcium diet. In both acute and chronic studies, fractional phosphate excretion declined as the content of dietary calcium was raised. Magnesium excretion was not altered by the dietary calcium levels. Although calcium excretion by rabbits is set proportionately higher than that of other species, renal calcium handling in the rabbit is appropriate. Phosphate handling by the rabbit kidney similarly responds appropriately to dietary calcium manipulation.

Animals↗

Effect of chronic high protein feeding on bone composition in the adult rat.

A study of the effect of feeding a high protein diet on bone metabolism was conducted using adult rats deep-labeled with 45Ca. A control diet (15% soy protein plus 0.2% methionine) and a high protein diet (control plus 20% lactalbumin) were fed for 10 months. Rats fed the high protein diet exhibited increases in urinary Ca, 45Ca, sulfate and volume. Total 45Ca excretion, urine calcium specific activity and urine phosphorus initially were depressed indicating an increase in the intestinal absorption of calcium, then were not significantly different from control values. After 10 months, analysis of the femur, tibia and mandible revealed no differences in wet weight, dry fat-free or ash weight, calcium, phosphorus, magnesium, or residual 45Ca content. Specific gravity and ash density also were unaffected by protein intake, as were femur length and midshaft cortical thickness. No changes in bone composition were found which would indicate that high protein diets promote bone loss in this species. The adult rat appears to be capable of compensating for the increased urinary loss of Ca associated with an increment in acid load (whether derived from an increase in diet acidity or in metabolic acid production) by reducing the fractional loss of endogenous Ca in the feces.

Animals↗

Effect of a chronic acid load as sulfate or sulfur amino acids on bone metabolism in adult rats.

Diets containing an acid load as either sulfur amino acids (SAA) or inorganic sulfate were fed to 45Ca-labeled adult male rats for 10 months. Radioisotope excretion and bone composition data (femur, tibia, mandibles) were compared with those for rats fed a control (15% soy protein) diet. Rats fed the SAA supplement (1.28% cystine plus 0.19% methionine) exhibited a significant reduction in femoral weight and A:R ratio and a tendency toward lower specific gravity, dry weight, fat-free weight and calcium content. Femoral radioautographs indicated a reduction in metaphyseal bone density in six of eight animals. We have postulated that the osteopenia produced by feeding excess free SAA may be due to decreased bone formation caused by a reaction between homocysteine and the aldehyde groups of collagen, as in genetic homo-cystinuric osteoporosis. Sulfate feeding (1.42% of the diet) produced a significant increase in 45Ca excretion, indicative of enhanced bone resorption, lasting about 2 months. There was a tendency for bone mass measurements to be lower than controls after 10 months, but the differences were not significant. Two of eight sulfate-fed rats showed radiographic evidence of osteopenia. No evidence of osteopenia was seen in the controls or in rats previously fed a high protein diet containing the same concentration of SAA.

Amino Acids, Sulfur↗

The role of sulfate in the calciuria of high protein diets in adult rats.

Diets containing different sources of protein were evaluated for their effect or urinary calcium (Ca) excretion in adult male rats. High protein diets were prepared by adding 24 g N/kg as lactalbumin (Hi-Lact), egg white (Hi-EW), casein (Hi-Cas) or gelatin (Hi-Gel) to a control diet containing 24 g N/kg ascasein (Cas). There were significant differences in the degree of hypercalciuria produced by different dietary protein mixtures. A peak in Ca excretion occurred at about 2 days, when the relative values were as follows (Cas = 100): Hi-Lact, 489; Hi-EW, 429; Hi-Cas, 340, and Hi-Gel, 263. Subsequently urinary Ca declined, but a moderate hypercalciuria persisted to the end of the 8-weekexperiment, when the corresponding values (% Cas) were 200, 183,160 and 136, respectively. The degree of hypercalciuria was proportional to the sulfur content of the diets, i.e., Hi-Lact greater than Hi-EW greater than Hi-Cas greater than Hi-Gel greater than Cas. Supplementing the Cas diet with sulfur amino acids to the level present in the Hi-Lact diet resulted in a comparable increase in Ca excretion. Supplementing the Cas diet with 1.42% sulfate produced a 570% increase in urinary Ca on day 2 and a 306% increase at 5 weeks. There was a linear relationship between Ca excretion and sulfate excretion. It is proposed that a major factor in the hypercalciuria of high protein feeding is the production and excretion of sulfate. Variability in the calciuric effect of different proteins appears to be related mainly to differences in their sulfur amino acid content.

Amino Acids, Sulfur↗

Effect of nutritional factors and cortisol on tyrosine aminotransferase activity in liver of brook trout, Salvelinus fontinalis Mitchill.

1. Starvation for over 50 days increased the activity of Tyrosine aminotransferase (TAT) from brook trout liver and decreased liver glycogen. 2. Cortisol (6-40 mg/100 g body wt) increased TAT activity, optimally 72 hr post-injection; liver glycogen response to cortisol was variable while tissue water either increased or remained constant. 3. Fish fed high-protein/low-carbohydrate had greater TAT activity than fish fed low-protein/high carbohydrate. There was food-induced peak of activity indicating a "diurnal rhythm" analogous to that of rat TAT. 4. TAT activity in brook trout appears to be correlated with protein catabolism.

Animals↗