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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute clearance studies were performed in normal subjects to establish the site(s) and mechanism of action of the new diuretic agent, bumetanide (3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid), in the human kidney. When the drug was administered during water diuresis, solute-free water formation was unchanged associated with a peak increment in fractional sodium excretion of approximately 15% of filtered load. However, studies performed in hydropenic subjects demonstrated a virtual abolition of free water reabsorption. The diuretic caused a mild phosphaturia which did not appear to be related to alterations in parathyroid hormone. Furthermore, whereas net hydrogen ion excretion and urinary pH were unchanged, the excretion of ammonium ion, titratable acidity and bicarbonate all increased mildly. Taken together, the data suggest that the primary site of action of bumetanide is the medullary portion of the ascending limb of the loop of Henle, but that in addition, bumetanide inhibits the transport of sodium in the proximal nephron. Despite the fact that the drug is a sulfonamide derivative, its proximal activity seems unrelated to a carbonic anhydrase inhibitory effect. More likely the agent interferes with proximal reabsorption by impairing sodium-phosphate linked transport.
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PMID:Study of the sites and mechanisms of action of bumetanide in man. 85 Jan 44

The kidney controls extracellular bicarbonate concentration and the pH of the body by modulating neat acid excretion (ammonium plus titratable acidity minus bicarbonate) according to the systemic acid-base balance. Proton, bicarbonate and phosphate transport and ammonium synthesis in the proximal tubules change in a homeostatic manner. The intercalycial A (proton secreting) and B cells (bicarbonate secreting) of the distal tubule and cortical collecting ducts have a high capacity of adaptation. The wide ascending branch of the loop of Henle also plays an important role in the bicarbonate and ammonium transport. Recent data suggest a pluri-hormonal regulation of urinary acidification. Therefore, the precision of the renal response to metabolic acidosis depends on the coordinated regulation of different segments of the nephron by the parathyroid hormone, aldosterone and the glucocorticosteroids.
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PMID:[Renal regulation of the acid-base equilibrium]. 223 99

Regulation of the acidity of osteoclasts was determined in situ on the endocranial surfaces of mouse calvaria using acridine orange, a fluorescent weak base. Osteoclasts could be identified by large size, multiple nuclei, relatively small numbers of cells, and the way and the extent to which they took up the dye. Nonosteoclastic cells were stained mainly in their nuclei and occasionally in a few lysosomes surrounding their nuclei, which were uniformly single in nonosteoclasts. Nuclei in osteoclasts were also stained, but the staining of the nuclei was partially masked by the intensity and completeness of the staining of the cytoplasm. In some cells the cytoplasmic staining appeared to be in discrete granules, giving the cytoplasm a bright, frothy appearance. This fluorescence was present in both treated and untreated cells and aided in identifying the osteoclasts. Acridine orange fluorescence at 624 nm intensity, and hence, osteoclast acidity, was increased by parathyroid hormone and prostaglandin E2. Parathyroid hormone-induced increases in acidity were inhibited by calcitonin, cortisol, sodium fluoride, and prostaglandin E2. Furthermore, osteoclast acidity was dependent largely or partially on maintenance of K+ and Na+ gradients, patent Na+ channels, chloride-bicarbonate exchange, and H+, K+-ATPase. These findings demonstrate that osteoclasts become acidified by mechanisms similar to those occurring in gastric parietal cells.
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PMID:Humoral and ionic regulation of osteoclast acidity. 243 48

We investigated the effects of calcitonin (CT) and parathyroid hormone (PTH) on the distribution of actin, tubulin, vimentin, and on cell size in cultured chick osteoclasts. In addition, we studied the effects of colchicine on intracellular acidity. Osteoclasts were isolated from the endosteum of 2-3-week chick tibias and were maintained under culture conditions for 5 days. The cells were treated with CT for 30 min or PTH for 60 min and were observed after immunocytochemical staining of cytoskeletal proteins. In untreated cells, actin was found in both a filamentous and a punctate staining pattern, with indented or invaginated regions free of punctate spots. The tubulin distribution in untreated cells was characterized by a pattern of microtubules radiating from the cell center and running parallel to the cell edge. Vimentin staining was usually localized to the perinuclear area. There were no changes in cytoskeletal element distribution or morphology attributable to PTH treatment. Osteoclasts treated with CT were more irregularly shaped, contained more retraction fibers, and were more rounded, with a denser array of cytoskeletal elements in the cell center. In addition, the mean area of the CT-treated cells was significantly less than that of the untreated cells. The actin distribution after CT treatment was still characterized by both a filamentous and a punctate pattern. After CT treatment, vimentin staining appeared more centrally localized than in untreated cells and tubulin staining revealed microtubules which now extended to the retracted cell margin. These results indicate that isolated osteoclasts respond to CT by significant morphological changes which are reflected in the distribution of the major cytoskeletal elements. Disruption of the microtubular system by colchicine treatment also resulted in an initial increase in intracellular acidity, suggesting the involvement of microtubules in the movement of acid-laden vesicles to the exterior.
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PMID:Characterization of the cytoskeleton of isolated chick osteoclasts: effect of calcitonin. 277 8

The effects of acetazolamide, calcitonin (CT), and parathyroid hormone (PTH) on acid production in isolated osteoclasts has been investigated. Osteoclasts were isolated from the endosteum of 3-week chick tibias and were maintained under culture conditions for 5 days. The cells were treated with acetazolamide (10 x 4 M and 10(-7) M), CT (1 mU/ml and 0.31 mU/ml) and PTH (6.5 U/ml and 0.40 U/ml) for 1, 3, 6, and 18 hr. The cells were stained with acridine orange and the intensity of fluorescence measured by a light microscope photometer. Acetazolamide treatment resulted in a steady decline in intracellular acidity, suggesting that carbonic anhydrase plays a major role in acid production in isolated osteoclasts. Treatment with PTH produced a decline in acidity at 1 hr, followed by a peak at 3 hr and then a decline at 6 and 18 hr. The transient increase in acidity may be due to activation of carbonic anhydrase by PTH. Calcitonin treatment also resulted in a decline in cell acidity which was similar, but less pronounced than that resulting from acetazolamide treatment. These results indicate that calcitonin may mediate osteoclast activity by alterations in intracellular acid production.
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PMID:Characterization of isolated and cultured chick osteoclasts: the effects of acetazolamide, calcitonin, and parathyroid hormone on acid production. 314 73

It has recently been documented that a small amount of aluminum is absorbed from a variety of different orally administered aluminum compounds. A variety of factors including gastric acidity, fluoride ingestion, parathyroid hormone, vitamin D and the quantity of aluminum ingested could theoretically modulate aluminum absorption from the gastrointestinal tract. However, partially because of the unavailability of an aluminum isotope, knowledge regarding factors which modify aluminum absorption is quite limited. In healthy individuals the absorbed aluminum is largely eliminated from the body by the kidneys. However, with renal failure the absorbed aluminum is retained and can markedly alter the body aluminum burden with resulting toxicity. In view of this finding, it is suggested that uremic patients receive the smallest amount possible of aluminum-containing, phosphate-binding gels consistent with the control of serum phosphorus levels and that alternate methods for the control of the serum phosphorus should be sought.
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PMID:Gastrointestinal absorption of aluminum. 391 61

Ingestion of protein is known to increase urinary calcium excretion. By studying the effect of intravenous amino acid infusion on calcium excretion, the variables of diets and intestinal absorption are avoided. Five patients on total parenteral nutrition with otherwise constant nutrient infusions containing 240 mg of calcium were randomized to two different levels of amino acid infusion. On 1 g/kg ideal body weight amino acid infusion, two patients excreted more than 240 mg of calcium in the urine, while on 2 g/kg ideal body weight amino acid infusion all five patients lost more calcium in urine than was infused. Mean urinary calcium excretion was increased from 287 to 455 mg/day. On the higher amino acid dose, mean glomerular filtration rate increased from 102 to 143 ml/min. There was no effect of amino acid dose on serum calcium, ionized calcium, parathyroid hormone, and 25 (OH) vitamin D. Calcium excretion corrected for the glomerular filtration rate was increased at the higher amino acid dose, indicating a decrease in renal calcium reabsorption. Daily urinary excretion of sulfate, ammonia, and titratable acidity were increased during the high amino acid infusion. Hypercalciuria induced by high levels of amino acid infusion during total parenteral nutrition may contribute to the development of metabolic bone disease.
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PMID:Amino acid-induced hypercalciuria in patients on total parenteral nutrition. 641 Aug 98

Metabolic acidosis increases urinary calcium excretion in humans as a result of administration of ammonium chloride, an increase in dietary protein intake, and fasting-induced ketoacidosis. An intense bout of exercise, exceeding aerobic capacity, also causes significant decrease in blood pH as a result of increase in blood lactate concentration. In this study we investigated changes in renal calcium handling, plasma parathyroid hormone concentration, and osteoclastic bone resorption after a single bout of resistance exercise. Ten male subjects completed a bout of resistance exercise with an intensity of 60% of one repetition maximum for the first set and 80% of one repetition maximum for the second and third sets. After exercise, blood and urine pH shifted toward acidity and urinary calcium excretion increased. Hypercalciuria was observed in the presence of an increased fractional calcium excretion and an unchanged filtered load of calcium. Therefore, the observed increase in urinary calcium excretion was due primarily to decrease in renal tubular reabsorption of calcium. Likely causes of the increase in renal excretion of calcium are metabolic acidosis itself and decreased parathyroid hormone. When urinary calcium excretion increased, urinary deoxypyridinoline, a marker of osteoclastic bone resorption, decreased. These results suggest that 1) strenuous resistance exercise increased urinary calcium excretion by decreasing renal tubular calcium reabsorption, 2) urinary calcium excretion increased independently of osteoclast activation, and 3) the mechanism resulting in postexercise hypercalciuria might involve non-cell-mediated physicochemical bone dissolution.
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PMID:A bout of resistance exercise increases urinary calcium independently of osteoclastic activation in men. 933 24

A study has claimed that at an equal elemental calcium dose, CaCO3 was not less but equally as efficient in controlling predialysis hyperphosphatemia as calcium acetate, provided both calcium salts were ingested 5 min before meals instead of during meals because the higher acidity of the fasting gastric juice would allow for better dissociation of CaCO3. However, this study did not directly demonstrate that the efficiency of CaCO3 in controlling hyperphosphatemia was actually greater when it was administered before a meal than during a meal. To examine this point, we performed a 3 month randomized crossover trial in 12 reliable and stable patients maintained on chronic hemodialysis. Their plasma concentrations of calcium, protein, phosphate, bicarbonate, urea, and creatinine were measured before the first dialysis of each week and the amount of intact parathyroid hormone (PTH) at the beginning and at the end of each of the 3 months. Comparison of the plasma concentrations measured during the 2 modes of administration showed no significant differences in creatinine, urea, bicarbonate, or intact PTH. The mean (+/-SD) plasma concentration of PO4 was not significantly lower (1.88+/-0.50 vs. 1.74+/-0.41 mM) whereas the corrected level of plasma Ca was significantly lower (2.30+/-0.17 vs. 2.38+/-0.16 mM; p < 0.04) when CaCO3 was given before meals than during meals. In conclusion, the administration of CaCO3 before a meal does not increase its efficiency in controlling hyperphosphatemia because the level of plasma PO4 was actually slightly higher with this timing of administration whereas the comparison of the creatinine and urea levels suggested a stability of phosphate intake and the comparison of the PTH and bicarbonate levels suggested the stability of osteolysis and of the transcellular membrane shift of phosphate. Also, administration of CaCO3 before a meal is associated with significantly lower plasma corrected calcium, suggesting less absorption of calcium, which may be an advantage but only in hypercalcemic patients. There is no reason other than the prevention of its hypercalcemic effect to recommend the administration of CaCO3 just before meals rather than during meals.
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PMID:Role of calcium carbonate administration timing in relation to food intake on its efficiency in controlling hyperphosphatemia in patients on maintenance dialysis. 968 92

Hypophosphatemia caused by renal phosphate loss occurs frequently after kidney transplantation. In assumption of systemic phosphorus depletion, the presumed deficit commonly is replaced by oral phosphate supplements. However, such treatment is debatable, because intracellular phosphorus stores have not been assessed in this setting and may not be accurately reflected by serum phosphate concentrations. Moreover, disturbances in mineral metabolism from chronic renal failure, such as hypocalcemia and hyperparathyroidism, may be prolonged with oral phosphate supplements. Conversely, a neutral phosphate salt might improve renal acid excretion and systemic acid/base homeostasis for its properties as a urinary buffer and a poorly reabsorbable anion. Twenty-eight patients with mild early posttransplantation hypophosphatemia (0.3-0.75 mmol/L) were randomly assigned to receive either neutral sodium phosphate (Na(2)HPO(4)) or sodium chloride (NaCl) for 12 weeks and examined with regard to (1) correction of serum phosphate concentration and urinary phosphate handling; (2) muscular phosphate content; (3) serum calcium and parathyroid hormone (PTH); and, (4) renal acid handling and systemic acid/base homeostasis. Mean serum phosphate concentrations were similar and normal in both groups after 12 weeks of treatment; however, more patients in the NaCl group remained hypophosphatemic (93% versus 67%). Total muscular phosphorus content did not correlate with serum phosphate concentrations and was 25% below normophosphatemic controls but was completely restored after 12 weeks with and without phosphate supplementation. However, the percentage of the energy-rich phosphorus compound adenosine triphosphate (ATP) was significantly higher in the Na(2)HPO(4) group, as was the relative content of phosphodiesters. Also, compensated metabolic acidosis (hypobicarbonatemia with respiratory stimulation) was detected in most patients, which was significantly improved by neutral phosphate supplements through increased urinary titratable acidity. These benefits of added phosphate intake were not associated with any adverse effects on serum calcium and PTH concentrations. In conclusion, oral supplementation with a neutral phosphate salt effectively corrects posttransplantation hypophosphatemia, increases muscular ATP and phosphodiester content without affecting mineral metabolism, and improves renal acid excretion and systemic acid/base status.
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PMID:Metabolic aspects of phosphate replacement therapy for hypophosphatemia after renal transplantation: impact on muscular phosphate content, mineral metabolism, and acid/base homeostasis. 1056 Nov 44


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