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Biomedical subjects

C Y Pak

Publications and source records attributed to C Y Pak.

At least 145 records · Page 8Linked to original sources
PubMed1988

Effect of prolonged bedrest on the propensity for renal stone formation.

The effect of prolonged bedrest immobilization on urinary risk factors for stone formation and on the propensity for the crystallization of calcium salts was examined in eight normal subjects. During 5 weeks of bedrest, the mean urinary calcium excretion rose during the first week and remained elevated (from 5.68 to approximately 7.50 mmol/day). Mean urinary phosphorus excretion increased by the second week of bedrest and remained elevated (from 2.70 to approximately 30.6 mmol/day). Urinary sodium and uric acid excretion rose slightly, as did urinary magnesium. Urinary pH, oxalate, and citrate changed slightly or not at all. Owing to these biochemical alterations, urinary saturation of calcium phosphate, calcium oxalate, and monosodium urate increased significantly during bedrest, but that of uric acid did not change. The inhibitor activity against the spontaneous nucleation of brushite (CaHPO4.2H2O) and calcium oxalate was not altered significantly by bedrest. Thus, the propensity for the crystallization of stone-forming calcium salts was enhanced by bedrest, suggesting that immobilization may confer increased risk for the formation of calcium-containing renal stones.

Adult↗
PubMed1988

Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism.

We wished to determine whether different types of dietary protein might have different effects on calcium metabolism and on the propensity for renal stone formation. Fifteen young normal subjects were studied during three 12-day dietary periods during which their diet contained vegetable protein, vegetable and egg protein, or animal protein. While these three diets were constant with respect to Na, K, Ca, P, Mg, and quantity of protein, they had progressively higher sulfur contents. As the fixed acid content of the diets increased, urinary calcium excretion increased from 103 +/- 15 ( +/- SEM) mg/day (2.6 +/- 0.4 mmol/day) on the vegetarian diet to 150 +/- 13 mg/day (3.7 +/- 0.3 mmol/day) on the animal protein diet (P less than 0.02). Despite the increased urinary calcium excretion, there was a modest reduction of urinary cAMP excretion and serum PTH and 1,25-dihydroxyvitamin D levels consistent with acid-induced bone dissolution. There was no change in fractional intestinal 47Ca absorption. The inability to compensate for the animal protein-induced calciuric response may be a risk factor for the development of osteoporosis. The animal protein-rich diet was associated with the highest excretion of undissociated uric acid due to the reduction in urinary pH. Moreover, citrate excretion was reduced because of the acid load. However, oxalate excretion was lower than during the vegetarian diet [26 +/- 1 mg/day (290 +/- 10 mumol/day) vs. 39 +/- 2 mg/day (430 +/- 20 mumol/day); P less than 0.02]. Urinary crystallization studies revealed that the animal protein diet, when its electrolyte composition and quantity of protein were kept the same as for the vegetarian diet, conferred an increased risk for uric acid stones, but, because of opposing factors, not for calcium oxalate or calcium phosphate stones.

Adult↗
PubMed1988

Preferential infiltration of macrophages during early stages of insulitis in diabetes-prone BB rats.

The subpopulation of lymphoid cells at the different stages of insulitis in BB rats was determined by immunohistochemical techniques with various monoclonal antibodies, including the recently developed OX41, which distinguishes macrophages from T-lymphocytes, OX19 for pan-T-lymphocytes, W3/25 for both helper T-lymphocytes and macrophages, OX8 for cytotoxic T-lymphocytes and natural killer cells, and OX12 for B-lymphocytes. The major population of infiltrated cells found during the early stages of insulitis appeared to be macrophages. This preceded invasion by a mixed population of cells, including both T- and B-lymphocytes and/or natural killer cells. The preferential infiltration of macrophages during the early stages of insulitis strongly suggested that there might be an initial change in the target beta-cells that precedes their immune destruction, although the amplification of immune response by activated T-lymphocytes and natural killer cells at a later stage seemed to be required for the clinical expression of the disease.

Animals↗
PubMed1988

Genetic control of organ-reactive autoantibody production in mice by obesity (ob) diabetes (db) genes.

Inbred strains of mice exhibited genetic and sex-dependent differences in spontaneous production of organ-reactive autoantibodies detected by indirect immunofluorescence. Antitestis autoreactivity was found primarily in sera from C57BL/6J (B6) mice, whereas antigastric autoreactivity was common to both CBA/J and 129/J strains. Autoantibodies against islet cell cytoplasmic antigens (ICAs) were uniquely expressed by C57BL/KsJ (BKs) males. Introduction of the diabetes (db) mutation into these various inbred-strain backgrounds induced expression of ICA, with stronger induction observed in males. The stress imposed by the db or obesity (ob) mutation induced ICA in BKs mice at a higher frequency than in B6 mice; this differential sensitivity was somehow related to a gene linked to the H-2 complex because BKs.B6 H-2b congenic mice resembled B6 mice. The db3J mutation increased the expression of these autoantibodies in 129/J mice, which, like B6, were H-2b and therefore presumably possessed the same H-2-linked inducibility allele as BKs. Cytotoxic autoantibodies against islet cell surface antigens were only observed in C3HeB/FeJ db/db males, and their presence was correlated with beta-cell necrosis. It is concluded that db and/or ob genes appear to play an important role in the production of autoantibodies to islet cells, and sex-linked factor(s) may modify the phenotypic expression of the autoantibodies.

Animals↗
PubMed1988

Excessive growth of cultured beta cells from an adult patient with beta cell hyperplasia.

We have studied a 25-year-old female with frequent, severe hypoglycemic episodes. Concurrent with low serum glucose levels, the concentrations of C-peptide and insulin were markedly elevated. Tests for sulfonylurea hypoglycemic agents were negative. Special tests did not disclose any neoplasm. Biopsy of the pancreatic tail revealed islet cell hyperplasia and adenomatosis. About two-thirds of the pancreas was resected, resulting in correction of all metabolic abnormalities. Specific fluorescein-labeled anti-insulin antibodies revealed staining in 60-80% of the cultured cells isolated from the patient's pancreas, while electron microscopy disclosed insulin storage granules in about 80%. By comparison, for each of these findings, the range for cells from normal pancreases was 30-50%. In contrast to these control cells, cells from the patient grew about 2 and 2.6 times more rapidly during the first two cell cycles, and the growth persisted through four cycles. The greater and more enduring growth of the patient's cells in culture must have been at least partly independent of circulating factors. Paracrine/autocrine principles from the beta cells or other islet cells may have been responsible.

Adult↗
PubMed1987

Inhibition by citrate of spontaneous precipitation of calcium oxalate in vitro.

Effect of citrate on the spontaneous precipitation of calcium oxalate was examined in synthetic media. Citrate significantly increased the formation product of calcium oxalate. This "direct" measure of inhibitor activity, representing activity product at the point of nucleation, rose by 76% by the addition of citrate sufficient to provide trivalent citrate concentration of 1.49 mM. Moreover, citrate inhibited calcium oxalate crystallization by complexing calcium and lowering calcium oxalate saturation. This "indirect" measure of inhibitor activity was assessed from the concentration product of calcium oxalate at the point of nucleation, since this measure should provide a reflection of both ion pair formation and direct inhibitor activity of citrate. The concentration product exceeded the formation product at all ionic (trivalent) citrate concentrations, particularly at high ionic citrate levels. At the ionic citrate concentration of 1.49 mM, the rise in the concentration product was 373%, which was nearly fivefold that observed for the formation product. The presence of ferric or aluminum cations at a physiologic concentration of 2 mg/l did not modify the increase in formation product produced by citrate. Thus, citrate inhibits calcium oxalate crystallization, largely by complexing citrate, but also by directly affecting nucleation. Presence of ferric or aluminum cations at a physiological concentration does not modify the inhibitor action of citrate.

Calcium Oxalate↗
PubMed1987

Hypercalciuria and altered intestinal calcium absorption occurring independently of vitamin D in incomplete distal renal tubular acidosis.

Negative calcium balance and calcium nephrolithiasis are two sequelae of chronic metabolic acidosis. To establish the effects of acidosis on calcium and vitamin D metabolism, we have examined a group of nine patients with incomplete distal renal tubular acidosis. Patients were studied during a control phase and after eight months of potassium citrate treatment, 60 to 80 meq daily. Potassium citrate caused a significant decrease in urinary calcium. The fractional intestinal calcium absorption increased significantly, yet no change was observed in serum vitamin D levels. The estimated calcium balance increased significantly from -70.2 +/- 63.8 to +66.7 +/- 48.7 mg/d (P less than 0.01). Thus, potassium citrate treatment improved the estimated calcium balance by lowering urinary calcium while increasing the fractional intestinal calcium absorption. The original hypercalciuric state, its correction to normocalciuria, and the augmentation of intestinal calcium absorption seen in these patients are probably independent of vitamin D control since there was no change noted in serum 1,25-dihydroxyvitamin D levels.

Acidosis, Renal Tubular↗
PubMed1987

Eventual attenuation of hypocalciuric response to hydrochlorothiazide in absorptive hypercalciuria.

The effect of long-term hydrochlorothiazide therapy on renal calcium excretion was measured in 12 well defined cases of absorptive hypercalciuria and 10 of renal hypercalciuria. Patients were studied during a control phase, at 3 to 6 months of therapy and after long-term treatment with hydrochlorothiazide (mean 61 months for absorptive hypercalciuria and 71 months for renal hypercalciuria). Evaluation comprised measurement of urinary calcium and fractional (intestinal) calcium absorption while patients were maintained on a constant metabolic diet (400 mg. calcium per day) for 3 days. In patients with absorptive hypercalciuria urinary calcium decreased significantly at 3 months of treatment (from 266 to 137 mg. per day, p less than 0.001). However, with continued treatment urinary calcium rebounded to 197 mg. per day. Of the patients with absorptive hypercalciuria 50 per cent were hypercalciuric (greater than 200 mg. per day) on long-term treatment, whereas none was hypercalciuric at 3 months. In contrast, urinary calcium in the patients with renal hypercalciuria decreased from 299 to 104 mg. per day (p less than 0.001) at 3 months of treatment and remained reduced (116 mg. per day) during long-term treatment. Intestinal calcium absorption was increased initially and remained unchanged throughout treatment in the patients with absorptive hypercalciuria. In patients with renal hypercalciuria intestinal calcium absorption decreased significantly after short-term treatment with hydrochlorothiazide and remained so after long-term therapy. The results suggest that, unlike patients with renal hypercalciuria, some with absorptive hypercalciuria lose the hypocalciuric effect of hydrochlorothiazide during long-term treatment.

Adult↗
PubMed1987

The preservation of urine samples for determination of renal stone risk factors.

A preservation technique for urine specimens before determination of stone risk factors was evaluated. The purpose of these experiments was to prove the effectiveness of the preservatives used to prevent changes in the concentrations of those constituents measured. Measured concentrations in fresh specimens were compared with those in the same specimens after storage with the preservatives. Refrigeration at 4 degrees C up to five days was appropriate in a laboratory setting, as no significant changes in urinary concentrations occurred. Refrigeration, however, did not offer a convenient method for shipping. Chemical preservation was found to be an effective alternative to refrigeration. Thymol prevented changes in concentration of pH, citrate, uric acid, sulfate, sodium, potassium, and cyclic AMP, while a mixture of hydrochloric (HCl) acid and boric acid prevented changes in calcium, magnesium, phosphorus, oxalate, ammonium, and creatinine. Thus, the addition of thymol or HCl/boric acid to urine specimens will prevent significant changes in the concentrations of stone risk factors.

Boric Acids↗
PubMed1987

Administration of pharmacological amounts of 25(s),26-dihydroxyvitamin D3 reduces serum 1,25-dihydroxyvitamin D3 levels in rats.

Pharmacological amounts of 25(s),26-dihydroxyvitamin D3 were administered to normal, vitamin D-replete rats in order to assess its pharmacological activity. Treatment with 25(s),26-dihydroxyvitamin D3 (20 micrograms/day for 1 week) caused a marked and significant fall in the circulating concentration of 1,25-dihydroxyvitamin D (16 +/- 5 SEM vs. 28 +/- 4 pg/ml, P = 0.02). This reduction of 1,25-dihydroxyvitamin D was dependent on the dose of 25,26-dihydroxyvitamin D3 administered since a 5 micrograms/day dosing regimen failed to alter serum 1,25-dihydroxyvitamin D levels. Despite the 25-66% reduction in circulating 1,25-dihydroxyvitamin D concentration produced by 25,26-dihydroxyvitamin D3 therapy, serum calcium and intestinal calcium absorption remained normal. These results suggested that 25,26-dihydroxyvitamin D has a weak agonist action or that a further metabolite that stimulates bone calcium resorption and/or intestinal calcium absorption is formed. Rats predosed with 25,26-dihydroxyvitamin D3 (20 micrograms/day) for 4 days and subsequently dosed with both 1,25-dihydroxyvitamin D3 (0.15 micrograms/day) and 25,26-dihydroxyvitamin D3 for an additional 3 days, demonstrated serum 1,25-dihydroxyvitamin D levels significantly higher than that found for control rats (47 +/- 5 vs. 25 +/- 4 pg/ml, P less than 0.001) but significantly reduced from the value observed for rats receiving only 1,25-dihydroxyvitamin D3 (47 +/- 5 vs. 187 +/- 38 pg/ml, P less than 0.001). These results suggest that 25,26-dihydroxyvitamin D3 has a previously unrecognized action in affecting the metabolism of 1,25-dihydroxyvitamin D3.

Animals↗
PubMed1987

Enhanced calcium bioavailability from a solubilized form of calcium citrate.

An improved formulation of calcium citrate with higher aqueous solubility and bioavailability was sought. Mixtures of calcium hydroxide and citric acid, with a calcium to citrate molar ratio ranging from 0.67-1.5, dissolved rapidly in water, creating a metastably supersaturated solution. The presence of an excess of citrate in the mixture delayed the precipitation of calcium citrate and kept calcium in solution longer. Thus, the mixture with a calcium to citrate molar ratio of 1.25, containing 500 mg elemental calcium, dissolved in 300 mL water within 2 min and could be kept in solution for 1 h at a wide pH range between 2 and 7. Intestinal calcium absorption, measured from the increment in urinary calcium during the second 2 h following an oral calcium load (500 mg) in 15 normal subjects was significantly higher from the mixtures (calcium to citrate molar ratios of 1.5 and 1.25) than from tricalcium dicitrate. The fractional calcium absorption, obtained from fecal recovery of radiocalcium after oral administration of 500 mg calcium prelabeled with 47Ca in 11 normal subjects, was also higher for the mixture with a calcium to citrate molar ratio of 1.25. The most efficient calcium absorption was obtained with the mixture of calcium hydroxide and citric acid with a calcium to citrate molar ratio of 1.25. The increment in urinary calcium after an oral load with this mixture was 62.4% greater than that obtained with tricalcium dicitrate [0.138 +/- 0.056 (+/- SD) vs. 0.085 +/- 0.086 mg/dL glomerular filtrate; P less than 0.05]. The fractional calcium absorption was 88.4% higher (0.324 +/- 0.107 vs. 0.172 +/- 0.061; P less than 0.05). This mixture provided the highest concentration of ionic calcium, indicating that calcium (rather than calcium-citrate complex) is the fraction absorbed from the intestinal tract. This study, therefore, suggests that a liquid calcium preparation formulated from the mixture of calcium hydroxide and citric acid is more effective than a solid preparation of tricalcium dicitrate in providing soluble and bioavailable calcium.

Adult↗
PubMed1987

Assessment of the pathogenetic role of physical exercise in renal stone formation.

The effects of moderate physical exercise (performed on a bicycle ergometer to 70-75% of maximum oxygen consumption) without fluid replenishment on urinary chemistries and crystallization of kidney stone-forming substances were compared to those of rest in six normal subjects. Moderate physical exercise significantly decreased urinary pH [from 6.35 +/- 0.32 (+/-SD) to 5.79 +/- 0.33; P less than 0.05] and citrate [from 121.1 +/- 63.5 to 88.2 +/- 44.4 mg/6-h period from initiation of physical exercise; P less than 0.05 (630 +/- 331 to 459 +/- 231 mumol/6 h)], owing to induced metabolic acidosis. The total renal excretion of stone-forming constituents decreased [for example, calcium from 31.2 +/- 15.8 to 21.4 +/- 6.5 mg/6 h (0.8 +/- 0.4 to 0.5 +/- 0.2 mmol/6 h), phosphorus from 155 +/- 42 to 127 +/- 27 mg/6 h (5.01 +/- 1.4 to 4.1 +/- 0.9 mmol/6 h), and uric acid from 172 +/- 60 to 117 +/- 13 mg/6 h (1.0 +/- 0.4 to 0.7 +/- 0.1 mmol/6 h), each P less than 0.05], probably due to extracellular volume contraction (from sweating) and enhanced renal tubular reabsorption. However, the urinary concentration of stone-forming constituents significantly increased during and after moderate exercise because of the fall in urinary volume from 847 +/- 312 to 290 +/- 36 ml/6 h (P less than 0.01). Thus, urinary calcium oxalate saturation increased significantly from 2.62- to 6.68-fold saturation (P less than 0.01). The urinary undissociated uric acid concentration significantly rose [from 31.6 +/- 24.8 to 125.7 +/- 60.3 mg/L (0.19 +/- 0.15 to 0.76 +/- 0.36 mmol/L; P less than 0.01)], due to higher total uric acid concentration and reduced urinary pH. The saturation of calcium phosphate (brushite) did not change significantly, because the rise in urinary calcium concentration was compensated for by reduced phosphate dissociation (from lower urinary pH). The propensity for spontaneous precipitation of calcium oxalate was greater after exercise, as less soluble oxalate was required to elicit nucleation of calcium oxalate [58.0 +/- 21.2 to 49.0 +/- 16.4 mg/L (644 +/- 236 to 544 +/- 182 mumol/L); P less than 0.05]. The results suggest that moderate physical exercise, without increased fluid intake to compensate for excessive sweating, may cause the crystallization of uric acid and calcium oxalate in urine and may enhance the risk of the formation of renal stones composed of these salts.

Adult↗
PubMed1987

Role of cyclosporin A in macromolecular synthesis of beta-cells.

Wistar rats developed hypoinsulinemia and hyperglycemia within 7 days when treated daily with 40 mg/kg body wt of cyclosporin A (CsA) and recovered from the metabolic alteration within 1 wk when CsA treatment was terminated. By light microscopy, there was no lymphocytic infiltration, but cytoplasmic vacuolization in the islets of Langerhans from the CsA-treated rats was seen. By electron microscopy, severe degranulation, cytoplasmic vacuolization, and dilation of endoplasmic reticulum were clearly seen in the pancreatic beta-cells. Islet cells isolated from the CsA-treated rats showed greater than 50% reduction in mRNA synthesis. A similar inhibitory pattern of mRNA synthesis was observed in in vitro CsA-treated (10 micrograms/ml) human pancreatic islet cells from one biopsy sample and in similarly treated rat insulinoma cells (RINm5F). The inhibitory effect of CsA on mRNA synthesis in RINm5F cells was dose dependent, with a 50%-inhibiting dose of 5 micrograms/ml. In addition to the inhibition of mRNA synthesis, CsA also inhibited protein and DNA syntheses, although the inhibitory effect on these macromolecular syntheses was significantly less than that on mRNA synthesis. However, there was only a minor effect of CsA on in vitro transcription and translation compared with that on RINm5F and islet cells. It is concluded that CsA-induced degranulation of the beta-cells in Wistar rats, accompanied by hypoinsulinemia and hyperglycemia, may be due to indirect, reversible interference of the cellular function primarily involved in mRNA synthesis.

Animals↗
PubMed1987

Citrate and renal calculi.

Potassium citrate is a new and exciting therapeutic approach which has considerably broadened our capability for the medical control of stone disease. The discussion summarizes the data supporting utility of potassium citrate in the management of renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate nephrolithiasis ('idiopathic', or secondary to chronic diarrheal syndrome or thiazide therapy) and uric acid lithiasis with or without calcium stones.

Citrates↗
PubMed1987

Effects of environmental factors on the development of insulin-dependent diabetes mellitus.

The development of insulin-dependent diabetes mellitus is thought to be dependent on either the autoimmunity or the interaction of environmental agents with the pancreatic beta cells, or both in a genetically susceptible host. As environmental factors affecting the induction of type I diabetes, diabetogenic chemicals and viruses are likely candidates as primary injurious agents for pancreatic beta cells in man and animal. A number of structurally diverse chemicals including alloxan, streptozotocin, chlorozotocin, vacor, and cyproheptadine are diabetogenic mainly in rodents and sometimes in man. The possible mechanisms for the beta cell destruction by these chemicals include (a) generation of oxygen free radicals and alteration of endogenous scavengers of these reactive species; (b) breakage of DNA and consequent increase in the activity of poly ADP ribose synthetase, and enzyme depleting NAD in beta cells; and (c) inhibition of active calcium transport and calmodulin-activated protein kinase activity. Regarding viruses, a number of different viruses including encephalomyocarditis virus, Mengovirus, Coxsackie B viruses, and Reoviruses can infect and destroy pancreatic beta cells mainly in rodents and sometimes in humans. In the murine model, the development of encephalomyocarditis and Coxsackie B virus-induced diabetes is dependent on the genetic background of the host and the genetic makeup of the virus. Mengo-2T virus has caused diabetes in strains of mice resistant to encephalomyocarditis virus-induced diabetes. In contrast to encephalomyocarditis virus, Coxsackie B viruses, and Mengovirus, reovirus type 1 seems to be somewhat associated with an autoimmune response in the induction of diabetes. In addition to the murine model, cotton rats become diabetic when inoculated with Mengovirus 2T. Furthermore, cumulative environmental insults with Coxsackie B viruses and chemicals result in diabetes in non-human primates. In man, there may be 2 possible roles for viruses in the pathogenesis of insulin-dependent diabetes mellitus. The one is acute cytolytic infection of beta cells (e.g., Coxsackie B viruses), which may sometimes induce diabetes in genetically predisposed individuals, and the other one is slow and persistent infection (e.g., congenital cytomegalovirus and Rubella), which may induce autoimmunity, leading to type I diabetes.

Animals↗