Search NASA⌕ Search

Engineering topics

Pak, C. Y.

Publications and source records attributed to Pak, C. Y..

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.

NASA Discipline Musculoskeletal↗
NASA NTRS1997

Renal stone risk assessment during Space Shuttle flights

PURPOSE: The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. MATERIALS AND METHODS: 24-hr. urine samples were collected prior to, during space flight, and following landing. Urinary and dietary factors associated with renal stone formation were analyzed and the relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. RESULTS: Urinary composition changed during flight to favor the crystallization of calcium-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. CONCLUSIONS: This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. Dietary and pharmacologic therapies need to be assessed to minimize the potential for renal stone formation in astronauts during/after space flight.

STS Shuttle Project↗
NASA NTRS1997

Medical therapy, calcium oxalate urolithiasis

The development of diagnostic protocols that identify specific risk factors for calcium oxalate nephrolithiasis has led to the formulation of directed medical regimens that are aimed at correcting the underlying metabolic disturbances. Initiation of these treatment programs has reduced markedly the rate of stone formation in the majority of patients who form stones. This article discusses the rationale that underlies the choice of medical therapy for the various pathophysiologic causes of calcium oxalate nephrolithiasis and the appropriate use of available medications.

Review↗
NASA NTRS1995

Prevention of hypercalciuria and stone-forming propensity during prolonged bedrest by alendronate

The bone loss and hypercalciuria induced by immobilization or the decreased gravitational forces of space are well described. Using a model of bedrest immobilization, the ability of a potent aminobisphosphonate, alendronate, to avert hypercalciuria and stone-forming propensity was tested. Sixteen male subjects participated in a randomized, placebo-controlled trial in which they received either 20 mg of alendronate or placebo 2 weeks prior to and during 3 weeks of strict bedrest. Parameters of bone and calcium metabolism and urinary crystallization of stone-forming salts were measured before and at the end of bedrest. In the placebo group, bedrest increased urinary calcium (209 +/- 47 to 267 +/- 60 mg/day, p < 0.01) and the saturation of calcium phosphate. Before bedrest, the alendronate group had a significantly lower serum calcium (8.8 +/- 0.4 vs. 9.6 +/- 0.5 mg/dl, p < 0.01) and higher serum PTH (62.4 +/- 33.1 vs. 23.1 +/- 7.5 pg/ml, p < 0.01) compared with the placebo group. Moreover, the alendronate group had a lower urinary calcium (75 +/- 41 mg/day) and saturation of calcium oxalate and calcium phosphate. These effects of alendronate were sustained during bedrest. Following bedrest in the alendronate group, urinary calcium rose to 121 +/- 50 mg/day, a value less than that in the placebo group before or during bedrest. Similarly, urinary saturation of calcium oxalate and calcium phosphate rose with bedrest in the alendronate-treated patients but remained lower than values obtained in placebo-treated patients before or during bedrest. Alendronate inhibits bone mineral loss and averts the hypercalciuria and increased propensity for the crystallization of stone-forming calcium salts which occurs during 3 weeks of strict bedrest.

Non-NASA Center↗
NASA NTRS1994

Citrate and renal calculi: an update

Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.

NASA Discipline Regulatory Physiology↗
NASA NTRS1993

Alterations in renal stone risk factors after space flight

Exposure to the microgravity environment of space produces a number of physiological changes of metabolic and environmental origin that could increase the potential for renal stone formation. Metabolic, environmental and physicochemical factors that influence renal stone risk potential were examined in 24-hour urine samples from astronauts 10 days before launch and on landing day to provide an immediate postflight assessment of these factors. In addition, comparisons were made between male and female crewmembers, and between crewmembers on missions of less than 6 days and those on 6 to 10-day missions. Results suggest that immediately after space flight the risk of calcium oxalate and uric acid stone formation is increased as a result of metabolic (hypercalciuria, hypocitraturia, pH) and environmental (lower urine volume) derangements, some of which could reflect residual effects of having been exposed to microgravity.

NASA Center JSC↗
NASA NTRS1993

The potential role of salt abuse on the risk for kidney stone formation

The kidney stone-forming risk of a high sodium diet was evaluated by assessing the effect of such a diet on the crystallization of stone-forming salts in urine. Fourteen normal subjects participated in 2 phases of study of 10 days duration each, comprising a low sodium phase (basal metabolic diet containing 50 mmol. sodium per day) and a high sodium phase (basal diet plus 250 mmol. sodium chloride per day). The high sodium intake significantly increased urinary sodium (34 +/- 12 to 267 +/- 56 mmol. per day), calcium (2.73 +/- 1.03 to 3.93 +/- 1.51 mmol. per day) and pH (5.79 +/- 0.44 to 6.15 +/- 0.25), and significantly decreased urinary citrate (3.14 +/- 1.19 to 2.52 +/- 0.83 mmol. per day). Arterialized venous blood bicarbonate and total serum carbon dioxide concentrations decreased significantly during the high sodium diet, whereas serum chloride concentration increased. However, no change in arterialized venous pH was detected. Thus, a high sodium intake not only increased calcium excretion, but also increased urinary pH and decreased citrate excretion. The latter effects are probably due to sodium-induced bicarbonaturia and a significant decrease in serum bicarbonate concentration, respectively. Commensurate with these changes, the urinary saturation of calcium phosphate (brushite) and monosodium urate increased, and the inhibitor activity against calcium oxalate crystallization (formation product) decreased. The net effect of a high sodium diet was an increased propensity for the crystallization of calcium salts in urine.

Non-NASA Center↗
NASA NTRS1993

Alkali absorption and citrate excretion in calcium nephrolithiasis

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

Non-NASA Center↗
NASA NTRS1993

Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys

It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967-1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an empty stomach at a recommended dose of 20 mmol calcium/day.

Non-NASA Center↗
NASA NTRS1992

Reduced vertebral bone density in hypercalciuric nephrolithiasis

Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

Non-NASA Center↗
NASA NTRS1992

Modification by food of the calcium absorbability and physicochemical effects of calcium citrate

The food-calcium (Ca) interaction was examined in 12 healthy women (mean age 38 years) maintained on a constant metabolic diet. They underwent three phases of study, comprised of control (no Ca), Ca citrate (1 g Ca/day) during meals, and Ca citrate separately from meals. Each phase was 7 days in length and two 24-hour urine samples were collected on days 6 and 7. The rise from the control phase in urinary Ca was slightly more prominent when Ca citrate was given with meals than without (68 and 62%, respectively). The fall in urinary phosphorus was equivalent at about 25% between Ca citrate phases. The rise in urinary citrate and pH and the decline in urinary ammonium were more prominent when Ca citrate was given with meals; however, the changes were small or nonsignificant. The urinary saturation of Ca oxalate, brushite or monosodium urate did not differ between the two Ca citrate phases. There was a nonsignificant rise in serum iron during Ca citrate phases. The results suggest that: 1) dissolution and absorption of Ca citrate might be slightly greater when given with food than without; 2) that the ability of Ca citrate to attenuate crystallization of stone-forming Ca salts in urine is not modified by food; and 3) that Ca citrate may not impair iron absorption from food.

Non-NASA Center↗
NASA NTRS1992

Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients

We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

NASA Discipline Regulatory Physiology↗
NASA NTRS1992

Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria

We present iliac bone histomorphometric data and related biochemical data from 16 nonalcoholic men (50 +/- 11 (SD) years) referred for evaluation of spontaneous skeletal and/or appendicular fractures and reduced spinal bone density. All men were eugonadal and had no known underlying disorder associated with osteopenia. For the group, mean serum chemistry values were within normal limits including immunoreactive parathyroid hormone, osteocalcin and serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Nine men demonstrated hypercalciuria (greater than or equal to 0.1 mmol/kg per day) while on a constant metabolic diet of 20 mmol/day Ca. Their 24-hour urinary calcium was significantly greater than that for the remaining 7 men (7.4 +/- 1.6 vs. 5.0 +/- 0.8 mmol/day, p = 0.003), as was their calciuric response to a 1 g oral calcium load (0.23 +/- 0.06 vs. 0.15 +/- 0.05 Ca/creatinine, p = 0.042). Serum parameters (including parathyroid hormone and 1,25(OH)2D) of hypercalciuric and normocalciuric men were not significantly different. Histomorphometric indices for cancellous bone demonstrated significant differences between the entire group of osteoporotic men and age-adjusted normal values for bone volume (11.4 +/- 4.0% vs. 23.2 +/- 4.4%), osteoid surface (5.6 +/- 3.9% vs. 12.1 +/- 4.6%), osteoblastic surface (2.0 +/- 2.3% vs. 3.9 +/- 1.9%), and mineralizing surface (1.9 +/- 2.4% vs. 5.1 +/- 2.7%); there were also significant differences in bone formation rate (total surface referent) (0.004 +/- 0.001 vs. 0.011 +/- 0.006 mm3/mm2 per year). Compared with the normocalciuric group the 9 hypercalciuric men had significantly lower osteoblastic surfaces (1.6 +/- 1.9% vs. 2.5 +/- 2.6%) and mineralizing surfaces (1.4 +/- 1.5% vs. 2.7 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Regulatory Physiology↗
NASA NTRS1992

Gastrointestinal citrate absorption in nephrolithiasis

Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

Non-NASA Center↗
NASA NTRS1992

Citraturic response to oral citric acid load

It is possible that some orally administered citrate may appear in urine by escaping oxidation in vivo. To determine whether this mechanism contributes to the citraturic response to potassium citrate, we measured serum and urinary citrate for 4 hours after a single oral load of citric acid (40 mEq.) in 6 normal subjects. Since citric acid does not alter acid-base balance, the effect of absorbed citrate could be isolated from that of alkali load. Serum citrate concentration increased significantly (p less than 0.05) 30 minutes after a single oral dose of citric acid and remained significantly elevated for 3 hours after citric acid load. Commensurate with this change, urinary citrate excretion peaked at 2 hours and gradually decreased during the next 2 hours after citric acid load. In contrast, serum and urinary citrate remained unaltered following the control load (no drug). Differences of the citratemic and citraturic effects between phases were significant (p less than 0.05) at 2 and 3 hours. Urinary pH, carbon dioxide pressure, bicarbonate, total carbon dioxide and ammonium did not change at any time after citric acid load, and did not differ between the 2 phases. No significant difference was noted in serum electrolytes, arterialized venous pH and carbon dioxide pressure at any time after citric acid load and between the 2 phases. Thus, the citraturic and citratemic effects of oral citric acid are largely accountable by provision of absorbed citrate, which has escaped in vivo degradation.

Non-NASA Center↗
NASA NTRS1992

Physicochemical action of potassium-magnesium citrate in nephrolithiasis

Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRS1991

A simple method for quantitating the propensity for calcium oxalate crystallization in urine

To assess the propensity for spontaneous crystallization of calcium oxalate in urine, the permissible increment in oxalate is calculated. The previous method required visual observation of crystallization with the addition of oxalate, this warranted the need for a large volume of urine and a sacrifice in accuracy in defining differences between small incremental changes of added oxalate. Therefore, this method has been miniaturized and spontaneous crystallization is detected from the depletion of radioactive oxalate. The new "micro" method demonstrated a marked decrease (p < 0.001) in the permissible increment in oxalate in urine of stone formers versus normal subjects. Moreover, crystallization inhibitors added to urine, in vitro (heparin or diphosphonate) or in vivo (potassium citrate administration), substantially increased the permissible increment in oxalate. Thus, the "micro" method has proven reliable and accurate in discriminating stone forming from control urine and in distinguishing changes of inhibitory activity.

NASA Discipline Regulatory Physiology↗