PubMed Health⌕ Search

Biomedical subjects

C H Hsu

Publications and source records attributed to C H Hsu.

At least 127 records · Page 7Linked to original sources
PubMed1991

Effects of purine derivatives on calcitriol metabolism in rats.

The effects of theophylline and sodium urate on metabolic production (PR) and clearance rate (MCR) of calcitriol were determined by the constant isotope infusion method in normal rats. Calcitriol PR was significantly reduced after infusion for 20 h of either theophylline (1 mg/h, PR = 22.3 +/- 1.6 ng.kg-1.day-1, P less than 0.001, n = 5) or sodium urate (0.5 mg/h, PR = 18.6 +/- 1.2 ng.kg-1.day-1, P less than 0.001, n = 5) compared with control rats infused with saline (PR = 32.0 +/- 1.5 ng.kg-1.day-1, n = 5). Renal 1 alpha-hydroxylase activity of kidney homogenate was significantly inhibited in rats infused with theophylline or urate. Suppression of 1 alpha-hydroxylase activity was also observed when the kidney homogenate was preincubated for 3 h with various concentrations of xanthine (0.11-3.0 mg/dl). In addition, the MCR of calcitriol was decreased in rats infused with either theophylline (MCR = 21.0 +/- 0.88 microliter.min-1.100 g-1, P less than 0.005) or urate (MCR = 22.9 +/- 0.91 microliter.min-1.100 g-1, P less than 0.05) compared with saline-infused control rats (MCR = 25.2 +/- 0.41 microliter.min-1.100 g-1). Because calcitriol degradation is a receptor-mediated process that requires binding of the receptor-hormone complex to chromatin, we studied the binding affinity of labeled calcitriol receptor for DNA-cellulose in the presence of theophylline or urate. Both theophylline and urate inhibited receptor binding affinity for DNA-cellulose. We conclude that these purine derivatives suppress calcitriol synthesis and inhibit receptor binding affinity for DNA. The altered receptor binding affinity could explain the decreased MCR of calcitriol.

Animals↗
PubMed1990

The effects of soman in vitro on catechol-O-methyltransferase and monoamine oxidase activities in rabbit tissues.

Soman (pinacolyl methylphosphonofluoridate) not only increases acetylcholine levels by inhibiting cholinesterases, it also alters the levels of some other neurotransmitters including norepinephrine, dopamine, and serotonin. Soman also causes an alteration in the activities of the enzymes metabolizing norepinephrine when it is administered to animals. Because these alterations may result from indirect effects on the enzymes, the effects of in vitro application of soman on catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) activities in rabbit tissues were investigated. Enzyme activities were determined in rabbit lung, liver, cerebellum, cerebrum, brain stem, mesenteric artery, pulmonary artery, renal artery, central ear artery, thoracic aorta, and diaphragm. MAO and COMT activities were not affected by soman in any tissues tested, except the lung and liver, where the activity of COMT was increased (p less than 0.05). Thus, reported effects of soman in vivo on norepinephrine, dopamine, or serotonin concentrations, and MAO and COMT activities do not seem to result from direct effects on the activities of these amine-metabolizing enzymes.

Animals↗
PubMed1990

Blockade of lordosis by androst-1,4,6-triene-3,17-dione (ATD) and tamoxifen in female hamsters primed with testosterone propionate.

Normal female hamsters display lordosis after testosterone propionate (TP) plus progesterone (P) treatments. Such effect is probably mediated through aromatization of testosterone (T) into estradiol. If so, then an aromatase inhibitor (ATD) or an estrogen antagonist (tamoxifen, TAM) should be able to block the activational effect of T on lordosis. To test this hypothesis, 48 ovariectomized female hamsters were assigned into six groups which, according to treatments received, were ATD + TP, TAM + TP, OIL + TP, ATD + EB (estradiol benzoate), TAM + EB, and OIL + EB groups. The groups received assigned treatments for 2 days and were injected with P on the third day. Five minutes of behavior test was conducted 4 hr after P injection. The OIL + TP, OIL + EB, and ATD + EB groups all had averaged total lordosis duration (TLD) longer than 200 sec. The TLD of the TAM + EB group was only 117 sec. The ATD + TP and TAM + TP groups showed almost no lordosis. The results showed that the estrogen antagonist (TAM) impaired lordosis no matter whether the animals were primed with TP or EB, but the aromatase inhibitor (ATD) blocked lordosis only in TP primed females. It is concluded that the aromatization of T to estrogen is required for testosterone activation of lordosis in female hamsters.

Androstatrienes↗
PubMed1990

Effects of soman on calcium influx into rabbit aorta.

The acute addition of 10 microM soman to rabbit aorta rings did not increase resting 45Ca2+ influx significantly in the absence or presence of 10 microM norepinephrine or 80 mM potassium (P greater than 0.05). However, agonist-induced 45Ca2+ influx into aorta rings from rabbits that received soman daily for 7 days was significantly reduced (P less than 0.05) compared to agonist-induced influx into rings from control rabbits. The resting influx of 45Ca2+ into aorta rings from 7 day soman-treated and control rabbits was not different (P greater than 0.05). The depression by soman of norepinephrine- and K(+)-induced 45Ca2+ influx may be due to adaptive changes resulting from the 7-day administration of soman.

Animals↗
PubMed1990

Factors influencing calcitriol metabolism in renal failure.

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol is decreased in experimental renal failure. In this experiment, we studied uremia and secondary hyperparathyroidism as possible causes of the abnormal calcitriol metabolism. Normal rats were made uremic by infusing phosphorus-free urine for 24 hours. Both the MCR (0.22 +/- 0.01 ml/min/kg, N = 6 P less than 0.001) and the PR (16.6 +/- 1.97 ng/kg/day, P less than 0.01) of calcitriol were significantly suppressed in normal rats following urine infusion when compared to saline infused rats (MCR, 0.30 +/- 0.01; PR, 32.9 +/- 4.1, N = 6). Different levels of protein intake by rats with renal failure produced by subtotal nephrectomy also alter the PR but not the MCR of calcitriol. Thus, the synthesis of calcitriol was significantly lower in rats with renal failure fed a high protein (50% protein) diet (17.6 +/- 0.7 ng/kg/day, N = 8, P less than 0.001) than in rats with renal failure fed a normal protein (20% protein) diet (22.2 +/- 1.4, N = 7). Thyroparathyroidectomy (TPTX) did not alter the MCR of calcitriol in renal failure, even though parathyroid hormone, which may suppress the degradation enzyme, could be elevated in this model of renal failure. The MCR of TPTXed rats with renal failure (0.15 +/- 0.01 ml/min/kg, N = 7) remained lower than that of the TPTXed control rats (0.19 +/- 0.01, N = 7, P less than 0.001), and chronic infusion of PTH to TPTXed rats with renal failure did not change the MCR of calcitriol (0.15 +/- 0.01, vs. control, 0.24 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit.

A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle-treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis.

Animals↗
PubMed1990

Effect of polyamines, methylguanidine, and guanidinosuccinic acid on calcitriol synthesis.

Previous study from our laboratory has demonstrated that infusion of uremic plasma ultrafiltrate to normal rats suppressed their calcitriol synthesis. In order identify the uremic toxins responsible for the suppression of the calcitriol synthesis, we studied the effects of known uremic toxins: spermidine, spermine, methylguanidine (MG), and guanidinosuccinic acid (GSA) on calcitriol metabolism in the rats. Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were measured in normal rats after they were infused for 24 hours with approximately 10 ml of normal saline containing one of the following substances: 0.8 mumoles spermidine, 0.3 mumoles spermine, 150 micrograms MG and 180 micrograms GSA. Control groups of rats were infused with 10 ml of normal saline for 24 hours. MCR of calcitriol was not altered by the infusion of each toxin; however, plasma concentration of calcitriol (controls, 105.3 +/- 6.7 pg/ml; versus GSA, 58.9 +/- 2.5 pg/ml, p less than 0.001) and PR of calcitriol (controls, 39.0 +/- 2.9 ng/kg/day, versus GSA, 22.5 +/- 1.62 ng/kg/day, p less than 0.001) were significantly suppressed by the infusion of GSA. The concentration (1.8 mg/dl) of GSA in the infusate was similar to that in the uremic plasma ultrafiltrate (2.32 +/- 1.41 mg/dl) used in the previous study, though the total amount of GSA infused to the rats was lower in the present study. GSA is, therefore, considered a uremic toxin that suppresses calcitriol synthesis.

Animals↗
PubMed1990

25-Hydroxyvitamin D metabolism and its effect on calcitriol metabolism in experimental renal failure.

We studied 25-hydroxyvitamin D3 (25(OH)D3) metabolism and its effect on calcitriol metabolism in renal failure achieved by partial nephrectomy in rats. Metabolic clearance rates (MCRs) of 25(OH)D3 were significantly decreased in rats with renal failure (creatinine clearance, 0.21 +/- 0.02 ml/min/100 gm; MCR, 54.6 +/- 3.5 microliters/min/kg, n = 6) in comparison with normal control rats (creatinine clearance, 0.56 +/- 0.03 ml/min/100 gm; MCR, 73.4 +/- 1.6 microliters/min/kg, n = 5, both p less than 0.01). Because production rates (PRs) of 25(OH)D3 were not different between the two groups of rats (renal failure, 1.8 +/- 1.1; control, 1.8 +/- 0.42 microgram/kg/day), the decreased MCR resulted in elevation of plasma levels of 25(OH)D3 (22.7 +/- 1.6 vs control 17.1 +/- 0.28 ng/ml, p less than 0.01). Injection of 600 ng 25(OH)D3 per day for 6 days significantly increased the MCR of 25(OH)D3 in both normal rats (89.6 +/- 3.2 microliters/min/kg, n = 6, p less than 0.01) and rats with renal failure (84.9 +/- 9.7 microliters/min/kg, n = 6, p less than 0.01) when compared with normal rats (73.4 microliters/min/kg) and rats with renal failure (54.6 microliters/min/kg) injected with vehicle, respectively. To study the effect of 25(OH)D3 on calcitriol metabolism, MCRs of calcitriol were measured in normal rats and in rats with renal failure that received daily injection of 600 ng 25(OH)D3 for 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of vitamin D metabolites on calcitriol metabolism in experimental renal failure.

Previous studies from our laboratory have demonstrated that metabolic clearance rate (MCR) of calcitriol is decreased in experimental renal failure. In this experiment, we examined the effects of calcitriol, 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) on the MCR of calcitriol in renal failure produced in rats by partial nephrectomy. The MCR of calcitriol in these rats with renal failure was significantly lower than in control rats with sham operations. Plasma concentrations of calcitriol did not differ between the rats with moderate renal failure and control rats (sham, 74.7 +/- 3.6 pg/ml, N = 7; renal failure, 67.7 +/- 6.0, N = 6; serum creatinine 0.56 +/- 0.02 mg/dl vs. 0.96 +/- 0.02); however, the levels were significantly lower in rats with severe renal failure (sham, 66.5 +/- 5.1 pg/ml, N = 7, severe renal failure, 49.6 +/- 2.1 pg/ml, N = 8; serum creatinine 0.53 +/- 0.01 mg/dl vs. 1.40 +/- 0.03). Subcutaneous infusion of calcitriol (10 ng/kg/day) in rats with severe renal failure for one week significantly increased the MCR of calcitriol (0.22 +/- .01 vs. 0.17 +/- .01 ml/min/kg, P less than 0.001). Infusion of 25(OH)D3 (600 ng/day) or 24,25(OH)2D3 (1 microgram/day) in rats with renal failure for one week also increased the MCR of calcitriol (25(OH)D3, 0.25 +/- 0.01 ml/min/kg; 24,25(OH)2D3, 0.25 +/- 0.01, both P less than 0.001) when compared to rats with renal failure infused with vehicle (0.21 +/- 0.01). Administration of 24,25(OH)2D3 significantly lowered the plasma levels of calcitriol in rats with renal failure (52.3 +/- 3.1 pg/ml, P less than 0.05) in comparison to the rats with renal failure infused with vehicle (67.7 +/- 6.0).(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1989

The effect of theophylline and cyclic adenosine 3',5'-monophosphate on renin release by afferent arterioles.

The effects of theophylline and cyclic adenosine 3',5'-monophosphate (cAMP) on renin release by afferent arterioles were studied. Rabbit afferent arterioles (seven to 10), obtained by a microdissection technique, were incubated for three consecutive 20 min periods in 100 microliters of Medium 199 with 0.1% bovine serum albumin (BSA). Afferent arterioles exposed to theophylline, 1 x 10(-4) mol/l, produced a greater than 100% increase in renin release (0.18 +/- 0.04 to 0.42 +/- 0.05 ng angiotensin l/h per arteriole per h incubation). The renin release stimulated by theophylline was completely abolished by indomethacin and meclofenamate. The stimulation of renin secretion was also blocked when extracellular calcium concentration was decreased to 10(-7) mol/l and the arterioles were permeabilized with calcium ionophore. Dibutyryl cAMP (db-cAMP), 1 x 10(-4) mol/l, and forskolin, 1 mumol/l or 100 mumol/l, failed to stimulate renin release by afferent arterioles. The results of this study therefore suggest that theophylline-stimulated renin release may be mediated through a prostaglandin pathway. The stimulation of renin secretion is also dependent on the extracellular concentration of calcium.

Animals↗
PubMed1989

Limitation of the alpha-methylnorepinephrine hypothesis in the hypotensive effect of alpha-methyldopa.

To test the hypothesis that alpha-methylnorepinephrine (MNE) is the principal active metabolite involved in the hypotensive action of alpha-methyldopa (MD), we determined the relationship between MD's depressor response and tissue levels of MD metabolites in critical sites. After administration of 250 mg/kg MD intraperitoneally to Sprague-Dawley rats (300 +/- 50 g), we studied both heart (left ventricle) and brainstem MD, MNE and endogenous NE levels using HPLC with electrochemical detection. We also measured systolic blood pressure before and during MD (25-250 mg/kg i.p.) treatment using the tail-cuff method. Our results indicate that: (1) peak MD hypotensive response was dose-dependent. (2) Central NE concentration was maximally reduced by 2 hours whereas peripheral NE was maximally reduced by 18 hours. The maximal hypotensive effect was closer to the central peak distribution of MNE than MD. (3) The MD concentrations and NE concentrations in brainstem and heart showed counterclockwise hysteresis while MNE showed clockwise hysteresis. Furthermore, the area of MNE hysteresis in brainstem was larger than that of NE. We conclude that MD's depressor effect can not be completely explained by the assumption that MNE is the sole active metabolite; alternate metabolites or mechanisms would appear to be operative.

Animals↗
PubMed1989

Effects of sonication and growth temperature on the cytochrome oxidase activity of Bacillus species.

The cytochrome oxidase activity of Bacillus strains was analyzed quantitatively by colorimetric N, N, N', N'-tetramethyl-p-phenylene-diamine (TMPD) oxidase assay. Twenty six type strains were readily grouped, the oxidase positive, the oxidase negative, and the oxidase indeterminate groups. TMPD-dependent oxidase activities for whole cells and sonicated cells were compared. Spectral absorbance analyses of membrane fractions showed that all 26 Bacillus type strains contained the o-type cytochrome oxidase; 19 strains contained cytochrome a + a3 and among which 5 strains contained cytochromed. All of the 10 thermophilic Bacillus strains, which were predominantly oxidase positive, exhibited maximum oxidase activity when grown at optimum temperature (65 degrees C). The other three "caldo-active" thermophiles exhibited maximum oxidase activities when grown at their optimum temperatures, 70 degrees C to 80 degrees C. Mesophilic B. cereus and B. subtilis exhibited maximum oxidase activity in cells grown at 42 degrees C and 55 degrees C, respectively. In no case did growth temperature induce oxidase negative strains to exhibit an oxidase positive reaction, and vice versa.

Bacillus↗
PubMed1989

The role of osmolarity in renin release from afferent arterioles.

We studied the role of sodium (Na) in renin release from isolated afferent arterioles incubated in Krebs-Ringer bicarbonate solutions with the Na concentrations adjusted to 145, 135, 125, 110 and 95 mmol/l. The arterioles were incubated for three consecutive periods, with the sequence of incubations randomized. Renin release increased by 119 and 275% in the media with Na concentrations of 135 and 125 mmol/l, respectively, as compared with the renin released from arterioles incubated in the medium with Na 145 mmol/l. When the Na concentrations of the incubation media were further lowered to 110 mmol/l and 95 mmol/l, renin release continued by 118 and 216%, respectively, in comparison with that in the medium having an Na concentration of 125 mmol/l. Regression analysis showed that renin release increased by 98% for each 10 mmol/l decrement of Na concentration. When the osmolarity of the incubation medium was held constant, varying the Na concentrations did not alter the renin secretion. This suggests that renin was released from the arterioles in response to the osmotic pressure exerted by Na rather than as an ionic effect. Renin release was suppressed by the osmotic effects of sucrose and urea, although the suppressive effect of urea was weaker.

Animals↗
PubMed1988

Calcitriol synthesis is decreased in spontaneously hypertensive rats.

To investigate the mechanisms of abnormal calcium metabolism, such as hypocalcemia, decreased intestinal calcium absorption and hypercalciuria in spontaneously hypertensive rats (SHR), we have measured the plasma concentration of calcitriol and its synthesis in 5-, 8-, 12-, 16-, and 20-week-old normotensive Wistar Kyoto rats (WKY) and SHR. Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were measured by the constant isotope infusion method. Plasma concentration of calcitriol and PR of calcitriol were decreased in SHR after 12 weeks of age. MCR of calcitriol, however, was not different between WKY and SHR in any age group. Therefore, the decreased synthesis of calcitriol accounts for the lower plasma level of calcitriol in SHR after 12 weeks of age. Metabolic acidosis or decreased renal function could not account for the decreased synthesis of calcitriol, since the blood pH and pCO2 and creatinine clearance were similar between WKY and SHR at times when the calcitriol synthesis was reduced in SHR. Plasma concentration of ionized calcium was also lower in SHR after 12 weeks of age. Plasma concentration of calcitonin was significantly higher in 16-week-old SHR (41.6 +/- 1.5 pg/ml) than in age-matched WKY (30.5 +/- 1.7, P less than 0.001). The values, however, were not different between 8- and 12-week-old WKY and SHR. We believe that the decreased synthesis of calcitriol could be the pathogenetic factor for the development of abnormal calcium metabolism in SHR. Age of animals should be considered when studying the calcium metabolism in SHR.

Aging↗
PubMed1988

Production and metabolic clearance of calcitriol in acute renal failure.

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were studied three and seven days after ischemic acute tubular necrosis (ATN). Creatinine clearance was decreased three days after clamping the renal arteries (0.42 +/- 0.03 ml/min/100 g, N = 6 in ATN vs. 0.68 +/- 0.09, N = 7 in sham controls; P less than 0.001). Plasma concentrations (24.1 +/- 1.9 pg/ml) and PR of calcitriol (9.8 +/- 0.91 ng/kg/day) were significantly lower in ATN rats three days after ischemic insult when compared to sham control rats, respectively (76.6 +/- 7.3 pg/ml, and 29.6 +/- 3.3 ng/kg/day; both P less than 0.01). The MCRs of calcitriol were not different between ATN (0.28 +/- 0.02 ml/min/kg) and sham control rats (0.27 +/- 0.01). By the seventh day after ischemic injury, when creatinine clearance of ATN rats returned to normal, both the PR and plasma concentrations of calcitriol also returned to normal values in these animals. In order to assess the effect of uremia on calcitriol metabolism, MCR and PR of calcitriol were measured in rats with reinfusion of their urines for 24 hours. The PR of calcitriol was significantly decreased (9.42 +/- 1.21; vs. controls, 20.5 +/- 2.9 ng/kg/day, P less than 0.001) in uremic animals. Since decreased PR of calcitriol was also accompanied by decreased MCR of calcitriol, plasma concentrations of calcitriol of the uremic rats with intact kidneys remained within normal values. We conclude that the PR of calcitriol is decreased early in ATN rats. Although the MCR was not decreased in mild ATN rats, it may decrease in severe acute renal failure.

Acute Kidney Injury↗