[Determination of adenosine in rabbit plasma using high pressure liquid chromatography methods].
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Biomedical subjects
Publications and source records attributed to C H Hsu.
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It is widely believed that skeletal resistance is the mechanism of impaired calcemic response to parathyroid hormone (PTH) in renal failure. The action of PTH not only involves skeletal mobilization of Ca, it may also stimulate intestinal absorption of Ca and renal conservation of Ca. We have examined each of these factors and studied the calcemic response to PTH in renal failure. PTH, 3 U/hr/100 gm, was infused for 5 hours in rats with renal failure 3 weeks after a five-sixths nephrectomy. In nonfasted animals, the post-PTH increments of total plasma Ca (0.71 +/- 0.06 mg/dl) and ionized Ca (0.37 +/- 0.06 mg/dl) of control sham-operated rats were significantly greater than those of rats with renal failure (plasma Ca 0.37 +/- 0.02 mg/dl and plasma ionized Ca 0.17 +/- 0.01 mg/dl both p less than 0.001). Urinary Ca excretion rate remained unchanged during PTH infusion despite the increase in plasma Ca. Plasma levels of calcitriol after PTH injection were higher in control rats (257 +/- 18 pg/ml) than in rats with renal failure (162 +/- 5 pg/ml, p less than 0.001). Pretreatment of rats with renal failure with 50 ng calcitriol intravenously corrected the abnormal calcemic response to PTH. To exclude the PTH effect on intestinal Ca absorption, PTH infusion was carried out in animals fasted for 18 hours. The post-PTH increments of Ca were no longer different between rats with renal failure (plasma Ca 0.37 +/- 0.04 mg/dl, plasma ionized Ca 0.20 +/- 0.01 mg/dl) and control rats (plasma Ca 0.37 +/- 0.03 mg/dl, plasma ionized Ca 0.19 +/- 0.01), suggesting that skeletal mobilization of Ca was similar between the two groups of animals. We conclude that lack of intestinal response to PTH rather than skeletal resistance was the mechanism of impaired calcemic response to PTH in this model of renal failure.
Plasma calcitriol concentration is unexpectedly low in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY) in view of previous findings of low plasma ionized calcium, hypophosphatemia, and hyperparathyroidism in SHR. Also, parathyroid hormone (PTH) and other exogenous stimuli cause a smaller increment in plasma calcitriol in SHR than in WKY. We investigated whether these differences in plasma calcitriol levels were due to decreased production rate (PR) or increased metabolic clearance rate (MCR) in SHR using the continuous infusion-isotope equilibration technique. In the basal state, MCR was 0.306 +/- 0.048 ml X min-1 X kg-1 in SHR and 0.284 +/- 0.026 ml X min-1 X kg-1 in WKY (P = NS). Estimated PR was lower in SHR (22.7 vs. 33.7 ng X day-1 X kg-1). With PTH infusion (3 U X h-1 X 100 g-1 for 20 h), MCR was 0.220 +/- 0.011 ml X min-1 X kg-1 in SHR and 0.256 +/- 0.017 ml X min-1 X kg-1 in WKY (P = NS). Measured PR was markedly lower in SHR (154 +/- 24 vs. 262 +/- 27 ng X day-1 X kg-1; P less than 0.02). Basal plasma PTH, total plasma calcium, and plasma inorganic phosphate were not different between SHR and WKY. Thus, SHR show diminished calcitriol production under basal condition and with PTH stimulation. MCR is not increased in SHR and does not appear to be influenced by PTH or the accompanying elevation in plasma calcium and calcitriol.
We have studied the effect of dietary vitamin D restriction on serum levels of vitamin D metabolites in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Both WKY and SHR were fed a vitamin D-deficient or a vitamin D-supplemented diet beginning at 4 wk of age. In vitamin D-supplemented animals, the serum 1,25-dihydroxycholecalciferol [1,25(OH)2D3] concentration of WKY (55.4 +/- 6.6 pg/ml, n = 5) was similar to the level of SHR (46.3 +/- 5.9 pg/ml, n = 5). Plasma calcium concentration was not different between WKY and SHR. In animals fed a vitamin D-deficient diet, the serum concentration of 1,25-(OH)2D3 of SHR (23.0 +/- 1.3 pg/ml, n = 5) was significantly lower than that of WKY (67.6 +/- 4.6 pg/ml, n = 5, P less than 0.01). Plasma 25-hydroxycholecalciferol level was markedly decreased in both WKY (3.6 +/- 0.5 ng/ml, n = 7) and SHR (2.8 +/- 0.4 ng/ml). The SHR, but not the WKY, developed hypocalcemia (WKY, 9.68 mg/dl; SHR, 6.70 mg/dl). Despite hypocalcemia, fasting urinary Ca2+ excretion of SHR exceeded that of WKY. We conclude that the lower 1,25(OH)2D3 level in SHR fed a vitamin D-deficient diet may be due to a defect in the synthesis of 1,25(OH)2D3. The low level of 1,25(OH)2D3 is associated with renal wasting of calcium and hypocalcemia in SHR.
We studied the metabolism of calcitriol in renal failure achieved by nephrectomy in three groups of rats. Group 1 (n = 7) had sham operation of nephrectomy. Group 2 (n = 8) had unilateral nephrectomy. Group 3 (n = 7) had 5/6 nephrectomy. Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were studied 3 wk after the surgery. Serum creatinine concentrations were increased after nephrectomy for groups 2 and 3. Endogenous plasma levels of calcitriol were not different between the rats with renal failure and the controls. MCR of calcitriol were decreased in renal failure rats compared with controls (group 1, 0.24 +/- 0.01; group 2, 0.20 +/- 0.01, P less than 0.01; group 3, 0.16 +/- 0.01 ml.min-1.kg-1, P less than 0.001). The MCR of calcitriol was correlated with the endogenous creatinine clearance by linear regression analysis (r = 0.72, P less than 0.001). The PR of calcitriol were also decreased in renal failure; however, the decreases were much less than the amount of renal tissue removed. We concluded that production of calcitriol is decreased in the remnant kidney. The decreased synthesis is associated with decreased degradation of calcitriol resulting in normal concentrations of calcitriol in mild to moderately severe renal failure.
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Adult male Sprague-Dawley rats maintained on a low sodium diet were administered 100 mg of cyclosporine per kg b.wt. per day s.c. for 4 to 10 days. Serum urea nitrogen was significantly elevated by day 4 and continued to rise, whereas serum creatinine was not elevated above control until day 10. Morphologic examination of perfusion-fixed kidneys from cyclosporine-treated rats revealed focal areas of tubular atrophy and interstitial fibrosis in the outer cortex and a generalized increase in interstitial cells in the outer medulla. No areas of acute tubular necrosis were identified. The effect of this dose of cyclosporine on renal hemodynamics was examined in conscious restrained rats. Renal blood flow, measured by microsphere injection, was 70% of control after four daily doses and remained near this level after eight daily doses. The glomerular filtration rate, measured by iodothalamate clearance, was 70% of control after four doses but fell to 34% of control after eight doses. [3H]Thymidine incorporation into renal DNA was used as a sensitive index of renal cell proliferation after cyclosporine administration (100 mg/kg/day). [3H]Thymidine incorporation was increased over control 3-fold in the outer cortex, 7-fold in the inner cortex and 11-fold in the medullary-papillary regions of the kidney after eight daily doses of cyclosporine. Histoautoradiographic examination of renal sections revealed an increase in the number of labeled nuclei in all three regions of the kidney from rats treated with cyclosporine. Morphometric analysis demonstrated that the majority of proliferating cells were located in the interstitium and not in renal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
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The role of renal papilla on solute excretion was studied in rats having one papillectomized kidney (PTX) and one partially nephrectomized kidney with intact papilla (PTN). Glomerular filtration rate (GFR) was similar between the PTX kidney (0.14 +/- 0.01 ml/min/100 g) and PTN kidney (0.16 +/- 0.03 ml/min/100 g). Urinary Na excretion (UNaV = 1.03 +/- 0.36 mu Eq/min) and fractional Na excretion (FENa = 1.72 +/- 0.56%) of PTX kidney were nearly 10-fold greater than those of PTN kidney, respectively (UNaV = 0.11 +/- 0.04, p less than 0.03; FENa = 0.19 +/- 0.05, p less than 0.02) during hydropenia. After 5% saline expansion GFR of PTX kidney (0.23 +/- 0.03 ml/min/100 g) and PTN kidney (0.25 +/- 0.05 ml/min/100 g) were increased significantly. Na excretion was greatly increased in both kidneys; however, PTX kidney still excreted nearly 4-fold more Na than the PTN kidney. Ca and P excretions were not different between the PTX kidney and PTN kidney. Neither was K excretion different between the two kidneys during hydropenia or after KCl infusion. The results indicate that renal papilla does not regulate Ca, P and K excretions in the presence of moderate reduction of GFR; however, it plays an important role in the final excretion of urinary Na.
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Spontaneously hypertensive rats (SHR) display lower ionized calcium (Pca++) concentrations when compared with normotensive Wistar Kyoto rats (WKY). This could be attributable to renal wasting of calcium, decreased intestinal calcium absorption, or decreased bone resorption, processes that are integrated by the parathyroid hormone (PTH) and vitamin D systems. We have studied the calcemic response to PTH infusion (3 U/hr/100 gm) for 5 hours in 13-week-old SHR and WKY. Pre-PTH Pca++ concentration of nonfasted SHR (4.68 +/- 0.06 mg/dl, N = 8) was significantly lower than that of WKY (4.84 +/- 0.03, N = 8, P less than 0.05). Pca++ concentration rose in both nonfasted WKY and SHR at the end of PTH infusion, but the increment of Pca++ in SHR (0.29 +/- 0.05 mg/dl, N = 8) was lower than that in WKY (Pca++, 0.60 +/- 0.07 mg/dl, N = 8, P less than 0.01). Urinary calcium excretion (UcaV) and creatinine clearances (Ccr) before and after PTH infusion were not different between WKY and SHR. Despite an increased filtered load of calcium, UcaV was not greater in either WKY or SHR during the PTH infusion. Pretreatment of SHR with calcitriol 50 ng intravenous bolus injection, which had no effect on Pca++ concentration (0.02 +/- 0.03 mg/dl, N = 7), corrected the lower calcemic response to PTH in SHR, and the Pca++ increment was no longer different between WKY (0.57 +/- 0.07 mg/dl, N = 7) and SHR (0.62 +/- 0.09, N = 7).(ABSTRACT TRUNCATED AT 250 WORDS)
A 25-day-old Chinese female baby developed necrotizing fasciitis (NF) with indurated erythematous patches with superficial necrosis over two thirds of the back. Skin cultures of the lesions yielded Streptococcus pyogenes, enterococcus, Pseudomonas aeruginosa, and Candida species. The patient had lymphopenia with low T cells and T cell subsets. The lymphoproliferative response to mitogen and macrophage migration (MIF) production were also poor. Her lymphocytes were unable to produce IgG in vitro. Also, IgG bearing cells were not demonstrable. The initial lymph node biopsy demonstrated an absence of follicular formation and depletion of lymphocytes in both thymic-dependent and thymic-independent areas. Five weeks after bovine thymic extract (Thymostimulin) treatment, a second lymph node biopsy demonstrated germinal centers containing IgG bearing cells. Three weeks later, a third lymph node biopsy showed germinal centers with cuffs of lymphocytes. Differentiation of the cortex and medulla of the node was demonstrated. IgG was also detectable in an in vitro Ig synthesis study. The total T cells, T cell subsets, lymphoproliferative response MIF production also increased gradually after Thymostimulin treatment. This investigation demonstrated the therapeutic effectiveness of Thymostimulin in NF with underlying combined immuno-deficiency, both serious and frequently fetal diseases, by the histologic and immunologic reconstitution of T and B cell function.
In the female golden hamster, Mesocricetus auratus, group housing permits the expression of male-like behavioral patterns including mounting and pelvic thrusting toward an estrous stimulus female. Sixty percent of females housed in groups of five showed these behaviors, while singly housed females were rarely observed to show mounting or thrusting. Females weaned at 19 or 35 days of age did not differ in their tendencies to show male-like behavioral patterns. Virtually all observations of mounting and pelvic thrusting behaviors were made on days when the females being tested were in behavioral estrus. These findings differ from previous studies which have reported that masculine behavioral patterns are rare in normal female hamsters. In previous studies females that were evaluated were typically not in behavioral estrus and were not housed for long periods of time with other intact females. Social factors interact with hormonal state to contribute to the expression of male-like behaviors in female hamsters.