STIMULATION BY LOW PHOSPHORUS AND LOW CALCIUM DIETS OF DUODENAL ABSORPTION OF PHOSPHATE IN BETAMETHASONE-TREATED CHICKS

1981 ◽  
Vol 88 (1) ◽  
pp. 147-153 ◽  
Author(s):  
J. FOX ◽  
N. W. BUNNETT ◽  
A. R. FARRAR ◽  
A. D. CARE
Keyword(s):  
Oral Administration ◽  
Inhibitory Effect ◽  
Lower Weight ◽  
Low Calcium ◽  
Low Phosphorus ◽  
Loop Technique ◽  
Reduced Rate ◽  
Normal Calcium ◽  
Daily Oral Administration

Although the inhibitory effect of glucocorticoids on the intestinal absorption of calcium is well recognized, their effect on the absorption of phosphate is less well documented. We studied the effect of the oral administration of betamethasone (BM; 25 μg/kg per day) on the duodenal absorption of phosphate in chicks fed normal calcium, normal phosphorus (NCaNP), normal calcium, low phosphorus (NCaLP) or low calcium, normal phosphorus (LCaNP) diets using the ligated loop technique in vivo. The daily oral administration of BM for 8 days significantly reduced the absorption of phosphate in chicks fed the NCaNP diet (21% decrease) but had less effect in chicks fed the NCaLP (14% decrease) or LCaNP (9% decrease) diets in which birds the absorption of phosphate was significantly raised (49 and 87% respectively). In one group of chicks, BM was administered for 9 days before the birds were transferred to the NCaLP or LCaNP diets. Adaptation was again unaffected by the treatment. Thirty-four per cent of the absorbed phosphate was retained in the duodenal tissue. Treatment with BM reduced the amount retained but this may have been caused by the lower weight of the duodenal segment in these chicks as BM administration markedly reduced growth rate. We have concluded that the duodenal absorption of phosphate in the chick can be inhibited by treatment with BM, although this may be secondary to the reduced rate of growth, but the increase in the absorption of phosphate caused by feeding NCaLP or LCaNP diets was unaffected by the steroid.

EFFECTS OF LOW CALCIUM AND LOW PHOSPHORUS DIETS ON THE DUODENAL ABSORPTION OF CALCIUM IN BETAMETHASONE-TREATED CHICKS

1978 ◽  
Vol 78 (2) ◽  
pp. 255-260 ◽  
Author(s):  
J. FOX ◽  
A. D. CARE ◽  
J. BLAHOS
Keyword(s):  
Growth Rate ◽  
Oral Administration ◽  
Low Calcium ◽  
Low Phosphorus ◽  
Treatment Administration ◽  
Loop Technique ◽  
Normal Calcium ◽  
Daily Oral Administration

SUMMARY The effect of oral administration of betamethasone (25 μg kg−1 day−1) on the duodenal absorption of calcium has been studied in chicks using the ligated loop technique in vivo. The chicks were fed normal calcium, normal phosphorus (NCaNP), low calcium, normal phosphorus (LCaNP) or normal calcium, low phosphorus (NCaLP) diets. Daily oral administration of betamethasone for 2–3 weeks markedly reduced the absorption of calcium in chicks fed the NCaNP diet, but did not significantly affect the adaptation in absorption when the NCaLP or LCaNP diets were fed for the same period of time. In one group of chicks, betamethasone was administered daily for 10 days before the birds were transferred to the NCaLP or LCaNP diets. Adaptation was again unaffected by betamethasone treatment. Administration of betamethasone caused a marked retardation in growth-rate, hypercalcaemia and an increased percentage of ash in the tibiae.

scholarly journals Hypocalcin from Stannius corpuscles inhibits gill calcium uptake in trout

1988 ◽  
Vol 254 (6) ◽  
pp. R891-R896 ◽  
Author(s):  
F. P. Lafeber ◽  
G. Flik ◽  
S. E. Wendelaar Bonga ◽  
S. F. Perry
Keyword(s):  
Rainbow Trout ◽  
Calcium Uptake ◽  
Inhibitory Effect ◽  
Whole Body ◽  
Transepithelial Potential ◽  
Low Calcium ◽  
Stannius Corpuscles ◽  
Normal Calcium

Bidirectional whole body flux and branchial Ca2+ influx were measured in freshwater rainbow trout. Intra-arterial injections of homogenates of Stannius corpuscles (CS) as well as of a 54-kDa isolated product (hypocalcin) exerted an inhibitory effect on whole body Ca2+ influx, but did not effect Ca2+ efflux. Hypocalcin was more effective in reducing Ca2+ influx in trout acclimated to low-calcium freshwater than in fish from normal-calcium water. We conclude that the isolated product (hypocalcin) represents the hypocalcemic principle of the CS. Similar doses of hypocalcin caused quantitatively similar decreases in Ca2+ influx in vivo and in the isolated perfused head preparation. This indicates that the gills form the principle target for hypocalcin in trout. The branchial transepithelial potential did not change during hormone treatments. Possible mechanisms of hypocalcin action are suggested.

Orally Active Inhibitors of the Imatinib Resistant Bcr-Abl Mutant T315I.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2180-2180 ◽  
Author(s):  
William C. Shakespeare ◽  
Frank Wang ◽  
Qihong Xu ◽  
Xiaotian Zhu ◽  
Narayana Narasimham ◽  
...  
Keyword(s):  
Oral Administration ◽  
Cellular Proliferation ◽  
Kinase Inhibitor ◽  
Tumor Regression ◽  
Point Mutations ◽  
Drug Binding ◽  
Separate Model ◽  
Daily Oral Administration

Abstract Resistance to the Bcr-Abl kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML) is associated with emergence of Bcr-Abl point mutations that preclude effective drug binding. Although most mutants are effectively inhibited with the second generation inhibitors dasatinib and nilotinib, neither compound inhibits the T315I mutant which represents ~ 25% of all clinically observed mutants. Through our program of structure-guided design, we have identified a series of compounds that inhibit the T315I mutant of Bcr-Abl both in vitro and in vivo. AP24534, a representative member of this new series, inhibited the kinase activity of both the wild-type enzyme and the T315I point mutant with IC50s of 3 and 31 nM respectively, and inhibited the proliferation of their respective BaF3-derived cell lines with IC50s of 2 and 14 nM. Additionally, AP24534 inhibited the proliferation of BaF3 cells expressing the clinically relevant mutants Y253F, E255K, H396P, or M351T with IC50s of 2, 7, 1, and 1 nM respectively. Inhibition of cellular proliferation directly correlated with decreased cellular phosphorylation of Bcr-Abl. Daily oral administration of AP24534 to mice bearing subcutaneous xenografts of Bcr-Abl-T315I-expressing BaF3 cells elicited dose-dependent tumor shrinkage, with complete tumor regression observed at the highest doses. In a separate model, daily oral administration of AP24534 significantly prolonged the survival of mice injected intravenously with these cells, at doses ranging from 5–30 mg/kg. These data indicate that this class of inhibitors has the potential to address CML refractory to current targeted agents.

Endocrinological effects of single daily ketoconazole administration in male beagle dogs

1984 ◽  
Vol 107 (2) ◽  
pp. 275-281 ◽  
Author(s):  
Roland De Coster ◽  
Dominiek Beerens ◽  
Jef Dom ◽  
Gustaaf Willemsens
Keyword(s):  
Oral Administration ◽  
Plasma Cortisol ◽  
Plasma Concentrations ◽  
The Other ◽  
Plasma Testosterone ◽  
Beagle Dogs ◽  
Basal Cortisol ◽  
High Doses ◽  
Daily Oral Administration

Abstract. Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3–4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17α-hydroxyprogesterone, progesterone and 17α,20α-dihydroxyprogesterone increased within 3–10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17α levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17–20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17β plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.

In vivo inhibitory effect of Aloe vera gel on the ability of mouse parental splenic lymphocytes to induce cutaneous angiogenesis in recipient F1 mice

2014 ◽  
Vol 17 (1) ◽  
pp. 131-136
Author(s):  
P. Skopiński ◽  
S. Lewicki ◽  
B.J. Bałan ◽  
J. Kocik ◽  
R. Zdanowski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oral Administration ◽  
Aloe Vera ◽  
Inhibitory Effect ◽  
Splenic Lymphocytes ◽  
Histocompatibility Antigens ◽  
Graft Versus Host ◽  
Aloe Vera Gel ◽  
Donor Lymphocytes

AbstractLymphocyte-induced angiogenesis test (LIA) is a model of local graft-versus-host (GVH) reaction, marker of the earliest events resulting from activation of donor lymphocytes after contact with host semi-allogeneic histocompatibility antigens. The effect of in vivo oral administration of Aloe vera gel for 21 days to maternal strain (Balb/c) donor mice on the ability of their splenic lymphocytes to induce cutaneous angiogenesis (LIA test) in F1 Balb/c x C3H recipients, was studied.Results: Neovascular reaction evaluated 72 hours after cells grafting was significantly lower in F1 mice grafted with lymphocytes collected from Aloe- fed donors, than in recipients of lymphocytes collected from respective controls. Conclusions: This observation opens the promise of safe and ethically acceptable possibility of use of Aloe vera gel in human donors in prevention of GVHD in recipients of bone marrow grafts.

ASP9521, a novel, selective, orally bioavailable AKR1C3 (type 5, 17ß-hydroxysteroid dehydrogenase) inhibitor: In vitro and in vivo characterization.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5046-5046 ◽  
Author(s):  
Aya Kikuchi ◽  
Kentaro Enjo ◽  
Takashi Furutani ◽  
Hidenori Azami ◽  
Tatsuya Nimi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Oral Administration ◽  
Hydroxysteroid Dehydrogenase ◽  
Inhibitory Effect ◽  
Enzymatic Conversion ◽  
Lead Compound ◽  
Lncap Cells ◽  
Orally Bioavailable

5046 Background: Aldo–keto reductase 1C3 (AKR1C3), also known as type 5, 17β-hydroxysteroid dehydrogenase, is reported to be highly expressed in human normal prostate and prostate cancer (PC) and the expression increases along with increasing malignancy or grade of PC. Since AKR1C3 converts the adrenal androgen, androstenedione (AD) into testosterone (T), combination with a GnRH analogue and AKR1C3 inhibitor would be expected to provide total androgen blockade in the treatment of castration-resistant prostate cancer (CRPC). We obtained a lead compound having a non-steroidal scaffold by high throughput screening (HTS) approaches for targeting enzyme activity of AKR1C3. After optimization of the lead compound, we found ASP9521 as a potent, selective, and orally bioavailable AKR1C3 inhibitor. Methods: The inhibitory effect of ASP9521 on enzymatic conversion from AD to T by AKR1C3 was evaluated in vitro, and in CWR22R xenograft models. Effect of PSA production and proliferation on LNCaP cells stably expressing AKR1C3 was examined. Pharmacokinetics in various animals were also investigated. Results: ASP9521 showed potent inhibitory effect on enzymatic conversion from AD to T by both human AKR1C3 and cynomolgus monkey homologues in a concentration-dependent manner, with IC50 values of 11 and 49 nmol/L, respectively ASP9521 suppressed both AD-dependent PSA production and cell proliferation in LNCaP cells exogenously expressing AKR1C3 in vitro. The bioavailability of ASP9521after oral administration of 1mg/kg were 30% and 78% in rat and dog, respectively. Furthermore, ASP9521 single oral administration of 3 mg/kg suppressed AD-induced intratumoral T production in CWR22R xenografted castrate nude mice, and this inhibitory effect was maintained for 24 h. In addition, ASP9521 was rapidly eliminated from plasma after oral administration while its intratumoral concentration remained high in tumors expressing AKR1C3. Conclusions: These preclinical in vitro and in vivo data are consistent with a potent inhibition of 17β-hydroxysteroid dehydrogenase. The results suggest that ASP9521 should be investigated further to elucidate its role as treatment for PC.

scholarly journals The inhibitory effect of anti-allergic agent suplatast tosilate (IPD–1151T) on methacholine- and allergen-induced bronchoconstriction in sensitized mice

2000 ◽  
Vol 9 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Kazuhito Asano ◽  
Tetsuya Mizutani ◽  
Toshikazu Shimane ◽  
Masataka Hisano ◽  
Tadashi Hisamitsu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Drug Administration ◽  
Intraperitoneal Injection ◽  
Keyhole Limpet Hemocyanin ◽  
Specific Ige ◽  
Inhibitory Effect

The influence of an anti-allergic agent, suplatast tosilate (IPD-1151T; (±)-[2-[4-(3-ethoxy–2-hydroxypropoxy)phenyl-carbamoyl]-ethyl] dimethylsulfonium p-toluenesulfonate) on allergic bronchoconstriction induced by allergen and methacholine (MCh) were examined in mice. BALB/c mice were sensitized by intraperitoneal injection of dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) mixed with Al(OH)3(DNP-KLH). IPD-1151T was administered orally once a day for either 5 or 14 days in doses of 10, 30 or 100 mg/kg. Bronchoconstriction was measured 24 h after the final drug administration. IPD-1151T inhibited both antigen- and MCh-mediated bronchoconstriction in actively sensitized mice. The inhibition induced was closely related to the dose and frequency of oral administration of the agent. We also examined the effect of IPD-1151T on IgE production in response to DNP-KLH immunization. IPD-1151T inhibited dose-dependently both total and specific IgE concentrations in serum prepared from mice 15 days after im munization. These results strongly indicate that IPD-1151T inhibits IgE productionin vivoand results in attenuating effect on bronchoconstriction.

Metabolism in Vitro of 25-Hydroxycholecalciferol in Chicks Fed on Phosphorus-Deficient Diets

1978 ◽  
Vol 54 (2) ◽  
pp. 197-200 ◽  
Author(s):  
R. Swaminathan ◽  
Barbara A. Sommerville ◽  
A. D. Care
Keyword(s):  
Calcium Absorption ◽  
Plasma Calcium ◽  
Hydroxylase Activity ◽  
High Phosphorus ◽  
Phosphorus Deprivation ◽  
Low Phosphorus ◽  
Loop Technique ◽  
25 Hydroxycholecalciferol

1. Three groups of 10-days-old chicks were fed on one of three diets having phosphorus contents of 0·08 mol/kg, 0·14 mol/kg or 0·21 mol/kg. Ten days later duodenal calcium absorption by the ligated loop technique in vivo, and plasma calcium and phosphorus concentrations, were measured. In addition the metabolism in vitro of 25-hydroxycholecalciferol [25-(OH)D3] by kidney homogenates was studied. 2. In the low phosphorus group (0·08 mol/kg) calcium absorption and the activity of 25-(OH)D3-1-hydroxylase were significantly higher than those of the high phosphorus group (0·21 mol/kg). However, in the medium phosphorus group (0·14 mol/kg), calcium absorption was significantly higher although the activity of 25-(OH)D3-1-hydroxylase was not significantly higher when compared with the high phosphorus group (0·21 mol/kg). 3. It is concluded that in phosphorus deprivation, unlike in calcium deprivation, a diet very low in phosphorus is required to stimulate the renal 25-(OH)D3-1-hydroxylase activity.

THE ROLE OF THE PARATHYROID GLANDS IN THE ABSORPTION OF CALCIUM FROM THE SMALL INTESTINE

1970 ◽  
Vol 47 (1) ◽  
pp. 65-72 ◽  
Author(s):  
M. WINTER ◽  
E. MORAVA ◽  
G. SIMON ◽  
J. SÓS
Keyword(s):  
Small Intestine ◽  
Calcium Absorption ◽  
Normal Diet ◽  
Calcium Excretion ◽  
Deficient Diet ◽  
High Calcium ◽  
Low Phosphorus ◽  
Loop Technique

SUMMARY The absorption of calcium from duodenal and jejunal segments of the small intestine was studied in rats using an in-vivo loop technique. Previous parathyroidectomy decreased calcium absorption from both segments in rats fed a normal diet. Reduced calcium transport was greater in rats fed a calcium-deficient diet after parathyroidectomy. The slower clearance of radioactive calcium from the lumen of the intestine was not due to increased endogenous calcium excretion. Thyroidectomy, either alone or combined with parathyroidectomy, decreased calcium absorption but the effect of thyroidectomy alone requires further study. The decrease in calcium absorption after removal of the parathyroids was minimal or absent when the animals were fed a high calcium, low phosphorus, vitamin D-deficient diet or fasted 48 hr. before the experiment.

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