Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Betamethasone topical nasal drops may have systemic corticosteroid activity and cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis and impairment of bone turnover. The aim of this study was to assess the effect of a standard 6-week regime of betamethasone topical nasal drops on the HPA axis (using a physiological dose (1 microg) ACTH test) and on bone turnover (using markers of bone turnover, urinary deoxypyridinoline and serum bone specific alkaline phosphatase). Eleven patients with nasal polyposis were included in a prospective cohort study. Plasma cortisol was lower after betamethasone treatment at all time intervals (P < 0. 0001). There was no change in urinary deoxypyridinoline corrected for creatinine or bone specific alkaline phosphatase. Six weeks' treatment with recommended doses of betamethasone suppresses the HPA axis, but has no significant effect upon markers of bone turnover. Topical betamethasone in subjects with nasal polyps should be viewed as systemic corticosteroid administration and the long and short-term sequelae should be borne in mind.
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PMID:The effect of six weeks topical nasal betamethasone drops on the hypothalamo-pituitary-adrenal axis and bone turnover in patients with nasal polyposis. 1060 95

We examined 170 patients with acute viral hepatitis B (AVH-B) and 10 patients with chronic hepatitis B (CH-B) exacerbation. 85% of them were under 40 years old. During the 12-hour night period we measured urine excretion of nitrites (NO2-) and nitrates (NO3-). It was significantly high in AVH-B but in CH-B exacerbation it did not differ from the controls. ACTH and hydrocortisone blood levels were significantly high in AVH-B and in CH-B exacerbation. Though hydrocortisonemia and nitrituria/nitraturia during AVH-B were both high, the correlation between them was negative due to nitric oxide (NO) synthesis suppression by hydrocortisone. A negative correlation between nitrituria/nitraturia and ALAT, ASAT, bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase is an indirect evidence for a protective role of NO against viral hepatitis B.
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PMID:[Changes in synthesis of nitric oxide, blood levels of ACTH and cortisol in viral hepatitis B]. 1181 Nov 11

We have previously reported that ACTH activates a phospholipase C that hydrolyzes glycosylphosphatidylinositol (GPI), which would release inositolphosphoglycan (IPG) to the extracellular medium, and that an IPG purified from Trypanosoma cruzi is able to inhibit ACTH-mediated steroid production in adrenocortical cells. In the present paper, it was found that anti-inositolphosphoglycan antibodies (anti-CRD) increased ACTH-mediated corticosterone production, which indicates that an endogenous IPG is a physiological inhibitor of ACTH response. On the other hand, we investigated the release to the extracellular medium of the GPI-anchored enzyme, alkaline phosphatase, by ACTH. We found that: (a) the released enzyme appeared in the aqueous phase after Triton X-114 partitioning, consistent with loss of the GPI, (b) the phospholipase C inhibitor, U73122, impaired the release of the enzyme by the hormone and (c) two inhibitors of IPG uptake, inositol 2-monophosphate and 2 M NaCl, increased the amount of alkaline phosphatase in the extracellular medium. These results suggest that ACTH releases alkaline phosphatase by activation of a phospholipase C. Dibutyryladenosine-3',5'-cyclic monophosphate (db-cAMP) was able to increase the release of alkaline phosphatase from adrenocortical cells and this effect was inhibited by U73122, suggesting that cAMP is involved in the activation of phospholipase C. In addition, it was found that a pertussis-toxin sensitive G-protein is required for ACTH- and db-cAMP-mediated release of alkaline phosphatase and that incorporation of anti-Gi antibodies in adrenocortical cells inhibited the release of alkaline phosphatase by ACTH. Our results suggest that ACTH increases the release of alkaline phosphatase by activation of a phospholipase C through cAMP and Gi which would contribute to produce IPG It was also found that the two inhibitors of IPG uptake, inositol-2-monophosphate and 2 M NaCl, increased the amount of alkaline phosphatase in the extracellular medium of ACTH-treated cells more than in control cells, indicating that ACTH also stimulates the uptake of IPG These data support a role of GPI and the involvement of Gi in ACTH action.
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PMID:ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositol-phosphoglycan. 1503 Jan 84

Syncollin is a 13 kDa protein that is highly expressed in the exocrine pancreas. Syncollin normally exists as a doughnut-shaped homo-oligomer (quite probably a hexamer) in close association with the luminal surface of the zymogen granule membrane. In the present study, we examine the effect of expression of syncollin in AtT-20 neuroendocrine cells, which do not normally express this protein. Efficient expression was achieved by infection of the cells with adenoviral constructs encoding either untagged or GFP (green fluorescent protein)-tagged syncollin. Both forms of the protein were sorted into corticotropin (ACTH)-positive secretory vesicles present mainly at the tips of cell processes. Neither form affected basal corticotropin secretion or the constitutive secretion of exogenously expressed secreted alkaline phosphatase. In contrast, regulated secretion of corticotropin was inhibited (by 49%) by untagged but not by GFP-tagged syncollin. In parallel, untagged syncollin caused a 46% reduction in the number of secretory vesicles present at the tips of the cell processes. Syncollin-GFP was without effect. We could also show that native syncollin purified from rat pancreas was capable of permeabilizing erythrocytes. We suggest that syncollin may induce uncontrolled permeabilization of corticotropin-containing vesicles and subsequently destabilize them. Both forms of syncollin were tightly membrane-associated and appeared to exist as homooligomers. Hence, the lack of effect of syncollin-GFP on regulated exocytosis suggests that the GFP tag interferes in a subtler manner with the properties of the assembled protein.
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PMID:Syncollin inhibits regulated corticotropin secretion from AtT-20 cells through a reduction in the secretory vesicle population. 1504 Jul 87

An exposure to ambient temperature of 25 degrees C had no perceptible effect on interrenal function but further increase of temperature to 35 degrees C caused nuclear hypertrophy with increase of nuclear diameter, RNA concentration, acid phosphatase and alkaline phosphatase activities, accompanied by quantitative depletions of cholesterol (free, esterified and total) and ascorbic acid levels in the interrenal gland of the soft-shelled turtle Lissemys p. punctata. Similar manifestations of stimulation, except in the nucleus, were marked after exposure to 38 degrees C, but the degree of response in respect of esterified and free cholesterol levels was higher at 38 degrees C than at 35 degrees C. Moreover, withdrawal of 38 degrees C temperature and subsequently maintaining at 25 degrees C for 15 days showed reverse manifestations to those of 35 degrees C/38 degrees C, leading to a tendency towards normalcy. It is suggested that high a ambient temperature of 35 degrees C significantly stimulates interrenal function of Lissemys turtles, but further increase of 38 degrees C does not cause further overall stimulation, and withdrawal of higher temperature (38 degrees C) shows a tendency towards normalcy. It is also suggested that (a) high ambient temperature causes thermal stress, (b) it is reversible and (c) it acts on interrenal activity presumably via CRF-ACTH-axis in turtles.
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PMID:Interrenal responses to high ambient temperature in soft-shelled turtle, Lissemys punctata punctata. 1524 89

To clarify whether ototopical glucocorticoid treatment is associated with impaired hypothalamic-pituitary-adrenal axis (HPA) activity and altered hepatic metabolism, one commercially available dexamethasone-containing ointment was tested. At present, very little is known about the effects of ototopical glucocorticoid treatment on HPA and liver function. Ten beagle dogs received two daily therapeutic doses of dexamethasone (0.6 mg/ear) in the outer auditory canal for 21 d in a single-blind, placebo-controlled study. Resting cortisol concentrations were assessed before, during, and after treatment using an RIA system. Adrenal function and HPA feedback sensitivity were measured by a standard dose (250 microg) ACTH stimulation test. Serum biochemical and hematological parameters were measured, whether ototopical glucocorticoids affect hepatic function was studied, and blood cell counts were made. Ototopical dexamethasone treatment induced a marked suppression (to about 100%) of resting plasma cortisol concentrations below the placebo effect (P < 0.0001) within the first 11 d, and these remained reduced during the entire treatment period up to d 19. As well, an ACTH stimulation test found a markedly reduced rise in plasma cortisol concentrations (P = 0.0004). Concomitantly, significant increases in serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were detected. Moreover, we found a significant reduction in differential leukocyte counts of eosinophils and lymphocytes, whereas neutrophils increased. Although cortisol levels and hematological parameters returned to baseline 7 d after treatment cessation, liver enzyme activities remained elevated. In conclusion, these findings suggest that after ototopical application, dexamethasone is sufficiently absorbed from the auditory canal to suppress HPA function as well as to alter metabolic and hemopoietic profiles. Thus, in long-term treatment of otitis externa or media, the systemic adverse suppression of HPA has to be considered in relation to stress exposure, whereas changes in serum enzyme activities may not be interpreted as hepathopathy.
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PMID:Evidence for ototopical glucocorticoid-induced decrease in hypothalamic-pituitary-adrenal axis response and liver function. 1580 95

A 39-yr-old man presented to our hospital with unexplained erythrocytosis and hypertension. His follow-up for erythrocytosis had begun 2 yr earlier in another hospital and he had been diagnosed with polycythemia rubra vera. On admission to our hospital he was hypertensive (165/95 mmHg) and, except for the presence of moon-like face and facial plethora, his physical examination was normal. His hemoglobin concentration was 19.2 g/dl, and hematocrit was 58.9% with an increased red blood cell mass of 58 ml/kg as measured by radioisotope (Cr51). Blood film, other hematological indices except for elevated leukocyte alkaline phosphatase score, arterial gas analysis, and examination of aspirated bone marrow were all normal. An abdominal ultrasonography showed no evidence of splenomegaly. A diagnosis of probable secondary erythrocytosis was made. Early-morning serum cortisol and 24-h urinary free cortisol concentration as well as serum ACTH were high. Serum cortisol was not suppressed by low-dose dexamethasone, but suppressed by high-dose dexamethasone. Pituitary magnetic resonance imaging showed no lesion. After inferior petrosal sinus sampling suggesting right-central ACTH secretion, the patient underwent transnasal-transsphenoidal pituitary adenomectomy. Both hypercortisolemia and erythrocytosis regressed completely after the adenomectomy. After the operation, the patient's hemoglobin concentration and hematocrit decreased steadily, and 1 month post-adenomectomy his hemoglobin is 14.9 g/dl and hematocrit 44.8%. Thus, Cushing's syndrome should be a routine part of evaluation of unexplained polycythemia.
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PMID:Polycythemia as the first manifestation of Cushing's disease. 1909 3

Otitis externa is common in atopic dogs and is frequently treated using potent glucocorticoids topically. These preparations can cause adrenal suppression and affect skin test reactivity. The purpose of this study was to determine if an otic product containing betamethasone could decrease skin reactivity in normal dogs. Sixteen laboratory beagles were used in a cross-over, blinded trial. Dogs were enrolled in two groups; one received placebo and the other a betamethasone-containing otic preparation (Otomax) twice daily for 2 weeks. After a 4-week wash-out period, treatments were switched. Dogs were intradermally tested on days 0 and 14 of each treatment period with histamine phosphate (1 : 100,000 and 1 : 200,000 w/v) and allergens common in the area. Adrenocorticotropic hormone (ACTH) stimulation tests were done before and after treatment to investigate adrenal suppression. After 2 weeks of otic betamethasone, Dermatophagoides farinae (P = 0.0034), Cynodon dactylon (P = 0.0459) and histamine 1 : 100,000 w/v (P = 0.0028) reactions were significantly reduced. Pre-treatment post-ACTH serum cortisol levels and those obtained after both treatments did not differ statistically (P = 0.6362). Betamethasone induced a slight but statistically significant elevation (P = 0.0002) of serum alkaline phosphatase. Despite the increase, values were within normal range. It is concluded that, although otic betamethasone did not suppress adrenal glands, it mildly suppressed intradermal reactions to 1 : 100,000 w/v histamine, D. farinae and C. dactylon.
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PMID:Effects of otic betamethasone on intradermal testing in normal dogs. 1761 Apr 84

Postoperative changes in endocrinological status and serum chemistry during the 4 years after transsphenoidal surgery (TSS) in 25 dogs with Cushing's disease were investigated in a prospective study. In all 25 dogs, Cushing's disease was diagnosed from resected pituitary tissues as a corticotroph adenoma in the anterior lobe of the pituitary. Prior to TSS, all 25 dogs showed hypercortisolemia. After TSS, the ACTH stimulation test showed continued low serum cortisol concentrations in 21 dogs (84%). In addition, the serum thyroid stimulating hormone concentrations decreased sequentially, while the serum T4 concentrations tended to increase due to the postoperative hormone substitution therapy utilized to avoid secondary hypothyroidism. In regard to serum chemistry, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total cholesterol are commonly increased in canine Cushing's disease. In this study, ALP, ALT and total cholesterol were increased in 23 cases (92%), 19 cases (76%) and 20 cases (80%), respectively. However, postoperatively, these concentrations gradually decreased. The postoperative serum concentrations of ALP at 1 year, that of ALT at six months to 2 years and that of total cholesterol over the course of the 4 years decreased significantly compared with the concentrations before TSS. These results show that TSS is an effective treatment for canine Cushing's disease and for long-term improvement of hypercortisolemia. Moreover, TSS is effective in improvement of hypercortisolism, such as increased concentrations of serum ALP, ALT and total cholesterol.
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PMID:Efficacy of transsphenoidal surgery on endocrinological status and serum chemistry parameters in dogs with Cushing's disease. 1999 57

In peripubertal female rats, we have previously found that 50% food restriction (FR) increases plasma IL-6, haptoglobin and both alanine transaminase (ALT) and alkaline phosphatase (AST) aminotransferases, indicating the existence of an inflammatory response. To study whether such FR influences the hypothalamic-pituitary-adrenal (HPA) axis, we examined by immunohistochemistry the morphofunctional features of pituitary adrenocorticotroppic (ACTH) cells. In FR rats the volume and volume density of ACTH cells as well as plasma ACTH levels were increased by 17.6%, 12.5% and 13.4%, respectively, in comparison with controls (p<0.05). We concluded that chronic FR is a systemic stressor in young females, capable to stimulate the HPA axis, probably as a result of IL-6 action.
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PMID:The effect of chronic food restriction on immunopositive ACTH cells in peripubertal female rats. 2195 42


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