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Biomedical subjects

M Clodi

Publications and source records attributed to M Clodi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Urinary excretion of apo(a) fragments in NIDDM patients.

Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA1c or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM.

Aged↗
PubMed1997

Effect of elevated serum prolactin concentrations on the immunophenotype of human lymphocytes, mitogen-induced proliferation and phagocytic activity of polymorphonuclear cells.

It has been suggested that the immune system is an important target tissue of prolactin (PRL). We therefore investigated several immune parameters in nine patients with chronically elevated serum prolactin concentrations. The immunophenotype of lymphocytes, mitogen-induced lymphocyte proliferation and phagocytic activity of polymorphonuclear cells were determined under high serum prolactin levels and 2 weeks after treatment with dopamine agonists. An increased CD4/CD8 ratio in the hyperprolactinaemic patients could be detected compared with healthy control subjects, which remained high after treatment and did not seem to correlate with serum prolactin concentrations. Peripheral blood B lymphocytes showed an increased expression of CD69 in the treated group but not in untreated patients compared with healthy control subjects. Interleukin 2 receptor, CD45RO, transferrin receptor or HLA-DR expression of CD4 or CD8 cells, as well as oxidative burst and phagocytic activity of granulocytes, were not affected in the patients with prolactinomas. Lymphocyte transformation response to phytohaemagglutinin in vitro was found not to be influenced by elevated prolactin levels except at the highest mitogen concentration tested. These data together with previous reports suggest that, although PRL is required for lymphocyte maturation to achieve normal immune function, elevated PRL levels do not lead to an 'overstimulation' of the immune system in men.

Adult↗
PubMed1997

Effect of successful parathyroidectomy on hematopoietic progenitor cells and parameters of red blood cells in patients with primary hyperparathyroidism.

Elevated levels of parathyroid hormone (PTH) in primary and secondary hyperparathyroidism inhibit hematopoiesis at the level of hematopoietic progenitor cells, mainly the burst forming units-erythroid (BFUe). Removal of parathyroid adenomas is associated with an increase in hematopoietic progenitor cells. In contrast, a certain amount of PTH and calcium is needed to correct anemia after bleeding demonstrating that PTH has also a stimulatory effect on the bone marrow. We examined the effect of parathyroidectomy (PTX) in 10 patients with histologically proven primary hyperparathyroidism on hematopoietic progenitor cells and several parameters of red blood cells before and at 5, 30 and 90 days after PTX. After successful surgery serum levels of iPTH (p < 0.01) and calcium (p < 0.001) decreased significantly. Subsequently a steady increase in all hematopoietic progenitor cell classes was observed reaching significance for BFUe only (p < 0.05). Red blood cells and hemoglobin reached nearly pretreatment values within 90 days after PTX after they had decreased due to surgery associated blood loss. 8 patients undergoing hemithyroidectomy without PTX showed a similar decrease in red blood cells and hemoglobin followed by a rise after the operation. The changes of these parameters did not differ significantly from the patients with pHPT. In contrast to the patients with pHPT, no changes in hematopoietic progenitor cells during the 90 days were observed. The presented data provide further evidence that increased PTH concentrations might inhibit hematopoiesis in humans in vivo. The inhibition can be reversed following PTX by normalisation of PTH concentrations.

Aged↗
PubMed1997

The long-acting dopamine agonist bromocriptine mesylate as additive immunosuppressive drug after kidney transplantation.

BACKGROUND: Acute rejection is an important risk factor for kidney graft loss. As evidence suggests that prolactin has important immunostimulatory properties, we conducted a randomized, prospective open trial in which bromocriptine, a drug suppressing prolactin secretion, was administered as an additive immunosuppressive drug after first cadaver kidney transplantation. METHODS: In the treatment group bromocriptine was given intramuscularly to 22 patients after their first kidney transplantation along with conventional immunosuppression (cyclosporin A, glucocorticoids). Twenty-three patients receiving only conventional immunosuppression served as control subjects. The incidence of acute graft rejections, graft losses, and infections was evaluated. RESULTS: Serum prolactin concentrations were slightly elevated above normal values before transplantation (32 +/- 5.3 ng/ml) and decreased to values between 13 and 16 ng/ml in the control group and were totally suppressed in the bromocriptine group. After 6 months of follow-up overall patient and allograft survival was 97.7% and 91% respectively. Acute rejection episodes occurred in 31 patients (77.5%): 15 in the bromocriptine group vs 20 in the control group (n.s.). In each group eight patients experienced a cytomegalovirus infection. The incidence of severe bacterial infections (i.e. pneumonia and sepsis) was five and six respectively. The necessity of haemodialysis after transplantation was 3.1% in the patients on bromocriptine and 23% in those without. CONCLUSIONS: Suppression of circulating prolactin concentration by bromocriptine did not improve the clinical outcome of patients after kidney transplantation receiving cyclosporin and prednisolone.

Acute Disease↗
PubMed1996

Beta-cell activity and hepatic insulin extraction following dexamethasone administration in healthy subjects.

Glucocorticoids induce an increase of hepatic glucose production and peripheral resistance to insulin action. It is further assumed that dexamethasone administration in humans causes insulin hypersecretion, although inferences on beta-cell activity have been made in absolute terms and mostly from observations of systemic insulin concentration. In fact, the role of hepatic insulin extraction in humans treated long-term with glucocorticoids has not been investigated. The aim of the present study was to factor out quantitatively the main components of the insulin pathway that are responsible for the peripheral hypersecretion observed after steroids. Frequently sampled intravenous (FSIGT) and oral (OGTT) glucose tolerance tests were performed in healthy subjects before and after 5 days of oral dexamethasone administration (4 mg/d). Insulin sensitivity, beta-cell secretion, and hepatic insulin extraction were estimated by means of mathematical modeling. After steroids, insulin sensitivity decreased from 6.00 +/- 1.29 to 4.23 +/- 1.04 min-1/(microU/mL) (P < .04). Basal beta-cell secretion increased from 45 +/- 7 to 104 +/- 26 pmol/L . min-1 (P < .004) during the FSIGT and from 40 +/- 6 to 88 +/- 21 (P < .05) during the OGTT; total insulin release increased from 19 +/- 5 to 36 +/- 7 nmol/L in 180 minutes (P < .005) and from 33 +/- 5 to 50 +/- 10 (P < .02), respectively, FSIGT data also showed that first-phase beta-cell sensitivity increased from 236 +/- 39 to 309 +/- 33 pmol/L . min-1/(mg/dL) (P < .04), and second-phase from 631 +/- 154 to 1,103 +/ 196 10(4) pmol/L . min-2/(mg/dL) (P < .03). Posthepatic insulin delivery increased only insignificantly during the FSIGT (from 3.4 +/- 0.6 to 4.5 +/- 0.5 nmol/L, P = .073) due to an augmented hepatic insulin extraction from 73.0% +/- 7.2% to 83.0% +/- 3.5% (P < .05). During the OGTT, posthepatic insulin delivery increased after treatment from 6.6 +/- 1.2 to 11.4 +/- 2.5 nmol/L (P < .035) due to an increase, although slight, of hepatic insulin extraction from 77.4% +/- 1.9% to 79.3% +/- 3.3% (P = .319). The increased overall beta-cell activity during both tests was observed also by analyzing OGTT profiles of islet amyloid polypeptide (IAPP), the secretion of which was higher after steroids (basal, 0.081 +/- 0.012 v 0.272 +/- 0.082 pmol/L/min, P < .02; total, 35 +/- 8 v 116 +/- 48 mpmol/L in 3 hours, P < .05). In conclusion, after dexamethasone administration, peripheral hyperinsulinemia due to marked prehepatic beta-cell insulin hypersecretion is partially ameliorated by a concomitant increase of hepatic insulin clearance, which is more evident during a FSIGT. Model-derived secretion parameters from the OGTT and FSIGT produced comparable results, indicating that both tests, when properly analyzed, are feasible tools to evaluate insulin secretion.

Administration, Oral↗
PubMed1996

The influence of growth hormone substitution therapy on erythroid and myeloid progenitor cells and on peripheral blood cells in adult patients with growth hormone deficiency.

It has been reported that hypophysectomized rats exhibit normochromic, normocytic anaemia. Pancytopenia with impaired DNA synthesis in the bone marrow can be restored in these hypophysectomized rats by syngeneic pituitary grafts placed under the kidney capsule or treatment with growth hormone (GH). Until now, adults with hypopituitarism have received adequate replacement therapy with thyroxine, cortisol and sex steroids, but not with GH. We therefore investigated the effects of GH replacement therapy on the proliferation and differentiation of erythroid and myeloid progenitor and peripheral blood cells in 11 adult patients with growth hormone deficiency in a double-blind, placebo-controlled study for the first 6 months of therapy. The placebo group showed no changes during the first 6 months without therapy in either insulin-like growth factor I (IGF-I) levels, erythroid and myeloid progenitor precursor cells or peripheral blood cells. After commencement of GH therapy, IGF-I levels rose significantly during 24 months of therapy from 75.3 +/- 13.5 to 225 +/- 34.7 ng mL-1 (P < 0.001). Erythroid and myeloid progenitor precursor cells showed a steep and significant increase after 18 and 24 months of therapy (erythroid: from 10.7 +/- 3.5 to 261.4 +/- 79.8, P < 0.02, after 18 months and to 276.8 +/- 149.8 x 10(5) mononuclear cell colonies, P < 0.03, after 24 months; granulocyte-macrophage colony-forming units: from 39.7 +/- 9.8 to 316.9 +/- 124.6, P < 0.002, after 18 months and to 366 +/- 188.7 x 10(5) mononuclear cell colonies, P < 0.03, after 24 months), whereas the peripheral red and white blood cells exhibited only minimal non-significant changes. The principal regulators of erythropoiesis, such as erythropoietin, and parameters reflecting erythropoiesis in the peripheral blood, such as reticulocytes, remained almost unchanged throughout the whole study period. We therefore conclude that patients with GH deficiency do not have anaemia, but have haematopoietic precursor cells in the lower normal range, and that GH substitution therapy over a period of 24 months has a marked effect on erythroid and myeloid progenitor precursor cells but only negligible effects on peripheral blood cells in GH-deficient adults.

Adult↗
PubMed1995

Effect of danazol-induced chronic hyperglucagonaemia on glucose tolerance and turnover.

It has been shown that danazol (14-ethinyltestosterone) induces hyperglucagonaemia. To investigate the effect of chronic glucagon excess on carbohydrate metabolism, we studied six patients before and after treatment with danazol for immunothrombopenia. Glucose tolerance and insulin, C-peptide and glucagon secretion during an oral glucose tolerance test (oGTT) as well as peripheral and hepatic insulin sensitivity were determined by means of euglycaemic clamp technique (40 mU m-2 min-1) before and after 3 months of danazol therapy. Overall glucose turnover (Rd) was assessed radioisotopically. (1) Plasma glucagon levels rose significantly from 88 +/- 16 pg mL-1 before to 683 +/- 148 pg mL-1 after therapy (P < 0.01). (2) Glucose levels during an oGTT were not significantly different before and after therapy. Glucose-stimulated insulin secretion at 60 and 120 min and the area under the curve (AUC) for insulin during the oGTT, were significantly increased after danazol treatment compared with pre-treatment values (P < 0.05), whereas glucagon secretion showed a similar decrease at both time points of investigation (NS). (3) Rd during steady state showed a significant decrease during the entire period of euglycaemic clamp following therapy (after 240 min, 3.8 +/- 0.6 vs. 5.3 +/- 0.7 mg kg-1 min-1, P < 0.05). The decline in glucagon during the clamp was similar during steady state before and after therapy. (4) Basal hepatic glucose output did not differ significantly before and after therapy (1.74 +/- 0.41 vs. 1.45 +/- 0.22 mg kg-1, NS), whereas hepatic glucose output during the clamp was significantly less suppressed after danazol therapy. The authors conclude that chronic glucagon excess leads to a decrease in peripheral and hepatic insulin action which is accompanied by an increase in insulin secretion.

Adult↗
PubMed1994

Iodine-123-IBZM-SPECT: studies in 15 patients with pituitary tumors.

Single photon emission computerized tomography (SPECT) using the Iodine 123 labeled dopamine D2 receptor antagonist S(-)Iodobenzamide [S (-)IBZM] was performed in 15 patients with pituitary tumors. Among them there were five prolactinoma patients with macroadenoma and two acromegalic patients with macroadenoma. Specific binding in the area of the adenoma was only observed in one subject, a macroprolactinoma patient, who was responsive to dopaminergic treatment. None of the other patients, among them one macroprolactinoma patient responsive to dopaminergic treatment showed specific binding in the area of the tumor. IBZM-binding in the striatum was found to be significantly lower in the group of pituitary tumor patients as compared to controls. The results show that D2 receptors in pituitary adenomas can be visualized using SPECT. However, the sensitivity of IBZM-SPECT appears to be too poor to visualize PRL- and GH- secreting macroadenomas in general.

Adenoma↗
PubMed1994

Role of islet amyloid polypeptide secretion in insulin-resistant humans.

Although it is generally accepted that islet amyloid polypeptide is cosecreted with insulin, relatively few data on its kinetics are available. We therefore studied the dynamics of islet amyloid polypeptide release following oral and frequently sampled intravenous glucose tolerance tests in comparison to insulin and C-peptide using mathematical model techniques in 14 control subjects, 10 obese and 11 hypertensive patients. The fractional clearance rate of islet amyloid polypeptide (0.034 +/- 0.004 min-1 in control subjects, 0.058 +/- 0.008 in the obese and 0.050 +/- 0.008 in the hypertensive patients) was significantly different (p < 0.01) in each group compared with that of insulin (0.14 +/- 0.03 min-1) and similar to that of C-peptide (0.061 +/- 0.007 min-1), at least in the insulin-resistant subjects. Based on the insulin sensitivity index derived from the minimal model analysis of intravenous glucose tolerance test data, both the hypertensive (2.4 +/- 0.4 min-1/(microU/ml); p < 0.0005) and the obese (2.7 +/- 0.5; p < 0.001) patients demonstrated severe insulin resistance compared to control subjects (8.1 +/- 1.3). Marked insulin hypersecretion was found in the hypertensive (57.6 +/- 5.2 nmol.l-1 in 180 min; p < 0.001) and obese (60.8 +/- 10.1; p < 0.003) patients in comparison with control subjects (32.4 +/- 3.2). The release of islet amyloid polypeptide was significantly higher in the hypertensive (83.1 +/- 16.6 pmol/l in 180 min; p < 0.02) and obese (78.6 +/- 13.1; p < 0.005) patients than in control subjects (40.5 +/- 6.4). No correlation was found between islet amyloid polypeptide release and the insulin sensitivity index in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The non ergot D2-dopamine agonist CV 205-502 decreases growth hormone concentrations in acromegalic patients.

It was the aim of this study to test for a possible effect of the new non ergot dopamine agonist CV 205-502 on plasma growth hormone (GH) concentrations in acromegaly. 10 acromegalic patients received a single oral dose of 150 micrograms CV 205-502 after an overnight fast. As a control group 7 acromegalic patients undertook the same procedure without receiving any drug. Blood samples were drawn hourly up to 7 hours thereafter for determination of GH. Plasma growth hormone concentrations decreased by 48.8 +/- 8.7%. The nadir was observed 3 hours after CV 205-502 was administered and GH concentrations remained suppressed throughout the 7 hours of the test period. In contrast GH plasma concentrations in the control group remained stable. We conclude that acute administration of CV 205-502 suppresses GH secretion in acromegalic patients and thus could serve as an alternative therapy in acromegaly.

Acromegaly↗
PubMed1994

Islet amyloid polypeptide inhibits insulin secretion in conscious rats.

To investigate the effect of islet amyloid polypeptide (IAPP, amylin) exposure on insulin secretion in vivo, the plasma glucose level of conscious rats was clamped at 11.1 mmol/l (hyperglycemic clamp) during the last 2 h of a 24-h infusion study. Group parameters were A, 24-h saline; B and C, 22-h saline followed by 2-h IAPP (B, 8.5 pmol/min; C, 85 pmol/min), and D, 24-h IAPP (85 pmol/min). Induced hyperglycemia increased plasma insulin concentration by 426 +/- 34 pmol/l in control rats (group A). This effect on plasma insulin was reduced by 31% and 53% during short-term IAPP infusion (group B, 8.5 pmol/min, 294 +/- 41 pmol/l; C, 85 pmol/min, 202 +/- 25 pmol/l; short-term effect, P < 0.0001), whereas insulin levels tended to increase after 24 h of continuous IAPP exposure (group D, 682 +/- 120 pmol/l; P < 0.05 vs. group A). Glucose infusion rate required to maintain constant hyperglycemia fell dose dependently during short-term but not during long-term IAPP infusion (mumol.kg-1.min-1: group A, 203 +/- 11; B, 154 +/- 7; C, 119 +/- 7; D, 212 +/- 9; short-term effect, P < 0.0001). In parallel, muscle glycogen content was dose dependently reduced by short-term IAPP exposure. We conclude that IAPP inhibits glucose-stimulated insulin secretion and decreases muscle glycogen storage in conscious rats in vivo.

Amyloid↗
PubMed1994

Effect of elevated growth hormone concentrations on the phenotype and functions of human lymphocytes and natural killer cells.

Over the past decades, strong evidence has accumulated that growth hormone (GH) has immunostimulatory properties. Therefore, an investigation was conducted on 10 acromegalic patients and 9 age- and sex-matched healthy controls to determine whether plasma GH concentrations correlate with changes in several immune parameters, including serum concentrations of immunoglobulins, lymphocyte subsets, lymphocyte transformation with phytohemagglutinin (PHA), natural killer (NK) cell activity as well as phagocytic and metabolic burst activity. While NK cell activity, serum concentrations of immunoglobulins (IgG, IgM, IgA) and metabolic burst activity were within the normal range in both groups, a significantly enhanced phagocytic activity was observed in the acromegalic patients. Surface markers on T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD19) and NK cells (CD16/56) were normal in both groups; however, in the acromegalic subjects, CD4+ and CD8+ cells showed a significant higher expression of transferrin receptors (CD71), indicating enhanced T-cell activity. The lymphocyte transformation response to PHA at the highest concentration tested showed a tendency to be elevated in acromegalics; however, the difference failed to be significant. Long-lasting and pronounced elevation of GH in acromegaly induces significantly enhanced phagocytic activity, but only negligible changes in most patients in lymphocyte phenotype and in the lymphocyte response to PHA.

Acromegaly↗
PubMed1994

Increased levels of circulating islet amyloid polypeptide in patients with chronic renal failure have no effect on insulin secretion.

To elucidate the metabolism of islet amyloid polypeptide (IAPP) with respect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAPP were significantly higher in uremic patients than in controls (15.1 +/- 3.2 vs. 3.2 +/- 0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenous IAPP on insulin secretion and insulin sensitivity, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed in a subset of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolerance (IGT). Insulin sensitivity index (SI) was 8.7 +/- 1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4 +/- 0.9 in HD (P < 0.05 vs. IGT), 3.1 +/- 1.0 in NGT, and 2.0 +/- 0.5 in IGT. First phase insulin secretion was increased in patients on HD compared with those of several control groups. The results of this study therefore indicate a renal route of metabolism of IAPP. Increased endogenous circulating IAPP levels over a long period of time do not lead to a decrease in insulin release in patients on HD and do not cause the insulin resistance commonly seen in obesity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM).

Adult↗
PubMed1994

[Disodium pamidronate (APD) in therapy of hypercalcemia in primary hyperparathyroidism].

The established pre-operative therapy for severe hypercalcemia caused by primary hyperparathyroidism (pHPT), i.e., rehydration with saline in combination with furosemide, calcitonin and hydrocortisone, rarely leads to satisfactory results. We examined the effect of pamidronate (APD, 45-60 mg), a diphosphonate of the 2nd generation in 6 patients (4 female, 2 male) with severe hypercalcemia caused by pHPT. Prior administration of saline, furosemide, calcitonin and oral diphosphonates of the 1st and 2nd generation had failed and the patients still suffered from symptoms of hypercalcemia. APD reduced serum calcium levels in all patients: values reached the normal range (2.1-2.6 mmol/l) in 3 patients, the upper normal range in 2 patients and fell transiently into the subnormal range in 1 patient. In parallel to the decreasing calcium levels a marked increase in PTH was registered in 4 out of 6 patients. One patient with an adenoma showed no change in PTH levels, whereas one patient with hyperplasia of 5 parathyroid glands showed a significant decrease in PTH. These results confirm the potent hypocalcemic effect of pamidronate even in patients whose serum calcium could not be reduced by other conservative therapeutic strategies. Thus, pamidronate is an effective drug in the treatment of the pre-operative phase of hypercalcemia caused by pHPT.

Aged↗
PubMed1993

Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans.

The response of islet amyloid polypeptide and insulin and their molar ratios were investigated in eight healthy volunteers before and after treatment with dexamethasone by oral and frequently-sampled intravenous glucose tolerance tests. Following dexamethasone treatment the insulin sensitivity index decreased significantly from 6.5 +/- 1.3 to 4.1 +/- 1.0 (microU.ml-1).min-1, p < 0.05. The area under the curve representing above-basal levels of insulin during oral glucose tolerance test increased significantly following dexamethasone treatment from 48132 +/- 9736 to 82230 +/- 14846 pmol.l-1 x 3 h-1, p < 0.05, the area under the curve of islet amyloid polypeptide increased from 1308 +/- 183 to 2448 +/- 501 pmol.l-1 x 3 h-1, p < 0.05. The overall insulin/islet amyloid polypeptide molar ratios calculated from the area under the curve during the 3-h period of the oral glucose tolerance test was not significantly different before and after dexamethasone treatment (42 +/- 5 vs 40 +/- 4). During the oral glucose tolerance test the insulin/islet amyloid polypeptide ratio increased significantly from baseline to 30 min (p < 0.05), then declined towards initial values before and after dexamethasone treatment. In conclusion, dexamethasone induced a significant decrease in insulin sensitivity and a significant increase in insulin secretion during the oral glucose tolerance test. However, in contrast to previous animal experiments we did not find a change in the insulin/islet amyloid polypeptide ratio before and after dexamethasone treatment.

Adult↗
PubMed1993

Interferon-alpha stimulates the hypothalamic-pituitary-adrenal axis in vivo and in vitro.

The successful therapeutic use of interferon-alpha (IFN-alpha) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-alpha therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-alpha a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-alpha therapy, no significant stimulation of the HPA axis occurred after administration of IFN-alpha. IFN-alpha-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-alpha treatment for 3 weeks. To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-alpha at concentrations of 5 x 10(-8) M or 10(-7) M respectively. In contrast, no direct IFN-alpha effect on pituitary ACTH secretion could be observed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Epidermal growth factor plasma concentrations in healthy control persons, acute and chronic stress and during pregnancy.

Plasma concentrations of Epidermal Growth Factor (EGF) in healthy control persons do not change significantly during adult lifetime and no diurnal changes could be detected. In addition, no alterations of plasma EGF concentrations occur during acute and chronic stress and in all three trimesters of pregnancy. Thus, the previously suggested theories that EGF might play a causative role in the activation of the hypothalamic-pituitary adrenal axis during the stress reaction and in the prevention of peptic ulcers in pregnancy could not be confirmed by the present data.

Acute Disease↗