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Biomedical subjects

A Conti

Publications and source records attributed to A Conti.

At least 145 records · Page 8Linked to original sources

Housestaff coverage in a nonteaching community hospital.

In August 1992, a project team of senior medical and administrative personnel was formed (Housestaff Coverage Project Team) at the Park Ridge Health System, Rochester, N.Y.. The team was given a mandate to address housestaff coverage, primarily from an economic standpoint. Through total quality management (TQM), the project team sought to develop a house coverage plan that was sustainable, efficient, and effective. A plan was developed that includes three layers of service. A minimum "standard hospital coverage" would be available to all physicians and their patients and cover the basic needs of admission, crisis intervention, and issues of length of stay. A complete level of service would be available under the title of "case management" and would consist of total patient management, under the direction of the attending physician, from admission through discharge. The third level of service available to both "standard" and "case managed" patients would be a "consultative service." The latter would function as a traditional in-house medical service and would bill for its services. Park Ridge Hospital believes it has developed a system of housestaff coverage that is sustainable, efficient, and effective. An evaluation mechanism, primarily addressed at length of stay, will tell if we are correct in this assumption.

Hospitals, Community↗

Analysis of human hematopoietic stem cell populations.

Purification of human hematopoietic stem cells (HSC) may be useful clinically for preparation of tumor-free grafts to be used for autologous transplantation and as targets for gene therapy. To analyze the phenotype of the human HSC, assays were used that measure the unique properties of stem cells, i.e., their long-term repopulating ability and their multilineage potential. These assays include: (1) an in vitro long-term hematopoietic culture system, using the murine bone marrow stromal cell line SyS1, which supports both B lymphopoiesis and myelopoiesis; (2) fetal human bone grafts implanted in SCID-hu mice, in which maintenance of CD34+ cells and B and myeloid differentiative capacity of candidate stem cell populations may be measured; (3) fetal human thymus grafts in SCID-hu mice, which allow the analysis of in vivo T-cell potential of a candidate stem cell population. Stem cells in adult bone marrow (ABM) or cytokine-mobilized peripheral blood (MPB) are thought to express CD34 but lack expression of markers indicating lineage commitment. This CD34+ Lineage- (Lin-) subpopulation has been isolated by fluorescence-activated cell sorting and tested for activity in the assays described here. CD34+ Lin- cells from both ABM and MPB demonstrated long-term engraftment in the SCID-hu bone model. This CD34+ Lin- population can be subfractionated further using an antibody to Thy-1. The Thy-1+ subset of CD34+Lin- cells is enriched for both long-term culture-initiating cells (LTC-1C) and has the ability to engraft in vivo.

Animals↗

[Serum levels of the carboxyterminal telopeptide of type I collagen in patients with thyroid disorders].

Serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) levels, marker of bone resorption, were evaluated in 35 patients with hyperthyroidism (age range: 21-68 years) and in 35 with hypothyroidism (age range: 28-69 years). Data obtained were compared with those recorded in an age and sex matched control group. In patients with hyperthyroidism, serum ICTP levels were significantly higher than in controls (mean +/- SE: 9.1 +/- 0.7 vs 4.1 +/- 0.3 ng/ml; p < 0.0001). In patients with untreated hypothyroidism ICTP levels were significantly reduced (2.5 +/- 0.2 ng/ml, p < 0.0001); seven patients with hypothyroidism, evaluated after substitutive L-thyroxine treatment, showed a significant increase of ICTP levels (6th month: 5.9 +/- 0.7 ng/ml, p < 0.02). Taking into consideration all the data recorded in patients with both hyper- and hypothyroidism, serum ICTP levels were positively correlated with those of free T3 and free T4 and negatively correlated with those of TSH. In conclusion, our data show that repeated determinations of ICTP levels, which directly reflect the bone resorption activity, might be usefully employed in the evaluation of bone turnover in patients with thyroid disorders.

Adult↗

Long-term follow-up of in situ carcinoma of the breast.

Eighty cases of duct carcinoma in situ (DCIS) of the breast have been investigated by a cohort-retrospective study. These consisted of 8.5 per 1,000 of 9,446 breast biopsies originally diagnosed as benign, between 1964 and 1976, with a mean follow-up of 17.5 years. There were forty-one cases (51%) of DCIS of clinging type (CC); 30 cases (37.%) of CC associated with other types of DCIS; nine cases of DCIS other than CC two of which were DCIS of comedo-type. Invasive duct carcinoma (IDC) subsequently developed in 11 patients (14%), whereas DCIS recurred in 5 (6%). The recurrence was ipsilateral in 12 of these 16 patients. IDC appeared more frequently, with high statistical significance, when the lesion present in the original biopsy showed pleomorphic (P) nuclei (ie, poorly differentiated cyto-nuclear morphology). The Standardized Morbidity Ratio (SMR) was 8.0 (95% CI; 2.9-17.5) with the general population as reference. IDC that developed following a lesion displaying P nuclei also showed a statistically significantly more aggressive behavior. It is suggested that when cases of DCIS are followed-up for a considerable length of time, a two-wave pattern of aggressiveness becomes apparent. IDC that develops after a poorly differentiated DCIS leads to death more precociously than that appearing after other types of DCIS, especially those showing more bland nuclear cytology.

Adult↗

Pharmacology of the new selective A2a adenosine receptor agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine.

The pharmacological profile of 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA, CAS 141018-30-6), a new selective A2a adenosine receptor agonist, was characterized. In binding studies on both rat and bovine brain, 2HE-NECA was more potent on A2a receptors (Ki = 2.2 and 1.5 nmol/l, respectively) than the reference A2a agonist, 2-[4-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoaden osi ne (CPEC) or the non-selective adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA). The drug displayed a good A2a vs A1 receptor selectivity in brain tissues of both animal species (60- and 160-fold, respectively). In functional studies, 2HE-NECA showed marked vasodilating properties in rat aorta, bovine and porcine coronary arteries. The vasodilatory response in the porcine coronary preparation was greater for 2HE-NECA (EC50 = 23.3 nmol/l) than for CPEC (EC50 = 58.7 nmol/l) or NECA (EC50 = 76.6 nmol/l). In the rat Langendorff model, in which global ischemia was induced, 2HE-NECA (100 nmol/l) significantly prevented the risk of diastolic pressure and coronary perfusion pressure occurring during postischemic reperfusion. The in vitro antiaggregatory activity of 2HE-NECA (IC50 = 0.07 mumol/l), as tested in rabbit platelets, was higher than that found with NECA (IC50 = 0.2 mumol/l) or CPEC (IC50 = 2.16 mumol/l). In spontaneously beating rat atria, which are responsive to A1-receptor stimulation, 2HE-NECA did not show any negative chronotropic activity up to micromolar concentrations. In conscious spontaneously hypertensive rats, 2HE-NECA administered intraperitoneally caused a dose-dependent reduction in systolic blood pressure (ED30 = 0.005 mg/kg) with minimal reflex tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Pharmacology of the highly selective A1 adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine.

The pharmacological profile of 2-chloro-N6-cyclopentyladenosine (CCPA, CAS 37739-05-2), a highly selective A1 adenosine receptor agonist, was characterized. Its effects were compared with those of the non-selective adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA). In binding studies on both rat and bovine brain, CCPA was highly potent on A1 receptors (Ki = 1.3 and 0.5 nmol/l, respectively) and displayed good A1 vs A2a receptor selectivity (500- and 920-fold, respectively). In functional studies, CCPA showed marked negative chronotropic activity in spontaneously beating rat atria (EC50 = 8.2 nmol/l). This effect was antagonized dose-dependently by the A1 selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). In the rat Langendorff model, in which global ischemia was induced, CCPA (3 nmol/l) prevented significantly the rise of diastolic pressure and coronary perfusion pressure during postischemic reperfusion. In vascular preparations, a functional activity responsive to A2a adenosine receptor stimulation, CCPA did not show any vasodilating properties up to micromolar concentrations, whereas NECA had a good relaxing activity in bovine coronary arteries (EC50 = 167 nmol/l). In rabbit platelets, a model sensitive only to A2a-receptor stimulation, CCPA did not elicit any relevant antiaggregatory properties, whereas NECA was found to be effective (IC50 = 200 nmol/l). Likewise, in an in vivo model of platelet aggregation in the rabbit using a non-invasive radioisotopic technique, CCPA (100 micrograms/kg, 30 min i.v. infusion) did not influence platelet function, whereas NECA (10 micrograms/kg, 30 min i.v. infusion) decreased peak value for platelet accumulation by 35%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

[The adult patient with a congenital GH deficiency. Cholesterol-lowering effects of therapy with biosynthetic GH].

In adults with childhood onset GH deficiency, serum total and LDL cholesterol levels were significantly higher (p < 0.05 and < 0.01, respectively), while serum HDL cholesterol levels were significantly lower (p < 0.05) than those recorded in an age and sex matched control group. These biochemical alterations determined the presence of a marked increase of coronary risk indexes (total/HDL cholesterol and LDL/HDL cholesterol) which were significantly higher (p < 0.0001) than in controls. Serum VLDL and triglycerides levels were similar to those found in controls. After recombinant GH treatment (0.5 IU/kg/week, sc), serum total and LDL cholesterol levels were significantly reduced, becoming similar to those recorded in controls after six months' therapy. Serum HDL cholesterol levels, which were slightly reduced after 3 months, significantly increased after 6 months of GH treatment, becoming similar to those recorded in controls; no significant modifications were observed in VLDL cholesterol and triglycerides levels during treatment. The coronary risk indexes fell during GH treatment, but still remained higher than in controls. On the basis of these promising data, it is tempting to speculate that more prolonged GH treatment might be able to ameliorate the risk for cardiovascular diseases in adults with GH deficiency. Although further additional studies with a larger number of patients are needed to confirm these preliminary observations, adults with GH deficiency should be recommended to take into great consideration the control of other risk factors involved in the genesis of coronary disease.

Adult↗

Modulation of hematopoiesis via alpha 1-adrenergic receptors on bone marrow cells.

We have recently demonstrated that adrenergic agents can affect hematopoiesis after syngeneic bone marrow transplantation in mice. In particular, chemical sympathectomy by 6-hydroxydopamine (6-OHDA) and/or administration of the alpha 1-adrenergic antagonist prazosin were shown to increase the concentration of blood granulocytes, platelets, and bone marrow colony-forming units-granulocyte/macrophage (CFU-GM), and to induce a granulocytic hyperplasia of the spleen. Here we show that prazosin can also enhance myelopoiesis and platelet formation in normal mice. Furthermore, noradrenaline and the alpha 1-adrenergic agonist methoxamine could directly inhibit the in vitro growth of GM-CFU. The effect of noradrenaline was counteracted by prazosin and by other alpha-adrenergic antagonists such as phentolamine and yohimbine, in the following order of potency: prazosin > phentolamine > yohimbine. In line with these results, we were able to demonstrate that 3H-prazosin binds specifically to both bone marrow cell membranes and intact bone marrow cells. Scatchard analysis of the binding to intact cells revealed the presence of two binding sites. A kd of 0.98 +/- 0.32 nM and a B max of 5 +/- 2.9 fM/2 x 10(6) cells characterized the higher affinity site, while the lower affinity site displayed a kd of 55.9 +/- 8.2 nM and a B max of 44 +/- 7.7 fM/mg protein. These saturation studies, together with competition experiments to evaluate the ability of various adrenergic compounds to displace 3H-prazosin binding, classified the higher affinity site as an alpha 1-adrenergic receptor. The remaining low affinity binding site remains to be characterized. Furthermore, separation of bone marrow cells by counterflow centrifugal elutriation (CCE) showed that the high-affinity binding is due to a lymphoid/stem cell fraction with no blasts and no GM-CFU progenitors. The low-affinity site was apparent on the rotor-off fraction, which was enriched with GM-CFU progenitor cells. These findings demonstrate that alpha-adrenergic receptors are present on bone marrow cells and participate in the regulation of hematopoiesis.

Animals↗

Release of extracellular matrix components by bovine bone endothelial cells in continuous culture.

Production of collagen type I (pIp), type III (pIIIp), type IV (CIV), type VI (CVI), fibronectin (FN), laminin and glycosaminoglycans (GAGs) has been investigated in a clonal line of Bovine Bone Endothelial (BBE) cells continuously growing in culture. BBE cells produced pIp, pIIIp and FN, whereas they did not synthetize significant amounts of CIV, CVI and laminin. pIp, pIIIp and FN syntheses were influenced by cell density:pIp secretory activity reached its maximum just after cell seeding, whereas pIIIp and FN production increased later, when cells were subconfluent. Furthermore, BBE cells produced and released significant amounts of GAGs into medium.

Animals↗

CD3-induced preferential hydrolysis of polyphosphoinositides and calcium regulation of inositol phosphate metabolism in a permeabilized murine T cell clone.

Murine T helper cloned cells permeabilized with the bacterial lysin, tetanolysin, were used to investigate the role of intracellular Ca2+ in regulating myo-[2-3H] inositol phospholipid (InsPL) hydrolysis triggered upon perturbation of the T cell receptor-CD3 complex. [Ca2+] was controlled by a calcium/magnesium/EGTA buffer. Antibody (mAb) aggregation of CD3 induced InsPL hydrolysis in the absence of added Ca2+. However, stimulated InsPL hydrolysis increased with the free [Ca2+], reaching a maximum at 100-300 nM [Ca2+]. Ca2+ increased the overall efficiency of hydrolysis without changes in EC50 of the anti-CD3 mAb. The response diminished at > 300 nM [Ca2+] due to a mixed type inhibition. Ca2+ alone had no effect on inositol phosphate levels. Polyphosphoinositides were preferentially cleaved, since no accumulation of Ins(1)P/Ins(3)P was detected, indicating that direct hydrolysis of phosphatidylinositol did not occur, irrespective of the Ca2+ concentration. [Ca2+] above 300 nM shifted the relative amounts of CD3-induced inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) in favor of the latter. Unlabeled permeabilized cells exposed to > or = 100 nM [Ca2+] showed enhanced conversion of [3H]Ins(1,4,5)P3 to [3H]Ins(1,3,4,5)P4. In conclusion, InsPL hydrolysis is optimally triggered by CD3 perturbation at intracellular Ca2+ levels approximating those observed in intact resting lymphocytes (100 nM). Ca2+ concentrations similar to those triggered by InsPL-derived metabolites may inhibit InsPL hydrolysis and promote Ins(1,3,4,5)P4 production, thus controlling the amounts of Ins(1,4,5)P3.

Algorithms↗

Beta 1 and beta 2 adrenoceptors are involved in mediating vasodilation in the human coronary artery.

We have characterized beta-adrenoceptors in the human coronary artery and investigated the mechanism underlying vasodilating activity of dilevalol, a non-selective beta-blocking agent with beta 2 agonist properties. Specific [125I]-pindolol binding was saturable, reversible and of high affinity (Kd = 91 +/- 7 pM; Bmax = 10 +/- 3 fmol/mg protein). Competition curves of [125I]-pindolol in the presence of ICI 118,551, a selective beta 2 antagonist, or CGP 20712A, a selective beta 1 antagonist, were best explained by a two-site binding model (48 +/- 5% beta 1 and 52 +/- 4% beta 2 receptors). In isolated coronary strips, isoproterenol induced a dose-dependent vasorelaxant effect which was blocked by either ICI 118,551 (100 nM) or CGP 20712A (100 nM). Dilevalol produced about 30-40% of vasodilating activity starting at a concentration of 100 nM. The response was antagonized selectively by ICI 118,551 suggesting that dilevalol produces vasodilation through the stimulation of beta 2 receptors. These findings show that in the human coronary artery both beta 1 and beta 2 receptor subtypes are present and mediate vasodilation. This suggests that the human coronary artery could be used for the evaluation of the vasodilating component of new beta-adrenoceptor blocking agents.

Adult↗

Effects of selective A1 and A2 adenosine receptor agonists on cardiovascular tissues.

We investigated the negative chronotropic and vasodilating properties of new selective A1 and A2 adenosine agonists such as 2-chloro-N6-cyclopentyladenosine (CCPA) and 2-hexynyl-5'-N-ethyl-carboxamidoadenosine (2-hexynyl-NECA) as compared with reference adenosine analogues. The potency of these compounds on heart rate was assessed in the rat atrial preparation and their activity on the vascular tone was determined in both rat aorta and bovine coronary artery. CCPA was found to be the most potent A1 agonist of those currently available in producing negative chronotropic effects (EC50 = 8.2 nM). The A1 antagonist 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX) blocked CCPA activity in a dose-dependent manner. There was also a significant correlation between its biological effect and the affinity for A1 receptors as measured in the rat brain by [3H]-N6-cyclohexyladenosine (3[H]-CHA) binding. The A2 selective agonist 2-hexynyl-NECA showed vasodilating properties comparable with those observed with the reference compounds, CGS 21680 and NECA. EC50 values were 596 and 569 nM in rat aorta and bovine coronary artery, respectively. Moreover, the rank order of potency was similar in the two vascular districts examined, suggesting that the rat aorta is a useful model for studying the effects of adenosine derivatives on vascular tone. In addition, the potency of the compounds in inducing vasodilation was found to be correlated with their affinity for A2 receptors as measured in the rat striatum by 3[H]-CGS 21680 binding. These data further support that A1 receptors are involved in depressing cardiac activity and A2 receptors in inducing vasorelaxation.

Adenosine↗

Galanin infusion partially restores the blunted growth hormone responses to repeated growth hormone releasing hormone stimuli in normal adults.

In order to understand the role exerted by the endogenous somatostatinergic tone in the blunting of GH responsiveness to repeated GHRH administration, we evaluated GH responses to the second GHRH bolus during a simultaneous infusion of galanin, which has been reported to inhibit the endogenous somatostatin release. Seven normal adults (3M/4F, age range 19-28 yr), admitted to the study after giving informed consent, were tested on three occasions, with a) two consecutive 1 micrograms/kg iv GHRH boluses administered at 0 min and 120 min, b) one GHRH bolus at 0 min followed by an infusion of 10 micrograms/kg bw galanin (diluted in 40 ml 0.9% NaCl) between 100 min and 140 min and c) two consecutive GHRH boluses (same dose and temporization of administration of test a) associated with a galanin infusion from 100 min to 140 min. GH responses were evaluated as the net incremental area under the curve (GH nAUC/h); all data were expressed as mean +/- SE. GH responses to the first GHRH bolus were similar in the three tests (mean GH nAUC, test A 990 +/- 80, test B: 1006 +/- 112, test C: 1077 +/- 80 ng/ml/h). In test A the second GHRH bolus was unable to sustain GH elevated levels (mean GH nAUC: 32 +/- 12 ng/ml/h vs first GHRH: 990 +/- 80 ng/ml/h, p < 0.0001). Similarly, in test B galanin infusion alone was unable to determine a clear GH rise (mean GH nAUC: -25 +/- 16 vs first GHRH: 1006 +/- 112 ng/ml/h, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Growth hormone treatment in adults with GH deficiency: effects on new biochemical markers of bone and collagen turnover.

Serum bone Gla protein (BGP) and bone alkaline phosphatase (B-AP), markers of bone formation, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), marker of bone resorption, and aminoterminal propeptide of type III procollagen (PIIINP) levels, index of collagen synthesis, were determined in 8 adults (mean age +/- SE: 29.6 +/- 1.2 yr) with childhood onset GHD before and after 3 and 6 months of recombinant GH treatment (0.5 IU/kg/week). Before treatment, mean BGP (3.8 +/- .5 ng/ml) and B-AP (44.9 +/- 6.9 IU/L) were significantly (P < 0.001 and p < 0.05, respectively) lower than those recorded in normals (5.4 +/- 0.1 ng/ml and 61.8 +/- 1.9 IU/L, respectively), while serum ICTP and PIIINP levels were similar to those found in controls (ICTP: 4.7 +/- 0.8 vs 4.1 +/- 0.3 ng/ml; PIIINP: 3.7 +/- 0.6 vs 3.2 +/- 0.2 ng/ml). BGP and ICTP levels significantly (p < 0.005) increased after 3 (28.4 +/- 5.3 ng/ml and 17.5 +/- 2.8 ng/ml, respectively) and 6 months (25.1 +/- 5.0 ng/ml and 15.0 +/- 1.9 ng/ml, respectively) of recombinant GH treatment. B-AP levels significantly (p < 0.01) increased during the treatment (basal: 44.9 +/- 6.9 IU/L, 3rd month: 173.6 +/- 40 IU/L, 6th month: 194.4 +/- 40 IU/L), while non B-AP levels remained similar to those recorded in basal condition. Serum PIIINP levels significantly (p < 0.0001) rose up after 3 (12.5 +/- 1.4 ng/ml) and 6 months (10.2 +/- 0.8 ng/ml). Serum BGP and ICTP levels were directly (r = 0.85, p < 0.001; r = 0.53, p < 0.01) correlated with serum IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neuroimmunotherapy of advanced solid neoplasms with single evening subcutaneous injection of low-dose interleukin-2 and melatonin: preliminary results.

On the basis of the demonstrated existence of immunoneuroendocrine interactions and on the previously observed synergistic action between the pineal hormone melatonin (MLT) and interleukin-2 (IL-2), we have designed a neuroimmunotherapeutic combination consisting of low-dose IL-2 and MLT in the treatment of advanced solid neoplasms. The study included 24 patients with advanced solid tumours (non-small cell lung cancer 9; colorectal cancer 7; gastric cancer 3; breast cancer 2; cancer of pancreas 1; hepatocarcinoma 1; unknown primary tumour 1), 21 of whom showed distant organ metastases. Not all patients responded to previous chemotherapies, or had tumours for which no standard therapy was available. Moreover, not all patients were able to tolerate IL-2 immunotherapy at the conventional doses. IL-2 was given subcutaneously at a dose of 3 x 10(6) U/day at 8:00 p.m. for 6 days/week for 4 weeks. MLT was given orally at a dose of 50 mg at 8:00 p.m. every day, starting 7 days before IL-2 injection. In non-progressed patients, a second cycle was given after a 21-day rest period. A partial response was seen in 3/24 patients (lung 2; stomach 1; duration: 11, 4, 4 months, respectively). Moreover, a minimal response (duration: 8+ months) was seen in 1 lung cancer patient. Stable disease was obtained in 14/24 patients (median duration: 6+ months), while the remaining 6 patients progressed. An improvement in performance status was seen in 7/24 patients. No important toxicity was observed. Mean eosinophil and lymphocyte levels significantly increased during the immunotherapy, and their rise was significantly higher in patients with response or stable disease than in those with progressive disease. These preliminary results show that neuroimmunotherapy with low-dose IL-2 and the pineal hormone MLT is a biologically active and well tolerated strategy, capable of determining an apparent control of tumour growth in patients with advanced solid neoplasms, for whom no standard effective therapy is available.

Adult↗

Plasma levels of brain natriuretic peptide in healthy subjects and patients with essential hypertension: response to posture.

1. To examine whether posture-induced changes in central volume affect brain natriuretic peptide secretion, plasma levels of human brain natriuretic peptide-32-like immunoreactivity (hBNP-32-li) were measured by radioimmunoassay in 11 healthy subjects and 20 patients with essential hypertension after 15 min supine, 15 min sitting and 15 min with the legs raised at 60 degrees, together with plasma atrial natriuretic peptide concentration, plasma renin activity and plasma aldosterone concentration. 2. In the supine position, the plasma hBNP-32-li level was 1.57 +/- 0.10 fmol/ml in healthy subjects and significantly higher in hypertensive patients (2.39 +/- 0.13 fmol/ml, P < 0.001). In both groups, plasma hBNP-32-li level significantly (P < 0.001) decreased when sitting (normotensive, 1.22 +/- 0.08 fmol/ml; hypertensive, 1.85 +/- 0.15 fmol/ml, P < 0.001 versus normotensive) and increased again after leg raising (normotensive, 2.13 +/- 0.12 fmol/ml; P < 0.002 versus resting; hypertensive, 2.84 +/- 0.16 fmol/min, P < 0.001 versus resting, P < 0.025 versus normotensive). 3. The plasma atrial natriuretic peptide concentration showed similar behaviour to the plasma hBNP-32-li, whereas plasma renin activity and plasma aldosterone concentration increased during sitting and decreased during leg raising in both healthy subjects and hypertensive patients, who had significantly higher plasma aldosterone levels when supine and sitting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone.

OBJECTIVE: There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release. DESIGN: The study consisted of four protocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 micrograms i.v. bolus). Study 2: GHRH (100 micrograms i.v. bolus) or placebo were administered at 0 minutes; oral melatonin or placebo were given at 60 minutes and were followed by a second GHRH stimulus (100 micrograms i.v. bolus) at 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions. Study 4: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3 micrograms i.v. bolus) of GHRH. SUBJECTS: Four groups of eight normal male subjects, ages 22-35 years, were randomly assigned to each protocol. MEASUREMENTS: Growth hormone was measured by RIA at 15-minute intervals. RESULTS: Oral melatonin administration had a weak stimulatory effect on GH basal levels. Prior melatonin administration approximately doubled the GH release induced by supramaximal (100 micrograms) or submaximal (3 micrograms) doses of GHRH. Melatonin administration restored the GH response to a second GHRH challenge, given 120 minutes after a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatonin. However, the simultaneous administration of melatonin and pyridostigmine was not followed by any further enhancement of GH release, either in the absence or in the presence of exogenous GHRH. CONCLUSIONS: Our data indicate that oral administration of melatonin to normal human males increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release, although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be established.

Administration, Oral↗