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Biomedical subjects

I Gil-Ad

Publications and source records attributed to I Gil-Ad.

At least 19 recordsLinked to original sources
PubMed2000

Suppression of serum gonadal steroids in rats by chronic treatment with dopamine and serotonin reuptake inhibitors.

The impact of chronic administration (3 weeks) of dopamine and serotonin reuptake inhibitors on serum gonadal steroid hormones and prolactin was studied in intact male and female rats. Both the dopamine and the serotonin reuptake inhibitors lowered serum estradiol and progesterone levels in the female rats. The dopamine transporter blockers suppressed testosterone serum levels in the male rats, whereas serotonin reuptake inhibitors induced only a non-significant reduction (30%) of this hormone. In contrast to the decrease in gonadal steroids, none of the serotonin or the dopamine reuptake blockers altered prolactin serum levels in either the male or female rats. It seems that the effect of these agents on ovarian and testicular hormones is related to the impact of the monoamine reuptake inhibitors on the hypothalamic-pituitary-gonadal axis.

Animals↗
PubMed2000

Neuroendocrinological response to standardized mixed meal in female anorectic patients during active and refeeding phases.

To evaluate the neuroendocrinological dysfunction in anorexia nervosa, plasma somatostatin, glucose, insulin, and growth hormone were monitored in ten patients with anorexia nervosa in the active and refeeding (remission) phases of the disorder and in nine age-matched healthy control subjects. Somatostatin levels were significantly higher in the anorectic patients in both the active and refeeding phases than in the controls at baseline (mean+/-SD 27.4 +/-5.5 and 31.1+/-2.6 vs 21.3+/-1.9 pg/ml; p<0.001), and significantly higher in the anorectic patients in the active phase compared to the refeeding phase and to the controls in response to a mixed meal (p<0.05). Insulin levels were significantly lower in the anorectic patients in both the active and refeeding phases compared to the controls at baseline (9.3+/-1.1, 7.6+/-1.0 vs 14.7+/-3.5 microU/ml; p<0.0001) and after a mixed meal (p<0.05). An attenuated glucose response discriminated the anorectic patients in the active state from the same patients in the refeeding state and the controls (p<0.0001). There was no significant difference in growth hormone response between the anorectic patients and the controls. These findings suggest that there is an augmented response of somatostatin and an attenuated response of insulin to mixed meal stimulation in active anorexia. The diminished insulin response persists during the refeeding phase. It seems that central and peripheral alterations in endocrine function occur in anorexia nervosa.

Adolescent↗
PubMed1999

Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma.

BACKGROUND: Leukotrienes are bronchoactive mediators secreted by inflammatory cells in the respiratory mucosa on exposure to asthma triggers. OBJECTIVE: We investigated the effect of montelukast, a leukotriene receptor antagonist, on the release of leukotrienes in the respiratory mucosa of children with persistent asthma. METHOD: Twenty-three children aged 6 to 11 years with moderately severe asthma were treated in a cross-over design starting, after a 2-week run in period, with either montelukast (n = 12) or cromolyn (n = 11) for 4 weeks with a 2-week washout period between treatments. Twelve of them were then treated with either montelukast or beclomethasone for 6 months. The use of beta(2)-agonists was recorded on a diary card. The concentration of leukotriene C(4) (LTC(4)) was measured by HPLC in nasal washes obtained before and at the end of each treatment period. Eosinophilic cationic protein (ECP) was measured in the nasal washes by RIA. RESULTS: The LTC(4) concentration significantly decreased in the children treated for the first 4 weeks with montelukast, from 5.03 +/- 1.17 to 1.42 +/- 0.33 ng/mL (P <.005), and a nonsignificant increase was noted in children treated with cromolyn, from 3.37 +/- 1.11 to 5.88 +/- 2.17 ng/mL (P =.17). ECP concentration also decreased in the children receiving montelukast (P =.12). The concentration of LTC(4) remained low after 3 and 6 months of treatment with montelukast (0.8 +/- 0.7 and 1.0 +/- 0.3 microg/mL) and was lower than with beclomethasone. Children treated with montelukast required significantly fewer beta(2)-agonists (P <.04), CONCLUSION: Montelukast reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma parallel to reduction in ECP and clinical improvement. This effect was not observed when the same children were treated with cromolyn.

Acetates↗
PubMed1999

Platelet peripheral-type benzodiazepine in pregnancy and lactation.

The aim of the present study was to investigate the impact of hormonal changes during pregnancy and lactation on the expression of peripheral-type benzodiazepine receptors in platelet membranes. Platelet peripheral benzodiazepine receptor binding characteristics, Hamilton anxiety and depression rating Scores, and progesterone and prolactin (PRL) levels were evaluated during pregnancy and lactation in 17 pregnant women [first (n = 9) and third (n = 8) trimesters], 10 lactating women, and 8 nonpregnant women. A significant decrease (38-41%) in peripheral benzodiazepine receptor density was observed in women during the third trimester of pregnancy when compared to nonpregnant controls and women in their first trimester of pregnancy. The decrease is peripheral benzodiazepine receptors was parallel to the peak in progesterone and PRL secretion. The reduction in peripheral benzodiazepine receptor expression is hormone-dependent and may play a regulatory role geared to prevent pregnancy-related overactivity of the hypothalamic-pituitary-ovarian, hypothalamic-pituitary-adrenal, and hypothalamic-PRL axes.

Adolescent↗
PubMed1999

Insulin-like-growth-factor-I (IGF-I) antagonizes apoptosis induced by serum deficiency and doxorubicin in neuronal cell culture.

We evaluated the effect of insulin-like growth factor (IGF)-I on neuronal cell viability and apoptosis induced by exposure to serum-free (SF) medium and to doxorubicin. In primary neuronal culture, IGF-I (0.5-2.0 microg/ml) slightly increased basal cell viability; SF medium tended to decrease viability (20-27%), and addition of IGF-I significantly antagonized this decrease (P< 0.05). In neuroblastoma (NB) SK-N-SH cell culture, IGF-I significantly increased viability (0.05-1.25 microg/ml) (P< 0.005); SF medium decreased it by 75%, and this decrease was prevented by IGF-I (0.5-1. 0 microg/ml) (P< 0.005). Flow cytometry studies showed an increased apoptosis on exposure to SF medium (88.8 vs 10.2%), which was suppressed to 38.3% by addition of IGF-I. Growth hormone (1-10 microU/ml) did not modify basal cell viability in either culture, and SF-induced cell death in NB cells. Doxorubicin (1-100 microM) caused neurotoxicity in primary and NB cultures (66-39% and 39-10% of controls, respectively), and increased apoptosis in NB cells (73. 8 vs 20.1%). IGF-I antagonized these neurotoxic/apoptotic effects (P< 0.05). This study suggests that IGF-I possesses a potent neuroprotective activity which may be involved in the resistance to doxorubicin.

Animals↗
PubMed1998

Interventional catheterization decreases plasma levels of atrial natriuretic peptide (ANP) in children with congenital heart defects.

Atrial natriuretic peptide (ANP) is one of the cardiac peptides implicated in volume and sodium homeostasis. We investigated the effect of interventional catheterization on plasma levels of ANP, aldosterone, and cortisol in 28 children with various congenital heart defects (CHD). Patients were divided by age into two groups: group A--infants and children over 3 months of age (n = 22), and group B--newborns (n = 6). These were compared to age-matched control groups. In group A, interventions included pulmonic valvotomy (n = 8), aortic valvotomy (n = 4), balloon angioplasty of native coarctation of the aorta (n = 3), balloon dilatation of the mitral valve (n = 1), and Rashkind double umbrella closure of patent ductus arteriosus (n = 6). Group B interventions included pulmonic valvotomy (n = 3), aortic valvotomy (n = 1), and balloon atrial septosomy (n = 2). In group A, mean ANP levels were markedly higher than in age-matched controls (125.2+/-15.8 vs. 24.6+/-4.6 pg/ml) (P <0.0001), and decreased immediately after intervention (75.6+/-11.4 pg/ml, P <0.02), and more markedly on follow-up (42.9+/-5.0 pg/ml, P < 0.0001). In group B (newborns), mean basal plasma levels were high before and after intervention and were not different from age-matched controls (243+/-42.1 vs. 220.8+/-16.2 pg/ml). There was a significant decrease on follow-up measurement (62.1+/-12.7 pg/ml, P < 0.005). In both groups, plasma cortisol levels increased significantly immediately following catheterization (P < 0.02), and normalized on follow-up. Basal aldosterone levels were normal in group A and high in Group B (9.9+/-3.8 vs. 167.6+/-16.9 ng/dl) (P < 0.001). It is suggested that plasma ANP levels are increased in children with CHD, without overt heart failure, and decrease significantly following successful intervention. In newborns with CHD, the physiological high ANP levels obscure the effect of the CHD.

Aldosterone↗
PubMed1997

Elevated levels of serum interleukin-1 beta in combat-related posttraumatic stress disorder.

Levels of serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) were assessed in 19 male patients with combat-related posttraumatic stress disorder (PTSD) in comparison to 19 age- and sex-matched healthy volunteers. Serum IL-1 beta levels (but not sIL-2R) were significantly higher (p < .001) in the PTSD patients than in the controls. IL-1 beta levels did not correlate with cortisol levels, severity of PTSD, anxiety, depressive symptoms, or alexithymia score; however, they did correlate significantly (r = .54, p < .005) with the duration of PTSD symptoms. It is possible that desensitization of the hypothalamic-pituitary-adrenal axis in chronic PTSD patients counteracts the stimulatory effect of IL-1 beta on cortisol secretion.

Adult↗
PubMed1997

Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters.

The present study was designed to investigate the modulatory effect of gonadal steroids on brain dopamine (DA) and serotonin (5-HT) presynaptic transporters in female and male rats. Female and male rats were castrated and treated with either vehicle or gonadal hormones. The pharmacodynamic characteristics of the DA and 5-HT transporters were analyzed by [3H]BTCP and [3H]imipramine binding respectively. Ovariectomy (OVX) resulted in an upregulation of the striatal DA transporter and this alteration was prevented by estradiol (E2) or E2 + progesterone (P) treatment but not by P alone. In contrast to the DA transporter, the hypothalamic 5-HT transporter was down-regulated by OVX in female rats and this decrease was reversed by the administration of E2, P or their combination. The striatal DA transporter and the hypothalamic 5-HT transporter in male rat were not affected by orchidectomy or by administration of testicular hormone. Our findings indicate that ovarian, but not testicular, steroid hormones may play an important role in the regulation of brain DA and 5-HT transporters. It appears that ovarian hormones modulate rat brain 5-HT and DA transporters in opposite directions. These interactions between ovarian steroids and presynaptic transporters may be relevant to DA- and 5-HT-related neuropsychiatric disorders.

Animals↗
PubMed1996

Is the heart a source for elevated circulating endothelin levels during aorta-coronary artery bypass grafting surgery in human beings?

Reports have shown increased systemic levels of endothelins during coronary artery bypass grafting in human beings. It was not known whether increased endothelin levels during coronary artery bypass grafting reflect a general systemic response to the surgical procedure or increased myocardial production of endothelins in response to ischemia and reperfusion. We therefore measured endothelin levels in the right atrium and proximal aorta of 15 patients undergoing coronary artery bypass grafting for anginal syndrome immediately before aortic crossclamping and again after cessation of cardiopulmonary bypass. In five patients, we also measured coronary sinus levels of endothelins during cardiopulmonary bypass circulation. We found that endothelin levels were elevated throughout the surgical procedure. Right atrial endothelin levels were significantly elevated after cessation of cardiopulmonary bypass circulation with respect to values immediately before aortic crossclamping (11.1 +/- 3.1 vs 14.2 +/- 3.7 pg/ml, p = 0.008), whereas endothelin levels in the proximal aorta did not rise significantly (10.5 +/- 2.3 vs 11.6 +/- 2.4 pg/ml, p > 0.5). Coronary sinus endothelin levels tended to decline temporarily during cardiopulmonary bypass circulation (11.1 +/- 2.1 pg/ml before aortic crossclamping, 7.9 +/- 1.9 1 minute after release of aortic crossclamp, and 9.9 +/- 2.1 pg/ml after release of partial aortic crossclamping, p = 0.06). We conclude that the rise in right atrial endothelin levels during coronary artery bypass grafting reflects systemic production and secretion of endothelins, probably by vasculature or organs distal to the proximal aorta, and is not the result of increased myocardial production and secretion of endothelins.

Aged↗
PubMed1996

Non-traditional risk factors for atherosclerosis in high risk children.

Non-traditional risk factors for atherosclerosis were examined in children whose fathers suffered from myocardial infarction up to age 48. Factors examined were hyperinsulinemia, insulin resistance, lipoprotein(a) [Lp(a)], fibrinogen, cardiovascular hyperreactivity, and autonomic nervous system dysfunction. Hyperinsulinemia was present in five cases (9%) and hypoinsulinemia in two. Insulin output following glucose load was significantly higher in obese children compared with controls. There was an increase in Lp(a) alone in 14 cases (24%) and with low density lipoprotein in 6 cases. Increased fibrinogen and positive correlation with insulin abnormality was present in 29% (76% females) (P >0.02). Cardiac hyperreactivity (increased systolic blood pressure) was present in 9% and increased blood pressure and pulse rate in 17%. Holter monitoring pattern was sympathetic in 39% and parasympathetic in 47% of cases. Thus a number of non-traditional risk factors were found to be higher than normal in a relatively large number of children at high risk for atherosclerosis, with 25 children having more than three risk factors.

Adolescent↗
PubMed1994

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin).

OBJECTIVE: Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS: Ten children with familial short stature (FSS) aged 5.5-15.5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS: All 12 subjects were submitted to i.v. (1 microgram/kg) and i.n. (20 micrograms/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS: Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (+/- SD) being 72.2 +/- 35.5 mU/l for the i.n. test and 79.6 +/- 53.0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15-30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response in either test. Plasma TSH decreased in the FSS children from a mean (+/- SD) of 1.0 +/- 0.26 to 0.64 +/- 0.2 mU/l (P < 0.005) during the i.n. test and from 1.0 +/- 0.3 to 0.7 +/- 0.3 mU/l (P < 0.05) during the i.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1.06 +/- 0.38 mU/l to 0.86 +/- 0.17 during the i.v. test and from 1.60 +/- 0.01 to 1.11 +/- 0.06 mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS: The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intranasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.

Administration, Intranasal↗
PubMed1994

Impact of the Gulf War on the anxiety, cortisol, and growth hormone levels of Israeli civilians.

OBJECTIVE: The authors investigated the impact of continuous and repeated stress on Israeli civilians exposed to missile attacks during the Gulf War. METHOD: Study 1 included 26 healthy volunteers aged 28-59 years. Their scores on the Hamilton Anxiety Rating Scale and levels of plasma cortisol and growth hormone (GH) were evaluated before, during, and after the war. Study 2 included 13 healthy volunteers aged 25-59 years. Their scores on the state portion of the State-Trait Anxiety Inventory and levels of cortisol and GH were measured three times daily (8:00 a.m., noon, and 6:00 p.m.) at two time points (during and after the war). RESULTS: Anxiety levels of civilians exposed to the threat of war and later to actual missile attacks were significantly higher before and during the war than afterward. Anxiety during the war reached a peak in the evening. The increase in anxiety was not accompanied by any change from basal morning cortisol and GH levels or by diurnal variations in these hormones. CONCLUSIONS: Anxiety levels during the war were similar to those 1 day before its onset, which can be explained by the nature of coping processes. During the war, anxiety levels were highest in the evening, reflecting the war routine (missile attacks occurred mostly at night). The unaltered hormone levels and their normal diurnal variations despite the subjects' persistent anxiety were probably due to adaptation of the hypothalamic-pituitary-adrenal and hypothalamic-somatotropin axes to continuous stress.

Adult↗
PubMed1993

Growth hormone-releasing activity of growth hormone-releasing peptide-1 (a synthetic heptapeptide) in children and adolescents.

The heptapeptide growth hormone-releasing peptide-1 (GHRP-1), one of a series of recently synthesized small growth hormone (GH)-releasing peptides, was administered as an iv bolus (1 microgram/kg) to 15 (six prepubertal, nine pubertal) short but healthy children and adolescents and to eight juvenile patients with pituitary insufficiency (four with isolated growth hormone deficiency, two with multiple pituitary hormone deficiencies, one with partial GH deficiency and one with GH-releasing hormone (GHRH) deficiency). Eleven out of 23 subjects also underwent an in GHRH (1-29) test (1 microgram/kg). All the healthy children responded with a progressive rise in plasma human GH (hGH) peaking at 15-30 min, with a significantly higher rise (p < 0.05) in the pubertal than prepubertal group. The hGH response to GHRH (1-29) in these children was similar or slightly higher. Six hypopituitary patients had no response to either GHRP-1 or GHRH; the patient with partial GH deficiency had a hGH peak of 6.5 micrograms/l (at 5 min) to GHRP-1 and 9.2 micrograms/l (at 15 min) to GHRH. One patient had no response of hGH to hypoglycemia, clonidine and GHRP-1, but the plasma hGH rose to 10 micrograms/l after GHRH. Following the GHRP-1 bolus there was a significant (p < 0.01) rise in plasma free thyroxine and a decrease of thyrotropin (p < 0.01), both in the limits of normal values. There was also a transitory rise of plasma cortisol (p < 0.05). Plasma prolactin, luteinizing hormone and follicle-stimulating hormone did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Platelet imipramine binding and plasma cortisol levels in Israeli civilians during the Gulf War.

[3H] Imipramine binding to platelets and plasma cortisol levels were measured in nine Israeli civilians before, during, and after repeated missile attacks. Hamilton Anxiety Rating Scale (HARS), and Beck Depression Inventory (BDI) were similar before and during the war and decreased significantly after the war. A trend toward increase in platelet imipramine binding values was observed during the war when compared with the postwar values (19%; p = 0.056), and/or when compared with prewar values (26%; p = 0.063). However, one-way analysis of variance with repeated measures did not reveal a significant statistical difference [F (2,6) = p = 2.07; NS] among the three time points. A significant correlation was found between HARS score, but not BDI, and imipramine binding values in the prewar and postwar time points (r = 0.87; 0.71, respectively). Plasma cortisol levels did not alter significantly during the study period.

Adjustment Disorders↗
PubMed1992

Growth hormone therapy in normal short children induces a transitory decrease in plasma growth hormone releasing hormone levels and in human growth hormone responsiveness to exogenous growth hormone releasing hormone.

A three-month study of the effect of growth hormone (hGH) therapy (0.1 U/kg/day sc) on plasma levels of GH releasing hormone (GHRH), somatostatin and insulin-like growth factor I (IGF-I) and on the hGH responsiveness to exogenous GHRH was carried out in 32 prepubertal short-stature children with normal GH secretion. Blood samples were collected prior to initiation of therapy, and at 5, 30 and 90 days of onset of therapy, as well as 2 and 90 days after termination of therapy. The nonconventional hGH therapy induced an increase in serum IGF-I levels which lasted as long as therapy was continued. Plasma GHRH levels showed an early transitory decrease after five days of therapy, whereas plasma somatostatin levels were unaltered. A slight suppression in hGH responsiveness to exogenous GHRH was found at 2 but not at 90 days after termination of hGH therapy. It is concluded that nonconventional hGH treatment does not cause permanent changes in physiological hGH secretion.

Adolescent↗
PubMed1992

Neuroendocrine response to trihexyphenidyl in depressed patients.

The effect of a single dose (10 mg P.O.) of trihexyphenidyl (THP) on plasma cortisol, growth hormone (GH), and immunoreactive beta-endorphin (ir-beta-EP) was studied in seven major depressed patients and seven controls. GH secretion was suppressed (34-41%) by THP in both groups. THP did not affect cortisol secretion in depressed patients and controls. An increase (18%; p less than 0.05) in plasma ir-beta-EP levels was detected in the healthy subjects only. The results of this study do not support the hypothesized altered responsiveness to anticholinergic provocation in major depression. The inhibitory activity of THP on GH secretion indicates the involvement of the cholinergic system in the regulation of GH release in humans.

Adult↗
PubMed1991

Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli.

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (greater than 500 to 42 ng/l and 15.4 micrograms/l to 0.8 microgram/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.

Acromegaly↗