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E Gilad

Publications and source records attributed to E Gilad.

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

Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity.

In vitro studies have demonstrated that melatonin is a scavenger of oxyradicals and peroxynitrite and an inhibitor of nitric oxide (NO) production. In the present study, we evaluated the effect of melatonin treatment in two models of acute inflammation (carrageenan-induced paw edema and pleurisy), where oxyradicals, NO, and peroxynitrite play a crucial role in the inflammatory process. Our data show that melatonin (given at 62.5 and 125 microg/paw in the paw edema model or 25 and 50 mg/kg in the pleurisy model) inhibits the inflammatory response (paw swelling, pleural exudate formation, mononuclear cell infiltration, and histological injury) in dose-dependent manner in both models. Furthermore, our data suggest that melatonin exerts an inhibitory effect on the expression of the inducible isoform of NO synthase. Melatonin also prevented the formation of nitrotyrosine, an indicator of peroxynitrite, in both models of inflammation. Taken together, the present results demonstrate that melatonin exerts potent antiinflammatory effects. Part of these antiinflammatory effects may be related to an inhibition of the expression of the inducible NO synthase, while another part may be related to oxyradical and peroxynitrite scavenging.

Animals↗
PubMed1997

Inactivation of melatonin receptors by protein kinase C in human prostate epithelial cells.

The pineal hormone melatonin regulates seasonal reproduction and pubertal development in mammals. We recently found melatonin receptors in the human benign prostate tissue, primarily associated with the microsome-enriched fraction of the epithelial cells. In cultured benign prostate epithelial cells, melatonin, at physiological concentrations, suppressed [3H]thymidine incorporation and cGMP levels. The effects of melatonin were transient, suggesting inactivation of the receptors. In the present study, the possibility of inactivation of the prostate melatonin receptors by protein kinase C (PKC) was explored. Treatment of the microsome-enriched fraction with crude rat brain PKC in the presence of phorbol 12-myristate 13-acetate (TPA) or CaCl2 abolished the specific [125I]melatonin binding. This effect was prevented by the PKC inhibitor bisindolylmaleimide (GF-109203). [125I]Melatonin binding could be reinstated by iodoacetamide treatment. In benign prostate epithelial cells in culture, TPA pretreatment markedly reduced the apparent affinity of [125I]melatonin binding. In addition, TPA ablated the cells responses to melatonin, namely the suppression of [3H]thymidine incorporation and cGMP levels. Pretreatment with GF-109203 prevented the TPA effects on [125I]melatonin binding and responses. In addition, GF-109203 slowed down the inactivation of the melatonin-mediated inhibition of [3H]thymidine incorporation. Taken together, these data show that melatonin receptors are desensitized by PKC and imply that the transient response to melatonin may be the outcome of a direct or indirect melatonin-mediated activation of endogenous PKC.

Aged↗
PubMed1997

Interplay between sex steroids and melatonin in regulation of human benign prostate epithelial cell growth.

Human benign prostatic epithelial cells contain functional melatonin receptors that can suppress cell growth and viability. The development of benign prostatic hyperplasia in men is assumed to result from androgen-estrogen imbalance. The impact of sex steroids on melatonin receptors in human benign prostate epithelial cells was investigated. The suppression by melatonin of [3H]thymidine incorporation and cGMP, and the enhancement of cAMP levels in the cells were used as markers of melatonin responses. Dihydrotestosterone (DHT) and 17 beta-estradiol (E2) separately increased [3H]thymidine incorporation into the cells, but suppressed it when combined. In cells grown with DHT, melatonin responses were extenuated. E2 greatly reduced the apparent affinity of [125I]melatonin binding in these cells without affecting binding site density. In parallel, the ability of melatonin to suppress [3H]thymidine incorporation into the cells was ablated within 1 h after the addition of E2. The melatonin-mediated increase in cAMP and decrease in cGMP concentrations were also ablated by E2. Preincubation of the cells with bis-indolylmaleimide (GF 102903X), a specific inhibitor of protein kinase C, prevented the E2-mediated inactivation of melatonin binding and the inhibitory action on [3H]thymidine incorporation. Prolonged (18-h) incubation of the cells with phorbol 12-myristate 13-acetate to down regulate protein kinase activity, partially restored [125I]melatonin binding and responsiveness in the E2-treated cells. These data indicate that 1) DHT and E2 enhance prostate epithelial cells growth, but reduce cell growth when combined; 2) DHT extenuates the inhibitory effects of melatonin on epithelial cell growth; and 3) E2 acts to inactivate melatonin receptors and consequently responses in human epithelial benign prostatic hyperplasia cells. This process is probably mediated by protein kinase C. Together, these results show an interplay between melatonin and sex steroids in the regulation of benign prostatic epithelial cell growth.

Aged↗
PubMed1996

Functional melatonin receptors in human prostate epithelial cells.

Melatonin, secreted nocturnally by the pineal gland, affects gonadal growth and pubertal development in rodents and, presumably, in humans. Recently, we have found, using 125I-labeled melatonin as a probe, specific melatonin binding sites in the human benign prostate tissue; these sites were primarily associated with the microsomal fraction of the epithelial cells. In the present study, we have explored 125I-melatonin binding sites in human benign prostate epithelial cells in culture and investigated the effects of melatonin on growth and viability of these cells. 125I-melatonin bound to the prostate cells with high (K(d) = 68 pM) affinity. Competition experiments revealed that specific binding was inhibited by subnanomolar concentrations of melatonin and 2-iodomelatonin, whereas serotonin and 5-methoxytryptamine reduced the binding only partially. Melatonin (10 pM-10 nM) inhibited the incorporation of 3H-thymidine and 3H-uridine into the prostate epithelial cells in a dose-dependent manner. Inhibition was transient, and the incorporation recovered to control levels within less than 24 h. Protein synthesis as measured by the incorporation of 35S-methionine into cell proteins decayed to minimal levels about 2 h after addition of melatonin, and its recovery was slower compared with that of 3H-thymidine or 3H-uridine incorporation. Melatonin treatment (1 nM) for 2-7 days inhibited cell growth and markedly increased the percentage of non-viable cells in culture, measured by the trypan blue exclusion assay. The results demonstrate high affinity melatonin receptors in the human benign prostate epithelial cells, which may affect cell growth and viability.

Binding Sites↗
PubMed1996

Putative melatonin receptors in benign human prostate tissue.

Melatonin, secreted by the pineal gland at night, inhibits pubertal development of rats and presumably men. In addition, it may directly suppress prostate growth in the adult rat. To investigate the possibility for a causal relationship between the age-related decline in melatonin production and increase in prevalence of benign prostate hypertrophy (BPH) in man, the presence of melatonin binding sites in human BPH tissue was examined. In vitro autoradiography indicated specific 125I-labeled melatonin (125I-melatonin) binding in the prostate, localized to the glandular epithelium. Separation and subcellular fractionation indicated that these sites were associated with the microsomal fraction of the epithelial cells. Kinetic and equilibrium 125I-melatonin binding experiments revealed that the binding was time dependent and reversible, with an apparent half saturation at 140 pmol/L. Competition experiments indicated high and low affinity melatonin binding sites; binding was inhibited by melatonin (IC50 1 nmol/L and 1 micromol/L, respectively) and partially by the putative melatonin antagonist, N-(2,4 dinitrophenyl)-5-methoxytryptamine (ML-23; IC50 0.1 nmol/L). Serotonin and 6-hydroxymelatonin were less potent, whereas up to 0.1 mmol/Lol/L of 5-methoxytryptamine, 6-methoxymelatonin, and tryptamine caused only a partial reduction in specific binding. The guanine nucleotide analogs, guanosine 5'-O-[3-thiotriphosphate] and guanosine 5'-O-[2-thio-diphosphate, inhibited specific 125I-melatonin binding, whereas 5'-guanylyl imidodiphosphate was less potent. The results indicate putative melatonin receptors in the human prostate epithelium.

Aged↗
PubMed1995

Plain radiography for diagnosis of gastrointestinal perforation in immune-compromised children--is it enough?

Gastrointestinal perforation is a surgical emergency in the pediatric patient and any delay in diagnosis might be hazardous. In immunocompromised children, the clinical signs of perforation may be blunted. We describe a child with acute lymphoblastic leukemia (ALL) and a perforated appendix and ileum in whom computerized tomography (CT) revealed extraluminal air that was not initially identified on plain abdominal film. Our case demonstrates the importance of early abdominal CT and ultrasound examination in detecting these potentially lethal complications.

Acute Disease↗
PubMed1995

High-affinity binding of melatonin to hemoglobin.

Determination of melatonin by radioimmunoassay in plasma samples from hemolyzed blood often yields flawed values. We studied the possibility that hemoglobin can bind melatonin and the iodinated tracer 125I-melatonin. The specific binding of 125I-melatonin to purified bovine hemoglobin was found to be rapid, saturable, and reversible (Kd = 315 pM, Bmax = 58 pmol/mg protein) and was inhibited by 2-iodomelatonin, serotonin, melatonin, and 5-methoxytryptamine. These data are compatible with the concept that hemoglobin can interfere with melatonin determinations by competing for melatonin and the iodinated tracer. Unlike melatonin receptor binding, the binding of 125I-melatonin to hemoglobin was not inhibited by guanine nucleotide analogs (i.e., GTP gamma S, GTP beta S, and Gpp(NH)p). Sodium cyanide had no effect on 125I-melatonin binding, indicating that 125I-melatonin does not bind to the heme group. On the other hand, 2,3-bisphosphoglycerate, at physiological concentrations (3-4 mM), decreased the apparent Bmax and Kd of 125I-melatonin binding to hemoglobin. These data suggest that 125I-melatonin binding to hemoglobin is conformation-specific and is unfavorable in the deoxyhemoglobin state. Hemoglobin may serve as a carrier protein for melatonin in the blood and discharge it in the target organs. Subsequently, the efficacy of melatonin's action as a hormone or antioxidant in target tissues may be enhanced.

2,3-Diphosphoglycerate↗
PubMed1994

Acute acalculous cholecystitis in an infant after cardiac surgery.

Acute acalculous cholecystitis is a virulent disease that occurs most commonly in critically ill patients. Imaging studies may facilitate earlier diagnosis and may decrease the morbidity and mortality rates. The authors report on a 30-month-old child with acute acalculous cholecystitis after surgical repair of tetralogy of Fallot. A review of the clinical pathogenesis, diagnosis, and treatment is included.

Acute Disease↗
PubMed1993

Oxytocin and estradiol concentrations in follicular fluid as a means for the classification of large bovine follicles.

Large antral follicles (13 to 20 mm in diameter) were collected from ovaries of 109 cows and 17 heifers that also had a regressed corpus luteum at slaughter. Thirty percent of the animals had been injected once with prostaglandin F(2)alpha 48 hours before slaughter. Follicles were divided into 3 groups based on estradiol and oxytocin concentrations in the follicular fluid: Group I follicles, estradiol>/=100 ng/ml and oxytocin<65 pg/ml (preovulatory and assumed pre-gonadotropin surge); Group II follicles, estradiol<100 ng/ml and oxytocin>/=65 pg/ml (preovulatory and assumed post-gonadotropin surge); and Group III follicles, estradiol<100 ng/ml and oxytocin<65 pg/ml (atretic follicles). Treatment with prostaglandin F(2)alpha significantly increased the number of viable granulosa cells and estradiol content in Group I follicles. The estradiol: progesterone ratio was significantly higher in Group I vs Groups II and III, but it was similar for Group II healthy follicles and Group III atretic follicles. To ascertain the classification of follicles, PGF(2)alpha was administered on Day 6 of the cycle to induce corpus luteum regression, and a GnRH analog was administered 24 hours later. At 23 hours after GnRH analog treatment, follicular oxytocin levels significantly rose to 103 pg/ml. Concomitantly, estradiol concentrations fell to below 100 ng/ml. This response was not evident by 13 h after injection of the GnRH analog. The results indicate that follicular estradiol and oxytocin concentrations may be used as a means for the physiological classification of large bovine follicles.

Journal Article↗
PubMed1993

Effect of heat stress on tonic and GnRH-induced gonadotrophin secretion in relation to concentration of oestradiol in plasma of cyclic cows.

Effects of acute and seasonal heat stress on tonic and GnRH-induced LH and FSH secretion were examined during the early follicular phase of the oestrous cycle of cows (n = 40). Prostaglandin F2 alpha was injected on day 11 +/- 1 of the oestrous cycle and on the next day blood samples were collected at intervals of 15-20 min for 14 h, and i.m. injection of GnRH was given after 7 h. Treatments compared were control versus acute heat stress during blood sampling in winter, and cooled versus chronic heat stress in summer. Before GnRH injection, chronic heat stress in summer did not affect basal concentrations of plasma LH, but did lower LH pulse amplitude. However, in cows with low plasma oestradiol (1.9 +/- 0.2 pg ml-1), the mean and basal concentrations and amplitude of tonic LH pulses were reduced by heat stress (3.1, 2.1 and 4.8 versus 1.9, 1.4 and 2.5 ng ml-1, respectively). In cows with high plasma oestradiol (6.3 +/- 0.5 pg ml-1), these parameters were not affected. In chronically heat stressed cows in summer, GnRH-induced increases in plasma LH and FSH concentrations were the same as in the cooled controls. However, in cows with low plasma oestradiol, mean concentrations of FSH in plasma (31.8 versus 25.5 ng ml-1), the peak of the GnRH-induced FSH and LH surge (FSH 47.4 versus 35.6 ng ml-1, LH 50.7 versus 37.3 ng ml-1) and the shape of the GnRH-induced FSH and LH curves (treatment by time interaction) were significantly lower in non-cooled versus cooled controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Necrosis and lymphocytic infiltration in choroidal melanomas.

Patient survival, tumor lymphocytic infiltration and tumor necrosis were studied and evaluated in 43 enucleated eyes with the same histological diagnosis of spindle 'B' malignant melanoma of the choroid. A significant difference (P less than 0.05) was found between the survival rate of melanoma patients with no evidence of lymphocytic infiltration and/or necrosis in the tumor, compared to those with any evidence of of lymphocytic infiltration and/or tumor necrosis.

Choroid Neoplasms↗
PubMed1990

Persistently raised intraocular pressure following extracapsular cataract extraction.

In this population based study we have reviewed the files of all patients who underwent an extracapsular cataract extraction (ECCE) between 1984 and 1987, were normotensives prior to surgery, and were followed up for at least 10 months after the ECCE. From a total of 1047 operations 746 qualified for the inclusion criteria; of these, 16 (2.1%) were found to have a consistently raised intraocular pressure (greater than 21 mmHg) on more than two occasions) at four months or later after surgery and throughout at least a six-month period. An increased incidence of secondary aphakic glaucoma was associated with anterior chamber IOL implantation (p less than 0.001) and posterior capsule rupture (p less than 0.01), but not with any of the other variables examined (age, sex, surgeon).

Adult↗
PubMed1988

Juxtapapillary exophytic retinal capillary hemangioma treated by yellow krypton (568 nm) laser photocoagulation.

A 30-year-old man was found to have juxtapapillary exophytic capillary hemangioma complicated by circinate maculopathy and peripapillary exudative retinal detachment. The diagnosis was made from the appearance of the tumor and confirmed by fluorescein angiography. The presence of intermittent hematuria associated with a cystic kidney supported the diagnosis of von- Hippel-Lindau disease. subsequently, and attempt to treat the vascular lesion by yellow krypton (586 nm) laser photocoagulation failed to arrest the progression of the exudative retinal detachment, which finally became total.

Adult↗
PubMed1987

'Rush' type retinopathy of prematurity: report of three cases.

Three premature infants observed to develop severe stage III retinopathy of prematurity (ROP) at 3 to 5 weeks of age received immediate treatment by cryoablation and photocoagulation, with good results. The critical importance of the ophthalmic examination of premature babies from the age of 2 weeks, so as not to overlook such cases of 'rush' type ROP is stressed and the difficulty involved in treating such small neonates is discussed.

Age Factors↗