Search PubMed⌕ Search

Biomedical subjects

S Melmed

Publications and source records attributed to S Melmed.

At least 217 records · Page 12Linked to original sources
PubMed1982

myo-inositol in the reproductive tract of the female rat.

1. myo-Inositol concentrations in oviduct, ovary and uterus were many-fold those of blood serum during all four stages of the estrous cycle of the female rat. 2. Inositol concentration was higher in oviduct than in ovary or uterus and was lower in uterine fluid than in uterus. 3. Estrus uteri had higher inositol concentrations than uteri in other phases of the cycle. 4. In order to measure dynamic aspects of the distribution of inositol, the distribution of radioactivity among organs of the reproductive tract of mature female rats was measured 45 min after i.p. injection of [2-3H]myo-inositol. 5. These organs concentrated inositol from the blood, and the tissue radioactivity (expressed as dpm/mg wet wt of tissue) increased in the sequence: vagina less than cervix less than uterus less than ovary less than oviduct. 6. The uterus and ovary concentrated myo-inositol more strongly during proestrus than during metestrus, diestrus of estrus. 7. The contents of proestrus follicles were more highly radioactive than was the ovary itself, whereas proestrus uterine fluid was less radioactive than the uterine tissue.

Animals↗
PubMed1982

Histidyl-proline diketopiperazine suppresses prolactin secretion in human pituitary tumour cell cultures.

Because histidyl-proline diketopiperazine (HPD), a metabolite of TRH, has been shown to suppress prolactin (PRL) release by rat pituitary tumour cells, human pituitary tumour cells were exposed to this compound. Monolayer cell cultures were initiated from pituitary tissue removed by transsphenoidal surgery from two patients with prolactin-secreting microadenomas. Tumour fragments were mechanically dispersed; cells were seeded into multiwell plates and incubated in Ham's F-10 medium enriched with fetal calf serum (20%). HPD (7.5 ng/ml) suppressed PRL release by both tumour cell cultures. Theophylline reversed the inhibition of PRL release induced by HPD. The data raise the possibility that HPD may act as an endogenous prolactin-inhibiting factor in man.

Cells, Cultured↗
PubMed1982

Pharmacokinetic significance of serum reverse T3 levels during amiodarone treatment: a potential method for monitoring chronic drug therapy.

We studied the antiarrhythmic effects of amiodarone, 600-1400 mg/day, in 18 patients with refractory arrhythmias, and related to drug efficacy and side effects to serum levels of T4, reverse T3 (rT3) and the QTc interval. In the 11 patients with ventricular arrhythmias, premature complexes were reduced by 90-98%, and complex ectopy and runs of ventricular tachycardia were abolished; in the seven patients with paroxysmal atrial flutter, there were no recurrences on stable drug therapy. The QTc lengthened by 11.6% (p less than 0.01), T4 increased by 31.6-63.3% (p less than 0.001) and rT3 increased by 82.9-176.8% (p less than 0.001) as a function of dose and duration of amiodarone therapy. A close correlation was found between rT3 (normal up to 50 ng/dl) and drug efficacy and some of the drug side effects; arrhythmia suppression occurred at levels of 55-100 ng/dl, and some of the known side effects at levels of 100-110 ng/dl. When amiodarone was stopped in nine patients, the changes in QTc, T4 and rT3 regressed toward normal and arrhythmia recurred in eight 2-20 weeks (mean 7.4 weeks) and when rT3 levels fell below 55 ng/dl; arrhythmia resuppression was achieved 3-28 days (mean 11 days) after resumption of amiodarone therapy. The indirect therapeutic half-life of amiodarone in seven patients, computed from the semilogarithmic plots of plasma rT3 after cessation of amiodarone therapy, ranged from 25 to 55 days (mean 35 days). The data suggest that rT3 levels may be useful in monitoring the efficacy and certain side effects of amiodarone.

Adult↗
PubMed1982

A comparison of methods for assessing thyroid function in nonthyroidal illness.

We studied various tests of thyroid function in sick patients with nonthyroidal illness (NTI) in order to determine the utility of each test for differentiating these patience from a group with hypothyroidism. We evaluated each test in 22 healthy volunteers who served as controls, 20 patients with hypothyroidism, 14 patients admitted to medical intensive care unit whose serum T4 was less than 5 micrograms/dl, 13 patients with chronic liver disease, 32 patients on chronic hemodialysis for renal failure, 13 ambulatory oncology patients receiving chemotherapy, 16 pregnant women, 7 women on estrogens, and 20 hyperthyroid patients. On all samples, we measured serum T4, the free T4 index by several methods, free T4 by equilibrium dialysis, free T4 calculated from thyronine-binding globulin (TBG) RIA, free T4 by three commercial kits (Gammacoat, Immophase, and Liquisol), T3, rT3, and TSH (by 3 different RIAs). Although all of the methods used for measuring free T4 (including free T4 index, free T4 by dialysis, free T4 assessed by TBG, and free T4 assessed by the 3 commercial kits) were excellent for the diagnosis of hypothyroidism, hyperthyroidism, and euthyroidism in the presence of high TBG, none of these methods showed that free T4 was consistently normal in patients with NTI; with each method, a number of NTI patients had subnormal values. In the NTI groups, free T4 measured by dialysis and the free T4 index generally correlated significantly with the commercial free T4 methods. Serum rT3 was elevated or normal in NTI patients and low in hypothyroid subjects. Serum TSH provided the most reliable differentiation between patients with primary hypothyroidism and those with NTI and low serum T4 levels.

Alpha-Globulins↗
PubMed1982

Radioimmunoassay detection of endorphins from long-term culture of human pituitary tumour cells.

Using a sensitive and precise radioimmunoassay for human beta-endorphin, we have demonstrated the sustained secretion of opioid peptides from human pituitary tumour cells. Pituitary tumour tissue obtained from a patient with Nelson's syndrome was maintained in continuous monolayer culture and secreted both beta-lipotropin and beta-endorphin, with predominance of the latter. This is compatible with the idea that the beta-endorphin in normal human serum is secreted as such despite the predominance of beta-lipotropin compared with beta-endorphin in the anterior pituitary.

Cells, Cultured↗
PubMed1981

The role of opiates and endogenous opioid peptides in the regulation of rat TSH secretion.

The administration of morphine to rats at room temperature is reported to suppress serum thyrotropin (TSH) levels by a hypothalamic mechanism. However, it is unknown whether endogenous opioid peptides (EOP) are involved in the control of TSH secretion. The present studies show that naloxone (10 mg/kg, i.p.) an opiate-receptor antagonist, prevented the decline in rat serum TSH which occurs with heat exposure. Morphine sulfate (20 mg/kg, i.p.) treatment prevented the cold-induced elevation in serum TSH and pretreatment with haloperidol (0.3 mg/kg, i.p.) eliminated morphine's influence. Medial-basal hypothalamic thyrotropin-releasing hormone (TRH) content, measured by RIA, increased in the morphine-treated rats which were exposed to 4 degrees C. A submaximal intravenous dose of TRH (300 ng/100 g) was given to determine whether morphine suppresses serum TSH through the release of hypothalamic thyrotropic inhibitors. Morphine pretreatment did not alter TSH stimulation by TRH. Morphine alone or combined with TRH did not alter basal or stimulated TSH secretion in vitro. These studies strongly suggest that, in rats, the EOP modulate TSH secretion under conditions such as acute heat exposure which was associated with a decline in serum TSH. Under specific circumstances, the suppression of serum TSH by morphine may be dopamine-dependent.

Animals↗
PubMed1981

A cyclic variation in thyroid-stimulating hormone in the fetal rhesus monkey.

Morning and evening simultaneous fetal and maternal plasma samples were analyzed for thyroid-stimulating hormone. An a.m.-p.m. variation in fetal concentrations was identified, whereas the majority of the maternal values (28 of 32) were below the sensitivity of the assay. The importance of this cyclic fetal activity is discussed.

Animals↗
PubMed1981

3,5-Dimethyl-3'-isopropyl-l-thyronine therapy in diabetic pregnancy: stimulation of rabbit fetal lung phospholipids.

Diabetes mellitus in pregnancy is associated with neonatal respiratory distress syndrome due to impaired synthesis of fetal lung surfactant. Pharmacologic agents that promote fetal lung maturity are diabetogenic and have limited use in the management of diabetic pregnancy for prevention of respiratory distress syndrome. Maternal administration of a thyroid analog 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) results in significant enhancement of fetal lung phospholipid synthesis and accelerated lung maturity. We therefore studied the effects of DIMIT (0.5 mg/kg per d, s.c.) administration to pregnant alloxan-diabetic rabbits on days 25 and 26 of gestation. DIMIT treatment of diabetic maternal rabbits (DD) was associated with reduction of maternal blood glucose (115 +/- 13 vs. 275 +/- 72 mg/dl, P less than 0.05) and fetal glucose (64 +/- 6 vs. 274 +/- 47 mg/dl, P less than 0.001) compared with saline-injected diabetic (D) mothers. Reduction of fetal insulin levels was also associated with maternal DIMIT therapy in diabetic rabbits (56 +/- 5 (D) vs. 24 +/- 4 microunits/ml, P less than 0.001). Maternal diabetes resulted in significant reduction of fetal lung weight (370 +/- 20 vs. 520 +/- 30 mg, P less than 0.005) and lung protein content (6.5 +/- 0.7 vs. 8.7 +/- 0.7 mg/gm, P less than 0.005), which were restored to normal in offspring of DIMIT-treated diabetic rabbits. Maternal DIMIT administration caused significant reduction in fetal lung glycogen content in control (62 +/- 5.8 vs. 25 +/- 5.9 micrograms/mg protein, P less than 0.001) and diabetic (56 +/- 7 vs. 34 +/- 5 micrograms/mg protein, P less than 0.02) offspring. Whereas maternal diabetes was associated with reduction of all major phospholipid species in fetal lung-comprising surfactant, these were restored with DIMIT therapy. The results demonstrate that short-term maternal administration of DIMIT in pregnant diabetic rabbits not only promotes fetal lung phospholipid synthesis, but also appears to ameliorate maternal hyperglycemia. Thus, DIMIT is of potential benefit in the management of diabetic pregnancy.

Animals↗
PubMed1981

Bromocriptine inhibits colony formation by rat pituitary tumor cells in a double-layered agar clonogenic assay.

In order to assess the possible antiproliferative action of bromocriptine on pituitary tumors, the effects of the drug on colony formation were studied using GH3 cells grown in double-layered agar. Bromocriptine (300 nM) clearly inhibited both the number of colonies arising from single tumor cells as well as the size of the tumor cell colonies (p less than 0.001). The drug did not inhibit colony formation by cells derived from 2 non-pituitary tumors. The data show that this dopamine agonist blocks proliferation of rat pituitary tumor cells in vitro and lend further support to the preliminary clinical observations of an anti-tumor effect of bromocriptine in man.

Animals↗
PubMed1981

Hyperthyroxinemia with bradycardia and normal thyrotropin secretion after chronic amiodarone administration.

Pituitary-thyroid function was tested in 15 euthyroid patients before, during, and after long term oral treatment with amiodarone (2-n-butyl-3,4'-diethylaminoethoxy-3',5'-diiodobenzoylbenzofurane; 600-1200 mg daily), an iodine-containing potent antiarrhythmic drug. The drug caused increases in serum total T4, free T4, and rT3, with a concomitant decrease in T3. Baseline serum TSH was significantly higher after 1 week of drug treatment and returned to normal levels after 12 weeks of treatment. All patients receiving amiodarone had a slowing of their heart rate (P less than 0.01), and heart rate gradually increased 6 weeks after drug withdrawal, concurrent with the slow fall in T4 and rT3 levels. Amiodarone did not cross-react in the iodothyronine RIAs. The results suggest that amiodarone inhibits the peripheral conversion of T4 to T3 and may block the metabolic action of thyroid hormone in man.

Aged↗
PubMed1980

Effect of vitamin A on the hypothalamo-pituitary-thyroid axis.

This study reports the effects of the administration of pharmacologic doses of vitamin A on multiple parameters of thyroid function. Vitamin A decreased total T4 and T3 levels. With vitamin A treatment, there was a marked increase in the percentage dialyzable T3 and T4 both in vivo and in vitro. The serum-free T3 and T4 levels as measured by dialysis were on the whole normal in vitamin A-treated rats. Following thyroidectomy, the total T4 levels were still decreased, suggesting that vitamin A produced its effects by increasing peripheral clearance of thyroxine. Vitamin A did not alter basal thyroid stimulating hormone (TSH) or its response to thyroid releasing hormone, suggesting a relatively normal hypothalamic-pituitary-thyroid axis in vitamin A-treated animals. Vitamin A may decrease tissue responsiveness to thyroid hormones as evidenced by the tendency to decreased Na-K-ATPase activity in the livers from vitamin A-treated rats and the decreased growth hormone response to T3 in GH3 pituitary cultures as shown in this study and by the decreased basal metabolic rate found after vitamin A in previous studies. Vitamin A decreased thyroid gland size and increases 125I thyroid uptake. In vitro, vitamin A enhanced T4 to T3 conversion in hepatic homogenates.

Administration, Oral↗
PubMed1980

Autofeedback of prolactin in cultured prolactin-secreting pituitary cells.

Cultured GH3 rat pituitary tumor cells which secrete prolactin (PRL) were used to study autoregulation of rat PRL (rPRL) secretion. Acute (1 h) release of rPRL by cells in monolayer culture was inhibited by ovine PRL (oPRL; 10(-7) and 10(-8) M). Intracellular rPRL accumulation was not inhibited by exogenous oPRL. No effect of oPRL was seen during long-term (12-day) incubation of cells with oPRL (10(-7) to 10(-9) M). oPRL exerts an acute suppressive effect on rPRL release at the cellular level, but does not inhibit rPRL synthesis or long-term release.

Animals↗
PubMed1980

Suppression of thyrotropin by 3,5-dimethyl-3'-isopropyl-L-thyronine in euthyroid and hypothyroid rats.

The effect of 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) a nonhalogenated thyroid hormone analog, on plasma and pituitary TSH levels was studied in euthyroid and 5-day-thyroidectomized (T-5d) rats. The minimal dose of DIMIT which suppressed basal plasma TSH for a 24-h period was 5.3 micrograms/100 g BW in the euthyroid rats and 5.2 micrograms/100 g BW in the T-5d group. The equipotent doses of T3 were 1.0 and 1.5 micrograms/100 g BW, respectively. Thus, the apparent DIMIT to T3 molar ratio ranged from 6.6 in the hypothyroid to 10 in the euthyroid group. The suppression of TRH-induced TSH release in the euthyroid rats required a high dose of DIMIT (9.2 micrograms/100 g BW), resulting in a DIMIT to T3 molar ratio of 17. Time-course studies comparing the effects of equipotent doses of DIMIT and T3 on TSH release rates in euthyroid and T-5d rats have shown a maximal suppression by 3--24 h after the administration of both T3 and DIMIT. However, the recovery from the effect was slower after T3. TSH synthesis in the T-5d group was similarly suppressed by DIMIT and T3. DIMIT has significant thyromimetic activity in euthyroid and hypothyroid rats, as evidenced by the suppresion of TSH synthesis and release.

Animals↗