Gonadotropins in rats with hereditary diabetes insipidus (Brattleboro strain).

In the Brattleboro strain of rats, the genetic defect in vasopressin synthesis seems to be accompanied by a defect in the synthesis of other structurally related nonapeptides, such as the pineal arginine vasotocin which has antigonadotropic properties in animals. It was therefore tempting to investigate gonadotropin secretion in rats with hereditary hypothalamic diabetes insipidus (DI rats).

Sandostatin LAR: a promising therapeutic tool in the management of acromegalic patients.

A stable and sustained suppression of growth hormone (GH) secretion was noted in 101 patients treated long term with individual doses (20 and 30 mg in 89 patients, 40 mg in 12 patients) of Sandostatin LAR (Sandoz Pharma Ltd, Basel, Switzerland). Doses of 20 mg and 30 mg at 4-week intervals delivered average octreotide concentrations of 1,348 +/- 483 ng/L and 2,631 +/- 1,026 ng/L, respectively, in steady-state conditions and provided adequate control of patients who had been well controlled during treatment with 0.1 mg and 0.2 mg thrice-daily subcutaneous (SC) Sandostatin. Suppression of GH serum concentrations to less than 5 micrograms, 2 micrograms, and even 1 microgram/L was recorded in more patients and more consistently during long-term treatment with Sandostatin LAR than Sandostatin. A marked decrease or even a normalization of insulin-like growth factor-1 (IGF-1) serum concentrations was observed after the first double-blind 10-, 20-, or 30-mg dose of Sandostatin LAR. A progressive improvement was recorded during long-term treatment, with normalization of IGF-1 serum concentrations in 65.3% of patients. A marked clinical improvement was observed in parallel, with 36 of 101 patients (35.6%) becoming asymptomatic after the nineteenth injection of Sandostatin LAR. A greater than 20% shrinkage of the GH-secreting adenoma was also recorded in 12 of 14 patients treated with Sandostatin LAR after receiving only 2 to 4 weeks of treatment with SC Sandostatin and in 11 of 18 patients receiving Sandostatin LAR as adjuvant therapy after failure of surgery. The systemic tolerability of Sandostatin LAR was good, and most adverse events were mild and short term (1 to 2 days). No impairment of thyroid function was detected. Newly occurring gallstones were recorded in four of 101 patients and microlithiasis in four of 101 after up to 30 months of treatment with Sandostatin LAR. Due to its excellent efficacy, good tolerability, convenience of administration, and acceptability by patients, Sandostatin LAR is considered a promising therapeutic tool in the management of acromegalic patients.

Hormonal and metabolic response in elite female gymnasts undergoing strenuous training and supplementation with SUPRO Brand Isolated Soy Protein.

BACKGROUND: This study evaluates the metabolic and hormonal response in elite female gymnasts undergoing strenuous training and supplementation with SUPRO Brand Isolated Soy Protein. METHODS. EXPERIMENTAL DESIGN: 14 top female gymnasts (Romanian Olympic Team), took part in a study to examine their hormonal metabolic profile and to investigate any possible changes resulting from a 4-month program of strenuous training and daily supplementation with soy protein at a level of 1 g/kg body weight. Gymnasts wtare randomly assigned to one of two groups seven to the Supplemented Group (A) and seven to the Non-Supplemented Group (B). Both groups took part in the same program, which consisted of strenuous training for 4-6 hours/day (except on Sunday, controlled food intake and supplements including vitamins and minerals. Group A received a supplement of Sports Beverage Protein Mix with SUPRO Isolated Soy Protein (ISP) twice daily. Group B received a placebo identical in appearance and flavour. Selected parameters were measured before and after the 4-month training program (lean body mass, fat mass, serum hemoglobin, protein, fats, urea and creatinine, liver enzymes, serum total calcium and magnesium, immunoglobulins, urinary mucoproteins, serum T3 and T4, estradiol, progesterone, prolactin, testosterone and urinary 17-ketosteroids). RESULTS: Results demonstrated that the Supplemented Group (A) had an increase in lean body mass and serum levels of prolactin (p < 0.01) and T4 and a decrease in serum alkaline phosphetases (p < 0.01). The Non-Supplemented Group (B) had a decreased level of serum T4 and an increased level of urinary mucoproteins (p < 0.05). CONCLUSIONS: Our preliminary conclusions might suggest lower metabolic-hormonal stress in elite female gymnasts undergoing strenuous training and who received daily supplementation with isolated soy protein.

Multipoint incremental motor unit number estimation as an outcome measure in ALS.

BACKGROUND: Improved outcome measures are necessary to reduce sample size and increase power in amyotrophic lateral sclerosis (ALS) clinical trials. Motor unit number estimation (MUNE) is a potentially attractive tool. MUNE methods previously employed in multicenter trials exhibited excessive variability and were prone to artifact. OBJECTIVE: To evaluate a modification of standard incremental MUNE in a multicenter natural history study of subjects with ALS. METHODS: Fifty healthy subjects were evaluated twice and 71 subjects with ALS were studied repeatedly for up to 500 days. Side and nerve studied was based on clinical examination findings. Nerves were stimulated at 3 specified locations and 3 increments were obtained at each location. Average single motor unit action potential (SMUP) amplitude was calculated by adding the amplitude of the third increment at each location and dividing by 9; SMUP was divided into maximum CMAP amplitude to determine the MUNE. RESULTS: Test-retest variability was 9% in normal subjects. Average MUNE for normal subjects was 225 (±87), and was 41.9 (±39) among subjects with ALS at baseline. Subjects with ALS showed clear decrements over time, with an overage rate of decline of approximately 9% per month. SMUP amplitude increased with time in a fashion consistent with the known pathophysiology of ALS. CONCLUSION: Multipoint incremental MUNE has a number of attributes that make it attractive as an outcome measure in ALS and other diseases characterized by motor unit loss. It can be rapidly performed on any EMG machine and has repeatability and rates of decline that favorably compare to other previously described methods.

Insulin radioimmunoassay measurement by the polyethyleneglycol separation technique using the ROTOP kit reagents. Some clinical applications.

The technique described in the instructions booklet of the radioimmunoassay Insulin kit commercially known as the ROTOP-Insulin kit (CCR) tested both in our and in other laboratories did not show the desired reproducibility. Using the main ROTOP reagents (anti-insulin serum and 125I-Insulin) in radioimmunoassay (RIA) systems with other separation techniques (double antibody, dextran-charcoal and polyethyleneglycol) we observed that these reagents are suitable for a sensitive and precise RIA system. The intra-assay variations observed were caused by the separation technique with 86% ethanol as proposed by the procedure. This work describes an insulin-RIA system modified in order to be able to use the ROTOP reagents with the polyethyleneglycol (PEG) separation technique. This variant is used for more than three years in our laboratory but was adopted also in other RIA laboratories in Romania.

Serum and pituitary prolactin variations under the influence of pyridoxine and pimozide in the male rat.

Prolactin was measured in the serum and hypophyses of the male rat after six days of i.p. administration of pyridoxine 5 mg (group B6), after a single dose of pimozide 2.5 mg/kg body (group PMZ), six days of pyridoxine and one dose of pimozide (group B6- PMZ) and a single dose of tartaric acid (controls). Both pyridoxine and pimozide increased the serum prolactin: 59.06 +/- 16.23 ng/ml and 68.45 +/- 10.78 ng/ml respectively (X +/- DS) by comparison to controls: 33.12 +/- 11.16 ng/ml, their effect being cumulative (83.75 +/- 13.86 ng/ml). However, the effect of pyridoxine and pimozide at the central level is different, pyridoxine producing an increase of the pituitary concentration of prolactin, while pimozide depleted the stored prolactin. Hypothetical mechanisms of pyridoxine action at the pituitary level are discussed.

RIA measurement of insulin antibodies in human sera using the polyethyleneglycol separation technique.

A radioimmunological method for the detection and measurement of insulin antibodies in human sera was developed using polyethyleneglycol (PEG) as separation agent. Studies were performed on 150 sera of nondiabetic subjects and on 27 sera collected from diabetic patients treated with insulin. The per cent binding of 125I-insulin in normal sera ranged similarly to control free-insulin serum while in sera from insulin-treated patients8 the binding was significantly greater. The technique is quick (24 hours) and the intra-assay precision (correlation coefficient for replicates) varies from 0.87 to 0.99%. The separation technique using PEG for the precipitation of the antigen-antibody complexes may be extended to the measurement of antibodies for any other substance of lo, molecular weight (under 10,000 daltons).

Studies on the action of pesticides upon the endocrines using in vitro human thyroid cells culture and in vivo animal models. II. Herbicides-prometrin and terbutrin.

The effects of prometrin and terbutrin in doses of 0.001--1 mg/1.5 ml culture medium on human thyroid cell cultures were studied following up their influence on cell multipliction, proteic synthesis, enzymatic activity of thyroid cells and hormonal synthesis. The results differed in relation to the dose and the type of thyroid cell under study. The acute experiment performed on rats treated with 50 ppm/prometrin or terbutrin/kg b.w. for 15 days revealed variations in T3, T4 and LH synthesis. Both prometrin and terbutrin stimulate T3 synthesis and inhibit T4 synthesis. LH synthesis appears much increased in the hypophysis of the rats treated with terbutrin, whereas the amount of LH released into the serum is much decreased as compared to the controls.

The action of chlorpromazine upon the serum and hypophyseal variations of growth hormone, prolactin and TSH in the male adult rat under continuous-lighting stress.

The influence of chlorpromazine (CPZ) on the serum and hypophyseal levels of growth hormone (GH), prolactin and TSH was studied in the male adult rat occurring under normal light-dark-rhythm conditions and under continuous 24-hour lighting, respectively. The serum and hypophyseal concentrations of GH decreased significantly (p less than 0.01 and p less than or equal to 0.02) one hour after the administration of 1.0 mg of CPZ in the animals under continuous light by comparison with the animals maintained on the same conditions. In the animals under normal light-dark rhythm, CPZ did not influence the peripheral or central concentrations of GH. The animals maintained either in normal or in continuous lighting conditions released prolactin under the influence of CPZ. The increased values of circulating TSH in light-exposed animals by comparison with the diurnal group (p less than 0.001) were some more augmented under the influence of CPZ, while this drug remained unefficient in the animals under normal light-dark-rhythm conditions. The mechanism of CPZ action upon the secretion of GH and prolactin, which are hormones lacking target gland, is discussed.

Labelling of octapeptide neurohormones for in vitro studies. Radioimmunologic assay for arginine-vasopressin.

Synthetic arginine-vasopressin (AVP), oxytocin (OXY) and arginine-vasotocin (AVT) were labelled with radioiodine at a moderate specific activity. The purity of the labelled octapeptides was checked by descendent paper chromatography in butanol-acetic acid-water (4 : 1 : 5 v/v) after a double filtration on a Sephadex G-25 column of the labelling mixtures. The rabbit anti-AVP serum bound 125I--AVP, the highest binding belling observed on the descendent eluates from the Sephadex column. The antiserum is specific to AVP, no binding being observed will AVT or oxytocin. The sensitivity of a RIA system using 125I--AVP, commercial anti-AVP serum and polyethyleneglycol separation technique, was of 5 pg/ml in terms of AVP with a biological activity of 385 IU/mg. The validity of the assay was tested on five patients (two with diabetes inspidus (DI) and three with other endocrine diseases) submitted to dehydration of hydration tests.

The influence of thiol derivatives on synthesis of thyroid hormones in human thyroid cultured cells.

The experiments were carried out on 26 lots of thyroid cell cultures treated with sodium sulphate, lithium sulphate, lithium carbonate, cystine, cysteine, and methionine, in 2 doses each, in the presence or absence of iodine in the culture medium. The monolayer culture was used in morphologic, cytochemical and cytoenzymatic studies, and the culture medium was used for assay of thyroglobulin and thyroxin. We found that addition of aminoacids with SH or S--S groups to the culture medium causes stimulation of protein synthesis overstrain on the oxydases system at the expense of dehydrogenases. Stimulation of protein synthesis in the thyroid cell cultures under study is not accompanied by a corresponding hormonal secretory activity, the process of hormonal biosynthesis being inhibited as compared to the control culture.

The value of thyroglobulin (TGL) assay in following the post-therapeutic course of differentiated thyroid cancer.

Serum TGL was assayed in 32 patients with total thyroidectomy performed on account of differentiated thyroid cancer, and in whom postoperative serum TGL values were above 60 ng/ml. The purpose of the study was to demonstrate the specific TGL response in differentiated thyroid cancer relapse and metastases, and the value of serum TGL assay as a test for early diagnosis of relapse and metastasis in this form of cancer. The results were compared to those from the following lots: 15 euthyroid volunteers, 15 patients with differentiated thyroid cancer diagnosed postoperatively whose serum TGL values were under 60 ng/ml and, 14 patients with non-thyroid cancer metastases.

Studies on the action of pesticides upon the endocrines using in vitro human thyroid cells culture and in vivo animal models. I. Herbicides--aminotriasole (amitrol) and atrazine.

The action of aminotriasole (amitrol) and atrazine in doses of 0.001--1 mg and 0.0001--.01 mg/1.5 ml medium, respectively, upon cell cultures of human thyroid was studied in order to find out their influence on cell multiplication, proteic synthesis, enzymatic activity of thyroid cells, and hormonal synthesis. The results varied according to the dose utilized and the type of thyroid cell studied. The acute experiment carried out on rats treated 15 days with 500 ppm amitol and 50 ppm atrazine revealed variations in the T3, T4 and LH synthesis. Amitrol showed a strong inhibitory action on T3 and T4 secretion, whereas atrazine stimulated it.

Mild stimulation of serum immunoreactive insulin (IRI) release following large doses of intravenously given glycine to children of normal pituitary function.

In healthy, sexually immature children of both sexes serum IRI levels rose more than expected from random inter-individual variation (i.e. more than 3 standard deviations of the basal level) in 10 out of 21 subjects loaded by glycine. The IRI release by glycine though moderate and not constant is, however, unquestionable. The growth hormone (GH) secretory response to glycine did not change according to the occurrence and/or magnitude of IRI release. It was concluded that GH and IRI stimulatory properties of glycine given intravenously in large doses are completely unrelated.

Testosterone in sera of workers exposed to acrylonitrile.

Testosterone was measured through three consecutive years in sera from young and adult male subjects working in a chemical factory exposed to some complex chemical noxae, the major exposure being acrylonitrile (vinylcyanid). In the first yr, (group A), the blood was collected on May 1975 (no 39), the II-nd yr (group B) on March (no 109) and the III-rd yr (group C) on May (no 149). The exposure time varied in each group between 6 mos and 7-10 yrs. For comparison, blood samples were collected from 145 men of comparable age grouped in nonexposed: blood donors (no 37) (group a), new workers (no 23) (group b) and exposed to other chemical noxae in the same factory: Na cyanid (group c, no 23), cyan derivatives (group d, no 22) and pyrolysis (group no 39). The seasonal testosterone variations being considered, the Student's 't' test applied to the hormonal levels in acrylonitrile groups A, B and C showed non significant differences. However, the comparison of the testosterone concentrations in sera of the groups A, B and C vs the control groups investigated during the same month of the year showed much lower levels of the hormone in the first groups (p less than 0.001). These data are suggesting that the exposure to acrylonitrile either by direct participation to the technological chain or by working in the same noxious environment may influence the testosterone synthesis and/or secretion.

The development of a radioimmunoassay system for testosterone (T) and dihydrotestosterone (DHT). Part 1. The preparation of the T-derivatives and T-protein conjugates.

Testosterone-17-hemisuceinate (T-17-HS) by esterification with succinic anhydride technique and Testosterone-3-carboxy-methyl-oxyme (T-3-CMO) derivatives were synthesized. The T-protein (BSA) conjugates were prepared by the condensation with carbodiimide technique, for the T-17-HS derivative and by the mixed anhydride technique, for the T-3-CMO. Both the derivatives and the T-BSA conjugates were characterized by melting point, ultraviolet and infrared spectra, thin layer chromatography. The physico-chemical characteristics and the hapten-protein incorporation being convenient: 28 mol T/mol BSA for T-17-HS-BSA and 38 mol T/mol BSA for T-3-CMO-BSA, the T-carrier conjugates are adequate for their use as immunogens.

Comparative study of the effects of lisuride and pimozide on the preovulatory surge of FSH, LH and prolactin in rat.

In experiments conducted on adult female Wistar rats, lisuride hydrogen maleate, injected before the critical period of proestrus (between 11 h-13 h) in a single s.c. dose of 0.125 mg/kg body, significantly elevated the preovulatory gonadotropin surge and slightly, non-significantly lowered that of prolactin (assessed between 15-16 h). Pimozide, a selective antidopaminergic neuroleptic, injected according to the same schedule in a dose of 2.5 mg/kg body, strongly augmented the LH surge and also prolactin secretion. Thus, stimulation of gonadotropin secretion by lisuride cannot be ascribed to its dopaminergic agonistic action, but may be attributed to its antiserotoninic activity or to the action on the presynaptic dopamine receptors of the tuberoinfundibular neurons, reducing their inhibitory influence on the gonadotropin surge. The results plead for the inhibitory role of DA in the LH and prolactin secretion; 5-HT may have a similar action in the preovulatory gonadotropin surge and a stimulatory one in the surge of prolactin.

Immunohistochemistry of thyroid hormones as a functional parameter in thyroid pathology.

The authors study by means of immunoperoxidase method the pattern of thyroglobulin, triiodothyronine and thyroxine distribution in 58 cases of thyroid disorders: 15 euthyroid goiters, 10 Graves' disease, 7 Hashimoto's thyroiditis, 11 folliculo-papillary carcinomas (6 primary tumors and 5 lymph node metastases), 8 follicular carcinomas, 4 anaplastic carcinomas and 3 medullary carcinomas. Thyroglobulin, triiodothyronine and thyroxine were present in most of the thyroid disorders, excepting anaplastic and medullary carcinomas. Thyroglobulin and thyroxine were localized both in the follicular epithelium and in the colloid, whereas triiodothyronine was present especially in the follicular cells. The thyroid hormones distribution in benign lesions is rather similar. In carcinomas, the pattern of thyroglobulin, triiodothyronine and thyroxine is more heterogeneous, but generally the triiodothyronine distribution is similar to that of thyroglobulin. In some carcinomas, triiodothyronine and thyroxine showed a weak or negative immunostaining. The immunoperoxidase method is a valuable tool in the study of functional disturbances in the thyroid pathology and in the diagnosis of thyroid carcinoma metastases as well. Positive thyroid hormones staining clearly indicates the thyroid origin of metastases.

Differential effects of some predominantly antiadrenergic and antidopaminergic neuroleptics on the preovulatory surge of FSH, LH and prolactin in rat.

In experiments performed on rats, single subcutaneous doses of predominantly antiadrenergic neuroleptics (thioridazine, propericiazine) significantly depressed the preovulatory serum LH surge. On the contrary, predominantly antidopaminergic drugs (pimozide and in lesser extent thiethylperazine) elevated the circulating LH levels, and reduced pituitary LH content. FSH titers were not altered significantly (excepting by thioridazine). All the neuroleptics increased serum prolactin. The present results, in conjunction with our previous data obtained on the estrous cycle, suggest a stimulatory role of norepinephrine/epinephrine in LH-RH secretion and an inhibitory action of dopamine on the same process. In our experiments only the predominantly antidopaminergic drugs had a pseudopregnancy-inducing effect, which not only elevated PRL levels, but also allowed (rather increased) preovulatory LH surge, and the subsequent development of new corpora lutea. The lack of pseudopregnancy after predominantly antiadrenergic neuroleptics may be attributed mainly to their antiovulatory action preventing the development of fresh corpora lutea.