Modulation by somatostatin of rat submandibular salivary secretion.

Although somatostatin (somatotrophin release inhibitory factor; SRIF) is a well-known inhibitory peptide, there are only a few reports of it acting as a positive modulator. In this work, the action of somatostatin upon rat submandibular protein secretion was studied. In vivo somatostatin infusion (35 microg/(kg h)) raised protein secretion stimulated by adrenergic and peptidergic agents. To rule out possible systemic effects of somatostatin, in vitro experiments were performed. Somatostatin (90 nmol/l) augmented protein release stimulated by noradrenaline (19 micromol/l) and substance P (10 micromol/l), but it did not affect isoprenaline (400 micromol/l)-induced protein release. Phenoxybenzamine (20 micromol/l) reduced the effect of somatostatin on noradrenaline-stimulated protein release. Propranolol (20 micromol/l) increased the noradrenaline-stimulated protein release and this effect was synergistic with the action of somatostatin. The absence of extracellular calcium did not significantly reduce somatostatin enhancement of agonist-induced secretion. Fluorescence measurements of the Ca(2+)-sensitive dye fluo3 showed that cytosolic calcium in acinar cells remained elevated during stimuli when somatostatin was present in the medium. It was concluded that somatostatin modulates rat submandibular protein secretion by prolonging the time that the cytosolic calcium signal remains high after stimulus.

Thyrotropin receptor antibodies in parotid saliva.

Parotid saliva was collected with a Carlson-Crittenden device, under citric acid stimulation, in 18 patients with autoimmune thyroid disease. Thyrotropin Receptor Antibodies (TRAb) were measured with a radioreceptor assay in parotid saliva and in serum in the same patients, and a statistical analysis of the data was performed. TRAb levels in parotid saliva were higher than in serum in the 3 pathologies studied (Graves' disease, Hashitoxicosis and Hashimoto's thyroiditis). There was good correlation between salivary and serum levels.

[TSH receptor antibodies as a recurrence index of Graves disease treated with antithyroid drugs]. / Anticuerpos anti-receptor de TSH como índice de recidiva en la enfermedad de Graves tratada con drogas antitiroideas.

TSH receptor antibodies (TRAb) measured by the TBI residual assay (TBIr) were studied in 3 groups of Graves disease patients, as follows: 54 non treated cases (Group 1), 20 cases under methimazol treatment (Group 2) and 23 patients who were euthyroid after one year of methimazol treatment (Group 3), in order to evaluate the usefulness of TBIr as a recurrence index in Graves disease following antithyroid drug treatment. In group 1, TBIr was positive in 77.7% (45/54) of the cases. In group 2: 45% (9/20) had positive values for TBIr, all of which had a recurrence of disease during the year following the suppression of the treatment. In group 3, 69.5% patients (16/23) were TBIr positive. In 75% (12/16) of them the abnormally high values of TBIr predicted the recurrence, while 71.43% (5/7) of the patients, TBIr negatives, continued the remission 12 months later. By comparing the TBIr values before and after treatment in the group 3 patients, different possibilities were observed: a) TBIr persistently elevated: 52.17% (12/23). The 83.3% (10/12) had a recurrence before 6 months following treatment termination. b) TBIr, initially elevated, but later showing 50% decrease or negative values: 26.09% (6/23). Every patient was euthyroid one year after the treatment ended. c) TBIr persistently negative: 13.04% (3/23). Two of them had recurrence of their disease. d) TBIr negative which changed later to positive: 8.70% (2/23). Both presented a recurrence. In accordance with these results, we believe that abnormally high TBIr values before or after treatment is a useful recurrence index.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticuerpos anti-receptor de TSH como índice de recidiva en la enfermedad de Graves tratada con drogas antitiroideas. / [TSH receptor antibodies as a recurrence index of Graves disease treated with antithyroid drugs]

TSH receptor antibodies (TRAb) measured by the TBI residual assay (TBIr) were studied in 3 groups of Graves disease patients, as follows: 54 non treated cases (Group 1), 20 cases under methimazol treatment (Group 2) and 23 patients who were euthyroid after one year of methimazol treatment (Group 3), in order to evaluate the usefulness of TBIr as a recurrence index in Graves disease following antithyroid drug treatment. In group 1, TBIr was positive in 77.7

(45/54) of the cases. In group 2: 45

(9/20) had positive values for TBIr, all of which had a recurrence of disease during the year following the suppression of the treatment. In group 3, 69.5

patients (16/23) were TBIr positive. In 75

(12/16) of them the abnormally high values of TBIr predicted the recurrence, while 71.43

(5/7) of the patients, TBIr negatives, continued the remission 12 months later. By comparing the TBIr values before and after treatment in the group 3 patients, different possibilities were observed: a) TBIr persistently elevated: 52.17

(12/23). The 83.3

(10/12) had a recurrence before 6 months following treatment termination. b) TBIr, initially elevated, but later showing 50

decrease or negative values: 26.09

(6/23). Every patient was euthyroid one year after the treatment ended. c) TBIr persistently negative: 13.04

(3/23). Two of them had recurrence of their disease. d) TBIr negative which changed later to positive: 8.70

(2/23). Both presented a recurrence. In accordance with these results, we believe that abnormally high TBIr values before or after treatment is a useful recurrence index.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticuerpos anti-receptor de TSH como indice de recidiva en la enfermedad de graves tratada con drogas antitiroideas / TSH receptor antibodies as a recurrence index of Graves disease treated with antithyroid drugs

Estudiamos anticuerpos anti-receptor de TSH (TRAb), medido por un ensayo radioreceptor en suero total (TBir) en 54 pacientes con enfermedad de Graves sin tratamiento (grupo 1), 20 pacientes bajo tratamiento con metimazol (grupo 2) y 23 pacientes eutiroideos luego de completado un año de tratamiento con metimazol, una vez suspendida la terapia (grupo 3), para evaluar si TBir es útil como índice de recidiva en la enfermedad de Graves luego del tratamiento con drogas antitiroideas. En el grupo 1, TBir fue positivo en el 77,7% (45/54) de los casos. En el grupo 2 el 45% (9/20) tuvo valors positivos de TBir. Todos ellos recidivaron la enfermedad dentro del año posterior a finalizar la terapia. El 55% (11/20) tuvo TBir negativos, de ellos sólo el 18,1% (2/20) presentó recidiva en el mismo lapso de tiempo. Considerando globalmente a los pacientes del grupo 3, el 69,5% (16/23) fue TBir positivo. En el 75% (12/16) de los casos los valores anormales elevados de TBI fueron predictivos de la recidiva, mientras que el 71,43% (5/7) de pacientes con TBir negativos permanecia en remisión 12 meses después. De acuerdo al comportamiento de los valores de TBir antes y después del tratamiento, se establecieron distintos patrones de cambio: a) TBir persistentemente elevados: 52,17% (12/23). El 83,3% (10/112) presentó recidiva dentro de los seis meses de finalizada la terapia. b) TBir inicialmente elevado que se negativizó o se redujo en más del 50%: 26,09% (6/23). Todos los casos permanecían eutiroideos un año después de interrumpida la medicación. c) TBir persistentemente negativos: 13,04% (3/23): Dos presentaron recidiva. d) TBI negativo que cambió a positivo: 8,70% (2/23): Los dos presentaron recidiva. De acuerdo a los resultados obtenidos, consideramos útil como índice de recidiva valores de TBI anormalmente elevados durante o depués del tratamiento. En cambio, valores negativos de TBir después de la terapia, considerados aisladamente, no tienen valor pronóstico, debiendo evaluarse si existió un cambio en los valores iniciales (AU)

Anticuerpos anti-receptor de TSH como indice de recidiva en la enfermedad de graves tratada con drogas antitiroideas / TSH receptor antibodies as a recurrence index of Graves' disease treated with antithyroid drugs

Estudiamos anticuerpos anti-receptor de TSH (TRAb), medido por un ensayo radioreceptor en suero total (TBir) en 54 pacientes con enfermedad de Graves sin tratamiento (grupo 1), 20 pacientes bajo tratamiento con metimazol (grupo 2) y 23 pacientes eutiroideos luego de completado un año de tratamiento con metimazol, una vez suspendida la terapia (grupo 3), para evaluar si TBir es útil como índice de recidiva en la enfermedad de Graves luego del tratamiento con drogas antitiroideas. En el grupo 1, TBir fue positivo en el 77,7% (45/54) de los casos. En el grupo 2 el 45% (9/20) tuvo valors positivos de TBir. Todos ellos recidivaron la enfermedad dentro del año posterior a finalizar la terapia. El 55% (11/20) tuvo TBir negativos, de ellos sólo el 18,1% (2/20) presentó recidiva en el mismo lapso de tiempo. Considerando globalmente a los pacientes del grupo 3, el 69,5% (16/23) fue TBir positivo. En el 75% (12/16) de los casos los valores anormales elevados de TBI fueron predictivos de la recidiva, mientras que el 71,43% (5/7) de pacientes con TBir negativos permanecia en remisión 12 meses después. De acuerdo al comportamiento de los valores de TBir antes y después del tratamiento, se establecieron distintos patrones de cambio: a) TBir persistentemente elevados: 52,17% (12/23). El 83,3% (10/112) presentó recidiva dentro de los seis meses de finalizada la terapia. b) TBir inicialmente elevado que se negativizó o se redujo en más del 50%: 26,09% (6/23). Todos los casos permanecían eutiroideos un año después de interrumpida la medicación. c) TBir persistentemente negativos: 13,04% (3/23): Dos presentaron recidiva. d) TBI negativo que cambió a positivo: 8,70% (2/23): Los dos presentaron recidiva. De acuerdo a los resultados obtenidos, consideramos útil como índice de recidiva valores de TBI anormalmente elevados durante o depués del tratamiento. En cambio, valores negativos de TBir después de la terapia, considerados aisladamente, no tienen valor pronóstico, debiendo evaluarse si existió un cambio en los valores iniciales

Effect of testosterone on proteoglycans in the submandibular glands of the rat.

The proteoglycans in the submandibular salivary glands of castrated male Wistar rats were studied before and after the daily administration of testosterone propionate (TP) for one month. Castration decreased the weight of the glands and their uronic acid content. The administration of TP reversed these effects. Chromatographic separation of the uronic acid fractions was performed on cellulose microcolumns. The principal fractions were hyaluronic acid, heparan sulfate and dermatan sulfate. There were also changes in the physical properties of the proteoglycans. Castration decreased the range of distribution of molecular weight and the density, while the lateral chains of smaller length disappeared. TP administration to castrated rats reversed these effects.

Effects of castration and androgens upon prostatic proteoglycans in rats.

In studies performed on male Wistar rats, castration induced atrophy of the prostate with a marked increase in the uronic acid content. The administration of testosterone propionate to castrated rats produced opposite effects. Fractionation of the glycosaminoglycans on cellulose microcolumns showed that the changes in uronic acid content in the dorsolateral lobes were due to variations in hyaluronic acid, chondroitin-4-sulfate, and dermatan sulfate, but in the ventral lobes, there were changes in all the chromatographic fractions. There were also changes in the physical properties of proteoglycans. In the ventral lobes, castration induced a wider distribution of molecular weight, increased density, and predominance of lateral chains of greater size. In the dorsolateral lobes, there was a decrease in molecular weight and density of proteoglycans and in the length of lateral chains. Opposite results were obtained when testosterone propionate was given to castrated rats. It is postulated that the effects of androgens upon prostatic growth would depend on an interrelationship between epithelium and stroma mediated by the proteoglycans.

Effects of isoproterenol on I131 uptake by the submaxillary glands in mice.

DL-isoproterenol hydrochloride (1 mg/kg body weight/day) was subcutaneously administered to male A2G mice during 15 or 45 days. The sympathetic superior cervical ganglion of each mouse was resected on the right side, two days before beginning the injections. At the end of the injection period, the I131 submaxillary/plasma ratios and I131 thyroid uptake (%) were measured 3 hours after a tracer dose. The administration of isoproterenol induced marked hypertrophy in both normal and denervated submaxillary glands. At 15 days the I131 submaxillary/plasma ratios of the isoproterenol treated mice were slightly decreased on the normal side and were not modified on the denervated side. At 45 days the I131 submaxillary/plasma ratios were markedly decreased on both sides. The thyroid weight and I131 uptake were not modified by the isoproterenol treatment.

Effects of isoproterenol on I131 uptake by the submaxillary glands in mice.

DL-isoproterenol hydrochloride (1 mg/kg body weight/day) was subcutaneously administered to male A2G mice during 15 or 45 days. The sympathetic superior cervical ganglion of each mouse was resected on the right side, two days before beginning the injections. At the end of the injection period, the I131 submaxillary/plasma ratios and I131 thyroid uptake (

) were measured 3 hours after a tracer dose. The administration of isoproterenol induced marked hypertrophy in both normal and denervated submaxillary glands. At 15 days the I131 submaxillary/plasma ratios of the isoproterenol treated mice were slightly decreased on the normal side and were not modified on the denervated side. At 45 days the I131 submaxillary/plasma ratios were markedly decreased on both sides. The thyroid weight and I131 uptake were not modified by the isoproterenol treatment.

Effects of isoproterenol on I131 uptake by the submaxillary glands in mice

DL-isoproterenol hydrochloride (1 mg/kg body weight/day) was subcutaneously administered to male A2G mice during 15 or 45 days. The sympathetic superior cervical ganglion of each mouse was resected on the right side, two days before beginning the injections. At the end of the injection period, the I131 submaxillary/plasma ratios and I131 thyroid uptake (

) were measured 3 hours after a tracer dose. The administration of isoproterenol induced marked hypertrophy in both normal and denervated submaxillary glands. At 15 days the I131 submaxillary/plasma ratios of the isoproterenol treated mice were slightly decreased on the normal side and were not modified on the denervated side. At 45 days the I131 submaxillary/plasma ratios were markedly decreased on both sides. The thyroid weight and I131 uptake were not modified by the isoproterenol treatment.

Changes in human parotid salivary protein and sialic acid levels during pregnancy.

Saliva was collected with a Carlson-Crittenden device, under citric acid stimulation, in 107 pregnant women, 9 puerperal and 7 non-pregnant controls. No significant changes were found in salivary flow rate, pH and amylase levels. The total protein levels were decreased during pregnancy and the puerperium. The sialic acid levels decreased gradually but markedly during pregnancy, returning to normal levels in the puerperium. These changes in parotid saliva may be related to the hormonal changes of pregnancy.

Effects of anabolic-androgenic steroids on hair waves in castrated mice.

The effects of nandrolone phenylpropionate and decanoate, androstanolone and testosterone propionate, in daily doses from 3 to 100 micrograms during a month, on the diffuse hair wave seen after gonadectomy, were studied in male C 57 mice. The androgenic effects upon anterior prostate weight and the anabolic effects upon levator ani muscle and submaxillary gland weight, were also evaluated. The four steroid compounds used in these experiments had a strong inhibitory effect upon the hair growth waves which was stronger in the anabolic steroids than with testosterone propionate.

Effects of anabolic-androgenic steroids on hair waves in castrated mice.

The effects of nandrolone phenylpropionate and decanoate, androstanolone and testosterone propionate, in daily doses from 3 to 100 micrograms during a month, on the diffuse hair wave seen after gonadectomy, were studied in male C 57 mice. The androgenic effects upon anterior prostate weight and the anabolic effects upon levator ani muscle and submaxillary gland weight, were also evaluated. The four steroid compounds used in these experiments had a strong inhibitory effect upon the hair growth waves which was stronger in the anabolic steroids than with testosterone propionate.

Influence of thyroid function upon "Substance P" induced secretion of saliva by submaxillary glands.

The effects of changes in thyroid function on the action of "Substance P" upon the secretion of saliva by the submaxillary glands was studied in male Wistar rats, with parasympathetic decentralization on the left side. The dose-response curves to increasing doses of "Substance P" showed in hyperthyroid animals increased salivary secretion while in hypothyroid animals the dose-response curve to the drug was decreased. Every animal showed supersentivity to "Substance P" in the decentralized gland. The influence of changes in thyroid function in the denervated glands was the same as that in the unoperated side, increased salivary secretion in hyperthyroidism and decreased in hypothyroidism.

Thyroid hormone modulation of VIP's induced salivary secretion in the submaxillary glands of rats.

The effect of changes in thyroid function upon vasoactive intestinal peptide (VIP) induced secretion of saliva were studied in male Wistar rats. Hyperthyroidism was induced by the sc administration every 12 h of 10 micrograms/100 g bw of I-triiodothyronine; hypothyroidism was induced by surgical thyroidectomy 2 weeks before the experiments. Preganglionar parasympathetic denervation was induced by sectioning the chorda tympani on the left side. The dose-response curves to increasing doses of VIP showed in the hypothyroid animals increased salivary secretion, while in the hyperthyroid ones the dose-response to the drug was reduced. This effect was seen on both sides, the denervated and the control ones. In the denervated glands there was a marked hypersensitivity to the administration of VIP producing greater responses with the same doses, in the 3 groups of animals. The negative modulation by thyroid hormones of the salivary response to VIP administration is compared with the positive modulation they induce in the salivary response to beta-adrenergic and cholinergic drugs.

Inhibitory action of dipyrone on rat thyroid peroxidase and lactoperoxidase activities.

Previous studies have shown that phenylbutazone, another pyrazolone, inhibits thyroid peroxidase activity and interferes with iodide organification. We have developed "in vitro" studies with rat particulated peroxidase and lactoperoxidase (LPO) to study the effects of dipyrone upon thyroid peroxidase and to determine the type of inhibition. The 3-monoiodothyrosine (MIT) and 3,5-diiodothyrosine (DIT) synthesis was markedly affected by 6 X 10(-4) M dipyrone with inhibitions of 59% and 30% respectively. No difference was observed with lower concentrations. Inhibition of peroxidase activity (Triiodide assay) was found when crude rat peroxidase preparations and LPO were incubated with dipyrone in concentrations ranging from 10(-3) M to 10(-8) M, with a Ki of 2.5 X 10(-5) M and 4 X 10(-5) M respectively. Guaiacol peroxidation was scarcely affected by the action of the drug; 10(-3) M produced inhibition of 50%. Line weaver-Burk: plots were used to investigate the inhibition of LPO activity by dipyrone. The inhibition by the drug was competitive with the iodide. We may conclude that dipyrone and other drugs of the pyrazolone group act upon peroxidase activity "in vitro", by an inhibition of competitive type and in presence of iodide.

Inhibitory action of dipyrone on rat thyroid peroxidase and lactoperoxidase activities.

Previous studies have shown that phenylbutazone, another pyrazolone, inhibits thyroid peroxidase activity and interferes with iodide organification. We have developed [quot ]in vitro[quot ] studies with rat particulated peroxidase and lactoperoxidase (LPO) to study the effects of dipyrone upon thyroid peroxidase and to determine the type of inhibition. The 3-monoiodothyrosine (MIT) and 3,5-diiodothyrosine (DIT) synthesis was markedly affected by 6 X 10(-4) M dipyrone with inhibitions of 59

and 30

respectively. No difference was observed with lower concentrations. Inhibition of peroxidase activity (Triiodide assay) was found when crude rat peroxidase preparations and LPO were incubated with dipyrone in concentrations ranging from 10(-3) M to 10(-8) M, with a Ki of 2.5 X 10(-5) M and 4 X 10(-5) M respectively. Guaiacol peroxidation was scarcely affected by the action of the drug; 10(-3) M produced inhibition of 50

. Line weaver-Burk: plots were used to investigate the inhibition of LPO activity by dipyrone. The inhibition by the drug was competitive with the iodide. We may conclude that dipyrone and other drugs of the pyrazolone group act upon peroxidase activity [quot ]in vitro[quot ], by an inhibition of competitive type and in presence of iodide.

Thyroid hormone regulation of adrenergic receptors and beta-adrenergic responsiveness in the rat submandibular gland.

The effects of altered thyroid function on the sensitivity of isoproterenol induced secretion of saliva and in the characteristics of adrenergic receptors from the rat submandibular gland were examined. Hyperthyroidism produced an increased sensitivity to beta-adrenergic stimulation of the gland, and this phenomenon was associated with an increase in the number of beta and alpha 1-adrenoceptors. On the other hand, surgical thyroidectomy produced a decrease sensitivity to isoproterenol stimulation of the submandibular gland and a diminished density of beta-adrenoceptors. In this case, no changes in alpha-adrenoceptors were observed. These results are discussed emphasizing the correlation between the functional control of saliva secretion and the adrenergic receptors in different thyroid states.

Effects of indomethacin on thyroid iodine metabolism.

Several alterations of thyroid function parameters have been reported in animals treated with indomethacin, and we have studied the effect of this drug on the intrathyroidal iodine metabolism in Wistar rats. Indomethacin was administered by an esophagic tube in two doses (total = 6 mg) given at 0 and 5 hours in experiment I and three doses (total = 9 mg) given at 0, 10 and 23 hours in experiment II. No significant differences in thyroid weight, thyroidal 131I uptake and (131I) iodoaminoacids distribution was observed between the controls and indomethacin treated rats in experiments I and II. In experiment II the intrathyroidal protein bound 131I was not affected by indomethacin, but the extrathyroidal protein bound 131I was markedly affected by the drug, with 72% inhibition. Thyroid peroxidase activity was scarcely affected by the action of the drug. In experiment I indomethacin produced a reduction in serum total thyroxine (T4) of 52%, with a significant elevation in serum total triiodothyronine (T3) of 37%. In experiment II the serum total T4 and T3 levels in indomethacin treated rats were significantly reduced when compared to those of the control rats (77% and 56%, respectively). Serum thyrotropin (TSH) levels did not change in any of the two experiments. In summary, we have found that administration of indomethacin to rats causes an inhibition of thyroid function, measured by decreased thyroid hormone blood levels, without any change in the iodine organification process in these glands.