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Immunoreactivity of neuroendocrine cells in the respiratory tract in rats with experimental uremia after thyroparathyroidectomy.

Animals with experimental uremia, which underwent thyroparathyroidectomy, reveal numerous metabolic disorders that can influence morphology and activity of endocrine cells of the scattered neuroendocrine system. The aim of the study was the evaluation of the influence of thyroparathyroidectomy in rats with chronic renal failure on APUD system cells localized in the respiratory tract. The examination was conducted on the group of 20 rats. Thyroparathyroidectomy was performed 30 days after nephrectomy. Fragments of the lungs and trachea were collected 14 days after the operation. Routinely prepared paraffin sections were stained with H+E and with silver method. The immunohistochemical reactions were conducted with the use of antibodies against calcitonin (CT), synaptophysin (SPh), somatostatine (ST), and neuron-specific enolase (NSE) The results were estimated in light microscope on the basis of stain reaction of endocrine cells. Our examination showed that chronic renal failure affects the functioning of endocrine cells. We also observed the increase in APUD system cell number in the trachea and the lungs after thyroparathyroidectomy in uremic rats.

Animals↗

Effects of thyroparathyroidectomy, phosphate depletion and diphosphonate therapy on acute uraemic extra-osseous calcification in the rat.

1. The effects of acute uraemia on arterial and visceral calcium concentrations were studied in acutely uraemic rats. The influences of thyroparathyroidectomy, phosphate depletion and diphosphonate therapy on extra-osseous calcium concentrations were assessed in this model. 2. Aortic and visceral calcium concentrations were greater in acutely uraemic rats than in non-uraemic rats. Both prior thyroparathyroidectomy and prior phosphate-depletion resulted in lower aortic and visceral calcium concentrations in non-uraemic rats and prevented the increase in aortic and visceral calcium concentrations with acute uraemia. Diphosphonate given for 5 days before and for 2 days after the induction of acute uraemia resulted in lower tissue calcium concentrations than in non-diphosphonate-treated acutely uraemic rats. In contrast, diphosphonate given only immediately before or only after induction of acute uraemia did not prevent the increase in extra-osseous calcium concentrations with acute uraemia. 3. It is concluded that acute uraemia results in an increase in arterial and visceral calcium concentrations. Both thyroparathyroidectomy and phosphate depletion are effective in preventing the increase in extra-osseous calcium concentrations in acute uraemia. Diphosphonates may have a future role in preventing such calcification.

Animals↗

Scanning electron microscopy and energy-dispersive X-ray analysis of defects in mature rat incisor enamel after thyroparathyroidectomy.

The surface and the structure of the erupted enamel of the continuously growing rat incisor were studied by scanning electron microscopy (SEM) to analyse the effect of thyroparathyroidectomy on enamel formation. Ten male 21-day-old Wistar rats were thyroparathyroidectomized and five sham-operated rats were used as controls. Two months after surgery the rats were perfused with 1% glutaraldehyde and their mandibles dissected. The erupted ends of the incisors were cut off and routinely processed for SEM. An energy-dispersive analysis of X-rays (EDX analysis) was performed for the calcium:iron ratio of the enamel surface defects. Thyroparathyroidectomy induced surface defects and structural abnormalities in the outer layer of the mature erupted enamel. It was established that the surface and structural defects were related. The EDX analysis of the outer enamel showed that the enamel defects were associated with an abnormal elevation of the iron content. The SEM appearance and the EDX analyses indicated that these defects were hypomineralized and rich in iron. The reddish colour of the enamel is due to the high concentrations of iron.

Animals↗

Serotonin and gastrin cells in rat gastrointestinal tract after thyroparathyroidectomy and induced hyperthyroidism.

Thyroidectomy appears to reduce the serotonin content in the rat brain, whereas hyperthyroidism has the opposite effect. As it is not known whether the serotonin-producing cells of the gastrointestinal tract are influenced by these conditions, the effects of thyroparathyroidectomy and induced hyperthyroidism were studied experimentally, particularly as regards the serotonin- and gastrin-immunoreactive cells of the gastrointestinal tract. Immunocytochemical and quantification techniques were used to localize and determine the numbers of serotonin and gastrin cells. In thyroparathyroidectomized rats the intestine was significantly shorter and the mucosa thinner than in sham-operated and untreated controls, whereas the converse was found in the hyperthyroid rats. Following thyroparathyroidectomy, there were fewer gastrin-immunoreactive cells in antrum and the serotonin-immunoreactive cells were significantly less dense throughout the gastrointestinal tract. In hyperthyroid rats, gastrin-immunoreactive cells were more numerous, as were the serotonin-immunoreactive cells in the small intestine, whereas these cells were fewer in antrum and caecum. In conclusion, the thyroid gland exerts a significant influence on the gastrointestinal tract and on the serotonin-and gastrin-immunoreactive cells. The observed alterations may reflect a direct effect of the thyroid hormones, although indirect factors must also be considered.

Animals↗

Effect of thyroparathyroidectomy of calcium metabolism in rats: role of 1,25-dihydroxyvitamin D3.

Thyroparathyroidectomy (TPTX) decreases plasma calcium, bone formation and resorption, and tubular reabsorption of calcium. It also reduces the production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] which very likely results in the decrease in the intestinal calcium absorption (Vna) observed after TPTX. We have examined whether the influence of TPTX on plasma calcium and bone calcium fluxes could be corrected by doses of 1,25-(OH)2D3 (2 X 13 pmol/day ip), which just normalize Vna. The study was made by calcium balance and 45Ca kinetics in rats receiving a normal supply of vitamin D3. The results show that in TPTX rats physiological doses of 1,25-(OH)2D3 increased plasma calcium and decreased plasma phosphate. Calcium retention was not fully corrected because 1,25-(OH)2D3 increased urinary calcium excretion. The deposition into and the release of calcium from bone were enhanced by 1,25-(OH)2D3 but remained lower than in pair-fed sham-operated animals. Thus, in as much as the diminished renal production of 1,25-(OH)2D3 in TPTX is entirely responsible for the reduced Vna, the decrease in 1,25-(OH)2D3 could only partly explain the effect of thyroparathyroidectomy on bone calcium fluxes.

Animals↗

Gastric endocrine cells in rats with uremia and after thyroparathyroidectomy.

The decrease in active kidney parenchyma amount causes disorders in hormone secretion processes and their inactivation failure. Experimental thyroparathyroidectomy is connected with an abrupt reduction in endocrine cells and hormones produced by them, which can be a stimulating factor as far as the increase and intensity of endocrine gastric cells activity is concerned. The aim of the study was the histomorphological and immunohistochemical evaluation of these cells in the gastric pylorus. Thyroparathyroidectomy was performed in rats 30 days after nephrectomy. Fragments of gastric pylorus were collected 14 days after the operation. Paraffin sections were stained with H+E and silver method. Immunohistochemical reactions were conducted using antibodies against calcitonin gene-related peptide (CGRP), somatostatin (ST), synaptophysin (SPh), neuron-specific enolase (NSE), and chromogranin (CgA). The results showed an increase in number of endocrine cells in stomachs of rats in experimental group as compared to controls. Endocrine cells were larger and contained more secretory granules.

APUD Cells↗

Preliminary evaluation of pancreatic islets in rats with experimental uremia and after thyroparathyroidectomy.

Hormonal disorders are the permanent symptoms of renal failure. They concern all known hormones and can be due to quantitative changes of the secretory activity and disturbances of endocrine cell functions. The aim of this study was to establish whether experimental thyroparathyroidectomy in uremic animals causes detectable histomorphological changes in endocrine cells of pancreatic islets. Thyroparathyroidectomy was performed in rats 30 days after nephrectomy. Fragments of pancreatic tissue were collected 14 days after the operation. Paraffin sections were stained with H+E and by silver salt impregnation. Immunohistochemical reactions were conducted using antibodies against calcitoningene-related peptide (CGRP), synaptophysin (SPh), somatostatin (ST), neuron-specific enolase (NSE), and chromogranin (CgA). It was shown that endocrine cells of pancreatic islets in thyroparathyroidectomized rats show intensified immunoreactivity to SPh and ST as compared to the control group of animals. Immunocytochemical reactions for NSE, CgA, and CGRP were negative.

Animals↗

Effect of thyroparathyroidectomy (TPX) on the zona reticularis: a quantitative ultrastructural study.

Atrophy of zona reticularis cells was observed two weeks after surgical thyroparathyroidectomy (TPX). Quantitative morphological techniques for electron microscopy showed significant decreases in the volume of cytoplasm, nucleus, mitochondria, smooth endoplasmic reticulum and lipid droplets in the zona reticularis of TPX rats. In addition, many mitochnodria contained lipid droplets, some of which occupied virtually the entire matrix of mitochondria. The volume per cell of mitochondria with these inclusions increased significantly after TPX. The lipid droplets may well arise from cytoplasmic droplets by increased transport or reduced metabolism of cholesterol, or by direct incorporation of droplets into the mitochondrial matrix. The serum corticosterone level of TPX rats sacrificed under quiescent conditions did not differ significantly from that of controls. Hypothyroidism induced a significant increase in the volume of peroxisomes per cell in TPX animals which may be related to changes in lipid metabolism or transport.

Adrenal Cortex↗

The effects of thyroparathyroidectomy and 1,25 dihydroxyvitamin D3 on changes in the activities of some cytoplasmic and nuclear protein kinases during liver regeneration.

Partial hepatectomy (HPX), which proliferatively activates the remaining liver cells, triggered two transient prereplicative surges in the total activities of cytoplasmic types I and II cyclic AMP-dependent protein kinase holoenzymes, and of nuclear catalytic subunits from cyclic AMP-dependent protein kinases. It also induced a transient prereplicative increase in the activities of a nuclear Ca2+-calmodulin-stimulable, protamine-phosphorylating protein kinase, and a nuclear poly(L-lysine)-phosphorylating, 105 kDa protein kinase. Thyroparathyroidectomy (TPTX) delayed and reduced the first surge and completely eliminated the second surge of both of the cytoplasmic cyclic AMP-dependent protein kinases, reduced the rises in the activity of nuclear catalytic subunits, and completely eliminated the surge of the Ca2+-calmodulin-stimulable protein kinase, but did not affect the surge of the nuclear 105 kDa protein kinase. The impairment of the responses of the two cyclic AMP-dependent protein kinases to HPX in TPTX rats was not accompanied by a rise in the level of heat-stable inhibitor of cyclic AMP-dependent protein kinase activity. One intraperitoneal injection of 1,25-dihydroxyvitamin D1 into TPTX rats immediately after HPX completely restored the post-HPX surges in the activity of type I cyclic AMP-dependent protein kinase, but the hormone, even in high doses, had little or not effect on the type II isoenzyme or the nuclear Ca2+-calmodulin-stimulable, protamine-phosphorylating enzyme.

Animals↗

Total thyroparathyroidectomy in patients with thyroid cancers and changes in erythrocytic Mg levels following parathyroautotransplantation.

Parathyroid hormone (PTH) rapidly decreases in patients with thyroid cancers, even after autotransplantation following total thyroparathyroidectomy. Simultaneously, serum calcium (Ca) and erythrocytic Ca levels also decrease, and in some cases, tetanic symptoms caused by hypocalcemia may occur. Assuming that magnesium (Mg) might participate in the alteration of Ca and PTH levels, the postoperative changes in intracytoplasmic Mg levels of erythrocyte were determined for several days. In the present paper, red blood cells (RBC) were used as a substitute for general somatic cells and controls were taken from patients with breast cancers. Although the erythrocytic Mg levels of the patients with thyroid cancers showed almost no change until day 7, an apparent decrease was noted in the patients with breast cancers during the period from day 1 to day 7, with a significant difference being seen between the two groups. Assuming that the operative invasions were compatible between these two groups of patients, the difference may be explained by a rapid decrease of postoperative serum PTH in the patients with thyroid cancers.

Calcium↗

Influence of thyroparathyroidectomy and thyroxine replacement on Cu and Zn cellular distribution and on the metallothionein level and induction in rats.

Thyroid hormones are involved in copper and zinc distribution in rat tissues. We examined the influence of thyroparathyroidectomy (TPTY) and of a replacement therapy by T4 on Cu and Zn organ distribution. MT levels were also measured both in basal conditions and after induction by cadmium. The results confirm that a lack of T4 modified Cu and Zn in serum and tissues. In serum, TPTY increased Cu (+15%) and ceruloplasmin (+18%), and decreased Zn (-18%). In tissues, Cu was altered in liver (+13%), kidney (-24%), heart (-16%) duodenum (-18%), and Zn in liver (+25%) and kidney (-10%). The soluble fractions (100,000 g supernatant) were mainly affected in liver and kidney, and the subcellular fractions in heart and duodenum. MT levels were modified in basal conditions only in liver (+57%) and kidney (-36%). T4 administration partially prevented the effect of TPTY on both elements and MT concentrations. Therefore, no evidence is provided for a direct role of T4 in the metabolism of MT in a way comparable to the effects of glucocorticoids. However, MT could mediate the consequences of TPTY on metal distribution in certain organs, such as liver and kidney.

Animals↗

Distribution of 14 elements in various rat tissues following hypophysectomy, thyroparathyroidectomy, adrenalectomy, and castration.

The tissue distribution of 14 elements was simultaneously determined in rats 28 d after hypophysectomy (HPY), thyroparathyroidectomy (TPTY), adrenalectomy (ADY), and castration (CTN). The elements Na, K, Ca, Mg, Fe, S, P, Rb, Sr, Mn, Cu, and Zn were investigated in whole blood, plasma, brain, liver, kidney, heart, skeletal muscle, and bone. Additionally Mo was determined in kidney and liver. The following results were obtained: 1) With regard to hormone deficiency: HPY induced the most noticeable variations on all the elements tested owing probably to the direct and indirect effects of adenohypophyseal hormones. ADY led to the expected modification of Na and K but also to a Sr accumulation and a Rb depletion. TPTY induced a sharp decrease in plasma and tissues Ca, an increase in plasma P, but did not disturb the two elements in bone. An increase of Rb in many tissues and of Fe in heart, kidney, and liver were also observed. CTN had little consequences except in bone whose Cu and Fe contents were increased; 2) With regard to element variations: K, Mg, and S underwent little change. Discriminations were revealed between elements such as K and Rb, Ca and Sr, Ca and Mg, and Cu and Zn. The changes of Rb and Sr were consistent with regulatory mechanisms. The accumulation of Fe and Cu in tissues such as liver after HPY, TPTY, and ADY, suggest that the hormonal deficiencies could worsen the hemochromatosis and Wilson's disease; 3) With regard to plasma and tissues: No correlation appeared in element levels between plasma and other tissues. Brain was the least affected and liver, kidney and bone the most.

Adrenalectomy↗

Effects of thyroparathyroidectomy and of thyroxin and calcitonin on the tissue distribution of twelve elements in the rat.

The effects of thyroparathyroidectomy (TPTY) and of replacement therapy using thyroxin (T4) and calcitonin (CT) on the tissue distribution of elements were studied in the rat under semichronic conditions. The elements Na, K, Ca, Mg, Fe, S, P, Rb, Sr, Mn, Cu, and Zn were determined in whole blood, plasma, brain, liver, heart, kidney, skeletal muscle, and bone. TPTY modified concentrations of all elements tested but only small changes were observed for K, Mg, S, and P. The mineral bone composition was slightly modified, 28 d after TPTY, whereas plasma was the most altered. The consequences of TPTY were corrected fairly well by T4 for Na, Cu, Zn, Fe, and S, and by CT for K, P, Rb but with less efficiency for Ca. This study revealed that hormones of the thyroid gland, mainly T4, play an important role in the plasma and tissue balance of elements. It is suggested that T4 participates in tissue fixation of Cu, Zn, and Fe and that CT influences phosphoremia and cellular Ca binding.

Animals↗

Effect of thyroparathyroidectomy on the activities of thymidylate synthetase and thymidine kinase during liver regeneration after partial hepatectomy.

Thyroparathyroidectomy (TPTX) carried out at 72 h before partial hepatectomy (PH) reduced the induction of hepatic thymidylate synthetase (TS) and thymidine kinase (TK), which are rate-determining enzymes in DNA synthesis, at 24 h after PH. When TPTX was carried out at 24 h before PH, TK activity at 24 h after PH was not reduced at all, yet TS activity was reduced significantly. Thus the effect of TPTX differed in time dependence between TS and TK. The depression of TK activity in rats which were subjected to TPTX at 72 h before PH, was recovered by Ca2+ supplementation. This result demonstrated that the rise of TK activity in regenerating liver is regulated by plasma Ca2+. Since a high dose of tri-iodothyronine (T3) was required to cause elevation of the activities of these enzymes and DNA content in 24 h-regenerating liver of TPTX rats, the relative contribution of T3 to liver regeneration may be small.

Animals↗

Calcitonin and hepatic fatty acid synthesis: effect of thyroparathyroidectomy on the elevation of ATP citrate lyase activity by refeeding of starved rats.

The effect of thyroparathyroidectomy (TPTX) on ATP citrate lyase regulation, a rate-limiting enzyme of fatty acid synthesis in hepatic cytosol, was investigated in rats refed after a 24 h fast. ATP citrate lyase activity in the hepatic cytosol was increased 2-fold by refeeding. This increase was suppressed about 50% by TPTX. The suppression of the enzyme activity by TPTX was completely restored by administration of calcitonin (CT; 80 MRC mU/100 g body weight). This hormonal effect was also observed at 20 MRC mU/100 g dose of CT. CT administration to refeeding-TPTX rats produced a significant increase in the calcium content of the liver tissue and the cytosol. The cytosolic ATP citrate lyase activity increase with CT administration was completely blocked by treatment of cytosol with EGTA (10 microM). This inhibition was clearly reversed by addition of calcium ion (1.25-5.0 microM). In addition, CT-induced rise in enzyme activity was markedly reduced by the presence of W-7 (5 and 50 microM), a calmodulin inhibitor, in the enzyme assay system. The present results suggest that CT plays a role in the elevation of hepatic ATP citrate lyase activity brought about by refeeding of fasted rats, and that this hormonal regulation might depend on Ca2+-calmodulin.

ATP Citrate (pro-S)-Lyase↗

Effects of thyroparathyroidectomy, exogenous calcium, and short-term calcitriol therapy on the growth plate in renal failure.

Several factors have been implicated in the development of adynamic bone, including the use of calcium-containing phosphate binding agents, aggressive calcitriol therapy, and parathyroidectomy. To evaluate the effects of these interventions on the growth plate, weanling rats underwent sham nephrectomy (Control, n = 10) and 5/6 nephrectomy (Nx). In the nephrectomized group, animals underwent (a) thyroparathyroidectomy (Nx-TPTX, n = 7), (b) received exogenous calcium (Nx-Calcium, n = 10), (c) received short-term calcitriol therapy (Nx-D, n = 10), or (d) nephrectomized control (Nx-Control, n = 10). Higher serum calcium and lower PTH levels were demonstrated in Nx-Calcium and Nx-D animals. A decline in growth was demonstrated in Nx-Calcium and Nx-TPTX accompanied by shorter tibial lengths. The width of the growth plate was wider in Nx-Calcium animals due to an increase in the width of the hypertrophic zone and a decrease in the proliferative zone; these changes were accompanied by an impairment of chondroclastic resorption, lower gelatinase B/MMP-9 activity, decline in insulin-like growth factor-I (IGF-I) receptor, and lower histone-4 mRNA expression. Such findings in the growth plate, may partially contribute to the diminution of growth in these animals. Although growth was impaired in the Nx-TPTX animals, there were no significant changes demonstrated in the growth plate cartilage. Histone-4 transcripts, IGF-I receptor expression, and histochemical staining for chondroclasts were decreased in Nx-D animals. Thus, treatments used in the management of secondary hyperparathyroidism in renal failure have diverse effects on the growth plate of the young skeleton, and concurrent use of these interventions needs further evaluation.

Acid Phosphatase↗

Effects of thyroparathyroidectomy, parathyroid hormone, and PTHrP on kidneys of ovine fetuses.

The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1-34)], PTHrP-(1-34), and PTHrP-(1-141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) into the jugular vein of TxPTx fetuses (n = 5) at the rate of 1 nmol/h for 2 h, after a 1-nmol loading dose, significantly decreased the excretion rate of total calcium and increased the excretion rate of cAMP in fetal urine. Infusions of all three peptides resulted in significant increases in the concentration of total calcium in fetal plasma but had no effect on the plasma concentrations or urinary excretion rates of phosphate. Infusion of either PTH-(1-34), PTHrP-(1-34), or PTHrP-(1-141) also resulted in an increase in fetal urine osmolality and pH and a decrease in free water clearance in TxPTx fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Role of calcium in bone maturation arrest after thyroparathyroidectomy in the rat.

Thyroparathyroidectomy in the rat results in decreased plasma calcium and magnesium and increased phosphorus. The associated bone changes are decreased calcium, hydroxyproline, carbonate, and wholebone density. Bone magnesium, sodium, mineral density, and percent crystallinity are increased. The delayed matrix formation and mineralization previously identified by histologic techniques are herein characterized by direct measurement as arrest of the normal increase of hydroxyproline/matrix and percent mineral. The bone mineral present is of high density and x-ray-diffraction crystallinity, suggesting a decrease in the mineralization front high in the amorphous phase and/or small nondiffracting crystalloids. The chemical studies reveal that in the absence of available Ca, Mg and Na are substituted, and CO3 is decreased. The restoration of these plasma and bone abnormalities to normal by a diet high in CaCO3 adds further emphasis to the essential role of Ca in bone cell function.

Animals↗