Mitotic Rate of Rat Thyroid Follicular Cells In Vivo In Response to A Single Injection of Thyrotropin (Tsh)

The mitotic rate of thyroid follicular cells was assessed by a stathmokinetic method at intervals from 15 min to 24 hr after a single injection of 1 iu/kg of thyrotropin (TSH). the mitotic rate was increased 15 min after TSH and remained elevated for 3 hr. Two further peaks of mitotic activity were present at 9 hr and 24 hr after TSH. Serum TSH concentrations were increased from 5 min to 3 hr with a maximum at 1 hr.     

Mitotic Response to Wounding In Goitrous and Normal Rat Thyroid: Implications For Thyroid Growth Control

Abstract. Thyroid growth in the rat in response to a sustained elevation of serum thyrotropin (TSH) is limited by a progressive desensitization of the follicular cells to the mitogenic action of TSH which is not reversed by withdrawal of stimulation or by reduction of cell number. This study shows that, in thyroids which have reached a 'plateau' of growth, wounding induces a marked local follicular cell mitotic response which is equal in magnitude to that seen in control glands. This demonstrates that these cells, which are refractory to TSH, have not lost the capacity to divide. It is concluded that limitation of TSH-induced thyroid growth is not due to a non-specific loss of mitotic capacity resulting from severe hypothyroidism or goitrogen toxicity, or to an inherent limitation of the number of divisions which a follicular cell can undergo. the implications of these findings are discussed.     

In Vitro Growth of Rat Blastocyst under the Effect of Azathioprine

Rat blastocysts were isolated from the uterus on the 5th day after fertilization and set in culture. The effect of azathioprine (Imuran) on the blastocyst's development and on the early trophoblastic differentiation in vitro was investigated. Azathioprine, added to the medium of the blastocyst culture at various concentrations, dose dependently arrested development and had definite cytotoxic effect. In order to study the mechanism of action, a minimal dose of 5 μg/ml, which allowed the survival of about 60% of the blastocysts, was added to the medium after 48 hr of culturing. Under the effect of the substance the area of the spreading blastocyst cells was significantly restricted.
It was found, by autoradiographic methods, that the azathioprine affects the development by restraining DNA synthesis in the throphoblastic cells. Concomitantly RNA synthesis was inhibited and protein synthesis was reduced. The observations indicate, that the impairment of the in vitro differentiation of the blastocysts can be a result of the intracellular inhibitory action of the substance.     

Negative Effect of Iodide On the Survival of Newly Divided Epithelial Cells In Chronically Stimulated Rat Thyroid

Abstract. The aim of this work was to investigate some aspects of the thyroid epithelial cell kinetics during the iodide-induced involution of a hyperplastic goitre in the rat. Rats were made iodine-deficient for 6 months, and propylthiouracil (PTU) (0.15%) was added to the diet during the last 2 months. Thereafter, rats were refed with iodide and PTU was removed (day 0).
Forty-eight hours previously, all the rats were injected with tritiated thymidine ([³H]TdR) (1 μCi/g). Some animals were killed 1 hr or 24 hr after [³H]TdR injection (i.e. on day -2 and -1, day O corresponding to the restoration of a normal iodine diet); the other animals were killed after different delay periods and following L³H]TdR injection. Autoradiography of thyroid sections, iodine determination of plasma iodide and protein-bound iodine (PBI), and RIA of plasma thyroid stimulatory hormone (TSH) were performed. Plasma TSH concentration was very high on day O of iodide refeeding (3000 ± 330 ng/ml) and remained at this level until day 8. Plasma PBI was very low on day O, remained so until day 4 and greatly increased on day 8. Plasma iodide was also very low on day O, but markedly increased on day 1, then did not vary significantly until day 43 of iodine refeeding. Thyroid weight, elevated on day O, decreased relatively quickly until day 30, then more slowly until day 73.     

The Association of Thyroid Hormones and Tsh with the Metabolic Syndrome in Euthyroid Taiwanese Individuals

Objective: There are conflicting studies in euthyroid males and females regarding associations between thyroidrelated hormones and parameters of the metabolic syndrome (MetS). We investigated the association between serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations and MetS in euthyroid men and women.Methods: Taiwanese subjects aged 20 to 65 years who had undergone a voluntary health examination at a preventive examination agency in Taipei were enrolled in this cross-sectional study. The definition of MetS was suggested by the Bureau of Health Promotion, Department of Health, Taiwan. Euthyroidism was defined as TSH and free thyroxine (FT4) levels within the normal reference ranges while not taking any thyroid medication. We conducted multiple logistic regression to identify the ability of serum triiodothyronine (T3), FT4, and TSH concentrations to identify the relative risk for the presence of MetS and components of the MetS in euthyroid Taiwanese individuals.Results: A total of 8,207 Taiwanese subjects (mean age: men, 45.3 ± 9.9 years; women, 43.5 ± 9.3 years) were enrolled in this study. A total of 1,672 subjects (20.4%) were defined as having MetS; these subjects had significantly higher (P<.0001) mean age (48.4 ± 9.1 years vs. 43.6 ± 10.7 years), prevalence of men (78.7% vs. 53.4%), and smoking (16.8% vs. 11.6%) than those without MetS. The median TSH, FT4, and T3 levels in all subjects were 1.70 mIU/L, 1.41 ng/dL, and 1.20 ng/mL, respectively. Higher T3 and lower FT4 values rather than TSH increased the odds ratio for MetS in men and women after adjusting for smoking and age, particularly for the association of T3 and MetS in women (uppermost quartile versus lowermost quartile: odds ratio, 2.4; 95% confidence interval, 1.6 to 3.5; P for trend <.0001).Conclusion: In euthyroid Taiwanese men and women, relatively high serum T3 concentrations was most strongly associated with the presence of the MetS; relatively low serum T4 was less strongly related, and serum TSH levels were not associated with the MetS. It is not known if the relationship of serum T3 and T4 to the MetS is causal.Abbreviations:BMI = body mass indexFT4 = free thyroxineMetS = metabolic syndromeOR = odds ratioT3 = triiodothyronineTSH = thyroid-stimulating hormoneWC = waist circumference     

In Vitro Reparative Dentin: a Biochemical and Morphological Study

In this study, starting from human dental pulp cells cultured in vitro, we simulated reparative dentinogenesis using a medium supplemented with different odontogenic inductors. The differentiation of dental pulp cells in odontoblast-like cells was evaluated by means of staining, and ultramorphological, biochemical and biomolecular methods. Alizarin red staining showed mineral deposition while transmission electron microscopy revealed a synthesis of extracellular matrix fibers during the differentiation process. Biochemical assays demonstrated that the differentiated phenotype expressed odontoblast markers, such as Dentin Matrix Protein 1 (DMP1) and Dentin Sialoprotein (DSP), as well as type I collagen. Quantitative data regarding the mRNA expression of DMP1, DSP and type I collagen were obtained by Real Time PCR. Immunofluorescence data demonstrated the various localizations of DSP and DMP1 during odontoblast differentiation. Based on our results, we obtained odontoblast-like cells which simulated the reparative dentin processes in order to better investigate the mechanism of odontoblast differentiation, and dentin extracellular matrix deposition and mineralization.Key words: dental tissue, in vitro differentiation, DMP1, DSP, type I collagen     

Growth Fraction and Cycle Duration of Hepatocytes In the Three-Week-Old Rat

The proliferation of hepatocytes in the liver of 3-week-old rats has been investigated by autoradiographic methods. This investigation is a continuation of earlier work on the same topic (Schultze & Maurer, 1972; 1973). 21 days after birth, 102 rats received a single injection of ³H-TdR. the percentage of labelled mitoses was then determined 1 hr later and at various times throughout the interval up to 12 days after application of ³H-TdR. In agreement with earlier work, a first peak of labelled mitoses was found 7 hr after ³H-TdR injection. the area under the peak indicates an S phase duration of 8 hr. In addition a second very broad peak of labelled mitoses was found between 2 and 12 days after pulse labelling. the analysis of the results leads to the conclusion that the hepatocytes of the 3-week-old rat have a growth fraction close to 1 and a doubling time of 6–7 days. This is at variance with earlier results of Post, Huang & Hoffman (1963) and Grisham (1969) who had derived a value of 21.5 hr for the duration of the cell cycle and a value of only 0. 1–0.2 for the growth fraction of the hepatocytes.     

Necrotic Debris In Thyroid Aspirates: A Feature of Follicular Carcinoma of the Thyroid

Fine needle aspirates from 44 follicular thyroid tumours (30 adenomas, 14 carcinomas) have been studied. All aspirates contained neoplastic cells in follicular and trabecular arrangements. The individual tumour cells showed varying degrees of anisonucleosis and nuclear pleomorphism. Colloid was scanty or absent from all smears. Granular or filamentous necrotic material was observed in both biopsies and smears from one moderately and two poorly differentiated follicular carcinomas, but in none of the adenomas. This suggests that necrotic debris may be a feature of follicular carcinoma of the thyroid.     

Iron Regulation in the Developing Rat Brain: Effect of In Utero Ethanol Exposure

Abstract: Fetal alcohol syndrome produces defects that parallel abnormalities associated with early iron deficiency. Hence, we examined the effects of prenatal exposure to ethanol on iron, transferrin, and ferritin concentrations. The subjects were the offspring of pregnant rats fed an ethanol-containing diet (Et), pair-fed an isocaloric control diet (Ct), or fed chow and water. The amounts of iron, transferrin, and ferritin were assessed in three CNS regions (cerebral cortex, subcortical forebrain, and brain-stem). In all three segments of the control rats, iron, transferrin, and ferritin levels decreased during the first 2 postnatal weeks, reached a minimum during week 3, and then rose to adult levels. This pattern was delayed by ethanol treatment, e.g., the minimal concentrations in iron, transferrin, and ferritin in the Et-treated rats were achieved later (3 days, 7 days, and 2 weeks, respectively) than they were in the Ct-treated rats. Ethanol-induced alterations in iron homeostasis persisted into adulthood; iron concentration was reduced, transferrin concentration was unaffected, and ferritin concentration was increased. The net result was that the timely delivery and bioavailability of iron were compromised by ethanol exposure. The defects in iron regulation are permanent and may underlie ethanol-induced abnormalities in iron-dependent growth processes such as myelination.     

Thyroid Hormone Receptors in the Developing Rat Brain

It is widely believed that the adult mammalian brain is insensitiveto thyroid hormones unlike the neonatal brain which is criticallydependent on these hormones for the development of normal structureand function. Recent studies have demonstrated the presenceof limited capacity, high affinity, triiodothyronine (T3) bindingnuclear sites in tissues that are considered responsive to thyroidhormones. Furthermore, there is evidence from studies on peripheraltissues that these T3 binding sites act as true receptors ininitiating thyroid hormone action. This report examines whetherthe higher sensitivity of neonatal brain to thyroid hormonesand the purported decline in sensitivity in adulthood are relatedto changes in the concentration and affinity characteristicsof thyroid hormone receptors in rat cerebral nuclei. Analysisof Scatchard plots of in vitro T3 binding data indicate thatcerebral nuclei from adult rats contain T3 specific nuclearbinding sites at a concentration comparable to that presentduring the period when the brain is critically dependent onthe presence of thyroid hormones and exceed that in the liver,a tissue generally considered thyroid sensitive. Neonatal thyroidectomysignificantly increased the number of binding sites. The resultsshow that the apparent unresponsiveness of the cerebral cortexof adult rats to thyroid hormones is not due to the absenceor a low density of T3 nuclear binding sites. The significanceof these results is discussed.     

Alterations In Thyroid Hormone Levels Following Growth Hormone Replacement Exert Complex Biological Effects

Objective: Alterations in the thyroid axis are frequently observed following growth hormone (GH) replacement, but uncertainty exists regarding their clinical significance. We aimed to compare fluctuations in circulating thyroid hormone levels, induced by GH, to changes in sensitive biological markers of thyroid hormone action.Methods: This was a prospective observational clinical study. Twenty hypopituitary men were studied before and after GH replacement. Serum thyroid-stimulating hormone (TSH), thyroid hormones, and insulin-like growth factor 1 were measured. Changes in thyroid hormone concentrations were compared to alterations in resting metabolic rate and cardiac time intervals. Health-related quality of life (QOL) was assessed by disease-sensitive and generic questionnaires.Results: Following GH replacement, free thyroxine concentration declined and free triiodothyronine level increased. Resting energy expenditure increased, particularly in subjects with profound hypopituitarism, including TSH deficiency (16.73 ± 1.75 kcal/kg/min vs. 17.96 ± 2.26 kcal/kg/min; P = .01). Alterations in the thyroid axis were more pronounced in subjects with a low/normal baseline respiratory quotient (RQ) who experienced a paradoxical rise in RQ (0.81 vs. 0.86; P = .01). Subjects with a high baseline RQ experienced a slight but nonsignificant fall in RQ without alteration in thyroid axis. The isovolumetric contraction time was shortened during the study; however, this did not reach statistical significance. Improvements in QOL were observed despite alterations in thyroid axis.Conclusion: Changes in the thyroid axis following GH replacement are associated with complex tissue-specific effects. These fluctuations may induce a hypothyroid phenotype in some tissues while appearing to improve the biological action of thyroid hormone in other organs.Abbreviations: AGHDA = Assessment of Growth Hormone Deficiency in Adulthood; CHOox = carbohydrate oxidation; ET = ejection time; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; GHD = growth hormone deficiency; HB-RQ = high baseline respiratory quotient; HPT = hypothalamic-pituitary-thyroid; ICT = isovolumetric contraction time; IGF-1 = insulin-like growth factor 1; IRT = isovolumetric relaxation time; LB-RQ = low baseline respiratory quotient; LV = left ventricular; NHP = Nottingham Health Profile; QOL = quality of life; REE = resting energy expenditure; RQ = respiratory quotient; rT3 = reverse triiodothyronine; SF-36 = Short Form 36; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; TT3 = total triiodothyronine; TT4 = total thyroxine     

Suppression of Reticuloendothelial Function in the Rat with Cyclophosphamide

Effects of cyclophosphamide immunosuppressive therapy upon reticuloendothelial function in the rat have been studied. Numerous side effects including leukopenia, hematuria, diarrhea, hemorrhagic cystitis, and petechial hemorrhage in the lungs and the small bowel were observed. Studies utilizing (32)P-labeled bacteria revealed no change in the ability of the liver, spleen, lungs, or kidneys to ingest Pseudomonas aeruginosa. Utilization of labeled Staphylococcus aureus revealed an impairment of splenic uptake in animals receiving the maximal dose of 100 mg/kg. However, the liver, lungs, and kidneys were not affected. Although no generalized defect in the ingestive powers of these organs was observed, the ability of the lungs and kidneys from treated animals to kill ingested bacteria was significantly impaired. Regardless of the bacterium employed, the lungs and kidneys revealed a decrease in bactericidal ability with increasing drug dosages. Neither the liver nor the spleen from treated animals exhibited any decrease in bactericidal effect. Possible causes of this reduction in the bactericidal ability of alveolar and renal tissue following immunosuppression with cyclophosphamide are discussed.     

重组人生长激素的主要药效学研究

参照文献方法,观察了ｒｈＧＨ对正常大鼠（３月龄,平台期）生长发育作用的影响,ｉｍ,ｒｈＧＨ（０．０５、０．１５、０．４５ｍｇ．ｋｇ＾－１．ｄ＾－１）,连续１５天,结果表明：ｒｈＧＨ（０．１５、０．４５ｍｇ．ｋｇ＾－１．ｄ＾－１）同阳性对照生长激素ＮＩＢＳＣ标准品）一样,均可明显促进正常平台期大鼠的体重及尾长增加,大剂量组还可明显促进肝、肾及骨骼的生长发育,使肝、肾重量增加,胫骨骨骺端距离增大,同     

Effect of Cold Exposure on Thyroid Hormone Metabolism and Nuclear Binding in Rat Brain

In this study we examined whether adult rat brain tissue (cerebral hemispheres) would under cold exposure respond with changes in the local metabolism and nuclear binding of thyroid hormones (T₃, T₄). Adult, control rats kept at 22°C and cold exposed (4°C, 20 h) rats were injected with trace of ¹²⁵I-T₄ or ¹²⁵I-T₃ returned to their respective environment and sacrificed four hours later. The radioactive hormonal forms were identified and quantified in the cytoplasmic and nuclear fractions. It was found that in cold exposed rats injected with ¹²⁵I-T₄, the total cytoplasmic radioactivity was higher than that of controls. This increase was not associated with ¹²⁵I-T₄ but it reflected an increase (88 %) in its deiodination product ¹²⁵I-T₃ (¹²⁵I-T₃ (T₄)). Although total cytoplasmic ¹²⁵I-T₄ did not change, there was a decrease (28%) in its protein free cytoplasmic fraction. ¹²⁵I-T₃ (T₄) and ¹²⁵I-T₄ bound to the nuclear fraction were found to decrease by 58 and 46% respectively. Cold exposed animals injected with ¹²⁵I-T₃ also showed an increase in cytoplasmic ¹²⁵I-T₃ (81%) and a decrease in ¹²⁵I^– (40%) whereas ¹²⁵I-T₃ bound to the nuclear fraction decreased by 64%. These results indicate that cold exposure of rats decreases brain local T₃ metabolism and nuclear binding while it does not effect local T₄ metabolism.     

Benzodiazepine Receptor and Thyroid Hormones: In Vivo and In Vitro Modulation

In rats rendered hyperthyroid by chronic treatment with L-triiodothyronine (T3) hormone there was a 21 and 27% decrease, respectively, in the number of binding sites for [3H]flunitrazepam ([3H]FNZ) and [3H]ethyl-beta-carboline-3-carboxylate ([3H]beta-CCE) without changes in affinity for the two ligands. Two weeks after thyroidectomy there was a 44% increase in [3H]FNZ sites and a 17% increase in [3H]beta-CCE binding sites. In vitro we found that T3 produces a decrease in Bmax and an increase in KD, both changes being characteristic of a mixed type of inhibition. Thyroid status dramatically affected the Ki of T3 in displacing [3H]FNZ from sites on isolated membranes of the cerebral cortex: in hypothyroid rats the Ki value was 0.9 microM, whereas in hyperthyroid rats, it was 83 microM, a 92-fold difference. In control rats, the Ki was 11 microM. These findings are discussed in relation to a possible modulation of benzodiazepine receptors by thyroid hormones.     

Effect of Sodium Taurocholate on the In Vitro Growth of Lactobacilli

Abstract The effect on growth of a conjugated bile salt (sodium taurocholate) at physiological concentration was determined using cultures of Lactobacillus strains of murine origin. The bile salt stimulated the growth of one strain, did not affect the growth of another, but inhibited the growth of strains that produced relatively large amounts of the enzyme bile salt hydrolase. Comparison of the growth of isogenic strains that differed in the ability to produce bile salt hydrolase demonstrated that inhibition of growth was due to the accumulation of cholic acid in the culture medium as a result of the enzyme activity. Received: 15 January 1996; Revised: 26 March 1996; Accepted: 29 March 1996     

Effect of 6-Phosphogluconate on Phosphoglucose Isomerase in Rat Brain In Vitro and In Vivo

The activity of phosphoglucose isomerase, its kinetic properties, and the effect of 6-phosphogluconate on its activity in the forward (glucose 6-phosphate----fructose 6-phosphate) and the reverse (fructose 6-phosphate----glucose 6-phosphate) reactions were determined in adult rat brain in vitro. The activity of phosphoglucose isomerase (in nmol/min/mg of whole brain protein) was 1,865 +/- 20 in the forward reaction and 1,756 +/- 32 in the reverse reaction at pH 7.5. It was 1,992 +/- 28 and 2,620 +/- 46, respectively, at pH 8.5. The apparent Km and Vmax of phosphoglucose isomerase were 0.593 +/- 0.031 mM and 2,291 +/- 61 nmol/min/mg of protein, respectively, for glucose 6-phosphate and 0.095 +/- 0.013 mM and 2,035 +/- 98 nmol/min/mg of protein, respectively, for fructose 6-phosphate. The activity of phosphoglucose isomerase was inhibited intensely and competitively by 6-phosphogluconate, with an apparent Ki of 0.048 +/- 0.005 mM for glucose 6-phosphate and 0.042 +/- 0.004 mM for fructose 6-phosphate as the substrate. With glucose 6-phosphate as the substrate, at concentrations from 0.05 to 0.5 mM, the activity of the enzyme was inhibited completely in the presence of 0.5-2.0 mM 6-phosphogluconate. With 0.05-0.2 mM fructose 6-phosphate as the substrate, it was inhibited greater than or equal to 85% at the same concentrations of the inhibitor. No significant changes were observed in the values of Km, Vmax, and Ki for phosphoglucose isomerase in the brain of 6-aminonicotinamide-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect Of Different Doses Of Noradrenaline Against Ischemia-induced Ventricular Arrhythmias In Rat Heart In Vivo

Background

The present study was designed to evaluate the preconditioning effect of different doses of noradrenaline on ischemia-induced ventricular arrhythmias in open chest anesthetized rats.

Methods

The anaesthetized rats were subjected to 25 min of regional ischemia by left descending coronary artery (LAD) occlusion. In sham group, surgical procedures were done but ischemia was not applied. In control rats, saline was injected prior to ischemia. In noradrenaline groups, rats pretreated with three different doses of noradrenaline (respectively, 0.5, 1 and 2 μg/kg, IV).

Results

In control rats, induction of ischemia shortened the QTc (corrected QT) interval (ms) and led to occurrence of ventricular arrhythmias. Administration of low-dose of noradrenaline prevented shortening of the QTc interval during ischemia but could not significantly attenuate severity and incidences of arrhythmias. Injection of mid-dose of noradrenaline stabilized the QTc during ischemia and reduced severity of arrhythmias. Pretreatment with high-dose of noradrenaline significantly prolonged the QTc interval and declined severity and incidence of arrhythmias.

Conclusions

Noradrenaline dose-dependently attenuated ischemia-induced ventricular arrhythmias.