Influence of oral administration of sulfamethazine on thyroid hormone levels in Fischer 344 rats

Fischer 344 rats (810 of each sex) were divided into treatment groups and fed diets containing 0, 10, 40, 600, 1200, or 2400 ppm sulfamethazine. Serum samples were analyzed for levels of thyroid-stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), and T3 uptake after 12, 18, or 24 mo of continuous dosing. There were no statistically significant differences in T3 levels or percent T3 uptake for either sex after any of the exposure periods. The serum T4 levels were lower (p less than 0.05) for females dosed at 1200 and 2400 ppm for 18 mo and for males dosed at 600, 1200, or 2400 ppm sulfamethazine for 24 mo than for those dosed at levels of 40 ppm or less. Serum TSH levels showed a general increasing trend (but not statistically significant) among animals receiving 600 ppm or more sulfamethazine. There was a significant dose-related reduction in (T3 + T4)/TSH ratio for both sexes (p less than 0.05) after 18 and 24 mo of exposure at dose levels of 600 ppm or more. A lack of response at 12 mo may have been due to the shorter treatment time. At each sacrifice period both sexes of rats fed sulfamethazine at 1200 and 2400 ppm had significantly heavier (p less than 0.05) thyroid weights than animals fed control diet. The heavier thyroid weights in the dosed animals may have resulted from increased TSH levels. The cause of reduction in serum T4 was not clearly evident. Therefore, the thyroid hormone to pituitary feedback mechanism apparently compensated for sulfamethazine effects in most animals. This would suggest that the thyroid gland was not irreversibly affected.     

甲状腺激素对免疫抑制药物作用的影响

甲状腺片(150mg.kg~(-1).d~(-1),ig×10d和200mg.kg~(-1).d~(-1),ig×10d)能显著促进正常成年小鼠对二硝基氯苯(DNCB)所致的皮肤迟发型超敏反应(DH)。在连续应用甲状腺片200mg.kg~(-1).d~(-1)ip×10d的小鼠,环磷酰胺(25mg.kg~(-1).kg~(-1)ip×10d和30mg.kg~(-1).d~(-1),ip×10d)以及氢化可的松(25mg.kg~(-1).d~(-1),im×10d)抑制小鼠的DNCB所致DH的作用减弱甚至消失。     

植物性神经对大鼠甲状腺T_4、T_3分泌的影响

本工作在观察去垂体大鼠血中T_4、T_3动态变化的基础上,主要对喉返神经在调节甲状腺激素分泌方面的作用作了初步的探讨,并观察了通过植物性神经传入的光和冷的刺激对甲状腺T_4、T_3分泌的影响。结果表明:大鼠在去垂体后11d中,血中T_4水平正常,此后逐渐下降;持续光照有助于对去垂体大鼠血中T_4、T_3正常水平的维持;喉返神经对甲状腺T_4、T_3的分泌可能有抑制作用;急性寒冷刺激的甲状腺T_4、T_3的分泌与下丘脑—垂体—甲状腺轴的活动有关。     

炎调方对脓毒症急性肺损伤大鼠肺组织髓过氧化物酶和丙二醛水平的影响

目的 观察炎调方对脓毒症急性肺损伤(ALI)大鼠肺组织髓过氧化物酶(MPO)、丙二醛(MDA)水平的影响。方法 清洁级健康雄性SD大鼠随机分为对照组、假手术组、模型组、炎调方组、地塞米松组,炎调方组ig 9.9 g/kg炎调方,地塞米松组ig 0.45 mg/kg地塞米松,每天给药1次,连续给药3 d。末次ig 2 h后采用盲肠结扎穿孔术(CLP)制备脓毒症ALI模型,分别于造模后24 h处死动物,进行肺组织HE染色,测定各组大鼠湿/干重比(W/D),肺组织MPO、MDA水平。结果 模型组大鼠肺组织损伤程度、MPO及MDA水平较对照组及假手术组显著增高(P<0.01),炎调方组、地塞米松组肺组织损伤程度、MPO及MDA水平较模型组显著降低(P<0.05、0.01)。结论 炎调方可有效减轻脓毒症ALI大鼠的炎症及氧化应激反应。     

Effect of amiodarone on phospholipid content and composition in heart, lung, kidney and skeletal muscle: relationship to alteration of thyroid function

To investigate the effect of chronic amiodarone treatment on tissue phospholipids, a marker of amiodarone-induced toxicity, and to test the hypothesis that tissue phospholipids changes are related to amiodarone-induced effects on thyroid function, male Wistar rats were treated with amiodarone and tissue phospholipid content and fractions were assessed. Twenty-six animals were allocated to 4 groups: (i) group 1 received amiodarone, 20 mg/kg per day, for 3 weeks (n = 6); (ii) group 2 received amiodarone for 5 weeks (n = 6); (iii) group 3 received drug for 6 weeks (n = 6), and (iv) group 4 (control group) received the diluent for 6 weeks (n = 8). Total phospholipid content of lung, kidney and skeletal muscle but not heart was increased after 3 weeks of amiodarone treatment. With longer durations of treatment, the phospholipid content was significantly (p < 0.05) reduced in all four organs. The proportion of phospholipids in different classes was modified by amiodarone treatment with the most consistent changes across different tissues being reductions in phosphatidylethanolamine and increases in phosphatidylserine. Serum thyroxine concentration was significantly (p < 0.05) reduced at 5 weeks of treatment and thereafter. There was a significant correlation between serum thyroxine and total phospholipid concentration in heart (r = 0.555; p < 0.05) and lung (r = 0.502; p < 0.05). For heart, there was a significant correlation between serum thyroxine and the distribution of phospholipid classes, mainly for phosphatidylserine even after considering amiodarone dose. The same was found in the lung. In the kidney and skeletal muscle, there was a significant (p < 0.05) correlation between serum thyroxine and the proportion of phospholipids in phosphatidylcholine and sphingomyelin. In conclusion, this study presents the novel finding of a biphasic tissue phospholipid response to amiodarone characterized by a short term increase in phospholipids in lung, kidney and skeletal muscle but not the heart followed by a long term decline in phospholipids in all four organs that is likely due to a direct action of amiodarone on phospholipid metabolism and potentially the result of amiodarone-induced reduction in thyroid function.     

Acute effect of thyroid hormone on insulin secretion in rats

To elucidate the mechanism of thyroid hormone-induced hyperinsulinemia, the acute and direct effect of thyroid hormone administration on insulin secretion was investigated in rats in vivo and in vitro. In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion. The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL, while blood glucose and plasma glucagon were unchanged. This phenomenon was inhibited completely by the preadministration of oxprenolol hydrochloride (2 mg/kg, s.c.), and inhibited partly by the preadministration of metoprolol tartrate (35 mg/kg, s.c.). These results suggest that thyroid hormone induces hyperinsulinemia via beta-adrenergic stimulation in the rat.     

抗癫痫药物对癫痫患儿甲状腺激素水平的影响

目的　观察抗癫痫药物对患儿甲状腺激素水平的影响。方法　用放射免疫法对患儿血清中三碘甲状腺原氨酸 (T3) ,甲状腺素 (T4 ) ,游离三碘甲状腺原氨酸 (FT3) ,游离甲状腺素 (FT4 )和促甲状腺素 (TSH)水平进行测定。结果　卡马西平、苯巴比妥及两药与丙戊酸钠合用的患儿血清 T4 ,FT4 水平明显降低。而单用丙戊酸钠的患儿血清中甲状腺激素无明显改变。结论　肝酶诱导剂的抗癫痫药物可影响血中甲状腺激素的水平 ,在药物控制癫痫发作的同时应注意其水平的改变     

Influence of Ukrain on the nuclear thyroid hormone receptors after short-term gamma-irradiation

The ability of Ukrain, a semi-synthetic alkaloid thiophosphoric acid derivative (NSC-631579), to influence thyroid hormone levels in plasma and nuclear thyroid hormone receptors in female rat liver, as well as to modify the effects of short-term whole body gamma-irradiation on nuclear thyroid-hormone receptors in the liver was evaluated after intraperitoneal administration of the drug at 0.4 mg/kg body weight. Ukrain had no effect on the concentration of thyroid hormones in rat blood and increased the concentration of thyroid hormone receptors in the liver of intact rats during the first 2 months after administration. Ukrain normalized the level of nuclear thyroid hormone receptors influenced by short-term whole body gamma-irradiation of rats with 1 Gy, beginning from the first day after administration of the drug. Thus, Ukrain can minimize the consequences of irradiation in the endocrine system of experimental animals.     

Influence of iodine-deficiency on thyroid hormones homeostasis in rats

Little is known about the kinetics and metabolism of thyroid hormones in the hypothyroid state. In order to optimize hormone replacement therapy, it is important to understand variations in the kinetics and metabolism of thyroid hormones. To investigate these factors, we monitored serum thyroxine (T?) and triiodothyronine (T?) levels in iodine-deficient diet (ID) rats using online solid-phase extraction liquid chromatography-mass spectrometry/mass spectrometry (Online SPE LC-MS/MS). Furthermore, we evaluated supply and turnover rates of T? in ID rats using a stable isotope-labeled T? ([13C?]T?). Although serum T? levels gradually declined after beginning ID treatment, T? levels were unchanged throughout the experimental period. After intravenous administration of [13C?]T? to ID rats, [13C?]T? levels were monitored. We previously reported that significant differences of supply and turnover rates for T? were observed in surgically thyroidectomized (Tx) rats. Surprisingly, there were no differences of supply and turnover rates for T? between ID rats and intact rats. In conclusion, there were significant differences of supply and turnover rates for T? between the hypothyroid states of ID and Tx rats. In ID rats, T? might be preferentially biosynthesized in the thyroid, and ID treatment might not affect T? kinetics. Our method, online SPE LC-MS/MS monitoring using a stable isotope tracer, has the potential to be used as a diagnostic tool to investigate the pathogenesis of thyroid disease and is valuable for optimizing the dosage in thyroid hormone replacement therapy.     

Effects of thyroid hormone on angiotensinogen and renin messenger RNA levels in rats

We studied the expression of angiotensinogen and renin genes in rats treated with 3,3',5-triiodo-L-thyronine (T3) at doses of 0.1 and 1 mg/kg of body weight. Liver angiotensinogen mRNA increased by 2 to 3 times 8 to 12 hours after T3-treatment. This increase was dose-related. Plasma angiotensinogen concentration (PAC) increased 12 hours after T3-treatment. Brain and renal angiotensinogen mRNA levels and the renal renin mRNA level remained the same throughout the experimental periods. These results suggest that the thyroid hormone initially increases angiotensinogen mRNA and leads to an increase in the production of angiotensinogen in the liver followed by an elevation of PAC.     

Influence of ambroxol on lung tissue penetration of amoxicillin

Lung amoxicillin levels were assessed in tissue obtained from 16 patients who underwent lung resection due to different pulmonary diseases. In this double-blind placebo controlled study patients were allocated to two groups in randomized order; one group received amoxicillin 1000 mg t.i.d. (n = 8) and the other amoxicillin 1000 mg + ambroxol 60 mg t.i.d. (n = 8). A trend towards higher antibiotic lung tissue levels was observed in patients who received the antibiotic together with the mucolytic agent. The ratio pulmonary tissue/serum amoxicillin levels reached a significant difference being higher in the amoxicillin plus ambroxol group than in the other one (0.411 +/- 0.04 vs 0.672 +/- 0.07; p less than 0.01), even if the amoxicillin plasma levels were lower. A possible effect of ambroxol on lung tissue penetration of amoxicillin is suggested and discussed.     

Phosphatidylcholine metabolism in lung microsomes and lung surfactant of rats exposed intratracheally to coal fly ash

The effect of intratracheal administration of fly ash has been studied on lung microsomal and lung surfactant phosphatidylcholine (PC) metabolism in rats using [methyl-14C]choline and [methyl-14C]methionine. Fly-ash administration significantly increased total phospholipids, PC, phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) of lung surfactant. Fly-ash administration stimulated the formation of lung microsomal PC (as measured by the incorporation of labeled precursors) both by the cytidine 5'-diphosphate (CDP)-choline pathway and by the N-methylation pathway, but this stimulation was fourfold higher in the latter case and only twofold higher in the former as compared to the control. Likewise, the secretion of PC formed by the N-methylation pathway was sixfold higher as compared to the control whereas secretion of PC formed by the CDP-choline pathway was only threefold higher as compared to the control. Fly-ash administration further increased total saturation and decreased unsaturation in PC, PE, and lysophosphatidylcholine (LPC) of lung and in PC, PE, LPC, and PG of lung surfactant as compared to the controls.     

甲状腺功能对地西泮及其代谢产物在大鼠体内代谢的影响

目的：研究甲状腺功能对地西泮及其代谢物的药代动力学影响。方法：采用HPLC技术，测定不同甲状腺功能状态时，大鼠血液中地西泮及其体内主要代谢产物去甲基地西泮的浓度。结果：甲亢组大鼠地西泮在体内消除加速，峰浓度下降，AUC减少，消除T1/2缩短。甲减组大鼠则消除减慢，峰浓度增高，AUC增大，消除孔。延长。而其主要代谢产物去甲地西泮的药动学参数则相反。结论：甲状腺功能提高时，大鼠对地西泮的代谢能力明显增加，消除加速；而甲腺功能降低则相反。     

Radon-induced proteomic profile of lung tissue in rats

The aim of this study was to investigate the differential expression of proteins in lung of rats following long-term exposure to radon. The total proteins of lung tissue from Wistar rats exposed to radon for cumulative doses up to 100, 200, or 400 WLM (working level months) were isolated by two-dimensional electrophoresis (2-DE) and analyzed with ImageMaster 2D Platinum software. Comparison of the 2-DE images between the control and radon-exposed groups resulted in 14 upregulated and 9 downregulated protein spots, of which 15 were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) or matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). The simultaneous up-expressions of RAGE and S100A6 indicated that both proteins might be applied as biomarkers for lung injury induced by long-term radon exposure.     

Influence of luteinizing hormone releasing hormone (LHRH) on the behavioral effects of amphetamine in rats

The influence of luteinizing hormone releasing hormone (LHRH) on the behavioral effects induced by several doses of D-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg IP) was studied. A dose response relation was previously established for the effects of LHRH (50, 100 and 200 micrograms/kg SC) on acquisition and retention of conditioned avoidance responses (CARs). The neuropeptide impaired acquisition and improved retention of CARs, without modifying spontaneous motor activity. Pretreatment with 100 micrograms/kg of LHRH antagonizes the enhancement in acquisition of CARs due to D-amphetamine 0.5, 1.0 and 2.0 mg/kg, the impairment in retention induced by amphetamine 1.0 and 2.0 mg/kg, and the hypermotility and the increased rearing behavior induced by amphetamine 1.0 and 2.0 mg/kg. These results suggest that brain catecholamines, particularly dopamine, could play a role in the behavioral effects of LHRH. Interactions between LHRH and central dopaminergic mechanisms are discussed.     

乌司他丁对失血性休克大鼠肺组织损伤的保护作用

目的研究乌司他丁预处理对失血性休克大鼠肺组织损伤的保护作用。方法将雄性SD大鼠随机分为对照组、模型组和乌司他丁3、6万U/kg组,每组各8只。对照组、模型组通过尾静脉在20 min内微量泵注5 mL生理盐水,乌司他丁组尾iv 3、6万U/kg乌司他丁溶液5 mL。4 h后,按30 mL/kg经大鼠股动脉通道在10 min之内匀速抽取血液诱发失血性休克。维持休克状态60 min后,抽取的血液和乳酸林格氏液(30 mL/kg)在30 min内通过尾静脉匀速输注到大鼠体内复苏。在复苏后4 h测定大鼠肺组织超氧化物歧化酶(SOD)、丙二醛(MDA);采用Western blotting法检测Bcl-2、Bax和caspase-3蛋白表达量;测量支气管肺泡灌洗液(BAL)中的蛋白质和白细胞(WBC)含量。进行肺组织学观察。结果与模型组比较,6万U/kg乌司他丁预处理使肺组织SOD活性显著升高,MDA下降(P0.05)。与模型组比较,6万U/kg乌司他丁预处理使肺组织Bcl-2表达显著上升,Bax和caspase-3表达显著减弱(P0.05)。与模型组比较,6万U/kg乌司他丁预处理使肺组织BAL中蛋白、WBC含量显著减少(P0.05)。结论 6万U/kg乌司他丁预处理对缺血再灌注大鼠肺损伤具有保护作用,其作用机制是改善肺组织的抗氧化作用。