糖尿病与血清甲状腺激素水平变化的关系探究

目的：探究糖尿病与甲状腺素及促甲状腺激素(TSH)血清水平的关系。方法选择本院2013年1月~2014年1月收治的120例糖尿病患者,同时选取120例年龄、性别相匹配的糖耐量正常体检者作为对照组,测定两组患者血清的FT3、FT4及TSH水平。结果对照组和糖尿病组FT3的平均值分别为(4.94±1.72)pmol/L和(4.13±1.44)pmol/L;对照组和糖尿病组FT4的平均值分别为(14.33±3.13)pmol/L和(14.27±4.32)pmol/L;对照组和糖尿病组TSH的平均值分别为(2.72±1.44)mIU/L和(2.81±1.36)mIU/L。对照组与糖尿病组患者FT3水平比较,差异有统计学意义(P<0.05)。结论加强对糖尿病患者甲状腺功能指标的检测,早期诊断防治糖尿患者中无症状的甲状腺功能异常。     

Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development

Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case–control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development.     

The effect of acute nicotine administration on plasma levels of the thyroid hormones and corticosterone in the rat

The effects of a single intraperitoneal injection of nicotine hydrogen tartrate (200 μg/kg) on the plasma levels of thyroxine, triiodothyronine and corticosterone were monitored over a 24 hour period. Nicotine did not alter the plasma levels of either of the thyroid hormones but did produce a significant increase in plasma corticosterone, an effect which peaked at 20 min post-injection and lasted for 45 min.     

Effects of Ibuprofen on hematological, biochemical and enzymological parameters of blood in an Indian major carp, Cirrhinus mrigala

In the present investigation, the most commonly used pharmaceutical drug Ibuprofen (IB) was exposed to an Indian major carp Cirrhinus mrigala under static bioassay method to estimate its toxicological effects for a period of 35 days. The median lethal concentration (LC 50) of IB to the fish C. mrigala for 24h was found to be 142 ppm. In sublethal treatment (1/10th of LC 50 24h value, 14.2 ppm), a significant decrease in erythrocyte (RBC), mean cellular hemoglobin concentration (MCHC) and plasma protein levels were observed throughout the study period when compare to that of their respective controls. In contrast, haemoglobin (Hb), hematocrit (Hct), mean cellular volume (MCV), mean cellular hemoglobin (MCH), leucocyte (WBC), plasma glucose and alanine transaminase (ALT) levels were increased in this study period. On the other hand, a mixed trend was noticed in aspartate aminotransaminase (AST) enzyme activity. Alterations of these parameters can be effectively used as potential biomarkers in monitoring of IB toxicity in the aquatic organisms. However, more detailed studies on these specific biomarkers are needed to assess the impacts of human pharmaceutical drugs in the field of pharmacotoxicology and aquatic toxicology.     

3-Cloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a rat thyroid gland carcinogen, does not affect serum levels of TSH and thyroid hormones

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking water, causes follicular adenomas and carcinomas in thyroid glands of Wistar rats with an unknown mechanism. We evaluated effects of MX on blood thyroid stimulating hormone (TSH), thyroxine (T₄), triiodothyronine (T₃), prolactin (PRL) and growth hormone (GH) levels in male and female Wistar rats to assess their role in the tumorigenesis. The levels of TSH, PRL and GH in serum of male rats were not significantly affected by a single dose of 1, 10 or 60 mg/kg of MX administered by gavage 2 h before sampling. In repeated dose experiments MX was administered at dose levels of 1, 10 or 60 mg/kg of MX (40 mg/kg for females) in water by gavage daily for 1 or 3 weeks. Thyroid glands, adrenal glands and the liver were evaluated for morphological changes and cell proliferation activity after staining with proliferating cell nuclear antigen (PCNA). The dose of 60 mg/kg MX was toxic upon repeated administration. Nevertheless, MX did not affect blood TSH and T₄ levels at any time point in either sex. T₃ concentration increased transiently in males (by 37% after week 1) at the highest MX dose but not in females. MX did not change the weights of thyroid glands, their morphology and cell proliferation activity by the end of the week 3. MX did not affect blood PRL levels but decreased GH levels in males at all doses after the first week of MX treatment. The results indicate that MX does not alter blood TSH and thyroid hormone levels in rats, and imply that MX may not cause thyroid follicular cell tumors by TSH-mediated hormonal promotion.     

Toxicological effects of arsenate exposure on hematological,biochemical and liver transaminases activity in an Indian major carp, Catla catla

The impact of acute and sublethal toxicity of arsenate on hematological, biochemical and enzymological parameters of an Indian major carp Catla catla were estimated. The median lethal concentration of sodium arsenate to the fish Catla catla for 96 h was found to be 43.78 mg/L. During acute treatment (43.78 mg/L), hemoglobin (Hb), hematocrit (Ht), red blood cell count (RBC), white blood cell count (WBC), plasma glucose, plasma protein, liver aspartate and alanine aminotransferase (AST and ALT) levels decreased, whereas corpuscular indices like mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) increased in arsenate treated fish. In sublethal treatment (4.378 mg/L), Hb, Ht, RBC, plasma protein levels decreased while MCHC and plasma glucose levels increased throughout the exposure period. A biphasic trend was noticed in WBC, MCV, MCH, liver AST and ALT levels. The alterations of these parameters can be effectively used as a rapid method to assess health of fish exposed to arsenate in the aquatic environment.     

Effects of clofibric acid on mRNA expression profiles in primary cultures of rat,mouse and human hepatocytes

The mRNA expression profile in control and clofibric acid (CLO)-treated mouse, rat, and human hepatocytes was analyzed using species-specific oligonucleotide DNA microarrays (Affymetrix). A statistical empirical Bayes procedure was applied in order to select the significantly differentially expressed genes. Treatment with the peroxisome proliferator CLO induced up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent but not of human origin. CLO treatment induced up-regulation of microsomal cytochrome P450 4a genes in rodent hepatocytes and in two of six human hepatocyte cultures. In addition, genes encoding phenobarbital-inducible cytochrome P450s were also up-regulated by CLO in rodent and human hepatocyte cultures. Up-regulation of phenobarbital-inducible UDP-glucuronosyl-transferase genes by CLO was observed in both rat and human but not in mouse hepatocytes. CLO treatment induced up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. However, while genes of the cytosolic, microsomal, and mitochondrial pathways involved in fatty acid transport and metabolism were up-regulated by CLO in both rodent and human hepatocyte cultures, genes of the peroxisomal pathway of lipid metabolism were up-regulated in rodents only. An up-regulation of hepatocyte nuclear factor 1alpha (HNF1alpha) by CLO was observed only in human hepatocyte cultures, suggesting that this trans-activating factor may play a key role in the regulation of fatty acid metabolism in human liver as well as in the nonresponsiveness of human liver to CLO-induced regulation of cell proliferation and apoptosis.     

Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal and postischemic performance of the isolated rat heart

The present study investigated the effects of dronedarone and amiodarone on plasma thyroid hormones and the possible consequences on the response of the heart to ischemia. Amiodarone (30 mg/kg/day per os) or dronedarone (30 mg/kg/day per os) were administered for 2 weeks in normal and thyroxine-treated animals (25 microg/100 g body weight od sc, for 2 weeks), while animals without amiodarone and dronedarone served as controls. Isolated rat hearts were perfused in a Langendorff mode and subjected to 20 and 30 min of zero-flow global ischemia followed by 45 min of reperfusion. Functional changes were assessed by measuring left ventricular developed pressure (LVDP) under resting conditions and in response to ischemia-reperfusion, LVDP%, as well as the severity of ischemic contracture. Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals. In thyroxine-treated animals, amiodarone increased T4/T3 ratio but T4, T3 and rT3 levels were not altered. Basal functional parameters and ischemic contracture did not change by amiodarone and/or dronedarone neither in normal nor in thyroxine-treated hearts. In normal hearts, postischemic functional recovery, LVDP%, was not altered by amiodarone or dronedarone administration. LVDP% was statistically higher in thyroxine-treated hearts than in normal and this beneficial effect was not abolished by amiodarone or dronedarone treatment.     

Effects of chronic alprazolam treatment on plasma concentrations of glucocorticoids,thyroid hormones,and testosterone in cardiomyopathic hamsters

In the first of two experiments, young male cardiomyopathic hamsters were injected intraperitoneally twice a day for 29 days with 8 mg alprazolam/kg body weight or saline. Three hours after the same injections on day 30, they were sacrificed and plasma hormone levels were measured. Alprazolam increased cortisol, total glucocorticoid and triiodothyronine levels. It did not affect corticosterone, thyroxine or testosterone levels. The same protocol was used in a second experiment, except the controls received vehicle and a third group was treated with 48 mg diazepam/kg body weight. Alprazolam again increased cortisol and total glucocorticoid levels, but not those of corticosterone. On the other hand, diazepam increased both cortisol and corticosterone levels. These experiments suggest that chronic benzodiazepine treatment can affect adrenocortical function and perhaps some aspects of thyroid function.     

Platelet aggregation and plasma levels of acetylsalicylic acid in stroke patients on long-term treatment with an enteric-coated aspirin formulation

Summary Enteric-coated formulations of acetylsalicylic acid (ASA) should be advantageous in prophylaxis after stroke because they cause fewer gastrointestinal side effects. However, the absorption of unchanged ASA and the effectiveness of these formulations have been questioned, which prompted the present investigation. Fourteen elderly stroke patients on long-term medication with enteric-coated ASA 1.5 g daily and four patients on placebo were studied. When tested with arachidonic acid platelet aggregation was completely inhibited in all ASA subjects whereas it was normal in the controls. Plasma samples, drawn every 1/2 h for 6 h after tablet intake, were analyzed by HPLC. The presence of ASA was short lasting with a mean peak concentration of 55 µmol/l reached after 2–3.5 h. Salicylic acid (SA) appeared later, having a mean peak value of 591 µmol/l after 2.5–6 h. Thus, absorption of ASA as well as inhibition of platelet aggregation were confirmed during long-term medication with enteric-coated ASA.     

Histamine mediates behavioural and metabolic effects of 3-iodothyroacetic acid,an endogenous end product of thyroid hormone metabolism

BACKGROUND AND PURPOSE

3-Iodothyroacetic acid (TA1) is an end product of thyroid hormone metabolism. So far, it is not known if TA1 is present in mouse brain and if it has any pharmacological effects.

EXPERIMENTAL APPROACH

TA1 levels in mouse brain were measured by HPLC coupled to mass spectrometry. After i.c.v. administration of exogenous TA1 (0.4, 1.32 and 4 μg·kg⁻¹) to mice, memory acquisition-retention (passive avoidance paradigm with a light-dark box), pain threshold to thermal stimulus (51.5°C; hot plate test) and plasma glucose (glucorefractometer) were evaluated. Similar assays were performed in mice pretreated with s.c. injections of the histamine H₁ receptor antagonist pyrilamine (10 mg·kg⁻¹) or the H₂ receptor antagonist zolantidine (5 mg·kg⁻¹). TA1 (1.32 and 4 μg·kg⁻¹) was also given i.c.v. to mice lacking histidine decarboxylase (HDC^−/−) and the corresponding WT strain.

KEY RESULTS

TA1 was found in the brain of CD1 but not of HDC mice. Exogenous TA1 induced amnesia (at 0.4 μg·kg⁻¹), stimulation of learning (1.32 and 4 μg·kg⁻¹), hyperalgesia (0.4, 1.32 and 4 μg·kg⁻¹) and hyperglycaemia (1.32 and 4 μg·kg⁻¹). All these effects were modulated by pyrilamine and zolantidine. In HDC^−/− mice, TA1 (1.32 and 4 μg·kg⁻¹) did not increase plasma glucose or induce hyperalgesia.

CONCLUSIONS AND IMPLICATIONS

Behavioural and metabolic effects of TA1 disclosed interactions between the thyroid and histaminergic systems.     

In vivo and in vitro effects of nafazatrom (Bay g 6575), an antithrombotic compound,on arachidonic acid metabolism in platelets and vascular tissue

Nafazatrom, given acutely to male volunteers, had no effect on platelet aggregation, associated thromboxane B₂ (TXB₂) formation or the evaluated hormonal, renal and cardiovascular parameters. Only slight increases in plasma levels of 6-keto-PGF_1α and in platelet counts were observed. However, a marked influence of nafazatrom on arachidonic acid metabolism in certain in vitro systems was found. Prostaglandin synthesis by rabbit kidney cortex microsomes was significantly enhanced, PGI₂ being stimulated the most. In normal human platelets arachidonic acid metabolism was not influenced significantly by nafazatrom which was taken up by the platelets in a dose-dependent manner. In contrast, in platelets with a high peroxide level probably due to depletion of reducing cofactors, 12-hydroperoxy-eicosatetraenoic acid was transformed to 12-hydroxy-eicosatetetraenoic acid by nafazatrom, while the formation of TXB₂ was stimulated. These findings suggest that nafazatrom may act as a reducing cofactor for the hydroperoxidase involved in the cyclooxygenase- and lipoxygenase-pathways of arachidonic acid metabolism.