The effect of radioiodine treatment on the characteristics of TRAb in Graves' disease.

BACKGROUND: Graves' disease (GD) is one of the most common autoimmune thyroid diseases (AITDs) in humans, and thyrotropin receptor antibody (TRAb) is a characterized autoantibody in GD. The use of radioactive iodine therapy (RAI) for GD treatment is increasing. OBJECTIVES: We studied the biological properties of TRAb and evaluated the effect of RAI therapy on TRAb in GD patients. METHODS: In total, 225 patients (22 onset GD patients without 131I therapy, 203 GD patients treated with 131I therapy) and 20 healthy individuals as normal controls were included in this study. Clinical assessments were performed, and we examined in vitro the biological properties of TRAb in the 22 onset GD patients and 20 controls as well as 84 GD patients with 131I therapy. RESULTS: Serum TRAb and thyroid peroxidase antibody (TPOAb) levels increased in the initial year of RAI treatment, and both antibodies decreased gradually after one year. After 5 years from radioiodine treatment, TRAb and TPOAb levels decreased in 88% and 65% of GD patients, respectively. The proportion of patients positive for thyroid-stimulatory antibody (TSAb) was significantly higher in the 7-12-month group, and thyroid-blocking antibody (TBAb) levels were elevated after one year in half of the patients who received 131I treatment. CONCLUSIONS: Treatment of GD patients with radioiodine increased TPOAb and TRAb (their main biological properties were TSAbs) within the first year after therapy, and the main biological properties of elevated TRAb were TBAbs after 1 year.

Molecular and clinical genetics of the transcription factor GLIS3 in Chinese congenital hypothyroidism.

The transcription factor GLIS3 is an important factor in hormone biosynthesis and thyroid development, and mutations in GLIS3 are relatively rare. Deletions of more than one of the 11 exons of GLIS3 occur in most patients with various extrathyroidal abnormalities and congenital hypothyroidism (CH), and only 18 missense variants of GLIS3 related to thyroid disease have been reported. The aim of this study was to report the family history and molecular basis of patients with CH who carry GLIS3 variants. Three hundred and fifty-three non-consanguineous infants with CH were recruited and subjected to targeted exome sequencing of CH-related genes. The transcriptional activity and cellular localization of the variants in GLIS3 were investigated in vitro. We identified 20 heterozygous GLIS3 exonic missense variants, including eight novel sites, in 19 patients with CH. One patient carried compound heterozygous GLIS3 variants (p.His34Arg and p.Pro835Leu). None of the variants affected the nuclear localization. However, three variants (p.His34Arg, p.Pro835Leu, and p.Ser893Phe) located in the N-terminal and C-terminal regions of the GLIS3 protein downregulated the transcriptional activation of several genes required for thyroid hormone (TH) biosynthesis. This study of patients with CH extends the current knowledge surrounding the spectrum of GLIS3 variants and the mechanisms by which they cause TH biosynthesis defects.

Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves' Disease and Hashimoto's Hypothyroidism.

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these closely related diseases. OBJECTS: To identify the susceptibility genes for HT in the Chinese cohort and compare susceptibility genes between GD and HT. DESIGN: In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2682 patients with HT, 4980 patients with GD, and 3892 controls. The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS, with the logistic regression analysis adjusted for sex and age. RESULTS: We identified 11 susceptibility loci for HT in the Chinese Han population, with 4 loci, including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in HLA-B, and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5 × 10-8. Five loci were reported to be associated with HT for the first time. We also identified 6 susceptibility loci with heterogeneity between GD and HT. Out of them, 4 loci were associated with GD but not with HT, including HLA-DPB1, CD40, TSHR, and TG; the association of HLA-B with GD was stronger than that with HT, but the association of SLAMF6 was reversed. CONCLUSION: Our findings suggested that the pathogenesis of HT and GD was different.

Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective: To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants: This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures: Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results: A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified: DCHS2 on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729: OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance: These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.

A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease.

OBJECTIVE: We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. DESIGN: Dense mapping studies based on GWAS. PATIENTS: A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. MEASUREMENTS: Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. RESULTS: After the first replication stage, four SNPs from three regions with Pfirst  < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined  = 7.55 × 10-11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined  = 5.59 × 10-8 , OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. CONCLUSIONS: Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.

Role of speckle tracking imaging in the assessment of myocardial regional ventricular function in experimental blunt cardiac injury.

PURPOSE: To evaluate the usefulness and information collecting ability of speckle tracking imaging techniques in the assessment of myocardial regional ventricular contractility in a rabbit model with blunt cardiac injury. METHODS: Fifteen healthy New Zealand rabbits weighing (2.70 ±0.28) kg were anesthetized (3% pentobarbital sodium/i.v) and impacted using the BIM-II biological impact machine to induce myocardial contusion (MC). Hemodynamic parameters, such as heart rate, systolic pressure, mean arterial pressure, diastolic pressure and central venous pressure, were determined before and after MC. Further, parameters reflecting left ventricular functions, such as left ventricular end systolic pressure, left ventricular end diastolic pressure, isovolumic pressure (IP) and the maximal increasing/decreasing rate of left intraventricular pressure (±dp/dtmax), were also determined before and after MC. Left ventricular functions were determined either by two dimensional transthoracic echocardiography or by speckle tracking imaging for segmental abnormal ventricular wall motions. RESULTS: Heart rate, systolic pressure, diastolic pressure and mean arterial pressure decreased significantly but transiently, while central venous pressure markedly increased after MC. In contrast to significant changes in diastolic functions, there was no significant change in cardiac systolic functions after MC. The speckle tracking imaging demonstrated that strain values of different myocardial segment significantly decreased post impact, and that of the ventricular segment decreased from segment to segment. CONCLUSION: Speckle tracking imaging is useful and informative to assess myocardial regional dysfunctions post MC.

Comparison of continuous subcutaneous insulin infusion and insulin glargine-based multiple daily insulin aspart injections with preferential adjustment of basal insulin in patients with type 2 diabetes.

The purpose of this study was to evaluate and compare multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine with continuous subcutaneous insulin infusion (CSII) with aspart in patients with type 2 diabetes mellitus (T2DM). It was assessed whether MDI was capable of controlling glycemic index with a higher efficacy than CSII by preferential adjustment of basal insulin with a lower total daily insulin dosage in T2DM. Two hundred patients with T2DM were enrolled in the study and randomly assigned to CSII (n=100) and MDI (n=100; aspart immediately prior to each meal and glargine at bedtime) groups for 12 weeks of therapy. During the last week of each treatment period, the subjects wore a continuous glucose monitoring system for 2-3 days. The dosage of basal insulin was preferentially adjusted to control prior-meal blood glucose levels, and the characteristics of insulin dosage were analyzed. No statistically significant differences were observed between the two groups in hemoglobin A1c (HbA1c), which dropped from 10-11% prior to therapy to 7-7.5% after 12 weeks. After 12 weeks, good glycemic level control was achieved in all patients in the MDI and CSII groups. A statistically significant difference in the dose of insulin between the CSII and MDI groups was observed (P<0.001). In conclusion, no significant differences were found between the two therapies in the incidence of hypoglycemia and HbA1c for the 12 weeks. The basal insulin dosage was significantly decreased in the MDI group compared with that in the CSII group, but the CSII group was superior to MDI group in decreasing fasting blood glucose and shortening the time required for hypoglycemia to meet the targeted level.

Refined association of TSH receptor susceptibility locus to Graves' disease in the Chinese Han population.

BACKGROUND: Convincing evidence has demonstrated the association of TSH receptor (TSHR) with Graves' disease (GD) in the Chinese Han population. OBJECTIVE: The aim of this study was to identify the causal variants for GD in the region encompassing TSHR by a refining association study. DESIGN AND METHODS: GD patients (1536) and 1516 sex-matched controls were recruited in the first stage, and an additional 3832 GD patients and 3426 sex-matched controls were recruited in the replication stage. Genotyping was performed using Illumina Human660-Quad BeadChips or TaqMan single nucleotide polymorphism (SNP) Genotyping Assays and the Fluidigm EP1 platform. RESULTS: When the results of regression analysis for 74 genotyped SNPs and 922 imputed SNPs in the first-stage cohort were combined, rs179243 and rs3783949 were the probable susceptibility SNPs associated with GD in TSHR. Eleven SNPs, including rs179243 and rs3783949, were selected to further refine the association in the replication study. Finally, rs12101261 and rs179243 were confirmed as independent GD susceptibility variants in the replication and combined populations. Further, we also found that the rate of persistent TSHR autoantibody positivity (pTRAb+) was significantly higher in the GD patients with the susceptible genotypes rs12101261 or rs179243 than in the GD patients carrying the protective genotypes, after the GD patients had been treated for more than 1 year. CONCLUSIONS: These findings indicate that rs12101261 and rs179243 are the possible causal SNPs for GD susceptibility in the TSHR gene and could serve as genetic markers to predict the outcome of pTRAb+ in GD patients.

Effect of intra-abdominal volume increment on kidneys in minipigs with intra-abdominal hypertension after hemorrhagic shock and resuscitation.

BACKGROUND: To investigate the effect of intra-abdominal volume increment (IAVI) on intra-abdominal hypertension (IAH) in the kidneys. METHODS: Eight minipigs were successfully established as IAH models and were randomly divided into two groups: the IAVI group and the sham-operated group. The intravesicular pressure, inferior vena cava pressure and urine volume were measured before shock, 2 h after IAH, and 22 h after surgery, respectively. The following indices were measured: serum creatinine, urea nitrogen, renal cortical thickness, ratio of abdominal anteroposterior diameter/transverse diameter, renal thickness, diameter of the renal sinus and the wet/dry ratio of renal tissues. RESULTS: The intravesicular pressure (IVP) of the 8 minipig IAH models was calculated to be 21.16 ± 4.63 mmHg. There was a significant increase in the abdominal anteroposterior diameter/transverse diameter ratio. The minipigs in the IAVI group survived during the observational period, whereas 2 minipigs died at 18 h and 20 h in the sham-operated group. Twenty-two hours after surgery, the animals in the IAVI group displayed increased urinary volume (UV) and decreased Cr and Ur and remarkable decreases of VP and IVCP. After IAH, the renal cortical thickness and the renal thickness increased significantly. The renal wet/dry ratio in the sham-operated group was higher than that in the IAVI group. CONCLUSION: IAVI helps to control renal dysfunction after IAH, which may be related to lowering the intra-abdominal pressure, thus alleviating renal edema and blood stasis.

Identification of BACH2 as a susceptibility gene for Graves' disease in the Chinese Han population based on a three-stage genome-wide association study.

The BACH2 gene regulates B cell differentiation and function and has been reported to be a shared susceptibility gene for several autoimmune diseases. Our previous genome-wide association study (GWAS) indicated that several single nucleotide polymorphisms (SNPs) in the BACH2 gene are associated with Graves' disease (GD) in the Chinese Han population; however, the association did not achieve genome-wide significance levels. Recently, this association of BACH2 with GD was confirmed in Caucasians in the UK population, but fine mapping in this region has not yet been reported. Here, we provide a refined analysis of a 331-kb region in the BACH2 gene, which harbors 359 SNPs, using GWAS data from 1,442 GD patients and 1,468 controls. The SNPs rs2474619 and rs9344996 were implied as the independent variants associated with GD by forward and two-locus logistic regression analysis. We genotyped eight out of 10 tagSNPs with P < 1 × 10(-3) in 3,508 GD patients and 3,209 controls, the results also showed that rs2474619 was independently associated with GD in the combined population from GWAS and the second stage (P = 1.81 × 10(-5)). The rs2474619 and rs9344996 were further genotyped in the third stage cohorts, and rs2474619 showed evidence of association with GD at genome-wide significance levels in the combined population (P = 3.28 × 10(-8), odds ratio = 1.13). The association of rs9344996 with GD can be explained by its linkage to rs2474619 in the combined population. Our study clearly demonstrated that BACH2 is a susceptibility gene for GD in the Chinese Han population and further supported rs2474619, in intron 2 of BACH2, is the best association signal with GD. However, the mechanism by which BACH2 confers increased risk of GD requires further study.

Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis.

Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.

Usefulness of speckle tracking imaging to assess myocardial contractility in intra-abdominal hypertension: study in a mini-pig model.

This study evaluated the usefulness of speckle tracking imaging (STI) in assessment of myocardial contractility in intra-abdominal hypertension experimentally induced in mini-pigs. To this effect, 12 mini-pigs were anesthetized with intravenous injection of 3 % sodium pentobarbital, hemorrhaged to reach the shock status, and resuscitated with excessive volume of lactated Ringer's solution. The animals were either sham-operated (study group 1) or underwent treatment with intra-abdominal volume increment (study group 2). Observations were made prior to induction of shock, 1 h after shock, 2 h after induction of intra-abdominal hypertension, and 8 and 12 h after treatment. The heart rate and mean artery pressure were conventionally measured. STI was used to assess radial and circumferential strains of segmental ventricular wall. The results obtained demonstrated that myocardial contractility, as manifested by radial and circumferential strains of different ventricular wall segments, was decreased after induction of intra-abdominal hypertension. Treatment with intra-abdominal volume increment was able to decrease heart rate and intra-bladder pressure (indicator of effectiveness of treatment) and significantly improved myocardial contractility of involved ventricular wall segments. In conclusion, STI is a useful method to assess myocardial regional functions.

Short-term effect of radioactive iodine therapy on CXCL-10 production in Graves' disease.

PURPOSE: To observe the short-term dynamic change in serum CXC chemokine ligand-10 (CXCL10) levels in patients with Graves' disease (GD) before and after iodine therapy and to analyze the relationship between CXCL10 levels and clinical disease indices. METHODS: ELISA was used to determine serum levels of CXCL10 in 43 patients with GD shortly before radioiodine therapy and on days six, 14, and 60, post-therapy. RESULTS: Patients with newly diagnosed GD showed significantly higher levels of serum CXCL10 compared with the control group (P < 0.01). The serum CXCL10 level increased slightly on day six after treatment of radioactive iodine (P < 0.01). There was no significant statistical difference in serum CXCL10 levels pre-treatment and on day 14 post-treatment. A significant reduction in serum CXCL10 level was observed on day 60 (P < 0.01). GD patients with exophthalmia showed higher serum CXCL10 level than GD patients without exophthalmia. No correlation was found between levels of CXCL10 and FT3, FT4 or TSH at any time point, but significant positive correlation was shown between thyroid peroxidase antibodies (TPOAb) and CXCL10 (r=0.50, P < 0.01). CONCLUSION: CXCL10 participates in the early inflammatory response after radioactive iodine therapy in patients with Graves' disease and shows a strong association with the autoimmune process.

Investigation of the insulin dose and characteristics of continuous subcutaneous insulin infusion in Chinese people with type 2 diabetes.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) for type 2 diabetes mellitus (T2DM) is a promising therapy. CSII therapy is flexible, but the required insulin dose for different people may vary. Few studies have investigated the insulin dose and characteristics of CSII for T2DM, and none has focused on an Asian Chinese population. METHODS: In total, 171 subjects with T2DM were using CSII and divided into different groups according to their body mass index (BMI) and the course of disease, respectively. The basal rate of CSII was set for four periods per day. We preferentially adjusted the basal insulin dose to control fasting and preprandial blood glucose. RESULTS: Good glycemic control was achieved after 4.8±2.5 days. The mean total daily insulin dose was 31.66±9.85 IU, and the dose per unit body weight was 0.48±0.19 IU/kg/day. The total daily basal and bolus doses were 21.14±7.64 IU and 10.38±3.62 IU, respectively (i.e., about 66.7±6.8% and 33.3±6.8% of the total daily dose). We did not observe any significant difference in total dose of insulin or basal and bolus doses of insulin per day among different groups divided by BMI. Only in the group with BMI of <23 kg/m(2) was the insulin dose of per kilogram of body weight (0.60±0.25 IU/kg/day) significantly higher than in the other two groups (P=0.0001). There was no relationship between the insulin dose and the course of disease. CONCLUSIONS: In individuals with T2DM on CSII short-term intensive therapy, proper increase of basal dose of insulin and preferential adjustment of the basal rate may be the effective method that can achieve good glycemic control with a lower total daily dose.

A genome-wide association study identifies two new risk loci for Graves' disease.

Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 × 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 × 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.

Glucocorticoids decrease body weight and food intake and inhibit appetite regulatory peptide expression in the hypothalamus of rats.

The aim of the present study was to investigate the effects of glucocorticoids (GCs) on appetite and gene expression of the hypothalamic appetite regulatory peptides, neuropeptide Y (NPY), agouti-related protein (AGRP) and cocaine and amphetamine-regulated transcript (CART), in non-obese and obese rats. Both non-obese and obese rats were randomly assigned to three groups: normal saline, low- and high-dose GC groups (NSG, LDG and HDG, respectively), which received an intraperitoneal injection with normal saline (0.2 ml/100 g) or hydrocortisone sodium succinate at 5 and 15 mg/kg, respectively, for 20 days. The expression levels of NPY, AGRP and CART mRNA in the hypothalamus were measured by real-time quantitative PCR. Non-obese and obese rats were found to undergo weight loss after GC injection, and a higher degree of weight loss was observed in the HDG rats. The average and cumulative food intakes in the obese and non-obese rats injected with high-dose GC were lower compared to that in the NSG (p<0.05). mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and the anorexigenic neuropeptide, CART, were significantly lower in the HDG than levels in the NSG for both the obese and non-obese rats (p<0.05). GC treatment decreased appetite and body weight, induced apparent glucolipid metabolic disturbances and hyperinsulinemia, while down-regulated mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and anorexigenic neuropeptide, CART, in the hypothalamus in the rats. The mechanism which induces this neuropeptide expression requires further study.

Glucocorticoids decrease serum adiponectin level and WAT adiponectin mRNA expression in rats.

OBJECTIVE: Accumulating evidence suggests that adiponectin plays an important role in the genesis of obesity and insulin resistance. Although it has been shown that glucocortocoids (GC) inhibit adiponectin expression in vitro, there exist discrepant results in vivo. In this study, we observe the effect of GC on the serum adiponectin level and adiponectin expression in white adipose tissue (WAT) in male SD rats. METHODS: An obese rat model was made by a high-fat diet. Both non-obese and obese rats were randomly divided into normal saline (intraperitoneal injection with normal saline 0.2ml/100gday for 20 days, NS), a low dose GC group (intraperitoneal injection with hydrocortisone sodium succinate 5mg/kgday for 20 days, LDG) and a high dose GC group, respectively (intraperitoneal injection with hydrocortisone sodium succinate 15mg/kgday for 20 days, HDG). Serum adiponectin levels were detected by ELISA and the adiponectin mRNA level was assayed by Northern blot. RESULTS: The serum adiponectin level significantly decreased after 80 days of the high-fat diet (P<0.05), while it was not decreased after 80 days of the chow diet (P>0.05). The serum adioponectin levels in both the non-obese and obese rats were significantly decreased after a 20-day GC injection period (P<0.01). The adiponectin mRNA levels in epididymal fat after high dose GC injection, in both non-obese and obese rats were also decreased (P<0.001). CONCLUSIONS: A high-fat diet decreased serum adiponectin levels in the rat. GC decreased serum adiponectin levels, and this might be due to inhibited adiponectin mRNA expression in WAT. High-fat diet and GC have a synergistic effect on inhibiting adiponectin expression in rats.

Influence of visceral adiposity on ghrelin secretion and expression in rats during fasting.

Although circulating ghrelin levels correlate inversely with adiposity at baseline, little is known about the effect of percent visceral adipose tissue value (PVATV) on ghrelin expression and secretion in response to fasting. Our study demonstrated that ghrelin increased with 24-h fasting in rats with the lowest PVATV (less than 6%), after 3 days in rats with intermediate PVATV (6-9%) and 5 days in rats with the highest PVATV (greater than 9%). Ghrelin mRNA in the stomach was increased after 3 days in low-PVATV (5.8+/-0.9%) rats but not in high-PVATV (14+/-1.6%) rats. Therefore, both ghrelin secretion and mRNA were delayed in response to fasting in rats with increased visceral fat. In rats matched for PVATV, but with different body weights, the fasting induced similar levels of increased ghrelin while in rats with different PVATV ghrelin secretion was different in response to fasting, even when body weights were matched in two groups. These data suggested that the initial PVATV, not lean mass, was related to the pattern of plasma ghrelin in response to fasting in rats.

Contrast-enhanced ultrasonographic imaging diagnosis on assessment of vascularity in liver metastatic lesions.

AIM: To investigate the vasculature of rabbit liver metastatic lesions by color Doppler imaging and power Doppler imaging (PDI) techniques. METHODS: Eight New Zealand rabbits with implanted VX2 liver tumors were used. All ultrasound examinations were performed with a HP 5500 color Doppler ultrasound scanner. Before and after the injection of contrast agent, the changes of gray scale and the periphery and intralesional blood flow of the liver metastatic lesion were carefully observed by B mode ultrasound, color Doppler flow imaging (CDFI) and PDI. RESULTS: Twelve lesions were found in the eight rabbits with implanted VX2 liver tumors, whose diameter ranged from 1.6 to 4.8 cm. Echoes of these lesions were not characterized and has lack of specificity. After the injection of contrast agent, the numbers of dot or strip-like flow messages increased both at the periphery and inside of these lesions under the mode of CDFI and PDI, and were more pronounced under PDI. Morphology of intralesional vessels extended, even branched and some signals were clearly found encircling the lesion. And some vessels were found penetrating into the center of the lesion. CONCLUSION: PDI after injection of self-made echo contrast agent can show a pronounced sensitivity than that of B mode ultrasound and CDFI in diagnosis of vascularity of a metastatic lesion.