[The Diagnostic Value of Captopril Challenge Test for Primary Aldosteronism].

OBJECTIVE: To investigate the diagnostic value of different captopril challenge test (CCT) diagnostic criteria for diagnosing primary aldosteronism (PA). METHODS: We collected the clinical data of 184 patients with hypertension retrospectively in West China Hospital of Sichuan University. Receiver operating characteristic (ROC) curves were used to analyze the post-CCT efficacy of aldosterone renin activity ratio (ARR), plasma aldosterone concentration (PAC), plasma renin activity (PRA) and PAC suppression rate for PA diagnosis. RESULTS: This study included 125 cases of primary aldehyde (PA group) and 59 cases of essential hypertension (EH group), and there were 38 normal renin primary hypertension (NREH group) and 21 low renin primary hypertension (LREH group) in EH group. The post-CCT PAC suppression rate (median (P 25, P 75)) of EH and PA group were 0.190 (0.083, 0.351) and 0.125 (0.024, 0.237), respectively. Compared with the NREH group, the basic and post-CCT PRA of LREH group were lower ( P<0.001), and there were no significant differences compared with the PA group ( P>0.05). We found significant overlap of post-CCT PRA and ARR between PA group and LREH group, while the overlap of post-CCT PAC between the two groups was small. In differential diagnosis of PA and EH, the areas under ROC curve of the post-CCT ARR, PAC, PRA and PAC suppression rate were 0.860 (95% confidence interval ( CI): 0.800-0.907), 0.881 (95% CI: 0.825-0.924), 0.771 (95% CI: 0.703-0.831) and 0.632 (95% CI: 0.558-0.701), respectively. There was no significant difference between the first two indexes ( Z=0.443, P=0.658), and both of them were higher than the latter two ( P<0.05). The optimal post-CCT cut-off values for ARR and PAC in differential diagnosis of PA and EH were 19.24 ng·dL -1 with a sensitivity of 78.4% and a specificity of 88.1%, and 32.47 (ng·dL -1)/(ng·mL -1·h -1) with a sensitivity of 84.17% and a specificity of 72.41%. CONCLUSION: Both ARR and PAC have higher diagnostic value than the post-CCT PAC suppression rate, post-CCT PAC is especially suitable as a confirmatory testing criterion of PA.

[The Value of Postural Stimulation Test Combined with Adrenal CT in the Diagnosis of Aldosterone-producing Adenoma].

OBJECTIVE: Adrenal vein sampling (AVS) and pathological report were selected as gold standard to assess the value of adrenal CT scan combined with postural stimulation test in diagnosing aldosterone-producing adenoma. METHODS: The clinical data of primary aldosteronism (PA) patients including aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were retrospectively collected in the West China Hospital of Sichuan University. The sensitivity and specificity of adrenal CT scan combined with postural stimulation test in diagnosing APA were studied. RESULTS: A total of 83 APA patients and 42 IHA patients were enrolled in this study. ROC curve was plotted with increase percentage of serum aldosterone in upright position compared with recumbent position. The optimal cutoff point for APA diagnosis by postural stimulation test was 11%, and the percentage less than 11% was taken as a positive result. The patients were diagnosed by postural stimulation test, with 60 cases positive and 23 cases negative in APA patients and 12 cases positive and 30 cases negative in IHA patients. When AVS and pathological report were selected as the gold standard, the sensitivity and specificity of postural stimulation test in diagnosing APA were 72.3% and 71.4% respectively. Among the 83 APA patients, 65 patients with unilateral nodules and 18 patients with bilateral nodules were diagnosed by CT scan. The coincidence rate in APA diagnosis between CT scan and AVS or pathological report was 78.3% (65/83). Among the 60 patients with positive result in postural stimulation test, who were diagnosed bilateral nodules by CT scan, 51 patients were diagnosed as APA by AVS or pathological report (51/60). CONCLUSION: Adrenal CT combined with postural test can increase the diagnostic accuracy of APA patients.

[The Pharmacokinetics, Pharmacodynamics and Bioequivalence of Insulin Aspart Produced by the United Laboratories Evaluated by Euglycemic Clamp Study].

OBJECTIVE: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of a rapid-acting insulin analog-insulin aspart (the tested formulation) which was manufactured by The United Laboratories and to evaluate the bioequiavailability to the reference formulation (NovoRapid ®) produced by Novo Nordisk in Chinese healthy volunteers. METHODS: A total of 24 male healthy volunteers were recruited from February to April 2016 to participant in this before-after, single dose, and randomized crossover study. And the experimental observation was conducted on 2 test days respectively with a between-period from 7 to10 d. According to a random number table, the volunteers were divided into group A or B, group A was administrated with tested insulin aspart (IAsp) for the first time and reference NovoRapid ® for the second time and group B had the revered order differed from group A. The PK/PD of these insulin analogs were estimated by euglycemic clamp study. RESULTS: The relative biological effectiveness (reflecting gloucose-lowing effect) and bioavailability on behalf of plasma-drug concentration were 98.3±18.8% and 97.3%±8.3% respectively. For PK parameters, the 90% confidence interval ( CI) of peak plasma insulin concentration ( C max) and area under the curve of insulin aspart concentration from 0 to 10 hours ( AUC IAsp, 0-10 h) of IAsp were 88.8%-106% (equivalent range 70%-143%) and 94.0%-100% (equivalent range 80%-125%) respectively; for PD parameters, the 90% CI of the maximum glucose infusion rate ( GIR max) and AUC GIR, 0-10 h were 95.5%-113% (equivalent range 70%-143%) and 89.9%-104% (equivalent range 80%-125%) respectively, which indicated that IAsp and NovoRapid® was bioequivalent. One of the subjects discovered hyperuricemia without clinical symptoms and the rest had no clinically significant abnormalities in the safety indexes before and after the tests. No hypoglycemic events, allergic reactions, or local injection adverse reaction occurred in this trial. CONCLUSION: The tested IAsp has comparable relative bioavailability to the reference NovoRapid ®.

[The Functional Analysis of Glucocorticoid Receptor in Peripheral Blood of Endogenous Cushing's Syndrome Patients].

OBJECTIVE: To evaluate the expression level and binding affinity glucocorticoid receptor (GR) in endogenous Cushing's syndrome patients. METHODS: The patients of endogenous Cushing's syndrome were enrolled in the department of endocrinology in West China Hospital of Sichuan University, and age- and sex-matched healthy volunteers were studied as control group. The expression level and binding affinity of GR in peripheral blood mononuclear cells (PBMCs) were examined by flow cytometry. The differences between the two groups were compared, and the correlations of GR level and affinity to serum cortisol concentration or 24 h urine free cortisol were also analyzed. RESULTS: There were 17 Cushing's syndrome patients and 17 healthy volunteers. The expression level and binding affinity of GR in Cushing's syndrome patients were 11.9±3.1 and 6.6±2.6, while the values of normal controls were 20.6±3.3 and 9.9±3.2. A significant decrease in GR expression and binding affinity in the patients with Cushing's syndrome was found. No correlation was observed between plasma cortisol concentration or 24 h urinary free cortisol and GR expression or binding affinity in Cushing's syndrome patients. CONCLUSION: The expression level and binding affinity of GR are obviously decreased in Cushing's syndrome patients, which suggests 1.6 times of physiological dose of glucocorticoid for the patients with hypocortisolism after surgery, in order to overcome glucocorticoid resistance and maintain physiological function of glucocorticoid.

[Risk Factors Associated with Thyroid Nodules in Patients with Acromegaly].

OBJECTIVE: To identify risk factors associated with thyroid nodular lesions in patients with acromegaly. METHODS: Clinical and thyroid ultrasonography data of patients with acromegaly diagnosed in the West China Hospital of Sichuan University from May 2009 to January 2018 were reviewed and analyzed. Multivariate linear regression models were established to identify factors associated with thyroid volumes and size of thyroid nodules. Multivariate binary logistic regression models were established to determine risk factors associated with thyroid nodules in patients with acromegaly. RESULTS: Of the 240 acromegaly patients, 70 received thyroid ultrasonography and 56 had thyroid nodules (56/70, 80%). The patients with thyroid nodules had a longer median duration of acromegaly than 14 patients who without thyroid nodules (8.0 years vs. 3.0 years, P＜0.05), but had a similar mean age and female to male ratio with the latter. The risk of thyroid nodules increased with the duration of acromegaly (odds ratio=1.306, 95% confidence interval (1.010, 1.688), P=0.042). The level of random growth hormone was linearly correlated with thyroid volumes. Gender, age, and serum growth hormone were not predictors of thyroid nodules in patients with acromegaly. CONCLUSION: Duration of acromegaly is an independent predictor of thyroid nodules.

[Quality Assessment of Euglycemic Glucose Clamp Test].

OBJECTIVE: To explorethe quality of euglycemic glucose clamptest performed in the West China Hospital from 2014 to 2017 and to evaluate whether the quality control indexes are suitable for the quality assessment of the clamp test. METHODS: The data collected from 80 euglycemic glucose clamp tests performed between 2014 and2017 were divided into 4 groups according to the coefficient of variation of the blood glucose concentrations (CVBG): group A (CVBG≤4.5%), group B (4.5% < CVBG≤5.0%), group C (5.0% < CVBG≤5.5%) and group D(CVBG > 5.5%).The differences in percentage of glucose excursion from target range (GEFTR), the duration of GEFTR, the area under curve (AUC) of GEFTR, the mean value of excursion from target glucose (GEFT) and the AUC of GEFT were calculated and compared. RESULTS: In group A, the mean value of CVBG was 3.75%. In group B, the mean value of CVBG was 4.76%. In group C, the mean value of CVBG was 5.28%. The median value of CVBG in group D was 6.07%. The percentage of GEFTR, the duration of GEFTR, the AUC of GEFTR, the mean value of GEFT and the AUC of GEFT in group A were all less than those of other groups (P < 0.05).For the same indexes, there were no significant differences between group B and C, while they were higher in group D compared with the other three groups. CVBG was positively correlated with other quality control indexes (correlation coefficient r was 0.770-0.805). Based on the cut-off point 5% of CVBG, the cut-off points of the percentage of GEFTR, the duration of GEFTR, the AUC of GEFTR, the mean value of GEFT and the AUC of GEFT were 5.8%, 14.6 min, 22.82 mg/dL×min, 3.23 mg/dL, 216.25 mg/dL×min/h respectively, with the sensitivity range from 79.3% to 100% and the specificity range from 74.5% to 89.7%.Combined with these indexes, 8.11% of euglycemic clamps were found to havepoor quality in group A, while 66.67% of euglycemic clamps showed acceptable quality in group C. CONCLUSIONS: The investigators should provide an estimation of the quality of the clamps when reporting the results of the insulin analogues' PK/PD characteristics using euglycemic clamps. CVBG less than 4.5% indicates a good quality, and the above-mentioned quality control indexes especially the AUC of GEFT(cut-off point: 216.25 mg·/dL×min/h) should be evaluated when CVBG is more than 4.5%.False high quality and false low quality euglycemic clamps will be detected and a more precise estimation of quality assessment should be made by the combination of these indexes.

[Pancreatic ß-cell Dysfunction and Apoptosis Induced by Elevated Free Fatty Acids Synergize with Hyperglycemia].

OBJECTIVES: To analysis the effects of glucoxicity and lipotoxicity on the function and apoptosis of pancreatic ß-cells. METHODS: The levels of circulating glucose and free fat acids (FFAs) were elevated by infusion dextrose and fat emulsion in high-fat obese rats. The insulin resistance model obese rats were divided into four gourp: obese group with saline infusion (OB-NS group, n=7), obese group with glucose infusion (OB-GS group, n=9), obese group with Lipid emulsion infusion (OB-FFA group, n=8), obese group with glucose and lipid emulsion infusion (OB-FG group, n=9). Five rats fed with general diet were taken as normal group (NC group).Plasma FFAs and ß-hydroxybutyric acid (ß-HBA) concentrations were determined by an enzymatic colorimetric method. An intravenous glucose tolerance test (IVGTT) was performed to examine the glucose-stimulated insulin secretion in vivo and immunohistochemical staining to detect the storage volume of insulin. FFA and ß-HBA concentrations were measured at baseline and post-infusion. The apoptosis of pancreatic ß-cell was detected byin situ end labeling technique (TUNEL). RESULTS: Glucose infusion rate (GIR) of obese rats was significantly lower than that in NC group [(10.82±1.8) mg/(kg·min) vs. (25.21±1.7) mg/(kg·min), P<0.05], confirming insulin resistance rat model successfully established. The insulin secretion peak load time of OB-FG group rats delayed, and the serum insulin level was significantly lower than that of NC group and OB-NS group during IVGTT. The differences were statistically significant ( P<0.05). Compared with OB-NS and NC groups, storage volume of insulin of OB-GS group reduced, and ß cell apoptosis rate elevated significantly. CONCLUSIONS: Glucolipotoxicity could induce ketone overproduction, insulin resistance and defective insulin secretion.

[Effects of GLP-1 Agonist Exenatide on Cardiac Diastolic Function and Vascular Endothelial Function in Diabetic Patients].

OBJECTIVE: To study the protective effect of glucagon-like peptide-1 (GLP-1) on the left ventricular diastolic function and endothelial function in patients with type 2 diabetes. METHODS: 27 patients with type 2 diabetes were randomly divided into two groups: GLP-1 treated group and insulin treated group. Patients in the GLP-1 group were given GLP-1 analogue and metformin hydrochloride. Patients in the insulin group were given insulin and metformin hydrochloride. The outcomes of treatments were measured by fasting plasma glucose (FBG) fasting lipid profile, glycosylated hemoglobin (HbA1c), blood pressure and general clinical features. High resolution Doppler ultrasound was performed to detect mitral early diastolic rapid filling (E-wave), atrial contraction late filling (A-wave), E/A ratio, early diastolic mitral annular velocity (e), late diastolic mitral annular velocity (a), e/a ratio, endothelium-dependent vasodilatation (EDV) mediated by brachial arterial blood flow, and endothelium-independent vasodilatation (EIV) mediated by nitroglycerin. RESULTS: The levels of FBG and HbA1c decreased significantly in both groups after treatments (P < 0.05). Patients in the GLP-1 group showed improved e, e/a ratio, and E/e ratio after treatments (P < 0.05), but no significant changed in E, A, and E/A ratio (P > 0.05). By contrast, patients in the insulin group showed no significant changes in e, a, E, A, E/A ratio, e/a ratio and E/e ratio after treatments (P > 0.05). EDV increased significantly after treatments in both groups (P < 0.05). A higher level of post-treatment EDV was found in patients in the GLP-1 group compared with those in the insulin group. No significant changes in EIV were found in both groups. CONCLUSION: GLP-1 may be able to mitigate the left ventricular diastolic dysfunction and improve endothelial function of patients with type 2 diabetes. Our findings suggest that GLP-1 has the potential to prevent or delay cardiovascular complications in patients with type 2 diabetes. Further studies are needed.

[Effects of sulfonylureas on patients with type 2 diabetes and acute nonlacunar ischemic stroke].

OBJECTIVE: To explore the influence of sulfonylurea (SU) on the patients with Type 2 Diabetes and nonlacunar ischemic stroke. METHODS: Patients with type 2 Diabetes and nonlacunar isehemic stroke met the standardized criteria were included and divided into sulfonylures (SU) group and Non-SU group. The primary outcomes were the scores of National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (MRS) and Barthel index (BI) evaluated at baseline, the end of 2nd week/discharge and the end of 12th week. We compared these Outcomes between SU group and NSU group, as well as among each subgroup of NSU group according to different hypoglycemic medications. We also compared these outcomes between subgroups of SU group according to patient taking SUs alone or combined other hypoglycemic medications. RESULTS: After exclusions, the cohort comprised 26 patients taking sulfonylurea before stroke (SU group) and 72 patients not taking sulfonylurea (non-SU group). No significant differences were observed among basic clinical characters, lipid profile, fast blood glucose and HbA1c between SU and non-SU group. No patient died during the 12-week follow-up in either group. No significant differences were observed among all the primary outcomes between SU and non-SU groups. Among non-SU group, the primary outcomes did not show any significant differences in no-medication subgroup, insulin subgroup and metformin subgroup. No significant differences were found between subgroup of SU alone and subgroup of SU combined other medicaiton. CONCLUSION: Sulfonylureas has no hypoglycemic-independent neuropretection function in the patients with Type 2 Diabetes and nonlacunar ischemic stroke.

[The protective effects of rosiglitazone on kidney in diet-induced obese rats].

OBJECTIVE: To investigate whether rosiglitazone has renal protective effects in diet-induced obese rats. METHODS: Wistar rats were randomly divided into normal control (NC), obesity (OB) and rosiglitazone (OB + R) group (n = 8 in each group). The NC group was fed with normal diet. The OB and OB + R groups were fed with high-fat diet. Four weeks later, rosiglitazone [4 mg/(kg x d)] was given to the OB + R group by oral gavage. The other two groups were given the same amount of physiological saline in the same manner. After 24 weeks, urinary albumin/creatinine ratio (ACR) was measured. Endothelial function was determined by measuring vasodilatation of aorta. Renal tissues were collected for morphological and CD31 immunohistochemistry. Glomerular vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels were measured. RESULTS: Body weight, visceral fat, plasma free fatty acids (FFAs), plasma triglyceride and ACR levels increased significantly in the obese rats (P < 0.01). Rosiglitazone intervention decreased visceral fat, plasma FFAs, plasma triglyceride and ACR levels (P< 0.01), which were still higher than NC group (P < 0.01). ACR levels of the OB group were higher than those of NC group (P < 0.01), while those of OB + R group were lower than those in OB group (P < 0.01), but still higher than those of NC group (P < 0.05). Endothelium-dependent vasodilatation was impaired in the obese rats. Rosiglitazone intervention could enhance acetylcholine-induced vasorelaxation and improved endothelium-dependent vasodilatation (P < 0.05), which was similar to that in NC group (P > 0.05). Morphological and immunohistochemistry results showed glomerulomegalia, increased glomerular CD31 expression and increased proliferation of glomerular endothelial cells, which were improved by rosiglitazone (P < 0.05). Obese rats showed increased glomerular VEGF and reduced NO levels (P < 0.05). This imbalance of VEGF/NO was partly improved by rosiglitazone intervention (P < 0.05). CONCLUSION: Rosiglitazone reduces urinary albumin excretion and has renal protective effects by improving the imbalance of VEGF/NO and endothelial dysfunction in diet-induced obese rats.

[A comparison of different estimation equations for glomerular filtration rate in Chinese diabetic patients].

OBJECTIVE: To compare the accuracy and precision of C-G equation, simplified MDRD equation, the Chinese equation, Ruijin equation, and CKD-EPI equation for estimating glomerular filtration rate (GFR) in Chinese diabetic patients. METHODS: Diabetic patients visiting the West China Hospital (both outpatient and inpatient departments) of Sichuan University who were older than 18 years old were enrolled in this study. Their general health and clinical characteristics were recorded. The GFR of those patients were evaluated by 99mTc-DTPA dynamic renal imaging (rGFR). We compared the accuracy and precision of C-G equation, simplified MDRD equation, the Chinese equation, Ruijin equation and CKD-EPI equation for estimating GFR (eGFR). We also tested whether levels of GFR, plasma creatinine (Scr) and fasting plasma glucose (FPG) influenced the accuracy and precision of the equations. RESULTS: 217 diabetic patients (139 males and 78 females) were enrolled in this study. Compared with rGFR, C-G equation underestimated GFR slightly; whereas simplified MDRD equation, the Chinese equation, Ruijin equation and CKD-EPI equation overestimated GFR. Ruijin equation had the best accuracy and precision in all the equations, followed by CKD-EPI equation. When patients had lower than 133 microml/L Scr, Ruijin equation had the best accuracy and precision. When patients had 133-177 micromol/L Scr, CKD-EPI equation had the best accuracy and precision. When patients had higher than 177 micromol/L Scr, there was no obvious difference in accuracy and precision among the equations. Regardless of the level of FPG, Ruijin equation had the best accuracy and precision in all the equations. CONCLUSION: Ruijin equation is the best equation for estimating GFR, followed by CKD-EPI equation.

[The relationship between hyperinsulinemia and hypokalemic periodic paralysis in overweight/obesity subjects].

OBJECTIVE: To study the relationship between hyperinsulinemia and primary periodic paralysis in overweight/obesity people. METHODS: Overweight/obesity people with primary hypokalemic periodic paralysis were administrated as disease group. Serum potassium, insulin and glucose were analyzed at different time (0 h, 1 h, 2 h, 3 h, 4 h) after taking 100 g carbohydrates and the results were compared with that of control group matched by gender, age and body mass index (BMI). RESULTS: (1) Males were much more than females in disease group (14 males and 2 females), the onset age ranged from 20 to 50 years old. (2) Both the highest insulin level and the lowest potassium level appeared at one hour after taking the carbohydrates. And the highest insulin level of disease group was significant higher than that of control group. (3) The area under the curve of insulin and insulin/potassium of disease group was significant higher than that of control group. CONCLUSION: The postprandial hyperinsulinemia was an important factor in overweight/obesity people with hypokalemic periodic paralysis.

[Clinical features and epidemiological trend of diabetic ketosis in patients admitted to West China Hospital].

OBJECTIVE: To evaluate the clinical features and epidemiological trend of diabetes ketosis (DK) in patients admitted to West China Hospital. METHODS: We reviewed medical records of diabetic patients with DK who were admitted to West China Hospital from 1997 to 2005. Their clinical and laboratory data were analysed with SAS 9.0. RESULTS: From 1997 to 2005, the proportion of diabetic patients with DK increased by 0.12% annually. The proportion of provoked DK patients (who had a clinically evident precipitating factor) in those with DK remained stable; whereas the proportion of T1D patients in those with DK declined by 2.00% annually and the proportion of ketosis prone obesity diabetes (KPD) in those with DK increased by 2.27% annually. The KPD patients displayed a striking male predominance (2.31:1, male:female) and were diagnosed at an older age compared with those with T1D [(46.3 +/- 12.9) yr. vs. (28.9 +/- 14.7) yr.]. The KPD patients were more likely to have a strong family history of diabetes and a better beta-cell function reserve, and be accompanied with dyslipidemia (52.7%), hypertension (23.3%), fatty liver (10.1%) and hyperuricemia/gout (8. 5%) compared with those with T1D. CONCLUSION: In recent years the proportion of KPD patients in the hospitalized DK patients is increasing. With different characteristics compared with typical T1D, KPD might belong to a subgroup of T2D.

[Comparing overnight dexamethasone suppression test, urine free cortisol, and midnight serum cortisol for the initial diagnosis of Cushing' s syndrome].

OBJECTIVE: To identify retrospectively the optimal cut-off points and the values of overnight dexamethasone suppression test, urine free cortisol, and midnight serum cortisol in the initial diagnosis of Cushing's syndrome in Chinese people. METHODS: The results of overnight low-dose dexamethasone suppression test (PTC-DST), urine free cortisol (UFC) and late-night plasma total cortisol (PTC-24 h) of 102 patients who had clinically confirmed Cushing's syndrome and 102 patients without Cushing's syndrome were extracted from West China Hospital. Receiver operating characteristic (ROC) curves were drawn to identify optimal cut-off points of the three assays and their values in diagnosing Cushing' s syndrome. RESULTS: The optimal cut-off point (the point on the ROC curve closest to 1) for PTC-DST was set at 86 nmol/L, with 98. 7% sensitivity and 97. 2% specificity (100% sensitivity and 94. 4% specificity was achieved at 50 nmol/L 100%o sensitivity and 95. 8% specificity was achieved at 60 nmol/L). The optimal cut-off point for PTC-24 h was set at 347 nmol/L, with 93. 4% sensitivity and 98. 4% specificity (98. 9% sensitivity and 85. 2% specificity was achieved at 207 nmol/L). The optimal cut-off point for UFC was set at 230. 15 icrog/24 h, with 92. 2 sensitivity and 95. 7% specificity (96. 1% sensitivity and 85. 1% specificity was achieved at 127. 55 microg/24 h). There was no significant difference between PTC-DST and PTC-24 h in the areas under the ROC curves, whereas both had a greater area under the ROC curve than that of UFC (P< 0. 05). CONCLUSION: Compared with the recommended 50 nmol/L cut-off point for PTC-DST in the USA and the European countries, the same sensitivity and a higher specificity can be achieved at a cut-off at 60 nmol/L for the Chinese people. PTC-DST and PTC-24 h have similar values in the initial diagnosis of Cushing's syndrome, but PTC-DST is more convenient to be used in outpatient environment.

[Exendin-4 improves impaired endothelial dependent vasodilation in obese rat].

OBJECTIVE: To determine whether exendin-4 (Ex-4 )might improve endothelial dysfunction in aorta isolated from high-fatty diet induced obese rats. METHODS: 20 male Wistar rats were divided into normal control and high-fat supplement (OB) groups (n= 10 for each group). The rats were sacrificed after 10 weeks feeding and thoracic aorta was dissected and cut into four rings of 3 mm length, the response to acethylcholine (Ach) and sodium nitroprusside (SNP) were examined in organ bath containing Krebs-Henseleit (K-H) solution. In order to study the direct effects of Ex-4 on obese rats vascular function, the aortic rings obtained from obese rats were incubated with K-H solution (OB-C group, n = 10),or with K-H solution plus Ex-4 (OB-Ex group, n = 10). Aortic rings obtained from normal control group (n = 10) were incubated with K-H solution. After 1 hour of incubation, the aortic rings were precontracted with norepinephrine (0.1 gmol/L), then the rings were exposed to cumulative concentration of Ach (10(9)-10(4) mol/L) or sodium SNP (10(9)-10 6(-6) mol/L) to test the endothelial dependent (EDV) and independent vasodilation (EIV). The blood plasma of the rats was collected for biochemical test and celiac fat and body mass data were also obtained. RESULTS: The levels of serum triglyceride, total cholesterol, and free fat acid were elevated in the obese group compared with that of normal control group (P < 0.01). The ratio of celiac fat and body mass in the obese rats was also higher than the control (P < 0.05). Ach caused a concentration dependent vascular relaxation in all pre-constricted aortic rings. Compared to the control group, maximal endothelium dependent relaxation in the obese group was impaired (P < 0.05). The EIV values were comparable between two groups. Pre-incubation of obese rat's vessels with Ex-4 significantly increased cumulative relaxation to Ach (P < 0.05). SNP induced vessels relaxation had no statistical significance each groups (P > 0.05). CONCLUSION: Endothelial function was impaired in obese rats. Ex-4 directly mitigates impaired endothelial-dependent vasorelaxation of isolated obese rat's aortas.

Unilateral adrenal tuberculosis whose computed tomography imaging characteristics mimic a malignant tumor: A case report.

BACKGROUND: Adrenal tuberculosis usually presents with bilateral involvement. It has special characteristics in computed tomography (CT) images, such as small size, low attenuation in the center, and peripheral rim enhancement, which differ from those of primary tumors. CASE SUMMARY: A 42-year-old female presented to the hospital with low back pain. She had been diagnosed with hypertension as well as pulmonary and cerebral tuberculosis but denied having any fever, fatigue, anorexia, night sweats, cough, or weight loss. Abdominal CT revealed an irregular 6.0 cm × 4.5 cm mass with uneven density in the right adrenal gland, while the left adrenal gland was normal. No abnormalities were observed in plasma total cortisol (8 am), adrenocorticotropic hormone, aldosterone/renin ratio, blood catecholamines, or urine catecholamines. A fine-needle aspiration biopsy of the right adrenal gland provided evidence of tuberculosis. After three years of anti-tuberculosis treatments, the large mass in the right adrenal gland was reduced to a slight enlargement. CONCLUSION: This is a case of unilateral adrenal tuberculosis with CT imaging characteristics mimicking those of a malignant tumor. Extended anti-tuberculosis therapy is recommended in such cases.

[Protective effects of Astragalus membranaceus on free fatty acid-induced vascular endothelial cell dysfunction].

OBJECTIVE: To investigate whether Astragalus membranaceus (AM) can protect endothelium-dependent vasodilatation (EDV) function of aorta from the damage induced by high level of free fatty acid (FFA). METHODS: Ten male SD rats, 8 weeks old and 250-300 g in weight, were sacrificed and thoracic aorta were harvested. Aorta rings incubated in organ baths were divided into three groups, Control group, FFA group and FFA+ AM group. The control group was incubated in 20 mL Krebs-Henseleit solution; the FFA group was incubated in 20 mL KH solution mixed with FFA(800 micromol/L) the FFA + AM group was incubated in 20 mL KH solution mixed with FFA (800 micromol/L) and AM (4 g/L). The relaxation levels of aorta rings response to acetylcholine and sodium nitroprusside were measured, the expression of NF-kappaB and the level of NOx in the organ bath were analyzed by immunohistochemistry. RESULTS: Severe endothelial dysfunction were induced in FFA group (maximal vasorelaxation in response to Ach: 61.1% +/- l6.9% vs. 93.1% +/- 2.7% in control, P < 0.05), while EDV in FFA+AM group was significantly improved by the incubation with AM (P < 0.05). Compared with the control group (104.1 +/- 14.2) micromol/g, NOx levels of FFA group was (83.1 +/- 8.4) micromol/g (P < 0.05), and the treatment of AM increased the levels of NOx (98.8 +/- 10.7) micromol/g (P < 0.05). The control vascular ring had a little NF-kappaB expression in endothelial nucleus, FFA increased the activation of NF-kappaB, while the treatment of AM lower the elevated NF-kappaB level. CONCLUSION: FFA can directly injure EDV, while AM may ameliorate it, with the possible mechanism related to the signal pathway of NF-kappaB and NO.

[Effect of inflammation factors on endothelial function in insulin resistance SD rats].

OBJECTIVE: To test the effect of inflammation factors on endothelial dysfunction in insulin resistance SD rats. METHODS: Male SD rats were divided randomly into three groups. The rats in the NC group, OB group and OB-AS group were fed with normal chow, high-fat chow, and high fat chow plus aspirin, respectively. The perifereal insulin sensitivity was detected with hyperinsulinemic euglycemic clamp. The endothelial dependent and independent vasodilatation were evaluated by measuring blood flow through femoral artery. Serum concentrations of high-sensitivity (hs) CRP and TNF-alpha were measured. Quantitative analysis of the expression of IKKbeta and NF-kappaB was performed. RESULTS: The rats in the OB group had significantly higher levels of serum hsCRP and TNF-alpha than the rats in the NC group (P < 0.05). There was a significant difference in endothelium-dependent (Ach-mediated dilation) vascular response and serum NO level between the OB group and the NC group (P < 0.05). Meanwhile, the rats in the OB group showed higher expression of NF-kappaBp65 (P < 0.05) and IKKbeta/NF-kappaBp65 (P < 0.05) than those in the NC group. Interestingly, compared with the rats in the OB group, the serum concentrations of TNF-alpha and CRP decreased significantly in the rats in the OB-AS group, to which high dose aspirin was given (P < 0.05). Better endothelium-dependent vascular response and higher serum NO level were observed in the rats in the OB-AS group than those in the NC group (P < 0.05). The rats in the OB-AS group also had significantly lower expression of NF-kappaBp65 (P < 0.05) and IKKbeta/NF-kappaBp65 (P < 0.05) than those in the OB group. CONCLUSION: Elevated inflammation factors are involved in the endothelial dysfunction by inactivating IKKbeta-NF-kappaB pathway in rats with insulin resistance.

[Protein kinase C activation is required for free fatty acid-induced impairment of endothelial nitric oxide synthase].

OBJECTIVE: To observe whether the impairment of endothelial nitric oxide synthase (eNOS) activity by elevated level of free fatty acid (FFA) is associated with activation of protein kinase C (PKC). METHODS: The cultured human umbilical vein endothelial cells were used for four groups: control group, oleic acid (OA) group (10, 50, 100, 150, 200 micromol/L), GFX group and OA+GFX group. The activity of eNOS in each group was examined, and the activity and expression of PKC were determined in both control and OA groups. The method of immunocytochemistry was performed to detect the expression of p-eNOS(1177) in control, OA (100 micromol/L), GFX and OA+GFX groups respectively. RESULTS: Compared with control group, the eNOS activity of endothelial cells in OA group was significantly reduced in a dose-dependent manner, and the expression of p-eNOS(1177) were also impaired (0.0854 +/- 0.017 vs. 0.0134 +/- 0.023, P < 0.05). PKC transposition from endochylema to cytomembrane was observed by confocal microscopy. The PKC activity was degraded in endochylema, while enhanced in cell membrane inversely, and the gross activity of PKC increased after all. When GFX, an inhibition of PKC, was added to endothelial cells at the present of OA or not, the impaired eNOS activity were partly improved. CONCLUSION: Elevated level of FFA (here is oleic acid) leading to endothelial dysfunction results from a loss of eNOS activity and its serine phosphorylation, and it may be related to activation of PKC.

Severe insulin allergy after percutaneous transluminal coronary angioplasty.

BACKGROUND: Insulin therapy is essential for type 1 and inadequately controlled type 2 diabetic patients. Insulin allergies have become less common since the introduction of highly purified human recombinant insulin. There are rare reports of severe insulin allergic reactions after percutaneous transluminal coronary angioplasty (PTCA) in patients with type 2 diabetes who had no previous allergic reactions. To better understand the causes and presentation of this rare acute reaction, we present the following observed case. CASE SUMMARY: A 63-year-old Chinese man (height, 172 cm; weight, 68.5 kg) with a 17-year history of type 2 diabetes and hypertension was first admitted to the West China Hospital, Sichuan University, Sichuan, People's Republic of China, for uncontrolled type 2 diabetes. He used regular human insulin, neutral protamine Hagedorn insulin, or premixed insulin without any allergic reactions. Four months later, PTCA was performed because of an acute myocardial infarction. The patient was administered 50 mg of protamine after active abdominal bleeding due to a right external iliac artery rupture. Three months later, recurrent raised, pruritic erythema occurred at the insulin injection site immediately after injection. Four weeks later, he experienced an attack of generalized urticaria at multiple previous injection sites (abdomen, upper arms, thighs) after injecting premixed insulin. It was accompanied by dizziness and palpitations. During the following 3 months, the symptoms recurred 3 times; one time, the patient reported losing consciousness for 2 to 3 minutes. The results of a skin prick test found that he was allergic to human recombinant insulin and insulin lispro. The allergy was resolved by changing his treatment regimen from insulin to oral hypoglycemic agents. A Naranjo score of 10 suggested a definite relationship (score >or=9) between the adverse drug reaction and the insulin administration. CONCLUSIONS: We present a definite case of allergy associated with insulin and insulin lispro administration. The patient had not experienced anaphylactic reactions prior to PTCA and protamine administration.