Adult ; Aged ; Cantharidin ; therapeutic use ; Carcinoma, Hepatocellular ; therapy ; Embolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Portal Vein ; Treatment Outcome

Objective To study the characteristics of pharmacokinetics and pharmacodynamics of insulin dry powder inhalation and its relative bioavailability as compared with subcutaneous injection of regular insulin. Methods In this open,single-center,randomized,two-period,cross-over,euglycemic glucose clamp study,18 healthy volunteers(14 men and 4 women),aged(24.9?1.7)years,with body mass index(20.6?1.2)kg/m~2, received the insulin dry powder inhalatin(80 U)or regular insulin(15 U)subcutaneous administration.The blood samples of this study at 0,20,30,40,50,60,70,80,90,100,110,120,135,150,165,180,195, 210,225,240,270,300,330,360,390,420,450 and 480 rain were taken for serum insulin measurement, meanwhile,glucose infusion rates(GIR)were determined per 5 minutes over a period of 8 hours.Results The C_(max)were(57.9?17.8 vs 114.5?29.7)mU/L(tested vs reference preparation),T_(max)were(46.7?45.6 vs 107.8?33.7)min,GIR_(max)were(3.35?0.98 vs 5.17?1.75)mg?kg~(-1)?min~(-1)and T_(GIRmax)were(88.3?17.0 vs 151.9?34.6)min.The relative bioavailability was(10.26?2.25)%,and the relative bioefficacy was(14.33?7.26)%.Conclusion The study shows that insulin dry powder inhalation is absorbed via lungs and its action sets in earlier than that of the regular insulin injected subcutaneously.These pharmacokinetie and pharmacodynamic data may provide a reliabe guide for further clinical trial.

Objective To observe the effects of 75 gram glucose oral tolerance test (75 g OGTT) and standard mixed meal test (SMMT) on insulin secretion function of the islets of Langerhans and plasma free fatty acid (FFA) in patients with type 2 diabetes mellitus.Methods Seventy-six patients with type 2 diabetes without using insulin and with no obvious complications were recruited for 75 g OGTT following overnight fasting on the first day and SMMT (bread 50 g,egg 50 g and milk 250 ml) on the 7th day.Blood specimens were collected from each patients before the tests and 30 min,60 min,120 min and 180 min after glucose or meal load to measure their levels of plasma glucose,serum insulin,C peptide,FFA and lipids (total cholesterol,triglyceride,high-density and low-density lipoprotein cholesterol).Results No difference in fasting plasma glucose,serum insulin,C peptide,FFA and lipids between 75 g OGTT and SMMT was found.Postprandial plasma glucose 30 min,60 min,120 min and 180 min after 75 g OGTT was significantly higher than that after SMMT,with (15.3?3.5) vs (9.9?3.4) mmol/L,(18.2?4.8) vs (12.8?4.0) mmol/L,(16.3?5.8) vs (12.2?4.9) mmol/L and (10.6?5.4) vs (9.5?4.5) mmol/L (F=28.1,P

OBJECTIVETo explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months.

METHODSExperiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo.

RESULTSLow dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead.

CONCLUSIONMelatonin is not suitable for normal and lead-exposed children.

Animals ; Female ; Lead ; toxicity ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Maze Learning ; drug effects ; Melatonin ; administration & dosage ; toxicity ; Rats ; Spatial Behavior ; drug effects

BACKGROUNDThis prospective, randomized, controlled study was designed to investigate the effects of a diabetes specific formula (Diason low energy: 313.8 kJ/100 ml), compared with a standard formula, on insulin sensitivity, serum C peptide, serum lipids and free fatty acid (FFA) in type 2 diabetics.

METHODSIn total of 71 type 2 diabetics completed the study. Enteral formulas were given orally as the sole source of nutrition to the subjects for 6 days. Venous blood samples (0.5, 1, 2, 3 hours) were collected at day-7 after a 75 g oral glucose tolerance test (OGTT), day 1 after a standard test meal (1673.6 kJ) and after 6 days of either the test diabetes specific formula or a standard formula. Plasma glucose, serum insulin, C peptide and lipids were measured.

RESULTSAfter the intervention period, the diabetes specific formula resulted in a significantly lower postprandial rise in blood glucose concentrations at 0.5 hour (P < 0.05) and 1 hour (P < 0.01); significantly lower peak height of plasma glucose (P = 0.05); significantly lower plasma insulin concentrations at 0.5 hour (P < 0.01), 1 hour (P < 0.01) and 2 hours (P < 0.01); and a significantly lower plasma insulin peak compared to controls; both OGTT and a standard test meal (P < 0.05). The glucose and insulin area under the curve after the diabetes specific formula compared to the standard formula were significantly lower. The C peptide level was lower after 6 days of both nutrition formulas compare to 75 g OGTT, but not different from the standard mixed meal. Both formulas were well tolerated.

CONCLUSIONSIn summary the diabetes specific formula with a relatively high monounsaturated fatty acid and high multi fiber proportion significantly improved glycemic control. On top of this, the insulin sensitivity (HOMA-IS) was significantly improved and may therefore directly improve the impact on long term complications. The disease specific formula should therefore be the preferred option to be used by diabetic and hyperglycemic patients in need of nutritional support.

C-Peptide ; blood ; Diabetes Mellitus, Type 2 ; blood ; diet therapy ; Diet, Diabetic ; Fatty Acids, Nonesterified ; blood ; Humans ; Insulin ; secretion ; Lipids ; blood ; Middle Aged ; Prospective Studies

The aim of this study is to investigate the effects of the metformin on the formation of hepatic fibrosis in type 2 diabetic rats and discuss its mechanism of liver-protecting activity. After SD rats were fed with high-fat and high-sucrose diet for four weeks, low-dose streptozotocin (STZ) was injected intraperitoneally to make the animal mode of type 2 diabetes. Then, all diabetic rats was fed with the high-fat diet and metformin (ig, 100 mg x kg(-1)) was given orally to metformin group for four months. After the last administration, fasting blood glucose was determined. The livers were removed to calculate the hepatic coefficient and to make HE and Picro acid-Sirius red staining, immunohistochemistry (alpha-SMA and TGFbeta1) and TUNEL staining in order to evaluate the effect of metformin on the hepatic fibrosis. The animal model of type 2 diabetes with hepatic fibrosis was successfully made. Metformin can significantly alleviate the lesions of hepatic steatosis and fibrosis, markedly reduce the expressions of alpha-SMA and TGFbeta1 in liver tissue of type 2 diabetic rats. However, TUNEL staining result suggested that metformin could not reduce apoptosis of hepatocytes. The results suggest that metformin can inhibit the formation of hepatic fibrosis in type 2 diabetes.
Actins ; metabolism ; Animals ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; etiology ; metabolism ; pathology ; Diabetes Mellitus, Type 2 ; drug therapy ; etiology ; metabolism ; pathology ; Diet, High-Fat ; Female ; Hepatocytes ; pathology ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Metformin ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVESTo confirm previous whole-genome scan results of mapping type 2 diabetes susceptibility genes in chromosome 1 in Northern Chinese Han population by conducting a new genome scan with both an enlarged number of type 2 diabetes families and a new set of microsatellite markers.

METHODSA genome scan method was applied. After multiplexed PCR, electrophoreses, genescan and genotyping analysis, size informations for all loci were obtained, and a further study was done using both parametric and non-parametric linkage analysis to calculate the P-values and Z-values of these loci.

RESULTSA total of 34 microsatellite markers distributed within 5 regions along chromosome 1 were surveyed, and 12,000 genotypes were screened. Evidence of linkage with diabetes was identified for 8 of the 34 loci (all the P-values of the 8 loci distributed in 3 regions were lower than 0.05, and the highest Z-value was 2.17). Interestingly, all the 5 markers at the P terminal 1p36.3-1p36.23 region, spanning a long range of 16.9 cM, suggested to be linked with the disease. The results of the other two regions were not consistent with the previous ones.

CONCLUSIONSThe study results have confirmed those gained in the previous genome-wide scan. The fact that all 5 loci at the P terminal region displayed linkage with diabetes suggests that more than 1 susceptibility gene may reside in this region.

Asian Continental Ancestry Group ; Chromosome Mapping ; Chromosomes, Human, Pair 1 ; Diabetes Mellitus, Type 2 ; genetics ; Ethnic Groups ; Genetic Linkage ; Genetic Predisposition to Disease ; Genetic Testing ; Genotype ; Humans ; Microsatellite Repeats ; genetics

BACKGROUNDAortic root replacement with pulmonary autograft (Ross procedure) has the advantages of good haemodynamics and growth potential without the need for anticoagulation. In this study, we reviewed our experience of the Ross procedure for patients with aortic valve disease.

METHODSFrom October 1994 to January 2005, 42 Ross procedures were performed in our centre. There were 30 males and 12 females. The mean age was 28 +/- 15 years (range, 5-56 years). Congenital heart disease (CHD) with aortic valve stenosis (AS) and/or aortic valve insufficiency (AI) in 40 cases including one associated with ventricular septal defect (VSD), degenerated aortic valve disease with AS in 1 and subacutive bacterial endocarditis (SBE) with AI in 1 were studied. The diagnosis was made by ultracardiography (UCG) in all patients. The mean aortic valve annulus diameter (AVD) was (2.45 +/- 0.31) cm and pulmonary valve annulus diameter (MPVD) was (2.34 +/- 0.21) cm. All patients had normal pulmonary valves. The New York Heart Association (NYHA) function class was II in 36 cases and III in 6 cases. The operation was performed under moderate hypothermic cardiopulmonary bypass (CPB) with aortic root replacement using pulmonary autograft and pulmonary valve replacement with a homograft.

RESULTSThere was no early hospital mortality. Postoperative UCG showed normal aortic valve function in all our patients. The mean gradient across the aortic valve was (6.11 +/- 0.12) mmHg. The left ventricular diastole diameter (LVDD) decreased significantly from (62 +/- 5) mm to (56 +/- 3) mm (P < 0.001). The mean postoperative left ventricular ejective fraction (LVEF) was 0.49 +/- 0.23. All patients were in NYHA class I-II. Follow-up was completed in 38 cases for a mean period of 3.2 years (range 1-10 years). All survivors were in NYHA class I with normal neo-aortic and pulmonary valve function. One patient died after secondary operation due to homograft fungal endocarditis 1 year after the Ross procedure. The cause of death was uncontrolled bleeding. Another patient suffered from cardiogenic shock and was on extracorporeal membrane oxygenation (ECMO) for 10 days postoperatively. This patient was subsequently self-discharged from hospital due to financial issues and he was excluded from follow-up.

CONCLUSIONThe Ross procedure is an excellent technique to treat aortic valve disease. Our data show that it can be performed safely with good early and mid-term clinical outcomes.

Adolescent ; Adult ; Aortic Valve Insufficiency ; surgery ; Aortic Valve Stenosis ; surgery ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Valve ; transplantation ; Transplantation, Autologous

BACKGROUNDHyperinsulinemic euglycemic clamp is the gold standard to evaluate the insulin sensitivity, but it is too complicated and expensive to use in clinic. We tried to find an alternative indicator to reflect insulin sensitivity. To evaluate the association between the four adipokines, adiponectin, leptin, resistin and tumor necrosis factor-alpha (TNF-alpha) with insulin sensitivity, we used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese patients with obesity and type 1 or type 2 diabetes mellitus versus controls.

METHODSIn this parallel control study, we tested insulin sensitivity using a hyperinsulinemic euglycemic clamp in different groups, then examined levels of adiponectin, leptin, resistin and TNF-alpha in serum, and the relationship between the different adipokines and glucose disposal rate (M value), as well as insulin sensitivity index (M value/insulin, M/I), which are the "gold standard" indices of insulin sensitivity.

RESULTSThere were significant differences in mean leptin values in the four adipokines from the four different groups (P < 0.001; comparison of the variation between different groups was analyzed by variance analysis). Compared to controls (using multiple comparison two-way Dunnett t test), only the leptin level showed significant differences in the four adipokines from the four different groups at the same time (P < 0.001). The association analysis between the different adipokines and M or M/I values also showed that only leptin negatively correlated with M (r = -0.64, P < 0.001) or M/I values (r = -0.56, P < 0.001); there was no relationship between the other three adipokines and M or M/I values.

CONCLUSIONOnly leptin was associated with M or M/I values. Therefore, leptin might be one of the predictive factors of the degree of insulin resistance and risk of the accompanying disease.

Adipokines ; blood ; Adiponectin ; blood ; Asian Continental Ancestry Group ; Diabetes Mellitus, Type 1 ; blood ; Diabetes Mellitus, Type 2 ; blood ; Glucose Clamp Technique ; Humans ; Insulin Resistance ; physiology ; Leptin ; blood ; Obesity ; blood ; Resistin ; blood ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo evaluate the efficacy and safety of nateglinide, a new antidiabetic agent, in the treatment of type 2 diabetes.

METHODSA total of 219 treatment-naïve patients with type 2 diabetes from 6 centers were enrolled in this study and blindly divided into nateglinide group (n = 105) and repaglinide group (n = 114). In all patients, the disease was confirmed for at least three months. The whole observation lasted for 12 weeks. The efficacy indicators measured include glycohemoglobin A1c (HbA1c), fasting blood glucose, and 2 hours postprandial blood glucose, and the safety parameters measured included renal and hepatic function, serum lipids, and blood and urea profiles.

RESULTSSimilar decreases in fasting blood glucose, 2 hours postprandial blood glucose, and HbA1 c were found in both nateglinide group and repaglinide group without significant differences. No severe adverse events were noted. The hypoglycemia event reports were not significantly different between these two groups.

CONCLUSIONNateglinide is an effective and safe drug in treating type 2 diabetes.

Blood Glucose ; drug effects ; Cyclohexanes ; administration & dosage ; adverse effects ; therapeutic use ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Administration Schedule ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Phenylalanine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome