Guanxinning tablet inhibits the interaction between leukocyte integrin Mac-1 and platelet GPIbα for antithrombosis without increased bleeding risk.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

Association Between Thyroid Hormones, Lipids and Oxidative Stress Markers in Subclinical Hypothyroidism.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of many chronic diseases. It is recognized in overt hypothyroidism while its existence in subclinical hypothyroidism (SCH) is not well established. The aim of this study was to determine whether there was increased oxidation of lipids and proteins in SCH, and examine their association with lipids and thyroid hormones. METHODS: Male adults (35-59 years) with SCH (n=467) and euthyroid controls (n=190) were studied. Anthropometric measurements, plasma lipids, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total antioxidant capacity (T-AOC), lipid peroxidation products, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and dityrosine concentrations were measured. RESULTS: Plasma concentrations of MDA were significantly higher (p<0.05) in SCH (8.11±1.39 nmol/mL) compared with euthyroid controls (7.34±1.31 nmol/mL) while AOPP, dityrosine and T-AOC levels were not different. MDA was not associated with TSH (ß=-0.019, P=0.759), FT4 (ß=-0.062, P=0.323) and FT3 (ß=-0.018, P=0.780) in SCH while levels increased with elevated total cholesterol (ß=0.229, P=0.001), LDL (ß=0.203, P=0.009) and triglycerides (ß=0.159, P=0.036) after adjustment for age and body mass index. T-AOC reduced (ß=-0.327, P=0.030) with increased MDA in euthyroid controls and not in SCH (ß=-0.068, P=0.349), while levels increased with elevated triglycerides in both groups. CONCLUSIONS: Oxidative stress was increased in subclinical hypothyroidism as evidenced by the elevated lipid peroxidation product, malondialdehyde, while protein oxidation was absent. Thus, reduction of oxidative stress may be beneficial in patients with subclinical hypothyroidism.

Elevated plasma dityrosine in patients with hyperlipidemia compared to healthy individuals.

BACKGROUND: Dityrosine, the modification of tyrosine residues, may contribute to metabolic disorders. This study was undertaken to investigate plasma dityrosine concentrations in patients with hyperlipidemia and to examine the correlation between dityrosine and lipid profiles. METHODS: Fluorescence spectrophotometry was used to measure dityrosine in the plasma of healthy subjects (n = 203) and dyslipidemic subjects, which included patients with mild hyperlipidemia (n = 246) and hyperlipidemia (n = 179). Advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were also assayed in all subjects. RESULTS: Dityrosine levels were higher by 9.3 and 22.9% in mildly hyperlipidemic and hyperlipidemic patients, respectively, compared to controls after adjustment for age, gender, and BMI. AOPP and MDA levels showed similar trends. The levels of dityrosine related positively (p < 0.05) to total cholesterol (r = 0.362), triglycerides (r = 0.449), and low-density lipoprotein cholesterol (r = 0.359). Moreover, plasma dityrosine (r = 0.408), AOPP (r = 0.488), and MDA (r = 0.181) levels were elevated with an increase in the atherosclerosis index in the subjects. CONCLUSIONS: These findings suggest that dityrosine formation may be an early event in the pathological process of hyperlipidemia. Dityrosine as a biomarker detected by fluorescence spectrophotometry might be a useful tool to evaluate the plasma redox state in hyperlipidemia.

Disparities in the Prevalence of Metabolic Syndrome (MS) and its Components Among University Employees by Age, Gender and Occupation.

BACKGROUND: Metabolic Syndrome (MS), a known risk factor for Cardiovascular Disease (CVD) and type II diabetes is an emerging epidemic in China. Studies carried out on the general population indicate a varied clustering of cardiovascular risks in many parts of the country. However, there is limited data on its prevalence in the working population. Workplace can serve as an important place for prevention, control and management of CVD risks. The aim of this study was to investigate the prevalence of MS and its components among University workers, and determine how the prevalence varied according to sex and occupation. METHODS: This was a cross-sectional study of 2,428 University employees (22-60 years) who received an annual clinical examination at the University hospital. Anthropometric measurements, blood pressure, Fasting Plasma Glucose (FPG), and lipid profiles were measured. MS was defined according to the National Cholesterol Education Program Adult Treatment panel III modified criteria. RESULTS: Overall prevalence of MS was 6.1%, higher in males (5.1%) than females (1.1%), and increased with age. The most prevalent MS components in all workers were hypertension (37.9%) and hypertryglyceridemia (20.8%), corresponding rates in males were 28.3% and 16.1% while females had a prevalence of 9.6% and 4.7%. After adjustment for age, administrative work was associated (p<0.05) with increased hypertension (odds ratio (OR) =1.474; 95% confidence interval (CI), 1.146-1.896) and hyperglycemia (OR=1.469; 95% CI, 1.082-1.993) in male workers, and with hypertension (OR=1.492; 95% CI, 1.071-2.080) in females. However, prevalence of hypertryglyceridemia was lower (OR=0.390; 95% CI, 0.204-0.746) in female administrators compared to those in academics. Obesity, MS and reduced High Density Lipoprotein (HDL) cholesterol prevalence was not different (p>0.05) between the two occupations in both sexes. CONCLUSIONS: Prevalence of MS and its components was higher in male workers than in females, increased with age, and were more common in administrative workers. The findings support the need for gender and occupation specific health interventions to prevent CVDs and type II diabetes in the workplace.