ABSTRACT
Objective To determine the relationship of cytochrome P-450 epoxygenase metabolites of arachidonic acids with impaired endothelium-dependent vasorelaxation in the healthy elderly. Methods A case-control study was employed.The study enrolled 60 healthy young adults (group A) and 60 healthy senior citizens (group B) of Han population in Shanghai. Serum contents of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) (a stable metabolite of 14,15-EET), 6-Kote-PGF1a (a stable metabolite of prostaglandin) and TXB2 (a stable metabolite of thromboxane A2) were measured using ELISA kits. The endothelium-dependent vasorelaxation (EDV) and endothelium-independent vasorelaxation (NEDV) in brachial arteries were determined by color Doppler ultrasound. Results Compared with group A, group B had significant higher levels of hemoglobin A1c, triglyceride and cholesterol levels (P＜0.01), and significant lower levels of 14,15-DHET and 6-Kote-PGF1a (P＜0.001), leading to increased values of TXB2/6-Kote-PGF1a and TXB2/14,15-DHET. There was bigger basal interior diameter of brachial arterials with reduced EDV and NEDV response (P＜0.01 and P＜0.05, vs. group A respectively) in group B. Moreover, the age was negatively correlated with 14,15-DHET and TXB2/14,15-DHET. Conclusions Our results indicate that the impaired EDV and NEDV in aging are associated with reduced production of arachidonic acid metabolites through cytochrome P-450 epoxygenase pathway and cyooxygenase pathway of endothelium in the healthy elderly.
ABSTRACT
<p><b>OBJECTIVE</b>To study the therapeutical effects of the Chinese medicinal herb, Sophora flavescens (SFA) on a rat model of chronic Pseudomonas aeruginosa (PA) biofilm pneumonia.</p><p><b>METHOD</b>Rats were challenged intratracheally with alginate embedded PA strain PAO579 at the concentration of 1 x 10(9) colony-forming units per milliliter (CFU x mL(-1)). After challeng on the second day, three different doses SFA or sterile normal saline (NS) were administered by gastric intubation once a day for two weeks. Two weeks post intratracheal challenge with P. aeruginosa, parameters were evaluated.</p><p><b>RESULT</b>Two weeks after challenge, a remarkable serum antibody response and significant infiltration of numerous polymorphonuclear leukocytes (PMN) with lower IFN-gamma production in the lungs were found in the model group. However, milder macroscopic and lower incidence of lung abscesses were found in all the three groups received different doses of SFA treatment compared to the model group (P < 0.001). Meanwhile, the microscopic lung pathology in all SFA-treated groups were characterized by chronic inflammation dominated by mononuclear leukocytes (MN). The rat number with acute inflammation in group II, III was significantly lower than that in the model group (P < 0.05). Furthermore, the serum level of anti-PA IgG was down-regulated in group II and III (P < 0.05 or P < 0.001), and serum IgG level was negatively correlated with the SFA doses (r = -0.95, P < 0.01). In all the SFA-treated groups higher IFN-gamma production in the lung was found compared to the model group (P < 0.001), and the lung IFN-gamma level was positively correlated with the SFA doses (r = 0.9, P < 0.02). These findings indicate that SFA has an effect on inducing Thl type of immune response. The anti-PA activity test of SFA was weakly positive whereas NS was negative.</p><p><b>CONCLUSION</b>SFA treatment significantly reduced pathology, which might be associated with a shift of local immune responding type from a Th2 like to Thl like that might provide a better protection to the rats with chronic P. aeruginosa lung infection. And these results also showed that the SFA dose of 12 g x kg(-1) was the best dosage in this present study.</p>