Prostaglandin E2 (PGE2) is a cyclooxygenase metabolite of arachidonic acid. It acts as a bioactive lipid and plays an important role in regulating many biological processes. PGE2 binds to 4 different G protein-coupled receptors including prostaglandin E2 receptor subtypes EP1, EP2, EP3 and EP4. The EP4 receptor is widely expressed in most of human organs and tissues. Increasing evidence demonstrates that EP4 is essential for cardiovascular homeostasis and participates in the pathogenesis of many cardiovascular diseases. Here we summarize the role of EP4 in the regulation of cardiovascular function and discuss potential mechanisms by which EP4 is involved in the development of cardiovascular disorders with a focus on its effect on inflammation.
Cardiovascular Diseases ; physiopathology ; Cyclooxygenase 2 ; Dinoprostone ; physiology ; Humans ; Receptors, Prostaglandin E, EP4 Subtype ; physiology

Objective To study the effects of ibuprofen on the growth and development of oligodendrocytes. Methods A total of 6 clean and healthy adult female SD (Sprague Dawley) rats were used for extracting and culturing of oligodendrocytes(OLs).Lysophosphatidic acid(LPA)was then added,and the morphological changes of OLs pre-treatment and post-treatment were observed. Then 6 newborn rats (born 24-48 h) were used for mixed glial cell extraction from the cortex, then the OPCs were inoculated into the culture plates and randomly divided into control group, ibuprofen group, lysophosphatidic acid(LPA)group and LPA+ibuprofen group.After the adhering of the cells in each group for three days, cell morphology was observed,and the drugs were added as interventions.The control group was treated with normal saline, and the other 3 groups were added with saline solution of ibuprofen(100 μmol/L),LPA(1.0 μmol/L)and the mixture of them. The cell morphological changes were observed after 7-day intervention.The morphology of OPCs and OLs were observed by immunofluorescence staining through OPCs'specific immune markers (platelet-derived growth factor receptor alpha, PDGFR-α)and OLs'specific immune markers(myelin basic protein,MBP)along with cell count of mature OLs.Western blot assay was used to detect the relative expression level of MBP in each group. Results After the treatment with LPA to the mature OLs,protrusions were shrinking and became very sparse.The morphology of cells developed well in each group after cell adhering for 3 days. After drug intervention for 7 days, more cell protrusions and branches were observed in ibuprofen group and LPA+ibuprofen group than those of the control group and LPA group.The results of cell count showed that the number of MBP positive cells was significantly higher in the ibuprofen group and LPA+ibuprofen group than that in the control group and LPA group(P<0.01).The results of Western blot assay showed that the MBP protein expression was significantly less in LPA group than the other three groups (P<0.01), and the expression was significantly higher in the ibuprofen group than that of LPA+ibuprofen group (P<0.01). Conclusion LPA has a toxic effect on the growth and development of OPCs, and it has an inhibitory effect on the normal growth of mature OLs. A certain concentration of ibuprofen can significantly inhibit the cytotoxicity of LPA on OPCs and OLs,and promote the formation and maintenance of mature OLs.

Objective To study the effects of different concentrations of hypertonic saline (HS) and 20%mannitol on decreasing intracranial pressure (ICP) in patients with moderate-sever traumatic brain injury (TBI). Methods A total of 60 patients were randomly assigned into 7.5%HS group, 3%HS group and 20%mannitol group, 20 patients in each group. All of patients were treated with conventional treatment according to the diagnostic and treatment practices of TBI. When ICP was above 20 mmHg for more than 5 minutes, patients were administered corresponding hypertonic dehydrator. The levels of ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), urine volume per hour and serum sodium were monitored continuously within 6 hours after the initiation of therapy. Results All agents could significantly decrease the ICP (P<0.05), but the onset time in 7.5%HS group was less than that of the other two groups (P<0.05), and the decreased magnitude of ICP and the effective time of decreasing ICP in 7.5%HS group were more than those of the other two groups (P < 0.05). Both 7.5%HS and 3%HS could increase MAP and CPP. There was no statistical difference in serum sodium between both groups , but the diuretic effect in both groups was worse than that of 20%mannitol group. Conclusion The rapidly infusion of 7.5%HS could significantly decrease the ICP, increase the MAP and CPP without obvious side-effect in patients with moderate-sever TBI, and which is a safe and effective therapy for intracranial hypertension after traumatic brain injury .

In the fast pace of modern life and under the heavy work pressure, the prevalence of depression has increased year by year. Meanwhile, the demands for antidepressant drugs have also grown, especially the high-efficiency and low-toxicity natural antidepressant drugs, mainly including polyphenols, flavonoids, organic acids, alkaloids and terpenoids. Cytochrome P450 (CYP450) is a type of enzymes involving oxidative metabolism of drugs in vivo, and can change the pharmacokinetics and efficacy of drugs. Therefore, it is of important significant to define the effect of natural antidepressant drugs on CYP450 in human bodies, in order to improve the rational clinical medication, avoid drug interactions and reduce adverse reactions.
Animals ; Antidepressive Agents ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; pharmacology ; Cytochrome P-450 Enzyme System ; metabolism ; Depression ; drug therapy ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Humans

OBJECTIVECentral obesity is considered to be a central component of metabolic syndrome. Waist circumference (WC) has been widely used as a simple indicator of central obesity. This study is aimed to evaluate the sensitivity of WC cut-off values for predicting metabolic risk factors in middle-aged Chinese.

METHODSThe study involved 923 subjects aged 40-65 years. The metabolic risk factors were defined according to the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. WC cut-off 85-90 cm and ⋝90 cm were used as cut-off values of central pre-obesity and central obesity in males, respectively, while WC 80-85 cm and ⋝85 cm were used as cut-off values of central pre-obesity and central obesity in females.

RESULTSFirst, WC values corresponding to body mass index (BMI) 24 kg/m2 and visceral fat area (VFA) 80 cm2 were 88.55 cm and 88.51 cm in males, and 81.46 cm and 82.51 cm in females respectively. Second, receiver operating characteristic curves showed that the optimal WC cut-off of value was 88.75 cm in males, higher than that in females (81.75 cm). Third, the subjects with higher WC values were more likely to have accumulating metabolic risk factors. The prevalence of metabolic risk factors increased linearly and significantly in relation to WC levels.

CONCLUSIONWC cut-off values of central pre-/central obesity are optimal to predict multiple metabolic risk factors.

Aged ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Intra-Abdominal Fat ; physiopathology ; Male ; Metabolic Syndrome ; diagnosis ; epidemiology ; physiopathology ; Middle Aged ; Obesity ; diagnosis ; ROC Curve ; Waist Circumference

OBJECTIVETo investigate the effects of a novel tripeptide analog of arginine on isoproterenol (ISO), a beta-adrenergic receptor agonist, induced the change in concentration transient cytosolic free calcium in cultured neonatal rat cardiac myocytes (CMs).

METHODSThe expression of inducible nitric oxide synthase (iNOS) was induced in cultured neonatal rat CMs by stimulation with lipopolysaccharide (LPS) and interleukin-6 (IL-6) for 24 h, and quantitatively measured using Western blotting. The CMs were incubated in the presence of the new arginine analog for 6 h and the changes of fluorescence signal of free calcium in response to isoproterenol (ISO) treatment were measured under laser scanning confocal microscope.

RESULTSIncubation of the CMs for 24 h in the presence of IL-6 and LPS resulted in significantly increased nitric oxide (NO) production, and also in increased iNOS protein accumulation in the cells. Specific inhibition of iNOS by the new arginine analog substantially inhibited NO production and increased the peak value of ISO-induced Ca2+ transient.

CONCLUSIONThe new arginine analog strongly inhibits IL-6 and LPS-induced NO production and increases beta-adrenergic responsiveness in cultured neonatal rat CMs.

Animals ; Animals, Newborn ; Arginine ; analogs & derivatives ; pharmacology ; Calcium ; metabolism ; Cells, Cultured ; Isoproterenol ; pharmacology ; Myocytes, Cardiac ; cytology ; drug effects ; metabolism ; Oligopeptides ; pharmacology ; Rats ; Rats, Sprague-Dawley