Clinical study of two routes of vancomycin assisted continuous drainage in the treatment of secondary intracranial infection after traumatic brain injury / 中国生化药物杂志

Objective To investigate the clinical effect of continuous infusion of vancomycin in the treatment of intracranial infection secondary to traumatic brain injury by intrathecal injection and intravenous infusion. Methods 96 patients with traumatic brain injury from December 2015 to March 2017 were randomly divided into study group and control group, the patients were randomly divided into study group and control group (n=48).The study group of patients with continuous drainage combined with vancomycin intrathecal injection treatment, the control group of patients with continuous drainage combined with vancomycin intravenous infusion. The clinical effects of two groups of patients with secondary intracranial infection after traumatic brain injury were recorded. Results After treatment, the total effective rate of clinical treatment in the study group was as high as 89.58%, compared with 70.83% in the control group, the differences were statistically significant(P<0.05). Conclusion Vancomycin intrathecal injection combined with continuous drainage is effective in the treatment of secondary intracranial infection after brain injury, and it is beneficial to protect the quality of life and life safety of the patients.

Clinical study of two routes of vancomycin assisted continuous drainage in the treatment of secondary intracranial infection after traumatic brain injury / 中国生化药物杂志

Objective To investigate the clinical effect of continuous infusion of vancomycin in the treatment of intracranial infection secondary to traumatic brain injury by intrathecal injection and intravenous infusion. Methods 96 patients with traumatic brain injury from December 2015 to March 2017 were randomly divided into study group and control group, the patients were randomly divided into study group and control group (n=48).The study group of patients with continuous drainage combined with vancomycin intrathecal injection treatment, the control group of patients with continuous drainage combined with vancomycin intravenous infusion. The clinical effects of two groups of patients with secondary intracranial infection after traumatic brain injury were recorded. Results After treatment, the total effective rate of clinical treatment in the study group was as high as 89.58%, compared with 70.83% in the control group, the differences were statistically significant(P<0.05). Conclusion Vancomycin intrathecal injection combined with continuous drainage is effective in the treatment of secondary intracranial infection after brain injury, and it is beneficial to protect the quality of life and life safety of the patients.

Role of CD44 in monocyte transmigration across Cryptococcus neoformans-infected blood-brain barrier in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of CD44 in monocyte adhesion to human brain microvascular endothelial cells (HBMECs) and monocyte migration across an in vitro model of blood-brain barrier (BBB) infected by Cryptococcus neoformans (Cn).</p><p><b>METHODS</b>An in vitro blood-brain barrier model was constructed using a transwell chamber covered with a HBMEC monolayer. The wild-type strain of Cn B4500FO2, TYCC645#32 strain with CPS1 gene deletion and PCIP strain with CPS1 complementation were chosen to infect the monolayer HBMECs. THP-1 cells were added to the upper chamber of transwell, and the relative migration rate was determined by counting the number of the cells entering the lower chambers. The inhibitory effects of anti-CD44 monoclonal antibody and the CD44 inhibitor bikunin were examined on THP-1 binding to and migration across HBMECs.</p><p><b>RESULTS</b>Cn infection of the HBMECs caused markedly enhanced THP-1 cell adhesion and migration across the monolyers (P<0.01) dependent on Cn concentration and exposure time. Addition of anti-CD44 monoclonal antibody and bikunin significantly lowered THP-1 adhesion and migration rates in the BBB model with Cn-infected HBMECs (P<0.01) with a dose dependence of the antibody (within 0-1 µg) and inhibitor (within 0-20 nmol/L). Both THP-1 adhesion rate and migration rate were lowered in the BBB model infected with CPS1 gene-deleted Cn but increased in the model infected with the complemented strain compared with those in the wild-type strain-infected model.</p><p><b>CONCLUSION</b>In the in vitro BBB model, CD44 expressed on HBMECs may play an essential role in monocyte adhesion to and migration across the BBB. The capsular hyaluronic acid may mediate Cn-induced monocyte adhesion and migration.</p>

Oxidized low density lipoprotein and peroxisome proliferator-activated receptor α induced endogenous fibroblast growth factor 21 upregulation is protective against apoptosis in cardiac endothelial cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of peroxisome proliferator-activated receptor (PPAR)α agonist bezafibrate and oxidized low density lipoprotein (ox-LDL) on fibroblast growth factor 21 (FGF21) expression and apoptosis in cardiac endothelial cells.</p><p><b>METHODS</b>The mRNA level of FGF21 was determined by real time-PCR and the protein concentration of FGF21 in culture media was detected by enzyme-linked immunosorbent assay in cultured cardiac microvascular endothelial cells (CMECs) incubated with 10, 50, 100 µg/ml ox-LDL, 50, 100 or 200 µmol/L bezafibrate alone or in combination with 100 µg/ml ox-LDL. CMECs apoptosis in various treatment groups was also determined.</p><p><b>RESULTS</b>FGF21 mRNA and protein expressions were significantly upregulated in proportion to increased ox-LDL, and 200 µmol/L bezafibrate alone also significantly upregulated FGF21 expression and CMECs apoptosis was significantly reduced in 200 µmol/L bezafibrate + 100 µg/ml ox-LDL group compared to 100 µg/ml ox-LDL group (P < 0.05).</p><p><b>CONCLUSIONS</b>Our data suggest that bezafibrate and ox-LDL induced upregulation of FGF21 might mediate the protective effect against apoptosis. Endogenous FGF21 could thus play important roles in improving the endothelial function at the early stage of atherosclerosis and slowing the development of coronary heart disease.</p>

Fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fibroblast growth factor 21 (FGF21) is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.</p><p><b>METHODS</b>The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein (ox-LDL), and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells (CMECs) were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMECs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.</p><p><b>RESULTS</b>The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 µmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis (P < 0.05).</p><p><b>CONCLUSIONS</b>FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.</p>

Protective effects of 11,12-epoxyeicosatrienoic acid preconditioning and postconditioning on myocardial ischemia/reperfusion injury in rats / 生理学报

To explore the effects of 11,12-epoxyeicosatrienoic acid (11,12-EET) preconditioning and postconditioning on myocardial ischemia/reperfusion (IR) injury in rats, the IR injury model was built by stopping perfusion for 40 min followed by reperfusion for 30 min, and the changes of mitochondrial functions, myocardial metabolism and function were measured. Langendorff-perfused isolated rat hearts were divided into 4 groups: control group, persistently perfused with Krebs-Henseleit (K-H) fluid for 100 min; IR group, stopped perfusion for 40 min followed by reperfusion for 30 min; Pre-EET group, preconditioned with 6.24×10(-9) mol/L 11,12-EET for 5 min twice before subjected to ischemia; Post-EET group, postconditioned with 6.24×10(-9) mol/L 11,12-EET for 30 s twice before reperfusion. The computer-based electrophysiological recording system was used to measure the changes of maximal rate of the pressure increase in contract phase (+dp/dt(max)), maximal rate of the pressure decrease in diastole phase of heart (-dp/dt(max)), left ventricular end-diastolic pressure (LVEDP) and difference of left ventricular pressure (DLVP). The activities of lactate dehydrogenase (LDH) in effluent, Ca(2+)-ATPase, Na(+)-K(+)-ATPase and succinate dehydrogenase (SDH) in mitochondria were measured with colorimetry method; superoxide dismutase (SOD) activity was measured with hydroxylamine method and malondialdehyde (MDA) content in myocardial tissues was measured with TBA method. The results showed that: (1) Compared with that in the control group, the myocardial functions, the values of SOD, SDH and Na(+)-K(+)-ATPase were decreased in IR group (P<0.05); the values of LDH, MDA and Ca(2+)-ATPase were increased (P<0.05) in IR group. (2) Compared with that in IR group, the values of SDH and Na(+)-K(+)-ATPase were increased (P<0.05) and the value of Ca(2+)-ATPase was decreased (P<0.05) in both Pre-EET and Post-EET groups. But no significant differences were detected between Pre-EET and Post-EET groups. (3) Compared with IR treatment, both 11,12-EET preconditioning and postconditioning caused significant decreases in MDA content and leakage of LDH, amendment of heart functions and increases in SOD activity (P<0.05). But there were no significant differences between 11,12-EET preconditioning and postconditioning. These results indicate that 11,12-EET preconditioning and postconditioning can protect myocardium from IR injury by improving mitochondrial functions, up-regulating the activities of Na(+)-K(+)-ATPase and SDH, and down-regulating the activity of Ca(2+)-ATPase in mitochondria. Moreover, 11,12-EET preconditioning and postconditioning also elevate the activity of SOD and reduce the content of MDA, suggesting that 11,12-EET can depress the oxidative stress in IR rat heart.

Effects of 11, 12-epoxyeicosatrienoic acid preconditioning and postconditioning on Ca(2+)- handling proteins in myocardial ischemia/reperfusion injury in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) preconditioning and postconditioning on Ca(2+)-handling proteins in myocardial ischemia/reperfusion (IR) injury in rats and reveal the effects and mechanism of 11, 12-EET on cardioprotection. METHODS The IR injury model was built by stopping perfusion for 40 minutes followed by reperfusion for 30 minutes. The isolated Langendorff-perfused rat hearts were divided into 4 groups: control group, IR group, EET preconditioning (Pre-EET) group and EET postconditioning (Post-EET) group. The computer-based electrophysiological recorder system was used to measure the changes of the maximal rate of pressure increased in the contraction phase (+dp/dt(max)), the maximal rate of pressure decreased in the diastole phase (-dp/dt(max)), the left ventricular end diastolic pressure (LVEDP) and the difference of left ventricular pressure (delta LVP). The activity of Ca(2+)-ATPase in sarcoplasmic reticulum was measured with colorimetric method. Reverse transcription-polymerase chain reaction was used to assess the gene expression of C(a2+)-handling protein [sarcoplasic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), ryanodine receptor type 2 (RyR,), and 1, 4, 5-trisphosphate inositol receptor type 2 (IP3 R2) ] mRNAs level.</p><p><b>RESULTS</b>Compared with IR group, the myocardial functions, the value of Ca(2+)-ATPase, and the expressions of IP3 R2 mRNA were significantly increased and the expression of PLB mRNA was significantly decreased in both Pre-EET group and Post-EET group (P < 0.05, P < 0.01). And the expression of SERCA mRNA was significantly increased in Pre-EET group (P < 0. 05). However, no significant differences were detected between Pre-EET and Post-EET groups. Moreover, the expression of RyR2 mRNA was not significantly different among all groups.</p><p><b>CONCLUSIONS</b>11, 12-EET preconditioning and post-conditioning can protect myocardium from IR injury by elevating the activity of Ca(2+)-ATPase in sarcoplasmic reticulum, up-regulating the expression of IP3 R2 mRNA, and down-regulating the expression of PLB mRNA. Moreover, up-regulating the expression of SERCA mRNA maybe one of mechanisms of 11, 12-EET preconditioning on cardio protection against IR injury.</p>

Effect of 11, 12-epoxyeicosatrienoic acids on hypoxia/reoxygenation injury in the human umbilical vein endothelial cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of 11, 12-epoxyeicosatrienoic acids (11, 12-EET) on the degree of hypoxia/reoxygenation injury in human umbilical vein endothelial cells ( HUVECs), and reveal the possible pathway of EET on protection.</p><p><b>METHODS</b>Primary cultured HUVECs were randomly divided into control group, hypoxia/reoxygenation group, 11, 12-EET control group, 11, 12- EET hypoxia/reoxygenation group, inhibition of extracellular signal-regulated kinase (ERKI/2) group, and inhibition of nitric oxide synthase (NOS) group. Hypoxia/reoxygenation injury model in HUVECs was established by exposure to hypoxia (2% O2, 5% CO2 and 93% N2) for 3 hours, followed by reoxygenation (95% air and 5% CO2) for 1 hour. The evaluation of the endothelial cells were made by immunohistochemistry. The cell viability was monitored by MTT assay. Colorimetry method was used to assay the lactate dehydrogenase (LDH) , malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in culture medium. Western blot was used to detect the expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated ERK1/2 in HUVECs.</p><p><b>RESULTS</b>11, 12-EET caused minor injury in normal oxygen incubated HUVECs; however, in hypoxia/reoxygenation HUVECs, it raised the cell viability markedly, decreased the LDH release and MDA content, and increased the activity of SOD and the expressions of eNOS and phosphorylated ERK1/2.</p><p><b>CONCLUSIONS</b>11, 12-EET may prevent against endothelial cell hypoxia/reoxygenation injury. The mechanism may be related to the increased activity of SOD, elimination of oxygen-derived free radicals, and reduction of eNOS and phosphorylated ERK1/2 lesion caused by hypoxia/reoxygenation.</p>

Cytochrome P450/epoxyeicosatrienoic acids system and myocardial ischemic-reperfusion injury / 中国医学科学院学报

Interests on the effects of cytochrome P450 (CYP450) monooxygenases and epoxyeicosatrienoic acids (EETs) on myocardial ischemic-reperfusion injury has been increased in recent years. The CYP450/EET system may influence the degree of myocardial ischemic-reperfusion injury through "poly-targets", such us oxygen free radical, calcium overload, leukocytes adherence, nitric oxide, ATP-sensitive K+ channels, and mitogen activated protein kinase. The exaggeration or recovery of injury depends on the physical status. Study of factors that affects CYP450/EET, particularly identification of their involvement in cardioprotective signaling and specific roles, will elucidate the mechanisms of myocardial ischemic-reperfusion injury, and find a new way of prevention and treatment. This article will review the relationship between the changes of CYP450/EETs system and myocardial ischemic-reper-

Effect of 11, 12-epoxyeicosatrienoic acid on nitric oxide synthase of ischemia-reperfusion myocardium in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effect of 11,12-epoxyeicosatrienoic acid (11,12-EET) on nitric oxide synthase (NOS) in myocardial ischemia/reperfusion injury and explore the protective role of NOS in myocardium.</p><p><b>METHODS</b>Rat myocardial ischemia/reperfusion model was produced by ischemia for 60 minutes and reperfusion for 30 minutes. Rats were divided into 5 groups: 11,12-EET ischemia/reperfusion groups (including EET1, EET2, and EET3 groups), EET control group, ischemia/reperfusion group, sham operation group, and control group. Changes of the maximal rates of rise and decrease of left ventricular pressure (+/-dp/dtmax) were observed. Activities of inducible nitric oxide synthase (iNOS) and constrictive nitric oxide synthase (cNOS) in myocardium were measured with chemocolorimetry.</p><p><b>RESULTS</b>During both ischemia period (60 min) and reperfusion period (30 min), +/-dp/dtmax was significantly lower in ischemia/reperfusion group than in sham operation group (P < 0.01), and was significantly higher in EET1, EET2 and EET3 groups than in ischemia/reperfusion group (P < 0.01). cNOS level was significantly lower in ischemia/reperfusion group than in sham operation group, was significantly higher in EET1, EET2 and EET3 groups than in sham operation group (P < 0.01), and was significantly higher in EET2 group than in EET group (P < 0.01). iNOS level was significantly higher in sham operation group than in EET control group (P < 0.05), was significantly higher in ischemia/ reperfusion group than in sham operation group (P < 0.01), and was significantly lower in EET1, EET2 and EET3 groups than in ischemia/reperfusion group (P < 0.01).</p><p><b>CONCLUSION</b>Exogenous 11,12-EET can improve ischemia/reperfusion injury, which may be related with the changes of NOS isozymes.</p>