ABSTRACT
Objective:To observe the effect of genetic inactivation of adenosine A 2A receptor on apoptosis in the prefrontal cortex and on the expression of phosphorylated p38 mitogen-active protein kinase (p38MAPK) in mice with chronic hypoxic hypercapnia. Methods:Sixteen male wild-type mice and 16 male mice in which the adenosine A 2A receptor gene had been knocked out were randomly divided into a 4 weeks group (including 4HH+ /+ and 4HH-/- subgroups) and a normal control group (including NC+ /+ and NC-/- subgroups). The 4HH+ /+ and 4HH-/- group mice were exposed to an atmosphere containing 9-11% O 2 and 5-6% CO 2 8 hours a day, 6 days a week for 4 weeks. The apoptosis index (AI) in their prefrontal cortices was then evaluated using terminal-deoxynucleoitide transferase mediated nick end labelling (TUNEL) staining. The expression of p38MAPK protein in the prefrontal cortices was measured using western blotting. Results:The average AI had increased significantly in the 4HH+ /+ and 4HH-/- groups compared with the controls, with significantly more apoptotic cells in the 4HH+ /+ group than in the 4HH-/- group. In the 4HH+ /+ and 4HH-/- groups the average expression of p38 protein in the prefrontal cortex was significantly higher than among their controls. Moreover, the average expression of p-p38MAPK protein in the prefrontal cortex of the 4HH-/- group was significantly lower than in the 4HH+ /+ group.Conclusion:Adenosine A 2A receptor knockout inhibits apoptosis in the prefrontal cortex and down-regulates the p38MAPK activation of mice after exposure to chronic hypoxic hypercapnia.
ABSTRACT
@#BACKGROUND: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury. METHODS: Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group. CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.
ABSTRACT
Objective To establish a stable and rapid separation and purification method for Astragalus membranaceus (Am) pathogenesis-related protein-10 (AmPR-10) using an automatic intelligent protein purification system AKTA Avant 25, and analyze its physiochemical and biological activity. Methods Am was extracted by Tris-HCl buffer. The crude extract was captured by anion exchange chromatography, and finely separated by hydrophobic chromatography and gel filtration chromatography. The relative molecular weight of AmPR-10 was measured by MALDI-TOF/TOF mass spectrometry, the protein identification was determined by mass spectrometry and MS/MS Ion Search, the glycoprotein identification was estimated by periodic acid-Schiff method, and the ribonuclease activity and effect factors were analyzed by agarose gel electrophoresis. Results The electrophoretically pure AmPR-10 was obtained by three-step purification of Q Sepharose Fast Flow, Butyl Sepharose High Performance and SuperdexTM 75 10/300 GL from the crude extraction. The relative molecular weight of AmPR-10 was 16 801. AmPR-10 was highly homologous to PR-10 and has no carbohydrate chains. Incubated at 56 ℃ for 30 min, AmPR-10 exhibited significant ribonuclease activity to total RNA of mammalian cells. The activity was insensitive to NaCl, pH value and mental ions, and weekly inhibited by 0.5 mol/L NaCl, pH 9.0, Mg2+ and Co2+. The activity was the same at EDTA as high as 20 mmol/L. Conclusion The three-step method of exchange chromatography-hydrophobic chromatography-gel filtration chromatography, a stable and rapid separation and purification method of AmPR-10, can be applied for other Chinese herbs. AmPR-10 might play an important role in resistance against virus.
ABSTRACT
Objective To investigate the influence of hydroxyethyl starch solution on exogenous coagulation and active protein C (APC) in the patients with septic shock.Methods A single-center prospective study was conducted.Eighty-four consecutive patients with septic shock admitted to intensive care unit (ICU) of Peking University People's Hospital from November 2009 to October 2014 were enrolled.The patients were randomized into two study groups by random digits table:Ringer lactate solution group (RL group,n =40) and hydroxyethyl starch group (HES group,n =44),and Ringer lactate solution or hydroxyethl starch 130/0.4 was used for resuscitation respectively.Peripheral blood was collected at four time points:before resuscitation,6,12,and 24 hours after resuscitation.The prothrombin time (PT),tissue factor (TF),tissue factor pathway inhibitor (TFPI) and APC were determined,and the length of ICU stay and the mortality were recorded.Results There were no significant differences in PT,TF,TFPI,and APC before and after resuscitation in RL group.No change in PT was found after resuscitation in HES group,and no significant difference was found as compared with RL group.TF after resuscitation in HES group was decreased gradually,and the level at the 24 hours after resuscitation was significantly lower than that before resuscitation (U/L:15.80±7.32 vs.31.40±2.75,P ＜ 0.05); but there was no significant difference at all time points when compared with that of RL group (all P ＞ 0.05).TFPI at 12 hours and 24 hours after resuscitation in HES group was increased when compared with before resuscitation (μg/L:1.32±0.22,1.14±0.09 vs.0.63±0.54).TFPI in HES group was significantly higher than that in RL group (μg/L:0.84 ± 0.69,0.95 ± 0.30),but there was no significant differences between two groups (both P ＞ 0.05).APC after resuscitation in HES group was decreased gradually,which was significantly lower than that in RL group at 6,12,24 hours after resuscitation (mg/L:3.38±3.00 vs.5.98±4.12,3.31 ± 1.94 vs.5.33 ± 3.71,3.42 ± 2.64 vs.7.53 ± 4.67,P ＜ 0.05 or P ＜ 0.01).The length of ICU stay in HES group was significantly shorter than that in RL group (days:12.50 ± 8.83 vs.17.10± 16.60,t =9.037,P ＜ 0.001),but there was no significant difference in mortality between HES group and RL group [40.9％ (18/44) vs.60.0％ (24/40),x 2=2.339,P =0.126].Conclusions Both RL and hydroxyethyl starch fluid resuscitation did not affect the PT of the patients.The use of hydroxyethyl starch probably inhibits excessive activation of the exogenous coagulation and hyper-coagulation in the early stage of sepsis,and inhibits activation of protein C as well.
ABSTRACT
Objective Clinical studies show that the level of C-reactive protein ( CRP ) markedly increases in the acute phase of cerebral hemorrhage .However , the correlation of the CRP level with early neurological deterioration ( END) in patients with basal ganglia hemorrhage remains unclear .This study investigated the correlation between CRP and END in basal ganglia hemorrhage . Methods This study included 142 cases of basal ganglia hemorrhage diagnosed by cranial CT between Jan 2010 and Dec 2012 .END was defined as any decrease in Canadian Stroke Scale ( CSS) score≥1 point in the first 48 hours after stroke onset .We compared the baseline data between the END and non-END patients and evaluated the correlation between CRP and END by logistic regression analy -sis. Results END was found in 31 (21.8%) of the 142 patients.Univariate analysis of the END versus non-END cases showed that hyperglycemia (29.03 vs 11.71%, P=0.018), neutrophil count ([11.8 ±1.2] vs [7.8 ±7.7] ×109/L, P=0.019), CRP (P=0.001), hematoma expansion (54.83 vs 19.81%, P=0.001), hematoma volume ([23.6 ±21.9] vs [14.8 ±12.7] mL, P=0.005), and intraventricular hemorrhage (68.75 vs 28.83%, P<0.001) were significantly associated with END .Logistic regression a-nalysis indicated that the CRP level (OR=1.072, 95%CI:1.034-1.112, P=0.001), intraventricular hemorrhage (OR=4.162, 95%CI: 1.498 -11.564, P =0.006), and hematoma expansion (OR=5.297, 95%CI:1.906-14.723, P=0.001) were correlated with END in the patients during their hospital stay .ROC analysis man-ifested the predictive value of the CRP level for END in basal ganglia hemorrhage (OR=0.812, 95%CI: 0.732 -0.891, P <0.001). Conclusion The elevated level of CRP is significantly correlated with END in patients with basal ganglia hemorrhage and therefore can be re-garded as a predictive factor for this condition .
ABSTRACT
Objective To investigate the plasma 8-iso-prostaglandin F2α(8-iso-PGF2α and the serum C-re-active protein(CRP) levels in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS) with and without hypertension(OSAHS + HT),and to explore the changes of pathophysiology in patients with OSAHS and the patho-genesis of OSAHS + HT. Methods All observed subjects were divided into 3 groups: control group (n=20),OS-AHS group(n=19),OSAHS + HT group (n=21). Plasma 8-iso-PGF2αand serum CRP concentrations levels were measured by ELISA and were compared. Results The plasma 8-iso-PGF2αand serum CRP levels,were higher in OSAHS patients than those in control subjects [(11.08±3.26)μg/L vs (7.49±2.10)μg/L,P<0.01;(1.75±0.82) mg/L vs (0.52±0.26 ) mg/L,P<0.01],and were higher in OSAHS + HT group than those in control group [14.84±3.43)μG/L vs(11.08±3.26)μg/L,P<0.01 ;(3.13±1.06)mg/L vs(1.75±0.82)mg/L,P<0.01]. Conclusions Oxidative stress and inflammation in OSAHS patients are increased,which are involved in the devel-opment of OSAHS associated hypertension.
ABSTRACT
Objective To study the effect of combination of Hydrochlorothiaside (HCTZ) with Captopril or spironolactone on serum high-sensitivity C-reactive protein (hsCRP) in hypertension patients. Methods A multi-centre, random and parallel control study was applied in this study. Slight and moderate hypertension patiens were se-lected. The patients were treated with placebo for two weeks and HCTZ 12.5 mga day for 6 weeks,wbo were then randomly divided into HCTZ group(12.5 mg once a day), spironolactone group(HCTZ 12.5 mg once a day + Spi-ronolactone 20 rag once a day) and captopril group(HCTZ 12.5 mg once a day + Captopril 25 rag twice a day) . By the end of one-year follow up, HCTZ group was randomly added to Spironolactone group and Captopril group because combination therapy was superior to single medication,which was recognized. During the treatment, the patients were followed up once a month ,for monitoring blood pressure, and serum hsCRP level was measured every year. Follow-up last for 4 years. By the end of 4 years, the patients were divided into treatment group and control group in order to compare the changes of serum hsCRP levels. Results At the end of 4 years, the blood pressure and serum hsCRP level were significantly decreased as compared with baseline, and were statistically different from that of control group (P <0.05 or 0.01). Multi-factor analysis showed that pre-treatment systolic blood pressue and serum hsCRP level, post-treatment decrease value of systolic blood pressue and age were the major influencing factors for the de-crease of serum hsCRP level(P < 0.05 for each). Conclusion The long-term combinaion of HCTZ with Spironolactone or Captopril not only effectivley decreases blood pressure but also decreases serum hsCRP level. The decrease value of systolic blood pressure is the major factor for influencing serum hsCRP level.