ObjectiveTo study the changes of levels of α subunits of stimulatory (Gsα) and inhibitory guanine nucleotide binding protein (Giα) in newborn guinea pig (0 2 days old) myocardium undergoing global ischemic reperfusion, and influences on the changes by St.Thomas Ⅱ and cold blood cardioplegic solution.MethodsThirty newborn guinea pigs were randomly assigned to three groups. GroupⅠ ( n = 10): the newborn hearts suffered by hypothermic global ischemia; group Ⅱ( n =10): the newborn hearts arrested by St. Thomas Ⅱ , and group Ⅲ ( n = 10): the newborn hearts arrested by cold blood cardioplegic solution. Levels of Gsα and Giα were investigated with Western blot analysis.ResultsNo differences of levels of Gsα and Giα were found in three groups before ischemia ( P gt;0.05). The level of Gsα after ischemia was significantly decreased than before ischemia in groupⅠand group Ⅱ ( P lt; 0 01), whereas no pronounced changes in group Ⅲ ( P gt;0.05) were noted after ischemia. The level of Gsα in group Ⅲ was not significantly changed after reperfusion compared with before ischemia( P gt;0 05), and it was much higher than those in groupⅠand group Ⅱ ( P lt; 0 01). Level of Giα was found not markedly changed in group Ⅲ after reperfusion compared with that before ischemia, but was notable higher in groupⅠand group Ⅱ( P lt;0.01). ConclusionsSignificant decrease of level of Gsα, whereas marked increase of level of Giα are found in myocardium of newborn guinea pig undergoing hypothermic (20℃) ischemic reperfusion. No impact of St. Thomas Ⅱ on these changes is verified, but recovery to the level of Gsα and Giα before ischemia is achieved by cold blood cardioplegic solution after ischemia and reperfusion. Unbalance between Gsα and Giα is the one of the mechanisms of ischemic reperfusion injury for immature myocardium.
ObjectiveTo investigate the protective effect and the regulation mechanism of oxaloacetate (OAA) on myocardial ischemia reperfusion injury in rats. MethodsSixty rats, weight ranged from 200 to 250 grams, were randomly divided into 6 groups:a negative control group, a sham operation control group, a model control group, an OAA pretreatment myocardial ischemia-reperfusion model group (three subgroups:15 mg/kg, 60 mg/kg, 240 mg/kg). We established the model of myocardial ischemia reperfusion of rats and recorded the internal pressure of left ventricle (LVSP), the maximal rate of left ventricular pressure change (±dp/dtmax) and left ventricular end diastolic pressure (LVEDP). We restored reperfusion 180 minutes after ligating the left anterior descending coronary artery 30 minutes and determinated cardiac troponin Ⅰ (cTn-I), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px). We took out heart tissues, stained it and calculated the infarcted size. We used the Western blot to detect the expression of NF-E2 related factor 2 (Nrf2), Kelch-like ECH-associated protein-1 (Keap1) and heme oxygenase-1 (HO-1). ResultsCompared with the sham operation group, heart function indexes in the negative control group had no significant difference (P>0.05). But in the model control group there was a decrease (P<0.05) And the serum levels of LDH, cTn-I, and myocardial infarcted size were significantly increased (P<0.01). Compared with the model control group, heart function indexes in the OAA pretreatment groups improved, the serum LDH, cTn-I activity, and infarct size decreased (P<0.05), SOD and GSH-Px activity increased (P<0.05). And these results were statistically different (P<0.01) in the high dose OAA pretreatment groups. Compared with the model control group, the expression of Keap1 in the OAA pretreatment group was down-regulated (P<0.001) while total Nrf2, nucleus Nrf2 and its downstream HO-1 was up-regulated (P<0.001), which suggested that OAA enhanced antioxidant capacity by (at least in part) Keap1-Nrf2 pathway, resulting in reducing myocardial damage and protecting myocardium after acute myocardial ischemia reperfusion injury. ConclusionOxaloacetate can provide protective effects on myocardial ischemia reperfusion injury through down-regulating the expression of Keap1 and up-regulating the expression of Nrf2 and its downstream peroxiredoxins to improve antioxidant capacity.
ObjectiveTo evaluate the effect of leucocyte- and platelet-rich plasma (L-PRP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in treating avascular necrosis of the femoral head (ANFH) in rabbits. MethodsTwenty-four New Zealand white rabbits (4-6 months old, both genders, weighing 2.0-3.0 kg) were used for the establishment of bilateral ANFH models and divided into 4 groups (n=6). BMSCs were isolated from the bone marrow of iliac crest, cultured and identified. L-PRP was prepared by Landesberg method. Core decompression only (group A), core decompression and L-PRP implantation (group B), core decompression and BMSCs implantation (group C), and core decompression and implantation of BMSCs and L-PRP were performed in 4 groups. To evaluate bone formation and remodeling of the defects, X-ray photography was taken at 2, 4, and 8 weeks postoperatively. The modified Lane-Sandhu scoring system was used to evaluate the bone formation. Two rabbits were sacrificed at 2, 4, 8 weeks after operation to harvest the specimens for histological observation, new blood vessel count and new bone area ratio. ResultsThe observations of radiology and histology displayed different degrees of bone regeneration at bone defect sites in each group. At 2, 4, and 8 weeks postoperatively, the results of Lane-Sandhu X-ray photography scoring, new blood vessel count, and new bone area ratio showed that groups C and D were significantly better than groups A and B, group D was significantly better than group C. and group B was significantly better than group A (P<0.05). ConclusionThese findings demonstrate that L-PRP can promote osteogenic differentiation of BMSCs in treating ANFH in rabbits, and core decompression associated with BMSCs and L-PRP is an effective and feasible method to treat ANFH.
Objective To systematically evaluate the influence of alcohol intervention on the outcome of rats and mice with ischemic stroke. Methods Databases including PubMed, EMbase, BIOSIS and CNKI were electronically searched from establishment dates of databases to June 2012 to retrieve animal experiments on the influence of alcohol intervention on the outcome of rats and mice with ischemic stroke. The relevant studies were identified according to the predefined inclusion and exclusion criteria, the data were extracted, and the quality was evaluated. Then meta-analysis was performed using RevMan 5.1 software. Results Eight studies were included. The results of meta-analysis showed that no significant difference was found between the alcohol intervention group and the control group (MD=−6.98%, 95%CI −20.38% to 6.43%, P=0.31). However, compared with the control group, low dose of acute alcohol intervention (less than 2 g/kg) improved the prognosis of ischemic stroke with a significant difference (MD=−22.83%, 95%CI −38.77% to −6.89%, P=0.005), and highly-concentrated of chronic alcohol intervention worsened the cerebral ischemic damage of rats and mice with a significant difference (MD=24.06%, 95%CI 10.54% to 37.58%, P=0.000 5). Conclusion Low dose of acute alcohol intervention (less than 2 g/kg) could improve the prognosis of rats and mice with ischemic stroke which has the potential neuro-protective effects. However, highly-concentrated chronic alcohol intervention could worsen the cerebral ischemic damage. Due to the limitations of the included studies such as publication bias, the influence of alcohol intervention on the outcome of rats and mice with ischemic stroke could be overestimated.
Objective Application of auditory brainstem response (ABR) in the study on the relationship of neonates with hypoxic-ischemic encephalopathy (HIE) and the children with hearing loss and auxiliary determine the prognosis of encephalopathy. Methods We prospectively selected neonates diagnosed as HIE in the department of neonatology of the Chengdu Women and Children Central Hospital from January, 2006 to June, 2008. Neonatal ABR was tested and the prognosis of neonates were observed through 3-year followed up in order to analyze the relationship between HIE severity and the severity of hearing handicap and the relationship between the severity of hearing handicap and prognosis. Statistical analysis was performed using SPSS 18.0. χ2 test was used to compare the rate between groups. Results 40 cases involving 80 ears were included, of which 33 cases accomplished the 3-year follow-up for prognosis. The results showed that, 86.3% HIE neonates had hearing handicap (mainly mild hearing loss, 40.0%). Medium-severe HIE groups had more serious hearing handicap than Mild HIE group with a statistical significance (continuity correction χ2=7.383, P=0.007). ABR results showed that, mild HIE is mainly manifested as I wave PL prolonged or poorly differentiated, accounting for 78.1%; medium - severe HIE are mainly manifested as III and V wave PL prolonged central segment abnormalities, accounting for 95.8%; the hearing threshold no more than 60 dB group had better prognosis than the hearing threshold more than 60 dB group prognosis (Fisher exact probability P=0.001). Conclusion ABR reflects that HIE severity and was positively related to the severity of hearing handicap. The more serious hearing loss in neonates is, the worse prognosis the neonates have. ABR can be used to assist the assessment of the prognosis of neonatal HIE.
Objective To assess the effects and safety of Tongxinluo (TXL) Capsule for patients with acute ischemic stroke. Methods PubMed (1966 to 2011.12.23), EMbase (1966 to 2011.12.23), Ovid CENTRAL (2011.10), CBM (1978 to 2011.12.23), VIP (1989 to 2011.12.23), CNKI (1980 to 2011.12.23), CDFD (1999 to 2011.12.23), and CDFD (1999 to 2011.12.23) were electronically searched for randomized controlled trials (RCTs) on TXL Capsule for patients with acute ischemic stroke. Meanwhile, relevant data were retrieved by hand search and data from pharmaceutical factories were collected. Two reviewers independently screened literature, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.1 software. Results Thirty nine RCTs (non-placebo-controlled trials) involving 3 906 patients were included. The quality of the included studies was generally low. The follow-up time started from the end of treatment (minimum: 7 days) to 6 months. The result of meta-analysis (16 trials, 1 445 patients) showed that the TXL group was better than the control group in improving neurological function (SMD= −1.09, 95%CI −1.68 to −0.49). The result of meta-analysis (21 trials, 2 500 patients) showed that, the effectiveness rate (91.3%) of the TXL group was significantly higher than that of the control group (RR=1.22, 95%CI 1.14 to 1.30). Eight trials reported adverse reactions such as nausea and gastric discomfort. Four trials reported that 5 patients in the control group died during the treatment. No studies reported the data of mortality, dependency rate during 3-month follow up, or quality of life. Conclusion Current studies show that, TXL Capsule improves neurological impairment of patients with acute ischemic stroke which has less adverse reactions. Further studies are still needed to verify the effects of TXL on long-term mortality and disability. It is necessary to conduct more high quality RCTs especially with placebo-controlled trials to confirm the efficacy of Tongxinluo for acute ischemic stroke.
Objective To assess the efficacy and safety of fibfinogen-depleting agents (snake venom extracts) in the treatment of acute ischemic stroke. Method A systematic review of all the relevant randomized controlled trails (RCTs) was performed. RCTs were identified from the Cochrane Stroke Group’s Specialized Trials Register, additional electronic and handsearching, and personal contract with pharmaceutical companies. We included all completed and unconfounded truly or quasi-randomized trials in patients with ischemic stroke comparing fibrinogen depleting agents for analysis. Results Ten completed and one ongoing RCTs have been identified so far. Up to 1998, only three trials using ancrod (182 patients) met the inclusion criteria. Ancrod was associated with a significant reduction in early deaths (5.6% vs. 16%; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13 to 0.85; 2P=0.02) suggesting that treatment of 100 patients would avoid about 10 early deaths. The frequency of asymptomatic intracranial hemorrhage shown by computed tomography was similar between ancrod-treated and control groups (7.6% vs. 9.6%; OR 0.78; 95%CI 0.26 to 2.33; 2P=0.65). No major intracranial or extracranial hemorrhages or recurrent ischemic strokes occurred in the ancord-allocated patients. There were nonsignificant trends in favor of ancrod in death from any cause (OR 0.57; 95%CI 0.27 to 1.23; 2P=0.15) and death or disability (OR 0.52; 95%CI 0.26 to 1.03; 2P=0.06) at the end of trial follow-up. Up to 2000, other two trials published results. This review will be updated with new trial results soon, which will provide more data. Conclusions There were too few patients and outcome events to draw reliable conclusions from the present data. Although ancrod-like agents appeared promising, their routine use cannot be recommended at the moment. Future trials should test simpler fixed-dose regimens to allow better generalizability.
Objective To assess the effect of different thrombolytic agents, and different regimens in acute ischaemic stroke. Methods A systematic review of all the relevant randomized controlled trials (RCTs) was performed. RCTs were identified from the Cochrane Stroke Group trials register, Embase (1980 to 1997), handsearching Japanese and Chinese journals, and personal contact with pharmaceutical companies. We included randomised and quasi-randomised trials in patients with confirmed acute ischaemic stroke comparing different doses of a thrombolytic agent, or different thrombolytic agent, or the same agent given by different routes. Results Eight trials involving 1 334 patients were included. Concealment of allocation was generally adequate. All the trials were conducted in Japan. Different doses (of tissue plasminogen activator or urokinase) were compared in six trials. Different agents (tissue plasminogen activator versus urokinase,or tissue-cultured urokinase versus conventional urokinase) were compared in three trials. Few data were available for functional outcomes. A higher dose of thrombolytic therapy was associated with a five-fold increase in fatal intracranial haernorrhages (odds ratio 5.02, 95% confidence interval 1.56 to 16.18). There was a non-significant trend towards more early deaths or clinically significant intracranial haemorrhages in higher dose group. No difference in late deaths or extra-cranial haemorrhages was shown between low and higher doses. However, very few of these events occurred. No difference was shown between the different thrombolytic agents tested. Conclusions There is not enough evidence to conclude whether lower doses of thrombolytic agents might be safer or more effective than higher doses in acute ischaemic stroke. It is not possible to conclude whether one agent might be better than another, or which route of administration might be best.
To evaluate the effectiveness and safety of anticoagulants in ischaemic stroke primary or secondary prevention and treatment, we searched The Cochrane Library and MEDLINE to find high quality evidence and summarized the available evidence. The results showed that routine immediate anticoagulant therapy in patients with acute ischaemic stroke should not be recommended because it increased the risk of hemorrhage with ineffective reduction to the risk of death or disability. For the high risk group with cardiogenic embolism, anticoagulant therapy could safely and effectively reduce the incidence of stroke or other vascular events. However, for non-cardiogenic embolism group, anticoagulant therapy was hard to balance the benefits and harms.
Objective To study the protective effects of pre-storing glycogen on warm ischemia reperfusion injury during partial hepatectomy. Methods Thirty-eight patients were randomly divided into a trial group (n=19) and a control group (n=19). In the trial group, patients were given high concentration glucose intravenously during the 24 hours before the operation. The hepatic lesion was resected after portal triad clamping in the two groups. Liver function of all patients was measured before the operation and the first and fifth days after the operation. Normal hepatic tissue was biopsied to measured hepatic tissue glycogen contents before the operation and the change of superoxide dismutase (SOD) at the point of pre-ischemia, post-ischemia, and reperfusion 2 hour. Bcl-2 mRNA, a well known anti-apoptotic factor, was also detected using quantitative polymerase chain reaction. Results The hepatic tissue glycogen content of the trial group was significantly higher than that of the control group before the operation (Plt;0.01). Liver function of the trial group was significantly better than that of the control group on the first and fifth day after operation (Plt;0.05). There was significant difference in SOD activity between the two groups at the end of hepatic vascular occlusion and at the point of 2-hour reperfusion (Plt;0.05). Furthermore Bcl-2 mRNA expression of the trial group was notably up-regulated at the point of 2-hour reperfusion compared to the control group. Conclusion Pre-store storing glycogen might protect liver ischemia reperfusion injury caused by hepatic vascular occlusion during partial hepatectomy. The potential mechanism might be that pre-storing glycogen enhances Bcl-2 expression.