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OBJECTIVE Only limited number of drugs are currently available for treating ischemic stroke. Therapeu?tic angiogenesis has recently emerged as one of the most promising therapies for cerebral ischemic injury. Isopropyl-β-(3,4-dihydroxyphenyl)-α-hydroxypropanoate (IDHP) is a metabolite derived from the botanical formulation for Dantonic?. Here, we investigated the angiogenic efficacy of IDHP in cerebral ischemia. METHODS The in vivo effects of IDHP were evaluated in the C57BL/6 mouse Matrigel plug and rat transient middle cerebral artery occlusion (tMCAO) models. Primary human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC) were used to explore the effects of IDHP on stimulating proliferation, migration and tube formation in vitro. ELISA and Western blotting were used to quantitate the release and expression of relevant target molecules and signaling path?ways. RESULTS IDHP reduced infarct volume and improved sensorimotor function in rats subjected to tMCAO by pro?moting angiogenesis, and promoted Matrigel neovascularization in mice. Moreover, IDHP produced a biphasic modula?tion on proliferation and migration both in HUVEC and HBMEC. It also induced tube formation in a 12-day HUVEC-HDF co-culture model and in Matrigel assays. IDHP-induced angiogenesis was accompanied by increased levels of p-AMPKα (Thr172) and p-eNOS (Ser1177) both in vitro and in vivo, and the decreased level of VEGF in rat brains on day 1 whereas enhanced level of VEGF on day 3 and 7 after tMCAO. Mechanistically, AMPK knockdown or pharmacologi?cally inhibiting AMPK and its upstream kinases (CaMKKβ) inhibited the eNOS phosphorylation induced by IDHP in HUVEC. Furthermore, selective eNOS inhibitor (L-NIO), selective CaMKKβ inhibitor (STO) and AMPKa inhibitor (Com?pound C) blocked the capillary-like tube formation in the co-culture model induced by IDHP (10 nmol · L-1). CONCLU?SION Collectively, these findings showed that IDHP protected rats from cerebral ischemia-reperfusion injury by promot?ing angiogenesis via activating CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling, and suggest it to be a promising new drug candidate for the prevention and/or treatment of cerebral ischemia and other vascular occlusive diseases.
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Objective To investigate the effects of naloxone injected into cisterna magna on S100β protein and neuron-specific enolase (NSE) levels in serum and the histopathology of brain tissue of rats following cardiopulmonary resuscitation(CPR). Methods Thirty adult male SD rats were randomly divided into 3 groups: Sham group, Conventional CPR group (intravenous injection of epinephrine, 0.2 mg/kg) and Naloxone CPR group(cisterna magna injection of naloxone, 2 mg/kg). Asphyxiation was used to set up rat cardiac arrest model, and corresponding drugs were given when the resuscitation was carried out. The blood samples were taken from orbital venous plexus at 0.5 h, 3 h, 6 h and 24 h after restoration of spontaneous circulation (ROSC). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of S100β protein and NSE. Brain tissue was taken after the last blood sampling and the pathology of brain was observed by hematoxylin-eosin (H-E) staining. Results Serum S100β protein levels of the Conventional CPR group and Naloxone CPR group were significantly higher than those of the Sham group at all time points (P <0.01); compared with the Conventional CPR group, S100β protein levels in Naloxone CPR group were significantly decreased at 3 h, 6 h, and 24 h after ROSC (P <0.05 or P <0.01). Serum NSE protein level of the Conventional CPR group at all time points and Naloxone CPR group at 6 h and 24 h after ROSC were significantly higher than those of the Sham group (P <0.05 or P <0.01). Serum NSE protein levels were significantly decreased at 6 h and 24 h after ROSC in Naloxone CPR group compared with the Conventional CPR group (P <0.05 or P <0.01). Moreover, hippocampus glial cells of Conventional CPR group were scattered and decreased, with condensed eosinophilic cytoplasm, narrowed nuclues, unclear nucleolus, and swollen and deformed capillaries. However, most nerve cells of Naloxone CPR group had rich cytoplasm and the nucleolus was clear; only a few nerve cells and capillaries showed edema-like changes of different degrees. Conclusion Naloxone injected into cisterna magna has a prominent protective effect on the brain of rats following cardiopulmonary resuscitation.
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There is continuous debate regarding the effectiveness of thymectomy in the treatment of non-thymomatous myasthenia gravis (MG). This systematic review was undertaken to determine whether thymectomy was effective in non-thymomatous MG. We retrieved articles published between January 1980 and September 2013. Sixteen cohort studies were included. Given the considerable heterogeneity, we used a descriptive method instead of statistical synthesis. The median relative rates (RRs) and their interquartile ranges were used to estimate the magnitude of benefit. Compared to conservatively treated MG patients, thymectomized patients had higher survival, clinical remission, pharmacologic remission and improvement rates, and RRs were 1.07 (1.01-1.17), 1.83 (0.82-2.99), 1.55 (1.22-1.95) and 1 (1.00-1.09), respectively. Subgroup analyses showed that patients with moderate to severe generalized MG benefited more from thymectomy, with RRs of survival and pharmacologic remission increasing to 1.35 (1.24-1.49) and 2.68 (1.73-4.17), respectively. These results suggested that thymectomy might be an effective procedure in non-thymomatous MG patients. The patients with moderate to severe generalized MG might benefit more. Taking into account the poor methodological quality of present studies, more well-designed prospective randomized controlled trials (RCTs) are still required to reach unequivocal conclusion.
Subject(s)
Humans , Disease-Free Survival , Myasthenia Gravis , Mortality , General Surgery , Survival Rate , ThymectomyABSTRACT
There is continuous debate regarding the effectiveness of thymectomy in the treatment of non-thymomatous myasthenia gravis (MG). This systematic review was undertaken to determine whether thymectomy was effective in non-thymomatous MG. We retrieved articles published between January 1980 and September 2013. Sixteen cohort studies were included. Given the considerable heterogeneity, we used a descriptive method instead of statistical synthesis. The median relative rates (RRs) and their interquartile ranges were used to estimate the magnitude of benefit. Compared to conservatively treated MG patients, thymectomized patients had higher survival, clinical remission, pharmacologic remission and improvement rates, and RRs were 1.07 (1.01-1.17), 1.83 (0.82-2.99), 1.55 (1.22-1.95) and 1 (1.00-1.09), respectively. Subgroup analyses showed that patients with moderate to severe generalized MG benefited more from thymectomy, with RRs of survival and pharmacologic remission increasing to 1.35 (1.24-1.49) and 2.68 (1.73-4.17), respectively. These results suggested that thymectomy might be an effective procedure in non-thymomatous MG patients. The patients with moderate to severe generalized MG might benefit more. Taking into account the poor methodological quality of present studies, more well-designed prospective randomized controlled trials (RCTs) are still required to reach unequivocal conclusion.
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<p><b>OBJECTIVE</b>To analyze the clinical and angiographic characteristics of patients with slow coronary flow (SCF).</p><p><b>METHODS</b>In this retrospective study, 140 patients with SCF and 140 control subjects without SCF were included. SCF were diagnosed by the combination of TIMI flow grade method and TIMI frame count method. All subjects had angiographically normal coronary arteries. The clinical and laboratory data were obtained from medical records at admission.</p><p><b>RESULTS</b>Compared to control group, patients with SCF were younger [(57.8 +/- 10.7) years vs. (59.8 +/- 8.2) years], rate of smokers (59.3% vs. 46.4%) and diabetes mellitus (49.3% vs. 30.7%), fasting blood glucose (FBG) level [(7.8 +/- 2.8) mmol/L vs. (6.2 +/- 2.0) mmol/L, P < 0.05] and triglyceride (TG) level [(2.11 +/- 1.93) mmol/L vs. (1.67 +/- 1.01) mmol/L, P < 0.05] were higher, while high density lipoprotein cholesterol (HDL-C) level [(1.05 +/- 0.35) mmol/L vs. (1.42 +/- 0.74) mmol/L, P < 0.01] and apolipoprotein A1 (apoA1) level [(1.10 +/- 0.19) mmol/L vs. (1.31 +/- 0.31) mmol/L, P < 0.01] were lower. Among the 140 SCF patients, left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA) were involved at the same time in 92 patients. Among the three vessels, RCA is the most frequent involved vessel (n = 119). After adjusting for other risk factors, current smoking (OR = 1.92, 95% CI: 1.04 - 3.57, P < 0.05), DM history (OR = 2.44, 95% CI:1.32-4.76, P < 0.01), FBG (OR = 2.13, 95% CI:1.16-3.98, P < 0.05), TG (OR = 1.47, 95% CI:1.03-2.13, P < 0.05), HDL-C (OR = 0.47, 95% CI:0.24-0.85, P < 0.05) and apoA1 (OR = 0.55, 95% CI:0.40 - 0.75, P < 0.01) were independent factors for SCF (all P < 0.05).</p><p><b>CONCLUSIONS</b>Our results demonstrated that patients with SCF were prone to have a significant metabolic disorder compared to the control group. Patients with high levels of FBG, TG and low levels of HDL-C were more likely to suffer from SCF, which maybe explained by the development of coronary endothelium and microvascular dysfunction.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Case-Control Studies , Coronary Angiography , Coronary Artery Disease , Diagnostic Imaging , Coronary Circulation , Coronary Vessels , Retrospective StudiesABSTRACT
<p><b>BACKGROUND</b>The success rate of antegrade approach for chronic total occlusions (CTO) recanalization has not dramatically increased, especially in complex CTO subset. The retrograde technique may hold great promise. This report aimed to describe our experience of retrograde recanalization for CTO, focusing on its safety and feasibility.</p><p><b>METHODS</b>We identified 42 patients who underwent revascularization in CTO with retrograde approach from July 2005 to November 2009 in our center.</p><p><b>RESULTS</b>Three kinds of strategy were applied: retrograde as primary strategy (50.0%), retrograde immediately after antegrade failure (26.2%) and repeat procedure after previous antegrade failure (23.8%). Septal collaterals were more frequently used as the retrograde access route (92.9%). Overall success rate was 88.1%. In patients with successful retrograde wire crossing collateral channel to the distal cap of CTO, the success rate of recanalization was 94.1%. In patient with failure to cross the collaterals, the success rate was 62.5%. Eight different kinds of retrograde techniques were used: kissing wire technique (35.3%), wire trapped and reverse wire trapped technique (17.6%), back-end balloon and microcatheter reversal technique (14.7%), controlled antegrade and retrograde subintimal tracking (CART) technique (8.8%), reverse CART and modified reverse CART technique (8.8%), retrograde wire crossing technique (2.9%). There were 4 complications occurred without in-hospital major adverse cardiac events (MACE). In-hospital MACE was 7.7%. All of them were non-Q wave myocardial infarction. There were no cases of death or target vessel revascularization, either surgery or percutaneous.</p><p><b>CONCLUSIONS</b>The retrograde approach can be an effective tool for increasing the success rate of recanalization in the very complex CTO. To ensure the success and safety of the approach, careful case selection and device handling by experienced operators is essential.</p>