Efficacy of cattle encephalon glycoside and ignotin in patients with acute cerebral infarction: a randomized, double-blind, parallel-group, placebo-controlled study.

Cattle encephalon glycoside and ignotin (CEGI) injection is a compound preparation formed by a combination of muscle extract from healthy rabbits and brain gangliosides from cattle, and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries. However, there is still a need for high-level clinical evidence from large samples to support the use of CEGI. We therefore carried out a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016. The patients were randomized at a 3:1 ratio into CEGI (n = 239; 155 male, 84 female; 61.2 ± 9.2 years old) and placebo (n = 80; 46 male, 34 female; 63.2 ± 8.28 years old) groups. All patients were given standard care once daily for 14 days, including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium, both taken orally, and intravenous infusion of 250-500 mL 0.9% sodium chloride containing 40 mg sodium tanshinone IIA sulfonate. Based on conventional treatment, patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water, respectively, in an intravenous drip of 250 mL 0.9% sodium chloride (2 mL/min) once daily for 14 days. According to baseline National Institutes of Health Stroke Scale scores, patients in the two groups were divided into mild and moderate subgroups. Based on the modified Rankin Scale results, the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group, and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment. In the CEGI group, neurological deficits were decreased on days 14 and 90 after treatment, as measured by the National Institutes of Health Stroke Scale and the Barthel Index. Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients. No drug-related adverse events occurred in the CEGI or placebo groups. In conclusion, CEGI may be a safe and effective treatment for acute cerebral infarction patients, especially for moderate stroke patients. This study was approved by the Ethical Committee of Peking University Third Hospital, China (approval No. 2013-068-2) on May 20, 2013, and registered in the Chinese Clinical Trial Registry (registration No. ChiCTR1800017937).

Clinical Correlation of Magnetic Resonance Imaging Features of Cerebral Small Vessel Disease.

OBJECTIVE: We have discussed the clinical features and neuroimaging findings and investigated the correlations between the clinical characteristics and different neuroradiologic phenotypes of cerebral small vessel disease (CSVD). METHODS: A total of 1106 patients with a diagnosis of CSVD were enrolled. The demographic data, medical history, laboratory test results, and neuroimaging findings were retrieved for analysis. The differences in clinical parameters between patient groups were examined. The relationships between the clinical parameters and neuroradiologic phenotypes (i.e., white matter lesions [WMLs] and enlarged perivascular spaces) were assessed. The magnetic resonance imaging features were clustered using the fast clustering algorithm. RESULTS: Approximately one third of our patients presented with a lacune, which was associated with atrial fibrillation (P = 0.029), lacunar syndrome (P < 0.001), periventricular WMLs (P = 0.001), cerebral WMLs (P = 0.021), basal ganglia perivascular space grade (P < 0.001) and severity (P = 0.001), and semiovale perivascular space grade (P = 0.010) and severity (P = 0.002). Hypertension was associated with periventricular WMLs (P = 0.048), centrum semiovale WMLs (P = 0.026), and basal ganglia perivascular space grade (P < 0.001) and severity (P < 0.001). A novel clustering algorithm was derived to stratify our cohort into 3 different groups according to the differing severity of the cerebral WMLs and perivascular space enlargement. CONCLUSION: The present study has provided a comprehensive analysis of the clinical correlation of characteristics and neuroradiologic phenotypes in patients with CSVD. The insights from these findings could be used to refine the management strategy for patients with CSVD.

Regulation of the activity and expression of aryl hydrocarbon receptor by ethanol in mouse hepatic stellate cells.

BACKGROUND: During the course of alcohol-induced liver damage, hepatic stellate cells are transformed into proliferative, fibrogenic, and contractile myofibroblasts. Aryl hydrocarbon receptor (AhR) is a transcription factor that controls the expression of genes involved in the metabolism of xenobiotics, inflammation, cell proliferation, and death. METHODS: Immortal mouse hepatic stellate cells (MHSCs) were isolated from transgenic mice that expressed a thermolabile SV40 tumor antigen. Quantitative real-time reverse transcription polymerase chain reaction assays, Western blot analysis, promoter activity assays, and chromatin immunoprecipitation analyses were performed for studying the effect of ethanol (EtOH) on AhR expression and transcriptional activity. RESULTS: Treatment of MHSCs with 50 to 200 mM EtOH for 6 hours induced AhR nuclear translocation, enhanced the promoter activity of cytochrome P450 (CYP) 1A1, increased the amount of AhR bound to the promoter of CYP1A1 and 1B1, and up-regulated the mRNA expression of these AhR target genes in a dose-dependent manner. In contrast, EtOH exposure down-regulated AhR mRNA and protein expression. Similarly, benzo(a)pyrene (BaP) at 10 nM reduced AhR and increased CYP1A1 and 1B1 mRNAs. Pretreatment of MHSCs with 50 mM EtOH for 7 days diminished the capacity of MHSCs to express CYP1A1 and 1B1 induced by a 200 mM EtOH challenge, or by 10 nM BaP. However, the up-regulatory effect of EtOH on solute carrier family 16, member 6 (SLC16a6) was unaffected by EtOH pretreatment. Similar to EtOH, dimethyl sulfoxide (DMSO) at concentrations of 50 to 100 mM down-regulated AhR and up-regulated CYP1A1 mRNA expression in a dose-dependent manner. CONCLUSIONS: These data, for the first time, demonstrate that EtOH activates MHSC AhR and down-regulates its expression. Chronic EtOH pretreatment lowers the availability of AhR, and specifically diminishes the inducibility of CYP genes. The effect on AhR appears to not be an EtOH-specific response, as DMSO alone (and possibly other organic solvents) was also able to activate AhR.

[Treatment of post stroke cognitive impairment by rTMS].

Repetitive transcranial of magnetic stimulation (rTMS), as a new electrophysiological technique, has been used in treating neurological and psychiatric diseases in clinical. In recent years, rTMS has also been employed to explore the treatment options for post stroke cognitive impairment (PSCI). Studies showed that rTMS was beneficial to recovery of post-stroke aphasia, improvement of memory dysfunction and alleviation of hemispatial neglect. Moreover, it is safe for patient within the recommended parameters of safety guidance. rTMS exerts therapeutic effects by interfering with the reconstruction of cortical network, improving the cerebral blood flow and metabolism, adjusting the ion balance by modulating cortical excitability. In addition, rTMS could enhance synaptic plasticity, inhibit the apoptosis, and regulate the transmission of a variety of neurotransmitters. It was reviewed that the basic principles of rTMS, the efficacy, safety and mechanism of rTMS in the treatment of PSCI, as well as the current problems and prospects in this paper.

[Measurement of cerebrovascular reserve of patients with symptomatic middle cerebral artery ischemia by perfusion CT and combined with CO2 test].

OBJECTIVE: To investigate the feasibility of assessment of the cerebrovascular reserve (CVR) by perfusion CT combined with CO(2) test in patients with symptomatic middle cerebral artery ischemia. METHODS: 38 healthy volunteers and 32 symptomatic middle artery ischemia inhaled mixed gas of 5% CO(2) and 95% O(2), and the changes of CO(2) concentration by the end of inhalation were measured among as pretest. Ten-row CT was with round area 24 mm in diameter at bilateral blood supply areas of middle cerebral artery as ROI. Forty patients with symptomatic middle cerebral artery ischemia underwent perfusion CT with 5% carbon dioxide and 95% oxygen. The end-expiratory CO(2) content after inhalation of mixture gas was tested in 36 volunteers and 32 patients with symptomatic middle cerebral artery ischemia. RESULTS: After inhalation of a gas mixture with 5% CO(2) and 95% oxygen the end-expiratory CO(2) content increased by 0.93% +/- 0.31% in the volunteers and 0.89% +/- 0.23% in the patients with symptomatic middle cerebral artery ischemia (P < 0.05). The CVR of the patients with symptomatic middle cerebral artery ischemia could be bigger than 20%. The CVR of middle cerebral artery supply area was correlated with the collateral circulation number and scale, but not with the stenosis degree of M1 segment of middle cerebral artery. CONCLUSION: It is safe and feasible to assess CVR with dynamic computer tomography and gas mixture with 5% CO(2) and 95% oxygen in the patients with symptomatic middle cerebral artery ischemia.

Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E.

Oxidative stress has been suggested to potentiate atherogenesis. However, studies that have investigated the effect of antioxidants on atherosclerosis showed inconsistent results, ie, atherosclerosis was either retarded or not changed by dietary antioxidants. This report directly examined the effect of overexpressing Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and/or catalase on atherosclerosis and lipid peroxidation in mice lacking apolipoprotein E (ApoE-/-). Based on lipid staining of the en face of the aorta tree and the serial sections of the proximal aorta, ApoE-/- mice overexpressing catalase or both Cu/Zn-SOD and catalase had smaller and relatively early stages of atherosclerotic lesions (eg, foam cells and free lipids) when compared with ApoE-/- mice, who developed more advanced lesions (eg, fibrous caps and acellular areas). In addition, the retarded development of atherosclerosis was correlated with a reduced F2-isoprostanes in the plasma and aortas in ApoE-/- mice overexpressing catalase or both Cu/Zn-SOD and catalase. In contrast, the levels of F2-isoprostanes and atherosclerosis in the ApoE-/- mice overexpressing Cu/Zn-SOD alone were comparable to ApoE-/- control mice. These observations implied that endogenously produced hydrogen peroxide, but not superoxide anions, contributed to the formation of oxidized lipids and the development of atherosclerosis in ApoE-/- mice.

[Investigation of the influence of nitric oxide on the survival of a random pattern skin flap].

OBJECTIVE: To investigate the changes of nitric oxide concentration in the distal portion of a random pattern skin flap and the influence of the exogenous L-arginine on the survival of the random pattern skin flap. METHODS: A random pattern skin flap (7 cm x 2 cm) was cranially designed and elevated on the back of a Wistar rat. An image analysis technology was used to evaluate the survival rate of the skin flap, while a biochemistry method was used to test the concentrations of the NO in the tissue. RESULTS: The survival area of the flap in the L-arginine-treated group was significantly enlarged (63.83 +/- 5.13)% (P < 0.01) in seven days postoperatively, compared with the control group (43.26 +/- 2.86)%. The NO concentration in the tissue was no statistic difference between all of the groups immediately after the operation (P > 0.05). But, the NO concentration in the control was decreasing at the beginning and then increasing slightly to reach the high level in 12 hours after the operation. It was thereafter slumped down to the baseline in 72 hours after the surgery. Although the changes in the L-arginine-treated group were quite similar to the control excepting of the extent, the NO concentration was kept in a higher level in the sequential time after the operation (P < 0.01, P < 0.01, P < 0.05 and P < 0.01). CONCLUSIONS: The NO concentration in skin flap tissue after the elevation was going up slightly for a short time. The exogenous L-arginine could promote the NO concentration in the random pattern skin flap to protect it from ischemic injury.