The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

Pre-stroke glycemic control is associated with early neurologic deterioration in acute atrial fibrillation-related ischemic stroke.

BACKGROUND: It has been suggested that AF-related ischemic stroke (IS) that is accompanied by atherosclerotic burden have poorer outcomes. The aim of this study was to investigate the importance of pre-stroke glycemic control (PSGC) on the early neurologic deterioration (END) of patients with acute AF-related IS. METHODS: We retrospectively recruited 121 patients with AF-related IS who also had Diabetes mellitus (DM). The HbA1C level was measured in all subjects. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score of 4 NIHSS points within 7 days of symptom onset compared to the initial NIHSS score. RESULTS: In this study, 20.7% (25 patients) were classified as having a poor PSGC status with a HbA1C level above 8.0%. In the univariate analysis, a poor PSGC status (p < 0.01), smoking (p = 0.01), severe neurologic deficits at admission (p = 0.01), and a larger size of ischemic lesions on DWI (p < 0.01) were associated with the occurrence of END. In the multivariate model, a poor PSGC status (p = 0.02) and larger size of ischemic lesions on MRI (p < 0.01) were independent predictors of END in acute AF-related IS. CONCLUSION: The HbA1c level upon admission was independently associated with significant prediction of END in acute AF-related IS.

ADP-induced platelet aggregation in acute ischemic stroke patients on aspirin therapy.

BACKGROUND AND PURPOSE: Aspirin is an important therapeutic regimen to prevent the recurrent ischemic events or death after acute ischemic stroke. In this study, we evaluated the relationship between the extent of adenosine diphosphate (ADP)-induced platelet aggregation and outcome in acute ischemic stroke patients on aspirin therapy. METHODS: We selected 107 acute ischemic stroke patients who had been prescribed aspirin and evaluated platelet function test by using optic platelet aggregometer test after 5 days of taking it and investigated the prognosis 90 days after ischemic events. Kaplan-Meyer curve was used for survival analysis. RESULTS: After stratification of the subjected patients by tertiles of ADP-induced platelet aggregation, the events rates were 7.4%, 9.3% and 30.8% (P = 0.023). In multiple logistic regression analysis, old age over 70 years (OR, 13.7; 95% CI, 2.14-88.07; P = 0.001) and the increased ADP-induced platelet aggregation had independent significance to the risk of primary end-points after acute ischemic stroke (OR, 1.1; 95% CI 1.01 to 1.20; P = 0.026). CONCLUSIONS: This study showed that the increased ADP-induced platelet aggregation under using aspirin is associated with poor outcome after acute ischemic stroke.

Circulating levels of interleukin-8 and vascular endothelial growth factor in patients with carotid stenosis.

Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) are important factors that induce the migration and proliferation of endothelial cells, increase the vascular permeability, and the modulate chemotaxis of monocytes. These molecules have been found in human atherosclerotic plaques. However, it is not clear whether the circulating levels of IL-8 and VEGF correlate with the extents of carotid stenosis. In this study, we investigated the relationship between circulating levels of IL-8 as well as VEGF and the extents of carotid stenosis. Sera from 41 patients with carotid stenosis were assessed for concentrations of IL-8 and VEGF by enzyme-linked immunosorbent assay. The degree of stenosis of extracranial carotid artery was calibrated by carotid B- mode ultrasonography. The serum concentration of IL-8 (r = -0.04733, p > 0.05) was not correlated with the degree of stenosis. However, the serum concentration of VEGF (r = 0.4974, p < 0.01) was significantly correlated with the degree of carotid stenosis. These findings suggest that increased serum level of VEGF might be a marker for higher degree of stenosis of extracranial carotid artery.

Facile synthesis of the tricyclic core of sarain A. 3-Oxidopyridinium betaine cycloaddition approach.

[formula: see text] A new approach to a suitably functionalized tricyclic core of sarains has been developed by means of Katritzky's cycloaddition using 3-oxidopyridinium betaines. A key step was the regioselective differentiation of the two nearly identical hydroxy groups derived from oxidative cleavage of the double bond in 8 to afford 14. A stereocontrolled construction of the tricyclic core 20 of sarains containing the requisite side chain at C-3' was achieved by an intramolecular conjugate addition.

Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy.

We have investigated the ability of swainsonine, an indolizidine alkaloid with pleiotropic in vivo effects, to confer protection against the cytotoxic effects of both cell cycle-specific and cell cycle-nonspecific cytotoxic anticancer agents. The intraperitoneal administration of swainsonine decreased the lethality of methotrexate (MTX), fluorouracil (5-FU), cyclophosphamide (CPM), and doxorubicin (DOX) in non-tumor-bearing C57BL/6 mice. The increased survival rate was found to correlate with stimulation of bone marrow cell proliferation, as measured by increases in 1) bone marrow cellularity, 2) in vivo and in vitro colony-forming activity, and 3) engraftment efficiency. These responses were critically dependent on the dose, sequence, and timing of swainsonine administration. If these results are confirmed in humans, swainsonine may offer promise in future intensive chemotherapy programs, allowing increased dosage and/or frequency of administration of cytotoxic agents without increasing toxic effects in bone marrow.

Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: modulation of tumor cell HLA class I antigens and host immune effector mechanisms.

Swainsonine, an indolizidine alkaloid, can decrease the organ colonization potential of metastatic murine tumor cells by augmentation of host immune effector mechanisms. In this report the above findings were extended by the demonstration that systemic administration of swainsonine strongly suppressed the growth of human breast carcinoma subcutaneous xenografts and experimentally induced lung metastases. This inhibition was not due to a direct effect of swainsonine on cell growth. However swainsonine treatment of tumor cells resulted in enhanced expression of HLA Class I antigens, and HLA class I mRNA. Swainsonine was a potent immunodulator as evidenced by the increased (a) cytotoxicity of splenocytes and macrophages, and, (b) proliferative potential of splenocytes and bone marrow cells. These data suggest that swainsonine-induced inhibition of tumor growth and metastases may be mediated via activation of host effector cells and/or alteration of tumor cell antigenicity.

Swainsonine modulation of protein kinase C activity in murine peritoneal macrophages.

The level of Ca2+, phospholipid-dependent, protein kinase C (PKC) activity in murine peritoneal macrophages treated with swainsonine, an indolizidine alkaloid, has been investigated. The present studies are based on our recent report that murine peritoneal macrophages are activated by swainsonine (Grzegorzewski, K.; Newton, S.A.; Akiyama, S.K.; Sharrow, S.; Olden, K.; White, S.L., Cancer Commun. 1:373-379, 1989). Presently, we have demonstrated that macrophages treated with swainsonine exhibited a substantial increase in PKC activity. The activity was enhanced as much as 4- to 5-fold over that obtained in untreated macrophages and was inhibited by H-7 (1-[5-isoquinoline sulphonyl]-2-methylpiperazine), D-sphingosine, or a monoclonal antibody specific for the active site of PKC. This represents the first report to demonstrate an effect of swainsonine on a second messenger system known to be involved in tumor promotion and macrophage activation. Elevation of PKC activity occurred much more slowly in swainsonine-treated cells than in cells treated with agents known to activate PKC directly, e.g., PMA (4-beta-phorbol-12-beta-myristate-13-gamma-acetate) or gamma-interferon (IFN-gamma). Furthermore the increase in PKC activity was inhibited by alpha-amanitine and cycloheximide, inhibitors of RNA and protein synthesis, respectively. These results suggest that swainsonine enhancement of PKC activity occurred by an indirect and possibly protein-synthesis-dependent mechanism. Whatever its precise mechanism of action, swainsonine provides a potentially important new probe to evaluate PKC mediated events. Selective enhancement of PKC activity may be important not only in elucidating the role of PKC in tumor promotion or macrophage activation but, also, in contributing to development of therapeutic regimens.