Adjunctive Cilostazol versus High Maintenance Dose of Clopidogrel in Patients with Hyporesponsiveness to Chronic Clopidogrel Therapy

Purpose

Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown.

Materials and Methods

We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35).

Results

Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0±10.2% versus 11.8±9.7%, p=0.61, and 286.3±54.7 versus 295.7±53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5±17.9% versus 28.3±16.6%, p=0.02, and 207.3±68.2 versus 241.3±76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7±8.7% to 15.8±18.4%, p=0.08, and from -18.6±58.0 to -61.9±84.3, p=0.08).

Conclusion

Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.     

Effects of black cohosh on the plasminogen activator system in vascular smooth muscle cells

Objective

The rhizome of the Cimicifuga racemosa plant (commonly known as black cohosh) has been used for menopausal complaints. Studies regarding the cardiovascular effects of black cohosh are lacking. We investigated the effect of black cohosh on the plasminogen activator system in cultured vascular smooth muscle cells (VSMCs).

Methods

VSMCs were isolated from rat aortae. Expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) proteins were evaluated by Western blot analysis and enzyme-linked immunosorbent assay, respectively. The activities of PAI-1 and t-PA in the conditioned media were assessed by fibrin overlay zymography. A 40% 2-propanol extract of black cohosh was used.

Results

Black cohosh extract (BcEx) stimulated the protein expression of PAI-1, but it did not affect that of t-PA. Vitamin E, a potent antioxidant, inhibited the BcEx-induced increase in PAI-1 expression, while ICI 182,780, an estrogen receptor antagonist, had no effect. Fibrin overlay zymography revealed that BcEx increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA by inducing a binding to PAI-1.

Conclusions

BcEx induces PAI-1 protein expression in the VSMCs likely via an oxidant mechanism. It also stimulates the enzyme activity of PAI-1 and reduces that of free t-PA. These findings suggest that black cohosh might exert a negative influence on fibrinolysis.     

Heat shock protein 70 (HSP70) expression is associated with poor prognosis in intestinal type gastric cancer

Heat shock protein 70 (HSP70) is a molecular chaperone which plays an important role in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. This study was conducted in gastric carcinoma (GC) to assess correlations of HSP70 expression with clinicopathological parameters and overall survival (OS). Tissue microarray blocks were constructed from 172 GCs and immunohistochemically stained for HSP70. Low HSP70 expression was found in 122 GCs (71 %), whereas 50 (29 %) had high expression. HSP70 expression was higher in tumours in the cardia (p?=?0.008), with non-signet ring cell histology (p?<?0.001), of intestinal type (p?=?0.045) and of higher pathological T stage (p?=?0.026). When considering the cohort as a whole, HSP70 expression did not correlate with OS (p?=?0.092). In intestinal type carcinomas, however, high HSP70 expression significantly correlated with worse OS (p?=?0.034). These results suggest that HSP70 expression might be an unfavourable prognostic factor in patients with GC, especially of intestinal type.     

Genetic diversity of avian paramyxovirus type 4 isolates from wild ducks in Korea from 2006 to 2011

Thirteen isolates of avian paramyxovirus type 4 (APMV-4) isolated from wild ducks in Korea from 2006 to 2011 were genetically characterized by sequence analysis of the N-terminal region of the APMV-4 fusion (F) protein gene. The results revealed that the amino acid sequence homology within Korean isolates was 97.5 % or greater. The homologies of the Korean isolates with the APMV-4/duck/HK/D3/75 and APMV-4/duck/BE/15129/07 strains were 86.9–88.0 and 95.5–96.1 %, respectively. All Korean isolates had sequence motifs of ¹¹⁶DIQPR↓F¹²¹ at the F0 cleavage site. Phylogenetic analysis based on the N-terminal region of the F protein gene of APMV-4 isolates revealed that all 2006–2011 Korean isolates formed a single genotypic cluster that was phylogenetically different from APMV-4/duck/HK/D3/75 or APMV-4/duck/BE/15129/07 strains. Korean APMV-4 isolates were more closely related to APMV-4/goose/ZA/N1468/10 (isolated in South Africa) than to the Belgium APMV-4 virus. Korean APMV-4 isolates were further divided into at least two subgroups (A and B) based on phylogenetic analysis. Subgroup A viruses were isolated throughout Korea, whereas subgroup B viruses were detected only in isolates from Cheju island in 2011, suggesting that Korean APMV-4 exhibits marked genetic diversity and differs from viruses currently circulating in Europe and other locations.     

Assessment of Rapid Optimized 96-well Tray Flow Cytometric Crossmatch (Halifax-FCXM) with Luminex Single Antigen Test

IntroductionFlow cytometric crossmatch assay (FCXM) is a sensitive cell-based method for evaluating the presence of donor-specific antibodies (DSA) before transplantation. Recently, 96-well tray FCXM protocol (Halifax FCXM) with improved test efficiency has been introduced. The objective of the present study was to assess the performance of Halifax FCXM by correlating with DSA results based on single antigen bead (SAB) assays (virtual crossmatch, VXM).MethodsA total of 341 FCXMs were evaluated for the detection of HLA-DSA. A positive VXM was defined as having at least one HLA - DSA (HLA-A, B, Cw, DR, DQB1) with ≥ 1000 MFI (mean fluorescence intensity) identified by SAB assay.ResultsOf a total 341 cases, 113 showed class I VXM (+) with class I DSA MFI ≥ 1000 exclusively against one or more donor HLA class I antigens (HLA-A, B, Cw), 72 had class I-/II + DSA, and 156 had VXM(-). Halifax T-FCXM showed a sensitivity of 87.6% (99/113) and a specificity of 98.2% (224/228) for detecting class I VXM (+). The concordance between T-FCXM and class I VXM was 94.7% (323/341). Halifax B-FCXM showed a sensitivity of 58.3% (42/72) and a specificity of 98.7% (154/156) for detecting class I-/II + DSAs. The concordance between B-FCXM and class I-/II + VXM was 86.0% (196/228). When we separately analyzed data, B-FCXM detected HLA-DR (+) (68.8%) and HLA-DQ (+) DSAs (71.0%) similarly (P > 0.05). T-FCXM detected 87.6%, 97.2%, and 98.2% of class I DSA-positive cases with MFI values (sumDSA) ≥ 1000, ≥ 3000, and ≥ 5000, respectively. B-FCXM detected 58.3% of class I-II + DSA -positive (≥1000) cases, but detected 76.7% (33/43) and 89.2% (33/37) of class I-II + DSAs if MFI values of sumDSA and immunodominant DSA (iDSA) were above 5000, respectively. Halifax FCXM had sensitivities of 91.5% and 96.2% for detecting VXM (+) having MFI values above 5000 for class I or class II sumDSA and iDSA, respectively.ConclusionHalifax FCXM showed a good correlation, especially with SAB assay-based high MFI DSA or sumDSA. Concurrent application of FCXM with VXM can improve pre-transplant risk assessment and progress organ allocation efficiency.     

Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma

PurposeExpression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation.Materials and MethodsTumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed.ResultsWe examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with high-grade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004).ConclusionOur findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acid-enhanced MRI in moderately differentiated HCC.     

Factors associated with Successful Responses to Ganglion Impar Block: A Retrospective Study

Background: The ganglion impar (ganglion of Walther) block has been used to manage coccygeal and perineal (perianal and genital) pain due to both benign and malignant causes. However, the factors associated with successful responses to ganglion impar block are unknown. Therefore, in the present study, we aimed to identify the independent factors associated with successful responses to ganglion impar block in patients with chronic pain in coccygeal and perineal regions.Methods: From January 2008 to December 2017, we performed a retrospective review of 106 patients who underwent ganglion impar block. Patients were considered successful responders if they reported a decrease of more than 50% or 4 points on the 11-point (0 = no pain and 10 = worst possible pain) numerical rating scale 1 month after the procedure, while others were considered non-responders. Logistic regression analysis was performed to identify factors independently associated with successful responses at 1 month after the procedure.Results: Multivariable logistic regression analysis showed that cancer-related causes were significantly associated with successful responses at 1 month after ganglion impar block (odds ratio = 2.60, 95% confidence interval = 1.05 to 6.43, P = 0.038).Conclusion: Ganglion impar block may be more effective in cancer-related pain than pain due to benign causes.