Distal shower embolization during directional coronary atherectomy and stenting for diffuse stenosis of right coronary artery: current limitations of intravascular ultrasonography for evaluating fragile plaque.

A 74 year-old male with old anterior and inferior myocardial infarctions was treated with staged percutaneous coronary intervention. A chronic total occlusion of the middle segment of the left anterior descending branch was successfully stented during the first stage, and during the second stage, preprocedural intravascular ultrasonography (IVUS) revealed that the proximal segment of the right coronary artery was diffusely stenosed by mixed plaque. Directional coronary atherectomy under IVUS guidance was performed, but coronary slow flow appeared during the procedure. After successfully bailing out with intracoronary nicorandil, percutaneous thrombectomy and manual blood pumping, 2 coronary stents were implanted to fully cover the lesion. Quite contrary to expectation, the no-reflow phenomenon appeared just after post-dilatation and a repeat of the same maneuver could not completely recover coronary flow. Plaque fragility could not be predicted from the IVUS examination.     

Magnetic resonance imaging in renal infarction and ischemia

Two cases of renal segmental infarction and 1 case of renal patchy ischemia demonstrated by magnetic resonance imaging (MRI) are reported. MRI of renal infarction in two renal grafts following surgical ligation revealed an area of noncorticomedullary differentiation and an area with a low signal intensity. Renal ischemia in 1 patient with acute renal dysfunction with severe loin pain and patchy renal vasoconstriction was visualized as an ill-defined focus of low signal intensity in the renal cortex, indicating a long T1 relaxation time. Delayed wedge-shaped contrast enhancement was demonstrated on CT scan in the same area. The common finding in renal infarction and ischemia in our cases was the area of low signal intensity on MRI.     

Additive therapeutic effects of the liver extract preparation mixture adelavin-9 on interferon-beta treatment for chronic hepatitis C

BACKGROUND/AIMS: We previously reported that intravenous interferon-beta administration was effective in treating patients with chronic hepatitis C and that there was no significant correlation between the response to therapy and host in vitro immunoglobulin production. The aims of this study were to evaluate the additive effect of a liver extract preparation and flavin adenine dinucleotide mixture and to reevaluate the correlation. METHODOLOGY: 65 patients with chronic hepatitis C received intravenously 6 million units of interferon-beta and 2 mL of a liver extract preparation and flavin adenine dinucleotide mixture. The results of this study were compared with those of our previous study, on interferon-beta monotherapy in 91 patients with chronic hepatitis C. In addition, peripheral blood mononuclear cells were obtained before interferon-beta administration and cultured. Immunoglobulin concentrations in their supernatants were measured and the correlation with the interferon response was evaluated. RESULTS: The virological end-of-treatment or sustained response occurred in 49 of 58 cases (84.5%), and 16 of 58 cases (27.6%), respectively. Biochemical end-of-treatment or sustained responses occurred in 22 of 58 cases (37.9%), and 30 of 58 cases (51.7%), respectively. These response rates were higher than those reported in our previous study of interferon monotherapy. Monovariate analysis indicated that the use of the liver extract preparation and flavin adenine dinucleotide mixture was a significant predictor of the virological end-of-treatment response and the sustained biochemical response, but by multivariate analysis these relationships were not significant. Immunoglobulin production was not correlated with the virological and biochemical responses. CONCLUSIONS: This study indicated that combination therapy with intravenous interferon-beta and the liver extract preparation and flavin adenine dinucleotide mixture was more effective than intravenous interferon-beta monotherapy. However, no correlation between the interferon response and in vitro immunoglobulin production was observed.     

Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum(II) in oral cancer cell lines

The DNA repair enzyme O⁶-methylguanine–DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell lines. CDDP depleted MGMT protein and mRNA levels in all four cell lines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N′-nitro-N-nitrosoguanidine and CDDP, whereas two other cell lines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O⁶-benzylguanine (O⁶-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O⁶-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy.     

Genotyping and the quantification of hepatitis C virus by the melting curves in light cycler

Detection of the HCV genome is crucial for diagnosis of HCV infection and for monitoring the efficacy of interferon treatment for patients with HCV. We developed a convenient screening test for HCV genotypes 1 and 2 based on the melting curve analysis with SYBER green I. Serum samples were drawn from 114 patients with known chronic HCV infection confirmed to be antibody-positive by immunoblot assay. A characteristic melting profile for each genotype was obtained by monitoring the fluorescence as the temperature increases through the melting point of the PCR product. Serum samples with HCV-RNA genotype (1b, 2a and 2b) were analyzed every test as standard samples and the genotype of unknown samples was determined by the comparison with the melting point of standard samples. Serum samples with known HCV-RNA genotype (1b, 2a and 2b) and HCV-RNA-negative sample were tested using the Light cycler system. The melting curve analysis indicated that melting points are 93.08 +/- 0.56 degrees C for genotype 1b (n = 63), 91.08 +/- 0.49 degrees C for genotype 2a (n = 33), and 91.77 +/- 0.28 degrees C for genotype 2b (n = 18). The melting points for genotypes 1b, 2a, and 2b differed by approximately 1 degree C in each other. The genotype was determined for all samples using Okamoto's method and Light cycler system, and both systems produced absolutely identical results for all the samples studied. Sixty-three of 114 were genotype 1b, 33 samples were genotype 2a, and 18 were genotype 2b. This melting curve analysis is a rapid and convenient screening test for differentiation of HCV genotypes 1 and 2.     

Cytotoxic activity of steroidal glycosides from solanum plants

Since some Solanum-genera plants have traditionally been used as anti-cancer and anti-herpes agents from olden times, we examined the cytotoxic activity of typical steroidal glycosides with the framework of spirostane, furostane, spirosolane, and pregnane obtained from Solanum plants. Among these steroidal glycosides, the spirostanol glycosides having a beta-lycotetraosyl moiety were the most effective against PC-12 and HCT-116 cell lines. The potency of activity was observed to be decreased in the order of spirostane, furostane, spirosolane, and pregnane type steroid glycosides. It was also suggested that the activity depend on the kind of oligosaccharide moiety and aglycone moiety.     

Increased protein expression of DNA methyltransferase (DNMT) 1 is significantly correlated with the malignant potential and poor prognosis of human hepatocellular carcinomas

Alteration of DNA methylation is one of the most consistent epigenetic changes in human cancers. DNA methyltransferase (DNMT) 1 is a major enzyme involved in establishing genomic methylation patterns. Most of the studies concerning DNMT1 expression in human cancers have been performed only at the mRNA level. To directly examine DNMT1 protein expression levels during human hepatocarcinogenesis, 16 histologically normal liver tissues, 51 noncancerous liver tissues exhibiting chronic hepatitis or cirrhosis, which are considered to be precancerous conditions, and 53 hepatocellular carcinomas (HCCs) were subjected to immunohistochemic examination. If more than 20% of the cells exhibited nuclear DNMT1 staining, the tissue sample was considered to be DNMT1-positive. DNMT1 immunoreactivity was observed in 23 (43%) of the HCCs, but in none (0%) of the histologically normal liver or noncancerous liver tissues exhibiting chronic hepatitis or cirrhosis. The incidence of increased DNMT1 protein expression in HCCs correlated significantly with poor tumor differentiation (p = 0.0006) and portal vein involvement (p = 0.0002). Moreover, the recurrence-free (p = 0.0001) and overall (p < 0.0001) survival rates of patients with HCCs exhibiting increased DNMT1 protein expression were significantly lower than those of patients with HCCs that did not exhibit increased expression. Increased DNMT1 protein expression may play a critical role in the malignant progression of HCCs and be a biologic predictor of both HCC recurrence and a poor prognosis in HCC patients.     

Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by Barbados cherry,a fruit of Malpighia emarginata DC

The extract of Barbados cherry (acerola fruit), a fruit of Malpighia emarginata DC., has been reported to display diverse biological activities such as prevention of age-related diseases. We investigated here the possible effect of Barbados cherry extract on nitric oxide (NO) production by activated macrophages. Barbados cherry was roughly separated into 4 or 5 fractions by two different methods, using various organic solvents such as hexane, acetone, methanol (70% and 100%) and water, and assayed for its ability to inhibit NO production by lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells. Among these fractions, AcOEt extracts (AE0) in Method I and acetone extract (A0) in Method II showed the highest inhibitory activity of NO production (SI > 20 and SI = 31, respectively). When these fractions were subjected to silica gel column chromatography, higher inhibitory activity for NO production was concentrated in AcOEt (AE6) (SI = 64) and benzene-AcOEt (1:4) (A10) fractions (SI > 59). Western blot analysis demonstrated that AE6 and A10 fractions reduced the intracellular concentration of inducible NO synthase (iNOS) by approximately one-third. ESR spectroscopy showed that these fractions scavenged various radical species such as superoxide anion (O2-) and NO radicals. These data suggest that the inhibitory effect on NO production by Barbados cherry extracts is partly due to the inhibition of iNOS expression, and scavenging of O2- and NO radicals.     

A glycine receptor antagonist,strychnine, blocked NMDA receptor activation in the neonatal mouse neocortex

The NMDA receptor (NMDAR) is a Ca (2+)-permeable cation channel that plays a critical role in neural network formation during brain development. Since it is blocked in a voltage-dependent manner by extracellular Mg(2+), in order for the NMDA to be activated, the membrane must be strongly depolarized. Immature neurons in the developing neocortex can be depolarized by ligand-gated Cl(-) channels, such as the glycine receptor (GlyR) or GABA(A) receptor (GABA(A) R). We here assess the contribution of GlyRs to Ca(2+) influx via NMDARs in neonatal mouse cortical neurons. The GlyR antagonist, strychnine, was more effective in suppressing postsynaptic Ca(2+) influx than the GABA(A) R antagonist, picrotoxin, suggesting greater potentiation of NMDARs by GlyRs than by GABA(A) Rs. The GlyR, known to be endogenously activated at this stage, may play a critical role in neocortical development.