Assessing the efficacy of saline flush in frequency-domain optical coherence tomography for intracoronary imaging.

BACKGROUND: The increased amount of contrast media in frequency-domain optical coherence tomography (FD-OCT) imaging during percutaneous coronary intervention (PCI) has raised potential concerns regarding impairment of renal function. OBJECTIVES: This study aimed to evaluate the effectiveness of heparinized saline flush in FD-OCT-guided PCI and identify clinical factors contributing to optimal image quality. METHODS: We retrospectively collected 100 lesions from 90 consecutive patients, and a total of 200 pullbacks were analyzed for the initial and final evaluation in which saline was used as the flushing medium. RESULTS: The study population had a mean age of 73, with 52% having chronic kidney disease (CKD). The median amount of contrast used was 28 ml, and no complications were observed associated with saline flush OCT. Imaging quality was then categorized as excellent, good, or unacceptable. Among the total runs, 87% demonstrated clinically acceptable image quality, with 66.5% classified as excellent images and 20.5% classified as good images. Independent predictors of excellent images included lumen area stenosis ≥ 70% (adjusted odds ratio [OR] 2.37, 95% confidence interval [CI] 1.02-5.47, P = 0.044), and the use of intensive flushing (adjusted OR 2.06, 95% CI 1.11-3.86, P = 0.023) defined as a deep engagement of guiding catheter (GC) or a selective insertion of guide extension catheter (GE). Intensive flushing was performed in 60% of the total pullbacks, and it was particularly effective in improving image quality in the left coronary artery (LCA). CONCLUSION: The use of saline flush during FD-OCT imaging was safe and feasible, which had a benefit in renal protection with adequate imaging quality.

Synthesis of High Molecular Weight Biobased Aliphatic Polyesters Exhibiting Tensile Properties Beyond Polyethylene.

Synthesis of high molecular weight polyesters prepared by acyclic diene metathesis (ADMET) polymerization of bis(undec-10-enoate) with isosorbide (M1), isomannide (M2), and 1,3-propanediol (M3) and the subsequent hydrogenation have been achieved by using a molybdenum-alkylidene catalyst. The resultant polymers (P1) prepared by the ADMET polymerization of M1 (in toluene at 25 °C) possessed high Mn values (Mn = 44400-49400 g/mol), and no significant differences in the Mn values and the PDI (Mw/Mn) values were observed in the samples after the hydrogenation. Both the tensile strength and the elongation at break in the hydrogenated polymers from M1 (HP1) increased upon increasing the molar mass, and the sample with an Mn value of 48200 exhibited better tensile properties (tensile strength of 39.7 MPa, elongation at break of 436%) than conventional polyethylene, polypropylene, as well as polyester containing C18 alkyl chains. The tensile properties were affected by the diol segment employed, whereas HP2 showed a similar property to HP1.

New high-throughput screening method for Chinese hamster ovary cell lines expressing low reduced monoclonal antibody levels: application of a system controlling the gas phase over cell lysates in miniature bioreactors and facilitating multiple sample setup.

Interchain disulfide bonds in monoclonal antibodies may be reduced during large-scale mAb production using Chinese hamster ovary (CHO) cells. This reaction lowers the mAb product yield and purity; however, it may be prevented by screening cell lines that are unsusceptible to reduction and using them in mAb production. Antibody reduction susceptibility may be cell line-dependent. To the best of our knowledge, however, an efficient method of screening reduction-unsusceptible CHO cell lines has not been previously reported. Here, we report a novel screening method that can simultaneously detect and identify mAb reduction susceptibility in lysates containing ≤ 48 CHO cell lines. This evaluation system was equally effective and generated similar results at all culture scales, including 250 mL, 3 L, and 1000 L. Furthermore, we discovered that reduction-susceptible cell lines contained higher total intracellular nicotinamide adenine dinucleotide phosphate (NADPH) and NADP+ concentrations than reduction-unsusceptible cell lines, regardless of whether they expressed immunoglobulin (Ig)G4 or IgG1. NADPH or NADP+ supplementation in the lysate of reduction-unsusceptible cells resulted in mAb reduction. Application of the innovative CHO cell line screening approach could mitigate or prevent reductions in large-scale mAb generation from CHO cells.

Administration of Jerusalem artichoke reduces the postprandial plasma glucose and glucose-dependent insulinotropic polypeptide (GIP) concentrations in humans.

Background: The consumption of Jerusalem artichoke has multiple beneficial effects against diabetes and obesity. Objective: The aim of this study was to determine the effect of a single administration of Jerusalem artichoke tubers on postprandial glycemia and the concentrations of incretin hormones in humans. Method: Grated Jerusalem artichoke was administered prior to a meal (Trial 1; white rice for prediabetic participants, n = 10). Dose-dependent effect of Jerusalem artichoke (Trial 2; white rice for prediabetic participants, n = 4) and effect prior to the fat-rich meal were also investigated (Trial 3; healthy participants, n = 5) in this pilot study. Circulating glucose, insulin, triglyceride, glucagon, active glucagon-like peptide-1 (GLP-1), and active glucose-dependent insulinotropic polypeptide (GIP) concentrations were subsequently measured in all the trials. Results: Jerusalem artichoke significantly reduced the glucose and GIP concentrations after the consumption of either meal in Trial 1 and Trial 3, whereas there were no differences in the insulin, glucagon, and active GLP-1 concentrations. Also, there was no significant difference in the triglyceride concentration after the ingestion of the fat-rich meal in Trial 3. The glucose and GIP-lowering effects were dose-dependent, and the consumption of at least 100 g of Jerusalem artichoke was required to have these effects in Trial 2. Conclusion: This study demonstrates that a single administration of Jerusalem artichoke tubers reduces postprandial glucose and active GIP concentrations in prediabetic and healthy individuals.

Nicotinamide phosphoribosyltransferase is a molecular target of potent anticancer agents identified from phenotype-based drug screening.

Phenotypic screening in drug discovery has been revived with the expectation of providing promising lead compounds and drug targets and improving the success rate of drug approval. However, target identification remains a major bottleneck in phenotype-based drug discovery. We identified the lead compounds K542 and K405 with a selective inhibition of cell viability against sphingosine-1-phosphate lyase 1 (SGPL1)-transduced ES-2 cells by phenotypic screening. We therefore performed an in vivo pharmacological examination and observed the antitumor activity of K542 in an HT-1080 tumor-bearing mouse xenograft model. SGPL1 was expected to be a therapeutic target in some cancers, suggesting that these lead molecules might be promising candidates; however, their mechanisms of action still remain unexplained. We therefore synthesized the affinity probe Ind-tag derived from K542 and identified the proteins binding to Ind-tag via a pull-down experiment. Proteomics and biochemical analyses revealed that the target molecule of these lead compounds was Nicotinamide phosphoribosyltransferase (NAMPT). We established K542-resistant DLD-1 and HT-1080 cells, and genetic analyses of these cells identified a missense mutation in the NAMPT-encoding gene. This enzymatic experiment clearly showed that K393 exerts enzymatic inhibition against NAMPT. These proteomics, genetics and biochemical analyses clarified that compounds K542 and K405 were NAMPT inhibitors.

A novel HCN4 mutation, G1097W, is associated with atrioventricular block.

BACKGROUND: Loss-of-function mutations in the HCN4 gene have been shown to be associated with sinus dysfunction, but there are no reports on HCN4-mediated atrioventricular (AV) block. A novel missense HCN4 mutation G1097W was identified in a 69 year-old Japanese male with AV block, and we characterized the functional consequences of If-like channels reconstituted with the heterozygous HCN4 mutation. METHODS AND RESULTS: Wild-type (WT) HCN4 or/and HCN4-G1097W were expressed in a heterologous cell expression system. A functional assay using a whole-cell patch-clamp demonstrated that the mutant If-like currents were activated at more negative voltages compared to WT currents, while they retained the sensitivity to changes in intracellular cyclic adenosine monophosphate (cAMP) levels. Co-expression of G1097W with WT channels showed dominant-negative effects, including a reduction in peak currents and a negative voltage shifting on reconstituted currents. CONCLUSIONS: The HCN4-G1097W mutant channels displayed a loss-of-function type modulation on cardiac If channels and thus could predispose them to AV nodal dysfunction. These data provide a novel insight into the genetic basis for the AV block.

Brain metastasis in a patient with a sarcomatoid variant RCC with well-controlled extracerebral metastases by temsirolimus.

BACKGROUND: The sarcomatoid variant of metastatic renal cell carcinoma (RCC) has often an aggressive course and a poor prognosis, particularly when accompanied with brain metastasis. CASE REPORT: We describe the case of a patient with sarcomatoid variant RCC in whom brain metastasis was observed as a new lesion during treatment with temsirolimus, despite other extracerebral metastatic lesions being well-controlled and progression-free. RESULTS: This discrepancy between the effectiveness of temsirolimus for extracerebral metastases and the simultaneous progression of brain metastases of RCC raises a concern that while vascular endothelial growth factor (VEGF)-targeted therapy may have clinical efficacy, it may also carry a risk for new brain metastases due to weakening of the structure of the blood brain barrier. CONCLUSION: This case indicates that computed tomography monitoring of the brain should be regularly performed during VEGF-targeted therapy in patients with sarcomatoid variant RCC, even if brain metastases are absent and extracerebral metastatic lesions are well controlled.

The association between morning hypertension and metabolic syndrome in hypertensive patients.

Morning hypertension (MHT) and metabolic syndrome (MS) have been reported as important risk factors for stroke and cardiovascular events. We investigated the prevalence of MHT and MS among hypertensive patients in our outpatient clinic from June to August, 2005. We studied 181 hypertensive patients (91 men and 90 women) in our outpatient clinic using home-use electronic sphygmomanometers. Seventy-nine of these 181 patients (43.6%) demonstrated MHT, defined as systolic blood pressure (SBP) > or = 135 mmHg in the morning. Only 48.1% of the patients demonstrated normal SBP both at the clinic and in the morning at home, whereas 72.9% of the patients demonstrated normal diastolic blood pressure (DBP) under the same conditions. Sixty-one patients (33.7%) had MS, and 34 patients had both MHT and MS. Twenty-seven of the 102 patients (26.5%) without MHT had MS. The frequency of MS was significantly higher among those with MHT than those without MHT (p = 0.019). Multiple logistic regression analysis including smoking, alcohol consumption, sex, and age as confounding factors showed significant association between MHT and MS (odds ratio: 1.99; 95% confidence interval: 1.04-3.80; p = 0.039). In conclusion, although 1 year has passed since the JSH 2004 guidelines, 43.6% of our patients still showed MHT, and there was a significantly higher prevalence of MS among those with MHT. Our results suggest the need for a more vigorous intervention for controlling BP.