Long-lived polymer radicals, 2. An ESR study on the reactions of the propagating polymer radicals of N-methylacrylamide and N-methylmethacrylamide with vinyl monomers at room temperature

Acrylamide (AAm), methacrylamide (MAm), N-methylacrylamide (NMAAm) and N-methylmethacrylamide (NMMAm) were found to yield long-lived propagating polymer radicals in the photo-sensitized polymerizations in 1,4-dioxane or benzene. The concentration of poly(NMAAm) radicals reached 1.10^?3 mol/l. Some post-effect was observed at room temperature in the photo-sensitized polymerization of AAm with di-tert-butyl peroxide in 1,4-dioxane, while no post-polymerization proceeded at room temperature in the polymerization of NMMAm in benzene. The reactions of poly(NMAAm) and poly(NMMAm) radicals with various vinyl monomers were found to produce long-lived propagating polymer radicals of the second monomers at room temperature. Polymer radicals of non-homopolymerizable monomers such as α-methylstyrene and 1,1-diphenylethylene were easily formed in such a block-copolymerization matrix. The formation of the propagating polymer radicals of the vinyl monomers was investigated by means of ESR spectroscopy.     

Correspondence of cue activity to reward activity in the macaque orbitofrontal cortex

It has been reported that neurons in the orbitofrontal cortex (OFC) respond to emotionally significant events such as reward-predicting cues and/or the reward itself. The responses to reward-predicting cues are considered to carry the information of the predicted reward. However, few studies have focused on the relationship of the neuronal activity during a cue period with that during a reward period. We can infer that the cue responses of OFC neurons are correlated to the reward responses if they carry the information of the predicted reward. In this study, we focused on neurons that showed responses during both the cue and reward periods, and compared the response characteristics between these periods. We found 94 of 369 OFC neurons showed significant responses during both the cue and reward periods, and 43 of which preserved their selectivity between these periods. Furthermore, population analysis showed that stronger cue responses corresponded to stronger reward responses, and stronger reward responses corresponded to stronger cue responses. These results suggest that individual neurons in the OFC associate visual information with reward information, and contribute to the prediction of future rewards by forming reward representations.     

Vinyl polymerization with dimethylaniline/cupric nitrate system

A study of vinyl polymerizations initiated with the system of dimethylaniline (DMA) and cupric [Cu(II)] nitrate has been made. This initiator system was found to induce the polymerization of vinyl monomers having an electron-attracting substituent such as methyl methacrylate (MMA) and acrylonitrile, but it does not initiate the styrene and vinyl acetate polymerizations. The rate of polymerization (R_p) of MMA with this system was expressed by the following Eqs., depending upon the Cu(II) concentration used: The apparent activation energy for this polymerization was found to be 16.5 and 14.4 kcal/mole for the above two Cu(II) concn. ranges, respectively. The polymer of MMA obtained by this system was found to contain an endgroup similar to dimethylaniline, probably a methylanilinomethyl group, from the determination of its UV spectrum.     

Metal-containing initiator systems, 34. Polymerization of vinyl monomers initiated by the binary system cobaltocene/bis(ethyl acetoacetato)copper (II)

The effect of some metallocenes such as ferrocene (Fe(C₅H₅)₂), nickelocene (Ni(C₅H₅)₂), and cobaltocene (Co(C₅H₅)₂), on the vinyl polymerization initiated with bis(ethyl acetoacetato)-copper(II) (Cu(eacac)₂) was investigated. Co(C₅H₅)₂ was found to exert a markedly accelerating effect on the polymerization of methyl methacrylate (MMA) with Cu(eacac)₂. The polymerization of MMA with the system Co(C₅H₅)₂/Cu(eacac)₂ at 50°C was found to be fairly affected by the solvent used. The results of copolymerization of MMA with styrene (St) and the effect of hydroquinone (HQ) on the polymerization of MMA with Co(C₅H₅)₂/Cu(eacac)₂ showed that the polymerization proceeds via a radical mechanism. The polymerization of MMA with Co(C₅H₅)₂/Cu(eacac)₂ was studied kinetically in acetone. The overall activation energy of the polymerization was calculated to be 86,3 kJ/mol (20,6 kcal/mol). This value was somewhat higher than that (17,6 kcal/mol) obtained for the polymerization of MMA with Cu(eacac)₂ alone. The polymerization rate (R_p) is represented by the following equation: R_p = k[Co(C₅H₅)₂]^0,5 [Cu(eacac)₂]^0,2 [MMA]^1,3. The high order in monomer concentration suggests a participation of the monomer in the initiation process of this polymerization. This is supported by the examination of the ESR spectrum of the system Co(C₅H₅)₂/Cu(eacac)₂/MMA/acetone, where reduction of Cu(II) to Cu(I) occurs. To elucidate the initiation mechanism, the spin trapping technique was applied to the system Co(C₅H₅)₂/Cu(eacac)₂/methyl acrylate. From these results, an initiation mechanism for the binary initiator system Co(C₅H₅)₂/Cu(eacac)₂ is proposed and discussed.     

Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.     

Pig kidney xenotransplantation: Progress toward clinical trials

Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ‐source pigs has largely been directed to two major aims—(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement‐ and coagulation‐regulatory proteins. Conventional (FDA‐approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non‐immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait‐list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.     

Iron,coronary artery calcification,and mortality in patients undergoing hemodialysis

ObjectiveA high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients.MethodsWe studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted.ResultsThe median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05).ConclusionWe have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.     

The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines

The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10–40 M dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.     

P-glycoprotein-associated resistance to taxol and taxotere and its reversal by dexniguldipine-HCl, dexverapamil-HCl, or cyclosporin A

A series of different human MDR (multidrug-resistant) cell lines including a HeLa-MDR1 transfectant which exhibit high overexpression of the MDR1/P-glycoprotein gene, but no enhanced expression of the MRP (multidrug resistance associated protein) gene, showed different ratios of relative resistances to the taxanes taxol and taxotere. Using these cell lines the chemosensitizing efficacies of several structurally different chemosensitizers, i.e. the dihydropyridine dexniguldipine-HC1 (B8509-035), its main pyridine metabolite M1 (B8909-008), the cyclic peptide cyclosporin A, or the phenylalkylamine dexverapamil-HCl, were examined applying a 72 h tetrazolium based colorimetric MTT-assay, or a 96 h sulforhodamine B assay. Remarkably, we observed in some instances that the modulating efficacy of a particular chemosensitizer was strongly dependent on the cell line used for experimentation. Thus, dexniguldipine-HCl efficiently modulated taxane resistances of the ovarian carcinoma MDR cell line 2780AD in the submicromolar concentration range, whereas cyclosporin A and the other chemosensitizers were rather ineffective. Dexniguldipine-HCl or cyclosporin A, however, both showed a similarly strong modulating activity on the HeLa-MDR1 transfectant in clear contrast to the effects observed using the pyridine B8909-008, or dexverapamil-HCl, respectively, at the same final concentrations. Our results point to additional, as yet unidentified factors beyond the expression levels of P-glycoprotein which could contribute to the susceptibility of MDR cells to a combined treatment using taxanes and different chemosensitizing compounds. This result appears to be important considering the clinical application of chemosensitizers for combination therapy of tumors of different origin.