Preparation of nanoparticles composed with bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer

The poly(L-lactic acid) nanoparticles immobilized with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, which has excellent blood compatibility, were prepared by a solvent evaporation technique using the water-soluble amphiphilic MPC polymer as an emulsifier and a surface modifier. The diameter and zeta-potential of the obtained nanoparticles strongly depended on the concentration of the MPC polymer. When the nanoparticles were prepared in 1.0 mg/ml of an MPC polymer aqueous solution, the diameter was 221 nm which was determined by atomic force microscopy and dynamic light scattering measurements. The X-ray photoelectron spectroscopic analysis indicated that the phosphorylcholine groups of the MPC unit were located at the surface of the nanoparticles, that is, the MPC polymer was immobilized on the PLA particles and the surface zeta-potential was -2.5 mV. Various hydrophobic fluorescence probes could permeate through the MPC polymer layer and adsorb on the PLA surface. The amount of bovine serum albumin adsorbed on the nanoparticles was significantly smaller compared with that on the conventional polystyrene nanoparticles. It is suggested that the nanoparticles immobilized with the MPC polymer have the potential for use as both a novel drug carrier and diagnostic reagent which can come in contact with blood components.     

Arg-gingipain a DNA vaccine induces protective immunity against infection by Porphyromonas gingivalis in a murine model

Arginine-specific cysteine proteinases (RgpA and RgpB) produced by the periodontal pathogen Porphyromonas gingivalis are suspected virulence factors and are involved in interrupting host defense mechanisms as well as in penetrating and destroying periodontal connective tissues. To induce a protective immune response against P. gingivalis, we constructed an rgpA DNA vaccine. BALB/c mice were immunized intradermally by Gene Gun with plasmid DNA carrying rgpA. Antibody responses against P. gingivalis were determined by an enzyme-linked immunosorbent assay. The rgpA DNA vaccine induced high levels of serum antibodies against P. gingivalis. Sera from the rgpA DNA vaccine-immunized mice diminished the proteolytic activity of RgpA and RgpB and inhibited the binding of P. gingivalis to a type I collagen sponge. Moreover, the sera effectively reduced the hemagglutination of P. gingivalis, indicating that the hemagglutinin activity of the organism is associated with RgpA. We found with a murine abscess model that mice immunized with the rgpA DNA vaccine were resistant to an invasive P. gingivalis W50 challenge. These results suggest that the rgpA DNA vaccine induced specific antibodies against the enzyme and that this vaccine could confer protective immunity against P. gingivalis infection.     

Role of JAK2 signal transductional pathway in activation and survival of human peripheral eosinophils by interferon-gamma (IFN-gamma)

The purpose of this study was to determine whether the JAK pathway is involved in eosinophil activation and survival through IFN-gamma receptor signalling in human peripheral eosinophils. Eosinophils were purified from the blood of six atopic disease patients by anti-CD16 magnetic bead-negative selection. IFN-gamma significantly up-regulated survival and CD69 expression in 24-48 h cultured eosinophils. Further, IFN-gamma induced tyrosine phosphorylation of JAK2 in eosinophils, as indicated by Western blot analysis. Finally, the specific JAK2 inhibitor AG-490 inhibited the tyrosine phosphorylation of JAK2, IFN-gamma-induced survival and CD69 expression in eosinophils. In conclusion, these results indicate that IFN-gamma induces eosinophil survival and CD69 expression through the activation of JAK2 in peripheral eosinophils, suggesting that JAK2 may play a significant role in eosinophil regulation by IFN-gamma-IFN-gammaR interaction.     

Polyethylene/phospholipid polymer alloy as an alternative to poly(vinylchloride)-based materials

To develop new biomaterials for making medical devices, polymer alloys composed of a phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and polyethylene (PE) were prepared. The PE/PMPC alloy membrane could be obtained by a combination of solution mixing and solvent evaporation methods using xylene and n-butanol mixture as a solvent. Moreover, thermal treatment was applied to improve the mechanical properties of the PE/PMPC alloy membrane. In the PE/PMPC alloy membrane, the PMPC domains were located not only inside the membrane but also at the surface. Surface analysis of the PE/PMPC alloy membrane with X-ray photoelectron spectroscopy, wettability evaluation, and dynamic contact angle measurements revealed that the phospholipid polar groups in the PMPC covered the surface even after thermal treatment. Blood compatibility tests with attention to platelet adhesion and change in morphology of adhered platelets showed that the PE/PMPC alloy membrane had excellent platelet adhesion resistance. We finally concluded that the PE/PMPC alloy could be used as biomaterials instead of poly(vinyl chloride)-based materials.     

Improvement of blood compatibility on cellulose dialysis membrane. 2. Blood compatibility of phospholipid polymer grafted cellulose membrane.

The blood compatibility of a cellulose haemodialysis membrane whose surface was grafted with a methacrylate having a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine, was evaluated with attention to platelet adhesion to the membrane surface and complement activation induced by the membrane. When the original cellulose membrane came in contact with platelet-rich plasma for 30 min, numerous platelets adhered to the surface and aggregated. On the other hand, the membrane grafted with 2-methacryloyloxyethyl phosphorylcholine effectively suppressed platelet adhesion and activation. This effect became more pronounced with increasing surface distribution. Especially, the 2-methacryloyloxyethyl phosphorylcholine grafted membranes, whose distribution exceeded 0.27, completely inhibited platelet adhesion, even when the contact time was 180 min. Moreover, the complement activation was also reduced with increased 2-methacryloyloxyethyl phosphorylcholine distribution on the surface of the membrane.     

Differences in sleep-wake habits and EEG sleep variables between active morning and evening subjects

This article is a survey study, followed by an experimental study, examining the differences of sleep-wake habits and sleep electroencephalographic (EEG) variables between morning and evening type subjects (Ss). In the survey study, the Japanese version of the Horne and Ostberg Morningness-Eveningness Questionnaire and Life Habits Inventory (LHI) were administered to approximately 1,500 university students. The survey results showed that the two types were significantly different from each other in terms of retiring and arising time, sleep latency, mood on arising, nap, adequate amount of sleep, number of times of staying awake all night, and variability in bedtime, arising time, and sleep length. These results suggested that evening type Ss had more irregular and/or flexible sleep-wake habits than morning type Ss. In the experimental study, 10 morning and 11 evening type Ss were selected from the population included in the survey study, and polysomnograms were obtained. The results showed that only in rapid eye movement (REM) latency did morning type Ss significantly differ from evening type Ss. REM latency might be related to personality factors, particularly to neuroticism and anxiety.     

Potential predictors of the onset of focal intestinal perforation in extremely low birth weight infants based on an analysis of coagulation and fibrinolysis markers at birth: A case-control study based on ten years of experience at a single institution

Purpose: We aimed to investigate potential predictors of focal intestinal perforation (FIP) in extremely low birth weight infants (ELBWIs) among coagulation and fibrinolysis markers at birth.Methods: We reviewed the medical records of FIP patients and their coagulation and fibrinolysis markers at birth between 2010 and 2019, and matched patients according to gestational age. FIP was diagnosed based on macroscopic intestinal perforation with a punched-out lesion without necrosis. Patient characteristics and blood test results, including coagulation and fibrinolysis marker levels, were compared between the groups.Results: Two hundred forty ELBWIs were enrolled in this study (FIP, n = 18; controls, n = 222). In the FIP group, the gestational age at birth was significantly younger (p = 0.023) and the birth weight was significantly lower (p = 0.007) in comparison to the control group. Furthermore, the FIP group showed significantly lower levels of fibrinogen (p = 0.027) and factor XIII (F-XIII) (p = 0.007). The receiver operating characteristics curves for fibrinogen and F-XIII revealed that the 95% confidence intervals of fibrinogen and F-XIII were 0.530–0.783 (p = 0.027), and 0.574–0.822 (p = 0.007), respectively.Conclusions: This is the first report focusing on coagulation and fibrinolysis markers in FIP patients at birth. The fibrinogen and F-XIII values at birth are potential predictors of FIP in ELBWIs.Type of Study: Study of Diagnostic Test (Case Control Study)Level of Evidence: Level IV     

Outcome of advanced renal cell carcinoma arising in end-stage renal disease: comparison with sporadic renal cell carcinoma

Clinical and Experimental Nephrology - The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. Patients diagnosed with...