Meito Sangyo (Japan)

BackgroundVaccination has been recommended in the midst of the COVID-19 pandemic, but some patients are not vaccinated due to concerns about adverse reactions.ObjectivesThe purpose of this study is to investigate the adverse reactions in rheumatic diseases and to guide the decision-making of patients and physicians.MethodsA questionnaire was sent to patients with rheumatic diseases, and patients who could be counted as of September 2021, when they consented to this study, were surveyed.ResultsThe subjects were 123 (male:female=10:113), 84 with rheumatoid arthritis and 39 with other immune diseases. The therapeutic agents used were PSL 31(25.2%), MTX 65(52.8%), NSAID/COX inhibitors 28(22.8%), bDMARDs 42(34.1%). adverse reactions after the first and second vaccination were fever 17(13.8%)/50(40.7%), joint symptoms 7(5.7%)/22(17.9%), local injection reactions (pain/irritation) 22(17.9%), local injection reactions (pain/erythema) 93(75.6)/98(79.7), systemic skin symptoms 0(0%)/2(1.6%), other symptoms (malaise, myalgia, etc.) 59(48.0%)/85(69.1%), and treatment intensification 5(4.1%)/12(9.7%). These responses differed in occurrence only for fever with and without PSL medication (22.5%: 47.3% (p=0.02)).The odds ratio for disease worsening after the first dose of vaccine and again after the second dose was 33.5 (p<0.01).ConclusionNo specific adverse reactions other than the commonly known ones were observed, but some patients experienced worsening of symptoms after vaccination, requiring intensified treatment. Based on the results of this study, we believe that adverse reactions to vaccination are acceptable. We plan to accumulate more cases and analyze them in the future.The exacerbation of disease after the first vaccination would predict the exacerbation after the second vaccination.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Establishing a rapid in vitro evaluation system for drug screening is essential for the development of new drugs. To reproduce tissues/organs with functions closer to living organisms, in vitro three-dimensional (3D) culture evaluation using microfabrication technology has been reported in recent years. Culture on patterned substrates with controlled hydrophilic and hydrophobic regions (Cell-ableTM) can create 3D liver models (miniature livers) with liver-specific Disse luminal structures and functions. MRI contrast agents are widely used as safe and minimally invasive diagnostic methods. We focused on anionic polysaccharide magnetic iron oxide nanoparticles (Resovist®) and synthesized the four types of nanoparticle derivatives with different properties. Cationic nanoparticles (TMADM) can be used to label target cells in a short time and have been successfully visualized in vivo. In this study, we examined the morphology of various nanoparticles. The morphology of various nanoparticles showed relatively smooth-edged spherical shapes. As 3D liver models, we prepared primary hepatocyte-endothelial cell heterospheroids. The toxicity, CYP3A, and albumin secretory capacity were evaluated in the heterospheroids labeled with various nanoparticles. As the culture period progressed, the heterospheroids labeled with anionic and cationic nanoparticles showed lower liver function than non-labeled heterospheroids. In the future, there is a need to improve the method of creation of artificial 3D liver or to design a low-invasive MRI contrast agent to label the artificial 3D liver.

Background and Objective: The effects of rumen mechanical stimulating (RMS) brushes on the health of Brahman crossbred steers were determined by measuring blood parameters and examining the rumen wall.Materials and Methods: This study used twenty Brahman crossbred steers divided into control and RMS groups.The steers were given low-forage diets (95.5% concentrate and 4.5% maize stover) based on 3% dry matter by body weight.The installation of RMS was conducted by a professional.Blood samples were collected at the end of the experiment from the coccygeal vein for blood profile and immunoglobulin G (IgG) measurements.The steers were slaughtered at the 93rd day of the experiment, samples of the rumen wall were collected and rumen histological observations were made.Results: The results showed that the RMS brush administration did not affect the hematocrit, hemoglobin (Hb), number of red blood cells (RBC), number of white blood cells (WBC) or IgG (p>0.05).However, there was a significant increase in neutrophils (p<0.05).The steers with RMS had a higher ratio of neutrophils to lymphocytes (p<0.05).Even though the treatment affected the neutrophil count and the ratio of neutrophils to lymphocytes, these values were in a normal range.The results of the rumen gross anatomy and histology observations showed that there was no tissue damage of the rumen, thus, it is in a normal state. Conclusion:The data indicate that the RMS brush utilization in steers does not result in adverse effects on the health of steers as measured by blood profiles, IgG concentrations and rumen histology.

Abstract Hyperthermia using magnetic nanoparticles and alternating magnetic field is promising for cancer therapy. In most cases, the usefulness of this magnetic nanoparticle-based hyperthermia has been shown by applying magnetic nanoparticles to tumor tissue such as a subcutaneous tumor with direct injection technique; however, if the magnetic nanoparticles can be cancer cell-specifically delivered at the cellular level, the magnetic field hyperthermia would have the potential to treat various sorts of disseminated cancer diseases. The aim of this study is to prove this concept. Maghemite nanoparticles (MNPs) were conjugated with the anti-HER2 antibody (Tmab) for cancer targeting, and the Tmab-MNPs were applied to the co-culture flask containing both HER2-expressing breast cancer AU565 cells and normal fibroblast FEF3 cells. Thirty minutes later from the Tmab-MNPs administration, the medium was removed and the cells were washed to remove excess Tmab-MNPs. Prussian blue iron staining and immunostaining for Tmab showed co-localization of the maghemite nanoparticles and Tmab only on the cancer cells, which suggested that MNPs conjugation with Tmab was successful and that cancer specific delivery of MNPs at the cellular level was achieved in vitro. Moreover, application of alternating current magnetic field at 280 kHz for 1 hour caused apoptotic-like cell death only to cancer cells without any cell damage to normal fibroblast FEF3 cells. Intracellular hyperthermia using cancer-specific antibody-modified magnetic nanoparticles have the potential to be applied to the treatment of disseminated cancer diseases. Citation Format: Tetsuya Kagawa, Hiroyuki Kishimoto, Toshiaki Ohara, Hiroshi Tazawa, Shunsuke Kagawa, Takeshi Nagasaka, Satoshi Nohara, Ichiro Kato, Adarsh Sandhu, Hiromichi Aono, Toshiyoshi Fujiwara. Hyperthermia at the single-cell level for disseminated cancer disease with immuno-magnetic nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3101. doi:10.1158/1538-7445.AM2017-3101

In this paper, anodic aluminum oxide (AAO) is introduced as a potential new material for making interposers, and a low cost process for building high density interposers is demonstrated. Hard anodic process was used to create thick anodic aluminum oxide (AAO) films containing high density vertical nanopores on aluminum substrates. Silicon dioxide (SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) deposition by plasma enhanced chemical vapor deposition (PECVD) was performed to form a hard mask against deep etching by a hydroxide based solution. Wet hydroxide etch produced nearly vertical openings in the AAO due to the highly anisotropic nature of the AAO material. Vias were metallized by bottom-up copper electroplating directly from the aluminum substrate, which acted as both a structural material and a seed layer for electroplating. After via plating, the top surface was polished to reach submicron surface roughness, the bottom surface was polished after etching away the aluminum carrier substrate to produce a final AAO interposer. This interposer benefits from high density vertical vias, low cost, and ease of manufacture.

BackgroundMolecular imaging using magnetic nanoparticles (MNPs)—magnetic particle imaging (MPI)—has attracted interest for the early diagnosis of cancer and cardiovascular disease. However, because a steep local magnetic field distribution is required to obtain a defined image, sophisticated hardware is required. Therefore, it is desirable to realize excellent image quality even with low-performance hardware. In this study, the spatial resolution of MPI was evaluated using an image reconstruction method based on the correlation information of the magnetization signal in a time domain and by applying MNP samples made from biocompatible ferucarbotran that have adjusted particle diameters.MethodsThe magnetization characteristics and particle diameters of four types of MNP samples made from ferucarbotran were evaluated. A numerical analysis based on our proposed method that calculates the image intensity from correlation information between the magnetization signal generated from MNPs and the system function was attempted, and the obtained image quality was compared with that using the prototype in terms of image resolution and image artifacts.ResultsMNP samples obtained by adjusting ferucarbotran showed superior properties to conventional ferucarbotran samples, and numerical analysis showed that the same image quality could be obtained using a gradient magnetic field generator with 0.6 times the performance. However, because image blurring was included theoretically by the proposed method, an algorithm will be required to improve performance.ConclusionsMNP samples obtained by adjusting ferucarbotran showed magnetizing properties superior to conventional ferucarbotran samples, and by using such samples, comparable image quality (spatial resolution) could be obtained with a lower gradient magnetic field intensity.

To monitor pancreatic islet transplantation efficiency, reliable noninvasive imaging methods, such as magnetic resonance imaging (MRI) are needed. Although an efficient uptake of MRI contrast agent is required for islet cell labeling, commercially-available magnetic nanoparticles are not efficiently transduced into cells. We herein report the in vivo detection of transplanted islets labeled with a novel cationic nanoparticle that allowed for noninvasive monitoring of islet grafts in diabetic mice in real time. The positively-charged nanoparticles were transduced into a β-cell line, MIN6 cells, and into isolated islets for 1 hr. MRI showed a marked decrease in the signal intensity on T1- and T2-weighted images at the implantation site of the labeled MIN 6 cells or islets in the left kidneys of mice. These data suggest that the novel positively-charged nanoparticle could be useful to detect and monitor islet engraftment, which would greatly aid in the clinical management of islet transplant patients.

To evaluate the effects of a new synbiotic consisting of Lactobacillus casei subsp. casei (Lcc) and dextran (Dex) on milk production, a total of 58 Holstein dairy cows, which became pregnant and gave birth to calves at regular intervals and lactated steadily and continuously, were selected. The study had a completely randomized design, and the animals were divided into two groups. Group A was fed with a basic diet only, and Group B was fed with a basic diet supplemented with the synbiotic consisting of freeze-dried Lcc and mixed feed containing Dex for one year from August 2004. After supplementation with the synbiotic, milk yields and components of Group B were compared with those of Group A in the August, December of 2004, April and August of 2005. Milk yields of Group B were greater than those of Group A. There were significant differences (p<0.01 or 0.05) between these groups for all values. Furthermore, total amounts of fat, protein and solid non-fat in Group B significantly increased in comparison with those of Group A. In addition, the somatic cell counts of Group A significantly increased in August of 2004 and 2005 in comparison with those of Group B. Thus, the new synbiotic consisting of Lcc and Dex can increase the milk production of Holstein dairy cows throughout the year.