Polyclonal IgM and IgA block in vitro complement deposition mediated by anti-ganglioside antibodies in autoimmune neuropathies.

Intravenous immunoglobulin (IVIG), consisting of IgG, is the first-line treatment for Guillain-Barré syndrome and multifocal motor neuropathy. IgG, but neither IgM nor IgA, has been demonstrated in vitro to inhibit complement deposition mediated by anti-ganglioside autoantibodies in sera from patients with both conditions. The objective of this study is to investigate the in vitro effectiveness of IgM and IgA in inhibiting complement deposition to ganglioside/anti-ganglioside antibody complexes. Serum samples were obtained from patients with multifocal motor neuropathy associated with anti-GM1 IgM antibodies, Guillain-Barré syndrome associated with anti-GM1 IgG antibodies and Miller Fisher syndrome associated with anti-GQ1b IgG antibodies. Inhibition of complement deposition using different immunoglobulin preparations was measured by enzyme-linked immunosorbent assay. IgM/A-enriched IVIG and immunoglobulin isotypes (polyclonal IgM and IgA) showed higher potential in inhibiting complement deposition than standard IVIG. Although the safety concerns about the use of IgM and IgA for an immunotherapy still remain, IgM and IgA may serve as an alternative immunotherapy in those anti-ganglioside antibody-mediated neuropathies

Different IVIG glycoforms affect in vitro inhibition of anti-ganglioside antibody-mediated complement deposition

Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain–Barré syndrome and multifocal motor neuropathy, which are caused by anti-ganglioside antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain–Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoantibody binding to ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases

Antibacterial, Hydrophilic Effect and Mechanical Properties of Orthodontic Resin Coated with UV-Responsive Photocatalyst

Photocatalysts have multiple applications in air purifiers, paints, and self-cleaning coatings for medical devices such as catheters, as well as in the elimination of xenobiotics. In this study, a coating of a UV-responsive photocatalyst, titanium dioxide (TiO2), was applied to an orthodontic resin. The antibacterial activity on oral bacteria as well as hydrophilic properties and mechanical properties of the TiO2-coated resin were investigated. ultraviolet A (UVA) (352 nm) light was used as the light source. Antibacterial activity was examined with or without irradiation. Measurements of early colonizers and cariogenic bacterial count, i.e., colony forming units (CFU), were performed after irradiation for different time durations. Hydrophilic properties were evaluated by water contact angle measurements. While, for the assessment of mechanical properties, flexural strength was measured by the three-point bending test. In the coat(+)light(+) samples the CFU were markedly decreased compared to the control samples. Water contact angle of the coat(+)light(+) samples was decreased after irradiation. The flexural strength of the specimen irradiated for long time showed a higher value than the required standard value, indicating that the effect of irradiation was weak. We suggest that coating with the ultraviolet responsive photocatalyst TiO2 is useful for the development of orthodontic resin with antimicrobial properties

Pathogenesis of Combined High-Grade Squamous Intraepithelial Lesion and Adenocarcinoma in Situ of the Uterine Cervix: Human Papillomavirus Genotype and Methylation Status and Immunohistochemical Study

To determine the etiology of combined high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS) of the uterine cervix, we examined human papillomavirus (HPV) subtypes, methylation status of the HPV-16 L1 gene, and immunohistochemical staining pattern of Krt7 in 8 cases of combined HSIL and AIS. Overall, 6 (75%) of 8 patients with combined HSIL and AIS were infected by the same subtype of HPV in both HSIL and AIS (cases 1–5, HPV-16; and case 6, HPV-18), whereas 2 (25%) patients showed infection with different subtypes of HPV (case 7, HPV-31 and -18; and case 8, HPV-52 and -16, in HSIL and AIS, respectively). The degrees of methylation at CpG islands within the HPV-16 L1 gene were almost equivalent between HSIL and AIS in cases 1–4, whereas a great difference in CpG methylation patterns between two was seen in only 1 case (case 5). In addition, both patients infected with different subtypes of HPV between HSIL and AIS were positive for Krt7 only within the AIS component. Based on these results, we propose two distinct developmental pathways of combined HSIL and AIS of the uterine cervix, the common pathway and the individual pathway

Stabilization of atherosclerotic plaque by pitavastatin in Watanabe heritable hyperlipidemic rabbits: A serial tissue-characterizing intravascular ultrasound study

AbstractBackgroundTo examine the effects of pitavastatin on atherosclerotic plaque in Watanabe heritable hyperlipidemic (WHHL) rabbits using serial in vivo tissue-characterizing intravascular ultrasound.MethodsA total of 11 WHHL rabbits of 10–12 weeks of age were divided into two groups, control and pitavastatin-administered groups. A total of 29 atherosclerotic plaque segments from control group and 43 plaque segments from the pitavastatin group were serially imaged by 40MHz intravascular ultrasound in vivo with a tissue characterization software (iMAP™, Boston Scientific, Natick, MA, USA) at the baseline and the follow-up (16th week).ResultsThe level of low-density lipoprotein cholesterol was significantly decreased in pitavastatin group. During the follow-up period, plaque area was significantly increased in the control group, whereas it was not significantly changed in the pitavastatin group. The fibrotic, necrotic, and necrotic plus lipidic areas were significantly increased in the control group, while no significant change was revealed for tissue profile in pitavastatin group. The change in the percent areas of fibrotic and lipidic plus necrotic tissues were significantly different between the two groups especially in the superficial half portion of plaque.ConclusionsThese data indicate that pitavastatin could attenuate atherosclerotic plaque formation and that it could stabilize the plaque in WHHL rabbits. Considering the fact that these were observed even with a high follow-up level of cholesterol, these data might come from the pleiotropic effects of pitavastatin

Acerola exosome-like nanovesicles to systemically deliver nucleic acid medicine via oral administration

Extracellular vesicles derived from mammalian cells could be useful carriers for drug delivery systems (DDSs); however, with regard to clinical application, there are several issues to be overcome. Acerola (Malpighia emarginata DC.) is a popular health food. In this study, the feasibility of orally administered nucleic acid drug delivery by acerola exosome-like nanoparticles (AELNs) was examined. AELNs were recovered from acerola juice using an affinity column instead of ultracentrifugation. MicroRNA (miRNA) was sufficiently encapsulated in AELNs by 30-min incubation on ice and was protected against RNase, strong acid, and base treatments. The administration of an AELN/miRNA mixture in cells achieved downregulation of the miRNA’s target gene, and this mixture showed cytoplasmic localization. AELNs orally delivered small RNA to the digestive system in vivo. The target gene-suppressing effect in the small intestine and liver peaked 1 day after administration, indicating potential for use as an oral DDS for nucleic acid in the digestive system