Dendritic cells in colonic patches and iliac lymph nodes are essential in mucosal IgA induction following intrarectal administration via CCR7 interaction

This study examined dendritic cells (DC) following intrarectal (IR) vaccination with the mucosal adjuvant cholera toxin (CT). Three rounds of IR vaccination with ovalbumin (OVA) and CT resulted in brisk levels of systemic and mucosal Ig responses. Immunohistochemical studies revealed that CD11c+ MHC class II+ cells accumulated primarily in the colonic patches (CP) and lamina propria of the large intestine (LI-LP), iliac LN (ILN) and MLN following IR vaccination with CT. Adoptively transferred CFSE-labeled OVA-specific CD4+ T cells proliferated significantly, secreting predominantly Th1-type cytokines in the CP (48 h after IR vaccination with CT) and Th2-type cytokines in the ILN (96 h after IR vaccination with CT). Following three IR vaccinations, CP-null mice that were generated by in utero treatment with anti-IL-7R Ab showed reduced levels of serum IgG and fecal IgA antibodies, suggesting a crucial role for CP in the initiation of systemic and mucosal immune responses. Of most interest, IR vaccination reduced IgA levels in fecal extracts significantly more in the CCR7-/- mice than in the wild-type mice. These results indicate that IR vaccination primarily mobilizes CD11c+ cells in the CP and ILN to induce optimal mucosal immune responses by CCR7 interaction.     

Myelin degeneration induced by mutant superoxide dismutase 1 accumulation promotes amyotrophic lateral sclerosis

Myelin is a specialized membrane that wraps around nerve fibers and is essential for normal axonal conduction in neurons. In the central nervous system, oligodendrocytes are responsible for myelin formation. Recent studies have reported pathological abnormalities in oligodendrocytes in human patients with amyotrophic lateral sclerosis (ALS) and a mouse model of ALS expressing the G93A mutation of the human superoxide dismutase 1 (mtSOD1). However, it is unclear whether oligodendrocyte pathology in ALS represents the primary dysfunction induced by mtSOD1 and how mtSOD1 contributes to oligodendrocyte degeneration and ALS pathogenesis. We analyzed GAL4-VP16-UAS transgenic zebrafish selectively expressing mtSOD1 in mature oligodendrocytes. We observed that mtSOD1 directly induced oligodendrocyte degeneration by disrupting the myelin sheath and downregulating monocarboxylate transporter 1 (MCT1), thereby causing spinal motor neuron degeneration. Pathological changes observed in this transgenic zebrafish were similar to the pathology observed in the SOD1^G93A mouse model of ALS, which is characterized by expression of mtSOD1 in all cells. In addition, oligodendrocyte dysfunction induced by mtSOD1 was associated with anxiety-related behavioral abnormalities, learning impairments, and motor defects in the early symptomatic stage. We also found that treatment with potassium channel inhibitors rescued behavioral abnormalities without rescuing MCT1 expression, suggesting that myelin disruption induces behavioral abnormalities independently of MCT1. These results indicate that mtSOD1-induced dysfunction of mature oligodendrocytes is sufficient to induce motor neuron degeneration, thus informing future therapeutic strategies targeted at oligodendrocytes in ALS.     

Clinical Impact of Natural Killer Group 2D Receptor Expression and That of Its Ligand in Ovarian Carcinomas: A Retrospective Study

PurposeNatural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptor expressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current study aimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it also examined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathological parameters, and prognosis.Materials and MethodsFormalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissue samples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands (MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the association between these results and clinical prognostic parameters was analyzed statistically.ResultsULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression of ULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression of ULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independent predictor of better survival.ConclusionHigh expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novel prognostic indicator in this subset of carcinomas.     

Dynamic Calibration for the In-Line NIR Monitoring of Film Thickness of Pharmaceutical Tablets Processed in a Fluid-Bed Coater

NIR spectroscopy has been extensively employed for the in-line monitoring of pharmaceutical processes as one of the key PAT implementation tools. Nevertheless, pharmaceutical processes such as fluid-bed coating have not fully made the most of the NIR in-line monitoring primarily due to a difficulty in handling random in-line spectra. In this study, novel approaches to develop a reasonable dynamic calibration model were proposed; averaging and clustering. Pharmaceutical test tablets were coated with HPMC-based materials using a fluid-bed processor. During the 160 min coating process under tangential spraying mode, 10 tablets were sampled out at every 10 min mark for actual coating thickness measurements. NIR spectra at and near each 10 min mark were treated and processed by the averaging and clustering operations. Averaging of 21 spectra resulted in a reasonably good dynamic calibration model whose determination coefficient was estimated as high as 0.9916. The PCA-based clustering turned out to be substantially helpful especially when a large number of NIR spectra were averaged. A prediction experiment verified that our dynamic calibration model can control the coating thickness in-line as good as 3% deviated from the actual thickness, which can offer a reasonable end-point for the fluid-bed coating process. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:325–335, 2010     

Effect of Dexmedetomidine Compared to Remifentanil During Bariatric Surgery on Postoperative Nausea and Vomiting: a Retrospective Study

Purpose

Postoperative nausea and vomiting (PONV) occurs frequently after bariatric surgery and is a major cause of adverse outcomes. This retrospective study investigated whether opioid-restricted total intravenous anesthesia using dexmedetomidine as a substitute for remifentanil can reduce PONV in bariatric surgery.

Materials and Methods

The electronic medical records of adult patients who underwent laparoscopic bariatric surgery between January and December 2019 were reviewed. The patients were divided into two groups according to the agents used for anesthesia: Group D, propofol and dexmedetomidine; Group R, propofol and remifentanil.

Results

A total of 134 patients were included in the analyses. The frequency of postoperative nausea was significantly lower in Group D than that in Group R until 2 h after discharge from the postanesthesia care unit (PACU) (P?=?0.005 in the PACU, P?=?0.010 at 2 h after PACU discharge) but failed to significantly reduce the overall high incidence rates of 60.5% and 65.5%, respectively (P?=?0.592). Postoperative pain score was significantly lower in Group D until 6 h after PACU discharge. The rates of rescue antiemetic and analgesic agent administration in the PACU were significantly lower in Group D than those in Group R.

Conclusion

Opioid-restricted total intravenous anesthesia using dexmedetomidine reduces postoperative nausea, pain score, antiemetic, and analgesic requirements in the immediate postoperative period after bariatric surgery.

Graphical abstract

     

Intravital imaging in zebrafish using quantum dots

Background/aims: Fluorescent quantum dots (QDs) are powerful multipurpose interfaces of nanotechnology providing long-term and multicolor imaging of cellular and molecular interactions. The application of QDs in living organisms is just beginning to be explored, and zebrafish embryos may be suitable vertebrate model organisms for intravital imaging with QDs. To investigate their potential in skin research, we used QDs as microangiography contrast agents and attempted to visualize the cardiovascular system in zebrafish. We also attempted to find the pathway relationship between the cardiovascular system and the nerve network using QDs together with the transgenic zebrafish line.
Method: Quantum Dot QD605, which reveals green color under the fluorescent microscope, was used as a microangiography contrast agent. The olig2-Dsred transgenic zebrafish line, which expresses motor neurons in red color, was used together with QDs. Images of QD605-injected embryos were recorded with a digital camera.
Results: Combining the green fluorescence of QD605 and the red fluorescence of olig2-Dsred transgenic zebrafish, we could obtain detailed images manifesting the spatial relationship between the vascular and the nervous system of zebrafish
Conclusion: QDs could easily be used as a bright microangiography agent in living embryos. Our image of the vascular and motor nervous system in zebrafish showed a similar pattern of trajectory overall. However, their segmented repetitive networks along the dorsoventral axis were not completely overlapped.     

Epidemiological Features and Economic Burden of Guillain-Barré Syndrome in South Korea: A Nationwide Population-Based Study

Background and PurposeGuillain-Barré syndrome (GBS) is rare, but its symptoms are severe and they occasionally lead to long-term disability. Country-specific epidemiological evidence is useful for detecting potential problems at the population level. This study investigated the epidemiological and economic characteristics of GBS in South Korea.MethodsThe Korean National Health Insurance Service claims data from 2010 to 2016 were used to identify incident cases as newly hospitalized patients with a primary diagnosis of GBS (the 10th revision of the International Classification Disease code of G61.0). New cases were defined as patients not having claim records for GBS within one year prior to the hospital admission for GBS.ResultsThe incidence rate increased by 45.6% between 2010 and 2016, from 1.28 to 1.82 per 100,000 population. All age groups other than <20 years showed increasing trends. The incidence rate was highest in those aged 65 years to 74 years. Approximately 72% of the incident GBS cases had antecedent infection within 42 days before GBS was diagnosed. Children younger than 10 years constituted the highest proportion of antecedent infections (93.7%). The average length of stay per GBS hospitalization was 33.5 days. Patients had an average of 7.48 outpatient visits for GBS treatment per year. The economic burden from a societal perspective of treating GBS during the first year was USD 16,428.ConclusionsThe increasing incidence trend and substantial economic burden of GBS strongly advocate the development of effective strategies for preventing and managing GBS.     

Protective effects of caffeic acid phenethyl ester (CAPE) against neomycin-induced hair cell damage in zebrafish

Objective

Caffeic acid phenethyl ester (CAPE) is known to reduce the generation of oxygen-derived free radicals, which is a major mechanism of aminoglycoside-induced ototoxicity. The objective of the present study was to evaluate the effects of CAPE on neomycin-induced ototoxicity in zebrafish (Brn3c: EGFP).

Methods

Five-day post-fertilization zebrafish larvae (n = 10) were exposed to 125 μM neomycin and one of the following CAPE concentrations for 1 h: 50, 100, 250, 500, or 1000 μM. Ultrastructural changes were evaluated using scanning electron microscopy (SEM). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) assay and 2-[4-(dimethylamino)styryl]-N-ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis and mitochondrial damage.

Results

CAPE decreased neomycin-induced hair cell loss in the neuromasts (500 μM CAPE: 12.7 ± 1.1 cells, 125 μM neomycin only: 6.3 ± 1.1 cells; n = 10, P < 0.05). In the ultrastructural analysis, structures of mitochondria and hair cells were preserved when exposed to 125 μM neomycin and 500 μM CAPE. CAPE decreased apoptosis and mitochondrial damage.

Conclusion

In the present study, CAPE attenuated neomycin-induced hair cell damage in zebrafish. The results of the current study suggest that neomycin induces apoptosis, and the apoptotic cell death can be prevented by treatment with CAPE in zebrafish.