CKD-712, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-κB Activation and Augments Akt Activation during TLR4 Signaling

Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-κB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-κB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-κB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator

Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial

Background To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB). Methods This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared. Results A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83–1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18–3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002). Conclusions In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019)

Clinicopathological Analysis of Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma with IgG4-Positive Cells.

This study aims to analyze clinical and pathological characteristics of ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) accompanying IgG4-positive cells. Fifty patients with a diagnosis of primary non-conjunctival ocular adnexal EMZL were enrolled in this study. The number of IgG4-positive cells and the ratio of IgG/IgG4 were evaluated by immunohistochemistry in the biopsy specimens. The patients were divided into two groups based on the absolute number and the ratio of IgG4-positive cells (IgG4-posivite vs IgG4-negative groups). The demographic data, clinical staging at diagnosis, histopathological characteristics, and response to initial treatment were comparatively analyzed between the 2 groups. Five (10%) of 50 patients were defined as IgG4-positive group, and all the cases showed characteristic histological features such as extensive plasma cell infiltration and dense fibrosis. Most of these patients (4 of 5 patients) had lymphoma of the lacrimal gland. The patients from the IgG4-positive group showed a lower response rate to initial treatment (87.5 vs 33%, p = 0.03) than IgG4-negative group with a median follow-up period of 38 months. A part of the ocular adnexal EMZLs were accompanied with IgG4-positive cells. Significantly, most IgG4-positive ocular adnexal EMZLs occurred in the lacrimal gland, and can be related with a more frequent treatment failure

Intraoperative neurological pupil index and postoperative delirium and neurologic adverse events after cardiac surgery: an observational study

Abstract Neurological pupil index (NPi) calculated by automated pupillometry predicts clinical outcomes in critically ill patients. However, there are few data on intraoperative NPi and postoperative outcome after cardiac surgery. We evaluated the relationships between intraoperative NPi and clinical outcomes, such as delirium, in cardiac surgery patients. NPi was measured at baseline, after anesthesia induction, at 30 min intervals after initiation of cardiopulmonary bypass or anastomosis of coronary artery bypass graft, and at skin closure. Abnormal NPi was defined as one or more measurements of NPi < 3.0 during surgery. The worst intraoperative NPi was recorded, then multivariate logistic regression analysis was performed to evaluate the relationship between abnormal NPi and postoperative delirium following cardiac surgery. Among 123 included patients, postoperative delirium developed in 19.5% (24/123) of patients. Intraoperative abnormal NPi was significantly associated with postoperative delirium (odds ratio 6.078; 95% confidence interval 1.845–20.025; P = 0.003) after adjustment for Society of Thoracic Surgeons Predicted Risk of Mortality score, coronary artery disease, and use of calcium channel blockers. In conclusion, abnormal intraoperative NPi independently predicted postoperative delirium following cardiac surgery. Intraoperative application of pupillometry may have prognostic value for development of postoperative delirium, thereby enabling close surveillance and early intervention in high-risk patients. Registry number: ClinicalTrials.gov (NCT04136210)

Introducing pulsed low-intensity ultrasound to culturing human umbilical cord-derived mesenchymal stem cells

The human umbilical cord (hUC) is a source of adult tissue-derived mesenchymal stem cells (MSCs). A pulsed low-intensity ultrasound (PLIUS) method is described for increasing the yield of MSCs from whole hUC without enzymatic digestion or growth factor supplementation. Analysis of the immunophenotype of cells and a differentiation study were performed to show the compatibility of MSCs. The mean number of cells recovered from primocultures of hUC was 6 x 10(5) cells/cm. PLIUS resulted in a 3.3-fold increase in MSC yield at passage 0. PLIUS exposure increases the yield of hUC-MSCs by promoting release and enhancing proliferation.Seshareddy K, 2008, METHOD CELL BIOL, V86, P101, DOI 10.1016/S0091-679X(08)00006-XKarahuseyinoglu S, 2007, STEM CELLS, V25, P319, DOI 10.1634/stemcells.2006-0286Lu LL, 2006, HAEMATOL-HEMATOL J, V91, P1017Min BH, 2006, SCAND J RHEUMATOL, V35, P305, DOI 10.1080/03009740600588418Weiss ML, 2006, STEM CELLS, V24, P781, DOI 10.1634/stemcells.2005-0330Mareschi K, 2006, J CELL BIOCHEM, V97, P744, DOI 10.1002/jcb.20681Sobolewski K, 2005, PLACENTA, V26, P747, DOI 10.1016/j.placenta.2004.10.008Sarugaser R, 2005, STEM CELLS, V23, P220, DOI 10.1634/stemcells.2004-0166Panepucci RA, 2004, STEM CELLS, V22, P1263, DOI 10.1634/stemcells.2004-0024Covas DT, 2003, BRAZ J MED BIOL RES, V36, P1179Mitchell KE, 2003, STEM CELLS, V21, P50Erices A, 2000, BRIT J HAEMATOL, V109, P235Doan N, 1999, J ORAL MAXIL SURG, V57, P409Nanaev AK, 1997, PLACENTA, V18, P53PILLA AA, 1990, J ORTHOP TRAUMA, V4, P246

Effect of Abdominal Massage before In Vitro Fertilization Injection on Alleviating Pain among Infertile Women

PURPOSE: The purpose of this study was to evaluate the effect of abdominal massage on alleviating pain caused by the injection of recombinant gonadotropin for In Vitro Fertilization (IVF) among infertile women. METHODS: This study employed a nonequivalent control group non-synchronized design. A total sample of 149 infertile women who never experienced in vitro fertilization was recruited at C fertility center. Seventy women were assigned into experimental group and 79 into controls. The experimental group had been informed to do abdominal massage prior to the injection and to record their subjective pain using visual analogue scale. The control group had been informed to record their subjective pain in the same way just after the injection. RESULTS: Compared to the pre-tested pain scores, the pain scores in experimental group were significantly reduced by 0.7 points, whereas the control group increased by 0.9 points (t=-4.55, p=.001). CONCLUSION: This study confirms that the use of abdominal massage prior to the injection is an effective way to alleviate pain on injection site. This massage may be a useful intervention for infertile women about pain alleviation

Treatment outcome in ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) patients according to the IgG4-positive plasma cell infiltration.

<p>*Fisher’s exact test.</p><p>^†Mann-Whitney U test.</p><p>IgG4-positive group, ocular adenexal EMZL with IgG4:IgG cell ratio > 40%, and IgG4-positive plasma cells ≥ 50 / HPF; IgG4-negative group, ocular adenexal EMZL with IgG4-positive plasma cells < 50 / HPF or IgG4:IgG cell ratio ≤ 40%.</p><p>CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.</p><p>Treatment outcome in ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) patients according to the IgG4-positive plasma cell infiltration.</p

(A) Computed tomographic image revealing an enlarged lacrimal gland of the left side, with homogenous enhancement.

<p>(B) Histological examination result showing lymphoplasma cell infiltration and background fibrosis (H&E, original magnification ×200). Immunohistochemical staining for (C) IgG and (D) IgG4 (original magnification ×200) showing that most of the IgG-positive cells are positive for IgG4.</p