Human B1 Cells are the Main Blood Group A-Specific B Cells That Have a Moderate Correlation With Anti-A Antibody Titer

BACKGROUND: Anti-carbohydrate antibody responses, including those of anti-blood group ABO antibodies, are yet to be thoroughly studied in humans. Because anti-ABO antibody-mediated rejection is a key hurdle in ABO-incompatible transplantation, it is important to understand the cellular mechanism of anti-ABO responses. We aimed to identify the main human B cell subsets that produce anti-ABO antibodies by analyzing the correlation between B cell subsets and anti-ABO antibody titers. METHODS: Blood group A-binding B cells were analyzed in peritoneal fluid and peripheral blood samples from 43 patients undergoing peritoneal dialysis and 18 healthy volunteers with blood group B or O. The correlation between each blood group A-specific B cell subset and anti-A antibody titer was then analyzed using Pearson's correlation analysis. RESULTS: Blood group A-binding B cells were enriched in CD27⁺CD43⁺CD1c− B1, CD5⁺ B1, CD11b⁺ B1, and CD27⁺CD43⁺CD1c+ marginal zone-B1 cells in peripheral blood. Blood group A-specific B1 cells (P=0.029 and R=0.356 for IgM; P=0.049 and R=0.325 for IgG) and marginal zone-B1 cells (P=0.011 and R=0.410 for IgM) were positively correlated with anti-A antibody titer. Further analysis of peritoneal B cells confirmed B1 cell enrichment in the peritoneal cavity but showed no difference in blood group A-specific B1 cell enrichment between the peritoneal cavity and peripheral blood. CONCLUSIONS: Human B1 cells are the key blood group A-specific B cells that have a moderate correlation with anti-A antibody titer and therefore constitute a potential therapeutic target for successful ABO-incompatible transplantation.

Protective effects of Acanthopanax divaricatus extract in mouse models of Alzheimer's disease

BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of beta-amyloid peptide (Abeta) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Abeta1-42 until evaluation) effectively blocked Abeta1-42-induced impairment in passive avoidance performance, and Abeta1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1alpha in the hippocampus. In addition, it alleviated the Abeta1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1beta in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.

Protective effects of Acanthopanax divaricatus extract in mouse models of Alzheimer's disease

BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of beta-amyloid peptide (Abeta) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Abeta1-42 until evaluation) effectively blocked Abeta1-42-induced impairment in passive avoidance performance, and Abeta1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1alpha in the hippocampus. In addition, it alleviated the Abeta1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1beta in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.

Lysophosphatidylcholine, Oxidized Low-Density Lipoprotein and Cardiovascular Disease in Korean Hemodialysis Patients: Analysis at 5 Years of Follow-up

Although oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (LPC) have been proposed as important mediators of the atherosclerosis, the long-term contribution to the risk of cardiovascular disease (CVD) in hemodialysis patients has not been evaluated. This study investigated the relation between oxidized LDL and LPC levels with long term risk of CVD. Plasma oxidized LDL and LPC levels were determined in 69 Korean hemodialysis patients as a prospective observational study for 5 yr. During the observation period, 18 cardiovascular events (26.1%) occurred including 6 deaths among the hemodialysis patients. The low LPC level group ( 254 microM/L) (P = 0.01). However, serum levels of oxidized LDL were not significantly different between groups with and without CVD. In adjusted Cox analysis, previous CVD, (hazard ratio [HR], 5.68; 95% confidence interval [CI], 1.94-16.63, P = 0.002) and low LPC level (HR, 3.45; 95% CI, 1.04-11.42, P = 0.04) were significant independent risk factors for development of CVD. It is suggested that low LPC, but not oxidized LDL, is associated with increased risk of CVD among a group of Korean hemodialysis patients.

Protective Effect of Decursinol on Mouse Models of Sepsis: Enhancement of Interleukin-10

The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol (1~100 mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN-induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-alpha, IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.

The Effect of Fluoxetine on Behaviors in Transient Forebrain Ischemic Gerbil / 대한정신약물학회지

OBJECTIVE: This study aims to explore the effect of fluoxetine on memory, locomotor and depressive behavior in transient forebrain ischemic model of gerbil. METHODS: Doses of fluoxetine (10, 40 mg/kg) or vehicle were intraperitoneally administered once 30 min before ischemic surgery in gerbil. Novel object recognition test, spontaneous motor activity, learned helplessness test were performed 4 days, 8 days, or 9 days, respectively, after sham or ischemic surgery. RESULTS: Fluoxetine treatment (40 mg/kg) significantly reduced recognition memory in sham operated gerbil. However, fluoxetine (10, 40 mg/kg) did not affect ischemia-induced impairment in recognition memory. The treatment of fluoxetine (10, 40 mg/kg) significantly inhibited locomotor hyperactivity induced by transient ischemia even though fluoxetine (40 mg/kg) did not affect spontaneous motor activity in the sham operated gerbils. Fluoxetine did not affect depressive behavior in sham and ischemic gerbils. CONCLUSION: The treatment of fluoxetine inhibited ischemia-induced hyperactivity, but did not affect memory and depressive behavior in transient forebrain ischemic gerbils.