Blood clot formation in reinfusion bag with CATSmart: Two case reports.

Autologous blood cell salvage reduces the need for postoperative allogeneic blood transfusion and alleviates immunologic reactions, so the technique is commonly used in cardiac surgery. The continuous autotransfusion system is a type of blood cell salvage device. Although the processing program of continuous autotransfusion system includes filtering of several materials from suctioned blood, such as clots, leukocytes, cytokines, and complement, we identified some unexpected blood clots in the reinfusion bag. Pathologic examination revealed that the clots were composed of fibrin, red blood cell aggregates, and histiocytes. We report two cases of these abnormal findings during the use of CATSmart in cardiac surgery.

Efficacy of Adjuvant S-1 Versus XELOX Chemotherapy for Patients with Gastric Cancer After D2 Lymph Node Dissection: A Retrospective, Multi-Center Observational Study.

BACKGROUND: After curative resection of gastric cancer with D2 lymph node dissection, postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin (XELOX) is considered to be standard therapy in Eastern countries. This study aimed to compare the efficacies of adjuvant S-1 and XELOX chemotherapy for gastric cancer patients after D2 dissection based on disease-free survival (DFS). METHODS: This retrospective observational study was conducted at 29 tertiary hospitals in Korea. Of 1898 patients who underwent curative resection and received adjuvant chemotherapy for gastric cancer between February 2012 and December 2013, 1088 patients who met the eligibility criteria were enrolled in the study. After propensity score-matching, the 3-year disease-free survival rate (DFS) was used to compare efficacies directly between adjuvant XELOX and S-1 chemotherapies for patients with stage 2 or 3 gastric cancer after D2 gastrectomy. RESULTS: The 3-year DFS rates for the S-1 and XELOX groups did not differ significantly among disease stages 2A, 2B, and 3A (all p > 0.05). However, the survival rates for the S-1 group were significantly lower than for the XELOX group for stage 3B (65.8% vs. 68.6%; p = 0.019) and stage 3C (48.4% vs. 66.7%; p = 0.002) gastric cancer. The hazard ratios (HRs) of S-1 chemotherapy for recurrence compared with XELOX for stages 3B and 3C were respectively 2.030 [95% confidence interval (CI), 1.110-3.715; p = 0.022] and 2.732 (95% CI 1.427-5.234; p = 0.002). CONCLUSIONS: Adjuvant XELOX chemotherapy was more effective than S-1 for patients with stage 3B or 3C gastric cancer after D2 lymph node dissection.

Endogenous conversion of n-6 to n-3 polyunsaturated fatty acids attenuates K/BxN serum-transfer arthritis in fat-1 mice.

It is suggested that n-3 polyunsaturated fatty acids (PUFAs) can be used in the preventive or therapeutic management of rheumatoid arthritis (RA); however, controversial results have been reported. Here, we examined the effects of a decrease in the n-6/n-3 PUFA ratio on RA using fat-1 transgenic mice. First, we tested whether fat-1 expression modulated signaling pathways in fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor α (TNF-α). TNF-α activated p38 mitogen-activated protein kinase and increased phosphorylation of the signal transducer and activator of transcription 3 in wild type (WT) FLSs but not in fat-1 FLSs. Arthritis was induced by injection of K/BxN serum. Based on clinical scores, ankle thickness and pathological severity, we showed that WT mice developed clinically overt arthritis, whereas fat-1 mice showed attenuated arthritis. Moreover, fat-1 mice exhibited down-regulated local and systemic levels of inflammatory cytokines. Lastly, bone marrow-derived macrophages (BMMs) of WT mice differentiated into tartrate-resistant acid phosphatase-positive multinucleated osteoclasts, whereas the osteoclastogenenic process was suppressed in BMMs of fat-1 mice. The endogenous conversion of n-6 to n-3 PUFAs via fat-1 plays a key role in attenuation of RA; therefore, dietary supplementation of n-3 PUFAs may have therapeutic potential for the management of RA.

Myeloid-specific deletion of SIRT1 increases hepatic steatosis and hypothalamic inflammation in mice fed a high-fat diet.

Obesity-induced fatty liver disease is associated with increased hypothalamic inflammation. Previous reports have demonstrated that the deletion of SIRT1 in hepatocytes increases hepatic steatosis and inflammation. Using myeloid cell-specific SIRT1 knockout (KO) mice, we investigated whether ablation of SIRT1 in macrophages plays a role in regulating hepatic steatosis and hypothalamic inflammation. When challenged with a high-fat diet (HFD) for 24 weeks, hyperleptinemia, hyperinsulinemia, hepatic steatosis and macrophage infiltrations in HFD-fed KO mice were increased compared with HFD-fed WT mice. Hypothalamic expression levels of iba1 were increased in HFD-fed KO mice compared with HFD-fed WT mice. In particular, the expression levels of choline acetyltransferase were decreased in the hypothalamus of HFD-fed KO mice compared with HFD-fed WT mice. Thus, our findings suggest that SIRT1 plays a key role for hepatic steatosis and hypothalamic inflammation and that anti-inflammatory effect of SIRT1 may be important for the prevention of obesity-induced metabolic syndromes.

Prevalence of atopic dermatitis in Korea: analysis by using national statistics.

We attempted to investigate the prevalence of atopic dermatitis (AD) in Korea by using national statistics. Data on AD patients who received medical service at least once a year from 2003 through 2008 were collected from health insurance research team of National Health Insurance Corporation. Data of estimated populations during the same period were obtained from the Statistics Korea. In 2008, the prevalence of AD was 26.5% in aged 12-23 months and decreased substantially to 7.6% at age 6 yr, 3.4% at age 12 yr and to 2.4% at age 18 yr. In males, the prevalence was higher than females until 2 yr of age, while the opposite was shown in children aged 2 yr or older. In children aged less than 24 months, the prevalence of AD has increased from 19.8% to 23.8% between the years 2003 and 2008, while the prevalence showed no increase in the older age group. In conclusion, the prevalence of AD in 2008 peaked during infancy up to 26.5% and decreased thereafter. Our findings also suggest that increasing prevalence of AD in children less than 24 months might be responsible for the recent increase in the prevalence of AD in Korean children.

Melatonin attenuates clock gene cryptochrome1, which may aggravate mouse anti-type II collagen antibody-induced arthritis.

Very recently, the circadian rhythm was proved to play an important role in the pathogenesis of arthritis. The role of melatonin in the development and progress of rheumatoid arthritis has been implicated for decades. This study was aimed to investigate the effect of melatonin on the expression of circadian clock genes in mouse anti-type II collagen antibody-induced arthritis (CIA). Mice were divided into 3 groups: control, CIA, and CIA + melatonin treatment (MLT). Both mRNA and protein levels of circadian clock gene Cryptochrome1 (Cry1) were markedly decreased in CIA + MEL group compared with those in control and CIA groups. MLT increased paw thickness. Histologic and X-ray assessment also revealed increased infiltration of inflammatory cells, synovial hyperplasia, and the destruction of articular cartilage and bone by MLT. The concentrations of anti-type II collagen antibody in CIA + MEL group mice were significantly higher than those in control and CIA groups (P < 0.05). Serum concentrations of TNF-α (P < 0.005) and IL-6 (P < 0.05) in CIA + MLT group were also increased. Taken together, these results implicate that clock gene Cry1 may be involved in the aggravation of MLT-mediated arthritis in mice anti-type II collagen antibody-induced arthritis.

Double anti-angiogenic and anti-inflammatory protein Valpha targeting VEGF-A and TNF-alpha in retinopathy and psoriasis.

Pathological angiogenesis usually involves disrupted vascular integrity, vascular leakage, and infiltration of inflammatory cells, which are governed mainly by VEGF-A and TNF-α. Although many inhibitors targeting either VEGF-A or TNF-α have been developed, there is no single inhibitor molecule that simultaneously targets both molecules. Here, we designed and generated a novel chimeric decoy receptor (Valpha) that can simultaneously bind to VEGF-A and TNF-α and block their actions. In this experimental design, we have shown that Valpha, which is an effective synchronous blocker of VEGF-A and TNF-α, can drastically increase treatment effectiveness through its dual-blocking characteristics. Valpha contains the VEGF-A-binding domain of VEGFR1, the TNF-α-binding domain of TNFR2, and the Fc domain of IgG1. Valpha exhibited strong binding characteristics for its original counterparts, VEGF-A and TNF-α, but not for the extracellular matrix, resulting in a highly favorable pharmacokinetic profile in vivo. Compared with VEGF-Trap or Enbrel, both of which block either VEGF-A or TNF-α, singularly, Valpha is a highly effective molecule for reducing abnormal vascular tufts and the number of F4/80(+) macrophages in a retinopathy model. In addition, Valpha showed superior relief effects in a psoriasis model with regard to epidermal thickness and the area of blood and lymphatic vessels. Thus, the simultaneous blocking of VEGF-A and TNF-α using Valpha is an effective therapeutic strategy and cost-efficient for treatment of retinopathy and psoriasis.

Dietary alpha lipoic acid supplementation prevents synovial inflammation and bone destruction in collagen-induced arthritic mice.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by chronic inflammation and joint destruction. In this study, we investigated whether dietary supplementation with alpha lipoic acid (ALA) suppresses collagen-induced arthritis (CIA) in mice. Mice were randomly divided into three groups: (1) a control CIA group was fed a normal diet, (2) a CIA group was fed a 0.1% ALA diet (average ALA intake of 160 mg/kg/day), and (3) a CIA group was fed a 0.5% ALA diet (average ALA intake of 800 mg/kg/day). The ALA-fed mice showed a decreased incidence and severity of arthritis compared to the normal diet group. Radiographic findings revealed a dramatic decrease in bone destruction, and histological findings showed extensively suppressed pathological changes in the ALA-fed mice. The ALA-fed mice exhibited inhibited generation of tartrate resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Additionally, ALA-fed mice reduced production of various proinflammatory cytokines and the soluble receptor activator of NF-κB ligand (sRANKL) in the joint tissues and the sera. In conclusion, dietary supplementation with ALA attenuated inflammatory responses and bone destruction in CIA mice.

A20 suppresses inflammatory responses and bone destruction in human fibroblast-like synoviocytes and in mice with collagen-induced arthritis.

OBJECTIVE: Nuclear factor-kappaB (NF-kappaB) has been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). The purpose of this study was to determine whether A20, a universal inhibitor of NF-kappaB, might have antiarthritic effects. METHODS: An adenovirus containing A20 complementary DNA (AdA20) was used to deliver A20 to human rheumatoid fibroblast-like synoviocytes (FLS) in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via intraarticular injection into the ankle joints bilaterally. RESULTS: In vitro experiments demonstrated that AdA20 suppressed NF-kappaB activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor alpha in FLS. Mice with CIA that were treated with AdA20 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels, than did control virus-injected mice. The protective effects of AdA20 were mediated by the inhibition of the NF-kappaB signaling pathway. The severity of arthritis was also significantly decreased in the untreated front paws, indicating a beneficial systemic effect of local suppression of NF-kappaB. Surprisingly, mice treated with AdA20 after the onset of CIA had significantly decreased arthritis severity from the onset of clinical signs to the end of the study. CONCLUSION: These results suggest that using A20 to block the NF-kappaB pathway in rheumatoid joints reduces both the inflammatory response and the tissue destruction. The development of an immunoregulatory strategy based on A20 may therefore have therapeutic potential in the treatment of RA.

Ethyl acetate fraction from Cudrania tricuspidata inhibits IL-1beta-stimulated osteoclast differentiation through downregulation of MAPKs, c-Fos and NFATc1.

BACKGROUND/AIMS: The present study was performed to determine the effects of the ethyl acetate extract of Cudrania tricuspidata (EACT) on interleukin (IL)-1beta-stimulated receptor activator of NF-kappaB ligand (RANKL)-mediated osteoclast differentiation. METHODS: Bone marrow cells were harvested from 6-week-old male imprinting control region mice, and the differentiation of osteoclasts from these cells was evaluated by tartrate-resistant acid phosphatase and resorption pit formation assay. Phosphorylated extracellular signal regulated kinase (p-ERK), phosphorylated p38, phosphorylated c-Jun amino-terminal kinase, NF-kappaB (p65), IkappaBalpha, c-Fos, and nuclear factor of activated T-cells c1 (NFATc1) expression was examined by immunoblotting and quantitative reverse transcription-polymerase chain reaction. RESULTS: EACT inhibits IL-1beta-stimulated RANKL-mediated osteoclast differentiation. EACT also inhibits IL-1beta-stimulated RANKL-mediated phosphorylation of ERK 1/2, p38 mitogen activated protein kinase, and expression of c-Fos and NFATc1. CONCLUSIONS: These results suggest that EACT may be involved in the inhibition of bone loss by preventing osteoclast formation and may be used to manage bone destruction in inflammatory diseases, such as rheumatoid arthritis.

Inhibitory effect of ethanol extract of Magnolia officinalis and 4-O-methylhonokiol on memory impairment and neuronal toxicity induced by beta-amyloid.

The components of the herb Magnolia officinalis have exhibited antioxidant and neuroprotective activities. In this study, we investigated effects of ethanol extract of M.officinalis and its major component 4-O-methylhonokiol on memory dysfunction and neuronal cell damages caused by A beta. Oral pretreatment of ethanol extract of M. officinalis (2.5, 5 and 10mg/kg) and 4-O-methylhonokiol (1mg/kg) into drinking water for 5 weeks suppressed the intraventricular treatment of A beta(1-42) (0.5 microg/mouse, i.c.v.)-induced memory impairments. In addition, 4-O-methylhonokiol prevented the A beta(1-42)-induced apoptotic cell death as well as beta-secretase expression. 4-O-methylhonokiol also inhibited H(2)O(2) and A beta(1-42)-induced neurotoxicity in cultured neurons as well as PC12 cells by prevention of the reactive oxygen species generation. 4-O-methylhonokiol also directly inhibited beta-secretase activity and A beta fibrilization in vitro. Thus, ethanol extract of M. officinalis may be useful for prevention of the development or progression of AD, and 4-O-methylhonokiol may be a major active component.

Antihyperglycemic effects of fruits of privet (Ligustrum obtusifolium) in streptozotocin-induced diabetic rats fed a high fat diet.

The protective effects of freeze-dried privet (Ligustrum obtusifolium) fruits (PFs) were observed in streptozotocin (STZ)-induced diabetic rats on a high fat diet by measuring levels of blood glucose, serum insulin, fructosamine, and hepatic reactive oxygen species generating and scavenging enzyme activities. A PF-supplemented diet was prepared by mixing an AIN-76 diet with powdered PF (final concentration, 1% or 2%). It was fed to STZ-induced diabetic rats on a high fat diet for 6 weeks. Diabetic animals receiving the PF-supplemented diet showed a significant increase in body weight, feed efficiency ratio, liver, kidney, and heart weight, and serum glucose, insulin, and fructosamine levels compared with high fat diet-fed diabetic animals. The treatment with PF showed improved hepatic glutathione S-transferase, superoxide dismutase, and xanthine oxidase activities as well as glutathione and lipid peroxide levels in the diabetic animals. Intracellular swelling and vacuole formation in diabetic pancreatic beta- and delta-cells were ameliorated by the PF-supplemented diet. Furthermore, necrosis of tubular epithelial cells and dilatation of luminal space in diabetic kidneys exhibited near-noninjured condition. This is the first time an antihyperglycemic effect of L. obtusifolium fruit in STZ-induced diabetic rats has been identified.

Antihyperglycemic effect of Fomitopsis pinicola extracts in streptozotocin-induced diabetic rats.

The antihyperglycemic effect of a water extract (WE) and an alkali extract (AE) of the Fomitopsis pinicola fruit body was studied in streptozotocin (STZ)-induced diabetic rats. The STZ-induced diabetes mellitus (DM) control group lost a significant amount of body weight, whereas the normal control group (NC) gained weight; however, the DM-AE group gained a significant amount of weight, with weight gain approaching normal. Feed intake by the DM-AE group was also similar to the NC group. The liver and kidney weights per body weight increased with the STZ treatment; however, the weights were lower in the F. pinicola-treated groups and nearly normalized in the DM-AE group. The weights of the heart, lungs, and spleen were not influenced by the STZ treatment. Blood glucose levels of F. pinicola-treated DM groups were significantly lower than that of the DM group. In particular, STZ-induced hyperglycemia was remarkably inhibited by the AE-supplemented diet. Serum insulin levels were decreased with STZ injection; however, the decreased levels were almost restored to the NC level with F. pinicola supplementation. The increased serum fructosamine levels associated with hyperglycemia were decreased with the F. pinicola treatment. Cells of the pericentral regions were found to have significant swelling, and some necrotic cells were observed in the pancreas of DM animals; however, pancreatic tissue damage by STZ in the F. pinicola-supplemented diet groups was ameliorated. In this study, the AE from F. pinicola showed the highest antidiabetic effect among the treatments. These results indicate that constituents of F. pinicola may regulate hyperglycemia via either increased insulin secretion during recovery or the prevention of STZ-induced pancreatic damage. This is the first report of antihyperglycemic effects of F. pinicola in STZ-induced DM rats.

Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells.

Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.

Use of complementary and alternative medicine by rheumatoid arthritis patients in Korea.

This study measured the prevalence of use of complementary and alternative medicine (CAM) in Korean patients with rheumatoid arthritis (RA). A trained nurse conducted 20-min questionnaire-based interviews at the hospitals when each patient visited as an outpatient. The questionnaire included questions on demographic information, clinical information, and the use of CAM. Of the 153 respondents, 125 (82%) had used CAM; 37% of those who used CAM had started taking CAM products following suggestions from family members and other relatives. In users of CAM, 35% considered that it improved the symptoms of RA, and 14% felt it was effective in achieving psychological relaxation. We categorized treatment into six CAM categories used by the respondents: 84.0% of patients used traditional Oriental medical treatments, 70.4% used plant- and animal-derived over-the-counter health care products, and 13.6% used manual therapies. Most RA patients (64%) would like to try a new type of CAM. About half of the respondents (48%) expected to receive information about CAM from their general practitioner even if most (72%) did not discuss their use of CAM with their doctor. Most of the RA patients in this study used CAM, and half reported beneficial effects. Despite the presence of adverse side effects, patients tended to use CAM without discussing it with their main physicians, suggesting that physicians should be actively involved in the prescription and use of CAM.

Wen-pi-tang-Hab-Wu-ling-san, an oriental herbal prescription, attenuates epithelial-mesenchymal transdifferentiation stimulated by TGF-beta1 in kidney cells.

Wen-pi-tang-Hab-Wu-ling-san (WHW), an oriental herbal prescription, is currently used in oriental clinics for the treatment of chronic renal failure (CRF). While its effectiveness has been supported by a series of modern studies, the underlying mechanism remains poorly understood. CRF progression involves tubulointerstitial fibrosis where transforming growth factor-beta1 (TGF-beta1) plays a critical role by inducing epithelial-mesenchymal transdifferentiation (EMT). This study examined whether WHW extract attenuated the TGF-beta1-induced EMT in Madin-Darby canine kidney cells. When the cells were stimulated by TGF-beta1 (2.5 ng/mL), they exhibited an elongated, spindle-shaped appearance but this morphological change was significantly suppressed by WHW extract (1 mg/mL). The WHW extract did not show notable cytotoxicity and even mitigated the cytotoxic effects of TGF-beta1. It inhibited the expression of alpha-smooth muscle actin (alpha-SMA), a marker of EMT, but not the secretion of matrix metalloproteinases stimulated by TGF-beta1. The WHW extract also inhibited the phosphorylation of Smad2 that mediates TGF-beta1 signaling leading to alpha-SMA expression. The present study suggests that WHW extract may provide renal protective effects through modulation of the TGF-beta1/Smad2/alpha-SMA pathway involved in fibrosis.

Knowledge of, attitudes toward, and experience of complementary and alternative medicine in Western medicine- and oriental medicine-trained physicians in Korea.

OBJECTIVES: We compared knowledge of, attitudes toward, and experience with complementary and alternative medicine (CAM) among Western medicine-trained doctors (WMDs) and Oriental medicine-trained doctors (OMDs). METHODS: In Korea, 502 WMDs and 500 OMDs were interviewed with a structured questionnaire. RESULTS: OMDs held more favorable attitudes toward CAM than did WMDs. OMDs possessed a deeper understanding of and greater experience with CAM. OMDs more readily endorsed health beliefs congruent with CAM. CONCLUSIONS: In the future, CAM can be more readily used by OMDs than by WMDs. Because evidence for the effectiveness of CAM remains sparse, more research is needed for the prudent use of CAM in Korea. An education and training system for potential CAM providers remains to be developed.