BACKGROUND: It has been well known that the degree of HLA matching in renal transplantation is important in graft and patient survival. Because HLA-identical living-related donor grafts are free from immunological attacks, they have benefits of one immunosuppressants or early withdrawal of steroids. However, there is acute rejection due to early withdrawal of immunosuppressants and graft loss due to recurrent glomerulonephritis following HLA- identical living-related renal transplantation. The purpose of this study is to determine the graft survival and the impact of recurrent glomerulonephritis on graft survival in HLA-identical living-related donor grafts. METHODS: From December 1984 to March 2004, 44 HLA-identical and 80 HLA-haploidentical living- related renal transplants in Bongsaeng Memorial Hospital were included in this study. We evaluated graft survivals, immunosuppressants and causes of graft failure. RESULTS: The mean graft survival for HLA-identical transplants is 198 months (16.5 years) and for HLA-haploidentical transplants is 166 months (13.8 years), respectively (p=NS). Acute rejection episodes occurred in 2 of the 44 (5%) identical transplants and 17 of the 80 (21%) haploidentical transplants, respectively (p=0.013). 6 grafts were lost in HLA- identical transplants and the causes are 4 recurrent glomerulonephritis (66.7%), 2 chronic rejections (33.4 %). 11 grafts were lost in HLA-haploidentical transplants and the causes are 6 chronic rejections (54.5 %), 1 acute rejection (9.1%), 1 drug toxicity (9.1%), 3 patient deaths (27.3%). Recurrent glomerulonephritis in HLA-identical transplants are three, but in HLA-haploidentical transplants are none. CONCLUSION: Our data revealed that there was no difference in graft survival between the two groups, but lower acute rejection rate in HLA-identical groups. Recurrent glomerulonephritis was the main cause of graft failure in HLA-identical groups and the impact of recurrent disease on graft survival needs to be investigated.
Drug-Related Side Effects and Adverse Reactions ; Glomerulonephritis ; Graft Survival ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Steroids ; Tissue Donors* ; Transplants

Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia play an important role in human neurodegenerative disorders. Here, we investigated whether celastrol, which has been used as a potent anti-inflammatory and anti-oxidative agent in Chinese medicine, attenuates excessive production of NO and proinflammatory cytokines such as TNF-alpha and IL-1beta in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-alpha, and IL-1beta in BV-2 cells was largely inhibited in the presence of celastrol, and the attenuation of inducible iNOS and these cytokines resulted from the reduced expression of mRNAs of iNOS and these cytokines, respectively. The molecular mechanisms that underlie celastrol-mediated attenuation were the inhibition of LPS-induced phosphorylation of MAPK/ERK1/2 and the DNA binding activity of NF-kappaB in BV-2 cells. The results indicate that celastrol effectively attenuated NO and proinflammatory cytokine production via the inhibition of ERK1/2 phosphorylation and NF-kappaB activation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders.
Animals ; Cell Line ; Cytokines/*biosynthesis/drug effects ; Gene Expression Regulation, Enzymologic/drug effects/immunology ; Inflammation/immunology ; Inflammation Mediators/immunology ; Mice ; Microglia/*drug effects/immunology ; Mitogen-Activated Protein Kinases/*physiology ; NF-kappa B/metabolism/*physiology ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase Type II/biosynthesis/drug effects ; RNA, Messenger/analysis ; Signal Transduction/*drug effects/physiology ; Transcription, Genetic/drug effects/immunology ; Triterpenes/*pharmacology

With focused ultrasound (FUS) and microbubbles, BBB can be transiently disrupted with a localized and non-invasive approach. BBB disruption induced by FUS has made progressions to move forward on delivery of therapeutic agents into a brain in a specific area of brain for better treatment of neurological diseases. In addition to be used as an improvement of drug delivery, BBB disruption has been found to induce biological effects such as a clearance of protein aggregation which cause Alzheimer's disease, regulation of proteins which facilitate drug uptake, and modulation of neuronal function and neurogenesis. In this review, we discuss overview about the principles of BBB opening with FUS and milestones in these biological effects of FUS-induced BBB disruption.
Alzheimer Disease ; Brain ; Microbubbles ; Neurogenesis ; Neurons ; Ultrasonography*

PURPOSE: Magnetocardiography (MCG) has been proposed as a noninvasive, diagnostic tool for risk-stratifying patients with acute myocardial infarction (AMI). This study evaluated whether MCG predicts long-term prognosis in AMI. MATERIALS AND METHODS: In 124 AMI patients (95 males, mean age 60±11 years), including 39 with ST-elevation myocardial infarction, a 64-channel MCG was performed within 2 days after AMI. During a mean follow-up period of 6.1 years, major adverse cardiac events (MACE) were evaluated. RESULTS: MACE occurred in 31 (25%) patients, including 20 revascularizations, 8 deaths, and 3 re-infarctions. Non-dipole patterns were observed at the end of the T wave in every patients. However, they were observed at T-peak in 77% (24/31) and 54% (50/93) of patients with and without MACE, respectively (p=0.03). Maximum current, field map angles, and distance dynamics were not different between groups. In the multivariate analysis, patients with non-dipole patterns at T-peak had increased age- and gender-adjusted hazard ratios for MACE (hazard ratio 2.89, 95% confidence interval 1.20–6.97, p=0.02) and lower cumulative MACE-free survival than those with dipole patterns (p=0.02). CONCLUSION: Non-dipole patterns at T-peak were more frequently observed in patients with MACE and were related to poor long-term prognosis. Thus, repolarization heterogeneity measured by MCG may be a useful predictor for AMI prognosis.
Follow-Up Studies ; Humans ; Magnetocardiography* ; Male ; Multivariate Analysis ; Myocardial Infarction* ; Population Characteristics* ; Prognosis*

OBJECTIVETo investigate the effects of the flower buds extract of Tussilago farfara Linné (Farfarae Flos; FF) on focal cerebral ischemia through regulation of inflammatory responses in activated microglia.

METHODSBrain ischemia was induced in Sprague-Dawley rats by a transient middle cerebral artery occlusion (tMCAO) for 90 min and reperfusion for 24 h. Twenty rats were randomly divided into 4 groups (n=5 per group): normal, tMCAO-induced ischemic control, tMCAO plus FF extract 300 mg/kg-treated, and tMCAO plus MK-801 1 mg/kg-treated as reference drug. FF extract (300 mg/kg, p.o.) or MK-801 (1 mg/kg, i.p.) was administered after reperfusion. Brain infarction was measured by 2,3,5,-triphenyltetrazolium chloride staining. Neuronal damage was observed by haematoxylin eosin, Nissl staining and immunohistochemistry using anti-neuronal nuclei (NeuN), anti-glial fibrillary acidic protein (GFAP), and anti-CD11b/c (OX42) antibodies in ischemic brain. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), and hypoxia-inducible factor-1a (HIF-1α) were determined by Western blot. BV2 microglial cells were treated with FF extract or its main bioactive compound, tussilagone with or without lipopolysaccharide (LPS). Nitric oxide (NO) production was measured in culture medium by Griess assay. The expressions of iNOS, COX-2 and pro-inflammatory cytokines mRNA were analyzed by reverse transcription-polymerase chain reaction. The expression of iNOS, and COX-2 proteins, the phosphorylation of ERK1/2, JNK, and p38 MAPK and the nuclear expression of NF-κB p65 in BV2 cells were determined by Western blot.

RESULTSFF extract significantly decreased brain infarctions in ischemic rats (P<0.01). The neuronal death and the microglia/astrocytes activation in ischemic brains were inhibited by FF extract. FF extract also suppressed iNOS, TNF-α, and HIF-1α expression in ischemic brains. FF extract (0.2 and 0.5 mg/mL, P<0.01) and tussilagone 20 and 50 μmol/L, P<0.01) significantly decreased LPS-induced NO production in BV2 microglia through downregulation of iNOS mRNA and protein expression. FF extract and tussilagone significantly inhibited LPS-induced expression of TNF-α, IL-1β, and IL-6 mRNA, and also suppressed the phosphorylation of ERK1/2, JNK and p38 MAPK and the nuclear expression of NF-κB in a dose-dependent manner.

CONCLUSIONSFF extract has a neuroprotective effect in ischemic stroke by the decrease of brain infarction, and the inhibition of neuronal death and microglial activation-mediated inflammatory responses.

AIM: To investigate the anti-inflammatory activities of the semen extract of Cuscuta chinensis Lam. (Cuscutae Semen; CS) on the production of inflammatory mediators, nitric oxide (NO), prostaglandin 2 (PGE2), and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 microglia. METHOD: BV-2 cells were treated with CS extract for 30 min, and then stimulated with LPS or without for 24 h. The levels of NO, PGE2 and proinflammatory cytokines were measured by Griess assay and ELISA. The expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 mRNA and protein was determined by RT-PCR and Western blot, respectively. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), and the nuclear expression of nuclear factor (NF)-κB p65 were investigated by Western blot analysis. RESULTS: CS extract significantly decreased the production of NO and PGE2 by suppressing the expression of iNOS and COX-2 in activated microglia. CS extract decreased the production of TNF-α, IL-1β, and IL-6 by down-regulating their transcription levels. In addition, CS extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. CONCLUSION These results indicate that CS extract is capable of suppressing the inflammatory response by microglia activation, suggesting that CS extract has potential in the treatment of brain inflammation.
Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Cuscuta ; Cyclooxygenase 2 ; metabolism ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Inflammation ; chemically induced ; drug therapy ; metabolism ; Inflammation Mediators ; metabolism ; Interleukin-1beta ; metabolism ; Lipopolysaccharides ; Mice ; Microglia ; drug effects ; metabolism ; Mitogen-Activated Protein Kinases ; metabolism ; NF-kappa B ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Phosphorylation ; Phytotherapy ; Seeds ; Tumor Necrosis Factor-alpha ; metabolism