Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Brain 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.</p><p><b>RESULTS</b>FF 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.</p><p><b>CONCLUSIONS</b>FF 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.</p>

Inhibitory effect of the extract of Phellodendron amurense ruprecht root on collagen-induced arthritis in mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether the dried root of Phellodendron amurense Ruprecht (Phellodendri cortex; PC) extract improves arthritic symptoms through anti-inflammatory and immune-modulatory effects in collagen-induced arthritis in mice.</p><p><b>METHODS</b>Rheumatoid arthritis (RA) was induced in male DBA/1 mice by immunization with type II collagen (ColII). CIA mice were divided into 5 groups (n=10 per a group) with normal, CIA control, PC extract (50 mg/kg and 100 mg/kg)-treated, and meloxicam (50 mg/kg)-treated as the reference drug. The PC extract or meloxicam were administered orally in CIA mice once a day for 14 days after arthritis induction. Arthritic score, levels of anti-ColII IgGantibody, prostaglandin E(PGE), tumor necrosis factor (TNF)-α, and interleukin (IL)-17 in the sera of CIA mice were measured. Histopathological changes in the ankle joints of CIA mice were also analyzed by staining with hematoxylin and eosin (H and E), safranin-O and immunohistochemistry using anti-TNF-α and anti-IL-17 antibodies.</p><p><b>RESULTS</b>The arthritic score was increased in CIA mice in a time-dependent manner, as were the serum levels of anti-ColII IgGantibody, PGE, TNF-α, and IL-17. However, the oral administration of PC extract at 50 and 100 mg/kg in CIA mice significantly decreased the arthritic scores, and the serum levels of anti-ColII IgG, PGE, TNF-α, and IL-17 compared with those in the CIA group (P<0.05 or P<0.01). Furthermore, histopathological improvement of the joint architecture in CIA mice was observed after administration of PC extract. PC extract also significantly inhibited the expression of TNF-α and IL-17 in the joints of CIA mice by suppressing the expression of their mRNA and proteins.</p><p><b>CONCLUSION</b>PC extract may improve the pathological progression of RA through the inhibition of joint destruction by synovial inflammation and immune-stimulation, therefore, it would be a potential anti-arthritic agent in RA.</p>

Epimedium koreanum Nakai and its main constituent icariin suppress lipid accumulation during adipocyte differentiation of 3T3-L1 preadipocytes / 中国天然药物

Obesity is associated with a number of metabolic abnormalities such as type 2 diabetes and has become a major health problem worldwide. In the present study, we investigated the effects of Epimedium koreanum Nakai (Herba Epimedii, HE) and its main constituent icariin on the adipocyte differentiation in 3T3-L1 preadipocytes. HE extract and icariin significantly reduced lipid accumulation and suppressed the expressions of PPARγ, C/EBPα, and SREBP-1c in 3T3-L1 adipocytes. They also inhibited fatty acid synthase (FAS), acyl-Co A synthase (ACS1), and perilipin. Moreover, HE extract and icariin markedly increased the phosphorylation of AMPK. These results indicated that HE extract and icariin can inhibit the adipocyte differentiation through downregulation of the adipogenic transcription factors, suggesting that HE containing icariin may be used as a potential therapeutic agent in the treatment and prevention of obesity.

Determination of total phenolics, flavonoid contents and antioxidant activity of different mBHT fractions: a polyherbal medicine

In this study, antioxidant activity, total phenolic and flavonoids content of four different fractions from the traditional Korean polyherbal medicine of Modified Bo-yang-Hwan-o-Tang [mBHT] was determined using spectrophotometric methods. Antioxidant activity of fractions was expressed as percentage of DPPH radicals inhibition and IC[50] values [[micro]g/ml]. Values in percentage ranged from 48.35 to 77.43%. The reducing powers of all the extracts were comparable with that of positive control sample of Butylated hydroxyl tolune [BHT] and ascorbic acid which was found to be dose dependent. Total phenolic content ranged from 106.83 +/- 0.002 to 188.661 +/- 0.002mg/g, expressed as gallic acid equivalents. The total flavonoid contents varied from 28.44 +/- 0.001 to 105.25 +/- 0.001mg/g, expressed as quarcetin equivalents. Ethyl acetate fractions of mBHT showed the highest phenolic [188.66 mg GAE/g] and flavonoids [105.25 mg QAE/g] contents and strong antioxidant activity. Total phenolics and flavonoid content of all the mBHT fractions were found reasonably correlated with IC50 of DPPH [R[2]=0.980 and 0.932, respectively]. The high contents of phenolic compounds indicated that these compounds responsible for antioxidant activity. Therefore, ethyl acetate fractions of mBHT can be regarded as promising candidates for natural plant sources of antioxidants

Effect of the semen extract of Cuscuta chinensis on inflammatory responses in LPS-stimulated BV-2 microglia / 中国天然药物

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.

Dioscorea Quinqueloba-Induced Tubulointerstitial Nephritis / 대한내과학회지

Drug-induced tubulointerstitial nephritis is one cause of acute kidney injury. Although traditional remedies have been widely used in South Korea, Dioscorea quinqueloba-induced tubulointerstitial nephritis has not been reported in the general population. A 72-year-old male patient was transferred to our hospital with pulmonary edema, oliguria, decreased mentality, severe generalized edema after taking D. quinqueloba 25 days ago. His initial lab findings showed a blood urea nitrogen level of 43.4 mg/dL, a creatinine level of 5.3 mg/dL. Urinalysis revealed SG (1.015), blood (many), protein (++) and WBC (0-3/HPF). Kidney biopsy demonstrated severe mononuclear cell infiltration into the renal interstitium with mild tubular atrophy. Aggressive renal replacement therapy and supportive care resulted in gradual restoration of his renal function. This case implies that D. quinqueloba may be one cause that induces tubulointerstitial nephritis in some patients.

Antioxidant and Proliferative Activities of Bupleuri Radix Extract Against Serum Deprivation in SH-SY5Y Cells

OBJECTIVE: Bupleuri Radix (BR) is a major component of several Oriental herbal medicines used to treat stress and mental illness. There are evidences that antidepressant drugs modulate oxidative damage implicated in the pathophysiology of neuropsychiatric disorder, including depression. The aim of the present study was to investigate antioxidant and proliferative effects of BR against oxidative stress induced by serum deprivation in SH-SY5Y cells. METHODS: We examined the antioxidant effects of BR on a number of measures, including cell viability, formation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and levels of both Bcl-2 and Bax. We also investigated the effects of BR on cell proliferation using the bromodeoxyuridine (BrdU) assay, and used Western blot analysis to measure changes in expression of the cell cycle phase regulators. RESULTS: 1) Serum deprivation significantly induced the loss of cell viability, the formation of ROS, the reduction of SOD activity, down-regulation of Bcl-2 expression and up-regulation of Bax expression. However, BR extract reversed these effects in dose-dependent manner. 2) Serum deprivation significantly reduced cell proliferation. Western blot analysis revealed that serum deprivation significantly decreased cyclinD1 and phosphorylated retinoblastoma (pRb) expression, and increased p27 expression. On the other hand, BR dose dependently reversed these effects. CONCLUSION: This study suggests that aqueous extract of BR may exert potent antioxidant effects and also play an important role in regulating cell cycle progression during neurogenesis. These effects of BR may be a potentially important mechanism of antidepressant underlying the observed antioxidant and proliferative effects.

A Rare Cause of Automated Peritoneal Dialysis-Related Peritonitis: Aeromonas caviae / 대한내과학회지

Peritonitis is a major cause of morbidity in peritoneal dialysis patients; however, Aeromonas caviae rarely causes peritonitis in these patients. We report peritonitis due to A. caviae in a 72-year-old male with end-stage renal failure who had been undergoing automated peritoneal dialysis for 1 year. The white blood cell (WBC) count in the peritoneal fluid was 2,722/mm3 with 85% neutrophils. Gram staining of the peritoneal fluid yielded Gram-negative rods. Empirical antibiotic therapy with ceftriaxone was initiated intraperitoneally. However, drug sensitivity testing revealed that the organism was resistant. On the third hospital day, A. caviae was cultured from the peritoneal effluent, and the antibiotic regimen was switched to ciprofloxacin. The patient recovered rapidly and the WBC count of the peritoneal effluent decreased. He was discharged and the intraperitoneal ciprofloxacin therapy was continued for 14 days. The peritoneal catheter was not removed.

Corni Fructus-Induced Acute Interstitial Nephritis / 대한내과학회지

Drug-induced interstitial nephritis is one cause of acute kidney injury. Although traditional remedies have been widely used in South Korea, Corni fructus-induced interstitial nephritis has not been reported in the general population. A 65-year-old female patient was admitted with sudden onset of gross hematuria after ingesting Corni fructus tea for 2 weeks. Her initial lab findings showed a blood urea nitrogen level of 35.1 mg/dL, creatinine level of 1.7 mg/dL, albumin level of 4.5 g/dL, and hemoglobin level of 10.3 g/dL. Urinalysis revealed SG (1.025), blood (many), protein (+), and WBC (0-3/HPF). Her 24-hour total protein level was 1,120 mg/day. No specific abnormalities were found on serum and urine protein electrophoresis. Kidney biopsy demonstrated severe mononuclear cell infiltration into the renal interstitium with mild tubular atrophy and pericapsular fibrosis. Immediate withdrawal of Corni fructus, appropriate education, and conservative management resulted in gradual restoration of her renal function. This case implies that Corni fructus may be a causative allergen that induces acute interstitial nephritis in some patients.

Corni Fructus-Induced Acute Interstitial Nephritis / 대한내과학회지

Drug-induced interstitial nephritis is one cause of acute kidney injury. Although traditional remedies have been widely used in South Korea, Corni fructus-induced interstitial nephritis has not been reported in the general population. A 65-year-old female patient was admitted with sudden onset of gross hematuria after ingesting Corni fructus tea for 2 weeks. Her initial lab findings showed a blood urea nitrogen level of 35.1 mg/dL, creatinine level of 1.7 mg/dL, albumin level of 4.5 g/dL, and hemoglobin level of 10.3 g/dL. Urinalysis revealed SG (1.025), blood (many), protein (+), and WBC (0-3/HPF). Her 24-hour total protein level was 1,120 mg/day. No specific abnormalities were found on serum and urine protein electrophoresis. Kidney biopsy demonstrated severe mononuclear cell infiltration into the renal interstitium with mild tubular atrophy and pericapsular fibrosis. Immediate withdrawal of Corni fructus, appropriate education, and conservative management resulted in gradual restoration of her renal function. This case implies that Corni fructus may be a causative allergen that induces acute interstitial nephritis in some patients.

Intraperitoneal Paricalcitol Treatment for Secondary Hyperparathyroidism in CAPD patient: A Case Report / 대한신장학회지

Secondary hyperparathyroidism is a major complication in ESRD patients undergoing dialysis. In hemodialysis patients with secondary hyperparathyroidism, intravenous administration of paricalcitol became widely utilized. In CAPD patients, however, the intravenous administration of paricalcitol which requires frequent visits to the clinic is not practical. The subject of this study was one CAPD patient with secondary hyperparathyroidism. He had already received oral calcitriol pulse therapy for 6 months and thereafter refused parathyroidectomy and intravenous paricalcitol which required frequent visits to the hospital. Furthermore, paricalcitol capsule is not yet introduced in Korea. Consequently, intraperitoneal paricalcitol therapy was tried whereby the patient was taught how to inject the paricalcitol (5 ug) directly into the dialysate for three times per week before bedtime. Blood samples for measurement of intact parathyroid hormone (iPTH), serum ionized calcium, serum phosphate, serum total alkaline phosphatase levels were obtained at baseline and after 1, 2, 3 and 4 months of treatment. After usage of intraperitoneal paricalcitol for 2 months, there was a significant decrease in iPTH level. In conclusion, intraperitoneal paricalcitol therapy might be effective for suppressing iPTH in CAPD patients with secondary hyperparathyroidism. A large-scale and long-term study must be conducted for safety and clinical effect.

Peritonitis by Achromobacter xylosoxidans in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis(CAPD): A Case Report / 대한신장학회지

Peritonitis is a major cause of morbidity in continuous ambulatory peritoneal dialysis (CAPD) patients. Achromobacter xylosoxidans is a rarely reported cause of peritonitis in CAPD patients. In this report, a peritonitis case due to Achromobacter xylosoxidans in a 60-year-old male patient with end-stage renal failure receiving CAPD for 7 years, has been reported. White blood cell (WBC) count in peritoneal fluid was 3,160/mm3 with 95% neutrophil. Gram staining of the peritoneal fluid yielded gram negative rod. Empirical antibiotic therapy with ceftriaxone was initiated intraperitoneally. But drug sensitivity test revealed these regimens were resistant. On fourth hospital day, Achromobacter xylosoxidans was cultured from peritoneal effluent, the antibiotic regimen was switched to piperacillin/tazobactam intraperitoneally. The patient rapidly recovered and the WBC count of the peritoneal effluent decreased. The therapy was continued for 14 days and then the patient was discharged. The peritoneal catheter was not removed.

A Case of Asymptomatic Disseminated Cryptococcosis in a Renal Transplant Patient / 대한신장학회지

Cryptococcosis is recognized as one of the most important complications in an organ transplant recipient. Cryptococcosis occurs in 2.5-39% of renal transplant recipients. This infection generally presents as symptomatic disseminated disease with an accelerated clinical course, involves multiple sites including the central nervous system, lungs, and skin. And if diagnosis or treatment is delayed, the prognosis is generally poor. The asymptomatic infection is rare and there are no case reports of asymptomatic disseminated cryptococcosis after renal transplantation in Korea. We experienced a case of asymptomatic cryptococcal multi-organ infection detected incidentally in a 51-year-old male received a living related renal transplant 35 months earlier for end-stage renal disease due to diabetic nephropathy. We treated successfully with amphotericin B and fluconazole and hereby report this case with a review of the relevant literature.

Combination Treatment of Rituximab and Plasmapheresis in Acute Cellular Rejection with Focal Segmental Glomerular Sclerosis after Renal Transplantation / 대한이식학회지

Focal segmental glomerular sclerosis (FSGS) accounts for recurrence in 20% to 40% of the renal allografts after transplantation, and it causes graft loss in 13% to 20% of the cases. We report here on successfully treating acute cellular rejection (ACR) combined with FSGS after a kidney transplantation with a combination treatment of plasmapheresis, rituximab and steroid pulse therapy. A 53-year-old female patient whose primary kidney disease was unknown developed massive proteinuria after living donor kidney transplantation. A urine protein/creatinine ratio of 13.42 and an elevated serum creatinine level was detected on postoperative days (POD) 10 and a renal biopsy showed acute cellular rejection (Banff IIb) combined with FSGS. We started steroid pulse therapy on POD 11. She underwent 5 plasmapheresis sessions in the first 3 week after transplantation and she received one dose of rituximab (375 mg/m2) on POD 12. The proteinuria decreased below the nephrotic range at POD 20 and the serum creatinine level was normalized. Three months later, the proteinuria was at 35 mg/day with stable graft function. Rituximab and plasmapheresis is a possible option to treat FSGS combined with a relapse of proteinuria after renal transplantation.

A case of amebic colitis in a renal-transplant recipient / 대한내과학회지

Intestinal amoebiasis is caused by the protozoan Entamoeba histolytica. Amoebic colitis is usually acquired by ingesting contaminated food or water, but it can be associated with cell-mediated immunosuppression in organ-transplant recipients. We present a case of invasive amoebic colitis in a kidney-transplant recipient who was treated successfully with metronidazole and adjusted immunosuppressive therapy. The patient was a 49-year-old man who had undergone renal transplantation 15 years earlier. He complained of diarrhea accompanied by mild lower abdominal pain over five weeks, and the diagnosis of amoebic colitis was made with a colonoscopic biopsy. The colonoscopic findings showed multiple, round, scattered ulcerations throughout the colon, and trophozoites of E. histolytica were identified in the base of these ulcers. We treated his colitis with metronidazole and a reduction in immunosuppressive therapy.

The Expression of C4d and CD20 in Graft Kidney with Acute Rejection / 대한이식학회지

PURPOSE: The presence of C4d in peritubular capillaries (C4d (PTC)) as a diagnostic in-situ marker of acute humoral rejection and CD20 as marker of B-cell deposition in graft kidney has been reported to be related to steroid resistance and poor outcome. In this retrospective study, we evaluated the clinical significance of C4d and CD20 in allograft renal biopsies by immunohistochemistry technique. And we also evaluated the relationships between C4d and CD20 positive B lymphocytes. METHODS: We studied 22 patients who had been biopsied for suspected acute rejection. Biopsies were classified by updated Banff 97 criteria. Of the 22 cases, borderline rejection and Banff 1A were 11 cases respectively and no case had a vascular lesion. Paraffin sections were stained with monoclonal antibodies (anti-C4d and -CD20) using an immunohistochemistry technique and the results of immunohistochemistry were analyzed by clinical data. RESULTS: Of the 22 cases, 22.7% (5/22) showed diffuse and 40.9% (9/22) showed focal C4d positivity in peritubular capillaries. The grafts failed to survive in 20% (1/5) of the diffuse (P), 44.4% (4/9) of the focal, and 0% (0/8) of the negative group for 2 years since postbiopsies, however, the C4d staining was not statistically related to graft loss and graft survival rates (P=0.091, P=0.106 respectively). The C4d positivity was significantly related to the level of serum creatinine (P=0.042) and to steroid pulsing therapy resistance (P=0.030). However C4d deposition was not associated with recipient gender, age, type of donor (living vs deceased), HLA matching, induction, and Banff classification. On the CD20 immunostaining, 50.0% (11/22) showed negative reactivity, 9.1% (2/22) one nodule, 40.9% (9/22) 2 nodules. The presence and the number of CD20 positive nodules were not correlated to the C4d clinical data. But, the degree of C4d staining was statistically related with the presence of CD20 positive nodules (P=0.029). CONCLUSION: The peritubular capillary C4d is clinically important however, not likely a significant predictor of grafts survival rates in mild rejection. The clinical implication of CD20 positive B lymphocyte nodules in acute rejection was not demonstrated in this study. But, CD20 positive B lymphocyte may be a positive linkage with C4d and participate in humoral rejection.

Comparison of heart rate variability between end stage renal disease patients on hemodialysis and hypertensive patients / 대한내과학회지

BACKGROUND/AIMS: Heart rate variability (HRV) can be used to assess the effects of drugs and other interventions, including exercise, respiration, metabolic changes, and psychological or physical stressors, on cardiac autonomic tone. HRV is regulated by the balance of sympathetic and parasympathetic tone. Few studies pertaining to HRV in end stage renal disease (ESRD) patients have been performed in Korea. Thus, autonomic nervous system activity as indicated by HRV was investigated in patients on hemodialysis due to ESRD. METHODS: We compared the pattern of cardiac sympathetic and parasympathetic activity through time- and frequency- domain analyses of HRV with 24-hour Holter monitoring in 30 ESRD patients and 64 hypertensive control subjects. The ESRD patients had undergone hemodialysis therapy at the Bongseng Hospital between January 2006 and June 2007. RESULTS: The mean age of ESRD patients and hypertensive controls was 51.17+/-11.91 and 55.02+/-13.72 years, respectively. In the ESRD group, all time- and frequency-domain HRV measures, including the standard deviation of all normal sinus R-R intervals over 24 hours (SDNN), the HRV index, the very low-frequency (VLF) normalized unit of low-frequency (LFnorm), and the ratio of low-frequency power to high-frequency power (LF/HF), were reduced; the normalized unit of high frequency (HFnorm) was increased in the ESRD patients compared with the control group. CONCLUSION: The autonomic tone in ESRD patients on hemodiaysis was decreased compared with hypertensive patients. The parasympathetic tone in ESRD patients on hemodyalysis was dominant over the sympathetic tone.

Celastrol inhibits production of nitric oxideandproinflammatory cytokines through MAPK signal transduction and NF-kappaB in LPS-stimulated BV-2 microglial cells

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.

A Case about Use of Mycophenolate Mofetil in Acute Renal Failure Associated with Lupus Nephritis / 대한신장학회잡지

Mycophenolate mofetil (MMF) is a immunosuppressive agent increasingly used in organ transplantation and autoimmune disease. We report a case about use of MMF in SLE patient with rapidly worsening renal function. A 24-year old female was admitted due to 1-week history of generalized edema. Despite use of diuretics and conventional supported care, generalized edema was more aggravated and serum creatinine was elevated up to 5.2 mg/dL. Ten days after the initial admission, we started hemodialysis. After hemodialysis, improvement of generalized edema was achieved. Eighteen days after initial hemodialysis, we started corticosteroids and MMF because she shows persistent heavy proteinuria and oliguria. After use of corticosteroids and MMF, clinical improvement of renal complication was achieved in this patient. About 6 weeks later, we could discontinue hemodialysis. On two year follow up duration, she shows good renal function and no evidence of lupus flare-up signs. We suggest MMF is one of therapeutic options for patients with severe lupus nephritis, especially those refractory or intolerant to conventional cytotoxic agents.

The clinical outcome of renal transplantation with a poor HLA matched living kidney donors / 대한내과학회지

BACKGROUND: Poor HLA matched donors may become an additional organ source for renal transplantation. This study is conducted to predict the clinical outcomes of renal transplantation in a poor HLA matched group (0 or 1 or 2 HLA matching) by comparing them with those of HLA haploidentical group. METHODS: This study compared a poor HLA matched group (N=89) with HLA haploidentical group (N=79) to analyze differences between two groups in graft survival, incidence of acute rejection, cause of graft failure, posttransplant serum creatinine at 1, 2, 3, 5 years. Total 168 cases, appeared in the medical records for more than six months in Bong-Saeng Hospital, from December, 1984 to March, 2004 were traced and identified as relevant cases for this study. RESULTS: Allograft survival rate at 1, 3, 5, 10 years for poor HLA matched group and HLA haploidentical group were 100%, 98.6%, 95.4%, 72.5% and 100%, 100%, 96.1%, 86.2% (p=not significant) respectively. Acute rejection developed in 25.8% of poor HLA matched group versus 18.9% of HLA haploidentical group (p=not significant). The most common causes of graft failure in both groups were chronic rejection. CONCLUSIONS: It should be actively encouraged to consider renal transplantation in a poor HLA matched group as the results of this study support that the clinical outcomes of renal transplantation in a poor HLA matched group are equivalent to those of HLA haploidentical group.