Imaging features of synovial chondromatosis of the temporomandibular joint: a report of 34 cases.

AIM: To investigate the imaging features of synovial chondromatosis of the temporomandibular joint (TMJ), which is a rare benign arthropathy with cartilaginous proliferation. MATERIALS AND METHODS: Computed tomography and magnetic resonance imaging examinations of 34 patients with histopathologically confirmed primary synovial chondromatosis of the TMJ were reviewed retrospectively. Imaging features including the lesion epicentre, destruction/sclerosis of surrounding bone, calcification, periosteal reaction, osteophyte, lesion size, and joint space dimensions were assessed. RESULTS: Thirty-one of thirty-four patients (91.2%) showed the superior joint space as the lesion epicentre. For the mandibular condyle, more than one-third of patients (14/34; 41.2%) showed no destruction, and more than half of patients (19/34; 55.9%) showed no sclerosis. Conversely, >70% of patients showed destruction and sclerosis of the articular eminence/glenoid fossa, while >80% of patients (28/34; 82.4%) presented with various calcifications, including the ring-and-arc (9/34; 26.5%) and popcorn (13/34; 38.2%) types. The mean joint space on the affected side was significantly larger than that of the unaffected side (p<0.001). More than three-fourths of patients (76.9%) experienced no interval increase in lesion size during an average of 1.6 years of follow-up. CONCLUSION: Synovial chondromatosis of the TMJ demonstrated several imaging features, including the lesion centre being located in the superior joint space, resultant articular eminence/glenoid fossa-oriented bone changes, ring-and-arc and popcorn calcification, joint space widening, and self-limiting growth. These imaging features may be helpful in differentiating synovial chondromatosis from other lesions of the TMJ.

Imaging features of chondrosarcoma of the temporomandibular joint: report of nine cases and literature review.

AIM: To investigate the imaging features of chondrosarcoma of the temporomandibular joint (TMJ) and review the literature. MATERIALS AND METHODS: Computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)/CT images of nine patients with histopathologically confirmed chondrosarcoma of the TMJ were reviewed retrospectively. Imaging features regarding the direction of lesion growth, bone destruction, infiltration into the tendon of the lateral pterygoid muscle (LPM) in the pterygoid fovea, enhancement pattern, calcification, periosteal reaction, markedly hyperintense T2 signal area, and qualitative PET signal intensity were evaluated. RESULTS: Seven of nine patients (77.8%) presented with lesion growth that was outward from the medulla of the mandibular condyle. Infiltration into the tendon of LPM in the pterygoid fovea was observed in all cases, and 77.8% (7/9) of them demonstrated >50% infiltration. All the lesions showed a mixed peripheral and internal enhancement, and revealed a markedly hyperintense T2 signal intensity area, which showed no enhancement. Although five of nine cases demonstrated higher FDG uptake compared with that of the liver, the other four cases showed less FDG uptake than that of the liver. CONCLUSION: Chondrosarcoma of the TMJ demonstrated several imaging features, including outward growth from the mandibular condyle, resultant infiltration into the tendon of LPM in the pterygoid fovea, various patterns of internal enhancement, and a markedly hyperintense T2 signal intensity area. These imaging features may be helpful to differentiate chondrosarcoma from other lesions of the TMJ.

Use of supplemental anti-HBc testing of donors showing non-discriminating reactive results in multiplex nucleic acid testing.

BACKGROUND AND OBJECTIVES: The Korean Red Cross began nucleic acid amplification testing (NAT) for HIV and HCV in February 2005, and added HBV NAT beginning in June 2012. The current NAT system utilizes a multiplex assay for simultaneous detection of HBV DNA, HCV RNA and HIV-1 RNA. For samples that are reactive in the multiplex assay, we do specific tests for each virus. However, there have been cases of non-discriminated reactive (NDR) results which appear to be the result of non-specific reactions or cross-contamination, although some cases are considered to arise from the presence of low levels of HBV DNA due to occult hepatitis B infection. MATERIALS AND METHODS: We examined the incidence of NDR results in previous donations of some NAT-reactive donors. Additionally, for those donors with NDR results, we performed an HBV core antibody (anti-HBc) assay. RESULTS: From November 2015 to March 2016, there were 408 NAT-reactive donors. Of these, nineteen HBV NAT-reactive donors showed a history of NDR results in the past donations. Seven donors showed NDR results more than once. Of 771 NDR donors, 362 (47·0%) were anti-HBc reactive. CONCLUSION: The NDR donors had a substantially higher rate of anti-HBc reactivity than other blood donors indicating that some with anti-HBc reactivity represent donors with occult HBV. Therefore, the incorporation of an anti-HBc testing for NDR donors could improve blood safety testing for the Korean Red Cross.

Serious fungal infections in Korea.

Information on the incidence and prevalence of fungal infections is of critical value in public health policy. However, nationwide epidemiological data on fungal infections are scarce, due to a lack of surveillance and funding. The objective of this study was to estimate the disease burden of fungal infections in the Republic of Korea. An actuarial approach using a deterministic model was used for the estimation. Data on the number of populations at risk and the frequencies of fungal infections in those populations were obtained from national statistics reports and epidemiology papers. Approximately 1 million people were estimated to be affected by fungal infections every year. The burdens of candidemia (4.12 per 100,000), cryptococcal meningitis (0.09 per 100,000), and Pneumocystis pneumonia (0.51 per 100,000) in South Korea were estimated to be comparable to those in other countries. The prevalence of chronic pulmonary aspergillosis (22.4 per 100,000) was markedly high, probably due to the high burden of tuberculosis in Korea. The low burdens of allergic bronchopulmonary aspergillosis (56.9 per 100,000) and severe asthma with fungal sensitization (75.1 per 100,000) warrant further study. Oral candidiasis (539 per 100,000) was estimated to affect a much larger population than noted in previous studies. Our work provides valuable insight on the epidemiology of fungal infections; however, additional studies are needed.

Nefopam as an adjunct to intravenous patient-controlled analgesia after renal transplantation: a randomised trial.

BACKGROUND: Nefopam has been used as an adjuvant to opioid analgesia after operation. We investigated the efficacy of nefopam as an adjunct to fentanyl-based intravenous patient-controlled analgesia (IV PCA) on post-operative pain relief in patients undergoing renal transplantation. METHODS: Ninety-eight patients undergoing elective renal transplantation were randomised into two groups: nefopam or control groups. The former received nefopam (160 mg in 200 ml at a rate of 4 ml/h) whereas the latter received normal saline during the first 48 h after reperfusion of grafted kidney. Pain intensity scores, cumulative dose of fentanyl, and the incidence of adverse events were assessed at 1, 6, 12, 24, and 48 h post-operatively. Serum creatinine and estimated glomerular filtration rate were evaluated on post-operative days 1, 2, 4, and 7. RESULTS: The cumulative fentanyl consumption during the first 48 h after operation was 19% less in the nefopam group than that in the control group (1005 ± 344 µg vs. 1246 ± 486 µg, mean ± SD; P = 0.006). Pain intensity scores at rest and on coughing were significantly lower in the nefopam group throughout the first 12 and 48 h after operation, respectively. Adverse events and early graft function were comparable between the groups, except a significantly lower incidence of drowsiness observed in the nefopam group (4% vs. 21%, P = 0.027). CONCLUSION: In combination with fentanyl PCA, nefopam reduced post-operative fentanyl consumption with superior analgesia after renal transplantation.

Risk factors for cytomegalovirus gastrointestinal diseases in adult patients with cancer.

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.

Incidence and clinical features of Clostridium difficile infection in Korea: a nationwide study.

The incidence and severity of Clostridium difficile infections (CDI) have increased in Western countries. However, there are limited data regarding the epidemiology of CDI in Eastern countries. This nationwide study was conducted in 17 hospitals to determine temporal trends in CDI incidence (from 2004 to 2008) in South Korea. The total incidence of CDI in Korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (P = 0·028). When analysing the clinical features of 1367 CDI patients diagnosed in 2008, oral metronidazole was effective as a first-line treatment for CDI (61·9%). Relapse rate was 8·9% and complicated CDI was only observed in 3·6%. The incidence of CDI increased significantly in Korea from 2004 to 2008. Although the clinical features were milder than in Western countries, the increasing burden of CDI needs ongoing surveillance systems.

Differentiation between Chondrosarcoma and Synovial Chondromatosis of the Temporomandibular Joint Using CT and MR Imaging.

BACKGROUND AND PURPOSE: Chondrosarcoma and synovial chondromatosis of the temporomandibular joint share overlapping clinical and histopathologic features. We aimed to identify CT and MR imaging features to differentiate chondrosarcoma from synovial chondromatosis of the temporomandibular joint. MATERIALS AND METHODS: The CT and MR images of 12 and 35 patients with histopathologically confirmed chondrosarcoma and synovial chondromatosis of the temporomandibular joint, respectively, were retrospectively reviewed. Imaging features including lesion size, center, enhancement, destruction/sclerosis of surrounding bone, infiltration into the tendon of the lateral pterygoid muscle, calcification, periosteal reaction, and osteophyte formation were assessed. A comparison between chondrosarcoma and synovial chondromatosis was performed with a Student t test for quantitative variables and the Fisher exact test or linear-by-linear association test for qualitative variables. Receiver operating characteristic analysis was performed to determine the diagnostic performance for differentiation of chondrosarcoma and synovial chondromatosis based on a composite score obtained by assigning 1 point for each of 9 imaging features. RESULTS: High-risk imaging features for chondrosarcoma were the following: lesion centered on the mandibular condyle, destruction of the mandibular condyle, no destruction/sclerosis of the articular eminence/glenoid fossa, infiltration into the tendon of the lateral pterygoid muscle, absent or stippled calcification, periosteal reaction, internal enhancement, and size of ≥30.5 mm. The best cutoff value to discriminate chondrosarcoma from synovial chondromatosis was the presence of any 4 of these high-risk imaging features, with an area under the curve of 0.986 and an accuracy of 95.8%. CONCLUSIONS: CT and MR imaging features can distinguish chondrosarcoma from synovial chondromatosis of the temporomandibular joint with improved diagnostic performance when a subcombination of 9 imaging features is used.

Identification of oxidized serum albumin in the cerebrospinal fluid of ischaemic stroke patients.

BACKGROUND AND PURPOSE: Extensive evidence has shown that oxidative stress mediates neuronal death in animal models of hypoxic-ischaemia. Brain biomarkers of oxidative stress need to be identified in order to better understand and treat brain damage in human stroke patients. The present study was conducted to identify potential target proteins of oxidative stress in the cerebrospinal fluid (CSF) of stroke patients with acute ischaemic brain injury. METHODS: We performed two-dimensional polyacrylamide gel electrophoresis to separate protein samples obtained from the CSF of control and stroke patients. To determine protein oxidation levels, oxyblot was then used to detect protein carbonyls that were determined by formation of a stable 2,4-dinitrophenylhydrazine (DNP) product using an anti-DNP antibody. RESULTS: We found that oxidation of serum albumin was increased in the CSF from stroke patients as well as rats who underwent permanent middle cerebral artery occlusion (6.5%, 23%, respectively). In stroke patients, oxidized albumin levels correlated to neurologic indications. CONCLUSIONS: The present study suggests that oxidized albumin in CSF can be utilized as an oxidative stress marker in human stroke patients.

RAGE regulates BACE1 and Abeta generation via NFAT1 activation in Alzheimer's disease animal model.

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor, and amyloid beta peptide (Abeta) is one of the ligands for RAGE. Because RAGE is a transporter of Abeta from the blood to the brain, RAGE is believed to play an important role in Alzheimer's disease (AD) pathogenesis. In the present study, the role of RAGE in Abeta production was examined in the brain tissue of an AD animal model, Tg2576 mice, as well as cultured cells. Because beta-site APP-cleaving enzyme 1 (BACE1), an essential protease for Abeta production, is up-regulated in cells overexpressing RAGE and in RAGE-injected brains of Tg2576 mice, the molecular mechanisms underlying RAGE, BACE1 expression, and Abeta production were examined. Because RAGE stimulates intracellular calcium, nuclear factor of activated T-cells 1 (NFAT1) was examined. NFAT1 was activated following RAGE-induced BACE1 expression followed by Abeta generation. Injection of soluble RAGE (sRAGE), which acts as a competitor with full-length RAGE (fRAGE), into aged Tg2576 mouse brains reduced the levels of plaques, Abeta, BACE1, and the active form of NFAT1 compared with fRAGE-injected Tg2576 mice. Taken together, RAGE stimulates functional BACE1 expression through NFAT1 activation, resulting in more Abeta production and deposition in the brain.

Association of meteorological factors and atmospheric particulate matter with the incidence of pneumonia: an ecological study.

OBJECTIVES: Inconsistent results have been found between pneumonia and meteorological factors. We aimed to identify principal meteorological factors associated with pneumonia, and to estimate the effect size and lag time. METHODS: This was nationwide population-based study used a healthcare claims database merged with a weather database in eight metropolitan cities in Korea. We applied a stepwise approach using the Granger causality test and generalized additive model to elucidate the association between weekly pneumonia incidence (WPI) and meteorological factors/air pollutants (MFAP). Impulse response function was used to examine the time lag. RESULTS: In total, 2 011 424 cases of pneumonia were identified from 2007 to 2017. Among MFAP, diurnal temperature range (DTR), humidity and particulate matter ≤2.5 µm in diameter (PM2.5) showed statistically significant associations with WPI (p < 0.001 for all 3 MFAPs). The association of DTR and WPI showed an inverted U pattern for bacterial and unspecified pneumonia, whereas for viral pneumonia, WPI increased gradually in a more linear manner with DTR and no substantial decline. Humidity showed a consistent pattern in all three pneumonia categories. WPI steeply increased up to 10 to 20 µg/m³ of PM2.5 but did not show a further increase in higher concentrations. On the basis of the result, we examined the effect of MFAP in different lag times up to 3 weeks. CONCLUSIONS: DTR, humidity and PM2.5 were identified as MFAP most closely associated with WPI. With the model, we were able to visualize the effect-time association of MFAP and WPI.

Sarcopenia is associated with non-alcoholic fatty liver disease in men with type 2 diabetes.

AIMS: Recent epidemiological studies have suggested an association between sarcopenia and non-alcoholic fatty liver disease (NAFLD) in the general population, prompting our investigation into the gender-specific association between sarcopenia and NAFLD in patients with type 2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study, 4210 patients with T2DM were recruited from the Seoul Metabolic Syndrome Cohort. Appendicular skeletal muscle mass (ASM) was estimated from bioimpedance analysis measurements, and the skeletal muscle mass index (SMI) was calculated by dividing the sum of ASM by body weight. Sarcopenia was defined as a gender-specific SMI value>2 standard deviations (SDs) below the mean for healthy young adults. NAFLD was defined as the presence of hepatic steatosis on ultrasonography with no other causes of chronic liver disease. RESULTS: Among the entire study population (mean age: 57.4±10.8 years), 1278 (30.4%) had NAFLD and 1240 (29.5%) had sarcopenia, and the prevalence of NAFLD was significantly higher in those with sarcopenia: 46.2% vs 25.1% (P<0.001) in men; 38.3% vs 25.4% (P<0.001) in women. Sarcopenia was significantly associated with higher risk of NAFLD in men (adjusted odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.15-2.17), whereas the association was attenuated in women after adjusting for clinical risk factors. CONCLUSION: Sarcopenia is independently associated with NAFLD in men with T2DM, which suggests that sarcopenia may be a risk factor for NAFLD in men with T2DM.

Early cidofovir administration might be associated with a lower probability of respiratory failure in treating human adenovirus pneumonia: a retrospective cohort study.

OBJECTIVE: To compare outcomes of early and delayed treatment with cidofovir for human adenovirus (HAdV) pneumonia. METHODS: A retrospective cohort study in Korean military hospitals was conducted between January 2012 and December 2018. Patients with potentially severe HAdV pneumonia with risk factors for respiratory failure were included and divided into early (within 7 days from symptom onset) and delayed (after 7 days from symptom onset) treatment groups. The primary outcome was respiratory failure development within 21 days after symptom onset. RESULTS: A total of 89 patients with potentially severe HAdV pneumonia were enrolled in the cohort; they included 62 early and 27 delayed treatment patients. All patients were males in their early 20s. Significantly fewer patients in the early treatment group progressed to respiratory failure (8/62, 12.9%), compared to the delayed group (18/27, 66.7%, p < 0.001). Early treatment was associated with a lower 21-day probability of respiratory failure by the Kaplan-Meier method (p < 0.001). On multivariate analysis, monocyte count, hypoxaemia, confusion, whole lung involvement, and early cidofovir treatment within 7 days from symptom onset were included, and monocyte count (HR 0.995, 95%CI 0.991-1.000, p 0.042), confusion (HR 4.964, 95%CI 1.189-20.721, p = 0.028), and early cidofovir treatment (HR 0.319, 95%CI 0.115-0.883, p = 0.028) were significantly associated with respiratory failure. CONCLUSIONS: Early administration of cidofovir was associated with a lower hazard for respiratory failure development. It is suggested that cidofovir be administered within 7 days from symptom onset to prevent respiratory failure in patients with potentially severe HAdV pneumonia.

Impact of posterior communicating artery on basilar artery steno-occlusive disease.

BACKGROUND: Acute brainstem infarction with basilar artery (BA) occlusive disease is the most fatal type of all ischaemic strokes. This report investigates the prognostic impact of the posterior communicating artery (PcoA) and whether its anatomy is a safeguard or not. METHODS: Consecutive patients who had acute brainstem infarction with at least 50% stenosis of BA upon CT angiography (CTA) were studied. The configuration of PcoA was divided into two groups upon CTA: "textbook" group (invisible PcoA with good P1 and P2 segment) and "fetal-variant of PcoA" group (only visible PcoA with absent P1 segment). Baseline demographics, radiological findings and stroke mechanisms were analysed. A multiple regression analysis was performed to predict clinical outcome at 30 days (modified Rankin disability Scale (mRS

Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts.

OBJECTIVES: The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction. METHODS: Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The "dominant" VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature. RESULTS: The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98). CONCLUSIONS: Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts.

Endoscopic evaluation of significant gastrointestinal lesions in patients with iron deficiency with and without anaemia: a Korean Association for the Study of Intestinal Disease study.

BACKGROUND: Although endoscopy is recommended for patients with iron deficiency anaemia, there is, currently, no consensus on the role of endoscopy for iron-deficient patients without anaemia. The goal of this study was to determine the prevalence of serious gastrointestinal (GI) lesions, identified by endoscopy in patients with iron deficiency and anaemia compared with patients with iron deficiency without anaemia. METHODS: One thousand five hundred and eighteen patients with a ferritin value of or=300 mg/dL were retrospectively investigated using oesophagogastroduodenoscopy and colonoscopy between January 2005 and September 2006. The lesions identified were classified as clinically important according to standard predetermined criteria. RESULTS: Among the 1518 cases, 749 patients had anaemia and 769 had normal haemoglobin levels. Clinically important lesions were identified in 24.6% of the patients with anaemia and in 22.8% of the patients without anaemia (P > 0.05). The frequency of lower GI tract lesions (13.6 vs 11.4%, P > 0.05) and upper GI tract lesions (11.9 vs 12.5%, P > 0.05) was similar in the comparisons between the two groups. However, the frequency of malignant GI lesions was higher in the patients with anaemia (5.1 vs 0.7%, P < 0.01). In addition, the patients without anaemia were significantly more likely to have early-stage neoplasia (adenoma, early gastric cancer and Dukes' A and B colon cancer) than were the patients with anaemia (98.4 vs 52.5%, P < 0.01). CONCLUSION: The results of this study suggest that patients with iron deficiency should undergo endoscopic evaluation of the GI tract, irrespective of whether they have anaemia. The endoscopic evaluation of the GI tract in patients with iron deficiency without anaemia could provide an opportunity for the detection of early-stage neoplasia at a curable stage.

Functional improvement of pig islet with exocrine encapsulation.

Porcine-specific obstacles in islet isolation frequently result from the low purity or contamination with exocrine tissues. We implemented a new technique involving as capsulation of islets with excess exocrine tissue as a beneficial material to address those difficulties. Pig islets were hand-picked as high purity (HI) or low purity (LO) islets containing significant amounts of exocrine tissue. We performed static (ST) or shaking (SK) cultures of HI and LO islets. Islet function was examined after 24 hours by a glucose challenge test. Insulin secretion into the culture media was continuously measured using ELISA during a 6-day culture period. Islet function after 24 hours exhibited better maintenance under SK than ST culture as assessed by a stimulation index. The ideal islet morphology was seen in LO islets at 3 days of SK culture with typical islet shapes of a smooth surface and a spherical configuration. In contrast, typical islet morphology was not observed in HI islets under SK culture; maintenance of typical spherical appearances was difficult. Insulin secretion from LO islets under SK culture was higher than under other conditions during the 6-day period. Under SK culture conditions, exocrine-encapsulated LO islets showed enhanced islet function by condensing loose islet aggregates into firm spheroids with native exocrine tissues as a natural scaffold.

Dynamics of population code for working memory in the prefrontal cortex.

Some neurons (delay cells) in the prefrontal cortex elevate their activities throughout the time period during which the animal is required to remember past events and prepare future behavior, suggesting that working memory is mediated by continuous neural activity. It is unknown, however, how working memory is represented within a population of prefrontal cortical neurons. We recorded from neuronal ensembles in the prefrontal cortex as rats learned a new delayed alternation task. Ensemble activities changed in parallel with behavioral learning so that they increasingly allowed correct decoding of previous and future goal choices. In well-trained rats, considerable decoding was possible based on only a few neurons and after removing continuously active delay cells. These results show that neural activity in the prefrontal cortex changes dynamically during new task learning so that working memory is robustly represented and that working memory can be mediated by sequential activation of different neural populations.

Molecular mechanisms of cell death of mycophenolic acid-treated primary isolated rat islets: implication of mitogen-activated protein kinase activation.

Optimal immunosuppression after pancreas islet transplantation has not yet been established to achieve long-term graft survival. Mycophenolic acid (MPA) is widely used as an immunosuppressive drug after transplantation including among recipients of pancreas islet cells. Previously, we reported MPA-induced islet apoptosis in the HIT-T15 cell line. In this study, we confirmed the effects of MPA on cell death and its potential implications on the mitogen-activated protein kinase (MAPK) family expression levels in primary isolated rat islets. Lewis islets isolated by collagenase digestion were purified by the density gradient method. Cell death was analyzed by methylthiazoletetrazolium assay. Activation of MAPK kinase 4 (MKK4), c-jun N-terminal protein kinase (JNK), p38 MAPK, and caspase-3 cleavage was examined by Western blot analyses. MPA treatments (> 25 micromol/L) increased cell death significantly at 24 hours and in a dose-dependent manner activated MKK4, JNK, and p38 MAPK at 20 hours. Caspase-3 cleavage was also increased by MPA treatment. These results suggested that MPA induced significant cell death among primary isolated rat islets by activation of MKK4, JNK, and p38 MAPK, as well as caspase-3 cleavage.

Effects of inosine monophosphate dehydrogenase inhibition on high glucose-induced cellular reactive oxygen species in mesangial cells.

Mesangial cell extracellular matrix (ECM) synthesis plays an important role in chronic renal diseases including chronic renal allograft dysfunction and diabetic nephropathy. Although inosine monophosphate dehydrogenase 2 (IMPDH2), as a target of mycophenolic acid (MPA), is important for de novo guanosine synthesis in lymphocytes, mesenchymal cells are not wholly dependent on it. To explore the importance of IMPDH2 on the inhibitory effects of MPA in mesangial cells (MC), we compared the effects of MPA and IMPDH2 siRNA on high glucose (HG)-induced fibronectin secretion and cellular reactive oxygen species (ROS). Mouse mesangial cells (MMC) were stimulated with HG (30 mmol/L D-glucose) in the presence or absence of MPA pretreatment or IMPDH2 siRNA transfection. Fibronectin secretion was measured by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS assessed by flow cytometry. HG increased fibronectin secretion by 1.8-fold at 24 hours and DCF-sensitive cellular ROS by 1.5-fold at 1 hour. MPA at 10 micromol/L totally inhibited HG-induced fibronectin secretion and cellular ROS in MMC. However, IMPDH2 siRNA only partially suppressed HG-induced fibronectin secretion and cellular ROS. These results suggested that MPA may inhibit HG-induced fibronectin secretion partially through inhibiting cellular ROS and the inhibition of IMPDH2 may be partially involved in the mechanism of MPA.