Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.
Anoxia ; Brain Neoplasms ; Cell Death* ; Cell Line ; Dichloroacetic Acid ; Glioblastoma* ; Glucose ; Glycolysis ; Metabolism ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphotransferases ; Pyruvic Acid

BACKGROUND: The primary site of action of pregabalin, i.e. the alpha-2-delta subunit of the voltage-dependent calcium channel, is located at the dorsal root ganglion and dorsal horn of the spinal cord. Therefore, the epidural administration of pregabalin could have advantages over oral administration. However, the possibility of its neurotoxicity should be excluded before any attempt at epidural administration. We evaluated the neuronal safety of epidurally-administered pregabalin by observing the sensory/motor changes and examining the histopathology of spinal cord in rats. METHODS: Sixty rats of 180-230 g were divided into three groups; 3 mg of pregabalin dissolved in 0.3 ml saline (group P, n = 20), 0.3 ml 40% alcohol (group A, n = 20), or 0.3 ml normal saline (group N, n = 20) was administered epidurally to the rats in each group. Pinch-toe test, motor function evaluation, and histopathologic examination of vacuolation, chromatolysis, meningeal inflammation, and neuritis were performed at the 1st, 3rd, 7th, and 21st day after each epidural administration. RESULTS: All rats enrolled in group P, like those in group N, showed neither sensory/motor dysfunction nor any histopathological abnormality over the 3-week observation period. In contrast, in group A, 80% of the rats showed abnormal response to the pinch-toe test and all rats showed decreased motor function during the entire evaluation period. In addition, all histopathologic findings of neurotoxicity were observed exclusively in group A. CONCLUSIONS: The epidurally administered pregabalin (about 15 mg/kg) did not cause any neurotoxic evidence, in terms of both sensory/motor function evaluation and histopathological examination in rats.
Administration, Oral ; Animals ; Calcium Channels ; gamma-Aminobutyric Acid ; Ganglia, Spinal ; Horns ; Inflammation ; Injections, Epidural ; Neuritis ; Neurons ; Rats ; Spinal Cord ; Pregabalin

BACKGROUND/AIMS: Pancreas transplantation (PT) as the ultimate treatment for insulin-dependent diabetes has been the subject of debate clinically. Marked improvements in patient and graft survival, and decreases in postoperative morbidity have been achieved due to technical refinements, improved immunosuppressants, and better postoperative management. Here, we report our 18-year experience with PT performed at our institute. METHODS: All recipients who underwent deceased donor or living donor PT between July 1992 and December 2009 were included. We reviewed the medical records, including operation records, progress, and laboratory findings during follow-up. Graft and patient survival were analyzed using the Kaplan-Meier method. RESULTS: In total, 119 cases of pancreas transplantation were performed between July 1992 and December 2009 at our institute. Indications for pancreas transplantation were type I diabetes in 93 (78.2%) patients and type II diabetes in 16 (13.4%) patients. The transplanted pancreas was obtained from a deceased donor in 108 cases (90.8%) and a living donor in 11 cases (9.2%). Median follow-up duration was 39.3 months posttransplantation (range 0~176 months). Overall graft survival rates at 1, 5, and 10 years were 81.6%, 63.4%, and 57.1%, respectively. Following the introduction of tacrolimus as an immunosuppressant in 1999, graft survival at 1, 5, and 10 years was 89.1%, 72.9%, and 66.2%, and overall patient survival at 1, 5, and 10 years was 93.0%, 86.0%, and 86.%, respectively. CONCLUSIONS: Considering the quality of life and long-term patient survival, PT is an effective treatment strategy in non-obese diabetic patients requiring insulin regardless of the type of diabetes.
Follow-Up Studies ; Graft Survival ; Humans ; Immunosuppressive Agents ; Insulin ; Korea ; Living Donors ; Medical Records ; Pancreas ; Pancreas Transplantation ; Quality of Life ; Tacrolimus ; Tissue Donors ; Transplants

A case of a 52-year-old man with retroperitoneal fibrosis and a horseshoe kidney is presented. Horseshoe kidney is one of the most common renal anomalies and complicated with urinary tract infection, hydronephrosis, calculi, tumor of the renal pelvis, and other multiple congenital abnormalities. Idiopathic retroperitoneal fibrosis is a rare disease characterized by the presence of a retroperitoneal tissue, consisting of chronic inflammation and marked fibrosis, which often entraps ureters or other abdominal organs. The correlation between horseshoe kidney and retroperitoneal fibrosis has not been described. We report a rare case of idiopathic retroperitoneal fibrosis with horseshoe kidney disease demonstrating good response to steroid therapy.
Calculi ; Congenital Abnormalities ; Fibrosis ; Humans ; Hydronephrosis ; Inflammation ; Kidney ; Kidney Diseases ; Kidney Pelvis ; Middle Aged ; Rare Diseases ; Retroperitoneal Fibrosis ; Steroids ; Ureter ; Urinary Tract Infections

PURPOSE: Idiopathic granulomatous mastitis is a rare benign inflammatory breast disease of an unknown etiology and the optimal treatment remains controversial. The aim of this study is to evaluate the efficacy of surgically complete excision in patients with idiopathic granulomatous mastitis. METHODS: Between March 2005 and November 2008, we treated 14 cases that were diagnosed with idiopathic granulomatous mastitis. Prospectively, we treated the cases with complete surgical excision with or without steroid therapy in all patients. RESULTS: The mean age of the patients was 36 years (range 30 to 53 years). All cases performed were complete excision with or without steroid therapy. The median follow up period was 26 months (range 5 to 50 months) and all cases had no recurrence. 13 patients out of the 14 were satisfied with the cosmesis of the treated breast. CONCLUSION: We conclude that the treatment of choice for idiopathic granulomatous mastitis is surgically complete excision.
Breast ; Breast Diseases ; Follow-Up Studies ; Granulomatous Mastitis ; Humans ; Prospective Studies ; Recurrence

BACKGROUND: There have been limited reports on the effectiveness of 5% lidocaine patches (L5Ps) for treating a few types of chronic pain. We utilized L5Ps for chronic pain patients with various diagnoses and who had incompletely responded to their current treatment regimen. This study aimed at describing the results of a retrospective review of an open-label L5P trial to assess L5Ps' effectiveness and safety for treating various chronic pain patients. METHODS: The chronic pain patients with pain lasting longer than 6-month duration were offered a 2-week L5P treatment trial. The patients were maintained on their other analgesic regimens. The treatment effect was measured according to the change from the baseline visual analog scale (VAS) to the week 2 VAS. After a 2-week trial, the patients were asked if they perceived pain improvement with L5Ps by using a four-item Pain Relief Scale (1 = a lot of relief, 2 = slight relief, 3 = no change, 4 = worse pain). RESULTS: In the combined patient population (n = 177), 2-week treatment with the L5Ps significantly improved the week 2 VAS (P = 0.000). Significant improvement in the VAS was reported by the chronic pain patients with postherpetic neuralgia, intercostal neuralgia, degenerative osteoarthritis at knee joint, and other maladies. A higher proportion of the chronic pain patients reported improving their pain by the L5Ps. Seven patients experienced mild or moderate patch-related adverse events. CONCLUSIONS: The L5P provided clinically meaningful pain relief in some refractory chronic pain patients without any severe adverse events.
Chronic Pain ; Humans ; Knee Joint ; Lidocaine ; Neuralgia ; Neuralgia, Postherpetic ; Osteoarthritis ; Retrospective Studies

BACKGROUND/AIMS: Steroid therapy is reported to improve the clinical outcome of IgA nephropathy. In addition, recent studies have revealed that deflazacort has fewer side effects than prednisolone. This study examined the effect of steroids and compared the clinical efficacy of deflazacort and prednisolone in patients with IgA nephropathy. METHODS: We retrospectively reviewed 136 patients with biopsy-proven IgA nephropathy who received deflazacort (n=50), prednisolone (n=29), or neither (n=59), and in whom blood pressure was controlled with angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The mean duration of steroid administration was 9.5+/-9.1 months. The initial clinical status and change in the amount of protein in the 24-hour urine were compared among the three groups. RESULTS: The baseline characteristics (age, blood pressure, serum creatinine level, initial protein in the 24-hour urine, and creatinine clearance) did not differ significantly among the groups. The decrement of protein in the 24-hour urine was higher in the deflazacort and prednisolone groups, as compared with the control group (4.4+/-5.4, 4.2+/-1.5, and 2.1+/-3.1 g/day, respectively, p=0.013). The increment in the creatinine clearance was higher in the deflazacort and prednisolone groups, as compared with the control group (11.5+/-16.4, 12.3+/-26.2, and 4.8+/-14.91.3+/-0.9, respectively, p=0.009). There were no significant differences in the above parameters between the deflazacort and prednisolone groups. CONCLUSIONS: Steroid therapy reduces urinary protein excretion in IgA nephropathy, and the clinical efficacy of deflazacort and prednisolone was found to be similar.
Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Blood Pressure ; Creatinine ; Glomerulonephritis ; Glomerulonephritis, IGA ; Humans ; Immunoglobulin A ; Prednisolone ; Pregnenediones ; Proteinuria ; Retrospective Studies ; Steroids

BACKGROUND: Severe graft dysfunction has been occasionally encountered following adult living donor liver transplantation (LDLT). This study intended to assess the effectiveness of plasmapheresis (PP) as a liver supportive measure in LDLT recipients showing severe graft dysfunction. METHODS: During 1 year of 2007, 276 adult LDLTs were performed in our institution. Of them 27 underwent PP therapy as a liver support. RESULTS: Seventeen underwent PP during the first month following LDLT and another 10 underwent PP after that period. The underlying causes of such liver support were acute and chronic rejections, ischemic damage, viral hepatitis recurrence and unknown causes. A total of 329 sessions of PP were performed for these 27 patients, indicating 12.2+/-9.9 times per patient for 28.1+/-32.2 days. Concurrent hemodiafiltration was done in 66.7%. Serum total bilirubin level was significantly reduced following PP therapy: 23.2+/-6.5 mg/dL before PP and 14.4+/-5.6 mg/dL at 1 week after completion of PP (P<0.001). Other biochemical parameters did not significantly affected by PP. Overall 1-year patient survival rate was 63.0%. Six-month graft survival rate after completion of PP was 82.6% in 17 patients undergoing PP during the first posttransplant month and 30% in 10 patients undergoing PP after 1 month (P= 0.013). CONCLUSIONS: The results of this study implicate that PP has a beneficial effect on the recovery of liver graft function, especially during the early posttransplant period. We suggest to perform active application of PP therapy for liver recipients showing severe graft dysfunction of total bilirubin greater than 15~20 mg/dL.
Adult ; Bilirubin ; Graft Survival ; Hemodiafiltration ; Hepatitis ; Humans ; Liver ; Liver Transplantation ; Living Donors ; Plasmapheresis ; Recurrence ; Rejection (Psychology) ; Survival Rate ; Transplants

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by severe neuropathic pain and disability, which can result in psychological and behavioral dysfunction. The goal of the present study was to evaluate neurocognitive disability, and to assess the relationship between clinical variables and neuropsychological features in CRPS patients. METHODS: We investigated the neuropsychological features of 15 CRPS I patients. The neuropsychological tests that we made comprised of a full intelligence quotient, memory quotient, trail-making test A, trail-making test B (TMT-B), and MMPI (Minnesota multiphasic personality inventory). RESULTS: The results showed severe disability in performance on TMT-B. There was no significant correlation between specific cognitive variables and MMPI scales. CONCLUSIONS: Decreased performance on TMT-B which shows mental flexibility in the prefrontal lobe exists independently from depressive disorders in CRPS patients.
Chronic Pain ; Depressive Disorder ; Executive Function ; Humans ; Intelligence ; Memory ; MMPI ; Neuralgia ; Neuropsychological Tests ; Pliability ; Trail Making Test ; Weights and Measures

BACKGROUND: Temporomandibular joint disorder (TMD) is a group of musculoskeletal conditions characterized by pain in the pre-auricular area, limitation of jaw movement and palpable muscle tenderness. Thermography is a nonionizing, noninvasive diagnostic alternative for the evaluation of TMD. This study was conducted to evaluate the usefulness of thermography in the assessment of TMD. METHODS: Thermography was conducted on the 61 patients who had been diagnosed with TMD, and on the 34 normal symptom-free volunteers. The temperature differences between opposite sides of the temporomandibular joint (DeltaTTMJ) and the masseter muscle (DeltaTMST) were calculated. The sensitivity and specificity of thermography was calculated at the cut off values of 0.2, 0.3, and 0.4 degrees C. RESULTS: In the patient group, the DeltaTTMJ was 0.42 +/- 0.38 degrees C and the DeltaTMST was 0.38 +/- 0.33 degrees C, whereas in the control group the DeltaTTMJ was 0.10 +/- 0.07 degrees C and the DeltaTMST 0.15 +/- 0.10 degrees C. In addition, the patient group demonstrated a significantly lower level of thermal symmetry than the control group (P < 0.001) in both the temporomandibular joints and the masseter muscles. The sensitivity of thermography at the cut off values of 0.2, 0.3 and 0.4 degrees C was 67.2, 49.2, and 42.6% in the temporomandibular joint (TMJ) and 60.7, 49.2 and 37.7% in the masseter muscle, respectively. The specificity of thermography at the cut off values of 0.2, 0.3 and 0.4 degrees C was 88.2, 100, and 100% in the TMJ and 61.8, 91.2 and 100% in the masseter muscles, respectively. The accuracy of thermography at the cut off values of 0.2, 0.3 and 0.4 degrees C was 74.7, 67.4, and 63.2% in TMJ and 61.1, 64.2 and 60.0% in the masseter muscles, respectively. CONCLUSIONS: Temperature differences exist between the opposite sides of the TMD and masseter muscles in patients with TMD. Although the sensitivity of thermography in the diagnosis of TMD is low, it has high specificity in the evaluation of TMD, and is therefore applicable to patients with TMD.
Diagnosis ; Diagnostic Imaging ; Humans ; Jaw ; Masseter Muscle ; Myalgia ; Sensitivity and Specificity ; Temporomandibular Joint Disorders ; Temporomandibular Joint* ; Thermography* ; Volunteers