BACKGROUND: Cisplatin chemotherapy often causes acute kidney injury in cancer patients. The causative mechanisms of cisplatin-induced acute kidney injury include renal inflammation, activation of p53 tumour suppressor protein and tubular apoptosis. Luteolin, a flavone found in medicinal herbs and plants, has been reported to exhibit anti-inflammatory, antioxidant and anticarcinogenic activities. The purpose of this study was to investigate the anti-apoptotic effect of luteolin on cisplatin-induced acute kidney injury and the molecular mechanism. METHODS: C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without treatment with luteolin (50 mg/kg for 3 days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of luteolin on cisplatin-induced expression of renal p53, PUMA-alpha and Bcl-2 family proteins were evaluated. RESULTS: Treatment of mice with cisplatin resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. Treatment of cisplatin-treated mice with luteolin significantly improved renal dysfunction, reducing tubular cell damage, oxidative stress and apoptosis. Examination of molecules involving apoptosis of the kidney revealed that treatment of cisplatin increased the levels of p53 and its phosphorylation, PUMA-alpha, Bax and caspase-3 activity that were significantly decreased by treatment with luteolin. CONCLUSION: These results indicate that cisplatin induces acute kidney injury by regulation of p53-dependent renal tubular apoptosis and that luteolin ameliorates the cisplatin-mediated nephrotoxicity through down-regulation of p53-dependent apoptotic pathway in the kidney.

Dendritic amine and guanidinium group-modified nanoparticles were investigated for the delivery of model peptide drug into primary osteoclast precursor cells (bone marrow macrophages; BMMs). The model peptide drug was encapsulated into the nanoparticle by dropping the drug/carrier dissolved in dimethylsulfoxide/methylene chloride cosolvent into water containing poly(vinyl alcohol) as a stabilizer. Flow cytometry and spectrofluorimetry analysis indicated that the model drug itself was not taken up by the BMMs; however, nanoparticle systems underwent significant cellular uptake. In particular, guanidinium group-modified nanoparticles were taken up more efficiently than amine group-modified ones. Cell viability studies showed that both amine and guanidinium group-modified nanoparticles exhibited no significant cytotoxicity up to 100 mug/mL against the cells.

Although much is known about the cerebral neural plasticity that occurs after deafness, it is unclear how much time is required for its development or what other cortical changes may consequently occur. This study provides a longitudinal assessment of cerebral cortical neural plasticity, as manifested in adult deafened cats. A total of 5 male cats were subjected to whole cortex analysis of glucose metabolic activity via 2-deoxy-2[(18)F] fluoro-D-glucose (FDG) micro-positron emission tomography (PET). The imaging was performed at the baseline state of normal hearing and then at 4, 9, 24, and 33months after the induction of deafness. We compared glucose metabolism between the normal hearing state and each deafened state by using voxel-based statistical analysis (P<0.005). Significant changes were observed in the primary auditory (A1) and primary visual (V1) cortices. A bilateral metabolic decrease was observed in A1 areas and in temporal auditory fields, the extent of which was significantly increased at Month 9. Then it was declined at Month 24. And finally it was disappeared by Month 33. Auditory cortical plasticity subsequent to deafness was thus demonstrated. Furthermore, a significant metabolic upsurge occurred in bilateral occipital areas at Month 33. This increase, involving bilateral occipital and thalamic areas of V1, suggests compensatory hyperactivity of the visual cortex after deafness.

Hemoptysis in patients with lung cancer is not uncommon and sometimes have dangerous consequences. Hemoptysis has been managed with various treatment options other than surgery and medicine, such as endobronchial tamponade, transcatheter arterial embolization and radiation therapy. However, these methods can sometimes be used only temporarily or are not suitable for a patient's condition. We present a case in which uncontrollable hemoptysis caused by central lung cancer was successfully treated by inserting a covered self-expanding bronchial stent. The patient could be extubated and was able to undergo further palliative therapy. No recurrent episodes of hemoptysis occurred for the following three months. As our case, airway stenting is a considerable option for the tamponade of a bleeding lesion that cannot be successfully managed with other treatment methods and could be used to preserve airway patency in a select group of patients.

Aim: To assess the expressions of vascular endothelial growth factor (VEGF), fms-like tyrosine kinase-1 (Flt-1), and soluble Flt-1 (sFlt-1) genes in healthy normotensive and pre-eclamptic placentas of Korean women. Methods: We investigated 12 healthy normotensive pregnant women and 10 pre-eclamptic pregnant women at Eulji University Hospital. The obtained placental tissues were analyzed using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction. Results: The sFlt-1 messenger ribonucleic acid (mRNA) level was elevated 2.6 times more in pre-eclamptic placentas than in normal control placentas. However, the VEGF mRNA level of pre-eclamptic placentas was decreased. There was no difference in the Flt-1 mRNA level between control and pre-eclamptic placentas. Conclusions: Our study showed that expressions of genes relating to angiogenesis were altered in Korean pre-eclamptic placentas. These results suggest that the alteration in expressions of sFlt-1 and VEGF genes might be associated with the pathogenesis of pre-eclampsia.

A Gram positive halophilic bacterium, strain CAU 9536T, was isolated from a tidal flat sediment in the Yellow sea, Republic of Korea. Its taxonomic position was investigated using a polyphasic approach. The strain CAU 9536T grew optimally at 30 degrees C, pH 9.0, with 13.0% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 9536T belonged to the genus Serinicoccus, which has two known members, Serinicoccus profundi MCCC 1A05965T (similarity 99.0%) and Serinicoccus marinus JC1078T (similarity 98.0%). DNA-DNA relatedness analysis showed that CAU 9536T displayed less than 44.0% relatedness to other strains in the Serinicoccus genus. Interestingly, strain CAU 9536T had cell-wall peptidoglycan based on meso-diaminopimelic acid, unlike other Serinicoccus species. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine and an unknown lipid. Whole-cell hydrolysates contained mainly glucose and ribose. The major isoprenoid quinone was MK-8 (H4), and the predominant cellular fatty acid was iso-C15:0. The DNA G+C content was 74.9 mol%. Based on phenotypic, chemotaxonomic, and genotypic data, strain CAU 9536T was classified as a novel member of the genus Serinicoccus, for which the name Serinicoccus chungangensis sp. nov. is proposed. The type strain is CAU 9536T (KCTC=19774T, CCUG=0000T).

Carbonic anhydrase (CA) plays a critical role in pH regulation, long-term synaptic transformation, and is associated with mental retardation, Alzheimer's disease (AD), and Down syndrome. There is accumulating evidence that CAII is increased in AD brain. The present study focused on the determination of CAII protein level in blood plasma samples using immunoblot and ELISA methods. We compared plasma from 91 AD patients (average age 74.8 y), 83 persons with amnestic mild cognitive impairment (MCI) (average age 73.5 y), and 113 cognitively normal controls (average age 70.8 y). The plasma level of CAII was significantly increased in AD patients, as compared to control groups. CAII levels were higher in males than females. There was an age-dependent increase of CAII. These results provide further evidence that changes in CAII level may play a role in the pathogenesis of AD.

Citation Park M-H, Galan HL, Arroyo JA. Effect of hypoxia on endothelial nitric oxide synthase, NO production, intracellular survival signaling (p-ERK1/2 and p-AKT) and apoptosis in human term trophoblast. Am J Reprod Immunol 2010 Problem Hypoxia is commonly associated with complicated pregnancies such as intrauterine growth restriction. We evaluated the effects of hypoxia on phospho (p)-eNOS, p-ERK, p-AKT and apoptosis in human trophoblast. Method of study Isolated trophoblast were cultured in 21% oxygen or 2% oxygen for 24, 48 and 72 hr. p-eNOS, p-ERK and p-AKT protein were assessed by Western blot and apoptosis by TUNEL assay. NOx was determined in the culture media. Results Compared to controls, hypoxia-exposed CT showed the following: (1) decreased eNOS at 48 and 72 hr, (2) increased p-eNOS at 48 hr, (3) no differences in total NOx production, (4) increased p-ERK at 24, 48 and 72 hr, (5) increased p-AKT at 24 hr (P < 0.05) and (6) increased apoptosis at 48 hr. Conclusion Hypoxia increases activation of p-ERK and induces apoptosis of cultured trophoblast. Hypoxia decreases overall total eNOS but increases p-eNOS, which may allow for NO production to be maintained in trophoblast cells.

OBJECTIVES: The objective of this study was to determine the various factors that affect the extrusion rate of ventilation tubes (VTs), including the nature of the middle ear effusion. METHODS: A retrospective chart review of 82 pediatric patients (177 ears) who received VT insertion surgery under general anesthesia was carried out to evaluate the relationship between various factors and the VT extrusion rate. The factors we analyzed included age, gender, the adenoid size, the amount and content of the middle ear effusion after myringotomy, bleeding events, associated adenoidectomy and the findings of the tympanic membrane status, the tympanometry and the audiometry of the air bone gap. RESULTS: The mean extrusion time was 254 days (range, 11 to 809 days). The patients with no history of previous VT insertion had a longer extrusion time (mean, 279 days) than did the patients who had undergone previous VT insertion (mean, 203 days). The patients with serous effusion had the shortest extrusion time (mean, 190 days) as compared to those patients with glue (273 days) and pus (295 days) effusions. Other factors had no statistical significant relationship with the extrusion time. CONCLUSION: The mean VT extrusion time was 254 days. The VT extrusion time was significantly related to the characteristics of the middle ear effusion and a history of previous VT insertion. Thus, the nature of middle ear effusion can provide a clinical clue to predict the VT extrusion time.

Human leukocyte antigen (HLA) gene region encodes a set of HLA molecules functioning critical roles in immune response. Each HLA gene locus shows extensive polymorphism with ever-increasing number of alleles. The HLA nomenclature system for alleles defined by DNA typing was first established in 1987 and has been revised several times. Recently, it has been revised again with a new frame that can accommodate ever-increasing number of new alleles. The new system has also introduced the novel suffixes, P and G, to simplify reporting of ambiguous strings of alleles in typing reports. This review introduces the HLA nomenclature system-2010 in conjunction with its clinical application in Koreans.

This study was designed to investigate whether dieckol may inhibit alpha-glucosidase and alpha-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. Dieckol isolated from Ecklonia cava, a brown algae, evidenced prominent inhibitory effect against alpha-glucosidase and alpha-amylase. The IC(50) values of dieckol against alpha-glucosidase and alpha-amylase were 0.24 and 0.66 mM, respectively, which evidenced the higher activities than that of acarbose. Dieckol did not exert any cytotoxic effect in human umbilical vein endothelial cells (HUVECs) at various concentrations (from 0.33 to 2.69 mM). The increase of postprandial blood glucose levels were significantly suppressed in the dieckol administered group than those in the streptozotocin-induced diabetic or normal mice. Moreover, the area under curve (AUC) was significantly reduced via dieckol administration (259 versus 483 mmolmin/l) in the diabetic mice as well as it delays absorption of dietary carbohydrates. Therefore, these result indicated that dieckol might be a potent inhibitor for alpha-glucosidase and alpha-amylase.

BACKGROUND: Differences in the clinical course of secondary acute myeloid leukemia according to the type of the preceding disorders are not defined. We compared the outcomes of therapy-related acute myeloid leukemia, acute myeloid leukemia following myelodysplastic syndrome and acute myeloiod leukemia following myeloproliferative neoplasm. We also intended to find prognostic factors in secondary acute myeloid leukemia overall. METHODS: Retrospective medical record review at Seoul National University Hospital was performed. We assessed response to induction chemotherapy and overall survival. RESULTS: Ninety-five secondary acute myeloid leukemia patients (median age of 56.4 years) were analyzed. Twenty-six, 57 and 12 patients had therapy-related leukemia, leukemia following myelodysplastic syndrome and myeloproliferative neoplasm, respectively. For patients receiving induction chemotherapy, complete remission rate was 47.5% and complete remission rate was different according to the type of the preceding disorders (P = 0.004). Compared to therapy-related leukemia (P = 0.027) and leukemia following myelodysplastic syndrome (P = 0.050), leukemia following myeloproliferative neoplasm had shorter overall survival. In secondary leukemia, presence of trisomy 8 had a prognostic impact (P = 0.003) along with cytogenetic risk group (P = 0.016). In multivariate analysis, the type of the preceding disorders (P = 0.026), 5q deletion (P = 0.015) and trisomy 8 (P = 0.040) were independent prognostic factors. CONCLUSIONS: Prognosis of secondary acute myeloid leukemia was different according to the type of the preceding disorders with the worst prognosis in leukemia following myeloprolfierative neoplasm. Along with cytogenetic risk grouping, trisomy 8 had a poor prognostic impact in secondary acute myeloid leukemia.

For human embryonic stem cells (hESCs) to be used clinically, it is imperative that immune responses evoked by hESCs and their derivates after transplantation should be prevented. Human leukocyte antigens (HLA) and ABO blood group antigens are important histocompatibility factors in graft rejection. HLA matching between recipient and unrelated donors, in particular, is important in improving outcomes in hematopoietic cell transplantation (HCT). We have established and successfully maintained 29 hESC lines and analyzed the HLA and ABO genotypes of these lines. HLA-A, -B, C- and -DR (DRB1) genotyping was performed by polymerase chain reaction (PCR)-sequence based typing and ABO genotyping was carried out by PCR-restriction fragment length polymorphism methods. To determine what proportion of the Korean population would be covered by these cell lines in organ transplantation, 27 cell lines with HLA-A, -B, and -DR data were evaluated for HCT (cord blood) donors and 28 cell lines with HLA-DR and ABO data were evaluated for solid organ (kidney) transplantation donors, and then compared the data with those from 6740 donated cord bloods. When 2 HLA mismatches are allowed for HCT, as currently accepted for cord blood transplantation, it was estimated that about 16% and 25% of the possible recipients can find one or more donor cell lines with </=2 mismatches at A, B, DRB1 allele level and at A, B antigen/DRB1 allele level, respectively. When HLA-DR antigen level matching and ABO compatibility was considered for solid organ (kidney) transplantation, it was estimated that about 29% and 96% of the possible recipients can find one or more ABO compatible donor cell lines with 0 and 1 DR mismatches, respectively. We provided the first report on the HLA and ABO genotypes of hESC lines, and estimated the degree of HLA and ABO matching in organ transplantation for the Korean population.

(Headache 2010;**:**-**) Spontaneous intracranial hypotension (SIH) is typically characterized by orthostatic headache; however, various atypical manifestations of SIH have been reported recently. We report here the case of a 46-year-old man with headache secondary to SIH, which was nonorthostatic, triggered only when the patient shook his head. We suggest that SIH should be suspected in patients with headache induced by head-shaking, even without orthostatic features, especially when the headache is accompanied by other symptoms commonly associated with SIH.

Cellular zinc plays a key role in lysosomal change and cell death in neurons and astrocytes under oxidative stress. Here, using astrocytes lacking metallothionein-3 (MT3), a potential source of labile zinc in the brain, we studied the role of MT3 in oxidative stress responses. H(2)O(2) induced a large increase in labile zinc in wild-type (WT) astrocytes, but stimulated only a modest rise in MT3-null astrocytes. In addition, H(2)O(2)-induced lysosomal membrane permeabilization (LMP) and cell death were comparably attenuated in MT3-null astrocytes. Expression and glycosylation of Lamp1 (lysosome-associated membrane protein 1) and Lamp2 were increased in MT3-null astrocytes, and the activities of several lysosomal enzymes were significantly reduced, indicating an effect of MT3 on lysosomal components. Consistent with lysosomal dysfunction in MT3-null cells, the level of LC3-II (microtubule-associated protein 1 light chain 3), a marker of early autophagy, was increased by oxidative stress in WT astrocytes, but not in MT3-null cells. Similar changes in Lamp1, LC3, and cathepsin-D were induced by the lysosomal inhibitors bafilomycin A1, chloroquine, and monensin, indicating that lysosomal dysfunction may lie upstream of changes observed in MT3-null astrocytes. Consistent with this idea, lysosomal accumulation of cholesterol and lipofuscin were augmented in MT3-null astrocytes. Similar to the results seen in MT3-null cells, MT3 knockdown by siRNA inhibited oxidative stress-induced increases in zinc and LMP. These results indicate that MT3 may play a key role in normal lysosomal function in cultured astrocytes. (c) 2010 Wiley-Liss, Inc.

Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD-related RLS (pRLS). Sixty-three PD patients (median age 64.6 +/- 10.6 years), 40 iRLS patients (53.1 +/- 11.7 years), and 40 healthy controls (69.1 +/- 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD-RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD-RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD. (c) 2010 Movement Disorder Society.

The authors have indicated no significant interest with commercial supporters.

Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings.

The clinical course of non-severe aplastic anemia is variable, and risk factors related to disease progression are not well known. We reviewed clinical and laboratory data of the patients who were diagnosed with non-severe aplastic anemia from 1997 to 2007 at Seoul National University Hospital and analyzed the clinical course and outcomes in these patients. We defined non-severe aplastic anemia as hypocellular marrow with cytopenia in the peripheral blood, which does not meet the criteria for severe aplastic anemia (at least two of the following: ANC < 500/mul, platelet < 20,000/mul or reticulocyte < 20,000/mul). Among a total of 96 patients, 53 (55.2%) were male and the median age was 37.6 years old. As much as 41.7% (40) of the patients were initially asymptomatic. Sixty-two patients who were treated with oxymetholone, ATG/ALG, cyclosporin or other agents after initial diagnosis showed significantly lower levels of initial hemoglobin, red blood cell count and platelet count than those who did not receive any treatment. During the follow-up period, 18 patients progressed to severe aplastic anemia. Their median age was 29.9 years and the median progression time was 18 months. Initial white blood cell count and absolute neutrophil count in the evolution group tended to be lower than in the other group. The patients whose thrombocytopenia did not respond to treatment showed markedly higher frequency of progression to severe aplastic anemia. Treatment itself and responsiveness in reticulocyte and absolute neutrophil count were not correlated with their clinical courses. Sixteen patients showed overall improvement, whereas three patients developed secondary hematologic disease, acute myeloid leukemia, myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria. Non-severe aplastic anemia has a relatively indolent and mild clinical course. However, 18.8% of the study population progressed to severe disease. White blood cell and absolute neutrophil count at diagnosis and treatment responsiveness of thrombocytopenia were associated with disease progression. Careful monitoring and early management are needed for patients at risk.