Benzyl Isothiocyanate-Induced Cytotoxicity via the Inhibition of Autophagy and Lysosomal Function in AGS Cells

Gastric adenocarcinoma is among the top causes of cancer-related death and is one of the most commonly diagnosed carcinomas worldwide. Benzyl isothiocyanate (BITC) has been reported to inhibit the gastric cancer metastasis. In our previous study, BITC induced apoptosis in AGS cells. The purpose of the present study was to investigate the effect of BITC on autophagy mechanism in AGS cells. First, the AGS cells were treated with 5, 10, or 15 μM BITC for 24 h, followed by an analysis of the autophagy mechanism. The expression level of autophagy proteins involved in different steps of autophagy, such as LC3B, p62/SQSTM1, Atg5-Atg12, Beclin1, p-mTOR/mTOR ratio, and class III PI3K was measured in the BITC-treated cells. Lysosomal function was investigated using cathepsin activity and Bafilomycin A1, an autophagy degradation stage inhibitor. Methods including qPCR, western blotting, and immunocytochemistry were employed to detect the protein expression levels. Acridine orange staining and omnicathepsin assay were conducted to analyze the lysosomal function. siRNA transfection was performed to knock down the LC3B gene. BITC reduced the level of autophagy protein such as Beclin 1, class III PI3K, and Atg5-Atg12. BITC also induced lysosomal dysfunction which was shown as reducing cathepsin activity, protein level of cathepsin, and enlargement of acidic vesicle. Overall, the results showed that the BITC-induced AGS cell death mechanism also comprises the inhibition of the cytoprotective autophagy at both initiation and degradation steps.

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

Purpose@#Since diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state. @*Materials and Methods@#The anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5'-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells. @*Results@#The protein levels of phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 μM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660. @*Conclusion@#In conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.

Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors

Background@#Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts. @*Methods@#To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity. @*Results@#Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase. @*Conclusion@#The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Hyaluronic Acid Coating on Hydrophobic Tracheal Scaffold Enhances Mesenchymal Stem Cell Adhesion and Tracheal Regeneration

BACKGROUND@#Long segmental tracheal repair is challenging in regenerative medicine due to low adhesion of stem cells to tracheal scaffolds. Optimal transplantation of stem cells for tracheal defects has not been established. We evaluated the role of hyaluronic acid (HA) coating of tracheal scaffolds in mesenchymal stem cell (MSC) adhesion and tracheal regeneration in a rabbit model. @*METHODS@#A three-dimensionally printed tubular tracheal prosthesis was incubated with dopa-HA-fluorescein isothiocyanate in phosphate-buffered saline for 2 days. MSCs were incubated with an HA-coated scaffold, and their adhesion was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. HA coated scaffolds with or without MSC seeding were transplanted at the circumferential tracheal defect in rabbits, and survival, rigid bronchoscopy, radiologic findings, and histologic findings were compared between the two groups. @*RESULTS@#HA-coated scaffolds showed better MSC adhesion than non-coated scaffolds. The HA-coated scaffolds with MSC group showed a wider airway and greater mucosal regeneration compared to the HA-coated scaffolds without MSC group. @*CONCLUSION@#HA coating of scaffolds can promote MSC adhesion and tracheal regeneration.

Hyaluronic Acid Coating on Hydrophobic Tracheal Scaffold Enhances Mesenchymal Stem Cell Adhesion and Tracheal Regeneration

BACKGROUND@#Long segmental tracheal repair is challenging in regenerative medicine due to low adhesion of stem cells to tracheal scaffolds. Optimal transplantation of stem cells for tracheal defects has not been established. We evaluated the role of hyaluronic acid (HA) coating of tracheal scaffolds in mesenchymal stem cell (MSC) adhesion and tracheal regeneration in a rabbit model. @*METHODS@#A three-dimensionally printed tubular tracheal prosthesis was incubated with dopa-HA-fluorescein isothiocyanate in phosphate-buffered saline for 2 days. MSCs were incubated with an HA-coated scaffold, and their adhesion was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. HA coated scaffolds with or without MSC seeding were transplanted at the circumferential tracheal defect in rabbits, and survival, rigid bronchoscopy, radiologic findings, and histologic findings were compared between the two groups. @*RESULTS@#HA-coated scaffolds showed better MSC adhesion than non-coated scaffolds. The HA-coated scaffolds with MSC group showed a wider airway and greater mucosal regeneration compared to the HA-coated scaffolds without MSC group. @*CONCLUSION@#HA coating of scaffolds can promote MSC adhesion and tracheal regeneration.

Hypothermia Inhibits Endothelium-Independent Vascular Contractility via Rho-kinase Inhibition

The present study was undertaken to investigate the influence of hypothermia on endothelium-independent vascular smooth muscle contractility and to determine the mechanism underlying the relaxation. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Hypothermia significantly inhibited fluoride-, thromboxane A2-, phenylephrine-, and phorbol ester-induced vascular contractions regardless of endothelial nitric oxide synthesis, suggesting that another pathway had a direct effect on vascular smooth muscle. Hypothermia significantly inhibited the fluoride-induced increase in pMYPT1 level and phorbol ester-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxing effect of moderate hypothermia on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activities.

Cardamonin inhibits agonist-induced vascular contractility via Rho-kinase and MEK inhibition

The present study was undertaken to investigate the influence of cardamonin on vascular smooth muscle contractility and to determine the mechanism(s) involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Cardamonin significantly relaxed fluoride-, phenylephrine-, and phorbol ester-induced vascular contractions, suggesting that it has an anti-hypertensive effect on agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, cardamonin significantly inhibited the fluoride-induced increase in pMYPT1 level and phenylephrine-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence that the relaxing effect of cardamonin on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activity.

Combined Skin Moisturization of Liposomal Serine Incorporated in Hydrogels Prepared with Carbopol ETD 2020, Rhesperse RM 100 and Hyaluronic Acid

We investigated the combined moisturizing effect of liposomal serine and a cosmeceutical base selected in this study. Serine is a major amino acid consisting of natural moisturizing factors and keratin, and the hydroxyl group of serine can actively interact with water molecules. Therefore, we hypothesized that serine efficiently delivered to the stratum corneum (SC) of the skin would enhance the moisturizing capability of the skin. We prepared four different cosmeceutical bases (hydrogel, oil-in-water (O/W) essence, O/W cream, and water-in-oil (W/O) cream); their moisturizing abilities were then assessed using a Corneometer(R). The hydrogel was selected as the optimum base for skin moisturization based on the area under the moisture content change-time curves (AUMCC) values used as a parameter for the water hold capacity of the skin. Liposomal serine prepared by a reverse-phase evaporation method was then incorporated in the hydrogel. The liposomal serine-incorporated hydrogel (serine level=1%) showed an approximately 1.62~1.77 times greater moisturizing effect on the skin than those of hydrogel, hydrogel with serine (1%), and hydrogel with blank liposome. However, the AUMCC values were not dependent on the level of serine in liposomal serine-loaded hydrogels. Together, the delivery of serine to the SC of the skin is a promising strategy for moisturizing the skin. This study is expected to be an important step in developing highly effective moisturizing cosmeceutical products.

Extremely Low Frequency Magnetic Field Modulates the Level of Neurotransmitters

This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and gamma -aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized.

Anti-inflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats

It has been shown that the extracts including eupatilin and quercetin-3-beta-D-glucuronopyranoside had mucoprotective effects on the esophagus and stomach through their antioxidant activities. This study was designed to investigate the anti-inflammatory effect of these flavonoid compounds in an animal model of inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulfonic acid. Experimental colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid. Extracts including eupatilin or quercetin-3-beta-D-glucuronopyranoside were orally administered to animals 48, 24, and 1 h prior to the induction of colitis and then again 24 h later. The animals were sacrificed 48 h after by 2,4,6-trinitrobenzene sulfonic acid treatment and the macroscopic appearance of the colonic lesions was scored in a blinded manner on a scale of 1 to 10. The inflammatory response to colitis induction was assessed by measuring myeloperoxidase activity, nitric oxide production, tumor necrosis factor-alpha expression, total glutathione levels, and malondialdehyde concentrations in the colon. The results indicated that extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside dose-dependently improved the morphology of the lesions induced by 2,4,6-trinitrobenzene sulfonic acid and reduced the ulcer index accordingly. In addition, rats receiving extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside showed significantly decreased levels of mucosal myeloperoxidase activity, nitric oxide production, tumor necrosis factor-alpha expression, and malondialdehyde levels, and increased total glutathione levels. Extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside ameliorated the inflammatory response and colonic injury in acute colitis by decreasing oxidative stress and neutrophil activation. Extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside may inhibit acute colitis.

Pectin Micro- and Nano-capsules of Retinyl Palmitate as Cosmeceutical Carriers for Stabilized Skin Transport

Retinyl palmitate (RP)-loaded pectinate micro- and nano-particles (PMP and PNP) were designed for stabilization of RP that is widely used as an anti-wrinkle agent in anti-aging cosmeceuticals. PMP/PNP were prepared with an ionotropic gelation method, and anti-oxidative activity of the particles was measured with a DPPH assay. The stability of RP in the particles along with pectin gel and ethanolic solution was then evaluated. In vitro release and skin permeation studies were performed using Franz diffusion cells. Distribution of RP in each skin tissue (stratum corneum, epidermis, and dermis) was also determined. PMP and PNP could be prepared with mean particle size diameters of 593~843 mum (PMP) and 530 nm (i.e., 0.53 mum, PNP). Anti-oxidative activity of PNP was greater than PMP due largely to larger surface area available for PNP. The stability of RP in PMP and PNP was similar but much greater than RP in pectin bulk gels and ethanolic solution. PMP and PNP showed the abilities to constantly release RP and it could be permeated across the model artificial membrane and rat whole skin. RP was serially deposited throughout the skin layers. This study implies RP loaded PMP and PNP are expected to be advantageous for improved anti-wrinkle effects.

Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model

BACKGROUND: It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1). METHODS: In this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice. RESULTS: The GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt)/phospho-glycogen synthase kinase3beta (p-GSK3beta), phospho-extracellular signal-related kinase (p-ERK), and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK), Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist. CONCLUSION: The results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

Effect of ECQ on Iodoacetamide-Induced Chronic Gastritis in Rats

This study investigated effect of extract containing quercetin-3-O-beta-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.

Anti-Oxidative Activity of Pectin and Its Stabilizing Effect on Retinyl Palmitate

The purpose of this study was to examine the anti-oxidative activity of pectin and other polysaccharides in order to develop a cosmeceutical base having anti-oxidative effects towards retinyl palmitate (RP). The anti-oxidative stabilizing effects of pectin and other polysaccharides on RP were evaluated by DPPH assay and then the stabilizing effect of pectin on RP was examined as a function of time. Among the polysaccharides we examined, pectin exhibited a considerably higher anti-oxidative activity, with an approximately 5-fold greater DPPH radical scavenging effect compared to other polysaccharides. The DPPH radical scavenging effect of pectin increased gradually with increasing concentrations of pectin. At two different RP concentrations, 0.01 and 0.1% in ethanol, addition of pectin improved the stability of RP in a concentration dependent manner. The stabilizing effect of pectin on RP was more effective for the lower concentration of RP (0.01%, v/v). Further, degradation of RP was reduced following the addition of pectin as measured over 8 hours. From the results obtained, it can be suggested that pectin may be a promising ingredient for cosmeceutical bases designed to stabilize RP or other pharmacological agents subject to degradation by oxidation.

Impact of Micellar Vehicles on in situ Intestinal Absorption Properties of Beta-Lapachone in Rats

The aim of the present study was to examine the effect of micellar systems on the absorption of beta-lapachone (b-lap) through different intestinal segments using a single-pass rat intestinal perfusion technique. B-lap was solubilized in mixed micelles composed of phosphatidylcholine and sodium deoxycholate, and in sodium lauryl sulfate (SLS)-based conventional micelles. Both mixed micelles and SLS micelles improved the in situ permeability of b-lap in all intestinal segments tested although the mixed micellar formulation was more effective in increasing the intestinal absorption of b-lap. The permeability of b-lap was greatest in the large intestinal segments. Compared with SLS micelles, the effective permeability coefficient values measured with mixed micelles were 5- to 23-fold higher depending on the intestinal segment. Our data suggest that b-lap should be delivered to the large intestine using a mixed micellar system for improved absorption.

The Inhibitory Effect of Eupatilin on the Agonist-Induced Regulation of Vascular Contractility

The present study was undertaken to investigate the influence of eupatilin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Eupatilin more significantly relaxed fluoride-induced vascular contraction than thromboxane A2 or phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, eupatilin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of eupatilin on agonist-induced vascular contraction regardless of endothelial function.

Protective Effect of Phosphatidylcholine on Lipopolysaccharide-Induced Acute Inflammation in Multiple Organ Injury

Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-alpha, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-alpha and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.

Nontuberculous Mycobacteria Isolated from Respiratory Specimens during Recent Two Years: Distribution and Clinical Significance / 대한임상미생물학회지

BACKGROUND: The isolation of nontuberculous mycobacteria (NTM) has been increasing worldwide as well as its clinical importance. The aim of this study was to investigate the distribution and clinical significance of NTM that has been isolated from respiratory specimens during a recent two-year period at a tertiary hospital. METHODS: We analyzed respiratory samples that were obtained between January 2009 and December 2010 for AFB culture. We retrospectively reviewed the electronic medical records of these patients to obtain both clinical and radiologic information. NTM pulmonary disease was defined by using the guidelines provided by the America Thoracic Society/Infectious Diseases Society of America. RESULTS: Among the 1,601 specimens that resulted in a positive AFB culture, 310 (19.4%) were NTM. In 189 patients, the most common isolate was M. avium-intracellulare complex (MAC) (127, 67.2%), which was then followed by M. abscessus (31, 16.4%), M. fortuitum (10, 5.3%), M. kansasii (9, 4.8%), and other NTM species. Of these, 93 (49.2%) patients were diagnosed with NTM pulmonary disease. MAC, M. abscessus, and M. kansasii were more virulent than the other species. None of the cases of NTM pulmonary disease were caused by M. fortuitum, M. chelonae, M. peregrinum, M. terrae complex, or M. gordonae. CONCLUSION: In Korea, the prevalence of NTM isolates is increasing, as are the cases of pulmonary disease. The pathogenic potential of NTM differs enormously by species and as a result the treatment of NTM lung disease depends on which species has caused the infection. The isolation and identification of NTM isolated from respiratory specimens are mandatory in order for clinical microbiology laboratories to make an accurate diagnosis and suggest the proper treatment of the NTM disease.

A Case of B-cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-cell Lymphoma and Burkitt Lymphoma in a Korean Child

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL), is a heterogeneous group with some features resembling DLBCL and others resembling BL. Here, we report a case of intermediate DLBCL/BL in a Korean child. A 2-yr-old male was admitted for evaluation and management of left hip pain. Immunohistochemistry of a biopsy of the femur neck revealed tumor cells positive for CD20, CD10, BCL2, BCL6, and Ki67. A bone marrow (BM) aspirate smear revealed that 49.3% of all nucleated cells were abnormal lymphoid cells, composed of large- and medium-sized cells. Immunophenotyping of the neoplastic cells revealed positivity for CD19, CD10, CD20, and sIg lambda and negativity for CD34, Tdt, and myeloperoxidase (MPO). Cytogenetic and FISH analyses showed a complex karyotype, including t(8;14)(q24.1;q32) and IGH-MYC fusion. Intensive chemotherapy was initiated, including prednisone, vincristine, L-asparaginase, daunorubicin, and central nervous system prophylaxis with intrathecal methotrexate (MTX) and cytarabine. One month after the initial diagnosis, BM examination revealed the persistent of abnormal lymphoid cells; cerebrospinal fluid cytology, including cytospin, showed atypical lymphoid cells. The patient was treated again with cyclophosphamide, vincristine, prednisone, adriamycin, MTX, and intrathecal MTX and cytarabine. The patient died of sepsis 5 months after the second round of chemotherapy.

Influence of Exposure to Extremely Low Frequency Magnetic Field on Neuroendocrine Cells and Hormones in Stomach of Rats

Extremely low frequency magnetic fields (ELF-MF) have the ability to produce a variety of behavioral and physiological changes in animals. The stomach, as the most sensitive part of the neuroendocrine organ of the gastrointestinal tract, is crucial for the initiation of a full stress response against all harmful stress. Thus, the purpose of this study was to examine whether ELF-MF stimuli induce changes in the activity of neuroendocrine cells, considering their involvement in endocrine or paracrine effect on surrounding cells. The exposure to ELF-MF (durations of 24 h and 1 or 2 weeks, 60 Hz frequency, 0.1 mT intensity) altered the distribution and occurrence of gastrin, ghrelin and somatostatin-positive endocrine cells in the stomach of rats. The change, however, in the secretion of those hormones into blood from endocrine cells did not appear significantly with ELF-MF exposure. Comparing with sham control, ELF-MF exposure for 1 and 2 week induced an increase in BaSO4 suspension propelling ratio of gastrointestinal tract, indicating that ELF-MF affects gastrointestinal motility. Our study revealed that ELF-MF exposure might influence the activity of endocrine cells, an important element of the intrinsic regulatory system in the digestive tract. The pathophysiological character of these changes and the mechanism responsible for neuroendocrine cell are still unclear and require further studies.