Experimental carcinogenesis with 7, 12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates / Carcinogénesis experimental con 7, 12-dimetilbenzantraceno (DMBA) y su inhibición con isitiocianatos

Introduction: DMBA is a chemical carcinogen that induces carcinomas within a few weeks of its application. We developed an experimental model of carcinogenesis induced by DMBA dissolved in 0,5% paraffin oil (DMBA-PO), verifying the inhibitory effect of the carcinogenicity of phenyl isothiocyanate (PhITC), phenethyl (PhnITC) and benzyl isothiocyanate (BITC). Material and Methods: For this, 88 hamsters were distributed into three groups: one exposed to DMBA-PO (Group 1, n=12), three subgroups (n=12) exposed to PhITC, PhnITC, BITC and DMBA-PO (Group 2, n=36) and four control subgroups (n=10) that were not exposed to the carcinogen in which PO (paraffin oil) and isothiocyanates were applied (Group 3, n=40). Results: The experiment had a duration of 20 weeks, at the end of which the inhibitory effect was established by comparing the lesions developed in the groups that received isothiocyanates with the group that was only treated with DMBA-PO. The carcinogenic effect of DMBA-PO is 100% (35 carcinomas) and the inhibitory effect was 0, whereas in the presence of isothiocyanates the carcinogenic effect decreases, with an inhibitory effect of 86% for BITC (5 carcinomas) and 74% for PhITC (9 carcinomas). Conclusion: The inhibitory effect for PhnITC is 80% in relation to invasive OSCC (1 carcinoma).

Introducción: El DMBA es un carcinógeno químico que induce carcinomas a las pocas semanas de su aplicación. Desarrollamos un modelo experimental de carcinogénesis inducida por DMBA disuelto en aceite de parafina al 0,5% (DMBA-Ap) comprobando el efecto inhibidor de la carcinogénesis de los isotiocianatos fenil (PhITC), fenetil (PhnITC) y bencil isotiocianato (BITC). Material y Métodos: Para ello, se distribuyeron 88 hámsteres en 3 grupos: uno expuesto al DMBA-Ap (Grupo 1, n=12), tres subgrupos (n=12) expuestos a PhITC, PhnITC, BITC y DMBA-Ap (Grupo 2, n=36) y cuatro subgrupos controles (n=10), no expuestos al carcinógeno en el que se aplicaron Ap e isotiocianatos (Grupo 3, n=40). Resultados:El experimento tuvo una duración de 20 semanas, al final de la cual se establece de forma comparativa el efecto inhibidor comparando las lesiones desarrolladas en los grupos que recibieron isotiocianatos con respecto al grupo tratado sólo con DMBA-Ap. El efecto carcinógeno del DMBA-Ap es del 100% (35 carcinomas) y el efecto inhibidor 0, mientras que en presencia de isotiocianatos el efecto carcinógeno disminuye, con un efecto inhibidor del 86% para BITC (5 carcinomas) y del 74% para el PhITC (9 carcinomas). Conclusión:El efecto inhibidor del PhnITC es del 80% en relación con el COCE invasivo (1 carcinoma).

Application of lectins for detection of glycomic differences in the epididymal duct in water buffalo (Bubalus bubalis) and dromedary camel (Camelus dromedarius) / Aplicación de lectinas para la detección de diferencias glucómicas en el conducto epididimario en búfalos de agua (Bubalus bubalis) y dromedarios (Camelus dromedarius)

SUMMARY: The present study was conducted to detect the differences in glycohistochemical features in the epididymal duct of the dromedary camel and the water buffalo. Epididymal sections (caput, corpus and cauda) from both species were stained with fluorescein isothiocyanate (FITC) conjugated lectins. Binding sites for five lectins (DBA, GSA-1, HPA, PNA and WGA) have been found in both species. The binding sites of different lectins showed significant variations in the pattern of distribution in both a species. This included both species-specific and region-specific order. Additionally, only three (GSA-1, PNA and WGA) out the five lectins studied exhibited binding sites in all epididymal regions in both species. The other two lectins (DBA and HPA) followed the same order recorded for the other three (GSA-1, PNA and WGA) in buffalo, but failed to show any binding sites in cauda epididymis in camel. In conclusion, the variable regional and species-specific distribution features of lectins revealed that both species have diverse glycomic characteristics that may be related to their different reproductive patterns. However, the glycome-associated functional capacities remain obscured and need further profound investigations.

RESUMEN: El presente estudio se realizó para detectar las diferencias en las características glicohistoquímicas del conducto epididimal del dromedario y el búfalo de agua. Las secciones del epidídimo (cabeza, cuerpo y cola) de ambas especies se tiñeron con lectinas conjugadas con isotiocianato de fluoresceína (FITC). Se encontraron sitios de unión para cinco lectinas (DBA, GSA-1, HPA, PNA y WGA) en ambas especies. Los sitios de unión de diferentes lectinas mostraron variaciones significativas en el patrón de distribución en ambas especies. Esto incluía tanto el orden específico de la especie como el específico de la región. Además, solo tres (GSA-1, PNA y WGA) de las cinco lectinas estudiadas exhibieron sitios de unión en todas las regiones del epidídimo en ambas especies. Las otras dos lectinas (DBA y HPA) siguieron el mismo orden registrado para las tres restantes (GSA-1, PNA y WGA) en búfalos, pero no mostraron ningún sitio de union en la cola del epidídimo en camellos. En conclusión, las características de distribución regionales y específicas de especies variables de las lectinas revelaron que ambas especies tienen características glucómicas diversas que pueden estar relacionadas con sus diferentes patrones reproductivos. Sin embargo, las capacidades funcionales asociadas con el glicoma permanecen desconocidas y requieren mayor investigación.

Effect and Mechanism of Sulforaphane on G / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of sulforaphane (SFN) on G@*METHODS@#KG1a and KG1cells were treated by different concentrations of SFN for 48 h. Flow cytometry (FCM) was used to analyze the phase distribution of cell cycle. High-throughput sequencing was used to detect the effect of SFN on the expression of cell cycle related genes in KG1a cells. The mRNA expression of P53, P21, CDC2 and CyclinB1 were detected by qPCR. The protein expression of P53, CDC2, P-CDC2 and CyclinB1 were detected by Western blot.@*RESULTS@#Cells in the G@*CONCLUSION@#SFN induces leukemia cells to block in G

Benzyl isothiocyanate inhibits invasion and induces apoptosis via reducing S100A4 expression and increases PUMA expression in oral squamous cell carcinoma cells

Benzyl isothiocyanate (BITC) has been shown to inhibit invasion and induce apoptosis of various types of cancer. However, its role on human oral squamous cell carcinoma (OSCC) cells is still not well elucidated. In the present study, we investigated the effect of BITC on apoptosis and invasion of SCC9 cells, and its underlying mechanisms in vitro and in vivo. SCC9 cells were exposed to BITC (5 and 25 μM) for 24 and 48 h. Cell growth, apoptosis, invasion, and migration were detected in vitro by MTT, FITC-conjugated annexin V/propidium iodide staining followed by flow cytometry, Matrigel-coated semi-permeable modified Boyden, and wound-healing assay. S100A4, PUMA, and MMP-9 expressions were detected to investigate its mechanisms. Xenotransplantation experiments were used to investigate the role of BITC on tumor growth and lung metastasis. BITC inhibited cell viability and induced cell apoptosis in a dose- and time-dependent manner through upregulation of PUMA signals. BITC inhibited cell invasion and migration by downregulation of S100A4 dependent MMP-9 signals. The ip administration of BITC reduced tumor growth but not lung metastasis of SCC9 cells subcutaneously implanted in nude mice. BITC treatment activated pro-apoptotic PUMA and inhibited S100A4-dependent MMP-9 signals, resulting in the inhibition of cell growth and invasion in cultured and xenografted SCC9 cells. Thereby, BITC is a potential therapeutic approach for OSCC.

Mechanism of Cinnamomi Ramulus improving rat model of intrahepatic cholestasis induced by ANIT by regulating FXR pathway / 中国中药杂志

To study the mechanism and action of Cinnamomi Ramulus in ameliorating intrahepatic cholestasis induced by α-isothiocyanate( ANIT) in rats by regulating FXR pathway. Forty SD rats were randomly divided into normal group,model group,positive control( ursodeoxycholic acid) group( 60 mg·kg~(-1)),Cinnamomi Ramulus treatment( 60 mg·kg~(-1)·d~(-1)) group,and Cinnamomi Ramulus treatment( 20 mg·kg~(-1)·d~(-1)) group,with 8 rats in each group. Except for the normal control group,the other groups were intragastrically administered with the corresponding concentrations of continuous aqueous solution( 0. 005 m L·g~(-1)),once a day,for 7 days.Except for the normal group,the other groups were treated with ANIT( 100 mg·kg~(-1)),once a day,for 3 days. Blood was taken from the abdominal aorta 24 hours after the last administration,and serum alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBi L),and total bile acid( TBA) were measured. 1. 5-2 cm of rat liver tissue was taken. After fixation with10% formaldehyde,paraffin-embedded sections were taken,HE staining was performed,and immunohistochemistry( IHC) was used to analyze the expression of FXR. RNA and protein were extracted from rat liver tissue to detect FXR mRNA expression,as well as bile acid synthesis and detoxification,transport related SHP,UGT2 B4,BSEP protein expressions at downstream of FXR. Compared with the normal group,serum ALT,AST,TBi L,and TBA levels were elevated in the model group( P<0. 01),liver damage was severe,FXR protein's optical density decreased,FXR mRNA expression decreased,and SHP,UGT2 B4,BSEP protein expressions were decreased( P<0. 05,P<0. 01). Compared with the model group,the drug group could reduce serum ALT,AST,TB,TBA levels to different degrees( P<0. 05,P<0. 01),alleviate liver tissue damage,increase the optical density of FXR protein,and promote the expressions of FXR mRNA and FXR,SHP,BSEP and UGT2 B4 proteins( P<0. 05,P<0. 01). Cinnamomi Ramulus can alleviate ANIT-induced intrahepatic cholestasis,and reduce hepatocyte injury and serum ALT,AST,TBi L and TBA levels. The mechanism may be through FXR-SHP,FXR-UGT2 B4,FXR-BSEP signaling pathways. Therefore,in the pathogenesis of intrahepatic cholestasis,we can try to further explore in alleviating intrahepatic cholestasis with Cinnamomi Ramulus,so as to provide effective drugs for clinical treatment of intrahepatic cholestasis.

Role of sulforaphane in improving negative symptoms and cognitive symptoms of schizophrenia and the underlying mechanism / 中南大学学报(医学版)

The negative symptoms and cognitive symptoms of schizophrenia patients are still clinical problems to be solved. Schizophrenia patients are abnormal in oxidative stress, immune regulation, and anti-histone deacetylase (HDAC), while sulforaphane plays a role in anti-oxidative stress, anti-inflammation, and anti-HDAC. Therefore, the sulforaphane could improve the negative symptoms and cognitive deficits of schizophrenia.

Alyssin and Iberin in Cruciferous Vegetables Exert Anticancer Activity in HepG2 by Increasing Intracellular Reactive Oxygen Species and Tubulin Depolymerization

To determine the chemopreventive potential of alyssin and iberin, the in vitro anticancer activities and molecular targets of isothiocyanates (ITCs) were measured and compared to sulforaphane in hepatocellular carcinoma cell HepG2. The SR-FTIR spectra observed a similar pattern vis-à-vis the biomolecular alteration amongst the ITCs-treated cells suggesting a similar mode of action. All of the ITCs in this study cause cancer cell death through both apoptosis and necrosis in concentration dependent manner (20–80 μM). We found no interactions of any of the ITCs studied with DNA. Notwithstanding, all of the ITCs studied increased intracellular reactive oxygen species (ROS) and suppressed tubulin polymerization, which led to cell-cycle arrest in the S and G₂/M phase. Alyssin possessed the most potent anticancer ability; possibly due to its ability to increase intracellular ROS rather than tubulin depolymerization. Nevertheless, the structural influence of alkyl chain length on anticancer capabilities of ITCs remains inconclusive. The results of this study indicate an optional, potent ITC (viz., alyssin) because of its underlying mechanisms against hepatic cancer. As a consequence, further selection and development of effective chemotherapeutic ITCs is recommended.

Analysis of a suppressive subtractive hybridization library of Alternaria alternata resistant to 2-propenyl isothiocyanate

Background Isothiocyanates (ITCs) are natural products obtained from plants of the Brassicas family. They represent an environmentally friendly alternative for the control of phytopathogenic fungi. However, as it has been observed with synthetic fungicides, the possibility of inducing ITC-resistant strains is a major concern. It is, therefore, essential to understanding the molecular mechanisms of fungal resistance to ITCs. We analyzed a subtractive library containing 180 clones of an Alternaria alternata strain resistant to 2-propenyl ITC (2-pITC). After their sequencing, 141 expressed sequence tags (ESTs) were identified using the BlastX algorithm. The sequence assembly was carried out using CAP3 software; the functional annotation and metabolic pathways identification were performed using the Blast2GO program. Results The bioinformatics analysis revealed 124 reads with similarities to proteins involved in transcriptional control, defense and stress pathways, cell wall integrity maintenance, detoxification, organization and cytoskeleton destabilization; exocytosis, transport, DNA damage control, ribosome maintenance, and RNA processing. In addition, transcripts corresponding to enzymes as oxidoreductases, transferases, hydrolases, lyases, and ligases, were detected. Degradation pathways for styrene, aminobenzoate, and toluene were induced, as well as the biosynthesis of phenylpropanoid and several types of N-glycan. Conclusions The fungal response showed that natural compounds could induce tolerance/resistance mechanisms in organisms in the same manner as synthetic chemical products. The response of A. alternata to the toxicity of 2-pITC is a sophisticated phenomenon including the induction of signaling cascades targeting a broad set of cellular processes. Whole-transcriptome approaches are needed to elucidate completely the fungal response to 2-pITC.

Cancer Therapy with Phytochemicals: Present and Future Perspectives / 生物医学与环境科学（英文）

Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e. rottlerin, berbamine, sparstolonin B, sulforaphane, plumbagin and 6-shogaol. These compounds are used as bioactive markers for cytotoxicity against tumors. As such, understanding their mode of action will provide the rationale for the combination strategies of these compounds with other drugs in the battle against cancer.

The Effects of Broccoli Sprout Extract Containing Sulforaphane on Lipid Peroxidation and Helicobacter pylori Infection in the Gastric Mucosa

BACKGROUND/AIMS: The aims of this study were to investigate whether a broccoli sprout extract containing sulforaphane (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosal damage. METHODS: The enrolled subjects were randomized in a double-blinded manner into three groups. Finally, 33 H. pylori (+) BSES treatment subjects (group A), 28 H. pylori (+) placebo subjects (group B), and 28 H. pylori (-) BSES treatment subjects (group C) were studied. H. pylori infection density was indirectly quantified by a 13C-urea breath test (UBT), and the ammonia concentration in gastric juice aspirates was measured through gastroscopic examination. Malondialdehyde (MDA), an oxidative damage biomarker, and reduced glutathione (GSH), an antioxidant biomarker, were measured in the gastric mucosa by an enzyme-linked immunosorbent assay. RESULTS: BSES treatment did not significantly affect the UBT values or ammonia concentration in group A (p=0.634 and p=0.505, respectively). BSES treatment did significantly reduce mucosal MDA concentrations in group A (p<0.05) and group C (p<0.001), whereas the gastric mucosal GSH concentrations did not differ before and after treatment in any of the groups. CONCLUSIONS: BSES did not inhibit the H. pylori infection density. However, BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis.

Protective effects of sulforaphane on the oxidative damage of kidney mitochondria complex in obese rats induced by high-fat diet / 中华预防医学杂志

<p><b>OBJECTIVE</b>To realize the oxidative damage of kidney mitochondrial complex in obese rats induced by high-fat diet and investigate the protective effects of sulforaphane against the damage.</p><p><b>METHODS</b>Eighty-eight adult male SD rats were used, after 1 week adaptability feeding, 8 rats were selected as control group and given low-fat diet. The other 80 rats were given high-fat diet. After 2 weeks, the 32 diet-induced obesity models were choosen whose weight gain was higher than 40%. The 32 rats were randomly divided into 4 groups, i.e. high fat group, high fat+sulforaphane low dose group, high fat+sulforaphane middle dose group and high fat+sulforaphane high dose group. The rats in the sulforaphane low, middle and high dose groups were orally administered with sulforaphane 5, 10 and 20 mg/kg, all the 4 groups were kept feeding high-fat diet for 5 weeks. All rats were sacrificed and their kidneys were removed to assay the index of oxidative damages.</p><p><b>RESULTS</b>The content of ROS (0.26 ± 0.04) and MDA((0.87 ± 0.05) U/mg) in the hight-fat group were significantly higher than those in the control group((0.20 ± 0.02),(0.57 ± 0.08) U/mg)(t values were -3.02 and -4.72, P < 0.05). The activity of T-AOC((0.43 ± 0.04) U/mg) and MMP (12.09 ± 1.56) were lower than the control group ((0.48 ± 0.04 U/mg, (16.08 ± 3.12) )(t values were 2.06 and 2.28, P < 0.05). Gavage intervention with sulforaphane, the MDA amount ((0.67 ± 0.05), (0.55 ± 0.05), (0.56 ± 0.07) U/mg) in the sulforaphane low, middle and high dose groups were lower than the hight-fat group ((0.87 ± 0.05) U/mg (t values were 3.65, 5.71 and 5.60. P < 0.05). The activity of T-AOC ((0.49 ± 0.05), (0.55 ± 0.05), (0.54 ± 0.04) U/mg), T-SOD ((61.07 ± 2.79), (55.95 ± 2.39), (60.26 ± 6.02) U/mg) and the level of MMP ((17.17 ± 2.52), (18.24 ± 2.54), (18.21 ± 3.65)) were higher than in the high-fat group ((0.43 ± 0.04) U/mg,(47.22 ± 2.43) U/mg,(12.09 ± 1.56)) (tT-AOC values were -2.36, -4.83 and -4.30; tT-SOD values were -6.37, -4.71 and -5.99; tMMP values were -2.90, -3.52 and -3.50, P < 0.05). The activity of GSH-Px in the sulforaphane low and middle dose groups ((69.12 ± 8.63), (64.43 ± 6.58) U/mg) were higher than those in the high-fat group((53.03 ± 5.70) U/mg)(t values were -3.82 and -2.71, P < 0.05). But there were no significant difference between the high dose group ((60.02 ± 7.05) U/mg) and the high-fat group (t = -1.66, P > 0.05).</p><p><b>CONCLUSION</b>High-fat diet can induce the mitochondrial oxidative dysfunction in kidney, and sulforaphane shows protective effect on the kidney mitochondrial complex from oxidative damage in obese rats induced by high-fat diet.</p>

A case-control study on the association between urinary levels of isothiocyanates and the risk of pancreatic cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between urinary levels of isothiocyanates (ITCs) and the risk of pancreatic cancer in urban Shanghai.</p><p><b>METHODS</b>A case-control study has been conducted in urban Shanghai. The cases (from December 2006 to December 2008) were identified through an newly established "instant case reporting" system. The high performance liquid chromatography (HPLC) method was applied to determine the urinary levels of isothiocyanates in 390 cases and 414 controls. A food-frequency questionnaire was administered to estimate cruciferous vegetables consumption and dietary ITC exposure.Non-conditional logistic regression model was used to analyze the relationship between dietary and urinary levels of isothiocyanates and the risk of pancreatic cancer.</p><p><b>RESULTS</b>The cruciferous vegetables intake and ITC consumption, urinary ITC levels (median (P25, P75)) were 95.0 (66.9, 135.8) g/d, 11.0 (7.1, 16.0) µmol/d, 0.95 (0.12, 2.92) µmol/g Cr respectively in cases, all lower than those in controls, separately 107.4 (80.1, 154.1) g/d, 12.3 (8.0, 18.0) µmol/d, 1.78 (0.53, 5.28) µmol/g Cr. The differences were statistically significant (t = 3.75, 3.03, 4.40, all P values <0.01). Urinary levels of ITCs in controls were correlated with cruciferous vegetables consumption and dietary ITC exposure (r = 0.189, 0.201, all P values <0.01). There was inverse association between urinary ITCs and the risk of pancreatic cancer after adjusting for possible confounding factors such as age, sex, history of diabetes and pancreatitis. Compared with the first tertile (<0.825 µmol/g Cr), the odds ratio (95%CI) for the second (0.825-3.342 µmol/g Cr) and third tertiles ( ≥ 3.343 µmol/g Cr) were 0.69 (0.49-0.97) and 0.47(0.33-0.68), respectively, Ptrend<0.01.High levels of cruciferous vegetables or ITC consumption were associated with a reduced risk of pancreatic cancer (all P trend <0.05).</p><p><b>CONCLUSION</b>indicated that high levels of dietary ITC exposure might reduce the risk of pancreatic cancer.</p>

Studies on statistical optimization of sulforaphane production from broccoli seed

Background: Natural sulforaphane (SF) has been of increasing interest for nutraceutical and pharmaceutical industries due to its anti-cancer effect. The main objective of the present work was to optimize the production of SF from broccoli seed using response surface methodology. Results: Three major factors (hydrolysis time, water volume and ethyl acetate volume) were screened out through Plackett-Burman (PB) factorial design. The methods of steepest ascent combined with central composite design (CCD) were employed for optimization of the SF production process. The optimal extraction conditions for SF production were a hydrolysis time of 13 min, a hydrolysis volume/weight ratio of 2.9:1 (v/g) and an extraction volume/weight ratio of 17.5:1 (v/g). The maximum SF yield was 14.8 ± 0.1 mg/g, a value that was in perfect agreement with the actual experimental value (14.8 mg/g). Conclusions: These results suggested that PB design combined with CCD were proved effective in screening and optimization of the parameters of SF production.

Effect of phenylhexyl isothiocyanate on Wnt/beta-catenin signaling pathway in Jurkat cell line / 中国实验血液学杂志

This study was purposed to investigate the effect of phenylhexyl isothiocyanate (PHI) on Wnt/β-catenin signaling pathway, histone acetylation, histone methylation and cell apoptosis in Jurkat cell line. The viability of Jurkat cells after treatment with PHI was tested by MTT. Apoptotic rate of Jurkat cells was measured by flow cytometry. The levels of Wnt/β-catenin related proteins including β-catenin, TCF, c-myc, and cyclinD1, histone acetylated H3 and H4, histone methylated H3K9 and H3K4 were detected by Western blot. The results showed that PHI inhibited the cell growth and induced apoptosis in Jurkat cells in time-and dose-dependent manners. Its IC50 at 48 h was about 20 µmol/L. Expression of histone acetylated H3, H4 and histone methylated H3k4 increased after exposure to PHI for 3 h, while histone methylated H3K9 decreased. Expression of β-catenin was not changed after exposure to PHI for 3 h, but expression of β-catenin, and its cell cycle-related genes such as TCF, c-myc and cyclinD1 decreased after exposure to PHI for 7 h. It is concluded that PHI regulates acetylation and methylation of histone, inhibits Wnt/β-catenin signal pathway, and is able to induce apoptosis and inhibits growth of Jurkat cells.

Effect of phenylhexyl isothiocyanate on drug-resistance to imatinib in K562/G01 cell line / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of phenylhexyl isothiocyanate (PHI) on the drug-resistance to imatinib in K562/G01 cell line and to elucidate its possible mechanisms.</p><p><b>METHODS</b>MTT assay was employed to access K562/G01 cell growth inhibition after exposure to PHI and/or imatinib at different concentrations. Apoptotic rate of K562/G01 cells was measured by flow cytometry. The levels of P-gp, P210(bcr-abl) and p-P210(bcr-abl) protein were detected by Western blot.</p><p><b>RESULTS</b>PHI inhibited proliferation and induced apoptosis of K562/G01 cells after treated with PHI alone for 24 h. PHI concentration increased from 0 to 40 µmol/L, the inhibitory rate of cell proliferation from 0 to (51.22 ± 1.41)%, and the apoptosis rate from (3.76 ± 1.46)% to (35.35 ± 3.70)%. Combination of 10, 20, 40 µmol/L PHI and various concentrations of imatinib, IC50 s of imatinib were (10.49 ± 1.24), (6.33 ± 1.42), and (0.85 ± 0.17) µmol/L, respectively. When K562/G01 cells treated with 20 µmol/L PHI combined with 10 and 20µmol/L imatinib for 24 hours, apoptosis rate were (43.62 ± 4.23)% and (55.41 ± 4.35)%, respectively, being significantly higher than that with imatinib or PHI alone. PHI concentrations increased from 0 to 40 µmol/L for 7 hours, the P210(bcr-abl)/β-actin decreased from (0.944 ± 0.034) to (0.392 ± 0.025), and the p-P210(bcr-abl)/β-actin decreased from (0.906 ± 0.019) to (0.361 ± 0.021), while the alteration of P-gp was not seen.</p><p><b>CONCLUSIONS</b>PHI inhibits the proliferation and induces apoptosis of K562/G01 cell line. PHI has synergistic effect with imatinib. It partially reverses the drug-resistance to imatinib. The mechanism of reversal of drug resistance in K562/G01 cells might be by inhibiting P210(bcr-abl) and p-P210(bcr-abl).</p>

Five Year Experience of Preexposure and Postexposure Rabies Prophylaxis in Korean Children at the National Medical Center / 소아감염

PURPOSE: This study aims to investigate preexposure prophylaxis and postexposure prophylaxis of rabies that the National Medical Center (NMC) handled and to check whether appropriate measures were performed according to the recent domestic and overseas guidelines after animal bites. METHODS: This study surveyed 41 people who were 18 years or under and received preexposure and postexposure prophylaxis of rabies at the NMC from November 2006 to December 2011. Their medical records were reviewed for their age, gender, the reason for preexposure prophylaxis, the body sites of animal bite, the kind of the animal that bit children, the region where the biting occurred and rabies vaccination and inoculation of immunoglobulin. RESULTS: Eleven children took rabies vaccination for preexposure prophylaxis and 30 children received post exposure prophylaxis of rabies. Of patients who were bitten by unvaccinated animals including wild animals or by animals which were not certain to be vaccinated, 50% (13 of 26 children) received postexposure prophylaxis, while 75% (3 of 4 children) of patients who were bitten by vaccinated animals received postexposure prophylaxis of rabies. Ten of 30 bitten patients knew whether or not the biting animals had received rabies vaccination. Of them, four people (40%) were bitten by animals which had received rabies vaccination. CONCLUSION: To prevent the occurrence of rabies, people and health care providers need to correctly understand latest guideline for rabies preexposure and postexposure prophylaxis and the information for bitten patient, biting animal and area at bitten by animal should be accurately recorded.

Physical stability of arginine-glycine-aspartic acid peptide coated on anodized implants after installation

PURPOSE: The aim of this study was to evaluate the stability of arginine-glycine-aspartic acid (RGD) peptide coatings on implants by measuring the amount of peptide remaining after installation. MATERIALS AND METHODS: Fluorescent isothiocyanate (FITC)-fixed RGD peptide was coated onto anodized titanium implants (width 4 mm, length 10 mm) using a physical adsorption method (P) or a chemical grafting method (C). Solid Rigid Polyurethane Foam (SRPF) was classified as either hard bone (H) or soft bone (S) according to its density. Two pieces of artificial bone were fixed in a customized jig, and coated implants were installed at the center of the boundary between two pieces of artificial bone. The test groups were classified as: P-H, P-S, C-H, or C-S. After each installation, implants were removed from the SRPF, and the residual amounts and rates of RGD peptide in implants were measured by fluorescence spectrometry. The Kruskal-Wallis test was used for the statistical analysis (alpha=0.05). RESULTS: Peptide-coating was identified by fluorescence microscopy and XPS. Total coating amount was higher for physical adsorption than chemical grafting. The residual rate of peptide was significantly larger in the P-S group than in the other three groups (P<.05). CONCLUSION: The result of this study suggests that coating doses depend on coating method. Residual amounts of RGD peptide were greater for the physical adsorption method than the chemical grafting method.

Polysomnographic Characteristics and Prescription Status of Restless Legs Syndrome Patients in Naturalistic Setting / 수면정신생리

OBJECTIVES: The aim of this study is to evaluate the polysomnographic characteristics and prescription status of restless legs syndrome (RLS) patients in naturalistic setting. METHODS: We reviewed medical record of the patients over 18 years olds who (i) satisfied the clinical RLS diagnostic criteria and (ii) had the polysomnography and got treatment related thereto. As a baseline, we evaluated the four diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG) and the International Restless Legs Scale (IRLS) of the subjects. Then the polysomnography and the suggested immobilization test (SIT) were conducted and, after one month of pharmacotherapy using dopamine agonist, the IRLS was evaluated again. RESULTS: A total of 211 subjects participated in this analysis and 94 (44.5%) of them were male and the other 117 (55.5%) were female and the average age of the 211 subjects was 46.9+/-14.2. Out of such 211 subjects, 136 subjects (64.5%) also had the obstructive sleep apnea (OSA), and 53 subjects (25.1%) also had the periodic limb movement disorder (PLMD). 185 subjects (87.7%) out of the 211 subjects had some other sleep disorders except RLS. The results of the polysomnography were as follows : 78.0% of sleep efficiency, 86.8 min of wake after sleep onset, and 3.4% of N3. More specifically, 12.4/h of the average apnea hypopnea index, 14.8/h of the periodic limb movement during sleep (PLMS), 41.2/h of the periodic limb movement during wake during SIT and 21.6/h of total arousal index during sleep. Out of the total subjects, 149 (70.6%) of them took the ropinirole and 47 (22.3%) of them took the pramipexole, and the average dosage of ropinirole was 0.9mg(dosage range 0.125-5 mg) while the average dosage of pramipexole was 0.5 mg (dosage range 0.125-4 mg). The dosage of the ropinirole showed a significant positive correlation with the age (r=0.25, p=0.002) and also with the IRLS (r=0.23, p=0.038). The IRLS at the baseline was 24.9 while the same was decreased down to 13.4 after one month. CONCLUSIONS: Analyzing the result of this study, a majority of clinical RLS subjects demonstrated comorbidity with some other sleep disorder such as the OSA or PLMD. 25.1% of the subjects showed a PLMD, which was less than in previous researches and the average PLMS was not very high as 14.8/h. The dosage of dopamine agonist taken was often a bit more than the amount recommended in Korea. A prospective research using a large scale controlled subjects will be necessary with respect to this topic.

El aceite canola y sus efectos en la salud / Canola oil and health effects

El término canola (Canadian Oil Low Acid), designa a una variedad de semillas desarrolladas durante la década de los setenta por métodos tradicionales de fitomejoramiento de la colza. La canola se ubica en el segundo lugar como planta oleaginosa cultivada en el mundo, y no sólo se utiliza en la fabricación de aceite para ensaladas y frituras, sino también en la elaboración de margarinas, mantecas y otros productos alimenticios. El presente trabajo tiene como objetivo realizar una revisión de la información científica disponible sobre los antecedentes que motivaron el surgimiento de las semillas variedad canola, así como la seguridad y efectividad del consumo de su aceite sobre algunos de los factores de riesgo de enfermedad cardiovascular (ECV). La búsqueda y localización de la información, incluyó una revisión de artículos científicos, para lo cual se utilizaron los descriptores: Canola, enfermedad cardiovascular, aterosclerosis, y antioxidantes, fundamentalmente. La mayoría de los artículos seleccionados estaban relacionados con el efecto de la composición de ácidos grasos de aceites comestibles en la ECV, así como estudios de análisis de antioxidantes en este aceite. Además, se localizaron artículos de organismos reguladores sobre la seguridad del consumo del aceite de canola(AU)

The term canola (Canadian Oil Low Acid) refers to a variety of seeds developed in the seventies by traditional breeding methods of rapeseed. Canola is located in the second most cultivated oilseed plant in the world, and not only used in the manufacture of salad oil and frying, but also in the development of margarines, shortenings and other food products. This paper aims to conduct a review of the available scientific information on the background that led to the emergence of canola seed variety and the safety and effectiveness of its oil consumption on some of the risk factors for cardiovascular disease (CVD). Finding and locating information, including a review of scientific articles. The descriptors were used: Canola, cardiovascular disease, atherosclerosis, and antioxidants, mainly. Most selected articles were related to the effect of fatty acid composition of edible oils in VCE and analysis studies of antioxidants in this oil. In addition, articles were located regulators about the safety of canola oil consumption(AU)

A Clinical Study of the Relationship between Obesity and Pubertal Development in Girls / 대한소아소화기영양학회지

PURPOSE: Recently, public interest in obesity and earlier pubertal development has been increasing. The purpose of this study was to analyze the relationship between obesity and pubertal development in girls. METHODS: A total of 158 girls presenting with earlier pubertal development from July 2008 to June 2010 were included in the study. Their mean age was 8.27+/-1.3 years and the mean bone age advancement was 1.86+/-0.3 years. RESULTS: Based on weight-for-height percentiles, their obesity rate was 9.2% and overweight rate was 15.8%. However, for body mass index (BMI), the result was a bit different; with an obesity rate of 13.2% and overweight rate of 24.3%. About 40% of the girls had a family history of early maturation. Among them, 25.7% had a maternal history, 4.6% paternal and 7.2% both. However, 60% of them had no family history. We then classified these girls into families with one son and one daughter, and those with two daughters. In one-son/one-daughter families, 69.3% were the first children and 30.7% were second. In two-daughter families, 65.3% were the first and 34.7% were second. We found that 67.5% had a history of taking herbal medicine. CONCLUSION: The obesity and overweight rates in girls with earlier pubertal development were higher than those of normal girls, but with a small discrepancy between weight-for-height percentile and BMI-based results. Furthermore, taking herbal medicine seems to be a potential factor for earlier pubertal development in Korea.