Eldorado Community:http://hdl.handle.net/2003/256182024-03-29T02:31:58Z2024-03-29T02:31:58ZOne pot synthesis of pyrrolidines type 3,7-diazabicyclo [3.3.0] octane and biological activityAmornraksa, KittiPrachayasittikul, VirapongWorachartcheewan, Apilakhttp://hdl.handle.net/2003/258912015-08-12T23:53:17Z2008-12-05T12:49:38ZTitle: One pot synthesis of pyrrolidines type 3,7-diazabicyclo [3.3.0] octane and biological activity
Authors: Amornraksa, Kitti; Prachayasittikul, Virapong; Worachartcheewan, Apilak
Abstract: Pyrrolidines type 2,4-disubstituted (alkyl, aryl or heteroaryl)-6,8-dioxo-3,7-diazabicyclo [3.3.0] octanes (8a-d) were successfully synthesized by an efficient one pot 1,3-dipolar cycloaddition of azomethine ylides (in situ generated from the reaction of aromatic aldehydes and methyl ester of alpha-amino acids) with dipolarophile (N-phenylmaleimide). The reaction of compounds 8a-d with hydrazine in ethanol at room temperature took place under nucleophilic substitution which furnished 5-amino-4,6-dioxo-octahydropyrrolo [3,4-b] pyrrole-3-carboxylic acid phenylamides (12a-d). Structures of the products were confirmed by IR and 1H NMR. The compounds (8b and 12a) were evaluated for antimicrobial (agar dilution method) and antioxidative (DPPH; 2,2-diphenyl-1-picrylhydrazyl and SOD; superoxide dismutase assays) activities. The results showed that at concentrations of 4-256 µg/mL, the tested compounds exhibited non-significant antimicrobial growth, whereas the 12a at 200 µg/mL began to exert some antioxidative activity.2008-12-05T12:49:38ZImmunomodulation and anticancer potentials of yogurt probioticJha, AlokMishra, Vijendra KumarMohammad, Ghulamhttp://hdl.handle.net/2003/258202015-08-13T00:15:20Z2008-10-30T09:06:21ZTitle: Immunomodulation and anticancer potentials of yogurt probiotic
Authors: Jha, Alok; Mishra, Vijendra Kumar; Mohammad, Ghulam
Abstract: Probiotics are defined as live microbial food ingredients that produce several beneficial ef-fects to human health. Probiotic bacteria have been mostly investigated in the prevention and treatment of different gastrointestinal diseases and allergies. Probiotic products, however, are usually consumed by the general, healthy population but not much is known on their immu-nomodulatory effects in healthy adults. It is not fully clear how probiotics exert their benefi-cial effects on health, but one of the most probable mechanisms of action is the modulation of immune responses via the mucosal immune system of the gut. Yogurt is one of the products that produce several beneficial effects on human health. The potentials of yogurt in various ways like improving immune system balancing gut micro flora, enhance immunity. The pur-pose of the present study was to review the immunomodulatory properties of yogurt contain-ing probiotic strains. Role of yogurt as probiotic in improvement of immunity, production of cytokines and on immune function has been evaluated. Taken together, all the beneficial im-munological potentials of yogurt in probiotic immunotherapy could be of clinical signifi-cance. The mechanisms of specific host-probiotic interactions in the gut resulting in systemic and clinical effects warrants further investigations.2008-10-30T09:06:21ZEnhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophagesAbe, ShuichiInoue, SumitoIshikawa, TomomiKubota, IsaoShibata, YokoTakabatake, NoriakiYamauchi, Keikohttp://hdl.handle.net/2003/258102015-08-12T16:50:17Z2008-10-21T12:42:53ZTitle: Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages
Authors: Abe, Shuichi; Inoue, Sumito; Ishikawa, Tomomi; Kubota, Isao; Shibata, Yoko; Takabatake, Noriaki; Yamauchi, Keiko
Abstract: Immunomodulatory effects of 14-member macrolides, namely erythromycin (EM) and clarithromycin (CAM), have been reported in chronic respiratory infectious diseases. It has been suggested that 14-member macrolides have immunomodulatory effects on various lung cells such as alveolar macrophages. Interleukin (IL)-10 is an immunomodulatory cytokine that performs an irreplaceable role in negatively regulating inflammation, primarily via a mechanism that selectively blocks the expression of pro-inflammatory genes. It activates sig-nal transducer and activator of transcription (STAT)-3, and subsequently induces the suppres-sor of cytokine signaling-3 (SOCS-3), resulting in the resolution of inflammatory response in macrophages. However, it has been still unclear whether 14-member macrolides exert immu-nomodulatory effects via IL-10 signaling pathway. We aimed to evaluate whether 14-member macrolides affect the IL-10 signaling pathway. The RAW264.7 macrophage cell line was pre-treated with EM or CAM, and stimulated with lipopolysaccharide (LPS). The levels of IL-10, IL-10 receptor, phosphorylated (p) STAT-3, and SOCS-3 were determined by RT-PCR, ELISA and immunoblotting. We observed increased levels of IL-10, p-STAT-3 and SOCS-3 in the treated cells. In addition, while the levels of tumor necrosis factor-α 6 h after LPS stimulation was equal between vehicle-treated and CAM-treated macrophage cells, those of CAM-treated cells were repressed 36 h following LPS stimulation, compared with those of the control cells. Therefore, the 14-member macrolides may initiate an early resolution of inflammation, in part, via the enhancement of the IL-10/STAT-3/SOCS-3 pathway.2008-10-21T12:42:53ZMitochondrial DNA might be influenced in calprotectin-induced cell deathMarashi, Sayed-AmirRezaei-Tavirani, MostafaShokrgozar, Mohammad AliZali, Hakimehhttp://hdl.handle.net/2003/258092015-08-12T20:47:01Z2008-10-21T12:27:12ZTitle: Mitochondrial DNA might be influenced in calprotectin-induced cell death
Authors: Marashi, Sayed-Amir; Rezaei-Tavirani, Mostafa; Shokrgozar, Mohammad Ali; Zali, Hakimeh
Abstract: It is generally believed that calprotectin acts via exclusion of extracellular zinc, and/or binding of calprotectin to a cell membrane receptor, and consequently, activation of a signaling pathway for apoptosis. Recently, we suggested that calprotectin may have an “internal target” within cells. Here, using target theory, we provided evidence that this internal target is DNA. Trypan blue (TB) and dimythylthiazol diphenyl tetrazolium bromide (MTT) assays were used to estimate survival of calprotectin-treated cells. TB assay relies on the viability of cell membrane, while MTT assay relies on the functionality of mitochondria. We demonstrated that MTT-based survival values fit to the “single-hit, single-target” model, while TB-based survival values are best matched to the “single-hit, multi-target” model with N=2. Assumption of DNA as the target of calprotectin is fully consistent with the models, since each mitochondrion contains one chromosome and each “cell” is diploid and contains two chromosome sets. To the best of our knowledge this is the first report that suggests mitochondrial DNA is affected during calprotectin-induced cell death. Furthermore, our results explain why toxicity measures (like LD50), when estimated based on TB assay, are sometimes significantly greater than toxicity measures based on MTT assay.2008-10-21T12:27:12ZRotavirus infectionSurendran, Sankarhttp://hdl.handle.net/2003/257992015-08-13T02:17:01Z2008-09-10T09:50:03ZTitle: Rotavirus infection
Authors: Surendran, Sankar
Abstract: Rotavirus infection causing gastroenteritis is one of the major health concerns throughout the world. Millions of children are affected by the disease. Studying molecular mechanism and pathophysiology of the disease is important to understand and interpret possible therapeutical targets. Studies suggest that rotavirus infection alters phosphorylation of p70S6K, mitogen activated kinase (MAPK/ERK) and myosin light chain; induced inflammatory agents such as prostaglandin E2 and nitric oxide levels; and enhanced corticosterone levels to damage villi enterocytes in the small intestine. These changes lead to malabsorption, abnormal motility and diarrhea. Although Rotarix and RotaTeq vaccines are available, proposals are emerged to produce new candidate vaccines.2008-09-10T09:50:03ZNonrandom gene distribution on human chromosomesMohsenzadeh, SasanRafiee, LalehSaadat, Mostafahttp://hdl.handle.net/2003/257482015-08-13T00:37:09Z2008-07-17T13:59:53ZTitle: Nonrandom gene distribution on human chromosomes
Authors: Mohsenzadeh, Sasan; Rafiee, Laleh; Saadat, Mostafa
Abstract: Human chromosomes are heterogeneous in structure and function. This is the reason for specific banding patterns produced by various chromosome staining techniques. The human genome is a mosaic of isochors and can be partitioned into five families, L1, L2, H1, H2 and H3, characterized by increasing GC level and gene concentrations. In this study we investigated the chromosome distribution of 22845 genes mapped at whole chromosomes reported in the Human Genome Data Base as of January 2007. Pearson correlation coefficient analysis showed that there is significant correlation between the number of mapped genes and percent of G-dark bands (r=-0.608, p=0.002). Also the correlation between the ratio (observed versus expected genes) and percent of G-dark bands was significant (r=-0.506, p=0.012). There was a significant difference between observed number of mapped genes and expected number of mapped genes on human chromosomes (?2=4842.7, df=23, p<0.00001). Taken together, these findings indicating the gene density in G-light bands is higher than that of the G-dark bands.2008-07-17T13:59:53ZA case study with breast cancer and brain metastasis encompassing acute onset of amnesia and altered mental status due to limbic encephalitis - biochemical and proteomic aspectsGhazal, Faten AbouHaddad, John J.Hatoum, HilanaItani, Osman S.Mattar, HannaSamaha, Ali A.http://hdl.handle.net/2003/257062015-08-12T18:02:11Z2008-05-19T00:00:00ZTitle: A case study with breast cancer and brain metastasis encompassing acute onset of amnesia and altered mental status due to limbic encephalitis - biochemical and proteomic aspects
Authors: Ghazal, Faten Abou; Haddad, John J.; Hatoum, Hilana; Itani, Osman S.; Mattar, Hanna; Samaha, Ali A.
Abstract: A biochemical case study is reported on a 50-year old lady known to have breast cancer. The woman was treated by mastectomy and this was followed by unraveling brain metastases three years post-diagnosis of the cancer, which was treated by radiation and chemotherapy. Two months after ending her treatment, she exhibited acute changes in her mental status manifested by severe amnesia and fever. A generalized analytical and biochemical assessment revealed the presence of paraneoplastic limbic encephalitis.2008-05-19T00:00:00ZTherapeutic potential of peripheral blood stem cell transplantation in one cirrhotic patient caused by HBV combined with HCVFan, DaimingHan, HuohongHan, YingHe, Yuang-longLiu, JingmeiWang, JianhongYan, LiZhou, Xinminhttp://hdl.handle.net/2003/257052015-08-13T00:41:21Z2008-02-08T00:00:00ZTitle: Therapeutic potential of peripheral blood stem cell transplantation in one cirrhotic patient caused by HBV combined with HCV
Authors: Fan, Daiming; Han, Huohong; Han, Ying; He, Yuang-long; Liu, Jingmei; Wang, Jianhong; Yan, Li; Zhou, Xinmin
Abstract: Stem cell based therapy was very attractive in decompensated liver cirrhosis currently. The possible mechanism might be due to its potential to help tissue regeneration with minimally invasive procedures. Here we report the case of a 44-year-old man, infected by hepatitis B virus (HBV) combined with hepatitis C virus (HCV) for longer than 10 years, who eventually developed decompensated liver cirrhosis. After being infused with mobilized peripheral blood stem cells, the patient showed significantly elevated serum albumin level, cholesterol (CHO), cholinesterase (CHE) and decreased PT (prothrombin time) during the 26 months of follow-up. To our knowledge, this is the first case of transplanting mobilized PBSCs to treat the HBV combined with HCV related decompensated liver cirrhosis.2008-02-08T00:00:00ZArsenic, GSTO2 Asp142 polymorphism, health and treatmentMasoudi, MohammadSaadat, Mostafahttp://hdl.handle.net/2003/257042015-08-12T20:39:34Z2008-04-29T00:00:00ZTitle: Arsenic, GSTO2 Asp142 polymorphism, health and treatment
Authors: Masoudi, Mohammad; Saadat, Mostafa
Abstract: Arsenic is a natural metallic element found in low concentrations in virtually every part of the environment, including waters and foods. The ingestion of arsenic by humans can cause a variety of disorders. Glutathione S-transferase omega (GSTO) is a member of phase II xenobiotic metabolizing enzymes. GSTO2 (a member of GST omega) participates in detoxification of inorganic arsenic. In human, the A>G transition at nucleotide position 424 of GSTO2 was reported. This variation causes an Asn142Asp substitution. The Asp142 allozyme was expressed at approximately 80 % of the level of Asn142 allozyme. It is hypothesized that the GSTO2 polymorphism may alter the risk of several diseases which are related to chronic arsenic poisoning. On the other hand, because arsenic trioxide is used for treatment of acute promyelocytic leukemia; it is possible that Asn142 allozyme may decrease the therapeutic effect(s) of the drug.2008-04-29T00:00:00ZDNA damageKumari, SunitaRastogi, Rajesh P.Singh, Kanchan L.Singh, Shailendra P.Sinha, Rajeshwar P.http://hdl.handle.net/2003/257032015-08-12T20:39:35Z2008-03-04T00:00:00ZTitle: DNA damage
Authors: Kumari, Sunita; Rastogi, Rajesh P.; Singh, Kanchan L.; Singh, Shailendra P.; Sinha, Rajeshwar P.
Abstract: Even under the best of circumstances, DNA is constantly subjected to chemical modifications.
Several types of DNA damage such as SSB (single strand break), DSB (double strand break),
CPDs (cyclobutane pyrimidine dimers), 6-4PPs (6-4 photoproducts) and their Dewar valence
isomers have been identified that result from alkylating agents, hydrolytic deamination, free
radicals and reactive oxygen species formed by various photochemical processes including
UV radiation. There are a number of strategies such as PCR (polymerase chain reaction),
comet, halo, TUNEL (Terminal deoxyribonucleotidyltransferase-mediated deoxyuridine
triphosphate nick end labeling) assay, HPLC-Electrospray tandem mass spectrometry, FISH
(Fluorescence in situ hybridization), FCM (Flow cytometry), annexin V labeling, immunological
assays including immunofluorescent and chemiluminescence thymine dimer detection,
immunohistochemical assay, Enzyme-linked immunosorbent assay (ELISA), Radio immunoassay
(RIA), Gas chromatography-mass spectrometry and electrochemical methods, that
are commonly used to detect DNA damage in various organisms. The main aim of this review
is to present a brief account of the above mentioned DNA damage detection strategies for the
convenience of interested readers.2008-03-04T00:00:00ZProtective effect of L-ornithine-L-aspartate and silymarin on chemically induced kidney toxicity and thyroid dysfunction in miceJatwa, RameshwarKar, Anandhttp://hdl.handle.net/2003/257022015-08-12T20:35:14Z2008-05-20T00:00:00ZTitle: Protective effect of L-ornithine-L-aspartate and silymarin on chemically induced kidney toxicity and thyroid dysfunction in mice
Authors: Jatwa, Rameshwar; Kar, Anand
Abstract: The present study was designed to reveal the hitherto unknown efficacy of two commonly
used hepatoprotective drugs, L-ornithine-L-aspartate (lornit) and silymarin in the regulation of
kidney toxicity and thyroid dysfunction in mice. Renal and hepatic lipid peroxidation (LPO)
was induced by the administration of carbon tetrachloride (CCl4) for 2 weeks (2.0 gm/kg
twice a week). In two separate groups, along with CCl4 animals were also treated with either
lornit (200 mg/kg) or silymarin (100 mg/kg) every day for the same duration. Other than hepatic
and renal LPO, alterations in the concentrations of serum triiodothyronine (T3), thyroxine
(T4), glucose and insulin and in hepatic type-1 iodothyronine 5’monodeiodinase (5’DI)
activity were considered as major parameters. Simultaneously activities of serum aspartate
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphahatase (ALP) and
hepatic and renal superoxide dismutase (SOD), catalase (CAT) and reduced glutathione content
(GSH) were also studied. Lornit or silymarin administration reversed almost all the toxic
effects exhibited by CCl4 including enhanced tissue LPO, serum ALT, AST and ALP activities
and the concentrations of insulin and glucose. Both test drugs also significantly increased
hepatic 5’DI activity, cellular antioxidants such as SOD, CAT and GSH and serum levels of
both the thyroid hormones.2008-05-20T00:00:00ZEffect of some natural antioxidants on aflatoxin B1-induced hepatic toxicityKheir Eldin, Adel A.Motawi, Tarek M. K.Sadik, Nermin A. H.http://hdl.handle.net/2003/257012015-08-12T20:39:38Z2008-05-08T00:00:00ZTitle: Effect of some natural antioxidants on aflatoxin B1-induced hepatic toxicity
Authors: Kheir Eldin, Adel A.; Motawi, Tarek M. K.; Sadik, Nermin A. H.
Abstract: Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. This hepatotoxicity is
thought to be mediated by their ability to generate reactive oxygen species and cause peroxidative
damage. In the present investigation we assessed the ability of some natural antioxidants
namely, vitamin E and Se, ß-carotene, silymarin and coenzyme Q10 on aflatoxin B1
(AFB1)-induced hepatotoxicity in a rat model. Alanine and aspartate aminotransferases and
alkaline phosphatase (ALP) were found to be significantly increased in the serum of AFB1
administered (250 µg/kg body weight/day for 2 weeks) rats, suggesting hepatic damage.
There was a marked increase in the lipid peroxide levels and a concomitant decrease in the
hepatic reduced glutathione (GSH) and serum protein thiol (PrSHs) along with a nearly twofold
increase in hepatic glutathione-S-transferase (GST) activity. The significant increase in
GST may be attributed to its being a phase ?? enzyme that predominately participates in the
detoxification of the ultimate electrophilic metabolite AFB1-8, 9 epoxide. On the other hand,
no significant change was detected in the activities of glutathione peroxidase (GPx), glutathione
reductase (GR), glucose-6-phosphate dehydrogenase (G-6-PDH), cytochrome creductase
and levels of DNA and RNA in the hepatic tissue of AFB1 administered rats. Results
also revealed that cotreatment with studied antioxidants offered substantial hepatoprotective
effects in the AFB1 administered rats. Moreover, results revealed that vitamin E and selenium
combination and ß-carotene are more efficient than coenzyme Q10 and silymarin in
modulating the liver antioxidant enzymatic system.2008-05-08T00:00:00ZInheritance involved in the pathogenesis of idiopathic scoliosisFan, XingLi, MingShangguan, Leihttp://hdl.handle.net/2003/257002015-08-12T16:37:05Z2008-04-22T00:00:00ZTitle: Inheritance involved in the pathogenesis of idiopathic scoliosis
Authors: Fan, Xing; Li, Ming; Shangguan, Lei
Abstract: Idiopathic scoliosis is a common cause of spinal deformity in children and adolescents. Although
the incidence of the scoliosis is up to 2 %-3 % of the world’s population, the pathogenesis
is still obscure. Recent evidences show that the disease has a hereditary basis. Clinical
manifestations as well as family studies reveal the familial tendency of idiopathic scoliosis,
and support that the heredity is an important cause of this disease. Many related genes, such
as SNTGI and CHD7, are believed to play a role in the development of idiopathic scoliosis
but the underlying mechanism is still not clear. This review focus on the mode of inheritance
of idiopathic scoliosis and some related molecules.2008-04-22T00:00:00ZCitric acid strongly inhibits visceral pain response in miceAbdel-Salam, Omar M. E.Baiuomy, Ayman R.http://hdl.handle.net/2003/256992015-08-12T16:37:01Z2008-04-17T00:00:00ZTitle: Citric acid strongly inhibits visceral pain response in mice
Authors: Abdel-Salam, Omar M. E.; Baiuomy, Ayman R.
Abstract: Citric acid introduced into the stomach of mice at increasing concentrations of 0.1, 1 or 10 %
(4.8 µM-0.48 mM; 95 µmol/kg-9.5 mmol/kg, 0.5 ml) caused dose-dependent inhibition of
abdominal constrictions induced 1 h later by i. p. acetic acid injection by -51 % to -69.5 %.
When administered at 10 % (0.48 mM, 0.5 ml) 15 min before nociceptive challenge, citric
acid inhibited the nociceptive response by 96.8 %. Inhibition of the acetic acid-induced abdominal
constrictions was also observed when lower doses of citric acid were introduced into
the stomach (0.2 ml of 0.1-1 %; 38.1 µmol/kg-0.38 mmol/kg). The effect was evident as early
as 5 min after administration of citric acid into the stomach and with the maximal effect being
at 15-30 min after dosing. Lidocaine given orally 5 min prior to citric acid (1 %, 48 µM;
0.38 mmol/kg, 0.2 ml) prevented antinociception by citric acid, but lidocaine given 15 min
before oral introduction of citric acid enhanced the citric acid-induced inhibition of the nociceptive
response to acetic acid. The antinociceptive effect of orally administered citric acid
(1 %, 48 µM; 0.38 mmol/kg, 0.2 ml) was increased by pre-treatment with propranolol
(4 mg/kg, s. c.), yohimbine (4 mg/kg, s. c.), guanethidine (32 mg/kg, s. c.), but reduced after
treatment with atropine (3 mg/kg, s. c.), which itself increased the nociceptive behavior. Similar
inhibition of the acetic acid-induced nociceptive behavior was also observed when sodium
citrate (pH 7.21) or 0.1 N HCl (pH 3) or 1 % sucrose solution (0.2 ml) was intragastrically
given. It is suggested that citric acid might act to stimulate sensory afferents and that transmission
of nociceptive information centrally leads to the activation of descending antinociceptive
mechanism to a noxious stimulus.2008-04-17T00:00:00ZErythropoietin stimulates hepatocyte regeneration after liver resectionBauer, AlexanderDonaubauer, BerndFaber, Sonya C.Hauss, Johann P.Hengstler, Jan G.Hogrebe, EstherJelkmann, WolfgangPietsch, Uta-CarolinSchön, Michael R.Tannapfel, AndreaThiery, Joachimhttp://hdl.handle.net/2003/256982015-08-12T16:37:03Z2008-03-31T00:00:00ZTitle: Erythropoietin stimulates hepatocyte regeneration after liver resection
Authors: Bauer, Alexander; Donaubauer, Bernd; Faber, Sonya C.; Hauss, Johann P.; Hengstler, Jan G.; Hogrebe, Esther; Jelkmann, Wolfgang; Pietsch, Uta-Carolin; Schön, Michael R.; Tannapfel, Andrea; Thiery, Joachim
Abstract: The increased relevance of liver surgery and transplantation as a therapeutic modality
over the last two decades mandates the development of novel strategies to improve liver regeneration.
Here we studied whether erythropoietin (EPO) improves liver regeneration after
hepatectomy in pigs.
Eighteen female pigs underwent laparoscopic left lateral liver resection and were
allocated randomly into three groups. No EPO was administered to the control group (group
1, n=6). Group 2 (n=6) received EPO topically to the liver resection surface in a fibrin sealant.
Group 3 (n=6) received EPO topically and systemically. Pigs were sacrificed 14 days after
hepatectomy. The fraction of proliferating hepatocytes was determined by ki-67 immunostaining.
Liver volume was determined by the principle of Archimedes,
Liver weight and volume were significantly increased in group 3 (1249 ± 223 g,
1073 ± 190 ml) compared to group 2 (1027 ± 167 g, 894 ± 105 ml) and group 1 (923 ± 186 g,
813 ± 165 ml). Ki-67 immunostaining of liver tissue close to the resection surface demonstrated
a significantly increased percentage of proliferating hepatocytes in group 3 (4.3 ± 1.96
%) and in group 2 (3.5% ± 0.98 %) as compared to group 1 (1.15 ± 1.2 %) 14 days after
hepatectomy.
Our results indicate for the first time that EPO supports liver regeneration after
hepatectomy.2008-03-31T00:00:00Z4-Hydroxy-2-nonenal induces endothelial cell injury via PKCdelta and biphasic JNK activationGoya, ShoHirata, HaruhikoHoshino, ShigenoriInoue, KojiKashiwa, YozoKawase, IchiroKijima, TakashiKumagai, ToruMayumi, MasahikoOsaki, TadashiSuzuki, MayumiTachibana, IsaoTakeda, YoshitoTakimoto, TakayukiYano, YukihiroYoshida, Yoshidahttp://hdl.handle.net/2003/256972015-08-12T20:32:19Z2008-03-10T00:00:00ZTitle: 4-Hydroxy-2-nonenal induces endothelial cell injury via PKCdelta and biphasic JNK activation
Authors: Goya, Sho; Hirata, Haruhiko; Hoshino, Shigenori; Inoue, Koji; Kashiwa, Yozo; Kawase, Ichiro; Kijima, Takashi; Kumagai, Toru; Mayumi, Masahiko; Osaki, Tadashi; Suzuki, Mayumi; Tachibana, Isao; Takeda, Yoshito; Takimoto, Takayuki; Yano, Yukihiro; Yoshida, Yoshida
Abstract: 4-Hydroxy-2-nonenal (4-HNE), a major product generated during oxidative stress, exhibits
cytotoxic effects; however, the mechanisms of 4-HNE-induced endothelial cell injury are not
well defined. To explore this issue, we examined how 4-HNE damages human umbilical vein
endothelial cells (HUVECs) and found that 4-HNE induced biphasic activation of c-Jun
N-terminal kinase (JNK). Both pre- and post-treatment of HUVECs with SP600125, a specific
JNK inhibitor, significantly suppressed the cytotoxic effects of 4-HNE. Inhibition of
protein kinase Cd (PKCd), which was also phosphorylated by 4-HNE, reduced endothelial
cell injury as well as late-phase JNK phosphorylation elicited by 4-HNE. Inversely,
pre-treatment of HUVECs with SP600125 suppressed PKCd activation. Taken together, these
results support the concept that 4-HNE induces vascular endothelial cell injury by the interaction
between biphasic JNK activation and the PKCd pathway.2008-03-10T00:00:00ZAntimicrobial and antioxidative activities of 1-adamantylthio derivatives of 3-substituted pyridinesIsarankura-Na-Ayudhya, ChartchalermPrachayasittikul, SupalukPrachayasittikul, VirapongRuchirawat, SomsakSuksrichavalit, Thummarukhttp://hdl.handle.net/2003/256962015-08-12T16:41:30Z2008-03-10T00:00:00ZTitle: Antimicrobial and antioxidative activities of 1-adamantylthio derivatives of 3-substituted pyridines
Authors: Isarankura-Na-Ayudhya, Chartchalerm; Prachayasittikul, Supaluk; Prachayasittikul, Virapong; Ruchirawat, Somsak; Suksrichavalit, Thummaruk
Abstract: Diverse biological activities of sulfur containing pyridines were reported. To investigate for
new lead compounds, thus, 1-adamantylthiopyridines bearing 3-substituents (OEt, OAc,
NAc2, Br and OH) were prepared and evaluated for antimicrobial and antioxidative activities.
The antimicrobial assay against 27 strains of microorganisms was performed using agar dilution
method. The results show that all the tested 2-(1-adamantylthio)-3-ethoxypyridine (4a),
2-(1-adamantylthio)-3-acetoxypyridine (4b), N-acetyl-2-(1-adamantylthio)-3-acetamidopyridine
(4c), 2-(1-adamantylthio)-3-bromopyridine (4d), 2-(1-adamantylthio)-5-hydroxypyridine
(5) and 3-(1-adamantylthio)-5-bromopyridine (6) exhibit antigrowth activity on
Streptococci at 30 µg/mL. Particularly, the thiopyridines 4c, 5 and 6 are the most active compounds,
displaying complete inhibition against ß-hemolytic Streptococcus group A at 30
µg/mL. These pyridyl sulfides 4a-d, 5 and 6 represent a new group of antimicrobial agents.
Antioxidative activity was analyzed using the DPPH assay. The sulfides 4a-d, 5 and 6 show
only a weak antioxidative activity. In contrast the 2-(1-adamantylthio)-3-bromopyridine (4d)
shows the highest radical scavenging activity.2008-03-10T00:00:00ZReactions of N-acetylcysteine adducts of aromatic (di)isocyanates with functional groups of organic moleculesFrank, PetraMormann, WernerSchupp, ThomasSeel, Klaushttp://hdl.handle.net/2003/256952015-08-12T20:32:21Z2008-02-21T00:00:00ZTitle: Reactions of N-acetylcysteine adducts of aromatic (di)isocyanates with functional groups of organic molecules
Authors: Frank, Petra; Mormann, Werner; Schupp, Thomas; Seel, Klaus
Abstract: Glutathione thiocarbamate conjugates of isocyanates play a key role in transport and final
reactions of isocyanates in the human body by transcarbamoylation. N-acetylcysteine is the
simplest model for thiocarbamate reactions. Therefore, transcarbamoylation of Nacetylcysteine
adducts of p-tolylisocyanate (pTI-AcCys) and 4,4’-diisocyanatodiphenyl-
methane (MDI(AcCys)2) with N-acetylcysteine methyl ester (thiolysis), morpholine (aminolysis),
methoxyethanol (alcoholysis), and water (hydrolysis) has been studied in aqueous
phosphate buffer solution and in dimethylacetamide (DMAc). Expected reaction products
have been synthesised as reference compounds for HPLC-analysis. Concentrations of adducts
and of reaction products were monitored by HPLC. Reaction rates and activation energies
were determined for pTI in both media, reactions of MDI(AcCys)2 were run at one temperature
only. Formation of insoluble reaction products and side reactions due to hydrolysis prevented
in depth kinetic analysis of the reactions. Two regimes of reaction rate were observed
in aqueous buffer, clear second order kinetics resulted in DMAc. In aqueous buffer (pH 7.4) a
reactivity thiolysis > aminolysis > hydrolysis was found, while in DMAc aminolysis was
faster than thiolysis. This can be explained by formation of thiolate at pH 7.4, which is not
possible in anhydrous DMAc. Reactions of (MDI(AcCys)2) are by a factor of 2 to 4 faster
than those of pTI-AcCys. p-Toluidine (pTA) was found in the aqueous system due to hydrolysis,
while no 4,4’-methylene dianiline (MDA) could be detected. Under physiological
conditions hydrolysis should compete with thiolysis under homogeneous conditions while
ureas and carbamates should be much more stable against hydrolysis. No free isocyanate
groups could be detected in any of the reactions. In conclusion the isocyanate moiety in thiocarbamates
is readily transferred to sulfhydryl- and amino groups but not to aliphatic hydroxy
groups. Under physiological conditions hydrolysis competes with these transcarbamoylation
reactions. Formation of free isocyanate groups in analytical quantities was shown to be highly
unlikely.2008-02-21T00:00:00ZAdrenaline inhibited cell proliferation and regulated expression of TGF-beta1 and bFGF in cultured human hypertrophic scar fibroblasts via alpha-receptorSong, LanTian, YingXu, Zhao-JunZhang, Cai-Pinghttp://hdl.handle.net/2003/256942015-08-12T16:41:28Z2008-01-08T00:00:00ZTitle: Adrenaline inhibited cell proliferation and regulated expression of TGF-beta1 and bFGF in cultured human hypertrophic scar fibroblasts via alpha-receptor
Authors: Song, Lan; Tian, Ying; Xu, Zhao-Jun; Zhang, Cai-Ping
Abstract: Adrenaline has been shown to modulate proliferation of mouse fibroblasts, adventitial fibroblasts
and synovial B (fibroblasts-like) cells. However, little is known about the response
of cultured human hypertrophic scar fibroblasts to adrenaline. In this study, we investigated
cell proliferation and involved mechanisms in hypertrophic scar fibroblasts in response to
adrenaline. Population doubling time (PDT) assay and MTT assay were performed to determine
the cell proliferation and cell viability, respectively. The expression of bFGF and TGF-
ß1 was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme
linked immunosorbent assay (ELISA). The results showed that adrenaline inhibited proliferation
of normal and hypertrophic scar fibroblasts in a dose-dependent manner. Moreover,
adrenaline up-regulated the expression of bFGF and down-regulated the expression of TGF-
ß1 in normal and hypertrophic scar fibroblasts. Interestingly incubation with the a receptor
antagonist regitine indicated that adrenaline mediated inhibition of cell proliferation and regulation
of TGF-ß1 and bFGF in cultured normal and hypertrophic scar fibroblasts were mediated
by the a receptor. These studies suggest that adrenaline inhibits proliferation and alters
the expression of TGF-ß1 and bFGF in human hypertrophic scar fibroblast involving an a
receptor mediated pathway.2008-01-08T00:00:00Z