Displaying publications 81 - 100 of 102 in total

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  1. Sosroseno W, Bird PS, Seymour GJ
    Anaerobe, 2009 Jun;15(3):95-8.
    PMID: 19402196 DOI: 10.1016/j.anaerobe.2009.01.002
    The aim of this study was to determine the effect of exogenous nitric oxide (NO) on the induction of murine splenic immune response to Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) in vitro. BALB/c mice were immunized with A. actinomycetemcomitans LPS and a control group was sham-immunized. Spleen cells were obtained, cultured and stimulated with A. actinomycetemcomitans LPS with or without the presence of S-nitroso acetyl-penicillamine (SNAP), a NO donor, and carboxy-PTIO, an NO scavenger. Culture supernatants were assessed for inducible nitric oxide synthase (iNOS) activity, specific IgG subclass levels, and both IFN-gamma and IL-4 levels. The results showed that in A. actinomycetemcomitans LPS-stimulated cells, SNAP enhances iNOS activity but inhibits the levels of specific IgG2a and IFN-gamma suggesting a Th1 response. The effect of SNAP on these immune parameters was ablated by carboxy-PTIO. These results suggest that exogenous NO may suppress the Th1-like immune response of A. actinomycetemcomitans LPS-stimulated murine spleen cells.
    Matched MeSH terms: Imidazoles/pharmacology
  2. Fahlman A, Bosi EJ, Nyman G
    J. Zoo Wildl. Med., 2006 Dec;37(4):558-61.
    PMID: 17315446
    Medetomidine (0.02-0.06 mg/kg) in combination with zolazepam-tiletamine (0.8-2.3 mg/kg) were evaluated for reversible anesthesia in four species of Southeast Asian primates: Bornean orangutan (Pongo pygmaeus pygmaeus), Bornean gibbon (Hylobates muelleri), long-tailed macaque (Macaca fascicularis), and pig-tailed macaque (Macaca nemestrina). Twenty-three anesthetic procedures of captive-held and free-ranging primates were studied in Sabah, Malaysia. The induction was smooth and rapid. Respiratory and heart rates were stable throughout anesthesia, whereas body temperature and systolic arterial blood pressure decreased significantly. Atipamezole at five times the medetomidine dose effectively reversed anesthesia, with first signs of recovery within 3-27 min.
    Matched MeSH terms: Imidazoles/administration & dosage
  3. Ghanem OB, Mutalib MI, El-Harbawi M, Gonfa G, Kait CF, Alitheen NB, et al.
    J Hazard Mater, 2015 Oct 30;297:198-206.
    PMID: 25965417 DOI: 10.1016/j.jhazmat.2015.04.082
    Tuning the characteristics of solvents to fit industrial requirements has currently become a major interest in both academic and industrial communities, notably in the field of room temperature ionic liquids (RTILs), which are considered one of the most promising green alternatives to molecular organic solvents. In this work, several sets of imidazolium-based ionic liquids were synthesized, and their toxicities were assessed towards four human pathogens bacteria to investigate how tunability can affect this characteristic. Additionally, the toxicity of particular RTILs bearing an amino acid anion was introduced in this work. EC50 values (50% effective concentration) were established, and significant variations were observed; although all studied ILs displayed an imidazolium moiety, the toxicity values were found to vary between 0.05 mM for the most toxic to 85.57 mM for the least toxic. Linear quantitative structure activity relationship models were then developed using the charge density distribution (σ-profiles) as molecular descriptors, which can yield accuracies as high as 95%.
    Matched MeSH terms: Imidazoles/chemistry*
  4. Voon YL, Ahmad M, Wong PF, Husaini R, Ng WT, Leong CO, et al.
    Oncol Rep, 2015 Oct;34(4):1692-700.
    PMID: 26252575 DOI: 10.3892/or.2015.4177
    The small-molecule inhibitor of p53-Mdm2 interaction, Nutlin-3, is known to be effective against cancers expressing wild-type (wt) p53. p53 mutations are rare in nasopharyngeal carcinoma (NPC), hence targeting disruption of p53-Mdm2 interaction to reactivate p53 may offer a promising therapeutic strategy for NPC. In the present study, the effects of Nutlin-3 alone or in combination with cisplatin, a standard chemotherapeutic agent, were tested on C666-1 cells, an Epstein-Barr virus (EBV)-positive NPC cell line bearing wt p53. Treatment with Nutlin-3 activated the p53 pathway and sensitized NPC cells to the cytotoxic effects of cisplatin. The combined treatment also markedly suppressed soft agar colony growth formation and increased apoptosis of NPC cells. The effect of Nutlin-3 on NPC cells was inhibited by knockdown of p53, suggesting that its effect was p53-dependent. Extended treatment with increasing concentrations of Nutlin-3 did not result in emergence of p53 mutations in the C666-1 cells. Collectively, the present study revealed supportive evidence of the effectiveness of combining cisplatin and Nutlin-3 as a potential therapy against NPC.
    Matched MeSH terms: Imidazoles/administration & dosage*
  5. Lah ZMANH, Ahmad SAA, Zaini MS, Kamarudin MA
    J Pharm Biomed Anal, 2019 Sep 10;174:608-617.
    PMID: 31265987 DOI: 10.1016/j.jpba.2019.06.024
    A facile electrochemical sandwich immunosensor for the detection of a breast cancer biomarker, the human epidermal growth factor receptor 2 (HER2), was designed, using lead sulfide quantum dots-conjugated secondary HER2 antibody (Ab2-PbS QDs) as a label. Using Ab2-PbS QDs in the development of electrochemical immunoassays leads to many advantages such as straightforward synthesis and well-defined stripping signal of Pb(II) through acid dissolution, which in turn yields better sensing performance for the sandwiched immunosensor. In the bioconjugation of PbS QDs, the available amine and hydroxyl groups from secondary anti-HER2 and capped PbS QDs were bound covalently together via carbonyldiimidazole (CDI) acting as a linker. In order to quantify the biomarker, SWV signal was obtained, where the Pb2+ ions after acid dissolution in HCl was detected. The plated mercury film SPCE was also detected in situ. Under optimal conditions, HER2 was detected in a linear range from 1-100 ng/mL with a limit of detection of 0.28 ng/mL. The measures of satisfactory recoveries were 91.3% to 104.3% for the spiked samples, displaying high selectivity. Therefore, this method can be applied to determine HER2 in human serum.
    Matched MeSH terms: Imidazoles/chemistry
  6. How YF, Lee CY
    Pest Manag Sci, 2011 Jun;67(6):734-40.
    PMID: 21370390 DOI: 10.1002/ps.2123
    Five formulated insecticides (lambda-cyhalothrin at 10 mg m⁻², bifenthrin at 50 mg m⁻², fipronil at 10 mg m⁻², fenitrothion at 50 mg m⁻², imidacloprid at 5 mg m⁻²) and one active ingredient (DDT at 500 mg m⁻²) were evaluated using a surface contact method against early and late instars and adults of two strains of the tropical bed bug, Cimex hemipterus (F.). Synergism of lambda-cyhalothrin and fipronil using piperonyl butoxide (PBO) was also assessed.
    Matched MeSH terms: Imidazoles/pharmacology
  7. Dang K, Singham GV, Doggett SL, Lilly DG, Lee CY
    J Econ Entomol, 2017 04 01;110(2):558-566.
    PMID: 28115498 DOI: 10.1093/jee/tow296
    The performance of five insecticides (bendiocarb, deltamethrin, DDT, malathion, and imidacloprid) using three application methods (oil-based insecticide films on filter paper, and acetone-based insecticide deposits on two substrates: filter paper and glass) was assessed against a susceptible strain of Cimex lectularius (L.) and two resistant strains of Cimex hemipterus (F.). Substrate type significantly affected (P 
    Matched MeSH terms: Imidazoles/pharmacology
  8. Goktaş MT, Hatta F, Karaca O, Kalkisim S, Kilic L, Akdogan A, et al.
    Eur J Clin Pharmacol, 2015 Oct;71(10):1223-8.
    PMID: 26233334 DOI: 10.1007/s00228-015-1899-7
    BACKGROUND: We previously reported on a Swedish patient with Behçet's disease (BD) who was an ultra-rapid metaboliser of drugs catalysed by CYP2C9. Was this extreme metabolism caused by the disease?

    AIM: This study aims to compare the genotype/phenotype of CYP2C9 in patients with BD and healthy subjects. As the occurrence of BD is high in Turkey, all subjects were recruited from this country.

    METHODS: Genotyping of CYP2C9 was performed using standard PCR-RFLP and allele-specific PCR methods. Phenotyping of CYP2C9 was performed by administration of a 50-mg single oral dose of losartan and by calculating the urinary metabolic ratio (MR) of probe drug to its metabolite E-3174. Quantitation was performed by HPLC.

    RESULTS: The frequency of CYP2C9*2 and *3 was not significantly different between the Behçet's disease patients (12.5 and 8.7%) and the healthy subjects (8.9 and 8.2%). The geometric mean losartan MR was higher in the 52 patients (1.75) than in the 96 healthy subjects (1.02) (p = 0.002; t-test). Within the genotypes *1/*1, there was a significant difference of MR between patients and healthy subjects (P = 0.006). All but three of the Behçet's disease patients were treated with colchicine. In nine subsequent patients, we found no significant effect of 2 weeks of treatment with colchicine on the CYP2C9 MR.

    CONCLUSION: Contrary to expectation, the CYP2C9 activity was lower in Turkish BD patients compared to healthy subjects. As this seems not to be due to colchicine treatment, our hypothesis is that inflammation related to BD might have caused the down-regulation of the CYP2C9 activity due to immune cytokine reactions. The ultra-rapid metabolism of CYP2C9 substrate drugs in the Swedish patient was not due to her BD.
    Matched MeSH terms: Imidazoles/urine
  9. Azmi N, Norman C, Spicer CH, Bennett GW
    Behav Pharmacol, 2006 Jun;17(4):357-62.
    PMID: 16914954
    Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 microg) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.
    Matched MeSH terms: Imidazoles/pharmacology
  10. Tan JY, Wijesinghe IVS, Alfarizal Kamarudin MN, Parhar I
    Cancers (Basel), 2021 Feb 04;13(4).
    PMID: 33557011 DOI: 10.3390/cancers13040607
    Paediatric gliomas categorised as low- or high-grade vary markedly from their adult counterparts, and denoted as the second most prevalent childhood cancers after leukaemia. As compared to adult gliomas, the studies of diagnostic and prognostic biomarkers, as well as the development of therapy in paediatric gliomas, are still in their infancy. A body of evidence demonstrates that B-Raf Proto-Oncogene or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) and histone H3 mutations are valuable biomarkers for paediatric low-grade gliomas (pLGGs) and high-grade gliomas (pHGGs). Various diagnostic methods involving fluorescence in situ hybridisation, whole-genomic sequencing, PCR, next-generation sequencing and NanoString are currently used for detecting BRAF and histone H3 mutations. Additionally, liquid biopsies are gaining popularity as an alternative to tumour materials in detecting these biomarkers, but still, they cannot fully replace solid biopsies due to several limitations. Although histone H3 mutations are reliable prognosis biomarkers in pHGGs, children with these mutations have a dismal prognosis. Conversely, the role of BRAF alterations as prognostic biomarkers in pLGGs is still in doubt due to contradictory findings. The BRAF V600E mutation is seen in the majority of pLGGs (as seen in pleomorphic xanthoastrocytoma and gangliomas). By contrast, the H3K27M mutation is found in the majority of paediatric diffuse intrinsic pontine glioma and other midline gliomas in pHGGs. pLGG patients with a BRAF V600E mutation often have a lower progression-free survival rate in comparison to wild-type pLGGs when treated with conventional therapies. BRAF inhibitors (Dabrafenib and Vemurafenib), however, show higher overall survival and tumour response in BRAF V600E mutated pLGGs than conventional therapies in some studies. To date, targeted therapy and precision medicine are promising avenues for paediatric gliomas with BRAF V600E and diffuse intrinsic pontine glioma with the H3K27M mutations. Given these shortcomings in the current treatments of paediatric gliomas, there is a dire need for novel therapies that yield a better therapeutic response. The present review discusses the diagnostic tools and the perspective of liquid biopsies in the detection of BRAF V600E and H3K27M mutations. An in-depth understanding of these biomarkers and the therapeutics associated with the respective challenges will bridge the gap between paediatric glioma patients and the development of effective therapies.
    Matched MeSH terms: Imidazoles
  11. Ting T, Crouse K, Ahmad H
    Sains Malaysiana, 2015;44:619-628.
    Three novel ruthenium(II) complexes of the general formula [Ru(II)(bpy)2
    L]2+ were synthesized, where L =
    1,10-phenanthroline derivatives of position 2 imidazole having 3,4-didecyloxy-phenyl (ddip), 3,4-ditetradecyloxy-phenyl
    (dtip) and 3,4-dihexadecyloxy-phenyl (dhip). All complexes were characterized by elemental analysis, 1
    H-NMR and ESI-MS.
    Their photophysical properties have also been studied by UV-visible spectroscopy and fluorescence spectroscopy. The
    complexes exhibit Ru(II) metal centered emission at approximately 610 nm in acetonitrile solution at room temperature. DNA
    binding studies were carried out by UV-visible titration, luminescence titration and viscosity studies. The results indicated
    that [Ru(bpy)2
    (ddip)]2+ binds to CT-DNA by partial intercalation mode, while [Ru(bpy)2
    (dtip)]2+ and [Ru(bpy)2
    (dhip)]2+
    bind intercalatively via extended ligands.
    Matched MeSH terms: Imidazoles
  12. Ng HS, Wan PK, Ng TC, Lan JC
    J Biosci Bioeng, 2020 Aug;130(2):200-204.
    PMID: 32389469 DOI: 10.1016/j.jbiosc.2020.04.003
    Ectoine is a zwitterionic amino acid derivative that can be naturally sourced from halophilic microorganisms. The increasing demands of ectoine in various industries have urged the researches on the cost-effective approaches on production of ectoine. Ionic liquids-based aqueous biphasic system (ILABS) was applied to recover Halomonas salina ectoine from cells hydrolysate. The 1-butyl-3-methylimidazolium tetrafluoroborate (Bmim)BF4 was used in the ILABS and the recovery efficiency of ILABS to recover ectoine from H. salina cells lysate was evaluated by determining the effects of phase composition; pHs; crude loading and additional neutral salt (NaCl). The hydrophilic ectoine was targeted to partition to the hydrophilic salt-rich phase. A total yield (YB) of 96.32% ± 1.08 of ectoine was obtained with ILABS of phase composition of 20% (w/w) (Bmim)BF4 and 30% (w/w) sulfate salts; system pH of 5.5 when the 20% (w/w) of crude feedstock was applied to the ILABS. There was no significant enhancement on the ectoine recovery efficiency using the ILABS when NaCl was added, therefore the ILABS composition without the additional neutral salt was recommended for the primary purification of ectoine. Partition coefficient (KE) of 30.80 ± 0.42, purity (PE) of 95.82% and enrichment factor (Ef) of 1.92 were recorded with the optimum (Bmim)BF4/sulfate ILABS. These findings have provided an insight on the feasibility of recovery of intracellular biomolecules using the green solvent-based aqueous system in one single-step operation.
    Matched MeSH terms: Imidazoles
  13. Sosroseno W, Sugiatno E, Samsudin AR, Ibrahim MF
    Biomed Pharmacother, 2008 Jun;62(5):328-32.
    PMID: 17988826
    The aim of the present study was to determine the effect of nitric oxide (NO) on the production of cyclic AMP (cAMP) by a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite. Cells were cultured on the HA surfaces with or without the presence of NO donors (SNAP and NAP) for 3 days. The effect of adenylyl cyclase inhibitor (SQ22536), NO scavenger (carboxy PTIO) or endothelial nitric oxide synthase (eNOS) inhibitor (L-NIO), was assessed by adding these to the cultures of HA-stimulated HOS cells with or without the presence of SNAP. Furthermore, HOS cells were pre-treated with anti-human integrin alphaV antibody prior to culturing on HA surfaces with or without the presence of SNAP. The levels of cAMP and cGMP were determined from the 3-day culture supernatants. The results showed that the production of cAMP but not cGMP by HA-stimulated HOS cells was augmented by SNAP. SQ22536 and carboxy PTIO suppressed but L-NIO only partially inhibited the production of cAMP by HA-stimulated HOS cells with or without the presence of exogenous NO. Pre-treatment of the cells with anti-human integrin alphaV antibody suppressed the production of cAMP by HA-stimulated HOS cells with or without the presence of NO. Therefore, the results of the present study suggest that NO may up-regulate the production of cAMP, perhaps, by augmenting adenylyl cyclase activity initiated by the binding between HOS cell-derived integrin alphaV and HA surface.
    Matched MeSH terms: Imidazoles/pharmacology
  14. Mustafa MR, Dharmani M, Kunheen NK, Sim MK
    Regul. Pept., 2004 Aug 15;120(1-3):15-22.
    PMID: 15177916
    An earlier study showed that des-aspartate-angiotensin I (DAA-I) attenuated the pressor action of angiotensin III in aortic rings of the spontaneously hypertensive rat (SHR) but not the normotensive Wistar Kyoto (WKY) rat. The present study investigated similar properties of DAA-I in isolated perfused kidneys and mesenteric beds of WKY and SHR. In the renal vasculature, angiotensin III induced a dose-dependent pressor response, which was more marked in the SHR than WKY in terms of significant greater magnitude of response and lower threshold. DAA-I attenuated the pressor action of angiotensin III in both the WKY and SHR. The attenuation in SHR was much more marked, occurring at doses as low as 10(-15) M DAA-I, while effective attenuation was only seen with 10(-9) M in WKY. The effects of DAA-I was not inhibited by PD123319 and indomethacin, indicating that its action was not mediated by angiotensin AT2 receptors and prostaglandins. However, the direct pressor action of angiotensin III in the SHR but not the WKY was attenuated by indomethacin suggesting that this notable difference could be due to known decreased response of renal vasculature to vasodilator prostaglandins in the SHR. Pressor responses to angiotensin III in the mesenteric vascular bed was also dose dependent, but smaller in magnitude compared to the renal response. The responses in the SHR, though generally smaller, were not significantly different from those of the WKY. This trend is in line with the similar observations with angiotensin III and II by other investigators. In terms of the effect of DAA-I, indomethacin and PD123319 on angiotensin III action, similar patterns to those of the renal vasculature were observed. This reaffirms that in the perfused kidney and mesenteric bed, where the majority of the vessels are contractile, femtomolar concentrations of DAA-I attenuates the pressor action of angiotensin III. The attenuation is not indomethacin sensitive and does not involve the angiotensin AT2 receptor. The findings suggest that DAA-I possesses protective vascular actions and is involved in the pathophysiology of hypertension.
    Matched MeSH terms: Imidazoles/pharmacology
  15. Ruzmi R, Ahmad-Hamdani MS, Mazlan N
    PLoS One, 2020;15(9):e0227397.
    PMID: 32925921 DOI: 10.1371/journal.pone.0227397
    The continuous and sole dependence on imidazolinone (IMI) herbicides for weedy rice control has led to the evolution of herbicide resistance in weedy rice populations across various countries growing IMI herbicide-resistant rice (IMI-rice), including Malaysia. A comprehensive study was conducted to elucidate occurrence, level, and mechanisms endowing resistance to IMI herbicides in putative resistant (R) weedy rice populations collected from three local Malaysian IMI-rice fields. Seed bioassay and whole-plant dose-response experiments were conducted using commercial IMI herbicides. Based on the resistance index (RI) quantification in both experiments, the cross-resistance pattern of R and susceptible (S) weedy rice populations and control rice varieties (IMI-rice variety MR220CL2 and non-IMI-rice variety MR219) to imazapic and imazapyr was determined. A molecular investigation was carried out by comparing the acetohydroxyacid synthase (AHAS) gene sequences of the R and S populations and the MR220CL2 and MR219 varieties. The AHAS gene sequences of R weedy rice were identical to those of MR220CL2, exhibiting a Ser-653-Asn substitution, which was absent in MR219 and S plants. In vitro assays were conducted using analytical grade IMI herbicides of imazapic (99.3%) and imazapyr (99.6%) at seven different concentrations. The results demonstrated that the AHAS enzyme extracted from the R populations and MR220CL2 was less sensitive to IMI herbicides than that from S and MR219, further supporting that IMI herbicide resistance was conferred by target-site mutation. In conclusion, IMI resistance in the selected populations of Malaysian weedy rice could be attributed to a Ser-653-Asn mutation that reduced the sensitivity of the target site to IMI herbicides. To our knowledge, this study is the first to show the resistance mechanism in weedy rice from Malaysian rice fields.
    Matched MeSH terms: Imidazoles/pharmacology
  16. Chowchaikong N, Nilwarangkoon S, Laphookhieo S, Tanunyutthawongse C, Watanapokasin R
    Int J Oncol, 2018 Jun;52(6):2031-2040.
    PMID: 29620273 DOI: 10.3892/ijo.2018.4353
    Colorectal cancer, which is the third most common type of cancer diagnosed in both men and women, is the leading cause of cancer-related deaths worldwide. Cowanin is a pure compound extracted from Garcinia cowa Roxb., a tree species present in Thailand, Malaysia and Myanmar. The crude extract has been demonstrated to have antitumor activity, inflammation induction, antibacterial activity, anti-inflammatory activity and antimalarial activity. In the present study, the effects of cowanin on apoptosis induction and on the apoptosis-related and mitogen-activated protein kinase (MAPK) pathways were investigated in the LoVo human colorectal cancer cell line. The cytotoxicity of cowanin in LoVo cells was determined by MTT assay. Hoechst 33342 and JC‑1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. The expression levels of BCL2 apoptosis regulator (Bcl‑2) family, MAPK and AKT serine/threonine kinase 1 (Akt) pathway proteins following cowanin treatment were determined by western blot analysis. The results demonstrated that cowanin inhibited cell proliferation and induced cell death via the apoptosis pathway. Cowanin treatment increased BCL2 associated X (Bax) and decreased Bcl‑2 expression. In addition, cowanin activated caspase‑9, -7 and poly-ADP-ribose-polymerase expression. Furthermore, cowanin decreased the levels of phosphorylated extracellular signal-regulated kinase (p‑ERK), p‑Akt, p‑3‑phosphoinositide‑dependent protein kinase‑1, while it increased p‑p38 expression, thus resulting in the induction of apoptosis. In conclusion, cowanin inhibited cell proliferation and induced apoptosis of LoVo cells via the MAPK and Akt signaling pathways. Notably, inhibition of p38 by using a p38 inhibitor (SB203580) prevented the cowanin-induced apoptosis in LoVo cells. These results suggested that cowanin may be a potential candidate for the treatment of colorectal cancer and provided important information on the molecular mechanisms underlying its antitumor activity.
    Matched MeSH terms: Imidazoles/pharmacology*
  17. Poh YW, Gan SY, Tan EL
    Exp Oncol, 2012 Jul;34(2):85-9.
    PMID: 23013758
    The aim of this study is to investigate whether IL-6, IL-10 and TGF-β are able to confer resistance to apoptosis in nasopharyngeal carcinoma cells by upregulating the expression of survivin.
    Matched MeSH terms: Imidazoles/pharmacology
  18. Sosroseno W, Sugiatno E, Samsudin AR, Ibrahim F
    J Oral Implantol, 2008;34(4):196-202.
    PMID: 18780564 DOI: 10.1563/0.910.1
    The aim of the present study was to test the hypothesis that the proliferation of a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite (HA) may be regulated by nitric oxide (NO). The cells were cultured on the surface of HA. Medium or cells alone were used as controls. L-arginine, D-arginine, 7-NI (an nNOS inhibitor), L-NIL (an iNOS inhibitor), L-NIO (an eNOS inhibitor) or carboxy PTIO, a NO scavenger, was added in the HA-exposed cell cultures. The cells were also precoated with anti-human integrin alphaV antibody. The levels of nitrite were determined spectrophotometrically. Cell proliferation was assessed by colorimetric assay. The results showed increased nitrite production and cell proliferation by HA-stimulated HOS cells up to day 3 of cultures. Anti-integrin alphaV antibody, L-NIO, or carboxy PTIO suppressed, but L-arginine enhanced, nitrite production and cell proliferation of HA-stimulated HOS cells. The results of the present study suggest, therefore, that interaction between HA and HOS cell surface integrin alphaV molecule may activate eNOS to catalyze NO production which, in turn, may regulate the cell proliferation in an autocrine fashion.
    Matched MeSH terms: Imidazoles/pharmacology
  19. Ng CT, Fong LY, Sulaiman MR, Moklas MA, Yong YK, Hakim MN, et al.
    J Interferon Cytokine Res, 2015 Jul;35(7):513-22.
    PMID: 25830506 DOI: 10.1089/jir.2014.0188
    Interferon-gamma (IFN-γ) is known to potentiate the progression of inflammatory diseases, such as inflammatory bowel disease and atherosclerosis. IFN-γ has been found to disrupt the barrier integrity of epithelial and endothelial cell both in vivo and in vitro. However, the mechanisms of IFN-γ underlying increased endothelial cell permeability have not been extensively elucidated. We reported that IFN-γ exhibits a biphasic nature in increasing endothelial permeability. The changes observed in the first phase (4-8 h) involve cell retraction and rounding in addition to condensed peripheral F-actin without a significant change in the F-/G-actin ratio. However, cell elongation, stress fiber formation, and an increased F-/G-actin ratio were noticed in the second phase (16-24 h). Consistent with our finding from the permeability assay, IFN-γ induced the formation of intercellular gaps in both phases. A delayed phase of increased permeability was observed at 12 h, which paralleled the onset of cell elongation, stress fiber formation, and increased F-/G-actin ratio. In addition, IFN-γ stimulated p38 mitogen-activated protein (MAP) kinase phosphorylation over a 24 h period. Inhibition of p38 MAP kinase by SB203580 prevented increases in paracellular permeability, actin rearrangement, and increases in the F-/G-actin ratio caused by IFN-γ. Our results suggest that p38 MAP kinase is activated in response to IFN-γ and causes actin rearrangement and altered cell morphology, which in turn mediates endothelial cell hyperpermeability. The F-/G-actin ratio might be involved in the regulation of actin distribution and cell morphology rather than the increased permeability induced by IFN-γ.
    Matched MeSH terms: Imidazoles
  20. Hassan BA, Yusoff ZB, Hassali MA, Othman SB, Weiderpass E
    Asian Pac J Cancer Prev, 2012;13(9):4373-8.
    PMID: 23167346
    INTRODUCTION: Hypercalcemia is mainly caused by bone resorption due to either secretion of cytokines including parathyroid hormone-related protein (PTHrP) or bone metastases. However, hypercalcemia may occur in patients with or without bone metastases. The present study aimed to describe the effect of chemotherapy treatment, regimens and doses on calcium levels among breast and lung cancer patients with hypercalcemia.

    METHODS: We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data.

    RESULTS: Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer.

    CONCLUSION: Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels.

    Matched MeSH terms: Imidazoles/therapeutic use
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