Assay method validation of triamcinolone acetonide (TA) to support the investigation of TA-loaded nanoparticles

Theaim of this study was to develop the valid analytical method which used for the assay of triamcinolone acetonide (TA) in the investigation of TA loaded nanoparticle formulations. High Performance Liquid Chromatography(HPLC) method was applied in  his study by using an Econosil column,C1810 m, 250x 4.6mm (Alltech Associates Inc, PA,USA )as the stationary phase. Themobile phase consisted of a composition of acetonitrile (ACN) and 20mM phosphate buffer solution (pH 4.2) in the proportion of 50:50 v/v. The HPLCassay of TA was validated for selectivity, linearity, precision, ecovery (accuracy),sensitivity and stability of TA during the assay. Results showed that the concentration of TA in the sample scan be determined against the standard in the concentration range of calibration curve. The system precision and level of recovery were considered to be acceptable, and the method was selective and sensitive.Key words:triamcinoloneacetonide,assay,validatio

Sitotoksisitas rimpang temu mangga (Curcuma Mangga Val. & V. Zijp.) dan kunir putih (Curcuma Zedoaria L) terhadap beberapa sel kanker manusia (in vitro) dengan metoda SRB

ABSTRACT Mae Sri Hartati W, Sofia Mubarika, R. L. H. Bolhuis, K. Nooter, R. G. Oostrum, A. W. M. Boersma, Subagus Wahyuono - Cytotoxic effect on human cancer cell using SRB method (in vitro) rimpang temu mangga (Curcuma Mangga Val. & V. Zijp.) dan kunir putih (Curcuma Zedoaria I.). Background: Temu mangga (Curcuma mangga) and kunir putih (Curcuma zedoaria) rhizomes have been utilized by people to treat cancer lately although clinically their activity has not been tested. Objectives: This study is aimed to prove their activity as anticancer on 7 major human cancers cell lines (in vitro), and to evaluate whether these two rhizomes are potential for new anticancer drug. Methods: The two rhizomes were separately extracted with chloroform followed by methanol to give chloroform extracts of C. mangga (CmCh) and C. zedoaria (CzCh)and methanol extracts of C. mangga (CmMe) and C. zedoaria (CzMe) respectively. These extracts were tested their cytotoxic effect on 7 major human cancer cell lines using SRB method (in vitro). Doxorubicin and cisplatin were used as positive controls, and their cytotoxic effects were measured by comparing their ID50 with that of the positive controls. Results: Those four extracts (CmCh, CzCh, CmMe and CzMe) practically did not perform cytotoxic effect on those human cancer cell lines, because the extract\u27s ID50 was far higher than the positive controls on those human, cancers cell lines Conclusion: The C. mangga and C. zedoaria rhizomes did not active as anticancer and they were not pOtential as the source of a new anticancer drug. Key words: anticancer - Curcuma mangga - Curcuma zedoaria - cytotoxic - drug discover

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort

Aims: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.// Methods and results: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).// Conclusion: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.// Clinical Trial Registration: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106

α-Tocopheryl succinate and TRAIL selectively synergise in induction of apoptosis in human malignant mesothelioma cells

Malignant mesothelioma (MM) is a fatal type of neoplasia with poor therapeutic prognosis, largely due to resistance to apoptosis. We investigated the apoptotic effect of alpha-tocopheryl succinate (alpha-TOS), a strong proapoptotic agent, in combination with the immunological apoptogen TNF-related apoptosis-inducing ligand (TRAIL) on both MM and nonmalignant mesothelial cells, since MM cells show low susceptibility to the clinically intriguing TRAIL. All MM cell lines tested were sensitive to alpha-TOS-induced apoptosis, and exerted high sensitivity to TRAIL in the presence of subapoptotic doses of the vitamin E analogue. Neither TRAIL or alpha-TOS alone or in combination caused apoptosis in nonmalignant mesothelial cells. Isobologram analysis of the cytotoxicity assays revealed a synergistic interaction between the two agents in MM cells and their antagonistic effect in nonmalignant mesothelial cells. TRAIL-induced apoptosis and its augmentation by alpha-TOS were inhibited by the caspase-8 inhibitor Z-IETD-FMK and the pan-caspase inhibitor Z-VAD-FMK. Activation of caspase-8 was required to induce apoptosis, which was amplified by alpha-TOS via cytochrome c release following Bid cleavage, with ensuing activation of caspase-9. Enhancement of TRAIL-induced apoptosis in MM cells by alpha-TOS was also associated with upregulation of the TRAIL cognate death receptors DR4 and DR5. Our results show that alpha-TOS and TRAIL act in synergism to kill MM cells via mitochondrial pathway, and are nontoxic to nonmalignant mesothelial cells. These findings are indicative of a novel strategy for treatment of thus far fatal MM

α-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate

BACKGROUND: A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H2O2 that promoted cell death. METHODS: The redox-silent vitamin E analogue a-tocopheryl succinate (a-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. RESULTS: Prostate cancer cells were sensitive to a-TOS and VK3 treatment, but resistant to AA upto 3.2mM. When combined, a synergistic effect was found for VK3\u2013AA, whereas a-TOS\u2013VK3 and a-TOS\u2013AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA\u2013VK3 combination combined with a sub-toxic dose of a-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal\u2013mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. CONCLUSION: These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity

MiR-17-92 and miR-221/222 cluster members target KIT and ETV1 in human gastrointestinal stromal tumours

Background:Gastrointestinal stromal tumours (GIST) are characterised by high expression of KIT and ETV1, which cooperate in GIST oncogenesis. Our aim was to identify microRNAs that are deregulated in GIST, have a role in GIST pathogenesis, and could potentially be used as therapeutic tool.Methods:Differentially expressed microRNAs between primary GIST (n=50) and gastrointestinal leiomyosarcomas (GI-LMS, n=10) were determined using microarrays. Selected microRNA mimics were transfected into GIST-882 and GIST-T1 cell lines to study the effects of microRNA overexpression on GIST cells. Luciferase reporter assays were used to establish regulation of target genes by selected microRNAs.Results:MiR-17-92 and miR-221/222 cluster members were significantly (P<0.01) lower expressed in GIST vs GI-LMS and normal gastrointestinal control tissues. MiR-17/20a/222 overexpression in GIST cell lines severely inhibited cell proliferation, affected cell cycle progression, induced apoptosis and strongly downregulated protein and - to a lesser extent - mRNA levels of their predicted target genes KIT and ETV1. Luciferase reporter assays confirmed direct regulation of KIT and ETV1 by miR-222 and miR-17/20a, respectively.Conclusion:MicroRNAs that may have an essential role in GIST pathogenesis were identified, in particular miR-17/20a/222 that target KIT and ETV1. Delivering these microRNAs therapeutically could hold great potential for GIST management, especially in imatinib-resistant disease.British Journal of Cancer advance online publication, 22 August 2013; doi:10.1038/bjc.2013.483 www.bjcancer.com.status: publishe

Stress and resilience in rheumatic diseases: a review and glimpse into the future

Item does not contain fulltextStress resilience factors, and interventions to ease stress and enhance resilience, are gaining increasing attention for the treatment of rheumatic conditions. This Review presents a digest of empirical work on the factors that determine the risk of adapting poorly to a rheumatic condition, and on the resilience factors that counteract such risks. We consider the types of stress-management and resilience treatments that are most effective in promoting the physical and psychological functioning of patients at risk of long-term adjustment problems. Prospective research shows that cognitive-behavioral and social risk and resilience factors predict the long-term physical and psychological functioning of patients with rheumatic conditions. Furthermore, validated screening instruments are becoming increasingly useful in clinical practice to identify and select patients at risk. Stress-management and resilience interventions offer promising ways to improve the long-term functioning of patients. These treatment methods might be especially useful when they are tailored to the specific risk and resilience factors of patients, and when they incorporate innovative approaches to the delivery of services, including internet applications such as eHealth, to increase efficiency and availability of treatments, and to optimize patient empowerment in rheumatic conditions