https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Qualitative study investigating the underlying motivations of healthy participants in phase I clinical trials https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34855 Wed 24 May 2023 12:20:01 AEST ]]> Efficacy of Indian polyvalent snake antivenoms against Sri Lankan snake venoms: lethality studies or clinically focussed in vitro studies https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30223 In vitro antivenom efficacy studies were compared to rodent lethality studies to test two Indian snake antivenoms (VINS and BHARAT) against four Sri Lankan snakes. In vitro efficacy was tested at venom concentrations consistent with human envenoming. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In binding studies EC50 for all VINS antivenoms were less than BHARAT for D. russelii [553 μg/mL vs. 1371 μg/mL;p=0.016), but were greater for VINS antivenoms compared to BHARAT for N. naja [336 μg/mL vs. 70 μg/mL;p<0.0001]. EC50 of both antivenoms was only slighty different for E. carinatus and B. caeruleus. For procoagulant activity neutralisation, the EC50 was lower for VINS compared to BHARAT - 60 µg/mL vs. 176 µg/mL (p<0.0001) for Russell's viper and 357 µg/mL vs. 6906µg/mL (p<0.0001) for Saw-scaled viper. Only VINS antivenom neutralized in vitro neurotoxicity of krait venom. Both antivenoms partially neutralized cobra and didn't neutralize Russell's viper neurotoxicity. Lethality studies found no statistically significant difference in ED50 values between VINS and BHARAT antivenoms. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans.]]> Wed 11 Apr 2018 16:22:51 AEST ]]> Norcantharidin suppresses colon cancer cell epithelial-mesenchymal transition by inhibiting the alpha v beta 6-ERK-ets1 signaling pathway https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30106 Wed 11 Apr 2018 14:52:18 AEST ]]> Repurposing existing therapeutics, its importance in oncology drug development: Kinases as a potential target https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45654 Wed 02 Nov 2022 15:37:57 AEDT ]]> Aminoguanidines: new leads for treatment of Giardia duodenalis infection https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34739 50 was as low as 0.2 μM with corresponding MLCs as low as 2.8 μM. This is in contrast to metronidazole which required 24 h to exhibit inhibitory activity. A modified adherence assay, developed for this study, demonstrated that three of the compounds inhibited in vitro adherence of the parasite. The lead compound exhibited rapid giardicidal activity (<5hr). In addition, microscopy studies demonstrated damage to the plasma membrane of trophozoites. In conclusion, a class of aminoguanidines, represented by robenidine, has shown antigiardial activity warranting further investigation.]]> Tue 03 Sep 2019 17:57:16 AEST ]]> The bispidinone derivative 3,7-Bis-[2-(S)-amino-3-(1H-indol-3-yl)-propionyl]-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride induces an apoptosis-mediated cytotoxic effect on pancreatic cancer cells in vitro https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34760 BisP1: 1,5-diphenyl-3,7-bis(2-hydroxyethyl)-3,7-diazabicyclo[3.3.1]nonan-9-one; BisP2: 3,7-bis-(2-(S)-amino-4-methylsulfanylbutyryl)-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride; BisP3: [2-{7-[2-(S)-tert-butoxycarbonylamino-3-(1H-indol-3-yl)-propionyl]-9-oxo-1,5-diphenyl-3,7-diazabicyclo[3.3.1]non-3-yl}-1-(S)-(1H-indol-3-ylmethyl)-2-oxoethyl]-carbamic acid tertbutyl ester; BisP4: 3,7-bis-[2-(S)-amino-3-(1H-indol-3-yl)-propionyl]-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride) was assessed against PC cell lines (MiaPaca-2, CFPAC-1 and BxPC-3). Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) colorimetric assay, while apoptotic cell death was confirmed using fluorescence microscopy and flow cytometry. Initial viability screening revealed significant cytotoxic activity from BisP4 treatment (1 µM⁻100 µM) on all three cell lines, with IC50 values for MiaPaca-2, BxPC-3, and CFPAC-1 16.9 µM, 23.7 µM, and 36.3 µM, respectively. Cytotoxic treatment time-response (4 h, 24 h, and 48 h) revealed a 24 h treatment time was sufficient to produce a cytotoxic effect on all cell lines. Light microscopy evaluation (DAPI staining) of BisP4 treated MiaPaca-2 PC cells revealed dose-dependent characteristic apoptotic morphological changes. In addition, flow cytometry confirmed BisP4 induced apoptotic cell death induction of activated caspase-3/-7. The bispidinone derivative BisP4 induced an apoptosis-mediated cytotoxic effect on MiaPaca-2 cell lines and significant cytotoxicity on CFPAC-1 and BxPC-3 cell lines. Further investigations into the precise cellular mechanisms of action of this class of compounds are necessary for potential development into pre-clinical trials.]]> Thu 17 Mar 2022 14:34:42 AEDT ]]> Bacterial transcription as a target for antibacterial drug development https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29829 Sat 24 Mar 2018 07:40:53 AEDT ]]> Inhibiting the NusB-NusE protein-protein interaction - a novel target for antibiotic drug development https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31976 Mon 23 Sep 2019 10:21:04 AEST ]]> In vivo experimental models of infection and disease https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40023 Mon 04 Jul 2022 09:22:32 AEST ]]> A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45453 Fri 28 Oct 2022 14:15:24 AEDT ]]> Contemporary anti-Ebola drug discovery approaches and platforms https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42239 Fri 26 Aug 2022 09:43:19 AEST ]]>