ORCID Profile
0000-0003-4554-6616
Current Organisations
Monash University Malaysia
,
Columbia University College of Physicians and Surgeons
,
International Medical University
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Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JGAR.2017.03.012
Abstract: Currently, only a few antibiotics are available to treat methicillin-resistant Staphylococcus aureus (MRSA). One alternative approach includes adjuvants to antibiotic therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are non-antibiotic drugs reported to exhibit antibacterial activity. The objective of this study was to investigate the interaction between NSAIDs with selected antibiotics (cefuroxime and chlor henicol) against strains of S. aureus. The antibacterial activity of four NSAIDs (aspirin, ibuprofen, diclofenac and mefenamic acid) were tested against ten pathogenic bacterial strains using the microdilution broth method. The interaction between NSAIDs and antibiotics (cefuroxime/chlor henicol) was estimated by calculating the fractional inhibitory concentration (FICI) of the combination. Aspirin, ibuprofen and diclofenac exhibited antibacterial activity against the selected pathogenic bacteria. The interaction between ibuprofen/aspirin with cefuroxime was demonstrated to be synergistic against methicillin-sensitive S. aureus (MSSA) and the MRSA reference strain, whereas for MRSA clinical strains additive effects were observed for both NSAIDs and cefuroxime combinations. The combination of chlor henicol with ibuprofen/aspirin was synergistic against all of the tested MRSA strains and displayed an additive effect against MSSA. A 4-8192-fold reduction in the cefuroxime minimum inhibitory concentration (MIC) and a 4-64-fold reduction of the chlor henicol MIC were documented. Overall, the NSAIDs ibuprofen and aspirin showed antibacterial activity against strains of S. aureus. Although in idually less potent than common antibiotics, these NSAIDs are synergistic in action with cefuroxime and chlor henicol and could potentially be used as adjuvants in combating multidrug-resistant MRSA.
Publisher: Wiley
Date: 22-05-2020
DOI: 10.1002/JBMR.3996
Publisher: Wiley
Date: 27-04-2021
DOI: 10.1002/JBMR.4284
Abstract: We prospectively assessed, with predefined criteria, the location and rates of all femur fractures (hip, subtrochanteric/femoral shaft [ST/FS], including atypical [AFF] and distal fractures) in women at increased fracture risk during treatment with the cathepsin K inhibitor, odanacatib (ODN), or placebo over 5 years in the Long‐Term ODN Fracture Trial (LOFT and LOFT Extension [NCT00529373, EudraCT 2007‐002693‐66]). ODN was an investigational antiresorptive agent previously in development as an osteoporosis treatment that, unlike bisphosphonates, reduces bone formation only transiently. Women aged ≥65 years with a bone mineral density (BMD) T ‐score ≤−2.5 at the total hip (TH) or femoral neck (FN) or with a radiographic vertebral fracture and T ‐scores ≤−1.5 at the TH or FN were randomized (1:1) to receive ODN 50 mg/week or placebo. All patients received vitamin D 3 (5600 IU/week) and calcium (total 1200 mg/d) the analysis included 16,071 women. Rates of all adjudicated low‐energy femoral fractures were 0.38 versus 0.58/100 patient‐years for ODN and placebo, respectively (hazard ratio [HR] = 0.65 95% confidence interval [CI] 0.51–0.82 nominal p .001), and for low‐energy hip fractures were 0.29 versus 0.56/100 patient‐years, respectively (HR = 0.52 95% CI 0.40–0.67 p .001). The cumulative incidence of combined hip and ST/FS or hip fractures alone in the ODN group was consistently lower than in the placebo group (1.93% versus 3.11% for combined fractures and 1.53% versus 3.03% for hip fractures at 5 years, respectively). However, low‐energy ST/FS fractures were more frequent in ODN‐treated women than in placebo‐treated women (24 versus 6, respectively). Among these, 12 fractures were adjudicated as AFF in 10 patients treated with ODN (0.03/100 patient‐years) compared with none in the 6 placebo‐treated women (estimated difference 0.03 95% CI 0.02–0.06). These results provide insight into possible pathogeneses of AFF, suggesting that the current criteria for diagnosing these fractures may need to be reconsidered. © 2021 American Society for Bone and Mineral Research (ASBMR)..
Publisher: Springer Science and Business Media LLC
Date: 07-06-2020
DOI: 10.1007/S00432-020-03274-Y
Abstract: Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells. The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively. LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation. There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.
Publisher: Springer Science and Business Media LLC
Date: 20-05-2019
DOI: 10.1007/S12035-019-1638-7
Abstract: The innate immune system and inflammatory response in the brain have critical impacts on the pathogenesis of many neurodegenerative diseases including Alzheimer's disease (AD). In the central nervous system (CNS), the innate immune response is primarily mediated by microglia. However, non-glial cells such as neurons could also partake in inflammatory response independently through inflammasome signalling. The NLR family pyrin domain-containing 1 (NLRP1) inflammasome in the CNS is primarily expressed by pyramidal neurons and oligodendrocytes. NLRP1 is activated in response to amyloid-β (Aβ) aggregates, and its activation subsequently cleaves caspase-1 into its active subunits. The activated caspase-1 proteolytically processes interleukin-1β (IL-1β) and interleukin-18 (IL-18) into maturation whilst co-ordinately triggers caspase-6 which is responsible for apoptosis and axonal degeneration. In addition, caspase-1 activation induces pyroptosis, an inflammatory form of programmed cell death. Studies in murine AD models indicate that the Nlrp1 inflammasome is indeed upregulated in AD and neuronal death is observed leading to cognitive decline. However, the mechanism of NLRP1 inflammasome activation in AD is particularly elusive, given its structural and functional complexities. In this review, we examine the implications of the human NLRP1 inflammasome and its signalling pathways in driving neuroinflammation in AD.
Location: United States of America
No related grants have been discovered for Felicia Cosman.