OBJECTIVE: In the present study, the standardized extract of P. amarus was investigated for its suppressive effects on type II collagen-induced rheumatoid arthritis (TCIA) in Sprague Dawley rats.
METHOD: The major components of the extracts, lignans and phenolic compounds were analysed by using a validated reversed phase HPLC and LC-MS/MS. A rheumatoid arthritis rat model was induced by administering a bovine type II collagen emulsion subcutaneously at the base of tail, on day 0 and 7 of the experiment. Effects of the extract on severity assessment, changes in the hind paw volume, bone mineral density, body weight and body temperature were measured. Concentrations of cytokines (TNF-α, IL-1β, IL-1α, IL-6) released, matrix metalloproteinases (MMP-1, MMP-3 MMP-9) and their inhibitor (TIMP-1), haematological and biochemical changes were also measured. ELISA was used to measure the cytokines and proteinases in the rat serum and synovial fluid according to manufacturer's instructions.
RESULTS: The extract dose-dependently modulated the progression in physical parameters (i.e. decrease in body weight, increase in body temperature, reduced hind paw volume, reduced the severity of arthritis), bone mineral density, haematological and biochemical perturbations, serum cytokines production and levels of matrix metalloproteinases and their inhibitor in the synovial fluid. Histopathological examination of the knee joint also revealed that the extract effectively reduced synovitis, pannus formation, bone resorption and cartilage destruction.
CONCLUSION: The results suggest that the oral administration of a standardized extract of P. amarus was able to suppress the humoral and cellular immune responses to type II collagen, resulting in the reduction of the development of TCIA in the rats.
METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection.
RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells.
CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.
RESULTS: We found hemoparasites in only two of 19 species sampled. Among them, all species that consume at least one food item known for its secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, were free from hemoparasites. In contrast, the infected parrots do not consume food items with antimalarial or even general antiparasitic properties. We found that the two infected species in this study consumed omnivorous diets. When we combined our data with data from studies previously investigating blood parasites in wild parrots, the positive relationship between omnivorous diets and hemoparasite infestation was confirmed. Individuals from open habitats were less infected than those from forests.
CONCLUSIONS: The consumption of food items known for their secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, as well as the higher proportion of infected species among omnivorous parrots, could explain the low prevalence of hemoparasites reported in many vertebrates.
METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability.
RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%.
CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system.
TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.
METHODS: A clinical efficacy study of oral artesunate (total target dose 12 mg/kg) daily for 3 days was conducted in patients with uncomplicated falciparum malaria and a parasite count
MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.
RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.
CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.