Oxidizes Low Density Lipoprotein Cytoxicity and Vascular Diseases

The formation of oxidized low density lipoprotien (oxLDL) within atherosclerotic plaques is a significant event, which appears to drive the transition from fatty streaks to advanced complex plaque cytotoxic agent that triggers a number of competing cell death machanisms

Pterins as diagnostic markers of mechanical and impact-induced trauma: A systematic review

We performed a systematic review of the literature to evaluate pterins as biomarkers of mechanical and impact-induced trauma. MEDLINE and Scopus were searched in March 2019. We included in vivo human studies that measured a pterin in response to mechanical or impact-induced trauma with no underlying prior disease or complication. We included 40 studies with a total of 3829 subjects. Seventy-seven percent of studies measured a significant increase in a pterin, primarily neopterin or total neopterin (neopterin + 7,8-dihydroneopterin). Fifty-one percent of studies measured an increase within 24 h or trauma, while 46% measured increases beyond 48 h. Pterins also showed promise as predictors of post-trauma complications such as sepsis, multi-organ failure and mortality. Exercise-induced trauma and traumatic brain injury caused an immediate increase in neopterin or total neopterin, while patients of multiple trauma had elevated pterin levels that remained above baseline for several days. Pterin concentration changes in response to surgery were variable with patients undergoing cardiac surgery having immediate and sustained pterin increases, while hysterectomy, liver resection or hysterectomy showed no change. This review provides systematic evidence that pterins, in particular neopterin and total neopterin, increase in response to multiple forms of mechanical or impact-induced trauma

Expression profiling of human renal carcinomas with functional taxonomic analysis

BACKGROUND: Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. RESULTS: We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p < 0.001) gene expression changes in clear cell renal carcinomas compared to normal kidney. These genes were classified with a tool to conceptualize expression patterns called "Functional Taxonomy". Each tumor type had a distinct "signature," with a high number of genes in the categories of Metabolism, Signal Transduction, and Cellular and Matrix Organization and Adhesion. CONCLUSIONS: Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data

Potential to Inhibit Growth of Atherosclerotic Plaque development through Modulation of Macrophage neopterin /7,8-dihydroneopterin synthesis

SP Gieseg, EM Crone, EA Flaval, Z Amit

Urinary neopterin and total neopterin measurements allow monitoring of oxidative stress and inflammation levels of knee and hip arthroplasty patients

Knee and hip arthroplasty are common surgeries within an aging population. Some data has suggested that knee arthroplasty is more traumatic to the body than hip arthroplasty due to the increased complexity and load bearing nature of the joint. Here, we compare the stress of the two surgeries by measuring urinary neopterin and total neopterin as biomarkers of oxidative stress and inflammation. Urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) levels were analysed in 28 knee and 22 hip arthroplasty patients pre- and post-operatively to determine oxidative stress and inflammation levels. Total neopterin was 31.1% higher with knee arthroplasty (p<0.05). Urinary neopterin was 32.8% higher in the knee arthroplasty group versus hips. The increase in neopterin and total neopterin following a post-surgical decrease in levels was significant in both groups. Levels of neopterin and total neopterin were varied between patients, but all increased following surgery and subsided by day 28. The increased levels of urinary neopterin and total neopterin from knee arthroplasty indicate that knee osteoarthritis and arthroplasty is a more significant trauma to the body than hip osteoarthritis and arthroplasty surgery. This is also shown by faster inflammatory resolution following hip arthroplasty

The effect of 1 week of repeated ischaemic leg preconditioning on simulated Keirin cycling performance: a randomised trial

Background Coaches continually seek new ways of doing things and also refine existing techniques to improve sporting performance. Coaches are currently experimenting using ischaemic preconditioning (IPC) over consecutive days in the hope of improving competitive performances. Aims First, to quantify the physiological impact of 1 week of IPC on simulated Keirin cycling performance. Second, to investigate if biochemical stress markers are affected over the treatment period. Methods Using a randomised, sham-controlled design, 18 active adults undertook seven consecutive days of IPC treatment (45 min occlusion/reperfusion) applied to each leg at either 220 mm Hg (treatment, n=9) or 20 mm Hg (sham, n=9). Urinary measures of inflammation, oxidative stress and indirect nitric oxide synthesis were undertaken daily. A simulated Keirin cycling competition (430 s Wingate tests) was performed on day 10, with baseline and postintervention cycling VO2max (days 1, 11 and 18) and 30 s Wingate tests (day 2) undertaken for comparison. Results The treatment group had enhanced mean cycling power (3.4%), while neopterin and biopterin in conjunction with total neopterin were significantly lower (p<0.05) and total biopterin significantly greater (p<0.05) during the simulated Keirin. Aerobic fitness measures significantly improved from baseline to postintervention (VO2peak: 12.8% ", maximal aerobic power: 18.5% "). Conclusions Seven consecutive days of IPC improved aerobic and anaerobic capacity measures, with modulations in oxidative stress, immune system activation and nitric oxide/catecholamine synthesis

The influence of tumor size and environment on gene expression in commonly used human tumor lines

BACKGROUND: The expression profiles of solid tumor models in rodents have been only minimally studied despite their extensive use to develop anticancer agents. We have applied RNA expression profiling using Affymetrix U95A GeneChips to address fundamental biological questions about human tumor lines. METHODS: To determine whether gene expression changed significantly as a tumor increased in size, we analyzed samples from two human colon carcinoma lines (Colo205 and HCT-116) at three different sizes (200 mg, 500 mg and 1000 mg). To investigate whether gene expression was influenced by the strain of mouse, tumor samples isolated from C.B-17 SCID and Nu/Nu mice were also compared. Finally, the gene expression differences between tissue culture and in vivo samples were investigated by comparing profiles from lines grown in both environments. RESULTS: Multidimensional scaling and analysis of variance demonstrated that the tumor lines were dramatically different from each other and that gene expression remained constant as the tumors increased in size. Statistical analysis revealed that 63 genes were differentially expressed due to the strain of mouse the tumor was grown in but the function of the encoded proteins did not link to any distinct biological pathways. Hierarchical clustering of tissue culture and xenograft samples demonstrated that for each individual tumor line, the in vivo and in vitro profiles were more similar to each other than any other profile. We identified 36 genes with a pattern of high expression in xenograft samples that encoded proteins involved in extracellular matrix, cell surface receptors and transcription factors. An additional 17 genes were identified with a pattern of high expression in tissue culture samples and encoded proteins involved in cell division, cell cycle and RNA production. CONCLUSIONS: The environment a tumor line is grown in can have a significant effect on gene expression but tumor size has little or no effect for subcutaneously grown solid tumors. Furthermore, an individual tumor line has an RNA expression pattern that clearly defines it from other lines even when grown in different environments. This could be used as a quality control tool for preclinical oncology studies

Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo

Senescence is a distinct cellular response induced by DNA-damaging agents and other sublethal stressors and may provide novel benefits in cancer therapy. However, in an ageing model, senescent fibroblasts were found to stimulate the proliferation of cocultured cells. To address whether senescence induction in cancer cells using chemotherapy induces similar effects, we used GFP-labelled prostate cancer cell lines and monitored their proliferation in the presence of proliferating or doxorubicin-induced senescent cancer cells in vitro and in vivo. Here, we show that the presence of senescent cancer cells increased the proliferation of cocultured cells in vitro through paracrine signalling factors, but this proliferative effect was significantly less than that seen with senescent fibroblasts. In vivo, senescent cancer cells failed to increase the establishment, growth or proliferation of LNCaP and DU145 xenografts in nude mice. Senescent cells persisted as long as 5 weeks in tumours. Our results demonstrate that although drug-induced senescent cancer cells stimulate the proliferation of bystander cells in vitro, this does not significantly alter the growth of tumours in vivo. Coupled with clinical observations, these data suggest that the proliferative bystander effects of senescent cancer cells are negligible and support the further development of senescence induction as therapy

MARS spectral molecular imaging of lamb tissue: data collection and image analysis

Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20 to 140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we are one of the first to present data from multi-energy photon-processing small animal CT systems, we make the raw, partial and fully processed data available with the intention that others can analyze it using their familiar routines. The raw, partially processed and fully processed data of lamb tissue along with the phantom calibration data can be found at [http://hdl.handle.net/10092/8531].Comment: 11 pages, 6 fig