Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: Study in paraffin tissue sections

BACKGROUND: Steroid action is mediated, in addition to classical intracellular receptors, by recently identified membrane sites, that generate rapid non-genomic effects. We have recently identified a membrane androgen receptor site on prostate carcinoma cells, mediating testosterone rapid effects on the cytoskeleton and secretion within minutes. METHODS: The aim of this study was to investigate whether membrane androgen receptors are differentially expressed in prostate carcinomas, and their relationship to the tumor grade. We examined the expression of membrane androgen receptors in archival material of 109 prostate carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA-coupled testosterone. RESULTS: We report that membrane androgen receptors are preferentially expressed in prostate carcinomas, and they correlate to their grade using the Gleason's microscopic grading score system. CONCLUSION: We conclude that membrane androgen receptors may represent an index of tumor aggressiveness and possibly specific targets for new therapeutic regimens

Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature

Joint arthroplasty registries show an increased rate of aseptic loosening in uncemented acetabular components as compared to cemented acetabular components. Since loosening is associated with particulate wear debris, we postulated that uncemented acetabular components demonstrate a higher polyethylene wear rate than cemented acetabular components in total hip arthroplasty. We performed a systematic review of the peer-reviewed literature, comparing the wear rate in uncemented and cemented acetabular components in total hip arthroplasty. Studies were identified using MEDLINE (PubMed), EMBASE and the Cochrane Central Register of Controlled Trials. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search resulted in 425 papers. After excluding duplicates and selection based on title and abstracts, nine studies were found eligible for further analysis: two randomised controlled trials, and seven observational studies. One randomised controlled trial found a higher polyethylene wear rate in uncemented acetabular components, while the other found no differences. Three out of seven observational studies showed a higher polyethylene wear in uncemented acetabular component fixation; the other four studies did not show any differences in wear rates. The available evidence suggests that a higher annual wear rate may be encountered in uncemented acetabular components as compared to cemented components

Bio-psychosocial determinants of cardiovascular disease in a rural population on Crete, Greece: formulating a hypothesis and designing the SPILI-III study

Background: In 1988, the SPILI project was established in order to evaluate the cardiovascular disease (CVD) risk profile of the inhabitants of Spili, in rural Crete, Greece. The first reports from this project revealed that against the unfavourable risk factors’ profile observed, only a few men with a previous myocardial infarction were encountered. A follow-up study (SPILI II) was performed twelve years after the initial examination, and the unfavourable cardiovascular risk profile was re-confirmed. Presentation of the Hypothesis: This paper presents a hypothesis formulated on the basis of previous research to investigate if dynamic psycho-social determinants, including social coherence of the local community, religiosity and spirituality, are protective against the development of coronary heart disease in a well-defined population. Testing the Hypothesis: A follow-up examination of this Cretan cohort is currently being performed to assess the link between psychosocial factors and CVD. Psychosocial factors including sense of control, religiosity and spirituality are assessed in together with conventional CVD risk factors. Smoking and alcohol consumption, as well as dietary habits and activity levels are recorded. Oxidative stress and inflammatory markers, as well as ultrasound measurement of carotid intima media thickness, a preclinical marker of atherosclerosis, will also be measured. Implications of the hypothesis tested: The issue of the cardio-protective effect of psycho-social factors would be revisited based on the results of this Cretan cohort; nevertheless, further research is needed across different subpopulations in order to establish a definite relationship. A comprehensive approach based on the aspects of biosocial life may result in more accurate CVD risk management

Genes in the postgenomic era

We outline three very different concepts of the gene - 'instrumental', 'nominal', and 'postgenomic'. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype

Suppression of Implanted MDA-MB 231 Human Breast Cancer Growth in Nude Mice by Dietary Walnut

Walnuts contain components that may slow cancer growth including omega 3 fatty acids, phytosterols, polyphenols, carotenoids, and melatonin. A pilot study was performed to determine whether consumption of walnuts could affect growth of MDA-MB 231 human breast cancers implanted into nude mice. Tumor cells were injected into nude mice that were consuming an AIN-76A diet slightly modified to contain 10% corn oil. After the tumors reached 3 to 5 mm diameter, the diet of one group of mice was changed to include ground walnuts, equivalent to 56 g (2 oz) per day in humans. The tumor growth rate from Day 10, when tumor sizes began to diverge, until the end of the study of the group that consumed walnuts (2.9 ± 1.1 mm3/day; mean ± standard error of the mean) was significantly less (P \u3e 0.05, t-test of the growth rates) than that of the group that did not consume walnuts (14.6 ± 1.3 mm 3 /day). The eicosapentaenoic and docosahexaenoic acid fractions of the livers of the group that consumed walnuts were significantly higher than that of the group that did not consume walnuts. Tumor cell proliferation was decreased, but apoptosis was not altered due to walnut consumption. Further work is merited to investigate applications to cancer in humans

Blood spots as an alternative to whole blood collection and the effect of a small monetary incentive to increase participation in genetic association studies

<p>Abstract</p> <p>Background</p> <p>Collection of buccal cells from saliva for DNA extraction offers a less invasive and convenient alternative to venipuncture blood collection that may increase participation in genetic epidemiologic studies. However, dried blood spot collection, which is also a convenient method, offers a means of collecting peripheral blood samples from which analytes in addition to DNA can be obtained.</p> <p>Methods</p> <p>To determine if offering blood spot collection would increase participation in genetic epidemiologic studies, we conducted a study of collecting dried blood spot cards by mail from a sample of female cancer cases (n = 134) and controls (n = 256) who were previously selected for a breast cancer genetics study and declined to provide a venipuncture blood sample. Participants were also randomized to receive either a $2.00 bill or no incentive with the blood spot collection kits.</p> <p>Results</p> <p>The average time between the venipuncture sample refusal and recruitment for the blood spot collection was 4.4 years. Thirty-seven percent of cases and 28$2.00 incentive vs. 26% for no incentive, p = 0.6), it was significantly associated with participation among the breast cancer cases (48% vs. 27%, respectively, p = 0.01). There did not appear to be any bias in response since no differences between cases and controls and incentive groups were observed when examining several demographic, work history and radiation exposure variables.</p> <p>Conclusion</p> <p>This study demonstrates that collection of dried blood spot cards in addition to venipuncture blood samples may be a feasible method to increase participation in genetic case-control studies.</p

Antifungal, anti-inflammatory and cytotoxicity activities of three varieties of Labisia pumila benth : from microwave obtained extracts.

Background: Labisia pumila, locally known as Kacip Fatimah, is a forest-floor plant that has tremendous potential in the herbal industry. It is one of the five herbal plants identified by the government as one of the national key economic areas to be developed for commercial purposes. There are three varieties of L. pumila namely, L. pumila var. pumila, L. pumila var. alata and L. pumila var. lanceolata and each has its own use.Methods: The leaves and roots of the three varieties of L. pumila Benth. were extracted using microwave assisted extraction (MAE). Antifungal activity of all plant extracts were characterized against Fusarium sp., Candida sp. and Mucor using the agar diffusion disc. Anti-inflammatory assays were performed using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-g and cytotoxic activity was determined using several cancer cell lines and one normal cell line.Results: The overall result demonstrated that leaf and root extracts of all three varieties of L. pumila exhibited moderate to appreciable antifungal activity against Fusarium sp., Candida sp. and Mucor compared to streptomycin used as positive control. Leaf and root extracts of all varieties significantly decreased NO release. However, the root extracts showed higher activity compared to the leaf extracts. Cytotoxic activity against MCF-7, MDA-MB-231 and Chang cell lines were observed with all extracts.Conclusions: These findings suggest the potential use of L. pumila Benth. as a natural medicine and indicated the possible application of this medicinal plant such anti inflammatory activity and cytotoxic agents

Aspects of bovine herpesvirus-1 infection in dairy and beef herds in the Republic of Ireland

<p>Abstract</p> <p>Background</p> <p>Infection with bovine herpesvirus-1 (BHV-1) causes a wide range of disease manifestations, including respiratory disease and abortion, with world-wide distribution. The primary objective of the present study was to describe aspects of BHV-1 infection and control on Irish farms, including herd-level seroprevalence (based on pooled sera) and vaccine usage.</p> <p>Methods</p> <p>The characteristics of a diagnostic indirect BHV-1 antibody ELISA test when used on serum pools were evaluated using laboratory replicates for use in the seroprevalence study. The output from this indirect ELISA was expressed as a percentage positivity (PP) value. A proposed cut off (PCO) PP was applied in a cross-sectional study of a stratified random sample of 1,175 Irish dairy and beef cattle herds in 2009, using serum pools, to estimate herd seroprevalence. The study was observational, based primarily on the analysis of existing samples, and only aggregated results were reported. For these reasons, ethical approval was not required. Bulk milk samples from a subset of 111 dairy herds were analysed using the same ELISA. Information regarding vaccine usage was determined in a telephone survey.</p> <p>Results</p> <p>A PCO PP of 7.88% was determined to give 97.1% sensitivity and 100% specificity relative to the use of the ELISA on individual sera giving maximization of the prevalence independent Youden's index, on receiver operating characteristics analysis of replicate results. The herd-level BHV-1 seroprevalence was 74.9% (95% CI - 69.9%-79.8%), with no significant difference between dairy and beef herds. 95.5% agreement in herd classification was found between bulk milk and serum pools. Only 1.8 percent of farmers used BHV-1 marker vaccine, 80% of which was live while 75% of vaccinated herds were dairy.</p> <p>A significant association was found between herd size (quartiles) and seroprevalence (quartiles).</p> <p>Conclusions</p> <p>The results from this study indicate BHV-1 infection is endemic, although BHV-1 vaccines are rarely used, in the cattle population in Ireland.</p

A high‐resolution view of the coordination environment in a paramagnetic metalloprotein from its magnetic properties

Metalloproteins constitute a significant fraction of the proteome of all organisms and their characterization is critical for both basic sciences and biomedical applications. A large portion of metalloproteins bind paramagnetic metal ions, and paramagnetic NMR spectroscopy has been widely used in their structural characterization. However, the signals of nuclei in the immediate vicinity of the metal center are often broadened beyond detection. In this work, we show that it is possible to determine the coordination environment of the paramagnetic metal in the protein at a resolution inaccessible to other techniques. Taking the structure of a diamagnetic analogue as a starting point, a geometry optimization is carried out by fitting the pseudocontact shifts obtained from first principles quantum chemical calculations to the experimental ones

Total and corrected antioxidant capacity in hemodialyzed patients

BACKGROUND: Oxidative stress may play a critical role in the vascular disease of end stage renal failure and hemodialysis patients. Studies, analyzing either discrete analytes and antioxidant substances, or the integrated total antioxidant activity of human plasma during hemodialysis, give contradictory results. METHODS: Recently, we have introduced a new automated method for the determination of Total Antioxidant Capacity (TAC) of human plasma. We have serially measured TAC and corrected TAC (cTAC: after subtraction of the interactions due to endogenous uric acid, bilirubin and albumin) in 10 patients before the onset of the dialysis session, 10 min, 30 min, 1 h, 2 h and 3 h into the procedure and after completion of the session. RESULTS: Our results indicate that TAC decreases, reaching minimum levels at 2 h. However, corrected TAC increases with t(1/2 )of about 30 min. We then repeated the measurements in 65 patients undergoing dialysis with different filters (36 patients with ethylene vinyl alcohol copolymer resin filter -Eval-, 23 patients with two polysulfone filters -10 with F6 and 13 with PSN140-, and 6 patients with hemophan filters). Three specimens were collected (0, 30, 240 min). The results of this second group confirm our initial results, while no significant difference was observed using either filter. CONCLUSIONS: Our results are discussed under the point of view of possible mechanisms of modification of endogenous antioxidants, and the interaction of lipid- and water-soluble antioxidants