Clinical implications in the shift of syndecan-1 expression from the cell membrane to the cytoplasm in bladder cancer

Background To determine the diagnostic and prognostic capability of urinary and tumoral syndecan-1 (SDC-1) levels in patients with cancer of the urinary bladder. Methods SDC-1 levels were quantitated by enzyme-linked immunosorbent assay (ELISA) in 308 subjects (102 cancer subjects and 206 non-cancer subjects) to assess its diagnostic capabilities in voided urine. The performance of SDC-1 was evaluated using the area under the curve of a receiver operating characteristic curve. In addition, immunohistochemical (IHC) staining assessed SDC-1 protein expression in 193 bladder specimens (185 cancer subjects and 8 non-cancer subjects). Outcomes were correlated to SDC-1 levels. Results Mean urinary levels of SDC-1 did not differ between the cancer subjects and the non-cancer subjects, however, the mean urinary levels of SDC-1 were reduced in high-grade compared to low-grade disease (p < 0.0001), and in muscle invasive bladder cancer (MIBC) compared to non-muscle invasive bladder cancer (NMIBC) (p = 0.005). Correspondingly, preliminary data note a shift from a membranous cellular localization of SDC-1 in normal tissue, low-grade tumors and NMIBC, to a distinctly cytoplasmic localization in high-grade tumors and MIBC was observed in tissue specimens. Conclusion Alone urinary SDC-1 may not be a diagnostic biomarker for bladder cancer, but its urinary levels and cellular localization were associated with the differentiation status of patients with bladder tumors. Further studies are warranted to define the potential role for SDC-1 in bladder cancer progression.

Clinical implications in the shift of syndecan-1 expression from the cell membrane to the cytoplasm in bladder cancer

Background To determine the diagnostic and prognostic capability of urinary and tumoral syndecan-1 (SDC-1) levels in patients with cancer of the urinary bladder. Methods SDC-1 levels were quantitated by enzyme-linked immunosorbent assay (ELISA) in 308 subjects (102 cancer subjects and 206 non-cancer subjects) to assess its diagnostic capabilities in voided urine. The performance of SDC-1 was evaluated using the area under the curve of a receiver operating characteristic curve. In addition, immunohistochemical (IHC) staining assessed SDC-1 protein expression in 193 bladder specimens (185 cancer subjects and 8 non-cancer subjects). Outcomes were correlated to SDC-1 levels. Results Mean urinary levels of SDC-1 did not differ between the cancer subjects and the non-cancer subjects, however, the mean urinary levels of SDC-1 were reduced in high-grade compared to low-grade disease (p < 0.0001), and in muscle invasive bladder cancer (MIBC) compared to non-muscle invasive bladder cancer (NMIBC) (p = 0.005). Correspondingly, preliminary data note a shift from a membranous cellular localization of SDC-1 in normal tissue, low-grade tumors and NMIBC, to a distinctly cytoplasmic localization in high-grade tumors and MIBC was observed in tissue specimens. Conclusion Alone urinary SDC-1 may not be a diagnostic biomarker for bladder cancer, but its urinary levels and cellular localization were associated with the differentiation status of patients with bladder tumors. Further studies are warranted to define the potential role for SDC-1 in bladder cancer progression.

Aspirin and statin use and the subsequent development of depression in men and women: Results from a longitudinal population-based study.

OBJECTIVE: Low-grade chronic inflammation is one potential mechanism underlying the well-established association between major depressive disorder (MDD) and increased cardiovascular morbidity. Both aspirin and statins have anti-inflammatory properties, which may contribute to their preventive effect on cardiovascular diseases. Previous studies on the potentially preventive effect of these drugs on depression have provided inconsistent results. The aim of the present paper was to assess the prospective association between regular aspirin or statin use and the incidence of MDD. METHOD: This prospective cohort study included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from the general population of an urban area. Subjects underwent a thorough physical evaluation as well as semi-structured interviews investigating DSM-IV mental disorders at baseline and follow-up (mean duration 5.2 years). Analyses were adjusted for a wide array of potential confounders. RESULTS: Our main finding was that regular aspirin or statin use at baseline did not reduce the incidence of MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19; 95%CI, 0.68-2.08; and statins: 1.25; 95%CI, 0.73-2.14; respectively). LIMITATIONS: Our study is not a randomized clinical trial and could not adjust for all potential confounding factors, information on aspirin or statin use was collected only for the 6 months prior to the evaluations, and the sample was restricted to subjects between 35 and 66 years of age. CONCLUSION: Our data do not support a large scale preventive treatment of depression using aspirin or statins in subjects aged from 35 to 66 years from the community.

Hercynian Metamorphism in the Catalonian Coastal Ranges

Paleozoic rocks in the Catalonian Coastal Ranges are in their largestpart affectedby alow-tovery-low grade Hercynian metamorphism. Amphibolite facies conditions are only found in restricted areas such as the southwestern part of the Guilleries massif where upper amphibolite facies conditions are reached. Metamorphic grade increases from top to bottom of the Paleozoic stratigraphic sequence and the metamorphic peak is diachronous, being progressively older in the lower grade metamorphic zones. The isograd pattern, mineral assemblages, mineral chemistry and preserved reaction textures are consistent with a low pressure metamorphism possibly evolving from a previous Barrovian type event. The metamorphic climax in the high grade zone was reached after the seconddeformational phase. Calculatedpeak P-Tconditions are 620-640 OC and around 3.5 Kb . A latter episode of decompression from the maximum conditions to 1-2 Kb, with an associated temperature decrease to 530-550 OC, is recognized. The intrusion of late Hercynian granitoids produced contact metamorphic aureoles where the pyroxene-hornfels facies is locally reached.

Asiantuntijajärjestelmä kattilakonseptin valintaan

Polttoaine asettaa puitteet kattilasuunnittelulle. Kiertoleijukattilakonseptin valinta kytkeytyy kiinteästi mitoitusarvoihin ja polttoaineen ominaisuuksiin. Asiakkaan vaatimuk-set kattilalle asettavat lähtökohdan kattilasuunnittelulle. Suorituskyky, kustannukset ja luotettavuus ovat asiakaslähtöisiä tekijöitä, joiden painotukset vaikuttavat kattilakonseptin valintaan. Korkeat lämpötilat tulistimien alueella tekevät tulistinjärjestelystä vaikean ja määräävän osan kattilakonseptin valintaa. Konvektiotulistimien altistuminen kuumille savukaasuille tekee niistä herkkiä likaantumiselle ja korroosiolle. Mitoitusarvojen ja tulistimien rakenteen oikeanlaisella valinnalla voidaan näitä polttoaineperäisiä ongelmia ehkäistä. Lisäksi kiertoleijukattiloissa käytetyt tulipesän ulkopuoliset tulistimet soveltuvat konvektiotulistimia korkeammille lämpötiloille huonolaatuisillakin polttoaineilla. Tässä työssä rakennettu asiantuntijajärjestelmä valitsee alustavan kattilakonseptin mitoitusta varten käyttäjän antamien vähäisten lähtötietojen pohjalta.

Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease

Background: Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease. Because atherosclerosis is considered a low-grade inflammatory disease, some feeding trials have analyzed the effects of cocoa (an important source of flavonoids) on inflammatory biomarkers, but the results have been controversial. Objective: The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients. Design: Forty-two high-risk volunteers (19 men and 23 women; mean 6 SD age: 69.7 6 11.5 y) were included in a randomized crossover feeding trial. All subjects received 40 g cocoa powder with 500 mL skim milk/d (C+M) or only 500 mL skim milk/d (M) for 4 wk. Before and after each intervention period, cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated. Results: Adherence to the dietary protocol was excellent. No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups. However, in monocytes, the expression of VLA-4, CD40, and CD36 was significantly lower (P = 0.005, 0.028, and 0.001, respectively) after C+M intake than after M intake. In addition, serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower (both P = 0.007) after C+M intake than after M intake. Conclusions: These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease. These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis. This trial was registered in the Current Controlled Trials at London, International Standard Randomized Controlled Trial Number, at controlled-trials.com as ISRCTN75176807.

Prevalence of ragweed allergy in rural Geneva - a pilot study.

OBJECTIVE: The prevalence of ragweed allergy is increasing worldwide. Ragweed distribution and abundance is spreading in Europe in a wide area ranging from the Rhone valley in France to Hungary and Ukraine, where the rate of the prevalence can peak at as high as 12%. Low-grade ragweed colonisation was seen in Geneva and Ticino, less than two decades ago. There were fears that allergies to ragweed would increase Switzerland. The intent of this study was to assess the rate of prevalence of sensitisation and allergy to ragweed in the population living in the first rural Swiss setting where ragweed had been identified in 1996, and to evaluate indirectly the efficacy of elimination and containment strategies. MATERIAL AND METHODS: In 2009, 35 adults in a rural village in the Canton of Geneva were recruited. Data were collected by means of questionnaires and skin-prick tests were done on each participant. The study was approved by the local Ethics Committee. RESULTS: Based on questionnaires, 48.6% had rhinitis (95% confidence interval [CI] 32.9-64.4; n = 17/35) and 17.1% asthma (95% CI 8.1-32.6; n = 6/35). Atopy was diagnosed in 26.4% (95% CI 12.9-44.4) of the sample (n = 9/34). Ragweed sensitisation was found in 2.9% (95% CI 0.7-19.7; n = 1/34), mugwort sensitisation in 2.9% (95% CI 0.1-14.9; n = 1/35), alder sensitisation in 17.1% (95% CI 6.6-33.6; n = 6/35), ash sensitisation in 12.5% (95% CI 3.5-29.0; n = 4/32) and grass sensitisation in 22.9% (95% CI 10.4-40.1; n = 8/35). Ragweed (95% CI 0.1-14.9; n = 1/34) and mugwort allergies (95% CI 0.1-14.9; n = 1/35) were both found in 2.9% of the population. CONCLUSION: This study showed a surprisingly low incidence of ragweed sensitisation and allergy, of 2.9% and 2.9%, respectively, 20 years after the first ragweed detection in Geneva. The feared rise in ragweed allergy seems not to have happened in Switzerland, compared with other ragweed colonised countries. These results strongly support early field strategies against ragweed.

Is the presence of an intrathecal synthesis of immunoglobulins associated with neurocognitive impairment in HIV-infected patients?

Worldwide, the incidence of HIV-associated dementia has decreased However, the prevalence of HIV-associated neurocognitive disorders (HAND), mostly the milder forms, i.e. mild neurocognitve disorders (MND) and asymptomatic neurocognitive impairments (ANI) has increased in the combined antiretroviral therapy (cART) era. Indeed, 20% to 60% of well- treated HIV-infected patients, i.e. with undetectable HIV viremia, still present HAND in the cART era. HAND are characterized by psychomotor slowing, memory loss, and attention deficit. Possible explanations for this paradoxical phenomenon encompass: increased survival of HIV- infected patients thank to cART, low grade inflammation of the brain insufficient penetrance of antiretroviral drugs through the blood brain barrier (BBB), or on the contrary, toxic effect of some antiretroviral drugs. These somewhat contradictory hypotheses underline our poor understanding of HAND physiopathology. Here, we aim at determining whether the intrathecal synthesis of immunoglobulins G (IgG), hereafter referred as cerebrospinal fluid oligoclonal band (CSF OB), may help us in better understanding the immunopathogenesis of cognitive disorders. By analogy with other infection, such as syphilis or neuroborreliosis (9, 10), one can assume that, in the case of HIV-infected patients, the CSF OB are directed against HIV proteins (11). Nevertheless, in the case of HIV, the meaning of such CSF OB is unclear. Indeed, it is unknown whether this intrathecal inflammatory reaction is beneficial (viral control) or harmful (brain parenchyma destruction by the different inflammatory factors). Here, we looked at the association between CSF OB and cognitive disorders in HIV-infected patients, hypothesizing that if these CSF OB are protective, one should see an inverse correlation with the presence of cognitive disorders.

Métodos de baixo custo para purificação de reagentes e controle da contaminação para a determinação de metais traços em águas naturais

Probably one of the most difficult and challenging aspects of measuring trace metals in natural waters is to avoid contamination during sampling, manipulation and analysis. This work discusses how to avoid contamination using simple procedures, and considers alternative methods to purify deionised water and low grade reagents to enable accurate determination of trace metals in natural waters in a common laboratory. Measurements were performed by cathodic stripping voltammetry and copper was used as a model metal to test the procedures. It was possible to evaluate copper speciation in natural waters even when total dissolved copper concentration was as low as 1.5 nmol L-1. The methods' accuracy was confirmed by analysis of certified seawater.

Rcor2 underexpression in senescent mice: a target for inflammaging?

BACKGROUND: Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program. METHODS: To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro. RESULTS: P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes. CONCLUSIONS: Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging

Feasibility Study and Market Review of Small Scale Bioenergy Heating Plants in North-West Russia

The paper is focused on feasibility study and market review of small scale bioenergy heating plants in the Russian North-West region. The main focus is effective and competitive usage of low-grade wood for heating purposes in the region. As example of economical feasibility estimation it was chosen the project of reconstruction of small scale boiler plant in Leningrad region that Brofta Oy is planning to implement the nearest time. It includes calculation the payback time with and without interest, the estimation of probable investments, the evaluation of possible risks and research on the potential of small scale heating plants projects. Calculations show that the profitability of this kind of projects is high, but payback time is not very short, because of high level of initial investments. Though, the development of small scale bioenergy heating plants in the region is considered to be the best way to solve the problems of heat supply in small settlements using own biomass resources.

Role of human hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) in steroid-dependent diseases in females –novel indications for HSD17B1 inhibitors. Phenotypic analysis of transgenic mice overexpressing human HSD17B1.

Hormone-dependent diseases, e.g. cancers, rank high in mortality in the modern world, and thus, there is an urgent need for new drugs to treat these diseases. Although the diseases are clearly hormone-dependent, changes in circulating hormone concentrations do not explain all the pathological processes observed in the diseased tissues. A more inclusive explanation is provided by intracrinology – a regulation of hormone concentrations at the target tissue level. This is mediated by the expression of a pattern of steroid-activating and -inactivating enzymes in steroid target tissues, thus enabling a concentration gradient between the blood circulation and the tissue. Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a family of enzymes that catalyze the conversion between low active 17-ketosteroids and highly active 17beta-hydroxysteroids. HSD17B1 converts low active estrogen (E1) to highly active estradiol (E2) with high catalytic efficiency, and altered HSD17B1 expression has been associated with several hormone-dependent diseases, including breast cancer, endometriosis, endometrial hyperplasia and cancer, and ovarian epithelial cancer. Because of its putative role in E2 biosynthesis in ovaries and peripheral target tissues, HSD17B1 is considered to be a promising drug target for estrogen-dependent diseases. A few studies have indicated that the enzyme also has androgenic activity, but they have been ignored. In the present study, transgenic mice overexpressing human HSD17B1 (HSD17B1TG mice) were used to study the effects of the enzyme in vivo. Firstly, the substrate specificity of human HSD17B1 was determined in vivo. The results indicated that human HSD17B1 has significant androgenic activity in female mice in vivo, which resulted in increased fetal testosterone concentration and female disorder of sexual development appearing as masculinized phenotype (increased anogenital distance, lack of nipples, lack of vaginal opening, combination of vagina with urethra, enlarged Wolffian duct remnants in the mesovarium and enlarged female prostate). Fetal androgen exposure has been linked to polycystic ovary syndrome (PCOS) and metabolic syndrome during adulthood in experimental animals and humans, but the genes involved in PCOS are largely unknown. A putative mechanism to accumulate androgens during fetal life by HSD17B1 overexpression was shown in the present study. Furthermore, as a result of prenatal androgen exposure locally in the ovaries, HSD17B1TG females developed ovarian benign serous cystadenomas in adulthood. These benign lesions are precursors of low-grade ovarian serous tumors. Ovarian cancer ranks fifth in mortality of all female cancers in Finland, and most of the ovarian cancers arise from the surface epithelium. The formation of the lesions was prevented by prenatal antiandrogen treatment and by transplanting wild type (WT) ovaries prepubertally into HSD17B1TG females. The results obtained in our non-clinical TG mouse model, together with a literature analysis, suggest that HSD17B1 has a role in ovarian epithelial carcinogenesis, and especially in the development of serous tumors. The role of androgens in ovarian carcinogenesis is considered controversial, but the present study provides further evidence for the androgen hypothesis. Moreover, it directly links HSD17B1-induced prenatal androgen exposure to ovarian epithelial carcinogenesis in mice. As expected, significant estrogenic activity was also detected for human HSD17B1. HSD17B1TG mice had enhanced peripheral conversion of E1 to E2 in a variety of target tissues, including the uterus. Furthermore, this activity was significantly decreased by treatments with specific HSD17B1 inhibitors. As a result, several estrogen-dependent disorders were found in HSD17B1TG females. Here we report that HSD17B1TG mice invariably developed endometrial hyperplasia and failed to ovulate in adulthood. As in humans, endometrial hyperplasia in HSD17B1TG females was reversible upon ovulation induction, triggering a rise in circulating progesterone levels, and in response to exogenous progestins. Remarkably, treatment with a HSD17B1 inhibitor failed to restore ovulation, yet completely reversed the hyperplastic morphology of epithelial cells in the glandular compartment. We also demonstrate that HSD17B1 is expressed in normal human endometrium, hyperplasia, and cancer. Collectively, our non-clinical data and literature analysis suggest that HSD17B1 inhibition could be one of several possible approaches to decrease endometrial estrogen production in endometrial hyperplasia and cancer. HSD17B1 expression has been found in bones of humans and rats. The non-clinical data in the present study suggest that human HSD17B1 is likely to have an important role in the regulation of bone formation, strength and length during reproductive years in female mice. Bone density in HSD17B1TG females was highly increased in femurs, but in lesser amounts also in tibias. Especially the tibia growth plate, but not other regions of bone, was susceptible to respond to HSD17B1 inhibition by increasing bone length, whereas the inhibitors did not affect bone density. Therefore, HSD17B1 inhibitors could be safer than aromatase inhibitors in regard to bone in the treatment of breast cancer and endometriosis. Furthermore, diseases related to improper growth, are a promising new indication for HSD17B1 inhibitors.

Caracterização química dos géis produzidos pelas bactérias diazotróficas Rhizobium tropici e Mesorhizobium sp.

The exopolysaccharides with characteristics of gel produced by Rhizobium tropici (EPS RT) and Mesorhizobium sp (EPS MR) are acidic heteropolysaccharide composed mainly of glucose and galactose in a molar ratio of 4:1 and 5:1 respectively, with traces of mannose (~ 1%). Chemical analysis showed the presence of uronic acid, pyruvate and acetyl-substituents in the structures of both polymers. Experiments of gel permeation chromatography and polyacrylamide gel electrophoresis showed that EPS RT and EPS MR are homogeneous molecules with low grade of polydispersity. The EPS were characterized using spectroscopic techniques of FT-IR, ¹H and 13C-NMR.

Salivary gland cancer in Finland: Incidence, histological distribution, outcome and prognostic factors

Salivary gland cancer (SGC) is a rare cancer. The histological classification of SGC is complex and its biological behavior highly variable: it may vary from a low-grade tumor to a high-grade and often fatal malignancy. These circumstances make this cancer a diagnostic and therapeutic challenge. Older age and exposure to ionizing radiation are known risk factors. The mainstay of treatment is surgery combined with adjuvant radiation therapy, when appropriate. In addition to the histological type, the only well known prognostic factor is the TNM classification, which describes the tumor size and the amount of metastases. This study was performed using a full population-based nationwide cohort of SGC patients and tumors diagnosed in Finland in 1991-1996. The annual incidence of SGC in the entire population was, on average, 47.7 per year. By histological re-evaluation of 237 specimens the most frequent histological types were the adenoid cystic carcinoma (n=65; 27%), the mucoepidermoid carcinoma (n=45; 19%) and the acinic cell carcinoma (n=41; 17%). The highest 10-year disease-specific survival rate occurred among patients with acinic cell carcinoma (90%), followed by mucoepidermoid carcinoma (81%) and adenoid cystic carcinoma (60%). A high volume-corrected index (VCI) of Ki-67 correlated with worse survival of patients with SGC. Computer-assisted morphometric analyses of CD34-positive vessels indicated an unfavorable prognosis for patients with mucoepidermoid carcinoma and an association with poor survival among patients with acinic cell carcinoma. A high level of expression of matrix metalloproteinase-9 (MMP-9) showed a trend for a poorer prognosis in salivary duct carcinoma, and a high level of MMP-13 and a low level of MMP-1 had a trend for a poorer prognosis of patients with SGC. A low level of MMP-7 was associated with a poor prognosis of patients with acinic cell and mucoepidermoid carcinoma.