Studies on the influence of ochratoxin A administration on Salmonella typhimurium infection in pigs

The aim of the study was to assess whether immunomodulating effects produced by ochratoxin A (OTA) may influence the course of an experimental infection of pigs with Salmonella Typhimurium 27 Nat (STM 27 Nair). 8-week old pigs were administered 50 g OTA per kg body weight per day via feed. Either 7 or 14 days after beginning of OTA application, these pigs and untreated controls were challenged orally with STM 27 Nair. Different systemic immune parameters in blood and OT A concentration in serum and organs were examined. The number of STM 27 Nair was detected in faecal samples of the pigs. Despite high concentrations of OTA in sera and organs, systemic immune parameters were not modified compared with controls. Significant changes in these parameters were induced only by the Salmonella infection. Pigs pretreated with OTA excreted STM 27 Nair in slightly higher (not significant) concentrations than untreated controls. As the immunomodul ating effects produced by OT A after oral administration seem to be considerably lower than the effects induced by a challenge with Salmonella Typhimurium in a high dose, experiments using reduced doses for infection should give further information on the effect on Salmonella shedding

Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study

<p>Abstract</p> <p>Background</p> <p>Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR) and albuminuria independently of each other. We also investigated the association of <it>MTHFR </it>polymorphisms related to homocysteine with albuminuria to get further insight into causality.</p> <p>Methods</p> <p>This was a cross-sectional population-based study in Caucasians (<it>n </it>= 5913). Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g.</p> <p>Results</p> <p>Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, <it>P </it>< 0.001). The prevalence of albuminuria increased across increasing homocysteine categories (from 6.4% to 17.3% in subjects with normal GFR and from 3.5% to 14.5% in those with reduced GFR, <it>P </it>for trend < 0.005). Hyperhomocysteinemia (OR = 2.22, 95% confidence interval: 1.60-3.08, <it>P </it>< 0.001) and elevated serum uric acid (OR = 1.27, 1.08-1.50, per 100 μmol/L, <it>P </it>= 0.004) were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. <it>MTHFR </it>alleles related to higher homocysteine were associated with increased risk of albuminuria.</p> <p>Conclusions</p> <p>In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.</p

Renal replacement therapy in acute kidney injury: controversy and consensus

Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future

Characterizing CD44 regulatory microRNAs as putative therapeutic agents in human melanoma

The multistructural and multifunctional transmembrane glycoprotein CD44 is overexpressed in many tumors of distinct origin including malignant melanoma and contributes to a poor prognosis by affecting cell proliferation, cell migration, and also the sensitivity for apoptosis induction. Previous studies reported so far 15 CD44 regulatory microRNAs (miRs) in different cell systems. Using a novel method for miR affinity purification miR-143-3p was identified as most potent binder to the 3' untranslated region (UTR) of CD44. Overexpression of miR-143-3p in melanoma cells inhibits CD44 translation, which is accompanied by a reduced proliferation, migration and enhanced daunorubicin induced apoptosis of melanoma cells in vitro. Analyses of discordant CD44 and miR-143-3p expression levels in human melanocytic nevi and dermal melanoma samples demonstrated medium to high CD44 levels with no association to tumor grading or staging. The CD44 expression correlated to PD-L1, but not to MART-1 expression in malignant melanoma. Interestingly, the CD44 expression was inversely correlated to the infiltration of pro-inflammatory immune effector cells. In conclusion, the tumor suppressive miR-143-3p was identified as the most potent CD44 inhibitory miR, which affects growth characteristics of melanoma cells suggesting the implementation of miR-143-3p as as a potential anti-CD44 therapy of malignant melanoma

Studies on the influence of ochratoxin A administration on Salmonella typhimurium infection in pigs

The aim of the study was to assess whether immunomodulating effects produced by ochratoxin A (OTA) may influence the course of an experimental infection of pigs with Salmonella Typhimurium 27 Nat (STM 27 Nair). 8-week old pigs were administered 50 g OTA per kg body weight per day via feed. Either 7 or 14 days after beginning of OTA application, these pigs and untreated controls were challenged orally with STM 27 Nair. Different systemic immune parameters in blood and OT A concentration in serum and organs were examined. The number of STM 27 Nair was detected in faecal samples of the pigs. Despite high concentrations of OTA in sera and organs, systemic immune parameters were not modified compared with controls. Significant changes in these parameters were induced only by the Salmonella infection. Pigs pretreated with OTA excreted STM 27 Nair in slightly higher (not significant) concentrations than untreated controls. As the immunomodul ating effects produced by OT A after oral administration seem to be considerably lower than the effects induced by a challenge with Salmonella Typhimurium in a high dose, experiments using reduced doses for infection should give further information on the effect on Salmonella shedding.</p

Dimethylarginines in patients with intracerebral hemorrhage: association with outcome, hematoma enlargement, and edema

Abstract Background Asymmetric dimethylarginine (ADMA)––the most potent endogenous NO-synthase inhibitor, has been regarded as mediator of endothelial dysfunction and oxidative stress. Considering experimental data, levels of ADMA and its structural isomer symmetric dimethylarginine (SDMA) might be elevated after intracerebral hemorrhage (ICH) and associated with clinical outcome and secondary brain injury. Methods Blood samples from 20 patients with acute ICH were taken at ≤ 24 h and 3 and 7 days after the event. Nine patients had favorable (modified Rankin Scale (mRS) at 90 days 0–2) outcome, and 11 patients unfavorable outcome (mRS 3–6). Patients’ serum ADMA, SDMA, and L-arginine levels were determined by high-performance liquid chromatography–tandem mass spectrometry. Levels were compared to those of 30 control subjects without ICH. For further analysis, patients were grouped according to outcome, hematoma and perihematomal edema volumes, occurrence of hematoma enlargement, and cytotoxic edema as measured by computed tomography and serial magnetic resonance imaging. Results Levels of ADMA––but not SDMA and L-arginine––were elevated in ICH patients compared to controls (binary logistic regression analysis: ADMA ≤ 24 h, p = 0.003; 3 days p = 0.005; 7 days p = 0.004). If patients were grouped according to outcome, dimethylarginines were increased in patients with unfavorable outcome. The binary logistic regression analysis confirmed an association of SDMA levels ≤ 24 h (p = 0.048) and at 3 days (p = 0.028) with unfavorable outcome. ADMA ≤ 24 h was increased in patients with hematoma enlargement (p = 0.003), while SDMA ≤ 24 h was increased in patients with large hematoma (p = 0.029) and perihematomal edema volume (p = 0.023). Conclusions Our data demonstrate an association between dimethylarginines and outcome of ICH. However, further studies are needed to confirm this relationship and elucidate the mechanisms behind