Taste, A New Incentive to Switch to (R)-Praziquantel in Schistosomiasis Treatment

Schistosomiasis, or Bilharzia, is a parasitic disease caused by flatworms, which affects about 200 million people worldwide. Praziquantel (PZQ) is the drug compound of choice in the control and treatment of this disease. Only half of the drug dose currently administered actually has activity against schistosomiasis, whereas the other half has no activity. Therefore, the WHO has assigned the low-cost preparation of the pure active component a key priority for future PZQ research and development. PZQ has two major administration drawbacks, the first being the high dose needed, the second its well documented bitter taste. Attempts of masking the unpleasant taste have not been successful. We hypothesized that the non-active component in PZQ would be the main contributor to the unpleasant taste of the drug. We determined the extent of bitterness for regular PZQ compared to the pure active component in a taste study in humans. We found that the pure active component alone is significantly less bitter than regular PZQ. This new finding should serve as an additional incentive for the PZQ research and development community to provide a low-cost, large-scale preparation route to the pure active component of PZQ

Computational Fluid Dynamic Investigations on a Small-Scale Liquid Sodium Loop

Liquid metal heat transfer systems are a technically attractive option to increase the efficiency of CSP plants. Sodium as heat transfer medium is promising especially due to high heat transfer rates. In this paper, basic considerations are made to match the requirements of a small-scale loop with sodium as heat transfer medium. The setup of the test facility KArlsruhe ReceIver test FAcility (KARIFA) to heat up this loop with a 20 kW IR laser is described. The loop is planned as an integrated design using an additive manufacturing process. Different technologies like selective laser melting (SLM) are established processes to realize an integrated design and to bring together components in one part. Some variations must be implemented to adapt these processes to liquid metal loops. The high heat fluxes also demand a flow simulation to ensure an efficient and safe operation. A Reynolds-averaged Navier-Stokes (RANS) steady state simulation was performed to show the surface and duct temperatures as well as dimensionless values to analyse the characteristics of the sodium flow

An augmented reality home-training system based on the mirror training and imagery approach

Trojan J, Diers M, Fuchs X, et al. An augmented reality home-training system based on the mirror training and imagery approach. Behavior Research Methods. 2013;46(3):634-640

Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets

<p>Abstract</p> <p>Background</p> <p>Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested.</p> <p>In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP), as a surrogate for ambient/urban particulate air pollutants.</p> <p>Methods</p> <p>Mice were fed a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and were compared to mice kept on a purified low fat (LF) diet, respectively. Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation.</p> <p>Results and discussion</p> <p>The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase.</p> <p>Conclusion</p> <p>The increase in BAL pro-inflammatory factors in high caloric groups and reductions in serum concentrations of anti-inflammatory factors in HF mice, clearly show diet-specific effects, pointing towards augmented systemic inflammatory conditions. Our data suggest that extended feeding periods, leading to manifest obesity, are necessary to generate an increased susceptibility to particle-induced lung inflammation; although the diet-challenge already was efficient in driving pro-inflammatory systemic events.</p

Linagliptin Improves Insulin Sensitivity and Hepatic Steatosis in Diet-Induced Obesity

Linagliptin (tradjenta™) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3–4 weeks) with 3 mg/kg/day or 30 mg/kg/day linagliptin on insulin sensitivity and liver fat content were determined in diet-induced obese C57BL/6 mice. Chow-fed animals served as controls. DPP-4 activity was significantly inhibited (67–89%) by linagliptin (P<0.001). Following an oral glucose tolerance test, blood glucose concentrations (measured as area under the curve) were significantly suppressed after treatment with 3 mg/kg/day (–16.5% to –20.3%; P<0.01) or 30 mg/kg/day (–14.5% to –26.4%; P<0.05) linagliptin (both P<0.01). Liver fat content was significantly reduced by linagliptin in a dose-dependent manner (both doses P<0.001). Diet-induced obese mice treated for 4 weeks with 3 mg/kg/day or 30 mg/kg/day linagliptin had significantly improved glycated hemoglobin compared with vehicle (both P<0.001). Significant dose-dependent improvements in glucose disposal rates were observed during the steady state of the euglycemic–hyperinsulinemic clamp: 27.3 mg/kg/minute and 32.2 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 20.9 mg/kg/minute with vehicle (P<0.001). Hepatic glucose production was significantly suppressed during the clamp: 4.7 mg/kg/minute and 2.1 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 12.5 mg/kg/minute with vehicle (P<0.001). In addition, 30 mg/kg/day linagliptin treatment resulted in a significantly reduced number of macrophages infiltrating adipose tissue (P<0.05). Linagliptin treatment also decreased liver expression of PTP1B, SOCS3, SREBP1c, SCD-1 and FAS (P<0.05). Other tissues like muscle, heart and kidney were not significantly affected by the insulin sensitizing effect of linagliptin. Long-term linagliptin treatment reduced liver fat content in animals with diet-induced hepatic steatosis and insulin resistance, and may account for improved insulin sensitivity

All-cause and Cardiovascular mortality among ethnic German immigrants from the Former Soviet Union: a cohort study

BACKGROUND: Migration is a phenomenon of particular Public Health importance. Since 1990, almost 2 million ethnic Germans (Aussiedler) have migrated from the former Soviet Union (FSU) to Germany. This study compares their overall and cardiovascular disease (CVD) mortality to that of Germany's general population. Because of high overall and CVD mortality in the FSU and low socio-economic status of Aussiedler in Germany, we hypothesize that their mortality is higher. METHODS: We conducted a retrospective cohort study for 1990–2002 with data of 34,393 Aussiedler. We assessed vital status at population registries and causes of death at the state statistical office. We calculated standardized mortality ratios (SMRs) for the whole cohort and substrata of covariables such as age, sex and family size. To assess multivariate effects, we used Poisson regression. RESULTS: 1657 cohort members died before December 31, 2002, and 680 deaths (41.03%) were due to CVD. The SMR for the whole cohort was 0.85 (95%-CI 0.81–0.89) for all causes of death and 0.79 (95%-CI 0.73–0.85) for CVD. SMRs were higher than one for younger Aussiedler and lower for older ones. There was no clear effect of duration of stay on SMRs. For 1990–93, SMRs were significantly lower than in subsequent years. In families comprising at least five members upon arrival in Germany, SMRs were significantly lower than in smaller families. CONCLUSION: In contrast to our hypothesis on migrants' health, overall and CVD mortality among Aussiedler is lower than in Germany's general population. Possible explanations are a substantially better health status of Aussiedler in the FSU as compared to the local average, a higher perceived socio-economic status of Aussiedler in Germany, or selection effects. SMR differences between substrata need further exploration, and risk factor data are needed

A comprehensive transcriptome and immune-gene repertoire of the lepidopteran model host Galleria mellonella

<p>Abstract</p> <p>Background</p> <p>The larvae of the greater wax moth <it>Galleria mellonella </it>are increasingly used (i) as mini-hosts to study pathogenesis and virulence factors of prominent bacterial and fungal human pathogens, (ii) as a whole-animal high throughput infection system for testing pathogen mutant libraries, and (iii) as a reliable host model to evaluate the efficacy of antibiotics against human pathogens. In order to compensate for the lack of genomic information in <it>Galleria</it>, we subjected the transcriptome of different developmental stages and immune-challenged larvae to next generation sequencing.</p> <p>Results</p> <p>We performed a <it>Galleria </it>transcriptome characterization on the Roche 454-FLX platform combined with traditional Sanger sequencing to obtain a comprehensive transcriptome. To maximize sequence diversity, we pooled RNA extracted from different developmental stages, larval tissues including hemocytes, and from immune-challenged larvae and normalized the cDNA pool. We generated a total of 789,105 pyrosequencing and 12,032 high-quality Sanger EST sequences which clustered into 18,690 contigs with an average length of 1,132 bases. Approximately 40% of the ESTs were significantly similar (<it>E </it>≤ e^-03) to proteins of other insects, of which 45% have a reported function. We identified a large number of genes encoding proteins with established functions in immunity related sensing of microbial signatures and signaling, as well as effector molecules such as antimicrobial peptides and inhibitors of microbial proteinases. In addition, we found genes known as mediators of melanization or contributing to stress responses. Using the transcriptomic data, we identified hemolymph peptides and proteins induced upon immune challenge by 2D-gelelectrophoresis combined with mass spectrometric analysis.</p> <p>Conclusion</p> <p>Here, we have developed extensive transcriptomic resources for <it>Galleria</it>. The data obtained is rich in gene transcripts related to immunity, expanding remarkably our knowledge about immune and stress-inducible genes in <it>Galleria </it>and providing the complete sequences of genes whose primary structure have only partially been characterized using proteomic methods. The generated data provide for the first time access to the genetic architecture of immunity in this model host, allowing us to elucidate the molecular mechanisms underlying pathogen and parasite response and detailed analyses of both its immune responses against human pathogens, and its coevolution with entomopathogens.</p