Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake

The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2′,7′-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 β-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes

No Pixel Left Behind: Interactively Visualizing ''Everything'' from NASA's Earth Observations

The problem: satellite swath overlaps. Polar orbiting satellites like Terra, Aqua, and the joint NASA/NOAA Suomi-NPP satellite circle the globe from pole to pole, collecting data daily, swath by swath. Having this density of data is great for building a comprehensive mosaic of the planet, but sometimes there is something interesting occurring in one swath but is covered by a subsequent swath when the satellite passes over 90 minutes later. With our new prototype based on Worldview and the Global Imagery Browse Services (GIBS), we combine the best of both worlds to interactively visualize the entire globe as a mosaic and allow the user to _peel away the overlaps_ to see every pixel that was observed by the satellite. This ability to look at every pixel - and to know when they were captured - is especially important near the poles where swath overlaps are most common

Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach

Citation: Lin, Z. M., Cuneo, M., Rowe, J. D., Li, M. J., Tell, L. A., Allison, S., . . . Gehring, R. (2016). Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach. Bmc Veterinary Research, 12, 10. https://doi.org/10.1186/s12917-016-0884-4Background: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. Results: All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. Conclusions: The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach for treating pulmonary infections in lactating goats, but a prolonged withdrawal time of at least 39 days after the second injection should be considered to prevent violative residues in milk and any dairy goat being used for meat should have an extended meat withdrawal time

Books in the News in Cromwellian England

This article offers detailed analysis of the patterns of book advertising in Marchamont Nedham’s government-sponsored newsbook, Mercurius Politicus. It contends that, for a brief period, Politicus was the nearest thing that the mid-seventeenth century had to a literary periodical and contests standard accounts that Politicus was only successful because government monopoly made it so. Instead I show that Politicus was instrumental in creating an image of the Commonwealth and Protectorate as a Republic of Letters; the cheap print of its small advertisements insisted that the publication of a book was an event, that London was a city of the book, and that its inhabitants might respond to the uncertainty of political revolution by eagerly imagining a future comprised of new books as yet unread

Role of Condom Negotiation on Condom use among Women of Reproductive Age in three Districts in Tanzania.

ABSTRACT: BACKGROUND: HIV/AIDS remains being a disease of great public health concern worldwide. In regions such as sub-Saharan Africa (SSA) where women are disproportionately infected with HIV, women are reportedly less likely capable of negotiating condom use. However, while knowledge of condom use for HIV prevention is extensive among men and women in many countries including Tanzania, evidence is limited about the role of condom negotiation on condom use among women in rural Tanzania. METHODS: Data originate from a cross-sectional survey of random households conducted in 2011 in Rufiji, Kilombero and Ulanga districts in Tanzania. The survey assessed health-seeking behaviour among women and children using a structured interviewer-administered questionnaire. A total of 2,614 women who were sexually experienced and aged 15--49 years were extracted from the main database for the current analysis. Linkage between condom negotiation and condom use at the last sexual intercourse was assessed using multivariate logistic regression. RESULTS: Prevalence of condom use at the last sexual intercourse was 22.2% overall, ranging from12.2% among married women to 54.9% among unmarried (single) women. Majority of the women (73.4%) reported being confident to negotiate condom use, and these women were significantly more likely than those who were not confident to have used a condom at the last sexual intercourse (OR = 3.13, 95% CI 2.22-4.41). This effect was controlled for marital status, age, education, religion, number of sexual partners, household wealth and knowledge of HIV prevention by condom use. CONCLUSION: Confidence to negotiate condom use is a significant predictor of actual condom use among women in rural Tanzania. Women especially unmarried ones or those in multiple partnerships should be empowered with condom negotiation skills to enhance their sexual and reproductive health outcomes

A new automated method for the determination of the Total Antioxidant Capacity (TAC) of human plasma, based on the crocin bleaching assay

BACKGROUND: Antioxidant molecules, which scavenge free radical species to prevent or delay oxidative damage of important macromolecules, membrane lipids and lipoproteins, are prevalent in plasma and other biological fluids. Among them, bilirubin, uric acid and protein thiols are the major endogenous antioxidants, while vitamins C and E, as well as a number of food-derived (poly)aromatic substances, belonging to stilbens, flavonoids and phenolic acids, are the main classes of nutritional antioxidants. Assays for total antioxidant capacity in plasma differ in their type of oxidation source, target and measurement used to detect the oxidized product. METHODS: In the present work we present an automated assay for the estimation of blood total antioxidant capacity (TAC assay), based on the crocin bleaching (oxidation) method. This method was adapted on a modern autoanalyzer, was linear over a wide range of values (0–3 mmol/L), and performed using an end point measurement. RESULTS: The TAC method presented a linear correlation with another automated commercial Total Antioxidant Status (TAS) test. Detection of the interference of different metabolites revealed a significant participation of TAC from uric acid, bilirubin, albumin, a minor interference from ascorbic acid, and no interference from hemoglobin. TAC was not modified by two freeze/thawing cycles, and was stable in samples stored at room temperature for 4 hours. K-EDTA and heparin were the best anticoagulants, while citrate decreased TAC by 20%. Reference values derived from samples of normal blood donors was 1.175 ± 0.007 mmol/L (mean ± SEM), while a diet rich in antioxidants more than doubled this value. CONCLUSIONS: The proposed TAC assay, is fully automated, stable and reliable, and could be of value in the estimation of the AC of plasma. It is further proposed to calculate the antioxidant capacity of plasma after a subtraction of all interference deriving from endogenous and/or exogenous metabolites. The antioxidant capacity of plasma thus calculated can be used as a useful indicator of the antioxidant value of foods and beverages in the daily diet

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease