Caracterización reológica del suero de tofu a temperaturas próximas a la congelación

El suero de tofu es un subproducto obtenido en la producciónindustrial a partir de la leche de soja. Este suero tiene componentes beneficiosos para la salud, como su contenidoen isoflavonas. Caracterizar reológicamente el suero de tofu a bajas temperaturas tiene interés con el fin de facilitar la recuperación de este efluente y sus compuestos activos sin que se deterioren. Además puede suponer una importante reducción del impacto ambiental debido a la elevada carga orgánica.En el presente trabajo se ha determinado un comportamientoreológico newtoniano en las muestras de suero fresco a 1,9 ºBrix inicial, crioconcentrado hasta 18,5º Brix y posteriormente evaporado hasta 60,2ºBrix. El rango de temperaturas ensayadas es próximo a la congelación (de -4ºC a 4ºC) debido al interés de ser procesadas bajo las condiciones que puedan preservar los compuestos activos

TNF-α is involved in activating DNA fragmentation in skeletal muscle

Intraperitoneal administration of 100 μg kg−1 (body weight) of tumour necrosis factor-α to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-α-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-α-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-α receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-α partly mediates DNA fragmentation during experimental cancer-associated cachexia

Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

Tissue protein hypercatabolism (TPH) is an important feature in cancer cachexia, particularly with regard to the skeletal muscle. The Yoshida AH-130 rat ascites hepatoma is a model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle wasting, primarily due to TPH. The present study was aimed at investigating if IL-15, which is known to favour muscle fibre hypertrophy, could antagonize the enhanced muscle protein breakdown in this cancer cachexia model. Indeed, IL-15 treatment partly inhibited skeletal muscle wasting in AH-130-bearing rats by decreasing (8-fold) protein degradative rates (as measured by14C-bicarbonate pre-loading of muscle proteins) to values even lower than those observed in non-tumour-bearing animals. These alterations in protein breakdown rates were associated with an inhibition of the ATP-ubiquitin-dependent proteolytic pathway (35% and 41% for 2.4 and 1.2 kb ubiquitin mRNA, and 57% for the C8 proteasome subunit, respectively). The cytokine did not modify the plasma levels of corticosterone and insulin in the tumour hosts. The present data give new insights into the mechanisms by which IL-15 exerts its preventive effect on muscle protein wasting and seem to warrant the implementation of experimental protocols involving the use of the cytokine in the treatment of pathological states characterized by TPH, particularly in skeletal muscle, such as in the present model of cancer cachexia. © 2000 Cancer Research Campaig

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)

Altres ajuts: Bayer HealthCare Pharmaceuticals Inc.Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm. Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C. Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924

Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology

Background: The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D). Methodology/Principal Findings: Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299) or T2D (n = 288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382) from control subjects (n = 315) with 94% (95% CI: 92-95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68) and T2D (n = 42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108) with 88% (95% CI: 81-94%) accuracy, and in patients with impaired renal function (n = 369) with 85% (95% CI: 81-88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed. Conclusions/Significance: These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary proteome of T1D and T2D, indicating significant differences in extracellular matrix remodeling

Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects

In a large multicentre study, Toledo et al. examine core Alzheimer's disease CSF biomarkers in 1233 cognitively normal subjects aged 40-85 years. Alzheimer disease-like changes in Aβ1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both Aβ1-42 and phosphorylated/total ta

Technological diversification within UK’s small serial innovators

This paper investigates the determinants of technological diversification among UK’s small serial innovators (SSIs). Using a longitudinal study of 339 UK-based small businesses accounting for almost 7000 patents between 1990 and 2006, this study constitutes the first empirical examination of technological diversification among SMEs in the literature. Results demonstrate that technological diversification is not solely a large firm activity, challenging the dominant view that innovative SMEs are extremely focused and specialised players with little technological diversification. Our findings suggest a nonlinear (i.e. inverse-U-shaped) relationship between the level of technological opportunities in the environment and the SSIs’ degree of technological diversification. This points to a trade-off between processes of exploration and exploitation across increasingly volatile technology regimes. The paper also demonstrates that small firms with impactful innovations focus their innovative activity around similar technological capabilities while firms that have introduced platform technologies in the past are more likely to engage in technological diversification