Autoimmune encephalomyelitis in NOD mice is not initially a progressive multiple sclerosis model.

OBJECTIVE: Despite progress in treating relapsing multiple sclerosis (MS), effective inhibition of nonrelapsing progressive MS is an urgent, unmet, clinical need. Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), provide valuable tools to examine the mechanisms contributing to disease and may be important for developing rational therapeutic approaches for treatment of progressive MS. It has been suggested that myelin oligodendrocyte glycoprotein (MOG) peptide residues 35-55 (MOG35-55 )-induced EAE in nonobese diabetic (NOD) mice resembles secondary progressive MS. The objective was to determine whether the published data merits such claims. METHODS: Induction and monitoring of EAE in NOD mice and literature review. RESULTS: It is evident that the NOD mouse model lacks validity as a progressive MS model as the individual course seems to be an asynchronous, relapsing-remitting neurodegenerative disease, characterized by increasingly poor recovery from relapse. The seemingly progressive course seen in group means of clinical score is an artifact of data handling and interpretation. INTERPRETATION: Although MOG35-55 -induced EAE in NOD mice may provide some clues about approaches to block neurodegeneration associated with the inflammatory penumbra as lesions form, it should not be used to justify trials in people with nonactive, progressive MS. This adds further support to the view that drug studies in animals should universally adopt transparent raw data deposition as part of the publication process, such that claims can adequately be interrogated. This transparency is important if animal-based science is to remain a credible part of translational research in MS.Stichting MS ResearchWellcome TrustMedical Research CouncilNational Multiple Sclerosis Society. Grant Number: RG4132A5/

DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function

The FOXO transcription factor family is a conserved regulator of longevity and the downstream target of insulin/insulin-like signaling. In Caenorhabditis elegans, the FOXO ortholog DAF-16A and D/F isoforms extend lifespan in daf-2 insulin-like receptor mutants. Here we identify the DAF-21/Hsp90 chaperone as a longevity regulator. We find that reducing DAF-21 capacity by daf-21(RNAi) initiated either at the beginning or at the end of larval development shortens wild-type lifespan. daf-21 knockdown employed from the beginning of larval development also decreases longevity of daf-2 mutant and daf-2 silenced nematodes. daf-16 loss-of-function mitigates the lifespan shortening effect of daf-21 silencing. We demonstrate that DAF-21 specifically promotes daf-2 and heat-shock induced nuclear translocation of DAF-16A as well as the induction of DAF-16A-specific mRNAs, without affecting DAF-16D/F localization and transcriptional function. DAF-21 is dispensable for the stability and nuclear import of DAF-16A, excluding a chaperone-client interaction and suggesting that DAF-21 regulates DAF-16A activation upstream of its cellular traffic. Finally, we show a selective requirement for DAF-21 to extend lifespan of DAF-16A, but not DAF-16D/F, transgenic daf-2 mutant strains. Our findings indicate a spatiotemporal determination of multiple DAF-21 roles in fertility, development and longevity and reveal an isoform-specific regulation of DAF-16 activity. © 2018, The Author(s)

Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

In order to establish accurately the exact effect of any drug therapy for symptomatic benign prostatic hyperplasia (BPH) it is important to define the effect of placebo treatment. This effect was assessed by thoroughly analyzing the placebo arm, which included 101 patients, from a randomized, double-blind, placebo-controlled trial of the selective alpha-blocker alfuzosin and comparing the data with those of a variety of independent studies which followed a placebo group of patients with clinical BPH. Following 16 weeks of placebo treatment a decrease of 24% (p <0.05) in Madsen-Iversen score and an increase of 14% (p <0.05) in peak flow rate was demonstrated. The percentages of patients who reported worsening, improvement or no change in symptoms were 9.2%, 73.6% and 17.2% respectively. The maximal effect of placebo, approximately 40% reduction in symptom scores, is likely to be achieved within the first four to six months. After this, the placebo effect stabilizes and gradually wears off but is still present following 12 months of treatment. The duration of the placebo effect and the time until it has totally worn off, if ever, remains to be studied in long-term, placebo-controlled trials, including an untreated cohort. The present study emphasizes the importance of properly designed, double-blind, placebo-controlled studies in evaluating any pharmacological intervention in clinical BPH

ALFUZOSIN IN THE TREATMENT OF BENIGN PROSTATIC HYPERPLASIA - EFFECTS ON SYMPTOM SCORES, URINARY FLOW-RATES AND RESIDUAL VOLUME - A MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

In order to assess the efficacy and safety of alfuzosin, a selective alpha-1 receptor antagonist, 205 patients with Benign Prostatic Hyperplasia (BPH) were randomly assigned in a double-blind, placebo-controlled manner, to receive either alfuzosin 2,5 mg TID or placebo TID during 12 weeks. After 12 weeks symptom scores assessed according to the Madsen-Iversen scale were significantly reduced in the alfuzosin group and peak flow rate significantly increased compared to the placebo group. There were no significant differences concerning adverse events or withdrawals. Alfuzosin proved to have a beneficial effect in patients with symptomatic BPH with few and minor adverse events

Apolipoprotein-E-deficient mice exhibit an increased susceptibility to disseminated candidiasis

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Recovery of Native Potato Protein Comparing Expanded Bed Adsorption and Ultrafiltration

Online First™, 14 January 2011Obtaining native protein from potato fruit water (PFW) acceptable for food consumption was attempted by comparing expanded bed adsorption (EBA) and ultrafiltration (UF).The methods were assessed on their process performance and the product quality. Extractable tuber proteins were recovered from lab-prepared PFW either by adsorption to an EBA column using a mixed mode resin (0.31 L) or by batch concentration in an UF (10 kDa MWCO, 0.093 m2) unit and then freeze dried. The yields on protein and esterase activity were higher (p < 0.05 and p < 0.01; Mann–Whitney U-test) in UF (3.2 g l−1 PFW and 3.17 kU l−1 PFW) than in EBA (1.8 and 1.21). The performance difference was also reflected in process productivity for esterase activity which was fivefold better (p < 0.01) in UF (4.30 kU h−1) than with EBA (0.84) due to the higher enzyme retention; protein productivities were the same. The content of solanidine glycoalkaloids was depleted to moderate levels but came out unaffected by the processing method: EBA 286 ppm, UF 213 ppm. The low levels of chlorogenic acid in all EBA preparations were negatively correlated to high brightness score (L* = 73.8%), a favorable attribute in food-quality proteins. Both methodologies produced native preparations of comparable protein content (75%). EBA processing, however, increased the fraction of the patatin protein which may offer advantages in food applications