43 research outputs found
Bone Status in Obese, Non-diabetic, Antipsychotic-Treated Patients, and Effects of the Glucagon-Like Peptide-1 Receptor Agonist Exenatide on Bone Turnover Markers and Bone Mineral Density
Background: Low bone mineral density (BMD) may constitute an underestimated comorbidity in schizophrenia patients undergoing long-term antipsychotic treatment. Glucagon-like peptide 1 (GLP-1) receptor agonists are antidiabetic drugs, which may also affect bone turnover.Methods: In planned secondary analyses of a 3 months, double-blind, randomized, placebo-controlled trial (n = 45), we explored effects of the GLP-1 receptor agonist exenatide 2 mg once-weekly (n = 23), or placebo (n = 22) on bone turnover markers (BTMs) and BMD in chronic, obese, antipsychotic-treated patients with schizophrenia spectrum disorder. Baseline BTMs were compared to sex- and age-adjusted reference values from a Danish population cohort, and T- and Z-scores were calculated for BMD.Results: In women (n = 24), all baseline BTM measurements of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were within reference values. In men (n = 21), 5% displayed lower PINP and 14% displayed lower CTX. One patient displayed BMD Z-score Conclusions: Sex- and age-adjusted measures of bone status in chronic, obese, antipsychotic-treated patients appeared comparable to the reference population. Subtle changes in bone markers during 3 months exenatide treatment may suggest beneficial effects of GLP-1 receptor agonists on bone status in antipsychotic-treated patients, and further studies should consider the potential influence of prolactin.</p
Gill transcriptomic responses to toxin-producing alga Prymnesium parvum in rainbow trout
This work was supported by the BBSRC EastBio PhD studentship awarded to MC, the Danish Strategic Research Council grant No 060300449B HABFISH, and the European Maritime and Fisheries Fund and the Danish Fisheries Agency joint grant âSundt Dambrugâ. Molecular work at University of Aberdeen was funded by Scottish Aquaculture Innovation grant SL 2017 08. EK was supported by BBSRC grant BB/R018812/1.The gill of teleost fish is a multifunctional organ involved in many physiological processes, including protection of the mucosal gill surface against pathogens and other environmental antigens by the gill-associated lymphoid tissue (GIALT). Climate change associated phenomena, such as increasing frequency and magnitude of harmful algal blooms (HABs) put extra strain on gill function, contributing to enhanced fish mortality and fish kills. However, the molecular basis of the HAB-induced gill injury remains largely unknown due to the lack of high-throughput transcriptomic studies performed on teleost fish in laboratory conditions. We used juvenile rainbow trout (Oncorhynchus mykiss) to investigate the transcriptomic responses of the gill tissue to two (high and low) sublethal densities of the toxin-producing alga Prymnesium parvum, in relation to non-exposed control fish. The exposure time to P. parvum (4â5 h) was sufficient to identify three different phenotypic responses among the exposed fish, enabling us to focus on the common gill transcriptomic responses to P. parvum that were independent of dose and phenotype. The inspection of common differentially expressed genes (DEGs), canonical pathways, upstream regulators and downstream effects pointed towards P. parvum-induced inflammatory response and gill inflammation driven by alterations of Acute Phase Response Signalling, IL-6 Signalling, IL-10 Signalling, Role of PKR in Interferon Induction and Antiviral Response, IL-8 Signalling and IL-17 Signalling pathways. While we could not determine if the inferred gill inflammation was progressing or resolving, our study clearly suggests that P. parvum blooms may contribute to the serious gill disorders in fish. By providing insights into the gill transcriptomic responses to toxin-producing P. parvum in teleost fish, our research opens new avenues for investigating how to monitor and mitigate toxicity of HABs before they become lethal.Publisher PDFPeer reviewe
Effect of GLP-1 Receptor Agonist Treatment on Body weight in Obese Antipsychotic-treated Patients with Schizophrenia:a Randomized, Placebo-controlled Trial Byline
AIMS: Schizophrenia is associated with cardiovascular coâmorbidity and a reduced lifeâexpectancy of up to 20 years. Antipsychotics are dopamine D(2) receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects such as obesity and diabetes. Glucagonâlike peptideâ1 receptor agonists (GLPâ1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLPâ1RA, exenatide onceâweekly, in nonâdiabetic, antipsychoticâtreated, obese patients with schizophrenia. MATERIAL AND METHODS: Antipsychoticâtreated, obese, nonâdiabetic, schizophrenia spectrum patients were randomized to doubleâblinded adjunctive treatment with onceâweekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for 3 months. The primary outcome was loss of body weight after treatment and repeated measures analysis of variance was used as statistical analysis. RESULTS: Between March 2013 and June 2015, 40 patients completed the trial. At baseline, mean body weight was 118.3 Âą 16.0 kg in the exenatide group and 111.7 Âą 18.0 kg in the placebo group, with no group differences ( P = .23). The exenatide and placebo groups experienced significant ( P = .004), however similar ( P = .98), weight losses of 2.24 Âą 3.3 and 2.23 Âą 4.4 kg, respectively, after 3 months of treatment. CONCLUSIONS: Treatment with exenatide onceâweekly did not promote weight loss in obese, antipsychoticâtreated patients with schizophrenia compared to placebo. Our results could suggest that the body weightâlowering effect of GLPâ1RAs involves dopaminergic signaling, but blockade of other receptor systems may also play a role. Nevertheless, antiâobesity regimens effective in the general population may not be readily implemented in antipsychoticâtreated patients with schizophrenia
An Integrated Metabolomic and Genomic Mining Workflow to Uncover the Biosynthetic Potential of Bacteria
Microorganisms are a rich source of bioactives; however, chemical identification is a major bottleneck. Strategies that can prioritize the most prolific microbial strains and novel compounds are of great interest. Here, we present an integrated approach to evaluate the biosynthetic richness in bacteria and mine the associated chemical diversity. Thirteen strains closely related to Pseudoalteromonas luteoviolacea isolated from all over the Earth were analyzed using an untargeted metabolomics strategy, and metabolomic profiles were correlated with whole-genome sequences of the strains. We found considerable diversity: only 2% of the chemical features and 7% of the biosynthetic genes were common to all strains, while 30% of all features and 24% of the genes were unique to single strains. The list of chemical features was reduced to 50 discriminating features using a genetic algorithm and support vector machines. Features were dereplicated by tandem mass spectrometry (MS/MS) networking to identify molecular families of the same biosynthetic origin, and the associated pathways were probed using comparative genomics. Most of the discriminating features were related to antibacterial compounds, including the thiomarinols that were reported from P. luteoviolacea here for the first time. By comparative genomics, we identified the biosynthetic cluster responsible for the production of the antibiotic indolmycin, which could not be predicted with standard methods. In conclusion, we present an efficient, integrative strategy for elucidating the chemical richness of a given set of bacteria and link the chemistry to biosynthetic genes. IMPORTANCE We here combine chemical analysis and genomics to probe for new bioactive secondary metabolites based on their pattern of distribution within bacterial species. We demonstrate the usefulness of this combined approach in a group of marine Gram-negative bacteria closely related to Pseudoalteromonas luteoviolacea, which is a species known to produce a broad spectrum of chemicals. The approach allowed us to identify new antibiotics and their associated biosynthetic pathways. Combining chemical analysis and genetics is an efficient âminingâ workflow for identifying diverse pharmaceutical candidates in a broad range of microorganisms and therefore of great use in bioprospecting
Rapport fra RobustFish temadag d. 5. april 2018
FormĂĽlet med RobustFish projektet var at:
⢠Styrke udviklingen af økologisk ørredproduktion i Danmark men ogsü til gavn for konventionelt opdrÌt
⢠Undersøge ørredyngels robusthed i forhold til start-fodrings adfÌrd, fedtsyreindholdet i foderet og følsomhed over for yngeldødeligheds-syndromet (YDS)
⢠Effekt af vandbehandling med hjÌlpestoffer
⢠Viden om markedsforhold, forbrugerkendskab, produktudvikling og øget afsÌtning.
Robustfish har adresseret ovennÌvnte problemstillinger, og pü grundlag af opnüede resultater kan der drages følgende konklusioner og deraf følgende anbefalinger og perspektiver for styrkelse af det økologiske opdrÌt af regnbueørred i Danmark.
⢠Yngel med tidlig fødesøgnings adfÌrd (swim-up) viste tendens til større robusthed over for de anvendte stress püvirkninger.
⢠Der var ingen statistisk forskel mellem dødelighed forĂĽrsaget af YDS-bakterien Flavobacterium psychrophilum og âTidligâ, âMellemâ og âSenâ swim-up adfĂŚrd.
⢠Udskiftning af marine protein kilder (kun 10 % fiskemel i diÌterne) med vegetabilske viste negativ effekt pü foderindtag, vÌkst og dødelighed i regnbueørred yngel.
⢠Lavt indhold af flerumĂŚttede fedtsyrer (HUFA) i foderet (> 1 % af total fedtsyrer (TFA)) havde tilsyneladende kun lille pĂĽvirkning pĂĽ vĂŚkst, foderkonvertering (FK) og enzymatisk aktivitet indtil 100 dage efter startfodring â i foder med optimal marin proteinkilde.
⢠Fedtsyre resultater indikerede, at ørred tilsyneladende kan syntetisere kortere kÌdede fedtsyrer til HUFA.
⢠De godkendte hjÌlpestoffer anvendes med større sikkerhed og dambrugerne er blevet fortrolige med produkterne, ligesom fiskene tilsyneladende tilpasser sig de grønne hjÌlpestoffer.
⢠Behov for optimering af driften med henblik pĂĽ dels at sikre en bedre og mere stabil vandkvalitet â og derved reducere brugen af hjĂŚlpestoffer og dels sikre fiskevelfĂŚrd, herunder ogsĂĽ vandcirkulation, beluftning, overdĂŚkning, mm.).
⢠Det vurderes at der vil vĂŚre gode muligheder for at opretholde en merpris (20 â 30 %) pĂĽ økologiske ørreder, og at markedsføring skal fokusere mere pĂĽ dyrevelfĂŚrd end miljø.
⢠Forbrugerne havde en negativ opfattelse af opdrĂŚttet fisk, der blev forbundet med noget negativt - pĂĽ linje med industrialiseret landbrug og i modsĂŚtning til âvile fiskâ.
⢠Kun fü forbrugere var i stand til at identificere regler for økologisk fisk og
ofte sammenblandedes de med MSC, ASC og andre certificeringer.
⢠Der behov for en systematisk kommunikations-/forbrugeroplysningskampagne med fokus pĂĽ større bevidsthed om âĂkologisk fiskâ, der er opdrĂŚttet og kontrolleret i forhold til specifikke regler for økologisk akvakultur og at økomĂŚrket adskiller sig fra f. eks. miljømĂŚrkerne MSC og ASC.
⢠Stigende efterspørgsel efter økologiske produkter i Europa vil vÌre et godt afsÌtningsmÌssigt grundlag for at fastholde mülsÌtningen i regeringens 2020-plan for dansk akvakultur. Det anbefales at der skabes yderligere incitament til omlÌgning af dambrug til økologisk produktion
Bone Status in Obese, Non-diabetic, Antipsychotic-Treated Patients, and Effects of the Glucagon-Like Peptide-1 Receptor Agonist Exenatide on Bone Turnover Markers and Bone Mineral Density
Background: Low bone mineral density (BMD) may constitute an underestimated comorbidity in schizophrenia patients undergoing long-term antipsychotic treatment. Glucagon-like peptide 1 (GLP-1) receptor agonists are antidiabetic drugs, which may also affect bone turnover.Methods: In planned secondary analyses of a 3 months, double-blind, randomized, placebo-controlled trial (n = 45), we explored effects of the GLP-1 receptor agonist exenatide 2 mg once-weekly (n = 23), or placebo (n = 22) on bone turnover markers (BTMs) and BMD in chronic, obese, antipsychotic-treated patients with schizophrenia spectrum disorder. Baseline BTMs were compared to sex- and age-adjusted reference values from a Danish population cohort, and T- and Z-scores were calculated for BMD.Results: In women (n = 24), all baseline BTM measurements of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were within reference values. In men (n = 21), 5% displayed lower PINP and 14% displayed lower CTX. One patient displayed BMD Z-score < â2, and 23% of patients (17% of women and 29% of men) displayed â2.5 < T-scores < â1 indicating osteopenia, but none had osteoporosis. After treatment, PINP decreased at trend level significance (P = 0.05), and body mass index BMD increased for L2âL4 (P = 0.016). No changes in bone markers were significant after correction for mean prolactin levels.Conclusions: Sex- and age-adjusted measures of bone status in chronic, obese, antipsychotic-treated patients appeared comparable to the reference population. Subtle changes in bone markers during 3 months exenatide treatment may suggest beneficial effects of GLP-1 receptor agonists on bone status in antipsychotic-treated patients, and further studies should consider the potential influence of prolactin
A genetically modified minipig model for Alzheimer's disease with SORL1 haploinsufficiency
The established causal genes in Alzheimerâs disease (AD), APP, PSEN1, and PSEN2, are functionally characterized using biomarkers, capturing an in vivo profile reflecting the diseaseâs initial preclinical phase. Mutations in SORL1, encoding the endosome recycling receptor SORLA, are found in 2%â3% of individuals with early-onset AD, and SORL1 haploinsufficiency appears to be causal for AD. To test whether SORL1 can function as an AD causal gene, we use CRISPR-Cas9-based gene editing to develop a model of SORL1 haploinsufficiency in GĂśttingen minipigs, taking advantage of porcine models for biomarker investigations. SORL1 haploinsufficiency in young adult minipigs is found to phenocopy the preclinical in vivo profile of AD observed with APP, PSEN1, and PSEN2, resulting in elevated levels of β-amyloid (Aβ) and tau preceding amyloid plaque formation and neurodegeneration, as observed in humans. Our study provides functional support for the theory that SORL1 haploinsufficiency leads to endosome cytopathology with biofluid hallmarks of autosomal dominant AD