scholarly journals Serjanic Acid Improves Immunometabolic Markers in a Diet-Induced Obesity Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1486
Author(s):  
Gustavo Gutiérrez ◽  
Deisy Giraldo-Dávila ◽  
Marianny Y. Combariza ◽  
Ulrike Holzgrabe ◽  
Jorge Humberto Tabares-Guevara ◽  
...  
Keyword(s):  
Mouse Model ◽  
Latin American ◽  
Metabolic Disorders ◽  
Adipocyte Differentiation ◽  
Fasting Blood Glucose ◽  
Pilot Scale ◽  
Transcriptional Level ◽  
Inflammation Markers ◽  
Diet Induced Obesity ◽  
The Impact

Plant extracts from Cecropia genus have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous reports have shown that roots of Cecropia telenitida that contains serjanic acid as one of the most prominent and representative pentacyclic triterpenes. The study aimed to isolate serjanic acid and evaluate its effect in a prediabetic murine model by oral administration. A semi-pilot scale extraction was established and serjanic acid purification was followed using direct MALDI-TOF analysis. A diet induced obesity mouse model was used to determine the impact of serjanic acid over selected immunometabolic markers. Mice treated with serjanic acid showed decreased levels of cholesterol and triacylglycerols, increased blood insulin levels, decreased fasting blood glucose and improved glucose tolerance, and insulin sensitivity. At transcriptional level, the reduction of inflammation markers related to adipocyte differentiation is reported.

1875-P: The Impact of Carbohydrate/Fat Intake Balance on Beta-Cell Dedifferentiation and Fatty Liver in Obese Mouse Model

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1875-P ◽  
Author(s):  
EMI ISHIDA ◽  
XIAO LEI ◽  
EIJIRO YAMADA ◽  
SHUICHI OKADA ◽  
MASANOBU YAMADA
Keyword(s):  
Mouse Model ◽  
Beta Cell ◽  
Fatty Liver ◽  
Obese Mouse ◽  
Fat Intake ◽  
Cell Dedifferentiation ◽  
The Impact

Heterotrophic Kinetic Parameter Estimation for Enhanced Biological Phosphorus Removal Processes Operated in Conventional and Membrane-Assisted Modes

2006 ◽  
Vol 41 (1) ◽  
pp. 72-83 ◽  
Author(s):  
Zhe Zhang ◽  
Eric R. Hall
Keyword(s):  
Parameter Estimation ◽  
Phosphorus Removal ◽  
Growth Yield ◽  
Pilot Scale ◽  
Enhanced Biological Phosphorus Removal ◽  
Biological Phosphorus Removal ◽  
Nitrogen And Phosphorus ◽  
Parameter Values ◽  
The Impact ◽  
Biological Phosphorus

Abstract Parameter estimation and wastewater characterization are crucial for modelling of the membrane enhanced biological phosphorus removal (MEBPR) process. Prior to determining the values of a subset of kinetic and stoichiometric parameters used in ASM No. 2 (ASM2), the carbon, nitrogen and phosphorus fractions of influent wastewater at the University of British Columbia (UBC) pilot plant were characterized. It was found that the UBC wastewater contained fractions of volatile acids (SA), readily fermentable biodegradable COD (SF) and slowly biodegradable COD (XS) that fell within the ASM2 default value ranges. The contents of soluble inert COD (SI) and particulate inert COD (XI) were somewhat higher than ASM2 default values. Mixed liquor samples from pilot-scale MEBPR and conventional enhanced biological phosphorus removal (CEBPR) processes operated under parallel conditions, were then analyzed experimentally to assess the impact of operation in a membrane-assisted mode on the growth yield (YH), decay coefficient (bH) and maximum specific growth rate of heterotrophic biomass (µH). The resulting values for YH, bH and µH were slightly lower for the MEBPR train than for the CEBPR train, but the differences were not statistically significant. It is suggested that MEBPR simulation using ASM2 could be accomplished satisfactorily using parameter values determined for a conventional biological phosphorus removal process, if MEBPR parameter values are not available.

scholarly journals Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 905
Author(s):  
Sangeeta Kumari ◽  
Madhuri Dandamudi ◽  
Sweta Rani ◽  
Elke Behaeghel ◽  
Gautam Behl ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Pilot Scale ◽  
Dry Eye Disease ◽  
Rapid Screening ◽  
Eye Disease ◽  
Topical Steroids ◽  
Nanostructured Lipid Carrier ◽  
The Impact ◽  
Ophthalmic Formulation

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.

scholarly journals Process Modeling and Simulation of Tableting—An Agent-Based Simulation Methodology for Direct Compression

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 996
Author(s):  
Niels Lasse Martin ◽  
Ann Kathrin Schomberg ◽  
Jan Henrik Finke ◽  
Tim Gyung-min Abraham ◽  
Arno Kwade ◽  
...  
Keyword(s):  
Raw Materials ◽  
Pilot Scale ◽  
Physical Models ◽  
Agent Based Simulation ◽  
Validation Data ◽  
Agent Based ◽  
Industrial Processing ◽  
Digital Twins ◽  
Product And Process ◽  
The Impact

In pharmaceutical manufacturing, the utmost aim is reliably producing high quality products. Simulation approaches allow virtual experiments of processes in the planning phase and the implementation of digital twins in operation. The industrial processing of active pharmaceutical ingredients (APIs) into tablets requires the combination of discrete and continuous sub-processes with complex interdependencies regarding the material structures and characteristics. The API and excipients are mixed, granulated if required, and subsequently tableted. Thereby, the structure as well as the properties of the intermediate and final product are influenced by the raw materials, the parametrized processes and environmental conditions, which are subject to certain fluctuations. In this study, for the first time, an agent-based simulation model is presented, which enables the prediction, tracking, and tracing of resulting structures and properties of the intermediates of an industrial tableting process. Therefore, the methodology for the identification and development of product and process agents in an agent-based simulation is shown. Implemented physical models describe the impact of process parameters on material structures. The tablet production with a pilot scale rotary press is experimentally characterized to provide calibration and validation data. Finally, the simulation results, predicting the final structures, are compared to the experimental data.

scholarly journals Structural and functional brain-wide alterations in A350V Iqsec2 mutant mice displaying autistic-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Lichtman ◽  
Eyal Bergmann ◽  
Alexandra Kavushansky ◽  
Nadav Cohen ◽  
Nina S. Levy ◽  
...  
Keyword(s):  
Social Behavior ◽  
Functional Connectivity ◽  
Mouse Model ◽  
Ampa Receptor ◽  
Social Preference ◽  
Autism Spectrum ◽  
Receptor Trafficking ◽  
Anterior Cingulate ◽  
The Impact ◽  
Ampa Receptor Trafficking

AbstractIQSEC2 is an X-linked gene that is associated with autism spectrum disorder (ASD), intellectual disability, and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cerebral cortex and hippocampus. Moreover, using a data-driven approach we identify putative alterations in structure–function relations of the frontal, auditory, and visual networks in A350V mice. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three-chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations.

scholarly journals OP0277-PARE METABERN, THE EUROPEAN REFERENCE NETWORK FOR RARE HEREDITARY DISEASES: STRUCTURE, OBJECTIVES, METABOLIC RMDS AND THE ROLES OF EUROPEAN PATIENT ADVOCACY GROUPS (EPAGS)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 168.2-168
Author(s):  
L. Wagner ◽  
S. Sestini ◽  
C. Brown ◽  
A. Finglas ◽  
R. Francisco ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Health Care ◽  
Social Science ◽  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Clinical Care ◽  
Single Point ◽  
Link Type ◽  
The Impact

Background:Inborn metabolic disorders (IMDs) currently encompass more than 1,500 diseases with new ones still to be identified1. Each of them is characterised by a genetic defect affecting a metabolic pathway. Only few of them have curative treatments, that target the respective metabolic pathway. Commonly, treatment examples include diet, substrate reduction therapies, enzyme replacement therapies, gene therapy and biologicals, enabling IMD-patient now to survive to adulthood. About 30 % of all IMDs involve the musculoskeletal system and are here referred to as rare metabolic RMDs. Generally, IMDs are very heterogenous with respect to symptoms and severity, often being systemic and affecting more children than adults. Thus, challenges include certified advanced training of adult metabolic experts, standardised transition plans, social support and development of therapies for diseases that do not have any cure yet.Objectives:Introduction of MetabERN, its structure and objectives, highlighting on the unique features and challenges of metabolic RMDs and describing the involvement of patient representation in MetabERN.Methods:MetabERN is stratified in 7 subnetworks (SNW) according to the respective metabolic pathways and 9 work packages (WP), including administration, dissemination, guidelines, virtual counselling framework, research/clinical trials, continuity of care, education and patient involvement. The patient board involves a steering committee and single point of contacts for each subnetwork and work package, respectively2. Projects include identifying the need of implementing social science to assess the psycho-socio-economic burden of IMDs, webinars on IMDs and their transition as well as surveys on the impact of COVID-193 on IMD-patients and health care providers (HCPs), social assistance for IMD-patients and analysing the transition landscape within Europe.Results:The MetabERN structure enables bundling of expertise, capacity building and knowledge transfer for faster diagnosis and better health care. Rare metabolic RMDs are present in all SNWs that require unique treatments according to their metabolic pathways. Implementation of social science to assess the psycho-socio-economic burden of IMDs is still underused. Involvement of patient representatives is essential for a holistic healthcare not only focusing on clinical care, but also on the quality of life for IMD-patients. Surveys identified unmet needs of patient care, patients having little information on national support systems and structural deficits of healthcare systems to ensure HCP can provide adequate clinical care during transition phases. These results are collected by MetabERN and forwarded to the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission (EC) to be addressed further.Conclusion:MetabERN offers an infrastructure of virtual healthcare for patients with IMDs. Thus, in collaboration with ERN ReCONNET, MetabERN can assist in identifying rare metabolic disorders of RMDs to shorten the odyssey of diagnosis and advise on their respective therapies. On the other hand, MetabERN can benefit from EULAR’s longstanding experience regarding issues affecting the quality of life, all RMD patients are facing, such as pain, stiffness, fatigue, rehabilitation, maintaining work and disability claims.References:[1]IEMbase - Inborn Errors of Metabolism Knowledgebase http://www.iembase.org/ (accessed Jan 29, 2021).[2]MetabERN: European Refence Network for Hereditary Metabolic Disorders https://metab.ern-net.eu/ (accessed Jan 29, 2021).[3]Lampe, C.; Dionisi-Vici, C.; Bellettato, C. M.; Paneghetti, L.; van Lingen, C.; Bond, S.; Brown, C.; Finglas, A.; Francisco, R.; Sestini, S.; Heard, J. M.; Scarpa, M.; MetabERN collaboration group. The Impact of COVID-19 on Rare Metabolic Patients and Healthcare Providers: Results from Two MetabERN Surveys. Orphanet J. Rare Dis.2020, 15 (1), 341. https://doi.org/10.1186/s13023-020-01619-x.Acknowledgements:The authors thank the MetabERN collaboration group, the single point of contacts (SPOC) of the MetabERN patient board and the Transition Project Working Group (TPWG)Disclosure of Interests:None declared

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