scholarly journals The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration

2018 ◽  
Vol 20 (4) ◽  
Author(s):  
Alexandros Kourentas ◽  
Maria Vertzoni ◽  
Vicky Barmpatsalou ◽  
Patrick Augustijns ◽  
Stefania Beato ◽  
...  
2019 ◽  
Author(s):  
T. Reid Alderson ◽  
Elias Adriaenssens ◽  
Bob Asselbergh ◽  
Iva Pritišanac ◽  
Heidi Y. Gastall ◽  
...  

HSP27 (HSPB1) is a systemically expressed human small heat-shock protein that forms large, dynamic oligomers and functions in various aspects of cellular homeostasis. Mutations in HSP27 cause Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. A particularly severe form of the disease is triggered by the P182L mutation within the highly conserved IxI/V motif of HSP27. Here, we observed that the P182L variant of HSP27 lacks the ability to prevent the aggregation of client proteins and formed significantly larger oligomers both in vitro and in vivo. NMR spectroscopy revealed that the P182L IxI/V motif binds its α-crystallin domain with significantly lower association rate, and thus affinity, rendering the binding site more available for other interactors. We identified 22 IxI/V-containing proteins that are known to interact with HSP27 and could therefore bind with enhanced affinity to the P182L variant. We validated this hypothesis through co-immunoprecipitation experiments, revealing that the IxI/V motif-bearing co-chaperone BAG3 indeed binds with higher affinity to the P182L variant. Our results provide a mechanistic basis for the impact of the P182L mutation on HSP27, and highlight the general importance of the IxI/V motif and its role in protein-protein interaction networks.


2020 ◽  
Vol 21 (10) ◽  
pp. 3631 ◽  
Author(s):  
Raffaella Boggia ◽  
Federica Turrini ◽  
Alessandra Roggeri ◽  
Guendalina Olivero ◽  
Francesca Cisani ◽  
...  

The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed the impact of the oral administration of a new oral ellagic acid micro-dispersion (EAm), that largely increased the EA solubility, in young and old mice. Oral EAm did not modify animal weight and behavioral skills in young and old mice, but significantly recovered changes in “ex-vivo, in vitro” parameters in old animals. Cortical noradrenaline exocytosis decreased in aged mice. EAm administration did not modify noradrenaline overflow in young animals, but recovered it in old mice. Furthermore, GFAP staining was increased in the cortex of aged mice, while IBA-1 and CD45 immunopositivities were unchanged when compared to young ones. EAm treatment significantly reduced CD45 signal in both young and old cortical lysates; it diminished GFAP immunopositivity in young mice, but failed to affect IBA-1 expression in both young and old animals. Finally, EAm treatment significantly reduced IL1beta expression in old mice. These results suggest that EAm is beneficial to aging and represents a nutraceutical ingredient for elders.


2014 ◽  
Vol 17 (1) ◽  
pp. 106 ◽  
Author(s):  
Yusuke Tanaka ◽  
Toshiyuki Baba ◽  
Koji Tagawa ◽  
Ryoichi Waki ◽  
Shunji Nagata

Purpose. This study aimed to develop a novel approach for predicting the oral absorption of low-solubility drugs by considering regional differences in solubility and permeability within the gastrointestinal (GI) tract. Methods. Simulated GI fluids were prepared to reflect rat in vivo bile acid and phospholipid concentrations in the upper and lower small intestine. The saturated solubility and permeability of griseofulvin (GF) and albendazole (AZ), a drug with low aqueous solubility, were measured using these simulated fluids, and fraction absorbed (Fa) at time t after oral administration was calculated. Results. The saturated solubility of GF and AZ, a drug with low aqueous solubility, differed considerably between the simulated GI fluids. Large regional differences in drugs concentration were also observed following oral administration in vivo. The predicted Fa values using solubility and permeability data of the simulated GI fluid were found to correspond closely to the in vivo data. Conclusion. These results indicated the importance of evaluating regional differences in drug solubility and permeability in order to predict oral absorption of low-solubility drugs accurately. The new methodology developed in the present study could be useful for new oral drug development. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5668
Author(s):  
Farid A. Badria ◽  
Abdelaziz E. Abdelaziz ◽  
Amira H. Hassan ◽  
Abdullah A. Elgazar ◽  
Eman A. Mazyed

Curcumin is a natural compound that has many medical applications. However, its low solubility and poor stability could impede its clinical applications. The present study aimed to formulate dry proniosomes to overcome these pitfalls and improve the therapeutic efficacy of Curcumin. Curcumin-loaded proniosomes were fabricated by the slurry method according to 32 factorial design using Design-Expert software to demonstrate the impact of different independent variables on entrapment efficiency (EE%) and % drug released after 12 h (Q12h). The optimized formula (F5) was selected according to the desirability criteria. F5 exhibited good flowability and appeared, after reconstitution, as spherical nanovesicles with EE% of 89.94 ± 2.31% and Q12h of 70.89 ± 1.62%. F5 demonstrated higher stability and a significant enhancement of Q12h than the corresponding niosomes. The docking study investigated the ability of Curcumin to bind effectively with the active site of DNA polymerase of Herpes simplex virus (HSV). The antiviral activity and the safety of F5 were significantly higher than Curcumin. F5 improved the safety of Acyclovir (ACV) and reduced its effective dose that produced a 100% reduction of viral plaques. Proniosomes could be promising stable carriers of Curcumin to be used as a safe and efficient antiviral agent.


2021 ◽  
Vol 22 (22) ◽  
pp. 12269
Author(s):  
Stephanie Kraft ◽  
Lisa Buchenauer ◽  
Tobias Polte

Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding the role of mold and mycotoxins in the development of immune diseases. While the induction of allergic immune responses by molds is generally acknowledged, other direct health effects like the toxic mold syndrome are controversially discussed. However, recent observations indicate a particular importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system, due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and even human immunodeficiency virus (HIV) disease progression. In this review, we focus on the impact of mycotoxins regarding their impact on disease progression in pre-existing immune dysregulation. This is complemented by experimental in vivo and in vitro findings to present cellular and molecular modes of action. Furthermore, we discuss hypothetical mechanisms of action, where evidence is missing since much remains to be discovered.


2019 ◽  
Vol 10 (11) ◽  
pp. 1131-1135
Author(s):  
Tomas Hambili Paulo Sanjuluca ◽  
◽  
Ricardo Correia ◽  
Anabela Antunes de Almeida ◽  
Ana Gloria Diaz Martinez ◽  
...  

Introduction: In order to have a good assessment of the quality of maternal and child health care, it is essential that there is up-to-date and reliable information. Objective: To evaluate the impact of the implementation of a computerized database of clinical processes in the admission, archive and medical statistics section, of Maternity hospital Irene Neto/Lubango-Angola. Methodology: A descriptive study with a quantitative and qualitative approach to carry out a retrospective case study deliveries and newborns, records from 2014 to 2017. Final considerations: The implementation of this project may contribute to the improvement of clinical management support management of the hospital as well as facilitating access to information for research and scientific production.


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