Development and long-term in vivo testing of a novel skin-button system for preventing driveline infection of an implantable VAD system

Systematical consumption of functional products has a significant positive effect on health and can reduce the risk of diseases. The aim of this study was to investigate the possibility of using whey protein hydrolysate (WPH) and pumpkin pectin as ingredients in a functional mousse, to evaluate the mousse’s antioxidant and hypotensive activities in vitro, and to evaluate the effect of the long-term intake of mousse samples on the progression of hypertension in spontaneously hypertensive rats (SHRs) and on the microbiome status in Wistar rats with antibiotic-induced dysbiosis. The experimental mousse’s in vitro antioxidant activity (oxygen radical absorbance capacity) increased by 1.2 times. The hypotensive (angiotensin-1-converting enzyme inhibitory) activity increased by 6 times in comparison with a commercial mousse. Moreover, the addition of pectin allowed the elimination of the bitter aftertaste of WPH. In vivo testing confirmed the hypotensive properties of the experimental mousse. The systolic blood pressure in SHRs decreased by 18 mmHg and diastolic blood pressure by 12 mmHg. The experimental mousse also showed a pronounced bifidogenic effect. The Bifidobacterium spp. population increased by 3.7 times in rats orally administered with the experimental mousse. The results of these studies confirm that WPH and pumpkin pectin are prospective ingredients for the development of functional mousses.

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Revertant Mosaicism in Epidermolysis Bullosa

Biomedicines ◽

10.3390/biomedicines10010114 ◽

2022 ◽

Vol 10 (1) ◽

pp. 114

Author(s):

Cameron Meyer-Mueller ◽

Mark J. Osborn ◽

Jakub Tolar ◽

Christina Boull ◽

Christen L. Ebens

Keyword(s):

Epidermolysis Bullosa ◽

Molecular Mechanisms ◽

Site Mutation ◽

Naturally Occurring ◽

Spontaneous Correction ◽

In Vivo Testing ◽

Mitotic Gene Conversion ◽

Systemic Therapies

Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by mechanically fragile skin and mucocutaneous involvement. Historically, disease management has focused on supportive care. The development of new genetic, cellular, and recombinant protein therapies has shown promise, and this review summarizes a unique gene and cell therapy phenomenon termed revertant mosaicism (RM). RM is the spontaneous correction of a disease-causing mutation. It has been reported in most EB subtypes, some with relatively high frequency, and has been observed in both keratinocytes and fibroblasts. RM manifests as identifiable patches of unaffected, blister-resistant skin and can occur through a variety of molecular mechanisms, including true back mutation, intragenic crossover, mitotic gene conversion, and second-site mutation. RM cells represent a powerful autologous platform for therapy, and leveraging RM cells as a therapeutic substrate may avoid the inherent mutational risks of gene therapy/editing. However, further examination of the genomic integrity and long-term functionality of RM-derived cells, as well in vivo testing of systemic therapies with RM cells, is required to realize the full therapeutic promise of naturally occurring RM in EB.

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Atlanto-occipital catheterization of young rats for long-term drug delivery into the lumbar subarachnoid space combined with in vivo testing and electrophysiology in situ

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2017.08.001 ◽

2017 ◽

Vol 290 ◽

pp. 125-132 ◽

Cited By ~ 1

Author(s):

Olga Kopach ◽

Volodymyr Krotov ◽

Nana Voitenko

Keyword(s):

Drug Delivery ◽

Subarachnoid Space ◽

Young Rats ◽

In Vivo Testing ◽

Lumbar Subarachnoid Space

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A muscle-powered energy delivery system and means for chronic in vivo testing

Journal of Applied Physiology ◽

10.1152/jappl.1999.86.6.2106 ◽

1999 ◽

Vol 86 (6) ◽

pp. 2106-2114 ◽

Cited By ~ 11

Author(s):

Dennis R. Trumble ◽

James A. Magovern

Keyword(s):

In Vitro Tests ◽

Access Port ◽

Wide Range ◽

Piston Displacement ◽

In Vivo Testing ◽

Implant Testing

Electrically stimulated skeletal muscle represents a potentially unlimited source of energy for the actuation of motor prostheses. Devices to harvest and deliver contractile power have proven mechanically feasible, but long-term efficacy has not been demonstrated. This report describes recent refinements in muscle energy converter (MEC) design and details the development of an implantable afterload chamber (IAC) designed to facilitate implant testing. The IAC comprises a fluid-filled bladder housed within a titanium cylinder that connects directly to the MEC. A vascular access port allows percutaneous measurement and adjustment of air pressure within the housing and provides a means both to monitor MEC function and to control hydraulic loading conditions. Data from in vitro tests show that IAC pressure mirrors changes in MEC-piston displacement over a wide range of actuation speeds and stroke lengths. Stroke lengths and actuation forces calculated from IAC pressure readings were typically found to be within 5% of measured values. This testing scheme may yield important information in regard to the ability to harness energy from in situ muscle over prolonged periods.

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Engraftment characterization of risk-stratified AML patients in NSGS mice

Blood Advances ◽

10.1182/bloodadvances.2020003958 ◽

2021 ◽

Author(s):

Rafael Diaz de la Guardia ◽

Talia Velasco-Hernandez ◽

Francisco Gutierrez-Agüera ◽

Heleia Roca-Ho ◽

Oscar Molina ◽

...

Keyword(s):

Myeloid Leukemia ◽

Risk Group ◽

Disease Heterogeneity ◽

Free Survival ◽

In Vivo Testing ◽

Comprehensive Characterization ◽

Serial Transplantation

Acute myeloid leukemia (AML) is the commonest acute leukemia in adults. Disease heterogeneity is well-documented and patient stratification determines treatment decisions. Patient-derived xenografts (PDXs) of risk-stratified AMLs are crucial for studying AML biology and testing novel therapeutics. Despite recent advances in PDX modeling of AML, reproducible engraftment of human AML is mainly limited to high-risk (HR) cases, with inconsistent or very protracted engraftment observed for favorable-risk (FR) and intermediate-risk (IR) patients. We have characterized the engraftment robustness/kinetics in NSGS mice of 28 AML patients grouped according to molecular/cytogenetic classification, and have assessed whether the orthotopic co-administration of patient-matched bone marrow mesenchymal stromal cells (BM-MSCs) improves AML engraftment. PDX event-free survival correlated well with the predictable prognosis of risk-stratified AML patients. The majority (85%-94%) of the mice were engrafted in BM independently of the risk group, although HR-AML patients showed engraftment levels significantly superior to those of FR- and IR-AML patients. Importantly, the engraftment levels observed in NSGS mice by week 6 remained stable overtime. Serial transplantation and long-term culture-initiating cell (LTC-IC) assays revealed long-term engraftment limited to HR-AML patients, fitter leukemia-initiating cells (LICs) in HR- than in FR- or IR-AML samples, and the presence of AML-LICs in the CD34- leukemic fraction, regardless the risk group. Finally, orthotopic co-administration of patient-matched BM-MSCs with AML cells resulted dispensable for BM engraftment levels but favored peripheralization of engrafted AML cells. This comprehensive characterization of human AML engraftment in NSGS mice offers a valuable platform for in vivo testing of targeted therapies in risk-stratified AML patient samples.

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