Oral Administration of the CCR5 Inhibitor, Maraviroc, Blocks HIV Ex Vivo Infection of Langerhans Cells within the Epithelium

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.

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ENDOTHELIAL FUNCTION MODULATION AND CONTROL OF VASCULAR AND THROMBOTIC DISORDERS: EXPERIMENTAL RESULTS WITH A POLYDEOXY RIBONUCLEOTIDE AGENT DEFIBROTIDE

10.1055/s-0038-1643149 ◽

1987 ◽

Author(s):

A Kumar ◽

J Fareed ◽

W H Wehrmacher ◽

D Hoppensteadt ◽

O Ulutin ◽

...

Keyword(s):

Endothelial Function ◽

Oral Administration ◽

Cell Function ◽

Vascular System ◽

Ex Vivo ◽

Smooth Muscles ◽

Venous Stasis ◽

Functional Protein ◽

Endothelial Cell Function ◽

Multiple Drugs

Numerous approaches with single and multiple drugs modulating protease cascade, platelet function and blood viscosity and to reduce blood lipids to manage thrombotic processes have been tried. Defibrotide, a polydeoxyribonucleotide, (Mr =17,000) offers a new approach to vascular and related thrombotic processes as it acts via modulation of endothelial cell function. We have used a primate model (Macaca mulatta) to study the endogenous action of this agent after the oral (10-25 mg/kg) and intravenous (5-10 mg/kg) administration. This agent produced no effect on clotting tests and ex vivo laboratory findings but rather it elevated the t-PA (antigen and functional), protein C (antigen and functional), prostacyclin and decreased thromboxane, 01.2-antiplasmin (functional) and t-PA inhibitor (functional) in both studies. These observations suggest that Defibrotide modulates endothelial function. Hepatic isolation in rabbits totally blocked the antithrombotic actions of Defibrotide suggesting that this agent is converted into an active product endogenously. Pretreatment of Defibrotide with nucleases also resulted in a complete loss of its actions. Defibrotide produced dose dependent antithrombotic actions in animal models (rabbit venous stasis and rat vena caval ligation) after either intravenous or oral administration. Blood pressure, heart rate, respiration and kidney function were not altered by it. No effect on bleeding time was noted in any studies. Upon oral administration this drug produced pharmacologic action after 2 hours whereas after intravenous administration, the action peaked at 30 minutes. Defibrotide exhibited cytoprotective effects towards endothelial lining of the vascular smooth muscles characterized by microscopic studies. In summary Defibrotide is an endothelial support agent whose multicomponent actions are primarily mediated via the physical and functional modulation of the endothelial cells in the vascular system.

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Probiotics Have a Different Immunomodulatory Potential in vitro versus ex vivo upon Oral Administration in Children with Food Allergy

International Archives of Allergy and Immunology ◽

10.1159/000099467 ◽

2007 ◽

Vol 143 (3) ◽

pp. 237-244 ◽

Cited By ~ 40

Author(s):

A.E. Flinterman ◽

E.F. Knol ◽

A.G. van Ieperen-van Dijk ◽

H.M. Timmerman ◽

A.C. Knulst ◽

...

Keyword(s):

Food Allergy ◽

Oral Administration ◽

Ex Vivo ◽

Immunomodulatory Potential

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HIV-infected human Langerhans cells transmit infection to human lymphoid tissue ex vivo

AIDS ◽

10.1097/00002030-200004140-00003 ◽

2000 ◽

Vol 14 (6) ◽

pp. 647-651 ◽

Cited By ~ 34

Author(s):

Andrew Blauvelt ◽

Svetlana Glushakova ◽

Leonid B. Margolis

Keyword(s):

Lymphoid Tissue ◽

Langerhans Cells ◽

Ex Vivo ◽

Human Lymphoid Tissue

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The effect of a highly purified betulin-based triterpene extract on human keratinocytes and epidermal Langerhans cells ex vivo and in vivo

Planta Medica ◽

10.1055/s-0028-1083903 ◽

2008 ◽

Vol 74 (09) ◽

Author(s):

U Wölfle ◽

MN Laszczyk ◽

C Huyke ◽

B Simon-Haarhaus ◽

A Scheffler ◽

...

Keyword(s):

Langerhans Cells ◽

Ex Vivo ◽

Human Keratinocytes ◽

Epidermal Langerhans Cells

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Antiplatelet drugs and generation of thrombin in clotting blood

Blood ◽

10.1182/blood.v80.8.2006.2006 ◽

1992 ◽

Vol 80 (8) ◽

pp. 2006-2011 ◽

Cited By ~ 84

Author(s):

A Szczeklik ◽

M Krzanowski ◽

P Gora ◽

J Radwan

Keyword(s):

Oral Administration ◽

Thrombin Generation ◽

Ex Vivo ◽

Coagulation Factors ◽

Antiplatelet Drugs ◽

Specific Marker ◽

Rate Of Increase ◽

Synthase Inhibitor ◽

Thrombin Formation

Abstract Platelets participate in formation of thrombin through secretion of coagulation factors and by providing a catalytic surface on which prothrombinase complex is assembled. We studied the effects of four antiplatelet drugs on thrombin formation in healthy volunteers. Thrombin generation was monitored both in vitro--in recalcified plasma-- and ex vivo--in blood emerging from a standardized skin microvasculature injury, which also served to determine bleeding time. A mathematical model has been developed to describe the latter reaction. It is based on estimation of the rate of increase in fibrinopeptide A (FPA), a specific marker of thrombin activity, in blood emerging from skin incisions. Two hours after the ingestion of 500 mg of aspirin, thrombin formation became significantly impaired both in vitro and ex vivo. In contrast, 2 hours after the oral administration of placebo, indomethacin 50 mg, or OKY-046 (a thromboxane synthase inhibitor) 400 mg, thrombinogenesis remained unaltered. Ticlopidine, studied either 3 hours after 500 mg oral administration, or after 5 days of intake at a daily dose of 500 mg, had no effect on thrombin generation. Thus, aspirin, contrary to other antiplatelet drugs, depresses thrombin formation in clotting blood, a phenomenon that might be of clinical relevance. It is suggested that aspirin exerts this effect by acetylating prothrombin and/or macromolecules of platelet membrane.

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Neuroprotective Effect of Ropinirole Lipid Nanoparticles Enriched Hydrogel for Parkinson’s Disease: In Vitro, Ex Vivo, Pharmacokinetic and Pharmacodynamic Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics12050448 ◽

2020 ◽

Vol 12 (5) ◽

pp. 448 ◽

Cited By ~ 7

Author(s):

Narendar Dudhipala ◽

Thirupathi Gorre

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Oral Administration ◽

Neurodegenerative Disorder ◽

Ex Vivo ◽

Neuroprotective Effect ◽

Topical Delivery ◽

Lipid Nanoparticles ◽

Oral Dosage

Parkinson’s disease (rp) is a progressive neurodegenerative disorder. Ropinirole (RP) is a newer generation dopamine agonist used for the treatment of PD. It is prescribed as oral dosage form. However, limited oral bioavailability and frequent dosing limits the RP usage. The objective of the current investigation was to develop, optimize, evaluate pharmacokinetic (PK) and pharmacodynamic (PCD) activity of RP loaded solid lipid nanoparticles (RP-SLNs) and nanostructured lipid carriers (RP-NLCs) and containing hydrogel (RP-SLN-C and RP-NLC-C) formulations for improved oral and topical delivery. RP loaded lipid nanoparticles were optimized and converted to hydrogel using carbopol 934 as the gelling polymer. PK and PCD studies in haloperidol-induced PD were conducted in male Wistar rats. In vitro and ex vivo permeation studies showed sustained release profile and enhanced permeation compared with control formulations. Differential scanning calorimeter and X-ray diffraction studies revealed amorphous transformation; scanning electron microscope showed the spherical shape of RP in lipid nanoparticles. PK studies showed 2.1 and 2.7-folds enhancement from RP-SLN and RP-NLC from oral administration, 3.0 and 3.3-folds enhancement from RP-SLN-C and RP-NLC-C topical administration, compared with control formulations, respectively. RP-SLN-C and RP-NLC-C showed 1.4 and 1.2-folds topical bioavailability enhancement compared with RP-SLN and RP-NLC oral administration, respectively. PCD studies showed enhanced dopamine, glutathione, catalase levels and reduced lipid peroxidation levels, compared with the haloperidol-induced PD model. Overall, the results demonstrated that lipid nanoparticles and corresponding hydrogel formulations can be considered as an alternative delivery approach for the improved oral and topical delivery of RP for the effective treatment of PD.

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