scholarly journals Chondroprotective Properties of Human-Enriched Serum Following Polyphenol Extract Absorption: Results from an Exploratory Clinical Trial

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3071
Author(s):  
Fabien Wauquier ◽  
Elsa Mevel ◽  
Stephanie Krisa ◽  
Tristan Richard ◽  
Josep Valls ◽  
...  
Keyword(s):  
Articular Chondrocytes ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
Clinical Approach ◽  
Age Related ◽  
Nutritional Strategy ◽  
Sparing Effect ◽  
The Relationship

Polyphenols are widely acknowledged for their health benefits, especially for the prevention of inflammatory and age-related diseases. We previously demonstrated that hydroxytyrosol (HT) and procyanidins (PCy), alone or in combination, drive preventive anti-osteoathritic effects in vivo. However, the lack of sufficient clinical evidences on the relationship between dietary phytochemicals and osteoarthritis remains. In this light, we investigated in humans the potential osteoarticular benefit of a grapeseed and olive extract (OPCO) characterized for its hydroxytyrosol (HT) and procyanidins (PCy) content. We first validated, in vitro, the anti-inflammatory and chondroprotective properties of the extract on primary cultured human articular chondrocytes stimulated by interleukin-1 beta (IL-1 β). The sparing effect involved a molecular mechanism dependent on the nuclear transcription factor-kappa B (NF-κB) pathway. To confirm the clinical relevance of such a nutritional strategy, we designed an innovative clinical approach taking into account the metabolites that are formed during the digestion process and that appear in circulation after the ingestion of the OPCO extract. Blood samples from volunteers were collected following ingestion, absorption, and metabolization of the extract and then were processed and applied on human primary chondrocyte cultures. This original ex vivo methodology confirmed at a clinical level the chondroprotective properties previously observed in vitro and in vivo.

Aging and dietary modulation of elastase and interleukin-1 beta secretion

1995 ◽  
Vol 268 (1) ◽  
pp. R208-R213 ◽  
Author(s):  
J. G. Cannon ◽  
M. A. Fiatarone ◽  
M. Meydani ◽  
J. Gong ◽  
L. Scott ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cell Function ◽  
Interleukin 1 ◽  
Lipid Peroxide ◽  
Arachidonic Acid Metabolism ◽  
Interleukin 1 Beta ◽  
Tension Development ◽  
Age Related

Aging is associated with diminished immune function that may stem from alterations in arachidonic acid metabolism and lipid peroxidation. This study sought to determine if dietary modification of fatty acids influenced neutrophil and monocyte secretion after an in vivo inflammatory stress in older human subjects. Volunteers participated in protocols that forced their quadriceps muscles to lengthen during tension development (eccentric stress). These protocols can cause inflammatory foci in the muscle as well as alterations in circulating leukocyte function. In this study, in vivo neutrophil degranulation was assessed by plasma elastase concentrations, and mononuclear cell function was assessed by interleukin-1 beta (IL-1 beta) secretion in vitro. In response to eccentric stress, older subjects (> 60 yr old) taking a placebo had no apparent elastase response, whereas those taking fish oil supplements responded with a 142% increase in plasma elastase (P = 0.011), similar to responses of younger reference subjects (< 33 yr old) taking no supplement. Overall, elastase responses correlated with individual plasma arachidonic acid-to-eicosapentaenoic acid ratios (r = -0.881, P = 0.004). Thus apparent age-related differences in elastase release were reconciled by individual differences in fatty acid nutriture. No significant temporal changes in urinary lipid peroxide excretion or IL-1 beta secretion were observed; however, age-associated differences were found.

scholarly journals MR imaging of model drug distribution in simulated vitreous

2015 ◽  
Vol 1 (1) ◽  
pp. 236-239 ◽  
Author(s):  
Sandra Stein ◽  
Christian Simroth-Loch ◽  
Sönke Langner ◽  
Stefan Hadlich ◽  
Oliver Stachs ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Ex Vivo ◽  
Drug Distribution ◽  
Injection Technique ◽  
Innovative Therapy ◽  
Age Related ◽  
The Impact

AbstractThe in vitro and in vivo characterization of intravitreal injections plays an important role in developing innovative therapy approaches. Using the established vitreous model (VM) and eye movement system (EyeMoS) the distribution of contrast agents with different molecular weight was studied in vitro. The impact of the simulated age-related vitreal liquefaction (VL) on drug distribution in VM was examined either with injection through the gel phase or through the liquid phase. For comparison the distribution was studied ex vivo in the porcine vitreous. The studies were performed in a magnetic resonance (MR) scanner. As expected, with increasing molecular weight the diffusion velocity and the visual distribution of the injected substances decreased. Similar drug distribution was observed in VM and in porcine eye. VL causes enhanced convective flow and faster distribution in VM. Confirming the importance of the injection technique in progress of VL, injection through gelatinous phase caused faster distribution into peripheral regions of the VM than following injection through liquefied phase. VM and MR scanner in combination present a new approach for the in vitro characterization of drug release and distribution of intravitreal dosage forms.

Elevated IL-1β contributes to antibody suppression produced by stress

2002 ◽  
Vol 93 (1) ◽  
pp. 207-215 ◽  
Author(s):  
Albert Moraska ◽  
Jay Campisi ◽  
Kien T. Nguyen ◽  
Steven F. Maier ◽  
Linda R. Watkins ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Acute Stress ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
Keyhole Limpet Hemocyanin ◽  
Acquired Immunity ◽  
Sprague Dawley

Acute stressor exposure can facilitate innate immunity and suppress acquired immunity. The present study further characterized the potentiating effect of stress on innate immunity, interleukin-1β (IL-1β), and demonstrated that stress-induced potentiation of innate immunity may contribute to the stress-induced suppression of acquired immunity. The long-term effect of stress on IL-1β was measured by using an ex vivo approach. Sprague-Dawley rats were challenged with lipopolysaccharide (LPS) in vivo, and the IL-1β response was measured in vitro. Splenocytes, mesenteric lymphocytes, and peritoneal cavity cells had a dose- and time-dependent ex vivo IL-1β response to LPS. Rats that were exposed to inescapable shock (IS, 100 1.6 mA, 5-s tail shocks, 60-s intertrial interval) and challenged with a submaximal dose of LPS 4 days later had elevated IL-1β measured ex vivo. To test whether the acute stress-induced elevation in IL-1β contributes to the long-term suppression in acquired immunity, IL-1β receptors were blocked for 24 h after stress. Serum anti-keyhole limpet hemocyanin (KLH) immunoglobulin (Ig) was measured. In addition, the acute elevation (2 h post-IS) of splenic IL-1β in the absence of antigen was verified. Interleukin-1 receptor antagonist prevented IS-induced suppression in anti-KLH Ig. These data support the hypothesis that stress-induced increases in innate immunity (i.e., IL-1β) may contribute to stress-induced suppression in acquired immunity (i.e., anti-KLH Ig).

scholarly journals Effect ofAngelica sinensisPolysaccharides on OsteoarthritisIn VivoandIn Vitro: A Possible Mechanism to Promote Proteoglycans Synthesis

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Jun Qin ◽  
Yan-song Liu ◽  
Jun Liu ◽  
Jing Li ◽  
Yang Tan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Articular Chondrocytes ◽  
Interleukin 1 ◽  
Knee Joints ◽  
Protective Effects ◽  
Interleukin 1 Beta ◽  
Degrading Enzymes ◽  
Matrix Degrading Enzymes

This study investigated the effect ofAngelica sinensispolysaccharides (APS-3c) on rat osteoarthritis (OA) modelin vivoand rat interleukin-1-beta- (IL-1β-) stimulated chondrocytesin vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilagein vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1β  in vitro. 2~50 μg/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1β. Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1βbut did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA modelin vivoand IL-1β-stimulated chondrocytesin vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.

scholarly journals Ref-1/APE1 inhibition with novel small molecules blocks ocular neovascularization

2018 ◽  
Author(s):  
Sardar Pasha Sheik Pran Babu ◽  
Kamakshi Sishtla ◽  
Rania S. Sulaiman ◽  
Bomina Park ◽  
Trupti Shetty ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ex Vivo ◽  
Age Related Macular Degeneration ◽  
Lesion Volume ◽  
Ocular Neovascularization ◽  
Age Related ◽  
Promising Therapeutic Approach ◽  
Dna Binding Assay

AbstractOcular neovascular diseases like wet age-related macular degeneration are a major cause of blindness. Novel therapies are greatly needed for these diseases. One appealing antiangiogenic target is reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1). This protein can act as a redox-sensitive transcriptional activator for NF-κB and other pro-angiogenic transcription factors. An existing inhibitor of Ref-1’s function, APX3330, previously showed antiangiogenic effects. Here, we developed improved APX3330 derivatives and assessed their antiangiogenic activity. We synthesized APX2009 and APX2014 and demonstrated enhanced inhibition of Ref-1 function in a DNA-binding assay compared to APX3330. Both compounds were antiproliferative against human retinal microvascular endothelial cells (HRECs; GI50 APX2009: 1.1 μM, APX2014: 110 nM) and macaque choroidal endothelial cells (Rf/6a GI50APX2009: 26 μM, APX2014: 5.0 μM). Both compounds significantly reduced the ability of HRECs and Rf/6a cells to form tubes at mid nanomolar concentrations compared to control, and both significantly inhibited HREC and Rf/6a cell migration in a scratch wound assay, reducing NF-κB activation and downstream targets.Ex vivo, both APX2009 and APX2014 inhibited choroidal sprouting at low micromolar and high nanomolar concentrations respectively. In the laser-induced choroidal neovascularization mouse model, intraperitoneal APX2009 treatment significantly decreased lesion volume by 4-fold compared to vehicle (p< 0.0001, ANOVA with Dunnett’s post hoc tests), without obvious intraocular or systemic toxicity. Thus, Ref-1 inhibition with APX2009 and APX2014 blocks ocular angiogenesisin vitroandex vivo, and APX2009 is an effective systemic therapy for CNVin vivo, establishing Ref-1 inhibition as a promising therapeutic approach for ocular neovascularization.

Effect of N-Acetylglucosamine on Function of Peritoneal Leukocytes

1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 365-369 ◽  
Author(s):  
Malgorzata Kuzlan-Pawlaczyk ◽  
Krzysztof Pawlaczyk ◽  
Katarzyna Wieczorowska Tobis ◽  
Alicja Polubinska ◽  
Justyna Wisniewska ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Count ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
Differential Cell Count ◽  
Dialysis Solution ◽  
Peritoneal Leukocytes ◽  
Factor Α

Objective To compare effects of N-acetylglucosamine (NAG) -based and glucose-based dialysis fluids on the function of peritoneal leukocytes in conditions of peritoneal dialysis. Design In vitro experiments on ex vivo isolated rat peritonealleukocytes. Materials Peritoneal leukocytes were isolated from rats on chronic peritoneal dialysis. On alternate days, fluid exchanges were performed with NAG-based or glucosebased dialysis solutions. After a 4-hour dwell, dialysate was drained and peritoneal leukocytes were incubated in vitro :I= lipopolysaccharide (LPS). Production of nitrites (index of NO synthesis), tumor necrosis factor α (TNFα), interleukin-1 β (IL -1 β), and interferon gamma (IFN-y) by unstimulated or stimulated peritoneal leukocytes originating from NAG-based or glucose-based fluid was measured. Results Dialysate cell count was lower during exchanges with NAG-based fluid (2113 :I= 615 cells/μL) as compared to glucose-based fluid (3643 :I= 1108 cells/μL; p < 0.01). Differential cell count was similar in both studied groups. Unstimulated peritoneal leukocytes from NAGbased dialysate produced more NO (nitrites) (0.65 ± 0.07 μmol per 106 cells) than did cells from glucose-based dialysate (0.26 :I= 0.09 μmol per 106 cells, p < 0.01). Stimulated peritoneal leukocytes from NAG-based dialysate produced more cytokines than did cells from glucose-based dialysate: TNFα, 135.2 ± 37.0 pg versus 70.2 :I= 21.8 pg per 106 cells respectively, p < 0.01; IL -1 β, 143.2 :I= 60.9 pg versus 99.1 :I= 22.4 pg per 106 cells respectively, p < 0.05; IFN-y, 16.2:1= 12.5 pg versus 6.0:1= 1.8 pg per 106 cells respectively, p <0.01. Conclusions We demonstrated that rat peritonealleukocytes exposed in vivoto NAG-based dialysis fluid have better ability to produce inflammatory mediators than do peritoneal leukocytes from the same donor, but exposed in vivo to glucose-based dialysis solution.

scholarly journals The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 833
Author(s):  
Alicia Rodríguez-Gascón ◽  
María Ángeles Solinís ◽  
Arantxa Isla
Keyword(s):  
Antimicrobial Agents ◽  
Ex Vivo ◽  
European Medicines Agency ◽  
In Vivo Models ◽  
Dosage Regimens ◽  
Optimal Dosing ◽  
The Relationship

Pharmacokinetic/pharmacodynamic (PK/PD) analysis has proved to be very useful to establish rational dosage regimens of antimicrobial agents in human and veterinary medicine. Actually, PK/PD studies are included in the European Medicines Agency (EMA) guidelines for the evaluation of medicinal products. The PK/PD approach implies the use of in vitro, ex vivo, and in vivo models, as well as mathematical models to describe the relationship between the kinetics and the dynamic to determine the optimal dosing regimens of antimicrobials, but also to establish susceptibility breakpoints, and prevention of resistance. The final goal is to optimize therapy in order to maximize efficacy and minimize side effects and emergence of resistance. In this review, we revise the PK/PD principles and the models to investigate the relationship between the PK and the PD of antibiotics. Additionally, we highlight the outstanding role of the PK/PD analysis at different levels, from the development and evaluation of new antibiotics to the optimization of the dosage regimens of currently available drugs, both for human and animal use.

scholarly journals Comparative characterization of the reassortant Orthobunyavirus Ngari with putative parental viruses, Bunyamwera and Batai: in vitro characterization and ex vivo stability

2020 ◽  
Author(s):  
M. Fausta Dutuze ◽  
E. Handly Mayton ◽  
Joshua D. Macaluso ◽  
Rebecca C. Christofferson
Keyword(s):  
Ex Vivo ◽  
Laboratory System ◽  
In Vitro Characterization ◽  
Significant Difference ◽  
The Relationship ◽  
Kinetics Of ◽  
Negative Sense

Bunyamwera (BUNV), Batai (BATV) and Ngari (NRIV) are mosquito-borne viruses that are members of the genus Orthobunyavirus in the order Bunyavirales. These three viruses are enveloped with single-stranded, negative-sense RNA genomes consiting of three segments, denoted as Small (S), Medium (M) and Large (L). Ngari is thought to be the natural reassortant progeny of Bunyamwera and Batai viruses. The relationship between these ‘parental’ viruses and the ‘progeny’ poses an interesting question, especially given that there is overlap in their respective transmission ecologies, but differences in their infection host ranges and pathogenesis. We compared the in vivo kinetics of these three viruses in a common laboratory system and found no significant difference in growth kinetics. There was, however, a tendency of BATV to have smaller plaques than either BUNV or NRIV. Furthermore, we determined that all three viruses are stable in extracellular conditions and retain infectivity for a week in non-cellular media, which has public health and biosafety implications. The study of this understudied group of viruses addresses a need for basic characterization of viruses that have not yet reached epidemic transmission intensity, but that have the potential due to their infectivity to both human and animal hosts. These results lay the groundwork for future studies of these neglected viruses of potential public and One Health importance.

scholarly journals Cyclooxygenases in Rat Leydig Cells: Effects of Luteinizing Hormone and Aging

Endocrinology ◽  
2007 ◽  
Vol 148 (2) ◽  
pp. 735-742 ◽  
Author(s):  
Haolin Chen ◽  
Lindi Luo ◽  
June Liu ◽  
Barry R. Zirkin
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Close Correlation ◽  
Dibutyryl Camp ◽  
Protein Levels ◽  
Testosterone Production ◽  
Age Related ◽  
The Relationship

Previous studies suggested that increased Leydig cell cyclooxygenase (COX)2 expression may be involved in the reduced testosterone production that characterizes aged Leydig cells. Our objective herein was to further elucidate the relationships among LH stimulation, Leydig cell COX2 and COX1 expression, aging, and testosterone production. Incubation of Leydig cells from young or aged rats with LH or dibutyryl cAMP resulted in increases in both intracellular COX2 protein expression and testosterone production. COX1 expression did not respond to LH or dibutyryl cAMP. Incubation of adult cells with a protein kinase A inhibitor suppressed the stimulatory effects of LH on COX2 and testosterone production. Short-term incubation of Leydig cells with TGF-α or IL-1β also increased COX2 protein levels; IGF-I had no effect. In vivo, LH also was found to stimulate both COX2 and testosterone, but not COX1. As reported previously, COX2 expression was greater in old than in young cells, and old Leydig cells responded to inhibition of COX2 in vitro with increased testosterone production. However, the effects of the COX2 inhibitors were not restricted to old cells; young Leydig cells also responded to COX2 inhibition with increased testosterone production. This and the observation that the incubation of young or old cells with LH resulted in increased COX2 and testosterone production in both cases suggests that the relationship between COX2 and testosterone production is not unique to aged Leydig cells. Moreover, the close correlation between increases in COX2 and testosterone in LH-stimulated young and aged Leydig cells is difficult to reconcile with the contention that the increased expression of COX2 in aged cells is responsible for age-related suppression of Leydig cell testosterone production.

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