Effect on radiolabelled-monoamine uptake in vitro of plasma taken from healthy volunteers administered the antidepressant sibutramine HCl

1990 ◽  
Vol 100 (3) ◽  
pp. 345-349 ◽  
Author(s):  
Graham P. Luscombe ◽  
Nigel A. Slater ◽  
Michael B. Lyons ◽  
Ronan D. Wynne ◽  
Monte L. Scheinbaum ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Monoamine Uptake ◽  
Sibutramine Hcl

scholarly journals In Vitro Effects of Sulforaphane on Interferon-Driven Inflammation and Exploratory Evaluation in Two Healthy Volunteers

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3602
Author(s):  
Elena Genova ◽  
Maura Apollonio ◽  
Giuliana Decorti ◽  
Alessandra Tesser ◽  
Alberto Tommasini ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Supportive Therapy ◽  
P Value ◽  
Type I ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Immune System Activation ◽  
In Vitro Effects

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.

scholarly journals Cystic Fibrosis Sputum Impairs the Ability of Neutrophils to Kill Staphylococcus aureus

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 703
Author(s):  
Kayla Fantone ◽  
Samantha L. Tucker ◽  
Arthur Miller ◽  
Ruchi Yadav ◽  
Eryn E. Bernardy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Healthy Volunteers ◽  
Airway Disease ◽  
Neutrophil Extracellular Trap ◽  
Lung Function Decline ◽  
Bacterial Killing ◽  
Cystic Fibrosis Sputum ◽  
Microbial Infections

Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. Staphylococcus aureus (S. aureus) is a major lung pathogen in CF that persists despite the presence of PMNs and has been associated with CF lung function decline. While PMNs represent the main mechanism of the immune system to kill S. aureus, it remains largely unknown why PMNs fail to eliminate S. aureus in CF. The goal of this study was to observe how the CF airway environment affects S. aureus killing by PMNs. PMNs were isolated from the blood of healthy volunteers and CF patients. Clinical isolates of S. aureus were obtained from the airways of CF patients. The results show that PMNs from healthy volunteers were able to kill all CF isolates and laboratory strains of S. aureus tested in vitro. The extent of killing varied among strains. When PMNs were pretreated with supernatants of CF sputum, S. aureus killing was significantly inhibited suggesting that the CF airway environment compromises PMN antibacterial functions. CF blood PMNs were capable of killing S. aureus. Although bacterial killing was inhibited with CF sputum, PMN binding and phagocytosis of S. aureus was not diminished. The S. aureus-induced respiratory burst and neutrophil extracellular trap release from PMNs also remained uninhibited by CF sputum. In summary, our data demonstrate that the CF airway environment limits killing of S. aureus by PMNs and provides a new in vitro experimental model to study this phenomenon and its mechanism.

scholarly journals Concurrent Upregulation of Urokinase Plasminogen Activator Receptor and CD11b during Tuberculosis and Experimental Endotoxemia

2001 ◽  
Vol 69 (8) ◽  
pp. 5182-5185 ◽  
Author(s):  
Nicole P. Juffermans ◽  
Pascale E. P. Dekkers ◽  
Annelies Verbon ◽  
Peter Speelman ◽  
Sander J. H. van Deventer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Healthy Volunteers ◽  
Plasminogen Activator ◽  
Urokinase Plasminogen Activator ◽  
Urokinase Receptor ◽  
Urokinase Plasminogen Activator Receptor ◽  
Cd11b Expression ◽  
Experimental Endotoxemia ◽  
Plasminogen Activator Receptor

ABSTRACT Patients with tuberculosis had higher expression of monocyte urokinase receptor (uPAR) and CD11b than controls. In vitro, lipoarabinomannan and lipopolysaccharide (LPS) from Escherichia coli shared the ability to enhance uPAR and CD11b expression on monocytes and granulocytes. In healthy volunteers, LPS induced increases in monocyte and granulocyte uPAR and CD11b.

scholarly journals Dose-response effects of omega-3 on platelet aggregation: an observational study

2018 ◽  
Vol 46 (12) ◽  
pp. 5074-5082 ◽  
Author(s):  
Thomas Kander ◽  
Erik Lindblom ◽  
Ulf Schött
Keyword(s):  
Fatty Acids ◽  
Platelet Aggregation ◽  
Healthy Volunteers ◽  
Dose Response ◽  
High Dose ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Positive Health ◽  
Inhibiting Effect

Objective This study aimed to evaluate the dose-response effects of supplemental omega-3 fatty acids on platelet function in healthy volunteers. Methods Twelve healthy volunteers ingested a normal supplemental dose of 1260 mg omega-3 fatty acids daily for 5 days, followed by a high dose of 2520 mg daily for another 5 days. Multiple electrode aggregometry (MEA) with four different agonists was used to measure platelet aggregation before and after the normal- and high-dose regimes. In vitro spiking using physiological doses of omega-3 fatty acids was also performed to determine whether MEA is capable of detecting a platelet-inhibiting effect due to omega-3 fatty acids. Results There were no differences in platelet aggregation measured by the MEA assay in healthy volunteers after intake of either the normal or high dose of omega-3 fatty acids. In the in vitro experiment, a platelet-inhibiting effect of omega-3 fatty acids was shown by an arachidonic acid agonist in MEA . Conclusions Supplemental omega-3 fatty acids do not evoke their positive health effects through inhibition of platelet aggregation measurable with MEA.

scholarly journals Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Vanessa Araujo Gomes Santaterra ◽  
Maiara Marx Luz Fiusa ◽  
Bidossessi Wilfried Hounkpe ◽  
Francine Chenou ◽  
Wouitchekpo Vincent Tonasse ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Healthy Volunteers ◽  
Sickle Cell ◽  
Endothelial Barrier ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Experimental Conditions ◽  
Cell Monolayers ◽  
Junction Protein

Free extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to reach inflamed tissues, non-localized/deregulated disruption of the EB can lead to widespread microvascular hyperpermeability and secondary tissue damage. In mouse models of sickle cell disease (SCD), EB disruption has been associated with the development of a form of acute lung injury that closely resembles acute chest syndrome (ACS), and that can be elicited by acute heme infusion. Here we explored the effect of heme on EB integrity using human endothelial cell monolayers, in experimental conditions that include elements that more closely resemble in vivo conditions. EB integrity was assessed by electric cell-substrate impedance sensing in the presence of varying concentrations of heme and sera from SCD patients or healthy volunteers. Heme caused a dose-dependent decrease of the electrical resistance of cell monolayers, consistent with EB disruption, which was confirmed by staining of junction protein VE-cadherin. In addition, sera from SCD patients, but not from healthy volunteers, were also capable to induce EB disruption. Interestingly, these effects were not associated with total heme levels in serum. However, when heme was added to sera from SCD patients, but not from healthy volunteers, EB disruption could be elicited, and this effect was associated with hemopexin serum levels. Together our in vitro studies provide additional support to the concept of heme as a DAMP in hemolytic conditions.

scholarly journals The effect of Kefir on The Immune Response of Healthy Volunteers In Vitro

2017 ◽  
Vol 3 (2) ◽  
pp. 28
Author(s):  
Desie Dwi Wisudanti
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Fermented Milk ◽  
Bioactive Components ◽  
Ifn Γ

Kefir is a functional foodstuff of probiotics, made from fermented milk with kefir grains containing various types of beneficial bacteria and yeast. There have been many studies on the effects of oral kefir on the immune system, but few studies have shown the effect of bioactive components from kefir (peptides and exopolysaccharides/ kefiran), on immune responses. The purpose of this study was to prove the effect of kefir supernatant from milk goat on healthy immune volunteer response in vitro. The study was conducted on 15 healthy volunteers, then isolated PBMC from whole blood, then divided into 5 groups (K-, P1, P2, P3 and P4) before culture was done for 4 days. The harvested cells from culture were examined for the percentage of CD4+ T cells, CD8+ T cells, IFN-γ, IL-4 using flowsitometry and IL-2 levels, IL-10 using the ELISA method. The results obtained that kefir do not affect the percentage of CD4+ T cells and CD8+ T cells. The higher the concentration of kefir given, the higher levels of secreted IFN- γ and IL-4, but a decrease in IL-2 levels. Significant enhancement occurred at levels of IL-10 culture PBMC given kefir with various concentrations (p <0.01), especially at concentrations of 1%. These results also show the important effects of kefir bioactive components on immune responses. The conclusion of this study is that kefir can improve the immune response, through stimulation of IL-10 secretion in vitro.

scholarly journals Effect of the French Oak Wood Extract Robuvit on Markers of Oxidative Stress and Activity of Antioxidant Enzymes in Healthy Volunteers: A Pilot Study

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Martina Horvathova ◽  
Zuzana Orszaghova ◽  
Lucia Laubertova ◽  
Magdalena Vavakova ◽  
Peter Sabaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Antioxidant Capacity ◽  
Healthy Volunteers ◽  
Total Antioxidant Capacity ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Total Antioxidant ◽  
Trolox Equivalent ◽  
Markers Of Oxidative Stress

We examinedin vitroantioxidant capacity of polyphenolic extract obtained from the wood of oakQuercus robur(QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found anin vitroantioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasmain vivo.

Immunoregulatory effects of paroxetine in healthy volunteers: An in vitro investigation

2021 ◽  
Vol 10 (1) ◽  
pp. 118
Author(s):  
Alireza Karimollah ◽  
Anahid Hemmatpur ◽  
Maryam Asadi ◽  
MohammadHossein Hadinedoushan
Keyword(s):  
Healthy Volunteers ◽  
In Vitro Investigation

scholarly journals Hyperbaric hyperoxia exposure in suppressing human immunodeficiencyvirus replication: An experimental in vitro in peripheral mononuclear blood cells culture

2020 ◽  
Author(s):  
Retno Budiarti ◽  
Siti Qamariyah Khairunisa ◽  
Nasronudin ◽  
Kuntaman ◽  
Guritno
Keyword(s):  
Hiv Infection ◽  
Healthy Volunteers ◽  
Hyperbaric Oxygen ◽  
Experimental Unit ◽  
Control Group ◽  
P24 Antigen ◽  
Hyperbaric Exposure ◽  
Interferon Α2 ◽  
Hiv 1

Cellular immune has an important role in response HIV infection, which is attack the infected cells to activate signaling molecule. Hyperbaric Oxygen (HBO) worked as complementary treatment for HIV infection. The production of ROS and RNS molecules during hyperbaric exposure can affect gene expression which contributes to cellular adaptative response. This study was conducted to explore the mechanisms of cellular adaptive response to HIV infection during hyperbaric exposure. This study was carried on in vitro using healthy volunteers’ PBMCs (Peripheral Blood Mononuclear Cells) cultures infected with HIV-1. The study was conducted as a post- test only group design. The experimental unit was PBMC from venous blood of healthy volunteers which were cultured in vitro and infected by co-culturing with HIV-1 in MT4 cell line. The experimental unit consist of treatment and control group. Each group examined the expression of transcription factor NFκB, Interferon α, reverse transcriptase inhibitors (p21), and the amount of HIV-1 p24 antigen. There were increasingly significant differences in the expression of the trancription factor of NFκB, p21, and HIV-1 p24 antigen,as well as mRNA transcription of interferon α2 between treatment and controlgroup. By decreasing p24 antigen showed that HBO exposure was able to suppress HIV-1 replication. The exposure to hyperbaric oxygen at the pressure of 2.4 ATAand 98% oxygen wasable to produce ROS and RNS molecules, which play a role in cellular adaptive responses through increasing the expression of nfĸb, p21 and mRNA of interferon α2 plays a role in inhibition mechanism of HIV-1 replication in cells.

scholarly journals Use of Preclinical Data for Selection of a Phase II/III Dose for Evernimicin and Identification of a Preclinical MIC Breakpoint

2001 ◽  
Vol 45 (1) ◽  
pp. 13-22 ◽  
Author(s):  
G. L. Drusano ◽  
S. L. Preston ◽  
C. Hardalo ◽  
R. Hare ◽  
C. Banfield ◽  
...  
Keyword(s):  
Protein Binding ◽  
Healthy Volunteers ◽  
Phase Ii ◽  
Drug Exposure ◽  
Clinical Isolates ◽  
Model Parameters ◽  
Test Drug ◽  
Dose Selection ◽  
Preclinical Data

ABSTRACT One of the most challenging issues in the design of phase II/III clinical trials of antimicrobial agents is dose selection. The choice is often based on preclinical data from pharmacokinetic (PK) studies with animals and healthy volunteers but is rarely linked directly to the target organisms except by the MIC, an in vitro measure of antimicrobial activity with many limitations. It is the thesis of this paper that rational dose-selection decisions can be made on the basis of the pharmacodynamics (PDs) of the test agent predicted by a mathematical model which uses four data sets: (i) the distribution of MICs for clinical isolates, (ii) the distribution of the values of the PK parameters for the test drug in the population, (iii) the PD target(s) developed from animal models of infection, and (iv) the protein binding characteristics of the test drug. In performing this study with the new anti-infective agent evernimicin, we collected a large number (n = 4,543) of recent clinical isolates of gram-positive pathogens (Streptococcus pneumoniae,Enterococcus faecalis and Enterococcus faecium, and Staphylococcus aureus) and determined the MICs using E-test methods (AB Biodisk, Stockholm, Sweden) for susceptibility to evernimicin. Population PK data were collected from healthy volunteers (n = 40) and patients with hypoalbuminemia (n = 12), and the data were analyzed by using NPEM III. PD targets were developed with a neutropenic murine thigh infection model with three target pathogens: S. pneumoniae (n = 5), E. faecalis(n = 2), and S. aureus (n= 4). Drug exposure or the ratio of the area under the concentration-time curve/MIC (AUC/MIC) was found to be the best predictor of microbiological efficacy. There were three possible microbiological results: stasis of the initial inoculum at 24 h (107 CFU), log killing (pathogen dependent, ranging from 1 to 3 log10), or 90% maximal killing effect (90%E max). The levels of protein binding in humans and mice were similar. The PK and PD of 6 and 9 mg of evernimicin per kg of body weight were compared; the population values for the model parameters and population covariance matrix were used to generate five Monte Carlo simulations with 200 subjects each. The fractional probability of attaining the three PD targets was calculated for each dose and for each of the three pathogens. All differences in the fractional probability of attaining the target AUC/MIC in this PD model were significant. For S. pneumoniae, the probability of attaining all three PD targets was high for both doses. For S. aureus and enterococci, there were increasing differences between the 6- and 9-mg/kg evernimicin doses for reaching the 2 log killing (S. aureus), 1 log killing (enterococci), or 90%E max AUC/MIC targets. This same approach may also be used to set preliminary in vitro MIC breakpoints.

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