scholarly journals Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.

1996 ◽  
Vol 40 (9) ◽  
pp. 2039-2042 ◽  
Author(s):  
C Wenisch ◽  
B Parschalk ◽  
K Zedtwitz-Liebenstein ◽  
A Weihs ◽  
I el Menyawi ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Ex Vivo ◽  
Reactive Oxygen ◽  
Fluorescein Isothiocyanate ◽  
Neutrophil Granulocytes ◽  
Oxygen Production ◽  
Phagocytic Cells ◽  
Phagocytic Capacity

Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.

scholarly journals 2,4,6-Tribromophenol Disposition and Kinetics in Rodents: Effects of Dose, Route, Sex, and Species

2019 ◽  
Vol 169 (1) ◽  
pp. 167-179 ◽  
Author(s):  
Gabriel A Knudsen ◽  
Andrew W Trexler ◽  
Alicia C Richards ◽  
Samantha M Hall ◽  
Michael F Hughes ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Ex Vivo ◽  
Systemic Exposure ◽  
Compartment Model ◽  
Repeated Administration ◽  
Environmental Matrices ◽  
Rat Skin ◽  
Sd Rats ◽  
Two Compartment Model

Abstract 2,4,6-tribromophenol (TBP, CAS No. 118-79-6) is widely used as a brominated flame retardant and wood antifungal agent. TBP is frequently detected in environmental matrices, biota, and humans. In female SD rats, systemically available TBP (10 µmol/kg, IV) was rapidly excreted primarily via urine, with approximately 61% of the dose recovered after 4 h, and 89%–94% in 24 h; 5% was recovered in feces; and 1%–2% in blood/tissues. TBP administered to female SD rats (0.1–1000 µmol/kg) by gavage was well absorbed, with approximately 25% eliminated via urine after 4 h and approximately 88% after 24 h. Approximately 11% of a single oral dose was recovered in bile. Male SD rats and B6C3F1/J mice of both sexes had similar disposition profiles when administered a single oral dose of TBP (10 µmol/kg). Following administration, fecal recoveries varied only slightly by dose, sex, or species. TBP readily passed unchanged through both human (ex vivo only) and rat skin with between 55% and 85% of a 100 nmol/cm2 passing into or through skin. Concentrations of TBP in blood fit a two-compartment model after IV-dosing and a one-compartment model after oral dosing. Urine contained a mixture of TBP, TBP-glucuronide, and TBP-sulfate. Fecal extracts contained only parent TBP whereas bile contained only TBP-glucuronide. TBP did not appear to bioaccumulate or alter its own metabolism after repeated administration. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23%–27%; 49% of TBP is expected to be dermally bioavailable in humans. From these data, we conclude that humans are likely to have significant systemic exposure when TBP is ingested or dermal exposure occurs.

Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers

AIDS ◽  
2015 ◽  
Vol 29 (16) ◽  
pp. 2149-2154 ◽  
Author(s):  
Josep Coll ◽  
José Moltó ◽  
Jaume Boix ◽  
Elisabet Gómez-Mora ◽  
Laura Else ◽  
...  
Keyword(s):  
Oral Dose ◽  
Hiv Infection ◽  
Single Oral Dose ◽  
Ex Vivo ◽  
Rectal Mucosa ◽  
Human Volunteers ◽  
Hiv 1

Effect of Pentoxifylline In Vitro on Neutrophil Reactive Oxygen Production and Phagocytic Ability Assessed by Flow Cytometry

1997 ◽  
Vol 13 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Christoph Wenisch ◽  
Konstantin Zedtwitz-Liebenstein ◽  
Bernhard Parschalk ◽  
Wolfgang Graninger
Keyword(s):  
Flow Cytometry ◽  
Reactive Oxygen ◽  
Oxygen Production ◽  
Phagocytic Ability

scholarly journals Thalidomide Inhibits Granulocyte Responses in Healthy Humans after Ex Vivo Stimulation with Bacterial Antigens

2001 ◽  
Vol 45 (5) ◽  
pp. 1547-1549 ◽  
Author(s):  
Nicole P. Juffermans ◽  
Annelies Verbon ◽  
Marc J. Schultz ◽  
C. Erik Hack ◽  
Sander J. H. van Deventer ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Ex Vivo ◽  
Lipoteichoic Acid ◽  
Neutrophil Activation ◽  
Activation Marker ◽  
Healthy Humans ◽  
Bacterial Antigens

ABSTRACT Ingestion of thalidomide was associated with a reduction in the upregulation of the granulocyte activation marker CD11b and a reduced capacity to release elastase and lactoferrin after stimulation with lipopolysaccharide or lipoteichoic acid. A single oral dose of thalidomide attenuates neutrophil activation upon ex vivo stimulation with bacterial antigens.

scholarly journals Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes

2019 ◽  
Vol 71 (1) ◽  
pp. 133-144
Author(s):  
Teodora Vidonja-Uzelac ◽  
Nikola Tatalovic ◽  
Milica Mijovic ◽  
Gordana Kozelj ◽  
Aleksandra Nikolic-Kokic ◽  
...  
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Rat Liver ◽  
Ex Vivo ◽  
Redox Homeostasis ◽  
Antioxidant Enzyme Activities ◽  
Glutathione S Transferase ◽  
Cellular Energy ◽  
Species Production

Ibogaine, administered as a single oral dose (1-25 mg/kg body weight), has been used as an addiction-interrupting agent. Its effects persist for up to 72 h. Ex vivo results showed that ibogaine induced cellular energy consumption and restitution, followed by increased reactive oxygen species production and antioxidant activity. Therefore, the aim of this work was to explore the effect of a single oral dose of ibogaine (1 or 20 mg/kg body weight) on antioxidative defenses in rat liver and erythrocytes. Six and 24 h after ibogaine administration, histological examination showed glycogenolytic activity in hepatocytes, which was highest after 24 h in animals that received 20 mg/kg ibogaine. There were no changes in the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in the liver and erythrocytes after ibogaine treatment, regardless of the dose. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls (p<0.01), suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls (p<0.01), suggesting mild oxidative stress. Our results show that ibogaine treatment influenced hepatic redox homeostasis, but not sufficiently to remodel antioxidant enzyme activities at 6 and 24 h post-ibogaine application.

High Throughput Screening, With a Flow Cytometry Automated Platform (Ex vivo Biotech), To Identify Potential Combination Partners, For The JAK 2 Inhibitor Ruxolitinib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2534-2534
Author(s):  
Alicia Arenas ◽  
Pilar Hernandez-Campo ◽  
Daniel Primo ◽  
Santiago Barrio ◽  
Rosa M. Ayala ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Clinical Trials ◽  
Cell Line ◽  
High Throughput Screening ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Fluorescein Isothiocyanate ◽  
Phase I Clinical Trials ◽  
Ex Vivo Model

Abstract Background Identifying the most promising synergistic drugs combinations for a drug is a challenge for researchers. Identification of optimal combinations are key and should be translated in better designed clinical trials with fewer patients and ultimately more effective treatments. Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated improved survival, rapid and durable improvements in splenomegaly, in patients with myelofibrosis (MF), however although improve survival in most of patients it does not change the natural history of the disease. There is however always a drive to improve outcomes and we hypothesize that treatment with a synergistic drug could enhance the activity in MF. Aim To design an ex-vivo model, based on flow cytometry, to identify the most synergistic drugs with Ruxolitinib in cell lines and primary samples from MF patients. Methods We have studied five secondary or primary MF patients (n = 5) and one cell line, BA/F3 transfected with mutated JAK2 V617F (BA/F3 JAK2V617F). We combined Ruxolitinib with a panel of 30 drugs whose mechanism of action is implicated in proliferation, differentiation and survival, cell-cycle inhibition, protein stabilisation, epigenetic, immune response. Briefly, mononuclear cells from peripheral blood, isolated, was cultured in Methocult TM GF_H4535 supplemented with 20 ng/ml interleukin (IL)-3, and 50 ng/ml stem-cell factor (SCF). After 2 weeks incubation, viable cells were plated at 15.000 per well in 96-well plates in increasing concentrations of each drug, alone or in combination with Ruxolitinib, in 8 or 5 point dose response curve. After 72 hr incubation, we performed a multiparametric flow cytometry, using Annexin V-fluorescein isothiocyanate (FITC) and CD13 to monitoring drug sensibility of myeloid lineage, in the ExviTech platform for screening by flow cytometry. Synergism will be evaluated by the Median Effect methods described by T-C Chou and P. Talalay. Regarding the cell line model, it confirms the results obtained in patients samples: Panobinostat was the most potent drugs tested in the assay with an IC50 of 86 nM and the most synergistic drugs with Ruxolitinib was Everolimus (CI = 0.613 when Ruxolitinib and Everolimus were 370 nM and 7.41 μM respectively). Conclusions This Vivia Ex vivo platform is highly efficient to study multiple synergisms of drugs in myeloproliferative diseases. We can test 30 drugs, inhibitors of multiple signaling pathways, epigenetics and immune response, alone or in combination with Ruxolitinib and test its activity and its potential synergy with Ruxolitinib. Based in these results, clinical trials combination Ruxolitinib with BKM120 (ongoing), Everolimus and LDE225 (ongoing) could potentially be explored in phase I clinical trials. Disclosures: Hernandez-Campo: Vivia Biotech: Employment. Primo:Vivia Biotech: Employment. Ballesteros:Vivia Biotech: Equity Ownership. Martínez-López:Vivia Biotech: Honoraria; Novartis: Research Funding.

Failure of Salicylate to Reduce Inhibition of Human Venous Prostacyclin in Synthesis by Conventional Dose Aspirin

1983 ◽  
Vol 49 (01) ◽  
pp. 051-052 ◽  
Author(s):  
S P Hanley ◽  
J Hughes
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Sodium Salicylate ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Conventional Dose ◽  
Dose Aspirin ◽  
Prostacyclin Synthesis

SummaryEx vivo venous prostacyclin synthesis was measured in 24 patients who received no medication, or a single oral dose of aspirin 300 mg, sodium salicylate, 500 mg, or a combination of sodium salicylate 500 mg followed by aspirin 300 mg 1 1/2 or 3 hr later. Aspirin alone substantially reduced PGI2 synthesis but sodium salicylate alone had no effect. Sodium salicylate administration prior to aspirin did not reverse the inhibitory effect of aspirin on PGI2 synthesis.

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