scholarly journals Respirable aerosol exposures of nicotine dry powder formulations to in vitro, ex vivo, and in vivo pre-clinical models demonstrate consistency of pharmacokinetic profiles

2019 ◽  
Vol 31 (6) ◽  
pp. 248-257 ◽  
Author(s):  
Davide Sciuscio ◽  
Julia Hoeng ◽  
Manuel C. Peitsch ◽  
Patrick Vanscheeuwijck
Keyword(s):  
Ex Vivo ◽  
Dry Powder ◽  
Pharmacokinetic Profiles ◽  
Clinical Models ◽  
Dry Powder Formulations

scholarly journals Complementarity of clinical trials, model systems, and metabolomic workflow to unravel the healthy effects of foods: BEBESANO vs MODELSANO: A case study

2021 ◽  
Vol 2 (3) ◽  
Author(s):  
Vicente Agulló ◽  
◽  
Raúl Domínguez-Perles ◽  
Cristina García-Viguera ◽  
◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Ex Vivo ◽  
In Vitro Models ◽  
Experimental Models ◽  
Model Systems ◽  
Food Science ◽  
Clinical Models ◽  
Safe Condition

Nowadays, the health benefits associated with the consumption of plant-based food constitute a hot topic. To further demonstrate such benefits, related to antioxidant, anti-microbial, and anti-inflammatory activities, as well as the reduction of the risk of several pathophysiological conditions, the study of bioaccessibility and bioavailability of specific food’s constituents, which require interdisciplinary networks, is essential. In this frame, although different experimental models can be developed, the workflow described in the present work support the application of intervention trials in humans as the first option to study the truly effects on health of foods (e.g., plant-based foods), due to the safe condition of them and the realistic approach of this kind of studies, later explored in depth resorting to in vitro, ex vivo, and pre-clinical models, as the most appropriate workflow to get reliable results in the field of Food Science and Nutrition, regarding mechanisms of actions and molecular interactions. Thereby, the work described in the present review is developed in the frame of two consecutive and interconnected projects: BEBESANO (concluded) and MODELSANO (in process) that demonstrate the efficiency of the workflow proposed for research in the Food Science and Nutrition fields. In this regard, in the frame of BEBESANO, acute and longitudinal interventions in humans, devoted to set-up bioavailability of bioactive compounds, followed by functional studies in vivo upon pre-clinical models were conducted to unravel the relationship between bioactive compounds in plant-based beverages and the use of sweetener replacer. Now, most relevant findings from BEBESANO are being further explored in the newly granted project MODELSANO, which is aimed to uncover gaps of knowledge about the mechanisms behind the descriptive results obtained in BEBESANO, using more restrictive in vitro models (allowing the development of studies on the cellular and molecular pathways involved), and integrative cutting edge mathematical modelling alternatives. Keywords: In vivo; in vitro; bioavailability; bioaccessibility; bioactivity; health-promoting foods; metabolomic; mechanistic studies

scholarly journals Original article. Pharmacodynamics of dry powder formulations of salbutamol for delivery by inhalation

2011 ◽  
Vol 5 (4) ◽  
Author(s):  
Nichakorn Sukasame ◽  
Narumon Nimnoo ◽  
Tan Suwandecha ◽  
Teerapol Srichana
Keyword(s):  
High Performance ◽  
Forced Expiratory Volume ◽  
Dry Powder ◽  
Andersen Cascade Impactor ◽  
Chromatography Method ◽  
Liquid Chromatography Method ◽  
Dry Powder Formulations ◽  
Powder Aerosols

AbstractBackground: Salbutamol is a βObjective: Evaluate the relationship of in vitro particle size characteristics and pharmacodynamics of formulations of inhaled salbutamol dry powder.Methods: Three formulations contained micronized salbutamol and a lactose carrier with different size ranges (40- 80, 20-40, and 10-20 μm for formulations 1, 2, and 3, respectively). Following formulation of the drug, resultant powders were characterized using scanning electron microscopy and the aerosolization performance determined using an Andersen Cascade Impactor analysis. A high-performance liquid chromatography method was used for measuring the salbutamol drug content. The in vivo pharmacodynamics of the formulations was monitored in 12 healthy and 12 asthmatic volunteers.Results: The percentage of the fine particle fractions (FPF) for formulations 1, 2, and 3 were 24.87±0.52%, 33.82±3.80%, and 41.50±2.86%, respectively. The mass median aerodynamic diameters (MMAD) were around 3 μm for all formulations. The pharmacodynamic parameters, forced vital capacity (FVC), forced expiratory volume in one second (FEVConclusion: The formulations of salbutamol dry powder aerosols with a fine lactose carrier produced a high deposition in the lower regions of the respiratory tract. Although the FEF

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Organische Nitrate und Thrombozytenfunktion

1988 ◽  
Vol 08 (02) ◽  
pp. 90-99 ◽  
Author(s):  
H. Schröder ◽  
K. Schrör
Keyword(s):  
Endothelial Cell ◽  
Angina Pectoris ◽  
Ex Vivo

ZusammenfassungOrganische Nitrate unterschiedlicher chemischer Struktur sowie Nitroprussidnatrium und Molsidomin (bzw. ihre biologisch aktiven Metaboliten) können die (primäre) Aggregation und Sekretion von Humanthrombozyten in vitro und ex vivo hemmen. Eine solche Wirkung wird für Molsidomin (SIN-1) und Nitroprussidnatrium in vitro in Konzentrationen beobachtet, die in der gleichen Größenordnung liegen wie die vasodilatierenden Effekte der Substanzen. Dagegen sind für eine direkte Antiplättchenwirkung organischer Nitrate (Glyzeryltrinitrat, Isosorbiddinitr at, Isosorbidmononitrate, Teopranitol) in vitro Konzentrationen erforderlich, die ca. 100- bis 1000fach höher sind als die Plasmaspiegel der Substanzen nach therapeutischer Dosierung bzw. die Konzentrationen, die isolierte Gefäßstreifen relaxieren. Als gemeinsamer Wirkungsmechanismus der direkten thrombozy-tenfunktionshemmenden und gefäßerweiternden Wirkung all dieser Substanzen kann heute eine Stickoxid-(NO)-vermittelte Stimulation der cGMP-Bildung angenommen werden, das aus organischen Nitraten als »Pro-drug« entsteht. Die Freisetzung von NO, eines »endothelial cell-derived relaxing factors« (EDRF) aus Nitroprussidnatrium und SIN-1 erfolgt spontan. Dagegen erfordert die Freisetzung von NO aus organischen Nitraten einen enzymatischen Stoffwechselweg, der in isolierten Thrombozyten nicht vorhanden ist. Eine Antiplättchenwirkung organischer Nitrate in vivo bzw. ex vivo wird daher über die Stimulation eines endothelialen, thrombozyteninhibitorischen Faktors erklärt. Hierbei sind Prostazyklin sowie ein bisher unbekannter Endothel-zellfaktor neben einer synergistischen Wirkung organischer Nitrate mit endogenem Prostazyklin in Diskussion. Eine thrombozytenfunktionshemmen-de Wirkung organischer Nitrate könnte in Kombination mit ihren hämody-namischen Effekten auch für die an-tianginöse Wirkung in der Klinik bedeutsam sein, insbesondere zur Verhinderung vasospastischer Zustände bei der instabilen Angina pectoris.

Repurposing N,N-Dimethylacetamide (DMA), a Pharmaceutical Excipient, as a Prototype Novel Anti-inflammatory Agent for the Prevention and/or Treatment of Preterm Birth

2018 ◽  
Vol 24 (9) ◽  
pp. 989-992 ◽  
Author(s):  
Samir Gorasiya ◽  
Juliet Mushi ◽  
Ryan Pekson ◽  
Sabesan Yoganathan ◽  
Sandra E. Reznik
Keyword(s):  
Preterm Birth ◽  
Ex Vivo ◽  
The United States ◽  
Occurrence Rate ◽  
Pharmaceutical Excipient ◽  
Ongoing Work ◽  
Exciting Line ◽  
Pregnant Mice

Background: Preterm birth (PTB), or birth that occurs before 37 weeks of gestation, accounts for the majority of perinatal morbidity and mortality. As of 2016, PTB has an occurrence rate of 9.6% in the United States and accounts for up to 18 percent of births worldwide. Inflammation has been identified as the most common cause of PTB, but effective pharmacotherapy has yet to be developed to prevent inflammation driven PTB. Our group has discovered that N,N-dimethylacetamide (DMA), a readily available solvent commonly used as a pharmaceutical excipient, rescues lipopolysaccharide (LPS)-induced timed pregnant mice from PTB. Methods: We have used in vivo, ex vivo and in vitro approaches to investigate this compound further. Results: Interestingly, we found that DMA suppresses cytokine secretion by inhibiting nuclear factor-kappa B (NF-κB). In ongoing work in this exciting line of investigation, we are currently investigating structural analogs of DMA, some of them novel, to optimize this approach focused on the inflammation associated with PTB. Conclusion: Successful development of pharmacotherapy for the prevention of PTB rests upon the pursuit of multiple strategies to solve this important clinical challenge.

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