The Source Of Thromboxane Formation Associated With Complement-Mediated Pulmonary Leukostasis In Sheep

1981 ◽  
Author(s):  
J W D McDonald ◽  
M Ali ◽  
J D Cooper ◽  
E R Townsend
Keyword(s):  
Pulmonary Artery ◽  
Blood Clotting ◽  
Ex Vivo ◽  
Lung Parenchyma ◽  
Mechanical Obstruction ◽  
Vascular Response ◽  
In Vivo Experiments ◽  
Pulmonary Arterial

The infusion of plasma containing Zymosan-activated complement (ZAC) into sheep produces leukopenia with pulmonary leukostasis and transient pulmonary arterial hypertension (PAH). Previous work has related PAH to elevations of plasma thromboxane B2 (TXB2) rather than to mechanical obstruction by sequestered leukocytes (WBC). We have investigated the source of the TXB2 formation in this model. Incubation of platelet-poor WBC preparations with arachi- donate resulted in negligible TXB2 formation. WBC-poor platelet preparations on the other hand formed significant amounts of TXB2 (approximately 6-18 ng/108 platelets). Incubation of whole sheep blood or plasma with ZAC failed to generate significant amounts of TXB2. Thus, WBC agglutination in vitro did not induce platelet TXB2 formation.Pretreatment of sheep with aspirin (ASA)(10 mg/kg IV) completely blocked TXB2 formation and PAH in response to infusion of plasma containing ZAC. The infusion of 10-50% nonnal platelets into sheep 4 hours after ASA pretreatment failed to restore TXB2 formation and pulmonary vascular response to subsequent challenge with ZAC. TXB2 formation during blood clotting ex vivo was restored by the platelet infusions. These experiments make it appear unlikely that platelets are the source of the TXB2. It is possible that the transfused platelets respond to thrombin but are unable to interact with sequestered leukocytes. Sheep lung and pulmonary artery were incubated in vitro with arachidonate. Lung formed 630 ng TXB2 and 39 ng 6-keto-PGF1α/g of wet tissue. Pulmonary artery formed 9 ng TXB2 and 180 ng 6-keto-PGF1α/g of wet tissue. The relative proportions of TXB2 and 6-keto-PGF1α formed by lung parenchyma but not pulmonary artery resemble the proportions observed in previous in vivo experiments with ZAC. It appears that lung tissue is the most likely source of TXB2 formation causing PAH in response to ZAC-mediated pulmonary leukostasis.

scholarly journals Development of a gel dedicated to gel immersion endoscopy

2021 ◽  
Vol 09 (06) ◽  
pp. E918-E924
Author(s):  
Tomonori Yano ◽  
Atsushi Ohata ◽  
Yuji Hiraki ◽  
Makoto Tanaka ◽  
Satoshi Shinozaki ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Porcine Model ◽  
Ex Vivo ◽  
In Vitro Experiments ◽  
Efficacy And Safety ◽  
Coagulative Necrosis ◽  
Novel Technique ◽  
In Vivo Experiments

Abstract Backgrounds and study aims Gel immersion endoscopy is a novel technique to secure the visual field during endoscopy. The aim of this study was to develop a dedicated gel for this technique. Methods To identify appropriate viscoelasticity and electrical conductivity, various gels were examined. Based on these results, the dedicated gel “OPF-203” was developed. Efficacy and safety of OPF-203 were evaluated in a porcine model. Results  In vitro experiments showed that a viscosity of 230 to 1900 mPa·s, loss tangent (tanδ) ≤ 0.6, and hardness of 240 to 540 N/cm2 were suitable. Ex vivo experiments showed electrical conductivity ≤ 220 μS/cm is appropriate. In vivo experiments using gastrointestinal bleeding showed that OPF-203 provided clear visualization compared to water. After electrocoagulation of gastric mucosa in OPF-203, severe coagulative necrosis was not observed in the muscularis but limited to the mucosa. Conclusions OPF-203 is useful for gel immersion endoscopy.

scholarly journals Entrectinib, a TRK/ROS1 inhibitor with anti-CNS tumor activity: differentiation from other inhibitors in its class due to weak interaction with P-glycoprotein

2020 ◽  
Vol 22 (6) ◽  
pp. 819-829 ◽  
Author(s):  
Holger Fischer ◽  
Mohammed Ullah ◽  
Cecile C de la Cruz ◽  
Thomas Hunsaker ◽  
Claudia Senn ◽  
...  
Keyword(s):  
Steady State ◽  
Lipid Membrane ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Intracranial Tumor ◽  
Brain Penetration ◽  
In Vivo Experiments ◽  
P Glycoprotein

Abstract Background Studies evaluating the CNS penetration of a novel tyrosine kinase inhibitor, entrectinib, proved challenging, particularly due to discrepancies across earlier experiments regarding P-glycoprotein (P-gp) interaction and brain distribution. To address this question, we used a novel “apical efflux ratio” (AP-ER) model to assess P-gp interaction with entrectinib, crizotinib, and larotrectinib, and compared their brain-penetration properties. Methods AP-ER was designed to calculate P-gp interaction with the 3 drugs in vitro using P-gp–overexpressing cells. Brain penetration was studied in rat plasma, brain, and cerebrospinal fluid (CSF) samples after intravenous drug infusion. Unbound brain concentrations were estimated through kinetic lipid membrane binding assays and ex vivo experiments, while the antitumor activity of entrectinib was evaluated in a clinically relevant setting using an intracranial tumor mouse model. Results Entrectinib showed lower AP-ER (1.1–1.15) than crizotinib and larotrectinib (≥2.8). Despite not reaching steady-state brain exposures in rats after 6 hours, entrectinib presented a more favorable CSF-to-unbound concentration in plasma (CSF/Cu,p) ratio (>0.2) than crizotinib and larotrectinib at steady state (both: CSF/Cu,p ~0.03). In vivo experiments validated the AP-ER approach. Entrectinib treatment resulted in strong tumor inhibition and full survival benefit in the intracranial tumor model at clinically relevant systemic exposures. Conclusions Entrectinib, unlike crizotinib and larotrectinib, is a weak P-gp substrate that can sustain CNS exposure based on our novel in vitro and in vivo experiments. This is consistent with the observed preclinical and clinical efficacy of entrectinib in neurotrophic tropomyosin receptor kinase (NTRK) and ROS1 fusion-positive CNS tumors and secondary CNS metastases.

Removal of obturation material in endodontic retreatment: a literature review

RSBO ◽  
2019 ◽  
Vol 16 (2) ◽  
pp. 109
Author(s):  
Carina Do Nascimento Menezes ◽  
Verydianna Frota Carneiro ◽  
Mônica Sampaio do Vale
Keyword(s):  
Literature Review ◽  
Latin American ◽  
Root Canal ◽  
Ex Vivo ◽  
Filling Material ◽  
Advantages And Disadvantages ◽  
In Vivo Experiments ◽  
Automated Method

Introduction: Removal of filling material from the root canal system is required when a previous endodontic treatment fails, what may result in the permanence of an unfavorable periapical condition. The intent is to completely remove the filling material inside of the root canal to achieve sufficient cleaning and shaping for successful retreatment. Objective: The aims of this article were to provide asystematic review of the different techniques of endodontic filling material associated or not with organic solvents and to analyze them critically in terms of advantages and disadvantages of each technique. Literature review: The descriptors used were “guttapercha”, “obturation,” and “retreatment” in the following databases: PubMed, MEDLINE, Latin American and Caribbean Center on Health Sciences Information (Bireme), Latin-American and CaribbeanHealth Sciences (Lilacs), Brazilian Dentistry Bibliography (BBO), and Scientific Electronic Library Online (SciELO). Publications of in vitro/ ex vivo and in vivo experiments without language restriction between the years 2010 and 2018 were selected. Conclusion: None of the techniques were capable of performing complete root canal cleaning, and the manual method was so effective as the automated method, although it requires longer working time. Furthermore, although this review confirmed that the solvent action did not allow a significantimprovement in the removal of the filling material, ultrasoundactivated irrigation proved to be an efficient adjunctive device as it could significantly reduce the volume of intracanal residuals.

BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium

Blood ◽  
2011 ◽  
Vol 118 (18) ◽  
pp. 5040-5049 ◽  
Author(s):  
Thomas Helbing ◽  
René Rothweiler ◽  
Elena Ketterer ◽  
Lena Goetz ◽  
Jennifer Heinke ◽  
...  
Keyword(s):  
Vascular Endothelial Cells ◽  
Ex Vivo ◽  
Leukocyte Adhesion ◽  
Vascular Inflammation ◽  
Bmp Signaling ◽  
In Vivo Models ◽  
In Vivo Experiments ◽  
And Migration

Abstract The endothelium plays a pivotal role in vascular inflammation. Here we study bone morphogenetic protein (BMP) signaling in endothelial inflammation and in particular the role of BMPER, an extracellular BMP modulator that is important in vascular development and angiogenesis. Using the BMP antagonist dorsomorphin or BMP2 as an agonist we show that BMP signaling is essential for the inflammatory response of vascular endothelial cells as demonstrated by intravital microscopy. We found that BMPER is decreased in inflammation similar to vascular protective genes like KLF2 and eNOS. Using in vitro and in vivo models we show that BMPER is down-regulated through the TNFα-NFκB-KLF2 signaling pathway. Functionally, lack of BMPER induced by siRNA or in BMPER+/− mice confers a proinflammatory endothelial phenotype with reduced eNOS levels and enhanced expression of adhesion molecules leading to increased leukocyte adhesion and extravasation in ex vivo and in vivo experiments. Vice versa, addition of BMPER exerts endothelium protective functions and antagonizes TNFα induced inflammation. Mechanistically, we demonstrate that these effects of BMPER are dependent on BMP signaling because of enhanced NFκB activity. In conclusion, the BMP modulator BMPER is a new protective regulator of vascular inflammation that modulates leukocyte adhesion and migration in vitro and in vivo.

Therapeutic potential of stem cells in lung disease: progress and pitfalls

2007 ◽  
Vol 114 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Michael R. Loebinger ◽  
Susana Aguilar ◽  
Sam M. Janes
Keyword(s):  
Stem Cells ◽  
Lung Disease ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Lung Parenchyma ◽  
Treatment Modalities ◽  
In Vivo Experiments ◽  
Wide Range

There has been increasing excitement over the last few years with the suggestion that exogenous stem cells may offer new treatment options for a wide range of diseases. Within respiratory medicine, these cells have been shown to have the ability to differentiate and function as both airway and lung parenchyma epithelial cells in both in vitro and increasingly in vivo experiments. The hypothesis is that these cells may actively seek out damaged tissue to assist in the local repair, and the hope is that their use will open up new cellular and genetic treatment modalities. Such is the promise of these cells that they are being rushed from the benchside to the bedside with the commencement of early clinical trials. However, important questions over their use remain and the field is presently littered with controversy and uncertainty. This review evaluates the progress made and the pitfalls encountered to date, and critically assesses the evidence for the use of stem cells in lung disease.

scholarly journals On the effect of salvarsan on blood clotting. Trost (Arch. f. Derm. u. Syph., 1922, Bd. 139)

2021 ◽  
Vol 19 (1) ◽  
pp. 107-107
Author(s):  
N. Yasnitsky
Keyword(s):  
Blood Clotting ◽  
Arsenic Compounds ◽  
In Vivo Experiments ◽  
Organic Arsenic

In order to find out the effect of organic arsenic compounds in the form of salvarsan and its derivatives on blood clotting the author set a series of in vitro and in vivo experiments by the methods of Brkеrʹa and Schultz'a. These experiments convinced the author that organic arsenic compounds such as salvarsan already in minimal amounts cause in vitro clotting retardation.

scholarly journals Rapid ratiometric biomarker detection with topically applied SERS nanoparticles

TECHNOLOGY ◽  
2014 ◽  
Vol 02 (02) ◽  
pp. 118-132 ◽  
Author(s):  
Yu "Winston" Wang ◽  
Altaz Khan ◽  
Madhura Som ◽  
Danni Wang ◽  
Ye Chen ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Clinical Success ◽  
Simultaneous Detection ◽  
Integration Time ◽  
In Vivo Experiments ◽  
Surface Enhanced Raman ◽  
Detection Probe ◽  
Multiple Cell

Multiplexed surface-enhanced Raman scattering (SERS) nanoparticles (NPs) offer the potential for rapid molecular phenotyping of tissues, thereby enabling accurate disease detection as well as patient stratification to guide personalized therapies or to monitor treatment outcomes. The clinical success of molecular diagnostics based on SERS NPs would be facilitated by the ability to accurately identify tissue biomarkers under time-constrained staining and detection conditions with a portable device. In vitro, ex vivo and in vivo experiments were performed to optimize the technology and protocols for the rapid detection (0.1-s integration time) of multiple cell-surface biomarkers with a miniature fiber-optic spectral-detection probe following a brief (5 min) topical application of SERS NPs on tissues. Furthermore, we demonstrate that the simultaneous detection and ratiometric quantification of targeted and nontargeted NPs allows for an unambiguous assessment of molecular expression that is insensitive to nonspecific variations in NP concentrations.

scholarly journals Antibacterial properties of thioridazine

2019 ◽  
pp. 96-104
Author(s):  
N. Hrynchuk ◽  
N. Vrynchanu
Keyword(s):  
Antibacterial Activity ◽  
Ex Vivo ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Antibiotic Resistant ◽  
In Vivo Experiments ◽  
Antistaphylococcal Activity ◽  
The Impact

The emergence and spread of antibiotic-resistant strains of microorganisms reduces the effectiveness of antibiotic therapy and requires finding solutions to problems, one of which is the study of antimicrobial properties in drugs of various pharmacological groups. The purpose of the work was to summarize the data on the antibacterial activity of thioridazine and its derivatives to determine the feasibility and prospects of creating new antibacterial drugs on their basis. The paper presents literature data on the effects of thioridazine on the causative agent of tuberculosis, antistaphylococcal activity, susceptibility of plasmodium and trypanosoma. The antibacterial activity of the drug was established within in vitro studies with the determination of MIC towards gram-positive and gram-negative microorganisms, ex vivo using macrophage lines, as well as within in vivo experiments on mice. It is established that the neuroleptic thioridazine is characterized by pronounced anti-tuberculosis activity, the mechanism of action is associated with the impact on the cell membrane of M. tuberculosis, inactivation by calmodulin and inhibition of specific NADH-dehydrogenase type II. The literature data indicate that thioridazine is able to increase the activity of isoniazid against the strains of mycobacteria that are susceptible and resistant to its action. It has been established that resistance to thioridazine in antibiotic-resistant M. tuberculosis strains is not formed. The drug is characterized by its ability to inhibit the growth and reproduction of both methicylin-sensitive (MSSA) and methicilin-resistant (MRSA) strains of Staphylococcus aureus, which has been proven within in vitro experiments. The effectiveness of thioridazine has been proven within in vivo experiments in case of skin infection and sepsis caused by S. aureus. Antimicrobial effect of the drug is also observed towards to plasmodium (P. falciparum) and trypanosomes (Trypanosoma spp.). Currently, the synthesis of thioridazine derivatives is carried out to identify compounds with a pronounced antibacterial effect. Some of the first synthesized compounds are not inferior or superior to thioridazine by the inhibitory effect. Thus, these data suggest that drugs of different pharmacological groups, including drugs that affect the nervous system - thioridazine and its derivatives, can be a source of replenishment of the arsenal of antimicrobial drugs to control such threatening infections as tuberculosis and diseases caused by polyresistant strains of microorganisms.

Abstract 582: A Novel Adipocytokine, Omentin, Prevents Monocrotaline-induced Pulmonary Arterial Hypertension In Rats

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
kyosuke kazama ◽  
Muneyoshi Okada ◽  
Hideyuki Yamawaki
Keyword(s):  
Inflammatory Responses ◽  
Ex Vivo ◽  
Negative Relationship ◽  
Weight Ratio ◽  
Vascular Wall ◽  
Structural Remodeling ◽  
Pulmonary Arterial ◽  
Hypertension Development

Background: Omentin is a novel adipocytokine mainly expressed in visceral rather than subcutaneous adipose tissue. Several epidemiological reports demonstrate the negative relationship between serum omentin level and occurrence of obesity, type 2 diabetes and hypertension. Increase of inflammatory responses, contractile reactivity and structural remodeling of vascular wall contributes to hypertension development. Our in vitro and ex vivo studies previously demonstrated that omentin prevented those hypertension-related pathological processes. In addition, our in vivo study demonstrated that intravenously injected omentin acutely inhibited agonists-induced increases of blood pressure in rats. However, the chronic effects of omentin on hypertension development are not determined. In the present study, we tested the hypothesis that chronic omentin treatment may prevent monocrotaline (MCT)-induced pulmonary arterial (PA) hypertension (PAH). Methods and Results: MCT-induced PAH was induced by a single intraperitoneal injection of MCT (60 mg/kg) to rats. Omentin (18 μg/kg/day) was intraperitoneally treated for 14 days. Chronic omentin inhibited MCT-induced increases in PA pressure (n=8-10, p<0.05). Omentin inhibited MCT-induced increases in right ventricular hypertrophy (n=6-8, p<0.01) as well as lung to body weight ratio (n=8, p<0.01). Histologically, omentin inhibited MCT-induced PA hyperplasia (n=8, p<0.01). Omentin prevented the impairment of both endothelium-dependent and-independent relaxations mediated by acetylcholine and sodium nitroprusside, respectively (n=7-13, p<0.01). Conclusion: We for the first time demonstrate that chronic omentin treatment inhibits MCT-induced PAH in rats via preventing endothelial dysfunction and/or vascular structural remodeling.

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