scholarly journals Dual-modal Assessment for in Vivo Investigation of Neurovascular Characteristic of Cerebral Edema Induced by Lipopolysaccharide

2021 ◽  
Author(s):  
Weitao Li ◽  
Yameng Zhang ◽  
Qian Xie ◽  
Yamin Yang ◽  
Liuye Yao ◽  
...  
Keyword(s):  
Cerebral Edema ◽  
Field Potential ◽  
Drug Efficacy ◽  
Technical Solution ◽  
Hemodynamic Parameters ◽  
Efficacy Evaluation ◽  
Important Indicator ◽  
Edema Model ◽  
Joint Method

Abstract The pathological features of cerebral edema are complicated, but usually only intracranial pressure (ICP) is regarded as the most important indicator for monitoring cerebral edema. The research focused on investigating the neurovascular characteristic of the lipopolysaccharide (LPS)-induced cerebral edema model in rats by using simultaneous electrophysical and hemodynamic recording. The results showed that neurophysiology (firing rate (FR), interval histogram index (ISI), and the power spectrum of local field potential (LFPs power)) and hemodynamic response (oxygenated hemoglobin (HbO2), deoxyhemoglobin (HbR) and relative cerebral blood flow (CBF)) were linearly related, and the Pearson’s correlation coefficient was determined by the BBB integrity after LPS injection. Furtherly, the improvement of treatment after two agents were observed successfully through these neurophysiological and hemodynamic parameters. The optical-electrical joint method provided a technical solution for cerebral edema functional monitoring and anti-edema drug efficacy evaluation. Our findings revealed the neurovascular and BBB impact of cerebral edema and improved the limitation of in vivo pathological diagnosis of cerebral edema.

scholarly journals The Importance of Routine Quality Control For Reproducible Pulmonary Measurements By in Vivo Micro-CT

2022 ◽  
Author(s):  
Martina Mambrini ◽  
Laura Mecozzi ◽  
Erica Ferrini ◽  
Ludovica Leo ◽  
Davide Bernardi ◽  
...  
Keyword(s):  
Disease Progression ◽  
Lung Diseases ◽  
Drug Efficacy ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Efficacy Evaluation ◽  
Lung Density ◽  
Before And After ◽  
The Impact

Abstract Micro-Computed Tomography (CT) imaging provides densitometric and functional assessment of lung diseases in animal models, playing a key role either in understanding disease progression or in drug discovery studies.The generation of reliable and reproducible experimental data is strictly dependent on a system’s stability. Quality Controls (QC) are essential to monitor micro-CT performance but, although QC procedures are standardized and routinely employed in clinical practice, detailed guidelines for preclinical imaging are lacking. In this work, we propose a routine QC protocol for in vivo micro-CT, based on three commercial phantoms. To investigate the impact of a detected scanner drift on image post-processing, a retrospective analysis using twenty-two healthy mice was performed and lung density histograms used to compare the Area Under Curve (AUC), the skewness and the kurtosis before and after the drift. As expected, statistically significant differences were found for all the selected parameters [AUC: 532 ± 31 vs. 420 ± 38 (p < 0.001); skewness: 2.3 ± 0.1 vs. 2.5 ± 0.1 (p < 0.001) and kurtosis: 4.2 ± 0.3 vs. 5.1 ± 0.5 (p < 0.001)], confirming the importance of the designed QC procedure to obtain a reliable longitudinal quantification of disease progression and drug efficacy evaluation.

scholarly journals Epidemiology of Sheep Lice and Efficacy Evaluation of 60% Diazinon and 1% Ivermectin against Bovicola ovis in Sayint District, South Wollo, Ethiopia

2020 ◽  
Author(s):  
Simegn Legesse ◽  
Mussie Hailemelekot ◽  
Habtamu Tamrat ◽  
Yeshwas Ferede
Keyword(s):  
Drug Efficacy ◽  
In Vitro Test ◽  
Efficacy Evaluation ◽  
Cross Sectional ◽  
Randomized Design ◽  
Present Study Area ◽  
Multistage Sampling ◽  
Associated Risk Factors

Abstract Background Sheep lice, caused by Bovicola ovis are very common in Ethiopia. It can result decreased production and reproduction, downgrading and rejection of skins in tannery industries. A cross-sectional and experimental study were conducted in Sayint District, South Wollo, Ethiopia which aims to determine the prevalence of sheep lice with the associated risk factors, identify the major sheep lice species and evaluate the efficacy of 60% Diazinon and 1% Ivermectin against Bovicola ovis. Study kebeles and animals were selected using purposive and multistage sampling techniques. Accordingly, a total of 232 sheep were sampled to estimate the prevalence of sheep lice. Fifteen sheep for in-vivo and 80 Bovicola ovis lice for in-vitro test were used for drug efficacy trial, by using completely randomized design. Results The overall prevalence of sheep lice in this study was 48%. Hair length (OR = 2, P = 0.00), body condition (OR = 1.9, P = 0.02), agro ecology (OR = 1.19, P = 0.00) and season (OR = 2, P = 0.01) were significantly (P < 0.05) associated with sheep lice infestation. The dominant sheep lice species in the study area were Bovicola ovis with prevalence of 83% and mixed infestation of 17% Bovicola ovis with Linognatus ovillus. In this study, the efficacy of 60% Diazinon and 1% Ivermectin against Bovicola ovis were 97% and 81%, respectively. Conclusion The overall prevalence of sheep lice infestation in the present study area was higher, in which Bovicola ovis was predominant and resistant against 1% Ivermectin. Therefore, tailor made intervention is required with a view to reducing the prevalence of sheep lice infestation and addressing drug resistance in the study area.

Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Triple Negative ◽  
Growth Factor Receptor ◽  
Engineered Nanoparticles ◽  
Efficacy Evaluation ◽  
Dual Action ◽  
Epidermal Growth ◽  
Laminin 411 ◽  
Immunologic Analysis

Engineered nanoparticles are widely used for delivery of drugs but frequently lack proof of safetyfor cancer patient's treatment. All-in-one covalent nanodrugs of the third generation have beensynthesized based on a poly(β-L-malic acid) (PMLA) platform, targeting human triple-negativebreast cancer (TNBC). They significantly inhibited tumor growth in nude mice by blockingsynthesis of epidermal growth factor receptor, and α4 and β1 chains of laminin-411, the tumorvascular wall protein and angiogenesis marker. PMLA and nanodrug biocompatibility and toxicityat low and high dosages were evaluated in vitro and in vivo. The dual-action nanodrug and singleactionprecursor nanoconjugates were assessed under in vitro conditions and in vivo with multipletreatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in vivo withdifferent drugs included blood hematologic and immunologic analysis after multiple intravenousadministrations. The present study demonstrates that the dual-action nanoconju-gate is highlyeffective in preclinical TNBC treatment without side effects, supported by hematologic andimmunologic assays data. PMLA-based nanodrugs of the Polycefin™ family passed multipletoxicity and efficacy tests in vitro and in vivo on preclinical level and may prove to be optimizedand efficacious for the treatment of cancer patients in the future.

scholarly journals A Novel Infection Protocol in Zebrafish Embryo to Assess Pseudomonas aeruginosa Virulence and Validate Efficacy of a Quorum Sensing Inhibitor In Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 401
Author(s):  
Pauline Nogaret ◽  
Fatima El El Garah ◽  
Anne-Béatrice Blanc-Potard
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Animal Model ◽  
Quorum Sensing ◽  
Drug Testing ◽  
Drug Efficacy ◽  
Embryo Viability ◽  
Immersion Method ◽  
Opportunistic Human Pathogen

The opportunistic human pathogen Pseudomonas aeruginosa is responsible for a variety of acute infections and is a major cause of mortality in chronically infected cystic fibrosis patients. Due to increased resistance to antibiotics, new therapeutic strategies against P. aeruginosa are urgently needed. In this context, we aimed to develop a simple vertebrate animal model to rapidly assess in vivo drug efficacy against P. aeruginosa. Zebrafish are increasingly considered for modeling human infections caused by bacterial pathogens, which are commonly microinjected in embryos. In the present study, we established a novel protocol for zebrafish infection by P. aeruginosa based on bath immersion in 96-well plates of tail-injured embryos. The immersion method, followed by a 48-hour survey of embryo viability, was first validated to assess the virulence of P. aeruginosa wild-type PAO1 and a known attenuated mutant. We then validated its relevance for antipseudomonal drug testing by first using a clinically used antibiotic, ciprofloxacin. Secondly, we used a novel quorum sensing (QS) inhibitory molecule, N-(2-pyrimidyl)butanamide (C11), the activity of which had been validated in vitro but not previously tested in any animal model. A significant protective effect of C11 was observed on infected embryos, supporting the ability of C11 to attenuate in vivo P. aeruginosa pathogenicity. In conclusion, we present here a new and reliable method to compare the virulence of P. aeruginosa strains in vivo and to rapidly assess the efficacy of clinically relevant drugs against P. aeruginosa, including new antivirulence compounds.

scholarly journals A Microfluidic Spheroid Culture Device with a Concentration Gradient Generator for High-Throughput Screening of Drug Efficacy

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3355 ◽  
Author(s):  
Wanyoung Lim ◽  
Sungsu Park
Keyword(s):  
High Throughput ◽  
Concentration Gradient ◽  
High Throughput Screening ◽  
3D Cell Culture ◽  
Drug Efficacy ◽  
Cancer Drug ◽  
Spheroid Culture ◽  
Gradient Generator ◽  
Micro Channels

Three-dimensional (3D) cell culture is considered more clinically relevant in mimicking the structural and physiological conditions of tumors in vivo compared to two-dimensional cell cultures. In recent years, high-throughput screening (HTS) in 3D cell arrays has been extensively used for drug discovery because of its usability and applicability. Herein, we developed a microfluidic spheroid culture device (μFSCD) with a concentration gradient generator (CGG) that enabled cells to form spheroids and grow in the presence of cancer drug gradients. The device is composed of concave microwells with several serpentine micro-channels which generate a concentration gradient. Once the colon cancer cells (HCT116) formed a single spheroid (approximately 120 μm in diameter) in each microwell, spheroids were perfused in the presence of the cancer drug gradient irinotecan for three days. The number of spheroids, roundness, and cell viability, were inversely proportional to the drug concentration. These results suggest that the μFSCD with a CGG has the potential to become an HTS platform for screening the efficacy of cancer drugs.

Safety and efficacy evaluation of the automatic stepwise recruitment manoeuvre in the neonatal population: An in‐vivo interventional study

2021 ◽  
Author(s):  
Clara Serrano Zueras ◽  
Verónica Guilló Moreno ◽  
Martín Santos González ◽  
Francisco Javier Gómez Nieto ◽  
Göran Hedenstierna ◽  
...  
Keyword(s):  
Recruitment Manoeuvre ◽  
Interventional Study ◽  
Efficacy Evaluation ◽  
Safety And Efficacy ◽  
Neonatal Population

scholarly journals In Vivo Biodistribution and Efficacy Evaluation of NeoB, a Radiotracer Targeted to GRPR, in Mice Bearing Gastrointestinal Stromal Tumor

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1051
Author(s):  
Christopher Montemagno ◽  
Florian Raes ◽  
Mitra Ahmadi ◽  
Sandrine Bacot ◽  
Marlène Debiossat ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Tumor Volume ◽  
Tumor Regression ◽  
Efficacy Evaluation ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Target Organs ◽  
G Protein Coupled ◽  
Complete Tumor

NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein–coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice bearing GIST-882 tumors were employed. [177Lu]Lu-NeoB biodistribution was evaluated up to seven days by organ sampling (200 pmol/0.8 MBq, i.v.). For efficacy evaluation, mice received either saline, 400 pmol or 800 pmol of [177Lu]Lu-NeoB (37MBq, 1/w, 3 w, i.v.). SPECT/CT imaging was performed at 24 h, and tumor volume was determined up to 100 days. Elevated and specific [177Lu]Lu-NeoB uptake was found in the GIST tumor, as demonstrated by in vivo competition (19.1 ± 3.9 %ID/g vs. 0.3 ± 0.1 %ID/g at 4h). [177Lu]Lu-NeoB tumor retention (half-life of 40.2 h) resulted in elevated tumor-to-background ratios. Tumor volumes were significantly reduced in both treated groups (p < 0.01), even leading to complete tumor regression at the 400 pmol dose. [177Lu]Lu-NeoB exhibited excellent pharmacokinetics with elevated and prolonged tumor uptake and low uptake in non-target organs such as pancreas. The potential of this new theragnostic agent in different indications, including GIST, is under evaluation in the FIH [177Lu]Lu-NeoB clinical trial.

scholarly journals Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE-Deficient Mice

2008 ◽  
Vol 3 ◽  
pp. BMI.S632 ◽  
Author(s):  
Birong Liao ◽  
Eileen McCall ◽  
Karen Cox ◽  
Chung-Wein Lee ◽  
Shuguang Huang ◽  
...  
Keyword(s):  
Whole Blood ◽  
Plasma Cholesterol ◽  
Drug Effects ◽  
Drug Efficacy ◽  
Vascular Wall ◽  
Atherosclerotic Plaques ◽  
Protein Markers ◽  
Novel Approach ◽  
Coa Reductase

Background Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol. Results ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro-and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1β, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis. Conclusion In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems.

scholarly journals Daily rhythms of both host and parasite affect antimalarial drug efficacy

2021 ◽  
Author(s):  
Alíz T Y Owolabi ◽  
Sarah E Reece ◽  
Petra Schneider
Keyword(s):  
Drug Treatment ◽  
Developmental Stage ◽  
Antimalarial Drug ◽  
Drug Sensitivity ◽  
Drug Efficacy ◽  
Time Of Day ◽  
Parasite Development ◽  
Daily Rhythms ◽  
Parasite Plasmodium

Abstract Background and objectives Circadian rhythms contribute to treatment efficacy in several non-communicable diseases. However, chronotherapy (administering drugs at a particular time-of-day) against infectious diseases has been overlooked. Yet, the daily rhythms of both hosts and disease-causing agents can impact the efficacy of drug treatment. We use the rodent malaria parasite Plasmodium chabaudi, to test if the daily rhythms of hosts, parasites, and their interactions, affect sensitivity to the key antimalarial, artemisinin. Methodology Asexual malaria parasites develop rhythmically in the host’s blood, in a manner timed to coordinate with host daily rhythms. Our experiments coupled or decoupled the timing of parasite and host rhythms, and we administered artemisinin at different times of day to coincide with when parasites were either at an early (ring) or later (trophozoite) developmental stage. We quantified the impacts of parasite developmental stage, and alignment of parasite and host rhythms, on drug sensitivity. Results We find that rings were less sensitive to artemisinin than trophozoites, and this difference was exacerbated when parasite and host rhythms were misaligned, with little direct contribution of host time-of-day on its own. Furthermore, the blood concentration of haem at the point of treatment correlated positively with artemisinin efficacy but only when parasite and host rhythms were aligned. Conclusions and implications Parasite rhythms influence drug sensitivity in vivo. The hitherto unknown modulation by alignment between parasite and host daily rhythms suggests that disrupting the timing of parasite development could be a novel chronotherapeutic approach. Lay Summary We reveal that chronotherapy (providing medicines at a particular time-of-day) could improve treatment for malaria infections. Specifically, parasites’ developmental stage at the time of treatment and the coordination of timing between parasite and host both affect how well antimalarial drug treatment works.

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