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

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.

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Safety and efficacy of repeated crosslinking assisted by transepithelial double-cycle iontophoresis in keratoconus progression after primary corneal crosslinking

Eye ◽

10.1038/s41433-020-01365-1 ◽

2021 ◽

Author(s):

Huping Wu ◽

Lan Li ◽

Shunrong Luo ◽

Xie Fang ◽

Xumin Shang ◽

...

Keyword(s):

Visual Acuity ◽

Corneal Thickness ◽

Good Alternative ◽

Persistent Epithelial Defect ◽

Safety And Efficacy ◽

Corneal Epithelial ◽

Epithelial Damage ◽

Corneal Confocal Microscopy

Abstract Objectives To evaluate the safety and efficacy of repeated corneal collagen crosslinking assisted by transepithelial double-cycle iontophoresis (DI-CXL) in the management of keratoconus progression after primary CXL. Methods A retrospective analysis was conducted in the patients who underwent repeated CXL between 2016 and 2018. These patients were treated with DI-CXL if keratoconus progression was confirmed after primary CXL. Scoring of ocular pain and corneal epithelial damage, visual acuity, corneal tomography, in vivo corneal confocal microscopy (IVCM) was performed before and at 3, 6, 12, and 24 months after DI-CXL. Results Overall, 21 eyes of 12 patients (mean age 17.3 ± 1.9 years) were included in this study. Before DI-CXL, an average increase of 4.26 D in Kmax was detected in these patients with a mean follow-up interval of (23.0 ± 13.7) months. After DI-CXL, corneal epithelial damage rapidly recovered within days. Visual acuity remained unchanged with follow-up of 24 months. When compared to baseline, significant decreases were observed in Kmax (at 3 months) and K2 (at 3 and 6 months) after DI-CXL. Corneal thickness of thinnest point significantly decreased at 3 months postoperatively. When compared to baseline, no significant differences were found in any of the refractive or tomographic parameters at 12 and 24 months. IVCM revealed trabecular patterned hyperdense tissues after DI-CXL in the anterior stroma at the depth of 200 μm or more. No corneal infiltration or persistent epithelial defect was recorded after DI-CXL. Conclusion DI-CXL is safe and effective as a good alternative in stabilizing keratoconus progression after primary CXL.

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

Cancers ◽

10.3390/cancers13051051 ◽

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.

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Ecallantide Antibodies: Clinical Safety and Efficacy Evaluation in Treatment of Acute HAE Attacks

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2010.12.1058 ◽

2011 ◽

Vol 127 (2) ◽

pp. AB266-AB266

Author(s):

H.H. Li ◽

P.T. Horn ◽

W.T. Pullman

Keyword(s):

Efficacy Evaluation ◽

Clinical Safety ◽

Safety And Efficacy

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The Safety and Efficacy Evaluation of Dexmedetomidine for Procedural Sedation and Postoperative Behaviors in Pediatric Populations: A Systematic Review and Meta-analysis

Annals of Pharmacotherapy ◽

10.1177/10600280211009845 ◽

2021 ◽

pp. 106002802110098

Author(s):

Linguang Gan ◽

Xiaohong Zhao ◽

Xiangjian Chen

Keyword(s):

Pediatric Population ◽

Meta Analysis ◽

Procedural Sedation ◽

Cochrane Library ◽

Control Group ◽

High Dose ◽

Efficacy Evaluation ◽

Safety And Efficacy ◽

Ovid Medline ◽

Pediatric Populations

Background: This study systematically evaluated the safety and efficacy of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population as well as whether the results met the information required to draw conclusions. Objective: To evaluate the safety and efficacy evaluation of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population. Methods: PubMed, Cochrane library, Web of Science and Ovid MEDLINE were searched to obtain randomized controlled trials (RCTs) comparing dexmedetomidine with control medicine and comparing different doses of dexmedetomidine. Results: There were a total of 16 RCTs for a total of 3240 patients. Dexmedetomidine slowed down the heart rate (HR; mean difference: −13.27; 95% CI: −16.41 to 10.14; P < 0.001) and reduced postoperative delirium (risk ratio [RR]: 0.31; 95% CI: 0.20-0.50; P < 0.001), the number of pain patients (RR: 0.48; 95% CI: 0.30-0.75; P = 0.002), and desaturation (RR: 0.34; 95% CI: 0.13-0.89; P = 0.03) compared with the control group. The limitation was that it was difficult to determine the range of low- and high-dose dexmedetomidine. Conclusion and Relevance: Dexmedetomidine slowed down intraoperative HR within the normal range, which might reduce myocardial oxygen consumption. It reduced postoperative pain and postoperative complications: delirium and desaturation. Dexmedetomidine showed no dose-dependent increase in the procedural sedation time of pediatric patients. Clinically, dexmedetomidine can improve pediatric procedural sedation and postoperative behavior, and it can be considered as a related medicine for safety in pediatric surgery.

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Serological biomarkers of zearalenone exposure in beef heifers receiving anti-mycotoxin additive

World Mycotoxin Journal ◽

10.3920/wmj2019.2548 ◽

2020 ◽

pp. 1-10

Author(s):

C. Tonini ◽

M.S. Oliveira ◽

E.B. Parmeggiani ◽

D.A.F. Sturza ◽

A.O. Mallmann ◽

...

Keyword(s):

Limit Of Detection ◽

Biological Fluids ◽

Basal Diet ◽

Beef Heifers ◽

Efficacy Evaluation ◽

Limit Of Quantification ◽

In Vivo Measurement ◽

Significant Difference ◽

Serological Biomarkers

The inclusion of anti-mycotoxin additives (AMA) in the diet of production animals has been widely used to avoid mycotoxin exposure. In order to confirm the efficacy of such products in vivo, measurement of mycotoxins and/or their metabolites in biological fluids is preconized. This study aimed at determining the serological biomarkers of zearalenone (ZEN), α-zearalenol, β-zearalenol, α-zearalanol, β-zearalanol (β-ZAL) and zearalanone, to evaluate the efficacy of an AMA in beef heifers. The trial lasted 37 days: 11 days of adaptation, 21 days of actual experiment, and 5 days of regression. Twenty-four heifers were randomly assigned to receive one of the following treatments (n=6/group): (T1) basal diet (control); (T2) basal diet + 5 mg/kg of ZEN; (T3) basal diet + 5 mg/kg of ZEN + 2.5 kg/t of AMA; and (T4) basal diet + 5 mg/kg of ZEN + 5.0 kg/t of AMA. Blood sampling was performed on different days after the diet was given. The samples were centrifuged to obtain the blood serum, and then analysed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). β-ZAL was detected above the limit of quantification both in the unconjugated (>0.60 ng/ml) and conjugated (>0.90 ng/ml) forms. The remaining metabolites presented concentrations under the limit of detection. In the efficacy evaluation of the AMA, there was no significant difference (P>0.05) between the treatments with and without additive at the tested levels of inclusion. Thus, β-ZAL may be employed as a biomarker of ZEN exposure via diet to evaluate the efficacy of an AMA through serological parameters. The technique applied in this study proved to be an adequate alternative for in vivo confirmation of the efficacy of products in adsorbing the toxin.

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Safety and efficacy of a bacteriophage cocktail in an in vivo model of Pseudomonas aeruginosa sinusitis

Translational Research ◽

10.1016/j.trsl.2018.12.002 ◽

2019 ◽

Vol 206 ◽

pp. 41-56 ◽

Cited By ~ 7

Author(s):

Stephanie A. Fong ◽

Amanda J. Drilling ◽

Mian Li Ooi ◽

Sathish Paramasivan ◽

John W. Finnie ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

In Vivo Model ◽

Safety And Efficacy

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Preclinical Pharmacology of CW002

Anesthesiology ◽

10.1097/aln.0000000000001254 ◽

2016 ◽

Vol 125 (4) ◽

pp. 732-743 ◽

Cited By ~ 6

Author(s):

Hiroshi Sunaga ◽

John J. Savarese ◽

Jeff D. McGilvra ◽

Paul M. Heerdt ◽

Matthew R. Belmont ◽

...

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Safety And Efficacy ◽

Circulatory Effects ◽

Autonomic Changes ◽

Train Of Four

Abstract Background CW002, a novel nondepolarizing neuromuscular blocking agent of intermediate duration, is degraded in vitro by l-cysteine; CW002-induced neuromuscular blockade (NMB) is antagonized in vivo by exogenous l-cysteine.1 Further, Institutional Animal Care and Use Committee–approved studies of safety and efficacy in eight anesthetized monkeys and six cats are described. Methods Mean arterial pressure, heart rate, twitch, and train-of-four were recorded; estimated dose producing 95% twitch inhibition (ED95) for NMB and twitch recovery intervals from 5 to 95% of baseline were derived. Antagonism of 99 to 100% block in monkeys by l-cysteine (50 mg/kg) was tested after bolus doses of approximately 3.75 to 20 × ED95 and after infusions. Vagal and sympathetic autonomic responses were recorded in cats. Dose ratios for [circulatory (ED20) or autonomic (ED50) changes/ED95 (NMB)] were calculated. Results ED95s of CW002 in monkeys and cats were 0.040 and 0.035 mg/kg; l-cysteine readily antagonized block in monkeys: 5 to 95% twitch recovery intervals were shortened to 1.8 to 3.6 min after 3.75 to 10 × ED95 or infusions versus 11.5 to 13.5 min during spontaneous recovery. ED for 20% decrease of mean arterial pressure (n = 27) was 1.06 mg/kg in monkeys; ED for 20% increase of HR (n = 27) was 2.16 mg/kg. ED50s for vagal and sympathetic inhibition in cats were 0.59 and >>0.80 mg/kg (n = 14 and 15). Dose ratios for [circulatory or autonomic changes/ED95 (NMB)] were all more than 15 × ED95. Conclusions The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by l-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.

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