scholarly journals Stability and in vivo safety of gold, titanium nitride and parylene C coatings on NdFeB magnets implanted in muscles towards a new generation of myokinetic prosthetic limbs

RSC Advances ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 6766-6775
Author(s):  
Veronica Iacovacci ◽  
Irene Naselli ◽  
Alice Rita Salgarella ◽  
Francesco Clemente ◽  
Leonardo Ricotti ◽  
...  
Keyword(s):  
Corrosion Resistance ◽  
Titanium Nitride ◽  
Rabbit Muscle ◽  
Parylene C ◽  
Ndfeb Magnets ◽  
Prosthetic Limbs ◽  
New Generation

NdFeB magnets implantation in muscles could enable limb prostheses control by means of a myokinetic interface. Parylene C proved as optimal coating for corrosion resistance, in vitro biocompatibility and safe implantability in rabbit muscle.

Flavonoids as P-gp Inhibitors: A Systematic Review of SARs

2019 ◽  
Vol 26 (25) ◽  
pp. 4799-4831 ◽  
Author(s):  
Jiahua Cui ◽  
Xiaoyang Liu ◽  
Larry M.C. Chow
Keyword(s):  
Molecular Mechanisms ◽  
Metastatic Cancer ◽  
Drug Candidates ◽  
Chemical Structures ◽  
Transporter Family ◽  
Promising Area ◽  
New Generation ◽  
Nontoxic Inhibitors

P-glycoprotein, also known as ABCB1 in the ABC transporter family, confers the simultaneous resistance of metastatic cancer cells towards various anticancer drugs with different targets and diverse chemical structures. The exploration of safe and specific inhibitors of this pump has always been the pursuit of scientists for the past four decades. Naturally occurring flavonoids as benzopyrone derivatives were recognized as a class of nontoxic inhibitors of P-gp. The recent advent of synthetic flavonoid dimer FD18, as a potent P-gp modulator in reversing multidrug resistance both in vitro and in vivo, specifically targeted the pseudodimeric structure of the drug transporter and represented a new generation of inhibitors with high transporter binding affinity and low toxicity. This review concerned the recent updates on the structure-activity relationships of flavonoids as P-gp inhibitors, the molecular mechanisms of their action and their ability to overcome P-gp-mediated MDR in preclinical studies. It had crucial implications on the discovery of new drug candidates that modulated the efflux of ABC transporters and also provided some clues for the future development in this promising area.

A Comparative Study of Bioceramics In Vitro and In Vivo

2005 ◽  
Vol 284-286 ◽  
pp. 11-14 ◽  
Author(s):  
Yang Leng ◽  
Ren Long Xin ◽  
Ji Yong Chen
Keyword(s):  
Calcium Phosphates ◽  
Glass Ceramics ◽  
Octacalcium Phosphate ◽  
Rabbit Muscle ◽  
In Vivo Experiments ◽  
Transmission Electron ◽  
Diffraction Patterns ◽  
Dental Applications

Bioactive calcium phosphate (Ca-P) formation in bioceramics surfaces in simulated body fluid (SBF) and in rabbit muscle sites was investigated. The examined bioceamics included most commonly used bioglass®, A-W glass-ceramics and calcium phosphates in orthopedic and dental applications. The Ca-P cyrstal structures were examined with single crystal diffraction patterns in transmission electron microscopy, which reduced possibility of misidentifying Ca-P phases. The experimental results show that capability of Ca-P formation considerably varied among bioceramics, particularly in vivo. Octacalcium phosphate (OCP) was revealed on the all types of bioceramics in vitro and in vivo experiments. This work leads us to rethink how to evaluate bioactivity of bioceramics and other orthopedic materials which exhibit capability of osteoconduction by forming direct bonding with bone.

scholarly journals In vitro and in vivo assessment of biomedical Mg–Ca alloys for bone implant applications

2018 ◽  
Vol 16 (3) ◽  
pp. 126-136 ◽  
Author(s):  
Preeti Makkar ◽  
Swapan Kumar Sarkar ◽  
Andrew R. Padalhin ◽  
Byoung-Gi Moon ◽  
Young Seon Lee ◽  
...  
Keyword(s):  
Corrosion Resistance ◽  
Bone Formation ◽  
Femoral Condyle ◽  
Immersion Test ◽  
Hydrogen Gas ◽  
In Vivo Studies ◽  
Biodegradable Implant ◽  
In Vitro Degradation

Background: Magnesium (Mg)-based alloys are considered to be promising materials for implant application due to their excellent biocompatibility, biodegradability, and mechanical properties close to bone. However, low corrosion resistance and fast degradation are limiting their application. Mg–Ca alloys have huge potential owing to a similar density to bone, good corrosion resistance, and as Mg is essential for Ca incorporation into bone. The objective of the present work is to determine the in vitro degradation and in vivo performance of binary Mg– xCa alloy ( x = 0.5 or 5.0 wt%) to assess its usability for degradable implant applications. Methods: Microstructural evolutions for Mg– xCa alloys were characterized by optical, SEM, EDX, and XRD. In vitro degradation tests were conducted via immersion test in phosphate buffer saline solution. In vivo performance in terms of interface, biocompatibility, and biodegradability of Mg– xCa alloys was examined by implanting samples into rabbit femoral condyle for 2 and 4 weeks. Results: Microstructural results showed the enhancement in intermetallic Mg2Ca phase with increase in Ca content. Immersion tests revealed that the dissolution rate varies linearly, with Ca content exhibiting more hydrogen gas evolution, increased pH, and higher degradation for Mg–5.0Ca alloy. In vivo studies showed good biocompatibility with enhanced bone formation for Mg–0.5Ca after 4 weeks of implantation compared with Mg–5.0Ca alloy. Higher initial corrosion rate with prolonged inflammation and rapid degradation was noticed in Mg–5.0Ca compared with Mg–0.5Ca alloy. Conclusions: The results suggest that Mg–0.5Ca alloy could be used as a temporary biodegradable implant material for clinical applications owing to its controlled in vivo degradation, reduced inflammation, and high bone-formation capability.

scholarly journals 1395. Defining the Magnitude of AUC:MIC Driver for Efficacy of the β-Lactamase Inhibitor VNRX-5133 When Combined with Cefepime Against KPC- and VIM/NDM-Producing Enterobacteriaceae and P. aeruginosa

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S429-S429 ◽  
Author(s):  
Denis Daigle ◽  
Salvador Vernacchio ◽  
Luigi Xerri ◽  
Daniel Pevear
Keyword(s):  
In Vitro Studies ◽  
Dose Fractionation ◽  
Infection Model ◽  
Type Model ◽  
E Coli ◽  
Dose Ranging ◽  
New Generation ◽  
Lactamase Inhibitor

Abstract Background VNRX-5133 is a cyclic boronate β-lactamase inhibitor (BLI) in clinical development with cefepime for treatment of infections caused by ESBL- and carbapenemase producing Enterobacteriaceae and P. aeruginosa. It is a new generation broad-spectrum BLI with direct inhibitory activity against serine-active site and emerging metallo-β-lactamases (e.g., VIM/NDM). In previous in vivo and in vitro studies, the PK-PD driver of efficacy of VNRX-5133 was defined as AUC:MIC. Described herein are in vitro studies to assess the magnitude of VNRX-5133 exposure (AUC:MIC) required to restore efficacy of cefepime against a broad collection of KPC- and VIM/NDM-producing Enterobacteriaceae (ENT) and P. aeruginosa (PSA) clinical isolates. Methods Dose-fractionation studies, consisting of four VNRX-5133 exposures fractionated into regimens administered every 4, 8, 12 and 24 hours, were performed in an in vitro infection model with simulated 2 g q8h dosing of cefepime against NDM-1 producing E. coli. A Hill-type model described the relationship between change in log10 CFU at 24 hours and VNRX-5133 exposure (AUC:MIC), where cefepime MIC was determined with 4 µg/mL VNRX-5133. To evaluate variability of efficacy enabled by VNRX-5133 between isolates as well as between Serine-BL and Metallo-BL producers, dose-ranging studies were completed for eight isolates (seven ENT and one PSA) producing KPC or VIM/NDM metallo-β-lactamases. Results The PK-PD exposure parameter AUC:MIC accurately described the efficacy of VNRX-5133 in rescuing cefepime activity against KPC and VIM/NDM carbapenemase-producing isolates of ENT and PSA. The AUC:MIC ratios associated with net bacterial stasis, 1-, and 2-log10 reductions in bacterial burden from baseline were 6.1, 18.4 and 45, respectively, for a collection of five VIM/NDM- and three KPC-producing isolates with cefepime MICs ranging from 4–8 µg/mL with no significant differences observed between Ser-BL and MBL producers. Conclusion These data confirm the equivalent in vitro activity of cefepime/VNRX-5133 against organisms producing serine- and metallo-β-lactamases and provides an initial PK-PD target for VNRX-5133 efficacy when used in combination with cefepime for the treatment of ESBL- and carbapenemase-producing ENT and PSA infections. Disclosures D. Daigle, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary. S. Vernacchio, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary. L. Xerri, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary. D. Pevear, VenatoRx Pharmaceuticals Inc.: Employee, Salary.

scholarly journals In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

2020 ◽  
Vol 9 (6) ◽  
pp. 734-740
Author(s):  
Yigit Sezer ◽  
Ayse Tarbin Jannuzzi ◽  
Marilyn A Huestis ◽  
Buket Alpertunga
Keyword(s):  
Oxidative Stress ◽  
Neuronal Cells ◽  
Underlying Mechanism ◽  
Synthetic Cannabinoid ◽  
Stress Effects ◽  
Legal High ◽  
New Generation ◽  
And Oxidative Stress

Abstract Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P < 0.05. Discussion/Conclusion: JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

scholarly journals Using backbone-cyclized Cys-rich polypeptides as molecular scaffolds to target protein–protein interactions

2019 ◽  
Vol 476 (1) ◽  
pp. 67-83 ◽  
Author(s):  
Dipankar Chaudhuri ◽  
Teshome Aboye ◽  
Julio A. Camarero
Keyword(s):  
Protein Interactions ◽  
Disulfide Bonds ◽  
Biological Degradation ◽  
Protein Protein Interactions ◽  
Molecular Scaffolds ◽  
Pharmaceutical Industries ◽  
Therapeutic Leads ◽  
New Generation

Abstract The use of disulfide-rich backbone-cyclized polypeptides, as molecular scaffolds to design a new generation of bioimaging tools and drugs that are potent and specific, and thus might have fewer side effects than traditional small-molecule drugs, is gaining increasing interest among the scientific and in the pharmaceutical industries. Highly constrained macrocyclic polypeptides are exceptionally more stable to chemical, thermal and biological degradation and show better biological activity when compared with their linear counterparts. Many of these relatively new scaffolds have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the disulfide bonds, able to cross cellular membranes and modulate intracellular protein–protein interactions both in vitro and in vivo. These properties make them ideal tools for many biotechnological applications. The present study provides an overview of the new developments on the use of several disulfide-rich backbone-cyclized polypeptides, including cyclotides, θ-defensins and sunflower trypsin inhibitor peptides, in the development of novel bioimaging reagents and therapeutic leads.

scholarly journals The mechanical property and corrosion resistance of Mg-Zn-Nd alloy fine wires in vitro and in vivo

2021 ◽  
Vol 6 (1) ◽  
pp. 55-63
Author(s):  
Ming Gao ◽  
Di Na ◽  
Xiangqiao Ni ◽  
Lihui Song ◽  
Iniobong P. Etim ◽  
...  
Keyword(s):  
Mechanical Property ◽  
Corrosion Resistance

scholarly journals The Mechanism of Action of Cyclophosphamide and Its Consequences for the Development of a New Generation of Oxazaphosphorine Cytostatics

2020 ◽  
Vol 88 (4) ◽  
pp. 42
Author(s):  
Georg Voelcker
Keyword(s):  
Mechanism Of Action ◽  
Active Metabolite ◽  
Dna Alkylation ◽  
In Vivo Metabolism ◽  
Pharmacologically Active ◽  
New Generation ◽  
Anti Tumor Activity ◽  
Oxazaphosphorine Cytostatics

Although cyclophosphamide (CP) has been used successfully in the clinic for over 50 years, it has so far not been possible to elucidate the mechanism of action and to use it for improvement. This was not possible because the basis of the mechanism of action of CP, which was found by lucky coincidence, is apoptosis, the discovery of which was honored with the Nobel Prize only in 2002. Another reason was that results from cell culture experiments were used to elucidate the mechanism of action, ignoring the fact that in vivo metabolism differs from in vitro conditions. In vitro, toxic acrolein is formed during the formation of the cytotoxic metabolite phosphoreamidemustard (PAM), whereas in vivo proapoptotic hydroxypropanal (HPA) is formed. The CP metabolites formed in sequence 4-hydroxycyclophosphamide (OHCP) are the main cause of toxicity, aldophosphamide (ALDO) is the pharmacologically active metabolite and HPA amplifies the cytotoxic apoptosis initiated by DNA alkylation by PAM. It is shown that toxicity is drastically reduced but anti-tumor activity strongly increased by the formation of ALDO bypassing OHCP. Furthermore, it is shown that the anti-tumor activity against advanced solid P388 tumors that grow on CD2F1 mice is increased by orders of magnitude if DNA damage caused by a modified PAM is poorly repairable.

scholarly journals In vitro and in vivo biostability assessment of chronically-implanted Parylene C neural sensors

2017 ◽  
Vol 251 ◽  
pp. 1001-1008 ◽  
Author(s):  
Aziliz Lecomte ◽  
Amélie Degache ◽  
Emeline Descamps ◽  
Lionel Dahan ◽  
Christian Bergaud
Keyword(s):  
Parylene C
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