scholarly journals How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 58
Author(s):  
Quyen N. Do ◽  
Robert E. Lenkinski ◽  
Gyula Tircso ◽  
Zoltan Kovacs
Keyword(s):  
Human Brain ◽  
Chemical Properties ◽  
Point Of View ◽  
Water Soluble ◽  
Soluble Form ◽  
Clinical Implications ◽  
Kinetic Properties ◽  
Gadolinium Retention ◽  
Open Question

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

scholarly journals A Review on Coordination Properties of Al(III) and Fe(III) toward Natural Antioxidant Molecules: Experimental and Theoretical Insights

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2603
Author(s):  
Luana Malacaria ◽  
Giuseppina Anna Corrente ◽  
Amerigo Beneduci ◽  
Emilia Furia ◽  
Tiziana Marino ◽  
...  
Keyword(s):  
Chemical Properties ◽  
Natural Antioxidants ◽  
Point Of View ◽  
Water Soluble ◽  
Natural Antioxidant ◽  
Theoretical Point ◽  
Structure And Properties ◽  
Coordination Properties ◽  
Soluble Molecule ◽  
Living Organisms

This review focuses on the ability of some natural antioxidant molecules (i.e., hydroxycinnamic acids, coumarin-3-carboxylic acid, quercetin, luteolin and curcumin) to form Al(III)- and Fe(III)-complexes with the aim of evaluating the coordination properties from a combined experimental and theoretical point of view. Despite the contributions of previous studies on the chemical properties and biological activity of these metal complexes involving such natural antioxidants, further detailed relationships between the structure and properties are still required. In this context, the investigation on the coordination properties of Al(III) and Fe(III) toward these natural antioxidant molecules might deserve high interest to design water soluble molecule-based metal carriers that can improve the metal’s intake and/or its removal in living organisms.

A Three-Component-System Hypothesis of Psychosis

1989 ◽  
Vol 155 (S5) ◽  
pp. 37-39 ◽  
Author(s):  
Hinderk M. Emrich
Keyword(s):  
Human Brain ◽  
Causative Factor ◽  
Microscopic Level ◽  
Point Of View ◽  
Component System ◽  
Pathogenetic Factor ◽  
Pet Scans ◽  
The Brain ◽  
Different Levels

Hypotheses as to the pathogenesis of schizophrenia can be discussed at different levels of a possible manifestation of the causative factor: the macroscopic-morphological, the microscopic-morphological, and the molecular. Some abnormalities have been observed on all of them: e.g. increased ventricular-brain ratios in CT, hypofrontality in SPECT and in glucographic PET-scans, and other macromorphological abnormalities (for reviews cf. Bogerts 1984; Mundt, 1986; Bogerts et al, 1987), gliosis on a microscopic level (Stevens, 1982), and an increased dopamine-binding in in vivo receptor studies (PET as well as in post-mortem studies; Cazzullo, 1988). However, the diversity and variability of these findings point to the view that rather than there being a single distinct pathogenetic factor responsible for the pathogenesis of schizophrenic psychoses, a constitutional disposition exists, which can be described as a functional dysequilibrium within the human brain. From this point of view, schizophrenia would not appear as an inherited disorder of metabolism, but as a weakness of a neurobiological ‘system’, i.e. as an interactional disorder of a complex of networks, in which the interaction between different substructures is labile in such a way that under special conditions (e.g. ‘stress’), a decompensation (functional breakdown) results. In this sense, ‘vulnerability’ to schizophrenia may be interpreted as a consequence of a constitutional deficiency of the brain which results in an inability to stabilise, under specially challenging conditions, the interaction between different substructures of the human brain. Before this ‘functional dysequilibrium-hypothesis’ (which is a special form of a constitutional structural deficiency-hypothesis) is discussed, and before the question is raised as to which are the relevant dysequilibrated components, some indication will be given as to why such an hypothesis appears plausible.

scholarly journals Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Andreas Kronbichler ◽  
Moin A. Saleem ◽  
Björn Meijers ◽  
Jae Il Shin
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Point Of View ◽  
Soluble Form ◽  
Glomerular Diseases ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
End Stage

Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

scholarly journals Biosynthesis of Cyanobacterial Phycobiliproteins in Escherichia coli: Chromophorylation Efficiency and Specificity of All Bilin Lyases from Synechococcus sp. Strain PCC 7002

2010 ◽  
Vol 76 (9) ◽  
pp. 2729-2739 ◽  
Author(s):  
Avijit Biswas ◽  
Yasmin M. Vasquez ◽  
Tierna M. Dragomani ◽  
Monica L. Kronfel ◽  
Shervonda R. Williams ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Biosynthetic Pathway ◽  
Expression System ◽  
Water Soluble ◽  
Soluble Form ◽  
Beta Subunits ◽  
Lyase Activity ◽  
Synechococcus Sp ◽  
Tetrapyrrole Chromophores

ABSTRACT Phycobiliproteins are water-soluble, light-harvesting proteins that are highly fluorescent due to linear tetrapyrrole chromophores, which makes them valuable as probes. Enzymes called bilin lyases usually attach these bilin chromophores to specific cysteine residues within the alpha and beta subunits via thioether linkages. A multiplasmid coexpression system was used to recreate the biosynthetic pathway for phycobiliproteins from the cyanobacterium Synechococcus sp. strain PCC 7002 in Escherichia coli. This system efficiently produced chromophorylated allophycocyanin (ApcA/ApcB) and α-phycocyanin with holoprotein yields ranging from 3 to 12 mg liter−1 of culture. This heterologous expression system was used to demonstrate that the CpcS-I and CpcU proteins are both required to attach phycocyanobilin (PCB) to allophycocyanin subunits ApcD (αAP-B) and ApcF (β18). The N-terminal, allophycocyanin-like domain of ApcE (LCM 99) was produced in soluble form and was shown to have intrinsic bilin lyase activity. Lastly, this in vivo system was used to evaluate the efficiency of the bilin lyases for production of β-phycocyanin.

scholarly journals Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Emiko Mihara ◽  
Hidenori Hirai ◽  
Hideki Yamamoto ◽  
Keiko Tamura-Kawakami ◽  
Mami Matano ◽  
...  
Keyword(s):  
Cellular Systems ◽  
Water Soluble ◽  
Biologically Active ◽  
Soluble Form ◽  
Wnt Ligands ◽  
Growth Assay ◽  
The Media ◽  
Highly Hydrophobic

Wnt plays important role during development and in various diseases. Because Wnts are lipidated and highly hydrophobic, they can only be purified in the presence of detergents, limiting their use in various in vitro and in vivo assays. We purified N-terminally tagged recombinant Wnt3a secreted from cells and accidentally discovered that Wnt3a co-purified with a glycoprotein afamin derived from the bovine serum included in the media. Wnt3a forms a 1:1 complex with afamin, which remains soluble in aqueous buffer after isolation, and can induce signaling in various cellular systems including the intestical stem cell growth assay. By co-expressing with afamin, biologically active afamin-Wnt complex can be easily obtained in large quantity. As afamin can also solubilize Wnt5a, Wnt3, and many more Wnt subtypes, afamin complexation will open a way to put various Wnt ligands and their signaling mechanisms under a thorough biochemical scrutiny that had been difficult for years.

EXTH-57. EFFICACY OF SOLUBLE PANOBINOSTAT (MTX110) IN PRECLINICAL MODELS OF ADULT GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi176-vi176
Author(s):  
Greg Palmer ◽  
Stephen T Keir ◽  
David M Ashley ◽  
Rhian Davies ◽  
Ben Williams ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Radiation Treatment ◽  
Water Soluble ◽  
Soluble Form ◽  
Cell Viability Assay ◽  
In Vivo Models ◽  
Drug Concentrations

Abstract INTRODUCTION One of the biggest challenges in treating glioblastoma is achieving effective local drug concentrations, and trials using systemic administration of therapeutics have failed in GBM despite compelling pre-clinical evidence. MTX110 (Midatech Pharma PLC) is a water-soluble form of panobinostat currently in clinical development for DIPG and medulloblastoma using direct tumor delivery. We have previously reported a significant positive benefit of MTX110 in a subcutaneous GBM mouse model in an IDH1 mutated cell line. Here we present follow on data on the potential for MTX110 synergy with radiation in pre-clinical in vivo models. We also present data on efficacy of MTX110 in a panel of GBM cell lines. METHODS In vitro: Cell lines were incubated with MTX110 for 72h over a range of concentrations (1nM-10µM). Each concentration was tested in triplicate with the appropriate blank controls included in each plate. After 72 hours, cell viability was measured via luminescence signal (Promega CellTiter-Glo Luminescent Cell Viability Assay kit (Promega-G7573) read via 2104 EnVision Multilabel Reader, PerkinElmer. In vivo: Tumor-bearing mice were stratified to either the vehicle control or treatment group based on median tumor volume and were treated with MTX110 at a dose of 15mg/kg IP, 5 days consecutively for 2 consecutive weeks, following radiation treatment at a dose of 4Gy delivered as a single fraction on day 1. RESULTS In vitro, MTX110 demonstrated cytotoxic activity in 4 GBM cell lines (U87MG, U251MG, U118MG and T98G) with an average IC50 value in the region of 40nM (17-43nM). In vivo MTX110 in combination with radiation treatment showed an enhanced delay in tumor growth of approximately 50% compared to MTX110 or radiation alone. The results are supportive of the planned exploratory trial in GBM with MTX110.

scholarly journals Carbon nanomaterials: Biologically active fullerene derivatives

2016 ◽  
Vol 144 (3-4) ◽  
pp. 222-231 ◽  
Author(s):  
Gordana Bogdanovic ◽  
Aleksandar Djordjevic
Keyword(s):  
Carbon Nanomaterials ◽  
Biomedical Application ◽  
Biological Activities ◽  
Chemical Properties ◽  
Water Soluble ◽  
Biologically Active ◽  
Fullerene Derivative ◽  
Potential Health

Since their discovery, fullerenes, carbon nanotubes, and graphene attract significant attention of researches in various scientific fields including biomedicine. Nano-scale size and a possibility for diverse surface modifications allow carbon nanoallotropes to become an indispensable nanostructured material in nanotechnologies, including nanomedicine. Manipulation of surface chemistry has created diverse populations of water-soluble derivatives of fullerenes, which exhibit different behaviors. Both non-derivatized and derivatized fullerenes show various biological activities. Cellular processes that underline their toxicity are oxidative, genotoxic, and cytotoxic responses. The antioxidant/cytoprotective properties of fullerenes and derivatives have been considered in the prevention of organ oxidative damage and treatment. The same unique physiochemical properties of nanomaterials may also be associated with potential health hazards. Non-biodegradability and toxicity of carbon nanoparticles still remain a great concern in the area of biomedical application. In this review, we report on basic physical and chemical properties of carbon nano-clusters - fullerenes, nanotubes, and graphene - their specificities, activities, and potential application in biological systems. Special emphasis is given to our most important results obtained in vitro and in vivo using polyhydroxylated fullerene derivative C60(OH)24.

scholarly journals In VivoInflammatory Effects of Ceria Nanoparticles on CD-1 Mouse: Evaluation by Hematological, Histological, and TEM Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Anna Poma ◽  
Anna Maria Ragnelli ◽  
Joaquin de Lapuente ◽  
David Ramos ◽  
Miquel Borras ◽  
...  
Keyword(s):  
Diesel Exhaust ◽  
Lethal Effect ◽  
Blood Stream ◽  
Water Soluble ◽  
Histological Evaluation ◽  
Soluble Form ◽  
Medical Applications ◽  
Ceria Nanoparticles ◽  
Tem Analysis

The attention on CeO2-NPs environmental andin vivoeffects is due to their presence in diesel exhaust and in diesel filters that release a more water-soluble form of ceria NPs, as well as to their use for medical applications. In this work, acute and subacutein vivotoxicity assays demonstrate no lethal effect of these NPs. Anyhow, performingin vivoevaluations on CD-1 mouse systems, we demonstrate that it is even not correct to assert that ceria NPs are harmless for living systems as they can induce status of inflammation, revealed by hematological-chemical-clinical assays as well as histological and TEM microscope observations. TEM analysis showed the presence of NPs in alveolar macrophages. Histological evaluation demonstrated the NPs presence in lungs tissues and this can be explained by assuming their ability to go into the blood stream and lately into the organs (generating inflammation).

Scanning Tunneling Microscopy and Atomic Force Microscopy of Enzymes and Enzyme Complexes

1990 ◽  
Vol 48 (3) ◽  
pp. 174-175
Author(s):  
Ronald D. Edstrom ◽  
Xiuru Yang ◽  
Mary E. Gurnack ◽  
Marcia A. Miller ◽  
Rui Yang ◽  
...  
Keyword(s):  
Cell Biology ◽  
Inorganic Ions ◽  
Bulk Liquid ◽  
Soluble Form ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Metabolic Channeling ◽  
Simplistic Notion ◽  
Soluble Enzymes

Many of the questions in biochemistry and cell biology are concerned with the relationships of proteins and other macromolecules in complex arrays which are responsible for carrying out metabolic sequences. The simplistic notion that the enzymes we isolate in soluble form from the cytoplasm were also soluble in vivo is being replaced by the concept that these enzymes occur in organized systems within the cell. In this newer view, the cytoplasm is organized and the “soluble enzymes” are in fact fixed in the cellular space and the only soluble components of the cell are small metabolites, inorganic ions etc. Further support for the concept of metabolic organization is provided by the evidence of metabolic channeling. It has been shown that for some metabolic pathways, the intermediates are not in free diffusion equilibrium with the bulk liquid in the cell but are passed along, more or less directly, from one enzyme to the next.

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