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).

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 PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: PASSIVE IMMUNITY TO REACTING FACTORS

1931 ◽  
Vol 54 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Gregory Shwartzman
Keyword(s):  
Intravenous Injection ◽  
Neutralizing Antibodies ◽  
Lethal Effect ◽  
Blood Stream ◽  
Immune Serum ◽  
Passive Immunity ◽  
Local Skin ◽  
Serum Therapy ◽  
The Law

It has proved possible to elicit passive immunity to B. typhosus reacting factors by means of normal and immune homologous neutralizing antibodies. The in vivo serum protection against these factors followed the law of multiple proportions. There was observed a considerable loss of antibodies from the blood stream. Passive immunity was best obtained when the immune serum was injected intravenously ½ hour before the intravenous injection of the reacting factors. It was possible to prevent the occurrence of the local skin reaction by an intravenous injection of serum after the intravenous injection of the reacting factors, provided the serum dose was very large and provided the serum injection was made immediately after the filtrate injection. A number of experiments clearly demonstrated the interesting fact that the greater the amount of antiserum injected intravenously, the more efficient was the in vivo neutralization, in a ratio distinctly greater than the quantitative increase of serum. It is suggested that there may be a practical value of the observation in relation to serum therapy. The results also demonstrated passive serum protection against the lethal effect of B. typhosus "agar washings" filtrates, in a ratio which seemed to suggest the law of multiple proportions.

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.

Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport

1982 ◽  
Vol 243 (6) ◽  
pp. G455-G462 ◽  
Author(s):  
G. M. Groothuis ◽  
M. J. Hardonk ◽  
K. P. Keulemans ◽  
P. Nieuwenhuis ◽  
D. K. Meijer
Keyword(s):  
Biliary Excretion ◽  
Low Dose ◽  
Blood Stream ◽  
Water Soluble ◽  
Salt Transport ◽  
High Doses ◽  
Pentobarbital Sodium Anesthesia ◽  
Taurocholate Transport ◽  
Bile Salt Transport

A combination of autoradiography of water-soluble compounds and normal and retrograde perfusions was used to study whether there was a heterogeneity in bile salt transport between zone 1 and zone 3 hepatocytes of the rat and, if so, whether such a heterogeneity was due to the localization of these cells in the liver blood-stream, to intrinsic cellular differences, or to both. When a low dose of [3H]taurocholate was administered under pentobarbital sodium anesthesia in vivo or to normally perfused livers, the label was localized primarily in zone 1; in livers perfused in a retrograde direction, it appeared predominantly in zone 3. High doses of [3H]taurocholate administered in vivo and in normal and retrograde perfusions resulted in a more homogeneous labeling of the acini. The plasma disappearance of [3H]taurocholate was similar in normal and retrograde perfusions, but in the latter biliary excretion occurred at a considerably slower rate. From these results it is concluded that at low doses bile salts are primarily transported by zone 1 cells. Zone 3 cells appear to be able to take up taurocholate with ease, but their biliary excretion is slower compared with zone 1 cells.

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.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

2018 ◽  
Vol 18 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Denis V. Mishchenko ◽  
Margarita E. Neganova ◽  
Elena N. Klimanova ◽  
Tatyana E. Sashenkova ◽  
Sergey G. Klochkov ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Toxicity ◽  
Histone Deacetylases ◽  
Hydroxamic Acids ◽  
Water Soluble ◽  
Male Rat ◽  
Hybrid Male ◽  
Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

scholarly journals Antidiabetic and antiulcerative potential of Garcinia lanceifolia Roxb. bark

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nilutpal Sharma Bora ◽  
Partha Sarathi Bairy ◽  
Abdus Salam ◽  
Bibhuti Bhusan Kakoti
Keyword(s):  
Body Weight ◽  
Serum Levels ◽  
Northeast India ◽  
Scientific Data ◽  
Antidiabetic Activity ◽  
Histological Evaluation ◽  
Albino Rats ◽  
Antiulcer Activity ◽  
Dose Dependent

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.

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