Category: 6055-19-2

Vasquez, Marie Z. published the artcile< Combining the in vivo comet and micronucleus assays: a practical approach to genotoxicity testing and data interpretation>, Electric Literature of 6055-19-2, the main research area is Comet assay micronucleus genotoxicity safety.

Despite regulatory directives requiring the reduction of animal use in safety testing, recent modifications to genotoxicity testing guidelines now propose the use of two in vivo genotoxicity assays as a follow-up to an in vitro pos. (International Conference on Harmonization Consensus Draft Guidance S2[R1] released March, 2008). To address both goals, the in vivo comet and micronucleus (MN) assays can be successfully combined into one informative study. Combining these two assays with such differences in sensitivity, endpoints measured and the type of data generated significantly improves upon the current standard capabilities for detecting genotoxicity without requiring addnl. animals. But to take full advantage of the benefits of incorporating the comet assay in safety testing, these same differences must be recognized and considered. Developed from over 15 years experience using the in vivo comet and MN assays in genotoxicity testing of chems. and pharmaceuticals, this paper presents guidelines for the appropriate exptl. design, dose selection and data interpretation for combined in vivo comet/MN assay studies. To illustrate the approach, data from combined assay studies are presented and discussed.

Mutagenesis published new progress about Blood. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Electric Literature of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Ellison, Corie A.; Tankersley, Kevin O.; Obringer, Cindy M.; Carr, Greg J.; Manwaring, John; Rothe, Helga; Duplan, Helene; Genies, Camille; Gregoire, Sebastien; Hewitt, Nicola J.; Jamin, Carine Jacques; Klaric, Martina; Lange, Daniela; Rolaki, Alexandra; Schepky, Andreas published the artcile< Partition coefficient and diffusion coefficient determinations of 50 compounds in human intact skin, isolated skin layers and isolated stratum corneum lipids>, Computed Properties of 6055-19-2, the main research area is partition coefficient diffusion human intact skin; Diffusion coefficient; Infinite dose; Partition coefficient; Skin absorption; Skin penetration.

A standard protocol was used to determine partition (K) and diffusion (D) coefficients in dermatomed human skin and isolated human skin layers for 50 compounds relevant to cosmetics ingredients. K values were measured in dermatomed skin, isolated dermis, whole epidermis, intact stratum corneum (SC), delipidized SC and SC lipids by direct measurements of the radioactivity in the tissue layers/lipid component vs. buffer samples. D determinations were made in dermatomed skin, isolated dermis, whole epidermis and intact SC using a non-linear regression of the cumulative receptor fluid content of radiolabeled compound, fit to the solution of Fick’s 2nd Law. Correlation anal. was completed between K, D, and physicochem. properties. The amount of interindividual (donor) and intraindividual (replicate) variability in the K and D data was characterized for each skin layer and chem. These data can be further used to help inform the factors that influence skin bioavailability and to help improve in silico models of dermal penetration.

Toxicology In Vitro published new progress about Bioavailability. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Computed Properties of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Kanno, Seiya; Okubo, Yusuke; Kageyama, Tatsuto; Yan, Lei; Fukuda, Junji published the artcile< Integrated fibroblast growth factor signal disruptions in human iPS cells for prediction of teratogenic toxicity of chemicals>, Electric Literature of 6055-19-2, the main research area is human iPS cell fibroblast growth factor chem teratogenic toxicity; Fibroblast growth factor; Pluripotent stem cells; Signal disruption; Signal reporter assay; Teratogenicity.

The number of man-made chems. has increased rapidly in recent decades, with certain chems. potentially causing malformations in fetuses. Although the toxicities of chems. have been tested in animals, chems. that are not teratogenic in rodents can cause severe malformations in humans, owing to the differences in the susceptibility to the teratogenicity of chems. among species. One possible cause of such species differences, other than pharmacokinetics, could be the difference in sensitivity to such chems. at the cellular level. Therefore, a human cell-based high-throughput assay system is needed for detecting potential teratogenic chems. In this study, we proposed a signal reporter assay using human induced pluripotent stem cells (iPSCs). Because developmental processes are governed by highly intricate and precisely programmed signaling pathways, external chem.-induced disruption of these pathways often triggers developmental toxicities. The reporter assay using hiPSCs was used to detect changes in the fibroblast growth factor (FGF) signaling pathway, a pathway essential for limb morphogenesis. The method was based on monitoring and time-accumulation of the signal disruption over time, rather than the classical endpoint detection of the signal disruption. This approach was useful for detecting signal disruptions caused by the malformation chems. listed in the ICH S5 guideline, including thalidomide. The human iPSC-based signal disruption assay could be a promising tool for the initial screening of developmental toxicants.

Journal of Bioscience and Bioengineering published new progress about Cell viability. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Electric Literature of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Kovalcik, Thomas R.; Guillory, J. Keith published the artcile< Stability of cyclophosphamide in lyophilized cakes. II. Urea, polyvinylpyrrolidone, and dextran as excipients>, COA of Formula: C7H17Cl2N2O3P, the main research area is cyclophosphamide stability lyophilization; excipient cyclophosphamide stability lyophilization.

Lyophilized products containing cyclophosphamide (I) and one of the following excipients: urea, polyvinylpyrrolidone (PVP-40), or dextran, were prepared All of the products were well-formed cakes. I in these lyophilized cakes underwent rapid (t90 < 30 days) degradation in the solid state at room temperature The lyophilized cakes were humidified with 5 μL water. In the cake containing urea, DSC and x-ray diffraction showed that I was converted from the amorphous to the monohydrate form when exposed to moisture, and exhibited improved stability. In the case of the cake containing PVP-40, the incorporation of moisture resulted in formation of a clear, semi-solid possessing poor stability. The I/dextran cake remained intact upon humidification. DSC and x-ray diffraction showed that I in this cake was not converted from the amorphous form to the monohydrate form, and exhibited no improvement in stability. Journal of Parenteral Science and Technology published new progress about Freeze drying. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, COA of Formula: C7H17Cl2N2O3P.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Munjal, Bhushan; Zode, Sandeep S.; Bansal, Arvind K. published the artcile< Crystallization of Cyclophosphamide Monohydrate During Lyophilization>, Related Products of 6055-19-2, the main research area is crystallization cyclophosphamide monohydrate lyophilization; crystallization; dehydration; freeze-drying; hydrates; lyophilization; processing.

The purpose of this study was to investigate the phase behavior of cyclophosphamide (CPA) during various stages of lyophilization, with special emphasis on obtaining crystalline CPA monohydrate (CPA-MH) in the lyophilized product. Subambient differential scanning calorimetry and low-temperature X-ray diffractometry (LTXRD) were used to study the phase behavior of CPA solution (3.7% w/v). In situ lyophilization in LTXRD chamber was used to monitor the phase transitions occurring during the drying stages. Finally, the implications of these findings were confirmed by freeze-drying the aqueous solution in a laboratory-scale freeze-dryer. The results suggested that CPA remains amorphous during freeze concentration, with a Tg’ of -50°C. However, its crystallization as CPA-MH can be induced by annealing the frozen solution between -5°C and -10°C. In situ lyophilization in LTXRD showed that the CPA-MH crystallized during annealing, rapidly dehydrated during primary drying, thereby causing structural collapse. The dehydration of CPA-MH can be prevented by lowering the escaping tendency of water mols. from the crystal lattice of CPA-MH by maintaining the chamber pressure to 300, 400, or 500 mTorr. This study highlights the relationship of process parameters used during lyophilization with the solid form of lyophilized CPA.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Crystallization. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Related Products of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Sakura, Mizuaki; Masuda, Hitoshi; Matsukoa, Yoh; Yokoyama, Minato; Kawakmi, Satoru; Kihara, Kazunori published the artcile< Rolipram, a specific type-4 phosphodiesterase inhibitor, inhibits cyclophosphamide-induced haemorrhagic cystitis in rats>, Application In Synthesis of 6055-19-2, the main research area is rolipram phosphodiesterase inhibitor cyclophosphamide monohydrate hemorrhagic cystitis iNOS antiinflammatory.

To investigate the protective roles of type 4 phosphodiesterase (PDE4) inhibitor in cyclophosphamide (CYP)-induced hemorrhagic cystitis, as the PDE4 inhibitor has anti-inflammatory effects but its characterization is still unknown in urinary tract diseases. In female Sprague-Dawley rats, CYP was administered i.p. and bladders were harvested 24 h after CYP injection. In another group, rolipram as a PDE4 inhibitor was administered before CYP treatment. The effects and mechanisms of CYP with/ without rolipram pretreatment were evaluated by microscopic features, bladder wet weight, myeloperoxidase (MPO) activity, nitric oxide (NO)-metabolite production and expression levels of inflammation-related genes. CYP injection resulted in severe cystitis. Pretreatment with rolipram significantly reduced the increase in bladder wet weight and MPO activity, and ameliorated histol. inflammatory changes caused by CYP. The levels of inflammation-related transcripts including inducible NO synthase (iNOS), interleukin-1β and tumor necrosis factor-α, induced by CYP, were down-regulated significantly by pretreatment with rolipram. Also, rolipram reduced the NO-metabolite production and iNOS protein expression in the immunohistochem. examination These results indicate that rolipram can attenuate the development of CYP-induced cystitis in rats by suppressing cytokine production and iNOS induction. Thus, treatment with PDE4 inhibitor has potential clin. implications of the prevention of bladder inflammatory diseases.

BJU International published new progress about Anti-inflammatory agents. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Application In Synthesis of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Shim, Soon-Mi; Bae, Eunkyung; Kim, Gun-Hee published the artcile< Single-dose oral acute toxicity and mutagenic effects of methanol extracts of Cirsium japonicum>, Electric Literature of 6055-19-2, the main research area is Cirsium acute oral toxicity mutagenicity chromosome flavone.

The purpose of this study was to evaluate safety on Cirsium japonicum extracts containing flavones by examining acute oral toxicity, bacterial reverse mutation and the chromosome aberration test. Mutagenicity of extracts were evaluated by a bacterial reverse mutation assay using Salmonella typhimurium TA98, TA100, TA102, TA1535, TA1537 and Escherichia coli (WP2uvrA) with and without metabolic activation. An in vitro chromosome aberration test in Chinese hamster lung cells was conducted at the concentrations of 0, 1,250, 2,500 and 5,000 μg/mL. No significant adverse effects on body weight, mortality and gross findings were observed for 15 days after a single dose (2,000 mg of extracts/kg body weight) of administration. In the bacterial reverse mutation assay, C. japonicum extracts ranging from 156 to 5,000 μg/plate did not induce base-pair substitution or frame shift. Any significant increase in structural aberration as well as reduction of cell cycle progression was not observed in the chromosome.

Journal of Food Biochemistry published new progress about Chromosome aberrations. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Electric Literature of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Rouissi, Kamel; Hamrita, Bechr; Kouidi, Soumaya; Messai, Yosra; Jaouadi, Bassem; Hamden, Khaled; Medimegh, Imen; Ouerhani, Slah; Cherif, Mohamed; Elgaaied, Amel Benammar published the artcile< In vivo prevention of bladder urotoxicity: purified hydroxytyrosol ameliorates urotoxic effects of cyclophosphamide and buthionine sulfoximine in mice>, Formula: C7H17Cl2N2O3P, the main research area is hydroxytyrosol bladder urotoxicity antioxidant cyclophosphamide monohydrate BSO.

Urotoxicity is a troublesome complication associated with cyclophosphamide (CP) and L-buthionine-SR-sulfoximine (BSO) treatment in chemotherapy. With this concern in mind, the present study investigated the potential effects of a hydroxytyrosol extract from olive mill waste (OMW) on urotoxicity induced by acute CP and BSO doses using a Swiss albino mouse model. Toxicity modulation was evaluated by measuring lipid peroxidation (LPO) and antioxidants in urinary bladder. The findings revealed that the hydroxytyrosol extract exerted a protective effect not only on LPO but also on enzymic antioxidants. When compared to the controls, the CP-treated animals underwent significant decreases in the glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GP), and catalase (CAT) activities. The level of glutathione (GSH) was also reduced with increased doses of LPO in the CP-treated animals. L-Buthionine-SR-sulfoximine treatment exerted an additive toxic effect on the CP-treated animals. Interestingly, pretreatment with the hydroxytyrosol extract restored the activities of all enzymes back to normal levels and exhibited an overall protective effect on the CP- and BSO-induced toxicities in urinary bladder. The restoration of GSH through the treatment with the hydroxytyrosol extract can play an important role in reversing CP-induced apoptosis and free radical-mediated LPO.

International Journal of Toxicology published new progress about Antioxidants. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Formula: C7H17Cl2N2O3P.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Sirenko, Oksana; Cromwell, Evan F.; Crittenden, Carole; Wignall, Jessica A.; Wright, Fred A.; Rusyn, Ivan published the artcile< Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity>, Application In Synthesis of 6055-19-2, the main research area is cardiotoxicity cardiomyocyte beating pluripotency stem cell; AUC; BMC; Calcium flux; Cardiotoxicity; DMSO; EC(50); Phenotypic screening; Predictive toxicology; area under the curve; benchmark concentration; dimethyl sulfoxide; effective concentration at 50% of the maximum response; hERG; iPSC; induced pluripotent stem cell.

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiol. parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, pos. (107) and neg. (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca2+ flux readouts synchronous with beating, and cell viability. A number of physiol. parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data anal. Concentration-response profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% DMSO)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicol. Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive “”cardiosafety”” ranking of tested compounds Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and anal. methods may be used widely for compound screening and early safety evaluation in drug development.

Toxicology and Applied Pharmacology published new progress about Anti-inflammatory agents. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Application In Synthesis of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Corton, J. Christopher; Witt, Kristine L.; Yauk, Carole L. published the artcile< Identification of p53 Activators in a Human Microarray Compendium>, Reference of 6055-19-2, the main research area is p53 activation human microarray DNA damage.

Biomarkers predictive of mol. and toxicol. effects are needed to interpret emerging high-throughput transcriptomic data streams. The previously characterized 63 gene TGx-DDI biomarker that includes 20 genes known to be regulated by p53 was previously shown to accurately predict DNA damage in chem.-treated cells. The authors comprehensively evaluated whether the mol. basis of the DDI predictions was based on a p53-dependent response. The biomarker was compared to microarray data in a compendium derived from human cells using the Running Fisher test, a nonparametric correlation test. Using the biomarker, the authors identified conditions that led to p53 activation, including exposure to the chem. nutlin-3 which disrupts interactions between p53 and the neg. regulator MDM2 or by knockdown of MDM2. The expression of most of the genes in the biomarker (75%) were found to depend on p53 activation status based on gene behavior after TP53 overexpression or knockdown. The biomarker identified DDI chems. that were strong inducers of p53 in wild-type cells; these p53 responses were decreased or abolished in cells after p53 knockdown by siRNAs. Using the biomarker, the authors screened ∼1950 chems. in ∼9800 human cell line chem. vs. control comparisons and identified ∼100 chems. that caused p53 activation. Among the pos. chems. were many that are known to activate p53 through direct and indirect DNA damaging mechanisms. These results contribute to the evidence that the TGx-DDI biomarker is useful for identifying chems. that cause DDI and activate p53.

Chemical Research in Toxicology published new progress about Algorithm. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Reference of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics