distribution study
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2022 ◽  
Author(s):  
Yaxin Li ◽  
Raina Dano ◽  
Cathy Li ◽  
Wenjing Zhang ◽  
Justin D. Lathia ◽  
...  

2022 ◽  
Vol 9 ◽  
Author(s):  
Cristina Sottani ◽  
Elena Grignani ◽  
Danilo Cottica ◽  
Serena Mazzucchelli ◽  
Marta Sevieri ◽  
...  

Indocyanine green (ICG) is one of the most commonly used fluorophores in near-infrared fluorescence-guided techniques. However, the molecule is prone to form aggregates in saline solution with a limited photostability and a moderate fluorescence yield. ICG was thus formulated using protein-based nanoparticles of H-ferritin (HFn) in order to generate a new nanostructure, HFn-ICG. In this study, an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) system was employed to develop and validate the quantitative analysis of ICG in liver tissue samples from HFn-ICG-treated mice. To precipitate HFn, cold acetone in acidic solution at pH 5.0 was used. The processed liver samples were injected into the UHPLC-MS/MS system for analysis using the positive electrospray ionization mode. Chromatographic separation was achieved on a Waters Acquity UPLC® HSS T3 Column (1.8 μm, 2.1 × 100 mm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. The selected reaction monitoring transitions of  m/z 753 →m/z 330 and m/z 827 →m/z 330 were applied for ICG and IR-820 (the internal standard, IS), respectively. The method was selective and linear over a concentration range of 50–1,500 ng/ml. The method was validated for sensitivity, accuracy, precision, extraction recovery, matrix effect, and stability in liver tissue homogenates. ICG extraction recoveries ranged between 85 and 108%. The intra- and inter-day precisions were less than 6.28%. The method was applied to a bio-distribution study to compare the amount of ICG levels from mice treated with HFn-ICG and free ICG. The analyses of the homogenate samples from the two types of treatment showed that the concentration levels of ICG is approximately six-fold higher than those of free ICG (1,411 ± 7.62 ng/ml vs. 235 ± 26.0 ng/ml) at 2 h post injection.


Author(s):  
Putu Wisnu Ekaputra ◽  
I Gede Partha Sindu ◽  
P Wayan Arta Suyasa

The purpose of this study is to determine (1) the design and impementation of the development of a 2-dimentional animation learning video for sad ripu of hindu religion subject for 6th grade at SD Negeri 1 Kalibukbuk. The result of 6th grade response shows that 2-dimentional animation learning video is suitable for learning media of sad ripu of hindu religion subject. Research method used for the development is MDLC (Multimedia Development Life Cycle) approach which contained several steps, they are concept, design, material collecting, assembly, testing, and distribution. Study result shows that the elementary student as user of the learning video gave positive response and very enthusiastic about learning sad ripu of hindu religion subject with learning video. (2) From the result of response test to 10 elementary student as respondent to see the feasibility of learning video obtained result of 85%, which means 2-dimentional animation learning video for sad ripu of hindu religion subject is included in the good category. Keywords: Learning Video, 2D Animation, Hinduism, Sad Ripu, MDLC (Multimedia Development Life Cycle).


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4595-4595
Author(s):  
Anna Guarnieri ◽  
Mark Chicarelli ◽  
Louann Cable ◽  
Karyn Bouhana ◽  
Francis Sullivan ◽  
...  

Abstract The molecular pathogenesis of Systemic Mastocytosis (SM) is driven by mutations in the KIT gene, with 95% of patients having a mutation in exon 17, D816V, leading to constant proliferation of mast cells (Garcia-Montero et al, 2006; Jara-Acevedo et al, 2015; Vaes et al, 2017). Targeted therapeutics have revealed clinical activity in these patients, but toxicities such as cognitive effects, intracranial hemorrhage, hypertension, and edema may limit dosing and availability of these therapies. While the exact cause of these effects is difficult to determine, numerous closely related kinases, such as wild type PDGFRα, PDGFRβ, KIT, VEGFR2 (KDR), and CSF1R (FMS), are considered to be anti-targets, with previous evidence of their inhibition linked to observed clinical toxicities (Liu & Kurzrock, 2015; Giles et al., 2009; Jayson et al., 2005). Bezuclastinib (CGT9486) was designed to selectively inhibit KIT D816V versus these other closely related kinase anti-targets. Additionally, we demonstrate that bezuclastinib has minimal brain penetration, together with no observed CNS-related toxicities in nonclinical studies. Herein, we present results from cell-based kinase profiling assays, which demonstrate that bezuclastinib has a significant and unique selectivity to KIT D816V relative to the aforementioned kinases when tested head-to-head against other clinically relevant compounds in SM. Additionally, a similar selectivity profile was observed for a broader panel of kinases, ion channels, transporters, and enzymes, which will be presented here, including drug concentrations and target engagement achieved with recent in vivo studies. Importantly, we also show that bezuclastinib has minimal brain penetration, a preferred feature of an anti-Kit molecule due to CNS-related adverse events observed in these indications. In a tissue distribution study performed in rats, bezuclastinib shows a brain:plasma ratio <0.1 following 3 day administration at 25 mg/kg, a dose that closely correlates with clinical plasma exposure. This was supported functionally by assessing neurobehavioral effects of bezuclastinib at dose levels up to 100 mg/kg in rats which showed no CNS related effects. This attractive selectivity and nonclinical safety profile, combined with early clinical data in advanced solid tumors (Trent et al, 2020), supports the potential for a best-in-class KIT inhibitor. Bezuclastinib is currently under clinical investigation in advanced SM with additional clinical studies planned in non-advanced SM and imatinib-resistant GIST. Disclosures Guarnieri: Cogent Biosciences: Current Employment. Cable: Cogent Biosciences: Current Employment. Bouhana: Cogent Biosciences: Current Employment. Sullivan: Cogent Biosciences: Current Employment. Ball: Cogent Biosciences: Current Employment. Sachs: Cogent Biosciences: Current Employment. Winski: Cogent Biosciences: Current Employment. Robinson: Cogent Biosciences: Current Employment.


2021 ◽  
Vol 32 (4) ◽  
pp. 353-373
Author(s):  
Khalid Ibrahim Hussein Al-Easawi ◽  
Qysser Abdullah Ahmed Farhan Al-Duliemi

The importance of population distribution study appears through its direct impact on various fields such as economy, social and political fields. The research aims to show the pictures of the distribution of population in Anbar Province for 2019 according to its administrative units, but differently from the distributions taken earlier. We will depend on the distribution in several quantitative methods using GIS through multiple quantitative maps to show the ability of digital programs to represent in more than one method for same data, as well as the possibility of modern technologies of achieving maps and conduct spatial analyze at the lowest time and cost. This is what we see in the preparation of population maps for the region research clarifying what are the quantitative maps and showing the steps of their production in GIS and the symbols used as well as using ARC GIS programs in all research stages such as the progress of geographic return and then multiple drawing operations with the establishment of a digital database. The search came out a set of different maps in terms of the way drawing and output.


2021 ◽  
pp. 117-127
Author(s):  
Raja Prabu Ramachandran ◽  
Vishveswaran Jothi ◽  
Mohamed I. Neamathulla ◽  
Sadasivam Pachamuthu ◽  
Kavitha Sankaranarayanan ◽  
...  

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3210
Author(s):  
Talib Hussain ◽  
Sathishbabu Paranthaman ◽  
Syed Mohd Danish Rizvi ◽  
Afrasim Moin ◽  
Devegowda Vishakante Gowda ◽  
...  

Gliomas are one of the prominent cancers of the central nervous system with limited therapeutic modalities. The present investigation evaluated the synergistic effect of paclitaxel (PAX) and resveratrol (RESV)-loaded Soluplus polymeric nanoparticles (PNPs) against glioma cell lines along with in vivo pharmacokinetics and brain distribution study. PAX-RESV-loaded PNPs were prepared by the thin film hydration technique and optimized for different dependent and independent variables by using DoE (Design-Expert) software. The in vitro physiochemical characterization of prepared PAX-RESV-loaded PNPs exhibited appropriate particle size, PDI and % encapsulation efficiency. Cytotoxicity assay revealed that PTX-RESV loaded PNPs had a synergistic antitumor efficacy against C6 glioma cells compared with single and combined pure drugs. Finally, the pharmacokinetic and brain distribution studies in mice demonstrated that the PNPs significantly enhanced the bioavailability of PTX-RESV PNPs than pure PAX and RESV. Thus, the study concluded that PAX-RESV PNPs combination could significantly enhance anti-glioma activity, and this could be developed into a potential glioma treatment strategy.


2021 ◽  
Vol 23 (09) ◽  
pp. 959-966
Author(s):  
M.B. Bindu ◽  
◽  
Linu Sam ◽  
Amrutha R ◽  
◽  
...  

The PED assignments are analysed for the title molecule. The Force Constants and Reduced masses are presented for reference. Vibrational assignments are made to the title molecule Beta Asarone. .The analysis of Vibrational Assignments is done with an intention to deduce the various properties of Beta Asarone that should aid in analysing the reported toxicity of Beta Asarone.


Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5644
Author(s):  
Yixuan Feng ◽  
Lele Li ◽  
Yuxuan Li ◽  
Xinxin Zhou ◽  
Xiaoying Lin ◽  
...  

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.


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