Structure-absorption relationships of a series of 6-fluoroquinolones.

1997 ◽  
Vol 41 (9) ◽  
pp. 1996-2000 ◽  
Author(s):  
E Escribano ◽  
A C Calpena ◽  
T M Garrigues ◽  
J Freixas ◽  
J Domenech ◽  
...  
Keyword(s):  
Structural Parameters ◽  
Molecular Surface ◽  
Molecular Volume ◽  
Log P ◽  
Linear Regression Method ◽  
Dipolar Moment ◽  
Interesting Compound ◽  
The One ◽  
Intrinsic Solubility

The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K(abs)) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MIC90s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K(abs), on the one hand, and lipophilic parameters and other physicochemical and structural parameters estimated. Of the nonlinear functions examined, the hyperbolic had the best correlation between K(abs) and P, which was in accordance with the Wagner-Sedman (J. G. Wagner and A. J. Sedman, J. Pharmacokinet. Biopharm. 1:23-50, 1973) equation, whereas, after application of the stepwise multiple linear regression method, a multiple linear correlation with some predictive value could be established only between K(abs) as a dependent variable and log P and log S0 as independent variables. In conclusion, the K(abs) and MIC90 of the quinolone CNV 8902 suggest that it is a sufficiently interesting compound to warrant the investigation of its potential therapeutic use orally.

Interaction of cisplatin anticancer drug with C20 bowl: DFT investigation

2021 ◽  
pp. 1-12
Author(s):  
Reza Ghiasi ◽  
Alireza Valizadeh
Keyword(s):  
Drug Interaction ◽  
Charge Transfer ◽  
Anticancer Drug ◽  
Structural Parameters ◽  
Orbital Energy ◽  
Molecular Volume ◽  
Log P ◽  
Water Partition Coefficient ◽  
The Stability ◽  
Precursor Molecules

This study investigated the cisplatin (anticancer drug) interaction with C20 bowl and C20H10(Bowl) molecule including hydrogen-saturated with using mPW1PW91 functional. The stability of the various isomers of drug interaction with C20 bowl was investigated. The interaction energy values were estimated in these systems. Changes in the structural parameters and the frontier orbital energy and HOMO-LUMO gap values were evaluated. Charge transfer between fragments were shown with electrophilicity-based charge transfer (ECT). The Octanol–water partition coefficient (log P) and molecular volume (Vm) of these drug precursor molecules were studied. Also, Pt-C bond characterizations were illustrated using QTAIM analysis. The results showed that C20 bowl can be a promising nanocarrier for cisplatin anticancer drug.

STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY

1973 ◽  
Vol 72 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Oddmund Søvik ◽  
Svein Oseid
Keyword(s):  
Biological Activity ◽  
Insulin Response ◽  
Epididymal Adipose Tissue ◽  
Large Individual ◽  
Immunoreactive Insulin ◽  
List Type ◽  
Glucose Load ◽  
Congenital Generalized Lipodystrophy ◽  
The One

ABSTRACT The biological activity of plasma insulin from 4 cases of congenital generalized lipodystrophy has been studied, using rat diaphragm and epididymal adipose tissue in vivo. The results are compared with previous data on plasma immunoreactive insulin obtained in these patients. 2 of the 4 cases exhibited unusually high biological insulin activities during the fasting state as well as after an intravenous (iv) glucose load. In the fat pad assay activities as high as 10 000 μU insulin per ml were observed. During childhood the biological insulin activities were generally high, although there were large individual variations. However, in the one case studied after the age of puberty, the insulin response to a glucose load was negligible. Taken together, the biological and immunological activities observed strongly suggest the presence of pancreatic insulin in these patients. It appears that the circulating insulin has a fully biological activity. The decreasing insulin activities after cessation of growth are in agreement with the appearance of frank diabetes at this time.

scholarly journals The One-Year In Vivo Comparison of Lithium Disilicate and Zirconium Dioxide Inlays

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 3102
Author(s):  
Rini Behera ◽  
Lora Mishra ◽  
Darshan Devang Divakar ◽  
Abdulaziz A. Al-Kheraif ◽  
Naomi Ranjan Singh ◽  
...  
Keyword(s):  
Zirconium Dioxide ◽  
Clinical Performance ◽  
Lithium Disilicate ◽  
Study Groups ◽  
Resin Cement ◽  
Internal Surfaces ◽  
Colour Match ◽  
One Year ◽  
The One

The objective of the present study was to evaluate the one-year clinical performance of lithium disilicate (LD) and zirconium dioxide (ZrO2) class II inlay restorations. Thirty healthy individuals who met the inclusion criteria were enrolled for the study. The patients were randomly divided into two study groups (n = 15): LD (IPS e.max press) and ZrO2 (Dentcare Zirconia). In the ZrO2 group, the internal surfaces of the inlays were sandblasted and silanized with Monobond N (Ivoclar, Leichsteistein, Germany). In the LD group, the internal surfaces of the inlays were etched with 5% hydrofluoric acid. The ceramic inlays were cemented with self-cure resin cement (Multilink N). Clinical examinations were performed using modified United State Public Health Codes and Criteria (USPHS) after 2 weeks, 4 weeks, 6 months and 1 year. The one-year survival rate was evaluated. In total, one failure was observed in the ZrO2 group. The survival probability after 1 year for the ZrO2 inlays was 93%, and for the LD inlays was 100%, which was statistically insignificant. The differences between both groups for most USPHS criteria (except for colour match) were statistically insignificant. Within the imitations of the present study, the lithium disilicate- and zirconia dioxide-based inlays exhibited comparable clinical performances. However, the colour and translucency match was superior for the lithium disilicate restorations.

Effect of microbial isolates on microbial yield estimation in RUSITEC system

1998 ◽  
Vol 22 ◽  
pp. 306-308
Author(s):  
M. D. Carro ◽  
E. L. Miller
Keyword(s):  
Protein Synthesis ◽  
Liquid Phase ◽  
Solid Phase ◽  
Liquid Fraction ◽  
Microbial Protein ◽  
Microbial Protein Synthesis ◽  
Continuous Culture System ◽  
The One

The estimation of rumen microbial protein synthesis is one of the main points in the nitrogen (N)-rationing systems for ruminants, as microbial protein provides proportionately 0.4 to 0.9 of amino acids entering the small intestine in ruminants receiving conventional diets (Russell et al., 1992). Methods of estimating microbial protein synthesis rely on marker techniques in which a particular microbial constituent is related to the microbial N content. Marker : N values have generally been established in mixed bacteria isolated from the liquid fraction of rumen digesta and it has been assumed that the same relationship holds in the total population leaving the rumen (Merry and McAllan, 1983). However, several studies have demonstrated differences in composition between solid-associated (SAB) and fluid-associated bacteria in vivo (Legay-Carmier and Bauchart, 1989) and in vitro (Molina Alcaide et al, 1996), as well in marker : N values (Pérez et al., 1996). This problem could be more pronounced in the in vitro semi-continuous culture system RUSITEC, in which there are three well defined components (a free liquid phase, a liquid phase associated with the solid phase and a solid phase), each one having associated microbial populations.The objective of this experiment was to investigate the effect of using different bacterial isolates (BI) on the estimation of microbial production of four different diets in RUSITEC (Czerkawski and Breckenridge, 1977), using (15NH4)2 SO4 as microbial marker, and to assess what effects any differences would have on the comparison of microbial protein synthesis between diets.This study was conducted in conjunction with an in vitro experiment described by Carro and Miller (1997). Two 14-day incubation trials were carried out with the rumen simulation technique RUSITEC (Czerkawski and Breckenridge, 1977). The general incubation procedure was the one described by Czerkawski and Breckenridge (1977) and more details about the procedures of this experiment are given elsewhere (Carro and Miller, 1997).

scholarly journals Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos

Reproduction ◽  
2004 ◽  
Vol 128 (3) ◽  
pp. 301-311 ◽  
Author(s):  
Paolo Rinaudo ◽  
Richard M Schultz
Keyword(s):  
Gene Expression ◽  
Preimplantation Embryos ◽  
Expression Analysis Systematic Explorer ◽  
Cell Stage ◽  
Global Pattern ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse ◽  
Global Patterns ◽  
The One

Culture of preimplantation embryos affects gene expression. The magnitude of the effect on the global pattern of gene expression, however, is not known. We compared global patterns of gene expression in blastocysts cultured from the one-cell stage in either Whitten’s medium or KSOM + amino acids (KSOM/AA) with that of blastocysts that developed in vivo, using the Affymetrix MOE430A chip. The analysis revealed that expression of 114 genes was affected after culture in Whitten’s medium, whereas only 29 genes were mis-expressed after culture in KSOM/AA. Expression Analysis Systematic Explorer was used to identify biological and molecular processes that are perturbed after culture and indicated that genes involved in protein synthesis, cell proliferation and transporter function were down-regulated after culture in Whitten’s medium. A common set of genes involved in transporter function was also down-regulated after culture in KSOM/AA. These results provide insights as to why embryos develop better in KSOM/AA than in Whitten’s medium, and highlight the power of microarray analysis to assess global patterns of gene expression.

Regulation of c-met expression in B16 murine melanoma cells by melanocyte stimulating hormone

1999 ◽  
Vol 112 (5) ◽  
pp. 623-630
Author(s):  
D. Rusciano ◽  
P. Lorenzoni ◽  
M.M. Burger
Keyword(s):  
Melanoma Cells ◽  
Parental Cell ◽  
Melanocortin Receptor ◽  
Parental Cell Line ◽  
Melanocyte Stimulating Hormone ◽  
Murine Melanoma ◽  
The One ◽  
Murine Melanoma Cells ◽  
Stimulating Hormone

B16 murine melanoma cells selected in vivo for enhanced liver metastatic ability (B16-LS9) show on the one hand an increased expression and constitutive activation of the proto-oncogene c-met (the receptor for hepatocyte growth factor/scatter factor), and on the other hand a more differentiated phenotype, when compared to the parental cell line, B16-F1. Following this observation, we have tried to establish whether there is a direct relationship between differentiation and c-met expression in B16 melanoma cells. Treatment of these cells with differentiating agents indicated that c-met expression was strongly induced by melanocyte stimulating hormone, while retinoic acid had almost no influence. c-met induction was triggered by engagement of the melanocortin receptor, cAMP elevation and PKA/PKC(α) activation, as respectively shown by the effects of ACTH, cAMP elevating agents and specific PK inhibitors. Regulation of c-met expression via the melanocortin receptor and cAMP raises the intriguing possibility that autocrine and/or paracrine mechanisms acting in vivo on this circuit might influence (through c-met expression and activation) the metastatic behavior of these tumor cells, which we have shown to be dependent on their c-met expression.

Topology Optimization of Dynamic Systems Under Uncertain Loads: An H∞-Norm-Based Approach

2019 ◽  
Vol 14 (2) ◽  
Author(s):  
Paolo Venini
Keyword(s):  
Topology Optimization ◽  
Structural Parameters ◽  
Goal Function ◽  
Dynamic Compliance ◽  
Case Scenario ◽  
Worst Case ◽  
Original Definition ◽  
Optimal Material ◽  
The One ◽  
Definition Of

An innovative approach to topology optimization of dynamic system is introduced that is based on the system transfer-function H∞-norm. As for the structure, the proposed strategy allows to determine the optimal material distribution that ensures the minimization of a suitable goal function, such as (an original definition of) the dynamic compliance. Load uncertainty is accounted for by means of a nonprobabilistic convex-set approach (Ben-Haim and Elishakoff, 1990, Convex Models of Uncertainty in Applied Mechanics, Elsevier Science, Amsterdam). At each iteration, the worst load is determined as the one that maximizes the current dynamic compliance so that the proposed strategy fits the so-called worst case scenario (WCS) approach. The overall approach consists of the repeated solution of the two steps (minimization of the dynamic compliance with respect to structural parameters and maximization of the dynamic compliance with respect to the acting load) until convergence is achieved. Results from representative numerical studies are eventually presented along with extensions to the proposed approach that are currently under development.

Leptin causes body weight loss in the absence of in vivo activities typical of cytokines of the IL-6 family

1998 ◽  
Vol 275 (3) ◽  
pp. R913-R919 ◽  
Author(s):  
Davide Agnello ◽  
Cristina Meazza ◽  
Christopher G. Rowan ◽  
Pia Villa ◽  
Pietro Ghezzi ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Body Weight Loss ◽  
Peripheral Blood Cell ◽  
Serum Corticosterone ◽  
Amyloid A ◽  
Cell Counts ◽  
Control Body ◽  
The One

To investigate if leptin shares in vivo activities with interleukin (IL)-6 family cytokines, it was tested in normal mice for the ability, after a single injection, to induce the acute-phase protein serum amyloid A, to potentiate the induction by IL-1 of serum corticosterone and IL-6, and to inhibit the induction by lipopolysaccharide of serum tumor necrosis factor and, after seven daily injections, to cause body weight loss and to change peripheral blood cell counts. At a 0.5 mg/kg dose, leptin caused body weight loss but did not show any of the other activities above. At a dose of 5 mg/kg, which also caused body weight loss, leptin potentiated the induction by IL-1 of serum corticosterone and IL-6 but did not show any other activity. In addition to causing body weight loss, leptin shows only some of the in vivo activities typical of IL-6 family cytokines and only if used at a dose that exceeds the one sufficient to affect body weight. In vivo, leptin seems to chiefly control body weight and not inflammatory or hematopoietic processes.

The one-pot synthesis of core/shell/shell CdTe/CdSe/ZnSe quantum dots in aqueous media for in vivo deep tissue imaging

2011 ◽  
Vol 21 (9) ◽  
pp. 2877 ◽  
Author(s):  
Shohei Taniguchi ◽  
Mark Green ◽  
Sarwat B. Rizvi ◽  
Alexander Seifalian
Keyword(s):  
Quantum Dots ◽  
Aqueous Media ◽  
Tissue Imaging ◽  
Core Shell ◽  
Deep Tissue ◽  
One Pot ◽  
One Pot Synthesis ◽  
Deep Tissue Imaging ◽  
The One

scholarly journals Lipophilicity and Click Reactivity Determine the Performance of Bioorthogonal Tetrazine Tools in Pretargeted in Vivo Chemistry

2020 ◽  
Author(s):  
Johanna Stéen ◽  
Jesper Tranekjær Jørgensen ◽  
Denk Christoph ◽  
Umberto Maria Battisti ◽  
Kamilla Nørregaard ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Rational Design ◽  
Structural Parameters ◽  
Early Time ◽  
High Rate ◽  
Drug Conjugates ◽  
Compound Libraries ◽  
Drug Concentrations ◽  
The Impact

<p>The development of highly selective and fast biocompatible reactions for ligation and cleavage has paved the way for new diagnostic and therapeutic applications of <i>in vivo</i> chemistry. The concept of bioorthogonal pretargeting has attracted considerable interest, in particular for the targeted delivery of radionuclides and drugs. In nuclear medicine, pretargeting can provide increased target-to-background ratios at early time-points compared to traditional approaches. This reduces the radiation burden to healthy tissue and, depending on the selected radionuclide, enables better imaging contrast or higher therapeutic efficiency. Moreover, bioorthogonally triggered cleavage of pretargeted antibody-drug conjugates represents an emerging strategy to achieve controlled release and locally increased drug concentrations. The toolbox of bioorthogonal reactions has significantly expanded in the past decade, with the tetrazine ligation being the fastest and one of the most versatile <i>in vivo</i> chemistries. Progress in the field, however, relies heavily on the development and evaluation of (radio)labeled compounds, preventing the use of compound libraries for systematic studies. The rational design of tetrazine probes and triggers has thus been impeded by the limited understanding of the impact of structural parameters on the <i>in vivo</i> ligation performance. In this work, we describe the development of a pretargeted blocking assay that allows for the investigation of the <i>in vivo</i> fate of a structurally diverse library of 45 unlabeled tetrazines and their capability to reach and react with pretargeted <i>trans</i>-cyclooctene (TCO)-tagged antibodies in tumor-bearing mice. This study enabled us to assess the correlation of click reactivity and lipophilicity of tetrazines with their <i>in vivo</i> performance. In particular, high rate constants (>50,000 M<sup>-1</sup>s<sup>-1</sup>) for the reaction with TCO and low calculated log<i>D</i><sub>7.4</sub> values (below -3) of the tetrazine were identified as strong indicators for successful pretargeted <i>in vivo</i> click chemistry. Click-radiolabeling gave access to a set of selected <sup>18</sup>F-labeled tetrazines, including highly reactive scaffolds, which were used in pretargeted PET imaging studies to confirm the results from the blocking study. These insights thus enable the rational design of tetrazine probes for <i>in vivo</i> application and will thereby assist the clinical translation of bioorthogonal pretargeting.</p>

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