Ion-pair strategy for enabling amifostine oral absorption: Rat in situ and in vivo experiments

2013 ◽  
Vol 49 (4) ◽  
pp. 499-504 ◽  
Author(s):  
N. Samiei ◽  
V. Mangas-Sanjuan ◽  
I. González-Álvarez ◽  
M. Foroutan ◽  
A. Shafaati ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Ion Pair ◽  
In Vivo Experiments

scholarly journals Enlisting the Ixodes scapularis Embryonic ISE6 Cell Line to Investigate the Neuronal Basis of Tick—Pathogen Interactions

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 70
Author(s):  
Lourdes Mateos-Hernández ◽  
Natália Pipová ◽  
Eléonore Allain ◽  
Céline Henry ◽  
Clotilde Rouxel ◽  
...  
Keyword(s):  
Cell Line ◽  
Peripheral Nerves ◽  
Ixodes Scapularis ◽  
Embryonic Cell ◽  
Cell Subpopulation ◽  
In Vivo Experiments

Neuropeptides are small signaling molecules expressed in the tick central nervous system, i.e., the synganglion. The neuronal-like Ixodes scapularis embryonic cell line, ISE6, is an effective tool frequently used for examining tick–pathogen interactions. We detected 37 neuropeptide transcripts in the I. scapularis ISE6 cell line using in silico methods, and six of these neuropeptide genes were used for experimental validation. Among these six neuropeptide genes, the tachykinin-related peptide (TRP) of ISE6 cells varied in transcript expression depending on the infection strain of the tick-borne pathogen, Anaplasma phagocytophilum. The immunocytochemistry of TRP revealed cytoplasmic expression in a prominent ISE6 cell subpopulation. The presence of TRP was also confirmed in A. phagocytophilum-infected ISE6 cells. The in situ hybridization and immunohistochemistry of TRP of I. scapularis synganglion revealed expression in distinct neuronal cells. In addition, TRP immunoreaction was detected in axons exiting the synganglion via peripheral nerves as well as in hemal nerve-associated lateral segmental organs. The characterization of a complete Ixodes neuropeptidome in ISE6 cells may serve as an effective in vitro tool to study how tick-borne pathogens interact with synganglion components that are vital to tick physiology. Therefore, our current study is a potential stepping stone for in vivo experiments to further examine the neuronal basis of tick–pathogen interactions.

Phosphofructokinase activity and acidosis during short-term tetanic contractions

1991 ◽  
Vol 69 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Lawrence L. Spriet
Keyword(s):  
Glycolytic Enzyme ◽  
Test Tube ◽  
Mammalian Skeletal Muscle ◽  
Short Term ◽  
Short Supply ◽  
In Vivo Experiments ◽  
Anaerobic Energy

Anaerobic energy production is essential for the production of muscular tension when the demand for energy is greater than can be provided aerobically and when oxygen is in short supply. The largest source of anaerobic energy is from the glycolytic pathway. With sustained tetanic contractions, muscle glycolytic activity is high and hydrogen ions (H+) accumulate while tension production decreases. The increasing [H+] and decreasing tension led to the suggestion that H+ inhibits the activity of the regulatory glycolytic enzyme phosphofructokinase (PFK). Early in vitro work confirmed the H+ sensitivity of PFK in the test tube, indicating that little PFK activity should persist at a pH of 6.9–7.0. However, in situ and in vivo experiments suggested that significant PFK activity was maintained during intense contractions when muscle pH decreased to 6.4–6.6. There are several concerns associated with the application of in vitro findings to in vivo exercise situations: (i) there is little in vitro work in mammalian skeletal muscle with substrate and modulator concentrations representative of exercise, (ii) most in vitro analyses of PFK activity are performed following the dilution of the enzyme in mediums with low protein concentration, and (iii) do the modulators identified in vitro exist in high enough in vivo concentrations at rest and during exercise to contribute to the regulation of PFK? More recent in vitro and in situ PFK experiments have overcome some of these concerns. They confirm that during intense, short-term tetanic contractions, PFK activity is well matched to the ATP demand despite decreases in pH to ~6.4–6.5. A combination of decreased inhibitor (ATP) and increased substrate (fructose 6-phosphate) contents coupled with increases in the contents of several positive modulators may be responsible for the maintained PFK activity. This combination reduces the pH-dependent ATP inhibition of PFK and extends the physiological pH range of the enzyme to the range normally measured during this type of muscular activity.Key words: glycolysis, phosphofructokinase, anaerobic metabolism, acidosis.

Antegrade in situ fenestration of aortic stent graft: in-vivo experiments using a pig model

2012 ◽  
Vol 53 (7) ◽  
pp. 754-758 ◽  
Author(s):  
Petri Saari ◽  
Markku Lähteenvuo ◽  
Krista Honkonen ◽  
Hannu Manninen
Keyword(s):  
Stent Graft ◽  
Pig Model ◽  
In Vivo Experiments ◽  
Aortic Stent Graft

scholarly journals Application of a simple device for "attracting" and "trapping" glioma cells in situ

2021 ◽  
Author(s):  
Haimin Song ◽  
Runwei Yang ◽  
Runbin Lai ◽  
Kaishu Li ◽  
Bowen Ni ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Adult Brain ◽  
Tumor Bed ◽  
In Vivo Experiments ◽  
New Strategy ◽  
New Treatment

Glioblastoma multiforme (GBM) is the most malignant adult brain tumor. The current adjuvant therapies for GBM are disappointing, which are based on cytotoxicity strategy. Thus, other ways should be explored to improve the curative effect. According to the strong invasive ability of GBM cells, we assume a new treatment strategy for GBM by developing a new cell trap device (CTD) with some kind of "attractive" medium loaded in it to attract and capture the tumor cells. The in vitro experiment showed that Hepatocyte Growth Factor（HGF）presented stronger chemotaxis on C6 and U87 cell line than the Epidermal Growth Factor (EGF) and Fibroblast Growth Factor (FGF). A simple in vitro CTD loaded with HGF was made and in vivo experiments results showed that HGF successfully attracted tumor cells from tumor bed in situ into the CTD. This study proposes the new strategy for GBM treatment of "attract and trap" tumor cells is proved to be feasible.

scholarly journals Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

1997 ◽  
Vol 41 (2) ◽  
pp. 445-448 ◽  
Author(s):  
N Ruiz-Balaguer ◽  
A Nacher ◽  
V G Casabo ◽  
M Merino
Keyword(s):  
Oral Administration ◽  
Oral Absorption ◽  
Cefuroxime Axetil ◽  
Point Of View ◽  
Kinetics Parameters ◽  
Rate Of Absorption ◽  
Membrane Bound ◽  
The Stability

Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solution were obtained: maximum rate of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17 microM. Cefuroxime axetil transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. On the other hand, the prodrug was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane before absorption occurred. This process reduces the prodrug fraction directly available for absorption. From a bioavailability point of view, therefore, the effects mentioned above can explain the variable and poor bioavailability following oral administration of cefuroxime axetil. Thus, future strategies in oral cefuroxime axetil absorption should focus on increasing the stability of the prodrug in the intestine by modifying the prodrug structure and/or targeting the compound to the absorption site.

Computational modelling of maternal interactions with spermatozoa: potentials and prospects

2011 ◽  
Vol 23 (8) ◽  
pp. 976 ◽  
Author(s):  
Mark Burkitt ◽  
Dawn Walker ◽  
Daniela M. Romano ◽  
Alireza Fazeli
Keyword(s):  
Reproductive Tract ◽  
Computational Modelling ◽  
Female Reproductive Tract ◽  
In Vivo Experiments ◽  
Complex Interactions ◽  
Maternal Communication ◽  
In Silico Models

Understanding the complex interactions between gametes, embryos and the maternal tract is required knowledge for combating infertility and developing new methods of contraception. Here we present some main aspects of spermatozoa interactions with the mammalian oviduct before fertilisation and discuss how computational modelling can be used as an invaluable aid to experimental investigation in this field. A complete predictive computational model of gamete and embryo interactions with the female reproductive tract is a long way off. However, the enormity of this task should not discourage us from working towards it. Computational modelling allows us to investigate aspects of maternal communication with gametes and embryos, which are financially, ethically or practically difficult to look at experimentally. In silico models of maternal communication with gametes and embryos can be used as tools to complement in vivo experiments, in the same way as in vitro and in situ models.

Molecular Biological Aspects of Fibrinolysis

1979 ◽  
Author(s):  
D. Collen
Keyword(s):  
Plasminogen Activator ◽  
Cell Transformation ◽  
Embryo Implantation ◽  
Tissue Destruction ◽  
In Vivo Experiments ◽  
Biological Aspects ◽  
Plasmin Inhibitor

The fibrinolytic enzyme system plays a role in the removal of fibrin from the blood vessels or urinary tract, and also in tissue repair (angiogenesis), cell transformation, macrophage function, ovulation and embryo implantation. Growing endothelial cells, malignant cells, macrophages, granulosa cells and trophoblast cells.produce plasminogen activators which activate plasminogen in the blood or interstitial fluids. Local plasmin formation appears to be a generalized mechanism involved in tissue destruction and repair. Fibrinolysis in the blood seems to be regulated by specific molecular interactions between (tissue) plasminogen activator, plasmin(ogen), fibrin and α2-antiplasmin, the physiological plasmin inhibitor. Plasmin(ogen) contains structures - lysine-binding sites - which mediate its interaction with fibrin and with α2-antiplasmin. When fibrin forms in plasma a small amount of plasminogen is bound via these structures. Plasminogen activator present or released in the blood is strongly adsorbed to the fibrin and activates bound plasminogen in situ. The formed plasmin, which remains transiently complexed to fibrin, both by its lysine-binding site(s) and active center, is only slowly inactivated by α2-antiplasmin, but plasmin which is released from digested fibrin is rapidly and irreversibly neutralized by α2-antiplasmin. Many in vitro and in vivo experiments support this hypothesis for the mechanism of fibrinolysis (Nature 272, 549,1978). Which allows speculation on more efficient therapeutic schemes for thrombolysis.

scholarly journals Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels

2019 ◽  
Vol 5 (3) ◽  
pp. eaav1281 ◽  
Author(s):  
Ehsan Shirzaei Sani ◽  
Ahmad Kheirkhah ◽  
Devyesh Rana ◽  
Zhongmou Sun ◽  
William Foulsham ◽  
...  
Keyword(s):  
Low Cost ◽  
Unmet Need ◽  
Defect Model ◽  
Sutureless Repair ◽  
In Vivo Experiments ◽  
High Adhesion ◽  
Common Causes ◽  
Corneal Regeneration

Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.

Multicompartmental lipid–protein nanohybrids for combined tretinoin/herbal lung cancer therapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (18) ◽  
pp. 2461-2479
Author(s):  
Nayra M Kamel ◽  
Maged W Helmy ◽  
Magda W Samaha ◽  
Doaa Ragab ◽  
Ahmed O Elzoghby
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Ion Pair ◽  
Pair Formation ◽  
Caspase Activation ◽  
Lung Cancer Therapy ◽  
Enhanced Stability

Aim: Multicompartmental lipid–protein nanohybrids (MLPNs) were developed for combined delivery of the anticancer drugs tretinoin (TRE) and genistein (GEN) as synergistic therapy of lung cancer. Materials & methods: The GEN-loaded lipid core was first prepared and then coated with TRE-loaded zein shell via nanoprecipitation. Results: TRE/GEN-MLPNs demonstrated a size of 154.5 nm. In situ ion pair formation between anionic TRE and the cationic stearyl amine improved the drug encapsulation with enhanced stability of MLPNs. TRE/GEN-coloaded MLPNs were more cytotoxic against A549 cancer cells compared with combined free GEN/TRE. In vivo, lung cancer bearing mice treated with TRE/GEN-MLPNs displayed higher apoptotic caspase activation compared with mice-treated free combined GEN/TRE. Conclusion: TRE/GEN-MLPNs might serve as a promising parenteral nanovehicles for lung cancer therapy.

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