scholarly journals Polysaccharide Chain Length of Lipopolysaccharides From Salmonella Minnesota Is a Determinant of Aggregate Stability, Plasma Residence Time and Proinflammatory Propensity in vivo

2019 ◽  
Vol 10 ◽  
Author(s):  
Wahib Sali ◽  
Danish Patoli ◽  
Jean-Paul Pais de Barros ◽  
Jérôme Labbé ◽  
Valérie Deckert ◽  
...  
Keyword(s):  
Chain Length ◽  
Residence Time ◽  
Aggregate Stability ◽  
Polysaccharide Chain

scholarly journals Ceramide chain length–dependent protein sorting into selective endoplasmic reticulum exit sites

2020 ◽  
Vol 6 (50) ◽  
pp. eaba8237
Author(s):  
Sofia Rodriguez-Gallardo ◽  
Kazuo Kurokawa ◽  
Susana Sabido-Bozo ◽  
Alejandro Cortes-Gomez ◽  
Atsuko Ikeda ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Chain Length ◽  
Secretory Pathway ◽  
Protein Sorting ◽  
Endoplasmic Reticulum Membrane ◽  
Lipid Chain ◽  
Secretory Transport ◽  
Dependent Protein ◽  
Cellular Compartmentalization

Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport is a longstanding fundamental question that still remains unanswered. Here, we conduct 3D simultaneous multicolor high-resolution live imaging to demonstrate in vivo that newly synthesized glycosylphosphatidylinositol-anchored proteins having a very long chain ceramide lipid moiety are clustered and sorted into specialized endoplasmic reticulum exit sites that are distinct from those used by transmembrane proteins. Furthermore, we show that the chain length of ceramide in the endoplasmic reticulum membrane is critical for this sorting selectivity. Our study provides the first direct in vivo evidence for lipid chain length–based protein cargo sorting into selective export sites of the secretory pathway.

scholarly journals Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride

2011 ◽  
Vol 61 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Komuravelly Someshwar ◽  
Kalyani Chithaluru ◽  
Tadikonda Ramarao ◽  
K. Kumar
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Release Kinetics ◽  
Hydroxypropyl Methylcellulose ◽  
Matrix Tablets ◽  
Physical Parameters ◽  
Floating Tablets ◽  
Gastric Residence Time

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.

scholarly journals Prenylation of Saccharomyces cerevisiae Chs4p Affects Chitin Synthase III Activity and Chitin Chain Length

2006 ◽  
Vol 6 (2) ◽  
pp. 328-336 ◽  
Author(s):  
Kariona A. Grabińska ◽  
Paula Magnelli ◽  
Phillips W. Robbins
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chain Length ◽  
Attachment Site ◽  
Chitin Synthase ◽  
Yeast Cells ◽  
Average Chain Length ◽  
Calcofluor White ◽  
Protein Factor

ABSTRACT Chs4p (Cal2/Csd4/Skt5) was identified as a protein factor physically interacting with Chs3p, the catalytic subunit of chitin synthase III (CSIII), and is indispensable for its enzymatic activity in vivo. Chs4p contains a putative farnesyl attachment site at the C-terminal end (CVIM motif) conserved in Chs4p of Saccharomyces cerevisiae and other fungi. Several previous reports questioned the role of Chs4p prenylation in chitin biosynthesis. In this study we reinvestigated the function of Chs4p prenylation. We provide evidence that Chs4p is farnesylated by showing that purified Chs4p is recognized by anti-farnesyl antibody and is a substrate for farnesyl transferase (FTase) in vitro and that inactivation of FTase increases the amount of unmodified Chs4p in yeast cells. We demonstrate that abolition of Chs4p prenylation causes a ∼60% decrease in CSIII activity, which is correlated with a ∼30% decrease in chitin content and with increased resistance to the chitin binding compound calcofluor white. Furthermore, we show that lack of Chs4p prenylation decreases the average chain length of the chitin polymer. Prenylation of Chs4p, however, is not a factor that mediates plasma membrane association of the protein. Our results provide evidence that the prenyl moiety attached to Chs4p is a factor modulating the activity of CSIII both in vivo and in vitro.

Preclinical Assessment of Nanostructured Liquid Crystalline Particles for the Management of Bacterial Keratitis: in-vivo and Pharmacokinetics Study

2021 ◽  
Author(s):  
Shreya Kaul ◽  
Upendra Nagaich ◽  
Navneet Verma
Keyword(s):  
Residence Time ◽  
Liquid Crystalline ◽  
Ex Vivo ◽  
Research Work ◽  
Poloxamer 407 ◽  
Pharmacokinetic Studies ◽  
Eye Drops ◽  
Statistical Experimental Design ◽  
Bacterial Keratitis

Abstract The research work was driven to develop novel nanostructured liquid crystalline particles of vancomycin for its improved pre-ocular residence time, ocular bio-availability, enhanced targeting, increased permeability, reduced dosing frequency, controlled drug release and reduced systemic side-effects. Formulation was developed by fragmenting cubic crystalline phase of glycerol monooleate, water and poloxamer 407. A four-factor, three-level Taguchi statistical experimental design was constructed to optimize the formulation. Formulations exhibited internal-cubic structure of the vesicles with particle size in the range of 51.11 ± 0.96 nm to 158.73 ± 0.46 nm and negative zeta potential. Ex-vivo transcorneal permeation studies demonstrated that the optimized cubosomes had 2.4-fold increase in apparent permeability co-efficient as compared to vancomycin solution. Whereas, in-vivo studies in rabbits demonstrated that the severity of keratitis was considerably lowered in day 3 with optimized cubosomes. Ocular pharmacokinetic studies evaluated level of drug in aqueous humor and results revealed that the time to peak concentration (Tmax) of vancomycin loaded cubosomal formulation was about 1.9-fold higher and mean residence time was 2.2-fold greater than vancomycin solution. Furthermore, histological examination revealed that the corneal layers displayed well-maintained morphology without any stromal swelling, consequently indicating safety of formulation. In conclusion, results manifested that the developed vancomycin loaded cubosomes could be a promising novel ocular carrier and an ideal substitute for conventional eye-drops for the management of bacterial-keratitis.

scholarly journals Single molecule tracking of Ace1p in Saccharomyces cerevisiae defines a characteristic residence time for non-specific interactions of transcription factors with chromatin

2016 ◽  
Vol 44 (21) ◽  
pp. e160-e160 ◽  
Author(s):  
David A Ball ◽  
Gunjan D Mehta ◽  
Ronit Salomon-Kent ◽  
Davide Mazza ◽  
Tatsuya Morisaki ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Residence Time ◽  
Single Molecule ◽  
Specific Binding ◽  
Underlying Mechanism ◽  
Specific Interactions ◽  
Single Molecule Tracking ◽  
Reliable Performance ◽  
Transient Interactions

Abstract In vivo single molecule tracking has recently developed into a powerful technique for measuring and understanding the transient interactions of transcription factors (TF) with their chromatin response elements. However, this method still lacks a solid foundation for distinguishing between specific and non-specific interactions. To address this issue, we took advantage of the power of molecular genetics of yeast. Yeast TF Ace1p has only five specific sites in the genome and thus serves as a benchmark to distinguish specific from non-specific binding. Here, we show that the estimated residence time of the short-residence molecules is essentially the same for Hht1p, Ace1p and Hsf1p, equaling 0.12–0.32 s. These three DNA-binding proteins are very different in their structure, function and intracellular concentration. This suggests that (i) short-residence molecules are bound to DNA non-specifically, and (ii) that non-specific binding shares common characteristics between vastly different DNA-bound proteins and thus may have a common underlying mechanism. We develop new and robust procedure for evaluation of adverse effects of labeling, and new quantitative analysis procedures that significantly improve residence time measurements by accounting for fluorophore blinking. Our results provide a framework for the reliable performance and analysis of single molecule TF experiments in yeast.

scholarly journals The relationship between lymphangion chain length and maximum pressure generation established through in vivo imaging and computational modeling

2017 ◽  
Vol 313 (6) ◽  
pp. H1249-H1260 ◽  
Author(s):  
Mohammad S. Razavi ◽  
Tyler S. Nelson ◽  
Zhanna Nepiyushchikh ◽  
Rudolph L. Gleason ◽  
J. Brandon Dixon
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Minimally Invasive ◽  
Chain Length ◽  
Maximum Pressure ◽  
Computational Simulations ◽  
A Chain ◽  
Lymphatic Pumping ◽  
The Relationship

The intrinsic contraction of collecting lymphatic vessels serves as a pumping system to propel lymph against hydrostatic pressure gradients as it returns interstitial fluid to the venous circulation. In the present study, we proposed and validated that the maximum opposing outflow pressure along a chain of lymphangions at which flow can be achieved increases with the length of chain. Using minimally invasive near-infrared imaging to measure the effective pumping pressure at various locations in the rat tail, we demonstrated increases in pumping pressure along the length of the tail. Computational simulations based on a microstructurally motivated model of a chain of lymphangions informed from biaxial testing of isolated vessels was used to provide insights into the pumping mechanisms responsible for the pressure increases observed in vivo. These models suggest that the number of lymphangions in the chain and smooth muscle cell force generation play a significant role in determining the maximum outflow pressure, whereas the frequency of contraction has no effect. In vivo administration of nitric oxide attenuated lymphatic contraction, subsequently lowering the effective pumping pressure. Computational simulations suggest that the reduction in contractile strength of smooth muscle cells in the presence of nitric oxide can account for the reductions in outflow pressure observed along the lymphangion chain in vivo. Thus, combining modeling with multiple measurements of lymphatic pumping pressure provides a method for approximating intrinsic lymphatic muscle activity noninvasively in vivo while also providing insights into factors that determine the extent that a lymphangion chain can transport fluid against an adverse pressure gradient. NEW & NOTEWORTHY Here, we report the first minimally invasive in vivo measurements of the relationship between lymphangion chain length and lymphatic pumping pressure. We also provide the first in vivo validation of lumped parameter models of lymphangion chains previously developed through data obtained from isolated vessel testing.

Prolonging the In Vivo Residence Time of Prostaglandin E1 with Biodegradable Nanoparticles

2008 ◽  
Vol 25 (7) ◽  
pp. 1686-1695 ◽  
Author(s):  
Tsutomu Ishihara ◽  
Miyuki Takahashi ◽  
Megumu Higaki ◽  
Mitsuko Takenaga ◽  
Tohru Mizushima ◽  
...  
Keyword(s):  
Residence Time ◽  
Prostaglandin E1 ◽  
Biodegradable Nanoparticles

Impact of PEG Chain Length on the Physical Properties and Bioactivity of PEGylated Chitosan/siRNA Nanoparticles in Vitro and in Vivo

2017 ◽  
Vol 9 (14) ◽  
pp. 12203-12216 ◽  
Author(s):  
Chuanxu Yang ◽  
Shan Gao ◽  
Frederik Dagnæs-Hansen ◽  
Maria Jakobsen ◽  
Jørgen Kjems
Keyword(s):  
Physical Properties ◽  
Chain Length ◽  
Peg Chain Length
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