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Optimal cpp

Tõnis Lehto, Luis Vasconcelos, Helerin Margus, Ricardo Figueroa, Margus Pooga, Mattias Hällbrink, Ulo Langel
Modifying cell-penetrating peptides (CPPs) with fatty acids has long been used to improve peptide-mediated nucleic acid delivery. In this study we have revisited this phenomenon with a systematic approach where we developed a structure-activity relationship to describe the role of the acyl chain length in the transfection process. For that we took a well-studied CPP, PepFect14, as the basis and varied its N-terminal acyl chain length from 2 to 22 carbons. To evaluate the delivery efficiency, the peptides were non-covalently complexed with a splice-correcting oligonucleotide (SCO) and tested in the HeLa pLuc705 reporter cell line...
February 17, 2017: Bioconjugate Chemistry
Sanjeev Sivakumar, Fabio S Taccone, Mohammed Rehman, Holly Hinson, Neeraj Naval, Christos Lazaridis
PURPOSE: To investigate multimodality systemic and neuro-monitoring practices in acute brain injury (ABI) and to analyze differences among "neurointensivists" (NI; clinical practice comprised >1/3 by neurocritical care), and other intensivists (OI). METHODS: Anonymous 22-question Web-based survey among physician members of SCCM and ESICM. RESULTS: Six hundred fifty-five responded (66% completion rate); 422 (65%) were OI, and 226 (35%) were NI...
January 21, 2017: Journal of Critical Care
Muhammad Vaseem Shaikh, Manika Kala, Manish Nivsarkar
Biodegradable nanoparticles (NPs) have gained tremendous interest for targeting chemotherapeutic drugs to the tumor environment. Inspite of several advances sufficient encapsulation along with the controlled release and desired size range have remained as considerable challenges. Hence, the present study examines the formulation optimization of doxorubicin loaded PLGA NPs (DOX-PLGA-NPs), prepared by single emulsion method for cancer targeting. Critical process parameters (CPP) were selected by initial screening...
January 24, 2017: European Journal of Pharmaceutical Sciences
A Kovács, Sz Berkó, E Csányi, I Csóka
The aim of our present work was to evaluate the applicability of the Quality by Design (QbD) methodology in the development and optimalization of nanostructured lipid carriers containing salicyclic acid (NLC SA). Within the Quality by Design methology, special emphasis is layed on the adaptation of the initial risk assessment step in order to properly identify the critical material attributes and critical process parameters in formulation development. NLC SA products were formulated by the ultrasonication method using Compritol 888 ATO as solid lipid, Miglyol 812 as liquid lipid and Cremophor RH 60® as surfactant...
March 1, 2017: European Journal of Pharmaceutical Sciences
Laurent Carteron, Fabio S Taccone, Mauro Oddo
Manipulation of blood pressure (BP) is a mainstay of therapy in patients with acute brain injury (ABI). In the early emergent phase (first hours from injury), depending on intracranial pathology, BP manipulation aims to 1) limit the progression of parenchymal hematomas or hemorrhagic transformation (in patients with ischemic/hemorrhagic stroke and aneurysmal subarachnoid hemorrhage [SAH]), and 2) attenuate hypoperfusion and secondary cerebral ischemic insults (in patients with traumatic brain injury [TBI])...
December 16, 2016: Minerva Anestesiologica
Christopher Hawthorne, Martin Shaw, Laura Moss, Ian Piper, Richard Elliott, Christine Lee, John Kinsella
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
Peter A Lee, Margaret Luce, Peter Bacher
BACKGROUND: Peak gonadotropin-releasing hormone or agonist (GnRHa) stimulated luteinizing hormone (LH) testing with leuprolide acetate (LA) is commonly used to document suppression during therapy for central precocious puberty (CPP). The objective of the study was to investigate suitability of using basal LH levels to monitor GnRHa treatment and to determine optimal transition from 1-month to 3-month LA formulations via a post hoc analysis of a randomized, open-label, 6-month study. METHODS: A total of 42 children with CPP, pretreated with 7...
November 1, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
Krista Freimann, Piret Arukuusk, Kaido Kurrikoff, Luís Daniel Ferreira Vasconcelos, Kadi-Liis Veiman, Julia Uusna, Helerin Margus, Alfonso T Garcia-Sosa, Margus Pooga, Ülo Langel
As the field of gene therapy progresses, an increasingly urgent need has arisen for efficient and non-toxic vectors for the in vivo delivery of nucleic acids. Cell-penetrating peptides (CPP) are very efficient transfection reagents in vitro, however, their application in vivo needs improvement. To enhance in vivo transfection we designed various CPPs based on previous knowledge of internalization studies and physiochemical properties of NickFect (NF) nanoparticles. We show that increment of the helicity of these Transportan10 analogues improves the transfection efficiency...
November 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Peter Lönn, Apollo D Kacsinta, Xian-Shu Cui, Alexander S Hamil, Manuel Kaulich, Khirud Gogoi, Steven F Dowdy
Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes...
2016: Scientific Reports
Kang Zhou, Shiwei He, Rui Song
Service routes optimization (SRO) of pallet service center should meet customers' demand firstly and then, through the reasonable method of lines organization, realize the shortest path of vehicle driving. The routes optimization of pallet service center is similar to the distribution problems of vehicle routing problem (VRP) and Chinese postman problem (CPP), but it has its own characteristics. Based on the relevant research results, the conditions of determining the number of vehicles, the one way of the route, the constraints of loading, and time windows are fully considered, and a chance constrained programming model with stochastic constraints is constructed taking the shortest path of all vehicles for a delivering (recycling) operation as an objective...
2016: Computational Intelligence and Neuroscience
Young Hyun Song, Eun Kyung Ji, Byung Woo Jeong, Mong Kwon Jung, Eun Young Kim, Dae Ho Yoon
We report on Y3Al5O12: Ce(3+) ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce(3+) concentration. The luminous properties of the Y3Al5O12: Ce(3+) CPP nano phosphor are improved when compared to the Y3Al5O12: Ce(3+) CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce(3+) CPP with an optimal Ce(3+) content of 0...
2016: Scientific Reports
A Kensche, S Pötschke, C Hannig, G Richter, W Hoth-Hannig, M Hannig
For the purpose of erosion prevention the present study aimed to compare the efficacy of two biomimetic products and a fluoride solution to optimize the protective properties of the pellicle. After 1 min of in situ pellicle formation on bovine enamel slabs, 8 subjects adopted CPP-ACP (GC Tooth Mousse), a mouthwash with hydroxyapatite microclusters (Biorepair), or a fluoride based mouthwash (elmex Kariesschutz) for 1 min each. Afterwards, samples were exposed in the oral cavity for 28 min. Native enamel slabs and slabs exposed to the oral cavity for 30 min without any rinse served as controls...
2016: TheScientificWorldJournal
Elodie Belnoue, Wilma Di Berardino-Besson, Hubert Gaertner, Susanna Carboni, Isabelle Dunand-Sauthier, Fabrice Cerini, Else-Marit Suso-Inderberg, Sébastien Wälchli, Stéphane König, Andres M Salazar, Oliver Hartley, Pierre-Yves Dietrich, Paul R Walker, Madiha Derouazi
Cell penetrating peptides (CPPs) from the protein ZEBRA are promising candidates to exploit in therapeutic cancer vaccines, since they can transport antigenic cargos into dendritic cells and induce tumor-specific T cells. Employing CPPs for a given cancer indication will require engineering to include relevant tumor-associated epitopes, administration with an appropriate adjuvant, and testing for antitumor immunity. We assessed the importance of structural characteristics, efficiency of in vitro transduction of target cells, and choice of adjuvant in inducing the two key elements in antitumor immunity, CD4 and CD8 T cells, as well as control of tumor growth in vivo...
September 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Loredana Luca, Alexandru Florin Rogobete, Ovidiu Horea Bedreag, Mirela Sarandan, Carmen Alina Cradigati, Marius Papurica, Anelore Gruneantu, Raluca Patrut, Corina Vernic, Corina Maria Dumbuleu, Dorel Sandesc
OBJECTIVE: Trauma patient requires a complex therapeutic management because of multiple severe injuries or secondary complications. The most significant injury found in patients with trauma is head injury, which has the greatest impact on mortality. Intracranial pressure (ICP) monitoring is required in severe traumatic head injury because it optimises treatment based on ICP values and cerebral perfusion pressure (CPP). METHODS: From a total of 64 patients admitted in the intensive care unit (ICU) 'Casa Austria', from the Polytraumatology Clinic of the Emergency County Hospital "Pius Brinzeu" Timisoara, Romania, between January 2014 and December 2014; only patients who underwent ICP monitoring (n=10) were analysed...
December 2015: Turkish Journal of Anaesthesiology and Reanimation
Marcel J H Aries, Robin Wesselink, Jan Willem J Elting, Joseph Donnelly, Marek Czosnyka, Ari Ercole, Natasha M Maurits, Peter Smielewski
OBJECTIVE: Cerebrovascular reactivity can provide a continuously updated individualized target for management of cerebral perfusion pressure, termed optimal cerebral perfusion pressure. The objective of this project was to find a way of improving the optimal cerebral perfusion pressure methodology by introducing a new visualization method. DATA SOURCES: Four severe traumatic brain injury patients with intracranial pressure monitoring. DATA EXTRACTION: Data were collected and pre-processed using ICM+ software...
October 2016: Critical Care Medicine
Edward Needham, Charles McFadyen, Virginia Newcombe, Anneliese J Synnot, Marek Czosnyka, David Menon
Traumatic brain injury (TBI) frequently triggers a disruption of cerebral autoregulation. The cerebral perfusion pressure (CPP) at which autoregulation is optimal ("CPPopt") varies between individuals, and can be calculated based on fluctuations between arterial blood pressure and intracranial pressure. This review assesses the effect of individualizing CPP targets to pressure reactivity index (a measure of autoregulation) in patients with TBI. Cochrane Central Register of Controlled Trials, MEDLINE®, Embase, and Cumulative Index of Nursing and Allied Health Literature were searched in March 2015 for studies assessing the effect of targeting CPPopt in TBI...
June 27, 2016: Journal of Neurotrauma
Karidia Konate, Mattias F Lindberg, Anaïs Vaissiere, Carole Jourdan, Gudrun Aldrian, Emmanuel Margeat, Sébastien Deshayes, Prisca Boisguerin
RNA interference provides a powerful technology for specific gene silencing. Therapeutic applications of small interfering RNA (siRNA) however require efficient vehicles for stable complexation and intracellular delivery. In order to enhance their cell delivery, short amphipathic peptides called cell-penetrating peptides (CPPs) have been intensively developed for the last two decades. In this context, the secondary amphipathic peptide CADY has shown to form stable siRNA complexes and to improve their cellular uptake independent of the endosomal pathway...
July 25, 2016: International Journal of Pharmaceutics
Victoria M Wu, Vuk Uskoković
BACKGROUND: Does chemistry govern biology or it is the other way around - that is a broad connotation of the question that this study attempted to answer. METHOD: Comparison was made between the solubility and osteoclastic resorbability of four fundamentally different monophasic calcium phosphate (CP) powders with monodisperse particle size distributions: alkaline hydroxyapatite (HAP), acidic monetite (DCP), β-calcium pyrophosphate (CPP), and amorphous CP (ACP)...
October 2016: Biochimica et Biophysica Acta
Bart Depreitere, Fabian Güiza, Greet Van den Berghe, Martin U Schuhmann, Gottlieb Maier, Ian Piper, Geert Meyfroidt
BACKGROUND: The concept of CPPopt, a variable cerebral perfusion pressure (CPP) target based on cerebrovascular autoregulatory capacity in severe traumatic brain injury (TBI), is promising. CPPopt calculation is based on the continuous plotting of the pressure reactivity Index (PRx) against CPP and requires processing of waveform quality data. The aim of this study is to investigate whether CPPopt can also be calculated based on minute-by-minute data. METHODS: A low-resolution autoregulation index (LAx) was defined as the minute-by-minute intracranial pressure-mean arterial pressure correlation over varying time intervals...
2016: Acta Neurochirurgica. Supplement
Carmen Nagel, Jennifer Diedler, Ines Gerbig, Ellen Heimberg, Martin U Schuhmann, Konstantin Hockel
OBJECTIVE: It could be shown in adults with severe traumatic brain injury (TBI) that the functional status of cerebrovascular autoregulation (AR), determined by the pressure reactivity index (PRx), correlates with and even predicts outcome. We investigated PRx and its correlation with outcome in infant and pediatric TBI. Methods Ten patients (median age 2.8 years, range 1 day to 14 years) with severe TBI (Glasgow Coma Scale score <9 at presentation) underwent long-term computerized intracranial pressure (ICP) and mean arterial pressure (MAP) monitoring using dedicated software for continuous determination of cerebral perfusion pressure (CPP) and PRx...
2016: Acta Neurochirurgica. Supplement
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