Editorial Board

Publication date: January 2017
Source:Acta Oecologica, Volume 78





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Pilot study: Post-operative rehabilitation pathway changes and implementation of functional closed kinetic chain exercise in total hip and total knee replacement patient

Publication date: Available online 18 January 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): C. Abbas, J. Daher
ObjectiveThe aim of this study was to assess the feasibility of introducing a functional closed kinetic chain exercise program to an acute care setting to reduce length of hospital stay and assess tolerance to exercise immediately following total hip or total knee arthroplasty.MethodsA protocol change implementing a functional closed kinetic chain based exercise program, post total hip (n = 535) and total knee (n = 695) arthroplasty, was performed at Windsor Regional Hospital Ouellette Campus in Windsor, Ontario Canada. A chart review was performed to compare the length of stay, post-surgery, of the new protocol to the length of stay of the previous range of motion and open kinetic chain based protocols of the previous two years.ResultsA significant (P-value <0.05) number of total hip and total knee arthroplasty patients reduced the length of hospital stay to less than 4 days using the closed kinetic chain program.ConclusionEvidence suggests that closed kinetic chain exercises are tolerated in the acute care setting and may be useful in reducing hospital length of stay post total hip and total knee arthroplasty.



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A novel and sensitive fluorescence sensor for glutathione detection by controlling the surface passivation degree of carbon quantum dots

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Jiahong Pan, Zengyao Zheng, Jianying Yang, Yaoyu Wu, Fushen Lu, Yaowen Chen, Wenhua Gao
A novel fluorescence sensor based on controlling the surface passivation degree of carbon quantum dots (CQDs) was developed for glutathione (GSH) detection. First, we found that the fluorescence intensity of the CQDs which was obtained by directly pyrolyzing citric acid would increased largely after the surface passivation treatment by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). In the light of this phenomenon, we designed a simple, rapid and selective fluorescence sensor based on the surface passivated CQDs. A certain and excess amount of EDC were mixed with GSH, part of EDC would form a stable complex with GSH owing to the exposed sulfhydryl group of GSH. As the synthesized CQDs were added into the above mixture solution, the fluorescence intensity of the (EDC/GSH)/CQDs mixture solution could be directly related to the amount of GSH. Compared to other fluorescence analytical methods, the fluorescence sensor we design is neither the traditional fluorescent "turn on" probes nor "turn off" probes. It is a new fluorescence analytical method that target object indirectly control the surface passivation degree of CQDs so that it can realize the detection of the target object. Moreover, the proposed method manifested great advantages including short analysis time, low cost and ease of operation.

Graphical abstract

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Spinel-type manganese ferrite (MnFe2O4) microspheres: A novel affinity probe for selective and fast enrichment of phosphopeptides

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Xing-Yu Long, Jia-Yuan Li, Dong Sheng, Hong-Zhen Lian
The spinel-type magnetic manganese ferrite (MnFe2O4) microspheres synthesized by simple solvothermal method were used as a novel adsorbent for selective enrichment and effective isolation of phosphopeptides. The uniform MnFe2O4 magnetic affinity microspheres (MAMSs) had a narrow particle size distribution between 250 and 260nm, and displayed superparamagnetism with a saturation magnetization value of 67.0emu/g. Comprehensively, the possible formation mechanism of MnFe2O4 microspheres with ferric and manganous sources as dual precursors was elucidated by comparison with those of Fe3O4 nanoparticles and MnOOH nanosheets respectively with either ferric or manganous source as single precursor. It was suggested that the spherical or sheet nanostructures could be achieved via secondary recrystallization or Ostwald ripening. The MnFe2O4 MAMSs probe exhibited excellent dispersibility in aqueous solution, and rapid magnetic separation within 15s, as well as good reusability. More importantly, MnFe2O4 was highly selective for phosphopeptides because of the strong coordination interaction between metal ions (Fe³⁺ and Mn²⁺) and phosphate groups of phosphopeptdies. This high specificity was demonstrated by effectively enriching phosphopeptides from digest mixture of β-casein and bovine serum albumin (BSA) with high content of non-phosphopeptides, and embodied further in phosphopeptides enrichment from non-fat milk digests and human serum. Consequently, the prepared MnFe2O4 affinity materials are expected to possess great potential in phosphoproteome research.

Graphical abstract

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Contraceptive use and its determinants amongst armed forces personnel

Publication date: Available online 17 January 2017
Source:Medical Journal Armed Forces India
Author(s): R.N. Hiremath, A.K. Yadav, Sandhya Ghodke, Jyoti Yadav
BackgroundNearly 1.5 billion adolescent girls are entering into child bearing age groups without effective knowledge regarding family planning practices which are essential to maintain their reproductive health. Timely and effective knowledge regarding family planning norms and practices among the young women during their initial married days are vital. Therefore the study was carried out with the aim to find out the factors associated with use of contraceptive among Armed Forces Personnel.MethodsA cross sectional survey was carried out among Armed Forces personnel living in a Military station with pre-validated and pre-tested questionnaire. Data was collected from 221 eligible couples. Univariate and logistic regression were done to find out the variables determining family planning.ResultsOut of 221 couples, 65.2% (144) of couples were practicing some or the other methods of family planning while 34.8% (77) didn't practice any methods. Age, age at marriage, sex of first child, type of family, empowerment and parity of women were significantly associated with contraceptive acceptance in univariate model. However in logistic regression analysis age at marriage, empowerment and parity were significant predictors of family planning. Major reason for not adopting any contraception was want of another child (20, 26%), girl child (18, 23%), male child (18, 23%) and worry about side effects (11, 14.3%).ConclusionThe study highlights the gap in preferences and practices of contraceptive and emphasized the need to highlight safety of contraceptive during Information, Education and Communication (IEC) campaign.



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Painful immunoglobulin G4-related thyroiditis treated by total thyroidectomy.

Related Articles

Painful immunoglobulin G4-related thyroiditis treated by total thyroidectomy.

Korean J Intern Med. 2016 Mar;31(2):399-402

Authors: Lee IS, Lee JU, Lee KJ, Jang YS, Lee JM, Kim HS

PMID: 26932403 [PubMed - indexed for MEDLINE]

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Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration.

Related Articles

Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration.

MBio. 2017 Jan 17;8(1):

Authors: Uhlemann AC, McAdam PR, Sullivan SB, Knox JR, Khiabanian H, Rabadan R, Davies PR, Fitzgerald JR, Lowy FD

Abstract
Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance.
IMPORTANCE: Unlike methicillin-resistant Staphylococcus aureus (MRSA), surprisingly little is known about the clonal evolution of methicillin-susceptible S. aureus (MSSA), although these strains account for the majority of S. aureus infections. To better understand how MSSA spreads and becomes established in communities, we applied comparative bacterial whole-genome sequencing to pandemic ST398-MSSA, a clone of clinical importance affecting humans and livestock in different geographic regions. Phylogeographic analyses identified that ST398-MSSA spread along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. We observed high within-host SNP variability compared to our previous studies on the dominant MRSA clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300 MRSA and ST398 MSSA.

PMID: 28096484 [PubMed - in process]

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Guided growth of auditory neurons: Bioactive particles towards gapless neural – electrode interface

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Hao Li, Fredrik Edin, Hisamitsu Hayashi, Olafur Gudjonsson, Niklas Danckwardt-Lillieström, Håkan Engqvist, Helge Rask-Andersen, Wei Xia
Cochlear implant (CI) is a successful device to restore hearing. Despite continuous development, frequency discrimination is poor in CI users due to an anatomical gap between the auditory neurons and CI electrode causing current spread and unspecific neural stimulation. One strategy to close this anatomical gap is guiding the growth of neuron dendrites closer to CI electrodes through targeted slow release of neurotrophins. Biodegradable calcium phosphate hollow nanospheres (CPHSs) were produced and their capacity for uptake and release of neurotrophins investigated using ¹²⁵I-conjugated glia cell line-derived neurotrophic factor (GDNF). The CPHSs were coated onto CI electrodes and loaded with neurotrophins. Axon guidance effect of slow-released neurotrophins from the CPHSs was studied in an in vitro 3D culture model. CPHS coating bound and released GDNF with an association rate constant 6.3 × 10³ M⁻¹s⁻¹ and dissociation rate 2.6 × 10⁻⁵ s⁻¹, respectively. Neurites from human vestibulocochlear ganglion explants found and established physical contact with the GDNF-loaded CPHS coating on the CI electrodes placed 0.7 mm away. Our results suggest that neurotrophin delivery through CPHS coating is a plausible way to close the anatomical gap between auditory neurons and electrodes. By overcoming this gap, selective neural activation and the fine hearing for CI users become possible.



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Safety and efficacy of cardiopoietic stem cells in the treatment of post-infarction left-ventricular dysfunction – From cardioprotection to functional repair in a translational pig infarction model

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Maximilian Y. Emmert, Petra Wolint, Andras Jakab, Sean P. Sheehy, Francesco S. Pasqualini, Thi Dan Linh Nguyen, Monika Hilbe, Burkhardt Seifert, Benedikt Weber, Chad E. Brokopp, Dominika Macejovska, Etem Caliskan, Arnold von Eckardstein, Ruth Schwartlander, Viola Vogel, Volkmar Falk, Kevin Kit Parker, Mariann Gyöngyösi, Simon P. Hoerstrup
To date, clinical success of cardiac cell-therapies remains limited. To enhance the cardioreparative properties of stem cells, the concept of lineage-specification through cardiopoietic-guidance has been recently suggested. However, so far, only results from murine studies and from a clinical pilot-trial in chronic heart-failure (CHF) are available, while systematic evidence of its therapeutic-efficacy is still lacking. Importantly, also no data from large animals or for other indications are available. Therefore, we here investigate the therapeutic-efficacy of human cardiopoietic stem cells in the treatment of post-infarction LV-dysfunction using a translational pig-model. Using growth-factor priming, lineage-specification of human bone-marrow derived MSCs was achieved to generate cardiopoietic stem cells according to GMP-compliant protocols. Thereafter, pigs with post-infarction LV-dysfunction (sub-acute phase;1-month) were randomized to either receive transcatheter NOGA 3D electromechanical-mapping guided intramyocardial transplantation of cardiopoietic cells or saline (control). After 30days, cardiac MRI (cMRI) was performed for functional evaluation and in-vivo cell-tracking. This approach was coupled with a comprehensive post-mortem cell-fate and mode-of-repair analysis. Cardiopoietic cell therapy was safe and ejection-fraction was significantly higher when compared to controls (p = 0.012). It further prevented maladaptive LV-remodeling and revealed a significantly lower relative and total infarct-size (p = 0.043 and p = 0.012). As in-vivo tracking and post-mortem analysis displayed only limited intramyocardial cardiopoietic cell-integration, the significant induction of neo-angiogenesis (∼40% higher; p = 0.003) and recruitment of endogenous progenitors (∼2.5x higher; p = 0.008) to the infarct border-zone appeared to be the major modes-of-repair. This is the first report using a pre-clinical large animal-model to demonstrate the safety and efficacy of cardiopoietic stem cells for the treatment of post-infarction LV-dysfunction to prevent negative LV-remodeling and subsequent CHF. It further provides insight into post-delivery cardiopoietic cell-fate and suggests the mechanisms of cardiopoietic cell-induced cardiac-repair. The adoption of GMP-/GLP-compliant methodologies may accelerate the translation into a phase-I clinical-trial in patients with post-ischemic LV-dysfunction broadening the current indication of this interesting cell-type.



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Targeting NF-kB signaling with polymeric hybrid micelles that co-deliver siRNA and dexamethasone for arthritis therapy

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Qin Wang, Hao Jiang, Yan Li, Wenfei Chen, Hanmei Li, Ke Peng, Zhirong Zhang, Xun Sun
The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers: polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing either Dex or siRNA on their own. In addition, the co-delivery system was able to switch macrophages from the M1 to M2 state. Injecting hybrid micelles containing Dex and siRNA into mice with collagen-induced arthritis led the therapeutic agents to accumulate in inflamed joints and reduce inflammation, without damaging renal or liver function. Thus, blocking NF-kB activation in inflammatory tissue using micelle-based co-delivery may provide a new approach for treating inflammatory disease.



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A π-π conjugation-containing soft and conductive injectable polymer hydrogel highly efficiently rebuilds cardiac function after myocardial infarction

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Rui Bao, Baoyu Tan, Shuang Liang, Ning Zhang, Wei Wang, Wenguang Liu
Previous studies suggested that a stiffer hydrogel system exhibited a better performance to promote heart function after myocardial infarction (MI). However, the nature of myocardium, a tissue that alternately contracts and relaxes with electrical impulses, leads us to hypothesize that a soft and conductive hydrogel may be in favor of mechanical and electrical signals transmission to enhance heart function after MI. In this work, π-π conjugation interaction was first employed to produce a soft injectable hydrogel with conductive property. Melamine with π-π conjugation ring was used as a core to synthesize a multi-armed crosslinker PEGDA700-Melamine (PEG-MEL), which could crosslink with thiol-modified hyaluronic acid (HA-SH) to form an injectable hydrogel rapidly. By incorporating graphene oxide (GO), the injectable PEG-MEL/HA-SH/GO hydrogel exhibited a soft (G' = 25 Pa) and anti-fatigue mechanical property and conductive property (G = 2.84 × 10⁻⁴ S/cm). The hydrogel encapsulating adipose tissue-derived stromal cells (ADSCs) was injected into MI area of rats. The significant increase in α-Smooth Muscle Actin (α-SMA) and Connexin 43 (Cx43) expression confirmed that the gel efficiently promoted the transmission of mechanical and electrical signals. Meanwhile, a significant improvement of heart functions, such as distinct increase of ejection fraction (EF), smaller infarction size, less fibrosis area, and higher vessel density, was achieved.



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A simple and powerful co-delivery system based on pH-responsive metal-organic frameworks for enhanced cancer immunotherapy

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Fei Duan, Xiaochen Feng, Xinjian Yang, Wentong Sun, Yi Jin, Huifang Liu, Kun Ge, Zhenhua Li, Jinchao Zhang
Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy. However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8⁺ cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm. TAAs can be loaded into MOFs in the one-pot synthesis process and released with the degradation of MOFs in the acidic environment of endo/lysosome as the result of relatively labile metal-ligand bonds. The endosomolytic nanoparticles would facilitate protein antigens escape from endo/lysosome and optimal for enhancing antigen cross-presentation. Furthermore, the introduction of immunostimulatory unmethylated cytosine-phosphate-guanine oligonucleotide (CpG) through Watson−Crick base pairing would further enhance CD8⁺ cytotoxic T lymphocyte responses. We demonstrated that the method to co-delivery antigens and immunostimulatory molecules was very simple, convenient and effective and showed no obvious toxicity both in vitro and in vivo. This method gave a high antigens-loading capacity and the maximal antigen encapsulating efficiency was about 55% (w/w). Additionally, the pH-responsive co-delivery system exerted enhanced antitumor outcome (about 100% survival) in B16-OVA melanoma cancers in vivo. Furthermore, we confirmed that this high rating of therapeutic effect was attributed to the recruitment of tumor-killing immunocyte. This work demonstrates the ability of pH-responsive, endosomolytic MOFs to induce strong cellular immune responses for cancer therapy by co-delivery of CpG ODN and antigens.



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Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Xin Zhao, Hao Wu, Baolin Guo, Ruonan Dong, Yusheng Qiu, Peter X. Ma
Injectable self-healing hydrogel dressing with multifunctional properties including anti-infection, anti-oxidative and conductivity promoting wound healing process will be highly desired in wound healing application and its design is still a challenge. We developed a series of injectable conductive self-healed hydrogels based on quaternized chitosan-g-polyaniline (QCSP) and benzaldehyde group functionalized poly(ethylene glycol)-co-poly(glycerol sebacate) (PEGS-FA) as antibacterial, anti-oxidant and electroactive dressing for cutaneous wound healing. These hydrogels presented good self-healing, electroactivity, free radical scavenging capacity, antibacterial activity, adhesiveness, conductivity, swelling ratio, and biocompatibility. Interestingly, the hydrogel with an optimal crosslinker concentration of 1.5 wt% PEGS-FA showed excellent in vivo blood clotting capacity, and it significantly enhanced in vivo wound healing process in a full-thickness skin defect model than quaternized chitosan/PEGS-FA hydrogel and commercial dressing (Tegaderm™ film) by upregulating the gene expression of growth factors including VEGF, EGF and TGF-β and then promoting granulation tissue thickness and collagen deposition. Taken together, the antibacterial electroactive injectable hydrogel dressing prolonged the lifespan of dressing relying on self-healing ability and significantly promoted the in vivo wound healing process attributed to its multifunctional properties, meaning that they are excellent candidates for full-thickness skin wound healing.



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TLR9 mediated regulatory B10 cell amplification following sub-total body irradiation: Implications in attenuating EAE

Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Jinsheng Hong, Jie Fang, Ruilong Lan, Qi Tan, Yeping Tian, Mei Zhang, Paul Okunieff, Lurong Zhang, Jianhua Lin, Deping Han
Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%–3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5Gy or 10Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9^−/− mice. TLR9 agonist ODN1826 stimulation in vitro for 5h induced more B10 cells to express cytoplasmic IL-10 in sub-TBI WT mice than in TLR9^−/− mice. Prolonged ODN1826 stimulation (48h) induced additional spleen CD19^hiCD5⁺CD1d^hi B cells to express IL-10. TLR9-dependent signaling molecules, MyD88, TRAF6 and IRF8 are involved in sub-TBI induced Breg/B10 cells development and expansion. Furthermore, using a mouse model for multiple sclerosis, we show here that sub-TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established experimental autoimmune encephalomyelitis (EAE). Adoptively transferred sub-TBI induced Breg cells significantly suppress inflammatory T cell responses of TH17 and TH1 types in EAE mice. In conclusion, sub-TBI can drive Breg/B10 cell development and expansion, which could be used as a novel tool for suppressing undesirable immunity. The ex vivo expansion and reinfusion of autologous Breg/B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.



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Thiolated polymers as mucoadhesive drug delivery systems

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Sarah Duggan, Wayne Cummins, Orla O' Donovan, Helen Hughes, Eleanor Owens
Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices.

Graphical abstract

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An innovative polysaccharide nanobased nail formulation for improvement of onychomycosis treatment

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Fernanda C. Flores, Roberta S. Rosso, Letícia Cruz, Ruy C.R. Beck, Cristiane B. Silva
Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL⁻¹), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid^® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.

Graphical abstract

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Generation of quercetin/cellulose acetate phthalate systems for delivery by supercritical antisolvent process

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): I. García-Casas, A. Montes, C. Pereyra, E.J. Martínez de la Ossa
Supercritical antisolvent process (SAS) has been used to precipitate microparticles of quercetin, a plant pigment found in many foods and used for medical treatments, pharmaceutical and cosmetic industries, together with nanoparticles of cellulose acetate phthalate (CAP), a polymer quite frequently used in drug delivery. Previously, precipitation of nanoparticles of CAP by the same process was studied at different conditions of pressure, temperature, CO2 and solution flow rates, nozzle diameter and initial concentration of the solution. Morphologies of the precipitates were analyzed by scanning electron microscopy (SEM). A range between 84 and 145nm of diameter in spherical particle were achievement in CAP precipitation. A same range of semi-spherical particles of CAP around 145nm and needle-like particle of quercetin was obtained in the coprecipitation experiments. X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) were carried out to find out the possible loss of crystallinity of the coprecipitates and the possible interactions between the polymer and quercetin, respectively. Release profiles of quercetin were carried out in simulated gastric and intestinal fluids. Higher quercetin:polymer ratios in the coprecipitates are recommended to achieve faster release and higher solubilities of quercetin in the assayed time. This fact would allow its use in pharmaceutical, cosmetic or nutraceutical applications.

Graphical abstract

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Sorption of organic phosphates and its effects on aggregation of hematite nanoparticles in monovalent and bivalent solutions

Abstract

Sorption of organic phosphates–myo-inositol hexakisphosphate (IHP) and glycerol phosphate (GP) and its effects on the early stage of hematite aggregation kinetics were investigated at different pH and electrolyte composition. KH₂PO₄ (KP) was taken as an inorganic P source for comparison. Results indicated that for all types of P, the sorption amounts decreased with increasing solution pH. Sorption amount of IHP was almost two times that of KP, while those of GP and KP were close. Both organic P and inorganic P interacted with hematite via ligand exchange through their phosphate groups, which conveyed negative charges to mineral surface and significantly decreased the zeta potential of hematite. In Na⁺ solution, critical coagulation concentrations (CCCs) of hematite suspensions increased with increasing P concentration and followed the order of KP < GP < IHP at pH 5.5. Compared with KP, the organic P could more effectively stabilize the hematite suspension not only through increasing the negative charges and electrostatic repulsive force, but also through steric repulsion between P-sorbed hematite nanoparticles. When the pH was increased from 5.5 to 10.0, the CCCs of the hematite suspensions with GP and IHP decreased mainly because of the great reductions in organic P sorption amounts and consequent decreases in electrostatic and steric repulsive forces. However, enhanced aggregation was observed in the presence of IHP at pH 4.5 and above in low Ca²⁺ solutions. The precipitation of calcium phytate formed net-like structure, which served as bridges to bind hematite nanoparticles and resulted in enhanced aggregation. These results have important implications for assessing the fate and transport of organic P and hematite nanoparticles in soil and aquatic environments.

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Myeloprotective effects of C-type natriuretic peptide on cisplatin-induced bone marrow granulocytopenia in mice

Abstract

Purpose

Cisplatin is an effective chemotherapeutic agent used to treat a variety of malignant tumors. The major toxicity associated with cisplatin treatment is granulocytopenia. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, protects against toxicity in many organs, including the heart, blood vessels, lung, and kidney. The objective of this study was to investigate the myeloprotective effects of CNP in a mouse model of cisplatin-induced granulocytopenia.

Methods

The mice were divided into two groups: cisplatin with vehicle and cisplatin with CNP. CNP (2.5 μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started two day before cisplatin injection, and continued until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), we counted total and living cells and granulocyte/macrophage colony-forming units (CFU-GM) in bone marrow. In addition, at 0, 1, 2, and 4 days after cisplatin injection, we measured mRNA levels of CXC chemokine receptor 4 (CXCR4) and chemokine CXC ligand 12 (CXCL12) in bone marrow.

Results

CNP significantly attenuated the reduction in bone marrow nucleated cell count and CFU-GM in bone marrow at 4 days after cisplatin injection. Four days after cisplatin injection, CNP significantly decreased the CXCR4 mRNA level in bone marrow, but had no effect on the level of CXCL12 mRNA.

Conclusions

CNP exerts myeloprotective effects in cisplatin-induced granulocytopenia and decreases CXCR4 expression.

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A mini-review of c-Met as a potential therapeutic target in melanoma

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Doa'a G.F. Al-U'datt, Belal A.A. Al-Husein, Ghazi Raji Qasaimeh
Melanoma is the third highest rated cancer in prevalence. Surgery, radiotherapy and targeted/biological therapies in addition to chemotherapy are available options for management of this cancer. Met is an appealing target for management of this type of cancer, since it targets many cancer vital processors, such as angiogenesis, cell growth, scattering and differentiation. In this review, we provide an overview about pathway abnormalities associated with melanoma. We also provide a summary about the events involved in Met signaling and related signaling molecules. We also show the evidence of the importance of Met signaling pathway as a target in cancer management. We also summarize clinical evidence about the use of Met signaling in management of cancer and summarize available trials related to targeting Met in other cancers.



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