Use of single-chain antibody derivatives for targeted drug delivery

Single-chain antibodies (scFvs), which contain only the variable domains of full-length antibodies, are relatively small molecules that can be used for selective drug delivery. In this review, we discuss how scFvs help improve the specificity and efficiency of drugs. Small interfering RNA (siRNA) delivery using scFv-drug fusion peptides, siRNA delivery using scFv-conjugated nanoparticles, targeted delivery using scFv-viral peptide-fusion proteins, use of scFv in fusion with cell-penetrating peptides for effective targeted drug delivery, scFv-mediated targeted delivery of inorganic nanoparticles, scFv-mediated increase of tumor killing activity of granulocytes, use of scFv for tumor imaging, site-directed conjugation of scFv molecules to drug carrier systems, use of scFv to relieve pain and use of scFv for increasing drug loading efficiency are among the topics that are discussed here. © 2016, University of Michigan. All rights reserved

Optimal Control of HIV Dynamic Using Embedding Method

This present study proposes an optimal control problem, with the final goal of implementing an optimal treatment protocol which could maximize the survival time of patients and minimize the cost of drug utilizing a system of ordinary differential equations which describes the interaction of the immune system with the human immunodeficiency virus (HIV). Optimal control problem transfers into a modified problem in measure space using an embedding method in which the existence of optimal solution is guaranteed by compactness of the space. Then the metamorphosed problem is approximated by a linear programming (LP) problem, and by solving this LP problem a suboptimal piecewise constant control function, which is more practical from the clinical viewpoint, is achieved. The comparison between the immune system dynamics in treated and untreated patients is introduced. Finally, the relationships between the healthy cells and virus are shown

The Prevalence of Restless Legs Syndrome in Patients Undergoing Hemodialysis: A Systematic Review and Meta-analysis Study

Introduction: Restless legs syndrome is a sensory-motor disorder that causes sleep disorder. The syndrome in patients undergoing hemodialysis associates with depression, sleep deprivation, performance disorder, day fatigue, excessive daytime sleepiness, stress, anxiety, and higher risk of cardiovascular diseases. The objective of this systematic meta-analysis study was to estimate prevalence of restless legs syndrome in patients undergoing hemodialysis. Methods: Twenty-six relevant articles published between 2000 and 2015 indexed in Iranian (MagIran and IranMedex) and international databases (SID, Google Scholar, ScienceDirect, PubMed, Pre Quest, and Scopus) were selected. Data analysis was carried out through metaanalysis (random effect model) and heterogeneity of the studies was determined using I2 index. The obtained data were analyzed in STAT (11.2). Results: Prevalence of the syndrome according to the found articles was 50 (95 CI: 38-61) in Iranian and 30 (95 CI: 23-37) in international databases. There was an ascending trend of prevalence of the syndrome corresponding to the publication year of the articles (P= 0.419), while the trend based on age of the patients was descending (P= 0.604). However, the variations were not significant. Conclusion: Given the high prevalence and considerable effects of restless legs syndrome on patients undergoing hemodialysis, it is recommended that these patients be screened for the syndrome

Keratin 13 is a more specific marker of conjunctival epithelium than keratin 19

PurposeTo evaluate the expression patterns of cytokeratin (K) 12, 13, and 19 in normal epithelium of the human ocular surface to determine whether K13 could be used as a marker for conjunctival epithelium.MethodsTotal RNA was isolated from the human conjunctiva and central cornea. Those transcripts that had threefolds or higher expression levels in the conjunctiva than the cornea were identified using microarray technique. Expression levels of three known signature genes and of two conjunctival genes, K13 and K19 were confirmed by using quantitative real-time PCR (qRT-PCR). Protein expression of K12, K13, and K19 was confirmed by immunostaining with specific antibodies on histologic sections of human sclerocornea that contained the conjunctiva, limbus, and cornea and on impression cytology (IC) specimens of the cornea and conjunctiva from normal donors. Double staining of K13/K12 and K19/K12 on histologic sections and IC specimens was performed.ResultsThere were 337 transcripts that were preferentially expressed in the conjunctiva. K13 and K19 were among the top twenty transcripts in the conjunctiva and this preferential expression pattern of K13 and K19 was confirmed by qRT-PCR. Immunohistochemical studies showed that K13 was expressed at the posterior limbal epithelium and conjunctival epithelium but was totally absent in the cornea. K12 was expressed in the corneal and anterior limbal epithelia except for the basal layer and was absent from the conjunctiva. In contrast, K19 was detected in the corneal, limbal and conjunctival epithelia. Immunostaining of the IC specimens showed K12(+) epithelial cells in the corneal region, K13(+) cells in the conjunctival area, and K19(+) cells in the corneal and conjunctival specimens. Expression of K13 and K12 on the ocular surface was mutually exclusive on both the histologic and IC samples using double immunostaining.ConclusionsK13 is more specific to the conjunctival epithelial cells than K19 and potentially could be used as a marker to identify conjunctival epithelial cells in limbal stem cell deficiency

Descripción matemática del desempeño electroanalítico de nanopartículas de derivados de níquel en la determinación cualitativa y cuantitativa de metanol

En este trabajo se desarrolló y se analizó, por medio de la teoría de estabilidad lineal y del análisis de bifurcaciones, el modelo matemático con que fue descrito el desempeño de nanopartículas de los derivados de níquel (solas y en compositos con el polímero conductor) en la determinación de metanol en el medio alcalino. Mediante el modelaje matemático, se derivaron las condiciones de estabilidad del estado estacionario, e inferidas las causas generales del comportamiento oscilatorio y monotónico. Los resultados del modelaje se compararon con los datos experimentales.In this work, the mathematical model for the electroanalytical action of Ni-containing nanoparticles (by themselves and in a composite with a conducting polymer) in electrochemical qualitative and quantitative methanol detection in alkaline media is developed and analyzed by using of linear stability theory and bifurcation analysis. By the mathematical modeling, the steady-state stability conditions (the most exact sensing action requirements) and the causes for oscillatory and monotonic instabilities are derived. The result of the modeling is compared with the experimental data

Is vascular endothelial growth factor a useful biomarker in giant cell arteritis?

Objectives To assess the performance of circulating vascular endothelial growth factor (VEGF) levels as a tool for diagnosing giant cell arteritis (GCA) in a cohort of patients referred for assessment of suspected GCA. Methods We selected 298 patients recruited to the multicentre study Temporal Artery Biopsy versus Ultrasound in diagnosis of suspected GCA (TABUL). In a random subset of 26 biopsy-proven GCA cases and 26 controls, serum from weeks 0, 2 and 26 was analysed for VEGF concentration using ELISA. VEGF concentration at week 0 was used to generate a receiver-operating characteristic curve and thereby identify a cut-off for an abnormal result which was used to analyse the full patient cohort. Sections of paraffin-embedded temporal artery were stained by immunohistochemistry for VEGF. Results The mean (95% CI) VEGF concentration at week 0 was 873 pg/mL (631 to 1110) in 26 patients versus 476 pg/mL (328 to 625) in 26 controls (p=0.017). This difference was not observed at any other time point. The optimal cut-off of 713 pg/mL was applied to the whole patient cohort (n=298), yielding sensitivity of 32% and specificity of 85%. This was not improved by combination with any clinical parameters. When patients with biopsy-proven GCA were compared with controls, sensitivity was 58% and specificity remained 85%. Sections of biopsy from biopsy-positive GCA showed intense staining in the adventitia which was not seen in controls. Conclusions Serum VEGF concentration predicts biopsy positivity but is not useful for differentiating clinical cases of GCA from controls. Further studies into VEGF as a prognostic marker and therapeutic target are warranted. Trial registration number NCT00974883; Post-results

Holographic dark energy with time varying c2c^2 parameter

We consider the holographic dark energy model in which the model parameter $c^2$ evolves slowly with time. First we calculate the evolution of EoS parameter as well as the deceleration parameter in this generalized version of holographic dark energy (GHDE). Depending on the parameter $c^2$, the phantom regime can be achieved earlier or later compare with original version of holographic dark energy. The evolution of energy density of GHDE model is investigated in terms of parameter $c^2$. We also show that the time-dependency of $c^2$ can effect on the transition epoch from decelerated phase to accelerated expansion. Finally, we perform the statefinder diagnostic for GHDE model and show that the evolutionary trajectories of the model in $s-r$ plane are strongly depend on the parameter $c^2$.Comment: 16 pages, 4 figures, accepted by Astrophys Space Sc

Protective Antiviral Immunity Conferred by a Nonintegrative Lentiviral Vector-Based Vaccine

Lentiviral vectors are under intense scrutiny as unique candidate viral vector vaccines against tumor and aggressive pathogens because of their ability to initiate potent and durable specific immune responses. Strategies that alleviate safety concerns will facilitate the clinical developments involving lentiviral vectors. In this respect, the development of integration deficient lentiviral vectors circumvents the safety concerns relative to insertional mutagenesis and might pave the way for clinical applications in which gene transfer is targeted to non-dividing cells. We thus evaluated the potential use of nonintegrative lentiviral vectors as vaccination tools since the main targeted cell in vaccination procedures is the non-dividing dendritic cell (DC). In this study, we demonstrated that a single administration of nonintegrative vectors encoding a secreted form of the envelope of a virulent strain of West Nile Virus (WNV) induces a robust B cell response. Remarkably, nonintegrative lentiviral vectors fully protected mice from a challenge with a lethal dose of WNV and a single immunization was sufficient to induce early and long-lasting protective immunity. Thus, nonintegrative lentiviral vectors might represent a safe and efficacious vaccination platform for the development of prophylactic vaccines against infectious agents