Comparative morphology,anatomy and palynological studies of perennial species of Onobrychis (Fabaceae) in northeast Iran

This study examined morphological, anatomical and palynological characters for six species, two subspecies and two varieties of perennial Onobrychis growing in northeast Iran. In the morphological study, shape, size and color of vegetative organs and legumes were assessed. For the anatomical study, cross sections of mature fresh or dried stems, leaflets and petioles were prepared and stained. In the palynological study, pollen were extracted, acetolysed and observed by SEM. The morphological study indicated that some characteristics varied among species, such as shape of stipules and calyx teeth, color and shape of corolla segments and legumes and an identification key is provided based on these characters. Also, in internal structure some differences were noticed in the shape of petiole cross sections, the thickness of cortex and pith shape in petioles and the arrangement of vessels in stems. Some anatomical characters proved useful to identify species, but not sections. Palynological results showed circular and obtuse triangular pollen in polar view and elliptical pollen in equatorial view with reticulate ornamentation. In addition, a cluster analysis was done based on morphological, anatomical and palynological features. The resulting dendrogram confirmed the taxonomic treatment suggested by Sirjaev and Rechinger.     

Assessment of eye doses to staff involved in interventional cardiology procedures in Kuwait

In this study, which is the first of its kind in the gulf region, eye doses of interventional cardiologists and nurses were measured using active dosimeters for left and right eyes, in 60 percutaneous coronary interventions in three main hospitals in Kuwait. The dose given in terms of H_p(0.07) per procedure when ceiling suspended screens were used by main operators ranged from 18.5 to 30.3 µSv for the left eye and from 12.6 to 23.6 µSv for the right eye. Taking into account typical staff workload, the results show that the dose limit of 20 mSv/year to the eyes can be exceeded for interventional cardiologists in some situations, which demonstrates the need of using additional effective radiation protection tools, e.g. protective eye spectacles, in addition to the regular and proper use of ceiling suspended screens. With indications of increase in workload, the need for availability of a dedicated active dosimeter for the regular monitoring of eye doses is emphasized.

     

Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics

Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells'' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.     

Vascular tissue engineering: Fabrication and characterization of acetylsalicylic acid-loaded electrospun scaffolds coated with amniotic membrane lysate

As the incidence of small-diameter vascular graft (SDVG) occlusion is considerably high, a great amount of research is focused on constructing a more biocompatible graft. The absence of a biocompatible surface in the lumen of the engineered grafts that can support confluent lining with endothelial cells (ECs) can cause thrombosis and graft failure. Blood clot formation is mainly because of the lack of an integrated endothelium. The most effective approach to combat this problem would be using natural extracellular matrix constituents as a mimic of endothelial basement membrane along with applying anticoagulant agents to provide local antithrombotic effects. In this study, we fabricated aligned and random electrospun poly-L-lactic acid (PLLA) scaffolds containing acetylsalicylic acid (ASA) as the anticoagulation agent and surface coated them with amniotic membrane (AM) lysate. Vascular scaffolds were structurally and mechanically characterized and assessed for cyto- and hemocompatibility and their ability to support endothelial differentiation was examined. All the scaffolds showed appropriate tensile strength as expected for vascular grafts. Lack of cytotoxicity, cellular attachment, growth, and infiltration were proved using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scanning electron microscopy. The blood compatibilities of different scaffolds examined by in vitro hemolysis and blood coagulation assays elucidated the excellent hemocompatibility of our novel AM-coated ASA-loaded nanofibers. Drug-loaded scaffolds showed a sustained release profile of ASA in 7 days. AM-coated electrospun PLLA fibers showed enhanced cytocompatibility for human umbilical vein ECs, making a confluent endothelial-like lining. In addition, AM lysate-coated ASA-PLLA-aligned scaffold proved to support endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells. Our results together indicated that AM lysate-coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.     

Human first trimester forebrain cells express genes for inflammatory and anti-inflammatory cytokines

Using in situ hybridization and immunohistochemistry the induction of potential cytokines [interleukin 1beta (IL-1beta), IL-4, IL-6, IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta (TGF-beta)] in human embryonic forebrain cells at weeks 5, 7 and 10 of gestation was studied. The aims were to investigate the capacity of these cells to express cytokines, to determine the kinetics of induction and to display the type of cytokine expressing cells in the developing brain. Constitutive cytokine gene expression was recorded from week 5, augmented by about 50% at week 7 and by more than 100% at week 19 (except TGF-beta at week 10). Among other cytokines, IL-1beta exhibited the highest expression at week 10. TGF-beta showed maximum expression at week 7 and declined at week 10. Combined techniques revealed that glial cells are a major source of cytokines. The study show and present for the first time the kinetics of spontaneous cytokine expression in human embryonic forebrain cells. The increased mRNA expressions with age suggest an important role for cytokines in promotion of brain development. The capacity of inducing these cytokines may, however, be implicated in the immunopathogenesis of several brain diseases. The distinctive TGF-beta profile suggests a further role for TGF-beta on modulation of cytokine responses during development.     

Defects formation and spiral waves in a network of neurons in presence of electromagnetic induction

Complex anatomical and physiological structure of an excitable tissue (e.g., cardiac tissue) in the body can represent different electrical activities through normal or abnormal behavior. Abnormalities of the excitable tissue coming from different biological reasons can lead to formation of some defects. Such defects can cause some successive waves that may end up to some additional reorganizing beating behaviors like spiral waves or target waves. In this study, formation of defects and the resulting emitted waves in an excitable tissue are investigated. We have considered a square array network of neurons with nearest-neighbor connections to describe the excitable tissue. Fundamentally, electrophysiological properties of ion currents in the body are responsible for exhibition of electrical spatiotemporal patterns. More precisely, fluctuation of accumulated ions inside and outside of cell causes variable electrical and magnetic field. Considering undeniable mutual effects of electrical field and magnetic field, we have proposed the new Hindmarsh–Rose (HR) neuronal model for the local dynamics of each individual neuron in the network. In this new neuronal model, the influence of magnetic flow on membrane potential is defined. This improved model holds more bifurcation parameters. Moreover, the dynamical behavior of the tissue is investigated in different states of quiescent, spiking, bursting and even chaotic state. The resulting spatiotemporal patterns are represented and the time series of some sampled neurons are displayed, as well.     

A product inhibition study on adenosine deaminase by spectroscopy and calorimetry

Kinetic and thermodynamic studies have been made on the effect of the inosine product on the activity of adenosine deaminase in a 50 mM sodium phosphate buffer, pH 7.5, at 27 degrees C using UV spectrophotometry and isothermal titration calorimetry (ITC). A competitive inhibition was observed for inosine as a product of the enzymatic reaction. A graphical-fitting method was used for determination of the binding constant and enthalpy of inhibitor binding by using isothermal titration microcalorimetry data. The dissociation-binding constant is equal to 140 microM by the microcalorimetry method, which agrees well with the value of 143 microM for the inhibition constant that was obtained from the spectroscopy method     

Anti-integrin as novel drug-discovery targets: potential therapeutic and diagnostic implications

The role of integrin and extracellular matrix proteins in various pathological processes (including angiogenesis, thrombosis, apoptosis and cell migration and proliferation), leading to both acute and chronic disease states (e.g. ocular diseases, metastasis, unstable angina, myocardial infarction, stroke, osteoporosis, a wide range of inflammatory diseases, vascular remodeling and neurodegenerative disorders) has been recently documented. A key success in this field is evident from the potential role of the platelet GPIIb/IIIa (alphaIIbbeta3) integrin in the prevention, treatment and perhaps diagnosis of various thromboembolic disorders. Additionally, progress has been shown in the development of leukocyte alpha4beta1 antagonists for various inflammatory indications and alphav integrin antagonists for angiogenesis and vascular-related disorders. However, the exact modes of action of certain integrin antagonists are still not fully clear. Integrin antagonists in clinical or pre-clinical development are expected to be used as a stand-alone therapy or, better, as an adjunct to other pharmacotherapy, radiotherapy or interventional procedures.