Insights into Exosome Transport through the Blood–Brain Barrier and the Potential Therapeutical Applications in Brain Diseases

Drug delivery to the central nervous system (CNS) is limited due to the presence of the blood–brain barrier (BBB), a selective physiological barrier located at the brain microvessels that regulates the flow of cells, molecules and ions between the blood and the brain. Exosomes are nanosized extracellular vesicles expressed by all cell types and that function as cargos, allowing for communication between the cells. The exosomes were shown to cross or regulate the BBB in healthy and disease conditions. However, the mechanistic pathways by which exosomes cross the BBB have not been fully elucidated yet. In this review, we explore the transport mechanisms of exosomes through the BBB. A large body of evidence suggests that exosome transport through the BBB occurs primarily through transcytosis. The transcytosis mechanisms are influenced by several regulators. Inflammation and metastasis also enhance exosome trafficking across the BBB. We also shed light on the therapeutical applications of exosomes for treating brain diseases. Further investigations are essential to provide clearer insights related to trafficking of exosomes across the BBB and disease treatment

Comparative study of the effects of pre and post natal administration of a thyroid drug on testicular activity in adult rat.

Thyroid hormone is known to play a critical role in growth and development of rat testes with a specific effect on the differentiation of Sertoli cells leading to a normal evolution of germ cells. In the present study, we aimed to compare the effect of induced hypothyroidism during fetal and post-natal life on the structure and function of the testis in adult. Pregnant or lactating mothers were treated with 6-propyl-2-thiouracil (PTU) during 21 days and weight gain of pups was steady until adult age. Plasma hormonal levels were determined by RIA and morphology of testis was studied on sections stained with Masson's trichrome. Pre and early post natal hypothyroidism resulted in an impairment of body development and a diminution of thyroid hormone levels of treated rats. No significant effect on testicular development has been observed when hypothyroidism is induced in fetal life while it was associated with reduction in testis weight, diameter of seminiferous tubules and hormonal levels and delay in maturation of germ cells, when induced during early post natal life

Effect of activated alloys on hydrogen discharge kinetics of MgH2 nanocrystals

This is the post-print version of the final paper published in Journal of Alloys and Compounds. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2007 Elsevier B.V.Activated alloys synthesized by arc-melting were examined as catalysts for improving the hydrogen sorption characteristics of nanostructured magnesium hydride, proposed as a reversible hydrogen storage material. The MgH2-catalyst absorbing materials were prepared by ball milling of pure MgH2 with hydrided Zr47Ni53, Zr9Ni11, and other investigated alloys. The nanostructured MgH2-intermetallic systems were tested at 250 °C and catalyst addition of eutectoid Zr47Ni53 resulted in the fastest desorption time and highest initial desorption rate. Also, the catalyzed Mg-hydride with activated Zr9Ni11 and Zr7Ni10 phases showed fast desorption kinetics. Moreover, the results demonstrated that the composition of dispersed ZrxNiy catalysts has a strong influence on the amount of accumulated hydrogen and desorption rate of Mg-nanocomposite.National Research Council Canad

Circulating microRNAs as potential biomarkers of early vascular damage in vitamin D deficiency, obese, and diabetic patients

Vitamin D3 deficiency, obesity, and diabetes mellitus (DM) have been shown to increase the risk of cardiovascular diseases (CVDs). However, the early detection of vascular damage in those patients is still difficult to ascertain. MicroRNAs (miRNAs) are recognized to play a critical role in initiation and pathogenesis of vascular dysfunction. Herein, we aimed to identify circulating miRNA biomarkers of vascular dysfunction as early predictors of CVDs. We have recruited 23 middle-aged Emiratis patients with the following criteria: A healthy control group with vitamin D ≥ 20ng, and BMI 1.5) in high-risk patients for CVDs vs healthy controls. Collectively, our result indicates that four specific circulating miRNA signature, may be utilized as non-invasive, diagnostic and prognostic biomarkers for early vascular damage in patients suffering from vitamin D deficiency, obesity and DM

Disulfonated tetraphenyl chlorin (TPCS2a)–induced photochemical internalisation of bleomycin in patients with solid malignancies: A first-in-man phase I dose escalation clinical trial

BACKGROUND: Photochemical internalisation, a novel minimally invasive treatment, has shown promising preclinical results in enhancing and site-directing the effect of anticancer drugs by illumination, which initiates localised chemotherapy release. We assessed the safety and tolerability of a newly developed photosensitiser, disulfonated tetraphenyl chlorin (TPCS2a), in mediating photochemical internalisation of bleomycin in patients with advanced and recurrent solid malignancies. METHODS: In this phase 1, dose-escalation, first-in-man trial, we recruited patients (aged ≥18 to <85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies who were clinically assessed as eligible for bleomycin chemotherapy from a single centre in the UK. Patients were given TPCS2a on day 0 by slow intravenous injection, followed by a fixed dose of 15 000 IU/m2 bleomycin by intravenous infusion on day 4. After 3 h, the surface of the target tumour was illuminated with 652 nm laser light (fixed at 60 J/cm2). The TPCS2a starting dose was 0·25 mg/kg and was then escalated in successive dose cohorts of three patients (0·5, 1·0, and 1·5 mg/kg). The primary endpoints were safety and tolerability of TPCS2a; other co-primary endpoints were dose-limiting toxicity and maximum tolerated dose. The primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00993512, and has been completed. FINDINGS: Between Oct 3, 2009, and Jan 14, 2014, we recruited 22 patients into the trial. 12 patients completed the 3-month follow-up period. Adverse events related to photochemical internalisation were either local, resulting from the local inflammatory process, or systemic, mostly as a result of the skin-photosensitising effect of TPCS2a. The most common grade 3 or worse adverse events were unexpected higher transient pain response (grade 3) localised to the treatment site recorded in nine patients, and respiratory failure (grade 4) noted in two patients. One dose-limiting toxicity was reported in the 1·0 mg/kg cohort (skin photosensitivity [grade 2]). Dose-limiting toxicities were reported in two of three patients at a TPCS2a dose of 1·5 mg/kg (skin photosensitivity [grade 3] and wound infection [grade 3]); thus, the maximum tolerated dose of TPCS2a was 1·0 mg/kg. Administration of TPCS2a was found to be safe and tolerable by all patients. No deaths related to photochemical internalisation treatment occurred. INTERPRETATION: TPCS2a-mediated photochemical internalisation of bleomycin is safe and tolerable. We identified TPCS2a 0·25 mg/kg as the recommended treatment dose for future trials. FUNDING: PCI Biotech

International Geomagnetic Reference Field: the eleventh generation

The eleventh generation of the International Geomagnetic Reference Field (IGRF) was adopted in December 2009 by the International Association of Geomagnetism and Aeronomy Working Group V-MOD. It updates the previous IGRF generation with a definitive main field model for epoch 2005.0, a main field model for epoch 2010.0, and a linear predictive secular variation model for 2010.0-2015.0. In this note the equations defining the IGRF model are provided along with the spherical harmonic coefficients for the eleventh generation. Maps of the magnetic declination, inclination and total intensity for epoch 2010.0 and their predicted rates of change for 2010.0-2015.0 are presented. The recent evolution of the South Atlantic Anomaly and magnetic pole positions are also examine

A new hereditary colorectal cancer network in the Middle East and eastern mediterranean countries to improve care for high-risk families

Colorectal cancer (CRC) has a very high incidence in the western world. Data from registries in the Middle East showed that the incidence of CRC is relatively low in these countries. However, these data also showed that CRC incidence has increased substantially over the past three decades and that a high proportion of cases are diagnosed at an early age (<50 years). In view of these findings, more attention should be paid to prevention. Because of the often limited financial resources, focused screening of individuals with hereditary CRC, in particular those with Lynch syndrome, appears to be the most cost-effective strategy. During recent meetings of the Palestinian Society of Gastroenterology and the Mediterranean Task force for Cancer Control (MTCC) in Jericho, and the Patient�s Friends Society of Jerusalem in Hebron the issue of hereditary CRC in the Middle East was discussed and the idea was conceived to establish a network on hereditary colorectal cancer (HCCN-ME) with the goal of improving care for high-risk groups in the Middle East and (Eastern) Mediterranean Countries. © 2017, The Author(s)

International Geomagnetic Reference Field: the eleventh generation

The eleventh generation of the International Geomagnetic Reference Field (IGRF)was adopted in December 2009 by the International Association of Geomagnetism and AeronomyWorking Group V-MOD. It updates the previous IGRF generation with a definitive main field model for epoch 2005.0, a main field model for epoch 2010.0, and a linear predictive secular variation model for 2010.0–2015.0. In this note the equations defining the IGRF model are provided along with the spherical harmonic coefficients for the eleventh generation. Maps of the magnetic declination, inclination and total intensity for epoch 2010.0 and their predicted rates of change for 2010.0–2015.0 are presented. The recent evolution of the South Atlantic Anomaly and magnetic pole positions are also examined

A new hereditary colorectal cancer network in the Middle East and eastern mediterranean countries to improve care for high-risk families

Colorectal cancer (CRC) has a very high incidence in the western world. Data from registries in the Middle East showed that the incidence of CRC is relatively low in these countries. However, these data also showed that CRC incidence has increased substantially over the past three decades and that a high proportion of cases are diagnosed at an early age (<50 years). In view of these findings, more attention should be paid to prevention. Because of the often limited financial resources, focused screening of individuals with hereditary CRC, in particular those with Lynch syndrome, appears to be the most cost-effective strategy. During recent meetings of the Palestinian Society of Gastroenterology and the Mediterranean Task force for Cancer Control (MTCC) in Jericho, and the Patient�s Friends Society of Jerusalem in Hebron the issue of hereditary CRC in the Middle East was discussed and the idea was conceived to establish a network on hereditary colorectal cancer (HCCN-ME) with the goal of improving care for high-risk groups in the Middle East and (Eastern) Mediterranean Countries. © 2017, The Author(s)