Potential new anti-human immunodeficiency virus type 1 compounds depress virus replication in cultured human macrophages

We report that the amiloride analogues 5-(N,N-hexamethylene)amiloride and 5-(N,N-dimethyl)amiloride inhibit, at micromolar concentrations, the replication of human immunodeficiency virus type 1 (HIV-1) in cultured human blood monocyte-derived macrophages. These compounds also inhibit the in vitro activities of the HIV-1 Vpu protein and might represent lead compounds for a new class of anti-HIV-1 drugs.     

Systematic review of the epidemiology of attention deficit hyperactivity disorder in Arab countries

Objective:

To assess the epidemiology of attention deficit hyperactivity disorder (ADHD) in Arab countries, and identify gaps for future research.

Methods:

We searched PubMed from July 1978 to July 2014 and reviewed local journals with cross-referencing. The keywords we used were ADHD, diagnosis, prevalence, incidence, factor, diagnosis, rate, risk, and each of the names of the 22 Arab countries (Jordan, Egypt, Lebanon, Saudi Arabia, and so on). Studies were eligible for inclusion if they investigated the epidemiology of ADHD in any Arab country, and were published in English. The search was conducted from 2nd to 5th August 2014 in King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Results:

A total of 22 articles were included in the review. Twenty studies were cross-sectional and found the prevalence of ADHD ranged between 1.3-16%, prevalence of hyperactive type ADHD between 1.4-7.8%, and the prevalence of inattention type between 2.1-2.7%. Only 2 case-control studies investigated potential risk factors. Evidence extracted from these studies shows a significant association between ADHD and male gender, previous psychiatric illness in the family, vitamin D deficiency, poor school performance, sleep problems, and nocturnal enuresis.

Conclusion:

The prevalence of ADHD in Arab countries is comparable to reports in North America, Africa, and other countries of the Middle East. Longitudinal studies are needed to investigate the prognosis and determinants of this condition in the Arab world.According to the Diagnostic and Manual of Mental Disorder (DSM-IV), attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by pervasive and impairing symptoms of inattention, hyperactivity, and impulsivity.1 It is a condition that occurs primarily in childhood, and presents profound impairments impacting every aspect of life.2 The ADHD symptoms are caused by a neurological dysfunction within the brain. The physiological mechanism of ADHD is still under study.1,2 This disorder has been associated with a broad range of negative outcomes for affected subjects,3 and with a significant financial burden.4 The prevalence of ADHD varies from 0.2-28%.5 Reported differences in prevalence across countries might be related to differences in diagnostic criteria used, but also might be related to biological, cultural, and family factors.6 A comprehensive systemic review conducted in 2007 documented the worldwide-pooled prevalence at 5.3% (95% confidence interval [CI]=5.01-5.56).6 The National Survey of Children’s Health in 2011 reported 11% prevalence of ADHD in children aged between 4 and 17 years of age.7 Attention deficit hyperactivity disorder is more common in boys than girls (ratio 4:1 for the predominantly hyperactive type, and 2:1 for the predominantly inattentive type).8 Accordingly, the DSM-IV proposed 3 subtypes of ADHD that are the inattentive type, hyperactive/impulsive type, and combined type.9 During the past decade, evidence has accumulated indicating that symptoms of ADHD persist into adulthood for 30-70% of children diagnosed with the disorder.10 Many studies have demonstrated conclusively that genetic and environmental influences play a role in the etiology of ADHD, as is true for virtually all psychological traits and disorders.11 Attention deficit hyperactivity disorder is 6-8 times higher among first-degree relatives with ADHD, where 30-35% of full siblings meet the ADHD criteria.12 Prenatal or perinatal complications significantly predicted the later development of ADHD.13 Virus infections, meningitis, encephalitis, head injury, epilepsy, toxins, and drugs, were among the childhood illnesses associated with ADHD. Furthermore, diet-related sensitivities and mineral deficiencies have always been controversial factors.14 Worldwide, several systematic reviews have been conducted to summarize the epidemiological evidence with respect to the occurrence and determinants of ADHD. In the Arab region only one systematic review was completed in 2009.15 However, with increased interest in research on ADHD, several new studies have been conducted in the Arab world. This systematic review provides an update on the current state of knowledge with respect to ADHD literature in the Arab world.     

Improvement of Corrosion Resistance of TiO2 Layers in Strong Acidic Solutions by Anodizing and Thermal Oxidation Treatment

By anodization and thermal oxidation at 600 °C, an oxide layer on Ti with excellent corrosion resistance in strong acid solutions was prepared. The structural properties of TiO₂ films before and after thermal oxidation were investigated with methods of Scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The electrochemical characterization was recorded via electrochemical impedance spectroscopy, potentiodynamic polarization and Mott–Schottky methods. XRD results show that a duplex rutile/anatase structure formed after oxidation, and the amount of anatase phase increased as the treatment time was prolonged from 3 to 9 h. XPS analysis indicates that as the thermal oxidation time increased, more Ti vacancies were present in the titanium oxide films, with decreased donor concentration. Longer thermal oxidation promoted the formation of hydroxides of titanium on the surface, which is helpful to improve the passive ability of the film. The anodized and thermally oxidized Ti samples showed relatively high corrosion resistance in 4 M HCl and 4 M H₂SO₄ solutions at 100 ± 5 °C. The passive current density values of the thermally oxidized samples were five orders of magnitude under the testing condition compared with that of the anodized sample. With the oxidation time prolonged, the passive current density decreased further to some extent.     

Outcome of diffuse large B-Cell lymphoma in the United States has improved over time but racial disparities remain: review of SEER data

BackgroundDiffuse large B-cell non-Hodgkin lymphoma (DLBCL) outcome in the United States has not been reported outside the context of clinical trials.Patients and MethodsWe reviewed the Surveillance, Epidemiology, and End Results (SEER) registry and compared survival trends among DLBCL patients from 1973 to 2004.ResultsWe identified 59,728 patients (mean age, 63 years; 54.4% men, 86.7% white) and had staging information for 57%, including 30% early-stage (I/II) and 27% advanced-stage (III/IV). Median overall survival (OS) from 1973 to 1979, 1980 to 1989,1990 to 1999, and 2000 to 2004 was 15, 18, 20, and 47 months, respectively (P < .005). For the period from 2000 to 2004, 4-year OS was 46%. Outcome was better in white patients than in black (47 months versus 29 months) (P = .001). Median OS for patients younger than 60 years old was not reached versus 23 months for patients older than 60 years.ConclusionThe outcome of DLBCL in the United States has improved significantly in the era of monoclonal antibodies; however, racial disparities remain.     

Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds

Recent experimental evidence suggests that transcellular propagation of fibrillar protein aggregates drives the progression of neurodegenerative diseases in a prion-like manner. This phenomenon is now well described in cell and animal models and involves the release of protein aggregates into the extracellular space. Free aggregates then enter neighboring cells to seed further fibrillization. The mechanism by which aggregated extracellular proteins such as tau and α-synuclein bind and enter cells to trigger intracellular fibril formation is unknown. Prior work indicates that prion protein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface to transmit pathologic processes. Here, we find that tau fibril uptake also occurs via HSPG binding. This is blocked in cultured cells and primary neurons by heparin, chlorate, heparinase, and genetic knockdown of a key HSPG synthetic enzyme, Ext1. Interference with tau binding to HSPGs prevents recombinant tau fibrils from inducing intracellular aggregation and blocks transcellular aggregate propagation. In vivo, a heparin mimetic, F6, blocks neuronal uptake of stereotactically injected tau fibrils. Finally, uptake and seeding by α-synuclein fibrils, but not huntingtin fibrils, occurs by the same mechanism as tau. This work suggests a unifying mechanism of cell uptake and propagation for tauopathy and synucleinopathy.Alzheimer’s disease (AD), frontotemporal dementia, and other tauopathies feature conversion of soluble, native tau protein into filamentous aggregates. In AD, tau pathology and its associated neural atrophy do not distribute randomly throughout the brain, but progress in association with neural networks (1–4), implying a role for connectivity and the transcellular movement of a pathological agent (1, 2, 4, 5). Prior studies by our laboratory and others have demonstrated that internalized tau aggregates can trigger fibrillization of native tau protein (6–11). We have previously observed that tau aggregates propagate the misfolded state among cells in culture via release of fibrils into the extracellular space. These aggregates trigger further fibrillization by direct protein–protein contact with native tau in the recipient cells (12). Thus, fibrillar tau appears to spread pathologic processes by mechanisms fundamentally similar to prion pathogenesis. Although the phenomenology is now well described, the basic mechanisms that mediate transcellular propagation of tau aggregation remain unknown, including the mechanism of aggregate uptake to seed intracellular fibrillization. Infectious prion protein is known to bind heparan sulfate proteoglycans (HSPGs) on the cell surface, a requirement for propagation of the pathological conformation (13, 14). This study elucidates a mechanism whereby tau aggregates bind HSPGs to stimulate cell uptake via macropinocytosis and seed further aggregation. Further, we find that HSPGs also mediate uptake and seeding of α-synuclein fibrils, but not huntingtin fibrils, consistent with a unifying mechanism for two major classes of neurodegenerative disease.     

Antioxidant and antimicrobial activities of the edible medicinal halophyte Tamarix gallica L. and related polyphenolic constituents

Tamarix gallica is a halophytic species having hepatotonic and stimulant properties, as it was traditionally used in the treatment of various liver disorders. Leaf and flower infusion have anti-inflammatory and anti-diarrheic proprieties. In this work, we have investigated antioxidant and antimicrobial activities of leaf and flower extracts and their phenolic composition. Results showed that flowers exhibit a higher antioxidant activity as compared to the leaves, IC₅₀ values of the flower extracts are being 1.3 (β-carotene bleaching) to 19 times (lipid peroxidation inhibition) lower than those for leaves. Accordingly, flower extracts exhibited the highest total phenolic content (135.35 mg GAE/g DW) and RP-HPLC analysis showed that syringic acid, isoquercitin as well as catechin were the major phenolics. Furthermore, Tamarix extracts showed appreciable antibacterial properties against human pathogen strains. The mean inhibition zone was from 0 to 6.5 mm when the concentration increased from 2 to 100 mg/l. The strongest activity was recorded against Micrococcus luteus and the lowest activity was observed against Escherichia coli. Moreover, organ extracts show a weakly to moderate activity against the tested Candida. These findings suggest that Tamarix may be considered as an interesting source of antioxidants for therapeutic or nutraceutical industries and for food manufactures.     

Haplotype structure of five SNPs within the ACE gene in the Tunisian population

BACKGROUND: The Angiotensin-Converting Enzyme (ACE) is a candidate gene in the aetiology of several common diseases. The study of the haplotype structure of this gene is of interest in diagnosis and in pharmacogenomics. AIM: The study investigated the haplotype profile of single nucleotide polymorphisms (SNPs) within the ACE gene in the Tunisian population and compared it with other populations. SUBJECTS AND METHODS: Five SNPs (rs1800764, rs4291, rs4309, rs4331, rs4340) covering a region of 15.6 kb of the ACE gene were typed by PCR-digestion in a sample of 100 healthy subjects. RESULTS: All SNPs were polymorphic and in Hardy-Weinberg equilibrium. A total of 21 haplotypes were identified but only eight had a frequency of more than 1%. The four most common haplotypes had a cumulative frequency of 87.4%. The 'Yin-Yang' phenomenon (the two major haplotypes are complementary at all sites) was found. Linkage disequilibrium between all pairs of loci was highly significant (p<10-5). A simple and efficient statistical procedure was used to identify three important SNPs. CONCLUSION: The Tunisian population showed a different haplotype structure from the European one for the ACE gene and three important SNPs were identified. These will be very helpful in future association studies in the Tunisian and North African populations.     

The heteroplasmic m.14709T>C mutation in the tRNAGlu gene in two Tunisian families with mitochondrial diabetes

Diabetes mellitus (DM) is a heterogeneous disorder characterized by the presence of chronic hyperglycemia. Genetic factors play an important role in the development of this disorder, and several studies reported mutations in nuclear genes implicated in the insulin function. Besides, DM can be maternally transmitted in some families, possibly due to the maternal mitochondrial inheritance. In fact, mitochondrial genes may be plausible causative agents for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells.Materials and MethodsIn this report, we screened two Tunisian families with mitochondrial diabetes for the m.3243A>G and the m.14709T>C mutations, respectively, in the tRNA^Leu(UUR) and the tRNA^Glu genes.ResultsThe polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and the sequence-specific primers by polymerase chain reaction (SSP-PCR) analysis in the leucocytes and the buccal mucosa in the members of the two families showed the absence of the m.3243A>G mutation and the presence of the heteroplasmic m.14709T>C mutation in the tRNA^Glu gene in the two tested tissues.ConclusionsWe conclude that the m.14709T>C mutation in the tRNA^Glu gene could be a cause of mitochondrial diabetes in Tunisian affected families. In addition, the heteroplasmic loads correlated with the severity and the onset of mitochondrial diabetes in one family but not in the other, suggesting the presence of environmental factors or nuclear modifier genes.