A systematic review of new advances in the management of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): focus on galsulfase

Regina P El Dib1, Gregory M Pastores21Department of Surgery, McMaster University, McMaster Institute of Urology, Hamilton, Ontario, Canada; 2Department of Neurology and Pediatrics, New York University School of Medicine, New York, NY, USAIntroduction: Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal storage disorder, characterized primarily by skeletal dysplasia and joint contracture. It is caused by a deficiency of N-acetylgalactosamine-4-sulfatase (arylsulfatase B), for which a recombinant formulation (galsulfase) is available as replacement therapy. Objective: To evaluate the effectiveness and safety of galsulfase compared to placebo or no interventions, for treating MPS VI. We also considered studies evaluating different doses of galsulfase.Methods: A systematic review of the literature was conducted. A computerized electronic search in MEDLINE, EMBASE, CENTRAL, SciELO, and LILACS was carried on to identify any randomized trials that met our inclusion criteria.Results: Two studies were included in the review. Because the number of studies was small, our analysis probably did not find any statistically significant difference. Long-term follow-up will be required to ascertain full clinical benefit, on both event-free survival and quality of life measures.Conclusions: There is some evidence to support the use of galsulfase in the treatment of MPS VI; however due to the very low quantity of included studies we could not analyze it in an appropriate way. This review highlights the need for continued research into the use of enzyme replacement therapy for MPS VI.Keywords: mucopolysaccharidosis VI, Maroteaux-Lamy syndrome, galsulfase, naglazyme, systematic revie

Reactivity of OH and CH3OH between 22 and 64 K: Modelling the gas phase production of CH3O in Barnard 1b

In the last years, ultra-low temperature chemical kinetic experiments have demonstrated that some gas-phase reactions are much faster than previously thought. One example is the reaction between OH and CH3OH, which has been recently found to be accelerated at low temperatures yielding CH3O as main product. This finding opened the question of whether the CH3O observed in the dense core Barnard 1b could be formed by the gas-phase reaction of CH3OH and OH. Several chemical models including this reaction and grain-surface processes have been developed to explain the observed abundance of CH$_3$O with little success. Here we report for the first time rate coefficients for the gas-phase reaction of OH and CH3OH down to a temperature of 22 K, very close to those in cold interstellar clouds. Two independent experimental set-ups based on the supersonic gas expansion technique coupled to the pulsed laser photolysis-laser induced fluorescence technique were used to determine rate coefficients in the temperature range 22-64 K. The temperature dependence obtained in this work can be expressed as k(22-64 K) = (3.6+/-0.1)e-12 (T/ 300)^(-1.0+/-0.2) cm3 molecule-1 s-1. Implementing this expression in a chemical model of a cold dense cloud results in CH3O/CH3OH abundance ratios similar or slightly lower than the value of 3e-3 observed in Barnard 1b. This finding confirms that the gas-phase reaction between OH and CH3OH is an important contributor to the formation of interstellar CH3O. The role of grain-surface processes in the formation of CH3O, although it cannot be fully neglected, remains controversial.Comment: Accepted for publication in The Astrophysical Journa

Giardia intestinalis assemblages among Egyptian symptomatic/asymptomatic cases in Cairo

Giardia intestinalis is frequent enteric protozoa, affecting humans worldwide. Human infections aremainly caused by two genetically different assemblages call A & B. This cross-sectional study characterizedthe Giardia genotypes isolated from the stool of symptomatic and asymptomatic Egyptians inCairo and correlated these genotypes with the demographic and clinical data of the cases. Stool sampleswere collected from 389 individuals (245 complaining of gastrointestinal (GIT) symptoms and144 apparently healthy asymptomatic individuals), and microscopically examined. Positive Samplesfor G. intestinalis were molecularly characterized by Copro-nPCR targeting beta-giardin gene, andthen analyzed by RFLP for assemblage identification. Giardia was detected in 62 samples (15.9%); 53samples in symptomatic cases (21.6%) and 9 samples in asymptomatic individuals (6.25%). DNA ofpositive samples was amplified by nPCR-RFLP assays. There was a significant predominance of assemblageB among symptomatic (82.7%) and asymptomatic (77.8%) groups, while the rest of sampleshad assemblage A. Among the clinical data, only flatulence was significantly associated with Giardiainfection with assemblage B. Assemblage B is the predominant genotype found in Egypt in symptomaticand asymptomatic patients suggesting an anthropologic transmission cycle.Key Words: Giardia; genotyping; Assemblage; nPCR-RFLP; beta-giardin

Pharmacy education and practice in 13 middle eastern countries

The Arab world has influenced the art and science of pharmacy for centuries. Pharmacy education and practice is continuing to evolve in the Arabic-speaking traditional Middle East countries, although relatively little information has been published in the English press. Our goal was to providea high-level synopsis of conditions in this region. We selected 13 countries for review. Information was obtained by reviewing the available published literature and individual university and program web sites, as well as contacting with program or country representatives. Seventy-eight active pharmacy schools in 12 countries were identified. At least 14,000 students (over 75% from Egypt) are admitted into baccalaureate degree programs every year. The 5-year baccalaureate degree remains the first professional degree to practice. While changes in pharmacy education have been relatively rapid over the past decade, the advancement of pharmacy practice, particularly in the private sector, appears to be slower. Hospital pharmacists often possess an advanced degree and tend to have a higher level of practice compared to that of community pharmacists. Despite the adversities that face academics and practitioners alike, there is a strong desire to advance the science and practice of pharmacy in the Middle East

Decay constants, semi-leptonic and non-leptonic decays in a Bethe-Salpeter Model

We evaluate the decay constants for the B and $D$ mesons and the form factors for the semileptonic decays of the B meson to $D$ and $D^*$ mesons in a Bethe-Salpeter model. From data we extract $V_{cb}=0.039 \pm 0.002$ from ${\bar B} \to D^* l {\bar{\nu}}$ and $V_{cb}=0.037 \pm 0.004$ from ${\bar B} \to D l {\bar{\nu}}$ decays. The form factors are then used to obtain non-leptonic decay partial widths for $B\to D \pi (K)$ and $B \to D D (D_s)$ in the factorization approximation.Comment: 15 Pages, 3 Postscript figures (available also from [email protected]

Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu. While therapeutic hypothermia has targeted the latent and secondary phase, we now need therapies that cover the continuum of brain injury that spans hours, days, weeks and months after the initial event. Most agents have several therapeutic actions but can be broadly classified under a predominant action (e.g., free radical scavenging, anti-apoptotic, anti-inflammatory, neuroregeneration, and vascular effects). Promising early/secondary phase therapies include Allopurinol, Azithromycin, Exendin-4, Magnesium, Melatonin, Noble gases and Sildenafil. Tertiary phase agents include Erythropoietin, Stem cells and others. We review a selection of promising therapeutic agents on the translational pipeline and suggest a framework for neuroprotection and neurorestoration that targets the evolving injury

First Principle Local Density Approximation Description of the Electronic Properties of Ferroelectric Sodium Nitrite

The electronic structure of the ferroelectric crystal, NaNO$_2$, is studied by means of first-principles, local density calculations. Our ab-initio, non-relativistic calculations employed a local density functional approximation (LDA) potential and the linear combination of atomic orbitals (LCAO). Following the Bagayoko, Zhao, Williams, method, as enhanced by Ekuma, and Franklin (BZW-EF), we solved self-consistently both the Kohn-Sham equation and the equation giving the ground state charge density in terms of the wave functions of the occupied states. We found an indirect band gap of 2.83 eV, from W to R. Our calculated direct gaps are 2.90, 2.98, 3.02, 3.22, and 3.51 eV at R, W, X, {\Gamma}, and T, respectively. The band structure and density of states show high localization, typical of a molecular solid. The partial density of states shows that the valence bands are formed only by complex anionic states. These results are in excellent agreement with experiment. So are the calculated densities of states. Our calculated electron effective masses of 1.18, 0.63, and 0.73 mo in the {\Gamma}-X, {\Gamma}-R, and {\Gamma}-W directions, respectively, show the highly anisotropic nature of this material.Comment: 13 Pages, 4 Figures, and 2 Table

Bose-Einstein Condensates in Optical Lattices: Band-Gap Structure and Solitons

We analyze the existence and stability of spatially extended (Bloch-type) and localized states of a Bose-Einstein condensate loaded into an optical lattice. In the framework of the Gross-Pitaevskii equation with a periodic potential, we study the band-gap structure of the matter-wave spectrum in both the linear and nonlinear regimes. We demonstrate the existence of families of spatially localized matter-wave gap solitons, and analyze their stability in different band gaps, for both repulsive and attractive atomic interactions

B --> D(D^*) Form Factors in a Bethe-Salpeter model

We calculate the form factors for the semileptonic decays of the $B$ meson to $D$ and $D^*$ mesons in a Bethe-Salpeter model. We show that our model is consistent with the constraints of Heavy Quark Effective Theory (HQET) and we extract the matrix elements that represent the $1/m_Q$ corrections to the form factors in HQET. With available data, we obtain $V_{cb}$=$(31.9 \pm 1.4)\times10^{-3}$.Comment: 15 pages, 5 figure