50 research outputs found
Release of sICAM-1 in Oocytes and In Vitro Fertilized Human Embryos
Background: During the last years, several studies have reported the significant relationship between the production of soluble HLA-G molecules (sHLA-G) by 48â72 hours early embryos and an increased implantation rate in IVF protocols. As consequence, the detection of HLA-G modulation was suggested as a marker to identify the best embryos to be transferred. On the opposite, no suitable markers are available for the oocyte selection. Methodology/Principal Findings: The major finding of the present paper is that the release of ICAM-1 might be predictive of oocyte maturation. The results obtained are confirmed using three independent methodologies, such as ELISA, Bio-Plex assay and Western blotting. The sICAM-1 release is very high in immature oocytes, decrease in mature oocytes and become even lower in in vitro fertilized embryos. No significant differences were observed in the levels of sICAM-1 release between immature oocytes with different morphological characteristics. On the contrary, when the mature oocytes were subdivided accordingly to morphological criteria, the mean sICAM-I levels in grade 1 oocytes were significantly decreased when compared to grade 2 and 3 oocytes. Conclusions/Significance: The reduction of the number of fertilized oocytes and transferred embryos represents the main target of assisted reproductive medicine. We propose sICAM-1 as a biochemical marker for oocyte maturation and grading
Low molecular weight heparins: Structural differentiation by spectroscopic and multivariate approaches
Various branded low molecular weight heparins (LMWHs) have been used for the treatment and prevention of thrombotic for over 20 years. With the introduction of generic LMWHs and the recent events involving heparin contamination, a great deal of effort is being expended in investigating ways of monitoring and regulating this class of complex drugs. in this paper, we present the characterization of different forms of LMWHs, as well as the comparison of 5 enoxaparin copies from different manufactures. the data suggests that, while some of these drugs are structurally comparable, specific analytical methods as well as biological and pharmacological tests may be used to address their similarity, quality and potential interchangeability. the proposed approach may also be useful in comparing biosimilar and branded LMWHs. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo Ă Pesquisa do Estado de SĂŁo Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de NĂvel Superior (CAPES)Conselho Nacional de Desenvolvimento CientĂfico e TecnolĂłgico (CNPq)Universidade Federal de SĂŁo Paulo, Dept Bioquim, BR-04044020 SĂŁo Paulo, SP, BrazilUniv Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, EnglandLoyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USAUniv Fed Parana, Lab Quim Carboidratos, Dept Bioquim & Biol Mol, BR-81531980 Curitiba, Parana, BrazilUniversidade Federal de SĂŁo Paulo, Dept Bioquim, BR-04044020 SĂŁo Paulo, SP, BrazilWeb of Scienc
Development of LGAD sensors with a thin entrance window for soft X-ray detection
We show the developments carried out to improve the silicon sensor technology
for the detection of soft X-rays with hybrid X-ray detectors. An optimization
of the entrance window technology is required to improve the quantum
efficiency. The LGAD technology can be used to amplify the signal generated by
the X-rays and to increase the signal-to-noise ratio, making single photon
resolution in the soft X-ray energy range possible. In this paper, we report
first results obtained from an LGAD sensor production with an optimized thin
entrance window. Single photon detection of soft X-rays down to 452~eV has been
demonstrated from measurements, with a signal-to-noise ratio better than 20.Comment: 10 pages, 6 figure
Characterization of iLGADs using soft X-rays
Experiments at synchrotron radiation sources and X-ray Free-Electron Lasers
in the soft X-ray energy range (eV--keV) stand to benefit from the
adaptation of the hybrid silicon detector technology for low energy photons.
Inverse Low Gain Avalanche Diode (iLGAD) sensors provide an internal gain,
enhancing the signal-to-noise ratio and allowing single photon detection below
keV using hybrid detectors. In addition, an optimization of the entrance
window of these sensors enhances their quantum efficiency (QE). In this work,
the QE and the gain of a batch of different iLGAD diodes with optimized
entrance windows were characterized using soft X-rays at the
Surface/Interface:Microscopy beamline of the Swiss Light Source synchrotron.
Above eV, the QE is larger than for all sensor variations, while
the charge collection efficiency is close to . The average gain depends
on the gain layer design of the iLGADs and increases with photon energy. A
fitting procedure is introduced to extract the multiplication factor as a
function of the absorption depth of X-ray photons inside the sensors. In
particular, the multiplication factors for electron- and hole-triggered
avalanches are estimated, corresponding to photon absorption beyond or before
the gain layer, respectively.Comment: 16 pages, 8 figure
Guidelines for diagnosis, monitoring and treatment of Fabry disease.
La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X, ocasionado por el dĂ©ficit de la enzima alfa galactosidasa A. El conocimiento sobre esta patologĂa, y en particular su manejo mĂ©dico, ha progresado notablemente en la Ășltima dĂ©cada, incluyendo el desarrollo de su tratamiento especĂfico. La presente guĂa fue desarrollada por profesionales mĂ©dicos de diversas especialidades involucrados en la atenciĂłn de pacientes con enfermedad de Fabry. La discusiĂłn y anĂĄlisis de las evidencias cientĂficas disponibles, sumado a la experiencia de cada uno de los participantes, ha permitido desarrollar los conceptos vertidos en esta guĂa con el objetivo de brindar una herramienta Ăștil para todos los profesionales que asisten a pacientes con enfermedad de Fabry.Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.Fil: Neumann, Pablo. Hospital Italiano de la Plata; ArgentinaFil: Antongiovanni, Norberto. Instituto de NefrologĂa. Pergamino; ArgentinaFil: Fainboim, Alejandro. Hospital de Niños Ricardo GutiĂ©rrez. Buenos Aires; ArgentinaFil: Kisinovsky, Isaac. Sanatorio Urquiza. Quilmes; ArgentinaFil: Amartino, Hernan. Hospital Universitario Austral. Pilar; ArgentinaFil: Cabrera, Gustavo Javier. Grupo MĂ©dico Del Viso. Buenos Aires; ArgentinaFil: Carmona, Sergio. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Ceci, Romina. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Ciceran, Alberto. Hospital General de Agudos Juan A. Fernandez. Buenos Aires; ArgentinaFil: Choua, Martin. Centro de NefrologĂa. TucumĂĄn; ArgentinaFil: Doxastakis, Griselda. Instituto de CardiologĂa y CirugĂa Cardiovascular. Posadas; ArgentinaFil: De Maio, Sonia. Hospital General de Agudos Juan A. Fernandez. Buenos Aires; ArgentinaFil: Ebner, Roberto. Hospital BritĂĄnico de Buenos Aires; ArgentinaFil: Escobar, Ana Maria. Hospital BritĂĄnico de Buenos Aires; ArgentinaFil: Ferrari, Gustavo. Hospital BritĂĄnico de Buenos Aires; ArgentinaFil: Forrester, Mariano. Hospital BritĂĄnico de Buenos Aires; ArgentinaFil: Guelbert, Norberto Bernardo. Hospital de Niños. CEMECO. CordĂłba; ArgentinaFil: Luna, Paula. Hospital Aleman; ArgentinaFil: Marchesoni, Cinthia. Hospital BritĂĄnico de Buenos Aires; ArgentinaFil: Masllorens, Francisca. Hospital Posadas. Haedo; ArgentinaFil: Politei, Juan. Hospital General de Agudos Juan A. Fernandez. Buenos Aires; ArgentinaFil: Reisin, Ricardo. Hospital BritĂĄnico de Buenos Aires; ArgentinaFil: Ripeau, Diego. Hospital Posadas. Haedo; ArgentinaFil: Rozenfeld, Paula Adriana. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Serebrinsky, Graciela. Laboratorio de BiologĂa y PatologĂa Molecular. Buenos Aires; ArgentinaFil: Tarabuso, Ana Lia. Centro de Especialistas En AudiciĂłn y Lenguaje. Trelew; ArgentinaFil: Tripoli, Juan. Hospital de Niños Ricardo GutiĂ©rrez. Buenos Aires; ArgentinaFil: Consenso de mĂ©dicos de AsociaciĂłn de Estudios y DifusiĂłn de las Enfermedades Lisosomales.Fil: Grupo Argentino de DiagnĂłstico y Tratamiento de la enfermedad de Fabry
Ion mobility spectrometry for the rapid analysis of over-the-counter drugs and beverages
In the pharmaceutical industry, there are increasing requirements for analytical methods in quality assessment for the production of drugs. In this investigation, ion mobility spectrometry (IMS) was used for the rapid qualitative separation and identification of active ingredients in generic over-the-counter drugs and food additives in beverages. The active ingredients determined in drugs were acetaminophen, aspartame, bisacodyl, caffeine, dextromethorphan, diphenhydramine, famotidine, glucosamine, guaifenesin, loratadine, niacin, phenylephrine, pyridoxine, thiamin, and tetrahydrozoline. Aspartame and caffeine were determined in beverages. Fourteen over-the-counter drugs and beverages were analyzed. Analysis times below 10Â s were obtained for IMS, and reduced mobilities were reported for the first time for 12 compounds. A quadrupole mass spectrometer coupled to a mobility spectrometer was used to assure a correct peak assignation. The combination of fast analysis, low cost, and inexpensive maintenance of IMS instruments makes IMS an attractive technique for the qualitative determination of the active ingredients in over-the-counter drugs and food additives in manufacture quality control and cleaning verification for the drug and food industries
Emerging targets for addiction neuropharmacology: From mechanisms to therapeutics
Drug abuse represents a considerable burden of disease and has enormous economic impacts on societies. Over the years, few medications have been developed for clinical use. Their utilization is endowed with several limitations, including partial efficacy or significant side effects. On the other hand, the successful advancement of these compounds provides an important proof of concept for the feasibility of drug development programs in addiction. In recent years, a wealth of information has been generated on the psychological mechanisms, genetic or epigenetic predisposing factors, and neurobiological adaptations induced by drug consumption that interact with each other to contribute to disease progression. It is now clear that addiction develops through phases, from initial recreational use to excessive consumption and compulsive drug seeking, with a shift from positive to negative reinforcement driving motivated behaviors. A greater understanding of these mechanisms has opened new vistas in drug development programs. Researchers' attention has been shifted from investigation of classical targets associated with reward to biological substrates responsible for negative reinforcement, impulse loss of control, and maladaptive mechanisms resulting from protracted drug use. From this research, several new biological targets for the development of innovative therapies have started to emerge. This chapter offers an overview of targets currently under scrutiny for the development of new medications for addiction. This work is not exhaustive but rather it provides a few examples of how this research has advanced in recent years by virtue of studies carried out in our laboratory
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
Leber's Optic Neuropathy Treated with Idebenone
Leber's Hereditary Optic Neuropathy (LHON) was diagnosed in a 17 yr-old boy (FM) on a clinical and laboratory basis. Mitochondrial DNA was positive for positions 11778, 3460 and 15257 as well as for other asyptomatic members of his family: patient's mother (NM-46 yr-old), patient's twin brother (JM-17 yr-old) and patient's younger sister (VM-7 yr-old)