Revisión prioritaria de la FDA para cladribina en EM - DiarioMedico.com

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Revisión prioritaria de la FDA para cladribina en EM
La compañía alemana Merck KGaA ha recibido el visto bueno de la agencia reguladora estadounidense FDA para solicitar la aprobación de cladribina en comprimidos para la esclerosis múltiple (EM) recurrente.

Redacción - Viernes, 30 de Julio de 2010 - Actualizado a las 00:00h.

Fuentes de la compañía señalan que la solicitud será revisada por el procedimiento prioritario, que la FDA reserva para los fármacos que pueden suponer un avance en el tratamiento de una enfermedad. Cladribina es una molécula pequeña que puede interferir con el comportamiento y proliferación leucocitaria, sobre todo en los linfocitos, que se cree están implicados en el proceso patológico de la EM.

Vía libre en la UE para 'Ozurdex'
La compañía estadounidense Allergan ha recibido la autorización de la agencia europea EMA para Ozurdex, un implante intravítreo de 700 microgramos de dexametasona. El implante se convierte así en el primer tratamiento con licencia en Europa para el edema macular en pacientes con oclusión venosa de la retina (OVR). El implante contiene un potente corticosteroide administrado mediante un aplicador desechable, libera lentamente la dexametasona en la cavidad vítrea y actúa localmente para controlar el edema.
Revisión prioritaria de la FDA para cladribina en EM - DiarioMedico.com

Identification of a Cell of Origin for Human Prostate Cancer -- Goldstein et al. 329 (5991): 568 -- Science

Science 30 July 2010:
Vol. 329. no. 5991, pp. 568 - 571
DOI: 10.1126/science.1189992

Reports
Identification of a Cell of Origin for Human Prostate Cancer
Andrew S. Goldstein,1 Jiaoti Huang,2,3,6 Changyong Guo,2,4 Isla P. Garraway,2,4 Owen N. Witte1,5,6,*

Luminal cells are believed to be the cells of origin for human prostate cancer, because the disease is characterized by luminal cell expansion and the absence of basal cells. Yet functional studies addressing the origin of human prostate cancer have not previously been reported because of a lack of relevant in vivo human models. Here we show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells and expansion of luminal cells expressing prostate-specific antigen and alpha-methylacyl-CoA racemase. Our results demonstrate that histological characterization of cancers does not necessarily correlate with the cellular origins of the disease.

1 Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
2 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
3 Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA 90095, USA.
4 Department of Urology, UCLA, Los Angeles, CA 90095, USA.
5 Department of Microbiology, Immunology and Molecular Genetics; Department of Molecular and Medical Pharmacology; Howard Hughes Medical Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
6 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.

* To whom correspondence should be addressed at Howard Hughes Medical Institute, UCLA, Los Angeles, 675 Charles E. Young Drive South, 5-748 MRL, Los Angeles, CA90095–1662, USA. E-mail: owenwitte@mednet.ucla.edu

Identification of a Cell of Origin for Human Prostate Cancer -- Goldstein et al. 329 (5991): 568 -- Science

Chemistry and Biology - Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains

Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains
Catarina R. Vieira, Jose M. Munoz-Olaya, Jesús Sot, Sonia Jiménez-Baranda, Nuria Izquierdo-Useros, Jose Luis Abad, Beatriz Apellániz, Rafael Delgado, Javier Martinez-Picado, Alicia Alonso, Josefina Casas, José L. Nieva, Gemma Fabriás, Santos Mañes, Félix M. GoñiSee

Affiliations: Rollover Authors and Affiliations Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, E-28049 Madrid, Spain Department of Biomedicinal Chemistry, Institute of Advanced Chemistry of Catalonia (IQAC)/CSIC, Jordi Girona 18, 08034 Barcelona, Spain Unidad de Biofísica (Centro Mixto CSIC-UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, E-48080 Bilbao, Spain irsiCaixa Foundation, Hospital Universitari Germans Trias i Pujol, E-08916 Badalona, Spain Hospital Universitario 12 de Octubre, Avenida. Andalucía s/n, E-28049 Madrid, Spain ICREA, Barcelona, Spain Corresponding author These authors contributed equally to this work These authors contributed equally to the design and direction of this work

Graphical Abstract
Highlights
•We show that dihydrosphingolipids form solid-ordered microdomains in model membranes
•Des1 inhibition increases dihydrosphingolipid levels in the membrane of living cells
•Chemical and genetic blockade of Des1 activity inhibits infection by HIV-1
•Dihydrosphingolipid-enriched membranes are less prone to HIV-1 gp41-mediated fusion

Summary
The lateral organization of lipids in cell membranes is thought to regulate numerous cell processes. Most studies focus on the coexistence of two fluid phases, the liquid crystalline (ld) and the liquid-ordered (lo); the putative presence of gel domains (so) is not usually taken into account. We show that in phospholipid:sphingolipid:cholesterol mixtures, in which sphingomyelin (SM) promoted fluid lo domains, dihydrosphingomyelin (DHSM) tended to form rigid domains. Genetic and pharmacological blockade of the dihydroceramide desaturase (Des1), which replaced SM with DHSM in cultured cells, inhibited cell infection by replication-competent and -deficient HIV-1. Increased DHSM levels gave rise to more rigid membranes, resistant to the insertion of the gp41 fusion peptide, thus inhibiting viral-cell membrane fusion. These results clarify the function of dihydrosphingolipids in biological membranes and identify Des1 as a potential target in HIV-1 infection.

open here please:
Chemistry and Biology - Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains
Chemistry & Biology, Volume 17, Issue 7, 766-775, 30 July 2010; doi:10.1016/j.chembiol.2010.05.023
http://www.cell.com/chemistry-biology/fulltext/S1074-5521(10)00214-0

Chemistry & Biology
http://www.cell.com/chemistry-biology/home

CNB/CSIC
http://www.cnb.uam.es/

research: (spanish version)
href="http://www.cnb.csic.es/content/research/immunoncology/lipidrafts/docs/sida.pdf">http://www.cnb.csic.es/content/research/immunoncology/lipidrafts/docs/sida.pdf

Hospital 12 de Octubre
http://www.madrid.org/cs/Satellite?pagename=Hospital12Octubre/Page/H12O_home

Instituto de Química Avanzada de Catalunya
http://www.iqac.csic.es/

IrsiCaixa
http://www.irsicaixa.org/

spanish version:
Actualidad Ultimas noticias - JANOes - Descubren como bloquear la entrada del virus del sida en las celulas - JANO.es - ELSEVIER

Blog.AIDS.gov: NIH-Led Scientists Find Antibodies that Prevent Most HIV Strains from Infecting Human Cells

Atomic structure of the antibody VRC01 (blue and green) binding to HIV (grey and red). The precise site of VRC01-HIV binding (red) is a subset of the area of viral attachment to the primary immune cells HIV infects.
View larger image
Credit: NIAID VRC

NIH-Led Scientists Find Antibodies that Prevent Most HIV Strains from Infecting Human Cells
By Laura Sivitz Leifman, National Institute of Allergy and Infectious Diseases, NIH

Scientists have discovered two potent human antibodies that can stop more than 90 percent of known global HIV strains from infecting human cells in the laboratory. The scientists also have demonstrated how one of these disease-fighting proteins accomplishes this feat. According to the scientists, these antibodies could be used to design improved HIV vaccines, or could be further developed to prevent or treat HIV infection. Plus, the method used to find these antibodies could be applied to isolate therapeutic antibodies for other infectious diseases as well.

Led by a team from the NIAID Vaccine Research Center (VRC), the scientists found two powerful antibodies called VRC01 and VRC02 in an HIV-infected individual's blood. They discovered the antibodies using a probe they developed that homes in on the specific cells that make antibodies against a very vulnerable spot on HIV.

The scientists found that VRC01 and VRC02 neutralize more HIV strains with greater overall strength than previously known antibodies to the virus.

The researchers also determined the atomic-level structure of VRC01 when it is attaching to HIV. This enabled the team to define how the antibody works and to precisely locate where it attaches to the virus. With this knowledge, they have begun to design components of a candidate vaccine that could teach the human immune system to make antibodies similar to VRC01 that might prevent infection by the vast majority of HIV strains worldwide.

NIAID scientists Peter D. Kwong, Ph.D., John R. Mascola, M.D., and Gary J. Nabel, M.D., Ph.D., led the research. A pair of articles about these findings was published July 8 in the online edition of Science.

Finding individual antibodies that can neutralize HIV strains anywhere in the world has been difficult because the virus continuously changes its surface proteins to evade immune system recognition. As a consequence, an enormous number of HIV variants exist worldwide. Even so, scientists have identified a few areas on HIV’s surface that remain nearly constant across all variants. One such area, located on the surface spikes used by HIV to attach to immune system cells and infect them, is called the CD4 binding site. VRC01 and VRC02 block HIV infection by attaching to the CD4 binding site, preventing the virus from latching onto immune cells.

“The discoveries we have made may overcome the limitations that have long stymied antibody-based HIV vaccine design,” says Dr. Kwong.
Blog.AIDS.gov: NIH-Led Scientists Find Antibodies that Prevent Most HIV Strains from Infecting Human Cells

Biomarkers found for postmenopausal cardiovascular disease

Contact: Graeme Baldwin
graeme.baldwin@biomedcentral.com
44-020-319-22165
BioMed Central

Biomarkers found for postmenopausal cardiovascular disease
Analysis of blood protein data from the Women's Health Initiative cohorts has revealed new biomarkers for stroke and coronary heart disease (CHD). Research published in BioMed Central's open access journal Genome Medicine found that beta-2 microglobulin (B2M) levels were significantly elevated in postmenopausal women with CHD, and insulin-like growth factor binding protein 4 (IGFBP4) was strongly associated with stroke.

Ross Prentice, from the Fred Hutchinson Cancer Research Centre, Seattle, USA, worked with a team of researchers to carry out proteomic analyses on samples from 800 women who developed CHD, 800 who developed stroke and a group of matched controls. He said, "We contrasted pools formed by equal plasma volumes from 100 cases or from 100 pair-matched controls, with eight such pool pairs for each of the study diseases. The two novel markers we identified, B2M and IGFBP4, have the potential to help elucidate hormone therapy effects on the cardiovascular diseases as observed in the WHI randomized controlled trials".

B2M has previously been associated with CHD risk factors including age, blood pressure, and C-reactive protein, and has been reported to show an inverse association with high-density lipoprotein (HDL) cholesterol. According to Prentice, "Our finding of B2M elevation in plasma obtained months or years prior to CHD diagnosis appears to be novel, however". The identification of IGFBP4 as a risk marker for stroke in postmenopausal women also appears to be a novel finding. Speaking about the results, Prentice said, "Blood protein concentrations provide a source for novel disease risk markers that may be modifiable by treatments or other exposures. As such, protein markers have potential to enhance the understanding of disease pathogenesis, and to elucidate biological processes whereby an exposure affects disease risk."


###
Notes to Editors

1. Novel proteins associated with risk for coronary heart disease or stroke among postmenopausal women identified by in-depth plasma proteome profiling
Ross L Prentice, Sophie J Paczesny, Aaron Aragaki, Lynn M Amon, Lin Chen, Sharon J Pitteri, Martin McIntosh, Pei Wang, Tina Busald Buson, Judith Hsia, Rebecca D Jackson, Jacques E Rossouw, JoAnn E Manson, Karen Johnson, Charles Eaton and Samir M Hanash
Genome Medicine (in press)

During embargo, article available here: http://genomemedicine.com/imedia/2741688533494666_article.pdf?random=109468
After the embargo, article available at the journal website: http://genomemedicine.com/

Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BioMed Central's open access policy.

Article citation and URL available on request at press@biomedcentral.com on the day of publication.

2. Genome Medicine is an online peer-reviewed journal which publishes open access research articles of outstanding quality in all areas of medicine studied from a genomic or post-genomic perspective. The journal has a special focus on the latest technologies and findings that have an impact on the understanding and management of human health and disease.

3. BioMed Central (http://www.biomedcentral.com/) is an STM (Science, Technology and Medicine) publisher which has pioneered the open access publishing model. All peer-reviewed research articles published by BioMed Central are made immediately and freely accessible online, and are licensed to allow redistribution and reuse. BioMed Central is part of Springer Science+Business Media, a leading global publisher in the STM sector.
Biomarkers found for postmenopausal cardiovascular disease

Genetics May Influence Social Drinking

Genetics May Influence Social Drinking
Editor's Choice
Main Category: Alcohol / Addiction / Illegal Drugs
Also Included In: Psychology / Psychiatry; Genetics
Article Date: 25 Jul 2010 - 0:00 PDT

Your friend walks into a bar to meet you for happy hour. He sidles up to the bar and orders a drink - does that make you more likely to get a drink yourself? According to new findings reported in Psychological Science, a journal of the Association for Psychological Science, genetics may determine the extent to which you are influenced by social drinking cues - signals such as advertisements, drinks placed on a bar, and seeing other people around you drinking.

Drinking alcohol increases levels of dopamine - a brain chemical that causes pleasure and makes us feel good. The dopamine D4 receptor gene (DRD4) has been shown to be involved in motivation of seeking out rewards. Research has suggested that carrying a specific form (or variant) of this gene - one that includes seven or more repeats of a certain section of the gene - may be associated with craving caused by alcohol-related cues. Psychological scientist Helle Larsen from Radboud University in The Netherlands and her colleagues wanted to investigate if this 7-repeat gene variant plays a role in how an individual responds to alcohol-related cues.

For this experiment, volunteers were brought into a laboratory bar (a room set up to look like a Dutch pub) to supposedly rate a series of commercials. After the volunteers rated a number of them, they were told there would be a 30-minute break - and that during this break, they could help themselves to any of the alcoholic and nonalcoholic drinks that were available at the bar. Confederates (participants who knew what the study was about) were trained to order drinks immediately - they were to initiate drink ordering and the researchers observed which volunteers followed their lead. In addition, saliva samples were obtained from the participants for DNA analysis.

The results showed an effect between how much the confederate drank and the gene variant on volunteers' alcohol consumption: When the confederate was seen consuming three or four drinks, carriers of the 7-repeat form of the gene drank more than twice as many glasses of alcohol than did noncarriers of the gene variant. However, when the confederate consumed only one drink, there was no difference in alcohol consumption between carriers and noncarriers. These findings suggest that individuals carrying this form of the DRD4 gene may be more sensitive than noncarriers to other people's drinking behavior.

The authors note, "Carrying the DRD4 7-repeat genotype may increase the risk for extensive alcohol use or abuse when spending time with heavy-drinking peers." They conclude, "Whether or not people are wired to adapt their drinking to the choice and pace of others may partly depend on their genetic susceptibility to drinking cues."

Source: Association for Psychological Science

Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Genetics May Influence Social Drinking

PHG Foundation | Timing of screening for Fragile X Syndrome

Timing of screening for Fragile X Syndrome
29 July 2010 | By Dr Philippa Brice | Research article

Fragile X syndrome is the most common inherited form of learning disability. Caused by expansion of a section of the X-chromosome, it affects around one in 3,600 men (see BBC Health); women are less frequently affected and may have milder symptoms. Pre-mutation carriers with smaller expansion regions may not show symptoms but can develop related health problems later in life and may have children affected by Fragile X.

Population screening for Fragile X has been considered in different countries for some years now (see previous news), but raises distinct issues compared with other inherited disorders, due to the variable risks to pre-mutation carriers and female mutation carriers; the latter show very variable clinical features ranging from unaffected to severe learning disability.

A newsystematic review has examined published evidence relating to population-based screening for fragile X in women of reproductive age (ten studies) and newborn babies (one study) between 1991 and 2009 [Hill MK et al. (2010) Genet Med. 2010 Jul;12(7):396-410]. This review included analysis of papers examining psychosocial elements of screening: two forming part of the screening studies, and nine additional articles.

The authors found a general lack of evidence; although published research showed population screening to be largely effective, all the studies were observational, as opposed to controlled (comparing screening with alternative screening or no screening). Uptake of testing was found to range from 7.9% to 92% in different prenatal screening studies, 79% for the newborn study. Women premutation carriers identified by screening largely took up the offer of fetal testing, with a variable proportion opting to terminate affected pregnancies.

The challenges of providing effective genetic counselling to affected women and families who knew little or nothing about fragile X syndrome were noted; although he condition is common, it is not well recognised in the general population in the way that some other genetic disorders such as cystic fibrosis are. The main conclusions were that controlled studies should be conducted to examine both the technical and psychosocial elements of screening for Fragile X, and that specialised guidance for genetic counselling would be required.

Newborn screening was found to have more limitations than adult carrier screening. As reiterated in an accompanying commentary, although prompt identification of full mutation carriers can allow improved care, it cannot predict which female carriers will show clinical symptoms, and also identifies premutation carriers at risk of adult-onset conditions and other forms of X-chromosomal abnormality [Coffee B. Genet Med. 2010 Jul;12(7):411-2 ].

In addition to improved education and counselling, the timing of screening would appear to be crucial, with preconception screening preferable to prenatal screening among adult women, and the suggestion that optional infant screening would be a better option than newborn screening
PHG Foundation | Timing of screening for Fragile X Syndrome