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Sabtu, 07 Juli 2012

The Origins Of Key Immune Cells

The Origins Of Key Immune Cells

Main Category: Immune System / Vaccines
Also Included In: Infectious Diseases / Bacteria / Viruses
Article Date: 07 Jul 2012 - 0:00 PDT

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Chronic inflammatory conditions are extremely common diseases in humans and in the entire animal kingdom. Both in autoimmune diseases and pathogen-caused diseases, the inflamed areas are rapidly colonized by antibody producing B lymphocytes - which organize themselves in highly structured areas called "lymphoid follicles". The scaffold of such follicles is provided by follicular dendritic cells (FDCs). FDCs have important roles in the development of immune responses, since they trap antigens for protracted periods, thereby training B lymphocytes to recognize the invaders. However, FDCs can also play deleterious roles in disease, because they can provide sanctuaries for infectious pathogens such as the human immunodeficiency virus and prions.

But where do FDCs come from? Because they can arise so quickly, it has been discussed that FDCs might arise from circulating blood cells. Conversely, if FDCs are immobile cells, they would have to be ubiquitous in order to support formation of lymphoid follicles in any given place of the body.

In a paper published in the journal Cell, Dr. Nike KrÃ¤utler in the team of Professor Adriano Aguzzi at the University of Zurich went after the latter question. Using novel markers identified in the Aguzzi laboratory in the past several years, they have identified clues suggesting that FDC precursor cells exist in the wall of blood vessels. This would explain many of the properties of FDCs, including the broad range of organs in which lymphoid follicles can arise during inflammatory conditions - because blood vessels are present in most organs of the body.

The specific morphology of the putative FDC precursor cells suggested that they be identical with mural cells, pluripotent cells which decorate vessel walls. One typical marker of mural cells is platelet derived growth factor receptor Î² (PDGFR-Î²). However, FDCs do not express PDGFR-Î². Aguzzi and colleagues reasoned that this may be due to mural cells losing expression of PDGFR-Î² during their maturation into FDCs. In order to test this hypothesis, they used a sophisticated cell-lineage tracing approach. "Reporter" mice were generated whose FDCs would be stained by a blue marker if they had expressed PDGFR-Î² at any point in their life, even if PDGFR-Î² expression was suppressed at the time of analysis. Under these conditions, KrÃ¤utler and Aguzzi found that FDCs express the blue marker, indicating that they stem from another cell type which had previously expressed PDGFR-Î².

The final piece of evidence nailing the origin of FDCs came from a transplantation experiment. KrÃ¤utler and colleagues isolated pure vascular mural cell populations from fat tissue of mice, which were then introduced into collagen sponges. The sponges were then transplanted into a special mouse strain that cannot develop FDCs. Upon induction of an inflammatory state, FDCs and lymphoid follicles were found to arise within the collagen sponges. Because the FDCs could not possibly have developed from the host animals, this experiment positively demonstrates that mural cells can give rise to FDCs.

The work that is currently published in Cell clarifies a question that has been controversially discussed for the last 25 years. The recognition that FDCs derive from pluripotent mural cells helps understanding autoimmune and pathogen-driven chronic inflammatory conditions, the generation of FDC-derived tumors, and certain aspects of the pathogenesis of acquired immunodeficiency syndrome (AIDS) and of prion infections. Because FDCs are an important site of prion-replication outside the brain, there is reason to hope that interfering with the differentiation of vascular FDC precursors may play a positive role in preventing prion infections.

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Literature: Nike Julia Krautler, Veronika Kana, Jan Kranich, Yinghua Tian, Dushan Perera, Doreen Lemm, Petra Schwarz, Annika Armulik, Jeffrey L. Browning, Michelle Tallquist, Thorsten Buch, JosÃ© B. Oliveira-Martins, Caihong Zhu, Mario Hermann, Ulrich Wagner, Robert Brink, Mathias Heikenwalder, and Adriano Aguzzi. Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors. Cell, 5 July, 2012.
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Some Patients With Multiple Sclerosis Experience Fewer Flu-Like Symptoms With Fingolimod

Some Patients With Multiple Sclerosis Experience Fewer Flu-Like Symptoms With Fingolimod

Main Category: Multiple Sclerosis
Article Date: 07 Jul 2012 - 0:00 PDT

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The immunosuppressive drug fingolimod (trade name: GilenyaÂ®) is approved for the treatment of highly-active relapsing-remitting multiple sclerosis (RRMS) in adults. In an early benefit assessment pursuant to "Act on the Reform of the Market for Medicinal Products" (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) assessed whether fingolimod offers an added benefit compared with the present standard therapy.

According to the findings of the assessment, patients with a rapidly progressive and severe course of disease who take fingolimod experience fewer flu-like symptoms. Under consideration of this advantage on the one hand and the uncertain evidence base on the other, IQWIG has concluded that the data provide a "hint" of a minor added benefit of fingolimod for this group of patients.

Due to a lack of evaluable data, an added benefit is not proven for two further groups of patients.

Separate assessment in three groups of patients

According to the different areas of application, IQWiG performed separate assessments of the drug in three groups of patients. Fingolimod was compared with glatiramer acetate in patients with highly active RRMS who had not responded to a complete and appropriate (usually at least one-year) cycle with beta-interferon (IFN-Î²).

In patients with highly active RRMS who had not received sufficient IFN-Î² therapy and in those with rapidly progressive severe RRMS, fingolimod was in each case compared with IFN-Î² 1a.

Evaluable data only for one group of patients

One relevant study was available for the early benefit assessment, an approval study on fingolimod (TRANSFORMS), which compared treatment with fingolimod versus IFN Î² 1a in adults with RRMS. However, the study only provided data for one of the three patient groups specified by the Federal Joint Committee (G-BA), namely for those with rapidly progressive severe RRMS.

The manufacturer dossier did not contain evaluable data for a benefit assessment in the other two groups, that is, patients with highly active RRMS who had already received a complete pre-treatment with IFN-Î² and patients with RRMS who had not received sufficient pre-treatment with IFN-Î². An added benefit of fingolimod is therefore not proven for these therapeutic indications.

Fewer flu-like symptoms in some patients

The study results in patients with rapidly progressive severe RRMS did not indicate significant differences between treatment groups for the outcomes "relapse", "progression of disability" and "health-related quality of life". No data were reported for the outcomes "fatigue" and "activities of daily living" for this patient group, even though such data were collected in the study. Likewise, no significant difference was shown between treatment groups regarding the overall rate of side effects (adverse events), serious adverse events, and study discontinuations due to adverse events.

However, for the outcome "frequency of flu-like symptoms" the data provided an indication of less harm: patients treated with fingolimod experienced fewer such symptoms.

Only "hint" of added benefit due to inadequate data

It should be noted that conclusions on the group of patients with rapidly progressive severe RRMS are somewhat uncertain. For example, according to the approval status, this patient group is defined by several disease criteria, but the study participants for whom the manufacturer had presented data did not fulfil all of these criteria and can only be identified indirectly as a patient group in the study pool.

Under consideration of this uncertain evidence base on the one hand and the potential advantage on the other, in summary IQWiG concludes that there is a "hint" of a minor added benefit of fingolimod in patients with rapidly progressive severe RRMS treated with fingolimod compared with those treated with beta-interferon.

G-BA decides on the extent of added benefit

The procedure for inferring the overall conclusion on the extent of added benefit is a proposal from IQWiG. The G-BA, which has opened a formal commenting procedure, decides on the extent of added benefit.

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Some People Suffer Allergy-Like Symptoms After Drinking Wine

Some People Suffer Allergy-Like Symptoms After Drinking Wine

Main Category: Food Intolerance
Also Included In: Alcohol / Addiction / Illegal Drugs
Article Date: 07 Jul 2012 - 0:00 PDT

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Around seven percent of adults suffer from an intolerance to wine. This is the result of a survey presented by Peter Wigand and co-authors in the current edition of Deutsches Arzteblatt International (Dtsch Arztelb Int 2012; 109 (25): 437-44).

The authors evaluated 948 questionnaires that were returned from the 4000 sent out to randomly selected people between the ages of 20 and 69 years. They found that women (8.9%) were more often affected by an intolerance to wine than men (5.2%). The most commonly reported reactions included flushed and itchy skin and a runny nose. The symptoms were particularly common after drinking red wine. Additionally, people with a wine intolerance were more likely to report other food intolerances.

The interpretation of Wigand et al. is that these results do not necessarily indicate a true allergy, but rather an intolerance to alcohol, biogenic amines, sulfites, or other ingredients.

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Obesity Linked To Acute Kidney Injury After Heart Surgery

Obesity Linked To Acute Kidney Injury After Heart Surgery

Main Category: Obesity / Weight Loss / Fitness
Also Included In: Cardiovascular / Cardiology;Â Â Urology / Nephrology
Article Date: 07 Jul 2012 - 0:00 PDT

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Obesity increases the risk of acute kidney injury (AKI) following cardiac surgery, according to a Vanderbilt study published in the Journal of the American Society of Nephrology.

Considered common after cardiac surgery, AKI represents a fivefold increase in mortality risk within 30 days after the procedure and is associated with longer hospital stays and a range of complications.

The study, led by anesthesiologist Frederic T. (Josh) Billings IV, M.D., M.Sc., followed a sample of 455 cardiac surgery patients at Vanderbilt University Hospital and Brigham and Women's Hospital in Boston. Some 25 percent of the patients developed AKI after their procedure.

The study found that patients with a higher body mass index (BMI) had a much greater risk. After adjusting for several other risk factors, the odds of AKI increased a staggering 26.5 percent for every five-point increase in a patient's BMI.

Billings and colleagues used a statistical technique called mediation analysis to discover that oxidative stress could be the mechanism by which obesity influences acute kidney injury. Oxidative stress is the toxic overabundance of reactive oxygen species, brought on by excess generation or insufficient elimination.

"By identification of this mechanism, we now may be able to target intraoperative oxidative stress with the hope of reducing kidney injury following cardiac surgery. That may be particularly appropriate for obese individuals," Billings said.

The authors noted that the finding is "consistent with the hypothesis that oxidative stress partially mediates the association between BMI and AKI."

"I think we learned something really important by doing the mediation analysis," said biostatistician Jonathan Schildcrout, Ph.D., one of the study's authors. "You could have just examined the BMI and AKI association, and everybody would have said, 'OK, obese people have higher risk of AKI.'

"When you learn the mechanism, you can start to learn how to intervene to prevent the injury," Schildcrout said.

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Jumat, 06 Juli 2012

Parenthood May Reduce the Risk of Catching a Cold

Parenthood May Reduce the Risk of Catching a Cold

Parenthood May Reduce the Risk of Catching a Cold

July 6, 2012 -- A new study suggests that being a parent may boost immunity to cold-causing viruses, though researchers acknowledge it may not always feel that way.

In a series of experiments where adults had viruses placed directly into their noses, parents were about half as likely to get sick as adults who did not have children.

Researchers are quick to say, however, that the study doesn't mean that parents get fewer colds, overall, than people who don't have kids.

"We're not saying that parents are exposed to fewer viruses. I think people will probably agree that parents are exposed to stuff constantly, whether you have kids going to day care or going to school or being around other children," says researcher Rodlescia S. Sneed, MPH, a doctoral student in the psychology department at Carnegie Mellon University in Pittsburgh, Pa. "But that's a little bit different than the question we're asking."

Natural Cold and Flu Remedies

Parenting and the Immune System

For the study, researchers took a second look at three different experiments where adults were exposed to viruses that cause colds. The three experiments included nearly 800 healthy adults who were between the ages of 18 and 55. Forty-two percent of adults in the study were parents.

Before the study, people were asked about a variety of things that are known to affect health, like sleep, smoking, alcohol use, stress, education, and marital status. They were also asked about social support they might get from friends, family, and co-workers. Blood tests were used to measure the level of antibodies that study participants might already have against the viruses that were used in the studies.

After spending a day in quarantine to make sure they weren't already coming down with some kind of bug, researchers put drops containing cold viruses directly into their noses. People in the studies then spent five to six days sequestered in a lab. Blood tests showed that about three quarters of study participants were infected by the viruses. But only about one-third (32%) developed the sneezy, watery-eyed, congested misery of a full-blown cold.

Parents were about half as likely to catch colds from the viruses as childless adults. The protection seemed to go up the more children a person had. Parents who did not live with their children saw the greatest protection of all. They were about 75% less likely to get sick after being exposed to the viruses compared to adults who didn't have children.

From an evolutionary perspective, Sneed says, it makes sense that parents would get an immune boost.

"One of the goals of having children is not even just having them, but raising them so that they can be successful, and in order to do that, you yourself have to be healthy," Sneed tells WebMD.

Meningitis Vaccine Is Being Developed From Common Cold Virus

Meningitis Vaccine Is Being Developed From Common Cold Virus

Editor's Choice
Main Category: Immune System / Vaccines
Also Included In: Infectious Diseases / Bacteria / Viruses;Â Â Pediatrics / Children's Health
Article Date: 06 Jul 2012 - 11:00 PDT

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A leading cause for meningitis and septicemia in the UK is meningococcus B (MenB) bacterium infection. Healthy children can become severely ill within just a few hours if they contract meningitis or septicemia, as both illnesses develop randomly and with alarming speed. It often occurs in babies, very young children or teenagers between the ages of 15 to 19 years.

Each year, over 1,300 cases of MenB diseases are reported in the UK and Ireland. 5% of those who contract the disease will die, three quarters of which are children below the age of 5, and those who survive can be left with permanent disabilities, including deafness or blindness, developing learning disabilities, and having digits or even entire limbs amputated.

Pioneering scientists hope to find a way to provide an effective protection against the devastating disease by developing a new meningitis vaccine in which a harmless version of the cold virus is inserted with part of the bacterium.

Even though antibiotics can save lives, some children are too ill by the time they arrive at the hospital to receive antibiotic treatment, which makes vaccination the best option to prevent the disease. Although there are vaccines available in the UK that protect against other bugs that cause meningitis and septicemia, no approved vaccine is available that can protect children from MenB.

Researchers from Oxford University are currently developing a new vaccine against MenB, which they hope will provide protection for children. Leading researcher, Professor Andrew Pollard who is director of the Oxford Vaccine Group, explained:

"Vaccines normally contain fragments of the bug that causes a particular disease, or bugs that have been killed or weakened in some way. They work by stimulating a child's immune system to recognize and attack the bug if it ever invades the body. We hope the new vaccine will give broad-ranging protection against the many, subtly different types of MenB bacteria. Evidence suggests that using the cold virus might stimulate a rapid, large and long-lasting immunity to MenB infection."

The researchers are testing the efficacy of the novel vaccine in a laboratory model and investigate whether it is possible to use the vaccine in conjunction with other vaccines against MenB that they are researching in other projects. They hope that a combination of the most promising vaccine candidates into one single formulation could be a feasible option to boost their overall potency.

Dr Caroline Johnston, Research Evaluation Manager at Action Medical Research, explained:

"An effective vaccine could save many children's lives and stop countless others from developing serious, lifelong disabilities, such as blindness, deafness and loss of limbs. Preventing disabilities could spare children from suffering and bring large cost savings - to the children, their families and society as a whole."

The researchers hope the novel vaccine will benefit children from all over the world at an affordable cost to ensure widespread use. If their research proves successful, they plan to conduct clinical trials on the vaccine as soon as possible.

Written by Petra Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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