How death spreads throughout an organism at the end of its life

Main Category: Seniors / Aging
Also Included In: Biology / Biochemistry
Article Date: 25 Jul 2013 - 0:00 PDT Current ratings for:
How death spreads throughout an organism at the end of its life

The final biological events in the life of a worm are described in a new article, published in the open access journal PLOS Biology. The paper reveals how death spreads like a wave from cell to cell until the whole organism is deceased.

The deaths of individual cells trigger a chemical chain reaction leading to the breakdown of cell components and a build-up of molecular debris. The molecular mechanisms of this process are reasonably well understood at a cellular level, but far less is known about how death spreads throughout an organism at the end of its life.

In worms, the spread of death can easily be seen under a microscope as a wave of blue fluorescence travelling through the gut of the worm. The new study, led by Professor David Gems from the Institute of Healthy Ageing at UCL, reveals that this fluorescence is caused by a cell death pathway called necrosis, and its spread throughout the organism is dependent on calcium signalling.

"We've identified the chemical pathways of self-destruction that propagate cell death in worms, which we see as this glowing blue fluorescence travelling through the body," explained Professor Gems. "It's like a blue Grim Reaper, tracking death as it spreads throughout the organism until all life is extinguished."

"We found that when we blocked this pathway, we could delay death induced by a stress such as infection, but we couldn't slow death from old age. This suggests that ageing causes death by a number of processes acting in parallel."

The mechanisms involved are similar to those active in mammals, confirming the worm can provide a useful model for understanding cell death, and how to prevent it, in other animals.

The study also links the mechanisms of cell death to the appearance of the blue fluorescence. The source of this fluorescence was previously thought to be a substance called lipofuscin, which emits light of a similar colour. Lipofuscin has previously been linked to ageing, since it accumulates with increasing molecular damage. However, the new findings implicate another molecule called anthranilic acid as the source of the blue hue and show that lipofuscin is not actually involved.

"Together, the findings cast doubt on the theory that ageing is simply a consequence of an accumulation of molecular damage. We need to focus on the biological events that occur during ageing and death to properly understand how we might be able to interrupt these processes," added Professor Gems.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Funding: CC, CA, FC, and DG acknowledge funding from the BBSRC, the EU (FP7-259679 IDEAL, FP6-036894 and FP6-518230), and the Wellcome Trust (Strategic Award 098565/Z/12/Z). ZP was supported by a Jane Coffin Child postdoctoral fellowship, and ZP and FJS were supported by NIH R01 AG033921. KWN acknowledges support from the NSF (IOS 0919848: KN). EA was supported in part by a Ruth L. Kirschstein National Research Service Institutional Training Grant T32 GM068411. FM is supported by a Special Research Fund fellowship from the University of Ghent. FCS and PM were supported in part by the NIH (AG033839 and GM088290). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Coburn C, Allman E, Mahanti P, Benedetto A, Cabreiro F, et al. (2013) Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans. PLoS Biol 11(7): e1001613. doi:10.1371/journal.pbio.1001613

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Easy and accurate identification of the Black Death

Main Category: Infectious Diseases / Bacteria / Viruses
Article Date: 27 Jul 2013 - 0:00 PDT Current ratings for:
Easy and accurate identification of the Black Death

Diagnosing the presence of Yersinia pestis, the cause of plague, may soon be easier than ever before. Scientists working with Peter Seeberger, Director at the Max Planck Institute of Colloids and Interfaces (MPIKG) in Potsdam and Professor at the Freie Universitat Berlin, have come up with a simple, inexpensive and reliable method of detecting the bacterium. The research team, specialising in glycochemistry glycobiology, first identified and synthesised an oligosaccharide structure on bacterial surface before combining it with a protein to heighten the immunological effect. The presence of antibodies against this surface glycan in the blood of infected patients can be a biomarker of diagnostic value in Yersinia pestis infections. The Potsdam-based scientists also used the antigen to create antibodies which can directly detect the plague pathogen in infected samples.

The Black Death is best known as a devastating medieval disease which affected Europe, Central Asia and China. The plague killed more than 200 million people through the ages. Yet it is by no means completely eradicated. In 2002 there was an outbreak of plague in the Indian state of Himachal Pradesh, and 2008 saw 18 cases reported in Madagascar. Ziketan, a city in north-west China, was quarantined after an outbreak in 2009, and in the same year there were 16 cases in Tobruk, Libya. Cases are also repeatedly reported in New Mexico, USA. As it is extremely infectious and indeed deadly, plague is one of the most dangerous bioweapons.

Although plague can be treated with antibiotics, survival rates decrease with every hour the disease remains undetected. Left untreated, plague can often lead to death within a very short time, depending on the disease type. "Early identification of an infection is of paramount importance for survival," says Chakkumkal Anish, Leader of the Glycobiology Research Group at the Max Planck Institute in Potsdam, "So our work may have direct and positive consequences on patient survival rates."

Antibodies are created with a glycoprotein as antigen

In order to specifically detect the plague pathogen, the scientists first had to identify an oligosaccharide in a lipopolysaccharide on the surface of Yersinia pestis. This oligosaccharide would serve as a specific antigen. They then synthesised the complex compound in a multi-step process. Subsequently, the chemists bound the sugar molecule to a protein which is used in many vaccines to heighten the immune reaction. The resulting glycoprotein produced by the sugar-protein compound was used to trigger an immune reaction in mice. The scientists used this circumstance to create antibodies to the plague pathogen using murine immune cells.

The antibodies can identify plague bacteria with high selectivity (accuracy) without the result being distorted by other bacteria biochemically related to plague. Thus the scientists have effectively produced a quick test for the Black Death. There are, in fact, many ways of using this particular research finding in medical practice. On the one hand, the glycan or its glycoconjugates can be applied to test strips where it acts as an antigen and catches antibodies from the blood of infected patients. The antigen-antibody complexes are very easy to detect with fluorescing proteins. On the other hand, the antibodies could provide a way of directly detecting the plague pathogen in infected tissue. Here, too, fluorescing proteins are used to identify whether the antibodies have docked onto the bacterial surface.

Advances in glycomics have a practical value in medicine

"These reliable tests are simple and economical to administer," says Peter Seeberger. This gives the new approach major advantages over the testing methods used to date. In the past, plague pathogens were detected by phenotyping or gene testing. The problem with these methods is that they are complex, expensive and slow - and, what's more, they have a high failure rate.

The new method is a direct result of research successes in glycomics. This field is dedicated to the study of carbohydrates, which includes all sugars, and their role in biology. Scientists are now able to identify and synthesise ever more complex carbohydrate molecules. "We have the ability to synthesise complex molecules from simple chemical building blocks, much like children using Lego bricks to build a space ship," explains Chakkumkal Anish. "This is just the start - we have only just begun exploiting the opportunities this brings." The chemical methods signify much more than just scientific advances. They also help scientists to come up with new methods of diagnosis and treatment, and to develop vaccinations for various diseases. "Basic research has an intrinsic value," says Peter Seeberger. "But in the field of glycomics, we are increasingly able to translate our research directly into applications with a practical value, very much like the value our latest development has for the medical world."

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In patients with kidney disease, calcium linked to increased risk of heart disease and death

Main Category: Urology / Nephrology
Also Included In: Nutrition / Diet;  Heart Disease
Article Date: 24 Jul 2013 - 0:00 PDT Current ratings for:
In patients with kidney disease, calcium linked to increased risk of heart disease and death

Kidney patients who take calcium supplements to lower their phosphorous levels may be at a 22 per cent higher risk of death than those who take other non-calcium based treatments, according to a new study by Women's College Hospital's Dr. Sophie Jamal.

The study, published in the Lancet, calls into question the long-time practice of prescribing calcium to lower phosphate levels in patients with chronic kidney disease. The researchers suggest some of the calcium is absorbed into the blood stream and may expedite hardening of the arteries, leading to a higher risk of heart disease and even death. Cardiovascular disease is a leading cause of death for people with chronic kidney disease.

"Doctors commonly prescribe calcium supplements to prevent elevated phosphate levels, which can damage the body, but a growing number of studies have shown calcium supplements may actually increase the risk of heart disease," explains Dr. Sophie Jamal, a physician at Women's College Hospital and an associate professor of medicine at the University of Toronto. "Our study validates these claims and, for the first time, shows the long-term consequences of taking calcium supplements can be dangerous for patients with kidney disease."

As part of their analysis, researchers reviewed 11 randomized, controlled studies that included more than 4,600 patients. The researchers assessed the risk of heart disease, including heart attack, stroke, and hardening of the arteries, along with death among individuals prescribed the medication containing calcium and those prescribed the medication without calcium. They found:

A 22% reduction in death among patients who took non-calcium based treatments sevelamer and lanthanum. Less artery calcification (hardening) in patients who did not take calcium supplements.

"Some researchers and physicians have been saying for years that kidney disease patients need to get off calcium, now we think our review shows there is much more solid evidence to argue for that change to clinical practice," the study's senior author Ross Tsuyuki from the University of Alberta's faculty of medicine and dentistry.

In the meantime, given the study's findings, the researchers suggest non-calcium containing treatments be used as a first line of treatment to lower phosphate for patients with chronic kidney disease.

"The findings of our study provides the best evidence as to what doctors should be prescribing their patients, but further research is necessary to help us understand how exactly calcium increases the risk of death, if non calcium-based treatments reduce the risk of death, and whether certain types of treatments may be more effective and beneficial than others," says Dr. Jamal.

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posted by Will Smith on 24 Jul 2013 at 3:46 am

Once again someone publishes a report on the bad impacts of calcium on health without specifing what type of calcium supplements that they referring to. There is a big difference between how the body uses calcium carbonate from how it uses calcium citrate. This article would be of more value if the authors had specified which calcium compound(s), they used in the study.

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Physician-assisted death laws: Hospice workers struggle on front lines

Main Category: Palliative Care / Hospice Care
Also Included In: Primary Care / General Practice
Article Date: 24 Jul 2013 - 1:00 PDT Current ratings for:
Physician-assisted death laws: Hospice workers struggle on front lines

Laws that allow physician-assisted death in the Pacific Northwest have provisions to protect the rights of patients, doctors and even the state, but don't consider the professionals most often on the front lines of this divisive issue - hospice workers who provide end-of-life care.

The existing system, a new analysis concludes, has evolved into a multitude of different and contradictory perspectives among hospice organizations and workers, who historically have opposed physician-assisted death but now are the professionals taking care of most of the people who use it.

The study - titled "Dignity, Death and Dilemmas" - was just published in the Journal of Pain and Symptom Management by researchers from Oregon State University, and outlines a complex system in which many well-intentioned caregivers struggle to organize their thoughts, beliefs and actions when dealing with a concept they traditionally oppose. It was based on an analysis of 33 hospice programs in Washington state.

When first proposed, it was feared by some that physician-assisted death might displace the palliative and supportive care offered by hospice. Now, in practice, between 85-95 percent of the people in Oregon and Washington who choose assisted death also use hospice - but the interplay they have with their caregivers can vary widely.

"It might seem a little surprising that most people who use physician-assisted death also use hospice," said Courtney Campbell, the Hundere Professor in Religion and Culture in the OSU School of History, Philosophy and Religion. "Some hospice workers were originally concerned this concept would make them unnecessary, but in fact the level of hospice usage has actually increased."

Hospice is a national program in which trained professionals provide care to terminally ill patients, ensuring they get proper medical care, adequate pain control, are involved in decision-making and have other needs met in a home environment. They work with both the patient and family to help make death a natural and accepted part of life.

However, hastening or actually causing death is not an accepted part of the hospice philosophy, even though hospice programs acknowledge the right of patients to make that choice where it's allowed by law. But balancing core beliefs, such as compassion and non-abandonment of a patient, with the new laws has been difficult at best for hospice professionals, Campbell said.

"About 75 percent of hospice organizations will not allow their workers to even be present when a fatal dose of medication is used," Campbell said.

The reaction in hospice to physician-assisted death varies from one national organization to another, from one agency to another, from one worker to another. There is little consistency to many complex questions about how, whether, and when hospice workers will get involved as individuals they care for make this choice. Approaches can range from outright opposition to non-participation or non-interference.

In recent years it's become even more difficult as assisted-death has become politicized, Campbell said. Even the words used in describing the serious issues involved are emotionally-charged and inherently contentious, the researchers noted in their report, making reference to legislation that embraced "ending life in a humane and dignified manner" while working its way around such topics as "suicide, assisted suicide, mercy killing and homicide."

Somewhat caught in the middle, and caring for the people who are affected by those laws, are the hospice workers with marginal guidance and conflicted reactions, researchers said.

"The conventional approach to the question of legalized physician-assisted death . . . has missed the issue of how the requirements of a new law are carried out by the primary caregiving institution, hospice care," the researchers wrote in their report.

The OSU research offered no simple solutions to this issue, but rather outlined a broad list of questions that could form the basis for more informed discussions - either among hospice providers, the organizations they work for or the general public.

These include such topics as the hospice mission, patient access to information, questions about legal options, how to discuss emotional or religious factors, response to specific patient requests, documentation of conversations, responsibility to the patient's family, and many other issues.

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BJP leader in TN hacked to death, party calls for statewide bandh on July 22

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Preventing Cell Death In Osteoarthritis

Main Category: Arthritis / Rheumatology
Also Included In: Bones / Orthopedics
Article Date: 12 Jul 2013 - 2:00 PDT Current ratings for:
Preventing Cell Death In Osteoarthritis

UK scientists have found a naturally occurring molecule in the body which may have important consequences for treating osteoarthritis.

Researchers from The University of Manchester and the University of Westminster have found that the molecule, known as Urocortin, protects cells in the joints from being destroyed.

The discovery could help lead to the development of new medicines to prevent joint degradation - a condition which affects millions of people in the UK each year.

Osteoarthritis, a painful condition associated with a loss of joint mobility particularly in the knees, hips, hands and vertebrae, is caused by the destruction and loss of cartilage within these joints and is on the rise as people live longer.

Specialised cells called chondrocytes are responsible for producing and maintaining healthy cartilage but in osteoarthritis the number of active cells is reduced.

Professor Paul Townsend, joint lead researcher along with Dr Ian Locke, the University of Westminster, in the study published in the journal Cell Death and Disease on 11 July, said: "In osteoarthritis many different programmed cell-death chemicals are produced which cause chondrocytes to die. Our research shows that the naturally occurring molecule, Urocortin, produced by the body is essential for these chondrocyte cells to survive."

Dr Ian Locke, director of Postgraduate Studies at the School of Life Sciences at the University of Westminster, said: "We now need to look in more detail at how Urocortin helps cells to survive in order to develop new medicines to prevent joint degradation.

"Discovering a role for this naturally occurring molecule in joint physiology opens up exciting new avenues of research towards the cause, prevention and, eventually, treatment of osteoarthritis" The researchers found that removing Urocortin caused large numbers of the chondrocyte cells to die. However adding it protected chondrocyte cells from programmed cell-death induced by chemicals present in osteoarthritic cartilage.

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The University of Manchester

University of Westminster

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posted by Su Su on 13 Jul 2013 at 7:17 am

Notice it takes another country and not a Big Drug company to find a natural way to help joints. When will this be on the market?

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posted by charlie on 13 Jul 2013 at 4:09 am

For those of us with severe osteo its good to hear about this discovery. The sad part is that any medication will likely come many years down the road, long after when some of us will get benefit (I'm 67 yrs old) and likely quite expensive. Never the less, thanks to the researchers for their good work.

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