GARLIC BROCCOLI BOOST FIGHT AGAINST CANCER

Cancer types such as melanoma, prostate cancer and certain types of leukemia weaken the body by over-activating the natural immune system. Researchers from the University of Copenhagen have now demonstrated that selenium -- naturally found in, e.g., garlic and broccoli -- slows down the immune over-response. In the long term, this may improve cancer treatment. The findings have been published in the Journal of Biological Chemistry.

The immune system is designed to remove things not normally found in the body. Cells undergoing change, e.g. precursors of cancer cells, are therefore normally recognised and removed by the immune system. Unfortunately, the different cancer cells contain mechanisms that block the immune system's ability to recognise them, allowing them to freely continue cancer development.

Certain cancer cells overexpress immunostimulatory molecules in liquid form. Such over-stimulation has a negative impact on the immune system:

"You can say that the stimulating molecules over-activate the immune system and cause it to collapse, and we are, of course, interested in blocking this mechanism. We have now shown that certain selenium compounds, which are naturally found in, e.g., garlic and broccoli, effectively block the special immunostimulatory molecule that plays a serious role for aggressive cancers such as melanoma, prostate cancer and certain types of leukemia," says Professor Søren Skov, Department of Veterinary Disease Biology, University of Copenhagen.

Dissolved molecules

In this study, the researchers are focusing on the so-called NGK2D ligands. There are eight variants, of which one in particular has caught the researchers' attention, because it assumes liquid form. It is precisely the molecular dissolution that causes serious problems, once the cancer is raging. The entire bloodstream is, so to speak, infected, and the molecule is therefore used as a marker of serious illness:

"Molecules are found both on the surface of the cancer cells and dissolved in the blood of the affected person. We are now able to show that selenium compounds appear to have a very beneficial effect when it comes to neutralising the special variant of the NGK2D ligand -- both in soluble form and when the molecule is placed on the cell surface," says Professor Søren Skov.

Better drugs in future

The researchers are constantly learning more about the disease mechanisms causing aggressive cancers in the skin, blood and reproductive organs:

"The overexpression seen in cancers such as melanoma, prostate cancer and certain types of leukemia significantly impairs the immune system. If we can find ways to slow down the over-stimulation, we are on the right track. The new results are yet another small step towards better cancer drugs with fewer adverse effects," says Søren Skov.

New Channel Found To Protect Against Pain

Today's post from medicalxpress.com (see link below) discusses the finding of a new ion channel which is present in the membranes of neurons and protects against pain sensations. Now this won't mean much to the average reader but basically, the mechanisms in nerve cells that cause burning pain (typical of neuropathy) have been and remain very poorly understood. It's now believed that this pain comes from continuous activity in the bundles of nociceptor fibers in and around nerve cells. A sort of continuous vibration of those fibers that causes irritation. The newly discovered channel of potassium ions is thought to calm this activity down thus reducing pain. This means that they can now look into ways of strengthening these channels so that they give better protection and strengthen their own activity, thus in theory, reducing pain. Again, it all sounds gobbledegook for most people but it's vitally important that this sort of close inspection of how nerve cells work continues, so that in the not too distant future, effective solutions can be developed. How long will it take? How long is a piece of string? However, it is encouraging that this sort of work is going on in the background so that one day we might be able to get off the chemical medications that are pretty ineffective in controlling our neuropathic symptoms.

Researchers identify innate channel that protects against pain
Provided by University of Bristol January 21, 2014

Scientists have identified a channel present in many pain detecting sensory neurons that acts as a 'brake', limiting spontaneous pain. It is hoped that the new research, published today [22 January] in the Journal of Neuroscience, will ultimately contribute to new pain relief treatments.

Spontaneous pain is ongoing pathological pain that occurs constantly (slow burning pain) or intermittently (sharp shooting pain) without any obvious immediate cause or trigger. The slow burning pain is the cause of much suffering and debilitation. Because the mechanisms underlying this type of slow burning pain are poorly understood, it remains very difficult to treat effectively.

Spontaneous pain of peripheral origin is pathological, and is associated with many types of disease, inflammation or damage of tissues, organs or nerves (neuropathic pain). Examples of neuropathic pain are nerve injury/crush, post-operative pain, and painful diabetic neuropathy.

Previous research has shown that this spontaneous burning pain is caused by continuous activity in small sensory nerve fibers, known as C-fiber nociceptors (pain neurons). Greater activity translates into greater pain, but what causes or limits this activity remained poorly understood.

Now, new research from the University of Bristol, has identified a particular ion channel present exclusively in these C-fiber nociceptors This ion channel, known as TREK2, is present in the membranes of these neurons, and the researchers showed that it provides a natural innate protection against this pain.

Ion channels are specialised proteins that are selectively permeable to particular ions. They form pores through the neuronal membrane. Leak potassium channels are unusual, in that they are open most of the time allowing positive potassium ions (K+) to leak out of the cell. This K+ leakage is the main cause of the negative membrane potentials in all neurons. TREK2 is one of these leak potassium channels. Importantly, the C-nociceptors that express TREK2 have much more negative membrane potentials than those that do not.

Researchers showed that when TREK2 was removed from the proximity of the cell membrane, the potential in those neurons became less negative. In addition, when the neuron was prevented from synthesizing the TREK2, the membrane potential also became less negative.

They also found that spontaneous pain associated with skin inflammation, was increased by reducing the levels of synthesis of TREK2 in these C-fiber neurons.

They concluded that in these C-fiber nociceptors the TREK2 keeps membrane potentials more negative, stabilizing their membrane potential, reducing firing and thus limiting the amount of spontaneous burning pain.

Professor Sally Lawson, from the School of Physiology and Pharmacology at Bristol University, explained: "It became evident that TREK2 kept the C-fiber nociceptor membrane at a more negative potential. Despite the difficulties inherent in the study of spontaneous pain, and the lack of any drugs that can selectively block or activate TREK2, we demonstrated that TREK2 in C-fiber nociceptors is important for stabilizing their membrane potential and decreasing the likelihood of firing. It became apparent that TREK2 was thus likely to act as a natural innate protection against pain. Our data supported this, indicating that in chronic pain states, TREK2 is acting as a brake on the level of spontaneous pain."

Dr Cristian Acosta, the first author on the paper and now working at the Institute of Histology and Embriology of Mendoza in Argentina, said "Given the role of TREK2 in protecting against spontaneous pain, it is important to advance our understanding of the regulatory mechanisms controlling its expression and trafficking in these C-fiber nociceptors. We hope that this research will enable development of methods of enhancing the actions of TREK2 that could potentially some years hence provide relief for sufferers of ongoing spontaneous burning pain."

The research, funded by the Wellcome Trust, was carried out in the School of Physiology and Pharmacology at the University of Bristol.

Explore further: Short circuit in molecular switch intensifies pain

More information: 'TREK2 Expressed Selectively in IB4-Binding C-Fiber Nociceptors Hyperpolarizes Their Membrane Potentials and Limits Spontaneous Pain' by Cristian Acosta, Laiche Djouhri, Roger Watkins, Carol Berry, Kirsty Bromage and Sally Lawson in the Journal of Neuroscience.

Journal reference: Journal of Neuroscience

http://medicalxpress.com/news/2014-01-innate-channel-pain.html 

COOLING OF DIALYSIS PROTECTS AGAINST BRAIN DAMAGE

While dialysis can cause blood pressure changes that damage the brain, cooling dialysis fluids can protect against such effects. The findings come from a study appearing in an upcoming issue of theJournal of the American Society of Nephrology (JASN). The cooling intervention can be delivered without additional cost and is simple to perform

While dialysis is an essential treatment for many patients with kidney disease, it can cause damage to multiple organs, including the brain and heart, due to the sudden removal of bodily fluids.

To characterize dialysis-induced brain injury and to see whether cooled dialysis fluids (called dialysate) might help reduce such injury, Christopher McIntyre, DM, and his colleagues randomized 73 new dialysis patients to dialyze with body temperature dialysate or dialysate cooled to 0.5◦C below body temperature for 1 year. (Dr. McIntyre was at the University of Nottingham in the UK while conducting this work but is now at the University of Western Ontario and the London Health Sciences Centre, in Canada.)

The study demonstrated that dialysis drives progressive white matter brain injury due to blood pressure instability; however, patients who dialyzed at 0.5◦C below body temperature were completely protected against such white matter changes.

"This study demonstrates that paying attention to improving the tolerability of dialysis treatment -- in this case by the simple and safe intervention of reducing the temperature of dialysate -- does not just make patients feel better, but also can completely protect the brain from progressive damage," said Dr. McIntyre.

FIGHT AGAINST ALZHEIMERS DISEASE NEW RESEARCH ON WALNUT

A new animal study published in the Journal of Alzheimer's Diseaseindicates that a diet including walnuts may have a beneficial effect in reducing the risk, delaying the onset, slowing the progression of, or preventing Alzheimer's disease.

Research led by Abha Chauhan, PhD, head of the Developmental Neuroscience Laboratory at the New York State Institute for Basic Research in Developmental Disabilities (IBR), found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet.

The researchers suggest that the high antioxidant content of walnuts (3.7 mmol/ounce) may have been a contributing factor in protecting the mouse brain from the degeneration typically seen in Alzheimer's disease. Oxidative stress and inflammation are prominent features in this disease, which affects more than five million Americans.

"These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer's disease -- a disease for which there is no known cure," said lead researcher Dr. Abha Chauhan, PhD. "Our study adds to the growing body of research that demonstrates the protective effects of walnuts on cognitive functioning."

The research group examined the effects of dietary supplementation on mice with 6 percent or 9 percent walnuts, which are equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. This research stemmed from a previous cell culture study led by Dr. Chauhan that highlighted the protective effects of walnut extract against the oxidative damage caused by amyloid beta protein. This protein is the major component of amyloid plaques that form in the brains of those with Alzheimer's disease.

Someone in the United States develops Alzheimer's disease every 67 seconds, and the number of Americans with Alzheimer's disease and other dementias are expected to rapidly escalate in coming years as the baby boom generation ages. By 2050, the number of people age 65 and older with Alzheimer's disease may nearly triple, from five million to as many as 16 million, emphasizing the importance of determining ways to prevent, slow or stop the disease. Estimated total payments in 2014 for all individuals with Alzheimer's disease and other dementias are $214 billion.

Walnuts have other nutritional benefits as they contain numerous vitamins and minerals and are the only nut that contains a significant source of alpha-linolenic acid (ALA) (2.5 grams per ounce), an omega-3 fatty acid with heart and brain-health benefits. The researchers also suggest that ALA may have played a role in improving the behavioral symptoms seen in the study.