REVOLUTIONARY DEVICE FOUND TO LOWER BLOOD PRESSURE

A revolutionary device has been shown to significantly lower blood pressure among patients with uncontrolled high blood pressure, compared to those treated with usual drug measures -- according to research from Queen Mary University of London and published in The Lancet.

 The device -- developed by ROX Medical and named the 'Coupler' -- is a paper clip sized implant which is inserted between the artery and vein in the upper thigh, in a procedure lasting around 40 minutes under local anaesthetic.

Researchers led a randomised, blinded endpoint clinical trial with patients from multiple European Centres of Hypertension Excellence -- including the Barts Blood Pressure Clinic at Barts Health NHS Trust in east London -- all of whom had resistant high blood pressure and had not responded to at least three types of drug treatment.

The team compared the effects of the Coupler versus usual medical treatment in 83 patients of whom 44 received the ROX Coupler therapy. Patients who received the Coupler experienced a significant and durable reduction in blood pressure. There was also a reduced number of hypertensive complications and hospital admissions for high blood pressure crises.

The Coupler also worked well among patients who had failed to respond to renal denervation (another new approach to treating high blood pressure), suggesting the Coupler targets different mechanisms of blood pressure control. However, patients who had not previously been treated with renal denervation experienced the same level or more of blood pressure reduction. In addition, unlike renal denervation, this new device-based treatment is fully reversible, immediate and pain-free.

Dr Melvin Lobo, Lead Author and Principal Investigator of the study at Queen Mary University of London, and Director of the Barts Blood Pressure Clinic at Barts Health NHS Trust, comments: "This is an entirely new and highly promising concept in high blood pressure treatment. Existing drugs focus on hormonal or neurological regulation of blood pressure, and newer treatments such as renal denervation are uniquely centred on the renal nervous system. The Coupler effectively targets the mechanical aspects of how blood circulation works -- so it's a totally new approach to controlling blood pressure. The Coupler also highlights the importance of arterial stiffness as a major cause of resistant high blood pressure and it targets this issue both safely and successfully. Once the Coupler is placed, the results are also immediate, which again is unique to this treatment."

The study findings show that blood pressure treatment with the ROX Coupler can give both patients and doctors an alternative option for treating high blood pressure in the future -- particularly when standard therapies have failed.

The study has also put the spotlight on how dangerous uncontrolled high blood pressure truly is. During the study there were five hospital admissions for hypertensive crises among the control group and none in the Coupler group.

However, the Coupler, like all therapies, did have a side effect. Around 29 percent of patients who received the Coupler did go on to develop leg swelling which meant another short procedure was needed to deal with this (usually a stent in the vein).

Dr Lobo concludes: "High blood pressure is very dangerous and leads to hospital treatment, stroke, heart attack and chronic kidney disease. We must find better means of treating high blood pressure as drugs do not work for everyone and the Coupler is a big step forward in our search for alternative treatment.

"It's a little too early to begin applying these findings to routine clinical care at this stage. We need more research to explore the long-term effects of the Coupler, better understand its safety and understand more about how it works within the body. However, an International Registry is commencing early this year which means we will be able to continue offering patients with uncontrolled high blood pressure the option of Coupler treatment, as long as conventional measures to get their blood pressure down to target have failed."

NEURON RESPONSIBLE FOR ALCOHOLISM FOUND

Scientists have pinpointed a population of neurons in the brain that influences whether one drink leads to two, which could ultimately lead to a cure for alcoholism and other addictions.

A study, published in the Journal of Neuroscience by researchers at the Texas A&M Health Science Center College of Medicine, finds that alcohol consumption alters the structure and function of neurons in the dorsomedial striatum, a part of the brain known to be important in goal-driven behaviors. The findings could be an important step toward creation of a drug to combat alcoholism.

"Alcoholism is a very common disease," said Jun Wang, M.D., Ph.D., the lead author on the paper and an assistant professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M College of Medicine, "but the mechanism is not understood very well."

Now, Wang and his team have helped come a little closer to that understanding. Using an animal model, the researchers determined that alcohol actually changes the physical structure of medium spiny neurons, the main type of cell in the striatum. These neurons can be thought of like a tree, with many branches, and many small protrusions, or spines, coming off of them. They each have one of two types of dopamine receptors, D1 or D2, and so can be thought of as either D1 or D2 neurons. D1 neurons are informally called part of a "go" pathway in the brain, while D2 neurons are in the "no-go" pathway. In other words, when D2 neurons are activated, they discourage action -- telling you to wait, to stop, to do nothing.

Although it is well known that the neurotransmitter dopamine is involved in addiction, this study goes further, showing that the dopamine D1 receptor also plays an important role in addiction. The team found that periodic consumption of large amounts of alcohol acts on D1 neurons, making them much more excitable, which means that they activate with less stimulation.

"If these neurons are excited, you will want to drink alcohol," Wang said. "You'll have a craving." That is to say, when neurons with D1 receptors are activated, they compel you to perform an action -- reaching for another bottle of tequila, in this case. This then creates a cycle, where drinking causes easier activation, and activation causes more drinking.

These changes in activation of D1 neurons might be related to the physical changes happening at the sub-cellular level in brains that have been exposed to alcohol. They have longer branching and more of the mature, mushroom-shaped spines -- the type that stores long-term memories -- than their abstaining counterparts.

Conversely, the placebo group, the ones not exposed to alcohol, tended to have more of the immature versions of the mushroom-shaped spines in D1 neurons of their brains. The total number of spines didn't change in the two groups, but the ratio between mature and immature was dramatically different between the alcohol group and the placebo group. This has important implications for memory and learning in drug addiction.

"When you drink alcohol, long-term memory is enhanced, in a way," Wang said. "But this memory process is not useful -- in fact, it underlies addiction since it affects the 'go' neurons." Because there was no difference in the number of each type of spine in the D2 (no-go) neurons of alcohol-consuming and control models, the researchers realized there was a specific relationship between D1 neurons and alcohol consumption.

"We're now able to study the brain at the neuron-specific and even spine-specific level," Wang said.

How do you determine which neuron, which type of neurons or which group of neurons is responsible for a specific disease? That's what the next part of the study tried to answer.

The alcohol-consuming animal models with the increased mature spines in D1 neurons also showed an increased preference to drink large quantities of alcohol when given the choice.

"Even though they're small, D1 receptors are essential for alcohol consumption," Wang said.

Furthermore, and perhaps most excitingly, when those same animal models were given a drug to at least partially block the D1 receptor, they showed much-reduced desire to drink alcohol. However, a drug that inhibited the D2 dopamine receptors had no effect. "If we suppress this activity, we're able to suppress alcohol consumption," Wang said. "This is the major finding. Perhaps in the future, researchers can use these findings to develop a specific treatment targeting these neurons."

The study, which was co-authored with researchers from the University of California San Francisco, was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

"My ultimate goal is to understand how the addicted brain works," Wang said, "and once we do, one day, we'll be able to suppress the craving for another round of drinks and ultimately, stop the cycle of alcoholism."

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 

SLEEPING ON ANIMAL FUR IN INFANCY FOUND TO REDUCE RISK OF ASTHMA

Sleeping on animal fur in the first three months of life might reduce the risk of asthma in later childhood a new study has found.

The new research, presented at the European Respiratory Society (ERS) International Congress in Munich, suggests that exposure to the microbial environment in animal skin and fur could have a protective effect against asthma and allergies.

Previous studies have suggested that exposure to a wider range of environments from a young age could be protective against asthma and allergies. These findings have not been confirmed conclusively in urban settings. In this new study, researchers investigated children from a city environment who had been exposed to animal skin by sleeping on the material shortly after birth.

Data from a German birth cohort called Lisaplus were used. The cohort included over 3,000 healthy newborns who were mainly recruited in 1998.

The researchers collected information on exposure to animal skin during the first three months of life, along with information on the health of children until the age of 10 years. Information on 2,441 children was used in the study, with 55% of those included sleeping on animal skin in the first three months of life.

The results showed that sleeping on animal skin was associated with a reduced risk of a number of factors connected to asthma. The chance of having asthma at the age of 6 years was 79% lower in children who had slept on animal skin after birth compared with those who were not exposed to animal skin. The risk decreased to 41% by the age of 10.

Dr Christina Tischer, from the Helmholtz Zentrum München Research Centre, said: "Previous studies have suggested that microbes found in rural settings can protect from asthma. An animal skin might also be a reservoir for various kinds of microbes, following similar mechanisms as has been observed in rural environments. Our findings have confirmed that it is crucial to study further the actual microbial environment within the animal fur to confirm these associations."