Viagra Cure for Erectile Dysfunction

When it comes to remodeling our bones-an ongoing process of break down and renewal that goes on throughout adulthood--researchers have new evidence that our guts play a surprisingly important role.

The findings point toward novel methods for increasing bone mass in patients with diseases characterized by impaired bone formation, including postmenopausal osteoporosis, according to the report in the November 26th issue of the journal Cell, a Cell Press publication.

"This is totally new," said Gerard Karsenty of Columbia University. "We had no clue that the gut had control over bone, and in such a powerful manner."

Too much serotonin released by the gut leads to a decline in bone mass; too little and bones bulk up beyond what is normal, their study shows. While serotonin is most familiar for its effects on the brain, 95 percent of all serotonin in the body is actually produced by the gut, Karsenty explained. Just what that serotonin did, however, had remained a matter of considerable debate.

The current study was aimed at clearing up the role of a gene that encodes LDL-receptor related protein 5 (LRP5), one of the most intensely studied regulators of bone remodeling. Patients with a genetic mutation that leads to a loss of that protein's function have a rare disease known as osteoporosis pseudoglioma (OPPG), characterized by a severe decline in bone formation and other symptoms. Other, presumably activating, mutations in LRP5 cause high bone mass syndrome. "That different mutations in this gene cause two bone diseases of opposite nature underscores the critical importance in the regulation of bone formation of the pathway or pathways controlled by Lrp5," the researchers said.

Earlier studies had suggested LRP5 might operate on bone through one developmental pathway, but Karsenty's team wasn't convinced that was the whole story. They've now confirmed that hunch.

They find that the bones of mice lacking Lrp5 show a rise in the activity of an enzyme called tryptophan hydroxylase 1 (Tph1). Tph1 limits the rate of serotonin production in the gut from the amino acid tryptophan. (Amino acids are the building blocks of proteins.) In other words, mice without Lrp5 have too much Tph1, leading them to overproduce gut serotonin.

Further study showed that decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice, and that gut- but not bone-specific Lrp5 inactivation decreases bone formation. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents bone loss in mice who have had their ovaries removed, a condition that mimics menopause.

Although the findings were made in mice, Karsenty says they have direct application to understanding bone remodeling in humans, and to the development of treatments designed to increase bone mass.

" This is not a mouse story," Karsenty said. "From the beginning it was a human story that we've now worked out in the mouse."

The findings suggest that OPPG and high bone mass syndrome are actually more gut- than bone-originating diseases. It also provides an explanation for another observation: that patients with autism who have high blood serotonin levels often have osteoporosis. Patients taking synthetic serotonin reuptake inhibitors (SSRIs) chronically, a class of antidepressant drugs that increase extracellular serotonin concentration, can also have reduced bone mass, the researchers noted. They emphasized however, that it's too soon to say whether this new connection between gut serotonin and bone will explain that side effect of the drugs or not.

So, given the gut's newfound pull over bone, might diet play a role?

While the researchers did show in mice that a diet low in the tryptophan-the raw ingredient for serotonin's manufacture--can have an effect on bone mass, at least in the Lrp5-deficient mice, Karsenty thinks that serotonin inhibiting drugs are a more likely method than diet for building bone mass in people. Coincidentally, however, one of the highest sources of tryptophan is the Thanksgiving turkey.

http://www.cellpress.com/

With the economy continuing it's downward turn, family caregivers are stepping up to the plate to help loved ones in need.

A new AARP report found the value of unpaid family caregiving in Illinois hits over $17 billion, more than a $1 billion increase since 2006. While nearly 1.5 million family and friends in the state provide care for relatives, that number climbs as high as 2.3 million when short-term caregivers are taken into account.

According to the AARP Public Policy Institute Report, nationally, the value of family caregiving is $375 billion - 7 percent higher than in 2006, when the estimated value was $350 billion. The value exceeds the $311 billion spent on Medicaid in 2007.

"Family caregivers are a vital and largely unrecognized part of Illinois' and the nation's health and long-term care system," said Bob Gallo, Sr. State Director for AARP in Illinois. "We often overlook how much family and friends contribute--whether it's picking up groceries each week or providing daily health care for their loved ones."

The AARP report, "Valuing the Invaluable, The Economic Value of Family Caregiving, 2008 Update," estimates that 34 million Americans provide more than 20 hours of care per week to another adult, making informal caregiving a cornerstone of U.S. health and long-term care.

"Family caregivers are likely to be stretched even further in today's tumultuous economy," added Gallo.

The AARP report notes that informal caregivers of people 50-plus spent an average of $5,531 out-of-pocket in 2007 to care for their loved ones. That spending is often coupled with lost workdays, wages, health insurance and retirement savings. More than one-third of informal caregivers are forced to quit their jobs or reduce their working hours, with women more likely to leave the labor force entirely. Caregivers also frequently struggle with health care bills and medical debt--and experience chronic stress. Even less noticed is the physical and emotional toll caregiving can take.

The AARP report makes several recommendations to assist caregivers, including adopting "family friendly" workplace policies; assessing caregivers' needs and providing them with needed supports; expanding funding for the National Family Caregiver Support Program and the Lifespan Respite Care Act; and supporting family caregivers in chronic care coordination programs and care transitions.

http://www.aarp.org/

The research council FORMAS, Sweden, has granted 5.9 million SEK to a new research project that will study the environmental fate and effects of the anti-viral drug Tamiflu on the development on influenza resistance.

Tamiflu is being stockpiled all over the world for use in fighting the next influenza pandemic. However, there are growing signs that influenza viruses may develope resistance to this vital pharmaceutical, because it is routinely prescribed for seasonal influenza.

This research project is interdisciplinary and will combine studies on the environmental fate of the drug with in vivo studies of the development of Tamiflu resistant viruses say the project leader Björn Olsen at the Department of Medical Sciences Uppsala University.

This research project presents an innovative approach to studying the development of Tamiflu resistance in influenza viruses caused by environmental contamination which is a potential threat to one of our few defences against a future influenza pandemic.

Scientists from Uppsala University, Umea University and Karolinska Institute will investigate the potential problem from an environmental chemical, virological and infectious diseases aspect.

A wide range of topics will be addressed; studies of the degradation of Tamiflu in sewage treatment plants will be combined with screening of the environmental levels in surface water in Japan. Japan is one of the world's top-per-capita consumers of Tamiflu and it has been estimated that approximately 40% of those that are infected by influenza viruses are treated with Tamiflu. This makes Japan one of the "Hot Spots" in the world and the research project has established collaboration with scientists at Kyoto University and several field sampling campaigns in Japan has been scheduled. Detected environmental levels will then be used in an in vivo Mallard infection model for detailed studies on the development of Tamiflu resistance in low pathogenic avian viruses. This will be combined with a screening study of the occurrence of resistant viruses in faecal samples from wild ducks in the vicinity of Japanese sewage treatment plants.

http://www.uu.se/

Brain researchers at the University of Oslo in Norway have penetrated deeply into the innermost secrets of the brain to find out how brain cells can survive a stroke.

Strokes are usually caused by occlusion of one of the blood vessels in the brain. When blood is prevented from supplying vital oxygen and energy to the brain cells, their electrochemical balance is upset, and they cause damage to themselves and to the surrounding brain cells before they collapse and die. Often this affects the memory centre, the hippocampus, where the cells are particularly vulnerable.

There is hope, however. New research results indicate that the brain cells are equipped with an ingenious mechanism that can save them in extreme emergencies.

You can call it an emergency brake in the brain if you like, says Professor Johan Storm at the Institute for Basic Medical Sciences and the Centre for Molecular Biology and Neuroscience at the University of Oslo. For the last 25 years, he has studied this emergency brake and other vital functions of the brain cells.

Our goal is to clarify how this emergency brake functions, and whether it protects against strokes or other extreme strains, like when a person nearly drowns or suffocates, or even in the case of extremely low blood-sugar levels, he says to the research magazine Apollon.

An incredible machinery

The brain cells float in a pool of brain fluid and have no direct contact with each other. Still, a single brain cell can communicate with more than 20 000 other brain cells.

As a means of communication, the brain cells use glutamate. The glutamate is stored in small vesicles at the end of the long, thin nerve fibres of the brain cell. When an electric impulse travels along the fibre, the vesicles release their content. The content spreads like a flash to the neighbouring cell, whereupon the vesicles are recharged.

It is an incredible piece of machinery. The glutamate can be compared to a relay baton being passed on to the next cell.

The concentration of calcium ions (electrically charged calcium atoms) decides how many batons will be passed on. Therefore, it is essential to keep the electrochemical balance in the brain as stable as possible.

The brain cell possesses advanced mechanisms that can both accept and release calcium ions. Both of these mechanisms are equally essential.

There are sufficient calcium reserves available. The concentration of calcium ions in the surrounding brain fluid is twenty thousand times higher than inside the brain cell itself.

Calcium ions flow into the brain cell through thousands of minute ion channels in the ultra-thin membrane on the nerve endings. These channels consist of tube-shaped molecules. There are a large number of these ion channels and each will allow passage of only one particular type of atom. The channels that accept calcium ions are referred to as calcium channels. The calcium from the ion channels is essential for connecting nerve impulses in the brain.

To maintain a low concentration of calcium ions, the brain cells pump them back out. These pumps are dependent on energy. A stroke, blocking the energy supply, is therefore a dramatic event.

The calcium piles up, causing the brain cell to be over-agitated and to release glutamate at random. An overdose of glutamate poisons the brain cells, and they risk dying.

Easing the crisis

Incredibly, the brain cells have developed an ingenious crisis-relief system. Johan Storm discovered the function of a specific emergency brake more than twenty years ago. The emergency brake serves to restrict the inflow of calcium ions.

Help is provided by the neighbouring channels of the calcium channels. The neighbouring channels are referred to as BK channels. Their job is to transport potassium out of the brain cell.

In less than a millisecond the calcium streaming in through the calcium channels will activate the BK channels. The BK channels create a voltage change that feeds back to the calcium channels, causing the inflow of calcium to stop very rapidly.

There are many indications that the BK channels are closed when the brain functions normally. We may surmise, however, that the channels are in use during the dramatic seconds before an infant draws its first breaths of air moments after being born.

The brain cell is so wisely constructed that the BK channels open only when the energy supply stops.

In other words, if scientists are able to produce a drug that can keep the BK channels open for longer periods, the calcium channels could close even faster. This could serve to restrict the inflow of calcium in emergencies.

That is why we refer to the BK channel as an emergency brake. You can compare it to having an extra drain in your bathroom. Usually, one drain is enough, but in emergencies, an extra drain could prove useful. Smart, isn't it?

The pharmaceutical industry is currently searching for drugs that can promote the opening of the BK channel and thereby make use of the natural braking mechanism in the treatment of stroke patients.

However, their success is far from taken for granted. There is the possibility that the BK channel already functions optimally.

Genetically modified mice

BK channels are not only found in the human brain. The channels have been discovered even in glandular and muscular cells and in peripheral nerve cells in snails, fruit flies and frogs.

This means that for hundreds of millions of years the BK channel has served as an important regulatory mechanism in many types of nervous systems spread throughout the animal kingdom. The mechanism even has roots back to monocellular animals and bacteria. Our brain is therefore the result of an evolution that has gone on for more than two billion years.

In order to study the importance of BK channels, Johan Storm is collaborating with Professor Peter Ruth at the University of T?n on a project studying what happens when genetically modified mice without BK channels suffer from a stroke.

Our main finding is that these mice have a lower survival rate following a stroke, and that more brain cells die among those who survive. The mice therefore suffer more strongly from a stroke than normal mice.

A stroke in a dish

The hypothesis is simultaneously tested using another scientific method. Because BK channels have been detected in the muscle cells of blood vessels, the emergency brake could be associated with the absence of BK channels in the vessels of the genetically modified mice.

To exclude this possibility, Johan Storm's research group has undertaken research on stroke in a dish.

In this experiment, the researchers cut half-millimetre thick sections from the memory centre, the hippocampus, of normal mice as well as genetically modified mice without BK channels.

The brain samples in the dish are fed with oxygen and sugar. Then the supply is stopped, causing the samples to suffer from acute energy shortage, simulating an acute stroke. Subsequently, the researchers resume the energy supply to the brain samples, observing what happens to them over the next hours and days.

Even here, it appears as if the brain cells from mice without BK channels have a reduced survival rate. This could therefore confirm the hypothesis that the emergency brake in fact works.

Epilepsy

Epilepsy researchers benefit from Johan Storm's studies. Two years ago his research team found that the BK channels at the root of the brain cell, where the nerve impulses are formed, do not function as an emergency brake. On the contrary.

These BK channels can increase the frequency of nerve impulses, and they are also active under normal conditions, when the cells receive sufficient oxygen.

This could explain another interesting discovery made in the US: A mutation causing the BK channels to open more often than they normally do may cause epilepsy.

It is therefore conceivable that closing the BK channels could prevent epilepsy. And vice versa: Promoting the opening of BK channels following a stroke may increase the risk of epilepsy, Johan Storm explains.

There is hope, however. Even though all BK channels have one gene in common, the BK channels have several variants. It is therefore conceivable that the BK channels are of a different nature in the various parts of the brain cell.

Using the HIV virus

Johan Storm now wishes to study what happens when different types of ion channels are turned off and on. Although we have a good overview of the active genes in the brain cells, the functions of the individual proteins and ion channels are still not conclusively established.

Genetically modified mice are costly, and isolating the manipulation to a specific location in the brain is complicated. In addition, breeding mice with new properties takes a long time. Johan Storm therefore has started to use viruses to change the genetic composition of the brain. This allows him to decide exactly what to manipulate in the brain cells.

We start with a reconstructed HIV virus. After the virus has been stripped of most of its normal genes, they are weakened, unable to proliferate and so harmless that they hardly can be referred to as viruses anymore. We can still use them to insert the desired genes. When the virus enters the cell, it injects its genes and modifies the genome in the cell core. In this manner, we can switch the ion channels on and off. This allows us to investigate the roles filled by the channels and the individual brain cells.

In the future, we can envisage using this method for purposes of medical treatment. We could correct congenital genetic disorders and manipulate the channels and proteins in the brain. It is an intriguing vision, but there is still a long way to go, Professor Johan Storm concludes to the research magazine Apollon at University of Oslo in Norway.

http://www.uio.no/english/

Although there has been an increase in the number of new arthritis treatments in recent years, the best results will come from more effective use of the drugs we have.

Research published today in BioMed Central's open access journal Arthritis Research and Therapy investigates the effectiveness of available arthritis drugs and concludes that better management is the most important factor.

Isidoro González-Alvaro from the Hospital Universitario de la Princesa, Spain, led a team of researchers who studied the treatment of 789 patients over four years between 2000 and 2004. He said, "Our work shows that the treatment of rheumatoid arthritis at tertiary hospitals in Spain has improved from the year 2000. It is likely that better management of available drugs, mainly methotrexate, has been learned during the last decade - along with the clinical development of most biologic agents."

The management of rheumatoid arthritis (RA) has changed a great deal over the last 10 years. The development of biologic therapies, as well as the rigorous clinical trials that have demonstrated their effectiveness, have probably contributed to this change. However, according to González-Alvaro, "In our study, we did not observe the amazing halt of radiological progression described in clinical trials."

When used outside trials, the effectiveness of new drugs may differ, since patients included in clinical trials are on average younger, have less comorbidity, and show greater disease activity than real-life patients. In order to ascertain the real-life effectiveness of new RA medication, the authors studied RA patients in terms of disease activity, disability and radiological progression in the period after the Spanish launch of Leflunomide and the TNF antagonists. They write, "The most relevant finding of our work is that disease activity in RA has improved, independently of the availability of new therapies, in patients with severe and mild disease."

The authors conclude, "It is clear that we need specific markers of RA severity that allow us to select adequate patients for early biologic treatment in order to improve their therapeutic response, as well as their functional outcome. These tools may also help to improve cost-effectiveness of these drugs avoiding unnecessary prescriptions."

http://www.biomedcentral.com/