Study discovers how diabetes lead to vascular disease

A team of scientists and physicians identified a cellular connection between diabetes and one of its major complications- narrowing of the blood vessel- which increases risks of several health conditions, including heart disease and stroke.

The same team previously found that high blood glucose, the hallmark symptoms of diabetes, activates an enzyme known as protein kinase A (PKA), which increases calcium channel activity and constricts blood vessels.

This was a surprise since PKA is typically associated with blood vessel widening and wasn't really on our radar. We wanted to understand the molecular processes that created this opposite reaction, said senior author.

For the new study, the team conducted a series of experiments on the effects of high glucose on cerebral blood vessels and arterial cells that control blood flow. The tests were conducted on a unique genetically modified mouse and  2 mouse models of diabetes that were developed for studies of cardiovascular health.

The researchers focused on the relationship between PKA and adenylyl cyclase (AC), an enzyme involved in cyclic AMP(cAMP) production, a cellular messenger with a critical role in vascular cell function.

Their results showed that one AC in particular, AC5 mediated cAMP and PKA activation, triggering increased calcium channel activity and blood vessel narrowing. They also found that AC5 was essential for blood-vessel constriction during diabetes.

The team hopes to test the effects of the AC5 chain reaction in high-glucose conditions in human cells. This step could confirm it as a treatment target for reducing the vascular complications of diabetes, which can include eye, kidney and cerebral, gastrointestinal and cardiovascular disease.

We see every day in our clinics the devastating impact of diabetes on the health and lives of our patients. Our work brings into much clearer focus on how high glucose can damage the vascular system and gives us a new target for blocking its effects, said the co-author of the study.

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Common BP drug may lead to Diverticulosis in elderly

A team of scientists have found that blood pressure drug belonging to class of calcium channel blockers may lead to diverticulosis in elderly. 

Diverticulosis causes small bulges or pouches to appear in the lining of the intestine and can in some cases can lead to a medical emergency if the pouches become infected or burst.

High blood pressure affects onw in ten adults across the globe and increases the risk of heart attack and stroke. The most common treatments for high bP are lifestyle changes and medications.

A team of scientists incestigated the effectiveness and side effects of 3 common BP medications- ACE inhibitors, beta-bloackers and calcium channel blockers.

The 3 main medications which are being taken by millions were investigated and their potential side effects as well as studying their effectiveness for treating other diseases can be difficult and often involves lengthy and expensive clinical trials.

Therefore in order to overcome this problem, the research team used genetic analyses to study the effects of the drugs. By investigating versions of genes that mimic the effects of these drugs, the team were able to study the drugs' effectiveness and their potential side effects.

First, the researchers identified the proteins targeted by the drugs, and which helps lower BP. Next, they analysed genetic data from around 750,000 people and identifies the so-called genetic variants that code for these proteins.

The team, then studies whether these gene variants which cause increased production of these proteins, were linked to an increased or decreased risk of other diseases.

The good news was that, as expected, these so-called genetic variants ( which coded for proteins involved in lowering BP) were linked to lower heart disease and stroke risk.

However after assessing the risk of around 900 different diseases- using data from the study, the team found that the versions of genes related to the effects of a particular type of calcium channel blocker- the non-dihydropyridine class, were linked to an increased the risk of a bowel condition called diverticulosis.

The team compared their findings with further genetic data, and supported the potential link with an increased risk of the bowel condition.

The link now needs further investigation with larger trials, explains the co-lead author of the research. This is the first time that this class of BP drug has been associated with diverticulosis. We're not sure of the underlying mechanism- although it may relate to effects on the fiction of intestine muscles, which perform contractions to transport food through the gut.

Senior author added, the study of genetic variants that mimic the effect of drugs is evolving as a powerful concept to help prioritise clinical trials and design clinical trials more likely to be successful.

The researchers caution the findings should not change current prescribing guidelines and that people should not stop taking their medications unless first consulting their doctor.

He added, these findings should not change clinical practice, but instead should act as a catalyst for further research.

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BP pill has potential to slow down Alzheimer's

A high blood pressure drug has the potential to slow down Alzheimer's disease by improving the flow of blood to parts of the brain linked to memory, a study suggests.

Researchers found the drug nilvadipine increased blood flow to the brain's memory and learning centre among people with Alzheimer's without affecting other parts of the brain.

The findings indicate that the known decrease in cerebral blood flow in patients with Alzheimer's can be reversed in some regions.

However, an important question is whether this observed increase in cerebral blood flow translates to clinical benefits, the researchers said.

Alzheimer's disease is the most common form of dementia.

The risk for the disease increases with age and the causes are largely unknown.

Previous research has shown that blood flow to the brain declines in early Alzheimer's disease.
Nilvadipine is a calcium channel blocker used to treat high blood pressure.

Researchers sought to discover whether nilvadipine could help treat Alzheimer's disease by comparing the use of nilvadipine and a placebo among people with mild to moderate Alzheimer's disease.

They randomly assigned 44 participants to receive either nilvadipine or a placebo for 6 months.

Neither researchers nor the participants knew who received the drug or the placebo that was evenly divided among the 2 groups.

At the study's start after 6 months, researchers measured blood flow to specific regions of the brain using a unique magnetic resonance imaging (MRI) technique.

Results showed that blood flow to the hippocampus- the brain's memory and learning center-increased by 20 % among the nilvadipine group compared to the placebo group.

Blood flow to other regions of the brain was unchanged in both groups.

This high BP treatment holds promise as it doesn't appear to decrease blood flow to the brain, which could cause more harm than benefit, said an associate Prof.

Even though no medical treatment is without risk, getting treatment for high BP could be important to maintain brain health in patients with Alzheimer's disease, said the Prof.

Researchers note that sample sizes were too small and follow-up time too short to reliably study the effects of this cerebral blood flow increase on structural brain measures and cognitive measures.

Study participants were screened between 2013 and 2015 as part of a larger research project comparing nilvadipine to placebo among more than 500 people with mild to moderate Alzheimer's disease.

In that larger project, effects on cerebral blood flow were not measured . Overall, no clinical benefit was noted with the use of nilvadipine.

However, a subgroup of patients with only mild symptoms of disease did show benefit, in the sense of a slower decline in memory.

Previous studies have hinted high blood pressure could reduce the risk of developing dementia.

The researchers think that beneficial effects on brain  blood flow could explain part of this effect.

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A high blood pressure drug has the potential to slow down Alzheimer's disease by improving the flow of blood to parts of the brain linked to memory, a study suggests.

Read more at: https://www.deccanherald.com/science-and-environment/bp-pill-has-potential-to-slow-down-alzheimers-study-741185.html

A high blood pressure drug has the potential to slow down Alzheimer's disease by improving the flow of blood to parts of the brain linked to memory, a study suggests.

Read more at: https://www.deccanherald.com/science-and-environment/bp-pill-has-potential-to-slow-down-alzheimers-study-741185.html

COMMON DRUGS MAY HELP TO FIGHT DEMENTIA BETTER !

Everyday medicines like antibiotics, acne pills and other 

routine treatments that are already in bathroom cabinets 

could be used in the battle against dementia as developing 

new drugs is too costly and slow, experts have suggested. 


According to experts, it is time to re-examine medicines 

already in circulation as cheaper, quicker alternatives to new 

treatments. 


Many have multiple effects on the body, so some could be 

able to ease the effects of Alzheimer's and other forms of 

dementia. 


There are only four Alzheimer's drugs in use which can help 

relieve symptoms but do nothing to stop damage to the brain. 

Defeating dementia is one of the biggest challenges facing 

both medicine and society as a whole.


Developing new drugs is incredibly important but it comes 

with a huge price tag and, for those affected by dementia, an 

unimaginable wait. 


It can take up to 20 years and 600 million pounds to create a 

drug from scratch. Hopes of quickly adding to available 

treatments were recently dashed when several promising 

new ones failed the final stage of testing. 


So  experts turned to the possibility of using everyday drugs. 

They drew up a short-list, which includes liraglutide - a 

diabetes treatment that also acts on the brain. 

Others include minocycline, an antibiotic for acne, and 

acitretin, which treats the skin condition psoriasis. There is 

also a family of blood pressure drugs called calcium channel 

blockers. 


Some of these medicines cost less than 50p a tablet. 

The idea that drugs for other conditions could fight 

Alzheimer's is appealing, according yo researchers.


But it's not yet clear that such a drug exists. Alzheimer's is a 

complex disease with many risk factors.