Brain blood flow finding gives hope for Alzheimer’s therapy

You know that dizzy feeling you get when, after lying down for an extended period, you stand up a little too quickly?

That feeling is caused by a sudden reduction of blood flow to the brain, a reduction of around 30 percent. Now imagine living every minute of every day with that level of decreased blood flow.
People with Alzheimer’s disease don’t have to imagine it. The existence of cerebral blood flow reduction in Alzheimer’s patients has been known for decades, but the exact correlation to impaired cognitive function is less understood.

“People probably adapt to the decreased blood flow, so that they don’t feel dizzy all of the time, but there’s clear evidence that it impacts cognitive function,” said an associate professor.

A new study, offers an explanation for this dramatic blood flow decrease: white blood cells stuck to the inside of capillaries, the smallest blood vessels in the brain. And while only a small percentage of capillaries experience this blockage, each stalled vessel leads to decreased blood flow in multiple downstream vessels, magnifying the impact on overall brain blood flow.

“It turns out that … the blockages we were trying to induce were already in there,” she said. “It sort of turned the research around – this is a phenomenon that was already happening.”

The researchers, determined that only about 2 percent of brain capillaries had “stalls” (blockages), but the cumulative effect of that small number of stalls was an approximately 20 percent overall decrease in brain blood flow, due to the slowing of downstream vessels by the capillaries that were stalled. Recent studies suggest that brain blood flow deficits are one of the earliest detectable symptoms of dementia.

To test the effect of the stalls on performance of memory tasks in Alzheimer’s mice, they were given an antibody that interfered with the adhesion of white blood cells to capillary walls, which caused the stalled capillaries to start flowing again and thus increased overall brain blood flow. Memory function was improved within a few hours, even in aged mice with more advanced stages of Alzheimer’s disease.

Researchers are quick to point out, however, that the antibody is not something that can be used in humans. Also, of course, interfering with white blood cell adhesion would render an individual immuno-compromised.

“What we’ve done is identify the cellular mechanism that causes reduced brain blood flow in Alzheimer’s disease models, which is neutrophils [white blood cells] sticking in capillaries,” the Dr. said. “We’ve shown that when we block the cellular mechanism [that causes the stalls], we get an improved blood flow, and associated with that improved blood flow is immediate restoration of cognitive performance of spatial- and working-memory tasks.”

“Now that we know the cellular mechanism,” he said, “it’s a much narrower path to identify the drug or the therapeutic approach to treat it.”

The team has identified approximately 20 drugs, many of them already FDA approved for human use, that have potential in dementia therapy. Some of them, however, were designed to be taken in high doses for short periods of time to treat sepsis, or in the immediate aftermath of a heart attack or stroke. “They weren’t really intended to be something that you take for the rest of your life,” he said. Nonetheless, the lab is screening these drugs in Alzheimer’s mice now. 

The Dr. said he’s “super-optimistic” that, if the same capillary-blocking mechanism is at play in humans as it is in mice, this line of research “could be a complete game-changer for people with Alzheimer’s disease.”

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Women with PCOS highly prone to diabetes

Women suffering from Poly Cystic Ovary Syndrome (PCOS), a problem in which a woman's hormones are imbalanced, are highly prone to diabetes, according to the new findings.

Doctors  after conducting several survey, researches and monitoring patients during the Out Patient Department (OPD) sessions, have discovered that insulin resistance' is an integral part of PCOS and that women with the syndrome are at a higher risk for diabetes than the general population.
"Insulin resistance has been recognised as a risk factor for diabetes and may be the earliest detectable abnormality in individuals who proceed to develop diabetes," said  a senior endocrinology consultant and assistant professor.
Insulin resistance is a condition in which the body produces insulin but does not use it effectively. When people have insulin resistance, glucose builds up in the blood instead of being absorbed by the cells, leading to type 2 diabetes or pre-diabetes.
PCOS is the most common endocrine disorder in women of reproductive age. Symptoms are irregular menstrual periods, irregular ovulation, hirutism, weight gain, hair loss and oily skin or acne. 

 PCOS symptoms vary from women to women thus making its diagnosis delayed or confusing.

Prof. said insulin resistance has been recognised as a risk factor for diabetes and may be the earliest detectable abnormality in individuals who proceed to develop diabetes.

India currently reports 10 per cent of the world's PCOS cases. The available data about PCOS suggests its prevalence to be around 4-10 per cent of it's population in USA, two per cent in European Countries, and 20 -25 per cent in women.

"PCOS is also associated with an increased risk of developing health problems in later life span, such as type 2 diabetes, hyper tension and heart disease, metabolic syndrome, NASG and sleep apnea. However, it has been seen that 50 per cent of affected women are not aware of it," reported a gynaecologist .
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Obscure virus found in women linked to unexplained infertility

A little-known virus infects the lining of the uterus in 43 per cent of women with unexplained infertility, a new study has found. 

The study from University of Ferrara in Italy also found that the response of the immune system to HHV-6A virus - a member of the human herpes virus family - infects may contribute to making the uterus less hospitable to a fertilised egg. 

The virus seems to activate immune cells called natural killer cells in the uterus, and lead those cells to produce chemicals called cytokines. 

Cytokines are tools the immune system uses to orchestrate an attack on a foreign invader, like a virus. 

However, the activated immune system cells and abnormal levels of certain cytokines may make it harder for a fertilised egg to lodge in the uterus, and grow into a baby. 

Infertility affects approximately six per cent of 15-44 year old women or 1.5 million women in the US, researchers said. 

About 25 per cent of female infertility cases are unexplained, leaving women with few options other than expensive fertility treatments.
"If confirmed, the finding may lead to treatments that improve the outcome for a large subset of infertile women," said Anthony Komaroff, a professor at Harvard Medical School. 

Little is known about HHV-6A, which was discovered in 1986 and is one of nine human herpes viruses. 


Since HHV-6A is typically not detectable in the blood or saliva, its true prevalence is unknown. 

A closely related virus, HHV6-B, is acquired by nearly 100 per cent of the population in early childhood and is spread through exposure to saliva. 

Currently, there are no approved drugs for HHV-6A or HHV-6B, but infectious disease specialists commonly use valganciclovir, foscarnet and cidofovir to treat HHV-6B reactivation in transplant patients.
These drugs were developed to treat human herpesvirus-5 (HHV-5), known as cytomegalovirus. 

More research is needed to confirm these findings and to determine whether antiviral treatment would help women with this uterine infection.

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