NASAL SPRAY WITH INSULIN EQUIVALENT SHOWS PROMISE AS TREATMENT FOR ADULTS WITH MILD COGNITIVE IMPAIRMENT, ALZHEIMER’S DEMENTIA


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A man-made form of insulin delivered by nasal spray may improve working memory and other mental capabilities in adults with mild cognitive impairment and Alzheimer’s disease dementia, according to a pilot study led by researchers at Wake Forest Baptist Medical Center.

The study’s subjects were 60 adults diagnosed with amnesic mild cognitive impairment (MCI) or mild to moderate Alzheimer’s dementia (AD). Those who received nasally-administered 40 international unit (IU) doses of insulin detemir, a manufactured form of the hormone, for 21 days showed significant improvement in their short-term ability to retain and process verbal and visual information compared with those who received 20 IU does or a placebo.

Additionally, the recipients of 40 IU doses carrying the APOE-e4 gene – which is known to increase the risk for Alzheimer’s – recorded significantly higher memory scores than those who received the loser dosage or placebo, while non-carriers across all three groups posted significantly lower scores.

Previous trials had shown promising effects of nasally-administered insulin for adults with AD and MCI, but this study was the first to use insulin detemir, whose effects are longer-lasting than those of “regular” insulin.

“The study provides preliminary evidence that insulin detemir can provide effective treatment for people diagnosed with mild cognitive impairment and Alzheimer’s-related dementia similar to our previous work with regular insulin,” said Suzanne Craft, Ph.D., professor of gerontology and geriatric medicine at Wake Forest Baptist and lead author of the study, which is published online in advance of the February issue of the Journal of Alzheimer’s Disease. “We are also especially encouraged that we were able to improve memory for adults with MCI who have the APOE-e4 gene, as these patients are notoriously resistant to other therapies and interventions.”

The researchers also sought to determine if the insulin detemir doses would cause any negative side effects, and found only minor adverse reactions among the subjects.

The study’s overall results support further investigation of the therapeutic value of insulin detemir as a treatment for Alzheimer’s and other neurodegenerative diseases, Craft said.

“Alzheimer’s is a devastating illness, for which even small therapeutic gains have the potential to improve quality of life and significantly reduce the overall burden for patients, families and society,” she said. “Future studies are warranted to examine the safety and efficacy of this promising treatment.”

Calcium, vitamin D failed to halt BMD loss in breast cancer.


Calcium plus vitamin D supplements are often suggested for patients at risk for osteoporosis and in women undergoing breast cancer treatment, but a recent analysis published in Critical Reviews in Oncology/Hematologyhighlights the insignificant data behind this methodology.

“We evaluated clinical trial evidence for calcium and vitamin D supplementation in maintaining skeletal health of women with breast cancer,” Gary G. Schwartz, PhD, a cancer epidemiologist at Wake Forest Baptist Medical Center in Winston-Salem, N.C., said in a press release. “At the doses recommended, the data show that these supplements are inadequate to prevent loss of [bone mineral density].”

Of 16 trials, researchers found that none of them evaluated calcium plus vitamin D supplements vs. no supplements in preventing BMD loss in women with breast cancer. Additionally, researchers reported inadequacies in the prevention of BMD loss when doses of 500 mg to 1,500 mg calcium and 200 IU to 1,000 IU vitamin D per day were administered among pre- and postmenopausal women with breast cancer.

However, exercise or pharmacologic interventions could prevent BMD loss in this patient population when such supplementation is not effective, researchers wrote. The researchers added that controversial literature exists regarding the risk for cardiovascular disease with the use ofcalcium supplements.

“The take-home message is that this very common practice of supplementation doesn’t really seem to be working,” Schwartz said. “Future trials are needed to evaluate the safety and efficacy of calcium and vitamin D supplementation in women undergoing breast cancer therapy.”

Source: Endocrine Today.

 

Will we ever grow replacement hands?


It might seem unbelievable, but researchers can grow organs in the laboratory. There are patients walking around with body parts which have been designed and built by doctors out of a patient’s own cells.

hand

Over the past few weeks on the BBC News website we have looked at the potential for bionic body parts and artificial organs to repair the human body. Now we take a look at “growing-your-own”.

There is a pressing need. A shortage of available organs means many die on waiting lists and those that get an organ must spend a lifetime on immunosuppressant drugs to avoid rejection.

The idea is that using a patient’s own stem cells to grow new body parts avoids the whole issue of rejection as well as waiting for a donor.

Dr Anthony Atala, director of the Institute for Regenerative Medicine at the Wake Forest Baptist Medical Center in North Carolina, US, has made breakthroughs in building bladders and urethras.

He breaks tissue-building into four levels of complexity.

  • Flat structures, such as the skin, are the simplest to engineer as they are generally made up of just the one type of cell.
  • Tubes, such as blood vessels and urethras, which have two types of cells and act as a conduit.
  • Hollow non-tubular organs like the bladder and the stomach, which have more complex structures and functions.
  • Solid organs, such as the kidney, heart and liver, are the most complex to engineer. They are exponentially more complex, have many different cell types, and more challenges in the blood supply.

“We’ve been able to implant the first three in humans. We don’t have any examples yet of solid organs in humans because its much more complex,” Dr Atala told the BBC.

Bladder builders

His technique for growing bladders starts with taking a tissue sample, about half the size of a postage stamp, from the bladder that is being repaired.

Over about a month, the cells are grown in the laboratory in large quantities. Meanwhile a scaffold in the shape of the organ, or part of the organ, being replaced is built.

“We coat the scaffold, basically like creating a layer cake. We place the cells on the structure one layer at a time with the cells in the correct positions,” Dr Atala said.

The cake is then “baked” for a two weeks in an oven, which has the same conditions as the inside of the human body. The new bladder is then ready to be implanted back into the body.

Eventually the scaffold is absorbed by the body, leaving the cells in place.

Building a scaffold for the bladder is one thing, building one for the heart is far more complicated. One of the problems when you move to larger organs is the getting the blood supply to work, connecting arteries, capillaries and veins to keep the organ alive.

It is why some researchers are investigating “decellularisation” – taking an existing donated organ, stripping out the original cells and replacing them with new cells from the patient who will receive the organ.

Prof Martin Birchall, a surgeon at University College London, has been involved in a number of windpipe transplants performed in this way.

The technique starts with a donor windpipe which is then effectively put through a washing machine. Repeated cycles of enzymes and detergents break down and wash away the host cells.

What is left behind is a web of proteins, mostly collagens and elastins, which give the windpipe its structure. It would look and feel like a windpipe, just without cells – a natural scaffold.

The next steps are very similar to those for making the bladder. Stem cells are taken, this time from bone marrow, and grown in a lab before being layered onto the scaffold.

The first patient was fitted with one of these windpipes in Spain in 2008.

Prof Birchall said: “We’ve made some inroads by starting with the windpipe. We’re looking at some other tissues now like the oesophagus and diaphragm and overseas the big breakthroughs have been in building the bladder and urethra.

“Those are the areas in which immediate breakthroughs have occurred, but I see a raft of further first-in-man studies in other organs happening in the next five years.”

Heartbeat

There are already strong hints of what the next steps could be.

Five routes to a solid organ

  • Build it on a scaffold
  • Strip an old organ of cells and put new ones in their place
  • Use a “bioprinter” to built an organ layer by layer
  • Inject cells into a living organ to repair
  • Use chemicals to trigger an organ to repair itself

Dr Doris Taylor, who is about to move to the Texas Heart Institute, has used the decellurisation technique on rats’ hearts andproduced beating organs.

The cells were stripped away leaving a “ghost heart” and were then injected with heart cells. Eight days later the heart was beating, albeit at just 2% of normal heart function.

She said the technique could “absolutely” be used on any organ that had a blood supply.

She told the BBC: “It’s not science fiction any more, but moving that to more complex organs is the challenge ahead of us.”

Other groups have also produced miniature organs or “organoids”. They are not the full-blown thing, but they perform the same functions at a smaller scale.

Wake Forest researchers have produced liver organoids which can break down drugs.

Dr Atala said: “The challenge for us is – how do we scale up?”

Bioprinting, just like an office printer except it “prints” cells layer by layer, has been used to “print” a kidney.

While these findings are a very long way from making it into hospitals, if indeed they ever do, the scientists involved are convinced these techniques will come good.

“The vision has to be tempered by the past and the number of false dawns that have occurred,” Prof Birchall said.

“But I genuinely do believe stem-cell technologies and tissue engineering is going to completely transform healthcare delivery in the future.

“I see it incrementally reaching out to replace transplantation. The writing is on the wall for it to do wonderful things.”

Dr Atala said: “The strategies are out there to someday be able to target every organ in the body we are not there yet. We are nowhere near there yet.

“But the goal of the field is to keep on advancing the number of tissues that we can target.”

Of course growing a hand is even more challenging than anything being tried in laboratories so far. Will it ever be possible?

“You never say never, but certainly it’s something I will most likely not see in my lifetime,” Dr Atala concluded.

Source: BBC

Calcium, vitamin D supplements failed to prevent BMD loss.


Calcium and vitamin D supplementation during androgen deprivation therapy did not prevent loss of bone mineral density among men with prostate cancer, according to study results.

Bone mineral density (BMD) loss is an adverse effect of ADT for men with prostate cancer. Doctors routinely recommend 500 mg to 1,000 mg calcium and 200 IU to 500 IU vitamin D per day as a supplement, according to background information in the study.

“Calcium and/or vitamin D supplementation to prevent loss of bone mineral density in these men seems so logical that no one had questioned whether it works,” Mridul Datta, PhD, a postdoctoral fellow at Wake Forest Baptist Medical Center, said in a press release.

Datta and colleagues reviewed guidelines for calcium and vitamin D supplementation.

They also analyzed the results of 12 clinical trials that evaluated a combined 2,399 men with prostate cancer who were undergoing ADT. Those trials compared the effects of calcium supplements, vitamin D supplements and other drugs on BMD.

Only one of the 12 trials showed an increase in BMD in the lumbar spine (0.99% in 12 months). The largest decrease in BMD in the lumbar spine was –4.9% in 12 months.

The trial results indicated that calcium supplementation of about 500 mg to 1,000 mg and vitamin D supplementation of 200 IU to 500 IU did not prevent BMD loss.

“It wouldn’t be so bad if there were simply no obvious benefit,” researcher Gary G. Schwartz, PhD, MPH, associate professor in the departments of cancer biology, urology, and epidemiology and prevention at Wake Forest Baptist Medical Center, said in the release. “The problem is that there is evidence that calcium supplements increase the risk of cardiovascular disease and aggressive prostate cancer, the very disease that we are trying to treat.”

Further studies are needed to evaluate the safety and efficacy of calcium and vitamin D supplementation in this patient population, the researchers wrote.

Clinical trials to determine the risk-benefit ratio of calcium and vitamin D supplementation in men undergoing ADT for prostate cancer are urgently needed,” they concluded.

Source: Endocrine Today.