Sunday, December 20, 2015

PKD & EVs: ExtraCellular Vehicles; Gift of Life from 70 year old woman

Gift of Life

From KHOU TV, Houston, Texas, by Kevin Reece, KHOU 11 News


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Two women in Simonton, Texas, with the help of doctors at Houston Methodist, are proving that age is no barrier to a successful living donor kidney transplant – even if that donor and her kidney are 70 years old.

Ann Hammermiller, 73, suffers from a genetic condition called polycystic kidney disease.

She was nearing the point when she would need to begin dialysis or search for a donor.

But as a member of Simonton Community Church, she learned her pastor suffered from the same condition.

He announced his need for a donor and remarkably, a member of the congregation offered to be his living donor and turned out to be a perfect match.

That's where Judy Peters comes in. She was willing to offer one of her kidneys to the pastor too. But learned her friend Ann Hammermiller was also in need. She didn't hesitate. Judy made the offer at a church dessert social.

"And she said what do you think about me being your donor? And of course I thought 'Oh gee she's had too much sugar,'" Hammermiller said with a laugh, politely questioning her friend's state of mind.

Peters turned out to be a perfect match. The surgery happened this past September. Doctors at Houston Methodist now say both women, at 70 and 73, are doing very well.

"We tend to be very conservative with donors. We are very protective of donors," said Dr. A. Osama Gaber, the director of Houston Methodist's J.C. Walter Jr. Transplant Center.

Gaber says the age of the kidney isn't the determining factor but that healthy kidney function is.

"Really our concern isn't the kidney we're going to take. It's what we're going to leave and how healthy the donor is going to be for the rest of their lives. That's really our major concern, said Gaber.

"I can't thank her enough for giving me a new life," Hammermiller said.

"I could say 'I'm too old, I can't possibly do that,'" Peters said when asked about any reservations she might have had about the kidney donation. "But when God calls you to do something, God makes it happen."

When the successful transplant took place at Houston Methodist, with the women recovering with just a four-day hospital stay, Judy Peters became the second oldest kidney donor ever at the hospital. The oldest was 71.

"Living donors are true heroes," said Gaber. "They are just these people that come in and they're willing to give of themselves, truly of themselves, to others. And it's a fantastic thing to watch this and to be part of it."

"There's no words," Hammermiller said seated next to her friend and kidney donor. "What can you say to someone like that? All you can do is say thank you, thank you and you're just so blessed in getting an offer like that. It's just a blessing that someone would step up and say I want to do this for you."

"We were good friends," Peters said.

And now?

"Better friends," she said as both broke into laughter. "We're connected. I'm just privileged to be a part of that. It was just very, very sweet, that is my sweet friend."

A verse in the bible says it is better to give than receive. The two women in Simonton would tell you that both at the same time, are pretty rewarding too.

If you would like to learn more about transplants and living donations click here.



PKD Research

From Medical News Today, by Catharine Paddock PhD
Cells send tiny parcels to each other - in sickness and health

Within the past decade, it has emerged that cells package various molecules into tiny bubble-like parcels called extracellular vesicles to send important messages - in sickness and health. The potential for using these vesicles in diagnosis and treatment is now under intense investigation.

Extracellular vesicles (EVs) are so small they can only be seen through high-tech electron microscopes. The membrane-covered structures are roughly in the same size range as viruses, bacteria and platelets.

For decades, scientists thought the cargo of EVs - which can consist of various molecules such as proteins and genetic material - was just debris.

More recently, they have begun to understand the importance of EVs in health and disease and how they might be used to ferry drugs to their targets.

However, there are still many large gaps in our understanding of EVs.

For example, because EVs are found in bodily fluids like blood, urine and cerebrospinal fluid, researchers are finding it nearly impossible to determine where they come from, how they are made or how they release their cargo of molecules.

Another mystery is why the same EV cargo can result in different outcomes.

Now, a new study - led by Rutgers University in Piscataway, NJ, and published in the journal Current Biology - offers some new clues about EVs.

Significant insight into biology of EVs and their role in human diseases

Lead author Maureen Barr, a professor of genetics at Rutger's, says EVs are both exciting and scary because we do not know the mechanisms that control what goes into them. She explains:

"It's like getting a letter in the mail and you don't know whether it's a letter saying that you won the lottery or a letter containing anthrax."

Prof. Barr says the more we find out about how a cell makes and packages proteins, lipids and bits of genetic material into EVs, the more we can use that knowledge to develop drugs and therapies to treat diseases. For example, one use could be to prevent cancer cells from using EVs to send messages that promote tumor growth.

For their study, the team investigated EVs in Caenorhabditis Elegans. The roundworm is a very useful model for understanding human biology at the level of cells - for example, many of its genes are similar to ours.

The researchers identified 355 genes that offer significant information about the biology of EVs and the role they might play in human diseases.

One in ten of the genes appear to control the formation, release and possible function of the vesicles.

The study also identifies new pathways that might control how cells produce EVs and choose their cargo, including proteins responsible for the most commonly inherited disease in humans - polycystic kidney disease.

Prof. Barr says cells secrete polycystic kidney disease gene proteins in EVs in both humans and worms, and no one knows why. She concludes:

"When we know exactly how they work, scientists will be able to use EVs for our advantage. This means that pathological EVs that cause disease could be blocked and therapeutic EVs that can help heal can be designed to carry beneficial cargo."

Meanwhile, from another recently published study of roundworms, Medical News Today learned that a Velcro-like molecule essential for sperm to be able to attach to eggs during fertilization is the same as one discovered in humans 10 years ago. The researchers suggest the finding could lead to better fertility treatments and contraceptives.


From 7th Space

Effects of pyrrolidine dithiocarbamate on proliferation and nuclear factor-κB activity in autosomal dominant polycystic kidney disease cells


Pyrrolidine dithiocarbamate (PDTC) reduces renal cyst growth in a rodent model of polycystic kidney disease (PKD) but the mechanism of action is not clear. Here, we investigated the hypothesis that PDTC reduces the proliferation of cystic epithelial cells in vitro in a nuclear factor (NF)-?B-dependent manner.

Methods: Immortalized autosomal dominant PKD (ADPKD) cells that are heterozygous (WT9-7) and homozygous (WT-9-12) for a truncating Pkd1 mutation, and immortalized normal human tubular cells (HK-2), were exposed to NF-?B-inducing agents with or without PDTC.

Cell proliferation and apoptosis were assessed by bromodeoxyuridine assay and Annexin V flow cytometry, respectively. NF-?B activity was assessed by luciferase reporter assay and western blotting for nuclear p65, p50, and RelB subunits and cytoplasmic phosphorylated-I?B?.

Results: Serum-induced proliferation was similar in all cell lines over 72 h.

PDTC demonstrated anti-proliferative effects that were delayed in ADPKD cells compared to HK-2. Basal NF-?B-dependent luciferase reporter activity was lower in ADPKD cells compared to normal cells.

Classical NF-?B stimulants, lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-?, increased NF-?B luciferase activity in HK-2, whereas in PKD cell lines, NF-?B activity was only induced by TNF-?. However, neither stimulant altered proliferation in any cell line.

PDTC reduced TNF-?-stimulated NF-?B activity in HK-2 only.

Conclusions: PDTC reduced proliferation in ADPKD cells but did not consistently alter NF-?B activation, suggesting that other signalling pathways are likely to be involved in its ability to attenuate renal cyst growth in vivo.

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