Tag Archives: Mayo Clinic

What helps you may hurt you (titanium dioxide nanoparticles and orthopedic implants)

From a Sept. 16, 2017 news item on Nanotechnology Now,

Researchers from the Mayo Clinic have proposed that negative cellular responses to titanium-based nanoparticles released from metal implants interfere in bone formation and resorption at the site of repair, resulting in implant loosening and joint pain. [emphasis mine]Their review of recent scientific evidence and call for further research to characterize the biological, physical, and chemical interactions between titanium dioxide nanoparticles and bone-forming cells is published in BioResearch Open Access, a peer-reviewed open access journal from Mary Ann Liebert, Inc., publishers. The article is available free on theBioResearch Open Access website.

A Sept. 14, 2017 Mary Anne Liebert (Publishing) news release, which originated the news item,  mentions the authors,

Jie Yao, Eric Lewallen, PhD, David Lewallen, MD, Andre van Wijnen, PhD, and colleagues from the Mayo Clinic, Rochester, MN and Second Affiliated Hospital of Soochow University, China, coauthored the article entitled “Local Cellular Responses to Titanium Dioxide from Orthopedic Implants The authors examined the results of recently published studies of titanium-based implants, focusing on the direct and indirect effects of titanium dioxide nanoparticles on the viability and behavior of multiple bone-related cell types. They discuss the impact of particle size, aggregation, structure, and the specific extracellular and intracellular (if taken up by the cells) effects of titanium particle exposure.

“The adverse effects of metallic orthopedic particles generated from implants are of significant clinical interest given the large number of procedures carried out each year. This article reviews our current understanding of the clinical issues and highlights areas for future research,” says BioResearch Open Access Editor Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

Before getting to the abstract, here’s a link to and a citation for the paper,

Local Cellular Responses to Titanium Dioxide from Orthopedic Implants by Yao, Jie J.; Lewallen, Eric A.; Trousdale, William H.; Xu, Wei; Thaler, Roman; Salib, Christopher G.; Reina, Nicolas; Abdel, Matthew P.; Lewallen, David G.; and van Wijnenm, Andre J.. BioResearch Open Access. July 2017, 6(1): 94-103. https://doi.org/10.1089/biores.2017.0017 Published July 1, 2017

This paper is open access.

Funding for graphene-based wireless sensor and artificial pancreas project announced

The project to create a graphene-based wireless sensor for an artificial panceres is one of tour Minnesota-based (US) projects to get funding, from the Aug. 13, 2013 news item on Nanwoerk (Note: A link has been removed),

The Minnesota Partnership for Biotechnology and Medical Genomics announced four research projects selected for funding from the 2013 Discovery Transformation Grant Program. Together, the selected researchers were awarded a total of $2 million to support their work in diabetes research. Minnesota Partnership funding comes from money appropriated by the Minnesota Legislature.

An Aug. 12, 2013 Mayo Clinic news release provides details about the four funded projects with the second one being of most interest for those following the graphene story,

Insulin Gene Therapy for Diabetes: Insulin gene therapy is a conceptually simple and feasible approach to diabetes management that, if successful, could replace long-acting insulin injections both in Type 1 and Type 2 diabetes. The investigators have created gene therapy vectors coding for insulin and a stop signal that can be activated by giving a drug, so production can be controlled. Based upon encouraging preclinical results, the current project is designed to rapidly advance the new vector to clinical testing in insulin-dependent patients with Type 1 or Type 2 diabetes.

The principal investigators of this research project are Stephen Russell, M.D.,Ph.D., professor in the Department of Molecular Medicine at Mayo Clinic and R. Scott McIvor, Ph.D., professor in the Department of Genetics, Cell Biology and Development at the University of Minnesota.

A Revolutionary Sensor Platform for Realizing the Artificial Pancreas: New technologies are making it possible to develop a system to automate insulin delivery by continually monitoring blood glucose. The investigators aim to develop a graphene-based wireless sensor that can be placed in blood vessels for accurate and continual monitoring of blood glucose levels. This level of data is key to achieving optimal glucose control with an artificial pancreas.

The principal investigators are Yogish Kudva, M.D. , professor in the Department of Endocrinology at Mayo Clinic and Steven Koester, Ph.D. , professor in the Department of Electrical and Computer Engineering at the University of Minnesota.

SERCA Activators for Advanced Diabetes Therapy: This project seeks a major advance in treatment for Type 2 diabetes, based on development of drugs that regulate movement of calcium within cells by targeting a naturally occurring pump abbreviated as SERCA. The investigators have already discovered several promising drug candidates that activate SERCA and alleviate mitochondrial dysfunction related to diabetes. The researchers will use high-throughput drug screening technology to find new drug candidates, and then chemically optimize their medicinal properties, paving the way for safety testing and clinical trials.

The principal investigators are David Thomas, Ph.D. and David Bernlohr, Ph.D., who are both professors in the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota.

A Novel Method for Detecting and Targeting Diabetes Specific CD4+ T Cells: Type 1 diabetes is a chronic T cell-mediated autoimmune disease that results in the destruction of the insulin secreting beta cells. Advances in biomarker technology have allowed the investigator and his team to identify, track and study individual CD4+ T lymphocytes present in Type 1 diabetes. In this study, the investigator will evaluate the potential of novel biomarkers to permit diagnosis of Type 1 diabetes before irreparable destruction of beta cell mass has occurred and to track auto-reactive cells during ongoing disease.

The principal investigator is Brian Fife, Ph.D., assistant professor in the Department of Medicine at the University of Minnesota.

You can find out more about the Minnesota Partnership for Biotechnology and Medical Genomics here.

SERCA Activators for Advanced Diabetes Therapy

Ponce de León, new therapies against aging, and Spain

ScienceDaily published an intriguing Oct. 3, 2012 news item about anti-aging research in Spain,

A team of Spanish scientists has developed an intelligent nanodevice that lays the foundations for the future development of new therapies against aging. The device consists of nanoparticles that can selectively release drugs in aged human cells. Its potential future use ranges from the treatment of diseases involving tissue or cellular degeneration such as cancer, Alzheimer’s or Parkinson’s, among others, to accelerated aging disorders (progeria).

“The nanodevice that we have developed consists of mesoporous nanoparticles with a galactooligosaccharide outer surface that prevents the release of the load and that only selectively opens in degenerative phase cells or senescent cells. The proof of concept demonstrates for the first time that selected chemicals can be released in these cells and not in others,” says Ramón Martínez Máñez, researcher at the IDN Centre — Universitat Politècnica de València and CIBER-BBN member.

The researchers have evaluated the utility of the new nanodevices in primary cell cultures derived of patients with accelerated aging syndrome dyskeratosis congenita (DC). Such cultures show a high percentage of senescence characterized by elevated levels of beta-galactosidase activity, an enzyme characteristic of senescent state. “The aging cells overexpress this enzyme so we have designed nanoparticles that open when detected and release their contents in order to eliminate senescent cells, prevent deterioration or even reactivate for their rejuvenation,” explains Murguía [José Ramón Murguía, a researcher at the Instituto de Biología Molecular y Celular de Plantas (UPV-CSIC) and also a CIBER-BBN member]. “There are a number of diseases associated with premature aging of tissues, many of which affect very young patients and for whom there is no therapeutic alternative, as in the case of DC or aplastic anemia. Other diseases affect adults, as idiopathic pulmonary fibrosis or liver cirrhosis. These nanoparticles represent a unique opportunity to selectively deliver therapeutic compounds to affected tissues and rescue their viability and functionality” explains Rosario Perona, researcher at the Instituto de Investigaciones Biomédicas (CSIC/UAM) and CIBERER member.

While this team is discussing therapeutic applications in the news item, they do note there are cosmetic applications.

Nicholas Wade in a Nov. 2, 2011 article for the New York Times explores some research in the US on senescent cells, aging, and possible therapies,

Senescent cells accumulate in aging tissues, like arthritic knees, cataracts and the plaque that may line elderly arteries. The cells secrete agents that stimulate the immune system and cause low-level inflammation. Until now, there has been no way to tell if the presence of the cells is good, bad or indifferent.

The answer turns out to be that the cells hasten aging in the tissues in which they accumulate. In a delicate feat of genetic engineering, a research team led by Darren J. Baker and Jan M. van Deursen at the Mayo Clinic in Rochester, Minn., has generated a strain of mouse in which all the senescent cells can be purged by giving the mice a drug that forces the cells to self-destruct.

Aging research is a relatively young field because until 20 or so years ago the prospect of defeating age seemed hopeless. Then researchers found that the lifespan of laboratory animals could be extended by manipulating certain genes, setting off a hunt for drugs that might influence the corresponding genes in people. This line of research remains promising but has produced few tangible results so far. The discovery that senescent cells seem to be the cause of tissue degeneration opens out a new direction for researchers on aging to explore.

In both mice and people, senescent cells are few in number but have major effects on the body’s tissues. Killing the cells should therefore have large benefits with little downside. The gene-altering approach used on the mice cannot be tried in people, but now that senescent cells appear to be harmful, researchers can devise ways of targeting them.

The purpose of research on aging, she said, is not to let people live a thousand years, as portrayed in science fiction, but to increase health span, the proportion of people’s natural lives that they live in good health.

“People used to see aging as a rusting nail — there’s nothing you can do about it,” Dr. Campisi [Judith Campisi, at the Buck Institute for Research on Aging] said. “But we now know that there are processes that are driving aging, and that those processes can be meddled with.”

It appears that this relatively new understanding of senescent cells has provided the basis for the work in Spain where they have successfully targeted senescent cells in vitro, the next step will be to test the device on animal models. You can find out more about this work in Spain at RUVID, although you will need Spanish language skills.

As for Juan Ponce de León, he was not quite the Fountain of Youth seeker we’ve been led to believe (from the Wikipedia essay; Note: I have removed links and footnotes),

Juan Ponce de León … (1474 – July 1521) was a Spanish explorer and conquistador. He became the first Governor of Puerto Rico by appointment of the Spanish crown. He led the first European expedition to Florida, which he named. He is associated with the legend of the Fountain of Youth, reputed to be in Florida.

According to a popular legend, Ponce de León discovered Florida while searching for the Fountain of Youth. Though stories of vitality-restoring waters were known on both sides of the Atlantic long before Ponce de León, the story of his searching for them was not attached to him until after his death. … Most historians hold that the search for gold and the expansion of the Spanish Empire were far more imperative than any potential search for the fountain.