Tag Archives: mice

Melting body fat with a microneedle patch

For many people this may seem like a dream come true but there is a proviso. So far researchers have gotten to the in vivo testing (mice)  with no word about human clinical trials, which means it could be quite a while, assuming human clinical trials go well, before any product comes to market. With that in mind, here’s more from a Sept.15, 2017 news item on Nanowerk,

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders like obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina.

A Sept. 15, 2017 Columbia University Medical Center news release on EurekAlert, which originated the news item, describes the research further,

Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat–a process named browning–which can happen naturally when the body is exposed to cold temperatures–as a treatment for obesity and diabetes.

“There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology and cell biology at CUMC. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.”

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter–too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

“The nanoparticles were designed to effectively hold the drug and then gradually collapse, releasing it into nearby tissue in a sustained way instead of spreading the drug throughout the body quickly,” said patch designer and study co-leader Zhen Gu, PhD, associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University.

The new treatment approach was tested in obese mice by loading the nanoparticles with one of two compounds known to promote browning: rosiglitazone (Avandia) or beta-adrenergic receptor agonist (CL 316243) that works well in mice but not in humans. Each mouse was given two patches–one loaded with drug-containing nanoparticles and another without drug–that were placed on either side of the lower abdomen. New patches were applied every three days for a total of four weeks. Control mice were also given two empty patches.

Mice treated with either of the two drugs had a 20 percent reduction in fat on the treated side compared to the untreated side. They also had significantly lower fasting blood glucose levels than untreated mice.

Tests in normal, lean mice revealed that treatment with either of the two drugs increased the animals’ oxygen consumption (a measure of overall metabolic activity) by about 20 percent compared to untreated controls.

Genetic analyses revealed that the treated side contained more genes associated with brown fat than on the untreated side, suggesting that the observed metabolic changes and fat reduction were due to an increase in browning in the treated mice.

“Many people will no doubt be excited to learn that we may be able to offer a noninvasive alternative to liposuction for reducing love handles,” says Dr. Qiang. “What’s much more important is that our patch may provide a safe and effective means of treating obesity and related metabolic disorders such as diabetes.” [emphasis mine]

The patch has not been tested in humans. The researchers are currently studying which drugs, or combination of drugs, work best to promote localized browning and increase overall metabolism.

The study was supported by grants from the North Carolina Translational and Clinical Sciences Institute and the National Institutes of Health (1UL1TR001111, R00DK97455, and P30DK063608).

Notice the emphasis on health and that the funding does not seem to be from industry (the National Institutes of Health is definitely a federal US agency but I’m not familiar with the North Carolina Translational and Clinical Sciences Institute).

Getting back to the research, here’s an animation featuring the work,

Here’s a link and a citation for the paper,

Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment by Yuqi Zhang†, Qiongming Liu, Jicheng Yu†, Shuangjiang Yu, Jinqiang Wang, Li Qiang, and Zhen Gu. ACS Nano, Article ASAP DOI: 10.1021/acsnano.7b04348 Publication Date (Web): September 15, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

I would imagine that Qiang and his colleagues will find a number of business entities will be lining up to fund their work. While the researchers may be focused primarily on health issues, I imagine business types will be seeing dollar signs (very big ones with many zeroes).

Free the rats, mice, and zebrafish from the labs—replace them with in vitro assays to test nanomaterial toxcicity

The July 9, 2012 Nanowerk Spotlight article by Carl Walkey (of the University of Toronto) focuses on research by Dr. André Nel and his coworkers at the California NanoSystems Institute (CNSI) and the University of California Los Angeles (UCLA) on replacing small animal model testing for nanomaterial toxicity with in vitro assays,

Currently, small animal models are the ‘gold standard’ for nanomaterial toxicity testing. In a typical assessment, researchers introduce a nanomaterial into a series of laboratory animals, generally rats or mice, or the ‘workhorse’ of toxicity testing – zebrafish (see: “High content screening of zebrafish greatly speeds up nanoparticle hazard assessment”). They then examine where the material accumulates, whether it is excreted or retained in the animal, and the effect it has on tissue and organ function. A detailed understanding often requires dozens of animals and can take many months to complete for a single formulation. The current infrastructure and funding for animal testing is insufficient to support the evaluation of all nanomaterials currently in existence, let alone those that will be developed in the near future. This is creating a growing deficit in our understanding of nanomaterial toxicity, which fuels public apprehension towards nanotechnology.

Dr. André Nel and his coworkers at the California NanoSystems Institute (CNSI) and the University of California Los Angeles (UCLA) are taking a fundamentally different approach to nanomaterial toxicity testing.

Nel believes that, under the right circumstances, resource-intensive animal experiments can be replaced with comparatively simple in vitro assays.  The in vitro assays are not only less costly, but they can also be performed using high throughput (HT) techniques. By using an in vitro HT screening approach, comprehensive toxicological testing of a nanomaterial can be performed in a matter of days. Rapid information gathering will allow stakeholders to make rational, informed decisions about nanomaterials during all phases of the development process, from design to deployment.

I’ve excerpted a brief description of Nel’s approach,

Rather than using in vitro systems as direct substitutes for the in vivo case, Nel is using a mechanistic approach to connect cellular responses to more complex biological responses, attempting to employ mechanisms that are engaged at both levels and reflective of specific nanomaterial properties.

“You need to align what you test at a cellular level with what you want to know at the in vivo” says Nel. “If oxidative stress at the cellular level is a key initiating element, then by screening for this outcome in cells you more are likely to yield something more predictive of the in vivo outcome. We can do a lot of our mechanistic work at an implementation level that allows development of predictive screening assays.”

By measuring many relevant mechanistic responses, and integrating the results, Nel believes that the in vivo behavior of a nanomaterial can be accurately predicted, provided that enough thinking goes into the devising the systems biology approach to safety assessment.

According to Walkey’s article, this approach could result in a ‘reverse’ nanomaterial development process,

Nel’s approach will influence not only the way in which nanomaterial toxicity is assessed, but also the way in which nanomaterials are developed. Currently, nanomaterials are designed to meet the need of a particular application. Toxicity is then evaluated retrospectively. Formulations that exhibit unacceptable toxicity at that point may be abandoned after a significant investment in development. Because Nel’s approach generates toxicity information much faster than traditional techniques, it will be possible to integrate toxicity during the design of a new nanomaterial. The proactive characterization of nanomaterial toxicity will provide feedback during the design process, producing formulations that maximize efficacy and minimize risk.

This is a very interesting article (illustrated with images and peppered with accessibly explanations of the issues) for anyone following the ‘nanomaterial toxicology’ story.

Math, science and the movies; research on the African continent; diabetes and mice in Canada; NANO Magazine and Canada; poetry on Bowen Island, April 17, 2010

About 10 years ago, I got interested in how the arts and sciences can inform each other when I was trying to organize an art/science event which never did get off the ground (although I still harbour hopes for it one day).  It all came back to me when I read Dave Bruggeman’s (Pasco Phronesis blog) recent post about a new Creative Science Studio opening at the School of Cinematic Arts at the University of Southern California (USC). From Dave’s post,

It [Creative Science Studio] will start this fall at USC, where its School of Cinematic Arts makes heavy use of its proximity to Hollywood, and builds on its history of other projects that use science, technology and entertainment in other areas of research.

The studio will not only help studios improve the depiction of science in the products of their students, faculty and alumni (much like the Science and Entertainment Exchange), but help scientists create entertaining outreach products. In addition, science and engineering topics will be incorporated into the School’s curriculum and be supported in faculty research.

This announcement reminds me a little bit of an IBM/USC initiative in 2008 (from the news item on Nanowerk),

For decades Hollywood has looked to science for inspiration, now IBM researchers are looking to Hollywood for new ideas too.

The entertainment industry has portrayed possible future worlds through science fiction movies – many created by USC’s famous alumni – and IBM wants to tap into that creativity.

At a kickoff event at the USC School of Cinematic Arts, five of IBM’s top scientists met with students and alumni of the school, along with other invitees from the entertainment industry, to “Imagine the World in 2050.” The event is the first phase of an expected collaboration between IBM and USC to explore how combining creative vision and insight with science and technology trends might fuel novel solutions to the most pressing problems and opportunities of our time.

It’s interesting to note that the inspiration is two-way if the two announcements are taken together. The creative people can have access to the latest science and technology work for their pieces and scientists can explore how an idea or solution to a problem that exists in a story might be made real.

I’ve also noted that the first collaboration mentioned suggests that the Creative Science Studio will be able to “help scientists create entertaining outreach products.” My only caveat is that scientists too often believe that science communication means that they do all the communicating while we members of the public are to receive their knowledge enthusiastically and uncritically.

Moving on to the math that I mentioned in the head, there’s an announcement of a new paper that discusses the use of mathematics in cinematic special effects. (I believe that the word cinematic is starting to include games and other media in addition to movies.)  From the news item on physorg.com,

The use of mathematics in cinematic special effects is described in the article “Crashing Waves, Awesome Explosions, Turbulent Smoke, and Beyond: Applied Mathematics and Scientific Computing in the Visual Effects Industry”, which will appear in the May 2010 issue of the NOTICES OF THE AMS [American Mathematical Society]. The article was written by three University of California, Los Angeles, mathematicians who have made significant contributions to research in this area: Aleka McAdams, Stanley Osher, and Joseph Teran.

Mathematics provides the language for expressing physical phenomena and their interactions, often in the form of partial differential equations. These equations are usually too complex to be solved exactly, so mathematicians have developed numerical methods and algorithms that can be implemented on computers to obtain approximate solutions. The kinds of approximations needed to, for example, simulate a firestorm, were in the past computationally intractable. With faster computing equipment and more-efficient architectures, such simulations are feasible today—and they drive many of the most spectacular feats in the visual effects industry.

This news item too brought back memories. There was a Canadian animated film, Ryan, which both won an Academy Award and involved significant collaboration between a mathematician and an animator. From the MITACS (Mathematics of Information Technology and Complex Systems)  2005 newsletter, Student Notes:

Karan Singh is an Associate Professor at the University of Toronto, where co-directs the graphics and HCI lab, DGP. His research interests are in artist driven interactive graphics encompassing geometric modeling, character animation and non-photorealistic rendering. As a researcher at Alias (1995-1999), he architected facial and character animation tools for Maya (Technical Oscar 2003). He was involved with conceptual design and reverse engineering software at Paraform (Academy award for technical achievement 2001) and currently as Chief Scientist for Geometry Systems Inc. He has worked on numerous film and animation projects and most recently was the R+D Director for the Oscar winning animation Ryan (2005)

Someone at Student Notes (SN) goes on to interview Dr. Singh (here’s an excerpt),

SN: Some materials discussing the film Ryan mention the term “psychorealism”. What does this term mean? What problems does the transition from realism to psychorealism pose for the animator, or the computer graphics designer?

KS: Psychorealism is a term coined by Chris {Landreth, film animator] to refer to the glorious complexity of the human psyche depicted through the visual medium of art and animation. The transition is not a problem, psychorealism is stylistic, just a facet to the look and feel of an animation. The challenges lies in the choice and execution of the metaphorical imagery that the animator makes.

Both the article and Dr. Singh’s page are well worth checking out, if the links between mathematics and visual imagery interest you.

Research on the African continent

Last week I received a copy of Thompson Reuters Global Research Report Africa. My hat’s off to the authors, Jonathan Adams, Christopher King, and Daniel Hook for including the fact that Africa is a continent with many countries, many languages, and many cultures. From the report, (you may need to register at the site to gain access to it but the only contact I ever get is a copy of their newsletter alerting me to a new report and other incidental info.), p. 3,

More than 50 nations, hundreds of languages, and a welter of ethnic and cultural diversity. A continent possessed of abundant natural resources but also perennially wracked by a now-familiar litany of post-colonial woes: poverty, want, political instability and corruption, disease, and armed conflicts frequently driven by ethnic and tribal divisions but supplied by more mature economies. OECD’s recent African Economic Outlook sets out in stark detail the challenge, and the extent to which current global economic problems may make this worse …

While they did the usual about challenges, the authors go on to add this somewhat contrasting information.

Yet the continent is also home to a rich history of higher education and knowledge creation. The University of Al-Karaouine, at Fez in Morocco, was founded in CE 859 as a madrasa and is identified by many as the oldest degree-awarding institution in the world.ii It was followed in 970 by Al-Azhar University in Egypt. While it was some centuries before the curriculum expanded from religious instruction into the sciences this makes a very early marker for learning. Today, the Association of African Universities lists 225 member institutions in 44 countries and, as Thomson Reuters data demonstrate, African research has a network of ties to the international community.

A problem for Africa as a whole, as it has been for China and India, is the hemorrhage of talent. Many of its best students take their higher degrees at universities in Europe, Asia and North America. Too few return.

I can’t speak for the details included in the report which appears to be a consolidation of information available in various reports from international organizations. Personally, I find these consolidations very helpful as I would never have the time to track all of this down. As well, they have created a graphic which illustrates research relationships. I did have to read the analysis in order to better understand the graphic but I found the idea itself quite engaging and as I can see (pun!) that as one gets more visually literate with this type of graphic that it could be a very useful tool for grasping complex information very quickly.

Diabetes and mice

Last week, I missed this notice about a Canadian nanotechnology effort at the University of Calgary. From the news item on Nanowerk,

Using a sophisticated nanotechnology-based “vaccine,” researchers were able to successfully cure mice with type 1 diabetes and slow the onset of the disease in mice at risk for the disease. The study, co-funded by the Juvenile Diabetes Research Foundation (JDRF), provides new and important insights into understanding how to stop the immune attack that causes type 1 diabetes, and could even have implications for other autoimmune diseases.

The study, conducted at the University of Calgary in Alberta, Canada, was published today [April 8, 2010?] in the online edition of the scientific journal Immunity.

NANO Magazine

In more recent news, NANO Magazine’s new issue (no. 17) features a country focus on Canada. From the news item on Nanowerk,

In a special bumper issue of NANO Magazine we focus on two topics – textiles and nanomedicine. We feature articles about textiles from Nicholas Kotov and Kay Obendorf, and Nanomedicine from the London Centre for Nanotechnology and Hans Hofstraat of Philips Healthcare and an interview with Peter Singer, NANO Magazine Issue 17 is essential reading, www.nanomagazine.co.uk.

The featured country in this issue is Canada [emphasis mine], notable for its well funded facilities and research that is aggressively focused on industrial applications. Although having no unifying national nanotechnology initiative, there are many extremely well-funded organisations with world class facilities that are undertaking important nano-related research.

I hope I get a chance to read this issue.

Poetry on Bowen Island

Heather Haley, a local Vancouver, BC area, poet is hosting a special event this coming Saturday at her home on Bowen Island. From the news release,

VISITING POETS Salon & Reading

Josef & Heather’s Place
Bowen Island, BC
7:30  PM
Saturday, April 17, 2010

PENN KEMP, inimitable sound poet from London, Ontario

The illustrious CATHERINE OWEN from Vancouver, BC

To RSVP and get directions please email hshaley@emspace.com

Free Admission
Snacks & beverages-BYOB

Please come on over to our place on the sunny south slope to welcome these fabulous poets, hear their marvelous work, *see* their voices right here on Bowen Island!

London, ON performer and playwright PENN KEMP has published twenty-five books of poetry and drama, had six plays and ten CDs produced as well as Canada’s first poetry CD-ROM and several videopoems.  She performs in festivals around the world, most recently in Britain, Brazil and India. Penn is the Canada Council Writer-in-Residence at UWO for 2009-10.  She hosts an eclectic literary show, Gathering Voices, on Radio Western, CHRWradio.com/talk/gatheringvoices.  Her own project for the year is a DVD devoted to Ecco Poetry, Luminous Entrance: a Sound Opera for Climate Change Action, which has just been released.
CATHERINE OWEN is a Vancouver writer who will be reading from her latest book Frenzy (Anvil Press 09) which she has just toured across the entirety of Canada. Her work has appeared in international magazines, seen translation into three languages and been nominated for honours such as the BC Book Prize and the CBC Award. She plays bass and sings in a couple of metal bands and runs her own tutoring and editing business.

I have seen one of Penn Kemp’s video poems. It was at least five years ago and it still resonates with me . Guess what? I highly recommend going if you can. If you’re curious about Heather and her work, go here.