Tapeworm holes

Tapeworm holes

I was interested in learning more about my dog’s tapeworm infection so Google sent me down the worm rabbit hole. She was asymptomatic. We had her stool checked as a requirement for a daycare center. It came back positive for tapeworm and she was given Panacur ™ (Fenbendazole). The handout that the vet gave us talked a lot about Dipylidium caninum, which is a tapeworm that is transmitted by fleas. We didn’t notice any fleas on our dog and she is not scratching excessively. So I talked to the vet and he said she has a different type of tapeworm. It was close to closing time so I didn’t press him for more information. I went down the rabbit hole, I mean wormhole looking for more information. It turns out that Panacur ™ only works for Taenia pisiformis, which is a type of tapeworm with rabbits as an intermediate host.

§ Life cycle

The general life cycle of a tapeworm starts with proglottids or eggs in the feces of the primary host. Proglottids is a segment of the tapeworm that contains a complete set of reproductive organs. The intermediate host gets infected with the eggs or proglottids, for D. caninum that would be fleas and for T. pisiformis it would be rabbits. The primary host gets D. caninum by eating the fleas, not by flea bites. If your dog or cat gets bitten, they would naturally scratch the bite with their teeth and would get the larvae into their mouths. So infants can get D. caninum by putting an infected flea in their mouth. That’s why it’s rare for humans to get D. caninum. For T. pisiformis, it’s a bit more gruesome because the main way to get infected is to bite an infected rabbit because it’s their viscera (internal organs, predominantly in the abdomen) that contains the larvae. The larvae travel from the rabbit’s intestines, into the blood stream, and then to the viscera. I’m still not sure how my dog got infected. I bet Tommy Leung can tell us more about tapeworms.

§ So how does Fenbendazole work?

Fenbendazole is in a class of drugs called anthelmintics, which are drugs that expel worms from the body by killing them or stunning them. In the case of Fenbendazole, it interferes with tubulin polymerization. Microtubules are part of the cytoskeleton. If tubulin polymerization is disrupted, the cells essentially dissolve/collapse.

More information and images here: http://goo.gl/qBZc4p

§ About the image:

It might look like a beautiful flower, but this image of the week is more the stuff of nightmares! The picture above shows a dog tapeworm (Taenia pisiformis) taken using a light microscope. The image clearly shows the hooks of the tapeworm on its head (scolex), which it uses (along with four suckers) to attach to the small intestine of canids like dogs and foxes.

The image was taken by Spike Walker. The tapeworm was on a microscope slide, giving it a slightly squashed look. The muscle and other tissue of the tapeworm were stained red, but the hooks (made of chitin) don’t stain. Therefore, Spike used a contrast enhancement technique called Rheinberg illumination, which gives the hooks their bright colours against a blue background. First demonstrated over a hundred years ago by Julius Rheinberg, this involves using coloured filters so a transparent sample can be seen.

Image source: http://goo.gl/hOAAJK

#ScienceSunday  

Go team USA

Go team USA

I hope team USA does well, especially better than this guy, against Portugal. The image below is from the International Museum of Surgical Science. I was there just before closing so I went through rather hurriedly. So I don’t recall what the placard said about this. I don’t think it is plastination but I don’t remember. I’ll be back and take notes. Here’s more from IMSS

https://plus.google.com/u/0/+ChadHaney/posts/YoinHSUCmTp

The plastination soccer/football display can be seen here:

http://www.bodyworlds.com/en/media/picture_database/preview.html?id=257

Enjoy the #Worldcup  and #ScienceSunday  

Breaking the hype before it spreads too fast

Breaking the hype before it spreads too fast

Well done, Buddhini Samarasinghe.

#ScienceEveryday  

Originally shared by Buddhini Samarasinghe

Pulling a Fast One on Cancer

There is a report making the rounds on social media that really needs to be explained, because as usual the media hype is distorting the findings. The article in question was published in the Cell Stem Cell journal, and is #OpenAccess (http://goo.gl/pnoiwa). I will explain the background, what these results mean, and more importantly, what they don’t mean.

✤ Traditional chemotherapy is toxic to cells. The only reason traditional chemotherapy works is because it kills cancer cells faster than it kills normal cells. The side effects from chemo often happen because normal cells are also affected. One such side effect is the suppression of the immune system. This happens because chemo damages adult stem cells too, which impairs tissue repair and regeneration. 

✤ Blood stem cells (known as hematopoietic stem cells) are responsible for replacing our blood cells; these reside in the bone marrow. In this study, scientists investigated the effect of prolonged fasting on hematopoietic stem cells.

✤ Mice used in this study were fasted for 48 hours, which the scientists defined as prolonged fasting. These mice received no food, only water. They then treated the mice with cyclophosphamide, a common chemotherapy drug. They found that cycles of prolonged fasting reduced the damage caused to hematopoietic stem cells when the mice were treated with cyclophosphamide. They also found that prolonged fasting cycles promoted the regeneration of blood cells through the protection of hematopoietic stem cells. 

✤ Next, the scientists tested whether the effects of prolonged fasting were independent of the toxic side effects of chemotherapy. Could prolonged fasting alone stimulate hematopoietic stem cells to self-renew? Indeed, it could. 

✤ What is the molecular mechanism for this process? A growth factor known as Insulin-like Growth Factor-1 (IGF-1) seemed to be involved. Growth factors are proteins that control the multiplication of cells. To examine this mechanism, the scientists used mice that were deficient in IGF-1.  If you’re curious about how these ‘knockout mice’ are generated, read http://goo.gl/jdbqbk. When these IGF-1 deficient mice were treated with cyclophosphamide, they showed similar results to the prolonged fasting mice; reduced levels of hematopoietic stem cell damage. So getting rid of IGF-1 induced the same protective effects on hematopoietic stem cells.  

✤ How does IGF-1 signalling protect hematopoietic stem cells? They found that the activity of an enzyme known as PKA was also reduced in these prolonged fasting/IGF-1 deficient mice. PKA controls the pathway involved in stem cell regeneration. So inhibiting IGF-1 or PKA signalling mimics the effect of prolonged fasting; it promotes the regeneration of hematopoietic stem cells, thereby reducing the immuno-suppressive side effect of chemotherapy. 

✤ This is really interesting data – this research has identified one of the signalling pathways in the intricate network of reactions controlling the behaviour of hematopoietic stem cells. The mechanism involves PKA and IGF-1 signalling.  

WHAT THE DATA DOESN’T SHOW

What this doesn’t show is that fasting is magically a cure-all for cancer. There isn’t a single study that shows lowered incidence of cancer in human populations that fast regularly. The fasting that these mice underwent also did not include the feasting that goes on every night as seen with human populations either. The scientists also conducted a small Phase I clinical trial in which patients undergoing chemotherapy fasted for 72h – the results are promising; their hematopoietic stem cells were protected when compared with the non-fasting control group. But obviously more data is needed, and it is highly inadvisable to fast before undergoing chemo, without the explicit guidance of a physician.

To summarise, fasting is not a cure for cancer. If anything, fasting does “cure” everything, eventually; this pathway involves a mechanism known as ‘death’. 

Image: fasting causes a major reduction in white blood cells followed by their replenishment after refeeding. These effects of prolonged fasting can result in the reversal of chemotherapy-induced immunosuppression. 

Image source: http://goo.gl/pnoiwa

#ScienceMediaHype   #ScienceEveryday  

Busting the hype, sorry kid

Busting the hype, sorry kid

This is a very interesting read about why the Ocean Cleanup Array project is full of naïveté. 

It’s nicely connected with Tommy Leung’s post:

Markers Of The Anthropocene

https://plus.google.com/u/0/111479647230213565874/posts/H87PSjm6sXT

h/t Cindy Brown 

#ScienceSunday  

Originally shared by Cindy Brown

Best place to start is at home.

Do read this.  It outlines the massive scope of the problem in the first place.  But it also points out the inherent problem with the “recyclability” of plastic in the first place:

But even when plastics do get recycled, in the vast majority of cases, recycling only kicks the can down the road one generation by creating a product that can’t or won’t (because of economic constraints) be recycled again. In short, the vast majority of the recycling industry isn’t doing anything to solve marine plastic pollution, and for the most part, recycling is just creating a secondary market for waste. Even if the economics of Slat’s Ocean Cleanup Array didn’t further impede its viability, more plastic would still be entering the ocean than his device would pull out. Placing fees on producers of virgin plastics, and giving breaks to those who use 100% recycled content or are actively working towards it, would help to balance this equation out and would be great news for the ocean.

h/t various sources including Cod Codliness 

http://inhabitat.com/the-fallacy-of-cleaning-the-gyres-of-plastic-with-a-floating-ocean-cleanup-array/

Science on Display, not just a Phage

Science on Display, not just a Phage

Rajini Rao’s post made me think of phage display libraries. Check out her post here:

The Enemy of My Enemy

https://plus.google.com/u/0/+RajiniRao/posts/LvxVPMLNyTV

What is a phage? A phage or more accurately a bacteriophage, is a virus that infects bacteria. You can read more about phages in Rajini’s post. Phage display libraries use phages to screen for peptides for diagnosis or treatment.

❈ What is a peptide?

Peptides are short chains (polymers) of amino acids. Think of peptides as the building blocks for proteins. So DNA gets translated into amino acids via mRNA, which make up peptides, which combine to make proteins. That’s an oversimplification but it’s easy to get the picture. 

You can read more here: http://goo.gl/aYzy7r

An example of two peptides are shown below.

❈ Phage display

George P. Smith at the University of Missouri developed phage display in 1985. He figured out that bacteriophages could be modified to incorporate “foreign” DNA and translate that to a peptide on their surface, hence the “display” aspect. After incorporating a DNA sequence into a phage, it can display the corresponding peptide on its surface. Why is that important and how can we take advantage of that? You can create a whole library of phages and see which phage has the best targeting for your particular model/system.

❈ Antibodies

You probably know that antibodies are part of the immune system and that they are specific for an antigen, e.g. bacterium. The thinking is that if you can make an antibody for say a particular tumor or protein involved with Alzheimer’s Disease, you could attach a therapeutic or diagnostic agent. Say you have such an antibody. You add a fluorescent component or radioactive element to make it diagnostic. Where ever the antibody binds, you will be able to image. Alternatively, say you take the antibody and add a drug so that the drug is now targeted. You can lower the dose because you don’t need to flood the whole body. So why doesn’t that really work? It has been tried. Antibodies are specific but have poor clearance and are bulky. When you have to add something to them, either a diagnostic or therapeutic component, it only gets more bulky, maybe too bulky to cross the blood brain barrier or too bulky to be cleared from the body in a reasonable time, so you end up with more side effects.

If you search Google Scholar for RGD (Arginine-Glycine-Aspartic acid) you’ll find over 50,000 hits. RGD is a peptide that’s associated with integrins. Integrins are cell surface receptors that are involved with cell signaling, for example in wound healing and cancer. Since a phage is smaller than an antibody, you can imagine that a phage display should be more effective than an antibody in terms of clearance, especially after adding a diagnostic or therapeutic agent as compared to an antibody.

❈ Radio labeled phage

Say you create a phage that presents a peptide that’s specific for a certain integrin. You add a radioisotope and test it against a tumor that has a lot of those integrins. That’s what’s shown in the picture below. A phage that was designed to bind with an alpha V beta 6 integrin with indium-111, which is a gamma radiation emitting isotope, was used in a mouse model with two tumor types. The tumor on the left side is negative for the alpha V beta 6 integrin and the right side is positive. You can see that the indium-111 labeled phage is accumulating on the right but not the left. The histogram shows the accumulation of radioactivity, i.e., labeled phage, for the positive vs. negative alpha V beta 6 tumors.

Sources:

Structural guided scaffold phage display libraries as a source of bio-therapeutics.

PLoS One. 2013 Aug 9;8(8):e70452.

http://goo.gl/Ky4D3l

Phage Display in Molecular Imaging and Diagnosis of Cancer

Chem. Rev., 2010, 110 (5), pp 3196–3211

Susan L. Deutscher

http://pubs.acs.org/doi/full/10.1021/cr900317f

#ScienceSunday