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Showing posts with label canine research. Show all posts
Showing posts with label canine research. Show all posts

New Dog Cancer Cure: Targeted Chemo Hylaplat Gets Results

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Canine Cancer is prevalent in Golden Retrievers
Photo Credit By cogdogblog 

A New Therapy for Dogs With Metastic Cancers Is Now Available And Getting Good Results


A new drug, HylaPlat, has produced high cure rates for many different forms of Canine Cancer. By way of targeting the cancer, and directly injecting it with Hylaplat chemotherapy, results have been dramatically improved locally, as well as systemically. So far the drug has proven highly effective on a variety of metastic cancers.  Trials are ongoing through veterinary practices, and your vet’s practice and your dog may be able to participate for free. Contact Information for canine cancer trial participation is located at the bottom of the article.

What is Hylaplat, The Injectable Chemotherapy?


The team at HylaPharm (a 2011 startup affiliated with the University of Kansas) blended Hyaluronan and Cisplatin to create HylaPlat.  The brain child of pharmaceutical chemist Laird Forrest Ph.D. and Daniel Aires, M.D., Director of dermatology at KU, Hylaplat is showing promise with canine cancers, and they hope to see it in human clinical trials as well in the future.
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Hyaluronan is a natural polymer found in the body throughout connective, epithelial and neural tissues. It contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors.

Discovered in 1845 and licensed for medical use in 1978, Cisplatin is a chemotherapy medication listed by the World Health Organization as one of the Essential Medications. Currently, it is used intravenously to treat a number of cancers, including testicular, breast, bladder, ovarian, cervical, lung, brain and esophageal cancers in humans. 

It works by binding to cancer cells and preventing DNA replication. However, it does have some serious side effects such as auditory, kidney and nerve damage as well as the nausea and vomiting often expected from chemotherapy treatments.
 
Utilizing a blend of Hyaluronan and Cisplatin, Hylaplat makes possible a non-destructive, local injection which “sticks” well to cancer cells, allowing for an efficient uptake of cisplatin into the tumor cells.

Localizing the treatment to the tumor site, allows for a lower, targeted dose to be administered, thereby minimizing some of the more threatening side effects to the kidneys, nerves and auditory organs.

Photo Credit Celsim Junior - Flickr


As explained by Dr. Ares, “Injecting it directly into the main cancer lesion results in a very high drug level compared to normal injections into the veins,” Aires said. “Furthermore, most cancer cells have a receptor on their surface that grabs onto hyaluronan. In general, more aggressive cancers and the hard-to-treat cancer stem cells have more of these receptors. This is another factor that can help target the drug to cancer cells.”

Additionally, with Hylaplat, the compound molecule itself is very small. Because the compound molecule of Hyaluronan and Cisplatin is only 20 nanometers in size, after doing its work in the tumor, HylaPlat drains easily into the lymph nodes, delivering a high dose of chemotherapy to any cancer cells that may be hiding there.

As a result, HylaPlat may have additional advantages for treating cancers that metastasize through the lymph nodes; a category that includes 85 percent of human cancers. Breast, ovarian, colon and lung cancer are included in this category of metastic cancers. Standard chemotherapy treatments, in use today, tend not to get into the lymph nodes at substantial therapeutic levels, resulting in a greater risk of relapse.


Use of Hylaplat to Treat Canine Cancer


Traditionally, researchers begin testing cancer treatment on laboratory animals by first inducing a laboratory derived cancer.  Unlike naturally occurring cancers, these tend to have homogenous cancer cells grown carefully under laboratory conditions.  They are not very hardy, unlike naturally occurring cancers, that tend to have diverse cells and are better at evading the body’s natural immune system. 

By using larger animals with systems more similar to that of the human anatomy, comparative oncology researchers can better understand how new drugs may affect human patients. Dogs with naturally occurring cancers are an ideal population for testing drugs on a diverse group of cancers. So far, HylaPlat has proven effective in animal models, and larger animal trials for submission to the Federal Drug Administration are currently under way.

Golden retriever receiving chemotherapy

The Initial Trial Results for Cancer in Large Breed Dogs

In the initial clinical trial, which started in 2012, seven large-breed dogs with small forms of oral cancer received a formulation of the Hylaplat chemotherapy. The dogs in this study were suffering with naturally occurring cancers.

Of those first seven dogs, the cancer in three patients disappeared, and two other dogs showed signs of partial remission or slowing of the disease. These promising results gave rise to a feature story on a local television news network. Hylapharm was suddenly flooded with requests from pet owners with dogs suffering from all forms of cancer that wanted in on the trial.

Faced with this tremendous demand and the potential for experimenting with all sizes of dogs and various metastic cancers, researchers lifted the restrictions on the size of the dogs and types of cancers being tested. Additionally, local veterinarians were trained to use the treatment for cancers all over the bodies of dogs, including muscle and bone tumors, melanomas, sarcomas and lymphoma.

Injection of Hylaplat is performed by first sedating the dog, then injecting the chemotherapy directly into the tumor. The original treatment protocol called for four injections over a period of several weeks, however, some dogs have responded after just one injection. In general, the dogs show little to no side-effects to the treatment, with them adapting to their normal routines shortly after treatment.

Better yet, at this time, it is a very affordable course of treatment, while traditional chemotherapy has been cost prohibitive for many pet owners. Currently, the owner need only pay for the sedation and administration of Hylaplat. Traditional courses of chemo can run into the thousands of dollars with side-effects that often cause owners to regret their decision to pursue it.

Getting a canine version of HylaPlat to market, however, appears to be on the fast track, which should come as a delight to pet owners and the drug's creators.


The Canine Cancer trial is still accepting patients. If you think your dog could be a candidate, please call 913-588-3840 or email jadams4@kumc.edu.

All photos licensed under the Creative Commons Attribution 2.0 Generic
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The Hypoallergenic Dog Breed Myth | The Surprising Study Results

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The AKC lists 19 breeds as having hypoallergenic qualities. Do the dog breeds on this list really produce less dander and allergens? A study, based in Detroit, Michigan, sought to find out. Here's what they learned.
Hypoallergenic Coton De Tulear Dog Breed
The Coton De Tulear, a low shed dog and recent addition to the AKC registry.  Image by CVF-pfs

The breeds listed below have been touted by the AKC and breeders as being hypoallergenic, mainly because they shed substantially less than other dog breeds.  However, hair itself is not allergenic; it's the dander attached to it that causes the sniffles and asthma attacks.

The assumption has been, less hair in the air means less dander floating around. As a result, an industry of mixed breeds claiming hypoallergenic status has flooded the dog market. Americans are prepared to spend big dollars ($1500-$5000) on purportedly low allergy mongrels.

The AKC's "Hypoallergenic" Dog Breeds List:


  • Afghan Hound
  • Bedlington Terrier
  •  Bichon Frise
  •  Chinese Crested
  • Coton De Tulear
  • Irish Water Spaniel
  • Kerry Blue Terrier
  • Maltese
  • Poodle
  • Portuguese Water Dog
  • Miniature Schnauzer
  • Standard Schnauzer
  • Soft Coated Wheaton Terrier
  • Zoloitzuintli (Mexican Hairless)
  • American Hairless Terrier
  • Lagotto Romagnolo
  • Spanish Water Dog
  • Peruvian Inca Orchid (Hairless) 
Three Mexican Hairless Dogs Hypoallerginc Dogs
Mexican Hairless Dogs. You might expect them to be as free from allergens as they are from hair.

Designer Mixes Claiming Hypoallergenic Qualities:

  • Goldendoodle - Golden Retrieve and Poodle cross
  • Maltipoos - Maltese Poodle mix
  • Maltichon - Maltese and Bichon mix
  • Mauxi - Dachshund - Maltese mix 
  • Anything else mixed with Poodle or Maltese
Despite the public interest in hypoallergenic pets, no one had ever tested the theory by testing the allergen levels in dog owners' homes.  Then came the study, published in The Journal of Rhinology and Allergy, that attempted to prove or disprove the hypoallergenic breed theory. 

The Allergen Results From the Study of 190 Detroit Homes 

The study[1], based in Detroit, selected participants from a pool of expectant mothers in their third trimester of pregnancy. 190 Expectant mothers who reported owning dogs as pets which where allowed in their homes were asked: the breed of their dog, how much time it spent in the home and if it would be allowed into the nursery. Researchers then went to their homes, one month postpartum, to collect dust samples by vacuum in the nurseries, and then measure the levels of allergens present.

Homes with pure breed, hypoallergenic breeds and hypoallergenic mixes were tested and the results were categorized into four test schemes. 

Scheme A compared allergen levels from pure breed "Hypoallergenic" dog homes and other pure breed dogs as identified by the AKC. 

Scheme B compared pure breed dogs with mixed breed dogs where at least one parent was considered hypoallergenic. 

Scheme C compared purebred dogs, mixed breed dogs with one hypoallergenic parent and mixed breed dogs with no hypoallergenic component in their lineage.

Scheme D Compared only AKC listed purebred Hypoallergenic dogs to all other dog breeds.

The Results: there was no statistically significant difference between the allergen levels of hypoallergenic pure bred dog, designer hypoallergenic dogs and all other dog homes. 

In fact the hypoallergenic dogs consistently produced more allergens, although the increased level did not rise high enough to meet the statistically significant standard deviation. Perhaps these dogs should be rebranded as Hyperallergenic dogs.

3 Tips to Keeping Dog Dander and Pet Allergens Down in Your Home

What might be the cause of these low shedding dogs putting off more dander that those that shed regularly? It may be that those shedding coat are also dropping off their dander on lost hairs outdoors as well as indoors, while the non-shed coat retains much of the dander clinging to their dense coats.

Regular brushing and monthly baths using both shampoo and coat conditioner, can substantially reduce allergens.  As master stylist, Les Bouska of Atlanta Hair Studio explains, "Shampoo causes the hair follicle to open, allowing it to release the dirt and dander attached to the shaft. The conditioner then seals the shaft back closed, making it more difficult for dirt and dander to cling to each hair shaft. Skipping the conditioner leaves the shaft open to quickly collect more allergens." However, he warns, bathing too often with cheap shampoos can actually cause dry skin conditions that can actually increase the allergen levels in your home.

Adding antioxidants such as fish oil and dog probiotics to your dog's diet can also help alleviate any skin conditions that result in excess dander being generated.

Dogs like to have their own personal space, so provide your dog with his own special bedding that can easily be washed. We like the dog beds whose fill is made from spun threads from recycled plastic bottles. These dry quickly and do not retain dander or pet odors after a quick cycle in the washing machine.

Citations:


[1] Dog allergen levels in homes with hypoallergenic compared with nonhypoallergenic dogs
Charlotte E. Nicholas, Ganesa R. Wegienka, Suzanne L. Havstad, Edward M. Zoratti, Dennis R. Ownby, Christine Cole Johnson
Am J Rhinol Allergy. 2011 Jul-Aug; 25(4): 252–256. doi: 10.2500/ajra.2011.25.3606




Breakthrough In Pain Treatment For Dogs With Osteosarcoma

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Between 6000-8000 dogs in the United States receive treatment for Osteosarcoma each year.  Typically a disease of large breed dogs, Osteosarcoma can affect breeds of all sizes.  As the disease progresses, it reshapes normal healthy bone tissue and changes it to tumorous bone.  In dogs as in people, this remodeling process becomes increasingly more painful as the disease progresses, impacting activity levels and quality of life.
Dr. Vladimir Osipov Sarcomaimages.com

The Dorothy Cimino Brown, DVM and Kimberly Agnello DVM University of Pennsylvania Study

Seventy dogs suffering from Osteosarcoma participated in this study.  A variety of breeds were represented including Rottweilers, Golden Retrievers, Labrador Retrieves and various mixed breeds. The average size of the dogs in the study was 90 pounds, and the average age fell between 8 and 9 years.  The study was conducted by splitting the group in half and treating both groups with standard care, while the second group also received a single injection of a Neurotoxin, SP-sap (P-saporin), near the tumor site.

A similar neurotoxin many of us are familiar with is Botox, the anti-wrinkle injection. Botox acts to block signals from the nerves to the muscles, so that the muscles can no longer contract.  When specific muscles cannot contract, the wrinkle appears to soften.

Similarly, SP-sap works by attaching itself to the pain sensing nerves. Once attached, the sap portion kills off the nerve.  The theory is, no more pain sensing nerve then no more pain.

Study Results

Six weeks into the study, 74% of the dogs in the control group (those receiving only standard care) had significant increases in pain levels, and needed to be removed from the control group or "unblinded" in order to have their pain management adjusted.  

In contrast with the control group, only 24% of the dogs in the SP-sap group needed to be "unblinded" for adjustments to their pain management.

Additionally, the dogs in the control group, who were receiving only standard care, experienced a 6% increase in pain severity testing.  The dogs who received the single SP-sap injection experienced no increase in pain severity.

And more encouraging, the dogs in the control group experienced and 8% decreases in how pain interferes with their daily activities, while the SP-sap group had a 5% improvement in their daily activities.

The Implications

As Osteosarcoma afflicts both dogs and people in the same manner, this study is potentially good news for both humans and canines.  Relieving pain is critical to improving the patient's quality of life, response to treatment and the overall patient outcome.  The positive results from this study are likely to spark further investigation into SP-sap and other neurotoxins for pain management of Osteosarcoma as well as other diseases with chronic pain symptoms as well.

To learn more about this study visit: American Society of Anesthesiologists (ASA) (2013, October 23). Chronic pain in dogs with bone cancer relieved with new treatment.

4 Promising Studies: Early Detection and Treatment Options for Canine Hemangiosarcoma

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Courtesy of Public Domain Images
Hemangiosarcoma is a form of cancer found almost exclusively in dogs. A relatively common canine cancer (6-8% of all canine cancers) it is estimated that 2 million of 73 million dogs currently alive in the United States will develop the disease and die from it.

At this time, it is considered incurable, as it remains symptomless until the advanced stages of the disease.  The current standard of care, surgery and chemotherapy, have proven to extend the life to the affected dog a mere median of 180 days with surgery alone, and an additionally 180 days with chemotherapy added to surgical intervention.

In the wake of these poor treatment outcomes, research has focused on early detection of the disease as well as a new, very promising alternative medicine approach.

Hemangiosarcoma

Hemangiosarcoma is an indolent cancer, meaning it initially develops very slowly, asymptomatically and painlessly.  The most common primary sites of the disease are the spleen, right atrium of the heart and the tissue beneath the skin.  In the later stages of the disease, the cancer aggressively metastasizes to the lungs, liver and intestines.   While dogs of any age and breed may be susceptible to hemangiosarcoma, it occurs more commonly in dogs beyond middle age, and has a higher incidence in breeds such as German Shepherd Dogs, Golden Retrievers, Portuguese Water Dogs and Skye Terriers, suggesting a genetic component is involved.

The Canine Genome

The completion of the Canine Genome Project has spurred research into the genetic components of a wide variety of physical ailments believed to have heritable factors. Researchers at Modiano Lab at the University of Minnesota have taken an interest in the genetic components contributing to hemangiosarcoma.   Three of the more promising approaches involve mapping the risk alleles associated with the disease, determining the genetic, breed-specific abnormalities of the tumors themselves and developing a blood test for early detection of cancer cells via flow cytology.

The first project, developed in collaboration with Dr. Matthew Breen, focused on the possibility of breed specific abnormalities that may be detectable in tumors arising in dogs of different breeds. The initial results were promising; the data showed that tumors from dogs of one specific breed are functionally and genetically more similar to each other than they are to tumors from dogs of other breeds. This information demonstrates that heritable risk factors contribute to the development of canine cancer. More importantly, these results are the first step toward developing prevention and treatment strategies that address the specific causes underlying the biology of canine hemangiosarcoma.

The second project of great promise, developed in collaboration with the National Human Genome Research Institute of the National Institutes of Health and the Broad Institute of MIT and Harvard, has begun the process of mapping the risk alleles for the development of both Lymphoma and Hemangiosarcoma in the following target breeds:

Turkey Tail Fungus - Penn State's Magic Mushrooms see below
Courtesy of Wallwork Family Pages

  • Australian Shepherd
  • Bernese Mountain Dog
  • Border Collie
  • Boxer
  • Briard
  • Bullmastiff
  • Cocker Spaniel
  • Flat-coated Retriever
  • German Shepherd Dog
  • Golden Retriever
  • Greyhound
  • Irish Setter
  • Keeshond
  • Labrador Retriever
  • Mastiff
  • Poodle
  • Portuguese Water Dog
  • Rottweiler
  • Vizsla
  • Saluki
Researchers are currently seeking samples for this research in the form of blood samples and tumor samples with associated pedigree information.  Samples from mixed breeds and other breeds are welcome from both healthy (aged) dogs and affected dogs.  To learn more about how to contribute to the project visit the Modiano Labs website.

Early Cancer Detection: Flow Cytometry

Once we have a genetic test that can forewarn us of a genetic predisposition to developing specific cancers, we will want to be able to detect the disease at an early stage of its development, well before it becomes symptomatic.

As cancer tumors grow, they shed cells into the blood stream.  However, the tumor cells are shed so infrequently that they cannot be detected in routine blood tests. Enter the technology called flow cytometry. Here cells are “tagged” with fluorescent molecules that identify their lineage of origin, they are then run through an instrument (the flow cytometer) that combines optics and fluidics information through a software capable of analyzing hundreds of thousands of cells in a matter of minutes.

Researchers have employed this technology, and have successfully shown proof of principle for this test. Idexx Laboratories has licensed the technology from the University of Colorado, although the ultimate affordability of employing this technology in local veterinary practices tests remains to be seen.  Another issue with this technology, is that it does not tell us where the site of origin of the tumor is. Early treatment will therefore need to be able to treat the disease independent of the site of origin.

The Biggest Breakthrough In Hemangiosarcoma Cancer Treatment: Penn State’s Magic Mushrooms

In a Penn State study funded by Chinese Medicine Holding LTD. and released in September 2012, dogs with hemangiosarcoma were treated with a compound derived from the Coriolus Versicolor mushroom, resulting in the longest survival times ever reported for dogs with the disease.

The Coriolus Versicolor mushroom, known commonly as the Yunzhi mushroom, has been used in traditional Chinese medicine for over 2,000 years. A compound within the mushroom, polysaccharopeptide, or PSP, is believed to have immune-boosting properties. Over the past two decades, studies have indicated that PSP may also have a tumor-fighting effect.

Penn State researchers studied dogs with naturally occurring hemangiosarcoma to see what effects, the Yunzhi mushroom would have on their patients. Fifteen dogs that had been diagnosed with hemangiosarcoma participated in the trial. Divided into three groups of five, each group received a different dose — 25, 50 or 100 mg/kg/day — of I’m-Yunity, a formulation of PSP which is also readily available over the Internet. The dog owners were instructed to give their dog a capsule of I’m-Yunity, daily. The owners brought their dogs to Penn’s Ryan Veterinary Hospital for follow-up visits on a monthly basis for blood sample testings and ultrasounds to determine the extent that tumors had developed or spread in the dogs’ bodies.

“We were shocked,” Cimino Brown said of Penn State. “Prior to this, the longest reported median survival time of dogs with hemangiosarcoma of the spleen that underwent no further treatment was 86 days. We had dogs that lived beyond a year with nothing other than this mushroom as treatment.”

Not only had the dog’s survival times increased with the use of PSP, but unlike chemotherapy, there were no reported side effects.  Dogs receiving the highest dosage, 100 mg/day, had the longest median survival time, however the difference in survival times between dosages was not statistically significant.

While not inexpensive, this treatment is certainly more affordable than chemotherapy.  Those on tight budgets, may consider using this supplement at the lower dosage without fear of significantly impacting survival rates.  However, it should be noted that while the PSP, I’m Yunity, extends life and improves quality of life, it has not been shown to be a cure for hemangiosarcoma.

The Penn State researchers are preparing to pursue further trials of I’m-Yunity in dogs with hemangiosarcoma to confirm and refine their results. One upcoming trial will compare I’m-Yunity to a placebo for those owners who choose not to pursue chemotherapy for their pet; the other will compare the compound with the current standard-of-care, chemotherapy.

Here are some options for Organic Turkey Tail Mushroom Extract 

 

The liquid form may be easier to administer.  The capsules are 500mg, so you would need to open the capsule and shake out 1/4 of the mushroom extract. For larger dogs (80 lbs and up) you may want to give them one third of a capsule or approximately 165mg.

We will keep you posted as more information comes in from the ongoing Penn State Research.

For information on Canine Osteosarcoma please click here.

5 Reasons Why Dogs Eat Dirt - And You Should Too!

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Why dogs eat dirt
By federico stevanin, published on 08 November 2008
Stock photo - image ID: 1001821
As scientists of various disciplines investigate the topic of dirt eating, or more accurately clay eating, they are discovering that it is more prevalent across geographic regions and species than previously imagined.  Humans, primates, dogs, cats, parrots, buffalo, deer and even fruit bats engage in clay eating or geophagia, a subset of pica.

Until now it has been assumed that the animals engaging in geophagia were either malnourished or suffering from a form of obsessive compulsive disorder originating from boredom.  New studies indicate that there may be other factors at work in the age old practice of clay eating. In our list of five reasons your dog eats clay, we offer up three traditional explanations as well as two new explanations that are gaining credence in the international dirt-eating research community.

Eating Soil From Boredom, Habit or OCD

It has been noted that bored dogs can get into the destructive habit of digging holes and then consuming the unearthed soil or clay as a by-product of the digging behavior.  In some dogs, this behavior takes on an obsessive quality, with dogs digging 2-3 new holes per day, leaving yards pock-marked with ankle-bending divots.  This behavior is different from that of the dog that returns to the same beloved spot in the yard for his daily dose of dirt, frequently an area of moist clay.  Habitual digging is a behavioral issue that should be addressed with training, increased interaction and exercise.

Clay Eating to Relieve Hunger

Some trainers have suggested that dogs fed a single meal a day are relieving hunger pains by adding a clay snack to their diet.  If your dog is on a single meal regimen and eating soil, you may try stepping him up to two meals a day to see if that curbs his clay appetite.  If that does not work, read on.
reasons why dogs eat dirt and clay
By Tina Phillips, published on 10 August 2012
Stock photo - image ID: 10095988

Dogs Eating Dirt For Missing Nutrients

Soil contains many trace elements and nutrients that are not readily available in packaged foods; clay eaters may be seeking minerals that their normal diet is lacking.  In fact, geophagia in expectant human mothers in Nigeria (an area low in available calcium) is a centuries-old indicator of pregnancy.  In other regions of Africa, where calcium is readily available, clay eating is not particularly prevalent among expecting mothers. Perhaps the pregnant, clay-eating women in Nigeria and other regions of the world are adding calcium, sodium and iron to supplement their diets for their developing fetus.

Clay Eating For Relief of Digestive Upset

For centuries man has used clay minerals to relieve vomiting, diarrhea and stomach upset.  In fact, Kaopectate, a remedy for relief of gas, bloat and diarrhea, was originally formulated with Kaolin, a clay mineral.  Ironically, clay can also contain parasites, which may create a vicious circle.  The dog eats clay to alleviate the discomfort created by the parasites, while ultimately re-infecting himself with greater numbers of parasites.  It’s a good idea to get a stool sample to the vet if your dogs is eating a lot of clay to rule out parasitic infestations.

People and Dogs Eat Dirt to Detoxify?

Clay has long been considered a detoxifier. The Mesopotamians and ancient Egyptians used mud as a treatment for wounds and to treat various digestive ailments.  Today spas worldwide offer mud baths as a path to detoxification.  As kaolin and other clay minerals have the ability to bind toxins and remove them from the system, this motive for clay eating has now moved to the forefront of scientific research. 

Returning to the subject of pregnant clay eaters, women across Sub-Saharan regions and the Southern United States have consumed clay to alleviate morning sickness.  It has been proposed that morning sickness is actually the body's attempt to remove toxins from the system.  Even pregnant fruit bats increase their daily diet of clay.  It is surmised that as they increase their diet of fruit as well as fruit seeds, which contain toxic properties, they are using the clay to remove the additional toxins from their bodies. The binding properties of clay may not only be removing toxins from the system; clay possesses the additional ability to bind food born bacteria and viruses that would be harmful to the mother and developing fetus. 

Ranchers too have long used clay when preparing livestock feed to inhibit toxin transmission. And now a few researchers are now proposing exploiting clay’s pathogen-binding talents to purify water.

Dogs eating packaged foods with traces of antibiotics or chemicals remaining in them or grass, weeds and run-off from treated lawns, may be attempting to remove toxins from their systems.  It is likely that geophagia is a specific defense that has evolved across a spectrum of species to combat toxicity and, also ease mineral deficiencies.

But, if you’re feeling that old kaolin craving, we suggest you stick with safe commercial products that have been heated or otherwise sterilized.  If you have a favorite dig in your neighborhood, heat the dirt or clay in the over at 200 degrees for at least 2 hours before consuming it.  That should eliminate most parasites.  Bon Apetite!

If your dog has been experiencing stomach upset for a prolonged period of time, including loose stools and gas, you may want to look at adding a probiotic to his diet. To learn more about how probiotics work, and which probiotics are the most effective visit Pet Helpful's article, The 5 Best Probiotics for Dogs.



Canine Hip Dysplasia Can Now Be Predicted At Birth By DNA

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http://www.flickr.com/photos/dimas_sc/3100685891/
A few breeders and I occasionally have a chuckle over the fact that pet buyers seem to be more concerned with knowing hip scores than are most other breeders.  Perhaps the other breeders have already done their homework on the OFA database or our websites; it certainly appears that the puppy buyers have done their homework regarding finding a reputable breeder. Good for them; that’s the kind of home I like my puppies to go to.

Canine Hip Dysplasia is a physically debilitating disorder that is both emotionally and financial draining for dog owners.  With no cure other than pain management or hip replacement surgery, diagnosis of hip dysplasia is the breeder’s as well as the pet owner’s heartbreak.  Stocky breeds such as the Bulldog and those weighing over 60 pounds such as the St. Bernard experience hip dysplasia rates of up to 72% and 46% respectively.  It is estimated by Cornell University that 22% of canine hospitalizations in the USA are hip dysplasia related. Interestingly, the disease’s occurrence is minimal in sight hounds such as the whippet, saluki, borzoi and greyhound with an average occurrence of just 1-2%.  Border collies fall in the middle range of dysplasia occurrence at around 11%.

For over 40 years, breeders have attempted to minimize the occurrence of canine hip dysplasia (CHD) through the use of phenotypical screening methods.   As a predictive method for removing poor breeding candidates from their breeding programs, responsible breeders have submitted x-rays of mature dogs for hip scoring to institutions such as the OFA, BVA, FCI and University of Pennsylvannia seeking to determine the laxity of the hip joint, and therefore the likelihood of the animal developing CHD as a trait that might be passed on to its progeny.

Various studies of the efficacy of these screening programs have met with mixed results.  Some studies show little to no improvement in the occurrence of CHD. Even in countries, such as Finland, where an enforced threshold of hip scores was applied to registrations, results were varied across breeds, with some breeds demonstrating a lower incidence of CHD and others showing an actual increase in CHD.

Canine hip dysplasia is understood to be influenced by both genetic and environmental factors.  As a polygenetic mode of inheritance has long been suspected, attempts to isolate the genetics of the disease have long been frustrated.  Breeders seeking to improve their lines and their breed have been marginally successful as a whole, despite their best efforts.  Forty years of breeders’ best efforts may call into question the scoring methodologies of the various institutions. 


OFA vs. PennHIP
OFA uses a single radiographic view, the hip-extended view, to determine laxity of the hip joint (a predictive measure of the likelihood of developing CHD).  By contrast, the PennHIP method uses 3 radiographic views (the distraction view, the compression view and the hip-extended view) to determine the laxity of the joint.  A study released in 2010 by the University of Pennsylvania (http://webcanine.com/2010/canine-hip-dysplasia-may-be-underreported/), compared results from dogs scored by both OFA and PennHIP to determine the likelihood of CHD onset. Their findings were disturbing. According to Penn researchers, “Even if breeders were to selectively breed only those dogs having OFA-rated “excellent” hips — the highest ranking but in some breeds, a very small gene pool, the study suggests that 52-100 percent of the progeny, depending on breed, would be susceptible to hip dysplasia based on the Penn Vet scoring method.”  In fact 52% of the dogs with OFA “excellent” scores, 82% of the OFA “good” scores and 95% of the OFA “fair” scores fell below the PennHIP threshold of.3, making them by PennHIP standards susceptible to CHD. (It should be noted that the University of Pennsylvania holds the patent for the PennHIP test, and a financial incentive could exist in their findings).  Could the PennHIP method provide the key to a significant reduction in incidence of CHD?

PennHIP allows for early testing of puppies; they may be tested as early as sixteen weeks, which is still well beyond the typical puppy placement age of around 8 weeks. By contrast, OFA scores may not be obtained until the dog has reached 2 years of age.  As 3 x-ray views are required for the PennHIP testing method, depending on your area of the country, the cost can be substantially greater than OFA testing.  Additionally, the PennHIP method does not currently have the same recognition international as the OFA methodology.  What if a genetic test existed that could predict the likelihood of developing CHD?

Genetic Testing
The canine genome project, begun in June 2003, determined that the canine genome contains approximately 2.5 billion DNA pairs, much like that of humans and other mammals.  In 2004, a preliminary set of about 600,000 single nucleotide polymorphisms (SNPs), which amounts to a SNP roughly every 5,000 DNA base pairs, was released to researchers to aid in the study of genetically transmitted diseases and disorders. Armed with this massive amount of data, researchers at the Department of Animal Science, China Agricultural University,Beijing, China  developed an algorithm that accurately predicts CHD from genomic data.  This means that puppies can be tested prior to weaning, in fact as soon as DNA is available, allowing for poor breeding prospects to be petted-out well before maturity. 

The Beijing researchers’ model was based on 359 dogs in the first sample and 38 dogs in the second sample.  The dogs whose results were used in the study came from the Baker Institute, The Guiding Eyes for the Blind and Cornell University Hospital for Animals (as the 38 dog control group).
They began by developing an Estimated Breeding Value (EBV) of each of the dogs based on 4 criteria: the dog’s Norberg Angle (NA), OFA score, the distraction index (DI) and the dorsolateral subluxation score (DLS). The former two are evaluated from the extended hip projection and are phenotypically as well as genetically correlated while the latter two are evaluated on different x-ray views and are also phenotypically and genetically correlated. It is interesting to note that the researchers believed that no measure alone completely represents hip morphology. In fact, their methodology was the similar to that of the PennHIP with the OFA score thrown in for good measure.  In the final analysis, the Norberg angle (NA) correlated to the OFA score and as most dogs had NAs measured, NA was chosen for this study to determine the EBV. The researchers then used 22,000 SNP’s across the genome and the EBV of the sample dogs to produce the predictive formula, an algorithm, termed the Genomic Breeding Value (GBV). 

Validation of the Formula Methodology:
The researchers performed two types of validations consisting of a cross validation and an independent validation. For the cross validation they used a Jackknife Cross Validation.  This consisted of hiding the dog’s EBV and removing its GBV from the dataset used to create the original predictive formula. The formula was then recalculated by using the EBV and genotype from the other 358 dogs in the study. This process was repeated for each of the 359 dogs. The cross validation performed showed a strong correlation (R>0.7) above 70% between the EBV (phenotype) and the GBV (genetic).
To develop the independent validation, the GBV formula was applied to 38 Labrador retriever dogs with no pedigree relationship to the original 359 dogs from which the GBV formula was derived. Correlations between the predicted GBV and the actual EBV (the physical conformation of the dog) were compared.

The Results:
When 5,000 SNPs out of the original 22,000 SNPs remained in the formula, the correlation was remarkable, above 0.98 or 98%. The researchers then identified the 100-500 most influential SNPs that had provided the most information to the GBV formula. The reduced number of SNPs showed that genomic prediction could remain effective with the most influential 100-500 SNPs chosen from the original 22,000SNPs.  However, as the number of SNPs in the reference panel dropped below 50, the formula became significantly less reliable.

The Beijing researchers expect that a reliable GBV predictive formula for hip conformation will be available for most breeds of interest, “Prediction of CHD from genomic data is feasible, and can be applied for risk management of CHD and early selection for genetic improvement to reduce the prevalence of CHD in breeding programs. The prediction can be implemented before maturity, at which age current radiographic screening programs are traditionally applied, and as soon as DNA is available.” However, phenotypical testing (hip x-ray grading) will continue to be necessary in order to retrain the GBV predictive formula, and thereby refine the accuracy of the genomic predictive model.

While the majority of the 359 dogs used in the study were Labrador retrievers and Lab crosses with Greyhounds, other minor breeds’ hip morphologies were also well predicted by the GBV formula. Therefore, we can expect that multiple breeds will be able to be integrated together into a single genetic test, even though they are from diversified phenotypic and genotypic populations.

Implications:
The possibility of a genetic test for predicting CHD in young puppies raises some interesting ethical questions.  Puppies genetically predisposed to CHD should be removed from breeding programs, but where do they go?  What are the ethics of breeders presenting puppies to pet puppy buyers knowing that they have a strong likelihood (70% or greater) of developing CHD?  Additionally, if the genetic statistics correspond with those of the University of Pennsylvania survey, we are left with a very small gene pool in many breeds.  Add to that other genetic disorders being researched, such as cancer and breed specific issues, and the gene pool of good breeding candidates is likely to grow even smaller.  Relying on a substantially reduced gene pool could have unintended consequences.  Recessive, genetic “trash” could manifest into new, more terrifying health issues. 

These are all questions that are sure to be discussed heatedly as understanding of the canine genome progresses. Once these tests are available to the public, they will have to be financially feasible in order to effectively make an impact on breeding programs.  As we approach this new era in breeding prospect selectivity, perhaps a stepped approach to improving breeding prospects is in order.  Under this approach, initially breeders would breed one dog with a relatively high EBV and GBV to one with a moderate EBV and GBV, and seek to improve the GBV threshold for the sire or dam on each successive generation.  This would be a measured approach, however canine generations evolve very quickly – every 2 years compared with 20 years in humans.  Your thoughts and comments are welcomed!

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