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Mark Billadeau

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About Mark Billadeau

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    Bill Nye Wannabe

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    Middletown, MD
  • Interests
    science, working dogs, sheep

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  1. Mark Billadeau

    MDR1 - can we eradicate?

    This study measured the plasma concentration of ivermectin and fluralaner after dosing with just one drug and after dosing with both. There was no interaction between these drugs altering the plasma levels as is the case with spinosad increasing ivermectin plasma concentrations as noted by Denise (quoted below from larger background section in this study). https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-015-1123-8 ”Ivermectin is registered for the use in dogs at monthly oral doses of 6 mcg/kg BW for heartworm protection [8]; some veterinarians may choose to administer ivermectin at higher off label doses to treat dogs for different worm or mite infestations (for example 0.05 mg/kg for hookworm, 0.1 mg/kg BW for whipworms, 0.2 mg/kg for Toxocara canis, 0.2-0.4 mg/kg for sarcoptic mange, 0.2 mg/kg for nasal mites Pneumonyssus caninum, 0.3 mg/kg for cheyletiellosis, 0.3–0.6 mg/kg for demodicosis; orally or subcutaneous as single or repeated treatments) [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]; however, such high doses of ivermectin cannot safely be administered to “ivermectin-sensitive” dogs carrying a MDR1 mutation [21, 22]. Ivermectin is a substrate for the p-glycoprotein (p-gp) transporter encoded by the MDR1 gene [22, 23]. This transporter limits the entry of its substrates into the body by an efflux-based mechanism, particularly at the blood–brain barrier [24]. Dogs with a homozygous defect of the MDR1 gene do not carry a functional p-glycoprotein transporter and are therefore more susceptible to neurotoxicity caused by ivermectin [21]. Furthermore, drug-drug interactions at the p-glycoprotein transporter may occur following the concurrent use of ivermectin and drugs, leading to an increased risk of neurotoxicity of ivermectin in MDR1 intact dogs. One example is spinosad that inhibits the p-glycoprotein transporter-mediated elimination of ivermectin in MDR1 intact dogs, thereby increasing ivermectin blood concentrations, which leads to a higher risk of neurotoxicity when administering high off-label doses of ivermectin concurrently with spinosad [25, 26, 27, 28, 29, 30].”
  2. Mark Billadeau

    MDR1 - can we eradicate?

    Denise, my biology is not good enough to understand “direct GABAergic effect”. What does this mean and will it alter the effective dose of ivermectin (and other heart worm preventatives)? l’m trying to determine if the combination of ivermectin and the flea and tick meds in the Group 2 dogs make the side effects observed in this group similar to the Group 1 dogs getting 200mcg/kg.
  3. Mark Billadeau

    MDR1 - can we eradicate?

    “High dose” will differ based upon the mdr1 genetic status of the dog. = The mdr1 genetic status of a dog will lower the dose of certain drugs where side effects can occur.
  4. Mark Billadeau

    MDR1 - can we eradicate?

    The authors main conclusion was to avoid a 200mcg/kg dose and they reported on the side effects of such a high dose. “High dose” will differ based upon the mdr1 genetic status of the dog.
  5. Mark Billadeau

    MDR1 - can we eradicate?

    The methods slide lists 200mg/kg but he corrected it to 200mcg/kg. The effective minimum dose is 6mcg/kg.
  6. Mark Billadeau

    Goodbye Peg

    My Peg’s health declined suddenly after New Years and Friday we said goodbye to Peg. She was 2 months shy of 16.y She was such a great partner for me. I will miss her.
  7. Mark Billadeau

    MDR1 - can we eradicate?

    You do realize the dogs in “group 1” were given 33x (200mcg/kg) the effective minimum heartworm preventative dose (possibly in the range of ivermectin toxicosis)? “Dogs that are homozygous for the mutation produce a severely truncated P-glycoprotein (<10% of the normal amino acid sequence) and will develop ivermectintoxicity at any of the dosages used to treat demodicosis. The critical point seems to be 120–150 mcg/kg, at which transient, nonfatal clinical signs (mydriasis, ataxia, tremors) are seen. At higher dosages, collapse, coma, and respiratory collapse may develop. Similar idiosyncratic reactions may develop in any breed, so a gradually increasing dose (daily progression of 50, 100, 150, 200, then 300 mcg/kg) should be given to identify susceptible individuals. Administration should be stopped if any adverse effects are seen.” source: Merck Veterinary Manual
  8. Mark Billadeau

    Report on the EAOD Research Project

    “Will it be definitive?” The answer to this question will depend upon your perspective (breeding prospects or health of that dog). To address this let me use CEA as an analogy. The CEA test will definitely determine how many copies of the mutation the dog has (genotype). This is what we need to know for breeding. The CEA test will not predict if the dog will have vision issues due to this mutation (phenotype). Two copies of the mutation are needed to develop CEA vision issues but not all dogs with 2 copies develop vision issues (“go normal”). This is what the owner wants to know for the future health of the dog. The EAOD genetic test being developed will definitely determine the genotype of the dog (key for breeding). It is not known how well the EAOD genetic test will predict if the dog will develop EAOD (phenotype) for dogs with 2 copies of the mutation. The EAOD test will be predictive for dogs with 0 or 1 copy of the mutation; the phenotype will not be EAOD.
  9. Mark Billadeau

    Report on the EAOD Research Project

    No updates are available
  10. Mark Billadeau

    What is considered inbreeding

    The point needs to be repeated often as long as people think inbreeding/line breeding with the “right dogs” has no ill effects. Let me try an analogy. Think of inbreeding like trace minerals. We need a little in order for the body (or a working breed) to function properly. However, like trace minerals inbreeding continues to accumulate in the breed (or body) until it reaches toxic levels. We have enough inbreeding for good functioning working dogs (needed inbreeding to form the breed/type); we don’t need more and more will turn toxic.
  11. Mark Billadeau

    What is considered inbreeding

    Nothing wrong? This is how breeders have identified recessive genetic mutations (mating two carriers); this is likely how we recognized EAOD. When breeds were first developed inbreeding was used to fix traits; traits included those breeders wanted and genetic diseases not wanted. Now that breeds (inbreed gene pool) have been established, additional inbreeding just increases the likelihood of crossing two dogs that both carry the same low frequency genetic mutation. Please explain how the “right dogs” will be bred when we don’t have tests for all recessive mutations in our gene pool? Keep in mind we didn’t know about EAOD until enough carriers were mated producing enough related dogs that went deaf.
  12. Mark Billadeau

    Fern's Thread

    Fern meet Fern
  13. Who else would fund university research studies (@100s of $1000) on canine nutrition than pet food companies (the government, breed associations, AVMA, pet owners)? If we do not accept the validity of peer reviewed studies based upon them being funded by pet food companies we would have no university research on this subject. The key is the journal in which the studies are published and that journal’s peer review process. If anyone is interested I can summarize what I learned in a graduate level class I took on writing research grant proposals and preparing the budget for a proposal. Here is a teaser: the university takes >50% of the grant funding off the top (tufts “overhead rate” is currently 65%) and you can’t increase your salary with a grant. It’s hard to be a paid shill when grant money goes to the university and they distribute it to the researcher.
  14. The fda has posted on this issue https://www.fda.gov/animalveterinary/newsevents/cvmupdates/ucm613305.htm https://www.americanveterinarian.com/news/fda-answers-questions-about-possible-link-between-diet-and-heart-disease-in-dogs
  15. Mark Billadeau

    Winter Swim

    Our first border collie enjoyed fetch in Lake MI (IN Dunes SP) in May till he was shivering badly; we had to take him away from the lake because his drive was stronger than his self preservation. I would not be surprised if you have to take it upon yourself to monitor your dog’s wellbeing and stop with enough time to get back inside before your dog gets too cold.