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Mark Billadeau

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About Mark Billadeau

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    Middletown, MD
  • Interests
    science, working dogs, sheep

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  1. Thanks Eileen for keeping up with this and getting it fixed
  2. Typically the dogs are on different whistle commands so they can be directed independently.
  3. As someone with allergies and having been tested several times throughout my life I can say for certain; allergies can come and go. Things I tested positive for as a child I am no longer positive for now and the reverse is also true. The only constants for me have been allergies to dust mites and dog dander. My mother developed gluten and dairy intolerances later in life.
  4. Thanks everyone. I recall the first time I met Peg. It was at a “puppy show” after a day of trialing in the fall at Edgeworth. Tom brought her out and she ran along in front of everybody watching until she got to me. I was sitting on the ground and she ran right up to me and flopped over on her side to be petted. She was 6-7months old.
  5. 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].”
  6. 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.
  7. “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.
  8. 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.
  9. The methods slide lists 200mg/kg but he corrected it to 200mcg/kg. The effective minimum dose is 6mcg/kg.
  10. 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.
  11. 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
  12. “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.
  13. 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.
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