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Author Topic: New AVMA article Sept '08  (Read 10439 times)
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Carol
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« on: September 22, 2008, 08:55:18 AM »

http://avmajournals.avma.org/doi/abs/10.2460/ajvr.69.9.1217

Abstract
American Journal of Veterinary Research
September 2008, Vol. 69, No. 9, Pages 1217-1228
doi: 10.2460/ajvr.69.9.1217



Evaluation of the renal effects of experimental feeding of melamine and cyanuric acid to fish and pigs

Renate Reimschuessel, VMD, PhD; Charles M. Gieseker, MS; Ron A. Miller, PhD; Jeffrey Ward, DVM, PhD; Jamie Boehmer, MS; Nathan Rummel, BS; David N. Heller, BS; Cristina Nochetto, BS; G. K. Hemakanthi de Alwis, PhD; Neal Bataller, ME, DVM; Wendy C. Andersen, PhD; Sherri B. Turnipseed, PhD; Christine M. Karbiwnyk, PhD; R. Duane Satzger, PhD; John B. Crowe, BS; Nancy R. Wilber, DVM; Mary K. Reinhard, DVM; John F. Roberts, DVM; Mark R. Witkowski, PhD
Center for Veterinary Medicine, US FDA, 8401 Muirkirk Rd, Laurel, MD 20708. (Reimschuessel, Gieseker, Ward, Boehmer, Rummel, Heller, Nochetto, de Alwis); 7500 Standish Pl, Rockville, MD 20855. (Miller); 7519 Standish Pl, Rockville, MD 20855. (Bataller); Animal Drugs Research Center, US FDA, Denver Federal Center, Bldg 20, W 6th Ave and Kipling Blvd, Denver, CO 80225-0087. (Andersen, Turnipseed, Karbiwnyk); Forensic Chemistry Center, US FDA, 6751 Steger Dr, Cincinnati, OH 45237. (Satzger, Crowe, Witkowski); Academy Animal Hospital, 4025 N Federal Hwy, Ft Lauderdale, FL 33308. (Wilber); Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611. (Reinhard, Roberts)
The authors thank Marleen Wekell, Randall Lovell, Deborah H. Brooks, Aleta Sindelar, Mark R. Madson, and Joseph M. Storey for assistance in data and sample collection; Badar Shaikh for the illustrations; and Eric Anderson and Mark McDonald for technical assistance.

Address correspondence to Dr. Reimschuessel.
Objective—To determine whether renal crystals can be experimentally induced in animals fed melamine or the related triazine compound cyanuric acid, separately or in combination, and to compare experimentally induced crystals with those from a cat with triazine-related renal failure.

Animals—75 fish (21 tilapia, 24 rainbow trout, 15 channel catfish, and 15 Atlantic salmon), 4 pigs, and 1 cat that was euthanatized because of renal failure.

Procedures—Fish and pigs were fed a target dosage of melamine (400 mg/kg), cyanuric acid (400 mg/kg), or melamine and cyanuric acid (400 mg of each compound/kg) daily for 3 days and were euthanatized 1, 3, 6, 10, or 14 days after administration ceased. Fresh, frozen, and formalin-fixed kidneys were examined for crystals. Edible tissues were collected for residue analysis. Crystals were examined for composition via Raman spectroscopy and hydrophilic-interaction liquid chromatography–tandem mass spectrometry.

Results—All animals fed the combination of melamine and cyanuric acid developed goldbrown renal crystals arranged in radial spheres (spherulites), similar to those detected in the cat. Spectral analyses of crystals from the cat, pigs, and fish were consistent with melamine-cyanurate complex crystals. Melamine and cyanuric acid residues were identified in edible tissues of fish.

Conclusions and Clinical Relevance—Although melamine and cyanuric acid appeared to have low toxicity when administered separately, they induced extensive renal crystal formation when administered together. The subsequent renal failure may be similar to acute uric acid nephropathy in humans, in which crystal spherulites obstruct renal tubules
 
« Last Edit: September 22, 2008, 09:51:11 AM by Carol » Logged

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JJ
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« Reply #1 on: September 22, 2008, 09:39:53 PM »

Carol good article. What I'm wondering then if this is similar to acute renal failure in humans would that mean the more livestock we eat the more we consume melamine that is in their feed and with the cumulative effect end up with kidney stones or renal problems too?
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Pita_Purr_Parler
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« Reply #2 on: September 23, 2008, 01:55:20 AM »

http://avmajournals.avma.org/doi/abs/10.2460/javma.233.5.729

Journal of the American Veterinary Medical Association
September 1, 2008, Vol. 233, No. 5, Pages 729-737
doi: 10.2460/javma.233.5.729


Clinicopathologic, histologic, and toxicologic findings in 70 cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid

Rachel E. Cianciolo, VMD; Karyn Bischoff, DVM, DABVT, MS; Joseph G. Ebel, BS; Thomas J. Van Winkle, VMD, DACVP; Richard E. Goldstein, DVM, DACVIM; Laurie M. Serfilippi, VMD, DACLAM
Department of Pathology and Toxicology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. (Cianciolo, Van Winkle); Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. (Bischoff); Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. (Ebel); Hospital for Animals, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. (Goldstein); Aspen Hollow Veterinary Services, RR1 Box 105, Thompson, PA 18465. (Serfilippi)
Dr. Cianciolo's present address is the Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

The authors thank Joseph Hillebrandt and Kerry Manzell for technical assistance, Randall Lovell and Scott Moroff for expertise and guidance, and Hollis Erb for assistance with statistical analysis.

Address correspondence to Dr. Bischoff.
Objective—To document clinicopathologic, histologic, and toxicologic findings in cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid.

Design—Case series.

Animals—70 cats from a single cattery inadvertently fed contaminated food that was the subject of a March 2007 recall.

Procedures—Clinical signs, clinicopathologic and histopathologic findings, and results of toxicologic analyses were recorded

Results—Clinical signs were identified in 43 cats and included inappetence, vomiting, polyuria, polydipsia, and lethargy. Azotemia was documented in 38 of the 68 cats for which serum biochemical analyses were performed 7 to 11 days after consumption of the contaminated food. One cat died, and 13 were euthanized. Histologic examination of kidney specimens from 13 cats revealed intratubular crystalluria, tubular necrosis with regeneration, and subcapsular perivascular inflammation characterized by perivascular fibroplasia or fibrosis and inflammation with intravascular fibrin thrombi. Toxicologic analyses revealed melamine and cyanuric acid in samples of cat food, vomitus, urine, and kidneys.

Conclusions and Clinical Relevance—In cats unintentionally fed pet food contaminated with melamine and cyanuric acid, the most consistent clinical and pathologic abnormalities were associated with the urinary tract, specifically tubular necrosis and crystalluria.
« Last Edit: September 23, 2008, 02:00:55 AM by Offy » Logged
Pita_Purr_Parler
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« Reply #3 on: September 23, 2008, 01:59:25 AM »

http://www.vetpathology.org/cgi/content/abstract/45/3/417

ENVIRONMENTAL PATHOLOGY

Characterization of Melamine-containing and Calcium Oxalate Crystals in Three Dogs with Suspected Pet Food–induced Nephrotoxicosis

M. E. Thompson, M. R. Lewin-Smith, V. F. Kalasinsky, K. M. Pizzolato, M. L. Fleetwood, M. R. McElhaney and T. O. Johnson
Armed Forces Institute of Pathology, Washington, DC (MET,1 MRL-S, VFK, KMP, MLF, TOJ,1), Idexx Veterinary Services, West Sacramento, CA (MRM)

Abstract

The histomorphologic characteristics and chemical composition of the crystals associated with suspected pet food–induced nephrotoxicosis in 3 dogs are described. Kidney specimens from 2 dogs, a 3-year-old Parson Russell Terrier and a 3-year-old Bernese Mountain Dog, were examined. Both developed acute renal failure after eating canned pet food on the 2007 Menu Foods recall list. The third case was a kidney specimen from a 1-year-old mixed-breed dog from a similar 2004 outbreak of canine renal failure in Taiwan, which occurred after eating a commercial dog food. Hematoxylin and eosin (HE), 72-hour Oil Red O (ORO72h), Alizarin Red S (pH 4.1–4.3), and Von Kossa stains; infrared (IR) spectroscopy; and scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDXA) were performed to determine the histomorphologic characteristics and chemical composition of the crystals observed in each case. Histomorphologic findings in each case included acute, marked tubular degeneration and necrosis with many intratubular birefringent crystals, and lymphoplasmacytic interstitial nephritis. In each case, most of the crystals were rough, pale brown, and stained with ORO72h but did not stain with Alizarin Red S (pH 4.1–4.3) or Von Kossa stains; these features were consistent with a plastic or lipid. IR spectroscopy and SEM/EDXA results were consistent with melamine-containing crystals. A second crystal type identified in each case was smooth and platelike with staining characteristics and IR spectroscopy and SEM/EDXA results consistent with calcium oxalate crystals. Melamine-containing crystals have distinct light microscopic, histochemical, and SEM/EDXA characteristics that facilitate their identification in tissue.
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Pita_Purr_Parler
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« Reply #4 on: September 23, 2008, 02:10:53 AM »

Carol good article. What I'm wondering then if this is similar to acute renal failure in humans would that mean the more livestock we eat the more we consume melamine that is in their feed and with the cumulative effect end up with kidney stones or renal problems too?

JJ, Here's an article from 2007 on the topic.. livestock .. I don't know if the US industries or our government will ever study the impact on health consequences to humans, cos they sure haven't done much to protect our pets.

http://www.vet.chula.ac.th/~tjvm/full_text/V37/v374/4_37_04.pdf


"On September 15, 2007, at the seminar of the Co-operative Promotion Department for the land animal and aquaculture producers, held in Nakhonpathom province, the faculty members of the Khon-kaen University together with the faculty member of the Kasetsart University revealed cases of melamine intoxication in nursery pigs which caused thousands of dead after some weeks of ingestion a ration composed of parts of imported protein rich feedstuff, mostly from the Chinese origin."

"Thousands of nursery pigs died in the months long incidence; whereas the affected survivors were poor doers. Culling was the best action at this point.

Results from the determination of the remaining imported portion of the only one suspected protein rich feed stuff sample from farm revealed the levels of melamine as high as 3,026 ppm, ammeline 958 ppm, and obviously, the amount of cyanuric acid was as high as 69,031 ppm.

Thus, the term chronic cyanuric acid together with melamine intoxication could be applied in this case incidence. Possibly, as suspected, the scrap from the melamine production  industry, collection of compositions, both the impurities and the rest of various raw materials,
has been intentionally mixed before export. "


snip


The Director General of the Department of Livestock Development declared as a strict action, effective from the third of August 2007, a zero tolerance level on any commercial feed, both finish feed and feed stuff, since there is no study on the safety level orally intake by any animal species. The official melaminefree certificate issued by the exporter government must be submitted to the veterinary inspector upon arrival of each shipment.

The lessons learned from both the domestic and oversea incidences in the past will bring all concerns to a more careful level. We definitely must give our consideration or judgment to the quality of animal feed and feedstuffs, which always play a major role in animal health."


Thanks to the animal feed industry and lobbyists in the USA and their AAFCO puppets, the FDA or USDA would never take this position IMO.  Case in point,  AFSS & FDAAA. Has anybody seen any change and the FDAAA implemented according to the law passed?

« Last Edit: September 23, 2008, 03:00:59 AM by Offy » Logged
Arlo
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« Reply #5 on: September 23, 2008, 03:07:48 AM »

So in Thailand they had thousands of baby pigs die because of contaminated feed.  Why do the US regulatory agencies ignore these studies? If someone makes a stink about it, they bash the science and the foreign university, when IMHO they are trying to protect the industries they were designed to regulate.

The US should have MD's, DVM's, and other scientists collecting info from everywhere about adulterated feed/food products. The evidence is there; we don't need to reproduce studies that cause fatalities. Except I think we are unwilling particpants in a very ugly experiment about profits vs. safety.
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Pita_Purr_Parler
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« Reply #6 on: September 23, 2008, 03:14:42 AM »

Arlo, I watch too much CSI  Grin Grin  What animal is used most in tests to determine the reaction in a human?  Pigs.

What I wish about that Thailand article.. that instead of "mostly" Chinese .. that they had named the other contributing sources.


ps.. this off the charts pet owner sent that article to AAFCO & FDA
« Last Edit: September 23, 2008, 03:19:27 AM by Offy » Logged
YesBiscuit!
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« Reply #7 on: September 23, 2008, 03:16:48 AM »

I agree Arlo.  Instead of being proactive, it seems like the FDA just hops from crisis to crisis, acting in a mostly reactive capacity.  I appreciate they are terribly understaffed, underfunded, etc, but if I was head of an agency that desperately needed manpower and funding from the govt., I'd be a fixture in the halls of Congress, nagging and lobbying for my requests in a very public way.  I don't see that from the FDA - the opposite actually.
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Carol
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« Reply #8 on: September 23, 2008, 03:36:06 AM »

found this ...does say we need further studies..."no kidding" Angry

http://ntp.niehs.nih.gov/files/9MelamineGGCosta.pdf

NTP Research Concept: Melamine/Cyanuric Acid
Gonçalo Gamboa da Costa, Ph.D.
National Center for Toxicological Research, FDA
NTP Board of Scientific Counselors Meeting,
June 11-12 2008, Research Triangle Park, NC


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“Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.” — Margaret Mead

United we stand     Divided we fall....
Pita_Purr_Parler
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« Reply #9 on: September 23, 2008, 03:42:30 AM »

Sigh. Pet owners told them. Vets told them. Now, a year later folks get grants to prove we were right.. those adulterations kill and damage.. pets, pigs, people.

And the dilution theories and risk assessments of our government agencies,  & the lobbyists "false science" that drives their decisions,  KNOWINGLY put it into our food supply.. chickens, fish, pigs... and most likely continues to put it into our food supply courtesy of the animal feed industries.

and this from the article Carol just posted:

Pet food toxicity outbreak – Spring 2007
? Sudden illness and kidney failure-related death of a
large number of cats (~1950) and dogs (~2200)


And, not one notation of what we all knoe - they stopped counting, too.  Maybe the journalists will realize how stupid they looked to pet owners and how we got lied to over & over keeping others from understanding the danger our pets were facing with the pet foods.. 16, right.

« Last Edit: September 23, 2008, 03:47:11 AM by Offy » Logged
Carol
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« Reply #10 on: September 23, 2008, 03:43:48 AM »

and I found this that stated fish fed melamine and CA on different days had crystals form...so the fatal combo can be fed separate I guess! (page 69)  Haven't read this all yet...just found the trout info.... Huh Shocked

http://www.csl.gov.uk/newsAndResources/documents/wekellPres.pdf

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“Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.” — Margaret Mead

United we stand     Divided we fall....
Pita_Purr_Parler
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« Reply #11 on: September 23, 2008, 03:51:56 AM »

That article has the first clues we possibly can use to help protect our pets!!!!
I'm taking that to give the vet for the next wellness checkup!

Phase 4- Biomarkers of nephrotoxicity
Investigate the occurrence of metabolomic and proteomic early biomarkers of melamine + cyanuric acid-induced nephrotoxicity, obtainable by non-invasive methods (urine)
>Homovanillic acid sulfate
>4-Hydroxyproline
>NAG
>-GST *
>-GST *
>RPA-1 *
>Clusterin *
>Kim-1
>Urine metabonomic profiling by 1H NMR
* Human nephrotoxicity biomarkers currently undergoing evaluation by the FDA


Oh, Carol! Thank you! Thank you! Thank you for finding that!!!   I just faxed it to my vet so she can check the lab & costs. I'd like her prepared before the visit.. maybe she'll have more info if she gets a chance to see it now.
« Last Edit: September 23, 2008, 04:07:30 AM by Offy » Logged
Carol
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« Reply #12 on: September 23, 2008, 04:19:23 AM »

and I found this..in 1944 melamine was considered a potent diuretic in the rat and DOGS! Angry 

http://jpet.aspetjournals.org/cgi/content/abstract/83/4/235

THE MODE OF ACTION OF THREE NEW DIURETICS: MELAMINE, ADENINE AND FORMOGUANAMINE
WERNER L. LIPSCHITZ 1 and EDGAR STOKEY 1
1 From the Lederle Laboratories, Pearl River, New York



1. Melamine, adenine sulfate and formoguanamine, which by the rat assay method were found to be potent diuretics, proved to be active also on the dog. Taking the urea potency as 1 in the dog the activities of the three compounds are in the order of 18.6, 72.5, 145, respectively. These correspond to the rat figures 76.5, 139, 347. The drugs increase the output of NaCl as well as water in proportion to the dose.

2. Melamine is excreted in the dog or rat partly as the crystalline dimelaminemonophosphate. The total can be isolated from the warm urine by precipitation with oxalic acid as the crystalline monomelamine-monooxalate, and 60-86.5 per cent of the melamine fed to dogs was recovered in the urine in 24 hours.

3. Melamine fed in diuretic doses to digitalized cats and dogs does not change the fatal digitalis dose.

4. Diuresis produced specifically by urea, caffeine, melamine, adenine or formoguanamine fed in saline to rats, is little affected by pitressin—in contrast to water diuresis. The hormone, therefore, cannot be considered as the limiting factor which controls xanthine diuresis.

5. No significant toxic effects of the three new diuretics were found when large doses were administered orally or intravenously to rats, rabbits or dogs. This is similar to common experience with urea, and in contrast to the xanthines and the mercury compounds.

Submitted on October 13, 1944
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“Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.” — Margaret Mead

United we stand     Divided we fall....
5CatMom
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« Reply #13 on: September 23, 2008, 04:58:04 AM »

Dr. Renate Reimschuessel

"Achievement: Made the scientific breakthrough to identify the cause of the largest pet food recall in history and is currently conducting critical research to guarantee the safety of imported foods."

http://servicetoamericamedals.org/SAM/finalists08/hsm/reimscheussel.shtml

--------------------------------------------------------------------------------
Didn't UC Davis determine that melamine and cyanuric acid causes MARF? 

Could it be that all this research is aimed toward determining allowable levels of melamine, et al, in human foodstuffs?

5CatMom
=^..^=
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Pita_Purr_Parler
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« Reply #14 on: September 23, 2008, 05:46:17 AM »

5Cat, that's what I'm thinking too.

I'm going to try to contact the company that makes the equipment to test for real protein and see what labs have it and see what I can find about labs that can measure non protein nitrogen content.

If we can monitor our pets for the biomarkers, test foods for non protein nitrogen (no matter the source) and become able to identify the real protein then, there's not much there for the pfcs to argue about with us. It might be the only way we can put the pfcs in a position where the need to change and the way they advertise has to give way to more truth and more honesty. How are they going to tell us the pet food has no melamine/cyanuric acid if our pet has the biomarkers?  It's also maybe a good way to monitor long term health consequences.

So, far, we're pretty much status quo with the pfc and maybe it's time for another strategy.
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