Use of phlebotomy treatment in Atlantic bottlenose dolphins with iron overload

Johnson, Shawn; Venn‐Watson, Stephanie; Cassle, Stephen E.; Smith, Cynthia R.; Jensen, Eric D.; Ridgway, Sam H.

doi:10.2460/javma.235.2.194

Cited by 37 publications

(39 citation statements)

References 21 publications

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“…Within the fasting samples, ALT and GGT were significantly higher in the iron overload group ( p = 0.0159 and 0.0476, respectively) while MCHC was significantly lower (Table S2 in Supplementary Material; p = 0.0317) compared to controls. Iron was not significantly different, which was expected since the iron overload samples were taken post-phlebotomy (21). Within the post-prandial set, ALT was also higher and MCHC (Table S2 in Supplementary Material) was lower in the iron overload group ( p = 0.0159 and 0.0159, respectively) compared to controls.…”

Section: Resultsmentioning

confidence: 63%

“…Iron overload cases in this study were previously reported to have chronically elevated serum aminotransferases, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as elevated serum iron (20). These four case animals had since undergone phlebotomy treatments in order to manage iron overload, and diagnoses of iron overload have been confirmed by live liver biopsies in three of the four animals (21). Control animals had normal blood values throughout the year before sample collection, specifically iron, ALT, and AST, based upon published reference ranges for healthy bottlenose dolphins (22).…”

Section: Methodsmentioning

confidence: 89%

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Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

Neely¹,

Carlin²,

Arthur³

et al. 2013

Front. Endocrinol.

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High molecular weight (HMW) adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus) diagnosed with hemochromatosis (iron overload) have higher levels of 2 h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n = 4) and without (n = 5) iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2 h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean ± SD) at 763 ± 298 and 727 ± 291 pmol/ml, respectively (p = 0.91); however, percent unmodified adiponectin was significantly higher in post-prandial cases compared to controls (30.0 ± 6.3 versus 17.0 ± 6.6%, respectively; p = 0.016). Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r = 0.999, p < 0.001), but not in cases, which is possibly a reflection of insulin resistance. Although total adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to HMW adiponectin reported for humans with metabolic disorders.

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Section: Resultsmentioning

confidence: 63%

Section: Methodsmentioning

confidence: 89%

Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

Neely¹,

Carlin²,

Arthur³

et al. 2013

Front. Endocrinol.

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“…The case dolphin had a clinical history of chronic, high liver enzymes (alanine transaminase >42 U/L, aspartate transaminase >263 U/L, and gamma-glutamyl transpeptidase >44 U/L) and serum iron that began at the age of 25 years and peaked at 42 years [Figure 1A; (23)]. A liver biopsy at that time demonstrated that this dolphin had diffuse, moderate hemosiderosis, mild multifocal vacuolar degeneration, mild amounts of granular intracellular iron in hepatocytes, and moderate amounts of intracellular iron visualized via staining in the Kupffer cells.…”

Section: Resultsmentioning

confidence: 99%

Development and Application of Specific Cytokine Assays in Tissue Samples from a Bottlenose Dolphin with Hyperinsulinemia

Eberle¹,

Waters²,

Jensen³

et al. 2013

Front. Endocrinol.

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Chronic inflammation has been associated with insulin resistance and type 2 diabetes (T2D) in humans. Postmortem hepatic and splenic tissue from a 46-year-old geriatric male bottlenose dolphin (Tursiops truncatus) with insulin resistance (chronic hyperinsulinemia with hyperglycemia), chronic inflammation (white blood cell count greater than 12,000 cells/μL), and mild fatty liver disease was evaluated for elevated pro-inflammatory mediators. Cytokine mRNA expression in postmortem hepatic and splenic tissue, as determined by real-time PCR, included an array of cytokines: TGF-β, TNF-α, IFN-γ, IL-2, IL-4, IL-10, IL-12p40, IL-13, and IL-18. Values from this dolphin were compared to a younger reference dolphin with no known chronic metabolic perturbations or inflammation. Levels of TGF-β, TNF-α, and IL-4 were higher in the case dolphin’s liver compared to that of the reference dolphin. In the case dolphin’s spleen, IL-10 and IFN-γ mRNA was upregulated while IL-4 was less than the reference dolphin. IL-18 and IL-13 were upregulated in both tissues. Fluorescent immunohistochemistry (IHC) utilized the following antibodies: anti-porcine IL-6, anti-bovine IFN-γ, IL-4, and IL-10, anti-human TGF-β, anti-ovine IL-1β, and anti-dolphin IL-8. Fluorescent IHC in spleen from the case dolphin revealed staining of IL-4, IL-6, IL-8, and TGF-β throughout the tissue. IL-10 and IFN-γ were seen to predominate in areas surrounding the follicles of splenic tissue. This is the first characterization of cytokine levels in dolphin hepatic and splenic tissue. While there are limitations to a case study, this report of inflammatory biomarkers in tissues of a dolphin with insulin resistance and fatty liver disease are similar to those observed in human patients.

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“…Veterinarians can now also consider stem cell therapy when evaluating the treatment options for common dolphin diseases such as corneal trauma and liver disease, both of which have shown promising therapeutic benefits with stem cell treatment in humans [31,32]. Several dolphin diseases have similar human counterparts, including type 2 diabetes [8], urate nephrolithiasis with renal failure [33], and iron overload with liver disease [9,34]. The dolphin may serve as a human model for several disease processes, as was recently proposed for type 2 diabetes [10] and aging studies [35], where new treatment modalities using stem cells could be realized.…”

Section: Discussionmentioning

confidence: 99%

Adipose-Derived Stem Cell Collection and Characterization in Bottlenose Dolphins (Tursiops truncatus)

Johnson

Catania

Harman

et al. 2012

Stem Cells and Development

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To assess the regenerative properties and potential therapeutic value of adipose-derived stem cells (ASCs) in the bottlenose dolphin, there is a need to determine whether an adequate adipose depot exists, in addition to the development of a standardized technique for minimally invasive adipose collection. In this study, an ultrasoundguided liposuction technique for adipose collection was assessed for its safety and efficacy. The ultrasound was utilized to identify and measure the postnuchal adipose depot and aid in the guidance of the liposuction cannula during aspiration. Liposuction procedures from 6 dolphins yielded 0.9-12.7 g of adipose. All samples yielded sufficient nucleated cells to initiate primary cell cultures, and at passage 2, were successfully differentiated into adipogenic, chondrogenic, neurogenic, and osteogenic cell lineages. The cultured dolphin cells expressed known stem-cell-associated CD markers, CD44 and CD90. Ultrasound-guided liposuction proved to be a safe and minimally invasive procedure that resulted in the successful isolation of ASCs in bottlenose dolphins. This is the first article that conclusively establishes the presence of stem cells in the dolphin.

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Use of phlebotomy treatment in Atlantic bottlenose dolphins with iron overload

Abstract: Although the cause of the iron overload and high serum aminotransferase activities remained unknown, phlebotomy treatment successfully resolved the clinicopathologic abnormalities, supporting a role of iron overload in the hepatopathy of the 3 dolphins.

Cited by 37 publications

References 21 publications

Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

Development and Application of Specific Cytokine Assays in Tissue Samples from a Bottlenose Dolphin with Hyperinsulinemia

Adipose-Derived Stem Cell Collection and Characterization in Bottlenose Dolphins (Tursiops truncatus)

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