Background
Babesia canis
infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis.
Hypothesis
Dogs with
B. canis
‐induced APR develop dyslipidemia with altered lipoprotein concentration and morphology.
Animals
Twenty‐nine client‐owned dogs with acute
B. canis
infection and 10 clinically healthy control dogs.
Methods
Observational cross‐sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA‐1 (radioimmunoassay) and SAA was determined.
Results
Dogs with
B. canis
infection had a marked APR (median SAA, 168.3 μg/mL; range, 98.1‐716.2 μg/mL) compared with controls (3.2 μg/mL, 2.0‐4.2 μg/mL) (
P
< .001). Dogs with
B. canis
infection had significantly lower median cholesterol (4.79 mmol/L, 1.89‐7.64 mmol/L versus 6.15 mmol/L, 4.2‐7.4 mmol/L) (
P
= .02), phospholipid (4.64 mmol/L, 2.6‐6.6 mmol/L versus 5.72 mmol/L, 4.68‐7.0 mmol/L) (
P
= .02), and α‐lipoproteins (77.5%, 27.7%‐93.5% versus 89.2%, 75.1%‐93.5%) (
P
= .04), and higher ApoA‐1 (1.36 U, 0.8‐2.56 U versus 0.95 U, 0.73‐1.54 U) concentrations (
P
= .02). Serum amyloid A correlated with high‐density lipoproteins (HDLs) diameter (rho = .43;
P
= .03) and ApoA‐1 (rho = .63,
P
< .001).
Conclusions and Clinical Importance
Major changes associated with
B. canis
‐induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA‐1 and SAA concentration increase is a unique still unexplained pathophysiological finding.
Radiolabelled superparamagnetic iron oxide nanoparticles (SPIONs) are promising nanomaterial for development of dual radiation/hyperthermia cancer therapy. To that purpose, flower-shaped SPIONs with an exceptional heating capability were synthesised and coated with citrate, dextran or (3-aminopropyl)triethoxysilane. Both non-coated and coated SPIONs were nontoxic to CT-26 mouse colon cancer cells up to 1.0 mg/mL in vitro. In an oscillating magnetic field, citrate-coated SPIONs (CA/SPIONs) displayed the highest heating rate (SAR253 W/g) and strongest hyperthermia effects against CT-26 cells. Labelling of CA/SPIONs by 90Y radionuclide, emitting β− radiation with average/maximum energy of 0.94/2.23 MeV and deep tissue penetration, generated 90Y-CA/SPIONs intended for therapy of solid tumours. However, intravenous injection of 90Y-CA/SPIONs in CT-26 xenografts-bearing mice resulted in low tumour accumulation. Contrary, intratumoral injection resulted in long-term retention at the injection site. A single intratumoral injection of 0.25 mg CA/SPIONs followed by 30-minute courses of magnetic hyperthermia for 4 consecutive days caused a moderate antitumor effect against CT-26 and 4T1 mouse tumour xenografts. Intratumoral application of 1.85MBq/0.25 mg 90Y-CA/SPIONs, alone or combined by hyperthermia caused a significant (P ≤ 0.01) antitumor effect without signs of systemic toxicity. The results confirm suitability of 90Y-CA/SPIONs for monotherapy or dual magnetic hyperthermia-radionuclide nanobrachytherapy (NBT) of solid tumours.
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