Handling and restraint induce a significant increase in plasma corticosterone in Hispaniolan Amazon parrots (Amazona ventralis).

OBJECTIVE: To measure baseline plasma corticosterone levels in Hispaniolan Amazon parrots (Amazona ventralis) and assess the effects of handling and restraint on corticosterone levels over 1 hour, reflective of what parrots might experience during veterinary care. ANIMALS: 10 male and 12 female Hispaniolan Amazon parrots. PROCEDURES: Each parrot was removed from its cage and wrapped in a towel for restraint similar to that performed in a clinical setting. An initial baseline blood sample was collected in < 3 minutes upon entrance into the parrot room, after which blood samples were taken every 15 minutes for 1 hour (a total of 5 blood samples). An enzyme-linked immunoassay was validated for Hispaniolan Amazon parrots and used to determine concentrations of plasma corticosterone. RESULTS: On average, parrots showed a significant increase in corticosterone between baseline samples and all subsequent postrestraint time points (average baseline corticosterone ± SD: 0.51 ± 0.65 ng/mL). Females, on average, displayed significantly higher corticosterone levels than males after 30, 45, and 60 minutes of restraint (P = .016, P = .0099, and P = .015, respectively). Birds with feather-destructive behavior did not have significantly higher corticosterone levels than birds without the condition (P = .38). CLINICAL RELEVANCE: Understanding the physiological stress response in companion psittacine birds during routine handling will allow clinicians to better evaluate how this may affect the patient's condition and diagnostic test results. Assessing how corticosterone correlates to behavioral conditions such as feather-destructive behavior will provide clinicians with the potential to develop treatment options.

Chiral resolution of a caged xanthone and evaluation across a broad spectrum of breast cancer subtypes.

Racemic resolution of (+/-)-MAD28, a representative caged xanthone, was accomplished using (1S, 4R)-(-)-camphanic chloride as the chiral agent. Selective crystallization of the resulting diastereomers in acetonitrile produced, after hydrolysis, the pure enantiomers. Screening of racemic MAD28 and both enantiomers across a broad spectrum of breast cancer cell lines revealed that they: (a) are equipotent in each of the breast cancer subtypes examined; and (b) exhibit a higher degree of cytotoxicity against breast cancer cell lines of basal-like subtype and triple negative receptor status. The results support the notion that MAD28 and related caged xanthones are promising drug leads against chemoresistant and metastatic cancers.

Synthesis, structure-activity relationship and in vitro pharmacodynamics of A-ring modified caged xanthones in a preclinical model of inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a highly metastatic, lethal form of breast cancer that lacks targeted therapeutic strategies. Inspired by the promising cytotoxicity of gambogic acid and related caged xanthones in spheroidsMARY-X, an in vitro preclinical IBC model, we constructed a library of synthetic analogs and performed structure-activity relationship studies. The studies revealed that functionalizing the A-ring of the caged xanthone framework can significantly affect potency. Specifically, introduction of hydroxyl or fluorine groups at discrete positions of the A-ring leads to enhanced cytotoxicity at submicromolar concentrations. These compounds induce complete dissolution of spheroidsMARY-X with subsequent apoptosis of both the peripherally- and centrally-located cells, proliferative and quiescent-prone (e.g. hypoxic), respectively. These results highlight the structural flexibility and pharmacological potential of the caged xanthone motif for the design of IBC-targeting therapeutics.