Safety and efficacy of a novel iron chelator (HBED; (N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis).

While iron overload disorder (IOD) and related disease states are not considered a common occurrence in domestic equids, these issues appear prevalent in black rhinoceroses under human care. In addressing IOD in black rhinos, altering dietary iron absorption and excretion may be the most globally practical approach. A main option for treatment used across other species such as humans, is chelation therapy using iron-specific synthetic compounds. As horses may serve as an appropriate digestive model for the endangered rhinoceros, we evaluated the potential use of the oral iron chelator N,N-bis(2-hydroxybenzyl)ethylenediamine-N,N-diacetic acid (HBED) in horses for safety and efficacy prior to testing in black rhinoceros. Health and iron digestibility and dynamics were assessed in horses (n = 6) before, and after treatment with HBED (50 mg/kg body weight) for 8 days using a crossover design with serum, faecal and urine collection. A preliminary pharmacokinetic trial was also performed but no trace of HBED was found in serially sampled plasma through 8 h post-oral dosing. HBED increased urinary iron output in horses compared to control by 0.7% of total iron intake (p < 0.01), for an average of 27 mg urinary iron/day, similar to human chelation goals. Blood chemistry, blood cell counts and overall wellness were not affected by treatment. As healthy horses are able to regulate iron absorption, the lack of change in iron balance is unsurprising. Short-term HBED administration appeared to be safely tolerated by horses, therefore it was anticipated it would also be safe to administer to black rhinos for the management of iron overload.

The yin and the yang of early classical pathway complement disorders.

The classical pathway of the complement cascade has been recognized as a key activation arm, partnering with the lectin activation arm and the alternative pathway to cleave C3 and initiate the assembly of the terminal components. While deficiencies of classical pathway components have been recognized since 1966, only recently have gain-of-function variants been described for some of these proteins. Loss-of-function variants in C1, C4, and C2 are most often associated with lupus and systemic infections with encapsulated bacteria. C3 deficiency varies slightly from this phenotypic class with membranoproliferative glomerulonephritis and infection as the dominant phenotypes. The gain-of-function variants recently described for C1r and C1s lead to periodontal Ehlers Danlos syndrome, a surprisingly structural phenotype. Gain-of-function in C3 and C2 are associated with endothelial manifestations including hemolytic uremic syndrome and vasculitis with C2 gain-of-function variants thus far having been reported in patients with a C3 glomerulopathy. This review will discuss the loss-of-function and gain-of-function phenotypes and place them within the larger context of complement deficiencies.

Primary Immune Deficiency Treatment Consortium (PIDTC) report.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

Vitamin A values of wild-caught Cuban tree frogs (Osteopilus septentrionalis) and marine toads (Rhinella marina) in whole body, liver, and serum.

Recent issues surrounding captive amphibians are often nutritionally related problems, such as hypovitaminosis A. Although supplementation of frogs with vitamin A is a topic of investigation, the underlying issue is understanding vitamin A metabolism in amphibian species. To develop a range of "normal" vitamin A concentrations for captive amphibians, baseline vitamin A concentrations must be established in wild amphibian species. In this study, two species, Cuban tree frogs (Osteopilus septentrionalis; n = 59) and marine toads (Rhinella marina; n = 20) were collected from the wild as part of an invasive species control program at Zoo Miami, Miami, Florida. Serum, liver, and whole body samples were analyzed for vitamin A content. The Cuban tree frogs showed higher concentrations on average of vitamin A in serum (82.8 ppb), liver (248.3 IU/g), and whole body (5474.7 IU/kg) samples compared with marine toads (60.1 ppb; 105.3 IU/g; 940.7 IU/kg, respectively), but differences were not significant (P = 0.22). What can be considered "normal" values of vitamin A concentrations across different amphibian species requires further investigation. Although all amphibians collected in this study appeared healthy, a larger sample size of animals, with known health histories and diets, may provide stronger evidence of normal expectations.

A comparison of oral and topical vitamin A supplementation in African foam-nesting frogs (Chiromantis xerampelina).

Vitamin A is essential for a variety of functions, including cellular differentiation, morphogenesis, growth, vision, immune response, and reproduction. A captive population of African foam-nesting frogs (Chiromantis xerampelina) with a known history of vitamin A deficiency had higher than expected incidence of sudden death, bacterial osteomyelitis, and stunted growth. Due to the high prevalence and untreatable nature of the diseases in the population, euthanasia of the population was recommended. Before euthanasia, the population was entered into a study to compare oral dietary supplementation of vitamin A to topical treatment with water-miscible vitamin A palmitate (AQUASOL A Parenteral, Mayne Pharma Inc., Paramus, New Jersey 07652, U.S.A.). Eighty-four frogs, weighing 2-7 g, were divided into a control and three treatment groups of 21 frogs per group, with normalized weight distribution. The control group received standard daily nutrition of crickets dusted with a supplement containing 342,000 international units (IU) vitamin A/kg. The treatment groups consisted of oral supplementation with crickets dusted with a fortified supplement containing 822,510 IU vitamin A/kg; topical vitamin A palmitate 50 IU every other day; and topical vitamin A palmitate 50 IU once a week. After 30 days, all frogs were euthanized, and 12 frogs from each group were analyzed for whole-body vitamin A levels. The control and treatment groups 1, 2, and 3 had average whole-body vitamin A levels of 1371.4 IU/kg (SE 284.4), 908.7 IU/kg (SE 186.5), 6385.9 IU/kg (SE 675.9), and 3521.8 IU/kg (SE 575.1), respectively. These results suggest that oral supplementation using a product high in vitamin A may be ineffective at raising whole-body vitamin A levels above those achieved with standard nutrition. Topical administration of vitamin A on an every other day and once a week dosing schedule achieved levels 4.5- and 2.5-fold higher than standard nutrition, respectively.

DiGeorge syndrome/velocardiofacial syndrome: the chromosome 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion (CH22qD) syndrome is also known as DiGeorge syndrome or velocardiofacial syndrome. This deletion syndrome is extremely common with nearly one in 4000 children being affected. Recent advances and a holistic approach to patients have improved the care and well-being of these patients. This review will summarize advances in understanding the health needs and immune system of patients with CH22qD syndrome. Patients will most often need interventions directed at maximizing function for many organ systems but can ultimately have a high level of functioning.