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.

Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress.

Parkinson's disease (PD) is associated with oxidative stress and decreased nigral glutathione (GSH), suggesting that therapies that boost GSH may have a disease-modifying effect. Intravenous administration of a high dose of N-acetylcysteine (NAC), a well-known antioxidant and GSH precursor, increases blood and brain GSH in individuals with PD and with Gaucher disease and in healthy controls. To characterize the pharmacokinetics of repeated high oral doses of NAC and their effect on brain and blood oxidative stress measures, we conducted a 4-week open-label prospective study of oral NAC in individuals with PD (n = 5) and in healthy controls (n = 3). Brain GSH was measured in the occipital cortex using 1 H-MRS at 3 and 7 tesla before and after 28 days of 6000 mg NAC/day. Blood was collected prior to dosing and at predetermined collection times before and after the last dose to assess NAC, cysteine, GSH, catalase, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations and the reduced-to-oxidized GSH ratio (GSH/ glutathione disulfide [GSSG]). Symptomatic adverse events were reported by 3 of the 5 subjects with PD. NAC plasma concentration-time profiles were described by a first-order absorption, 1-compartment pharmacokinetic model. Although peripheral antioxidant measures (catalase and GSH/GSSG) increased significantly relative to baseline, indicators of oxidative damage, that is, measures of lipid peroxidation (4-HNE and MDA) were unchanged. There were no significant increases in brain GSH, which may be related to low oral NAC bioavailability and small fractional GSH/GSSG blood responses. Additional studies are needed to further characterize side effects and explore the differential effects of NAC on measures of antioxidant defense and oxidative damage.

Dietary management, husbandry, and body weights of African elephants (Loxodonta africana) during successful pregnancies at Disney's Animal Kingdom.

Successful pregnancy in African elephants is influenced by biological and environmental factors. For managed elephants many of these factors are set directly or indirectly by their human care takers, including nutrition and husbandry. While African elephants often struggle to conceive and produce healthy offspring under human care, Disney's Animal Kingdom (DAK) has effectively managed six gestations to fruition in three cows. Despite differences between mothers in terms of BW and growth curves during gravidity, each pregnancy successfully resulted in the birth of a healthy calf. Body weight (BW) gain during pregnancy ranged from 245 to 558 kg. Obesity in elephants is associated with increased occurrence of dystocia and mortality of the fetus and mother, hence understanding normal weight gains is an integral concept. Diet (dry matter basis) included high levels of fiber throughout pregnancies (60-70% neutral detergent fiber), vitamin E supplementation (116-214 mg/kg diet of alpha-tocopherol), as well as low levels of starch (2.5-5.1%) and crude fat (1.9-2.4%). Caretaker directed exercise during pregnancy at DAK served to prevent ventral edema, and increase muscle tone to prepare cows for parturition. Demonstrating techniques for effective care of pregnant females, as well as normal growth curves and fluctuations under ex situ conditions are necessary for future positive outcomes. Ensuring reproductive success through proper husbandry and nutrition are a key to long-term conservation of elephants. Zoo Biol. 35:574-578, 2016. © 2016 Wiley Periodicals, Inc.

Roller-massager application to the quadriceps and knee-joint range of motion and neuromuscular efficiency during a lunge.

CONTEXT: Roller massagers are used as a recovery and rehabilitative tool to initiate muscle relaxation and improve range of motion (ROM) and muscular performance. However, research demonstrating such effects is lacking. OBJECTIVE: To determine the effects of applying a roller massager for 20 and 60 seconds on knee-joint ROM and dynamic muscular performance. DESIGN: Randomized controlled clinical trial. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten recreationally active men (age = 26.6 ± 5.2 years, height = 175.3 ± 4.3 cm, mass = 84.4 ± 8.8 kg). INTERVENTION(S): Participants performed 3 randomized experimental conditions separated by 24 to 48 hours. In condition 1 (5 repetitions of 20 seconds) and condition 2 (5 repetitions of 60 seconds), they applied a roller massager to the quadriceps muscles. Condition 3 served as a control condition in which participants sat quietly. MAIN OUTCOME MEASURE(S): Visual analog pain scale, electromyography (EMG) of the vastus lateralis (VL) and biceps femoris during roller massage and lunge, and knee-joint ROM. RESULTS: We found no differences in pain between the 20-second and 60-second roller-massager conditions. During 60 seconds of roller massage, pain was 13.5% (5.7 ± 0.70) and 20.6% (6.2 ± 0.70) greater at 40 seconds and 60 seconds, respectively, than at 20 seconds (P < .05). During roller massage, VL and biceps femoris root mean square (RMS) EMG was 8% and 7%, respectively, of RMS EMG recorded during maximal voluntary isometric contraction. Knee-joint ROM was 10% and 16% greater in the 20-second and 60-second roller-massager conditions, respectively, than the control condition (P < .05). Finally, average lunge VL RMS EMG decreased as roller-massage time increased (P < .05). CONCLUSIONS: Roller massage was painful and induced muscle activity, but it increased knee-joint ROM and neuromuscular efficiency during a lunge.

Challenges with effective nutrient supplementation for amphibians: A review of cricket studies.

Over the last 25 years, numerous studies have investigated the impact of insect supplementation on insect nutrient content. In light of recent nutrition related challenges with regards to zoo amphibians fed an insect based diet, this review attempts to comprehensively compile both anecdotal and published data in the context of practical application on this topic. Insects, primarily crickets, used for amphibian diets historically demonstrate low concentrations of key nutrients including calcium and vitamin A. Commonly used practices for supplementation involving powder dusting or gut loading have been shown to improve delivery of calcium and vitamin A, though often not reaching desired nutrient concentrations. The large variety of factors influencing insect nutrient content are difficult to control, making study design, and results often inconsistent. Formulation and availability of more effective gut loading diets, combined with a standardized protocol for insect husbandry and dietary management may be the most effective way to supplement insects for use in amphibian feeding programs. Ideally, the nutritional improvement of feeder insects would begin at the breeder level; however, until this becomes a viable choice, we confirm that supplementation of crickets through both gut-loading and dusting appear necessary to support the nutritional health of amphibians and other insectivores in managed collections.

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.

Roller-massager application to the hamstrings increases sit-and-reach range of motion within five to ten seconds without performance impairments.

BACKGROUND: Foam rollers are used to mimic myofascial release techniques and have been used by therapists, athletes, and the general public alike to increase range of motion (ROM) and alleviate pressure points. The roller-massager was designed to serve a similar purpose but is a more portable device that uses the upper body rather than body mass to provide the rolling force. OBJECTIVES/PURPOSE: A roller massager was used in this study to examine the acute effects on lower extremity ROM and subsequent muscle length performance. METHODS: Seven male and ten female volunteers took part in 4 trials of hamstrings roller-massager rolling (1 set - 5 seconds, 1 set - 10 seconds, 2 sets - 5 seconds, and 2 sets - 10 seconds) at a constant pressure (13 kgs) and a constant rate (120 bpm). A group of 9 participants (three male, six female) also performed a control testing session with no rolling intervention. A sit and reach test for ROM, along with a maximal voluntary contraction (MVC) force and muscle activation of the hamstrings were measured before and after each session of rolling. RESULTS: A main effect for testing time (p<0.0001) illustrated that the use of the roller-massager resulted in a 4.3% increase in ROM. There was a trend (p=0.069) for 10s of rolling duration to increase ROM more than 5s rolling duration. There were no significant changes in MVC force or MVC EMG activity after the rolling intervention. CONCLUSIONS: The use of the roller-massager had no significant effect on muscle strength, and can provide statistically significant increases in ROM, particularly when used for a longer duration.

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.