Systemic Erysipelas Outbreak among Free-Ranging Bottlenose Dolphins, San Diego, California, USA, 2022.

We diagnosed fatal Erysipelothrix rhusiopathiae sepsis in 3 stranded bottlenose dolphins (Tursiops truncatus) during summer 2022, in San Diego, California, USA. The previously undetected disease in this relatively small, regional population of dolphins most likely indicates an environmental or biological change in the coastal ocean or organisms.

Chronic nonchylous lymphatic pleural effusion in a bottlenose dolphin (Tursiops truncatus).

CASE DESCRIPTION: A 19-year-old male bottlenose dolphin (Tursiops truncatus) presented with inappetence and avoidant behavior. CLINICAL FINDINGS: Ultrasound revealed a large-volume left-sided pleural effusion, which was consistent with chronic nonchylous lymphatic effusion and mild chronic hemorrhage by cytology. Computed tomography identified ipsilateral rib fractures, atelectasis, nodular pleuritis, marginal lymph node enlargement, and suspected dilation of the thoracic duct and internal thoracic veins. Fifteen lipids were significantly higher in serum of the dolphin as compared with controls (n = 3) using nontargeted lipidomics. TREATMENT AND OUTCOME: A series of thoracentesis procedures were performed. Follow-up CT demonstrated marked reduction in pleural effusion with persistence of thoracic duct dilation and mass-like areas of pleural thickening. Ultrasonographic resolution of pleural effusion occurred 14 months after presentation; however, recrudescence was noted 5 months later. Over a total of 24 months, 21.52 L of pleural effusion was removed. Despite the presence of pleural effusion, the patient was clinically stable during this time and quality of life was considered good on the basis of continuous animal welfare evaluations. Humane euthanasia was elected following acute clinical decline 27 months after initial diagnosis. Necropsy confirmed severe pleural effusion, chronic severe pleural fibrosis with chronic hemorrhage, and mediastinal fibrosis with entrapped lymph nodes and thymic tissue. CLINICAL RELEVANCE: Pleuritis and effusion were suspected sequelae of previous rib fractures. To our knowledge, this is the first report of nonchylous lymphatic pleural effusion with repeated pleural drainage and diagnostic imaging for clinical management in a bottlenose dolphin.

Cutaneous and splenic mastocytosis in a juvenile Malayan tiger.

A male Malayan tiger cub developed well-circumscribed, erythematous, alopecic lesions on the face, torso, and paws when 1-wk-old. Biopsies of a torso lesion and a right front paw lesion at 1-mo-old confirmed cutaneous mast cell tumors (MCTs). MCTs on the paws grew into pendulous masses up to 6.5 cm in diameter by 3-mo-old, but those on the face and torso regressed. Fine-needle aspiration of the spleen at 3-mo-old revealed marked mast cell infiltration. The spleen and the right paw cutaneous MCT were removed; the paw MCT recurred within 7 d. A 12-bp tandem duplication, suggesting a somatic mutation, was identified in exon 8 of c-KIT in DNA extracted from the cutaneous MCT on the right paw and from one over the torso, but not from the spleen. Remaining MCTs on the paws regressed slowly following splenectomy and had completely regressed by 1-y-old. At 7-y-old, there was no recurrence of any mast cell disease. Mast cell disease in this tiger cub is similar to a report in a domestic kitten and to pediatric mastocytosis in humans, which commonly begins in infancy, improves by adolescence, and is associated with somatic c-kit mutations. To our knowledge, mastocytosis has not been reported previously in a juvenile exotic felid.

GENOTYPE IDENTIFICATION OF TOXOPLASMA GONDII IN MACROPODS FROM A ZOOLOGICAL PARK IN FLORIDA, USA.

There are limited reports of the genetic characterization of Toxoplasma gondii infecting captive macropods in North America. A novel genotype, ToxoDB PCR-RFLP genotype 263, was reported from six wallabies at a zoological facility in Virginia, USA, prompting an investigation into the genotypes from T. gondii strains infecting macropods at a zoological park in Florida, USA. Cardiac muscle and/or lung samples from an agile wallaby (Macropus agilis, n = 1), red kangaroos (Macropus rufus, n = 8), red-necked wallaby (Macropus rufogriseus, n = 1), and a tammar wallaby (Macropus eugenii, n = 1) that died between 2014 and 2018 were collected. All 11 cases were confirmed to have died from systemic toxoplasmosis by histopathology and immunohistochemical staining. Multilocus PCR-RFLP genotyping of T. gondii was performed directly on tissue samples or on parasites isolated from myocardium by mouse bioassay. Two cases of toxoplasmosis were identified as the reported novel genotype, ToxoDB PCR-RFLP genotype 263, but no common source of exposure could be identified. Five cases were identified as genotype 2 (type III strain, haplogroup 3), and four cases were identified as genotype 216, which has been previously reported in North American wildlife. There were no overt differences in lesion severity or distribution related to genotype. These results suggest that the premise was contaminated with at least three genotypes of T. gondii causing systemic toxoplasmosis in macropods. The largest cluster of fatal toxoplasmosis in macropods in the study period occurred following severe rainfall flooding of the exhibit, suggesting the transmission of T. gondii by water and pointing out the importance of this transmission mechanism. In summary, our study revealed three T. gondii outbreaks that caused significant loss of macropods within 5 yr in a zoological facility in Florida. More studies are needed to understand transmission and prevention of toxoplasmosis in sensitive zoo animals.

Diagnosis and Surgical Management of a Paratesticular Cyst in a Rehabilitating Juvenile Male Green Turtle (Chelonia mydas).

A juvenile green turtle (Chelonia mydas) undergoing rehabilitation for cold stunning exhibited an asymmetric bulging of the left caudal plastron and was diagnosed with a large intra-coelomic mass based on radiographical findings. Ultrasonography further identified a fluid-filled structure within the caudal coelom. Cytological evaluation of fluid obtained from the structure was consistent with a transudate, and thus, a cyst of unknown origin was suspected. Computed tomography imaging was pursued to further characterize the extent and location of the mass, which occupied ~50% of the total coelomic cavity volume. Conservative management with monitoring and occasional drainage of the mass did not result in improvements; thus, an exploratory laparoscopy for further investigation and surgical planning was elected. Intra-coelomic surgery was performed to remove a thick-walled cystic mass associated with the left gonad. Histopathology confirmed a paratesticular cyst continuous with, and possibly originating from, the epididymis. Post-surgical recurrence of the cyst was not appreciated, and the animal was successfully released 1 year after admission. Unrelated to the cyst, the turtle developed acute severe anemia on two occasions throughout rehabilitation that responded to modification of antimicrobial treatment and subsequent steroid administration. To the authors' knowledge, this is the first report of a paratesticular cyst in a reptile.

Epidemiological Investigation of a Mortality Event in a Translocated Gopher Tortoise (Gopherus polyphemus) Population in Northwest Florida.

Nokuse Plantation, a 22,055 ha private conservation preserve in northwest Florida, is a recipient site for gopher tortoises translocated from development sites in Florida. Since 2006, Nokuse has received over 5,000 tortoises from multiple development sites. During 2013-2015, 52 tortoises were found sick (n = 14) or dead (n = 38) in multiple soft-release enclosures in which tortoises consistently exhibited clinical signs, with additional sick (n = 5) and dead (n = 5) tortoises presenting similarly during 2016-2017. When found alive, tortoises behaved abnormally (e.g., frequently out of burrows during cold weather, pacing along enclosure fencing), appeared emaciated, were lethargic, and had developed redness under plastron scutes. Similar numbers of male (n = 28) and female (n = 32) tortoises were recovered along with two of unidentified sex, including mainly adults (n = 59) and three subadults. Physical examination, blood analysis, and other diagnostics were indicative of starvation and dehydration. Most sick tortoises provided with supportive care recovered. Necropsy findings generally confirmed starvation, with no evidence of infectious pathogens or contaminants. There were no apparent differences in quality of habitat, plant community, or soil or water among affected and unaffected enclosures. Botanical surveys indicated adequate forage quality and quantity, with no poisonous exotic or native plants detected. No land management practices changed prior to this event. Analysis of epidemiological data and demographic factors from before and during this mortality event identified initial density of tortoises in the enclosures as exerting the strongest influence on detection of tortoise morbidity and mortality. We believe that the stress associated with mixing tortoises from different populations and at higher densities during translocation impacted an individual tortoise's ability to obtain or absorb adequate nutrients from foraging, ultimately leading to a wasting condition consistent with starvation. Based on our findings, we recommend a maximum of 3 gopher tortoises per ha in soft-release enclosures for translocation, but further research is warranted to investigate the complexity of stress and social pressures associated with translocation.

Introduction and Establishment of Raccoon Rabies on Islands: Jekyll Island, Georgia, USA as a Case Study.

The introduction of rabies virus (RABV) to barrier islands, which are often popular tourist destinations with resource-rich habitats and connectivity and proximity to the mainland, is especially concerning because it can easily become endemic due to factors like dense rabies-vector populations (e.g., raccoons [ Procyon lotor]), high inter- and intraspecies contact rates, and anthropogenic activities such as supplemental feeding of feral cats ( Felis catus). In January 2013, a neurologic raccoon found on the Jekyll Island (JI), Georgia, US causeway tested positive for rabies. Mortality investigations of 29 raccoons have been conducted between December 2012-May 2017. The two most common diagnoses were RABV ( n=11) and canine distemper virus (CDV; n=8). Parvoviral enteritis was diagnosed in four raccoons but no coinfections were diagnosed. There was no apparent seasonality for rabies cases, but all CDV cases occurred in spring-fall. Most (64%) rabies submissions came from residential or recreational use areas located near feral cat feeding stations. Jekyll Island is a popular destination where tourists engage in numerous outdoor activities which facilitate human-wildlife interactions. Concerns regarding public and animal health highlight the importance of rabies surveillance, prevention, and control on islands. This is the first report of rabies on JI and emphasizes the importance of disease investigations because the assumption that neurologic raccoons have CDV, an endemic pathogen, can miss the establishment of novel pathogens such as RABV.

RETROSPECTIVE EVALUATION OF HISTOPATHOLOGIC FINDINGS IN CAPTIVE GAZELLE SPECIES.

Capturing disease trends among different species has indisputable value to both veterinary clinicians and zoo managers for improving the welfare and management of zoo species. The causes of mortality for eight species of gazelle (addra gazelle, Nanger dama; dorcas gazelle, Gazella dorcas; Grant's gazelle, Nanger granti; sand gazelle, Gazella leptoceros; Saudi goitered gazelle, Gazella subgutturosa; Soemmerring's gazelle, Nanger soemmerringii; Thomson's gazelle, Eudorcas thomsonii; and Speke's gazelle, Gazella spekei) are presented from an 18-yr period (1996 2014). The leading cause of mortality for all species was trauma, followed by bronchopneumonia, and failure to thrive/maternal neglect. Nephritis and rumenitis/abomasitis/enteritis were common ancillary lesions across all species. On average, female gazelle lived twice as long as male gazelle, with an average overall adult survival time of 9.3 yr. Dorcas, Thomson's and addra gazelle females had the longest average survival time (10-13 yr). Calves up to 6 mo of age died most frequently from failure of passive transfer or maternal neglect. Thyroid carcinoma was frequently identified in Thomson's gazelle. Sand and Speke's gazelle frequently died from systemic amyloidosis, and Saudi goitered gazelle were more likely to have renal amyloidosis. Hematuria syndrome was the second most common cause of death in Grant's gazelle. The majority of lesions identified in this study that cause or contribute to mortality are preventable with appropriate management. Knowledge of disease trends in captive gazelle populations can help guide veterinary care, management decisions, and collection management planning.

HEALTH AND NUTRITIONAL ASSESSMENT OF FREE-RANGING EASTERN INDIGO SNAKES (DRYMARCHON COUPERI) IN GEORGIA, UNITED STATES.

Clinical pathology and nutritional parameters are useful in evaluating and monitoring threatened and endangered wildlife populations, but reference ranges for most snake species are lacking. From 2001 to 2005, health assessments were performed on 58 eastern indigo snakes (EIS) (Drymarchon couperi) captured in the wild in southeastern Georgia, United States. Health and nutritional assessments performed included hematology, serum biochemistry, fat-soluble vitamins, heavy metals, pesticide contaminants, parasitology, and surveys of other pathogens. Significant differences in total solids, packed cell volume, glucose, blood urea nitrogen, albumin : globulin ratio, amylase, triglycerides, and bile acids between males and females were observed. Additionally, there was a significant difference between liver and kidney concentrations for vitamins A and E. As previously noted in captive EIS, total Ca was elevated in comparison to concentrations reported in other snake species. Parasitism was a common finding in sampled EIS, but the overall health status of this free-ranging population appeared good. A winter-time dermatitis was found in most snakes, which resolved in the summer months. This study represents the first health and nutritional assessment of free-ranging EIS, and provides needed data to guide monitoring and conservation efforts.

Case descriptions of fibropapillomatosis in rehabilitating loggerhead sea turtles Caretta caretta in the southeastern USA.

Fibropapillomatosis (FP) is a debilitating neoplastic disease that affects all species of hard-shelled sea turtles, including loggerhead turtles Caretta caretta. FP can represent an important clinical concern in rehabilitating turtles, since managing these infectious lesions often requires special husbandry provisions including quarantine, and FP may affect clinical progression, extend rehabilitation duration, and complicate prognoses. Here we describe cases of rehabilitating loggerhead turtles with FP (designated FP+). Medical records of FP+ loggerhead cases from 3 sea turtle rehabilitation facilities in the southeastern USA were reviewed. Between 2001 and 2014, FP was observed in 8 of 818 rehabilitating loggerhead turtles (0.98% overall prevalence in admitted patients). FP+ loggerhead size classes represented were large juvenile (straight carapace length, SCL: 58.1-80 cm; n=7) and adult (SCL>87 cm; n=1). Three turtles presented with FP, and 5 developed tumors during rehabilitation within a range of 45 to 319 d. Sites of new tumor growth included the eyes, sites of trauma, neck, and glottis. FP+ turtles were scored as mildly (3/8), moderately (4/8), or heavily (1/8) afflicted. The mean total time in rehabilitation was 476±355 d (SD) (range: 52-1159 d). Six turtles were released without visible evidence of FP, 1 turtle was released with mild FP, and 1 turtle with internal FP was euthanized. Clinical decision-making for FP+ loggerhead patients can be aided by such information as time to tumor development, anatomic locations to monitor for new tumor growth, husbandry considerations, diagnostic and treatment options, and comparisons to FP in rehabilitating green turtles Chelonia mydas.

Identification of a novel herpesvirus in captive Eastern box turtles (Terrapene carolina carolina).

Herpesviruses are significant pathogens of chelonians which most commonly cause upper respiratory tract disease and necrotizing stomatitis. Herpesvirus infection was identified in two populations of captive Eastern box turtles (Terrapene carolina carolina) using histopathology and polymerase chain reaction (PCR) with DNA sequencing. Necrotizing lesions with eosinophilic to amphophilic intranuclear inclusion bodies were identified in the tissues of one hatch-year individual in January 2013, which was herpesvirus positive by PCR. A separate captive group of adults had an observed herpesvirus prevalence of 58% using PCR in July 2011. In these cases, a novel herpesvirus, Terrapene herpesvirus 1 (TerHV1), was identified and serves as the first herpesvirus sequenced in the genus Terrapene. Similar to the other herpesviruses of the Order Testudines, TerHV1 clusters with the genus Scutavirus of the subfamily Alphaherpesvirinae.

Splenic marginal zone lymphoma in an Asian small-clawed otter (Aonyx cinerea).

Severe splenomegaly was found during routine examination of a clinically normal 7-yr-old male Asian small clawed otter. The spleen and three enlarged splenic lymph nodes were immediately removed. The spleen weighed 310 g (approximately 8% of body weight). The spleen and resected lymph nodes were diffusely infiltrated by coalescing sheets of neoplastic lymphocytes that occasionally surrounded remnants of preexisting lymphoid follicles. Immunohistochemical confirmation of B lymphocyte origin and microscopic pattern were consistent with primary splenic marginal zone lymphoma (MZL) with metastasis to the splenic lymph nodes. The otter received no additional treatment and survived for 16 mo following splenectomy. Necropsy confirmed metastasis to multiple abdominal and extra-abdominal lymph nodes, liver, and kidney, and renal failure related to glomerulosclerosis. The prolonged survival in this otter is typical for MZL, an indolent form of B-cell lymphosarcoma that spreads slowly to the abdominal and extra-abdominal lymph nodes.

Cloacolithiasis and intestinal lymphosarcoma in an African black-footed penguin (Spheniscus demersus).

A 13-yr-old male African black-footed penguin (Spheniscus demersus) presented thrice over 7 mo with gastrointestinal obstruction secondary to cloacolithiasis. Clinical signs consistently resolved with cloacolith removal and supportive care. However, 10 mo after initial presentation, it presented with similar signs, plus significant weight loss. No cloacolith was found, and it subsequently died. Significant gross findings included bilateral cecal masses, colonic perforation, and marked secondary coelomitis, multifocal tan to pale hepatic nodules, and pale kidneys with miliary white foci. Histopathologic diagnoses were intestinal lymphosarcoma with hepatic and renal metastases, secondary intestinal rupture, and subacute severe bacterial coelomitis. To the authors' knowledge, this is the first full report of either cloacolithiasis or lymphosarcoma in a penguin.

IL-21 receptor is required for the systemic accumulation of activated B and T lymphocytes in MRL/MpJ-Fas(lpr/lpr)/J mice.

MRL/MpJ-Fas(lpr/lpr)/J (MRL(lpr)) mice develop lupus-like disease manifestations in an IL-21-dependent manner. IL-21 is a pleiotropic cytokine that can influence the activation, differentiation, and expansion of B and T cell effector subsets. Notably, autoreactive CD4(+) T and B cells spontaneously accumulate in MRL(lpr) mice and mediate disease pathogenesis. We sought to identify the particular lymphocyte effector subsets regulated by IL-21 in the context of systemic autoimmunity and, thus, generated MRL(lpr) mice deficient in IL-21R (MRL(lpr).IL-21R(-/-)). Lymphadenopathy and splenomegaly, which are characteristic traits of the MRL(lpr) model were significantly reduced in the absence of IL-21R, suggesting that immune activation was likewise decreased. Indeed, spontaneous germinal center formation and plasma cell accumulation were absent in IL-21R-deficient MRL(lpr) mice. Correspondingly, we observed a significant reduction in autoantibody titers. Activated CD4(+) CD44(+) CD62L(lo) T cells also failed to accumulate, and CD4(+) Th cell differentiation was impaired, as evidenced by a significant reduction in CD4(+) T cells that produced the pronephritogenic cytokine IFN-γ. T extrafollicular helper cells are a recently described subset of activated CD4(+) T cells that function as the primary inducers of autoantibody production in MRL(lpr) mice. Importantly, we demonstrated that T extrafollicular helper cells are dependent on IL-21R for their generation. Together, our data highlighted the novel observation that IL-21 is a critical regulator of multiple pathogenic B and T cell effector subsets in MRL(lpr) mice.

Cytosolic phospholipase A2α blockade abrogates disease during the tissue-damage effector phase of experimental autoimmune encephalomyelitis by its action on APCs.

Cytosolic phospholipase A(2)α (cPLA(2)α) is the rate-limiting enzyme for release of arachidonic acid, which is converted primarily to PGs via the cyclooxygenase 1 and 2 pathways and to leukotrienes via the 5-lipoxygenase pathway. We used adoptive transfer and relapsing-remitting forms of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, in two different strains of mice (SJL or C57BL/6) to demonstrate that blockade of cPLA(2)α with a highly specific small-molecule inhibitor during the tissue-damage effector phase abrogates the clinical manifestation of disease. Using the adoptive transfer model in SJL mice, we demonstrated that the blockade of cPLA(2)α during the effector phase of disease was more efficacious in ameliorating the disease pathogenesis than the blockade of each of the downstream enzymes, cyclooxygenase-1/2 and 5-lipooxygenase. Similarly, blockade of cPLA(2)α was highly efficacious in ameliorating disease pathogenesis during the effector phase of EAE in the adoptive transfer model of EAE in C57BL/6 mice. Investigation of the mechanism of action indicates that cPLA(2)α inhibitors act on APCs to diminish their ability to induce Ag-specific effector T cell proliferation and proinflammatory cytokine production. Furthermore, cPLA(2)α inhibitors may prevent activation of CNS-resident microglia and may increase oligodendrocyte survival. Finally, in a relapsing-remitting model of EAE in SJL mice, therapeutic administration of a cPLA(2)α inhibitor, starting from the peak of disease or during remission, completely protected the mice from subsequent relapses.

Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas (Iguana iguana).

OBJECTIVE: To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity. ANIMALS: 21 healthy green iguanas (Iguana iguana). PROCEDURES: To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg). RESULTS: There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 µg•h/mL and 5.83 ± 2.49 µg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 µg/mL) versus PO (0.19 ± 0.07 µg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 µg/mL for approximately 24 hours.

Mice lacking Tbk1 activity exhibit immune cell infiltrates in multiple tissues and increased susceptibility to LPS-induced lethality.

TBK1 is critical for immunity against microbial pathogens that activate TLR4- and TLR3-dependent signaling pathways. To address the role of TBK1 in inflammation, mice were generated that harbor two copies of a mutant Tbk1 allele. This Tbk1(Δ) allele encodes a truncated Tbk1(Δ) protein that is catalytically inactive and expressed at very low levels. Upon LPS stimulation, macrophages from Tbk1(Δ/Δ) mice produce normal levels of proinflammatory cytokines (e.g., TNF-α), but IFN-ß and RANTES expression and IRF3 DNA-binding activity are ablated. Three-month-old Tbk1(Δ/Δ) mice exhibit mononuclear and granulomatous cell infiltrates in multiple organs and inflammatory cell infiltrates in their skin, and they harbor a 2-fold greater amount of circulating monocytes than their Tbk1(+/+) and Tbk1(+/Δ) littermates. Skin from 2-week-old Tbk1(Δ/Δ) mice is characterized by reactive changes, including hyperkeratosis, hyperplasia, necrosis, inflammatory cell infiltrates, and edema. In response to LPS challenge, 3-month-old Tbk1(Δ/Δ) mice die more quickly and in greater numbers than their Tbk1(+/+) and Tbk1(+/Δ) counterparts. This lethality is accompanied by an overproduction of several proinflammatory cytokines in the serum of Tbk1(Δ/Δ) mice, including TNF-α, GM-CSF, IL-6, and KC. This overproduction of serum cytokines in Tbk1(Δ/Δ) mice following LPS challenge and their increased susceptibility to LPS-induced lethality may result from the reactions of their larger circulating monocyte compartment and their greater numbers of extravasated immune cells.

Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells.

OBJECTIVE: Patients with psoriasis and psoriatic arthritis respond well to tumor necrosis factor alpha (TNFalpha) blockers in general; however, there is now mounting evidence that a small cohort of patients with rheumatoid arthritis who receive TNFalpha blockers develop psoriasis. This study was undertaken to explore the mechanisms underlying TNFalpha blockade-induced exacerbation of skin inflammation in murine psoriasis-like skin disease. METHODS: Skin inflammation was induced in BALB/c scid/scid mice after they received CD4+CD45RB(high)CD25- (naive CD4) T cells from donor mice. These mice were treated with either anti-interleukin-12 (anti-IL-12)/23p40 antibody or murine TNFRII-Fc fusion protein and were examined for signs of disease, including histologic features, various cytokine levels in the serum, and cytokine or FoxP3 transcripts in the affected skin and draining lymph node (LN) cells. In a separate study, naive CD4+ T cells were differentiated into Th1 or Th17 lineages with anti-CD3/28 magnetic beads and appropriate cytokines in the presence or absence of TNFalpha. Cytokine gene expression from these differentiated cells was also determined. RESULTS: Neutralization of TNFalpha exacerbated skin inflammation and markedly enhanced the expression of the proinflammatory cytokines IL-1beta, IL-6, IL-17, IL-21, and IL-22 but suppressed FoxP3 expression in the skin and reduced the number of FoxP3-positive Treg cells in the draining LNs. TNFalpha also demonstrated a divergent role during priming and reactivation of naive T cells. CONCLUSION: These results reveal a novel immunoregulatory role of TNFalpha on Th17 and Treg cells in some individuals, which may account for the exacerbation of skin inflammation in some patients who receive anti-TNF treatments.

Proventricular nematodiasis in wrinkled hornbills (Aceros corrugatus).

Three immature Sunda wrinkled hornbills (Aceros corrugatus) were diagnosed postmortem with proventricular spirurid nematodiasis. Concurrent severe disseminated larval granulomatosis in other visceral organs was considered contributory to mortality in each case. Clinical signs of nematodiasis were vague but generally consisted of weight loss, anorexia, and lethargy. Frequent antemortem fecal examinations were negative for spirurid eggs. In these present cases, based on routine histopathology, both prophylactic and empirically based therapeutic anthelmintic treatments had no evident benefit in the elimination of the proventricular nematodes. Spirurid nematodiasis may be an important cause of mortality in young hornbills.

Disruption of G protein-coupled receptor 39 impairs insulin secretion in vivo.

GPR39 is a G protein-coupled receptor expressed in liver, gastrointestinal tract, adipose tissue, and pancreas. We have recently shown that young GPR39(-/-) mice have normal body weight, food intake, and fasting glucose and insulin levels. In this study, we examined the role of GPR39 in aging and diet-induced obese mice. Body weight and food intake were similar in wild-type and GPR39(-/-) mice as they aged from 12 to 52 wk or when fed a low-fat/high-sucrose or high-fat/high-sucrose diet. Fifty-two-week-old GPR39(-/-) mice showed a trend toward decreased insulin levels after oral glucose challenge. When fed either a low-fat/high-sucrose or high-fat/high-sucrose diet, GPR39(-/-) mice had increased fed glucose levels and showed decreased serum insulin levels during an oral glucose tolerance test in the face of unchanged insulin tolerance. Pancreas morphology and glucose-stimulated insulin secretion in isolated islets from wild-type and GPR39(-/-) mice were comparable, suggesting that GPR39 is not required for pancreas development or ex vivo insulin secretion. Small interfering RNA-mediated knockdown of GPR39 in clonal NIT-1 beta-cells revealed that GPR39 regulates the expression of insulin receptor substrate-2 and pancreatic and duodenal homeobox-1 in a cell-autonomous manner; insulin receptor substrate-2 mRNA was also significantly decreased in the pancreas of GPR39(-/-) mice. Taken together, our data indicate that GPR39 is required for the increased insulin secretion in vivo under conditions of increased demand, i.e. on development of age-dependent and diet-induced insulin resistance. Thus, GPR39 agonists may have potential for the treatment of type 2 diabetes.