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Babesiosis is a disease of significant veterinary importance with worldwide distribution. It is caused by intra-erythrocyte protozoal parasites, with Babesia rossi causing the most severe clinical signs of all the large Babesia parasites infecting dogs. The disease can be clinically classified into uncomplicated and complicated forms with a wide range of clinical presentations from a mild, subclinical illness to complicated forms and death. The aim of this study was to assess serum proteomic profiles from dogs with babesiosis and healthy dogs using a label-based proteomics approach. Altogether 32 dogs naturally infected with B. rossi (subdivided into 18 uncomplicated cases and 14 complicated cases of babesiosis) and 20 healthy dogs were included. There were 78 proteins with significantly different abundances between the three groups of dogs. Elucidation of proteins and pathways involved in canine babesiosis caused by B. rossi have revealed key differences associated with haemostasis, innate immune system, lipid metabolism and inflammation. Shotgun proteomic profiling allowed identification of potential serum biomarkers for differentiation of disease severity in canine babesiosis caused by B. rossi. These findings may be applicable to the study of host-parasite interactions and the development of novel therapeutic targets.

Staphylococcus pseudintermedius (SP) is an important opportunistic pathogen, frequently associated with pyoderma and otitis in dogs. The emergence and rapid expansion of methicillin-resistant Staphylococcus pseudintermedius (MRSP) is problematic due to multidrug resistance and reduced treatment options. The aim of this study was to determine i) the prevalence of MRSP in dogs with pyoderma or otitis externa, ii) the antimicrobial resistance patterns of MRSP from South African isolates, and iii) the risk factors for MRSP-associated pyoderma or otitis externa in dogs in South Africa (RSA). Sixty-eight presumptive clinical SP isolates (collected from 65 dogs) from five geographically dispersed laboratories in RSA were collected over 2 years. Possible MRSP isolates were flagged when resistance to oxacillin was observed. Thereafter, all isolates were confirmed as SP by polymerase chain reaction (PCR) and further genotyped for the mecA gene. Fifty-seven of 68 isolates were confirmed to be SP (83.8%), while 49/57 (85.9%) carried mecA. Our findings showed that preliminary phenotypic methods supplemented by genotypic methods increased the accuracy of correctly identifying SP. All isolates were resistant to at least one antimicrobial drug. There was a high incidence of amoxicillin (70.1%) and enrofloxacin (65%) resistance. Important risk factors for mecA positive carriage were previous hospital admission, pruritus, and previous antibacterial failure. This study demonstrates a high prevalence of mecA positive carriage (85.9% of samples) in MRSP pyoderma and otitis in dogs in RSA. There is an urgent need for better laboratory diagnosis of MRSP and surveillance of dogs presenting with pyoderma and otitis in South Africa.

Few reports of clinical Bluetongue virus (BTV) infections have been described in dogs. Most cases were linked to inoculation with a BTV-contaminated canine modified live vaccine. In dogs, cases have only been described in pregnant females with clinical signs of fever and abortion followed by severe dyspnoea and death. A pregnant Rottweiler dog was presented with a three-day history of progressive lethargy and anorexia. The patient was a guard dog living in an enclosure where sheep were kept at night. High mortalities had been experienced in the sheep but had not been investigated. On presentation, the major clinical findings were dyspnoea and hypoxia. Clinicopathological tests showed hypoxia and systemic inflammation. Radiological findings were consistent with non-cardiogenic pulmonary oedema. The patient was treated symptomatically and recovered but did not retain the pregnancy. Bluetongue virus was identified in the patient's blood using BTV RT-PCR (Ct value 24.7). At a follow-up farm visit, an ongoing BTV outbreak in the sheep was diagnosed with affected sheep testing positive for BTV on RT-PCR. This report describes the clinical presentation, diagnostic investigations and successful treatment of a dog with BTV infection. This is the first case report of a naturally occurring clinical BTV infection in a dog. Possible routes of infection were direct contact, midgeborne, or ingestion of infected afterbirth or abortus from sheep.

Babesia rossicauses severe morbidity and mortality in dogs in sub-Saharan Africa, and the complications associated with this disease are likely caused by an unfocused, excessive inflammatory response. During this experimentalB. rossistudy we investigated inflammatory marker and cytokine kinetics during infection and after treatment. We aimed to determine whether infectious dose and treatment would influence the progression of the inflammatory response and clinical disease. Five healthy male beagle dogs were infected withB. rossi, three with a high infectious dose (HD group) and two with a low infectious dose (LD group). Clinical examination, complete blood count (CBC) and C-reactive protein (CRP) were determined daily. Cytokines were quantified on stored plasma collected during the study, using a canine specific cytokine magnetic bead panel (Milliplex©). The experiment was terminated when predetermined endpoints were reached. Parasitemia occurred on day 1 and 3 in the HD group and LD group respectively. The rate of increase in parasitemia in the HD group was significantly faster than that seen in the LD group. Significant differences were found in heart rate, blood pressure, interferon gamma (INFγ), keratinocyte chemoattractant (KC), INFγ-induced protein 10 (IP10), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP1), tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), IL-6, IL-7, IL-8, IL-10 IL-15, IL-18, CRP, neutrophils and monocytes between groups at multiple time points during the course of the infection. Our findings suggest that the initiation of inflammation occurs before the onset of clinical disease inB. rossiinfection and infectious dose influences the onset of the inflammatory response. Treatment not only fails to curb the inflammatory response but may enhance it. Finally, we found that there is an imbalance in pro/anti-inflammatory cytokine concentrations during infection which may promote parasite replication.

Introduction: The high demand for critical care beds and the need for mechanical ventilation generated by the pandemia of COVID-19 led the Ministry of Health of Chile to authorize both the conversion of beds and the use of anesthesia machines to mechanically ventilate COVID-19 patients. At Clínica Alemana de Santiago (CAS), these converted units were managed by non-intensivist anesthesiologists with technical support from the Intensive Care Unit (ICU). The objective of this study was to compare the survival rate of patients managed at converted and traditional ICU units. The secondary objective was to analyze the factors that may affect morbidity and mortality of these patients. Method: This prospective observational study included mechanically ventilated COVID-19 patients in both traditional and converted units. Patients were followed for 90 days starting at intubation day. Survival rate was determined at 30 and 90 days. A survival analysis was then performed. Results: 41 and 42 patients were admitted to CAS trough converted and traditional ICU units, respectively, between May 24 and June 30, 2020. There was not significant difference in survival rate between converted and traditional ICU units. Age (HR 1.1 per year) and SOFA (HR 1.4 per point) were associated with survival. Conclusions: At CAS, the survival of COVID-19 patients who required mechanical ventilation in converted units was not different as in those patients treated in traditional ICU units. Both age and SOFA were variables that can inform about prognosis of these patients.

BackgroundBabesia rossiis a leading cause of morbidity and mortality among the canine population of sub-Saharan Africa, but pathogenesis remains poorly understood. Previous studies ofB. rossiinfection were derived from clinical cases, in which neither the onset of infection nor the infectious inoculum was known. Here, we performed controlledB. rossiinoculations in canines and evaluated disease progression through clinical tests and whole blood transcriptomic profiling.ResultsTwo subjects were administered a low inoculum (104parasites) while three received a high (108parasites). Subjects were monitored for 8 consecutive days; anti-parasite treatment with diminazene aceturate was administered on day 4. Blood was drawn prior to inoculation as well as every experimental day for assessment of clinical parameters and transcriptomic profiles. The model recapitulated natural disease manifestations including anemia, acidosis, inflammation and behavioral changes. Rate of disease onset and clinical severity were proportional to the inoculum. To analyze the temporal dynamics of the transcriptomic host response, we sequenced mRNA extracted from whole blood drawn on days 0, 1, 3, 4, 6, and 8. Differential gene expression, hierarchical clustering, and pathway enrichment analyses identified genes and pathways involved in response to hemolysis, metabolic changes, and several arms of the immune response including innate immunity, adaptive immunity, and response to viral infection.ConclusionsThis work comprehensively characterizes the clinical and transcriptomic progression ofB. rossiinfection in canines, thus establishing a large mammalian model of severe hemoprotozoal disease to facilitate the study of host-parasite biology and in which to test novel anti-disease therapeutics. The knowledge gained from the study ofB. rossiin canines will not only improve our understanding of this emerging infectious disease threat in domestic dogs, but also provide insight into the pathobiology of human diseases caused byBabesiaandPlasmodiumspecies.

Additional file 3: Table S3. Pearson correlation values of erythroblast transcript trajectory with reticulocyte count. The expression level of each gene (in CPM) was correlated with the reticulocyte count (109/L) on each day. This allowed for correlation based on expression trajectory through time.

Additional file 1: Table S1. A summary of MultiQC data. Shown are the number of reads mapped (in millions), percent of these reads aligned to the canine reference genome, and percent GC content of these reads. Samples corresponding to low inoculum day 4 and high inoculum days 3 and 4 were not included in the mean.

Additional file 2: Table S2. DEGs on every day in both inoculum cohorts. Genes that were differentially expressed on every experimental day in both cohorts (except day 1 in the low inoculum) are shown, along with their corresponding cluster.

To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061−0.069; n = 346), and that 88% (95% CI 80.7−93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83−2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24−7.69) and the HR in males 0.79 (95% CI 0.41−1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11−0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.

Dogs with babesiosis can present with multiple complications, including acute kidney injury (AKI). The objective of this study was to characterize AKI in dogs with babesiosis caused by Babesia rossi at presentation and after treatment. Thirty-five client-owned dogs with B. rossi infection and 10 control dogs were included in this prospective observational study. Blood and urine were collected in Babesia-infected dogs at presentation (T-0, n = 35), after 24 h (T-24h, n = 11), and after 1 month (T-1m, n = 9). The following urinary kidney injury biomarkers were assessed: urinary protein to creatinine ratio (UPC), urinary glomerular injury biomarkers (immunoglobulin G (uIgG) and C-reactive protein (uCRP)), and urinary tubular injury biomarkers (retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL)). Serum functional renal biomarkers were creatinine (sCr) and symmetric dimethylarginine (sSDMA). Post-mortem kidney biopsies were analyzed by light and transmission electron microscopy. At T-0, all kidney injury biomarkers were significantly higher in Babesia-infected dogs compared to healthy controls (P < 0.001), while functional renal biomarkers were not significantly different (P > 0.05). At T-24h, all urinary tubular injury biomarkers and UPC decreased significantly (P < 0.01), while glomerular injury biomarkers did not (P = 0.084). At T-1m, all urinary kidney injury biomarkers decreased to values not significantly different from healthy controls (P > 0.5). Significant changes in functional renal biomarkers were not seen after treatment (P > 0.05). Dogs with complicated babesiosis had significantly higher glomerular injury biomarkers, UPC, and sSDMA compared to uncomplicated cases (P < 0.05), while all tubular injury biomarkers and sCr were not significantly different (P > 0.1). Dogs with babesiosis caused by B. rossi showed transient kidney injury, which was detected by all kidney injury biomarkers, but remained undetected by functional biomarkers. All infected dogs, irrespective of disease severity, suffered comparable kidney injury based on tubular injury biomarker concentrations, while loss of function was seen more often in dogs with complicated babesiosis based on sSDMA results.

Babesia rossi is an important, tick-borne intraerythrocytic protozoan parasite; however, its natural history and epidemiology is poorly understood. Babesia rossi is the most virulent Babesia sp. in domestic dogs and is generally considered to cause severe babesiosis, which is fatal if left untreated. However, subclinical infections and mild disease from B. rossi have been reported, although the clinical progression of these cases was not reported. Therefore, to better understand B. rossi under field conditions, we evaluated its clinical progression and seroprevalence in an owned, free-roaming dog population in Zenzele, South Africa, where the parasite is endemic and prevention is not routine. The entire dog population in Zenzele was monitored intensively at the individual level from March 2008 until April 2014, primarily for a longitudinal study on rabies control. Subsequent evaluation of B. rossi comprised analyses of clinical and laboratory data collected from the Zenzele dog population during the 6 year study period. A substantial proportion (31% (n = 34)) of 109 dogs (randomly selected from every available dog in February/March 2010 older than ~6–8 weeks (n = 246)) tested by Indirect Fluorescent Antibody Test had seroconverted strongly to B. rossi. All 34 dogs were generally consistently healthy adults, determined from regular clinical examinations between March 2008 and April 2014. Blood smear examinations at multiple time points between July 2009 and February 2011 were also undertaken for almost all of these (34) seropositive dogs and all those tested were consistently negative for Babesia spp. Subclinical infections and mild disease were also the main findings for a separate group of 18 dogs positive for Babesia spp. on blood smear examination and confirmed to be infected with B. rossi by Polymerase Chain Reaction – Reverse Line Blot. Almost all of these dogs were positive at only one time point from repeat blood smear examinations between July 2009 and February 2011. We suggest that these observations are consistent with immunity acquired from repeated, low-level exposure to the parasite, generating transient subclinical infections or mild disease. Should this be the case, the use of tick control, particularly in adult dogs in free-roaming populations in B. rossi endemic regions, should be carefully considered.

// Benjamin Garcia-Bloj 1, 2, 4 , Colette Moses 1, 2 , Agustin Sgro 1 , Janice Plani-Lam 1 , Mahira Arooj 1, 5 , Ciara Duffy 1, 2 , Shreyas Thiruvengadam 1 , Anabel Sorolla 1 , Rabab Rashwan 1 , Ricardo L. Mancera 5 , Andrea Leisewitz 4 , Theresa Swift-Scanlan 6 , Alejandro H. Corvalan 3, 4 , Pilar Blancafort 1, 2 1 Cancer Epigenetics group, The Harry Perkins Institute of Medical Research, Perth, WA, 6009, Australia 2 School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, WA, 6009, Australia 3 Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Catolica de Chile, Santiago, RM, 8330034, Chile 4 Faculty of Medicine, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, RM, 8330034, Chile 5 School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth WA 6845, Australia 6 School of Nursing, Virginia Commonwealth University, Richmond, Virginia, 23298, USA Correspondence to: Pilar Blancafort, email: pilar.blancafort@uwa.edu.au Keywords: CRISPR/dCas9, ZF, TALE, tumor suppressor genes, gene reactivation Received: June 01, 2016 Accepted: July 19, 2016 Published: August 09, 2016 ABSTRACT The aberrant epigenetic silencing of tumor suppressor genes (TSGs) plays a major role during carcinogenesis and regaining these dormant functions by engineering of sequence-specific epigenome editing tools offers a unique opportunity for targeted therapies. However, effectively normalizing the expression and regaining tumor suppressive functions of silenced TSGs by artificial transcription factors (ATFs) still remains a major challenge. Herein we describe novel combinatorial strategies for the potent reactivation of two class II TSGs, MASPIN and REPRIMO , in cell lines with varying epigenetic states, using the CRISPR/dCas9 associated system linked to a panel of effector domains (VP64, p300, VPR and SAM complex), as well as with protein-based ATFs, Zinc Fingers and TALEs. We found that co-delivery of multiple effector domains using a combination of CRISPR/dCas9 and TALEs or SAM complex maximized activation in highly methylated promoters. In particular, CRISPR/dCas9 VPR with SAM upregulated MASPIN mRNA (22,145-fold change) in H157 lung cancer cells, with accompanying re-expression of MASPIN protein, which led to a concomitant inhibition of cell proliferation and induction of apoptotic cell death. Consistently, CRISPR/dCas9 VP64 with SAM upregulated REPRIMO (680-fold change), which led to phenotypic reprogramming in AGS gastric cancer cells. Altogether, our results outlined novel sequence-specific, combinatorial epigenome editing approaches to reactivate highly methylated TSGs as a promising therapy for cancer and other diseases.

The occurrence of acute kidney injury in canine babesiosis is not well documented. Furthermore, interpretation of urine specific gravity (USG) to assess renal concentrating ability is hampered by the frequent presence of hemoglobinuria in this disease. This cross-sectional study aimed to test the hypothesis that renal azotemia (RA) is underdiagnosed according to current canine babesiosis literature by determining its occurrence at presentation, using urine osmolality instead of USG to measure urinary concentration. The second objective was to examine potential associations between the presence of RA and selected clinical and laboratory variables at presentation. Medical records available from 3 previously performed prospective data collections were reviewed retrospectively. Client-owned dogs that were diagnosed with babesiosis caused by Babesia rossi, were included if a complete blood count, biochemistry profile, and urinalysis was performed at admission. Urine osmolality was measured to identify dogs with RA. Differences between dogs with RA and dogs without RA were assessed by nonparametric statistics. One hundred and fifty-two dogs were included, of which 26 (17%) were azotemic at admission. The occurrence of RA was 14% (21/152), hence 81% (21/26) of all azotemic dogs were diagnosed with RA. In contrast, when diagnosis of RA was based on an admission USG 1.030, only 23% (6/26) of the azotemic dogs would have been considered to have RA. Several signalment and clinicopathological findings were found to be associated with the presence of RA, including older age, and the presence of collapse, hypoglycemia, hyperphosphatemia, cerebral babesiosis, and acute respiratory distress syndrome. Lastly, survival at discharge was significantly lower in dogs diagnosed with RA at presentation. Our results clarified that RA is more common than previously reported in B. rossi. This study also demonstrated that USG determination is not a reliable method to evaluate renal concentrating ability in azotemic dogs with babesiosis. Thus, if available, urine osmolality should be part of the diagnostic work-up of dogs infected with B. rossi to avoid misclassification of dogs with RA as having prerenal azotemia. If urine osmolality cannot be measured, clinicians should realize that most azotemic dogs with B. rossi infection have RA.

Immunity to Babesia infection requires both innate and acquired responses, including cell mediated- and humoral responses. The aims of this study were to investigate the variation in selected peripheral blood lymphocyte phenotypes in dogs with virulent babesiosis at presentation and over time after treatment, and to determine whether these were correlated with the severity of clinical signs. Forty-four dogs naturally infected with B. rossi were studied and 5 healthy dogs were included as controls. Blood samples were collected from the jugular vein at admission, prior to any treatment, and at 24 hours and 48–72 hours. Leukocytes were incubated with canine specific, fluorochrome conjugated anti-CD3, anti-CD4, anti-CD8, and anti-B cell markers. Babesia-infected dogs were divided into complicated or uncomplicated groups on clinical grounds and in-house laboratory assays. The percentage CD3+ lymphocytes in the complicated group was lower compared to the controls (P = 0.014) and uncomplicated group (P = 0.007). The percentage CD4+ T lymphocytes in the complicated group was lower compared to the controls (P = 0.027) and uncomplicated group (P = 0.014). Both the complicated as well as the uncomplicated groups expressed a lower percentage CD8+ T lymphocytes compared to the control group (P < 0.001 and P = 0.005, respectively). The percentage B lymphocytes was higher in the complicated group at 48–72 hours. These findings could indicate the presence of a functional immune suppression secondary to increased apoptosis or redistribution of effector lymphocytes and/or a combination of other immune modulatory mechanisms induced by B. rossi infection.

The acid–base disturbances in canine parvoviral (CPV) enteritis are not well described. In addition, the mechanisms causing these perturbations have not been fully elucidated. The purpose of the present study was to assess acid–base changes in puppies suffering from CPV enteritis, using a modified strong ion model (SIM). The hypothesis of the study was that severe acid–base disturbances would be present and that the SIM would provide insights into pathological mechanisms, which have not been fully appreciated by the Henderson–Hasselbalch model. The study analysed retrospective data, obtained from 42 puppies with confirmed CPV enteritis and 10 healthy control dogs. The CPV-enteritis group had been allocated a clinical score, to allow classification of the data according to clinical severity. The effects of changes in free water, chloride, l-lactate, albumin and phosphate were calculated, using a modification of the base excess algorithm. When the data were summated for each patient, and correlated to each individual component, the most important contributor to the metabolic acid–base changes, according to the SIM, was chloride (P

Canine parvovirus (CPV) enteritis has, since its emergence in 1978, remained a common and important cause of morbidity and mortality in young dogs. The continued incidence of parvoviral enteritis is partly due to the virus' capability to evolve into more virulent and resistant variants with significant local gastrointestinal and systemic inflammatory sequelae. This paper reviews current knowledge on historical-, signalment-, and clinical factors as well as several haematological-, biochemical- and endocrine parameters that can be used as diagnostic and prognostic biomarkers in CPV enteritis. These factors include season of presentation, purebred nature, bodyweight, vomiting, leukopaenia, lymphopaenia, thrombocytopaenia, hypercoagulability, hypercortisolaemia, hypothyroxinaemia, hypoalbuminaemia, elevated C-reactive protein and tumour necrosis factor, hypocholesterolaemia and hypocitrullinaemia. Factors contributing to the manifestations of CPV infection are multiple with elements of host, pathogen, secondary infections, underlying stressors and environment affecting severity and outcome. The availability of several prognosticators has made identification of patients at high risk of death and their subsequent targeted management more rewarding.

Acute myeloid leukemia (AML) has a high mortality rate despite chemotherapy and transplantation. Both CXCR4/SDF-1 and VLA-4/VCAM1 axes are involved in leukemia protection but little is known about the role of CCL2/CCR2 in AML biology and protection against chemotherapy. We measured CCR2 expression in AML cell lines and primary AML cells by flow cytometry (FCM), real time PCR (RT-PCR) and western blot (WB). CCL2 production was quantified by solid phase ELISA in peripheral blood (PB) and bone marrow (BM) serum. We measured chemotaxis in a transwell system with different concentrations of CCL2/CCR2 blockers; cell cycle with BrDU and propidium iodide and proliferation with yellow tetrazolium MTT. We determined synergy in in vitro cell apoptosis combining chemotherapy and CCL2/CCR2 blockade. Finally, we performed chemoprotection studies in an in vivo mouse model. Of 35 patients, 23 (65%) expressed CCR2 by FCM in PB. Two cell lines expressed high levels of CCR2 (THP-1 and murine AML). RT-PCR and WB confirmed CCR2 production. CCL2 solid phase ELISA showed significantly lower levels of CCL2 in PB and BM compared to normal controls. Chemotaxis experiments confirmed a dose-dependent migration in AML primary cells expressing CCR2 and THP-1 cells. A significant inhibition of transmigration was seen after CCL2/CCR2 blockade. Proliferation of CCR2+ AML cell lines was slightly increased (1.4-fold) after axis stimulation. We observed a non-significant increase in phase S THP-1 cells exposed to CCL2 and a concomitant decrease of cells in G1. The chemotherapy studies did not show a protective effect of CCL2 on cytarabine-induced apoptosis or synergy with chemotherapy after CCL2/CCR2 blockade both in vitro and in vivo. In conclusion, CCL2/CCR2 axis is expressed in the majority of monocytoid AML blasts. The axis is involved in cell trafficking and proliferation but no in vitro and in vivo chemotherapy protective effect was seen.

The major defence mechanism in frogs is via the secretion of toxins from their skin. In humans, intoxication may occur when part of the amphibian integument is ingested, as in the form of herbal medicines. Two groups of South African frogs have skin secretions that are potentially lethal to humans and animals. Toad (Bufo and Schismademra pecies), the amphibian with which man and his pets most frequently have contact, secrete potent toxins with cardiac glycoside activity. Topical and systemic intoxication, while seen in humans, remains predominantly a veterinary problem. Intoxication by the red-banded rubber frog, which secretes an unidentified cardiotoxin, is far less common. The probable mechanisms of intoxication and management of a poisoned patient are discussed.