314 research outputs found

    Atrial Fibrillation in Eight New World Camelids.

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    BackgroundThere is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC).ObjectiveDescribe clinical signs and outcome of AF in NWC.AnimalsEight New World Camelids admitted with AF.MethodsA retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG).ResultsAll animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8).Conclusions and clinical importanceAtrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions

    Silencing cytokeratin 18 gene inhibits intracellular replication of Trypanosoma cruzi in HeLa cells but not binding and invasion of trypanosomes

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    <p>Abstract</p> <p>Background</p> <p>As an obligatory intracellular parasite, <it>Trypanosoma cruzi</it>, the etiological agent of Chagas' disease, must invade and multiply within mammalian cells. Cytokeratin 18 (CK18) is among the host molecules that have been suggested as a mediator of important events during <it>T. cruzi</it>-host cell interaction. Based on that possibility, we addressed whether RNA interference (RNAi)-mediated down regulation of the CK18 gene could interfere with the parasite life cycle <it>in vitro</it>. HeLa cells transiently transfected with CK18-RNAi had negligible levels of CK18 transcripts, and significantly reduced levels of CK18 protein expression as determined by immunoblotting or immunofluorescence.</p> <p>Results</p> <p>CK18 negative or positive HeLa cells were invaded equally as well by trypomastigotes of different <it>T. cruzi </it>strains. Also, in CK18 negative or positive cells, parasites recruited host cells lysosomes and escaped from the parasitophorous vacuole equally as well. After that, the growth of amastigotes of the Y or CL-Brener strains, was drastically arrested in CK18 RNAi-treated cells. After 48 hours, the number of amastigotes was several times lower in CK18 RNAi-treated cells when compared to control cells. Simultaneous staining of parasites and CK18 showed that in HeLa cells infected with the Y strain both co-localize. Although the amastigote surface protein-2 contains the domain VTVXNVFLYNR previously described to bind to CK18, in several attempts, we failed to detect binding of a recombinant protein to CK-18.</p> <p>Conclusion</p> <p>The study demonstrates that silencing CK18 by transient RNAi, inhibits intracellular multiplication of the Y and CL strain of <it>T. cruzi </it>in HeLa cells, but not trypanosome binding and invasion.</p

    Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse

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    The amyloid precursor protein (APP) is well known for giving rise to the amyloid-β peptide and for its role in Alzheimer's disease. Much less is known, however, on the physiological roles of APP in the development and plasticity of the central nervous system. We have used phage display of a peptide library to identify high-affinity ligands of purified recombinant human sAPPα695 (the soluble, secreted ectodomain from the main neuronal APP isoform). Two peptides thus selected exhibited significant homologies with the conserved extracellular domain of several members of the semaphorin (Sema) family of axon guidance proteins. We show that sAPPα695 binds both purified recombinant Sema3A and Sema3A secreted by transfected HEK293 cells. Interestingly, sAPPα695 inhibited the collapse of embryonic chicken (Gallus gallus domesticus) dorsal root ganglia growth cones promoted by Sema3A (Kd≤8·10−9 M). Two Sema3A-derived peptides homologous to the peptides isolated by phage display blocked sAPPα binding and its inhibitory action on Sema3A function. These two peptides are comprised within a domain previously shown to be involved in binding of Sema3A to its cellular receptor, suggesting a competitive mechanism by which sAPPα modulates the biological action of semaphorins

    Perspectives on the Trypanosoma cruzi-host cell receptor interaction

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    Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

    Dynasore, a Dynamin Inhibitor, Inhibits Trypanosoma cruzi Entry into Peritoneal Macrophages

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    BACKGROUND: Trypanosoma cruzi is an intracellular parasite that, like some other intracellular pathogens, targets specific proteins of the host cell vesicular transport machinery, leading to a modulation of host cell processes that results in the generation of unique phagosomes. In mammalian cells, several molecules have been identified that selectively regulate the formation of endocytic transport vesicles and the fusion of such vesicles with appropriate acceptor membranes. Among these, the GTPase dynamin plays an important role in clathrin-mediated endocytosis, and it was recently found that dynamin can participate in a phagocytic process. METHODOLOGY/PRINCIPAL FINDINGS: We used a compound called dynasore that has the ability to block the GTPase activity of dynamin. Dynasore acts as a potent inhibitor of endocytic pathways by blocking coated vesicle formation within seconds of its addition. Here, we investigated whether dynamin is involved in the entry process of T. cruzi in phagocytic and non-phagocytic cells by using dynasore. In this aim, peritoneal macrophages and LLC-MK2 cells were treated with increasing concentrations of dynasore before interaction with trypomastigotes, amastigotes or epimastigotes. We observed that, in both cell lines, the parasite internalization was drastically diminished (by greater than 90% in LLC-MK2 cells and 70% in peritoneal macrophages) when we used 100 microM dynasore. The T. cruzi adhesion index, however, was unaffected in either cell line. Analyzing these interactions by scanning electron microscopy and comparing peritoneal macrophages to LLC-MK2 cells revealed differences in the stage at which cell entry was blocked. In LLC-MK2 cells, this blockade is observed earlier than it is in peritoneal macrophages. In LLC-MK2 cells, the parasites were only associated with cellular microvilli, whereas in peritoneal macrophages, trypomastigotes were not completely engulfed by a host cell plasma membrane. CONCLUSIONS/SIGNIFICANCE: Taken together our results demonstrate that dynamin is an essential molecule necessary for cell invasion and specifically parasitophorous vacuole formation by host cells during interaction with Trypanosoma cruzi

    The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007-2012)

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    BACKGROUND: Information about treatment protocols, adverse effects and outcomes with intrapleural recombinant tissue plasminogen activator (rTPA) use in horses with fibrinous pleuropneumonia is limited. HYPOTHESIS/OBJECTIVES: Describe factors that contribute to clinical response and survival of horses treated with rTPA intrapleurally. ANIMALS: Horses with bacterial pneumonia and fibrinous pleural effusion diagnosed by ultrasonography, that were treated with rTPA intrapleurally. METHODS: Retrospective multicenter case series from 2007-2012. Signalment, history, clinical and laboratory evaluation, treatment, and outcome obtained from medical records. Regression analysis used to identify associations between treatments and outcomes. RESULTS: Thirty three hemithoraces were treated in 25 horses, with 55 separate treatments. Recombinant tissue plasminogen activator (375-20,000 μg/hemithorax) was administered 1-4 times. Sonographically visible reduction in fibrin mat thickness, loculations, fluid depth, or some combination of these was seen in 32/49 (65%) treatments. Response to at least 1 treatment was seen in 17/20 (85%) horses with sonographic follow-up evaluation after every treatment. Earlier onset of rTPA treatment associated with increased survival odds. No association was found between cumulative rTPA dose or number of rTPA doses and survival, development of complications, duration of hospitalization or total charges. Clinical evidence of hypocoagulability or bleeding was not observed. Eighteen horses (72%) survived to discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment with rTPA appeared safe and resulted in variable changes in fibrin quantity and organization within the pleural space. Recombinant tissue plasminogen activator could be a useful adjunct to standard treatment of fibrinous pleuropneumonia, but optimal case selection and dosing regimen remain to be elucidated

    Hemodynamic parameters to guide fluid therapy

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    The clinical determination of the intravascular volume can be extremely difficult in critically ill and injured patients as well as those undergoing major surgery. This is problematic because fluid loading is considered the first step in the resuscitation of hemodynamically unstable patients. Yet, multiple studies have demonstrated that only approximately 50% of hemodynamically unstable patients in the intensive care unit and operating room respond to a fluid challenge. Whereas under-resuscitation results in inadequate organ perfusion, accumulating data suggest that over-resuscitation increases the morbidity and mortality of critically ill patients. Cardiac filling pressures, including the central venous pressure and pulmonary artery occlusion pressure, have been traditionally used to guide fluid management. However, studies performed during the past 30 years have demonstrated that cardiac filling pressures are unable to predict fluid responsiveness. During the past decade, a number of dynamic tests of volume responsiveness have been reported. These tests dynamically monitor the change in stroke volume after a maneuver that increases or decreases venous return (preload) and challenges the patients' Frank-Starling curve. These dynamic tests use the change in stroke volume during mechanical ventilation or after a passive leg raising maneuver to assess fluid responsiveness. The stroke volume is measured continuously and in real-time by minimally invasive or noninvasive technologies, including Doppler methods, pulse contour analysis, and bioreactance
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