Downregulation of L3T4+ cytotoxic T lymphocytes by interleukin-2

Proliferation of activated cytotoxic T lymphocytes (CTLs) that recognize foreign histocompatibility antigens is induced by interleukin-2, a potent immunoregulatory molecule originally described as T cell growth factor. Interleukin-2 (IL-2) is widely used to isolate and induce clonal expansion of CTLs for functional studies in vitro and in vivo. However, in studies with CTLs specific for class I and class II histocompatibility antigens, IL-2 rapidly downregulated the lytic activity of some class II-specific CTLs in a time- and dose-dependent manner. Lytic activity of L3T4+ CTLs specific for the murine class II antigen I-Ek was repeatedly up- and downregulated in vitro by alternate exposure to specific (alloantigen) and nonspecific (recombinant IL-2) signals, respectively. These results demonstrate that some CTLs modulate their functional property (cytolysis) while undergoing IL-2-driven cell proliferation without loss of antigen specificity or ability to revert to a lytic phenotype.     

Suppression of HIV infection in AZT-treated SCID-hu mice

The SCID-hu mouse, engrafted with human hematolymphoid organs, is permissive for infection with the human immunodeficiency virus (HIV). This mouse model was used to test compounds for antiviral efficacy. Two weeks after infection with HIV, 100 percent (40/40) of SCID-hu mice were positive for HIV by the polymerase chain reaction. When first treated with 3'-azido-3'-deoxythymidine (AZT), none (0/17) were HIV-positive by this assay. However, AZT-treated SCID-hu mice did have a few infected cells; after AZT treatment was stopped, viral spread was detected by polymerase chain reaction in such mice. Thus, the SCID-hu mouse provides a means to directly compare new antiviral compounds with AZT and to further improve antiviral efficacy.     

Suspected fatal venous air embolism during anaesthesia in a Pomeranian dog with pulmonary calcification

CASE HISTORY: Death occurred in a 1.25 kg, 9-month-old female Pomeranian dog undergoing anaesthesia for surgical repair of partially healed fractures of the radius and ulna.

CLINICAL FINDINGS: Following sedation, anaesthesia was induced using thiopentone and maintained with halothane in oxygen. An acute decrease in the dog's end-tidal carbon dioxide (EtCO₂) measurements was noted approximately 50 min after induction, immediately following delivery of a 5-ml bolus of lactated Ringer's solution (LRS) administered to flush a small (0.06 ml) volume of fentanyl via a pre-placed intravenous (I/V) catheter. Venous air embolism (VAE) was suspected and the dog died despite interventive therapy. On post-mortem examination, several air bubbles were noted when the right ventricle was opened under water. Histologically, the kidneys appeared abnormal with immature glomeruli, and the lungs appeared diffusely mineralised. The origin of the air was probably small bubbles and microbubbles that may have been present in the extension set and 20 ml syringe used for the administration of fentanyl and I/V fluids to the dog.

DIAGNOSIS: Renal dysplasia and diffuse pulmonary calcification, with VAE as the probable cause of death.

CLINICAL RELEVANCE: In this case of VAE-associated anaesthetic death, it is further speculated that underlying pulmonary disease, in the form of pulmonary calcification, may have contributed to an increased sensitivity to the adverse effects of VAE.     

Chlorella 11-Peptide Inhibits the Production of Macrophage-Induced Adhesion Molecules and Reduces Endothelin-1 Expression and Endothelial Permeability

The inflammation process in large vessels involves the up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are also known as the markers of atherosclerosis. We have reported that Chlorella 11-peptide exhibited effective anti-inflammatory effects. This peptide with an amino sequence Val-Glu-Cys-Tyr-Gly-Pro-Asn-Arg-Pro-Gln-Phe was further examined for its potential in preventing atherosclerosis in this study. In particular, the roles of Chlorella 11-peptide in lowering the production of vascular adhesion molecules, monocyte chemoattractant protein (MCP-1) and expression of endothelin-1 (ET-1) from endothelia (SVEC4-10 cells) were studied. The production of E-selectin, ICAM-1, VCAM-1 and MCP-1 in SVEC4-10 cells was measured with ELISA. The mRNA expression of ET-1 was analyzed by RT-PCR and agarose gel. Results showed that Chlorella 11-peptide significantly suppressed the levels of E-selectin, ICAM, VCAM, MCP-1 as well as ET-1 gene expression. The inhibition of ICAM-1 and VCAM-1 production by Chlorella 11-peptide was reversed in the presence of protein kinase A inhibitor (H89) which suggests that the cAMP pathway was involved in the inhibitory cause of the peptide. In addition, this peptide was shown to reduce the extent of increased intercellular permeability induced by combination of 50% of lipopolysaccharide (LPS)-activated RAW 264.7 cells medium and 50% normal SEVC cell culture medium (referred to as 50% RAW-conditioned medium). These data demonstrate that Chlorella 11-peptide is a promising biomolecule in preventing chronic inflammatory-related vascular diseases.     

Temporohyoid osteoarthropathy in two young horses

Two cases of temporohyoid osteoarthropathy (THO) in young Australian horses are described. The pathogenesis of THO is yet to be fully elucidated, but current theories include extension of infection from otitis media or interna to the temporohyoid joint or a primary but non‐infectious degenerative condition within the temporohyoid joint. The young age of the horses and the unilateral distribution suggested an infectious aetiology. Both horses partially responded to treatment with broad‐spectrum antimicrobial and anti‐inflammatory drugs with concurrent management of ulcerative keratitis. The management of violent head shaking in one horse included the administration of gabapentin, an anticonvulsant known to have antihyperalgesic effects and reduce neuropathic pain.     

Cardiopulmonary effects of a new inspiratory impedance threshold device in anesthetized hypotensive dogs

ObjectiveTo compare the hemodynamic and respiratory effects of an inspiratory impedance threshold device (ITD) in anesthetized normotensive and hypotensive dogs.Study designProspective randomized study.AnimalsTen adult dogs.MethodsDogs were anesthetized with propofol followed by isoflurane. During spontaneous ventilation, tidal volume ( $\dot{\mathrm{V}}$), systolic (SAP), mean (MAP) and diastolic arterial blood pressure, central venous pressure, gastric PCO₂ as an indicator of gastric perfusion, subcutaneous oxygen tension, subcutaneous blood flow, cardiac index (CI), systemic vascular resistance and blood lactate were monitored. To monitor respiratory compliance (RC) and resistance (ResR), animals were briefly placed on mechanical ventilation. Dogs were studied under four different conditions: 1) normotension (MAP > 60 mmHg) with and without the ITD and 2) hypotension (target MAP = 40 mmHg) with and without ITD. These four conditions were performed during one anesthetic period, allowing for stabilization of parameters for each condition. Data were analyzed by anova repeated measure mixed models.ResultsNo cardiovascular changes were detected between no ITD and ITD in the normotensive state. During hypotension, CI was higher with the ITD (5 ± 1.0 L minute^?1 m^?2) compared with no ITD (4 ± 1.3 L minute^?1 m^?2). During hypotension, SAP was increased with ITD (80 ± 14 mmHg) versus without ITD (67 ± 13 mmHg). There was an increase in ResR and decreased RC with the ITD in both normotensive and hypotensive state.Conclusion and clinical relevanceImpedance threshold device in dogs during isoflurane-induced hypotension improved CI and SAP but had negative effects on RC and ResR.     

Social structure in a critically endangered Indo‐Pacific humpback dolphin (Sousa chinensis) population

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