When mixed with self PBMC one or three years after successful treatment the CD8+ T cells decreased Leishmania antigen specific proliferation and IFN-γ secretion and increased IL-10 secretion. Depletion of CD8+ T cells from VL PBMC stopped endogenous IL-10 secretion but increased Leishmania antigen specific IL-10 secretion, suggesting that CD8+ regulatory T cells are responsible for endogenous IL-10 secretion. CD4+ clones could only be isolated from VL PBMC after CD8+ T cell depletion. The CD4+ clones had little effect on IL-10 secretion but decreased IFN-γ secretion when mixed with self PBMC collected after successful treatment.Regulatory B cells are known to favor development of regulatory T cells and suppress development of Type 1 T helper cells by producing IL-10 and other down-regulatory cytokines. IL-10 levels are elevated in B cells from VL PBMC. A study of dogs with naturally acquired VL showed that the percentage of regulatory B cells increased three-fold during VL. Depletion of B cells increased CD4+ T cell proliferation and IFN-γ secretion but decreased IL-10 secretion. Blocking IL-10 or programmed cell death receptors on B cells increased Leishmania antigen specific T cell proliferation and IFN-γ secretion. Co-culture of T cells with B cells decreased the percentage of CD4+ T cell proliferation and IFN-γ secretion four-fold. Diagnosis
The gold standard for diagnosis is visualization of the amastigotes in splenic aspirate or bone marrow aspirate. This is a technically challenging procedure that is frequently unavailable in areas of the world where visceral leishmaniasis is endemic.Serological testing is much more frequently used in areas where leishmaniasis is endemic.
Poractant alfa is a pulmonary surfactant sold under the brand name Curosurf by Chiesi Farmaceutici. Poractant alfa is an extract of natural porcine lung surfactant. As with other surfactants, marked improvement on oxygenation may occur within minutes of the administration of poractant alfa. The new generic form of surfactant is Varasurf (Sheep Lung Surfactant) developed in PersisGen Co. and commercialized by ArnaGen Pharmad. It has fully comparable quality profile with Curosurf. Pharmacology
Each milliliter of poractant alfa contains 80 mg of surfactant (extract) that includes 76 mg of phospholipids and 1 mg of protein of which 0.2 mg is surfactant protein B (SP-B). Depending on local country registration, CUROSURF is available in 1.5 mL vials, 3.0 mL vials, and/or twin packs containing two 1.5 mL vials.The amount of phospholipids is calculated from the content of phosphorus and contains 55 mg of phosphatidylcholine of which 30 mg is dipalmitoylphosphatidylcholine. Other adverse effects
Transient episodes of bradycardia, decreased oxygen saturation, hypotension, or endotracheal tube blockage may occur. Mechanism of action
Endogenous pulmonary surfactant reduces surface tension at the air-liquid interface of the alveoli during mechanical ventilation and stabilizes the alveoli against collapse at resting transpulmonary pressures.A deficiency of pulmonary surfactant in preterm infants results in respiratory distress syndrome. Poractant alfa compensates for the surfactant deficiency and restores surface activity to the lung tissue. History
Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959.