endothelin-1 and Acquired-Immunodeficiency-Syndrome

Despite increase in survival of HIV patients due to highly active antiretroviral therapy (HAART), non-infectious complications are still prevalent such as presentation of lung vasculopathy, even in asymptomatic patients. Endothelin-1 (ET-1) is a potent vasoconstrictor that causes pulmonary vasculopathy. Participation of this protein in the pulmonary circulation in HIV patients has not been elucidated. In this work we studied the presence and expression of ET-1 in pulmonary complex vascular lesions associated with human immunodeficiency virus (PCVL/HIV).. We used immunohistochemistry and immunochemiluminescence (imagej) to determine the different degrees of expression of ET-1 in PCVL/HIV in comparison with non-PCVL/HIV. Reagents used were anti-endothelin-1 and an automated system. All data are presented as mean and standard deviation (SD). Differences were analyzed with one-way ANOVA; p < 0.05 was accepted as statistically significant.. Lung tissues from 56 patients who died from complications of HIV pulmonary infection and with PCVL were studied. Histological evidence of pulmonary vasculopathy was shown as different types (proliferative, obliterative and plexiform). A statistically significant increase in ET-1 expression was observed in all PCVL/HIV tissue samples and is associated directly with different grades of severity of endothelial dysfunction.. ET-1 has a relevant role in the pathogenesis of pulmonary vasculopathy in acquired immunodeficiency syndrome (AIDS) patients. It is necessary to determine in the future the participation of ET-1 and other mechanisms involved in PCVL/HIV.

Topics: Acquired Immunodeficiency Syndrome; Adult; Endothelin-1; Female; Humans; Lung; Lung Diseases; Male; Middle Aged; Pulmonary Artery; Pulmonary Circulation; Vascular Diseases; Young Adult

We examined the HIV-inhibitory effects previously found to be associated with scrub typhus infection. Individual 500 ml units of plasma from donors with mild scrub typhus were safety-tested, subjected to virucidal heat treatment, and administered to 10 HIV-1-infected recipients who were not receiving antiretroviral drugs. HIV-1 copy number fell three-fold or more in two recipients, and virus burden was reduced for 8 weeks in 70% (7/10) of recipients of a single plasma infusion, compared with the mean of three pre-infusion measurements. Scrub typhus donor plasma inhibited HIV-1 in vitro compared with normal human plasma and media controls. In the clearest in vivo response, reduction in viral load was accompanied by clinical improvement, a switchback from the syncytia-inducing to the non-syncytia-inducing phenotype, and decreases in CD8 cells and IL-6 levels. Scrub typhus infections can generate heat-stable, transferable plasma factors that exert prolonged anti-HIV effects. Whether variability in the results is due to different scrub typhus infections, different HIV infections or different individual responses, is unclear.

Topics: Acquired Immunodeficiency Syndrome; Adoptive Transfer; Adult; Blood Component Transfusion; DNA, Viral; Endothelin-1; Female; HIV-1; Humans; Immunoglobulin E; Interleukin-6; Interleukin-8; Lymphocyte Subsets; Male; Middle Aged; Orientia tsutsugamushi; Phenotype; Plasma; Proteinase Inhibitory Proteins, Secretory; Proteins; Scrub Typhus; Viral Load

Widespread digital ischemic changes and gangrene of the hands and feet is an uncommon but dramatic presentation in patients with human immunodeficiency virus (HIV) infection. We describe a patient in whom these clinical findings were associated with elevated serum endothelin levels. Because endothelin may affect the fibrinolytic system, we elected to treat with tissue plasminogen activator (tPA), which resulted in salvage of tissue of the fingers and toes. Patients with HIV infection with widespread ischemic necrosis and gangrene may require treatment with corticosteroids (in the event of possible vasculitis), thrombolytic agents (for the thrombotic component), or both, unless there are contraindications to either.

Topics: Acquired Immunodeficiency Syndrome; Adult; Endothelin-1; Fingers; Gangrene; Humans; Ischemia; Male; Necrosis; Recombinant Proteins; Tissue Plasminogen Activator; Toes