Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

Background: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy.

Infection of a Nylon Foil Orbital Implant Due to Fusarium brachygibbosum and Lomentospora prolificans After Intranasal Methamphetamine Use.

The authors describe a case of nylon foil implant infection caused by Fusarium brachygibbosum , and Lomentospora prolificans following medial orbital wall fracture repair in the setting of postoperative nasal methamphetamine use. A 61-year-old male presented with OS pain and swelling after a physical assault on his face. A CT of maxillofacial bones without contrast showed a moderately comminuted fracture of the medial wall of the left orbit with depression of fracture fragments into the left ethmoid air cells.

Auranofin Resistance in Decreases the Accumulation of Reactive Oxygen Species but Does Not Target Parasite Thioredoxin Reductase.

Auranofin, a reprofiled FDA-approved drug originally designed to treat rheumatoid arthritis, has emerged as a promising anti-parasitic drug. It induces the accumulation of reactive oxygen species (ROS) in parasites, including . We generated auranofin resistant lines through chemical mutagenesis to identify the molecular target of this drug.

Two key cathepsins, TgCPB and TgCPL, are targeted by the vinyl sulfone inhibitor K11777 in in vitro and in vivo models of toxoplasmosis.

Although toxoplasmosis is one of the most common parasitic infections worldwide, therapeutic options remain limited. Cathepsins, proteases that play key roles in the pathogenesis of toxoplasmosis and many other protozoan infections, are important potential therapeutic targets. Because both TgCPB and TgCPL play a role in T.

New drug target in protozoan parasites: the role of thioredoxin reductase.

Amebiasis causes approximately 70,000 deaths annually and is the third cause of death due to parasites worldwide. It is treated primarily with metronidazole, which has adverse side effects, is mutagenic and carcinogenic, and emergence of resistance is an increasing concern. Unfortunately, better therapeutic alternatives are lacking.

Acute HIV infection presenting as fulminant meningoencephalitis with massive CSF viral replication.

A 22-year-old man presented to the emergency department with 10 days of malaise, generalized rash, sore throat, oral ulcers, headache, nausea, and vomiting. On examination he had fever (101.5°F), hepatosplenomegaly, generalized maculopapular rash, and lymphadenopathy.

Auranofin is highly efficacious against Toxoplasma gondii in vitro and in an in vivo experimental model of acute toxoplasmosis.

Background: The mainstay of toxoplasmosis treatment targets the folate biosynthetic pathways and has not changed for the last 50 years. The activity of these chemotherapeutic agents is restricted to one lifecycle stage of Toxoplasma gondii, they have significant toxicity, and the impending threat of emerging resistance to these agents makes the discovery of new therapies a priority. We now demonstrate that auranofin, an orally administered gold containing compound that was FDA approved for treatment of rheumatoid arthritis, has activity against Toxoplasma gondii in vitro (IC50 = 0.

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target.

Entamoeba histolytica, a protozoan intestinal parasite, is the causative agent of human amebiasis. Amebiasis is the fourth leading cause of death and the third leading cause of morbidity due to protozoan infections worldwide(1), resulting in ~70,000 deaths annually. E.

HIV-1 inhibits autophagy in bystander macrophage/monocytic cells through Src-Akt and STAT3.

Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act upstream of autophagy proteins.

Accelerated damage accrual among men with systemic lupus erythematosus: XLIV. Results from a multiethnic US cohort.

Objective: To determine the impact of the patient's sex on the manifestations and outcome of systemic lupus erythematosus (SLE).

Methods: We studied SLE patients who were ages 16 years or older and had a disease duration of < or =5 years at the time of enrollment in the LUpus in MInorities, NAture versus nurture cohort, a multiethnic cohort consisting of Hispanic, African American, and Caucasian patients. Socioeconomic/demographic, clinical, and serologic features, as well as disease activity (by the Systemic Lupus Activity Measure, Revised) and damage accrual (by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were compared between male and female patient groups.

Systemic lupus erythematosus in a multiethnic US cohort: XLIII. The significance of thrombocytopenia as a prognostic factor.

Objective: To examine the clinical correlates of thrombocytopenia and the value of thrombocytopenia as a predictor of disease activity, damage accrual, and mortality in patients with systemic lupus erythematosus (SLE).

Methods: SLE patients participating in a longitudinal multiethnic cohort were studied. Thrombocytopenia was defined as a platelet count <100,000/mm(3) at or before enrollment (baseline).

CD40-TRAF6 and autophagy-dependent anti-microbial activity in macrophages.

A fundamental question in host-pathogen interaction is to determine if the immune system activates fusion with the lysosomes to eradicate pathogens. We recently reported that this task is accomplished by the interaction between CD40 expressed on macrophages and CD154 expressed on activated CD4+ T cells. CD40 stimulation of macrophages induces vacuole-lysosome fusion through autophagy and results in killing of the obligate intracellular pathogen Toxoplasma gondii.

CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes.

Many intracellular pathogens, including Toxoplasma gondii, survive within macrophages by residing in vacuoles that avoid fusion with lysosomes. It is important to determine whether cell-mediated immunity can trigger macrophage antimicrobial activity by rerouting these vacuoles to lysosomes. We report that CD40 stimulation of human and mouse macrophages infected with T.

TNF receptor-associated factor 6-dependent CD40 signaling primes macrophages to acquire antimicrobial activity in response to TNF-alpha.

IFN-gamma is considered an essential stimulus that allows macrophages to acquire activity against intracellular pathogens in response to a second signal such as TNF-alpha. However, protection against important pathogens can take place in the absence of IFN-gamma through mechanisms that are still dependent on TNF-alpha. Engagement of CD40 modulates antimicrobial activity in macrophages.

CD40 signaling in macrophages induces activity against an intracellular pathogen independently of gamma interferon and reactive nitrogen intermediates.

Gamma interferon (IFN-gamma) is the major inducer of classical activation of macrophages. Classically activated mouse macrophages acquire antimicrobial activity that is largely dependent on the production of reactive nitrogen intermediates. However, protection against important intracellular pathogens can take place in the absence of IFN-gamma and nitric oxide synthase 2 (NOS2).

Pathogen-specific induction of CD154 is impaired in CD4+ T cells from human immunodeficiency virus-infected patients.

The pathogenesis of immunodeficiency associated with human immunodeficiency virus (HIV) infection remains incompletely understood. CD154, a molecule that is expressed primarily on activated CD4(+) T cells, is pivotal for regulation of cell-mediated and humoral immunity and is crucial for control of many opportunistic infections. We investigated whether CD4(+) T cells from HIV-infected patients exhibit defective induction of CD154 in response to opportunistic pathogens.

CD154 activates macrophage antimicrobial activity in the absence of IFN-gamma through a TNF-alpha-dependent mechanism.

Protection against certain intracellular pathogens can take place in the absence of IFN-gamma through mechanisms dependent on TNF-alpha. In this regard, patients with partial defect in IFN-gamma receptor 1 are not susceptible to toxoplasmosis. Thus, we used a model of Toxoplasma gondii infection to investigate whether CD154 modulates IFN-gamma-independent mechanisms of host protection.