Relationship Between Exhaled Carbon Monoxide and Airway Hyperresponsiveness in Asthmatic Patients

The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose-response curves were characterized by their sensitivity (PD₂₀) and reactivity. Dose-response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 ± 0.4 vs. 5.74 ± 0.57 ppm, p = 0.025) and in the negative response group (2.84 ± 0.25 vs 4.00 ± 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD₂₀ was found (r = - 0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r² = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.     

Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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Characterization of the major secreted zinc metalloprotease- dependent glycerophospholipid:cholesterol acyltransferase, PlaC, of Legionella pneumophila

Legionella pneumophila, an intracellular pathogen causing a severe pneumonia, possesses distinct lipolytic activities which have not been completely assigned to specific enzymes so far. We cloned and characterized a gene, plaC, encoding a protein with high homology to PlaA, the major secreted lysophospholipase A of L. pneumophila and to other hydrolytic enzymes belonging to the GDSL family. Here we show that L. pneumophila plaC mutants possessed reduced phospholipase A and lysophospholipase A activities and lacked glycerophospholipid:cholesterol acyltransferase activity in their culture supernatants. The mutants' reduced phospholipase A and acyltransferase activities were complemented by reintroduction of an intact copy of plaC. Additionally, plaC conferred increased lysophospholipase A and glycerophospholipid:cholesterol acytransferase activities to recombinant Escherichia coli. Furthermore, PlaC was shown to be another candidate exported by the L. pneumophila type II secretion system and was activated by a factor present in the bacterial culture supernatant dependent on the zinc metalloprotease. Finally, the role of plaC in intracellular infection of Acanthamoeba castellanii and U937 macrophages with L. pneumophila was assessed, and plaC was found to be dispensable. Thus, L. pneumophila possesses another secreted lipolytic enzyme, a protein with acyltransferase, phospholipase A, and lysophospholipase A activities. This enzyme is distinguished from the previously characterized phospholipases A and lysophospholipases A by its capacity not only to cleave fatty acids from lipids but to transfer them to cholesterol. Cholesterol is an important compound of eukaryotic membranes, and an acyltransferase might be a tool for host cell modification to fit the needs of the bacterium.     

Role of hepatitis C virus genotype in the development of severe transaminase elevation after the introduction of antiretroviral therapy

OBJECTIVE: To assess the role of different hepatitis C virus (HCV) genotypes in the development of transaminase elevation after treatment with highly active antiretroviral therapy (HAART). DESIGN: Retrospective cohort study at one referral HIV outpatient clinic. METHODS: HCV genotype was determined in plasma samples from all consecutive HCV-HIV coinfected patients initiating HAART between March 1998 and January 2000. Clinical and laboratory data were recorded during the following 9 months. Severe transaminase elevation was defined as > or = fivefold increase over upper normal limits (AIDS Clinical Trials Group grades 3 or 4) when baseline alanine transaminase (ALT) and aspartate transaminase (AST) values were normal, and as > or = 3.5-fold increase above baseline ALT and AST values if they were abnormal. RESULTS: Twelve of 70 subjects (17%) developed severe transaminase elevation. Their HCV genotypes were distributed as follows: type 1, 5/39 (13%); type 2, 0/3 (0%); type 3, 7/21 (33%); and type 4, 0/7 (0%). The incidence of severe transaminase elevation was significantly higher among subjects with HCV genotype 3 (HCV-3) compared with those with non-type 3 (OR, 4.4 [95%CI, 1.2-16.1]; P =.02). In the multivariate analysis, HCV-3 remained associated with severe transaminase elevation when adjusted for baseline HCV viral load and degree of immune recovery seen during follow-up evaluation. CONCLUSIONS: HCV-3 is an independent risk factor for developing severe transaminase elevation after HAART. HCV genotyping before initiating antiretroviral therapy may be useful for assessing the risk of hepatotoxicity and for choosing the most appropriate drugs to prescribe for HIV-HCV coinfected patients. Given that the best response to interferon plus ribavirin occurs in patients with HCV-3, treatment should be specially encouraged in coinfected persons carrying HCV-3.     

Activity of tenofovir on hepatitis B virus replication in HIV-co-infected patients failing or partially responding to lamivudine

Treatment of hepatitis B virus (HBV) with lamivudine may not completely suppress viral replication and often fails as a result of lamivudine resistance. Tenofovir is a new HIV inhibitor with further activity against HBV, which was explored in 12 HBV/HIV-co-infected patients with detectable levels of serum HBV-DNA, despite receiving a lamivudine-containing antiretroviral regimen. Lamivudine-resistance mutations were found in HBV from seven patients. HBV-DNA levels dropped a median of 3.78 logs from baseline to 24 weeks. Tenofovir was very effective at reducing HBV-DNA levels in HIV/HBV-co-infected patients carrying either wild-type or lamivudine-resistant viruses.     

Epicardial delivery of collagen patches with adipose-derived stem cells in rat and minipig models of chronic myocardial infarction

Although transplantation of adipose-derived stem cells (ADSC) in chronic myocardial infarction (MI) models is associated with functional improvement, its therapeutic value is limited due to poor long-term cell engraftment and survival. Thus, the objective of this study was to examine whether transplantation of collagen patches seeded with ADSC could enhance cell engraftment and improve cardiac function in models of chronic MI. With that purpose, chronically infarcted Sprague–Dawley rats (n = 58) were divided into four groups and transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function were assessed 4 months after transplantation. In addition, Göttingen minipigs (n = 18) were subjected to MI and then transplanted 2 months later with CS or CS seeded with autologous minipig ADSC (CS-pADSC). Functional and histological assessments were performed 3 months post-transplantation. Transplantation of CS-rADSC was associated with increased cell engraftment, significant improvement in cardiac function, myocardial remodeling, and revascularization. Moreover, transplantation of CS-pADSC in the pre-clinical swine model improved cardiac function and was associated with decreased fibrosis and increased vasculogenesis. In summary, transplantation of CS-ADSC resulted in enhanced cell engraftment and was associated with a significant improvement in cardiac function and myocardial remodeling.