Activation of the endocannabinoid system mediates cardiac hypertrophy induced by rosiglitazone.

Rosiglitazone (RSG) is a synthetic agonist of peroxisome proliferator-activated receptor-γ (PPARγ), which plays a central role in the regulation of metabolism. Meta-analyses have suggested that RSG is associated with increased cardiovascular risk. However, the mechanisms underlying such adverse cardiac effects are still poorly understood. Here, we found that activation of PPARγ by RSG stimulated the endocannabinoid system (ECS), a membrane lipid signaling system, which induced cardiac hypertrophy. In neonatal rat cardiomyocytes, RSG increased the level of anandamide (AEA); upregulated the expression of N-acyl phosphatidylethanolamine phospholipase D (NapePLD), a key enzyme for AEA synthesis; and downregulated the expression of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of AEA. Importantly, PPARγ activation increased the expression of cannabinoid receptor type 1 (CB1) through an identified binding site for PPARγ in the CB1 promoter region. Moreover, both the in vitro and in vivo results showed that inhibition of the ECS by rimonabant, an antagonist of CB1, attenuated RSG-induced cardiac hypertrophy, as indicated by decreased expression of cardiac hypertrophy markers (ANP and BNP), deactivation of the mTOR pathway, and decreased cardiomyocyte size. Thus, these results demonstrated that the ECS functions as a novel target of PPARγ and that the AEA/CB1/mTOR axis mediates RSG-induced cardiac remodeling.

[Invasive aspergillosis after near-drowning: case reports and review of the literature].

OBJECTIVE: The purpose of this study was to analyze the clinical presentations and disease courses of invasive aspergillosis (IA) in patients after near-drowning. METHODS: The clinical data of 3 cases of invasive aspergillosis after near-drowning from Oct. 2005 to Aug. 2010 in this hospital were retrospectively analyzed, and the related literature was reviewed. RESULTS: There were 1 male and 2 female patients, aged from 18 to 72 years. All of them had been immunocompetent before drowning. Two patients drowned because of traffic accident, and 1 fell in sewage by accident. All of the 3 patients were intubated because of acute respiratory failure, and received broad-spectrum antibiotic therapy. One had transient leucopenia, and 2 patients received glucocorticoid therapy. The condition of the 3 cases deteriorated 9 to 11 days after near-drowning. Aspergillus was isolated from sputum samples of 2 patients at the same time. Thoracic CT findings included multiple nodules, consolidation and cavity formation. Multiple abscesses in cerebral parenchyma were found in 1 patient with invasive cerebral aspergillosis. One patient died, whose lungs, cerebral parenchyma, myocardium and kidney were all infected by aspergillus. The other 2 patients, whose infection limited to the lungs, had a positive prognosis. Using the terms "aspergillosis" and "near-drowning" a PUBMED search yielded 7 articles, published between 1984 and 2010. Using the terms "invasive pulmonary aspergillosis" and "near-drowning", searching Wangfang data and CHED data, encompass 1 article, published in 2009. In all of the 8 articles, there are 5 final diagnosis cases and 3 clinical diagnosis cases. CONCLUSIONS: IA was very rare in immunocompetent hosts but had been reported in previously healthy individuals after near-drowning. Aspergillosis might develop 1 to 2 weeks after near-drowning, and the prognosis was poor in patients with central nervous system involvement.

[Evaluation of the galactomannan assay for the diagnosis of invasive aspergillosis in patients].

OBJECTIVE: To assess the value of Aspergillus galactomannan (GM) double-direct sandwich enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA). METHODS: Forty nine patients were divided into IA group (n = 11), other invasive fungal infection group (n = 20) and Aspergillus colonization group (n = 18). The serum samples of all patients and 6 patients with IA after 7 day treatment were used for GM detection. A double-direct sandwich ELISA was employed to detect GM optical density index (ODI) in the serum samples. Measurement data followed the Gaussian distribution were expressed as x +/- s. Differences among groups were tested using a one factor analysis of variance. The significance of variation before and after therapy was tested with paired t test. P < 0.05 were considered to represent a significant difference. Statistical analyses were performed by SPSS statistical package. RESULTS: The serum GM ODI in IA patients was higher (1.63 +/- 0.29) than that in other IFI patients (0.96 +/- 0.49) and Aspergillus colonization patients (0.83 +/- 0.43) , F = 12.681, P < 0.05. The serum GM ODI of 6 patients with IA before and after treatment were 1.67 +/- 0.24 and 1.62 +/- 0.28 (t = 0.475, P > 0.05), respectively. If the cutoff GM ODI was 1.5, the sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of IA in the patients were 72.7% , 84.2%, 57.1% and 94.1%, respectively. CONCLUSIONS: The serum GM detection has diagnostic value for IA and could distinguish Aspergillus infection from other invasive fungal infections and Aspergillus colonization. A cutoff GM ODI of 1.5 showed the best sensitivity and specificity for IA in the patients.

[The diagnostic value of detecting plasma 1, 3-beta-D-glucan for invasive fungal infections].

OBJECTIVE: To evaluate the diagnostic value of the detection of plasma 1, 3-beta-D-glucan for invasive fungal infections (IFI). METHODS: Plasma of patients with IFI, bacterial pneumonia, and oral pharyngeal fungal colonization, and healthy controls were collected from January 2005 to February 2006 in Nanjing General Hospital of Nanjing Military Command of PLA. G-test was used to measure the concentration of 1, 3-beta-D-glucan in the plasma. RESULTS: The concentration of 1, 3-beta-D-glucan in plasma of patients with IFI [(29.5+/-11.5) ng/L] was significantly higher than that of patients with bacterial pneumonia [(13.1+/-5.2) ng/L], fungal colonization [(12.7+/-5.1) ng/L], and healthy controls [(11.7+/-3.5) ng/L], P<0.01. The concentration of 1, 3-beta-D-glucan in patients with bacterial pneumonia was not different as compared to that of patients with fungal colonization, and healthy controls, P>0.05. The concentration of 1, 3-beta-D-glucan in plasma of patients with invasive aspergillosis and invasive candidiasis were (24.7+/-5.8) ng/L and (33.3+/-11.4) ng/L, respectively, the difference being not significant, P>0.05. The concentration of 1, 3-beta-D-glucan in plasma of a patients with invasive pulmonary Cryptococcus neoformans infection and a patient with histoplasmosis were 13.6 ng/L and 25.7 ng/L, respectively. If 20 ng/L was taken as the cut-off value, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 1, 3-beta-D-glucan were 84%, 91%, 84% and 91% respectively. CONCLUSION: The concentration of 1, 3-beta-D-glucan in plasma of patients with IFI increases markedly, which indicates that the detection of 1, 3-beta-D-glucan in plasma is a useful method to diagnose IFI, but can not be used to differentiate aspergillosis from yeast fungus infection. If Fungitec-G kit is used to detect 1, 3-beta-D-glucan and 20 ng/L is used as the cut-off value, the sensitivity and specificity for IFI are high.

[Evaluation of the galactomannan assay for the diagnosis of invasive aspergillosis in an animal model].

OBJECTIVE: To assess the value of Aspergillus galactomannan (GM) double-direct sandwich enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive pulmonary aspergillosis (IPA). METHODS: Ninety adult SD rats were randomly divided into 5 groups, including 4 groups of pulmonary infection by Aspergillus fumigatus (A. fumigatus), Candida albicans, mucor, and Streptococcus pneumoniae, respectively, and a colonization group by A. fumigatus in the pharynx oralis (n = 18 each). For the infection models, suspensions of pathogenic bacteria and fungi were instilled into the lungs of the rats by tracheal intubation. For the colonization model, the suspension of A. fumigatus was applied to the nasal cavity and pharynx oralis of the rats. The animals were sacrificed on days 3, 7, and 12 after inoculation, and blood samples were obtained by cardiac puncture and used for GM detection. The lung tissues were prepared for routine pathology examination, and hexamethylene tetramine silver staining was used to detect the fungi. A double-direct sandwich ELISA was employed to detect GM optical density index in the serum samples. RESULTS: The lung tissues of rats infected with A. fumigatus, Candida albicans, mucor and Streptococcus pneumoniae all showed remarkable inflammatory reactions, and hyphae were observed in rats with fungal infection (including A. fumigatus and mucor), and spores in rats infected with Candida albicans. The lung tissues of the A. fumigatus colonization rats showed no inflammatory reactions. The serum GM optical density index of the groups infected with A. fumigatus, Candida albicans, mucor and Streptococcus pneumoniae, and the A. fumigatus colonization group were 1.69 +/- 0.29, 0.89 +/- 0.46, 0.87 +/- 0.39, 0.77 +/- 0.34 and 0.90 +/- 0.49, respectively. The serum GM optical density index of the IPA group was higher than those of the other 4 groups (P < 0.05). If the cutoff ODI was 1.5, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosis of IPA in the rats were 78.6%, 87.5%, 57.9% and 94.9%, respectively. The sensitivity for A. fumigatus infection on days 3, 7, and 12 was 60.0%, 80% and 100%, and the specificity was 95.5%, 81.0% and 85.7%, respectively. CONCLUSION: GM detection could distinguish Aspergillus infection from Candida albicans, mucor, Streptococcus pneumoniae infection and Aspergillus colonization. The sensitivity of the test for the diagnosis of IPA tended to be higher with longer duration of infection. A cutoff ODI of 1.5 showed the best sensitivity and specificity for IPA in this rat model.

Rapid development of metastatic pulmonary calcifications in primary hyperparathyroidism: a case report and literature review.

BACKGROUND: Metastatic pulmonary calcification (MPC) is rarely reported in primary hyperparathyroidism, especially MPC develops quickly. We report such a case here with a literature review. CASE PRESENTATION: A 41-year-old woman presented with cough and dyspnea. Data from clinical, radiological, pathological, technetium (99mTc)-methylene diphosphonate (MDP) bone scintillation imaging, and 99mTc-methoxy isobutyl isonitrile (MIBI) thyroid imaging were studied. 99mTc-MIBI thyroid imaging indicated hyperparathyroidism. Chest computed tomography (CT) scans showed rapidly progressive bilateral pulmonary multiple high-density shadows with mass consolidation and exudation in only five days. 99mTc-MDP bone scintillation imaging indicated bilateral pulmonary calcifications. CT-guided lung biopsy showed multifocal irregularities of calcium deposition and calcified bodies in the pulmonary interstitium. The patient showed gradually clinical and radiological improvement after surgical removal of the parathyroid adenoma. CONCLUSION: Rapidly progressive MPC tends to be misdiagnosed as many primary pulmonary diseases. 99mTc-MDP bone scintillation imaging and pulmonary biopsy could be performed to differentiate metastatic pulmonary calcification from other diseases. Surgical resection of the parathyroid gland is helpful for treatment of MPC in patients with primary hyperparathyroidism and is regularly recommended.

Important factors mediates the adhesion of aspergillus fumigatus to alveolar epithelial cells with E-cadherin.

Aspergillus is widely distributed in the Earth's biosphere. It has strong adaptive capacity, and lives as saprophytic or parasitic life. This study aims to investigate the role of E-cadherin for adhesion of Aspergillus fumigatus blastospores in a human epithelial cell line (A549) and search the correlated molecule in aspergillus. A. fumigatus blastospores were incubated with the total protein of A549 to investigate the binding of E-cadherin and blastospores followed by an affinity purification procedure. After establishing the adhesion model, the adhesion of A. fumigatus blastospores by A549 cells was evaluated by down-regulating E-cadherin of A549 cells with small interfering RNA (siRNA). FVB mice constructed with E-cadherin down-regulation were infected with aspergillus fumigatus. Preliminary exploration of E-cadherin interacting protein on the surface of aspergillus fumigates by immunoprecipitation and mass spectrometry analysis. E-cadherin was adhered to the surface of A. fumigatus blastospore. Adhesion of the blastospores was reduced by blocking or down-regulating E-cadherin in A549 cells. E-cadherin showed limited significance in the process of mice against aspergillus fumigates. Mass spectrometry (MS) analysis indicated the following proteins AFUA_8G07080, AfA24A6.130c, XP_747789 can bind to E-cadherin. In conclusion, E-cadherin is a receptor for adhesion of A. fumigatus blastospores in epithelial cells. This may open a new approach to treat this fungal infection.

Acute fibrinous and organizing pneumonia: A case report and literature review.

Acute fibrinous and organizing pneumonia (AFOP) is a rare lung disease with distinct histological characteristics that include the diffuse presence of intra-alveolar fibrin, and the absence of eosinophils and hyaline membrane. In the present study, a case of AFOP that was diagnosed by lung biopsy is described. The patient presented with high fever and a cough with expectoration. Computed tomography of the lung showed the presence of bilateral patchy infiltrates, predominantly in the lower lobes. Histopathological examination of lung biopsy from the lower pulmonary lobe confirmed the pathological diagnosis. The patient showed a poor response to treatment with prednisone. Based on a review of literature pertaining to documented AFOP cases, a summary of the clinical features, radiological characteristics, treatment outcomes and prognoses associated with AFOP are presented. The most common pulmonary symptoms included cough, dyspnea and fever. The primary imaging findings in AFOP were consolidation and ground-glass opacity in the bilateral lung.

E-cadherin mediates adhesion and endocytosis of Aspergillus fumigatus blastospores in human epithelial cells.

BACKGROUND: Aspergillus fumigatus (A. fumigatus) is a ubiquitous saprophytic fungus responsible for the majority of invasive mold infections in patients undergoing chemotherapy, organ transplantation or with persistent neutropenia. This study aimed to determine the role of E-cadherin for adhesion and endocytosis of A. fumigatus blastospores in the human epithelial cell line A549. METHODS: A. fumigatus blastospores were incubated with the total protein of A549 to investigate the binding of E-cadherin and blastospores followed by an affinity purification procedure. After establishing the adhesion model, the adhesion and endocytosis of A. fumigatus blastospores by A549 cells were evaluated by down-regulating E-cadherin of A549 cells using blocking antibody or small interfering RNA (siRNA). RESULTS: E-cadherin was adhered to the surface of A. fumigatus blastospore. Adhesion and endocytosis of the blastospores were reduced by blocking or down-regulating E-cadherin in A549 cells. CONCLUSIONS: E-cadherin is a receptor for adhesion and endocytosis of A. fumigatus blastospores in epithelial cells. This may open a new approach to treat this fungal infection.

[The effects of rhG-CSF and rhSCF on peripheral blood leukocytes and CFU-GM in rhesus monkeys].

To evaluate the effects of rhG-CSF and rhSCF on mobilization of the peripheral blood stem cells, 15 monkeys were divided into control, rhG-CSF 10 micro g/(kg x day) and rhG-CSF 10 micro g/(kg x day) + rhSCF 50 micro g/(kg x day) treated groups. Monkeys were administered with vehicle, rhG-CSF and rhG-CSF + rhSCF subcutaneously once daily for 14 days, respectively. The results showed that the highest counts of leukocyte of rhG-CSF treated group were 411% of baseline value on day 7 after administration, compared with that of rhG-CSF + rhSCF treated group which were 538% on day 9. The highest counts of leukocytes lasted for 3 days in combined treated group. CFU-GM from peripheral blood in the two groups were 8.37 and 11.75 times higher at 5 and 9 days respectively after the mobilization. It is concluded that rhG-CSF significantly increases the number of peripheral blood leukocytes and CFU-GM, and a better effect can be obtained by rhSCF + rhG-CSF combined administration.