[Show abstract][Hide abstract] ABSTRACT: The mammalian target of rapamycin (mTOR) pathway, a key cellular signaling pathway associated with various cellular functions, has distinct roles in the inflammatory process. In this study, the mTOR inhibitor rapamycin (Rapa) was used to test whether inhibition of mTOR activation attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a murine model.
Mice pretreated with Rapa or vehicle were given LPS intratracheally. Local cell numbers and inflammatory cytokines present in the bronchoalveolar lavage fluid (BAL), wet-to-dry weight ratio, histopathology of the lungs, and survival were evaluated.
The phosphorylation of S6, a major downstream target of mTOR, had a 3-fold increase in lung tissue after LPS stimulation, but the increase was blocked by Rapa. Rapa reduced the levels of TNF-α (LPS vs. LPS + Rapa, (1672.74 ± 193.73) vs. (539.17 ± 140.48) pg/ml, respectively; P < 0.01) and IL-6 (LPS vs. LPS + Rapa: (7790.88 ± 1170.54) vs. (1968.57 ± 474.62) pg/ml, respectively; P < 0.01) in the BAL fluid. However, Rapa had limited effects on the overall severity of ALI, as determined by the wet-to-dry weight ratio of the lungs, number of neutrophils in the BAL fluid, and changes in histopathology. In addition, Rapa failed to reduce mortality in the LPS-induced ALI model.
We confirmed that mTOR was activated during LPS-induced ALI and strongly inhibited by Rapa. Although Rapa reduced the levels of the mediators of inflammation, the overall severity and survival of the ALI murine model were unchanged.
Preview · Article · Oct 2011 · Chinese medical journal
[Show abstract][Hide abstract] ABSTRACT: It is well known that lipids abnormally accumulate in the alveoli during idiopathic pulmonary alveolar proteinosis (PAP). It is unclear, however, whether lipids also abnormally accumulate in serum. This study investigated the serum lipid panels in idiopathic PAP patients and explored the relationships between serum levels and the severity of idiopathic PAP.
Clinical data including the level of serum lipids were evaluated in 33 non-diabetic idiopathic PAP patients and 157 healthy volunteers. Serum levels of triglyceride were higher in PAP patients than in healthy subjects (median: 192.00 mg/dl (P25: 104.36, P75: 219.00) vs 119.56 mg/dl (P25: 78.81, P75: 193.03), P < 0.05), while high-density lipoprotein cholesterol (HDL-C) levels were lower in patients than in the control group (42.50 ± 10.30 vs 51.34 ± 12.06 mg/dl, P < 0.01). Forced expiratory volume in one second and forced vital capacity in hypertriglyceridemia patients were lower than those in patients with normal triglyceride. Serum LDL-C and HDL-C ratio correlated negatively with PaO2 (r = -0.403, P < 0.05) and positively with lactate dehydrogenase (r = 0.381, P < 0.05).
PAP associates with high triglyceride and low HDL levels in the serum, and these lipids provide potential intervention strategy for treatment.
Full-text · Article · Apr 2011 · Lipids in Health and Disease
[Show abstract][Hide abstract] ABSTRACT: To explore the influences of rapamycin (RAPA) upon the cytokine changes of activated spleen γδT lymphocytes and lung tissue macrophages in acute lung injury of mice induced by lipopolysaccharide (LPS).
A total of 24 healthy male C57BL/6 mice, 6-8 weeks old, were randomly divided into phosphate buffered saline (PBS), LPS, RAPA and LPS + RAPA groups. Acute lung injury was induced by a single intratracheal instillation of LPS in mice. And spleen γδT lymphocytes and lung macrophages were purified by immunomagnetic beads at Day 1. The purified spleen γδT lymphocytes and lung macrophages were adjusted to 10(6) cell/ml. And 24-well plates were used for 4 groups. Each group were further separated with spleen γδT lymphocytes alone, lung tissue macrophages alone and co-culturing. Supernatant fluid was collected after 24 hours. The expressions of IFN-γ and TNF-α were analyzed by ELISA (enzyme-linked immunosorbent assay). And the expressions of mRNA were analyzed by real-time quantitative PCR (polymerase chain reaction).
The total cells numbers and lymphocytes numbers of bronchoalveolar lavage fluid were significantly higher in LPS group than those in PBS and LPS + RAPA groups (P < 0.05). And the level of IFN-γ was significantly higher in LPS group than that in PBS, RAPA and LPS + RAPA groups by co-culture (P < 0.05). The level of TNF-α was significantly higher in LPS group than that in RAPA gand LPS + RAPA groups by co-culture (P < 0.05). However, the mRNA of IFN-γ was higher in LPS group than that in PBS and RAPA groups (P < 0.05).
RAPA inhibits the secretion levels of IFN-γ and TNF-α in spleen γδT lymphocytes and lung tissue macrophages in acute lung injury of mice induced by LPS.
No preview · Article · Mar 2011 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: To analyze the clinical characteristics of chylous effusion and boost its diagnostic and therapeutic level.
A retrospective analysis was conducted for 123 cases of chylous effusion at our hospital between January 1990 and December 2009.
The main clinical manifestations of chylous effusion included dyspnea (55.3%), edema (26.8%), abdominal distention (22.8%) and loss of weight (17.1%). Hypoalbuminemia was common (45.5%) and it was even more so in patients with idiopathic lymphopathies or of unknown causes (95.2%). The positive rates of identifying chylous effusion by Sudan III test, high triglyceride levels (> 1.25 mmol/L), lymphangiography or lymphangioscintigraphy were 89.1%, 80.6%, 70.6% and 89.5% respectively. Its common etiologies included injury (14.6%), malignancy (9.0%), infections (7.3%), lymphatic disorders or idiopathic lymphopathies (40%), drug-associated (2.4%) or associated with underlying disorders (16.3%). Efficacy was achieved in 63.6% of the patients and 21.8% died.
Chylous effusion is a special type of serous effusion with multiple causes. Its clinical manifestations are often nonspecific. But malnutrition is common. Its causes are identified after a systematic evaluation. Treatment modalities include dietary modification, management of underlying causes and surgical approaches.
No preview · Article · Feb 2011 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: To examine the correlation between the health-related quality of life measured by the St. George's Respiratory Questionnaire (SGRQ) and the commonly used physiological measures in lymphangioleiomyomatosis (LAM).
This study retrospectively analyzed the SGRQ scores and other measures (the Borg scale of breathlessness at rest, 6-minute walking distance, blood oxygen levels, and pulmonary function) of patients diagnosed and confirmed with LAM. Altogether 38 patients between June 2007 and November 2009 were included.
The mean values of the SGRQ three components (symptoms, activity, and impacts) and total scores in the LAM patients were 46.95 +/- 28.90, 58.47 +/- 25.41, 47.89 +/- 29.66, and 51.11 +/- 26.35, respectively. The SGRQ total or component scores were correlated well with the Borg scale of breathlessness, 6-minute walking distance, partial pressure of oxygen in arterial blood, spirometry and diffusion capacity of lung. There were poor correlations between SGRQ score and residual volume or total lung capacity. In our preliminary observation, sirolimus improved the SGRQ total and three component scores and the Borg scale of breathlessness significantly after 101-200 days of treatment (n = 6).
The SGRQ score in LAM is correlated well with physiological measures (Borg scale of breathlessness, 6-minute walking distance, blood oxygen levels, and pulmonary function tests). The SGRQ could therefore be recommended in baseline and follow-up evaluation of patients with LAM. Treatment with sirolimus, an inhibitor of mammalian target of rapamycin, may improve the quality of life and patient's perception of breathlessness in LAM.
No preview · Article · Sep 2010 · Chinese Medical Sciences Journal