Synthesis of phosphatidylcholine in rats with oleic acid-induced pulmonary edema and effect of exogenous pulmonary surfactant on its <i>De Novo</i> synthesis

<div><p>In mammals, oleic acid (OA) induces pulmonary edema (PE), which can initiate acute lung injury (ALI) and lead to acute respiratory distress syndrome (ARDS). Pulmonary surfactant (PS) plays a key role in a broad range of treatments for ARDS. The aim of the present investigation was to assess changes in the synthesis of phosphatidylcholine (PC) from choline and determine the effect of exogenous PS on its <i>de novo</i> synthesis in rats with OA-induced PE. Experimental rats were randomized into three groups, including a control group, OA-induced PE group, and OA-induced group treated with exogenous PS (OA-PS). Twenty-four rats were sacrificed 4 h after induction of the OA model, and tissue was examined by light and electron microscopy to assess the severity of ALI using an established scoring system at the end of the experiment. After 15 μCi ³H-choline chloride was injected intravenously, eight rats in each group were sacrificed at 4, 8, and 16 h. The radioactivity of ³H incorporated into total phospholipid (TPL) and desaturated phosphatidylcholine (DSPC) was measured in bronchoalveolar lavage fluid (BALF) and lung tissue (LT) using a liquid scintillation counter and was expressed as counts per minute (CPM). Results showed that TPL, DSPC, and the ratio of DSPC/total protein (TP) in lung tissue decreased 4 h after challenge with OA, but the levels recovered after 8 and 16 h. At 8 h after injection, ³H-TPL and ³H-DSPC radioactivity in the lungs reached its peak. Importantly, ³H-DSPC CPM were significantly lower in the PS treatment group (LT: Control: 62327 ± 9108; OA-PE: 97315 ± 10083; OA-PS: 45127 ± 10034, <i>P</i> < 0.05; BALF: Control: 7771 ± 1768; OA-PE: 8097 ± 1799; OA-PE: 3651 ± 1027, <i>P</i> < 0.05). Furthermore, DSPC secretory rate (SR) in the lungs was significantly lower in the PS treatment group at 4 h after injection (Control: 0.014 ± 0.003; OA-PE: 0.011 ± 0.004; OA-PS: 0.023 ± 0.006, <i>P</i> < 0.05). Therefore, we hypothesize that exogenous PS treatments may adversely affect endogenous <i>de novo</i> synthetic and secretory phospholipid pathways via feedback inhibition. This novel finding reveals the specific involvement of exogenous PS in endogenous synthetic and secretory phospholipid pathways during the treatment of ARDS. This information improves our understanding of how PS treatment is beneficial against ARDS and opens new opportunities for expanding its use.</p></div

Alveolar structure and schematic design of isotope tracing.

<p>³H-labeled methyl chloride choline is involved in surfactant phospholipid synthesis of alveolar type II cells. The level of ³H in phospholipids was monitored to detect the amount originating from endogenous phospholipid synthesis. The radioactivity of TPL and DSPC in BALF and LT indicates the total content of ³H-labeled choline chloride incorporated into TPL and DSPC, which reflects the newly synthesized TPL and DSPC and the body’s ability to synthesize PC. The secretory rate of TPL was expressed as the ratio of radioactivity in BALF and the whole lung (BALF+LT). The secretory rates of TPL and DSPC indicate the ability of alveolar type II epithelial cells to secrete PC into the alveolar space.</p

Electron microscopy observations of pulmonary surfactant layer (PSL) and vascular endothelial cells.

<p>A and D: Normal control group, B and E: OA-PE group, C and F: OA-PS treatment group. A, B, C: PSL; D, E, F: vascular endothelial cells.</p

Changes in ³H-TPL and ³H-DSPC levels in LT and BALF.

<p>A: Changes in ³H-TPL and ³H-DSPC levels in LT. B: Changes in ³H-TPL and ³H-DSPC levels in BALF. C: Changes in TPL SR and DSPC SR.</p

Changes in TPL and DSPC in lung tissue.

<p>Changes in TPL and DSPC in lung tissue.</p

Table_1_Development and validation of a predictive model for stroke associated pneumonia in patients after thrombectomy for acute ischemic stroke.XLSX

ObjectiveThis study aims to identify the risk factors associated with stroke-associated pneumonia (SAP) in patients who have undergone thrombectomy for acute ischemic stroke and to develop a nomogram chart model for predicting the occurrence of pneumonia.MethodsConsecutive patients who underwent thrombectomy for acute ischemic stroke were enrolled from three hospitals at Taizhou Enze Medical Center. They were randomly divided into a training group and a validation group in a 7:3 ratio. The training group data was used to screen for effective predictive factors using LASSO regression. Multiple logistic regression was then conducted to determine the predictive factors and construct a nomogram chart. The model was evaluated using the validation group, analyzing its discrimination, calibration, and clinical decision curve. Finally, the newly constructed model was compared with the AIS-APS, A2DS2, ISAN, and PANTHERIS scores for acute ischemic stroke-associated pneumonia.ResultsOut of 913 patients who underwent thrombectomy, 762 were included for analysis, consisting of 473 males and 289 females. The incidence rate of SAP was 45.8%. The new predictive model was constructed based on three main influencing factors: NIHSS ≥16, postoperative LMR, and difficulty swallowing. The model demonstrated good discrimination and calibration. When applying the nomogram chart to threshold probabilities between 7 and 90%, net returns were increased. Furthermore, the AUC was higher compared to other scoring systems.ConclusionThe constructed nomogram chart in this study outperformed the AIS-APS, A2DS2 score, ISAN score, and PANTHERIS score in predicting the risk of stroke-associated pneumonia in patients with acute ischemic stroke after thrombectomy. It can be utilized for clinical risk prediction of stroke-associated pneumonia in patients after thrombectomy for acute ischemic stroke.</p