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Most known chemiluminescence (CL) systems are flash-type that generate weak luminescence and decline quickly after dozens of seconds, while the glow-type CL systems have stable emission for an extended period to achieve accurate quantitation. In this work, a long-term CL system based on hydrazine-hydrate (N 2 H 4 ·H 2 O) modified carbon quantum dots (N-CQDs) as a luminescent probe, with K 2 S 2 O 8 and H 2 O 2 as co-reactants, was proposed. The CL emission enhanced by H 2 O 2 increased 18-fold more than that of N-CQDs and K 2 S 2 O 8 direct reaction, and decayed by 5% of the maximum intensity over 700 s. In the reaction system, K 2 S 2 O 8 and H 2 O 2 co-reactants can promote each other to continuously generate corresponding radicals (•OH, O 2 •- , 1 O 2 ), which in turn trigger the CL emission of N-CQDs. This phenomenon was identified as the primary cause for the production of persistent CL. In addition, a stable and selective CL sensor based on the N-CQDs-K 2 S 2 O 8 -H 2 O 2 CL enhancing system was developed for ascorbic acid quantitation in the linear range from 0.1 to 10.0 mM with a detection limit of 0.036 mM. The method has been applied to the analysis of tablet samples and holds potential in pharmaceutical analysis field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Stair climbing test (SCT) and gait speed test (GST) are two physical performance measures, both of which are associated with postoperative outcomes. However, few studies have compared these two tests for the prognostic value., Methods: A prospective study was conducted in patients undergoing radical gastrectomy for gastric cancer. Handgrip strength (HGS) test, 7-steps SCT and 6-m GST were performed before surgery. Body compositions were analyzed using abdominal computed tomography (CT). Sarcopenia was diagnosed by low HGS plus either low muscle mass or quality., Results: A total of 548 patients were included in this study. Time of GST and SCT were both significantly correlated with HGS, skeletal muscle index and skeletal muscle density, but not with subcutaneous or visceral fat area. Low SCT performance (SCT time ≥12.65s) was associated with higher incidence of postoperative complications and longer postoperative length of stay, whereas low GST performance (GST time ≥5.45s) did not. Low performance in SCT and GST were both associated with worse overall survival (OS) and disease-free survival (DFS) after surgery. Low SCT performance was an independent predictor for postoperative complications, OS, and DFS, whereas low GST performance was not significant in multivariate analyses adjusting for the same covariates. The combination of sarcopenia with low SCT performance showed higher accuracy in predicting postoperative complications and mortality compared with sarcopenia combined with low GST performance., Conclusion: SCT outperformed GST in predicting outcomes after radical gastrectomy for gastric cancer, either as a singular indicator or in combination with sarcopenia assessments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: There is a lack of data on the role of characteristics of injured vessels on the outcomes of patients with blunt cerebrovascular injuries (BCVIs). The aim of this study was to assess the effect of the number (single vs multiple) of injured vessels on outcomes., Methods: This is a retrospective study at two American College of Surgeons Level I trauma centers (2017-2021). Adult (>16 years) trauma patients with BCVIs are included. Injuries were graded by the Denver Scale based on the initial computed tomography angiography (CTA). Early repeat CTA was performed 7 to 10 days after diagnosis. Patients were stratified by the number (single vs multiple) of the involved vessels. Outcomes included progression of BCVIs on repeat CTA, stroke, and in-hospital mortality attributable to BCVIs. Multivariable regression analyses were performed to identify the association between the number of injured vessels and outcomes., Results: A total of 491 patients with 591 injured vessels (285 carotid and 306 vertebral arteries) were identified. Sixty percent were male, the mean age was 44 years, and the median Injury Severity Score was 18 (interquartile range, 11-25). Overall, 18% had multiple-vessel injuries, 16% had bilateral vessel injuries, and 3% had multiple injuries on the same side. The overall rates of progression to higher-grade injuries, stroke, and mortality were 23%, 7.7%, and 8.8%, respectively. On uni- and multivariable analyses, multiple BCVIs were associated with progression to higher-grade injuries on repeat imaging, stroke, and mortality compared with single-vessel injuries., Conclusions: BCVIs with multiple injured vessels are more likely to progress to higher grades on repeat CTA, with multiple injuries independently associated with worse clinical outcomes, compared with those with single injuries. These findings highlight the importance of incorporating the number of injured vessels in clinical decision-making and in defining protocols for repeat imaging., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition., Methods: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively., Results: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity., Conclusion: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Diagnostic Criteria Study BACKGROUND: The morbidity and mortality associated with ischemic stroke attributable to blunt cerebrovascular injury (BCVI) warrant aggressive screening. The Denver Criteria (DC) and Expanded Denver Criteria (eDC) have imprecise elements that can be difficult and subjective in application and can delay or prevent screening. We hypothesize these screening criteria lack adequate ability to consistently identify BCVI and that the use of a liberalized screening approach with CT angiography (CTA) is superior without increasing risk of acute kidney injury (AKI)., Methods: This was a multi-institutional retrospective cohort study of trauma patients who presented between 2015-2020 with radiographically confirmed BCVI diagnosed using each institutions' liberalized screening protocol, defined as automatic CTA of the head and neck for all patients undergoing head and neck CT. Outcomes of interest included AKI, stroke, and death due to BCVI. Outcomes were reported as frequency, percent, and 95% confidence interval as calculated by the Clopper-Pearson method. Incidence of medical follow-up within 1 year of first medical visit was quantified as the median and inter-quartile range of days to follow-up visit., Results: We identified 433 BCVI patients with a mean age of 45.2 (standard deviation 18.9) years, 256 men and 177 women, 1.73 m (0.10) tall, and weighed 80.3 kg (20.3). Forty-one patients had strokes (9.5% [95% confidence interval 6.9, 12.6] and 12 patients (2.8% [1.4, 4.5]) had mortality attributable to BCVI. Of 433 total cases, 132 (30.5% [26.2, 35.1]) would have been missed by DC and 150 (34.6% [30.2, 39.3]) by eDC. Incidence of AKI in our BCVI population was 6 (1.4% [0.01, 3.0])., Conclusions: BCVI would be missed over 30% of the time using the DC and eDC compared to liberalized use of screening CTA. Risk of AKI due to CTA did not occur at a clinically meaningful level, supporting liberal CTA screening., (Copyright © 2023. Published by Elsevier Ltd.)

High particulate matter (PM) pollution episodes still occur occasionally in urban China, despite of improvements in recent years. Investigating the influencing factors of high-PM episodes is beneficial in the formulation of effective control measures. We herein present the effects of weather condition, emission source, and chemical conversion on the occurrence of high-PM episodes in urban Shanghai using multiple online measurements. Three high-PM episodes, i.e., locally-accumulated, regionally-transported, and dust-affected ones, as well as a clean period were selected. Stagnant air with temperature inversion was found in both locally-accumulated and regionally-transported high-PM episodes, but differences in PM evolution were observed. In the more complicated dust-affected episode, the weather condition interacted with the emission/transport sources and chemical conversion, resulting in consecutive stages with different PM characteristics. Specifically, there were (1) stronger local accumulation in the pre-dust period, (2) dust-laden air with aged organic aerosol (OA) upon dust arrival, (3) pollutants being swept into the ocean, and (4) back to the city with aged OA. Our results suggest that (a) local emissions could be rapidly oxidized in some episodes but not all, (b) aged OA from long-range transport (aged in space) had a similar degree of oxygenation compared to the prolonged local oxidation (aged in time), and (c) OA aged over land and over the ocean were similar in chemical characteristics. The findings help better understand the causes and evolution of high-PM episodes, which are manifested by the interplays among meteorology, source, and chemistry, providing a scientific basis for control measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The present study aims to determine the correlations between Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition and body composition and functional parameters, and to comprehensively analyze the predictive value of GLIM-defined malnutrition for postoperative outcomes in the context of detailed measurement of body composition and functional parameters in elderly patients who underwent radical gastrectomy for gastric cancer., Methods: Elderly patients (aged ≥65 years) who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index (SMI), skeletal muscle density (SMD), subcutaneous fat area (SFA), and visceral fat area (VFA) were analyzed using abdominal computed tomography (CT) images. Handgrip strength and 6-m gait speed were measured., Results: A total of 597 elderly patients were included in this study, in which 45.7% were at risk of malnutrition identified using Nutritional Risk Screening 2002 (NRS 2002), and 34.5% were diagnosed with malnutrition. Patients with malnutrition had lower SMI, SMD, SFA, VFA, lower handgrip strength and gait speed. Low handgrip strength and age ≥80 years were independent risk factors for postoperative complications, rather than GLIM-defined malnutrition. GLIM-defined malnutrition was independently associated with overall survival and disease-free survival after adjusting to the body composition and functional parameters in the multivariate analyses., Conclusions: GLIM-defined malnutrition was a better predictive factor than single parameters of body composition or physical function for survival in elderly gastric cancer patients. Handgrip strength can be used as a supportive measure to further improve the definition of malnutrition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The present study aims to investigate the prognostic value of Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition in overweight patients who underwent gastrectomy for gastric cancer, and to explore whether the addition of muscle quality, strength and gait speed could improve the predictive power for postoperative outcomes., Methods: Overweight patients (body mass index (BMI) ≥23 kg/m 2 ) who underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the two-step approach following the GLIM criteria. Skeletal muscle mass and quality was assessed using computed tomography (CT) determined skeletal muscle index (SMI) and skeletal muscle density (SMD), respectively. Hand-grip strength and 6-m gait speed were measured before surgery., Results: A total of 587 overweight patients were included, in which 262 patients were identified as having obesity (BMI ≥25 kg/m 2 ). The prevalence of malnutrition was 11.9% and 10.7% for overweight and obese patients, respectively. GLIM-defined malnutrition alone was not predictive for postoperative complications in overweight patients. The addition of low gait speed or muscle quality to GLIM-defined malnutrition led to a significant predictive value for postoperative complications. Low gait speed plus GLIM-defined malnutrition remained significant in the multivariate analysis. GLIM-defined malnutrition was predictive for overall survival (OS) and disease-free survival (DFS). Addition of low gait speed to GLIM-defined malnutrition increased the hazard ratio (HR) for the prediction of OS and DFS (univariate analysis: 2.880 vs. 2.238 for OS, 2.410 vs. 1.937 for DFS; multivariate analysis: 2.836 vs. 1.841 for OS, 2.433 vs. 1.634 for DFS). Addition of low hand-grip strength to GLIM-defined malnutrition led to a higher HR for the prediction of OS (2.144 vs. 1.841) in the multivariate analysis., Conclusion: Muscle quality, strength and gait speed added prognostic value to GLIM-defined malnutrition for the prediction of postoperative complications and/or survival in overweight patients who underwent radical gastrectomy for gastric cancer, especially gait speed, which could be incorporated into nutritional assessment protocols., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer., Methods: A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery., Results: There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI <25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients., Conclusion: There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs., Methods: Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma. Patients took 20-240 mg osimertinib per day until disease progression or development of intolerable side-effects. Plasma samples were collected every 6 weeks and tumour tissue biopsy was done at study entry and was optional after disease progression. We tested samples for resistance mechanisms, including EGFR-activating, Thr790Met, and Cys797Ser mutations, and assessed associations with overall survival, progression-free survival, and survival after disease progression., Findings: Of 71 patients enrolled in AURA, 53 were eligible for this analysis. Median progression-free survival was 11·1 months (95% CI 8·4-13·9) and overall survival was 16·9 months (11·7-29·1). 47 patients had disease progression. Median overall survival after osimertinib progression was 5·4 months (95% CI 4·1-10·0). Plasma samples were available for 40 patients after disease progression. 12 (30%) of these had the Thr790Met mutation (four of whom also had Cys797Ser mutations). Patients without detectable EGFR-activating mutations in plasma before treatment had the best overall and post-progression survival (22·4 months, 95% CI 15·6-not reached, and 10·8 months, 7·2-not reached, respectively). Loss of the Thr790Met mutation but presence of EGFR-activating mutations in plasma were associated with the shortest progression-free survival (median 2·6 months, 95% CI 1·3-not reached). In 22 post-progression tumour samples, we found one squamous cell and two small-cell transformations. We detected Thr790Met in nine (50%) of 18 samples, Cys797Ser in two (17%) of 12, cMET amplification in five (50%) of ten, BRAF mutation in one (8%) of 13, and KRAS mutation in one (8%) of 13., Interpretation: Heterogeneous resistance mechanisms developed in patients receiving osimertinib. Differences in resistance mechanisms might dictate future development strategies for osimertinib in clinical trials., Funding: AstraZeneca, Taiwan Ministry of Science and Technology., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Current researches showed that TLR family plays an important role in liver fibrosis, yet the molecular mechanism by which this occurs is not fully explained. In this study, we investigated the role of TLR5 in carbon tetrachloride-induced liver fibrosis, and further examined wether TLR5 knockout attenuated tetrachloride-induced liver fibrosis by inhibiting hepatic stellate cells activation via modulating NF-κB and MAPK signaling pathways. Our results found that carbon tetrachloride induced liver function injury in WT mice with a inflammatory responses through the activation of NF-κB and MAPK signaling pathways, resulting in hepatic stellate cells activation. In contrast, TLR5 deficiency mice after carbon tetrachloride administration reduced NF-κB and MAPK signaling pathways activation, which down regulated hepatic stellate cells activation. In addition, alpha smooth muscle-actin as marker of hepatic stellate cells further indicated that TLR5 knockout mice have a lower collagen accumulation in liver tissue than WT mice after carbon tetrachloride administration, resulting in inhibition of NF-κB and MAPK signaling pathways activation. Moreover, in vitro experiment of hepatic stellate cells challenged with LPS or TGF-β, further indicated that NF-κB and MAPK were involved in liver fibrosis development, leading to α-SMA expression and inflammation infiltration. However, cells from TLR5(-)(/-) may weaken phosphorylation levels of signal pathways, finally suppress progress of collagen accumulation and inflammatory responses. These results suggest a new therapeutic approach or target to protect against fibrosis caused by chronic liver diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate the short-term safety and long-term benefits of radical gastrectomy for gastric cancer in elderly patients., Methods: A total of 729 patients undergoing gastrectomy for adenocarcinoma between December 2008 and December 2011 were enrolled in this retrospective study. Patients were divided into three groups: young group (<65 years), young-old group (65-79 years) and old-old group (≥80 years)., Results: Lower albumin levels, higher ASA grades, comorbidities, tumors located in the upper third of the stomach and advanced TNM stages were more common in the young-old and old-old age groups. Overall complications increased significantly with advancing age (15.4%, 24.9%, 48.7%, respectively); respiratory complications largely contributed to the dramatic increase. Severe complications were similar between the young and young-old groups (3.9%, 3.7%), but were significantly increased in the old-old group (12.8%). In multivariate analysis, old-old age, multiple comorbidities and no epidural use were strong predictors for overall complications. Both overall survival and disease-specific survival (DSS) rates declined with advancing age. Multivariate analysis showed that old-old age and TNM stage ≥ II were major independent risk factors for the DSS rate. When adjusted for confounding factors, young-old age was not a risk factor. The median survival time for the old-old patients with stage III tumors was 12.9 months., Conclusions: It is relatively safe and beneficial for young-old patients to undergo radical gastrectomy as the young patients. However, the decision to perform radical gastrectomy for old-old patients with TNM stage III tumors should be made carefully., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Planar imaging of (188)Re-labeled vascular endothelial growth factor (VEGF)(189) exon 6-encoded peptide (QKRKRKKSRYKS) with single photon emission computed tomography (SPECT) in tumor-bearing nude mice and effects of the transfecting truncated KDR gene on its imaging were investigated, so as to provide a basis for further applying the peptide to tumor-targeted radionuclide treatment., Methods: QKRKRKKSRYKS, coupling with mercaptoacetyltriglycine (MAG(3)) chelator was labeled with (188)Re; then in vivo distribution, planar imaging with SPECT and blocking experiment in tumor-bearing nude mice were analyzed. Recombinant adenovirus vectors carrying the truncated KDR gene were constructed to transfect tumor tissues to evaluate the effects of truncated KDR on the in vivo distribution and tumor planar imaging of (188)Re-MAG(3)-QKRKRKKSRYKS in tumor-bearing nude mice., Results: The labeled peptide exhibited a sound receptor binding activity. Planar imaging with SPECT demonstrated significant radioactivity accumulation in tumor 1 h after injection of the labeled peptide and disappearance of radioactivity 3 h later. Significant radioactivity accumulation was also observed in the liver, intestines and kidneys but was not obvious in other tissues. An hour after injection of the labeled peptide, the percentage of the injected radioactive dose per gram (%ID/g) of tumor and tumor/contralateral muscle tissues ratio were 1.98+/-0.38 and 2.53+/-0.33, respectively, and increased to 3.08+/-0.84 and 3.61+/-0.59 in the group transfected with the truncated KDR gene, respectively, and radioactivity accumulation in tumor with planar imaging also increased significantly in the transfection group., Conclusion: (188)Re-MAG(3)-QKRKRKKSRYKS can accumulate in tumor tissues, which could be increased by the transfection of truncated KDR gene. This study provides a basis for further applying the peptide to tumor targeted radionuclide imaging and treatment.

Background/aims: MicroRNAs are a small non-coding family of genes involved in the regulation of gene expression in a post-transcriptional manner and contribute to cell proliferation, differentiation and apoptosis. Our aims were to identify statistically unique miRNA profiles in human intrahepatic cholangiocarcinoma for diagnosis and investigate their specific involvement in various cell biological processes in cholangiocarcinoma., Methods: Laser capture microdissection techniques and TaqMan miRNA assays for mature miRNAs were performed to assess the genomewide expression of miRNAs in 27 human ICCs, 10 normal cholangiocyte cells and 8 normal liver tissues precisely and quantitatively. Two selected miRNAs, mir-204 and mir-320, were introduced into cholangiocarcinoma cell lines to examine their effects on potential target genes, Bcl-2 and Mcl-1, respectively., Results: A cluster of 38 miRNAs was markedly distinguishable between tumor and normal tissues. At least two distinct clusters of tumor samples could be identified that were associated with the higher or lower expression levels of carbohydrate antigen 19-9. Moreover, the exogenous expression of mir-320 or mir-204 could negatively regulate Mcl-1 or Bcl-2 expression and facilitate chemotherapeutic drug-triggered apoptosis., Conclusions: miRNA expression profiles are closely associated with the biological and clinical behavior of ICC. The modulation of aberrantly expressed miRNAs might prove a promising therapeutic strategy.

We have established an assay based on gas chromatography-mass spectrometry to profile and quantitate endogenous cytochrome P450 monooxygenase (P450)-hydroxyeicosatetraenoic acids (HETEs) exiting the isolated perfused rabbit kidney in response to hormonal stimulation. In response to angiotensin II (Ang II) P450-derived HETEs (16-, 17-, 18-, 19- and 20-) are released from the isolated Kreb's perfused rabbit kidney. Ang II produced a several-fold increase in the levels of P450-HETEs above basal levels in both urinary (such as for 20-HETE from 0.93 +/- 0.7 to 2.31 +/- 0.9 ng/min) and venous (from 0.1 +/- 0.05 to 0.3 +/- 0.05 ng/min) effluents. However, inhibition of P450, which reduced basal release, did not prevent Ang II-induced release of P450-AA products from the rabbit kidney; for example, urinary 20-HETE in the presence of 17-ODYA (1 microM) was undetectable and increased to 0.93 +/- 0.4 ng/min with Ang II and venous 20-HETE increased from 0.06 +/- 0.03 to 0.24 +/- 0.07 ng/min. Similar results were obtained with clotrimazole (1 microM). As 16-, 18-, 19- and 20-HETEs are vasodilators in the rabbit kidney and 16- and 17-HETEs inhibit proximal tubular ATPase activity, we investigated their possible sites of esterification. Cortical and medullary lipids were extracted, separated by HPLC and P450-HETEs quantitated following alkaline hydrolysis. The P450-HETEs were incorporated into both neutral lipids (NL) and phospholipids [phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and phosphatidylcholine (PC)]. However, the assignment of a HETE to a specific phospholipid pool must be regarded as tentative as the appropriate standards containing P450-HETEs in the Sn-2 position (such as 20-HETE-PF., 20-HETE-PC, etc.) were not available. Esterified HETEs were found in larger quantities in the cortex as compared to the medulla (34.40 +/- 1.12 versus 22.76 +/- 0.53 ng/g). The PI fraction in the cortex yielded the largest quantity of HETEs and the PC fraction the lowest. In the medulla, the largest quantities of esterified HETEs were found in neutral lipids and only slightly lesser amounts in PE and PI. Esterified 18-HETE was localized only to the NI fraction. This fraction also contained the other HETEs, 19- and 20-HETE being the most abundant. Notably only 16- and 17-HETE were present in PF, whereas, 19- and 20-HETE were also present in PI, PS and PC. Thus, P450-HETEs, like EETs are stored in the kidney and are, presumably, subject to release by peptide activation of acylhydrolases.