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This study explores the potential mechanisms of obstructive sleep apnoea (OSA) complicates type 2 diabetes mellitus (T2DM) by which chronic intermittent hypoxia (CIH) induces insulin resistance and cell apoptosis in the pancreas through oxidative stress. Four‐ and eight‐week CIH rat models were established, and Tempol (100 mg/kg/d), was used as an oxidative stress inhibitor. This study included five groups: 4‐week CIH, 4‐week CIH‐Tempol, 8‐week CIH, 8‐week CIH‐Tempol and normal control (NC) groups. Fasting blood glucose and insulin levels were measured in the serum. The expression levels of 8‐hidroxy‐2‐deoxyguanosine (8‐OHdG), tribbles homologue 3 (TRB3), c‐Jun N‐terminal kinase (JNK), phosphorylated JNK (p‐JNK), insulin receptor substrate‐1 (IRS‐1), phosphorylated IRS‐1 (Ser307) (p‐IRS‐1ser307), protein kinase B (AKT), phosphorylated AKT (Ser473) (p‐AKTser473), B cell lymphoma protein‐2 (Bcl‐2), cleaved‐caspase‐3 (Cl‐caspase‐3), and the islet cell apoptosis were detected in the pancreas. CIH induced oxidative stress in the pancreas. Compared with that in the NC group and CIH‐Tempol groups individually, the homeostasis model assessment of insulin resistance (HOMA‐IR) and apoptosis of islet cells was increased in the CIH groups. CIH‐induced oxidative stress increased the expression of p‐IRS‐1Ser307 and decreased the expression of p‐AKTSer473. The expression levels of TRB3 and p‐JNK were higher in the CIH groups than in both the CIH‐Tempol and NC groups. Meanwhile, the expressions of Cl‐caspase‐3 and Bcl‐2 were upregulated and downregulated, respectively, in the CIH groups. Hence, the present study demonstrated that CIH‐induced oxidative stress might not only induce insulin resistance but also islet cell apoptosis in the pancreas through TRB3 and p‐JNK. [ABSTRACT FROM AUTHOR]

Background: Monocytes and fibrinogen (FIB) play important roles in driving acute and reparative inflammatory pathways after myocardial infarction (MI). In humans, there are three subsets of monocytes, namely, CD14++CD16− (Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). During the inflammatory response, monocyte subsets express high levels of integrin αMβ2 and protease‐activated receptors 1 and 3 to interact with FIB. Hypothesis: However, whether there is a synergistic role of FIB combined with Mon2 counts in prioritizing patients at high risk of future major adverse cardiovascular events (MACEs) after MI remains unknown. Methods: The MI patients who treated with primary percutaneous coronary intervention were enrolled. MI patients were categorized into four groups, that is, low FIB/low Mon2, low FIB/high Mon2, high FIB/low Mon2, and high FIB/high Mon2, according to cutoff values of 3.28 g/L for FIB and 32.20 cells/μL for Mon2. Kaplan−Meier survival analysis and Cox proportional hazards models were used to estimate the risk of MACEs of MI patients during a median follow‐up of 2.7 years. Mediating effects of high FIB levels and MACEs associated with high monocyte subsets were calculated by mediation analysis. Results: High FIB/high Mon2 group had the highest risk of MACEs during a median follow‐up of 2.7 years. Moreover, mediation analysis showed that a high FIB level could explain 24.9% (p <.05) of the increased risk of MACEs associated with Mon2. Conclusion: This work provides evidence indicating the translational potential of a synergistic role of FIB combined with Mon2 in prioritizing patients at high risk of future MACEs after MI. [ABSTRACT FROM AUTHOR]

Background: In experimental animal models, implantation location might influence the heterogeneity and overall development of the tumor, leading to an interpretation bias. Purpose To investigate the effects of implantation location in experimental tumor model using magnetic resonance imaging (MRI) and pathological findings. Study Type: Prospective. Subjects: Forty‐five breast cancer‐bearing mice underwent orthotopic (N = 15) and heterotopic (intrahepatic [N = 15] and subcutaneous [N = 15]) implantation. Field Strength/Sequence: Sequences including: T1‐weighted turbo spin echo sequence, T2‐weighted blade sequence, diffusion‐weighted imaging, pre‐ and post‐contrast T1 mapping, multi‐echo T2 mapping at 3.0 T. Assessment MRI was performed at 7, 14, and 21 days after implantation. Native T1, post‐contrast T1, T2, and apparent diffusion coefficient (ADC) of tumors, the tumor volume and necrosis volume within tumor were obtained. Lymphocyte cells from H&E staining, Ki67‐positive, and CD31‐positive cells from immunohistochemistry were determined. Statistical Tests: One‐way analysis of variance and Spearman's rank correlation were performed. P value <0.05 was considered statistically significant. Results: The tumor volume (intrahepatic vs. orthotopic vs. subcutaneous: 587.50 ± 77.62 mm3 vs. 814.00 ± 43.85 mm3 vs. 956.13 ± 119.22 mm3), necrosis volume within tumor (89.10 ± 26.60 mm3 vs. 292.41 ± 57.92 mm3 vs. 179.91 ± 31.73 mm3, respectively), ADC at day 21 (543.41 ± 42.28 vs. 542.92 ± 99.67 vs. 369.83 ± 42.90, respectively), and post‐contrast T1 at all timepoints (day 7: 442.00 ± 11.52 vs. 435.00 ± 22.90 vs. 394.33 ± 29.95; day 14: 459.00 ± 26.11 vs. 436.83 ± 26.01 vs. 377.00 ± 27.83; day 21: 463.50 ± 23.49 vs. 458.00 ± 34.28 vs. 375.00 ± 30.55) were significantly different between three groups. Necrosis volumes of subcutaneous and intrahepatic tumors were significantly lower than those of orthotopic tumors. The CD31‐positive rate in the intrahepatic implantation was significantly higher than in orthotopic and subcutaneous groups. Necrosis volume (r = −0.71), ADC (r = −0.85), and post‐contrast T1 (r = −0.75) were strongly correlated with vascular invasion index. Data Conclusion: Orthotopic and heterotopic tumors have their unique growth kinetics, necrosis volume, and vascular invasion. Non‐invasive MR quantitative parameters, including ADC and post‐contrast T1, may reflect vascular invasion in mice. Level of Evidence: 1 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: KEYNOTE‐063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second‐line therapy in Asian patients with advanced programmed death ligand 1 (PD‐L1)–positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer. Methods: This randomized, open‐label, phase 3 study was conducted at 36 medical centers in China (mainland), Malaysia, South Korea, and Taiwan. Patients were randomly assigned 1:1 to 200 mg of pembrolizumab intravenously every 3 weeks for ≤2 years or 80 mg/m2 of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression‐free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety. Results: Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE‐061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval [CI], 4‐10 months) with pembrolizumab versus 8 months (95% CI, 5‐11 months) with paclitaxel (hazard ratio [HR], 0.99; 95% CI, 0.63‐1.54). Median PFS was 2 months (95% CI, 1‐3 months) with pembrolizumab versus 4 months (95% CI, 3‐6 months) with paclitaxel (HR, 1.62; 95% CI, 1.04‐2.52). ORR was 13% for pembrolizumab versus 19% for paclitaxel. Any‐grade treatment‐related adverse events occurred in 28 pembrolizumab‐treated patients (60%) and 42 paclitaxel‐treated patients (96%); grades 3 to 5 events occurred in 5 patients (11%) and 28 patients (64%), respectively. Conclusions: Definitive conclusions about the efficacy of second‐line pembrolizumab in Asian patients with advanced PD‐L1–positive gastric/GEJ cancer are limited because of insufficient power, but pembrolizumab was well tolerated in this patient population. Efficacy followed a trend similar to that observed in the phase 3 KEYNOTE‐061 trial. In this small sample of Asian patients with advanced PD‐L1–positive (combined positive score [CPS] ≥1) gastric/gastroesophageal junction (GEJ) cancer enrolled in the randomized, open‐label, phase 3 KEYNOTE‐063 study, definitive conclusions on clinical outcomes are limited; however, second‐line pembrolizumab monotherapy seems to be well tolerated in this patient population. These findings are consistent with those of the larger global KEYNOTE‐061 study in patients with CPS ≥1 gastric/GEJ cancer. [ABSTRACT FROM AUTHOR]

CLEC10A, (C‐type lectin domain family 10, member A), as the member of C‐type lectin receptors (CLRs), plays a vital role in modulating innate immunity and adaptive immunity and has shown great potential as an immunotherapy target for cancers. However, there is no functional research of CLEC10A in prognostic risk, immunotherapy or any other treatment of lung adenocarcinoma (LUAD). We performed bioinformatics analysis on LUAD data downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analysed with online databases such as HPA, LinkedOmics, TIMER, ESTIMATE and TISIDB. We found that lower expression of CLEC10A was accompanied with worse outcomes of LUAD patients. Moreover, CLEC10A expression was significantly correlated with a variety of the tumour‐infiltrating immune cells (TIICs). As a promising prognosis predictor and potential immunotherapy target, the potential influence and mechanisms of CLEC10A in LUAD deserve further exploring. [ABSTRACT FROM AUTHOR]

The rapid onset of resistance to cetuximab (CTX) limits its clinical utility in colorectal cancer (CRC) patients. This study aims to understand a potential role of mismatch repair gene mutL homolog 1 (MLH1) in CTX response. Functional analysis of MLH1 in Her‐2/phosphoinositide 3‐kinases (PI3K)/PKB protein kinase (AKT)‐regulated CTX sensitivity is performed using human CRC specimens, CRC cell lines with different MLH1 expression levels, and a subcutaneous xenograft model. Overexpression, knockdown, small interfering RNA, and inhibitors are used to examine the role of MLH1 and HER‐2 downstream signaling and apoptotic targets in CTX sensitivity. Reduced MLH1 expression is correlated with unfavorable prognosis in cetuximab‐treated patients. MLH1 loss decreases CTX sensitivity through Her‐2/PI3K/AKT signaling and apoptosis resistance in culture and in xenografts, while MLH1 overexpression increases CTX sensitivity. Blocking Her‐2 signaling increases CTX sensitivity of microsatellite instability CRC in vitro and in vivo. MLH1 loss induces activation of Her‐2/PI3K/AKT signaling and leads to cetuximab resistance in colon cancer. [ABSTRACT FROM AUTHOR]

An ionic liquid‐based microwave‐assisted extraction method was developed to extract luteolin from peanut shells effectively. A series of hydrophilic 1‐alkyl‐3‐methylimidazolium ionic liquids with different anions (Br−, Cl− and BF4−) and different cations ([C2mim]+, [C4mim]+, [C8mim]+ and [C10mim]+) were screened, and [C10mim]Br was found to be the optimal extraction solvent. The reason is that when the cations are the same, the hydrogen bonding between Br− and the phenolic hydroxyl group on luteolin is the strongest; when the anions are the same, the carbon chain growth enhances the van der Waals force between the ionic liquid and the luteolin. The concentration of ionic liquid, extraction temperature, liquid‐solid ratio and extraction time were optimized by both single factor experiments and response surface methodology. Under the optimized conditions of [C10mim]Br concentration 1.00 mol/L, extraction temperature 85 °C, liquid‐solid ratio 11.63:1 mL/g, extraction time 12 min, the extraction yield of luteolin reached 80.36±0.67%. In addition, compared with conventional solvents, [C10mim]Br showed an excellent extraction yield to extracting luteolin from peanut shells. [ABSTRACT FROM AUTHOR]

Aberrant long noncoding RNAs (lncRNA) have been proved to be associated with the many types of malignant tumors (including hepatocellular carcinoma [HCC]). In this study, a lncRNAs and mRNAs microarray analysis was performed in three pairs of HCC patitents' tumor. We found lncRNA LIM and SH3 protein 1 antisense (LASP1‐AS) and its sense‐cognate gene LIM and SH3 protein 1 (LASP1) were upregulated in HCC and both are correlated with poorer prognosis and lower survival of HCC patients. Meanwhile, the expression of LASP1‐AS correlated positively with LASP1 expression in HCC tissues. LASP1‐AS promoted the proliferation, migration, and invasion abilities of HCC in vitro and vivo by enhancing LASP1 expression. Our study explored lncRNA LASP1‐AS as an oncogene in HCC and promoted proliferation and metastasis capabilities of HCC via increasing the expression of its sense‐cognate gene LASP1. LncRNA LASP1‐AS might be a potential valuable prognostic biomarker and potential therapeutic target of HCC. [ABSTRACT FROM AUTHOR]

Abstract: rCCK8PE38 is a novel immunotoxin that targets choleystokinin B receptor, which is over‐expressed in some tumor tissues. Although we constructed a prokaryotic expression vector to express rCCK8PE38 in our laboratory, thorough purification was necessary to quantitatively assess its anti‐tumor effect. In this study, we established a purification protocol to obtain rCCK8PE38 with high purity from E. coli. Three different types of chromatography, hydrophobic chromatography, ion exchange chromatography and size exclusion chromatography, were used in combination. The purification technological parameters of each chromatography type were optimized. The whole process of purification was arranged to minimize the purification steps and achieve purity and bioactivity. Finally, through this optimized scheme, we obtained a recombinant protein with a purity of >95%; then, the protein was stored at −80°C after lyophilization. The purified protein was used in a tumor inhibition experiment and was effective in killing tumor cells that over‐expressed choleystokinin B receptor. The results of this study may provide some valuable information about protein purification and lay the foundation for further clinical experiments with rCCK8PE38. [ABSTRACT FROM AUTHOR]

Background and Purpose: Abnormal glycolytic metabolism contributes to joint inflammation in rheumatoid arthritis (RA). The aims of this study were to investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a bifunctional enzyme that controls the glycolytic rate, in regulating fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and invasiveness in RA.Experimental Approach: A specific inhibitor of PFKFB3, PFK15, and siRNA were used to evaluate the role of PFKFB3. Protein expression was measured by Western blotting or immunofluorescence staining. The expression of cytokines was determined by quantitative real-time PCR. Migration and invasion were measured using a Boyden chamber assay. A mouse model of collagen-induced arthritis (CIA) was used to evaluate the in vivo effect of PFK15.Key Results: PFKFB3 expression was increased in the synovial tissue and FLSs from RA patients compared with osteoarthritis patients. PFKFB3 inhibition decreased the expression of IL-8, IL-6, CCL-2 and CXCL-10 and the proliferation, migration and invasion of RA FLSs. PFK15 suppressed TNF-α-induced activation of NF-κB and p38, JNK and ERK MAPK signals in RA FLSs. PFK15 treatment also suppressed glucose uptake and lactate secretion. Lactate reversed the inhibitory effect of PFK15 or PFKFB3 siRNA on cytokine expression and migration of RA FLSs. Lactate was also involved in PFKFB3-mediated activation of NF-κB and MAPKs. Intraperitoneal injection of PFK15 in mice with CIA attenuated joint inflammation.Conclusion and Implications: Elevated PFKFB3 expression might contribute to synovial inflammation and aggressive behaviours of RA FLSs, suggesting a novel strategy of targeting PFKFB3 to prevent synovial inflammation and joint destruction in RA. [ABSTRACT FROM AUTHOR]

To probe the role of protein arginine methyltransferase 5 ( PRMT5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast-like synoviocytes ( FLSs) from patients with rheumatoid arthritis ( RA). FLSs were separated from synovial tissues ( STs) from patients with RA and osteoarthritis ( OA). An inhibitor of PRMT5 ( EPZ015666) and short interference RNA (si RNA) against PRMT5 were used to inhibit PRMT5 expression. The standard of protein was measured by Western blot or immunofluorescence. The excretion and genetic expression of inflammatory factors were, respectively, estimated by enzyme-linked immunosorbent assay ( ELISA) and real-time polymerase chain reaction ( PCR). Migration and invasion in vitro were detected by Boyden chamber assay. FLSs proliferation was detected by BrdU incorporation. Increased PRMT5 was discovered in STs and FLSs from patients with RA. In RA FLSs, the level of PRMT5 was up-regulated by stimulation with IL-1β and TNF-α. Inhibition of PRMT5 by EPZ015666 and si RNA-mediated knockdown reduced IL-6 and IL-8 production, and proliferation of RA FLSs. In addition, inhibition of PRMT5 decreased in vitro migration and invasion of RA FLSs. Furthermore, EPZ015666 restrained the phosphorylation of IκB kinaseβ and IκBα, as well as nucleus transsituation of p65 as well as AKT in FLSs. PRMT5 regulated the production of inflammatory factors, cell proliferation, migration and invasion of RA FLS, which was mediated by the NF-κB and AKT pathways. Our data suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA. [ABSTRACT FROM AUTHOR]

Background and Purpose: There is increasing evidence indicating that bromodomain and extra-terminal domain (BET) proteins play a critical role in the regulation of immune and inflammatory responses; however, their contribution to vascular inflammation has not yet been elucidated. In this study, we investigated the effect of inhibiting BET bromodomain on vascular inflammation and the underlying mechanisms.Experimental Approach: HUVECs were isolated from fresh umbilical cords. JQ1, a specific BET bromodomain inhibitor, and Brd shRNA were used to evaluate the regulation of the BET proteins in vascular inflammation. Leukocyte adhesion to HUVECs was measure by an adhesion assay. Western blot or immunohistochemical analysis was used to detect the protein expression. Real-time PCR was used to evaluate mRNA expression. Leukocyte accumulation in vivo was determined by an acute lung inflammation model.Key Results: BET bromodomain inhibition suppressed the expression of adhesion molecules induced by TNF-α- or LPS, including ICAM-1, VCAM-1 and E-selectin, and inhibited leukocyte adhesion to activated HUVEC monolayers. Treatment with JQ1 also attenuated the LPS-induced accumulation of leukocytes and expression of endothelial adhesion molecules in the acute lung inflammation model in vivo. Furthermore, BET bromodomain inhibition reduced the activity of p38 and JNK MAPKs and NF-κB in TNF-α-stimulated HUVECs. TNF-α-induced NF-κB activation was also blocked by inhibitors of p38 (SB203580) or JNK (SP600125).Conclusions and Implications: BET bromodomain is important for regulating endothelial inflammation. Strategies targeting endothelial BET bromodomain may provide a new therapeutic approach for controlling inflammatory-related diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Poultry husbandry is a very important aspect of the agricultural economy in China. However, chicks are often susceptible to infectious disease microorganisms, such as bacteria, viruses and parasites, causing large economic losses in recent years. In the present study, we isolated an Acinetobacter baumannii strain, CCGGD201101, from diseased chicks in the Jilin Province of China. Regression analyses of virulence and LD50 tests conducted using healthy chicks confirmed that A. baumannii CCGGD201101, with an LD50 of 1.81 (±0.11) × 104 CFU, was more virulent than A. baumannii ATCC17978, with an LD50 of 1.73 (±0.13) × 107 CFU. Moreover, TEM examination showed that the pili of A. baumannii CCGGD201101 were different from those of ATCC17978. Antibiotic sensitivity analyses showed that A. baumannii CCGGD201101 was sensitive to rifampicin but resistant to most other antibiotics. These results imply that A. baumannii strain CCGGD201101 had both virulence enhancement and antibiotic resistance characteristics, which are beneficial for A. baumannii survival under adverse conditions and enhance fitness and invasiveness in the host. A. baumannii CCGGD20101, with its high virulence and antimicrobial resistance, may be one of the pathogens causing death of diseased chicks. [ABSTRACT FROM AUTHOR]

Cancers are thought to be the result of accumulated gene mutations in cells. Carcinomas, which are cancers arising from epithelial tissues usually go through several stages of development: atypical hyperplasia, carcinoma in situ and then invasive carcinoma, which might further metastasize. However, we think that the present pathological data are enough to prove that there might be an alternative way of carcinogenesis. We propose that majority of invasive cancers arise in the connective tissue stroma de novo, from the misplaced epithelial stem cells which come to the wrong land of connective tissue stroma by accident. The in situ carcinomas, which are mostly curable, should not be considered genuine cancer, but rather as quasi-cancer. We design this new theory of carcinogenesis as the stem cell misplacement theory ( SCMT). Our SCMT theory chains together other carcinogenesis theories such as the inflammation-cancer chain, the stem cell theory and the tissue organization field theory. However, we deny the pathway of somatic mutation theory as the major pathway of carcinogenesis. [ABSTRACT FROM AUTHOR]

The aim of the present study is to profile differentially expressed protein markers between left-sided colon cancer ( LSCC) and right-sided colon cancer ( RSCC). Fresh tumor tissue samples from LSCC ( n = 7) and RSCC ( n = 7) groups were analyzed by two-dimensional electrophoresis coupled with MALDI- TOF- MS, followed by Western blotting. In 50 paraffin embedded samples from each group, levels of four differentially expressed proteins (identified by proteomics analysis) were measured by tissue microarray with immunohistochemistry staining to compare the different protein markers between LSCC and RSCC. Sixteen proteins were found to be differentially expressed between LSCC and RSCC. Ten proteins including HSP-60 and PDIA1 were identified to be highly expressed in LSCC ( P < 0.01 or P < 0.05), while the expression of six proteins including EEF1 D and HSP-27 were higher in RSCC ( P < 0.01 or P < 0.05). Virtually all of the indentified proteins were involved in cellular energy metabolism, protein folding/unfolding, and/or oxidative stress. Human colon tumors at various locations have different proteomic biomarkers. Differentially expressed proteins associated with energy metabolism, protein folding/unfolding and oxidative stress contribute to different tumorigenesis, tumor progression, and prognosis between left- and right-sided colon cancer. ( Cancer Sci 2013; 104: 141-135) [ABSTRACT FROM AUTHOR]

Cancer has been considered to be the result of accumulated gene mutations, which result in uncontrolled cell proliferations for a long time. Cancers are also regarded to be capable of immune evasion. Furthermore, resistance to apoptosis was recognized as an important trait of cancer in the last score of years. However, there are numerous paradoxical issues in this whole set of theory. For example, there is no known set of genes of which mutations are responsible for human cancers. As for the trait of 'resistance to apoptosis', the fact is that cancer has increased frequency of apoptosis. The more malignant the tumour is, the more apoptosis shows. In this study, we propose a new theory that apoptosis plays a key role in the malignant progression and metastasis of cancer. The growth of tumour is the difference between tumour cell proliferation and attrition plus the hyperplastic growth of stroma. Increased and unpreventable death caused by innate or environmental factors such as ischaemia and inflammation drives the tumour cells to proliferate relentlessly, move to new lands to establish colonies. In short, increased cell death is the origin of malignancy. [ABSTRACT FROM AUTHOR]

Both chordoma and Rathke's cleft cyst are relatively rare diseases in the central nervous system. In this paper we report the first case of a chordoma coexisting with a Rathke's cleft cyst. A 49-year-old man presented with a 19-month history of distending pain, movement dysfunction and diplopia of the left eye. The preoperative diagnosis was consistent with chordoma with cystic change. Final pathological diagnosis of chordoma coexisting with Rathke's cleft cyst was made according to histological and immunohistochemical studies and the clinical and radiological features are discussed. Considering the close relationship between the notochordal tissue and Rathke's pouch during early embryogenic development, a possible mechanism is also discussed with the literature review. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 27-year-old woman who was admitted to the Xijing Hospital in China due to neuromuscular and vascular hamartoma (NMVH), a special phase of Crohn's disease. It states that the patient has a medical history of anemia, fecal occult blood, and ileum mucosal edema and has eventfully recovered after anastomosis and laparotomy. It discusses the history NMVH which was first described as an extremely rare stricturous condition of the small intestine in 1982.

Background: This study was designed to investigate the effect of captopril on systolic pulmonary arterial pressure (PAP) and circulating endothelin-1 (ET-1) following surgical repair of tetralogy of Fallot (TOF)., Methods and Results: Seventy-six consecutive patients were divided into captopril and control groups following successful repair of TOF. The captopril group was treated with oral captopril (0.2 mg/kg/day) for 12 months. Venous blood was taken before and after the surgery for the analysis of ET-1. Systolic PAP and ventricular function were assessed by Doppler echocardiography. In the control group, there was an increase in ET-1 and systolic PAP following the surgery (p < 0.05). In the captopril group, there was no significant increase in the systolic PAP and ET-1 during the 12-month follow-up. The PAP and ET-1 values in the captopril group were lower than those in the control group following the surgery (p < 0.05)., Conclusions: Systolic PAP is elevated following the complete surgical repair of TOF. Increased circulating ET-1 may be responsible for the elevation of PAP. Captopril treatment prevents postsurgical increases in systolic PAP and circulating ET-1.