[Efficacy of Pulmonary Vein Isolation in the Surgical Treatment of Atrial Fiburillation].

BACKGROUND: Maze surgery is often performed for atrial fibrillation during cardiac surgery, and a certain number of therapeutic effects are observed. However, the effectiveness of pulmonary vein isolation (PVI) remains unclear. METHODS: 329 arrhythmia surgeries was performed between 2012 and 2021. The patients were divided into three groups:paroxysmal atrial fibrillation (PAf) group, persistent atrial fibrillation group (PerAf), and long persistent atrial fibrillation( LongPerAf) group. In the PVI and maze groups, postoperative sinus rhythm rate and the rate of freedom from Af recurrence were compared. RESULTS: In PAf, PerAf cases, there was no difference between PVI and maze groups in the rate of freedom from recurrent Af and postoperative sinus rhythm rate. In LongPerAf cases, the rates of freedom from recurrent Af and postoperative sinus rhythm were significantly lower in the PVI group. CONCLUSION: PVI was considered effective in patients with atrial fibrillation of less than one year duration due to the simplicity of the procedure and low complications.

[Staged Fenestrated Endovascular Repair of Thoracoabdominal Aneurysm].

Fenestrated endovascular repair (FEVAR) can be a treatment option for thoraco-abdominal aneurysm( TAAA), especially in the cases with high surgical risks. Spinal cord ischemic injury( SCI) continues to be the most devastating complication, that has multifactorial etiologies including embolic events and coverage of Adamkiewicz's artery (AKA). Recently, we experienced a case of Crawford III TAAA. The 77 year-old male had multiple comorbidities including recent myocardial infarction, chronic heart failure with reduced ejection fraction, and an end-stage renal disease. A colostomy was located on the left side of the abdomen after the surgical resection of rectal cancer. The AKA was originated from the intercostal artery at the level of the tenth thoracic vertebra( THV), which was intended to be covered by a stent-graft. To reduce the risk of SCI, FEVAR was scheduled in a staged fashion, with the proximal coverage up to the tenth THV and a branch-typed endovascular reconstruction of the celiac artery performed as the first stage treatment. The completion repair was achieved in 4 weeks, with the remaining superior mesenteric and renal arteries successfully stented. Neither SCI nor endoleak was detected periprocedurally.

Dynamic Behavior of Intermediate Adsorbates to Control Activity and Product Selectivity in Heterogeneous Catalysis: Methanol Decomposition on Pt/TiO2(110).

Dynamic behavior of intermediate adsorbates, such as diffusion, spillover, and reverse spillover, has a strong influence on the catalytic performance in oxide-supported metal catalysts. However, it is challenging to elucidate how the intermediate adsorbates move on the catalyst surface and find active sites to give the corresponding products. In this study, the effect of the dynamic behavior of methoxy intermediate on methanol decomposition on a Pt/TiO2(110) surface has been clarified by combination of scanning tunneling microscopy (STM), temperature-programmed desorption (TPD), and density functional theory (DFT) calculations. The methoxy intermediates were formed by the dissociative adsorption of methanol molecules on Pt nanoparticles at room temperature followed by spillover to the TiO2(110) support surface. TPD results showed that the methoxy intermediates were thermally decomposed at >350 K on the Pt sites to produce CO (dehydrogenation) and CH4 (C-O bond scission). A decrease of the Pt nanoparticle density lowered the activity for the decomposition reaction and increased the selectivity toward CH4, which indicates that the reaction is controlled by diffusion and reverse spillover of the methoxy intermediates. Time-lapse STM imaging and DFT calculations revealed that the methoxy intermediates migrate on the five-fold coordinated Ti (Ti5c) sites along the [001] or [11¯0] direction with the aid of hydrogen adatoms bonded to the bridging oxygens (Obr) and can move over the entire surface to seek and find active Pt sites. This work offers an in-depth understanding of the important role of intermediate adsorbate migration in the control of the catalytic performance in oxide-supported metal catalysts.

Size-Dependent Corrosion of Al-Fe Intermetallic Particles at Al-Mg Alloy Surfaces Investigated by In-Liquid Nanoscale Potential Measurement Technique.

Corrosion of Al alloy often starts from the nanoscale corrosion around the surface-exposed Al-Fe intermetallic particles (IMPs) and leads to a serious damage limiting its application range in the automobile industry. To solve this issue, understanding of the nanoscale corrosion mechanism around the IMP is essential, yet it is impeded by the difficulties in directly visualizing nanoscale distribution of reaction activity. Here, this difficulty is overcomed by open-loop electric potential microscopy (OL-EPM) and investigate nanoscale corrosion behavior around the IMPs in H2 SO4 solution. The OL-EPM results reveal that the corrosion around a small IMP settles down in a short time (<30 min) after transient dissolution of the IMP surface while that around a large IMP lasts for a long time especially at its edges and results in a severe damage of the IMP and matrix. This result suggests that an Al alloy with many small IMPs gives a better corrosion resistance than that with few large IMPs if the total Fe content is the same. This difference is confirmed by corrosion weight loss test using Al alloys with different IMP sizes. This finding should give an important guideline to improve the corrosion resistance of Al alloy.

Intermittent endoleak via an aneurysm-iliac venous fistula after endovascular aneurysm repair.

We have reported the rare case of an intermittent endoleak via an aneurysm-venous fistula (AVF). An 89-year-old woman had experienced postoperative sac expansion 6 years after she had undergone endovascular aneurysm repair. During aneurysmorrhaphy, we detected a small AVF, which was the source of the endoleak responsible for the aneurysmal sac expansion. This AVF had a check valve-like mechanism that allowed the inflow of blood from the iliac vein to the sac when the venous pressure exceeded the endotension. Our case has demonstrated the occurrence of an AVF after endovascular aneurysm repair that had resulted in an endoleak that was invisible on imaging studies and the presence of endotension.

First-line osimertinib for poor performance status patients with EGFR mutation-positive non-small cell lung cancer: A prospective observational study.

OBJECTIVE: The clinical outcomes of poor performance status (PS) patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive EGFR mutations. MATERIALS AND METHODS: We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered osimertinib (80 mg/day) as the initial treatment. RESULTS: Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78 years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred. CONCLUSION: Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies with larger cohorts are warranted.

A Prospective Observational Study of Osimertinib for Chemo-Naive Elderly Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer.

BACKGROUND: The clinical outcomes of elderly patients with EGFR-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. PATIENTS AND METHODS: We assessed the clinical effects of osimertinib as a first-line treatment for elderly NSCLC patients (≥75 years of age) with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered 80 mg/day osimertinib as initial treatment. RESULTS: Forty-three patients (24 women and 19 men) with adenocarcinoma who were treated between August 2018 and July 2021 were included in this study; their median age was 79 years (range, 75-90 years). The overall objective response rate was 60.5%. The median progression-free survival (PFS) and time to treatment failure (TTF) of the entire patient population were 22.1 months and 14.6 months, respectively. The most common adverse event was rash acneiform (42%), followed by diarrhea (33%) and paronychia (28%); none of these were grades ≥3. Interstitial lung disease developed in 8 patients (18.6%); however, no treatment-related deaths occurred. Multivariate analysis identified performance status and disease stage as predictors of PFS and TTF. CONCLUSION: Considering the findings of this study and despite an observed discordance between PFS and TTF, osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies in a larger elderly population are warranted.

Impact of neutrophil-to-lymphocyte ratio in patients with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors.

Background Exon 19 deletion and L858R point mutation in exon 21 of the epidermal growth factor receptor (EGFR) are the most commonly encountered mutations in patients with non-small cell lung cancer (NSCLC) and predict better clinical outcomes following treatment with EGFR-tyrosine kinase inhibitors (TKIs). The inflammatory indicator neutrophil-to-lymphocyte ratio (NLR) in peripheral blood serves as a predictive factor for NSCLC patients treated with chemotherapy. Here, we aimed to evaluate the correlation between NLR and clinical efficacy of EGFR-TKIs in NSCLC patients harboring EGFR mutations. Methods We retrospectively collected information of 205 patients with advanced NSCLC harboring exon 19 deletion or L858R point mutation and receiving gefitinib or erlotinib. The clinical outcomes in the NSCLC patients were evaluated based on NLR level before EGFR-TKI therapy. Results The optimal cut-off value for NLR was 3.55. The response rates in the low-NLR and high-NLR groups were 69.2% and 51.5%, respectively. The median progression-free survival (PFS) in the low-NLR and high-NLR groups were 15.7 months and 6.7 months, respectively. The median overall survival (OS) in the low-NLR and high-NLR groups were 37.6 months and 19.2 months, respectively. The multivariate analysis identified performance status (PS), NLR, stage, and smoking status as independent predictors of PFS. Moreover, the PS and NLR were identified as independent predictors of OS. Conclusions NLR was a significant predictor of clinical efficacy and OS in NSCLC patients harboring EGFR mutations treated with gefitinib or erlotinib.

Current status and progress of concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer prior to the approval of durvalumab.

BACKGROUND: The standard treatment for patients with unresectable locally advanced (LA) non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA-NSCLC patients based on the PACIFIC criteria. METHODS: We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA-NSCLC treated with CRT between January 2012 and June 2018. RESULTS: We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum-based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41-317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two-year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two-year survival rate: 87% vs. 41%, respectively; P = 0.001). CONCLUSIONS: Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA-NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.

Evaluation of osimertinib efficacy according to body surface area and body mass index in patients with non-small cell lung cancer harboring an EGFR mutation: A prospective observational study.

BACKGROUND: Osimertinib is recommended for non-small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M-positive advanced NSCLC who progress on prior EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We conducted a prospective observational cohort study. Median BSA and BMI were used as cut-off values to evaluate the impact of body size variables on osimertinib chemotherapy. RESULTS: The median BSA and BMI of 47 patients were 1.50 m2 and 21.5 kg/m2 , respectively. Clinical outcomes did not significantly differ between the high and low BSA groups, with response rates of 59.1% and 56.0% (P = 0.83) and progression-free survival (PFS) of 7.6 and 9.1 months (P = 0.69), respectively. Similarly, there were no significant differences between the high and low BMI groups relative to response rates, which were 60.8% and 54.1% (P = 0.64), respectively, and PFS, which was 7.6 months in both groups (P = 0.38). No significant differences were observed among toxicity profiles in relation to BSA or BMI. Multivariate analysis identified better performance status, young age, and EGFR exon 19 deletion as independent favorable predictors of PFS. CONCLUSION: The efficacy of osimertinib does not significantly vary relative to body size variables of patients with T790M-positive NSCLC who progress on prior EGFR-TKIs.

Real-world evaluation of carboplatin plus a weekly dose of nab-paclitaxel for patients with advanced non-small-cell lung cancer with interstitial lung disease.

BACKGROUND: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. PATIENTS AND METHODS: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. RESULTS: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59-83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. CONCLUSION: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD.

Comparison of carboplatin plus etoposide with amrubicin monotherapy for extensive-disease small cell lung cancer in the elderly and patients with poor performance status.

BACKGROUND: Carboplatin plus etoposide (CE) is a standard treatment for elderly patients with extensive-disease small cell lung cancer (ED-SCLC). However, amrubicin monotherapy (AMR) may be a feasible alternative. We compared the efficacies and safety profiles of CE and AMR for ED-SCLC in elderly patients and chemotherapy-naive patients with poor performance status (PS). METHODS: The records of SCLC patients who received CE or AMR as first-line chemotherapy were retrospectively reviewed and their treatment outcomes evaluated. RESULTS: Eighty-four patients (median age 72 years; 42 each received CR and AMR) were analyzed; 34 patients had a PS score of 2. There were no significant differences in patient characteristics between the treatment groups. The median progression-free survival rates of patients in the CE and AMR groups were 5.8 and 4.8 months, respectively (P = 0.04); overall survival was 14.0 and 8.5 months, respectively (P = 0.089). Twenty-three CE group patients received AMR as second-line chemotherapy; their median overall survival from first-line chemotherapy was 18.5 months. Grade 3 or higher neutropenia occurred more frequently in patients treated with AMR (64% vs. 40%; P = 0.02), as did febrile neutropenia (14% vs. 7%). CONCLUSIONS: CE remains a suitable first-line treatment for ED-SCLC in elderly patients or those with poor PS in comparison with AMR.

Smoking History as a Predictor of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Harboring EGFR Mutations.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) therapy has been recognized as the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, resistance to EGFR-TKIs has been observed in certain subpopulations of these patients. We aimed to evaluate the impact of smoking history on the efficacy of EGFR-TKIs. METHODS: The records of patients (n = 248) with NSCLC harboring activating EGFR mutations who were treated with gefitinib or erlotinib at our institution between March 2010 and June 2016 were retrospectively reviewed, and the treatment outcomes were evaluated. RESULTS: The overall response rate and median progression-free survival (PFS) were 59.7% and 10.7 months, respectively. The overall response rate was significantly higher in the ex- and nonsmokers than in the current smokers (64.6 vs. 51.1%, p = 0.038). PFS also differed significantly between the current smokers and the ex- and nonsmokers (12.4 vs. 7.4 months, p = 0.016). Multivariate analysis identified smoking history as an independent predictor of PFS and overall survival. CONCLUSION: The clinical data obtained in this study provide a valuable rationale for considering smoking history as a predictor of the efficacy of EGFR-TKI in NSCLC patients harboring activating EGFR mutations.

Efficacy of Platinum-Based Chemotherapy for Relapsed Small-Cell Lung Cancer after Amrubicin Monotherapy in Elderly Patients and Patients with Poor Performance Status.

BACKGROUND: Previous studies have shown amrubicin to be an effective first- or second-line treatment option for small-cell lung cancer (SCLC). However, there have been few studies reporting the efficacy of platinum-based chemotherapy after amrubicin therapy. We aimed to evaluate the efficacy of platinum-based chemotherapy as second-line treatment for elderly patients and those with SCLC with poor performance status (PS) previously treated with amrubicin monotherapy. METHODS: The records of SCLC patients who received platinum-based chemotherapy as a second-line chemotherapy after first-line treatment with amrubicin monotherapy were retrospectively reviewed and the treatment outcomes were evaluated. RESULTS: A total of 48 patients were enrolled in this study. Forty-one patients (85%) received carboplatin plus etoposide. The overall response rate was 39.6%. The median progression-free survival and overall survival were 3.7 and 7.6 months, respectively. The efficacy of the platinum-based regimen did not differ with the type of relapse after amrubicin monotherapy. The most common adverse events were hematological toxicities, including grade 3 or 4 neutropenia (38%), leukopenia (33%), and thrombocytopenia (10%). CONCLUSIONS: Platinum-based chemotherapy is potentially a valid treatment option for elderly patients or those with extensive-stage SCLC with poor PS as second-line chemotherapy, who progressed after first-line treatment with amrubicin monotherapy.

Interstitial pneumonia following administration of pegfilgrastim during carboplatin and etoposide chemotherapy for small-cell lung cancer.

Pegfilgrastim is a long-acting granulocyte colony-stimulating factor formulation that has been approved for the prevention of febrile neutropenia. We herein report a case of interstitial pneumonia following administration of pegfilgrastim. A 65-year-old man with stage IV small-cell lung cancer was treated with carboplatin and etoposide as third-line chemotherapy. Pegfilgrastim was administered during the second cycle of chemotherapy. On the day after the administration of pegfilgrastim, interstitial pneumonia developed. The respiratory condition improved with pulse steroid therapy; however, the patient eventually succumbed to cancer progression. In conclusion, interstitial pneumonia due to pegfilgrastim is rare; however, physicians should be aware of the possibility of this adverse effect.

Induction of the Escherichia coli yijE gene expression by cystine.

Cystine is formed from two molecules of the cysteine under oxidized conditions, but is reversibly converted to cysteine by reduction. Growth of Escherichia coli is retarded in the presence of excess cystine. Transcriptome analysis showed 11 up-regulated and 26 down-regulated genes upon exposure to excess cystine. The reporter assay confirmed regulation by cystine of the expression of one up-regulated membrane gene, yijE, and two down-regulated membrane genes, yhdT and yihN. In order to identify the as yet unidentified gene encoding cystine efflux transporter, the putative cystine efflux candidate, yijE gene, was over-expressed. Expression of the yijE gene suppressed the slow growth of E. coli in the presence of high concentration of extracellular cystine. In good agreement, the knock-out of yijE gene increased the sensibility to cystine. These observations altogether imply that the yijE gene is involved in response to cystine in E. coli.

A novel approach to monitor coating amount by short-wavelength near-infrared spectroscopy using a tracer with a long-chain hydrocarbyl group.

Investigation into the use of near-infrared (NIR) as a Process Analytical Technology has been conducted for in-process monitoring of coating amounts for oral pharmaceutical products. However, the low specificity of NIR spectra has made it time consuming and costly to establish quantitative calibration models for commercial production. Here we revealed that long-chain hydrocarbyl group compounds containing saturated hydrocarbon chains, such as cetyl and stearyl, exhibit specific and strong absorption in the short wavelength (SW)-NIR region (800-1,100 nm) with limited interference from peaks corresponding to other components. To simplify the quantitative model, we used cetanol as a model tracer of coating amount to enhance detection sensitivity and analytical precision. The coating amount on crystalline cellulose granules was determined only from the intensity of NIR absorption at a single wavelength, which was attributed to the tracer. The results showed close agreement with quantitative analyses from gas chromatography and measurement of weight gain. In conclusion, we determined coating amount with considerable accuracy from NIR absorption at a single wavelength in the SW-NIR region using the long-chain hydrocarbyl containing compound as a tracer, thereby eliminating the need for complicated statistics.

Effect of paraquat-induced oxidative stress on insulin regulation of insulin-like growth factor-binding protein-1 gene expression.

Oxidative stress is thought to play a role in the development of insulin resistance. In order to elucidate the molecular effect of oxidative stress on liver insulin signaling, we analyzed the effect of paraquat (1,1-dimethyl-4,4-dipyridynium; PQ)-derived oxidative stress on the expression of insulin-dependent genes and activation of liver insulin signaling pathway. Incubation of primary cultured rat hepatocytes with 2 mM PQ for 6 h impaired the suppressive effect of insulin on insulin-like growth factor-binding protein-1 (IGFBP-1) gene expression, but did not influence glucose-6-phosphatase gene expression. Insulin-dependent phosphorylation or activation of insulin receptor, insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase, Akt and forkhead in rhabdomyosarcoma were not affected by PQ pre-treatment. In contrast, PQ treatment impaired insulin-dependent phosphorylation of mammalian target of rapamycin (mTOR). These results indicate that PQ-induced oxidative stress impairs insulin-dependent mTOR activation and that this impairment probably causes inhibition of insulin-dependent repression of IGFBP-1 expression.

Intraluteal release of angiotensin II and progesterone in vivo during corpora lutea development in the cow: effect of vasoactive peptides.

The newly formed corpus luteum (CL) develops rapidly and has the features of active vascularization and mitosis of steroidogenic cells. Such local mechanisms must be strictly regulated by the complex relationship between angiogenic growth factors and vasoactive peptides such as angiotensin (Ang) II, atrial natriuretic peptide (ANP), and endothelin (ET)-1. Thus, the objective of the present study was to determine 1) the changes in vasoactive peptides and progesterone (P) concentrations within the developing CL, along with the changes in concentration in ovarian venous plasma (OVP) and jugular venous plasma (JVP) in the cow, 2) the effects of CL exposure to vasoactive peptides on Ang II and P secretion, and 3) the expression of mRNA for ANP type C receptor in the bovine CL and endothelial cells (ETC) from bovine developing CL. A microdialysis system (MDS) was surgically implanted into multiple CL of six cows on Day 3 after a GnRH injection that induced superovulation, and a catheter was simultaneously inserted into the ovarian vein. The Ang II concentration in OVP was higher than that in JVP throughout the experiment, while the intraluteal release of Ang II was stable. During the experimental period, the concentrations of other vasoactive peptides (ANP and ET-1) showed no clear changes in plasma and were below detectable levels in the MDS perfusate. Exposure of CL to Ang II using the MDS stimulated P release, while exposure to ANP enhanced Ang II release within the developing CL. However, ET-1 had no effect on either P or Ang II release. The expression of mRNA for ANP type C receptor was mainly observed in early CL and ETC. The results suggest that the ET-Ang-ANP system in the preovulatory follicle switches to an Ang-ANP system to enhance both the angiogenesis and steroidogenesis that are actively occurring in developing CL.