Distinct genomic landscapes of gastroesophageal adenocarcinoma depending on PD-L1 expression identify mutations in RAS-MAPK pathway and TP53 as potential predictors of immunotherapy efficacy.

BACKGROUND: The impact of molecular alterations on programmed death-ligand 1 (PD-L1) combined positive score (CPS) is not well studied in gastroesophageal adenocarcinomas (GEAs). We aimed to characterize genomic features of tumors with different CPSs in GEAs. PATIENTS AND METHODS: Genomic alterations of 2518 GEAs were compared in three groups (PD-L1 CPS ≥ 10, high; CPS = 1-9, intermediate; CPS < 1, low) using next-generation sequencing. We assessed the impact of gene mutations on the efficacy of immune checkpoint inhibitors (ICIs) and tumor immune environment based on the Memorial Sloan Kettering Cancer Center and The Cancer Genome Atlas databases. RESULTS: High, intermediate, and low CPSs were seen in 18%, 54% and 28% of GEAs, respectively. PD-L1 positivity was less prevalent in women and in tissues derived from metastatic sites. PD-L1 CPS was positively associated with mismatch repair deficiency/microsatellite instability-high, but independent of tumor mutation burden distribution. Tumors with mutations in KRAS, TP53, and RAS-mitogen-activated protein kinase (MAPK) pathway were associated with higher PD-L1 CPSs in the mismatch repair proficiency and microsatellite stability (pMMR&MSS) subgroup. Patients with RAS-MAPK pathway alterations had longer overall survival (OS) from ICIs compared to wildtype (WT) patients [27 versus 13 months, hazard ratio (HR) = 0.36, 95% confidence interval (CI): 0.19-0.7, P = 0.016] and a similar trend was observed in the MSS subgroup (P = 0.11). In contrast, patients with TP53 mutations had worse OS from ICIs compared to TP53-WT patients in the MSS subgroup (5 versus 21 months, HR = 2.39, 95% CI: 1.24-4.61, P = 0.016). CONCLUSIONS: This is the largest study to investigate the distinct genomic landscapes of GEAs with different PD-L1 CPSs. Our data may provide novel insights for patient selection using mutations in TP53 and RAS-MAPK pathway and for the development of rational combination immunotherapies in GEAs.

Assessment of immune biomarkers and establishing a triple negative phenotype in gynecologic cancers.

OBJECTIVE: Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers. METHODS: A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts. RESULTS: Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types. CONCLUSIONS: The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMBH. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMBH. The incidence of 'triple positive" cases was less than 2%.

Preliminary results of tubal surgery with pregnancy outcome.

PURPOSE OF INVESTIGATION: To assess the preliminary results of tubal surgery and its effect on pregnancy outcome. MATERIALS AND METHODS: The study included 440 patients with unilateral or bilateral tubal disease as the only cause of the infertility. All patients undergoing a laparoscopy for infertility were studied in reproductive surgery centre. The fallopian tube was classified into class I-IV. The studied outcomes were live birth, ectopic pregnancy, and miscarriage. After 12 months, cumulative conception rate was calculated. RESULTS: In the 440 patients, 172 patients with mild salpinx abnormality (class I) had a 34% cumulative pregnancy rate, 151 patients with moderate salpinx abnormality (class II) had a 16% cumulative pregnancy rate, and 77 patients with severe salpinx abnormality (class III) had a 10% cumulative pregnancy rate. No intrauterine pregnancies were observed in the severe group of 40 patients (class IV). CONCLUSION: Surgical laparoscopy is helpful for class I and II tubal abnormality, while it is not for class III and IV abnormalities.

Near-infrared luminescence from Y2O3:Eu3+, Yb3+ prepared by sol-gel method.

Eu3+ and Yb3+ codoped Y2O3 phosphors were synthesized by the sol-gel method. The phosphors possess absorption in the region of 300-550 nm, exhibiting an intense NIR emission of Yb3+ around 1000 nm, which is suitable for matching the maximum spectral response of c-Si solar cells. The optimum composition of Eu3+ and Yb3+ codoped Y2O3 was (Y1.94Yb0.04Eu0.02)2O3. It is observed that two-step energy transfer occurs from the 5D2 level of Eu3+ situated around (466 nm) exciting two neighboring Yb3+ ions to the 2F5/2 level (1000 nm). The down-conversion material based on Eu(3+)- Yb3+ couple may have great potential applications in c-Si solar cells to enhance their photovoltaic conversion efficiency via spectral modification.

Luminescent properties of BaAl12O19:Tb, Dy phosphors prepared by sol-gel method.

BaAl12O19:Tb, Dy phosphor was prepared by the sol-gel technique using citric acid as a complextant. XRD was used to characterize the relevant crystallization behavior of the phosphor. The luminescence properties and energy transfer between Tb3+ and Dy3+ were investigated. The results revealed that energy transfer exists between Dy3+ and Tb3+ at appropriate Tb3+ concentrations. The emission intensity of Tb3+ increases and energy transfer happens from Dy3+ to Tb3+ ions at the higher content of Tb3+ when Tb3+ and Dy3+ ions were co-doped. BaAl12O19 phosphors doped with Tb3+ or Dy3+ ions only were studied to compared with BaAl12O19:Tb, Dy phosphors. The results showed that the maximum excitation peak of BaAl12O19:Tb is 240 nm and the emission spectrum consists of four peaks at 490, 545, 590, and 625 nm, originating from 5D4 --> 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ ion, respectively. The excitation peaks of BaAl12O19:Dy are at 291, 324 nm and the emissions of Dy3+ are at 370, 447 and 578 nm, originating from 4F9/2 --> 6P5/2, 4F9/2 --> 6H15/2 and 4F9/2 --> 6H13/2 transitions of Dy3+ ion, respectively.

Genetically modified microorganism Spingomonas paucimobilis UT26 for simultaneously degradation of methyl-parathion and γ-hexachlorocyclohexane.

Bioremediation of pesticide residues by bacteria is an efficient and environmentally friendly method to deal with environmental pollution. In this study, a genetically modified microorganism (GMM) named UT26XEGM was constructed by introducing a parathion hydrolase gene into an initially γ-hexachlorocyclohexane (γ-HCH) degrading bacterium Spingomonas paucimobilis UT26. In order to reduce its potential risk of gene escaping into the environment for the public concern on biosafety, a suicide system was also designed that did not interfere with the performance of the GMM until its physiological function was activated by specific signal. The system was designed with circuiting suicide cassettes consisting of killing genes gef and ecoRIR from Escherichia coli controlled by Pm promoter and the xylS gene. The cell viability and original degradation characteristics were not affected by the insertion of exogenous genes. The novel GMM was capable of degrading methyl-parathion and γ-HCH simultaneously. In laboratory scale testing, the recombinant bacteria were successfully applied to the bioremediation of mixed pesticide residues with the activity of self-destruction after 3-methylbenzoate induction.

[An intelligent model for classifying supraventricular tachycardia mechanisms based on 12-lead wearable electrocardiogram devices].

OBJECTIVE: To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT) using 12-lead wearable electrocardiogram devices. METHODS: A total of 356 samples of 12-lead supraventricular tachycardia (SVT) electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model, and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October, 2021 to March, 2023 were selected as the testing set. The changes in electrocardiogram parameters before and during induced tachycardia were compared. Based on multiscale deep neural network, an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated. The 3-lead electrocardiogram signals from Ⅱ, Ⅲ, and Ⅴ1 were extracted to build new classification models, whose diagnostic efficacy was compared with that of the 12-lead model. RESULTS: Of the 101 patients with SVT in the testing set, 68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study. The pre-trained model achieved a high area under the precision-recall curve (0.9492) and F1 score (0.8195) for identifying AVNRT in the validation set. The total F1 scores of the lead Ⅱ, Ⅲ, Ⅴ1, 3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597, 0.6061, 0.3419, 0.6003 and 0.6136, respectively. Compared with the 12-lead classification model, the lead-Ⅲ model had a net reclassification index improvement of -0.029 (P=0.878) and an integrated discrimination index improvement of -0.005 (P=0.965). CONCLUSION: The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

The role of EZH2 in ocular diseases: a narrative review.

EZH2, acting as a catalytic subunit of PRC2 to catalyze lysine 27 in histone H3, induces the suppression of gene expression. EZH2 can regulate cell proliferation and differentiation of retinal progenitors, which are required for physiological retinal development. Meanwhile, an abnormal level of EZH2 has been observed in ocular tumors and other pathological tissues. This review summarizes the current knowledge on EZH2 in retinal development and ocular diseases, including inherited retinal diseases, ocular tumors, corneal injury, cataract, glaucoma, diabetic retinopathy and age-related retinal degeneration. We highlight the potential of targeting EZH2 as a precision therapeutic target in ocular diseases.

EZH2 is a protein that helps to regulate the activity of genes in cells. It works as a part of a complex called PRC2 to control a chemical group called lysine 27 in histone H3 and then inhibit the expression of genes. EZH2 is important for the normal development of the retina. Abnormal levels of EZH2 are associated with various eye diseases. This review summarizes the role of EZH2 in different ocular diseases and the potential mechanisms. Targeting EZH2 may be a novel way to treat or prevent ocular diseases.

[Application of wearable 12-lead electrocardiogram devices in pre-hospital diagnosis of acute ST segment elevation myocardial infarction].

OBJECTIVE: To assess the value of wearable 12-lead electrocardiogram (ECG) devices in pre-hospital diagnosis of acute ST segment elevation myocardial infarction (STEMI). METHODS: This analysis was conducted among 441 patients selected from the''National ECG Network'', who used wearable 12-lead ECG device with critical situation warning of ST change between January 2019, and August, 2021.The general characteristics, response time and complaints of the patients with STEMI were analyzed.The accuracy of pre-hospital diagnosis of STEMI was compared between clinician's interpretation of ECGs and AI diagnosis by the wearable ECG device. RESULTS: In 89 of the patients, a pre-hospital diagnosis of STEMI was made by physicians based on ECGs from the wearable devices, and 58 of them sought medical attention after online warning, with a referral rate of 65.17%.The average time for diagnostic assessment of the ECGs was 153.02 s, and the average time for confirmation of the diagnosis was 178.06 s.The sensitivity for pre-hospital diagnosis of STEMI by clinician's interpretation of the ECGs and by AI diagnosis was 100% and 88.37%, respectively, with a specificity of 95.40% and 79.31%, respectively.The pre-hospital diagnosis by clinicians and AI diagnosis of STEMI both showed a high consistency with the subsequent definite clinical diagnosis of STEMI. CONCLUSION: Wearable 12-lead ECG devices can accurately record ECG characteristics of STEMI patients outside the hospital and allow immediate data uploading for an early diagnosis.The diagnoses of STEMI made based on AI technology are highly consistent with those by clinicians, demonstrating excellent clinical performance of the wearable ECG devices.

Inhibitory effect of TGF-ß gene modified human amniotic mesenchymal stem cells on rejection after xenotransplantation of peripheral nerves.

OBJECTIVE: To explore the inhibitory effect of transforming growth factor-beta (TGF-ß) gene modified human amniotic mesenchymal stem cells on rejection after xenotransplantation of peripheral nerves. MATERIALS AND METHODS: In this study, 6 placentas collected in our hospital were selected as the source of human amniotic mesenchymal stem cells. A total of 60 C57BL/6 experimental mice (mouse sciatic nerves were removed before the experiment) were taken as research objects. Mice were randomly divided into experimental group 1, experimental group 2 and experimental group 3 (xenogenous peripheral nerves were introduced to all experimental groups), and a control group (autologous peripheral nerves were introduced). Among them, TGF-ß gene modified (overexpression) human amniotic mesenchymal stem cells were introduced to experimental group 1; TGF-ß gene modified (inhibition) human amniotic mesenchymal stem cells were introduced to experimental group 2; normal human amniotic mesenchymal stem cells were introduced to experimental group 3; and autologous sciatic nerves were introduced to control group. The messenger ribonucleic acid (mRNA) and protein expressions of the TGF-ß in different human amniotic mesenchymal stem cells were detected by quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. Mouse sciatic nerve function in each group after 2 weeks of procedures was detected via the CatWalk system. Expression level of interleukin-22 (IL-22) in the peripheral tissues of transplanted nerves and blood was detected using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Its mRNA level was examined via fluorescence quantitative PCR. RESULTS: TGF-ß1 was highly expressed in mice of experimental group 1, but lowly expressed in experimental group 2 relative to that of experimental group 3 (p<0.05). CatWalk test results revealed that the main indexes in experimental group 1 were superior to those in other groups, while the main indexes in experimental group 2 were inferior to those in other groups. According to immunohistochemistry and ELISA results, there were significant differences in the expression level of IL-22 in mice of different treatment groups (p<0.05). IL-22 level was the lowest in control group [(5.05±0.15) pg/mL], followed by that in experimental group 1 [(6.52±0.24) pg/mL], and it was the highest in experimental group 2 [(9.47±0.31) pg/mL]. CONCLUSIONS: Human amniotic mesenchymal stem cells overexpressing TGF-ß can inhibit rejection after xenotransplantation of peripheral nerves.

Degradation of ATM-independent decatenation checkpoint function in human cells is secondary to inactivation of p53 and correlated with chromosomal destabilization.

DNA topoisomerase II is required in the cell cycle to decatenate intertwined daughter chromatids prior to mitosis. To study the mechanisms that cells use to accomplish timely chromatid decatenation, the activity of a catenation-responsive checkpoint was monitored in human skin fibroblasts with inherited or acquired defects in the DNA damage G2 checkpoint. G2 delay was quantified shortly after a brief incubation with ICRF-193, which blocks the ability of topoisomerase II to decatenate chromatids, or treatment with ionizing radiation (IR), which damages DNA. Both treatments induced G2 delay in normal human fibroblasts. Ataxia telangiectasia fibroblasts with defective G2 checkpoint response to IR displayed normal G2 delay after treatment with ICRF-193, demonstrating that ATM kinase was not required for signaling when chromatid decatenation was blocked. The G2 delay induced by ICRF-193 was reversed by caffeine, indicating that active checkpoint signaling was involved. ICRF-193-induced G2 delay also was independent of p53 function, being evident in cells expressing HPV16E6 to inactivate p53. However, as fibroblasts expressing HPV16E6 aged in culture, they lost the ability to delay entry to mitosis, both after DNA damage and when decatenation was blocked. This age-related loss of G2 delay in response to ICRF-193 and IR in E6-expressing cells was blocked by induction of telomerase. Expression of telomerase also prevented chromosomal destabilization in aging E6-expressing cells. These observations lead to a new model of genetic instability, in which attenuation of G2 decatenatory checkpoint function permits cells to enter mitosis with insufficiently decatenated chromatids, leading to aneuploidy and polyploidy.

Synthesis and the Evaluations in vitro Antiplatelet Aggregation Activities of 4-Ethoxyisophthalamides.

In our search for new compounds among the structural analogues of the Picotamide acting on antiplatelet aggregation activities, a new series 2 of 4-ethoxyisophthal-amides were synthesized and their in vitro anti-platelet aggregation activities were evaluated by Born's test in comparison with their structural analogues of the series 1 of 4-methoxyisophthal-amides. The results revealed, among the series 2, six compounds 200, 2a, 2k, 2n, 2q and 2r displayed good antiplatelet aggregation activities in vitro induced by 5.0 mM ADP with IC50 values ranging over 0.35 µM - 0.77 µM. And of which, compound 2a exhibited the highest in vitro activity superior than two control drugs Picotamide and Aspirin. From a structure-affnity-'Relationship (SAR) pointed of some insight in the view of the role played by 4-ethoxy derivatives.

Technetium-99m MIBI uptake in recurrent parathyroid carcinoma and brown tumors.

Demonstrable parathyroid adenoma in delayed (3-hr) 99mTc-MIBI neck imaging and localization of 201Tl-chloride in brown tumors mimicking skeletal metastases have been reported. Technetium-99m-MIBI scintigraphy is currently the imaging modality of choice for localizing parathyroid tumors in patients with recurrent hyperparathyroidism. This report is a good example of the use of 99mTc-MIBI in the diagnostic work-up of a patient with recurrent hyperparathyroidism, which turned out to be due to parathyroid carcinoma rather than the initial histopathologic diagnosis of parathyroid adenoma. Additionally, the patient's total body 99mTc-MIBI and 99mTc-MDP bone images showed multiple focal lesions in the bone-mimicking metastases.

[The diagnosis of pleural diseases with a fiberbronchoscope under open pneumothorax].

Thoracoscopy, using a fiberbronchoscope under open pneumothorax, was performed in 27 cases suffering from pleural diseases undiagnosed. The overall diagnostic rate was 92.3%. The items observed included pulse rate, respiration rate, blood pressure, blood gas analysis, electrocardiography and thoracic pressure measure. It was found that this method has little influence on cardiopneumatic function, no harm fiberbronchoscope, and is simple and safe.

Pyrosequencing for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a meta-analysis.

BACKGROUND: Multidrug-resistant tuberculosis is a major threat to the control of tuberculosis and to public health. Whereas most conventional methods of drug susceptibility testing (DST) are precise but time consuming, pyrosequencing is a rapid, high-throughput technique. OBJECTIVE: To conduct a meta-analysis to evaluate the overall accuracy of pyrosequencing for the detection of rifampicin (RMP) resistance. METHODS: We searched PubMed, Web of Science, Elsevier and BIOSIS databases according to a written protocol and explicit study selection criteria. A summary receiver operating characteristic curve (SROC) and Cochrane (Q*) index were calculated to perform this meta-analysis using Meta-Disc software. RESULTS: Twelve studies involving 594 specimens with RMP resistance and 793 RMP-susceptible specimens met the inclusion criteria. Of these, 11 were based on Mycobacterium tuberculosis clinical isolates. The overall sensitivity and specificity were estimated at respectively 0.94 (95%CI 0.92-0.96) and 0.98 (95%CI 0.97-0.99). The area under the SROC curve was 0.99 and the Cochrane (Q*) index was 0.96. For clinical specimens, the overall sensitivity and specificity estimates were respectively 0.89 (range 0.52-1.00) and 0.99 (range 0.95-1.00). CONCLUSIONS: This meta-analysis shows that pyrosequencing is a highly sensitive and specific tool for the detection of RMP resistance in M. tuberculosis. The pyrosequencing assay is conducted in a high-throughput format, with a turnaround time of <2 h, making it substantially faster than conventional DST methods. We propose that pyrosequencing applied directly to clinical specimens instead of M. tuberculosis isolates could be of greater clinical value.

[Repair and functional reconstruction of severe electrical burns of wrist].

OBJECTIVE: To reduce amputation rate of severe electrical burn of wrist and to promote partial recovery of the injuried hand. METHODS: From 1987 to 1999, 44 cases, with 55 limbs of severe electrical burn were classified into 4 types, according to criteria of Dr Shen Zuyao, and were all treated by primary adequate decompression, timely debridement, reconstruction of blood circulation in cases complicated with blood vessel injury, and skin flap grafting from chest, abdomen or inguinal area, followed by treatment of anti-coaggluation and anti-infection. Once the wound healed, auto- or allo-transplantation or transferring of tendons were performed to repair tendon defect, and auto-nerve or fetal nerve transplantation performed for nerve defect. RESULTS: After the primary treatment of the 55 burned limbs, all limbs of type IV were amputated, and most of other 3 types survived. The function, including sensation and movement, of survived hands partially recovered. CONCLUSION: Primary reconstruction of blood circulation, cover of wound with skin flap, and timely repair of sensation and motor function are very crucial approach to reduce amputation rate and to promote the survived hand function of severe electrical burns of wrists.

Physicochemical surface properties and phagocytosis by polymorphonuclear leucocytes of different serogroups of Salmonella.

Salmonella isolates belonging to different serogroups have been analysed with respect to physicochemical surface properties and interaction with human polymorphonuclear granulocytes (PMNs). Most (22/34) recent isolates of the different serotypes showed hydrophilic surface properties and little if any negative charge accompanied by resistance to phagocytosis by PMN similar to the old laboratory S strains Salmonella typhimurium 395MS and Salmonella minnesota S99 (main group). However, all isolates belonging to the serogroups C1 (5 isolates), E4 (2), O43 (1), and one out of three E1 isolates (C1/E4 group) differed from the main group. In aqueous biphasic partition in dextran-polyethyleneglycol (PEG) systems the bacteria in the main group accumulated in the PEG-rich phase to 55-97%, those in the C1/E4 group to less than 10%, and R-mutants only to 1-2%. The bacteria in the C1/E4 group displayed a negative surface charge and a susceptibility to phagocytosis by PMNs that were greater than those for strains in the main group but much lower than those shown by the R-mutants. Bacteria belonging to serogroup C1 also displayed a significant susceptibility to hydrophobic interaction. The results are discussed in relation to the pathogenicity of salmonella.

Effects of long-term enalapril and losartan therapy of hypertension on cardiovascular aldosterone.

BACKGROUND: Plasma aldosterone escape is found during long-term angiotensin-converting enzyme inhibitor therapy. Evidence for aldosterone production in cardiovascular tissues raised the question of whether or not aldosterone escape occurs in these tissues. METHOD: Spontaneously hypertensive rats were treated with enalapril (20 mg/kg/day) and losartan (50 mg/kg/day) for 20 weeks; untreated spontaneously hypertensive and Wistar rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high-performance liquid chromatography, and radioimmunoassay for aldosterone were performed. RESULTS: The results showed that enalapril failed to significantly inhibit aldosterone production in mesenteric artery, myocardium and plasma. Losartan significantly inhibited aldosterone production to that of Wistar rats in the mesenteric artery, myocardium and plasma. CONCLUSION: This study provides the first evidence that long-term angiotensin-converting enzyme inhibition therapy induces aldosterone escape in hypertensive cardiovascular tissues, and angiotensin II subtype 1 receptor antagonist does not induce aldosterone escape in mesenteric artery, myocardium and plasma of spontaneously hypertensive rats.

Effects of long-term enalapril and losartan therapy of heart failure on cardiovascular aldosterone.

Plasma aldosterone escape is found during long-term ACE inhibitor therapy of chronic heart failure. Evidence for aldosterone production in cardiovascular tissues raised the question of whether aldosterone escape occurs or not in these tissues. Rats with infarction-induced chronic heart failure were treated with enalapril (20 mg/kg/d) and losartan (15 mg/kg/d) for 20 weeks. Untreated chronic heart failure and sham-operated rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high performance liquid chromatography, and RIA for aldosterone were performed. Chronic heart failure due to myocardial infarction was associated with tissue-specific activation of cardiovascular aldosterone synthesis. In the mesenteric artery, enalapril significantly inhibited aldosterone production compared to untreated, chronic heart failure rats, and losartan lowered aldosterone production to that of sham rats. In myocardium, enalapril failed to significantly inhibit aldosterone production, and losartan significantly inhibited aldosterone production compared to untreated, chronic heart failure rats. These results provide the first evidence that long-term ACE inhibition therapy induces aldosterone escape in myocardium but not in mesenteric artery of chronic heart failure. The angiotensin II subtype 1 receptor blocker losartan tranquilized aldosterone levels in the cardiovascular tissues of chronic heart failure rats.