Beliefs, preferences, and acceptance of personal protective equipment for a shock room team in a tertiary care center.

BACKGROUND: During coronavirus disease of 2019 pandemic a standard usage of personal protective equipment (PPE) in healthcare was mandatory, while actually the usage of PPE is currently decreasing. This raises the question about the further use of PPE in the clinical setting because healthcare workers (HCW) are at greater risk of being infected with SARS-CoV-2 than the general population. The primary objective of this study is to determine the proportion of shock room team members approving the further use of PPE including a FFP2 respirator in simulation training and reality. The secondary objectives are to describe the expertise and difficulties faced while using PPE in the shock room care. METHODS: Fifty-four HCW participated in a shock room simulation training at a large urban tertiary care hospital in Germany, utilizing a PPE comprising an FFP2 mask, gloves, goggles, and gown. Subsequently, participants completed an online questionnaire featuring 15 questions presented on a 5-point Likert scale or as multiple-choice questions with predefined answers. RESULTS: Sixty-eight point five percent of our participants voted for an established standard PPE in shock room care. The largest fraction of our participants (40.7%) favors a standard PPE consisting of FFP2 mask, gown, and gloves. Less HCW (31.5%) want to wear PPE in shock room simulation training. Except for goggles we could not detect relevant difficulties faced while using PPE in the shock room environment. Incorrect use of PPE was observed in 14.8%. CONCLUSION: A majority of our participants favored a standard PPE including a FFP2 respirator in shock room care. In addition, we recommend the use of PPE in shock room simulation training, while further awareness of and training in proper use of PPE seems to be necessary to reduce risk of infectious diseases for HCW.

Interprofessional Therapeutic Drug Monitoring of Carbapenems Improves ICU Care and Guideline Adherence in Acute-on-Chronic Liver Failure.

(1) Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing disease in patients with liver cirrhosis. Meropenem is crucial for treating severe infections. Therapeutic drug monitoring (TDM) offers an effective means to control drug dosages, especially vital for bactericidal antibiotics like meropenem. We aimed to assess the outcomes of implementing TDM for meropenem using an innovative interprofessional approach in ACLF patients on a medical intensive care unit (ICU). (2) Methods: The retrospective study was conducted on a medical ICU. The outcomes of an interprofessional approach comprising physicians, hospital pharmacists, and staff nurses to TDM for meropenem in critically ill patients with ACLF were examined in 25 patients. Meropenem was administered continuously via an infusion pump after the application of an initial loading dose. TDM was performed weekly using high-performance liquid chromatography (HPLC). Meropenem serum levels, implementation of the recommendations of the interprofessional team, and meropenem consumption were analyzed. (3) Results: Initial TDM for meropenem showed a mean meropenem serum concentration of 20.9 ± 9.6 mg/L in the 25 analyzed patients. Of note, in the initial TDM, only 16.0% of the patients had meropenem serum concentrations within the respective target range, while 84.0% exceeded this range. Follow-up TDM showed serum concentrations of 15.2 ± 5.7 mg/L (9.0-24.6) in Week 2 and 11.9 ± 2.3 mg/L (10.2-13.5) in Week 3. In Week 2, 41.7% of the patients had meropenem serum concentrations that were within the respective target range, while 58.3% of the patients were above this range. In Week 3, 50% of the analyzed serum concentrations of meropenem were within the targeted range, and 50% were above the range. In total, 100% of the advice given by the interprofessional team regarding meropenem dosing or a change in antibiotic therapy was implemented. During the intervention period, the meropenem application density was 37.9 recommended daily doses (RDD)/100 patient days (PD), compared to 42.1 RDD/100 PD in the control period, representing a 10.0% decrease. (4) Conclusions: Our interprofessional approach to TDM significantly reduced meropenem dosing, with all the team's recommendations being implemented. This method not only improved patient safety but also considerably decreased the application density of meropenem.

Implementing an interprofessional point-of-care ultrasound protocol for dyspneic patients in an emergency department as a blended learning concept-Feasibility of Employing Thoracic Ultrasound in Shortness of Breath.

Objective: Dyspnea is a common symptom in the Emergency Department, with a wide variety of differential diagnoses. Previous research has demonstrated the diagnostic accuracy of Point-of-Care Ultrasound (POCUS) in this field of interest. Our goal was to better establish sonography in our emergency department with a practicable and time effective method. Therefore, we implemented a sonography protocol in an interprofessional emergency team using blended learning as a modern didactic approach and evaluated the learning and teaching success. We named the study FETUS, which stands for "Feasibility of Employing Thoracic Ultrasound in Shortness of Breath." Methods: A demonstration of the POCUS protocol was given, followed by individual supervision during clinical routine. A written manual, a pocket card, and further materials for personal training supplemented the training. A post-training questionnaire measured several parameters regarding the training, e.g., subjective skill-acquisition or media use. Results: 32 medical and nursing staff participated in this study, 14 of whom completed the questionnaire. All training modalities offered were well received. A pre-post comparison of subjective sonographic competence shows a significant increase in both medical and nursing staff.The other items surveyed also indicate the success of the intervention undertaken. Conclusion: The use of different media as a blended learning approach can support the implementation of new measures in the ongoing working routine within an interprofessional team.

[Recommendations for Education in Sonography in Prehospital Emergency Medicine (pPOCUS): Consensus paper of DGINA, DGAI, BAND, BV-ÄLRD, DGU, DIVI and DGIIN]. / Empfehlungen zur Sonografieausbildung in der prähospitalen Notfallmedizin (pPOCUS): Konsensuspapier von DGINA, DGAI, BAND, BV-ÄLRD, DGU, DIVI und DGIIN.

Point-of-care sonography is a precondition in acute and emergency medicine for the diagnosis and initiation of therapy for critically ill and injured patients. While emergency sonography is a mandatory part of the training for clinical acute and emergency medicine, it is not everywhere required for prehospital emergency medicine. Although some medical societies in Germany have already established their own learning concepts for emergency ultrasound, a uniform national training concept for the use of emergency sonography in the out-of-hospital setting is still lacking. Experts of several professional medical societies have therefore joined forces and developed a structured training concept for emergency sonography in the prehospital setting. The consensus paper serves as quality assurance in prehospital emergency sonography.

[Recommendations for Education in Sonography in Prehospital Emergency Medicine (pPOCUS): Consensus paper of DGINA, DGAI, BAND, BV-ÄLRD, DGU, DIVI and DGIIN]. / Empfehlungen zur Sonografieausbildung in der prähospitalen Notfallmedizin (pPOCUS): Konsensuspapier von DGINA, DGAI, BAND, BV-ÄLRD, DGU, DIVI und DGIIN.

Point-of-care sonography is a precondition in acute and emergency medicine for the diagnosis and initiation of therapy for critically ill and injured patients. While emergency sonography is a mandatory part of the training for clinical acute and emergency medicine, it is not everywhere required for prehospital emergency medicine. Although some medical societies in Germany have already established their own learning concepts for emergency ultrasound, a uniform national training concept for the use of emergency sonography in the out-of-hospital setting is still lacking. Experts of several professional medical societies have therefore joined forces and developed a structured training concept for emergency sonography in the prehospital setting. The consensus paper serves as quality assurance in prehospital emergency sonography.

Simulation of Aerosol and Droplet Spread during Upper Airway and Gastrointestinal Endoscopy.

BACKGROUND AND AIMS: Aerosols and droplets are the main vectors in transmission of highly contagious SARS-CoV-2. Invasive diagnostic procedures like upper airway and gastrointestinal endoscopy have been declared as aerosol-generating procedures. Protection of healthcare workers is crucial in times of the COVID-19 pandemic. METHODS: We simulated aerosol and droplet spread during upper airway and gastrointestinal endoscopy with and without physico-mechanical barriers using a simulation model. RESULTS: A clear plastic drape as used for central venous access markedly reduced visualized aerosol and droplet spread during endoscopy. CONCLUSION: A simple and cheap drape has the potential to reduce aerosol and droplet spread during endoscopy. In terms of healthcare worker protection, this may be important particularly in low- or moderate-income countries.

Leg-heel chest compression as an alternative for medical professionals in times of COVID-19.

OBJECTIVE: To evaluate leg-heel chest compression without previous training as an alternative for medical professionals and its effects on distance to potential aerosol spread during chest compression. METHODS: 20 medical professionals performed standard manual chest compression followed by leg-heel chest compression after a brief instruction on a manikin. We compared percentage of correct chest compression position, percentage of full chest recoil, percentage of correct compression depth, average compression depth, percentage of correct compression rate and average compression rate between both methods. In a second approach, potential aerosol spread during chest compression was visualized. RESULTS: Our data indicate no credible difference between manual and leg-heel compression. The distance to potential aerosol spread could have been increased by leg-heel method. CONCLUSION: Under special circumstances like COVID-19-pandemic, leg-heel chest compression may be an effective alternative without previous training compared to manual chest compression while markedly increasing the distance to the patient.

Exploration of strategies to reduce aerosol-spread during chest compressions: A simulation and cadaver model.

OBJECTIVE: To evaluate the effect of strategies to reduce the spread of simulated aerosol during chest compressions on manikin and cadaver experimental models. METHODS: To evaluate aerosol-spread we nebulized ultraviolet sensitive detergents into the artificial airway of a resuscitation dummy and performed CPR. The spread of the visualized aerosol was documented by a camera. In a further approach we applied nebulized detergents into the airways of human cadavers and detected the simulated spread on the same way. Among others we did recordings with undergoing compression-only-CPR, with a surgical mask or an oxygen mask on the patients face and with an inserted supraglottic airway device with and without a connected airway filter. RESULTS: Most aerosol-spread at the direction of the provider was visualized during compression-only-CPR. The use of a surgical mask and of an oxygen mask on the patient's face deflected the spread. Inserting a supraglottic airway device connected to an airway filter lead to a remarkable reduction of aerosol-spread. CONCLUSION: The early insertion of a supraglottic airway device connected to an airway filter before starting chest compression may be beneficial for staff protection during CPR.

Local adaptation does not lead to genome-wide differentiation in lava flow lizards.

Adaptation can occur with or without genome-wide differentiation. If adaptive loci are linked to traits involved in reproductive isolation, genome-wide divergence is likely, and speciation is possible. However, adaptation can also lead to phenotypic differentiation without genome-wide divergence if levels of ongoing gene flow are high. Here, we use the replicated occurrence of melanism in lava flow lizards to assess the relationship between local adaptation and genome-wide differentiation. We compare patterns of phenotypic and genomic divergence among lava flow and nonlava populations for three lizard species and three lava flows in the Chihuahuan Desert. We find that local phenotypic adaptation (melanism) is not typically accompanied by genome-wide differentiation. Specifically, lava populations do not generally exhibit greater divergence from nonlava populations than expected by geography alone, regardless of whether the lava formation is 5,000 or 760,000 years old. We also infer that gene flow between lava and nonlava populations is ongoing in all lava populations surveyed. Recent work in the isolation by environment and ecological speciation literature suggests that environmentally driven genome-wide differentiation is common in nature. However, local adaptation may often simply be local adaptation rather than an early stage of ecological speciation.

Surgical Treatment of Extrapulmonary Oligometastatic Non-small Cell Lung Cancer.

The prognosis of metastatic non-small cell lung cancer (NSCLC) is poor, and platinum-based chemotherapy improves the median survival for only a few months. A subgroup of patients with oligometastatic disease may benefit from surgical resection, but only very limited data are available to date. We conducted a retrospective review of all patients with synchronous extrapulmonary oligometastatic NSCLC undergoing surgical resection in our department. Data regarding medical history, histology, number of metastases, and survival status were extracted from the medical database of the University Medical Center, Freiburg. Fifty-six patients underwent surgical resection for oligometastatic lung cancer. Five patients were lost during follow-up and therefore censored. One patient died perioperatively due to acute respiratory distress syndrome. The remaining 50 patients had an overall median survival time of 14.6 months. Analyzing the influence of metastatic site, we found a median overall survival of 23.4 months for patients with soft tissue metastasis, 16.7 months for patients with brain metastasis, 9.5 months for patients with adrenal gland involvement, and only 4.3 months for patients with bone metastasis (p < 0.005). Upon multivariate analysis, bone metastasis was the only significant parameter influencing median overall survival (p < 0.004). Based on our data, we conclude that an aggressive surgical approach for oligometastatic NSCLC can be performed with acceptable mortality and morbidity. In this rare constellation, surgical therapy may be an option in selected cases.

Tumor cell heterogeneity in Small Cell Lung Cancer (SCLC): phenotypical and functional differences associated with Epithelial-Mesenchymal Transition (EMT) and DNA methylation changes.

Small Cell Lung Cancer (SCLC) is a specific subtype of lung cancer presenting as highly metastatic disease with extremely poor prognosis. Despite responding initially well to chemo- or radiotherapy, SCLC almost invariably relapses and develops resistance to chemotherapy. This is suspected to be related to tumor cell subpopulations with different characteristics resembling stem cells. Epithelial-Mesenchymal Transition (EMT) is known to play a key role in metastatic processes and in developing drug resistance. This is also true for NSCLC, but there is very little information on EMT processes in SCLC so far. SCLC, in contrast to NSCLC cell lines, grow mainly in floating cell clusters and a minor part as adherent cells. We compared these morphologically different subpopulations of SCLC cell lines for EMT and epigenetic features, detecting significant differences in the adherent subpopulations with high levels of mesenchymal markers such as Vimentin and Fibronectin and very low levels of epithelial markers like E-cadherin and Zona Occludens 1. In addition, expression of EMT-related transcription factors such as Snail/Snai1, Slug/Snai2, and Zeb1, DNA methylation patterns of the EMT hallmark genes, functional responses like migration, invasion, matrix metalloproteases secretion, and resistance to chemotherapeutic drug treatment all differed significantly between the sublines. This phenotypic variability might reflect tumor cell heterogeneity and EMT during metastasis in vivo, accompanied by the development of refractory disease in relapse. We propose that epigenetic regulation plays a key role during phenotypical and functional changes in tumor cells and might therefore provide new treatment options for SCLC patients.

Changes in lung function after surgery for mesothelioma.

BACKGROUND: The effect of pleurectomy/decortication or extrapleural pleuropneumonectomy on pulmonary function has not yet been evaluated. The aim of this study was to determine the parameters of pulmonary function before and after pleurectomy/decortication or extrapleural pleuropneumonectomy. METHODS: We conducted a review of 48 patients with unilateral malignant pleural mesothelioma who underwent pleurectomy/decortication or extrapleural pleuropneumonectomy. Data including medical history, histology, survival, and pre- and postoperative pulmonary function were extracted from the medical database of the University Medical Center Freiburg, or sought by telephone interview with the general practitioner or patients. RESULTS: 25 patients underwent extrapleural pleuropneumonectomy and 23 had pleurectomy/decortication. Pulmonary function was not significantly reduced in the pleurectomy/decortication group postoperatively. In the extrapleural pleuropneumonectomy group, the median preoperative total lung capacity of 4.8 L (77.7%) differed significantly from the postoperative total lung capacity of 3.5 L (55.3%; p <0.0006). The median vital capacity was significantly reduced from 2.8 L (77.7%) preoperatively to 1.8 L (47.6%) postoperatively (p <0.0002). Other parameters were also highly significantly reduced after extrapleural pleuropneumonectomy. CONCLUSIONS: Pleurectomy/decortication preserved good pulmonary function, whereas extrapleural pleuropneumonectomy significantly reduced pulmonary function, which may lead to dyspnea and influence the quality of life of these patients.

CC-chemokine ligand 18 induces epithelial to mesenchymal transition in lung cancer A549 cells and elevates the invasive potential.

Lung cancer is one of the leading causes of cancer related death worldwide with more than a million deaths per year. The poor prognosis is due to its high aggressiveness and its early metastasis. Although the exact mechanisms are still unknown, the process of epithelial to mesenchymal transition (EMT) seems to be involved in these neoplastic processes. We already demonstrated that serum levels of CCL18, a primate specific chemokine, are highly elevated in patients with lung cancer and correlate with their survival time of patients with adenocarcinoma of the lung. Therefore, we hypothesized that CCL18 may be directly involved in pathological processes of lung cancer, e.g. EMT. We investigated the effect of CCL18 on A549, an adenocarcinoma cell line of the lung, on EMT and other cell functions like proliferation, chemotaxis, invasion, chemoresistance and proliferation. Exposure of A549 lung cancer cells to CCL18 in various concentrations decreases the epithelial marker E-cadherin, whereas FSP-1, a marker of the mesenchymal phenotype increases. Accordingly, CCL18 induced the transcriptional EMT regulator SNAIL1 in a dose dependent fashion. In contrast, an increasing CCL18 concentration was associated with a decline of cell proliferation rate. In addition, CCL18 induced chemotaxis of these cells and increased their chemoresistance. Therefore, CCL18 may be an interesting therapeutic target for NSCLC.

Serum level of CC-chemokine ligand 18 is increased in patients with non-small-cell lung cancer and correlates with survival time in adenocarcinomas.

CC-chemokine ligand 18 (CCL18) is mainly expressed by alternatively activated macrophages and DCs and plays an important role in lung fibrosis, arthritis and other diseases. Here CCL18 was measured in sera of 31 healthy volunteers and 170 patients with lung cancer and correlated these data with histology, tumor stage and clinical parameters. Mean CCL18 serum level of the patients with non-small-cell lung cancer was 150(857) ng/ml vs. 32(61) ng/ml in the healthy control group. Patient groups differ significantly according their histology (adenocarcinoma 143(528) ng/ml vs squamous cell carcinoma 187(857) ng/ml, p<0.02). In addition, we found a significant difference between patients with lower versus higher T-stage (p<0.003). Receiver operating characteristic (ROC) analyses revealed a cutoff point of 83 ng/ml (area under the curve (AUC): 0.968; p<0.0001) to discriminate between healthy controls and non-small-cell lung cancer patients. ROC analyses to discriminate between patients, who died because of cancer related death and those who died for other reasons did not lead to a valid AUC. To stratify the tumor patients, a criterion value plot was performed leading to a point of equal sensitivity and specificity (54%) of 162 ng/ml. Patients with a CCL18 serum level higher than 160 ng/ml had a mean survival time of 623 days. In contrast, those in patients with a baseline level between 83 ng/ml and 160 ng/ml the mean survival time was 984 days (p<0.005). Survival-analysis revealed in adenocarcinoma a mean survival of 1152 days in the group below 83 ng/ml. In the median group the mean survival time was 788 days and in the group with the highest levels the mean survival time was 388 days (p<0.001). In contrast, we found no correlation between the FEV1 and the CCL18 baseline level. In conclusion, in patients suffering from adenocarcinoma increased serum CCL18 levels predict a diminished survival time.

Surgical treatment of early stage small cell lung cancer.

BACKGROUND: Chemotherapy with radiation has to be considered the standard therapy for limited-stage small cell lung cancer but surgical resection is possible in a small subgroup in which it may improve survival. Surgery is not recommended as the standard treatment, but a few small studies have demonstrated a benefit of surgery in highly selected cases of limited-stage small cell lung cancer. METHODS: We conducted a retrospective study of 29 patients with limited-stage small cell lung cancer undergoing surgical resection in our department. There were 7 (24%) women and 22 (76%) men with a median age of 62 years (range, 46-82 years). Medical history, histology and survival status were extracted from the medical database of the University Medical Center Freiburg. RESULTS: The median overall survival was 20.7 months. In 15 patients who received neoadjuvant treatment, the median survival was 89.4 months. Karnofsky performance status and neoadjuvant chemotherapy had a significant influence on median survival (p <0.0004). CONCLUSIONS: We concluded that surgical resection can be beneficial in a highly selected group of patients as a part of a multidisciplinary approach. In addition, surgical resection is safe with acceptable mortality and morbidity.

Test of recrudescence hypothesis for overwintering of eastern equine encephalomyelitis virus in gray catbirds.

Eastern equine encephalitis virus (EEEV; family Togaviridae, genus Alphavirus) epizootics are infrequent, but they can lead to high mortality in infected horses and humans. Despite the importance of EEEV to human and animal health, little is known about how the virus overwinters and reinitiates transmission each spring, particularly in temperate regions where infected adult mosquitoes are unlikely to survive through the winter. One hypothesis to explain the mechanism by which this virus persists from year to year is the spring recrudescence of latent virus in avian reservoir hosts. In this study, we tested the recrudescence hypothesis with gray catbirds (Dumatella carolinensis) captured in northern Ohio (July-August 2007). Birds were experimentally infected with EEEV on 1 October 2007. In January 2008, they were then exposed to exogenous testosterone and/or extended photoperiod to initiate reactivation of latent EEEV infection. All birds became viremic with EEEV, with mean viremia of 6.0 log10 plaque-forming units/ml serum occurring at 1 d postinoculation. One male in the testosterone, long-day treatment group had EEEV viral RNA in a cloacal swab collected on 18 January 2008. Otherwise, no other catbirds exhibited reactivated infections in cloacal swabs or blood. Antibody titers fluctuated over the course of the study, with lowest titers observed in January 2008, which corresponded with the lowest mean weight of the birds. No EEEV viral RNA was detected in the blood, kidney, spleen, brain, liver, and lower intestine upon necropsy at 19 wk postinfection.

CXCR4 receptor positive spheroid forming cells are responsible for tumor invasion in vitro.

Stem cells have been found to be involved in breast cancer growth, but the specific contribution of cancer stem cells in tumor biology, including metastasis, is still uncertain. We found that murine breast cancer cell lines 4T1, 4TO7, 167Farn and 67NR contains cancer stem cells defined by CXCR4 expression and their capability of forming spheroids in suspension culture. Importantly, we showed that CXCR4 expression is essential for tumor invasiveness because both CXCR4 neutralizing antibody and shRNA knockdown of the CXCR4 receptor significantly reduced tumor cell invasion.

Tissue-resident stem cells promote breast cancer growth and metastasis.

Mesenchymal stem cells derived from bone marrow have recently been described to localize to breast carcinomas and to integrate into the tumor-associated stroma. In the present study, we investigated whether adipose tissue-derived stem cells (ASCs) could play a role in tumor growth and invasion. Compared with bone marrow-derived cells, ASCs as tissue-resident stem cells are locally adjacent to breast cancer cells and may interact with tumor cells directly. Here, we demonstrate that ASCs cause the cancer to grow significantly faster when added to a murine breast cancer 4T1 cell line. We further show that breast cancer cells enhance the secretion of stromal cell-derived factor-1 from ASCs, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. The tumor-promoting effect of ASCs was abolished by knockdown of the chemokine C-X-C receptor 4 in 4T1 tumor cells. We demonstrated that ASCs home to tumor site and promote tumor growth not only when co-injected locally but also when injected intravenously. Furthermore, we demonstrated that ASCs incorporate into tumor vessels and differentiate into endothelial cells. The tumor-promoting effect of tissue-resident stem cells was also tested and validated using a human breast cancer line MDA-MB-231 cells and human adipose tissue-derived stem cells. Our findings indicate that the interaction of local tissue-resident stem cells with tumor stem cells plays an important role in tumor growth and metastasis.

Atrial fibrillation down-regulates renal neutral endopeptidase expression and induces profibrotic pathways in the kidney.

AIMS: Recent studies suggest that atrial fibrillation (AF) substantially influences microvascular flow in ventricular myocardium. This process may contribute to the occurrence of heart failure in AF. In general, development of heart failure and renal dysfunction go hand-in-hand causing systemic fluid overload and oedema. So far, it is unknown whether AF itself influences renal function. The aim of the present study was to determine the impact of AF on renal gene expression in a closed chest rapid atrial pacing model. METHODS AND RESULTS: A total of 14 pigs were studied. In five pigs, rapid atrial pacing (AT) was performed for 7 h (600 bpm); in five additional animals, rapid atrial pacing was performed in the presence of irbesartan infusion (irbesartan group). Four pigs were instrumented without interventions (sham). After the pacing period, renal expression of collagen I alpha 1 and I alpha 3, transforming growth factor-beta (TGF-beta), neutral endopeptidase (NEP; the main enzyme involved in natriuretic protein metabolism), and atrial natriuretic peptide (ANP) were determined by RT-PCR and immunoblot analysis. Functional in vitro experiments were performed using HEK-293 kidney cells. Renal mRNA expression of NEP was substantially down-regulated during AT (AT: 12.7 +/- 9.3% vs. sham: 100 +/- 43.4%; P < 0.01). Results at the mRNA level were confirmed at the protein level. Irbesartan therapy did not prevent down-regulation of NEP. In contrast, TGF-beta1 mRNA expression was up-regulated (AT: 208.5 +/- 79.3% vs. sham: 100 +/- 34.6% P< 0.05). Collagen and angiotensin II type 1 receptor (AT1R) expression were not significantly altered by AT. HEK-293 cells were used to determine the potential humoral factors involved in down-regulation of NEP. Application of aldosterone, ANP, asymmetric dimethylarginine, and angiotensin peptides failed to cause down-regulation of renal NEP expression in vitro. CONCLUSION: AT reduces NEP expression and stimulates TGF-beta1 signalling in the kidneys. Thus, even brief episodes of AT affect renal gene expression, which may account for structural renal changes and alterations of renal function in the long term.