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1.
J Surg Educ ; 81(5): 639-646, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556439

RESUMO

INTRODUCTION: Esophageal surgery is an essential component of general surgery training and encompasses several types of cases that are logged by general surgery residents. There is a scarcity of data on the quality and volume of esophageal surgery experience during surgical residency in the United States. We analyzed trends for 9 different esophageal procedure categories logged by residents in the United States, with the aim to identify areas for improvement in training. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from programs accredited by the ACGME over a fourteen-year period from 2009 to 2023. Data on mean esophageal cases reported by graduates, including mean in each procedure subcategory were retrieved. Cases were categorized as either surgeon chief or surgeon junior for each procedure category. Mann-Kendall trend test was used to obtain tau statistics and p-value for trends in mean operative surgical volume for the total number of cases in each operative category over the study period. Trends in surgeon chief and surgeon junior cases were also investigated for each operative category. RESULTS: The mean number of all esophageal procedures performed per resident during their training increased significantly from 10.5 in 2009 to 16 in 2022 (τ = 0.833, p < 0.001). This trend observed among all esophageal procedures during this 14-year study can be largely attributed to the steady increase in the number and proportion of laparoscopic esophageal antireflux procedures performed (τ = 0.950, p < 0.001). Additionally, esophagectomy procedures had a statistically significant, but modest, increase during the study period (τ = 0.505, p = 0.023), from a mean of 1 case during training in 2009 to a peak of 1.3 in 2020. Although the general trend of esophagus procedures increased during the study period, most categories (7 out of 9) either decreased or did not significantly change. Esophagogastrectomy volume decreased significantly by 30%, from 1 per resident during their training in 2009 to 0.7 in 2022 (τ = -0.510, p = 0.018), esophageal diverticulectomy procedures decreased by 50% from 0.2 to 0.1 (τ = -0.609, p = 0.009), and operations for esophageal stenosis decreased by 75% from 0.4 to 0.1 (τ = -0.734, p = 0.001). Mean number of esophageal bypasses (τ = -0.128, p = 0.584), repair of perforated esophageal disease (τ = -0.333, p = 0.156), and other major esophagus procedures (τ = 0.416, p = 0.063) did not significantly change. CONCLUSION: The operative volume of esophageal surgery that general surgery residents in the United States are exposed to has significantly risen over the past 14 years, largely driven by the increase in laparoscopic antireflux procedures. However, given the recent advances and the resultant heterogeneity in both esophageal surgery, the increase in resident operative volume is still inadequate to ensure the training of safe and adept esophageal surgeons, necessitating postresidency specialized training for trainees interested in esophageal surgery.


Assuntos
Competência Clínica , Educação de Pós-Graduação em Medicina , Cirurgia Geral , Internato e Residência , Estudos Retrospectivos , Humanos , Estados Unidos , Cirurgia Geral/educação , Esôfago/cirurgia , Acreditação , Masculino , Feminino
2.
Surgery ; 175(6): 1518-1523, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503604

RESUMO

BACKGROUND: Gastric surgery is a crucial component of general surgery training. However, there is a paucity of high-quality data on operative volume and the diversity of surgical procedures that general surgery residents are exposed to. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from the American College of Graduate Medical Education-accredited program from 2009 to 2022. Data on the mean number of gastric procedures, including the mean in each subcategory, were retrieved. A Mann-Kendall trend test was used to investigate trends in operative volume. RESULTS: Between 2009 and 2022, the mean overall logged gastric procedures rose significantly (τ = 0.722, P < .001) from 36.2 in 2009 to 49.2 in 2022 (35.9% increase). The most substantial growth was seen in laparoscopic gastric reduction for morbid obesity (mean 1.9 in 2017 to 19 in 2022; τ = 0.670, P = .009). A statistically significant increase was also seen in laparoscopic partial gastric resections, repair of gastric perforation, and "other major stomach procedures" (P < .05 for all comparisons). Open gastrostomy, open partial gastric resections, and open vagotomy all significantly decreased (P < .05 for all comparisons). There was no significant change in the volume of laparoscopic gastrectomy, total gastric resections, and non-laparoscopic gastric reductions for morbid obesity (P > .05 for all comparisons). CONCLUSION: There has been a substantial increase in the volume of gastric surgery during residency over the past 14 years, driven mainly by an increase in laparoscopic gastric reduction. However, there may still be a need for further gastric surgical training to ensure well-rounded general surgeons.


Assuntos
Competência Clínica , Cirurgia Geral , Internato e Residência , Humanos , Estudos Retrospectivos , Internato e Residência/estatística & dados numéricos , Internato e Residência/tendências , Estados Unidos , Cirurgia Geral/educação , Cirurgia Geral/tendências , Competência Clínica/estatística & dados numéricos , Laparoscopia/tendências , Laparoscopia/estatística & dados numéricos , Laparoscopia/educação , Gastrectomia/tendências , Gastrectomia/educação , Gastrectomia/estatística & dados numéricos , Feminino , Masculino
3.
Surg Endosc ; 38(3): 1491-1498, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242988

RESUMO

INTRODUCTION: Endoscopy is a major part of surgical training. Accreditation Council for Graduate Medical Education (ACGME) has set standards regarding the minimum volume of endoscopy cases required for graduation. However, there is paucity of high-quality data on the number of cases that most surgical graduates perform. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from ACGME-accredited programs from 2010 to 2023. Data on mean number of endoscopy cases, including mean in each subcategory, were retrieved. Mann-Kendall trend test was used to investigate trends in endoscopy experience. RESULTS: Between 2010 and 2023, the mean overall endoscopy procedures per resident remained stable, with 129.5 in 2010 and 132.1 in 2023 (t = 0.429; p-value = 0.037). The majority of these cases were performed as surgeon junior (76.6% in 2010; 80.9% in 2023), while the remaining cases were logged as surgeon chief. The most substantial contribution to the overall volume was from flexible colonoscopy (mean: 64.1 in 2010 and 67.2 in 2023). The volume for colonoscopy remained fairly stable (t = 0.429; p-value = 0.036). This was followed by esophagogastroduodenoscopy (mean: 35.3 in 2010 and 35.5 in 2023), which saw a significant increase in volume (t = 0.890; p-value ≤ 0.001). There was a significant increase in the number of overall upper endoscopic procedures (t = 0.791; p-value ≤ 0.001), while lower endoscopic procedures did not change significantly (t = 0.319; p-value = 0.125). The procedural volume for endoscopic retrograde cholangiography, sigmoidoscopy, cystoscopy/ureteroscopy, laryngoscopy, and bronchoscopy decreased significantly (p-value < 0.05 for all). CONCLUSION: The overall endoscopy volume for general surgery residents has largely remained stable, with a minor increase in esophagogastroduodenoscopy and no change in colonoscopy. Future research should investigate whether simulation-based exercises can bridge the gap between procedural volume and learning curve requirements for endoscopy.


Assuntos
Cirurgia Geral , Internato e Residência , Laparoscopia , Cirurgiões , Humanos , Estados Unidos , Estudos Retrospectivos , Educação de Pós-Graduação em Medicina , Endoscopia Gastrointestinal , Competência Clínica , Cirurgia Geral/educação , Acreditação , Carga de Trabalho
4.
J Surg Educ ; 81(3): 382-387, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296724

RESUMO

INTRODUCTION: Surgical Critical Care (SCC) fellowship applications are made through March-July the year prior to the fellowship, while the match process takes place through the National Resident Matching Program (NRMP). There is paucity of high quality data on matching trends in SCC fellowship in the United States. METHODS: We conducted a retrospective cohort study of all applicants in the SCC match over a period of fifteen years (2009-2023). Publicly published data about the SCC fellowship match were retrieved from the NRMP online portal. Mann Kendall trend test was used to obtain a Tau statistic and p-values for temporal trends over time. Chi-square test was used to investigate association between categorical variables. RESULTS: From 2009 to 2023, the number of SCC fellowship positions increased from 143 to 340 (138% increase) while the number of applicants rose from 95 to 289 (204% increase). The overall match rate for applicants significantly rose from 89.5% to 93.4% (7.7% increase; t = 0.600, p = 0.002). The percentage of positions filled also increased from 59.4% in 2009 to 79.4% in 2023. The match rate over the past five years (2019-2023) was 90.8%. US-MD applicants had a significantly higher 94.8% match rate throughout the study period than non-US MD applicants (94.8% vs. 87.3%, p<0.001). While the match rate for US-MD applicants has stayed consistent from 2009 to 2023 (τ = 0.371, p = 0.054), the match rate for non-US-MD applicants increased from 77.3% in 2009 to 86.9% in 2023 (τ = 0.771, p<0.001). CONCLUSION: SCC fellowship continues to grow with more positions and applicants. Match rates into SCC fellowships have increased over the past fifteen years, primarily helping non-US MDs match successfully.


Assuntos
Internato e Residência , Humanos , Estados Unidos , Bolsas de Estudo , Estudos Retrospectivos , Cirurgia de Cuidados Críticos
5.
Am Surg ; 90(5): 985-990, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38054447

RESUMO

BACKGROUND: Colon and Rectal Surgery fellowships are training programs that aim to train surgeons in the management of small bowel, colon, rectal, and anal pathologies. OBJECTIVE: We investigated trends in Colon and Rectal Surgery fellowship match to help applicants anticipate future fellowship application cycles. DESIGN: This was a retrospective cohort study of applicants in the Colon and Rectal Surgery match from 2009 to 2023. Proportion of positions filled, match rates, and rank-order lists were collected. The impact of US-MD, non-US-MD, and DO status on match rate was assessed. We used the Mann Kendall trend test to obtain tau statistic and P-value for temporal trends over time, while associations between categorical variables were investigated by a chi-square test. RESULTS: Fellowship programs increased from 43 to 67, positions increased from 78 to 110, and number of applicants rose from 113 to 135. Nearly all positions were filled from 2009 to 2023 (range: 96.3%-100%). The overall match rate fluctuated between 67.3% and 80.7%. The match rate over the past 5 years was 72.0%. The match rate for US-MDs was 80.0%, while non-US-MDs had a 56.2% match rate. The percentage matching at each rank were first choice 28.0%, second choice 10.4%, third choice 6.9%, and fourth choice or lower 23.5%. CONCLUSION: Despite an increase in Colon and Rectal Surgery fellowship positions, the overall match rate has not changed significantly over the years, mainly as a result of increased applicants.


Assuntos
Internato e Residência , Humanos , Estados Unidos , Bolsas de Estudo , Estudos Retrospectivos , Educação de Pós-Graduação em Medicina , Colo
6.
Mar Drugs ; 21(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36827167

RESUMO

Microalgae produce a plethora of primary and secondary metabolites with possible applications in several market sectors, including cosmetics, human nutrition, aquaculture, biodiesel production and treatment/prevention of human diseases. Diatoms, in particular, are the most diversified microalgal group, many species of which are known to have anti-cancer, anti-oxidant, anti-diabetes, anti-inflammatory and immunomodulatory properties. Compounds responsible for these activities are often still unknown. The aim of this study was to de novo sequence the full transcriptome of two strains of the diatom Asterionellopsis thurstonii, sampled from two different locations and cultured in both control and phosphate starvation conditions. We used an RNA-sequencing approach to in silico identify transcripts potentially involved in the synthesis/degradation of compounds with anti-cancer and immunomodulatory properties. We identified transcript coding for L-asparaginase I, polyketide cyclase/dehydrase, bifunctional polyketide phosphatase/kinase, 1-deoxy-D-xylulose-5-phosphate synthase (fragment), inositol polyphosphate 5-phosphatase INPP5B/F, catechol O-Methyltransferase, digalactosyldiacylglycerol synthase (DGD1), 1,2-diacylglycerol-3-beta-galactosyltransferase and glycerolphosphodiester phosphodiesterase. Differential expression analysis also allowed to identify in which culturing condition these enzymes are more expressed. Overall, these data give new insights on the annotation of diatom genes, enzymatic pathways involved in the generation of bioactive molecules and possible exploitation of Asterionellopsis thurstonii.


Assuntos
Diatomáceas , Policetídeos , Humanos , Diatomáceas/metabolismo , Transcriptoma , Análise de Sequência de RNA , Óxido Nítrico Sintase/metabolismo , Policetídeos/metabolismo
7.
Nanomaterials (Basel) ; 12(11)2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35683776

RESUMO

The predominant aim of the current study was to synthesize the nanofertilizer nanoparticles ZnO_MnO-NPs and FeO_ZnO-NPs using Andean blueberry extract and determine the effect of NPs in the growth promotion of cabbage (Brassica oleracea var. capitata) and Andean lupin (Lupinus mutabilis sweet) crops. The nanoparticles were analyzed by visible spectrophotometry, size distribution (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Solutions of nanoparticle concentrations were applied to cabbage, with solutions of 270 and 540 ppm of ZnO_MnO-NPs and 270 and 540 ppm of FeO_ZnO-NPs applied to Andean lupin. Zinc was used in both plants to take advantage of its beneficial properties for plant growth. Foliar NPs sprays were applied at the phenological stage of vegetative growth of the cabbage or Andean lupin plants grown under greenhouse conditions. The diameter of the NPs was 9.5 nm for ZnO, 7.8 nm for FeO, and 10.5 nm for MnO, which facilitate the adsorption of NPs by the stomata of plants. In Andean lupin, treatment with 270 ppm of iron and zinc indicated increases of 6% in height, 19% in root size, 3.5% in chlorophyll content index, and 300% in leaf area, while treatment with 540 ppm of iron and zinc yielded no apparent increases in any variable. In cabbage, the ZnO_MnO-NPs indicate, at a concentration of 270 ppm, increases of 10.3% in root size, 55.1% in dry biomass, 7.1% in chlorophyll content, and 25.6% in leaf area. Cabbage plants treated at a concentration of 540 ppm produced increases of 1.3% in root size and 1.8% in chlorophyll content, compared to the control, which was sprayed with distilled water. Therefore, the spray application of nanofertilizers at 270 ppm indicated an important improvement in both plants' growth.

8.
Mar Drugs ; 20(6)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35736153

RESUMO

Jellyfish are commonly considered a nuisance for their negative effects on human activities (e.g., fisheries, power plants and tourism) and human health. However, jellyfish provide several benefits to humans and are commonly eaten in eastern countries. Additionally, recent studies have suggested that jellyfish may become a source of high-value molecules. In this study, we tested the effects of the methanolic extracts and enriched fractions, obtained by solid-phase extraction fractionation, from the scyphomedusae Pelagia noctiluca, Rhizostoma pulmo, Cotylorhiza tuberculata and the cubomedusa Caryddea marsupialis on different human cancer cell lines in order to evaluate a potential antiproliferative activity. Our results indicated that fraction C from Caryddea marsupialis-(CM) and C. tuberculata oral arms (CTOA) were the most active to reduce cell viability in a dose-dependent manner. LC/MS based dereplication analyses highlighted that both bioactive fractions contained mainly fatty acids and derivatives, with CM additionally containing small peptides (0.7-0.8 kDa), which might contribute to its higher biological activity. The mechanism of action behind the most active fraction was investigated using PCR arrays. Results showed that the fraction C of CM can reduce the expression of genes involved in apoptosis inhibition in melanoma-treated cells, which makes jellyfish a potential new source of antiproliferative drugs to be exploited in the future.


Assuntos
Cnidários , Cifozoários , Animais , Linhagem Celular , Sobrevivência Celular , Humanos , Peptídeos/farmacologia , Cifozoários/química
9.
Biology (Basel) ; 11(5)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35625500

RESUMO

Haptophytes are important primary producers in the oceans, and among the phylum Haptophyta, the flagellate Isochrysis galbana has been found to be rich in high-value compounds, such as lipids, carotenoids and highly branched polysaccharides. In the present work, I. galbana was cultured and collected at both stationary and exponential growth phases. A transcriptomic approach was used to analyze the possible activation of metabolic pathways responsible for bioactive compound synthesis at the gene level. Differential expression analysis of samples collected at the exponential versus stationary growth phase allowed the identification of genes involved in the glycerophospholipid metabolic process, the sterol biosynthetic process, ADP-ribose diphosphatase activity and others. I. galbana raw extracts and fractions were tested on specific human cancer cells for possible antiproliferative activity. The most active fractions, without affecting normal cells, were fractions enriched in nucleosides (fraction B) and triglycerides (fraction E) for algae collected in the exponential growth phase and fraction E for stationary phase samples. Overall, transcriptomic and bioactivity data confirmed the activation of metabolic pathways involved in the synthesis of bioactive compounds giving new insights on possible Isochrysis applications in the anticancer sector.

10.
Int J Mol Sci ; 22(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922258

RESUMO

Microalgae are known to produce a plethora of compounds derived from the primary and secondary metabolism. Different studies have shown that these compounds may have allelopathic, antimicrobial, and antipredator activities. In addition, in vitro and in vivo screenings have shown that several compounds have interesting bioactivities (such as antioxidant, anti-inflammatory, anticancer, and antimicrobial) for the possible prevention and treatment of human pathologies. Additionally, the enzymatic pathways responsible for the synthesis of these compounds, and the targets and mechanisms of their action have also been investigated for a few species. However, further research is necessary for their full exploitation and possible pharmaceutical and other industrial applications. Here, we review the current knowledge on the chemical characteristics, biological activities, mechanism of action, and the enzymes involved in the synthesis of microalgal metabolites with potential benefits for human health.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Microalgas/química , Animais , Humanos
11.
Sci Rep ; 10(1): 4929, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188923

RESUMO

Mesopelagic organisms form huge biomass aggregations, supporting important pelagic trophic webs and several top predators. Although some studies on the occurrence, biology and ecology of these organisms are available, to date there are no investigations on their potential use for anticancer and antimicrobial biotechnological applications. The aim of this study was to screen extracts of seven mesopelagic species for possible anticancer (Lung cell line A549, skin cell line A2058, liver cell line HepG2, breast cell line MCF7 and pancreas cell line MiaPaca-2) and antibacterial (Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae, the Gram-positive bacteria methicillin resistant/sensitive Staphylococcus aureus, and Mycobacterium tuberculosis) activities. Results showed that only two species were active, the lanternfish Myctophum punctatum and the Mediterranean krill Meganyctiphanes norvegica. In particular, M. punctatum showed strong activity against the A549 and MCF7 cells, while M. norvegica was more active against HepG2 cells. Regarding antibacterial assays, both species were active against methicillin resistant S. aureus. Fractionation and LC/MS dereplication of the fractions showed that the main compounds found in extracts of both species were EPA, DHA and ETA. For some of the detected compounds anticancer and/or antibacterial activity are already known, but this is the first time that such activities have been found for mesopelagic species.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Espectrometria de Massas , Mar Mediterrâneo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos
12.
Pain Med ; 21(6): 1122-1141, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040149

RESUMO

OBJECTIVE: To determine the effectiveness of lumbar medial branch thermal radiofrequency neurotomy based on different selection criteria and procedural techniques. DESIGN: Comprehensive systematic review. METHODS: A comprehensive literature search was conducted, and all authors screened and evaluated the studies. The Grades of Recommendation, Assessment, Development, and Evaluation system was used to assess all eligible studies. OUTCOME MEASURES: The primary outcome measure assessed was the success rate of the procedure, defined by varying degrees of pain relief following neurotomy. Data are stratified by number of diagnostic blocks and degree of pain relief, as well as procedural technique with perpendicular or parallel placement of electrodes. RESULTS: Results varied by selection criteria and procedural technique. At six months, 26% of patients selected via single medial branch block with 50% pain relief and treated via perpendicular technique achieved at least 50% pain relief; 49% of patients selected via dual medial branch blocks with 50% pain relief and treated via parallel technique achieved at least 50% pain relief. The most rigorous patient selection and technique-two diagnostic medial branch blocks with 100% pain relief and parallel electrode placement-resulted in 56% of patients experiencing 100% relief of pain at six months. CONCLUSIONS: This comprehensive systematic review found differences in the effectiveness of lumbar medial branch radiofrequency neurotomy when studies were stratified by patient selection criteria and procedural technique. The best outcomes are achieved when patients are selected based on high degrees of pain relief from dual medial branch blocks with a technique employing parallel electrode placement.


Assuntos
Articulação Zigapofisária , Denervação , Humanos , Região Lombossacral/cirurgia , Manejo da Dor , Resultado do Tratamento , Articulação Zigapofisária/cirurgia
13.
Mar Drugs ; 17(7)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252576

RESUMO

Due to the unique biodiversity and the physical-chemical properties of their environment, marine microorganisms have evolved defense and signaling compounds that often have no equivalent in terrestrial habitats. The aim of this study was to screen extracts of the dinoflagellate Amphidinium carterae for possible bioactivities (i.e., anticancer, anti-inflammatory, anti-diabetes, antibacterial and antifungal properties) and identify bioactive compounds. Anticancer activity was evaluated on human lung adenocarcinoma (A549), human skin melanoma (A2058), human hepatocellular carcinoma (HepG2), human breast adenocarcinoma (MCF7) and human pancreas carcinoma (MiaPaca-2) cell lines. Antimicrobial activities were evaluated against Gram-positive bacteria (Staphylococcus aureus MRSA and MSSA), Gram-negative bacteria (i.e., Escherichia coli and Klebsiella pneumoniae), Mycobacterium tuberculosis and the fungus Aspergillus fumigatus. The results indicated moderate biological activities against all the cancer cells lines and microorganisms tested. Bioassay-guided fractionation assisted by HRMS analysis allowed the detection of one new and two known amphidinols that are potentially responsible for the antifungal and cytotoxic activities observed. Further isolation, purification and structural elucidation led to a new amphidinol, named amphidinol 22. The planar structure of the new compound was determined by analysis of its HRMS and 1D and 2D NMR spectra. Its biological activity was evaluated, and it displayed both anticancer and antifungal activities.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Dinoflagellida/química , Policetídeos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Aspergillus fumigatus/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Relação Estrutura-Atividade
15.
Basic Res Cardiol ; 106(3): 343-54, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21347618

RESUMO

Increasing evidence indicates that high levels of serum erythropoietin (Epo) can lessen ischemia-reperfusion injury in the heart and multiple cardiac cell types have been suggested to play a role in this Epo effect. To clarify the mechanisms underlying this cardioprotection, we explored Epo treatment of coronary artery endothelial cells and Epo cardioprotection in a Mus musculus model with Epo receptor expression restricted to hematopoietic and endothelial cells (ΔEpoR). Epo stimulation of coronary artery endothelial cells upregulated endothelial nitric oxide synthase (eNOS) activity in vitro and in vivo, and enhanced nitric oxide (NO) production that was determined directly by real-time measurements of gaseous NO release. Epo stimulated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathways, and inhibition of PI3K, but not MEK activity, blocked Epo-induced NO production. To verify the potential of this Epo effect in cardioprotection in vivo, ΔEpoR-mice with Epo response in heart restricted to endothelium were treated with Epo. These mice exhibited a similar increase in eNOS phosphorylation in coronary artery endothelium as that found in wild type (WT) mice. In addition, in both WT- and ΔEpoR-mice, exogenous Epo treatment prior to myocardial ischemia provided comparable protection. These data provide the first evidence that endothelial cell response to Epo is sufficient to achieve an acute cardioprotective effect. The immediate response of coronary artery endothelial cells to Epo stimulation by NO production may be a critical mechanism underlying this Epo cardioprotection.


Assuntos
Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Eritropoetina/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Transdução de Sinais/fisiologia , Animais , Imunofluorescência , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Isquemia Miocárdica/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Receptores da Eritropoetina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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