Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 142
Filtrar
1.
J Arthroplasty ; 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38072098

RESUMEN

BACKGROUND: Sleep quality following arthroplasty procedures is important for patient recovery and satisfaction, but remains poorly understood. The purpose of this study was to report risk factors for sleep disturbances in the perioperative period in patients undergoing primary total joint arthroplasty procedures. METHODS: Sleep surveys were prospectively collected on 751 consecutive patients undergoing total joint arthroplasty at our institution between June 2019 and February 2021 at their preoperative and postoperative visits (2 and 6 weeks). Data were collected on patient demographics, opioid use (preoperatively and postoperatively) as well as tobacco and alcohol use, and specific medical diagnosis that may influence sleep patterns (ie, depression). Statistical analyses were performed using the Student's t-tests and 1-way analysis of variances. RESULTS: For both total hip and total knee patients, worse sleep patterns preoperatively were found in patients who used opioids prior to surgery (P < .001), were current smokers (P < .001), and were aged less than 65 years (P < .001). Postoperative persistent opioid use (more than 3 months) was seen in patients who had worse reported sleep quality preoperatively (P < .001). In comparison to total hip arthroplasty, patients who underwent total knee arthroplasty were more likely to report less sleep in the postoperative period. Patients who were current smokers (compared to nonsmokers or previous smokers) (P = .014) had worse sleep quality at all time points that persisted at 6 weeks, although these differences were seen more in total hip patients than in total knee patients (P = .006 versus P = .059). CONCLUSIONS: Sleep quality disturbances around the time of surgery appear to be multifactorial. LEVEL OF EVIDENCE: Therapeutic Level III.

4.
Surgery ; 174(2): 252-258, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37277308

RESUMEN

BACKGROUND: Operating rooms contribute up to 70% of total hospital waste. Although multiple studies have demonstrated reduced waste through targeted interventions, few examine processes. This scoping review highlights methods of study design, outcome assessment, and sustainability practices of operating room waste reduction strategies employed by surgeons. METHODS: Embase, PubMed, and Web of Science were screened for operating room-specific waste-reduction interventions. Waste was defined as hazardous and non-hazardous disposable material and energy consumption. Study-specific elements were tabulated by study design, evaluation metrics, strengths, limitations, and barriers to implementation in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: A total of 38 articles were analyzed. Among them, 74% of studies had pre- versus postintervention designs, and 21% used quality improvement instruments. No studies used an implementation framework. The vast majority (92%) of studies measured cost as an outcome, whereas others included disposable waste by weight, hospital energy consumption, and stakeholder perspectives. The most common intervention was instrument tray optimization. Common barriers to implementation included lack of stakeholder buy-in, knowledge gaps, data capture, additional staff time, need for hospital or federal policies, and funding. Intervention sustainability was discussed in few studies (23%) and included regular waste audits, hospital policy change, and educational initiatives. Common methodologic limitations included limited outcome evaluation, narrow scope of intervention, and inability to capture indirect costs. CONCLUSION: Appraisal of quality improvement and implementation methods are critical for developing sustainable interventions for reducing operating room waste. Universal evaluation metrics and methodologies may aid in both quantifying the impact of waste reduction initiatives and understanding their implementation in clinical practice.


Asunto(s)
Benchmarking , Quirófanos , Humanos
5.
bioRxiv ; 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-37090642

RESUMEN

Alzheimer's disease (AD) is the leading cause of dementia worldwide, but there are limited therapeutic options and no current cure. While the involvement of microglia in AD has been highly appreciated, the role of other innate and adaptive immune cells remains largely unknown, partly due to their scarcity and heterogeneity. This study aimed to study non-microglial immune cells in wild type and AD-transgenic mouse brains across different ages. Our results uncovered the presence of a unique CD8+ T cell population that were selectively increased in aging AD mouse brains, here referred to as "disease-associated T cells (DATs)". These DATs were found to express an elevated tissue-resident memory and Type I interferon-responsive gene signature. Further analysis of aged AD mouse brains showed that these CD8+ T cells were not present in peripheral or meningeal tissues. Preventing CD8+ T cell development in AD-transgenic mice via genetic deletion of beta-2 microglobulin ( B2m ) led to a reduction of amyloid-ß plaque formation in aged mice, and improved memory in AD-transgenic mice as early as four months of age. The integration of transcriptomic and epigenomic profiles at the single-cell level revealed potential transcription factors that reshape the regulomes of CD8+ T cells. These findings highlight a critical role for DATs in the progression of AD and provide a new avenue for treatment.

6.
Arthroscopy ; 39(5): 1320-1329, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36708748

RESUMEN

PURPOSE: To evaluate the role of platelet-rich plasma (PRP) for adhesive capsulitis (AC) as compared with other injectables. METHODS: A literature search of the PubMed and Embase online databases was performed to identify articles evaluating injection therapy for the treatment of AC. The inclusion criteria included prospective studies comparing PRP against alternative injectables with a minimum of 15 patients in each treatment arm and a minimum 12-week follow-up period. Pain scores, range of motion, and function scores were the primary outcomes assessed. RESULTS: Five articles comparing PRP with corticosteroid or saline solution injections met the inclusion criteria. A total of 157 patients were treated with PRP, with a follow-up duration ranging from 3 to 6 months. All 5 studies showed statistically significant improvements in pain scores, motion, and function scores in patients receiving PRP, corticosteroid, and saline solution injections. However, PRP was consistently superior on intergroup analyses in all but 1 study. In 4 studies, pain and function scores favored PRP over control at final follow-up (range in mean difference, -2.2 to 0.69 for visual analog scale pain score [n = 5] and -50.5 to -4.0 for Shoulder Pain and Disability Index score [n = 3]), whereas 3 studies found greater improvement in shoulder motion after PRP (range in mean difference, 0.7° to 34.3° for forward flexion and -2.3° to 20.4° for external rotation [n = 4]). One study found no significant difference between PRP and corticosteroid injections but noted that the results were comparable. CONCLUSIONS: According to a limited number of prospective studies, PRP injections for AC are at least equivalent to corticosteroid or saline solution injections and often lead to improved pain, motion, and functional outcomes at 3- to 6-month follow-up. Given the small number of studies, with design heterogeneity, there is insufficient evidence to routinely recommend PRP for AC. However, the results are promising and do support considering PRP as an adjunct treatment option for AC, especially for patients refractory and/or averse to corticosteroids or alternative treatment modalities. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.


Asunto(s)
Bursitis , Plasma Rico en Plaquetas , Humanos , Estudios Prospectivos , Solución Salina/uso terapéutico , Inyecciones Intraarticulares , Corticoesteroides , Bursitis/tratamiento farmacológico , Dolor de Hombro , Resultado del Tratamiento
7.
Am J Pathol ; 191(12): 2231-2244, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34509440

RESUMEN

B cell-activating factor (BAFF), part of a tumor necrosis factor family of cytokines, was recently identified as a regulator of atherosclerosis; however, its role in aortic aneurysm has not been determined. Here, the study examined the effect of selective BAFF antagonism using an anti-BAFF antibody (blocks binding of BAFF to receptors BAFF receptor 3, transmembrane activator and CAML interactor, and B-cell maturation antigen) and mBaffR-mFc (blocks binding of BAFF to BAFF receptor 3) on a murine model of abdominal aortic aneurysm (AAA). In a prevention strategy, the antagonists were injected before the induction of AAA, and in an intervention strategy, the antagonists were injected after the induction of AAA. Both strategies attenuated the formation of AAA. In the intervention group, BAFF antagonism depleted most of the mature B-cell subsets in spleen and circulation, leading to enhanced resolution of inflammation in AAA as indicated by decreased infiltration of B cells and proinflammatory macrophages and a reduced number of apoptotic cells. In AAA tissues, B cells and macrophages were found in close contact. In vitro, B cells, irrespective of treatment with BAFF, impaired the efferocytosis activity of macrophages, suggesting a direct innate role of B cells on macrophage function. Altogether, BAFF antagonism affects survival of the mature B cells, promotes resolution of inflammation in the aorta, and attenuates the growth of AAA in mice.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Aneurisma de la Aorta Abdominal/terapia , Factor Activador de Células B/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/farmacología , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/inmunología , Aneurisma de la Aorta Abdominal/patología , Factor Activador de Células B/genética , Factor Activador de Células B/inmunología , Factor Activador de Células B/fisiología , Subgrupos de Linfocitos B/patología , Recuento de Células , Células Cultivadas , Quimiotaxis de Leucocito/fisiología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Fragmentos Fc de Inmunoglobulinas/farmacología , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
8.
Artículo en Inglés | MEDLINE | ID: mdl-33807955

RESUMEN

This study examines the statewide service coverage of emergency medical services (EMS) in view of public health planners, policy makers, and ambulance service managers. The study investigates the statewide service coverage in a mixed region of urban, rural, and frontier regions to address the importance of ambulance service coverage at a large scale. The study incorporated statewide road networks for ambulance travel time, census blocks for population, and backup service coverage using geographic information systems (GIS). The catchment areas were delineated by the travel time after subtracting chute time for each Census Block as an analysis zone. Using the catchment areas from the ambulance base to the centroid of Census Block, the population and land coverage were calculated. The service shortage and multiple coverage areas were identified by the catchment areas. The study found that both reducing chute time and increasing the speed of emergency vehicles at the same time was significantly more effective than improving only one of two factors. The study shows that the service is improved significantly in frontier and urban areas by increasing driving time and chute time. However, in rural areas, the improvement is marginal owing to wider distribution than urban areas and shorter threshold response time than frontier areas. The public health planners and EMS managers benefit from the study to identify underserved areas and redistribute limited public resources.


Asunto(s)
Ambulancias , Servicios Médicos de Urgencia , Sistemas de Información Geográfica , Humanos , Población Rural , Viaje
9.
J Surg Res ; 260: 488-498, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33341252

RESUMEN

BACKGROUND: Female sex protects against abdominal aortic aneurysms (AAAs); however, the mechanisms behind these sex-based differences remain unknown. The purpose of this study was to explore the role of sex and sex hormones in AAA formation among swine. MATERIALS AND METHODS: Using a previous validated model, infrarenal AAA were surgically created in uncastrated male (n = 8), female (n = 5), and castrated male (n = 4) swine. Aortic dilation was measured on postoperative day 28 during the terminal procedure and compared to initial aortic diameter measured during the index procedure. Tissue was analyzed for immunohistochemistry, cytokine array, gelatin zymography, serum 17ß-estradiol, and testosterone assay. RESULTS: Uncastrated males had significantly larger maximal aortic dilation compared to castrated males (113.5% ± 11.4% versus 38.1% ± 4.5%, P = 0.0012). Females had significantly higher mean aortic dilation compared to castrated males (96.2% ± 7.5% versus 38.1% ± 4.5%, P = 0.0004). Aortic diameters between females and uncastrated males were not significantly different on day 28. Female swine had significantly higher concentrations of 17ß-estradiol compared with uncastrated males (1590 ± 873.3 ng/mL versus 95.2 ± 2.3 ng/mL, P = 0.047), with no significant difference between females and castrated males. Uncastrated male AAA demonstrated significantly more elastin degradation compared with female and castrated males (P = 0.01 and <0 .01, respectively). No differences existed for T-cells or smooth muscle cells between groups. Multiple proinflammatory cytokines were elevated within uncastrated male aortic walls compared to females and castrated males. CONCLUSIONS: Sex hormones, specifically 17ß-estradiol and testosterone, influence experimental swine AAA formation as demonstrated by increased aneurysm size, collagen turnover, and elastolysis in uncastrated males in processes reflective of human disease.


Asunto(s)
Aneurisma de la Aorta Abdominal/etiología , Citocinas/metabolismo , Estradiol/metabolismo , Caracteres Sexuales , Testosterona/metabolismo , Animales , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Biomarcadores/metabolismo , Femenino , Inmunohistoquímica , Masculino , Factores Protectores , Factores de Riesgo , Sus scrofa
14.
BMC Pediatr ; 20(1): 347, 2020 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-32669131

RESUMEN

BACKGROUND: Testing for HIV at birth has the potential to identify infants infected in utero, and allows for the possibility of beginning treatment immediately after birth; point of care (POC) testing allows rapid return of results and faster initiation on treatment for positive infants. Eswatini piloted birth testing in three public maternities for over 2 years. METHODS: In order to assess the acceptability of POC birth testing in the pilot sites in Eswatini, interviews were held with caregivers of HIV-exposed infants who were offered birth testing (N = 28), health care workers (N = 14), and policymakers (N = 10). Participants were purposively sampled. Interviews were held in English or SiSwati, and transcribed in English. Transcripts were coded by line, and content analysis and constant comparison were used to identify key themes for each respondent type. RESULTS: Responses were categorized into: knowledge, experience, opinions, barriers and challenges, facilitators, and suggestions to improve POC birth testing. Preliminary findings reveal that point of care birth testing has been very well received but challenges were raised. Most caregivers appreciated testing the newborns at birth and getting results quickly, since it reduced anxiety of waiting for several weeks. However, having a favorable experience with testing was linked to having supportive and informed family members and receiving a negative result. Caregivers did not fully understand the need for blood draws as opposed to tests with saliva, and expressed the fears of seeing their newborns in pain. They were specifically grateful for supportive nursing staff who respected their confidentiality. Health care workers expressed strong support for the program but commented on the high demand for testing, increased workload, difficulty with errors in the testing machine itself, and struggles to implement the program without sufficient staffing, especially on evenings and weekends when phlebotomists were not available. Policymakers noted that there have been challenges within the program of losing mothers to follow up after they leave hospital, and recommended stronger linkages to community groups. CONCLUSIONS: There is strong support for scale-up of POC birth testing, but countries should consider ways to optimize staffing and manage demand.


Asunto(s)
Cuidadores , Infecciones por VIH , Esuatini , Femenino , Personal de Salud , Humanos , Lactante , Recién Nacido , Sistemas de Atención de Punto , Embarazo
15.
FASEB J ; 34(7): 9787-9801, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32506673

RESUMEN

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. This study investigates the role of TRPV4 channels, which are transmembrane calcium channels that can regulate vascular tone, in modulating AAA formation. The elastase-treatment model of AAA in C57BL6 (WT) mice and Angiotensin II treatment model in ApoE-/- mice were used to confirm our hypotheses. The administration of a specific TRPV4 antagonist, GSK2193874, in elastase-treated WT mice and in AngII-treated ApoE-/- mice caused a significant attenuation of aortic diameter, decrease in pro-inflammatory cytokines (IL-1ß, IL-6, IL-17, MCP-1, MIP-1α, MIP-2, RANTES, and TNF-α), inflammatory cell infiltration (CD3 + T cells, macrophages, and neutrophils), elastic fiber disruption, and an increase in smooth muscle cell α-actin expression compared to untreated mice. Similarly, elastase-treated TRPV4-/- mice had a significant decrease in AAA formation, aortic inflammation, and vascular remodeling compared to elastase-treated WT mice on Day 14. In vitro studies demonstrated that the inhibition of TRPV4 channels mitigates aortic smooth muscle cell-dependent inflammatory cytokine production as well as decreases neutrophil transmigration through aortic endothelial cells. Therefore, our results suggest that TRPV4 antagonism can attenuate aortic inflammation and remodeling via decreased smooth muscle cell activation and neutrophil transendothelial migration during AAA formation.


Asunto(s)
Aneurisma de la Aorta Abdominal/prevención & control , Inflamación/prevención & control , Macrófagos/efectos de los fármacos , Piperidinas/farmacología , Quinolinas/farmacología , Canales Catiónicos TRPV/antagonistas & inhibidores , Animales , Aneurisma de la Aorta Abdominal/etiología , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Elastasa Pancreática/metabolismo
16.
J Surg Res ; 247: 387-396, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31699539

RESUMEN

BACKGROUND: Male gender is a well-established risk factor for abdominal aortic aneurysm (AAA), whereas estrogen is hypothesized to play a protective role. Although rupture rates are higher in women, these reasons remain unknown. In the present study, we sought to determine if female mice are protected from AAA rupture. MATERIALS AND METHODS: Apolipoprotein E-deficient male and female mice (aged 7 wk; n = 25 per group) were infused with angiotensin II (AngII; 2000 ng/kg/min) plus ß-aminopropionitrile (BAPN) in the drinking water for 28 d to test the effects of gender on AAA rupture. Separately, a second group of male apolipoprotein E-deficient mice underwent AngII infusion + BAPN while being fed high-fat phytoestrogen free or a high-fat phytoestrogen diet to assess effects of phytoestrogens on rupture. In a third group, female mice either underwent oophorectomy or sham operation 4 wk before infusion of AngII and BAPN to further test the effects of female hormones on AA rupture. Surviving mice abdominal aorta were collected for histology, cytokine array, and gelatin zymography on postoperative day 28. RESULTS: Female mice had decreased AAA rupture rates (16% versus 46%; P = 0.029). Female mice expressed fewer elastin breaks (P = 0.0079) and decreased smooth muscle cell degradation (P = 0.0057). Multiple cytokines were also decreased in the female group. Gelatin zymography demonstrated significantly decreased pro-matrix metalloproteinase 2 in female mice (P = 0.001). Male mice fed a high dose phytoestrogen diet failed to decrease AAA rupture. Female mice undergoing oophorectomy did not have accelerated aortic rupture. CONCLUSIONS: These data are the first to attempt to tease out hormonal effects on AAA rupture and the possible role of gender in rupture.


Asunto(s)
Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/complicaciones , Rotura de la Aorta/epidemiología , Administración Oral , Aminopropionitrilo/administración & dosificación , Aminopropionitrilo/toxicidad , Angiotensina II/administración & dosificación , Angiotensina II/toxicidad , Animales , Aneurisma de la Aorta Abdominal/inducido químicamente , Rotura de la Aorta/etiología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados para ApoE , Factores Protectores , Factores Sexuales
17.
J Vis Exp ; (153)2019 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-31814612

RESUMEN

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called ß-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease. Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone. Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% ± 47.4% at day 7, 105.4% ± 58.1% at day 14, and 113.5% ± 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p < 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease. Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.


Asunto(s)
Aneurisma de la Aorta Abdominal , Modelos Animales de Enfermedad , Enfermedades de los Porcinos/etiología , Aminopropionitrilo , Angioplastia de Balón , Animales , Aorta Abdominal , Aneurisma de la Aorta Abdominal/inducido químicamente , Colagenasas , Humanos , Masculino , Elastasa Pancreática , Circulación Renal , Reproducibilidad de los Resultados , Porcinos , Enfermedades de los Porcinos/inducido químicamente
18.
Arterioscler Thromb Vasc Biol ; 39(1): 73-88, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30580567

RESUMEN

Objective- The goal of this study was to determine the role of ZFP148 (zinc-finger protein 148) in aneurysm formation. Approach and Results- ZFP148 mRNA expression increased at day 3, 7, 14, 21, and 28 after during abdominal aortic aneurysm formation in C57BL/6 mice. Loss of ZFP148 conferred abdominal aortic aneurysm protection using ERTCre+ ZFP148 flx/flx mice. In a third set of experiments, smooth muscle-specific loss of ZFP148 alleles resulted in progressively greater protection using novel transgenic mice (MYH [myosin heavy chain 11] Cre+ flx/flx, flx/wt, and wt/wt). Elastin degradation, LGAL3, and neutrophil staining were significantly attenuated, while α-actin staining was increased in ZFP148 knockout mice. Results were verified in total cell ZFP148 and smooth muscle-specific knockout mice using an angiotensin II model. ZFP148 smooth muscle-specific conditional mice demonstrated increased proliferation and ZFP148 was shown to bind to the p21 promoter during abdominal aortic aneurysm formation. ZFP148 smooth muscle-specific conditional knockout mice also demonstrated decreased apoptosis as measured by decreased cleaved caspase-3 staining. ZFP148 bound smooth muscle marker genes via chromatin immunoprecipitation analysis mediated by NF-1 (neurofibromin 1) promote histone H3K4 deacetylation via histone deacetylase 5. Transient transfections and chromatin immunoprecipitation analyses demonstrated that NF-1 was required for ZFP148 protein binding to smooth muscle marker genes promoters during aneurysm formation. Elimination of NF-1 using shRNA approaches demonstrated that NF-1 is required for binding and elimination of NF-1 increased BRG1 recruitment, the ATPase subunit of the SWI/SWF complex, and increased histone acetylation. Conclusions- ZFP148 plays a critical role in multiple murine models of aneurysm formation. These results suggest that ZFP148 is important in the regulation of proliferation, smooth muscle gene downregulation, and apoptosis in aneurysm development.


Asunto(s)
Aneurisma de la Aorta Abdominal/etiología , Proteínas de Unión al ADN/metabolismo , Miocitos del Músculo Liso/metabolismo , Neurofibromina 1/metabolismo , Factores de Transcripción/metabolismo , Acetilación , Angiotensina II/farmacología , Animales , Aneurisma de la Aorta Abdominal/metabolismo , Apoptosis , Proliferación Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Histonas/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Destructora del Antagonista Homólogo bcl-2/genética
19.
J Vasc Surg ; 70(1): 252-260.e2, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30591288

RESUMEN

OBJECTIVE: Few large-animal models exist for the study of aortic aneurysms. ß-Aminopropionitrile (BAPN) is a compound known to cause aortic aneurysms by inhibiting lysyl oxidase, a collagen cross-linking enzyme. It is hypothesized that BAPN plus aneurysm induction surgery would result in significant aneurysm formation in swine with biologic properties similar to human disease. METHODS: Initial experiments were performed in uncastrated male swine not treated with BAPN (surgery alone). Subsequently, uncastrated male swine were fed BAPN (0.15 g/kg) for 7 days before undergoing surgery; the infrarenal aorta was circumferentially dissected and measured, balloon dilated, and perfused with elastase (500 units) and type I collagenase (8000 units), with extraluminal elastase application. In the BAPN groups, daily BAPN feedings continued until swine harvest at postoperative days 7, 14, and 28. RESULTS: Swine undergoing surgery alone (n = 12) had significantly less dilation at 28 days compared with BAPN + surgery swine (51.9% ± 29.2% [0%-100%] vs 113.5% ± 30.2% [52.9%-146.2%]; P < .0003). Mean aortic dilation in animals undergoing treatment with surgery and BAPN was 86.9% ± 47.4% (range, 55.6%-157.1%), 105.4% ± 58.1% (50%-133.3%), and 113.5% ± 30.2% (52.9%-146.2%) at 7, 14, and 28 days, respectively. In the BAPN + surgery group, significant elastolysis was present at all time points, whereas aortic wall collagen content was not significantly different. Smooth muscle cells were significantly depleted at 14 and 28 days, and M1 macrophages were increased at 14 and 28 days (P < .05, all). Matrix metalloproteinase 2 was elevated at 7 days (P < .05). Multiple proinflammatory cytokines were elevated within the aortic wall of BAPN + surgery swine. CONCLUSIONS: BAPN plus surgery resulted in significantly larger aortic aneurysms than surgery alone and was critical to aneurysm formation in this novel swine model. Hallmarks of human disease, such as elastin fragmentation, smooth muscle cell depletion, macrophage infiltration, matrix metalloproteinase activation, and proinflammatory cytokine expression, were observed in BAPN-treated swine. This model better parallels many of the characteristics of human AAAs and may be suitable for prehuman drug trials.


Asunto(s)
Aminopropionitrilo , Angioplastia de Balón , Aorta Abdominal , Aneurisma de la Aorta Abdominal/inducido químicamente , Colagenasas , Elastasa Pancreática , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Citocinas/metabolismo , Dilatación Patológica , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Sus scrofa , Factores de Tiempo , Remodelación Vascular
20.
J Vasc Surg ; 68(6S): 93S-103S, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30470363

RESUMEN

OBJECTIVE: Resolvins have been shown to attenuate inflammation, whereas NETosis, the process of neutrophils releasing neutrophil extracellular traps (NETs), produces increased inflammation. It is hypothesized that treatment of animals with resolvin D1 (RvD1) would reduce abdominal aortic aneurysm (AAA) formation by inhibiting NETosis. METHODS: Wild-type 8- to 12-week-old C57BL/6 male mice (n = 47) and apolipoprotein E-deficient (ApoE-/-) mice (n = 20) were used in two models to demonstrate the effects of RvD1 on AAA growth. In the topical elastase AAA model, wild-type mice were divided into three groups: a deactivated elastase control group, in which sham surgery was performed using deactivated elastase and mice were intravenously injected with phosphate-buffered saline (PBS) once a day until harvest; an elastase group, in which active elastase was used to induce AAA and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which AAA was induced and mice were injected with RvD1 daily until harvest. In the angiotensin II (Ang II)-induced AAA model, ApoE-/- mice were fed a high-fat diet and implanted with osmotic infusion pumps containing Ang II (1000 ng/kg/min). The Ang II model was divided into two groups: an Ang II control group, in which Ang II was delivered and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which Ang II was delivered and mice were injected with RvD1 daily until harvest. On postoperative day 3, day 14, or day 28, aortic and blood samples were collected for Western blot, histology, cytokine array, enzyme-linked immunosorbent assay, and gelatin zymography after aortic diameter measurement. RESULTS: The day 14 RvD1-treated group demonstrated 42% reduced AAA diameter compared with the elastase group (P < .001). On postoperative day 3, the RvD1-treated group showed decreased levels of NETosis markers citrullinated histone H3 (P = .04) and neutrophil elastase (P = .002) compared with the elastase group. Among important cytokines involved in AAA formation, interleukin (IL) 1ß was downregulated (P = .02) whereas IL-10, a protective cytokine, was upregulated (P = .01) in the RvD1-treated group. Active matrix metalloproteinase 2 also decreased in the RvD1-treated group (P = .03). The RvD1-treated group in the Ang II AAA model, a second model, demonstrated reduced AAA diameter compared with the Ang II control group on day 28 (P < .046). The RvD1-treated group showed decreased levels of citrullinated histone H3 on day 3 (P = .002). Cytokines interferon γ, IL-1ß, C-X-C motif chemokine ligand 10, monocyte chemotactic protein 1, and regulated on activation, normal T cell expressed and secreted (RANTES) were all decreased on day 28 (P < .05). CONCLUSIONS: RvD1-mediated inhibition of NETosis may represent a future medical treatment for the attenuation of AAA growth.


Asunto(s)
Antiinflamatorios/farmacología , Aorta Abdominal/efectos de los fármacos , Aneurisma de la Aorta Abdominal/prevención & control , Ácidos Docosahexaenoicos/farmacología , Trampas Extracelulares/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Citrulinación , Citocinas/metabolismo , Modelos Animales de Enfermedad , Trampas Extracelulares/metabolismo , Histonas/metabolismo , Mediadores de Inflamación/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Neutrófilos/metabolismo , Neutrófilos/patología , Elastasa Pancreática , Remodelación Vascular/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...