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1.
Front Cardiovasc Med ; 10: 1206541, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37534280

RESUMEN

The burden of atherosclerotic cardiovascular disease contributes to a large proportion of morbidity and mortality, globally. Vaccination against atherosclerosis has been proposed for over 20 years targeting different mediators of atherothrombosis; however, these have not been adequately evaluated in human clinical trials to assess safety and efficacy. Inflammation is a driver of atherosclerosis, but inflammatory mediators are essential components of the immune response. Only pathogenic forms of sTNFR2 are acted upon while preserving the membrane-bound (wild-type) TNFR2 contributions to a non-pathogenic immune response. We hypothesize that the inhibition of sTNRF2 will be more specific and offer long-term treatment options. Here we describe pre-clinical findings of an sTNFR2-targeting peptide vaccine (AtheroVax™) in a mouse model. The multiple pathways to synthesis of the soluble TNFRII receptor (sTNFRII) were identified as sTNFRII(PC), sTNFRII(Δ7), and sTNFRII(Δ7,9). The sTNFRII(Δ7) peptide, NH2-DFALPVEKPLCLQR-COOH is specific to sTNFR2 based on an mRNA splice-variant in which exon 6 is joined to exon 8. The role of sTNFRII(Δ7) as a mediator of prolonged TNFα activity by preventing degradation and clearance was investigated. Inflammation is a critical driver of onset, progression and expansion of atherosclerosis. The TNFα ligand represents a driver of inflammation that is mediated by a splice variant of TNFR2, referred to as sTNFRII(Δ7). The multiple forms of TNFRII, both membrane bound and soluble, are associated with distinctly different phenotypes. sTNFRII(PC) and sTNFRII(Δ7) are not equivalent to etanercept because they lack a clearance mechanism. The unique peptide associated with sTNFRII(Δ7) contains a linear B-cell epitope with amino acids from both exon 6 and exon 8 supporting the vaccine design. Animal studies to evaluate the vaccine are ongoing, and results will be forthcoming. We describe a peptide vaccine targeting sTNFR2 in limiting the progression of atherosclerosis. A therapeutic vaccine limiting the progression of atherosclerosis will greatly contribute to the reduction in morbidity and mortality from cardiovascular disease. It is likely the vaccine will be used in combination with the current standards of care and lifestyle modifications.

2.
Nephrol Dial Transplant ; 27(3): 1219-24, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22241793

RESUMEN

BACKGROUND: Neointimal hyperplasia causes a high rate of hemodialysis synthetic graft failure. Thus, therapies that inhibit neointimal hyperplasia are urgently needed. The Coll-R is a sirolimus-eluting collagen matrix designed for intra-operative perivascular implantation around the graft-venous anastomosis. Sirolimus is an anti-proliferative drug that has proven clinical utility in suppressing neointimal tissue growth in coronary artery disease when delivered locally to the vascular wall by an endovascular drug eluting stent. METHODS: A cohort of 12 chronic hemodialysis patients underwent surgical placement of 13 polytetrafluoroethylene grafts + Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokinetics of sirolimus release, success of Coll-R implantation and primary unassisted graft patency. RESULTS: There were no technical failures, infections, vascular anastomotic or wound-healing problems. Whole blood sirolimus levels rose to a mean peak of 4.8 ng/mL at 6 h and fell to <1 ng/mL at 1 week (n = 5). Twelve and 24-month primary unassisted patencies were 76 and 38%, respectively, and the thrombosis rate was 0.37/patient-year. CONCLUSIONS: Perivascular implantation of the Coll-R during graft surgery safely delivered sirolimus to the vascular wall. Systemic sirolimus levels were sub-therapeutic for immunosuppression. This small first-in-human study supports the concept that the Coll-R can safely deliver sirolimus to the graft-venous anastomosis. Safety and patency in this small study were sufficiently encouraging to justify randomized controlled trials to further test the efficacy of the Coll-R.


Asunto(s)
Implantación de Prótesis Vascular , Sistemas de Liberación de Medicamentos , Hipertensión/tratamiento farmacológico , Politetrafluoroetileno , Diálisis Renal , Sirolimus/administración & dosificación , Grado de Desobstrucción Vascular/efectos de los fármacos , Adolescente , Adulto , Anciano , Materiales Biocompatibles Revestidos , Colágeno/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/mortalidad , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Seguridad , Tasa de Supervivencia , Trombosis/prevención & control , Adulto Joven
3.
Stem Cells Int ; 2022: 8418509, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35756754

RESUMEN

The acute respiratory distress syndrome (ARDS) is one of the main causes of high mortality in patients with coronavirus (COVID-19). In recent years, due to the coronavirus pandemic, the number of patients with ARDS has increased significantly. Unfortunately, until now, there are no effective treatments for ARDS caused by COVID-19. Many drugs are either ineffective or have a low effect. Currently, there have been reports of efficient use of mesenchymal stem cells (MSCs) for the treatment of ARDS caused by COVID-19. We investigated the influence of freeze-dried human placenta-derived mesenchymal stem cells (HPMSCs) in ARDS rat model. All animals have received intratracheal injection of 6 mg/kg of lipopolysaccharide (LPS). The rats were randomly divided into five groups: I: LPS, II: LPS+dexamethasone, III: LPS+HPMSCs, IV: HPMSC, and V: saline. ARDS observation time was short-term and amounted to 168 hours. The study has shown that HPMSCs are able to migrate and attach to damaged lung tissue, contributing to the resolution of pathology, restoration of function, and tissue repair in the alveolar space. Studies have also shown that the administration of HPMSCs in animals with ARDS model significantly reduced the levels of key cytokines such as IL-1ß, IL-6, and TNF-α. Freeze-dried placental stem cell is a very promising biomaterial for the treatment of ARDS. The human placenta can be easily obtained because it is considered as a medical waste. At the same time, a huge number of MSCs can be obtained from the placental tissue, and there is no ethical controversy around their use. The freeze-dried MSCs from human placental tissue can be stored sterile at room temperature for a long time before use.

4.
Oncol Lett ; 23(1): 13, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34820012

RESUMEN

The present study describes a local drug delivery system with two functions, which can suppress tumor growth and accelerate wound healing. Thе system consists of a two-layer multicomponent fibrin-based gel (MCPFTG). The internal layer of MCPFTG, which is in direct contact with the wound surface, contains cisplatin placed on a CultiSpher-S collagen microcarrier. The external layer of MCPFTG consists of a CultiSpher-S microcarrier with lyophilized bone marrow stem cells (BMSCs). The efficacy of MCPFTG was evaluated in a rat model of squamous cell carcinoma of the tongue created with 4-nitroquinoline 1-oxide. The results of the study showed that, within 20-25 days, a non-healing wound of the tongue was formed in animals that underwent only 85% resection of squamous cell carcinoma, while rapid progression of the residual tumor was concomitantly observed. Immunohistochemical methods revealed high expression of cyclin D1 and low expression of E-cadherin in these animals. Additionally, high expression of p63 and Ki-67 was noted. In 80% of animals with squamous cell carcinoma of the tongue that were treated with MCPFTG after 85% tumor resection, a noticeable suppression of tumor growth was evident throughout 150 days, and tumor recurrence was not detected. Immunohistochemistry revealed low or moderate expression of cyclin D1, and high expression of E-cadherin throughout the whole observation period. The MCPFTG-based local drug delivery system was shown to be effective in suppressing tumor growth and preventing recurrence. MCPFTG decreased the toxicity of cisplatin and enhanced its antitumor activity. In addition, lyophilized paracrine BMSC factors present in MCPFTG accelerated wound healing after tumor removal. Thus, the present study suggests novel opportunities for the development of a multifunctional drug delivery system for the treatment of squamous cell carcinoma.

5.
J Am Coll Cardiol ; 76(20): 2305-2317, 2020 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-33183504

RESUMEN

BACKGROUND: Obesity is well-appreciated to result in poor cardiovascular and metabolic outcomes. Dietary and medical weight loss strategies are frequently unsuccessful and unsustainable. Bariatric surgery is quite effective, but is reserved for the most obese patients because of the associated intraoperative/post-operative risks. In preclinical and early clinical case series, a novel therapy, transcatheter bariatric embolotherapy (TBE) of the left gastric artery, has been reported to promote weight loss by reducing ghrelin, an appetite-stimulating hormone secreted from the gastric fundus. OBJECTIVES: The purpose of this study was to examine TBE in a single-blind, sham procedure randomized trial. METHODS: Obese subjects (body mass index 35 to 55 kg/m2) were randomized 1:1 to either sham or TBE targeting the left gastric artery using an occlusion balloon microcatheter to administer 300- to 500-µm embolic beads. All patients entered a lifestyle counseling program. Patients and physicians performing follow-up were blind to the allocated therapy. Endoscopy was performed at baseline and 1-week post-procedure. The primary endpoint was 6-month total body weight loss (TBWL). RESULTS: Eligible subjects (n = 44; age 45.5 ± 9.4 years; 8 men/36 women; body mass index 39.6 ± 3.8 kg/m2) were randomized to undergo the sham or TBE procedure with no device-related complications and 1 vascular complication. Patients reported mild nausea and vomiting, and endoscopy revealed only minor self-limiting ulcers in 5 patients. At 6 months, in both the intention-to-treat and per-protocol populations, the TBWL was greater with TBE (7.4 kg/6.4% and 9.4 kg/8.3% loss, respectively) than sham (3.0 kg/2.8% and 1.9 kg/1.8%, respectively; p = 0.034/0.052 and p = 0.0002/0.0011, respectively). The TBWL was maintained with TBE at 12 months (intention-to-treat 7.8 kg/6.5% loss, per-protocol 9.3 kg/9.3% loss; p = 0.0011/0.0008, p = 0.0005/0.0005, respectively). CONCLUSIONS: In this randomized pilot trial, we have established the proof-of-principle that transcatheter bariatric embolotherapy of the left gastric artery is well-tolerated and promotes clinically significant weight loss over a sham procedure.(The Lowering Weight in Severe Obesity by Embolization of the Gastric Artery Trial [LOSEIT]; NCT03185949).


Asunto(s)
Embolización Terapéutica/estadística & datos numéricos , Obesidad/terapia , Adulto , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Femenino , Artería Gástrica , Ghrelina/sangre , Humanos , Hambre , Hipertensión/etiología , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/psicología , Calidad de Vida , Respuesta de Saciedad
6.
Clin Appl Thromb Hemost ; 26: 1076029620954911, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32936689

RESUMEN

Definitive pharmacological therapies for COVID-19 have yet to be identified. Several hundred trials are ongoing globally in the hope of a solution. However, nearly all treatments rely on systemic delivery but COVID-19 damages the lungs preferentially. The use of a targeted delivery approach is reviewed where engineered products are able to reach damaged lung tissue directly, which includes catheter-based and aerosol-based approaches. In this review we have outlined various target directed approaches which include microbubbles, extracellular vesicles including exosomes, adenosine nanoparticles, novel bio-objects, direct aerosol targeted pulmonary delivery and catheter-based drug delivery with reference to their relative effectiveness for the specific lesions. Currently several trials are ongoing to determine the effectiveness of such delivery systems alone and in conjunction with systemic therapies. Such approaches may prove to be very effective in the controlled and localized COVID-19 viral lesions in the lungs and potential sites. Moreover, localized delivery offered a safer delivery mode for such drugs which may have systemic adverse effects.


Asunto(s)
Antivirales/administración & dosificación , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Pulmón , Microtúbulos , Neumonía Viral/epidemiología , SARS-CoV-2
7.
Front Cardiovasc Med ; 11: 1446992, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011495
8.
Catheter Cardiovasc Interv ; 71(7): 921-6, 2008 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-18412251

RESUMEN

OBJECTIVES: This study evaluated the feasibility of percutaneous patent foramen ovale (PFO) closure using a transcatheter suture (Superstitch), leaving no device behind. BACKGROUND: PFO has been implicated in cryptogenic strokes and migraine with auras. Percutaneous PFO closure, being less invasive than surgical closure, is increasingly performed. There are, however, early and long-term risks including device embolization, fracture, thrombosis, or infection, erosions into the free atrial wall and aorta, arrhythmias, and death. Furthermore, device implantation may complicate future percutaneous access to the left atrium. Partially reabsorbable devices and tissue welding to close PFO have recently been introduced. The first-in-man transcatheter suture closure of a PFO in an 18-year-old female with chronic migraine with aura and a well documented stroke is described. METHODS: The right femoral vein was cannulated under mild sedation and local anesthesia. Using intracardiac echocardiography imaging, bubble study demonstrated a right-to-left shunt through the PFO at rest. A Superstitch device was advanced across the PFO and sutures were delivered through the septum primum and secundum. The sutures were exteriorized and a knot was advanced to the right atrial septum and cut. RESULTS: Bubble study confirmed successful PFO suture closure. Transesophageal and transthoracic echocardiograms with bubble studies at 1 and 2 months, respectively showed complete closure with no right-to-left shunt even during Valsalva maneuver. At 6 months, the patient remained free of symptoms or migraine episodes. CONCLUSION: Percutaneous transcatheter suture closure of a PFO can be successfully achieved with no residual shunt and leaving no device behind. Technological refinements are required for wider scale use.


Asunto(s)
Cateterismo Cardíaco , Procedimientos Quirúrgicos Cardíacos/instrumentación , Foramen Oval Permeable/cirugía , Migraña con Aura/etiología , Accidente Cerebrovascular/etiología , Engrapadoras Quirúrgicas , Técnicas de Sutura/instrumentación , Adolescente , Enfermedad Crónica , Ecocardiografía Transesofágica , Diseño de Equipo , Femenino , Fluoroscopía , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/patología , Humanos , Migraña con Aura/cirugía , Accidente Cerebrovascular/cirugía , Resultado del Tratamiento
10.
Cardiovasc Revasc Med ; 8(4): 230-5, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18053943

RESUMEN

BACKGROUND: A novel antisense phosphorodiamidate morpholino oligomer, AVI-4126, was shown to be effective in reducing neointimal formation in different animal models following delivery by pluronic gels, porous balloon catheters, and coated stents. The purpose of the AVAIL study was to investigate both the safety and the efficacy of AVI-4126 delivered locally via Infiltrator catheter after percutaneous coronary intervention in humans. METHODS: The AVAIL trial is a prospective, evaluator-blinded, randomized study including clinical follow-up at 30 days and 6 months after intervention and 6-month angiographic and intravascular ultrasound (IVUS) follow-up. An Infiltrator catheter was advanced to target lesion and either drug was delivered (Groups A and B) or catheter was advanced (Group C) after stent implantation in de novo lesions or percutaneous transluminal coronary angioplasty in restenotic lesions. Primary end points include major adverse cardiovascular events (MACE), target vessel revascularization (TVR), angiographic restenosis, and IVUS at 6 months. RESULTS: Forty-four patients with either de novo lesions or restenosis were randomized into three groups: (A) low dose, 3 mg (19 patients); (B) high dose, 10 mg (15 patients), and (C) control (10 patients). Baseline angiographic characteristics did not differ between the groups (reference vessel diameter, 2.5-4 mm; lesion length, <16 mm). Procedural success was 81. 82% (unable to advance Infiltrator catheter to target lesion in 8 patients, 5 from Group B and 3 from Group C). There was no in-hospital or 30-day MACE recorded in any group. Clinical follow-up was available in 25 patients. At 6 months, four patients (50%) from the control group (Group C, n=8) and 7 (100%) patients from the low-dose group (Group A, n=7) required TVR. In contrast, in the high-dose group (Group B, n=10) only 1 patient (10%) needed TVR. Angiographic follow-up in 25 patients (Group A, 8 patients; Group B, 7 patients; and Group C, 10 patients) demonstrated late loss of 1.4+ to 0.54, 0.8+ to 0.55, and 1.5+ to 0.65, respectively (P=.025). Binary restenosis was 38% in Group C (control), 29% in Group A (low dose), and 0% in Group B (high dose). CONCLUSION: Local delivery of antisense is feasible. These preliminary findings from the small cohort of patients require confirmation in a larger trial utilizing more sophisticated drug-eluting technologies.


Asunto(s)
Reestenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/tratamiento farmacológico , Stents Liberadores de Fármacos , Morfolinas/administración & dosificación , Anciano , Angioplastia Coronaria con Balón , Angiografía Coronaria , Reestenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Morfolinos , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía Intervencional
11.
J Invasive Cardiol ; 29(3): 97-103, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28089998

RESUMEN

AIMS: To evaluate the feasibility and safety of a novel targeted neuromodulatory treatment for sympathetic hypertension involving a one-time local injection of neurotropic agents near renal nerves. METHODS AND RESULTS: Seven patients suffering from uncontrolled hypertension per ESH-ESC guidelines were treated using a single dose of NW2013, a neurotropic Na+/K+ ATPase antagonist. A microneedle catheter was used to administer 1.2 mL of NW2013 (0.6 mL per artery) to the perivascular space surrounding renal arteries using percutaneous endovascular procedures under fluoroscopic guidance. All patients were successfully treated without any procedural complications. Patients were followed for 12 months post procedure, and office and 24-hour ambulatory blood pressure measurements were made. Both office and ambulatory blood pressures were lower at 24 hours, 1 month, and 3 months after treatment. The decrease in office blood pressure was greater than the decrease in ambulatory blood pressure. A reduction in medication regimen was also observed in 2 patients. One patient suffered a cerebrovascular event after 6-month follow-up and died from stroke, unrelated to the treatment. Overall, the reduction in office and ambulatory blood pressure was sustained over the course of 12 months. CONCLUSIONS: Treatment of hypertension using local administration of NW2013 near renal nerves appears to be feasible and safe. Large, controlled, randomized, and blinded clinical studies with monitoring of patient compliance to daily oral medication are recommended to further establish the efficacy of this novel treatment.


Asunto(s)
Procedimientos Endovasculares/métodos , Hipertensión/terapia , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Simpatectomía Química/métodos , Cuidados Posteriores/métodos , Anciano , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial/métodos , Estudios de Factibilidad , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Neurotransmisores/administración & dosificación , Arteria Renal/inervación , Resultado del Tratamiento
12.
Cardiovasc Revasc Med ; 7(1): 25-33, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16513520

RESUMEN

OBJECTIVE: Perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles bind the antisense to the c-myc protooncogene (anti-c-myc) which prevents neointimal hyperplasia following vascular endothelial injury. The microbubbles also adhere to sites of damaged vascular endothelium and thus may be a method of systemically targeting delivery of anti-c-myc. METHODS: Laser scanning microscopy was performed on the aorta of 10 mice (five which were complement depleted) that received intravenous FITC-PESDA following aortic endothelial injury. C-myc expression was quantified following selective intracoronary injury in nine pigs that received intravenous (IV) anti-c-myc bound to PESDA. Finally, neointimal formation was measured following intracoronary stent deployment in 30 pigs that received either IV anti-c-myc alone or the same dose bound to PESDA. RESULTS: Fluorescent microscopy confirmed selective PESDA microbubble adherence to aortic endothelium in all mice with aortic injury. This binding was nearly abolished when serum complement was depleted prior to injury. C-myc expression at the site of coronary endothelial injury was significantly lower in pigs treated with systemic anti-c-myc bound to PESDA. There was a 33% reduction in % stenosis and a 28% reduction in intimal area at 45 days post-stent deployment in pigs that received IV antisense plus PESDA. The stent margins also had reduced neointimal formation. CONCLUSION: Systemic administration of anti-c-myc bound to PESDA microbubbles may be a good method for preventing coronary neointimal formation within and around implanted stents.


Asunto(s)
Aorta/efectos de los fármacos , Aorta/patología , Proteínas de Unión al ADN/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Microburbujas , Oligonucleótidos Antisentido/farmacología , Factores de Transcripción/metabolismo , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patología , Análisis de Varianza , Animales , Proteínas de Unión al ADN/efectos de los fármacos , Fluorocarburos/farmacología , Ratones , Microscopía Confocal , Microscopía Fluorescente , Albúmina Sérica/farmacología , Stents , Porcinos , Factores de Transcripción/efectos de los fármacos
15.
J Am Coll Cardiol ; 44(4): 733-9, 2004 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-15312851

RESUMEN

Restenosis at the site of an endoluminal procedure remains a significant problem in the practice of interventional cardiology. We present current data on intimal hyperplasia, which identify the major role of endothelial cells (ECs) in the development of restenosis. Considering endothelial denudation as one of the most important mechanisms contributing to restenosis, we focus more attention on methods of accelerating restoration of endothelial continuity. Prevention of restenosis may be achieved by promoting endothelial regeneration through the use of growth factors, EC seeding, vessel reconstruction with autologous EC/fibrin matrix, and the use of estrogen-loaded stents and stents designed to capture progenitor ECs.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria , Endotelio Vascular/patología , Stents , Humanos
16.
J Am Coll Cardiol ; 39(10): 1686-91, 2002 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-12020498

RESUMEN

OBJECTIVES: We evaluated the long-term influence of intramural delivery of advanced c-myc neutrally charged antisense oligonucleotides (Resten-NG) on neointimal hyperplasia after stenting in a pig model. BACKGROUND: Neointimal hyperplasia after percutaneous coronary interventions is one of the key components of the restenotic process. The c-myc is a critical cell division cycle protein involved in the formation of neointima. METHODS: In short-term experiments, different doses (from 500 microg to 5 mg) of Resten-NG or saline were delivered to the stent implantation site with an infiltrator delivery system (Interventional Technologies, San Diego, California). Animals were euthanized at 2, 6 and 18 h after interventions, and excised vessels were analyzed for c-myc expression by Western blot. In long-term experiments, either saline or a dose of 1, 5 or 10 mg of Resten-NG was delivered in the same fashion, and animals were euthanized at 28 days after the intervention. RESULTS: Western blot analysis demonstrated inhibition of c-myc expression and was dose dependent. Morphometry showed that the intimal area was 3.88 +/- 1.04 mm(2) in the control. There was statistically significant reduction of intimal areas in the 5 and 10 mg groups (2.01 +/- 0.66 and 1.95 +/- 0.91, respectively, p < 0.001) but no significant reduction in the 1 mg group (2.81 +/- 0.56, p > 0.5) in comparison with control. CONCLUSIONS: This study demonstrated that intramural delivery of advanced c-myc neutrally charged antisense morpholino compound completely inhibits c-myc expression and dramatically reduces neointimal formation in a dose dependent fashion in a porcine coronary stent restenosis model, while allowing for complete vascular healing.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria/patología , Reestenosis Coronaria/patología , Displasia Fibromuscular/patología , Oligonucleótidos Antisentido/farmacología , Stents , Túnica Íntima/patología , Animales , División Celular/fisiología , Femenino , Masculino , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Porcinos
17.
Am J Cardiol ; 95(1): 13-9, 2005 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-15619387

RESUMEN

We previously found that contrast-induced nephropathy (CIN) complicating percutaneous coronary intervention adversely affects patients with chronic kidney disease (CKD). Therefore, we further investigated whether the predictors and outcome of CIN after percutaneous coronary intervention differ among patients with versus without CKD. Among 7,230 consecutive patients, CIN (>or=25% or >or=0.5 mg/dl increase in preprocedure serum creatinine 48 hours after the procedure) developed in 381 of 1,980 patients (19.2%) with baseline CKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m(2)) and in 688 of 5,250 patients (13.1%) without CKD. Decreased eGFRs, periprocedural hypotension, higher contrast media volumes, lower baseline hematocrit, diabetes, pulmonary edema at presentation, intra-aortic balloon pump use, and ejection fraction <40% were the most significant predictors of CIN in patients with CKD. Apart from intra-aortic balloon pump use, predictors of CIN in patients without CKD were the same as mentioned, plus older age and type of contrast media. Regardless of baseline renal function, CIN correlated with longer in-hospital stay and higher rates of in-hospital complications and 1-year mortality compared with patients without CIN. By multivariate analysis, CIN was 1 of the most powerful predictors of 1-year mortality in patients with preexisting CKD (odds ratio 2.37, 95% confidence interval 1.63 to 3.44) or preserved eGFR (odds ratio 1.78; 95% confidence interval 1.22 to 2.60). Thus, regardless of the presence of CKD, baseline characteristics and periprocedural hemodynamic parameters predict CIN, and this complication is associated with worse in-hospital and 1-year outcomes.


Asunto(s)
Medios de Contraste/efectos adversos , Enfermedad Coronaria/terapia , Ácido Yoxáglico/efectos adversos , Enfermedades Renales/inducido químicamente , Anciano , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Incidencia , Enfermedades Renales/complicaciones , Enfermedades Renales/epidemiología , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo
18.
Photomed Laser Surg ; 23(6): 536-42, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16356143

RESUMEN

OBJECTIVE: The objective of this observational study was to investigate safety and efficacy of laser phototherapy (LPh) in prevention of restenosis after percutaneous coronary intervention (PCI). BACKGROUND DATA: Laser irradiation is known to cause a limitation of the local inflammatory cascade and a stimulation of proliferation of specific cells. Based on the results of previous experiments proving the beneficial effects of laser light on the activity of vascular and inflammatory cells, we attempted to use these properties to prevent restenosis. METHODS: Laser phototherapy was performed in 41 patients after stent implantation or balloon angioplasty. Illumination power of 100 mW and energy dose equal to 9 J/cm(2) was used. Patients were monitored for major adverse cardiac events (MACE) after 30 days and 6 months. At 6 months, angiography as a control was performed to assess the influence of LPh on restenosis rate. RESULTS: Angiographic follow-up (n = 30) revealed restenosis in 9% and 25% of patients after stent implantation and balloon angioplasty, respectively. The MACE rate was 4.5% and 12.5% in stent and balloon-treated patients, respectively. CONCLUSIONS: Laser phototherapy gives very promising results in restenosis prevention, especially after stent implantation. The treatment method is safe, with a low rate of MACE in follow-up.


Asunto(s)
Reestenosis Coronaria/prevención & control , Angioplastia de Balón , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Fototerapia/métodos , Stents
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