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1.
J Electrocardiol ; 49(4): 504-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27003375

RESUMEN

Identification of acute myocardial infarction (AMI) in the presence of left bundle branch block (LBBB) remains challenging. European guidelines recommend prompt reperfusion therapy in patients with suspected ongoing myocardial ischemia and new or presumably new LBBB, whereas AHA/ACC guidelines state that LBBB should not be considered diagnostic of AMI in isolation. Sgarbossa criteria and their recent modified version with the introduction of ST/S ratio can be helpful in this setting. A clinical-instrumental algorithm to manage suspected AMI in the presence of LBBB has been recently proposed. We present five paradigmatic clinical cases.


Asunto(s)
Bloqueo de Rama/complicaciones , Bloqueo de Rama/diagnóstico , Dolor en el Pecho/complicaciones , Electrocardiografía/normas , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Guías de Práctica Clínica como Asunto , Adulto , Anciano de 80 o más Años , Cardiología/normas , Dolor en el Pecho/diagnóstico , Diagnóstico Diferencial , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad
2.
Med Oral Patol Oral Cir Bucal ; 21(6): e743-e750, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-27694788

RESUMEN

BACKGROUND: The prevalence of impacted maxillary canine is reported to be between 1% and 3%. The lack of monitoring and the delay in the treatment of the impacted canine can cause different complications such as: displacement of adjacent teeth, loss of vitality of neighbouring teeth, shortening of the dental arch, follicular cysts, canine ankylosis, recurrent infections, recurrent pain, internal resorption of the canine and the adjacent teeth, external resorption of the canine and the adjacent teeth, combination of these factors. An appropriate diagnosis, accurate predictive analysis and early intervention are likely to prevent such undesirable effects. The objective is to evaluate, by means of a retrospective observational study, the possibility of carrying out a predictive analysis of root resorption adjacent to the impacted canines by means of orthopantomographs, so as to limit the prescription of additional 3D radiography. MATERIAL AND METHODS: 120 subjects with unilateral or bilateral maxillary impacted canine were examined and 50 patients with 69 impacted maxillary canine (22 male, 28 female; mean age: 11.7 years) satisfied the inclusion criteria of the study. These patients were subjected to a basic clinical and radiographic investigation (orthopantomographs and computerized tomography). All panoramic films were viewed under standardized conditions for the evaluation of two main variables: maxillary canine angulations (a, b, g angles) and the overlapping between the impacted teeth and the lateral incisor (Analysis of Lindauer). Binary logistic regression was used to estimate the likelihood of resorbed lateral incisors depending on sector location and angle measurements. RESULTS: Results indicated that b angle has the greatest influence on the prediction of root resorption (predictive value of b angle = 76%). If ß angle <18° and Lindauer = I, the probability of resorption is 0.06. CONCLUSIONS: Evaluation of b angle and superimposition lateral incisor/impacted canine analysed on orthopantomographs could be one of the evaluation criteria for prescribing second level examination (CT and CTCB) and for detecting root resorption of impacted maxillary canine adjacent teeth.


Asunto(s)
Diente Canino , Resorción Radicular , Diente Impactado , Niño , Femenino , Humanos , Masculino , Maxilar , Estudios Retrospectivos
3.
Eur J Paediatr Dent ; 14(1): 73-6, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23597226

RESUMEN

AIM: Cherubism is characterised by mesenchymal alterations during the development of the jaws secondary to perivascular fibrosis. According to the ALARA (As Low As Reasonably Achievable) principle, it is important to avoid conditions where the amount of radiation used is more than that needed for the procedure, because there is no benefit from unnecessary radiation. However, the use of MRI has been poorly studied in cherubism. MATERIALS AND METHODS: The patient underwent head and neck MRI and 3D CT for imaging assessment. RESULTS: MRI is necessary to evaluate the extension of dysplastic tissue and the cystic part of the lesions. Bone window CT only allows evaluation of strong densitometric alterations of cherubism lesions. Moreover, on radiographic film it is not always possible to distinguish fibrous tissue from mucous pseudocystic tissue. By contrast, these differences are readily evident on MRI. CONCLUSION: MRI, in addition to other traditional radiographs and CT, could be useful in helping the clinician in the diagnosis and treatment of cherubism.


Asunto(s)
Querubismo/diagnóstico , Imagen por Resonancia Magnética/métodos , Planificación de Atención al Paciente , Tomografía Computarizada por Rayos X/métodos , Absorciometría de Fotón/métodos , Densidad Ósea/fisiología , Enfermedades del Desarrollo Óseo/diagnóstico , Querubismo/terapia , Niño , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Imagenología Tridimensional/métodos , Masculino , Enfermedades Mandibulares/diagnóstico , Mucocele/diagnóstico , Radiografía Panorámica/métodos
4.
G Ital Nefrol ; 26 Suppl 45: S64-8, 2009.
Artículo en Italiano | MEDLINE | ID: mdl-19382097

RESUMEN

Stem cells are a potential source for the regeneration of many tissues, including damaged kidneys. The present study describes the adoption of hyaluronic- butyric acid monoesters (HB) to induce expression of nephrogenic genes by mesenchymal cells isolated from human placental membranes. HB at a concentration of 1 mg/mL induces chromatin opening and increases the expression of the observed markers (cadherin 11, CD24, RAR-alpha, stearoyl-CoA desaturase 2, 14-3-3 0, Ewing sarcoma homolog.). These results open new routes toward cell regeneration after kidney injury.


Asunto(s)
Riñón/lesiones , Riñón/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Antígenos de Diferenciación/metabolismo , Diferenciación Celular , Femenino , Humanos , Técnicas In Vitro , Riñón/cirugía , Placenta , Embarazo , Estearoil-CoA Desaturasa/metabolismo
6.
Am J Cardiol ; 74(6): 590-5, 1994 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-8074043

RESUMEN

The aim of this study was to assess the comparative diagnostic value of transesophageal echocardiography (TEE) and retrograde aortography for morphologic evaluation and anatomic mapping of aortic dissection. Seventy patients (aged 18 to 79 years) were prospectively evaluated with both techniques for suspected aortic dissection. In 64 patients, findings on aortography and TEE could be validated against intraoperative (n = 53) and postmortem (n = 11) findings. Examination time was significantly shorter for TEE (9 +/- 6 vs 48 +/- 25 minutes; p < 0.001). For the detection of aortic dissection, aortography showed lower sensitivity (87.5% vs 97.5%) and negative predictive value (85.3% vs 96.7%; both trends did not reach statistical significance) due mostly to the inability to identify noncommunicating dissection (dissection without intimal tears). For the epiphenomena of aortic dissection, aortography was significantly more accurate (97.2% vs 78%; p < 0.05) in assessing the site of entry, and TEE was more accurate in identifying thrombus formation (90% vs 65%; p < 0.05). There was no significant difference between aortography and TEE with regard to assessing secondary tears, aortic regurgitation, coronary dissection, and extension of the dissection. Thus, both TEE and aortography offer detailed anatomic mapping for guided surgical interventions. In elective patients, integration of both techniques seems the best approach; in unstable patients, TEE may be preferential because it is less invasive, requires no contrast injection, and provides accurate diagnosis in a short time at the bedside.


Asunto(s)
Aneurisma de la Aorta Torácica/diagnóstico , Disección Aórtica/diagnóstico , Aortografía , Ecocardiografía Transesofágica , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aortografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
7.
Am J Med Genet ; 88(5): 527-32, 1999 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-10490711

RESUMEN

Tyrosine hydroxylase (TH), the rate-limiting enzyme in the metabolism of catecholamines, is considered a candidate gene in bipolar affective disorder (BPAD) and has been the subject of numerous linkage and association studies. Taken together, most results do not support a major gene effect for the TH gene in BPAD. Genetic and phenotypic heterogeneity may partially explain the difficulty of confirming the exact role of this gene using both association and linkage methods. Four hundred one BPAD patients and 401 unrelated matched controls were recruited within a European collaborative project (BIOMED1 project in the area of brain research, European Community grant number CT 92-1217, project leader: J. Mendlewicz) involving 14 centers for a case-control association study with a tetranucleotide polymorphism in the TH gene. Patients and controls were carefully matched for geographical origin. Phenotypic heterogeneity was considered and subgroup analyses were performed with relevant variables: age at onset, family history, and diagnostic stability. No association was observed in the total sample or for subgroups according to age at onset (n = 172), family history alone (n = 159), or high degree of diagnostic stability and a positive family history (n = 131). The results of this association study do not confirm the possible implication of TH polymorphism in the susceptibility to BPAD.


Asunto(s)
Trastorno Bipolar/genética , Fenotipo , Polimorfismo Genético , Tirosina 3-Monooxigenasa/genética , Adulto , Edad de Inicio , Alelos , Estudios de Casos y Controles , Europa (Continente) , Europa Oriental , Femenino , Variación Genética , Heterocigoto , Homocigoto , Humanos , Israel , Masculino , Persona de Mediana Edad
8.
Psychiatr Genet ; 8(4): 197-205, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9861637

RESUMEN

Despite strong evidence provided by genetic epidemiology of genetic involvement in the aetiology of bipolar and unipolar affective disorders, the exact nature of the predisposing gene(s) is still being investigated through linkage and association studies. The interaction of susceptibility genes and environmental factors in these diseases is also of fundamental importance and requires proper investigation. Interesting theories have recently been proposed examining the possible role of various chromosomal regions, candidate genes and mutations in affective disorders. Reliable multicentre-based methodology is currently being employed to examine these theories, with attention given to statistical analysis and the statistical power of the sample. The present article describes the European Collaborative Project on Affective Disorders (ECPAD) 'Interactions between genetic and psychosocial vulnerability factors', involving 15 European centres. A description is given of the association and family samples collected for the project and also the methodology used to analyse interactions in the gene-psychosocial environment. This material provides a powerful tool in the search for susceptibility genes in affective disorders and takes into account non-genetic aetiological factors.


Asunto(s)
Trastornos del Humor/epidemiología , Adolescente , Adulto , Edad de Inicio , Trastorno Bipolar/epidemiología , Trastorno Bipolar/etiología , Trastorno Bipolar/genética , Trastorno Bipolar/psicología , Estudios de Casos y Controles , Mapeo Cromosómico , Cromosomas Humanos/genética , Susceptibilidad a Enfermedades , Ambiente , Europa (Continente)/epidemiología , Femenino , Ligamiento Genético , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/etiología , Trastornos del Humor/genética , Trastornos del Humor/psicología , Neurotransmisores/genética , Neurotransmisores/metabolismo , Fenotipo , Psicología , Muestreo
9.
Int J Cardiol ; 23(2): 215-21, 1989 May.
Artículo en Inglés | MEDLINE | ID: mdl-2722288

RESUMEN

The electrophysiologic effects and efficacy of diltiazem were evaluated with programmed electrical stimulation of the heart in 12 patients with supraventricular re-entrant tachycardia (five with atrioventricular nodal tachycardia and seven with circus movement tachycardia the accessory pathway being concealed in 4). Diltiazem was infused over 1 minute at the dose of 0.25 mg/kg and the electrophysiologic parameters were evaluated at 5 and 30 minutes. Diltiazem prolonged the AH interval from 83.5 +/- 58 to 99 +/- 55 msec (P less than 0.05), effective and functional refractory periods of atrioventricular node from 244 +/- 40 to 268 +/- 56 msec (P less than 0.05) and from 432 +/- 124 to 468 +/- 130 msec (P less than 0.005) respectively, lowered the atrial pacing rate inducing second-degree atrioventricular block from 159 +/- 32 to 134 +/- 33 beats/min (P less than 0.005) and decreased systolic and diastolic blood pressure from 143.5 +/- 33 to 132.5 +/- 22 mm Hg (P less than 0.05) and from 90 +/- 15 to 82.5 +/- 9 (P less than 0.05), respectively. Diltiazem prevented the reinduction of the tachycardia in 4 of 5 patients with atrioventricular nodal tachycardia and in 4 of 7 with circus movement tachycardia. The mechanism of action of diltiazem consisted of depression of conduction in atrioventricular node in anterograde fashion while there were no effects on refractoriness of the accessory pathway. The drug was well tolerated with no adverse effects. Diltiazem, therefore, appears an effective and safe drug in the acute treatment of re-entrant supraventricular tachycardia.


Asunto(s)
Diltiazem/administración & dosificación , Taquicardia Supraventricular/tratamiento farmacológico , Adolescente , Adulto , Anciano , Nodo Atrioventricular/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Estimulación Cardíaca Artificial , Diltiazem/farmacología , Diltiazem/uso terapéutico , Electrofisiología , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Taquicardia Supraventricular/fisiopatología
10.
Int J Clin Pharmacol Res ; 4(3): 185-94, 1984.
Artículo en Inglés | MEDLINE | ID: mdl-6149196

RESUMEN

The sensitivity of the prenalterol test has been evaluated in 21 patients with pseudoischaemic T waves and no documented organic heart disease. The sensitivity of the test (40 micrograms/kg i.v. in 3 min) was 90.4%. In comparison, the isoproterenol test, performed in 10 of these patients, showed a similar sensitivity but prenalterol had a lower positive chronotropic effect than isoproterenol (p less than 0.0005). The possible advantages of the introduction of the prenalterol test in clinical practice are analysed.


Asunto(s)
Agonistas Adrenérgicos beta , Enfermedad Coronaria/diagnóstico , Electrocardiografía , Practolol/análogos & derivados , Adulto , Anciano , Diagnóstico Diferencial , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Isoproterenol , Masculino , Persona de Mediana Edad , Prenalterol
11.
Parassitologia ; 32(3): 305-11, 1990 Dec.
Artículo en Italiano | MEDLINE | ID: mdl-2132442

RESUMEN

Some cases of visceral leishmaniasis in children and in adults have been diagnosed in the last fifteen years in Western Sicily and an increasing number of cases of canine leishmaniasis has been recorded, mainly in the province of Palermo. Such a human leishmaniasis recrudescence, after the antimalaria campaign had reduced the transmission, and the increase of canine leishmaniasis in the city of Palermo and its suburbs suggest that transmission in urban areas may be possible. Using the oiled paper method, a survey of phlebotomine sandflies was carried out during June and July 1988 both in the centre and suburbs of Palermo, and during July and August '88 in the Madonie mountains (at 800 to 1200 meters above sea level) and in two Eolian Islands: Lipari and Filicudi. Details of collected species are given. In both surveys, the oiled paper method did not turn out to be selective towards any given species of sandflies.


Asunto(s)
Insectos Vectores , Leishmania donovani , Psychodidae , Adulto , Animales , Animales Domésticos , Niño , Brotes de Enfermedades , Enfermedades de los Perros/epidemiología , Perros/parasitología , Femenino , Humanos , Incidencia , Italia/epidemiología , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/transmisión , Leishmaniasis Visceral/veterinaria , Masculino , Islas del Mediterráneo/epidemiología , Psychodidae/clasificación , Sicilia/epidemiología
12.
Parassitologia ; 33(2-3): 127-31, 1991 Dec.
Artículo en Italiano | MEDLINE | ID: mdl-1844502

RESUMEN

A survey on phlebotomine sandflies (Diptera, Psychodidae) was carried out in the province of L'Aquila, Abruzzo region (Italy). Ten collecting sites at altitudes between 700 and 1,070 m a.s.l., produced a total of 324 specimens (81.1% males), 72.86% being Phlebotomus perniciosus, 3.08% P. mascittii, 0.30% P. papatasi and 23.76% Sergentomyia minuta. The collecting sites at 1,070, 950 and 775 m a.s.l. are the highest levels recorded in Italy for P. perniciosus, P. mascittii and P. papatasi, respectively. P. perfiliewi, the proven vector of cutaneous leishmaniasis (CL) in the Abruzzo region (Maroli et al., 1987) was absent. The probable role of P. perniciosus in the transmission of the sporadic CL cases reported from the area is discussed.


Asunto(s)
Insectos Vectores , Leishmania donovani , Phlebotomus , Animales , Animales Domésticos , Reservorios de Enfermedades , Femenino , Italia , Leishmaniasis Cutánea/transmisión , Masculino , Especificidad de la Especie
13.
Parassitologia ; 20(1-3): 143-52, 1978 Dec.
Artículo en Italiano | MEDLINE | ID: mdl-553265

RESUMEN

Cephenemya stimulator (Clark) (Diptera Oestridae) is first recorded in Italy parasiting roe deer (Capreolus capreolus). Diagnosis was made by examination of II-III instar larvae (fig. 1-2) from roe deers killed in Trient province. In these last years in the Trentin region, there was an increasing of roe deers number (actually about 20.000); at the same time growed roe deers infestation by C. stimulator (Tab. 1). Females of C. stimulator probably attack young roe-deers lying down on field-pastures near forest (fig. 3). From examination of killed roe-deers (Tab. 2) there is evidence of debilitation status of infested specimens. Location and dislocations of parasitising larvae in the head cavity was that shown in fig. 4 and 5.


Asunto(s)
Ciervos/parasitología , Dípteros/aislamiento & purificación , Infestaciones Ectoparasitarias/veterinaria , Enfermedades de los Animales/epidemiología , Animales , Infestaciones Ectoparasitarias/epidemiología , Femenino , Italia , Larva/aislamiento & purificación , Masculino
14.
Ann Ist Super Sanita ; 25(4): 675-9, 1989.
Artículo en Italiano | MEDLINE | ID: mdl-2631630

RESUMEN

The trend of imported malaria cases in Italy from 1960 to 1988 is discussed. Comparative analysis of its incidence in the last three years is also presented. Since 1985, a rapid increase has been recorded with 191 cases in 1986, 287 in 1987 and 350 in 1988. In 1986-88 Plasmodium falciparum has been responsible for 74% of the total number, followed by P. vivax (21%), P. malariae (2%) and P. ovale (1%). 86% of the imported cases have been acquired in African countries, 8% in Asia and 3% in South America. As far as travelers categories are concerned workers represent 45.6% of the total population, tourists 36.6%, seamen and aircrew 2.1% and strangers coming from endemic malaria areas and traveling to Italy 15.7%. In 1986, 1987, and 1988 one, two and two deaths, respectively, due to malaria, are reported.


Asunto(s)
Malaria/epidemiología , Europa (Continente) , Humanos , Italia , Estudios Retrospectivos
15.
Ital Heart J Suppl ; 2(7): 719-32, 2001 Jul.
Artículo en Italiano | MEDLINE | ID: mdl-11508290

RESUMEN

Stent implantation is the only technique that has proven to reduce restenosis rate for selected lesion types after procedures of percutaneous coronary revascularization. Yet restenosis, although reduced, continues to exert a negative impact on long-term clinical outcome of treated patients. In-stent restenosis is almost exclusively due to neointimal hyperplasia, which appears more pronounced following stent than after other types of devices. A new revascularization procedure is clinically required in almost one half of the cases of in-stent restenosis; its angiographic pattern represents a major determinant of the efficacy of repeat intervention, a diffuse pattern being associated with a worse prognosis. The most powerful predictors of in-stent restenosis include diabetes mellitus, vessel caliber, cumulative stent length and its minimal lumen diameter after expansion; genetic variables and biological individual factors may also play an important role in conditioning the local response to stent placement. Intravascular ultrasound-guided stent deployment and the use of very high pressure to assure full stent expansion have not demonstrated to improve long-term clinical and angiographic results of the procedure. Some observational studies have suggested that plaque removal with directional or rotational atherectomy prior to stent implantation may reduce the risk of restenosis; the usefulness of this approach is currently evaluated in randomized clinical trials. Absence of restenosis has recently been reported in small pilot studies in which stents coated with antiproliferative drugs were used; these findings warrant further confirmation and represent one of the most promising issues for the next future.


Asunto(s)
Estenosis Coronaria/cirugía , Stents , Angiografía Coronaria , Estenosis Coronaria/diagnóstico , Predicción , Humanos , Valor Predictivo de las Pruebas , Pronóstico
16.
J R Soc Health ; 110(3): 88-9, 1990 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2114489

RESUMEN

The trend of imported malaria cases in Italy from 1960 to 1988 is discussed. Comparative analysis of malaria incidence in the last three years is also presented. Since 1985, a rapid increase was recorded with 191 cases in 1986, 287 in 1987 and 350 in 1988. In 1986-1988 Plasmodium falciparum was responsible for 74% cases of the total number, followed by P. vivax (21%), P. malariae (2.2%) and P. ovale (1%). 86% of the imported cases was acquired in African countries, 8% in Asia and 3% in South America. As far as travellers categories are concerned, workers represented 46% of the total population, tourists 37%, seamen and aircrew 2% and strangers coming from endemic malaria areas and travelling to Italy 16%. In 1986, 1987 and 1988 three, four and two deaths respectively, due to malaria, were reported.


Asunto(s)
Malaria/epidemiología , Viaje , Animales , Humanos , Incidencia , Italia/epidemiología , Plasmodium falciparum , Plasmodium vivax
17.
Int J Oral Maxillofac Surg ; 42(2): 264-75, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22789635

RESUMEN

The aim of the present study was to assess the clinical relevance of the potential mechanical error (intrinsic error) caused by the cylinder-burr gap in a 'single type' stereolithographic surgical template in implant guided surgery. 129 implants were inserted in 12 patients using 18 templates. The pre- and postoperative computed tomography (CT) scans were matched allowing comparison of the planned implants with the placed ones. Considering only the angular deviation values, the t test was used to determine the influence of the guide fixation and the arch of support on accuracy values. The Pearson correlation coefficient was used to correlate angular deviation and bone density. The intrinsic error was mathematically evaluated. t test results indicated that the use of fixing screws (P=009) and the upper arch support (P=027) resulted in better accuracy. The Pearson correlation coefficient (0.229) indicated a significant linear correlation between angular deviations and bone density (P=009). A mean intrinsic error of 2.57 was mathematically determined considering only the angular deviation, as it was not influenced by other variables. The intrinsic error is a significant factor compared to all the variables that could potentially affect the accuracy of computer-aided implant placement.


Asunto(s)
Implantación Dental Endoósea/instrumentación , Procesamiento de Imagen Asistido por Computador , Arcada Edéntula/diagnóstico por imagen , Errores Médicos , Fotografía Dental , Cirugía Asistida por Computador/instrumentación , Densidad Ósea , Diseño Asistido por Computadora , Arco Dental/diagnóstico por imagen , Implantación Dental Endoósea/métodos , Diseño de Prótesis Dental , Precisión de la Medición Dimensional , Femenino , Humanos , Arcada Edéntula/cirugía , Masculino , Persona de Mediana Edad , Diseño de Software , Estadísticas no Paramétricas , Tomografía Computarizada por Rayos X
18.
Int J Cardiol ; 168(3): 2426-34, 2013 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-23561919

RESUMEN

BACKGROUND: Vasculogenesis is a hallmark of myocardial restoration. Post-ischemic late remodeling is associated with pathology and function worsening. At the same time, neo-vasculogenesis helps function improving and requires the release of vascular endothelial growth factor type A (VEGF-A). The vasculogenic role of C-type natriuretic peptide (CNP), a cardiac paracrine hormone, is unknown in infarcted hearts with preserved left ventricular (LV) ejection fraction (EF). We explored whether myocardial VEGF-dependent vasculogenesis is affected by CNP. METHODS AND RESULTS: To this end, infarcted swine hearts were investigated by magnetic resonance imaging (MRI), histological and molecular assays. At the fourth week, MRI showed that transmural myocardial infarction (MI) affected approximately 13% of the LV wall mass without impairing global function (LVEF>50%, n=9). Increased fibrosis, metalloproteases and capillary density were localized to the infarct border zone (BZ), and were associated with increased expression of CNP (p=0.03 vs. remote zone (RZ)), VEGF-A (p<0.001 vs. RZ), BNP, a marker of myocardial dysfunction (p<0.01 vs. RZ) and the endothelial marker, factor VIII-related antigen (p<0.01 vs. RZ). In vitro, CNP 1000 nM promoted VEGF-dependent vasculogenesis without affecting the cell growth and survival, although CNP 100 nM or a high concentration of VEGF-A halted vascular growth. CONCLUSIONS: CNP expression is locally increased in infarct remodeled myocardium in the presence of dense capillary network. The vasculogenic response requires the co-exposure to high concentration of CNP and VEGF-A. Our data will be helpful to develop combined myocardial delivery of CNP and VEGF-A genes in order to reverse the remodeling process.


Asunto(s)
Infarto del Miocardio/fisiopatología , Péptido Natriurético Tipo-C/fisiología , Neovascularización Fisiológica/fisiología , Factor A de Crecimiento Endotelial Vascular/fisiología , Función Ventricular Izquierda , Remodelación Ventricular , Animales , Masculino , Porcinos
19.
Br J Pharmacol ; 162(6): 1261-73, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21175567

RESUMEN

BACKGROUND AND PURPOSE: Cystine-knot miniproteins are characterized by a similar molecular structure. Some cystine-knot miniproteins display therapeutically useful biological activities, as antithrombotic agents or tumour growth inhibitors. A critical event in the progression of tumours is the formation of new blood vessels. The aim of this work was to test two tomato cystine-knot miniproteins for their effects on endothelial cell proliferation and angiogenesis in vitro. EXPERIMENTAL APPROACH: Two tomato cystine-knot miniproteins (TCMPs) were expressed and purified either as recombinant or as native proteins from tomato fruits. The Matrigel assay was used to investigate the effects of TCMPs on in vitro angiogenesis. Viability and proliferation of endothelial cells were tested. Extracellular signal-regulated kinase (ERK)1/2 phosphorylation was assayed in either HUVEC or A431 epidermal growth factor receptor (EGFR)-overexpressing cells treated with TCMPs. EGFR phosphorylation was tested in A431 cells. KEY RESULTS: Both recombinant and native TCMPs inhibited in vitro angiogenesis of HUVEC cells at concentrations of 15-100 nM. The anti-angiogenic effect of TCMPs was associated with the inhibition of ERK phosphorylation. The two miniproteins did not alter the viability and proliferation of the endothelial cells. CONCLUSIONS AND IMPLICATIONS: The anti-angiogenetic properties of TCMPs are of potential pharmacological interest because they are common and natural components of the human diet, they possess low toxicity, they are active at submicromolar concentrations, they share a common molecular structure that can be used as a molecular platform for the design of molecules with enhanced biological activity.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Miniproteínas Nodales de Cistina/farmacología , Células Endoteliales/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Solanum lycopersicum/química , Inhibidores de la Angiogénesis/química , Línea Celular , Ensayos de Migración Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Miniproteínas Nodales de Cistina/química , Receptores ErbB/análisis , Frutas , Humanos , Proteína Quinasa 1 Activada por Mitógenos/análisis , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacos
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