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1.
Neurol Sci ; 44(12): 4233-4245, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37542547

RESUMEN

OBJECTIVE: The scope of this paper is to review the subtypes of transient ischemic attack (TIA) and minor stroke (mS) in which a surgical treatment is needed, discussing the importance and the timing of a multidisciplinary approach, in order to achieve an optimized management and prevent major strokes or other critical complications. MATERIALS AND METHODS: The keywords "transient ischemic attack," "minor stroke," "surgical treatment," "vascular surgery," "heart surgery," "neurosurgery," and "multidisciplinary" were searched using MEDLINE, EMBASE, and Scopus. Relevant search results were discussed by the authors for references inclusion. RESULTS: Notwithstanding that best medical therapy is usually the first choice for the most part of cases, there are specific but recurrent etiologies that must be properly recognized because of a potential surgical approach, even in urgency. In fact, symptomatic carotid stenosis, or particular cases of hemodynamic cerebrovascular events, should be promptly referred to vascular surgeon, since increasing evidences highlighted a benefit from an early artery revascularization. In addition, beyond arrhythmic causes, cardioembolic events due to bacterial endocarditis and atrial myxoma should be quickly diagnosed, possibly in emergency department, because they are a presumptive urgency for heart surgery. In addition to the above-mentioned conditions, in patients suffering from vertebrobasilar TIA or mS, clinicians should keep in mind the Bow Hunter disease, because surgical artery decompression can represent the only suitable treatment in selected cases. CONCLUSIONS: TIA and mS require a multidisciplinary in order to discuss therapeutic options, comparing risks and benefits and determining the best timing for an optimized management.


Asunto(s)
Estenosis Carotídea , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Cirujanos , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/terapia , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/diagnóstico , Estenosis Carotídea/complicaciones , Prevención Secundaria , Factores de Riesgo
2.
Phys Rev Lett ; 127(13): 131802, 2021 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-34623867

RESUMEN

Searches for the lepton number violating K^{+}→π^{-}µ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}µ^{-}e^{+} and π^{0}→µ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}µ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}µ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→µ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

4.
Eur Rev Med Pharmacol Sci ; 22(12): 3873-3887, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29949163

RESUMEN

OBJECTIVE: We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations causing it. MATERIALS AND METHODS: We searched PubMed with a larger emphasis on the physiology, genetics and current management of AIS. RESULTS: AIS is an X-linked recessive Disorder of Sex Development (DSD). It is caused by mutations of the Androgen Receptor, and their large amount and heterogeneity (missense and nonsense mutations, splicing variants, deletions, and insertions) are responsible for the wide spectrum of possible phenotypes of patients, divided into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory investigations have laid the foundation for a diagnostic hypothesis, it is important to identify the actual karyotype of the individual and search for the mutation in the Androgen Receptor to diagnose with certainty the syndrome. Alternatively, in the absence of such evidence, the diagnosis should more properly be an AIS-like condition, which we describe as well in our report. CONCLUSIONS: The management of this DSD is based on pharmacotherapies, surgery and psychological support: all of them must be directed to facilitate the patient's life, considering his/her sexual identity.


Asunto(s)
Síndrome de Resistencia Androgénica/genética , Mutación , Receptores Androgénicos/genética , Síndrome de Resistencia Androgénica/diagnóstico , Síndrome de Resistencia Androgénica/terapia , Humanos , Masculino
5.
Biosens Bioelectron ; 93: 315-321, 2017 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-27567262

RESUMEN

Lab-on-Chip are miniaturized systems able to perform biomolecular analysis in shorter time and with lower reagent consumption than a standard laboratory. Their miniaturization interferes with the multiple functions that the biochemical procedures require. In order to address this issue, our paper presents, for the first time, the integration on a single glass substrate of different thin film technologies in order to develop a multifunctional platform suitable for on-chip thermal treatments and on-chip detection of biomolecules. The proposed System on-Glass hosts thin metal films acting as heating sources; hydrogenated amorphous silicon diodes acting both as temperature sensors to monitor the temperature distribution and photosensors for the on-chip detection and a ground plane ensuring that the heater operation does not affect the photodiode currents. The sequence of the technological steps, the deposition temperatures of the thin films and the parameters of the photolithographic processes have been optimized in order to overcome all the issues of the technological integration. The device has been designed, fabricated and tested for the implementation of DNA amplification through the Polymerase Chain Reaction (PCR) with thermal cycling among three different temperatures on a single site. The glass has been connected to an electronic system that drives the heaters and controls the temperature and light sensors. It has been optically and thermally coupled with another glass hosting a microfluidic network made in polydimethylsiloxane that includes thermally actuated microvalves and a PCR process chamber. The successful DNA amplification has been verified off-chip by using a standard fluorometer.


Asunto(s)
Técnicas Biosensibles , ADN/aislamiento & purificación , Dispositivos Laboratorio en un Chip , ADN/química , Dimetilpolisiloxanos/química , Vidrio/química , Reacción en Cadena de la Polimerasa , Silicio/química
6.
Nanoscale ; 8(39): 17304-17313, 2016 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-27714135

RESUMEN

Recent progress in nanotechnology and its application to biomedical settings have generated great advantages in dealing with early cancer diagnosis. The identification of the specific properties of cancer cells, such as the expression of particular plasma membrane molecular receptors, has become crucial in revealing the presence and in assessing the stage of development of the disease. Here we report a single cell screening approach based on Surface Enhanced Raman Scattering (SERS) microimaging. We fabricated a SERS-labelled nanovector based on the biofunctionalization of gold nanoparticles with folic acid. After treating the cells with the nanovector, we were able to distinguish three different cell populations from different cell lines (cancer HeLa and PC-3, and normal HaCaT lines), suitably chosen for their different expressions of folate binding proteins. The nanovector, indeed, binds much more efficiently on cancer cell lines than on normal ones, resulting in a higher SERS signal measured on cancer cells. These results pave the way for applications in single cell diagnostics and, potentially, in theranostics.


Asunto(s)
Ácido Fólico/química , Nanopartículas del Metal , Análisis de la Célula Individual , Espectrometría Raman , Línea Celular , Oro , Humanos , Propiedades de Superficie
7.
Acta Diabetol ; 51(4): 587-93, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24509841

RESUMEN

The aim of this study was to investigate the severity of coronary artery disease (CAD) and the plaque composition in neuropathic type 2 diabetic subjects with and without Charcot neuroarthropathy (CN) undergoing multidetector computed tomography coronary angiography (MDCT-CA). The study was a single-center, observational, with unmatched case-control design. We selected 17 CN patients and 18 patients with diabetic neuropathy (DN) without CN. In all the patients, multidetector computed tomography was performed to assess the coronary artery calcium score (CACS) and degree of coronary artery stenosis. Patients were classified as positive in the presence of significant CAD if there was at least one stenosis >50 % on MDCT-CA. The invasive coronary angiography was performed in case of significant stenosis detected with MDCT-CA, both as reference to standard and eventually as treatment. Groups were matched for age, sex, and traditional CAD risk factors. As compared to DN individuals, CN exhibited higher rates of significant coronary stenoses (p = 0.027; OR 7.7 [1.3-43.5]). However, no significant differences were observed in the CACS, which reflects plaque burden, in the two groups (p = 0.759). No significant differences were observed comparing CACS distribution in all subjects for stenosis higher/equal or lower than 50 % (p = 0.320). Finally, no significant differences were observed comparing CACS distribution in CN and DN subjects for coronary stenoses higher/equal or lower than 50 %. Our results suggest that CN patients have a higher prevalence of severe coronary plaques compared to DN patients. Nevertheless, coronary plaques in CN patients did not exhibit an increased degree of calcification.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Neuropatías Diabéticas/complicaciones , Enfermedades del Pie/complicaciones , Anciano , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/etiología , Neuropatías Diabéticas/diagnóstico por imagen , Neuropatías Diabéticas/patología , Femenino , Enfermedades del Pie/diagnóstico por imagen , Enfermedades del Pie/patología , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica , Pronóstico
8.
Acta Otorhinolaryngol Ital ; 34(6): 434-8, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25762837

RESUMEN

We present a new surgical technique for the treatment of snoring and mild obstructive sleep apnoea syndrome. This is a modification of anterior palatoplasty, and its main features are the use of self-locking (barbed) threads and the possibility of stabilise the palatal suture by fixing it to anatomical bone and fibrous structures. The technique is described in detail and some preliminary results are presented.


Asunto(s)
Paladar Blando/cirugía , Faringe/cirugía , Apnea Obstructiva del Sueño/cirugía , Ronquido/cirugía , Adulto , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
9.
Acta Otorhinolaryngol Ital ; 33(4): 261-6, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24043914

RESUMEN

The aim of this study was to analyze and report sites and patterns of obstruction observed during sleep endoscopy in a large group of patients and suggest consequent therapeutic prescriptions. 614 consecutive patients who approached the Centre for Diagnosis and Treatment of Respiratory Sleep Disorders underwent sleep endoscopy. We used propofol to induce sleep, monitoring the value of bispectral index to evaluate the depth of sedation. For each patient, we recorded obstruction sites,obstruction patterns and the effects of the mandibular pull-up manoeuvre on both obstruction and snoring. We ascertained that, in almost all patients, the noise of snoring was generated at the oropharyngeal level. The obstruction at the oropharyngeal level, either in isolation or in combination with other structures, is far more common. The mandibular pull-up manoeuvre was effective in reducing or resolving the obstruction in a large number of patients, even though their AHI values were high. For those patients having an AHI over 15, we point out the various therapeutic indications gained from the sleep endoscopy examinations. Drug-induced (propofol) sleep endoscopy can be considered be a safe procedure, easily practicable, valid and reliable; we therefore consider it a fundamental clinical investigation that can be essential when choosing treatment.


Asunto(s)
Endoscopía , Apnea Obstructiva del Sueño/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Mandíbula , Persona de Mediana Edad , Apnea Obstructiva del Sueño/etiología , Apnea Obstructiva del Sueño/terapia , Adulto Joven
10.
Mol Ecol ; 18(9): 1980-94, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19344353

RESUMEN

Previous studies on the common ragworm Hediste diversicolor (Polychaeta: Nereididae) revealed a marked genetic fragmentation across its distribution and the occurrence of sibling taxa in the Baltic Sea. These results suggested that the phylogeographic patterns of H. diversicolor could reflect interactions between cryptic differentiation and multiple colonization events. This study aims to describe the large-scale genetic structuring of H. diversicolor and to trace the phylogeographic origins of the genetic types described in the Baltic Sea. Samples of H. diversicolor (2 < n < 28) were collected at 16 locations across the NE Atlantic coasts of Europe and Morocco and in the Mediterranean, Black and Caspian Seas and sequenced at two mitochondrial gene fragments (COI and cytb, 345 and 290 bp, respectively). Bayesian analyses revealed deep phylogeographic splits yielding three main clades corresponding to populations (i) from the NE Atlantic coasts (from Germany to Morocco) and from part of the Western Mediterranean, (ii) from the Mediterranean Sea, and (iii) from the Black and Caspian Seas. These clades are further divided in well-supported subclades including populations from different regions of NE Atlantic and Mediterranean (i.e. Portugal/Morocco, Western Mediterranean, Adriatic Sea). The Baltic Sea comprises three sympatric lineages sharing a common evolutionary history with populations from NE Atlantic, Western Mediterranean and Black/Caspian Seas, respectively. Hence, the current patterns of genetic structuring of H. diversicolor appear as the result of allopatric isolation, multiple colonization events and possible adaptation to local environmental conditions.


Asunto(s)
Evolución Molecular , Genética de Población , Filogenia , Poliquetos/genética , Animales , Secuencia de Bases , Teorema de Bayes , ADN Mitocondrial/genética , Geografía , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN , Especificidad de la Especie
11.
Cephalalgia ; 29(4): 453-64, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19170692

RESUMEN

Fibromyalgia syndrome (FMS) is a chronic pain condition of unknown aetiology characterized by diffuse pain and tenderness at tender points. The aim of the study was to assess the prevalence and clinical features of FMS in the different forms of primary headaches, in a tertiary headache centre. Primary headache patients (n = 217) were selected and submitted to the Total Tenderness Score, anxiety and depression scales, Migraine Disability Assessment, allodynia questionnaire, Short Form 36 Health Survey and the Medical Outcomes Study-Sleep Scale. In patients with FMS, the Multidimensional Assessment of Fatigue, the Pain Visual Analog Scale, the Manual Tender Point Survey and the Fibromyalgia Impact Questionnaire were employed. FMS was present in 36.4% of patients and prevailed significantly in tension-type headache and in patients with higher headache frequency. Headache frequency, pericranial muscle tenderness, anxiety and sleep inadequacy were especially associated with FMS comorbidity. In the FMS patients, fatigue and pain at tender points were significantly correlated with headache frequency. FMS seems increasingly prevalent with increased headache frequency, for the facilitation of central sensitization phenomena favoured by anxiety and sleep disturbances.


Asunto(s)
Fibromialgia/epidemiología , Cefaleas Primarias/epidemiología , Adolescente , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Comorbilidad , Femenino , Fibromialgia/diagnóstico , Fibromialgia/tratamiento farmacológico , Cefaleas Primarias/diagnóstico , Cefaleas Primarias/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Síndrome , Triptaminas/uso terapéutico , Adulto Joven
12.
Acta Otorhinolaryngol Ital ; 28(1): 26-9, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18533552

RESUMEN

After evaluating approaches proposed, over the last few years, by several Authors, to make the procedure of adenoidectomy safer and more accurate, we have developed a new procedure based on the combined use of a rigid 70 degrees endoscope with a video attachment and a microdebrider, both introduced through the oral cavity. This procedure offers several advantages: an improved field of vision, continuous suction of blood, and extreme precision in removing the adenoid tissue. Compared with current practices which employ the adenotome or curette, it is possible with our approach to remove adenoid tissue in the most important centres: the choanal and tubaric regions. The validity and safety of this videoendoscopic adenoidectomy with microdebrider has been demonstrated in 201 patients.


Asunto(s)
Adenoidectomía/instrumentación , Adenoidectomía/métodos , Cirugía Asistida por Video , Adolescente , Adulto , Niño , Preescolar , Humanos
13.
Mol Ecol ; 16(24): 5168-82, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17986195

RESUMEN

In the past decades, anthropogenic disturbance has increased in marine costal habitats, leading to dramatic shifts in population size structure of various marine species. In the temperate region, the gorgonian coral (Corallium rubrum) is one of the major disturbed species, mostly owing to the exploitation of its red skeleton for jewellery purposes. Red coral is a gonocoric species inhabiting subtidal rocky habitats in the Mediterranean and neighbouring Atlantic coasts. In order to investigate the spatial genetic structuring of C. rubrum, five microsatellite markers and the ribosomal internal transcribed spacer 1 (ITS-1) sequences were analysed in 11 samples from the northwestern Mediterranean Sea. Phylogenetic reconstructions obtained from ITS-1 sequences analysis showed that samples from Minorca and Sardinia islands were the most divergent while the three samples from the Tuscan archipelago (Argentario, Giannutri and Elba) appeared genetically homogeneous. Both markers revealed a strong structuring over large spatial scales (though to a different extent) with no isolation by distance pattern. Microsatellite-based F(ST) estimates appeared much smaller than ITS-based estimates and not significantly correlated, likely due to microsatellite allele size homoplasy typical of these highly polymorphic loci. Our study shows that the absence of clear patterns of genetic structuring over large spatial scales together with strong genetic structuring should be interpreted with caution because such patterns may hide underlying small-scale genetic structuring. Our results further confirm that effective larval dispersal in red coral is highly restricted in the northwestern Mediterranean Sea, suggesting that an increase of anthropogenic disturbance could aggravate the disappearance of red coral, not only along the Mediterranean coasts but also, and with more intensity, in the main Mediterranean islands.


Asunto(s)
Antozoos/genética , Núcleo Celular/genética , Repeticiones de Microsatélite/genética , Alelos , Animales , Antozoos/clasificación , Secuencia de Bases , Análisis por Conglomerados , Mar Mediterráneo , Datos de Secuencia Molecular , Filogenia
14.
Urologia ; 74(3): 160-3, 2007.
Artículo en Italiano | MEDLINE | ID: mdl-21086395

RESUMEN

Prostatic endoscopic resection (TURP) is a reference method in the treatment of prostatic obstruction. In the past decades, the method used a monopolar resectoscope. In the last years, various technologies have been studied to improve the efficacy of endoscopic resection. As per our experience, we have thence ascertained the variations of the hematic crasis and of the mictional asset in TURP patients treated with bipolar knives. 20 patients underwent bipolar plasmakinetic resection of the prostate. Their age ranged between 58 yrs and 82 yrs (av.: 70.2 yrs), the adenoma volume, checked with TR ultrasound scanning, was between 33 and 44 cc (av.: 37.6), the Qmax was between 6.4 and 9.0 mL/min (av.: 7.42 mL/min). A 24Ch resectoscope and spinal anesthesia were used. Bleeding during resection was never relevant; therefore resection never had to be stopped. After about 36 hours from surgery, the patients' sanguification was checked again: a 6.53% reduction of the number of erythrocytes, compared to pre-surgery data, was observed, together with a 6.73% decrease of hemoglobin concentration, and a 6.3% decrease of hematocrit. Continuous irrigation was suspended during the first day, catheter was removed on the 48th hour in 15 cases, and on the 72nd in 5 cases: the patients were discharged on day 3 in 16 cases, and on day 4 in 4 cases. A flux evaluation was performed after 3 months, which showed a Qmax between 16.6 and 24 mL/min (av.: 19.11), with a significant increase in the maximum flow rate. The use of the new technologies in prostatic endoscopic resection has allowed us to improve the efficacy of such a method. Above all, the use of a bipolar electrosurgical knife enables us to associate a basal hemostasis with the resection of the prostatic tissue. Thus, the hematic loss is low, as we have been able to ascertain also in our own experience. This gave us the possibility to quickly stop continuous irrigation and to early remove the catheter. This way, hospitalization was sensibly reduced (av. 76.8 hours). The maximum flow rate, in the short term, has been good. We have been able, in our experience, to assess that this technology represents a useful guarantee to improve the results of prostatic endoscopic resection.

15.
Urologia ; 74(2): 95-8, 2007.
Artículo en Italiano | MEDLINE | ID: mdl-21086406

RESUMEN

Diabetes is an important risk factor in erectile dysfunction (ED), acting via several mechanisms. We assessed the efficacy of intracavernous injections (ICI) rehabilitation and oral systematic therapy in diabetic patients, as well as the response of controls to oral therapy 'on demand'. MATERIALS AND METHODS. Sixteen diabetic patients with ED were treated with vasoactive drugs orally when needed, without satisfactory erections. The patients underwent then ICI rehabilitation with PGE1 20 mcg twice weekly for 4 weeks, followed by the administration of oral drugs twice weekly for 4 weeks. Before and after rehabilitation, the patients completed a detailed anamnestic protocol to study their libido (always present); they answered questions Q3 and Q4 of the IIEF questionnaire. During ICI, a study with dynamic echocolordoppler (ECCD) was carried out. All patients had Type 2 diabetes: 10 were treated with oral antidiabetics, 4 were treated with insulin, and in the other 2 patients, treated with insulin, a sensitive neuropathy of the lower limbs was diagnosed. Fourteen patients were treated with antihypertensive drugs. RESULTS. Before rehabilitation, the mean responses to questions 3 and 4 of the IIEF (International Index of Erectile Function) questionnaire were 1.6 and 1.5 respectively; after rehabilitation, the mean responses were 2.68 and 2.5, respectively. The ECCD test showed an arterial component in 4 cases and a high end-diastolic velocity (EDV) in 14 cases. Four patients (25%), 2 of which had neuropathy, and 2 were in advanced age, did not respond to PGE1 or to oral therapy, 4 patients (25%) (2 treated with insulin and 2 by oral therapy) responded to ICI but not to oral therapy, while 8 patients (50%) showed a good response to both injectable and oral therapy, with good Q3 and Q4 scores. CONCLUSIONS. Good endothelial function appears to be essential for the maintenance of acceptable erectile function. Diabetes has a negative effect on this function, as does hypoxia and low perfusion. Based on the principle that a good erection improves endothelial function, we tried to determine if oral systematic and intracavernous rehabilitation would improve erectile function in diabetic patients. The results indicate that diabetes interferes with erectile function, compromising the effects of the vasoactive drugs. However, integrated systematic rehabilitation appears to allow a good erectile response to both intracavernous and oral therapy in a large number of cases. Therefore, we support this kind of rehabilitative protocol in the treatment of ED in diabetic patients.

16.
Heart ; 89(7): 773-9, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12807855

RESUMEN

OBJECTIVE: To investigate whether enhanced oxidant stress in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher concentration of non-high density lipoprotein (HDL) cholesterol at baseline, and whether this contributes to the inflammatory reaction and luminal renarrowing after PTCA. DESIGN: An ex vivo and in vitro study of 46 patients who underwent PTCA and who had repeat angiograms after six months. Blood samples were collected immediately before PTCA, and at 24 hours, 48 hours, and 15 days after. SETTING: Tertiary referral centre. SUBJECTS: 46 patients (30 male, 16 female; mean (SD) age, 62 (5) years) with stable or unstable angina who underwent elective PTCA. MAIN OUTCOME MEASURES: Continuous variable luminal loss as defined by change in minimum lumen diameter during follow up, normalised for vessel size; lag phase of low density lipoprotein to in vitro oxidation; plasma fluorescent products of lipid peroxidation (FPLP); plasma vitamin C and E; interleukin (IL) 1beta secretion from unstimulated monocytes; plasma C reactive protein (CRP). RESULTS: Restenosis occurred in 12 patients (26%). Oxidant stress after PTCA was greater (p < 0.0001 at 15 days) in the patients with restenosis and showed a significant correlation with the preprocedural concentration of non-HDL cholesterol (p < 0.001). Inflammatory reaction (as reflected by IL-1beta production and CRP) and late lumen loss were linearly correlated (p < 0.001) with lag phase and FPLP throughout the study, and inversely (p < 0.05) with vitamin C and E measured at two and 15 days after PTCA. CONCLUSIONS: This study provides evidence for the critical role of cholesterol dependent oxidant stress in the pathophysiology of restenosis after PTCA. The findings raise the possibility that drugs capable of modulating oxidant status might provide a novel form of adjuvant treatment in patients with hypercholesterolaemia undergoing PTCA.


Asunto(s)
Angioplastia Coronaria con Balón , LDL-Colesterol/sangre , Reestenosis Coronaria/etiología , Monocitos/fisiología , Estrés Oxidativo , Proteína C-Reactiva/análisis , Reestenosis Coronaria/sangre , Femenino , Humanos , Interleucina-1/análisis , Activación de Linfocitos , Masculino , Persona de Mediana Edad
17.
J Cell Biol ; 155(6): 1055-64, 2001 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-11739413

RESUMEN

Axin is a component of the canonical Wnt pathway that negatively regulates signal transduction by promoting degradation of beta-catenin. To study the role of Axin in development, we developed strains of transgenic mice in which its expression can be manipulated by the administration of doxycycline (Dox). Animals carrying both mouse mammary tumor virus (MMTV)-reverse tetracycline transactivator and tetracycline response element (TRE)2-Axin-green fluorescent protein (GFP) transgenes exhibited Dox-dependent Axin expression and, when induced from birth, displayed abnormalities in the development of mammary glands and lymphoid tissues, both sites in which the MMTV promoter is active. The transgenic mammary glands underwent normal ductal elongation and side branching during sexual maturation and early pregnancy, but failed to develop lobulo-alveoli, resulting in a defect in lactation. Axin attenuated the expression of cyclin D1, a Wnt target that promotes the growth and differentiation of mammary lobulo-alveoli. Increased apoptosis occurred in the mammary epithelia, consistent with the inhibition of a Wnt/cyclin D1 survival signal by Axin. High levels of programmed cell death also occurred in the thymus and spleen. Immature thymocytes underwent massive apoptosis, indicating that the overexpression of Axin blocks the normal development of T lymphocytes. Our data imply that the Axin tumor suppressor controls cell survival, growth, and differentiation through the regulation of an apoptotic signaling pathway.


Asunto(s)
Tejido Linfoide/crecimiento & desarrollo , Tejido Linfoide/fisiología , Glándulas Mamarias Animales/crecimiento & desarrollo , Glándulas Mamarias Animales/fisiología , Proteínas/genética , Proteínas Represoras , Animales , Antibacterianos/farmacología , Apoptosis/fisiología , Proteína Axina , Doxiciclina/farmacología , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/fisiología , Etiquetado Corte-Fin in Situ , Lactancia/fisiología , Ratones , Ratones Transgénicos , Embarazo , Transducción de Señal/fisiología , Timo/crecimiento & desarrollo , Timo/fisiología
18.
Genes Dev ; 15(18): 2433-44, 2001 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-11562352

RESUMEN

The RET receptor tyrosine kinase has a critical role in kidney organogenesis and the development of the enteric nervous system. Two major isoforms, RET9 and RET51, differ in the amino acid sequence of the C-terminal tail as a result of alternative splicing. To determine the roles of these isoforms in vivo, we used targeted mutagenesis to generate mice that express either RET9 or RET51. Monoisoformic RET9 mice, which lack RET51, are viable and appear normal. In contrast, monoisoformic RET51 animals, which lack RET9, have kidney hypodysplasia and lack enteric ganglia from the colon. To study the differential activities of the two RET isoforms further, we generated transgenic mice expressing ligand-dependent and constitutively active forms of RET9 or RET51 under the control of the Hoxb7 regulatory sequences. Such RET9 transgenes are capable of rescuing the kidney agenesis in RET-deficient mice or causing kidney hypodysplasia in wild-type animals. In contrast, similar RET51 transgenes fail to rescue the kidney agenesis or cause hypodysplasia. Our findings show that RET9 and RET51 have different signaling properties in vivo and define specific temporal and spatial requirements of c-Ret function during renal development and histogenesis of the enteric nervous system.


Asunto(s)
Proteínas de Drosophila , Desarrollo Embrionario y Fetal , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Empalme Alternativo , Animales , Genes Homeobox , Ratones , Ratones Transgénicos , Isoformas de Proteínas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret , Proteínas Tirosina Quinasas Receptoras/genética , Transgenes
19.
Blood ; 98(2): 475-7, 2001 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-11435319

RESUMEN

Erythropoietin and its receptor are required for definitive erythropoiesis and maturation of erythroid progenitor cells. Mice lacking the erythropoietin receptor exhibit severe anemia and die at about embryonic day 13.5. This phenotype can be rescued by the human erythropoietin receptor transgene. Animals expressing only the human erythropoietin receptor survived through adulthood with normal hematologic parameters and appeared to respond appropriately to induced anemic stress. In addition to restoration of erythropoiesis during development, the cardiac defect associated with embryos lacking the erythropoietin receptor was corrected and the increased apoptosis in fetal liver, heart, and brain in the erythropoietin receptor null phenotype was markedly reduced. These studies indicate that no species barrier exists between mouse and human erythropoietin receptor and that the human erythropoietin receptor transgene is able to provide specific expression in hematopoietic and other selected tissues to rescue erythropoiesis and other organ defects observed in the erythropoietin receptor null mouse.


Asunto(s)
Eritropoyesis/genética , Receptores de Eritropoyetina/deficiencia , Receptores de Eritropoyetina/genética , Anemia/inducido químicamente , Anemia/genética , Anemia/terapia , Animales , Apoptosis , Médula Ósea/metabolismo , Células de la Médula Ósea/citología , Ensayo de Unidades Formadoras de Colonias , Cruzamientos Genéticos , Eritropoyetina/fisiología , Femenino , Expresión Génica , Células Madre Hematopoyéticas/química , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , Etiquetado Corte-Fin in Situ , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , ARN Mensajero/análisis , Bazo/metabolismo
20.
J Am Geriatr Soc ; 49(5): 533-7, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11380744

RESUMEN

OBJECTIVES: To assess whether systemic oxidative stress can predict the risk of first myocardial infarction, ischemic stroke, and congestive heart failure. DESIGN: A longitudinal study started in 1992 and completed in 1997. SETTING: Community-based, outpatient. PARTICIPANTS: 102 apparently healthy, community-dwelling subjects age 80 and older from the Vibrata valley, Teramo, Italy. MEASUREMENTS: Plasma vitamin E, beta-carotene, vitamin C, fluorescent products of lipid peroxidation (FPLPs), and serum lipids were determined at enrollment. RESULTS: Thirty-two cardiovascular events were recorded in 47.4 months of follow-up. The subjects with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth those with vitamin E levels in the lowest quartile (relative risk (RR) = 0.16; 95% confidence interval (CI) = 0.04-0.55). The subjects with FPLPs in the highest quartile had a risk seven times greater than those with FPLPs in the lowest quartile (RR = 7.61; 95% CI = 2.23-25.96). No association was observed for vitamin C, beta-carotene, or total cholesterol. Multivariate adjustment for known risk factors did not significantly change the results. CONCLUSIONS: Our results suggest that in apparently healthy, community-dwelling very old subjects, base-line plasma concentration of vitamin E and FPLPs predicts the risk of future cardiovascular events. We confirm previous data showing that total cholesterol is not a predictor of cardiovascular disease in people age 80 and older.


Asunto(s)
Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Peróxidos Lipídicos/sangre , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Estrés Oxidativo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Vitamina E/sangre , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Ácido Ascórbico/sangre , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Incidencia , Italia/epidemiología , Estudios Longitudinales , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Factores de Riesgo , Triglicéridos/sangre
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