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We demonstrate the first simplified coherent receiver using a 120° hybrid on silicon-on-insulator (SOI) for high speed PON applications. This coherent receiver integrates an inverse taper edge coupler for the received signal, a vertical grating coupler for the local oscillator input, a polarization splitter and rotator (PSR), a 120° hybrid based on a 3×3 multimode interference (MMI) coupler, and three germanium photodetectors. We achieved 25 Gbit/s two-level pulse amplitude modulation (PAM-2) transmission over 30 km standard single mode fiber (SMF) in the C-band without any digital signal processing (DSP) (e.g., pre-emphasis, pulse shaping, equalization, nonlinearity compensation) and dispersion compensation (e.g., optical or digital) either at the transmitter or at the receiver. The requirements for frequency and phase locking of the local oscillator (LO) were avoided due to the use of intensity modulated signals. Receiver sensitivities of -23.70 dBm, -20.30 dBm, and -15.10 dBm are achieved at a bit error rate (BER) below the hard-decision forward error correction (HD-FEC) threshold (i.e., 3.8 × 10-3) in back-to-back (B2B), after 21 km and 30 km, respectively. We also demonstrate 25 Gbit/s PAM-4 transmission achieving receiver sensitivities of -15.30 dBm, -13.90 dBm, and -9.50 dBm below the HD-FEC threshold in B2B, after 10.5 km and 21 km, respectively.
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Sub-Nyquist time frequency packing technique was demonstrated for the first time in a super-channel field trial transmission over long-haul distances. The technique allows a limited spectral occupancy even with low order modulation formats. The transmission was successfully performed on a deployed Australian link between Sydney and Melbourne which included 995 km of uncompensated SMF with coexistent traffic. 40 and 100 Gb/s co-propagating channels were transmitted together with the super-channel in a 50 GHz ITU-T grid without additional penalty. The super-channel consisted of eight sub-channels with low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness and reduced complexity with respect to higher order formats. At the receiver side, coherent detection was used together with iterative maximum-a-posteriori (MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully transmitted between Sydney and Melbourne within four 50GHz WSS channels (200 GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR = 15.8 dB, comparable to the OSNR of the installed 100 Gb/s channels. The system reliability was proven through long term measurements. In addition, by closing the link in a loop back configuration, a potential SEâd product of 9254 bit/s/Hz·km was achieved.
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PURPOSE: Existing ways of assessing CVID patients at risk of pulmonary infections are not universally accepted. The need to identify additional prognostic factors allowed us to evaluate the anti-polysaccharide IgA and IgM responses in 125 CVID patients immunized with the 23-valent pneumococcal polysaccharide (PS) vaccine (Pneumovax(®)). METHODS: We used a new anti-PS23 IgM and IgA ELISA assay, which evaluates a global response to all 23 polysaccharides contained in Pneumovax(®). RESULTS: Anti-PS23 IgM and/or IgA antibodies were detectable in a minority of CVID patients. Antibody responses were correlated to B cell subpopulations and serum immunoglobulin concentrations. The non responders had a higher incidence of pneumonia and bronchiectasis and responders had the lowest incidence of respiratory complications. CONCLUSIONS: This new ELISA assay allows for studying vaccine response in patients on Ig replacement therapy. This test also is an additional method of evaluation of specific antibody responses representing a valuable contribution to identify prognostic marker in CVID patients.
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Cápsulas Bacterianas/inmunología , Inmunodeficiencia Variable Común/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina A/inmunología , Inmunoglobulina M/inmunología , Infecciones Neumocócicas/diagnóstico , Vacunas Neumococicas/inmunología , Polisacáridos Bacterianos/inmunología , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Biomarcadores Farmacológicos/metabolismo , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/inmunología , Inmunodeficiencia Variable Común/terapia , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/efectos adversos , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/complicaciones , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/terapia , Vacunas Neumococicas/administración & dosificación , Pronóstico , Adulto JovenRESUMEN
We report the observation of non-metallic electrical conduction, resistive switching, and a negative temperature coefficient of resistance in nanostructured gold films above the electrical percolation and in strong-coupling regime, from room down to cryogenic temperatures (24 K). Nanostructured continuous gold films are assembled by supersonic cluster beam deposition of Au aggregates formed in the gas phase. The structure of the cluster-assembled films is characterized by an extremely high density of randomly oriented crystalline nanodomains, separated by grain boundaries and with a large number of lattice defects. Our data indicates that space charge limited conduction and Coulomb blockade are at the origin of the anomalous electrical behavior. The high density of extended defects and grain boundaries causes the localization of conduction electrons over the entire investigated temperature range.
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BACKGROUND: Tumor necrosis factor-alpha (TNFalpha)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFalpha dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFalpha. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFalpha dose and doxorubicin (Dx). PATIENTS AND METHODS: HILP with TNFalpha (at a dosage of either
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Doxorrubicina/administración & dosificación , Hipertermia Inducida , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia del Cáncer por Perfusión Regional/métodos , Supervivencia sin Enfermedad , Extremidades/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perfusión , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNFalpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNFalpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable dose (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFalpha was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNFalpha-based ILP and identify prognostic factors for response, locoregional control and survival. PATIENTS AND METHODS: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>or=10 nodules
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Melanoma/tratamiento farmacológico , Melanoma/patología , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Extremidades , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Melanoma/mortalidad , Melfalán/farmacología , Persona de Mediana Edad , Metástasis de la Neoplasia , Perfusión , Pronóstico , Resultado del TratamientoRESUMEN
Liver dysfunction is an important cause of morbidity and mortality after orthotopic liver transplantation (OLT). The Molecular Adsorbent Recirculating System (MARS) is an albumin-based dialysis system designed to enhance the excretory function of a failing liver. MARS has been successfully used in patients affected by advanced liver disease and presenting with severe cholestasis. The aim of this study was to evaluate the safety and clinical efficacy of MARS in patients with liver dysfunction after OLT. Seven patients (primary nonfunction, 2 patients; graft dysfunction, 5 patients) fulfilled the inclusion criteria of serum bilirubin level >15 mg/dL and least 1 of the following clinical signs: hepatic encephalopathy (HE) > or = grade II, hepatorenal syndrome (HRS), and intractable pruritus. Graft and patient survival rates at 6 months were 42.8% and 57.1%, respectively. All patients tolerated MARS treatment, with no adverse event. In all patients, a decrease in serum bilirubin (P < .05), bile acids (P < .05), serum creatinine, and ammonia levels was observed after treatment with MARS. A considerable improvement of HE, as well as renal and synthetic liver functions, was observed in 4 of 5 patients with graft dysfunction, but not among those with primary nonfunction. The patients with intractable pruritus showed significant improvement of this symptom after MARS therapy. Thus, MARS is a safe, therapeutic option for the treatment of liver dysfunction after OLT. Further studies are necessary to confirm whether this treatment is able to improve both graft and patient survival.
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Trasplante de Hígado/fisiología , Desintoxicación por Sorción/métodos , Adulto , Síndrome de Budd-Chiari/cirugía , Carcinoma Hepatocelular/cirugía , Hemocromatosis/cirugía , Humanos , Pruebas de Función Renal , Cirrosis Hepática Alcohólica/cirugía , Pruebas de Función Hepática , Neoplasias Hepáticas/cirugía , Persona de Mediana Edad , Selección de Paciente , Diálisis Renal , Reoperación/estadística & datos numéricos , Donantes de Tejidos , Insuficiencia del TratamientoRESUMEN
A Radio Frequency Quadrupole Cooler (RFQC) prototype was adapted for insertion into a high uniformity magnetic field, with Bz up to 0.2 T, to improve radial confinement. While the RFQC purpose is to reduce (by gas collisions) the energy spread and emittance of a beam of radioactive nuclei, to finely select ion mass in nuclear physics, the prototype is tested in a setup including a stable ion source, a pepper pot emittance meter, and two Faraday cups; this makes a precise characterization of the RFQC feasible. The ion extraction was studied in detail by simulations, both to match it to the emittance meter granularity and to verify the effect of the typical nonuniformity of the longitudinal electric field Ez inside the RFQC; an average motion description (including friction force from gas collisions) was used, introducing the ballistic and diffusive regimes. With a preliminary optimization of the electrode shape, buffer gas pressure pg, and radio frequency voltage, the ion beam can be extracted with a significant cooling margin.
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Loss of retinal ganglion cells occurs in a variety of pathological conditions, including central retinal artery occlusion, diabetes and glaucoma. Using an experimental model of retinal ischemia induced by transiently raise the intraocular pressure (IOP), In this study, we report the original observation that ischemic retinal ganglion cells death is associated with the transient deactivation of the pro-survival kinase Akt and activation of GSK-3beta followed, during reperfusion, by a longer lasting, PI3K-dependent, activation of Akt and phosphorylation of GSK-3beta. Under these experimental conditions, retinal ischemia induced the expression of Bad, a pro-apoptotic protein, member of the Bcl-2 family. The detrimental effects yielded by the ischemic stimulus were minimized by intravitreal administration of the NMDA receptor antagonist, MK801, that reduced the expression of Bad and significantly increased Akt phosphorylation. In conclusion, our present results contribute to unravel the mechanisms underlying retinal damage by high IOP-induced transient ischemia in rat. In addition, these data implicate the pro-survival PI3K/Akt pathway and the observed reduced expression of Bad in the neuroprotection afforded by MK801.
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Receptores de N-Metil-D-Aspartato/fisiología , Daño por Reperfusión/fisiopatología , Enfermedades de la Retina/fisiopatología , Transducción de Señal/fisiología , Análisis de Varianza , Androstadienos/farmacología , Animales , Muerte Celular/fisiología , Cromonas/farmacología , Maleato de Dizocilpina/farmacología , Inhibidores Enzimáticos/farmacología , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Presión Intraocular/fisiología , Isquemia/complicaciones , Isquemia/fisiopatología , Masculino , Morfolinas/farmacología , Proteína Oncogénica v-akt/metabolismo , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Daño por Reperfusión/etiología , Enfermedades de la Retina/complicaciones , Enfermedades de la Retina/patología , Serina/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Wortmanina , Proteína Letal Asociada a bcl/metabolismoRESUMEN
BACKGROUND: We measured noise intensity and perceived noisiness during continuous positive airway pressure (CPAP) performed with two interfaces (face-mask, helmet) and four delivery systems. METHODS: Eight healthy volunteers received CPAP in random order with: two systems provided with a flow generator using the Venturi effect and a mechanical expiratory valve (A: Venturi, Starmed; B: Whisperflow-2, Caradyne Ltd); one 'free-flow' system provided with high flow O(2) and air flowmeters, an inspiratory gas reservoir, and a water valve (C: CF800, Drägerwerk, AG); and a standard mechanical ventilator (Servoventilator 300, Siemens-Elema). Systems A, B, and C were tested with a face-mask and a helmet at a CPAP value of 10 cm H(2)O; the mechanical ventilator was only tested with the face mask. Noise intensity was measured with a sound-level meter. After each test, participants scored noisiness on a visual analog scale (VAS). RESULTS: The noise levels measured ranged from 57+/-11 dBA (mechanical ventilator plus mask) to 93+/-1 and 94+/-2 dBA (systems A and B plus helmet) and were significantly affected by CPAP systems (A and B noisier than C and D) and interfaces (helmet CPAP noisier than mask CPAP). Subjective evaluation showed that systems A and B plus helmet were perceived as noisier than system C plus mask or helmet. CONCLUSIONS: Maximum noise levels observed in this study may potentially cause patient discomfort. Less noisy CPAP systems (not using Venturi effect) and interfaces (facial mask better than helmet) should be preferred, particularly for long or nocturnal treatments.
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Presión de las Vías Aéreas Positiva Contínua/instrumentación , Ruido , Aceptación de la Atención de Salud/psicología , Adulto , Percepción Auditiva , Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Presión de las Vías Aéreas Positiva Contínua/métodos , Presión de las Vías Aéreas Positiva Contínua/psicología , Diseño de Equipo , Femenino , Humanos , Masculino , Máscaras , Persona de Mediana Edad , Ruido/efectos adversosRESUMEN
A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/terapia , Hipertermia Inducida , Neoplasias Peritoneales/terapia , Peritoneo/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Terapia Combinada , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Peritoneo/patología , Tasa de SupervivenciaRESUMEN
Colorectal tissue biopsies were obtained from 110 patients diagnosed with primary colorectal carcinoma (tumor and normal colonic mucosa samples), 20 patients diagnosed with benign colorectal disease, and 31 healthy donors. The level of expression of tumor-associated glycoprotein 72 (TAG-72) was quantitatively measured in each sample using a double-determinant RIA with monoclonal antibodies B72.3 and CC49 and detecting the sialyl-Tn epitope; this assay was termed CA 72-4. Statistical analysis revealed a significant (approximately 10-fold) increase of TAG-72 expression in the colon tumor biopsies when compared with the expression in normal colonic mucosa from the same patients. A regression analysis revealed a significant correlation (r = 0.459; P < 0.001) between TAG-72 levels measured in biopsies from the tumor lesions and those found in the corresponding normal colonic mucosa. Furthermore, regression analysis showed a significant positive correlation between TAG-72 levels in the tumors and sera of the same patients (r = 0.491; P < 0.001). TAG-72 levels in normal colonic mucosa from healthy donors and patients diagnosed with colorectal cancer were compared. TAG-72 expression was 5-fold higher in the normal mucosa from the colorectal carcinoma patients. No relationship between TAG-72 tumor tissue content and stage of disease was found. Moreover, the correlation between TAG-72 distribution and degree of tumor differentiation observed (P < 0.05) was not any more evident when mucinous carcinomas were excluded. Finally, the results provide further evidence that TAG-72 may be considered an important early marker for colorectal cancer and/or other dysplastic colonic diseases. The statistical correlation between TAG-72 levels in tumors and circulating TAG-72 indicates that patients with elevated levels of serum TAG-72, as measured by the CA 72-4 assay, would be most suited for diagnostic and/or therapeutic intervention with the anti-TAG-72 monoclonal antibodies B72.3 or CC49 or vaccine trials using the sialyl-Tn epitope.
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Antígenos de Neoplasias/análisis , Neoplasias Colorrectales/química , Glicoproteínas/análisis , Proteínas de Neoplasias/análisis , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/sangre , Neoplasias Colorrectales/sangre , Femenino , Glicoproteínas/sangre , Humanos , Mucosa Intestinal/química , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/sangreRESUMEN
Electromagnetic traps are a flexible and powerful method of controlling particle beams, possibly of exotic nuclei, with cooling (of energy spread and transverse oscillations) provided by collisions with light gases as in the Radio Frequency Quadrupole Cooler (RFQC). A RFQC prototype can be placed inside the existing Eltrap solenoid, capable of providing a magnetic flux density component B(z) up to 0.2 T, where z is the solenoid axis. Confinement in the transverse plane is provided both by B(z) and the rf voltage V(rf) (up to 1 kV at few MHz). Transport is provided by a static electric field E(z) (order of 100 V/m), while gas collisions (say He at 1 Pa, to be maintained by differential pumping) provide cooling or heating depending on V(rf). The beamline design and the major parameters V(rf), B(z) (which affect the beam transmission optimization) are here reported, with a brief description of the experimental setup.
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PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Carcinoma/secundario , Neoplasias Colorrectales/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Atención Perioperativa , Neoplasias Peritoneales/cirugía , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
In the present work, we used a unique cortical/striatal/subventricular zone organotypic model in order to analyze the role of resident microglia in oxygen/glucose deprivation and to check the presence and modulation of several P2 receptors in the cortex. Immunofluorescence with the microglial marker OX42 and pharmacological experiments with indomethacin indicate that activation and recruitment of microglia after the insult is linked to cellular loss, mainly in the cortex. The confocal analysis with OX42 shows that, among the P2 receptors tested, P2X4, and P2X7 are expressed on microglia, while P2X1 and P2Y(1-2-12), although present in the slices, did not co-localize, whereas P2X6 is not detected. The upregulation of P2X4 and P2X7 on microglia and the toxic effect that different P2 agonists exert on cortical slices during oxygen/glucose deprivation indicate that a purinergic mechanism is related to the microglia activity; the protective effect of the P2 antagonist TNP-ATP is also described. In order to better understand the relationship between P2 receptors and OGD-activated microglia, we induced oxygen/glucose deprivation in co-cultures of organotypic slices and N9 microglia cell line. The presence of the N9 (which expresses P2X4 and P2X7 protein) in the cultures increases the damage in the cortex by 40% and the use of P2 antagonist PPADS reduced the cell damage due to the N9 activation. Our results show that microglia recruitment after a metabolic impairment is associated with cellular loss and that P2X4 and P2X7, are involved in microglia activity. The neuroprotective action exerted by TNP-ATP and PPADS and the possible use of purinergic antagonist in the pharmacological treatment of oxygen/glucose deprivation is also addressed.
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Encefalopatías/etiología , Corteza Cerebral/patología , Glucosa/deficiencia , Hipoxia/complicaciones , Microglía/fisiología , Receptores Purinérgicos P2/fisiología , Adenosina Trifosfato/farmacología , Análisis de Varianza , Animales , Animales Recién Nacidos , Western Blotting/métodos , Encefalopatías/patología , Antígeno CD11b/metabolismo , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Células Cultivadas , Técnica del Anticuerpo Fluorescente/métodos , Microglía/efectos de los fármacos , Microscopía Confocal/métodos , Técnicas de Cultivo de Órganos/métodos , RatasRESUMEN
Squamous and adenosquamous cell carcinomas (ASC and SCC) are rare subtypes of gallbladder cancer, traditionally considered more aggressive and with a poorer prognosis than adenocarcinoma. We report about two patients affected by an advanced squamous cell carcinoma of the gallbladder. Both had a large tumour in the gallbladder fossa region with infiltration of the liver. Surgical resection was radical in one, but palliative in the other. pTNM was T3 N0 M0, G3, R0 in the former and T3 N0 M0, G2 R1 in the latter. Patients died for local recurrence after 12 and 5 months, respectively. Natural history, clinical findings, prognosis and outcome of this rare gallbladder tumour are discussed on the basis of a review of the English literature. In conclusion, an aggressive and radical surgical treatment of advanced squamous and adenosquamous cell gallbladder carcinomas seems to be indicated for their low proclivity to distant spreading.
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Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/patología , Neoplasias de la Vesícula Biliar/patología , Anciano , Carcinoma Adenoescamoso/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Humanos , Estadificación de Neoplasias , Radiografía , Tasa de Supervivencia , Tomógrafos Computarizados por Rayos XRESUMEN
The effects of a Wigner molecule on the current noise and conductance of a one-dimensional quantum dot with two electrons are investigated. Focusing on a lateral transport setup, the sequential regime is considered. Tunnelling rates through the dot are evaluated within an exact diagonalisation scheme. They strongly depend on electron interactions, showing a markedly different behaviour in the presence of a Wigner molecule with respect to the weak interactions case, and thus modify the transport and current noise and the dot. For weak interactions negative differential conductance and super-Poissonian noise are found. As interactions increase, a Wigner molecule develops: it suppresses the negative differential conductance and turns the shot noise to sub-Poissonian values. In particular, the noise is found to be a sensitive probe of the Wigner molecule.
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The pheochromocytoma PC12 cell line that develops neuronal characteristics of sympathetic cells after treatment with nerve growth factor (NGF) represents a well-established cellular model system for studying NGF signalling. Interesting information on the different mechanistic pathways of NGF can be obtained by adopting the pharmacological approach of inhibiting P2 receptors, expressed in naive PC12 cells and recognised as important biological mediators of neurotransmitters and growth factors. We show here that Basilen Blue, an antagonist of P2 receptor, reversibly prevents NGF-dependent neurite outgrowth with an IC(50) in the 5-10 microM range. Suramin, oxidised-ATP and diisothiocyanatostilbene-disulfonic acid, differently from other purinoceptor ligands, are also effective in this regard. NGF-dependent regeneration and stability of neurites, selected NGF-dependent extracellular and intracellular protein phosphorylations, binding of [(3)H] ATP to PC12 cell membranes are also modulated by Basilen Blue. On the contrary, cell adhesion, cellular duplication, 5'-nucleotidase activity, NGF-induced tyrosine autophosphorylation of TrkA receptors are not affected. NGF furthermore directly modulates the extracellular release of ATP and especially the levels of P2X(2) receptor protein in PC12 cells. In addition, extracellular ATP improves the neuritogenic effect of sub-optimal concentrations of NGF. Our study identifies P2 receptor ligands, particularly Basilen Blue, as useful tools to dissect different NGF-evoked functions, suggesting a mechanistic role for P2 receptors in the signalling pathways of NGF.
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Factor de Crecimiento Nervioso/fisiología , Neuritas/fisiología , Antagonistas del Receptor Purinérgico P2 , 5'-Nucleotidasa/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Autorradiografía , Western Blotting , Electroforesis en Gel de Poliacrilamida , Ligandos , Factor de Crecimiento Nervioso/farmacología , Neuritas/efectos de los fármacos , Células PC12 , Fosforilación , Pruebas de Precipitina , Unión Proteica , Ratas , Receptor trkA/metabolismoRESUMEN
In this study we investigate the presence, modulation and biological function of P2 receptors and extracellular ATP in cultured cerebellar granule neurons. As we demonstrate by RT-PCR and western blotting, both P2X and P2Y receptor subtypes are expressed and furthermore regulated as a function of neuronal maturation. In early primary cultures, mRNA for most of the P2 receptor subtypes, except P2X(6), are found, while in older cultures only P2X(3), P2Y(1) and P2Y(6) mRNA persist. In contrast, P2 receptor proteins are more prominent in mature neurons, with the exception of P2Y(1). We also report that extracellular ATP acts as a cell death mediator for fully differentiated and mature granule neurons, for dissociated striatal primary cells and hippocampal organotypic cultures, inducing both apoptotic and necrotic features of degeneration. ATP causes cell death with EC(50) in the 20-50 microM range within few minutes of exposure and with a time lapse of at most two hours. Additional agonists for P2 receptors induce toxic effects, whereas selected antagonists are protective. Cellular swelling, lactic dehydrogenase release and nuclei fragmentation are among the features of ATP-evoked cell death, which also include direct P2 receptor modulation. Comparably to P2 receptor antagonists previously shown preventing glutamate-toxicity, here we report that competitive and non-competitive NMDA receptor antagonists inhibit the detrimental consequences of extracellular ATP. Due to the massive extracellular release of purine nucleotides and nucleosides often occurring during a toxic insult, our data indicate that extracellular ATP can now be included among the potential causes of CNS neurodegenerative events.
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Adenosina Trifosfato/toxicidad , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Receptores Purinérgicos P2/fisiología , Adenosina Trifosfato/fisiología , Animales , Células Cultivadas , Sistema Nervioso Central/citología , Cerebelo/citología , Cerebelo/fisiología , Relación Dosis-Respuesta a Droga , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Líquido Intracelular/efectos de los fármacos , Líquido Intracelular/fisiología , Potenciales de la Membrana/efectos de los fármacos , Microelectrodos , Neuronas/clasificación , Neuronas/citología , Técnicas de Placa-Clamp , Agonistas del Receptor Purinérgico P2 , Ratas , Ratas WistarRESUMEN
ATP released in the extracellular space by neuronal injury can influence neighboring neurons via activation of purinergic receptors. In vitro data suggest the involvement of ATP and purinergic receptors as trophic agents in different biological events such as neuritogenesis and cell survival. Recently, in vivo studies have demonstrated modifications in the glial expression of ionotropic purinergic receptors after CNS lesions. In the present study, we investigated the effects of CNS lesion on the neuronal expression of P2X(1) and P2X(2) receptor subunits by immunohistochemistry and western blotting techniques. In the precerebellar structures of normal animals the expression of P2X(1) and P2X(2) was lower than previously reported. P2X(1) immunostaining was confined only to fibers, while P2X(2) immunostaining demonstrated a neuronal expression. After unilateral cerebellar lesion (hemicerebellectomy) axotomized precerebellar neurons underwent marked cell loss; however, some precerebellar neurons did not degenerate. Seven to 35 days after hemicerebellectomy, a transient, time-dependent, marked increase in the number of immunopositive P2X(1) and P2X(2) neurons was observed in the precerebellar nuclei of the experimental side. An even distribution of immunopositive neurons was present in almost all precerebellar nuclei examined, except for the inferior olive. In this latter structure, differences in the distribution of immunopositive neurons were evident among the subnuclei. Up-regulation of immunoreactivity over relatively long time periods, distribution selectivity and absence of degenerating morphological features in immunopositive neurons suggest that purinergic receptors may have a role in mediating the survival of neuronal responses to axotomy. The present findings are the first report in the CNS of P2X(1) and P2X(2) receptor subunit involvement in neuronal reaction to axotomy. They provide in vivo evidence of a correlation between purinergic receptor subunit up-regulation and survival of injured neurons.