The application of three-dimensional printing in the management of a difficult airway due to Treacher Collins syndrome.

We describe the use of three-dimensional printing to create precise airway models for a patient with Treacher Collins syndrome who presented for bimaxillary temporomandibular joint prostheses, and for whom airway management was predicted to be difficult. The model was based on pre-operative cone beam computed tomography images and printed in the 3D Lab of Hospital Universitario La Paz. Transparent models allowed clear visualisation for simulation and iterative refinement of airway management techniques and aided in risk assessment and instrument sizing. This case report emphasises the utility of this approach in complex airway scenarios.

The role of brain oscillations in feature integration.

Our sensory system is able to build a unified perception of the world, which although rich, is limited and inaccurate. Sometimes, features from different objects are erroneously combined. At the neural level, the role of the parietal cortex in feature integration is well-known. However, the brain dynamics underlying correct and incorrect feature integration are less clear. To explore the temporal dynamics of feature integration, we studied the modulation of different frequency bands in trials in which feature integration was correct or incorrect. Participants responded to the color of a shape target, surrounded by distractors. A calibration procedure ensured that accuracy was around 70% in each participant. To explore the role of expectancy in feature integration, we introduced an unexpected feature to the target in the last blocks of trials. Results demonstrated the contribution of several frequency bands to feature integration. Alpha and beta power was reduced for hits compared to illusions. Moreover, gamma power was overall larger during the experiment for participants who were aware of the unexpected target presented during the last blocks of trials (as compared to unaware participants). These results demonstrate that feature integration is a complex process that can go wrong at different stages of information processing and is influenced by top-down expectancies.

Papel de la radioterapia en el manejo de las metástasis vertebrales: últimas novedades / Role of radiotherapy in the management of spine metastases

Las metástasis vertebrales son una causa común de dolor en el paciente oncológico, lo cual puede generar limitación funcional, además de complicaciones derivadas de una posible compresión medular, radicular y fracturas. Se requiere de un abordaje complejo de estas metástasis por el riesgo de secuelas permanentes. Con el aumento de las supervivencia gracias a los nuevos tratamientos emergentes, las posibilidades de presentar metástasis vertebrales son cada vez mayores, por ende, el manejo de estas lesiones debe ir encaminado al alivio del dolor y el mantenimiento de la deambulación. La radioterapia juega un papel fundamental en el manejo de estas lesiones, y disponemos de avances tecnológicos en los últimos años que han permitido mejorar la calidad e intencionalidad de los tratamientos, pasando de ser meramente paliativos a proponer tratamientos que mejoren el control local. En este articulo hacemos una descripción de como la técnica de SBRT (stereotactic body radiotherapy), en pacientes seleccionados puede mejorar el control local de forma más duradera, y el valor que tiene en paciente oligometastásico y tras cirugía.(AU)

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.(AU)

[Translated article] Role of radiotherapy in the management of spine metastases / Papel de la radioterapia en el manejo de las metástasis vertebrales: últimas novedades

Las metástasis vertebrales son una causa común de dolor en el paciente oncológico, lo cual puede generar limitación funcional, además de complicaciones derivadas de una posible compresión medular, radicular y fracturas. Se requiere de un abordaje complejo de estas metástasis por el riesgo de secuelas permanentes. Con el aumento de las supervivencia gracias a los nuevos tratamientos emergentes, las posibilidades de presentar metástasis vertebrales son cada vez mayores, por ende, el manejo de estas lesiones debe ir encaminado al alivio del dolor y el mantenimiento de la deambulación. La radioterapia juega un papel fundamental en el manejo de estas lesiones, y disponemos de avances tecnológicos en los últimos años que han permitido mejorar la calidad e intencionalidad de los tratamientos, pasando de ser meramente paliativos a proponer tratamientos que mejoren el control local. En este articulo hacemos una descripción de como la técnica de SBRT (stereotactic body radiotherapy), en pacientes seleccionados puede mejorar el control local de forma más duradera, y el valor que tiene en paciente oligometastásico y tras cirugía.(AU)

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.(AU)

[Translated article] Role of radiotherapy in the management of spine metastases.

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article, we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.

Role of radiotherapy in the management of spine metastases. / Papel de la radioterapia en el manejo de las metástasis vertebrales: últimas novedades.

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.

Relevance of subclinical right ventricular dysfunction measured by feature-tracking cardiac magnetic resonance in non-ischemic dilated cardiomyopathy.

BACKGROUND: Right ventricular (RV) dysfunction in patients with non-ischemic dilated cardiomyopathy (NICM) is associated with cardiovascular events. To analyze the feasibility of assessing RV myocardial deformation by feature tracking (FT)-cardiac magnetic resonance (CMR), and its usefulness as a prognostic marker. METHODS: Retrospective study of NICM patients undergoing CMR. Longitudinal FT-RV free wall (LFT-RVFW) and fractional area change (FAC) were obtained. Correlation with standard RV parameters was studied. An association with combined event (heart failure (HF), ICD implantation or cardiovascular death) was assessed using a logistic regression model. RESULTS: 98 patients (64 ± 13 years) were included. Left ventricular (LV) systolic function (LVEF 29.5 ± 9.6%, 47% with LVEF ≥ 30%) and RV (RVEF 52.2 ± 14.6%, 72% with RVEF ≥ 45%). Follow-up of 38 ± 17 months, 26.5% presented at least one admission for HF. An excellent correlation of LFT-RVFW (r = 0.82) and FAC (r = 0.83) with RVEF was evident. No association of RV-FT parameters with prognosis entire study population was found. However, in patients with LVEF ≥ 30%, admissions for HF were associated with lower LFT-RVFW (-21.6 ± 6.6% vs -31.3 ± 10%; p = 0.006) and FAC (36.6 ± 9.6% vs 50.5 ± 13.4%; p < 0.001) values. Similar differences were observed when only patients with RVEF ≥ 45% were considered. An LFT-RVFW cut-off point of -19.5% and FAC of 36.5% showed good prognostic performance. Decreased LFT-RVFW or FAC represented an independent predictor of combined event in patients with LVEF ≥ 30%. CONCLUSIONS: In NICM patients without severe LV dysfunction, decreased values of LFT-RVFW and/or FAC were associated with HF admissions, independently of RVEF.

Simultaneous determination of 210Pb and 90Sr and 210Po isolation in sludge samples using a plastic scintillation resin.

This study describes a new and fast method for separating 210Po from 210Pb and 90Sr, before simultaneously measuring the individual activities of the latter two radionuclides using a plastic scintillation resin (PSresin) in sludge samples taken from a drinking water treatment plant. This method speeds up the analysis process significantly by simultaneously measuring 210Pb and 90Sr in a single step. The method is reproducible and has a relative standard deviation of less than 25% for 210Pb, 210Po and 90Sr. The method was satisfactorily validated with an intercomparison sample and applied to sludge samples from a drinking water treatment plant. The minimum detectable activities for 0.9 g of sludge are 5.5 Bq/kg and 8 Bq/kg for 210Pb and 90Sr respectively when measured for 180 min, and 0.5 Bq/kg for 210Po when measured for 5000 min.

Removal of 17α-ethynylestradiol and ß-estradiol using bench-scale constructed wetlands.

Aquatic ecosystems have been devastated by the continued persistence of the synthetic estrogen compounds ß-estradiol and 17α-ethynylestradiol. Common wastewater treatment methods do not reduce these compounds in effluent below problematic concentrations. An emerging cost-effective solution to this problem is the use of constructed wetlands to remove these estrogen compounds. This study analyzed the ability of duckweed (Lemna minor), water hyacinth (Eichhornia crassipes), and water cabbage (Pistia stratiotes) to remove ß-estradiol and 17α-ethynylestradiol through the use of bench-scale constructed wetlands over a 15-week period. Estrogen concentration in water was collected over time along with plant nutrient content, contaminant extractions, and media extractions. Results indicated that estrogen concentration was reduced by the plants and soil media. Duckweed was the most effective at 96% removal, followed by water hyacinth at 72% removal, then water cabbage at 35% removal, and lastly sediment media at 9% removal. This study provides evidence for the ability of constructed wetlands to be used as a means to remove estrogen compounds from wastewater and demonstrates differences in plants removal efficiencies, with duckweed being the most effective of the selected plants.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus from different population groups in Argentina.

OBJECTIVES: In Latin America, methicillin-resistantStaphylococcus aureus (MRSA) is a leading cause of nosocomial infections. Limited studies have addressed the molecular epidemiology of MRSA clones in Argentina, characterised by continuous human migratory movements. The aim of this study was to describe the MRSA epidemiology, including distinct patient populations from different regions of the country. METHODS: MRSA strains were collected in epidemiological studies conducted from 2009 to 2015 in three cities (Formosa, Córdoba and Tucumán) and involving four population groups: community adult patients; hospitalised adults; hospitalised children; and healthy children (nasal colonisation). Antimicrobial susceptibility testing, SCCmec and Panton-Valentine leukocidin (PVL) typing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed. RESULTS: A total of 120 MRSA isolates were recovered with an important population diversity in the groups studied; in community adult patients, MRSA isolates corresponded to ST5, ST267 and ST1619; from hospitalised adults they were ST97, ST5, ST72, ST125, ST200, ST647, ST747, ST935 and ST2941; from hospitalised children they were ST5, ST30, ST34, ST1163 and ST1619; and from colonised children they were ST5, ST125, ST34, ST100, ST1619, ST207 and ST1163. Results of SCCmec typing showed SCCmec I, SCCmec IIIA, SCCmec IV and SCCmec ND associated or not with PVL genes. CONCLUSIONS: MRSA genetic lineages have differing distribution in the three regions. The most prevalent was ST5 in colonisation, community and invasive settings. Here we describe ST34-SCCmec IV clone for the first time in the hospitalised paediatric population. These findings contribute to the understanding of epidemiological changes in recent years.

Relationship Between Body Mass and Forewing Length in Neotropical Ichneumonidae (Insecta: Hymenoptera).

Biomass is an important indicator of various ecological factors in insect populations and communities. Although the utility of this variable is proven, it is usually dismissed in ecological studies, generally, because of the difficulty of measuring it. Considering that insect biomass is apparently declining worldwide, here, we aimed to test the accuracy of forewing length as an estimator of body mass in Neotropical Ichneumonidae to help in monitoring insect biomass. Forewing length and dry body mass were measured in 728 individuals from distinct localities in Venezuela and Ecuador. A clear log-linear relationship existed between the two variables, and a log-linear regression had significant and strong predictive power of mass based on wing length. To derive the final values of mass from predictions made using our equation, we used an exponential transformation. We present an R function for predicting mass from wing length. We consider our findings applicable to many Neotropical species of Ichneumonidae, and helpful especially when specimens are measured in dry collections.

Potential Spatial Distribution of the Newly Introduced Long-horned Tick, Haemaphysalis longicornis in North America.

The North American distributional potential of the recently invaded tick, Haemaphysalis longicornis, was estimated using occurrence data from its geographic range in other parts of the world and relevant climatic data sets. Several hundred candidate models were built using a correlative maximum entropy approach, and best-fitting models were selected based on statistical significance, predictive ability, and complexity. The median of the best-fitting models indicates a broad potential distribution for this species, but restricted to three sectors-the southeastern United States, the Pacific Northwest, and central and southern Mexico.

Hipertensión arterial e insuficiencia renal crónica: repercusiones estomatológicas, una revisión / Hypertension and chronic renal failure: stomatologic Impact, a review

Tanto la enfermedad cardiovascular como la enfermedad renal constituyen dos realidades fisiopatológicas de reconocimientos mortales crecientes en el ámbito mundial y de prioridades en materia de salud integral. En efecto, mientras que la Hipertensión Arterial (HTA) y la aterosclerosis son causas, cada vez más frecuentes de nefropatía, este deterioro crónico de la función renal genera un estado vasculopático que facilita el desarrollo de lesiones del sistema cardiovascular considerándose, así como enfermedades que van de la mano. Estos signos, no van aislados, a su vez se comportan como factores desencadenantes de afecciones bucodentales, como xerostomía, agrandamiento gingival, edema gingival, enfermedad periodontal, hemorragias petequiales, entre otras lesiones estomatológicas que empeoran el pronóstico de la enfermedad sistémica, afectando la calidad de vida del paciente y en diversas ocasiones dichas condiciones orales, según la gravedad, se comportan como factores etiológicos de enfermedad sistémica. Estas manifestaciones patológicas normalmente son vistas como de baja importancia por parte de los pacientes, debido a que sus prioridades, corresponden a atender su situación sistémica. El propósito de esta revisión narrativa es describir las principales repercusiones bucales de cardiopatías y nefropatías, aportándole a la comunidad científica, académica y médico-odontológica, conceptos actuales y elementales en la relación directa que poseen estas dos entidades sistémicas con la cavidad bucal

Both cardiovascular disease and kidney disease are two pathophysiological deadly realities of growing worldwide recognition and priorities for overall health. Indeed, while high blood pressure (hypertension) and atherosclerosis are becoming more common causes of kidney disease, this chronic deterioration of kidney function generates a vasculopatic state that facilitates the development of lesions of the cardiovascular system as well as diseases that are considered to the hand. These systemic conditions, they will not isolated, in turn behave as triggers of oral conditions, such as dry mouth, gingival enlargement, gingival edema, periodontal disease, petechial hemorrhages, including oral manifestations that worsen the prognosis of systemic disease, affecting quality of life of patients and on several occasions oral conditions such as gravity, act as etiological factors of systemic disease. These effects are usually cause for impairment by patients, because their priorities are to address systemic situation and is not cause for concern. The purpose of this narrative review is to describe the main impact of oral disease and kidney disease, bringing the basic direct relationship in the scientific, academic, medical and dental, current concepts and possess both systemic institutions with the oral cavity

Sterility and Safety Validation for Transport Packaging of Organs and Tissues.

The bags used in the transport of organs and tissues must be sterile, nontoxic, pyrogen free, and must serve as a barrier throughout their useful life. The goal of this study was to show the sterility, safety, and functionality of the bags subjected to irradiation, through validated procedures and techniques. The selected sterilization method was the use of gamma radiation. The sterilization dose was determined based on validated standards for the sterilization of medical products, ISO 11137-2: 2013 and ISO/TS 13004: 2013, using the Verification Dose Maximum method on samples belonging to 3 manufacturing lots. The ISO 10993-5: 2009 standard was used in the cytotoxicity tests, by means of extracts test and quantitative technique of MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The tests to determine the expiration date of the kit were performed by ASTM F1980, accelerated aging, and ASTM D3078 to evaluate hermeticity. The irradiation dose validated to reach the required sterility safety level was 22.5 kGy. The constituent materials and the sterilization method do not generated cellular toxicity, and the product was not modified during the simulated time of 5 years. Sterilization by irradiation is a method that leaves no residue, does not harm the properties of the material because it is conducted in cold, and as the sterilizing agent, the energy absorbed by the product is highly penetrating and can be treated in its final packaging, with no risk of postcontamination. It is for this reason that it is prioritized over other methods of sterilization.

Epidemiologic Study and Genotyping of BK Virus in Renal Transplant Recipients.

BK virus (BKV) infection occurs during childhood and remains latent in the urinary tract. The virus is reactivated in immunosuppressed patients, particularly in those with cellular immunity deficiency, allowing its detection in urine and blood. Nephropathy caused by the virus in renal transplantation recipients may lead to graft failure. The purpose of this study is to know the prevalence of BKV variables in renal transplantation recipients and to evaluate their clinical evolution through molecular methods of "in house" development. Urine and peripheral blood samples from 66 renal transplantation recipients from the province of Buenos Aires, Argentina, were systematically analyzed every 3 months as well as when there was graft dysfunction. Renal biopsies, which were included in the BKV detection study, were performed on those patients with graft dysfunction. Genotyping of 24 BKVs was performed, and the following distribution was found: 21 (87.5%) belonged to subtype I, 3 (12.5%) to subtype II. BKV belonging to subtypes III or IV were not found. As regards subtype I subgroups, the following were identified: 1 (4.76%) from Ia, 10 (47.61%) from Ib1 and 10 (47.61%) from Ib2. Presence of subgroup Ic was not shown. Viremia presented in 33.33% of cases, whereas 75% corresponded to subgroup Ib 1. Genotype Ib1 is prevailing in Southeast Asia, while Ib2 is prominent in Europe. Although an important proportion of the inhabitants of the province of Buenos Aires are European descendants, the prevailing genotype is Ib1, the Asian type. Genotyping might be related to the evolution of the disease in the recipient.

A 63-Year-Old Man With Progressive Visual Symptoms.

A 63-year-old man presented with a 4-year history of insidious onset and gradual progression of visual symptoms including right homonymous hemianopsia, alexia, and simultanagnosia with preserved memory. Magnetic resonance imaging, perfusion single-photon emission computed tomography, and fluorodeoxyglucose positron emission tomographic scans revealed strikingly asymmetric left parieto-occipital abnormality. Neuropsychological testing was performed. The differential diagnosis, pathologic findings, genetic testing results, and diagnosis are discussed.

Rol del virus del papiloma humano en el desarrollo de carcinoma oral: Una revisión / Role of human papillomavirus in the development of oral carcinoma: A review

El carcinoma escamocelular (CEC) representa la entidad patológica maligna de mayor prevalencia en la cavidad bucal. Aunque múltiples estudios respaldan que la aparición de esta enfermedad es de carácter idiopático, factores de riesgo como el alcohol y la exposición al tabaco son elementos directamente desencadenantes de la aparición de esta entidad oncológica, sin dejar a un lado la predisposición a padecer cáncer oral (CO) por parte de la codificación genética entre otros aspectos hereditarios. En la actualidad, se ha evidenciado que la infección por virus del papiloma humano (VPH) y las lesiones que lo relacionan, están profundamente asociados como etiología potencial del CO y suelen tener relación con hábitos sexuales modificados. La profundización de conceptos, efectos y medios de diagnóstico eficaces para establecer relaciones existentes del VPH con el CO, biología del virus y comportamiento cancerígeno, fueron los objetivos de la presente publicación así mismo determinar factores de riesgo predisponentes a la malignización de las lesiones propias del VPH, su incidencia y prevalencia en la comunidad. La identificación clínica oportuna de las lesiones originadas por el VPH, permiten establecer de manera certera el comportamiento, evolución de la lesión y a su vez determinar la presencia de actividad displásica y/o anaplásica propiamente dicha. Cabe resaltar la importancia del empleo de exámenes auxiliares a la clínica, como lo es la citología exfoliativa, la biopsia, los análisis moleculares y genéticos, para establecer mancomunadamente y de manera certera el comportamiento, evolución y pronóstico de una afección por VPH (AU)

Introduction: Squamous cell carcinoma (SCC) represents the malignant disease entity most prevalent in the oral cavity. Although multiple studies support that the appearance of this disease is idiopathic nature, risk factors such as alcohol and exposure to snuff are directly triggers the onset of this cancer entity, leaving aside the predisposition to oral cancer (CO) by the hereditary genetic coding among other aspects. Today it has been demonstrated that infection with human papillomavirus (HPV) and related injuries that are deeply associated CO as a potential etiology and are usually related to changed sexual habits. Objectives: The deepening of concepts, effects and effective means of diagnosis to establish relationships with the CO HPV, the virus biology and carcinogenic behavior, were the objectives of this publication likewise determine predisposing risk factors for malignant lesions own HPV incidence and prevalence in the community. Methods: A search of scientific papers was conducted in Spanish and English in the last 15 years in the database PubMed to do relationship, oral cancer, HPV and SCC. Conclusions: Timely clinical lesions caused by HPV, accurate identification can be established from the behavior, evolution of the injury and in turn the presence of dysplastic activity and/or anaplastic itself. It should highlight the importance of using auxiliary to clinical examinations, such as the exfoliative cytology, biopsy, genetic and molecular analyzes to establish jointly and accurate way the behavior, evolution and prognosis of a condition HPV (AU)

First epidemiologic study in Argentina of the prevalence of BK viruria in kidney transplant patients.

BACKGROUND: The worldwide seroprevalence of human BK polyomavirus (BKV) in adults is 80%. About 10%-60% of renal transplant recipients experience BKV infection, nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation. METHODS: An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10(7) copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included. RESULTS: Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10(7) copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3-7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed. CONCLUSIONS: This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.

FAS system deregulation in T-cell lymphoblastic lymphoma.

The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding FAS mutations or FAS signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). The available data on acute lymphoblastic leukemia, of precursor origin as well, indicate a low frequency of FAS mutations but often report a serious reduction in FAS-mediated apoptosis as well as chemoresistance, thus suggesting the occurrence of mechanisms able to deregulate the FAS signaling pathway, different from FAS mutation. Our aim at this study was to determine whether FAS-mediated apoptotic signaling is compromised in human T-LBL samples and the mechanisms involved. This study on 26 T-LBL samples confirms that the FAS system is impaired to a wide extent in these tumors, with 57.7% of the cases presenting any alteration of the pathway. A variety of mechanisms seems to be involved in such alteration, in order of frequency the downregulation of FAS, the deregulation of other members of the pathway and the occurrence of mutations at FAS. Considering these results together, it seems plausible to think of a cumulative effect of several alterations in each T-LBL, which in turn may result in FAS/FASLG system deregulation. Since defective FAS signaling may render the T-LBL tumor cells resistant to apoptotic cell death, the correct prognosis, diagnosis and thus the success of anticancer therapy may require such an in-depth knowledge of the complete scenario of FAS-signaling alterations.

Ornithine phenylacetate targets alterations in the expression and activity of glutamine synthase and glutaminase to reduce ammonia levels in bile duct ligated rats.

BACKGROUND & AIMS: In liver failure, ammonia homeostasis is dependent upon the function of the ammonia metabolising enzymes, glutamine synthetase (GS) and glutaminase (GA) but data about their protein expression and activity are lacking. The aims of this study were to determine the protein expression and activity of GS and GA in individual organs in a rat model of chronic liver disease and to test whether the treatment with the ammonia-lowering agent ornithine phenylacetate (OP) modulates their activities. METHODS: 49 SD rats were studied 35 days after sham-operation or bile duct ligation (BDL). The BDL group received: L-ornithine (0.6 mg/kg/day), Phenylacetate (0.6 mg/kg/day), OP (0.6 mg/kg/day) or placebo (saline) for 5 days prior to sacrifice. Arterial ammonia, amino acids and liver biochemistry were measured. Expressions of GS and GA were determined by Western-blotting and activities by end-point methods in liver, muscle, gut, kidney, lung, and frontal cortex. RESULTS: In BDL rats, hepatic GS enzyme activity was reduced by more than 80% compared to sham rats. Further, in BDL rats GA activity was reduced in liver but increased in the gut, muscle and frontal cortex compared to sham rats. OP treatment resulted in a reduction in hyperammonemia in BDL rats, associated with increased GS activity in the muscle and reduced gut GA activity. CONCLUSIONS: In a rat model of chronic liver failure, hyperammonemia is associated with inadequate compensation by liver and muscle GS activity and increased gut GA activity. OP reduces plasma ammonia by increasing GS in the muscle and reducing GA activity in the gut providing additional insights into its mechanism of its action. GS and GA may serve as important future therapeutic targets for hyperammonemia in liver failure.