Crustal structure in the Campanian region (Southern Apennines, Italy) from potential field modelling.

We present a 3D model of the main crustal boundaries beneath the Campanian region and the onshore and offshore surrounding areas, based on high-resolution potential field data. Our main objective is the definition of the main structural interfaces in the whole Campanian region from gravity and magnetic data, thanks to their ability to define them on a regional and continuous way. The complex morphology of the Mesozoic carbonate platform, which is fundamental to constrain the top of geothermal reservoir, was reconstructed by inverting the vertical gradient of gravity. We assumed local information from seismic models and boreholes to improve the model. We modeled the deep crustal structures by spectral analysis of Bouguer gravity and magnetic data. The inferred depth estimates indicate a shallow crystalline basement below the Tyrrhenian crust and the Apulian foreland and a significant depression beneath the Bradanic foredeep. The map of the Moho boundary shows a NE-SE verging trough below the Southern Apennine chain and two pronounced uplifts beneath the foreland and the Tyrrhenian crust. We also estimated the depth to the magnetic bottom, showing a thick magnetic crust below the mountain chain and shallow depths where the crustal heat flow is high. The models were compared with seismic sections along selected profiles; a good agreement was observed, despite of some inherent lower resolution for the gravity modelling from spectral methods. The regional covering and the continuity of our estimated crustal interfaces make it a new and valid reference for further geological, geophysical and geothermal studies, especially in areas such as northern and eastern Campania, where there is an incomplete geophysical and geological information.

Late Toxicity and Long-Term Local Control in Patients With Ultra-Central Lung Tumours Treated by Intensity-Modulated Radiotherapy-Based Stereotactic Ablative Body Radiotherapy With Homogenous Dose Prescription.

AIMS: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes. RESULTS: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm3 and 57.4 (range 7.7-426.6) cm3, respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED3 for 4 cm3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively. CONCLUSION: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment.

Crustal structure of Sicily from modelling of gravity and magnetic anomalies.

We aim at modeling the main crustal and thermal interfaces of Sicily (Italy), a key area for understanding the geological complexity at the collisional boundary between the African and European plates. To this end, we analyze the gravity and magnetic fields, integrated with information from well logs, geology, heat flow, and seismic data. In order to make the most accurate description of the crustal structure of the area, we modeled with different methodologies the carbonate and crystalline top surfaces, as well as the Moho and the Curie isotherm surface. The reconstruction of the carbonate platform is achieved using a nonlinear 3D method constrained by the available seismic and borehole data. The crystalline top, the Curie, and the Moho are instead estimated by spectral analysis of both gravity and magnetic data. The results show a complex carbonate basement and a deep crystalline crust in central Sicily, with a prominent uplift beneath the Hyblean Plateau. Maps of the Moho and the Curie isotherm surface define a variable thermal and structural setting of Sicily, with very thin crust in the southern and eastern sectors, where high heat flow is found, and deep and cold crust below the Caltanissetta Basin.

Time-course of transcriptome response to respiratory syncytial virus infection in lung epithelium cells.

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection in infants. Winter outbreaks in Chile result in 5% of infected children hospitalized, with 0.01% mortality. Increased evidence indicates that viral and host factors modulate the severity of infection. Using DNA microarrays, we characterized the genome-wide transcriptional response of lung mucoepidermoid cells (NCI-H292) at 0, 24, 48, 72 and 96 hours post-infection (hpi) with a single dose of RSV/A. During the whole studied period, a bi-phasic gene expression profile was observed by a total of 330 differentially expressed genes. About 60% of them were up-regulated between 24-72 hpi and then turned-off at 96 hpi. This transient, early gene expression pattern was significantly enriched in biological processes like interferon signaling, antigen processing and presentation, double-stranded RNA binding and chemokine activity. We detected 27 common genes up-regulated between 24-72 hpi, from which IFIT1, IFI44, MX1, CXCL11 and OAS1 had the highest expression. The second pattern comprised over 120 genes, which remained silenced until 72 hpi, but were steeply up-regulated by 96 hpi. Biological processes of this late-response profile included cell cycle division and microtubule cytoskeleton organization. Conversely, the genes belonging to virus response pathway showed a decreased expression at 96 hpi. We conclude that RSV induces an early innate immune activation profile response until 72 hpi. Thereafter, the viral response is inhibited, leading to host cell recovery. The presented cellular model allows to study the specific pathways involved in elimination of infection at prolonged time intervals and their subsequent analysis in severe RSV disease of infants and/or older adults.

Particulate matter phagocytosis induces tissue factor in differentiating macrophages.

Airborne exposure to particulate matter with diameter < 10 mcM (PM10) has been linked to an increased risk of thromboembolic events, but the mechanisms are not completely understood. The aim of this study was to evaluate the effect of PM10 phagocytosis on the release of procoagulant molecules in human differentiating macrophages, and that of PM10 inhalation in an experimental model in rats. Human monocytes were separated from the peripheral blood by the lymphoprep method, differentiated in vitro and treated with standard PM10 or vehicle. Sprague-Dawley rats were instilled intratracheally with PM10 or vehicle alone. The outcome was expression of proinflammatory genes and of tissue factor (TF). In human differentiating macrophages, PM10 exposure upregulated inflammatory genes, but most consistently induced TF mRNA and protein levels, but not TF protein inhibitor, resulting in increased TF membrane expression and a procoagulant phenotype. Differentiation towards the anti-inflammatory M2 phenotype inhibited PM10 -mediated TF expression. TF induction required phagocytosis of PM10 , whereas phagocytosis of inert particles was less effective. PM10 phagocytosis was associated with a gene expression profile consistent with intracellular retention of iron, inducing oxidative stress. Both PM10 and iron activated the stress kinases ERK1/2 pathway, involved in the induction of TF expression. In rats, alveolar exposure to PM10 was associated with pulmonary recruitment of inflammatory cells and resulted in local, but not systemic, induction of TF expression, which was sufficient to increase circulating TF levels. In conclusion, TF induction by differentiating lung macrophages, activated following phagocytosis, contributes to the increased risk of thromboembolic complications associated with PM10 exposure.

Long-term survival among Hodgkin's lymphoma patients with gastrointestinal cancer: a population-based study.

BACKGROUND: The increased risk of gastrointestinal (GI) cancers after Hodgkin's lymphoma (HL) is well established. However, no large population-based study has described the actuarial survival after subsequent GI cancers in HL survivors (HL-GI). PATIENTS AND METHODS: For 209 patients with HL-GI cancers (105 colon, 35 stomach, 30 pancreas, 21 rectum, and 18 esophagus) and 484 165 patients with first primary GI cancers (GI-1), actuarial survival was compared, accounting for age, gender, race, GI cancer stage, radiation for HL, and other variables. RESULTS: Though survival of HL patients who developed localized stage colon cancer was similar to that of the GI-1 group, overall survival (OS) of HL patients with regional or distant stage colon cancer was reduced [hazard ratio, (HR)=1.46, P=0.01]. The HL survivors with regional or distant stage colon cancer in the transverse segment had an especially high risk of mortality (HR: 2.7, P=0.001 for OS). For localized stomach cancer, OS was inferior among HL survivors (HR=3.46, P=0.006). CONCLUSIONS: The HL patients who develop GI cancer experience significantly reduced survival compared with patients with a first primary GI cancer. Further research is needed to explain the inferior survival of HL patients and to define selection criteria for cancer screening in HL survivors.

Increased insulin receptor substrate 2 expression is associated with steatohepatitis and altered lipid metabolism in obese subjects.

OBJECTIVE: The aim of this study was to evaluate whether dysregulation of molecules involved in FOXO1-dependent insulin signaling in the liver is associated with de novo lipogenesis (DNL) and altered lipid metabolism in severely obese subjects. DESIGN: Observational retrospective study. SUBJECTS: We considered 71 obese subjects (age 20-68 years; body mass index (BMI)>40 kg m(-2) or BMI>35 kg m(-2) in the presence of metabolic complications) classified into three groups according to liver histology: normal liver (n=12), simple steatosis (n=27) and nonalcoholic steatohepatitis (NASH; n=32). Key nodes in insulin signaling and gene expression of molecules implicated in insulin-dependent glucoregulatory pathway and DNL were evaluated by quantitative real-time PCR and western blotting. RESULTS: Patients with steatosis had decreased phosphorylation of the insulin kinase AKT1, mediating insulin receptor signaling, and the transcription factor FOXO1, which was therefore more active mediating insulin resistance at transcriptional level. Despite no changes in insulin receptor substrate (IRS)1 mRNA levels, the mRNA and protein levels of the FOXO1 target IRS2 increased progressively with the severity of steatosis from normal liver to NASH. IRS2 expression was correlated with the severity of steatosis, dyslipidemia and liver damage. In patients with NASH, upregulation of IRS2 was associated with preserved activation of AKT2, mediating the stimulating effect of insulin on DNL, and overexpression of its target sterol regulatory element-binding protein 1c (SREBP1c), inducing DNL at transcriptional level. Both FOXO1 and SREBP1c overexpression converged on upregulation of glucokinase, providing substrates for DNL, in NASH patients. CONCLUSION: Differential regulation of IRS1 and IRS2 and of their downstream effectors AKT1 and AKT2 is consistent with upregulation of FOXO1 and may justify the paradoxical state of insulin resistance relative to the glucoregulatory pathway and augmented insulin sensitivity of the liporegulatory pathway typical of steatosis and the metabolic syndrome in obese patients.

Un nuevo caso familiar del síndromede Jackson-Sertoli. Revisión de los aspectos clínicos y genéticos / A new familial case of Jackson-Sertoli syndrome. A review of the clinical

La paquioniquia congénita es una alteración infrecuente de la queratina, cuyo principal signo clínico es la onicodistrofia. Puede ser clasificada en dos principales subtipos clínicos: paquioniquia congénita tipo 1 y 2. La tipo 2 esta asociada con la mutación en los genes de queratina: K6b y K17.El esteatocistoma múltiple es una alteración infrecuente de la queratina de la unión pilosebásea caracterizado por el desarrollo de múltiples quistes dérmicos que contienen sebo. La mutación en K17 también se ha demostrado en pacientes con esta entidad. Reportamos una familia con variable y oligosintomática forma de paquioniquia congénita y esteatocistoma múltiple. La asociación de ambas entidades de acuerdo a la clasificación de Schonfeld corresponde un nuevo caso familiar del síndrome de Jackson-Sertoli (AU)

Pachyonychia congenita (PC) is a rare keratin disorder which the main clinical sign is onychodystrophy. PC can be classified into two main clinical subtypes: pachyonychia congenita type 1 and 2. The type 2 is associated with mutations in keratin gene: K6b y K17. Steatocystoma multiplex is an uncommon keratin disorder of the pilosebaceous unit characterized by the development of numerous sebum-containing dermal cysts. Mutationsin K17 have been too demonstrated in patients with this entity. We report a family with variable and oligosymptomatic form of pachyonychia congenita and steatocystoma multiplex. The association of both entities according to the Schonfeld classification correspond a new familial case of Jackson-Sertoli syndrome (AU)

Inhibition of hepatitis B virus and human immunodeficiency virus (HIV-1) replication by Warscewiczia coccinea (Vahl) Kl. (Rubiaceae) ethanol extract.

The primary objective of this study was to search for natural products capable of inhibiting hepatitis B virus (HBV) replication. The research design, methods and procedures included testing hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest on the cell line HepG2 2.2.15, which constitutively produces HBV. The main outcomes and results were as follows: the species Euterpe precatoria, Jacaranda copaia, Jacaranda obtusifolia, Senna silvestris, Warscewiczia coccinea and Vochysia glaberrima exerted some degree of inhibition on HBV replication. The leaves of W. coccinea showed a significant antiviral activity: 80% inhibition with 100 µg mL⁻¹ of extract. This extract also exerted inhibition on covalently closed circular deoxyribonucleic acid (cccDNA) production and on HIV-1 replication in MT4 cells (more than 90% inhibition with 50 µg mL⁻¹ of extract). Initial fractionation using organic solvents of increasing polarity and water showed that the ethanol fraction was responsible for most of the antiviral inhibitory activities of both the viruses. It was concluded that Warscewiczia coccinea extract showed inhibition of HBV and HIV-1 replication. Bioassay-guided purification of this fraction may allow the isolation of an antiviral compound with inhibitory activity against both viruses.

Prevención de adherencias peritoneales postoperatorias mediante uso de antagonista de receptores de neurokinina tipo 1 / Peritoneal adhesions prevention: neurokinin-1 receptor antagonist

Background: The fibrinolytic activity plays an important role in Peritoneal Adhesions (PA) develop-ment. It's well known that de substance P decreased the fibrinolysis by binding the neurokinin-1 receptor, improving the PA formation. Objectives: To evaluate the effectiveness of intraperitoneal treatment with a Neurokinin-1 receptor antagonist (NK-R1A) in peritoneal adhesión prevention in animal model. Materials and Methods: In 40 male wistar rats, PA were induced, and then randomly assigned to 2 groups: A group treated with Aprepitant (NK-Rl A), and a control group. The animals were killed at 7 or 14 postoperative day, and the number, severity and histopathology of PA were evaluated. Results: NK-Rl A decreased the number (40 percent less) and severity (p = 0.001) of PA when compare to control group. The NK-Rl A group had less PA in manipulated and no manipulated organs during surgery. Besides presented less fibrosis (p = 0.001), less inflamation (p = 0.005) and less vascular proliferation (p = 0.047) than control group. Conclusions: The NK-Rl A is effective as in PA prevention.

Introducción: La actividad fibrinolítica juega un papel fundamental en el desarrollo de las adherencias peritoneales (AP), y se conoce que la Sustancia P al actuar sobre receptores de neurokinina tipo 1 a nivel peritoneal, disminuye la fibrinólisis, favoreciendo la formación de las mismas. Objetivos: Evaluar la efectividad del tratamiento intraperitoneal con antagonista de receptores 1 de neurokinina (NK-R1A) en la prevención de AP en modelo animal. Materiales y Métodos: A 40 ratas wistar se les practicó cirugía formadora de AP y fueron distribuidas de forma aleatoria en 2 grupos, un grupo que recibió Aprepitant (NK-R1A), y el otro como grupo control. Los animales fueron sacrificados a los 7 ó 14 días, y se evaluó el número, severidad e histopatología de las AP. Resultados: El NK-Rl A disminuyó el número (40 por ciento menos) y severidad de las AP (p = 0,001) en relación al grupo control y presentó menos AP en órganos manipulados y no manipulados durante la cirugía. Ademßs presentó menor grado de fibrosis (p = 0,001), menor inflamación (p = 0,005) y menor proliferación vascular (p = 0,047) que el grupo control. Conclusión: El tratamiento peritoneal con NK-R1A es eficaz en la prevención de la formación de AP.

Adenocarcinoma primario de pulmón metastásico a schwannoma: un caso de metástasis de tumor a tumor / Tumor-to-tumor metastasis: pulmonary adenocarcinoma metastatic to Schwannoma

The coexistence of multiple primary malignant tumors in the same host is not unusual; however, tumor-to-tumor metastasis is rare. According to previous publications, the most common recipient tumor is renal cell carcinoma, and lung carcinoma is the most frequent donor site. According our bibliographic search we are presenting the first published case of primary pulmonary moderately differentiated adenocarcinoma metastatic to a schwannoma, demonstrated with Thyroid Transcription Factor 1 (TTF-1); immunostaining has become an important tool for guiding diagnosis of adenocarcinoma.

La coexistencia de múltiples tumores malignos primarios en un huésped no es un evento infrecuente. Sin embargo, la presencia de una neoplasia con metástasis en otra neoplasia (metástasis de tumor a tumor) es una entidad inusual, según lo publicado en la literatura el tumor receptor más frecuente es el carcinoma de células renales y el donante el carcinoma de pulmón. En el siguiente reporte se presenta un caso de adenocarcinoma moderadamente diferenciado metastásico a schwannoma, donde por inmunomarcaje con el Factor 1 de Transcripción Tiroidea (TTF-1) se demostró el origen pulmonar de la lesión, este correspondería al primer caso según nuestra revisión bibliográfica.

Recent advances in targeted therapies for colorectal cancer.

BACKGROUND: Recent advances in the molecular biology and genetics of colorectal cancer have led to the identification of potential therapeutic targets such as epidermal growth factor receptor, vascular endothelial growth factor and endothelial receptors. OBJECTIVE: This review will examine the major therapeutic advances along with the preclinical basis justifying their combination with conventional therapeutic tools. This review will also critically consider current possibilities offered to identify responding patients. DATA SOURCES: Preclinical and primary clinical trial results published in peer-review journals. The authors examined the relevance and subsequent inclusion of the data. CONCLUSIONS: Cetuximab and bevacizumab provide new benefits in terms of the response rate and survival. There remain, however, important questions concerning, for instance, optimal combinations between conventional cytotoxic agents and targeted therapies and also between targeted drugs themselves. These new targeted treatments are costly and in this context the question of the identification of the right drug for the right patient is particularly relevant. Adequate tools in predicting the efficacy of targeted treatments are still needed.

gamma-H2AX as a therapeutic target for improving the efficacy of radiation therapy.

Exposure to ionizing radiation (IR) results in the formation of DNA double strand breaks, resulting in the activation of phosphatidylinositol 3'-kinase-like kinases ATM, ATR and DNK-PKcs. A physiologically important downstream target is the minor histone H2A variant, H2AX, which is rapidly phosphorylated on Ser 139 of the carboxyl tail after IR. Recent work suggests that phosphorylated H2AX (gamma-H2AX) plays an important role in the recruitment and/or retention of DNA repair and checkpoint proteins such as BRCA1, MRE11/RAD50/NBS1 complex, MDC1 and 53BP1. H2AX-/- mouse embryonic fibroblasts are radiation sensitive and demonstrate deficits in repairing DNA damage compared to their wildtype counterparts. Cells treated with peptide inhibitors of gamma-H2AX demonstrate increased radiosensitivity following radiation compared with untreated irradiated cells. Analysis of the kinetics of gamma-H2AX clearance after IR or other DNA damaging agents reveals a correlation between increased gamma-H2AX persistence and unrepaired DNA damage and cell death. These data highlight the potential of post-translational modifications of chromatin as a therapeutic target for enhancing the efficacy of radiotherapy. Therapies that either block gamma-H2AX foci formation by inhibiting upstream kinase activity or that directly inhibit H2AX function may interfere with DNA damage repair processes and warrant further investigation as potential radiosensitizing agents. Agents that increase persistence of gamma-H2AX after IR are likely to increase unrepaired DNA damage.

Intensity-modulated radiation therapy in the treatment of gastric cancer: early clinical outcome and dosimetric comparison with conventional techniques.

The purpose of this study was to assess the efficacy and toxicity of intensity-modulated radiation therapy (IMRT) in the treatment of gastric cancer. Seven patients with gastric cancer were treated with IMRT. Six patients (all Stage III) received post-operative chemoradiotherapy with concurrent 5-fluorouracil and leucovorin. One received planned pre-operative radiation, though did not proceed to surgery. All patients were planned to receive 50.4 Gy in 1.8 Gy fractions. IMRT planning was compared with opposed anterior-posterior: posterior-anterior (AP/PA) and 3-field conventional three-dimensional plans. When compared with either AP/PA or 3-field plans, IMRT significantly reduced the volume exceeding the threshold dose of the liver and at least one kidney. Target coverage with IMRT was excellent, with 98+/-1% of the target receiving >or=100% of the dose. Compared with AP/PA and 3-field plans, IMRT plans had a greater percentage of target receiving the prescribed dose, but also a greater volume receiving >110% of the dose. IMRT was well tolerated; no patients developed acute gastrointestinal toxicity greater than grade 2. All seven experienced grade 2 nausea, three had grade 2 diarrhoea and two had grade 2 oesophagitis. Weight loss ranged from 0-12% (mean 6.1% and median 5.8%). IMRT in the treatment of gastric malignancies reduces the mean and above threshold doses to critical normal tissues. In an initial cohort of seven patients, 50.4 Gy delivered by IMRT is well tolerated and safe.

Glucagonoma una evalución estadística de 136 casos reportados en la literatura: informe de un caso / Glucagonoma a statistical evaluation of 136 reported cases of the literature: case presentation

Conocer las principales características clínico-patológicas del glucagonoma, mediante la realización de un estudio descriptivo. Se revisaron artículos publicados en la literatura internacional referente a la patología, que abarcaron un período de 25 años (1979 – 2004), de los cuales se seleccionaron 135 casos, a estos se les sumó un caso examinado por el grupo de investigadores. La edad promedio del estudio general fue de 53.08 años; donde 58.82 por ciento de los pacientes eran hombres y 41.18 por ciento mujeres. El grupo etario predominante fue el de 50 a 59 años que representó 29.41 por ciento de la población total en estudio. Entre las principales características clínicas tenemos que 64.71 por ciento de los pacientes presentaron eritema migratorio necrolítico, 48.53 por ciento pérdida de peso y 43.38 por ciento diabetes mellitus, 6.62 por ciento de los casos fue asintomático. La ubicación más frecuente fue a nivel de la cola del páncreas con 41.91 por ciento. El 9.56 por ciento se encontró asociado a neoplasia endocrina múltiple tipo I (MEN – I). El Glucagonoma es una entidad clínico-patológica inusual, asociada a tumor de las células alfa 2 de los islotes pancreático que secreta excesiva cantidad de glucagón. Está caracterizado por: eritema migratorio necrolítico, diabetes mellitus, pérdida de peso, anemia normocítica y normocrómica, hipoaminoacidemia, trombosis venosa, entre otros. Localizado más frecuentemente en la cola del páncreas. Se presenta típicamente en la quinta década de vida; aunque estudios previos reportaron ser más frecuente en el sexo femenino, en nuestro estudio no se observó esta tendencia

[EGF receptor in head and neck cancer]. / Le récepteur à l'EGF et les cancers des voies aérodigestives supérieures.

EGFR is overexpressed and is associated with a poor prognosis in head and neck cancer. Among the biological and cellular effects resulting from EGFR targeting in head and neck cancer there is the capacity to restore apoptotic capacities. Other experimental results put into evidence that DNA-repair activity was reduced by the application of EGFR targeting agents. This context was in favor of a research oriented towards combination between anti-EGFR drugs and cytotoxic agents, particularly irradiation. Supra-additive cytotoxic effects have been observed at the experimental level when combining anti-EGFR drugs with irradiation in head and neck cancer. These experimental data were recently confirmed at the clinical level in locally advanced head and neck cancer.

Erythropoietin and neuroprotection: a therapeutic perspective.

Recombinant erythropoietin (EPO) is used to correct for anaemia caused by chronic renal failure or cancer therapy. Improvement of the quality of life of anaemic patients treated with EPO was recently demonstrated and preliminary clinical results suggest an improvement of cognitive functions in patients receiving EPO. High expression of EPO and its receptor in the brain during embryonic development has led to the investigation of not only the neurotrophic role of EPO but also its neuroprotective properties. The neuroprotective effects of EPO have various complementary actions including antagonism of the effects of glutamate, increased expression of antioxidant enzymes, changes in production of neurotransmitters and induction of neuroglobin. Convincing experimental results suggest a blood-brain transport of EPO whereas clinical pharmacokinetic data do not as yet support this. The neuroprotective effects of EPO and its therapeutic promise need to be underlined.

Glucagonoma: Caso clínico

Objetivos. A propósito de un caso de glucagonoma, describir las principales características clínico-patológicas. Métodos. Se resume la historia clínica de una paciente a quien se le diagnóstico por inmunohistoquímica glucagonoma. Se revisa la literatura. Resultados. Paciente femenina de 54 años de edad, quien consulta por presentar dolor abdominal de moderada intensidad, mal definido, localizado a nivel de epigástrico con irradiación a mesogastrio; concomitantemente presenta pérdida de peso, poliuria, nicturia, estreñimiento severo y cifras de glucemias elevadas. Antecedentes de colecistectomía por litiasis biliar hace 3 años. En el examen físico refirió dolor a la palpación profunda a nivel de epigastrio y mesogastrio, resto del examen físico dentro de la normalidad. El estudio de laboratorio reveló una glucemia en ayunas de 325 mg/dL y postprandial de 531 mg/dL. Se inició tratamiento con insulina sin mejoría del control metabólico, por lo cual se aumento la dosis de insulina asociándola con un sensibilizador de la misma. Se realizó tomografía axial computarizada del abdomen observándose una tumoración ecomixta, bien delimitada, de 55.3 x 54.8 x 51.7 mm, localizada en el abdomen posterior, sin compromiso de la cabeza del páncreas. Debido al mal control metabólico y ante la sospecha de tumor funcionante del páncreas, se planteó la utilización de análogos de somatostatina, sin que pudiera ser utilizado por el costo del medicamento. La paciente fue llevada a quirófano realizándose recesión total de la tumoración. El control metabólico mejoró posterior a la cirugía. Los hallazgos histológicos fueron compatibles con células insulares pancreáticas con inmunohistoquímica positiva para glucagon. Conclusiones. El Glucagonoma es una entidad clínico-patológica poco frecuente pudiéndose presentar como una diabetes. La dificultad para un buen control metabólico de la diabetes y la pérdida incontrolada de peso pueden ser la clave para el diagnóstico.

Objectives. Based on a patient with a glucagonome, the clinical and histopathological characteristics of this tumor are described. Methods. A brief clinical history of a patient who was diagnosed to have a glucagonome, based on immunohistochemical analyses, is presented. Medical literature is reviewed about this entity. Results. A 54 years-old female patient, was admitted because of moderate, abdominal poorly localized pain, at the epigastric level, and referred to the mesogastric area. Concomitantly body-weight loss, polyuria, severe constipation, and hyperglycemia, were present. Cholecistectomy was performed because of cholelithiasis three years prior to admission. On physical examination, she presented pain with deep palpatory maneuvers at the epigastric and mesogastric areas. Without other particular findings. She presented fasting-blood glucose of 325 mg/dL, and 531 mg/dL in postprandial conditions. Insulin treatment was started, without improvement of the metabolic alteration. Consequently, insulin was administered associated with a sensitized, improving the glycemic control. An abdominal TAC was performed, revealing a mixed tumor, located in the posterior abdomen, well delimited, and measuring 55.3 x 54.8 x 51.7 mm. The head of the pancreas was not compromised. Due to difficulties in the control of the metabolic alterations, and under the suspicion of a pancreas functional tumor, it was considered the use of a somatostin analogous, which was never applied because of its high cost. Laparotomy was performed, and a total tumor resection was accomplished. The metabolic conditions improved after surgery. The histopathological findings were compatible with pancreatic insular cells, and immunohistochemically positive for glucagon. Conclusions. The glucagonome is rare clinical and pathological entity. It could be expressed as a diabetes. The difficulties to achieve a good metabolic control of the diabetes, and the continued weight loss, could be the clue for the diagnosis.