Resultados quirúrgicos y oncológicos de pacientes operados por cáncer de recto con asistencia robótica / Surgical and oncological results of patients operated for rectal cancer with robotic assistance

Resumen Objetivo: Analizar los resultados quirúrgicos y oncológicos de pacientes con adenocarcinoma de recto (AR) operados con asistencia robótica. Materiales y Método: Cohorte prospectiva entre 2014-2019. Criterios de inclusión: pacientes con AR primario, sometidos a una resección de recto con asistencia robótica con intención curativa. Criterios de exclusión: histología no adenocarcinoma. Evaluación de datos clínico-quirúrgicos. Análisis estadístico descriptivo. Resultados: Se incluyeron 37 pacientes; 20 (54%) fueron hombres y la edad promedio fue 58,7 años. La distancia promedio desde el margen anal al borde distal del tumor fue 6,6 cm (i: 2-12 cm). La quimiorradioterapia (neoadyuvancia) se indicó en 26 pacientes. La cirugía más frecuente fue la resección anterior baja de recto y el tiempo operatorio promedio fue 266 min. Se realizaron dos conversiones a laparotomía. Una o más complicaciones se observaron en 17 (45,9%) pacientes, 9 de ellos fueron Clavien-Dindo III o IV y se reoperaron 5 pacientes (13%). No hubo transfusiones sanguíneas ni mortalidad posoperatoria. La estancia hospitalaria postoperatoria promedio fue 9,6 días (i: 3-34 d). El promedio de linfonodos resecados fue 15 (i 4-45). Los márgenes quirúrgicos fueron negativos en todos los pacientes. Se restituyó el tránsito intestinal en 28/32 (87,5%) pacientes. El promedio de seguimiento fue 21 meses (1-56), la sobrevida global y libre de enfermedad fue 100%. Discusión y Conclusión: La proctectomía con asistencia robótica ha demostrado ser segura en términos de resultados quirúrgicos tempranos y en criterios oncológicos de la pieza operatoria.

Aim: To analyze the surgical and oncological results of patients with rectal adenocarcinoma (RA) operated with robotic assistance. Materials and Method: Prospective cohort study, consecutive sample of patients between 2014-2017. Inclusion criteria: patients with primary RA, undergoing rectal resection, with robotic assistance with curative intention. Exclusion criteria: histology not adenocarcinoma. Evaluation of clinical-surgical data. Descriptive statistical analysis. Results: 37 patients were included; 20 (54%) were men and average age was 58.7 years. The average distance from the anal margin to the distal edge of the tumor was 6.6 cm (2-12 cm). Chemoradiotherapy (neoadyuvant) was indicated in 26 patients. The most frequent surgery was low anterior resection of the rectum and the average operating time was 266 minutes. Two conversions to laparotomy were performed. One or more complications were observed in 17 (45.9%) patients, 9 of them were Clavien-Dindo III or IV, 5 patients (13%) were reoperated. There were no blood transfusions and no postoperative mortality. The average postoperative hospital stay was 9.6 days (3-34). The average of resected lymph nodes was 15. Surgical margins were negative in all patients. Intestinal transit was restored in 28/32 (87.5%) patients. The average follow-up was 21 months (1-56), the overall and disease-free survival was 100%. Discussion and Conclusion: Proctectomy with robotic assistance has proved to be safe in terms of early surgical results and oncologic indicators of the surgical piece.

[Analysis of polymorphism rs1051730 of CHRNA3 in patients with dual pathology in a Mexican population]. / Analisis del polimorfismo rs1051730 de CHRNA3 en pacientes con patologia dual en poblacion mexicana.

INTRODUCTION: Epidemiological studies have described a high comorbidity of substance use disorders with another psychiatric disorder, which has been called dual pathology. However, the aetiological mechanisms underlying this association are still not fully understood. AIM: To carry out a preliminary study of the effect of polymorphism rs1051730 of the gene group CHRNA5-CHRNA3-CHRNB4 through a case-control study. SUBJECTS AND METHODS: A total of 225 subjects were selected and divided into three groups: those diagnosed with bipolar disorder, those with nicotine dependence, and subjects without nicotine dependence or any other psychiatric disorder. Genotyping was performed by real-time polymerase chain reaction. Genetic association analysis was performed using chi-square tests and multivariate logistic regressions. RESULTS: On comparing allelic frequencies with the control group, we found that polymorphism rs1051730 was associated with nicotine dependence (p = 0.03), but not with bipolar disorder (p = 0.94). CONCLUSION: Variant rs1051730 was associated with nicotine dependence in the Mexican population and showed the same effect in dual pathology. However, further studies are recommended to obtain conclusive results.

TITLE: Analisis del polimorfismo rs1051730 de CHRNA3 en pacientes con patologia dual en poblacion mexicana.Introduccion. Estudios epidemiologicos han descrito una alta comorbilidad de los trastornos de uso de sustancias con otro trastorno psiquiatrico, al cual se le ha llamado patologia dual. Sin embargo, los mecanismos etiologicos de esta asociacion continuan siendo dificiles de entender. Objetivo. Realizar un estudio preliminar del efecto del polimorfismo rs1051730 del grupo de genes CHRNA5-CHRNA3-CHRNB4 a traves de un estudio de casos y controles. Sujetos y metodos. Se selecciono a un total de 225 sujetos, divididos en tres grupos: con diagnostico de trastorno bipolar, con dependencia a la nicotina y sujetos sin dependencia a la nicotina o cualquier otro trastorno psiquiatrico. La genotipificacion se realizo mediante reaccion en cadena de la polimerasa en tiempo real. El analisis de asociacion genetica se realizo mediante pruebas de chi cuadrado y regresiones logisticas multivariables. Resultados. Al comparar las frecuencias alelicas con el grupo control, encontramos que el polimorfismo rs1051730 se asocio con el grupo de dependencia a la nicotina (p = 0,03), pero no con el de trastorno bipolar (p = 0,94). Conclusion. La variante rs1051730 se asocio con dependencia a la nicotina en la poblacion mexicana y mostro el mismo efecto en la patologia dual. Sin embargo, se recomiendan estudios adicionales para tener resultados concluyentes.

Resultados a largo plazo de pacientes con adenocarcinoma de recto inferior tratados con resección anterior ultrabaja interesfintérica / Long-term results of patients with adenocarcinoma of the lower rectum treated with anterior intersphinteric ultra-low-resection

INTRODUCCIÓN: La resección anterior ultrabaja interesfintérica (RAUBIE), permite preservar la función esfinteriana en pacientes seleccionados con cáncer de recto (CR). No obstante, puede producir alteraciones en la función evacuatoria y esfinteriana. OBJETIVO: Analizar los resultados oncológicos y funcionales luego de una RAUBIE. MATERIAL Y MÉTODO: Estudio observacional, analítico, transversal, durante el período 2007 a 2016. Criterios de inclusión: Pacientes sometidos a RAUBIE por CR con intención curativa. Todos los pacientes tuvieron un seguimiento el año 2017. Para la evaluación funcional se usó la escala de Jorge-Wexner, LARS y Kirwan. Análisis estadístico: Estadística descriptiva y método de Kaplan-Meier. RESULTADOS: De 21 pacientes; catorce (67%) fueron varones, edad promedio: 59 años. Ubicación tumoral: 4 cm (2-6 cm) del margen anal. Dieciocho (85,7%) pacientes recibieron neoadyuvancia. Todos los márgenes quirúrgicos distales y radiales fueron negativos. Un paciente (4,8%) tuvo metástasis a distancia y no hubo recurrencia locorregional. Con una mediana de seguimiento de 76,3 (9,8-126,8) meses, la sobrevida global y libre de enfermedad a 5 años fue de: 100% y 95% (IC: 90,1-99,9%), respectivamente. Con una mediana de seguimiento de 90 meses (21,7-124,2); se realizó la evaluación funcional a 15/21 pacientes. El puntaje de Jorge-Wexner tuvo una mediana de 13 (4-17) puntos, la escala de LARS de 34 puntos y en la escala de Kirwan, cuatro pacientes (26,7%) mostraron una buena función (Kirwan I-II). CONCLUSIÓN: Si bien los resultados oncológicos de los pacientes sometidos a una RAUBIE son satisfactorios, se debería tomar en cuenta los resultados funcionales al momento de proponer esta alternativa quirúrgica.

INTRODUCTION: Intersphinteric resection (ISR) allows preserve sphincter function in selected patients with rectal cancer (RC). Notwithstanding, it can produce alterations in defecation. AIM: To analyze the oncological and functional results after an ISR. MATERIAL AND METHOD: Observational, analytical, cross-sectional study, in the period 2007-2016. Inclusion criteria: Patients submitted to ISR by RC with curative intention. All the patients had a follow-up in 2017. Analysis of functional evaluation were performed by Jorge-Wexner, LARS and Kirwan scale. Statistical analysis: Descriptive statistics and Kaplan-Meier method. RESULTS: Of 21 patients; Fourteen (67%) were male, average age: 59 years. Tumor location: 4 cm (2-6 cm) from anal verge. Eighteen (85.7%) patients received neoadjuvant therapy. All distal and radial margins were negative. One patient (4.8%) had distant metastases and there was no locoregional recurrence. With a median follow-up of 76.3 (9.8-126.8) months, the 5-year global and disease-free survival was: 100% and 95% (CI: 90.1-99.9%), respectively. With a median follow-up of 90 months (21.7-124.2); Functional evaluation was performed on 15/21 patients. The Jorge-Wexner score had a median of 13 (4-17) points, the LARS scale of 34 points and in Kirwan scale, four patients (26.7%) showed good function (Kirwan I-II). CONCLUSION: The oncological results of patients undergoing ISR are satisfactory, however, functional results should be taken into account when proposing this surgical procedure.

Intranasal Erythropoietin Protects CA1 Hippocampal Cells, Modulated by Specific Time Pattern Molecular Changes After Ischemic Damage in Rats.

Erythropoietin, a multitarget molecule exhibited neuroprotective properties, especially against cerebral ischemia. However, little effort has been made to determinate both the administration pathway and doses that diminishes neuronal damage. In this study, we investigate the effect on CA1 region of different intranasal doses of rHuEPO (500, 1000 and 2500 IU/kg) applied in distinct post-damage times (1, 6, and 24 h) against ischemic cellular damage. Furthermore, most effective dose and time were used to evaluate gen and protein expression changes in 3 key molecules (EPO, EPOR, and ßcR). We established that CA1-region present histopathological damage in this ischemia model and that rHuEPO protects cells against damage, particularly at 1000 IU dose. Molecular data shows that EPO and EPOR gene expression are upregulated in a short term after damage treatment with rHuEPO (1 h); oppositely, BcR is upregulated in ischemic and Isc + EPO. Protein expression data displays no changes on EPO expression in evaluated times after treatment, but a tendency to increase 24 h after damage; in the opposite way, EPOR is upregulated significantly 6 h after treatment and this effect last until 24 h. So, our data suggest that a single intranasal dose of rHuEPO (1 h post-injury) provides histological neurorestoration in CA1 hippocampal region, even if we did not observe a dose-dependent dose effect, the medium dose evaluated (1000 UI/kg of b.w.) was more effective and sufficient for induces molecular changes that provides a platform for neuroprotection.

Detection and differentiation of Entamoeba histolytica and Entamoeba dispar in clinical samples through PCR-denaturing gradient gel electrophoresis.

Amebiasis is one of the twenty major causes of disease in Mexico; however, the diagnosis is difficult due to limitations of conventional microscopy-based techniques. In this study, we analyzed stool samples using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) to differentiate between Entamoeba histolytica (pathogenic) and E. dispar (non-pathogenic). The target for the PCR amplification was a small region (228 bp) of the adh112 gene selected to increase the sensitivity of the test. The study involved 62 stool samples that were collected from individuals with complaints of gastrointestinal discomfort. Of the 62 samples, 10 (16.1%) were positive for E. histolytica while 52 (83.9%) were negative. No sample was positive for E. dispar. These results were validated by nested PCR-RFLP (restriction fragment length polymorphism) and suggest that PCR-DGGE is a promising tool to differentiate among Entamoeba infections, contributing to determine the specific treatment for patients infected with E. histolytica, and therefore, avoiding unnecessary treatment of patients infected with the non-pathogenic E. dispar.

rs3918242 MMP9 gene polymorphism is associated with myocardial infarction in Mexican patients.

Several studies have demonstrated that matrix metalloproteinases (MMPs) play a major role in atherosclerotic plaque disruption and lead to myocardial infarction (MI). We investigated the association between the MMP1 -1607 1G/2G (rs1799750), MMP3 -1612 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms and the risk of developing MI in a Mexican mestizo cohort. The genotype analysis was performed using the restriction fragment length polymorphism-polymerase chain reaction technique in a group of 236 patients with a history of MI and 285 healthy controls. Similar distributions of rs1799750 and rs3025058 were observed in both groups; however, the MMP9 rs3918242 T allele and the CT genotype were associated with the risk of developing MI (OR = 2.32, pC = 0.02 and OR = 2.40, pC = 0.02, respectively). Multiple logistic analysis was performed between MI patients and controls to estimate the risk, and after adjusting for identified risk factors, the CT + TT genotypes of MMP9 rs3918242 were found to be significantly associated with increased risk of developing MI than those with the CC genotype (OR = 2.88, P < 0.01). In summary, our results reveal that the rs3918242 polymorphism of the MMP9 gene plays a major role in the risk of developing MI.

MHC2TA and FCRL3 genes are not associated with rheumatoid arthritis in Mexican patients.

Rheumatoid arthritis (RA) is a multifactorial disease. A combination of genetic and environmental risk factors contributes to its etiology. Several genes have been reported to be associated with susceptibility to the development of RA. The MHC2TA and FCRL3 genes have been associated previously with RA in Swedish and Japanese populations, respectively. In two recent reports, we show an association between FCRL3 and juvenile rheumatoid arthritis (JRA), and MHC2TA and acute coronary syndrome (ACS) in Mexican population. We assessed the association between three single nucleotide polymorphisms (SNPs) of the MHC2TA (-168G/A; rs3087456, and +16G/C; rs4774) and FCRL3 (-169T/C; rs7528684) genes and rheumatoid arthritis in Mexican population through a genotyping method using allelic discrimination assays with TaqMan probes. Our case-control study included 249 patients with RA and 314 controls. We found no evidence of an association between the MHC2TA -168G/A and +1614G/C or FCRL3 -169T/C polymorphisms and RA in this Mexican population. In this cohort of Mexican patients with RA, we observed no association between the MHC2TA or FCRL3 genes and this autoimmune disease.

Relación entre el grado de incontinencia fecal y el daño del esfínter anal externo / Relationship between faecal incontinence severity and external anal sphincter disruption

Introduction: Faecal incontinence (FI) represents an important psychological and social condition for an individual. There are several causes for FI, therefore its study and management is complex. Among different aetiologies, anatomical disruption of the external anal sphincter (EAS) as a consequence of anorrectal surgery or obstetric injury can be studied by endoanal ultrasound (EAUS). This study focus on anatomical assessment of sphincter muscle injury of EAS and its relationship with clinical presentation con FI. Objective: Compare anatomical and disruption of EAS features studied by 3D-EAUS between patients with FI, according to its severity. Methods: 3D-EAUS images were obtained from selected patients studied for FI between January 2008 and July 2010 at Clínica las Condes. Wexner Score (SW) was used to evaluate severity of FI, dividing patients into two categories: Mild FI (SW < 9) and Severe FI (SW ≥ 9). A single observer evaluated different morphological variables: width, length, percentage and angle of EAS disruption. Parametrical and non-parametrical analysis was used as appropriate. P-value < 0.05 was considered statistically significant. Results: From 31 female patients studied, mean SW was 11.7 +/- 0.8 points, range from 5 to 20 points. When dividing into two groups, 9 patients had mild FI and 22 had severe FI. Studied variables in EAUS 3D cubes: width, length, percentage and angle of EAS disruption, did not reach statistical significance between groups. Conclusion: No relationship was found between external anal sphincter anatomic injury variables studied and severity of faecal incontinence.

Introducción: La incontinencia fecal (IF) se refleja en una condición psicológica y social importante para el individuo. Las causas de IF son múltiples, siendo su estudio y manejo complejo. La disrupción anatómica del esfínter anal externo (EAE), secundaria, entre otras, a cirugía anorrectal o lesión obstétrica, es posible de ser estudiada por endosonografía anal (EAUS). El presente artículo se centra en el daño anatómico del EAE y su relación con la presentación clínica de la IF. Objetivo: Comparar las características anatómicas y daño del EAE objetivadas mediante endosonografía en 3 dimensiones (EAUS3D), entre los pacientes con IF según su severidad. Material y Método: Se obtuvo las EAUS3D realizadas en Clínica Las Condes por estudio de IF entre enero de 2008 y julio de 2010. Se utilizó el score de Wexner (SW) para separar la población en dos grupos, IF leve (SW < 9) e IF grave (SW ≥ 9). Un único observador evaluó las diferentes variables: grosor, longitud, porcentaje de defecto y ángulo de lesión del EAE. Se utilizó estadística paramétrica o no-paramétrica según corresponda. Se consideró significativo p < 0,05. Resultados: De un total de 31 pacientes femeninas estudiadas, el SW promedio fue de 11,7 +/- 0,8 con rango entre 5 y 20 puntos. Al separar según grupos, 9 pacientes tenían IF leve y 22 IF grave. De las variables estudiadas por EAUS3D: el promedio, grosor, longitud, porcentaje de defecto y el ángulo de lesión del EAE no lograron diferencia estadística entre los grupos. Conclusión: No existe una relación directa entre las variables estudiadas de daño anatómico del EAE y el grado de IF.

Caracterización del infiltrado linfocitario (CD, CD4, CD8, CD45RO y FOXP3) e inestabilidad microsatelital en pacientes con cáncer colorrectal / Lymphocyte infiltration and microsatellite instability in colorectal cancer patients

Background: In colorectal cancer (CRC) patients, lymphocyte infiltration (LI) and microsatellite instability (MSI) have been associated with better prognosis. Aim: To analyze the association between components of LI (CD3/CD4/CD8/CD45R0/FoxP3) and MSI status with metastatic stages in CRC patients. Material and Methods: Prospective study of 109 patients diagnosed with CRC. The expression of CD3, CD4, CD8, CD45R0 and FoxP3 markers, was evaluated by immunohistochemical analysis, and tumors were classified into negative, low and intense expression. The MSI was assessed with seven markers amplified by PCR from normal and tumoral DNA. Tumors were grouped in MSS (stable)/MSI-low and MSI-high. Statistical analysis was performed with Fischer's exact test. Results: 29 percent, 28 percent, 12 percent and 86 percent of tumors exhibits intense expression of CD3+, CD4+, CD8+ and CD45RO+ lymphocytes, respectively. 84 percent of the tumors presented MSS/ MSI-low and 16 percent had MSI-high. Tumors that show a high density of T cells (CD3+, CD4+ y CD45R0+) are associated with early stage tumors (I and II) (p = 0.023; p = 0.030 and p = 0.003, respectively). Additionally, there was a significant association between the MSS/MSI-low tumors and a reduced ability to recruit CD8+ cytotoxic T lymphocytes (p = 0.037) and CD3+ (p = 0.064). Conclusion: There is an association between high densities of CD3+, CD4+ and CD45RO+ lymphocytes and non-metastatic tumors. In addition, MSS/ MSI-low tumors are associated with a lower recruitment of CD8+ and CD3+ lymphocytes.

Introducción: En el cáncer colorrectal (CCR), se sugiere que un mejor pronóstico podría asociarse a una respuesta inmune antitumoral (del huésped) y/o a la presencia de una alta inestabilidad microsatelital (MSI). Objetivo: Determinar si los niveles de expresión de los marcadores de linfocitos T (CD3/CD4/CD8/ CD45RO/FoxP3) y el estado de MSI se asocian a estadios metastásicos en pacientes con CCR. Material y Método: Estudio prospectivo de 109 pacientes con diagnóstico de CCR. El análisis de expresión de los marcadores CD3/CD4/CD8/CD45RO/FoxP3 fue realizado por inmunohistoquímica; los tumores fueron clasificados en negativo, débil e intenso. La MSI fue evaluada con siete marcadores amplificados desde ADN normal y tumoral; los tumores fueron agrupados en: MSS (estable)/MSI-baja y MSI-alta. El análisis estadístico fue realizado con el test exacto de Fischer. Resultados: Una intensa expresión de los marcadores CD3+, CD4+, CD8+ y CD45RO+, fue observada en el 29 por ciento, 28 por ciento, 12 por ciento y 86 por ciento de los tumores, respectivamente. El 16 por ciento de los tumores presentó MSI-alta. Los tumores que presentan una alta densidad de linfocitos T (CD3+, CD4+ y CD45RO+) se asocian a estadios tempranos I-II (p = 0,023; p = 0,030 y p = 0,003, respectivamente). Adicionalmente, se identificó una asociación estadística significativa entre los tumores con MSS/MSI-baja y una menor capacidad de reclutar linfocitos T citotóxicos CD8+ (p = 0,037) y totales CD3+ (p = 0,064). Conclusión: Existe una asociación entre altas densidades de linfocitos T CD3+, CD4+ y CD45RO+ y tumores con estadios no metastásicos. Además, tumores con MSS/MSI-baja se asocian a un menor reclutamiento de linfocitos T CD8+ y CD3+.

Rehabilitación pelviperineal multimodal en pacientes con incontinencia fecal / Multimodal pelviperineal rehabilitation in patients with fecal incontinence

Fecal incontinence (FI) is associated with low self-esteem and quality of life. Nowadays, multimodal pelviperineal rehabilitation (MPPR) has become the preferred treatment. Purpose: To evaluate our results of multimodal pelviperineal rehabilitation (MPPR) in patients diagnosed with fecal incontinence (FI). Methods: Historic cohort study using a prospectively maintained database from patients with FI that underwent MPPR between years 1999 and 2012. FI was classified according to Jorge-Wexner´s scale, at the beginning (Winitial) and the end (Wfinal) of treatment. In July 2013 a survey was carried out to measure follow-up Wexner score (Wfollow-up) and pelvic muscle training. Statystical analysis was performed using Chi square test, Fisher Test, Mann-Whitney and Odds Ratio. Significant p value < 0.05. Results: One hundred and thirteen patients completed treatment, median age 67 years-old (r: 24-91) and 83 percent female. Median scores for Winitial and Wfinal were 9 points (r: 3-19) and 3 points (r: 0-13), respectively (p < 0.001). In July 2013, 68 (61 percent) patients were available for follow-up. Wexner score at the beginning, end and follow-up were as follows: 9 (i: 3-19), 3 (i:0-12) and 4 (i:0-19), respectively. There were significant differences between Winitial and Wfollow-up (p < 0.001), but not between Wfinal and Wfollow-up (p = 0.23). There were 20 patients (29 percent) who kept training their pelvic muscles and 48 (71 percent) who did it very rarely or did not do it at all. It was the latter group who showed an increased risk to obtain worst score in Wfollow-up (OR = 3.89; CI 95 percent: 1.26-11.9; p = 0.0175). Conclusion: FI patients treated with MPPR show good short and long-term results.

Introducción: La incontinencia fecal (IF) se asocia a menor calidad de vida en quienes la sufren. Actualmente, la rehabilitación pelviperineal multimodal (RPPM) es el tratamiento inicial de elección. Objetivo: Evaluar los resultados de la RPPM en pacientes con IF. Método: Estudio de cohorte histórica de pacientes con IF que recibieron RPPM entre 1999-2012. Se utilizó la escala de Jorge-Wexner para medir laIF, al inicio (Wi) y fin (Wf) del tratamiento. Se aplicó una encuesta en julio de 2013 para medir el Wexner de seguimiento (Ws) y mantención de ejercicios terapéuticos. Análisis estadístico: prueba de c2, prueba exacta de Fisher, Mann-Whitney y Odds Ratio. Significancia estadística p < 0,05. Resultados: Hubo 113 pacientes que completaron el tratamiento. La mediana de edad fue 67 años (i: 24-91) y 83 porciento género femenino. La mediana de Wi fue de 9 puntos (i: 3-19) y la mediana de Wf fue de 3 puntos (i: 0-13) (p < 0,001). Se logró contactar a 68 pacientes para el seguimiento, en ellos la mediana del puntaje de Wi, Wf y Wsfue de 9 (i: 3-19), 3 (i:0-12) y 4 (i:0-19), respectivamente. Hubo diferencia significativa entre Wi y Ws (p < 0,001), pero no entre Wf y Ws (p = 0,23). Veinte pacientes (29 por ciento) realizaron ejercicios terapéuticos regularmente y 48 (71 por ciento) nunca o raramente; este último grupo es factor de riesgo para obtener peores resultados (OR = 3,89; CI 95 porciento: 1,26-11,9; p = 0,0175). Conclusión: El tratamiento con RPPM en pacientes con IF tiene buenos resultados a corto y largo plazo.

Glutamate excitotoxicity activates the MAPK/ERK signaling pathway and induces the survival of rat hippocampal neurons in vivo.

Current knowledge concerning the molecular mechanisms of the cellular response to excitotoxic insults in neurodegenerative diseases is insufficient. Although glutamate (Glu) has been widely studied as the main excitatory neurotransmitter and principal excitotoxic agent, the neuroprotective response enacted by neurons is not yet completely understood. Some of the molecular participants have been revealed, but the signaling pathways involved in this protective response are just beginning to be identified. Here, we demonstrate in vivo that, in response to the cell damage and death induced by Glu excitotoxicity, neurons orchestrate a survival response through the extracellular signal-regulated kinase (ERK) signaling pathway by increasing ERK expression in the rat hippocampal (CA1) region, allowing increased neuronal survival. In addition, this protective response is specifically reversed by U0126, an ERK inhibitor, which promotes cell death only when it is administered together with Glu. Our findings demonstrate that the ERK signaling pathway has a neuroprotective role in the response to Glu-induced excitotoxicity in hippocampal neurons. Therefore, the ERK signaling pathway may be activated as a cellular response to excitotoxic injury to prevent damage and neural loss, representing a novel therapeutic target in the treatment of neurodegenerative diseases.

Meningitis de Mollaret: reporte de caso / Mollaret´s meningitis: A case report

La meningitis de Mollaret es una enfermedad rara caracterizada por episodios recurrentes y autolimitados de meningitis linfocítica. Se presenta un caso de meningitis de Mollaret asociado a la infección por herpes simple tipo 2 en una mujer de 27 años con confirmación por reacción en cadena de la polimerasa (PCR) del líquido cefalorraquídeo y se hace una revisión del tema.

Mollaret´s meningitis is a rare disease characterized by recurrent and self-limited episodes of lymphocytic meningitis. We present a case of a 27-year-old woman with Mollaret´s meningitis related to viral infection with herpes simplex virus type 2 confirmed by cerebrospinal fluid polymerase chain reaction ( PCR ).

Translating neurotrophic and cellular plasticity: from pathophysiology to improved therapeutics for bipolar disorder.

OBJECTIVE: Bipolar disorder (BD) likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes. Therapeutic properties of mood stabilizers are presumed to result from a restoration of the function of these altered pathways and processes through a wide range of biochemical and molecular effects. We aimed to review the altered pathways and processes implicated in BD, such as neurotrophic factors, mitogen-activated protein kinases, Bcl-2, phosphoinositol signaling, intracellular calcium and glycogen synthase kinase-3. METHODS: We undertook a literature search of recent relevant journal articles, book chapter and reviews on neurodegeneration and neuroprotection in BD. Search words entered were 'brain-derived neurotrophic factor,''Bcl-2,''mitogen-activated protein kinases,''neuroprotection,''calcium,''bipolar disorder,''mania,' and 'depression.' RESULTS: The most consistent and replicated findings in the pathophysiology of BD may be classified as follows: i) calcium dysregulation, ii) mitochondrial/endoplasmic reticulum dysfunction, iii) glial and neuronal death/atrophy and iv) loss of neurotrophic/plasticity effects in brain areas critically involved in mood regulation. In addition, the evidence supports that treatment with mood stabilizers; in particular, lithium restores these pathophysiological changes. CONCLUSION: Bipolar disorder is associated with impairments in neurotrophic, cellular plasticity and resilience pathways as well as in neuroprotective processes. The evidence supports that treatment with mood stabilizers, in particular lithium, restores these pathophysiological changes. Studies that attempt to prevent (intervene before the onset of the molecular and cellular changes), treat (minimize severity of these deficits over time), and rectify (reverse molecular and cellular deficits) are promising therapeutic strategies for developing improved treatments for bipolar disorder.

El deporte y la actividad física en la prevención del cáncer / Sports and physical activity in cancer prevention

El cáncer es la primera causa de muerte en la mayoría de los países desarrollados. Chile se acerca cada vez más a esta realidad, ya que esta enfermedad es la segunda causa de muerte en el país. Lamentablemente, nuestra expectativa es al alza y de este modo debemos actuar con energía en la promoción de factores protectores. La práctica del deporte ha evidenciado múltiples ventajas en el estado general de quienes lo practican y en relación al cáncer, se han realizado estudios que demuestran que la práctica deportiva es relevante en distintos niveles. A nivel celular el deporte disminuiría la activación de cascadas inflamatorias que están implicadas en el desarrollo de diversos tipos de cánceres, como el de pulmón, colorrectal, gástrico y pancreático entre otros. Además, a nivel de prevención existe una relación inversa entre actividad física y el riesgo de desarrollar cáncer de mama y de colon. En pacientes oncológicos el ejercicio puede ser útil en la reducción de la fatiga y la depresión, y así contribuir a una mejor calidad de vida.

Cancer is the main cause of mortality in most developed countries. In Chile, cancer is the second cause of mortality and we expect further increases on the years to come. For this reason is imperative an active promotion of protective factors, such as sports. This practice has shown relevant benefits in patients affected with cancer in different levels, for example it has been demonstrated that sports decrease inflammatory cascade, usually over activated in patients with lung, pancreatic, gastric and colorectal cancer. Furthermore, evidence suggests an inverse relationship between physical activity and the risk of developing breast and colorectal cancer. Programmed and regular physical activity could be beneficial in patients with cancer, by reducing fatigue or depression, thus inducing an improvement in their quality of life.

Cáncer de recto: diagnóstico, estudio y estadificación / Rectal cancer: diagnosis, study and staging

Rectal cancer is defined as a tumour located between the anal verge and 15 cm within anal verge. In rectal cancer, a precise preoperative staging allows to categorize patients for different available treatments, as well as decide the best surgical treatment. Preoperative staging is performed by several radiological techniques. Currently available procedures are endorectal ultrasound (EUS), computed tomography (CT) magnetic resonance (MRI), positron emission tomography-computed tomography (PET/CT) and intraoperative ultrasound. EUS is a procedure performed by the colorrectal surgeon that allows the evaluation of the depth of tumour invasion as well as lymph node status; nevertheless its main shortcoming is the inability to assess mesorectal fascia involvement. Nowadays, MRI is the best method to assess mesorectal fascia involvement in addition to tumour invasion and lymph nodes involved. CT is a widely available procedure, and its main use is evaluation of distant metastases, with lower accuracy to assess tumour invasion and lymph node status. PET/CT is currently gaining importance, however its role in preoperative staging it's not widely accepted. IOUS allows evaluation of liver metastases during surgery, and therefore determines management and prognosis. Consequently, is necessary for surgeons to maintain an up-to-date knowledge of current methods, its advantages and limitations.

El cáncer rectal se define como el tumor ubicado entre el margen anal y los 15 cm hacia proximal. En el cáncer de recto, una precisa estadificación preoperatoria permite clasificar correctamente a los pacientes para las diversas terapias existentes, así como seleccionar el mejor tratamiento quirúrgico. La estadificación preoperatoria se realiza con el apoyo de métodos imagenológicos. Dentro de los métodos actualmente disponibles están la endosonografía rectal (EUS), tomografía computada (TC), resonancia magnética (RM), tomografía por emisión de positrones (PET/CT) y ultrasonido intraoperatorio (IOUS). La EUS es un método realizado por el cirujano colorrectal, que permite la evaluación de la invasión de la pared, así como también de los linfonodos, sin embargo, su principal limitación es la evaluación del compromiso de la fascia mesorrectal. La RM es, hasta el momento, el mejor método para evaluar el compromiso de la fascia mesorrectal, además de informar el compromiso de pared y una adecuada evaluación de linfonodos comprometidos. La TC es un método ampliamente disponible, cuya principal utilidad es la evaluación de metástasis a distancia. El PET/CT está cobrando actualmente mayor importancia, sin embargo, su uso en estadificación preoperatoria aún no es ampliamente aceptado. La IOUS permite evaluar el compromiso metastásico del hígado durante la cirugía y por lo tanto, determina conducta y pronóstico. Por lo anterior, es necesario un conocimiento actualizado del cirujano en cuanto a esta metodología, sus ventajas y limitaciones.

Urgencias proctológicas / Proctology emergencies

Las urgencias proctológicas son una causa frecuente de consulta en Servicios de Urgencia. Para los pacientes este tipo de problemas implican, además de los propios síntomas, en muchos casos pudor o vergüenza, lo cual puede redundar en una consulta tardía en relación al inicio del cuadro clínico. Para el médico de urgencia es un desafío poder determinar de forma clara el diagnóstico y el tratamiento adecuado, así como la necesidad de hospitalizar o indicar la consulta por un especialista. Es por esto que se hace necesario el poseer los conocimientos básicos para el diagnóstico y el manejo inicial de las patologías más frecuentes tales como el dolor anal, sangrado vía anal o aumento de volumen en la zona perianal. El objetivo de esta revisión es entregar las bases para un adecuado diagnóstico y manejo de las patologías proctológicas que más frecuentemente requieren una atención de urgencia.

Proctologic emergencies are a frequent cause of consultation in the emergency room. For these patients, such problems involve not only a physical discomfort or pain, but also shame in many cases, which can result in a late consultation in relation of the onset of symptoms. These problems are a chellenge, in order to perform an accurate diagnosis and appropriate treatment. Like wise it is necessary to determine the need for hospitalization or evaluation by a specialist. This is why it is necessary to have the basic knowledge and skills for diagnosis and initial management of most common diseases such as anal pain, rectal bleeding or increased volume in the perianal area. The aim of this review is to provide the basis for a proper diagnosis and management of proctologic pathologies most frequently evaluated in an emergency room.

HIF-1α expression in the hippocampus and peripheral macrophages after glutamate-induced excitotoxicity.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a master transcription factor that regulates the response to hypoxia and ischemia and induces the expression of various genes, including vascular endothelial growth factor (VEGF) and erythropoietin (EPO). This study shows the systemic response of increased HIF-1α, EPO, and VEGF mRNA and protein. In addition, VEGF expression was increased in neurons and over-expressed in glial cells in a model of neuroexcitotoxicity in the hippocampus, in which rats were neonatally exposed to high glutamate concentrations. Simultaneous increases in HIF-1α, EPO and VEGF mRNA in peritoneal macrophages were also observed. Our study is consistent with the hypothesis that these genes exert a protective effect in response to neurotoxicity.

Protective effects of tryptophan on neuro-inflammation in rats after administering lipopolysaccharide.

Tryptophan (TRP), which plays an important role in immune system regulation, protein synthesis, serotonin (5-HT) and melatonin production, is a potent endogenous free radical scavenger and antioxidant. The aim of this work was to determine the efficacy of TRP in neuro-inflammation induced by systemic administration of lipopolysacharide (LPS, 20mg/kg) which promotes the synthesis of free radical (LPO: MDA and 4-HDA), and pro-inflammatory cytokine Interferon-γ (IFN-γ) in different brain regions (cerebral cortex and hippocampus) of rats. Experiments were performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein), cerebral cortex and hippocampus were evaluated for lipid peroxidation (LPO) products, nitrites, nitrates and plasmatic concentration of IFN-γ. LPO levels in LPS+TRP groups were significantly decreased than that obtained in the LPS group. However, there were no observed differences in plasmatic levels of nitrites and nitrates as well as IFN-γ, neither in the cerebral cortex or hippocampus. The TRP has protective effect in the oxidative damage in a model of endotoxic shock in the breading nurslings induced by the systemic administration of LPS, acting as a scavenger of free radicals. So, it can be proposed as an innocuous protector agent in the endotoxic shock process.

Expression of HIF-1 alpha, VEGF and EPO in peripheral blood from patients with two cardiac abnormalities associated with hypoxia.

OBJECTIVES: HIF-1 alpha (hypoxia-inducible factor-1 alpha) mediates the responses of mammalian cells to hypoxia/ischemia by inducing the expression of adaptive gene products (e.g., vascular endothelial growth factor (VEGF) and erythropoietin (EPO)). Persistent pulmonary hypertension of the newborn (PPHN) and cyanotic congenital heart disease (CCHD) are common neonatal diseases considered as paradigms of hypoxemia. Since the expression HIF-1 alpha, VEGF and EPO in newborns diagnosed with these diseases has yet to be studied, we set out to define the expression of these genes in peripheral blood from newborn infants diagnosed with PPHN and CCHD. DESIGN AND METHODS: The mRNA transcripts encoding HIF-1 alpha, VEGF and EPO were measured by RT-PCR in healthy newborn infants and infants diagnosed with PPHN and CCHD. RESULTS: An important increase in HIF-1 alpha expression was observed in both pathological conditions, accompanied by significant increases in VEGF and EPO expression when compared to healthy infants. CONCLUSIONS: HIF-1 alpha mRNA expression increases in newborn infants with PPHN or CCHD, as does the expression of its target genes VEGF and EPO.