Tumor miofibroblástico inflamatorio de laringe: a propósito de un caso / Inflammatory myofibroblastic tumor of the larynx: a case report

Resumen El tumor miofibroblástico inflamatorio (TMI) es una patología muy poco frecuente. Los TMI localizados en laringe pueden ocasionar disfonía o sensación de cuerpo extraño. El diagnóstico se realiza a través de pruebas de imagen y visualización directa con obtención de muestras para estudio histopatológico. Presentamos el caso de una mujer de 43 años, con antecedentes personales de carcinoma indiferenciado de nasofaringe, tratado con radioterapia y quimioterapia, que acude a revisiones periódicas en consulta de otorrinolaringología. Se objetiva por nasofibroscopia una lesión rugosa en cuerda vocal izquierda. Se realiza biopsia con fibroscopio de canal, compatible con tumoración fusocelular atípica, con áreas celulares y mixoides, sospechosa de malignidad, con necesidad de completar estudio inmunohistoquímico. En comité de tumores de cabeza y cuello se decide cirugía programada (laringectomía supracricoidea con cricohioidoepiglotopexia) y posterior tratamiento adyuvante con quimioterapia y/o radioterapia, según resultados del estudio histopatológico. Como conclusión, el TMI es una patología que se encuentra predominantemente en el pulmón, siendo rara la afectación laríngea. Su pronóstico es favorable y el diagnóstico histopatológico es de vital importancia. El diagnóstico correcto va seguido de una escisión local amplia para prevenir la recurrencia, sin embargo, el tratamiento debe adaptarse a la ubicación del tumor y al estado del paciente.

Abstract Inflammatory myofibroblastic tumor (IMT) is a very rare pathology. IMTs located in the larynx can cause dysphonia or foreign body sensation. The diagnosis is made through imaging tests and direct visualization and confirmation with samples for histopathological study. We present the case of a 43-year-old woman with a personal history of undifferentiated carcinoma of the nasopharynx treated with radiotherapy and chemotherapy, who attended periodic check-ups in an otolaryngology clinic. A rough granulomatous lesion was observed by nasofibrolaryngoscopy in the left vocal cord. A canal fibroscope biopsy is performed, compatible with an atypical spindle cell tumor, with cellular and myxoid areas, suspicious of malignancy, requiring an immunohistochemical study to be completed. The head and neck tumor committee decides on scheduled surgery (supracricoid laryngectomy with cricohyoidoepiglottopexy) and subsequent adjuvant treatment with chemotherapy and/or radiotherapy, according to the results of the histopathological study. As a conclusion finally, the IMT is a pathology found predominantly in the lung, laryngeal involvement being rare. Its prognosis is favorable and the histopathological diagnosis is of vital importance to be able to be differentiated from other malignant neoplasms. The correct diagnosis is followed by a wide local excision to prevent recurrence, however, treatment must be tailored to the location of the tumor and the condition of the patient.

Melanoma nasofaríngeo: caso clínico / Nasopharyngeal melanoma: clinical case

Resumen El melanoma mucoso primario (MM) de la cavidad nasal y los senos paranasales sigue siendo un tumor maligno poco frecuente. El pico de incidencia se sitúa entre 50 y 60 años, siendo la epistaxis y la obstrucción nasal unilateral los síntomas más frecuentes. La resección quirúrgica es el tratamiento primario con radioterapia y quimioterapia adyuvante si es necesario, el pronóstico depende de la extensión. Presentamos el caso de una paciente mujer de 81 años con hemoptisis y halitosis de un año de evolución. La nasofibrolaringoscopia mostró una lesión parduzca, excrecente, irregular y friable, en el borde derecho del rodete tubárico derecho. El resultado histopatológico fue MM nasofaríngeo. Perfil inmunohistoquímico: S100 +, MelanA +, HMB45 +, SOX10 +, AE1AE3 negativo. El PET-CT mostró una hipercaptación a nivel del rodete tubárico derecho, sin evidencia de adenopatías o metástasis a distancia. Se realizó la resección tumoral completa mediante abordaje endoscópico. El Comité de Oncología del Melanoma decidió que no era necesario un tratamiento adyuvante debido a la resección completa de la lesión y considerando la edad y el deterioro cognitivo de la paciente.

Abstract Primary mucous melanoma (MM) of the nasal cavity and paranasal sinuses remains a rare malignancy. The peak of incidence is between 50 and 60 years old, being epistaxis and unilateral nasal obstruction the most frequent symptoms. Surgical resection is the primary treatment with radiotherapy and adjuvant chemotherapy if necessary, the prognosis depends on the spreading. We present the case of an 81-year-old female patient attending for hemoptysis and halitosis of a year of evolution. The nasofibrolaryngoscopy showed a brownish, excrescent, irregular and friable lesion, outgrowth of the right tube rim. Histopathology result was nasopharyngeal MM. Immunohistochemical profile: S100 +, MelanA +, HMB45 +, SOX10 +, AE1AE3 negative. PET-CT showed a hypercaptation at the level of the right tube rim, without evidence of adenopathies or distant metastases. Complete tumor resection was performed by endoscopic surgery. Melanoma Oncology Committee decided no need of adjuvant therapy due to the complete resection of the lesion and considering the age and cognitive deterioration of the patient.

Evaluación de la efectividad del Triclabendazol como fasciolicida en caprinos de la provincia de Neuquén, Argentina / Evaluation of the efficacy of Triclabendazol to treat liver worm in goats in Nequen province, Argentina

Resumen Debido al uso frecuente del triclabendazol (TCBZ) por parte de los productores, sumado al reporte reciente de resistencia de Fasciolahepatica al fármaco detectada en rodeos y majadas de Neuquén, se llevó a cabo el presente trabajo con el objetivo de evaluar la eficacia del TCBZ como fasciolicida en caprinos bajo un sistema de producción trashumante del norte de la provincia de Neuquén, Argentina. La eficacia se evaluó mediante un test de reducción de conteo de huevos de F. hepatica en caprinos Criollo Neuquino parasitados naturalmente. Se utilizaron dos grupos de animales: un Grupo Control (n: 10) que no recibió tratamiento y un Grupo Tratado (n: 10) al que se le administró TCBZ al 10% (Biofasiolex T10-Biogénesis Bagó ®) vía oral a dosis de 10 mg/kg PV. Al día 0 y 21 post tratamiento, se tomaron muestras de materia fecal para análisis coproparasitológicos. Se evidenció una reducción del conteo de huevos de F. hepatica del 100%, indicando el mantenimiento de la eficacia del fasciolicida en los caprinos evaluados. Se discuten los alcances del uso del test de reducción de conteo de huevos en zonas con producción trashumante del ganado.

Abstract Because of the frequent use of triclabendazole TCBZ by farmers and the recent reports of Fasciola hepatica resistance to this drug in herds and flocks from Neuquén, we carried out this study with the aim to evaluate the efficacy of TCBZ as fasciolicide in goats under a transhumance system from northern of Neuquén, Argentina. A fecal egg count reduction test (FECRT) was performed on Creale Neuquino goats naturally parasitized with F. hepatica. Twenty goats were divided into two groups: A control group (n: 10) which was left untreated, and a treatment group (n: 10) that was dosed orally with TCBZ 10% (Biofasiolex T10-Biogénesis Bagó ®). On Day 0 and Day 21 post-treatment, fecal samples were taken and analyzed by coproscopical examination. According to the FECRT, drug efficacy was 100 % and confirms that TCBZ maintains its efficacy against F. hepatica on goats. The usefulness of the FECRT in these zones under transhumance livestock production is discussed.

Doramectin efficacy against Psoroptes ovis in sheep: Evaluation of pharmacological strategies.

The aims of this study were to evaluate the efficacy of two injectable formulations of doramectin (DRM) against Psoroptes ovis in sheep infested under controlled experimental conditions and to characterize the DRM plasma disposition kinetics in the infested animals. To this end, sheep were experimentally infested with a P. ovis strain from a farm with a history of treatment failure, and then treated either with DRM 1% (traditional preparation) on days 0 and 7 or with DRM 3.15% (long-acting formulation) on day 0. The efficacy of each treatment was calculated by counting live mites in skin scrapings. Plasma samples were obtained from each animal and DRM concentrations were measured by HPLC. After the two doses of DRM 1%, the maximum efficacy (98.8%) was reached on day 28, whereas after the single dose of DRM 3.15%, the maximum efficacy (100%) was reached on day 35 and ratified on day 42. The long-acting formulation allowed obtaining higher exposure and more sustained concentrations of DRM than the traditional preparation. Although both DRM formulations studied were effective according to international protocols, they did not reach 100% effectiveness in the time required for approved pharmaceutical products against sheep scab, according to Argentine regulations.

Falla en la eficacia de dos formulaciones de ivermectina contra Psoroptes ovis (Hering, 1838) en ovinos / Failure of efficacy of two ivermectin formulations against Psoroptes ovis (Hering, 1838) in sheep

Resumen El presente trabajo evaluó la relación entre la eficacia y la farmacocinética de dos formulaciones comerciales inyectables de ivermectina (IVM) en ovinos merino adultos artificialmente infestados con Psoroptes ovis. Los animales fueron tratados por vía subcutánea con IVM 1 % en dos dosis con un intervalo de aplicación de 7 días, (0.2 mg/kg) o con una única dosis de IVM 3.15%, (1.05 mg/kg). Se realizaron conteos semanales de ácaros vivos mediante raspajes de piel entre el día 0 y 28 post-tratamiento para determinar la eficacia de los tratamientos, y se tomaron muestras de sangre para medir las concentraciones de IVM en plasma. Se observó una disminución significativa en los conteos de ácaros a partir del día 14 post-tratamiento, sin embargo, se encontraron ácaros vivos en todos los muestreos para ambos grupos. En el Grupo IVM 1%, la máxima eficacia se observó el día 28 post tratamiento (93.3%), mientras que en el Grupo IVM 3,15% este registro se obtuvo el día 21 (95.9%). Mayores concentraciones de IVM fueron observadas en los animales tratados con la formulación 3.15 %. La falla para obtener una cura parasitológica tras el tratamiento con ambas formulaciones de IVM puede ser indicativo de la presencia de ácaros resistentes a este principio activo.

Abstract The current work evaluated the relationship between efficacy and pharmacokinetics of two commercial injectable formulations of ivermectin (IVM) in adult merino sheep artificially infested with Psoroptes ovis. Animals were treated subcutaneously with IVM 1% formulation (two doses on days 0 and 7) at 0.2 mg / kg or with a single dose of IVM 3.15% preparation at 1.05 mg / kg. Live mites were counted weekly by performing skin scrapings between days 0 and 28 post-treatment to determine the efficacy of each IVM formulation. Blood samples were taken up to 35 days post-treatment to measure IVM plasma concentrations. A significant decrease in mite counts was observed from day 14 post-treatment. However, live mites were found in all samples for both groups throughout the entire trial. After IVM 1% administration, the highest effcacy was observed on day 28 (93.3% whereas in the IVM 3,15% group was obtained on day 21 post treatment (95.9%). Higher IVM plasma concentrations were observed in animals treated with the IVM 3.15% formulation. Failure to obtain a parasitological cure after treatment with both IVM formulations may reflect the presence of resistant mites to this drug.

Hypofractionation vs. conventional radiotherapy fractionation in the conservative treatment of T1 glottic cancer: a prospective cohort study.

BACKGROUND: Definitive radiotherapy is an effective single-modality in T1 glottic cancer. Hypofractionated schemes could offer excellent results in a shorter treatment period. We aimed to evaluate the clinical outcomes and toxicity comparing conventional vs. hypofractionated radiotherapy treatment in T1N0M0-glottic cancer. PATIENTS AND METHODS: Between Jan-1st, 2005 and August-1st, 2017, in a prospective cohort study, with 10-year follow-up, 138 patients were treated with conventional schedule 2 Gy/day, total dose 70 Gy/7 weeks (N = 71) or hypofractionated schedule 2, 2-2, 25 Gy/day, total dose 63, 8-63 Gy/5, 5 weeks (N = 67). Endpoints were clinical-response rate, local relapse-free survival (LRFS), laryngectomy-free survival (LFS), toxicity rates, relapse-free survival (RFS), metastasis-free survival (MFS), second tumour-free survival (2TFS), and overall survival (OS). RESULTS: All patients showed a complete clinical response. No differences were found for LRFS (p = 0.869), LFS (p = 0.975), RFS (p = 0.767), MFS (p = 0.601), 2TFS (p = 0.293), or OS (p = 0.685). Acute toxicity for skin and mucosae was similar (p = 0.550 and p = 0.698). Acute laryngeal toxicity was higher in the hypofractionation group (p = 0.004), due to an increase in slight moderate grade. No differences in late laryngeal edema were found (p = 0.989). CONCLUSION: Radiotherapy offers high rate survival, local control, and larynx preservation after 5-10-year follow-up. A hypofractionation could be preferable, since it offers the same results as conventional with fewer treatment sessions.

Allopregnanolone reversion of estrogen and progesterone memory impairment: interplay with serotonin release.

Previously, we found out that in ovariectomized female rats, estrogen and progesterone produce a memory deficit which is reverted by the intrahippocampal administration of allopregnanolone. Here, we study the possible interplay between allopregnanolone and hippocampal serotonergic activity. Ovariectomized rats injected subcutaneously with estrogen and progesterone were subsequently injected in the dorsal hippocampus with vehicle, allopregnanolone alone or allopregnanolone shortly after 8OH-DPAT, a predominantly 5HT1A-7 receptor agonist. Then, the subjects were sequentially tested in: (1) an inhibitory avoidance task and (2) K+-evoked [3H]-serotonin ex vivo release through superfusion experiments. Allopregnanolone increased the K+-evoked [3H]-serotonin release compared to control. 8OH-DPAT infusions reversed the effects of allopregnanolone on memory and K+-evoked [3H]-serotonin release. These results suggest that allopregnanolone memory improvement could be mediated, at least in part, through modulation of the hippocampal serotonergic system reactivity.

Oestrogens and Progestagens: Synthesis and Action in the Brain.

When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side-chain cleavage, 3ß-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase, cytochrome P450arom, steroid 5α-reductase and 3α-hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.

The challenge of improving boiling: lessons learned from a randomized controlled trial of water pasteurization and safe storage in Peru.

Boiling is the most common method of household water treatment in developing countries; however, it is not always effectively practised. We conducted a randomized controlled trial among 210 households to assess the effectiveness of water pasteurization and safe-storage interventions in reducing Escherichia coli contamination of household drinking water in a water-boiling population in rural Peru. Households were randomized to receive either a safe-storage container or a safe-storage container plus water pasteurization indicator or to a control group. During a 13-week follow-up period, households that received a safe-storage container and water pasteurization indicator did not have a significantly different prevalence of stored drinking-water contamination relative to the control group [prevalence ratio (PR) 1·18, 95% confidence interval (CI) 0·92-1·52]. Similarly, receipt of a safe-storage container alone had no effect on prevalence of contamination (PR 1·02, 95% CI 0·79-1·31). Although use of water pasteurization indicators and locally available storage containers did not increase the safety of household drinking water in this study, future research could illuminate factors that facilitate the effective use of these interventions to improve water quality and reduce the risk of waterborne disease in populations that boil drinking water.

Análisis preliminares de la versión adaptada en población chilena de la escala de adherencia terapéutica en diabetes mellitus tipo 2 - EATDM-III / Psychometric properties of the diabetes mellitus 2 treatment adherence scale version III (EATDM-III) adapted for Chilean patients

Background: The Diabetes Mellitus 2 treatment adherence scale version III (EATDM-III) was devised in Costa Rica. Its seven factors are family support, community organization and support, physical exercise, medical control, hygiene and self-care and assessment of physical condition. Aim: To assess the psychometric properties of the scale in Chilean patients. Material and Methods: The results of the EATDM-III scale, applied to 274 patients with Diabetes Mellitus 2 aged 59 ± 11 years (59% women), were analyzed. Reliability, item, exploratory and confirmatory factorial analyses were carried out both in the initial and the proposed model. Results: We propose a version of 30 items grouped in six dimensions, improving the fit indices obtained with the original scale. The review of item factor loadings shows that all are appropriate both in magnitude and statistical significance, with values between 0.46 and 0.93. Internal consistency measured by Cronbach s alpha, was 0.85 for the total scale. Conclusions: The adapted EATDM-III scale is reliable and can be used to assess treatment adherence in Chilean patients.

Rehabilitación respiratoria en pacientes EPOC: experiencia en Atención Primaria de Salud / Respiratory rehabilitation in COPD patients: Experience in a rural Primary Health Care Center

Respiratory rehabilitation improves physical capacity and quality of life in COPD patients as it has been previously reported. In Chile there are few and unpublished experiences on respiratory rehabilitation programs (RRP) implemented in primary health care (PHC). Our aim was to evaluate RRP outcome in COPD patients carried out in a rural PHC center. Methods: A prospective descriptive study of RRP in a PHC center implemented in Talagante (a village located 40 km from Santiago). COPD patients were enrolled in the study from July 2012 to May 2014. Patients having the inclusion criteria were admitted to a 12 weeks-long RPP This program included a 90 minute-long sessions of aerobic training (walking), strength training of upper and lower limbs (dumbbell, ankle support and elastic bands) and respiratory muscle training (threshold valve), twice a week. Quality of life, strength of trained muscles, six-minutes walking test (TM6), BODE index and dyspnea index, were measured before and after completing RRP Results were expressed as mean ± SD. Results: Out of 79 patients initially assessed, 54 were admitted to the RRP and 39 patients completed the program and were included in the analysis. Their mean age was 67.3 ± 8.5 years, 64% were female. In average BMI was 26.97 ± 4.3 kg/m², and FEVi was 1.17 ± 0.57 liters. We demonstrated a statistically significant improvement after RRP in 6-minute walk test (445.9 ± 77.9 m versus 498.2 ± 82.8 m, p < 0.001); Saint George’s Respiratory Questionnaire score (45.1 ± 16.1 versus 18.5 ± 11.5, p < 0.0001), PIMax (48.95 ± 18.8 versus 57.2 ± 19.4 cm H2O, p < 0.0001), BODE index (2.76 ± 1.37 versus 1.53 ± 1.0, p < 0.0001), and mMRC dyspnea scale (2.54 ± 0.75 versus 1.18 ± 0.56, p < 0.0001). Conclusions: Our results are consistent with those reported in the literature, demonstrating that COPD patients get beneficial effects with the respiratory rehabilitation program. We also showed that RRP can be implemented in primary health care using simple tools, with reasonable costs.

La rehabilitación respiratoria ha demostrado beneficios en mejorar la capacidad física y calidad de vida en los pacientes con EPOC. Sin embargo, en Chile no existe información de programas de rehabilitación respiratoria (PRR) en la atención primaria de salud. El objetivo de nuestro trabajo fue evaluar los resultados de la implementación de un programa de rehabilitación respiratoria (PRR) en pacientes con EPOC en la atención primaria de salud. Material y Método: Estudio prospectivo descriptivo realizado en un centro de salud familiar de Talagante en pacientes con diagnóstico confirmado de EPOC, durante el período julio de 2012 a mayo de 2014. Fueron ingresados al PRR, de 12 semanas de duración, aquellos pacientes que cumplían los criterios de inclusión. Se realizó entrenamiento aeróbico (caminata), entrenamiento de fuerza de extremidades superiores e inferiores (mancuernas, tobilleras y bandas elásticas) y entrenamiento de musculatura respiratoria (válvula umbral), 2 veces por semana y de 90 min de duración cada sesión. Al iniciar y al finalizar el PRR se evaluó: calidad de vida, fuerza muscular, test de marcha de 6 min (TM6); índice BODE y disnea. Resultados: De un total de 79 pacientes con EPOC evaluados, 54 ingresaron al PRR y 39 finalizaron el programa. La edad promedio fue 67,3 ± 8,5 años, 64% de género femenino, índice de masa corporal: 26,97 ± 4,3 kg/m² y VEF1 1,17 ± 0,57 L. Al comparar los valores iniciales y finales del PRR se encontraron diferencias estadísticamente significativas en: TM6 (445,9 ± 77,9 vs 498,2 ± 82,8 m, p < 0,001); Puntaje del cuestionario de St. George (45,1 ± 16,1 vs 18,5 ± 11,5, p < 0,0001), PIMáx 48,95 ± 18,8 vs 57,2 ± 19,4 cm H2O, p < 0,0001), índice BODE (2,76 ± 1,37 vs 1,53 ± 1,0, p < 0,0001), y escala de disnea mMRC (2,54 ± 0,75 vs 1,18 ± 0,56, p < 0,0001). Conclusiones: Los resultados de nuestro estudio son concordantes con lo descrito en la literatura y demuestran los beneficios significativos obtenidos con la rehabilitación respiratoria en pacientes con EPOC. También, se demuestra que en Chile se puede implementar un PRR en la atención primaria utilizando implementos simples y con un bajo costo.

Manejo laparoscópico de embarazo ectópico en cicatriz uterina por cesárea previa: reporte de un caso

El embarazo ectópico es la gestación que se anida fuera del endometrio que recubre la cavidad uterina. Se estima una incidencia de 0,94 a 2,6% de todas las gestaciones. Su localización en cicatriz uterina de cesárea previa (0,15%) -una rara presentación de esta patología- representa 6,15% de los casos de embarazo ectópico que ocurren en mujeres con antecedente de cesárea. En el presente artículo se analiza el caso de una paciente de 28 años, gesta 5, para 0412, con antecedente de 3 cesáreas, que acudió al Hospital Nacional Docente Materno Infantil (HONADOMANI) San Bartolomé en febrero 2013 con diagnóstico de embarazo ectópico localizado en cicatriz uterina por cesárea previa, por ecografía transvaginal, y que fue resuelto exitosamente mediante manejo laparoscópico. El embarazo ectópico localizado en la zona de cicatriz uterina por cesárea previa, aunque raro, va en aumento debido al incremento de la tasa de cesáreas. La ultrasonografía transvaginal es crucial para su diagnóstico, y actualmente no existe un consenso o guía clínica que nos oriente en su manejo.

Ectopic pregnancy is a gestation that nests outside of the uterus endometrial lining. Incidence is estimated at 0.94-2.6% of all pregnancies. Its location in a previous cesarean section uterine scar is a rare (0.15%) presentation of this disease, accounting for 6.15% of ectopic pregnancy cases occurring in women with previous cesarean section. A case of a 28 year-old woman G: 5 P: 0412, with history of 3 cesarean sections was hospitalized in Hospital Nacional Docente Materno Infantil (HONADOMANI) San Bartolomé in February 2013 because of transvaginal ultrasound diagnosis of ectopic pregnancy located in previous uterine cesarean scar; it was successfully resolved by laparoscopic management. Cases of ectopic pregnancy located in the uterine scar from previous cesarean are increasing due to the rising cesarean section rate. Transvaginal ultrasonography is crucial for diagnosis. There is no current consensus or guidelines for its management.

Value of sentinel lymph node biopsy in papillary thyroid cancer: initial results of a prospective trial.

The objectives of the study were to evaluate the performance of sentinel lymph node biopsy (SLNB) in detecting occult metastases in papillary thyroid carcinoma (PTC) and to correlate their presence to tumor and patient characteristics. Twenty-three clinically node-negative PTC patients (21 females, mean age 48.4 years) were prospectively enrolled. Patients were submitted to sentinel lymph node (SLN) lymphoscintigraphy prior to total thyroidectomy. Ultrasound-guided peritumoral injections of (99m)Tc-phytate (7.4 MBq) were performed. Cervical single-photon emission computed tomography and computed tomography (SPECT/CT) images were acquired 15 min after radiotracer injection and 2 h prior to surgery. Intra-operatively, SLNs were located with a gamma probe and removed along with non-SLNs located in the same neck compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted to histopathology analysis. Sentinel lymph nodes were located in levels: II in 34.7 % of patients; III in 26 %; IV in 30.4 %; V in 4.3 %; VI in 82.6 % and VII in 4.3 %. Metastases in the SLN were noted in seven patients (30.4 %), in non-SLN in three patients (13.1 %), and in the lateral compartments in 20 % of patients. There were significant associations between lymph node (LN) metastases and the presence of angio-lymphatic invasion (p = 0.04), extra-thyroid extension (p = 0.03) and tumor size (p = 0.003). No correlations were noted among LN metastases and patient age, gender, stimulated thyroglobulin levels, positive surgical margins, aggressive histology and multifocal lesions. Sentinel lymph node biopsy can detect occult metastases in PTC. The risk of a metastatic SLN was associated with extra-thyroid extension, larger tumors and angio-lymphatic invasion. This may help guide future neck dissection, patient surveillance and radioiodine therapy doses.

Metabolic impact of an NADH-producing glucose-6-phosphate dehydrogenase in Escherichia coli.

In Escherichia coli, the oxidative branch of the pentose phosphate pathway (oxPPP) is one of the major sources of NADPH when glucose is the sole carbon nutrient. However, unbalanced NADPH production causes growth impairment as observed in a strain lacking phosphoglucoisomerase (Δpgi). In this work, we studied the metabolic response of this bacterium to the replacement of its glucose-6-phosphate dehydrogenase (G6PDH) by an NADH-producing variant. The homologous enzyme from Leuconostoc mesenteroides was studied by molecular dynamics and site-directed mutagenesis to obtain the NAD-preferring LmG6PDH(R46E,Q47E). Through homologous recombination, the zwf loci (encoding G6PDH) in the chromosomes of WT and Δpgi E. coli strains were replaced by DNA encoding LmG6PDH(R46E,Q47E). Contrary to some predictions performed with flux balance analysis, the replacements caused a substantial effect on the growth rates, increasing 59 % in the Δpgi strain, while falling 44 % in the WT. Quantitative PCR (qPCR) analysis of the zwf locus showed that the expression level of the mutant enzyme was similar to the native enzyme and the expression of genes encoding key enzymes of the central pathways also showed moderate changes among the studied strains. The phenotypic and qPCR data were integrated into in silico modelling, showing an operative G6PDH flux contributing to the NADH pool. Our results indicated that, in vivo, the generation of NADH by G6PDH is beneficial or disadvantageous for growth depending on the operation of the upper Embden-Meyerhof pathway. Interestingly, a genomic database search suggested that in bacteria lacking phosphofructokinase, the G6PDHs tend to have similar preferences for NAD and NADP. The importance of the generation of NADPH in a pathway such as the oxPPP is discussed.

Allopregnanolone and puberty: modulatory effect on glutamate and GABA release and expression of 3α-hydroxysteroid oxidoreductase in the hypothalamus of female rats.

The hypothalamic release of glutamate and GABA regulates neurosecretory functions that may control the onset of puberty. This release may be influenced by neurosteroids such as allopregnanolone. Using superfusion experiments we examined the role of allopregnanolone on the K(+)-evoked and basal [(3)H]-glutamate and [(3)H]-GABA release from mediobasal hypothalamus and anterior preoptic area in prepubertal, vaginal opening and pubertal (P) rats and evaluated its modulatory effect on GABAA and NMDA (N-methyl-d-aspartic acid) receptors. Also, we examined the hypothalamic activity and mRNA expression of 3α-hydroxysteroid oxidoreductase (3α-HSOR) - enzyme that synthesizes allopregnanolone - using a spectrophotometric method and RT-PCR, respectively. Allopregnanolone increased both the K(+)-evoked [(3)H]-glutamate and [(3)H]-GABA release in P rats, being the former effect mediated by the modulation of NMDA receptors - as was reverted by Mg(2+) and by the NMDA receptor antagonist AP-7 and the latter by the modulation of NMDA and GABAA receptors - as was reverted by Mg(2+) and the GABAA receptor antagonist bicuculline. The neurosteroid also increased the basal release of [(3)H]-glutamate in VO rats in an effect that was dependent on the modulation of NMDA receptors as was reverted by Mg(2+). On the other hand we show that allopregnanolone reduced the basal release of [(3)H]-GABA in P rats although we cannot elucidate the precise mechanism by which the neurosteroid exerted this latter effect. The enzymatic activity and the mRNA expression of 3α-HSOR were both increased in P rats regarding the other two studied stages of sexual development. These results suggest an important physiological function of allopregnanolone in the hypothalamus of the P rat where it might be involved in the 'fine tuning' of neurosecretory functions related to the biology of reproduction of the female rats.

Allopregnanolone alters the luteinizing hormone, prolactin, and progesterone serum levels interfering with the regression and apoptosis in rat corpus luteum.

Steroids synthesized in the central nervous system are termed "neurosteroids". They are synthesized and metabolized in several brain areas. The objective of this work was to determine if 1 intracerebroventricular allopregnanolone injection in rats can interfere in luteal regression in a close relationship with modifications in LH, progesterone, and prolactin serum concentrations. Allopregnanolone was injected during proestrus morning and the animals were sacrificed on oestrous morning. Ovulation test and histological analysis were performed in the oestrus morning with light and electron microscopy. Serum prolactin, LH, and progesterone levels were measured by radioimmunoassay. The allopregnanolone injection significantly decreased luteinizing hormone serum level and the number of oocytes on oestrus. Progesterone and prolactin serum levels were increased after this injection. The inhibition of apoptotic figures due to allopregnanolone administration was detected in the already formed corpora lutea belonging to the previous ovary cycle and it was significantly lower than in vehicle group (control). When the GABA(A) antagonist (bicuculline) was administered alone or previously to allopregnanolone, no effect on the ovulation rate was observed. No changes in the apoptotic cell numbers were observed with respect to those of vehicle group. These results show that the effect of centrally injected allopreganolone over reproductive function could be due to a centrally originated LH mediated effect over ovarian function that affects luteal regression, through the inhibition of apoptosis and stimulation of progesterone and prolactin release.

Poliposis adenomatosa familiar: presentación de un caso y revisión de la literatura / Familial adenomatous polyposis: case report and literature review

Colorectal cancer (CRC) is a genetic and epigenetic disease. Approximately one third of the CRC has an hereditary component. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition that has its origins in the line of APC gene mutation, which occurs with a frequency of approximately 1:10,000 live births. We report a case of a patient of 25 years with FAP. This review provides current knowledge on the broad clinical spectrum of this disease, also referring to the optimal method of diagnosis, differential diagnosis and management.

El cáncer colorrectal (CCR) es una enfermedad genética y epigenética. Aproximadamente un tercio del CCR tiene un componente hereditario. La poliposis adenomatosa familiar (PAF) es una condición hereditaria autosómica dominante que tiene su origen en la línea de mutación del gen APC, el cual ocurre con una frecuencia aproximada de 1:10.000 nacidos vivos. Se reporta el caso de una paciente de 25 años con PAF. La presente revisión proporciona los conocimientos actuales sobre el amplio espectro clínico de esta enfermedad, refiriéndose también al método óptimo de diagnóstico, diagnóstico diferencial y su manejo.