Triple neurectomía transperitoneal laparoscópica y con asistencia robótica para el tratamiento del dolor inguinal crónico: descripción de la técnica, nuestra experiencia y resultados preliminares / Robot-assisted laparoscopic triple neurectomy for chronic inguinal pain: Description of the technique, our experience and preliminary results

Introducción. El dolor inguinal crónico o inguinodinia posthernioplastia es una complicación relativamente común y que puede llegar a ser muy incapacitante. El tratamiento quirúrgico mediante triple neurectomía es una opción terapéutica ante el fracaso de tratamientos previos (terapia oral, local o neuromodulación).ObjetivoDescripción retrospectiva de la técnica quirúrgica y resultados de la triple neurectomía laparoscópica y con asistencia robótica en el tratamiento de la inguinodinia crónica.Material y métodosSe describen los criterios de inclusión/exclusión, así como la técnica quirúrgica empleada en 7 pacientes intervenidos en el Complejo Asistencial Universitario de León (Servicio de Urología) tras no responder a otras alternativas terapéuticas.ResultadosLos pacientes presentaban dolor crónico inguinal reportando una valoración en la escala EVA del dolor prequirúrgica de 7,43 sobre 10. Tras la cirugía, dicha valoración se redujo a 3,71 al primer día postoperatorio y a 4,2 puntos al año de la intervención. El alta hospitalaria se produjo a las 24h de la cirugía y no se reportaron complicaciones relevantes.ConclusionesLa triple neurectomía laparoscópica o con asistencia robótica es una técnica segura, reproducible y eficaz en el tratamiento del dolor inguinal crónico refractario a otros tratamientos. (AU)

Introduction. Chronic inguinal pain or inguinodynia following hernioplasty is a relatively common complication that can be very incapacitating. Surgical treatment by triple neurectomy is a therapeutic option when previous treatments (oral/local therapy or neuromodulation) have failed.ObjectiveRetrospective description of the surgical technique and results of laparoscopic and robot-assisted triple neurectomy for chronic inguinodynia.Material and methodsWe describe the inclusion/exclusion criteria as well as the surgical technique applied in 7 patients operated on at the University Health Care Complex of León (Urology Department) after failure of other treatment options.ResultsThe patients presented chronic groin pain, reporting a preoperative pain VAS of 7.43 out of 10. After surgery, this score was reduced to 3.71 on the first postoperative day and to 4.2 points one year after surgery. Hospital discharge occurred 24hours after surgery with no relevant complications being reported.ConclusionsLaparoscopic or robot-assisted triple neurectomy is a safe, reproducible, and effective technique for the treatment of chronic groin pain refractory to other treatments. (AU)

Robot-assisted laparoscopic triple neurectomy for chronic inguinal pain: Description of the technique, our experience and preliminary results.

INTRODUCTION: Chronic inguinal pain or inguinodynia following hernioplasty is a relatively common complication that can be very incapacitating. Surgical treatment by triple neurectomy is a therapeutic option when previous treatments (oral/local therapy or neuromodulation) have failed. OBJECTIVE: Retrospective description of the surgical technique and results of laparoscopic and robot-assisted triple neurectomy for chronic inguinodynia. MATERIAL AND METHODS: We describe the inclusion/exclusion criteria as well as the surgical technique applied in 7 patients operated on at the University Health Care Complex of León (Urology Department) after failure of other treatment options. RESULTS: The patients presented chronic groin pain, reporting a preoperative pain VAS of 7.43 out of 10. After surgery, this score was reduced to 3.71 on the first postoperative day and to 4.2 points one year after surgery. Hospital discharge occurred 24 h after surgery with no relevant complications being reported. CONCLUSIONS: Laparoscopic or robot-assisted triple neurectomy is a safe, reproducible, and effective technique for the treatment of chronic groin pain refractory to other treatments.

Correction: The anti-metastatic activity of collagenase-2 in breast cancer cells is mediated by a signaling pathway involving decorin and miR-21.

The original microRNA hybridization data for this article, which has been available for the scientific community upon request, has now been deposited in the GEO repository under accession number GSE124432.

The anti-metastatic activity of collagenase-2 in breast cancer cells is mediated by a signaling pathway involving decorin and miR-21.

Matrix metalloproteinases (MMPs) have been traditionally implicated in cancer progression because of their ability to degrade the extracellular matrix. However, some members of the MMP family have recently been identified as proteases with antitumor properties. Thus, it has been described that collagenase-2 (MMP-8) has a protective role in tumor and metastasis progression, but the molecular mechanisms underlying these effects are unknown. We show herein that Mmp8 expression causes a decrease in miR-21 levels that in turn leads to a reduction in tumor growth and lung metastasis formation by MDA-MB-231 (4175) breast cancer cells. By using both in vitro and in vivo models, we demonstrate that the mechanism responsible for these MMP-8 beneficial effects involves cleavage of decorin by MMP-8 and a subsequent reduction of transforming growth factor ß (TGF-ß) signaling that controls miR-21 levels. In addition, miR-21 downregulation induced by MMP-8 increases the levels of tumor suppressors such as programmed cell death 4, which may also contribute to the decrease in tumor formation and metastasis of breast cancer cells overexpressing this metalloproteinase. These findings reveal a new signaling pathway for cancer regulation controlled by MMP-8, and contribute to clarify the molecular mechanisms by which tumor-defying proteases may exert their protective function in cancer and metastasis.

La docencia del área de Toxicología de la Universidad de La Laguna / The teaching of Toxicology at the University of La Laguna

La docencia de Toxicología en la Universidad de La Laguna (ULL) se integra en diversas Licenciaturas y Grados tales como Farmacia, Ciencia y Tecnología de los Alimentos (CTA), Medicina, Náutica y Transporte Marítimo y el Máster Oficial de Seguridad y Calidad de los Alimentos. En la Licenciatura de Farmacia en la ULL, el Área de Toxicología imparte la asignatura troncal Toxicología de 7 créditos y dos asignaturas optativas, Drogodependencias y Toxicología Clínica y Laboral, de 4,5 créditos cada una. En el Grado en Farmacia, se imparte la asignatura obligatoria de Toxicología (9 ECTS) y la asignatura optativa de Drogodependencias (6 ECTS). Asimismo, se imparte un total de 11 créditos en la Licenciatura de CTA quedando ésta extinguida en el curso académico 2013/2014. En la Licenciatura de Medicina, se imparte docencia de Toxicología en las asignaturas de Medicina Legal y Toxicología (asignado 1 crédito) y Toxicología clínica (4,5 créditos) mientras que en el Grado de Medicina se integra en las asignaturas Farmacología, anestesia y tratamiento del dolor (9 ECTS) y Aspectos éticos, aspectos legales y aspectos humanísticos de la Medicina (6 ECTS). En ellas, la Toxicología tiene asignado 1 y 0,5 ECTS, respectivamente. La Licenciatura de Náutica y Transporte Marítimo, la docencia de Toxicología se engloba en una asignatura obligatoria mientras que en el Grado en Ingeniería Radioelectrónica se incluye en una asignatura optativa (3 ECTS). En la docencia de Postgrado, la Toxicología se imparte en el Máster Oficial en Seguridad y Calidad de los Alimentos desde dos módulos con 6 ECTS cada uno de ellos (AU)

The Toxicology Department at the University of La Laguna (ULL) offers courses included in the curricula of several degrees such as Pharmacy, Food Science and Technology, Medicine, Marine and Maritime Transport, and Food Safety and Quality Master program. In the Bachelor of Pharmacy at ULL that will end in 2014/2015, the Toxicology Department offers the mandatory subject "Toxicology", with 7 credits, as well as two optional subjects ("Clinical and Professional Toxicology", and "Drug Addiction"), with 4.5 credits each. In the Degree in Pharmacy, the "Toxicology" course is a compulsory subject worth 9 credits in the European Credit Transfer System (ECTS) and the optional "Drug Addiction" subject remains, and will be worth 6 ECTS. The Toxicology Department also gives a total of 11 credits in the Food Science and Technology Bachelor that will end in the academic course 2013/2014. In the Bachelor of Medicine, Toxicology is taught in two courses: "Pharmacology, anesthesia and pain management" (9 ECTS, of which 1 ECTS is for toxicology) and "Ethical, legal and humanistic aspects of medicine" (6 ECTS, of which 0.5 ECTS is for toxicology). In the Bachelor of Nautical and Maritime Transport, Toxicology is included in a mandatory subject while in the Bachelor of Radio Electronics Engineering, Toxicology is an optional subject (3 ECTS). As for postgraduate teaching, Toxicology is taught in the Master program in Food Safety and Quality, in two modules of 6 ECTS each (AU)

[Ochratoxin A in foods for human consumption: review]. / La ocratoxina A en alimentos de consumo humano: revisión.

INTRODUCTION: Ochratoxin A is a neurotoxic, immunosuppressive, genotoxic, carcinogenic and teratogenic mycotoxins present in human food, mainly cereals and cereals products, alcoholic beverages and mill products (coffee, cocoa). The levels of Ochratoxin A in food are closely related with the production and conservation conditions. OBJECTIVE: This review aims to assess the presence of OTA in different food groups, and to update the knowledge about its toxicity, mechanism of action, methods of analysis used for detection and quantification, and different aspects about regulations. METHODS: References and publications related to the mechanism of action, toxicity, analysis and regulations about OTA in foods were searched and selected based on inclusion criteria. MEDLINE/PubMed, Scielo, Science Direct, Ebscohost were used as databases. RESULTS: The presence of OTA keeps on being observed in different food groups. The detected OTA levels are below those permitted by limits set by the regulations However, inadequate agrotechnological production practices and improper storage of foods remain as critical control points to avoid the toxic hazards resulting from human exposure to this toxin. CONCLUSIONS: It's recommended to promote the correct use of agrotechnological practices for raw materials and processed products to reduce the concentration of OTA in foods and to avoid the toxicity resulting from the consumption of OTA contaminated foods.

[Comparison of intrathecal fentanyl and bupivacaine in combined spinal-epidural obstetric analgesia]. / Comparación del efecto de fentanilo frente a bupivacaína intratecal en una técnica anestésica combinada durante la analgesia obstétrica.

OBJECTIVES: To compare intrathecal injection of the opioid fentanyl to injection of bupivacaine, in terms of their effect of labour in the context within the combined spinal-epidural analgesia. METHODS: Prospective single-blind trial in primiparas randomized to 2 groups for sedation with 25 microg of fentanyl or 2.5 mg of bupivacaine, followed in both cases by epidural infusion of ropivacaine. We measured time from puncture to delivery of the neonate, rescue analgesia, pain assessed on a visual analog scale (VAS), motor block, side effects, sensory level, Apgar score, and maternal satisfaction. RESULTS: Sixty-four women were studied. The mean time elapsed between puncture and birth was 168.59 minutes (95% confidence interval [CI], 134.16 to 203.03 minutes) in the bupivacaine group and 189.13 minutes (95% CI, 151.93 to 226.32 minutes) in the fentanyl group. The mean difference was -20.53 minutes (95% CI, -70.21 to 29.15 minutes). Survival analysis applied to duration of labor, using type of delivery as the final outcome, also failed to show a significant between-group difference (chi2=0.59, P=.447). No significant differences in use of rescue analgesia, VAS scores, or motor block were observed. The incidence of pruritus in the fentanyl group was 34.37%, but there were no differences in maternal satisfaction. CONCLUSIONS: Our findings do not support the use of intradural fentanyl with the aim of shortening labor. Fentanyl leads to more pruritus, although this side effect does not affect maternal satisfaction.

Comparación del efecto de fentanilo frente a bupivacaína intratecalen una técnica anestésica combinada durante la analgesia obstétrica / Comparison of intrathecal fentanyl and bupivacaine in combined spinal-epidural obstetric analgesia

OBJETIVOS: Valorar el efecto de los opiáceos intratecalessobre la progresión del trabajo de parto, comparando elefecto del fentanilo frente a bupivacaína.MÉTODOS: Estudio prospectivo randomizado simple ciegoa parturientas primíparas divididas en dos grupos; grupoF en el que se administraron 25 μg de fentanilo, y grupoB tratado con 2,5 mg de bupivacaína, seguidos ambosde perfusión de ropivacaína epidural. Las variables medidasfueron tiempo desde punción hasta nacimiento delfeto, analgesia rescate, EVA, bloqueo motor, efectos secundarios,nivel sensitivo, Apgar y satisfacción.RESULTADOS: Se analizaron 64 parturientas, siendo laduración media desde el momento de la punción hasta elnacimiento en el grupo B de 168,59 min. (IC 95%: 134,16a 203,03) por 189,13 min. (IC95%: 151,93 a 226,32) en elgrupo F, diferencia de medias -20,53 min. (IC 95%: -70,21a 29,15). El análisis de supervivencia de la duración delparto valorando como resultado final el tipo de parto tampocoobjetivó diferencias entre grupos, χ2 = 0,59 p = 0,447.No se encontraron diferencias estadísticamente significativasen la analgesia de rescate, EVAy bloqueo motor. Huboun 34,37% de casos de prurito en el grupo F, sin mostrardiferencias en el grado de satisfacción.CONCLUSIONES: No se evidencian datos que justifiquenla utilización del fentanilo intradural con el objetivo deacortar el tiempo del trabajo de parto. El fentanilo produceun mayor número de efectos adversos en modo de prurito,a pesar de no tener repercusión sobre el grado desatisfacción de la parturienta (AU)

OBJECTIVES: To compare intrathecal injection of theopioid fentanyl to injection of bupivacaine, in terms oftheir effect of labour in the context within the combinedspinal-epidural analgesia.METHODS: Prospective single-blind trial in primiparasrandomized to 2 groups for sedation with 25 μg of fentanylor 2.5 mg of bupivacaine, followed in both cases by epiduralinfusion of ropivacaine. We measured time from punctureto delivery of the neonate, rescue analgesia, pain assessed ona visual analog scale (VAS), motor block, side effects,sensory level, Apgar score, and maternal satisfaction.RESULTS: Sixty-four women were studied. The meantime elapsed between puncture and birth was 168.59minutes (95% confidence interval [CI], 134.16 to 203.03minutes) in the bupivacaine group and 189.13 minutes(95% CI, 151.93 to 226.32 minutes) in the fentanylgroup. The mean difference was –20.53 minutes (95%CI, –70.21 to 29.15 minutes). Survival analysis applied toduration of labor, using type of delivery as the finaloutcome, also failed to show a significant between-groupdifference (χ2=0.59, P=.447). No significant differences inuse of rescue analgesia, VAS scores, or motor block wereobserved. The incidence of pruritus in the fentanylgroup was 34.37%, but there were no differences inmaternal satisfaction.CONCLUSIONS: Our findings do not support the use ofintradural fentanyl with the aim of shortening labor.Fentanyl leads to more pruritus, although this side effectdoes not affect maternal satisfaction(AU)

Plasminogen gene expression is regulated by nerve growth factor.

BACKGROUND: Studies have documented a requirement for an intact plasminogen (Plg) activation system in neurite outgrowth induced by nerve growth factor (NGF). OBJECTIVE: In this study we addressed the effect of NGF on Plg synthesis in model NGF-responsive PC-12 cells. METHODS: The effect of NGF on Plg gene expression was assessed using Western blotting, quantitative polymerase chain reaction, luciferase reporter assays, site directed mutagenesis, electrophoretic mobility shift assays and chromatin immunoprecipitation. RESULTS: NGF treatment increased Plg expression 3-fold and steady state levels of Plg mRNA were increased 6.82-fold. This effect also was observed in cortical neurons. PC-12 cells transfected with a luciferase reporter gene under the control of a 2400 bp fragment of the murine Plg promoter exhibited a 5-fold increase in luciferase activity following treatment with NGF. This response was dependent on Ras/ERK and PI3 K signaling because treatment with PD98059 together with wortmannin decreased promoter activity, in response to NGF, to the level exhibited by untreated cells. Furthermore, co-transfection with a dominant-negative mutant Ha-Ras completely blocked NGF-induced luciferase activity. In deletional and mutational studies we identified two Sp1 binding sites located between nucleotides -255 and -106 of the Plg promoter that were required for the full response of the Plg promoter to NGF. In chromatin immunoprecipitation assays the Sp1 transcription factor bound to the endogenous Plg promoter. CONCLUSIONS: These results suggest that Plg gene expression is up-regulated by neurotrophins that may provide a previously unrecognized mechanism for enhancing the effects of neurotrophins via the proteolytic activity of plasmin.

La acrilamida, contaminante químico de procesado: revisión / Acrylamide formation in foods: a review Acrylamide

La acrilamida, 'probable carcinógeno para los humanos',mutágeno de categoría 2 y tóxico para la reproducción de categoría 3según la UE, se comporta como neurotóxico tras exposiciones agudas. A pesar de que se recomienda disminuir los niveles de exposición, el tabaquismo, la exposición ocupacional y la exposición dietética son fuentes de acrilamida para el hombre. De entre todos los alimentos, son los ricos en carbohidratos y los elaborados a altas temperaturas, los que mayores niveles de este tóxico presentan. En la presente revisión se explica la formación de acrilamida en los alimentos, se describen sus efectos tóxicos, se citan los métodos analíticos usados en su determinación, se recopilan datos sobre los niveles detectados en distintos alimentos y se enumeran los datos más recientes sobre la ingesta en distintas poblaciones (AU)

Acrylamide formation in foods: A review Acrylamide,'probable carcinogenic for humans', mutagenic type 2 and toxic for reproduction type 3 for the European Union, produces neurotoxicity after acute expositions. Although recommendations are given to minimize the exposition levels to this compound, smoking and occupational and dietary exposures are important acrylamide sources. Among foods, those rich in carbohydrates and those cooked at high temperatures present the highest acrylamide concentrations. The present revision points out the acrylamide formation in foods, its toxic effects and the analytical methods used in its determination. Moreover, data are given about acrylamide levels in foods and dietary intakes in different populations (AU)

A genomic view of the complexity of mammalian proteolytic systems.

Proteolytic enzymes play an essential role in different physiological processes, including development, reproduction and host defence, as well as in numerous pathologies, like inflammatory diseases, neurological disorders or cancer. The completion of the human genome sequence allowed us to determine that more than 2% of all human genes are proteases or protease inhibitors, reflecting the importance of proteolysis in human biology. To understand better the complexity of proteases in human and other model organisms, we have used the available genome sequences of different mammalian organisms, including mouse, rat and chimpanzee, to identify and compare their degradomes, the complete set of protease genes in these species. Surprisingly, the rodent protease complement is more complex when compared with that of primates, mainly due to the expansion of protease families implicated in reproduction and host defence. Similarly, most differences between human and chimpanzee proteases are found in genes implicated in the immune system, which might explain some of the differences between both organisms. We have also found several genes implicated in reproduction, nutrition and the immune system, which are functional in rat, mouse or chimpanzee, but have been inactivated by mutations in the human lineage. These findings suggest that pseudogenization of specific protease genes has been a mechanism contributing to the evolution of the human genome. Finally, we found that proteases implicated in human hereditary diseases, and especially in neurodegenerative disorders, are highly conserved among mammals.

Interleukin-6-induced plasminogen gene expression in murine hepatocytes is mediated by transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta).

An emerging area of research has demonstrated that plasminogen functions in the acute-phase response to tissue injury, neoplastic growth or infection. We have previously shown that the acute-phase mediator, interleukin (IL)-6, increases circulating plasminogen levels via upregulation of plasminogen promoter activity. We also identified a putative IL-6 responsive element (nt -791 to -783; IL6-RE) in the plasminogen gene that is required for maximal stimulation of promoter activity by IL-6. For the present study, we investigated the transcription factors and signaling pathway mediating the response of the plasminogen gene to IL-6. In electrophoretic mobility shift assays (EMSAs), a radiolabeled oligonucleotide IL6-RE probe formed specific complexes with nuclear proteins from untreated hepatocytic cells. The extent of complex formation was markedly increased using nuclear proteins from IL-6-treated cells. Complex formation was abolished by an oligonucleotide with the consensus CCAAT/enhancer binding protein (C/EBP) sequence. Furthermore, complexes were supershifted by antibodies to C/EBPbeta. Treatment of Hepa 1-6 cells with the mitogen-activated protein kinase (MAPK) inhibitor, PD-98059, inhibited IL-6-stimulated plasminogen promoter activity. These results suggest that transcription factor C/EBPbeta and the MAPK pathway play key roles in the response of the plasminogen gene to IL-6, thus elucidating a major mechanism by which the plasminogen system is upregulated to perform its crucial functions in the acute-phase response.