Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC.

Paclitaxel (PTX) is a frequently used anticancer drug that causes peripheral neuropathy. Transient receptor potential ankyrin 1 (TRPA1), a plasma membrane calcium channel, has been associated with PTX toxicity and with other chemotherapy agents such as oxaliplatin and vincristine. However, the effect of PTX on the functional expression and calcium currents of TRPA1 has not been determined. The present study shows the effect of PTX on TRPA1 activity in a neuronal cell line (SH-SY5Y). The effect of PTX on the expression of TRPA1 was assessed through quantitative PCR and Western blot analyses to determine the relative mRNA and protein expression levels. To assess the effect on calcium flux and currents, cells were exposed to PTX; simultaneously, a specific agonist and antagonist of TRPA1 were added to evaluate the differential response in exposed versus control cells. To assess the effect of PKA, PKC and PI3K on PTX-induced TRPA1 increased activity, selective inhibitors were added to these previous experiments. PTX increased the mRNA and protein expression of TRPA1 as well as the TRPA1-mediated Ca2+ currents and intracellular Ca2+ concentrations. This effect was dependent on AITC (a selective specific agonist) and was abolished with HC-030031 (a selective specific antagonist). The inhibition of PKA and PKC reduced the effect of PTX on the functional expression of TRPA1, whereas the inhibition of PI3K had no effects. PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.

Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity.

BACKGROUND: Intracellular calcium (Ca2+) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca2+ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes. METHODS: Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated. RESULTS: Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect. CONCLUSION: Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

Hill Modified, a Novel Approach: Technique Description and Experience in Patients with Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease among patients with obesity, with an associated prevalence of 39 to 61% between the population who attends a bariatric surgery evaluation. Laparoscopic sleeve gastrectomy (LSG) has become a popular and valid option for obesity treatment, even though the literature is ambivalent regarding the increase or decrease in GERD after this surgery. Thus, it is necessary to propose new surgical techniques as a solution to GERD in patients with a concomitant LSG or with a history of it. Therefore, we present a modified technique based on Hill's gastropexy described originally in 1967. OBJECTIVE: Describe and propose a surgical procedure for GERD management based on the Hill technique that can be applied in all patients who undergo an LSG or with a history of it. METHODS: Retrospective observational study with a prospective database in which we described, Hill modified technique in a group of 16 patients with GERD who underwent this procedure concomitantly with an LSG or who presented with GERD after LSG with a 3-year follow-up. The surgical technique is based on an intra-abdominal esophageal length of a minimum of 3 cm and posterior fixation of the gastroesophageal junction to the crus. RESULTS: Postoperative controls have shown satisfactory results in the control and management of GERD symptoms in this group of patients, with very few to no complications associated with the procedure and without reintervention or medication out of the standard protocol. CONCLUSION: Hill modified technique can be used and presented as an option for GERD control in patients with LSG.

Effect of flipped classroom methodology on the student performance of gastrointestinal and renal physiology entrants and repeaters.

BACKGROUND: Physiology is a subject that is considered difficult; it is associated with academic failure and causes high levels of stress and anxiety in students. METHODS: This study compared the effectiveness of a traditional lecture-based methodology with that of a flipped classroom scheme focusing on cooperative ludic learning among gastrointestinal and renal physiology students. Two groups were subjected to these two different methods to teach gastrointestinal and renal physiology content divided into 14 topics. Additionally, two subgroups were identified in each group: entrants and repeaters. There were no differences in age or gender between the subgroups. RESULTS: Levels of self-perceived stress (measured by the SISCO scale), biological stress (measured by awakening salivary cortisol levels), and anxiety (measured by the Zung scale) were high in all of the students; the cortisol levels increased in the entrants and some of the scores in SISCO scale increased in the repeaters, throughout the study. The self-reported study time was longer in the students subjected to the flipped classroom-based method. The final exam results were better only in the new students facing the flipped methodology, but not in the repeaters, who scored lower on the final evaluation. The quantitative and qualitative assessments completed by the participants regarding the different aspects of the flipped-classroom-based methodology were favorable; however, the participants believed that traditional lectures should be maintained for specific topics. CONCLUSIONS: A methodology based on flipped teaching was an effective strategy to improve academic performance ingastrointestinal and renal physiology, but only in new students.

NCS-1 en la función neuronal / NCS-1 in neuronal function

NCS-1 es una proteína unidora de calcio, que regula el funcionamiento de otras proteínas, con las cuales interactúa a nivel molecular. Su expresión es amplia y no limitada a neuronas. Sus efectos incluyen la regulación de receptores, canales iónicos y enzimas que intervienen en múltiples funciones neuronales. NCS-1 regula la actividad del receptor D2 de dopamina y del receptor A2A de adenosina, ambos fundamentales en diversos procesos de comunicación que involucran control emocional y control de movimientos en varios circuitos. NCS-1 también regula la actividad del receptor de IP3, un canal de calcio intracelular fundamental en la regulación de la homeostasis de este ion, interactúa con IP kinasas, las cuales a su vez desencadenan cascadas de señalización intracelular y modula la actividad de canales de calcio presinápticos; todos estos efectos redundan en regulación de la liberación de neurotransmisores y por ende, de la plasticidad sináptica, lo cual ha sido probado en diversos modelos experimentales. NCS-1 también parece estar involucrada en la regulación de otros canales iónicos de calcio y de potasio que podrían influir en la homeostasis eléctrica de las neuronas y en la supervivencia neuronal a través de la regulación de vías proapoptóticas. Estos amplios efectos de NCS-1 motivan a profundizar la investigación en los mecanismos involucrados en la regulación que ejerce sobre sus proteínas blanco y en nuevos efectos que ayuden a entender el rol de esta proteína en diversos procesos fisiológicos y fisiopatológicos(AU)

NCS-1 is a calcium-binding protein, which regulates the functioning of diverse proteins, with which interacts to a molecular level. Its expression is widespread and it is not limited to neurons. Its effects include the regulation of receptors, ion channels and enzymes, which intervene in multiple neuronal functions. NCS-1 regulates the functioning of D2 dopamine receptor and adenosine A2A receptor, both fundamental in diverse communication processes that involve emotional and movement control in a variety of neural circuits. NCS-1 also regulates the activity of IP 3 receptor, an intracellular calcium ion channel (which is crucial in the regulation of calcium homeostasis), interacts with the IP kinases, which trigger intracellular signaling cascades, and modulates the activity of presynaptic calcium channels. All these effects lead to the regulation of neurotransmitters release and thus, synaptic plasticity, which had been proved in diverse experimental models. NCS-1 also appears to be involved in the regulation of other calcium and potassium channels, which can influence the neuron electric homeostasis and survival through the modulation of proapoptotic pathways. These broad NCS-1 effects motivates further research of the specific mechanisms that are involved in the regulation that this protein exerts on its target proteins and in new effects that may help to understand the role of this protein in physiological and pathophysiological processes(AU)

Effectiveness of nursing intervention for adult patients experiencing chronic pain: a systematic review.

OBJECTIVES: To determine the best available evidence regarding the effectiveness of nursing interventions for adult patients experiencing chronic pain. TYPES OF STUDIES: Randomized Controlled Trials (RCT) and Quasi-Randomized Controlled Trials. TYPES OF PARTICIPANTS: Participants were adults, aged at least 18 years, suffering from chronic pain (lasting for longer than six months). Pain of oncological origin and patients admitted in a hospital, were excluded. TYPES OF INTERVENTIONS: Non pharmacological nursing interventions for chronic pain. TYPES OF OUTCOME MEASURES: The primary outcome measure was chronic pain, and secondary outcome measures were: disability, depression, dependence and health related quality of life. SEARCH STRATEGY: All studies, published and unpublished, in English and Spanish, carried out between January 1997 and December 2007 were retrieved.. SELECTION OF STUDIES: The methodological quality of included articles was assessed by two independent reviewers using appropriate critical appraisal tools from the Joanna Briggs Institute. DATA EXTRACTION AND ANALYSIS: Data were independently extracted by two reviewers, using the standardised data extraction tool from the Joanna Briggs Institute.A meta-analysis was not possible as the trials were heterogeneous in their interventions, characteristics of the populations, intervention duration measurement instruments and outcomes measures. RESULTS: 1,666 references were identified that fit the aim of the review. 92 articles were retrieved, of which 13 were chosen to be critically appraised for their methodological quality. In the end, eight controlled trials were included.The main results were:Other outcome measures showed an improvement in the quality of life (sensorial stimulation and guided imagery), in depression, disability and empowerment (music therapy) and physical functioning (program of psycho-education).The main limitations of this review were: excluding studies were the professional performing the interventions were not detailed or the intervention was not carried out by a nurse and that the search strategy was limited up to 2007. IMPLICATIONS FOR PRACTICE: Listening to music, a cognitive-behavioural treatment programme, magnetic therapy, sensorial stimulation, a psychoeducation programme and guided imagery are nursing interventions that helps to reduce the chronic pain in adults and may be used as contributory to the pharmacological treatment. Short exercises for increasing endurance does not reduce pain. IMPLICATIONS FOR RESEARCH: For future reviews we do not recommend the inclusion of different interventions for the reduction of chronic pain, due to the great number and variability of intervention, but the development of a SR on specific interventions.

Evaluación de la técnica anestésica con remifentanilo y midazolam en el legrado obstétrico / Evaluation of the anesthesic technology (skill) with remifentanilo and midazolam in the obstetric legrado

El legrado uterino obstétrico es un procedimiento muy frecuente, realizado de manera ambulatoria. La anestesia para procedimientos ambulatorios debe propender por la seguridad, la satisfacción del paciente y una rápida recuperación sin efectos secundarios, como náuseas y vómito o dolor en el periodo postoperatorio. El uso de opioides de acción ultracorta no se ha estudiado como posibilidad anestésica para este tipo de procedimientos. Objetivos. El siguiente estudio prospectivo pretende evaluar, según la satisfacción, la viabilidad de la analgesia intravenosa con remifentanilo y el control de la ansiedad con midazolam. Métodos. En esta serie de casos prospectiva se incluyeron pacientes programadas para legrado obstétrico ambulatorio. Durante el procedimiento se administró midazolam como ansiolítico a dosis de 0,03 mg/kg y bolos intraoperatorios de remifentanilo, 0,5 a 1 mg/kg, a discreción del anestesiólogo. Para la analgesia postoperatoria se administró dipirona, 50 mg/kg. Se evaluó la satisfacción del paciente y del cirujano, los consumos analgésicos y las variables hemodinámicas, así como la necesidad de soporte respiratorio, las náuseas, el vómito y el dolor en el postoperatorio. Resultados. La efectividad de la técnica fue mayor de 88 por cien, la satisfacción de las pacientes y la del cirujano fueron buenas: 9,5 y 8,8, respectivamente en una escala donde 10 es óptimo. No se presentaron cambios hemodinámicos relevantes ni complicaciones respiratorias. Conclusión. La técnica empleada es viable, logra una adecuada satisfacción, sin efectos adversos mayores, y podría ser aplicable a otros procedimientos de carácter similar. Este estudio abre el espacio y plantea interrogantes susceptibles de posterior investigación, con diferente diseño y un mayor número de pacientes.