Cholinergic signaling plasticity maintains viscerosensory responses during Aspiculuris tetraptera infection in mice small intestine

"Intestinal parasites alter gastrointestinal (GI) functions like the cholinergic function. Aspiculuris tetraptera is a pinworm frequently observed in laboratory facilities, which infests the mice cecum and proximal colon. However, little is known about the impact of this infection on the GI sensitivity. Here, we investigated possible changes in spontaneous mesenteric nerve activity and on the mechanosensitivity function of worm-free regions of naturally infected mice with A. tetraptera. Infection increased the basal firing of mesenteric afferent nerves in jejunum. Our findings indicate that nicotinic but not muscarinic receptors, similarly affect spontaneous nerve firing in control and infected animals; these axons are mainly vagal. No difference between groups was observed on spontaneous activity after nicotinic receptor inhibition. However, and contrary to the control group, during infection, the muscarinic signaling was shown to be elevated during mechanosensory experiments. In conclusion, we showed for the first time that alterations induced by infection of the basal afferent activity were independent of the cholinergic function but changes in mechanosensitivity were mediated by muscarinic, but not nicotinic, receptors and specifically by high threshold nerve fibers (activated above 20 mm Hg), known to play a role in nociception. These plastic changes within the muscarinic signaling would function as a compensatory mechanism to maintain a full mechanosensory response and the excitability of nociceptors during infection. These changes indicate that pinworm colonic infection can target other tissues away from the colon.

Métodos de aprendizaje colaborativos, creativos e interdisciplinarios en petrología

Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasFALSEsubmitte

Physiological concentrations of zinc have dual effects on P2X myenteric receptors of guinea pig

"We, hereby, characterize the pharmacological effects of physiological concentrations of Zinc on native myenteric P2X receptors from guinea-pig small intestine and on P2X2 isoforms present in most myenteric neurons. This is the first study describing opposite effects of Zinc on these P2X receptors. It was not possible to determine whether both effects were concentration dependent, yet the inhibitory effect was mediated by competitive antagonism and was concentration dependent. The potentiating effect appears to be mediated by allosteric changes induced by Zinc on P2X myenteric channels, which is more frequently observed in myenteric neurons with low zinc concentrations. In P2X2-1 and P2X2-2 variants, the inhibitory effect is more common than in P2X myenteric channels. However, in the variants, the potentiatory effect is of equal magnitude as the inhibitory effect. Inhibitory and potentiatory effects are likely mediated by different binding sites that appear to be present on both P2X2 variants. In conclusion, in myenteric native P2X receptors, Zinc has quantitatively different pharmacological effects compared to those observed on homomeric channels: P2X2-1 and P2X2-2. Potentiatory and inhibitory Zinc effects upon these receptors are mediated by two different binding sites. All our data suggest that myenteric P2X receptors have a more complex pharmacology than those of the recombinant P2X2 receptors, which is likely related to other subunits known to be expressed in myenteric neurons. Because these dual effects occur at Zinc physiological concentrations, we suggest that they could be involved in physiological and pathological processes.

Hyperinsulinemic Hypoglycemia Secondary to Multiple β cell Adenomas in a Boxer Bitch

Background: The most frequent pancreatic tumours are derived from insulin-secreting β cells, commonly called insulinomas; these are characterised by high insulin secretion causing hypoglycaemia and clinical signs such as seizures, tremors, weakness, and polyphagia, among others. In dogs, this tumour represents 30 is indicative of insulinoma. Unfortunately, the specificity of the amended insulin:glucose ratio is poor. In the past, there has been confusion with respect to their biological nature, because, based on histological and electron microscopic evaluations, 60% of these neoplasms are carcinomas and 40% are adenomas. Nevertheless, these claims were not substantiated and most insulinomas are currently considered to be malignant (carcinomas). The objective of this paper was to present a rare case of a Boxer dog that had three β cell tumours of the pancreas, which produced hyperinsulinemia and hypoglycemia. Although this is not a malignant tumour, we demonstrated, as described in the literature, that regardless of the histopathological classification, insulin-producing tumours have a poor prognosis in dogs

Genomic organization of purinergic P2X receptors

"Purinergic P2X receptors are a family of ligand-gated cationic channels activated by extracellular ATP. P2X subunit protein sequences are highly conserved between vertebrate species. However, they can generate a great diversity of coding splicing variants to fulfill several roles in mammalian physiology. Despite intensive research in P2X expression in both central and peripheral nervous system, there is little information about their homology, genomic structure and other key features that can help to develop selective drugs or regulatory strategies of pharmacological value which are lacking today. In order to obtain clues on mammalian P2X diversity, we have performed a bioinformatics analysis of the coding regions and introns of the seven P2X subunits present in human, simian, dog, mouse, rat and zebrafish. Here we report the arrangements of exon and intron sequences, considering its number, size, phase and placement; proposing some ideas about the gain and loss of exons and retention of introns. Taken together, these evidences show traits that can be used to gain insight into the evolutionary history of vertebrate P2X receptors and better understand the diversity of subunits coding the purinergic signaling in mammals.

Tratamiento farmacológico para COVID-19 en protocolos latinoamericanos: Una revisión narrativa de la eficacia y seguridad

Introduction: The pandemic caused by SARS-CoV-2 has put the global scientific community in an accelerated pace of research for an effective treatment for COVID-19. Objective: To identify and evaluate drugs in Latin American protocols of pharmacological treatment for COVID-19. Method: The evidence and mega trial results available to date on the most frequent medications are analyzed. Results: The most common drugs in national protocols are hydroxychloroquine, lopinavir/ritonavir, and remdesivir. None of the drugs that collect the most data from clinical studies, with the except for dexamethasone in a small subgroup of patients, so far showed significant differences in mortality. Conclusions: The emerging situation of COVID-19 has determined hasty and controversial decision-making based on questionable and/or low-quality studies. This highlights the provisional nature of the information and the possibility of generating changes as more results become available. Advance medication authorization exposes a known problem. Although regulatory agility is required at this time, speed should not overlap with basic ethical standards and trust in evidence.TÍTULO PT: Tratamento farmacológico para COVID-19 em protocolos latinoamerica: uma revisão narrativa da eficácia e da segurança Introducción: La pandemia causada por el SARS-Cov-2 ha puesto a la comunidad científica mundial en ritmo acelerado de investigación y busca por un tratamiento efectivo para COVID-19. Objetivo: Identificar y evaluar medicamentos en protocolos latinoamericanos de tratamiento farmacológico para el COVID-19. Método: Se analiza la evidencia y resultados de mega ensayo disponibles hasta la fecha sobre los medicamentos más frecuentes. Resultados: Los medicamentos más frecuentes en protocolos nacionales son hidroxicloroquina, lopinavir/ritonavir y remdesivir. Ninguno de los medicamentos que recopilan mayor cantidad de datos provenientes de estudios clínicos, a excepción de la dexametasona en un subgrupo reducido de pacientes, mostró, hasta el momento, diferencias significativas en la mortalidad. Conclusión: La situación emergente de la COVID-19 ha determinado la toma de decisiones apresuradas y controversiales con base a estudios cuestionables y/o de baja calidad. Esto pone de relieve el carácter provisorio de la información y la posibilidad de generar cambios a medida que se dispongan de más resultados. La autorización anticipada de medicamentos expone un problema conocido. A pesar de que la agilidad regulatoria es necesaria en este momento, la velocidad no debe sobreponerse a los patrones básicos éticos y de confianza en la evidencia.Título PT: Tratamento farmacológico para COVID-19 em protocolos Latinoamérica: Uma revisão narrativa da eficácia e da segurança Introducción: La pandemia causada por el SARS-Cov-2 ha puesto a la comunidad científica mundial en ritmo acelerado de investigación y busca por un tratamiento efectivo para COVID-19. Objetivo: Identificar y evaluar medicamentos en protocolos latinoamericanos de tratamiento farmacológico para el COVID-19. Método: Se analiza la evidencia y resultados de mega ensayo disponibles hasta la fecha sobre los medicamentos más frecuentes. Resultados: Los medicamentos más frecuentes en protocolos nacionales son hidroxicloroquina, lopinavir/ritonavir y remdesivir. Ninguno de los medicamentos que recopilan mayor cantidad de datos provenientes de estudios clínicos, a excepción de la dexametasona en un subgrupo reducido de pacientes, mostró, hasta el momento, diferencias significativas en la mortalidad. Conclusiones: La situación emergente de la COVID-19 ha determinado la toma de decisiones apresuradas y controversiales con base en estudios cuestionables y/o de baja calidad. Esto pone de relieve el carácter provisorio de la información y la posibilidad de generar cambios a medida que se dispongan de más resultados. La autorización anticipada de medicamentos expone un problema conocido. A pesar de que la agilidad regulatoria es necesaria en este momento, la velocidad no debe sobreponerse a los patrones básicos éticos y de confianza en la evidencia

Correlation Analysis of People Attitude and the Development of Chemical Processes in the Human Body

This chemical science investigation was made to efficiently understand the way in which ionic substances operate in the human body and its correlation that they can have with the attitude of people, whose evaluation was carried out according to the analysis of three actions developed in the human body, such as digestion factors, family, work and social relationships (emotional actions) and the health of 10 people surveyed in the city of Tijuana, Baja California. This evaluation had a main hypothesis at the beginning of the investigation, indicating that, of the three factors mentioned, the one that links emotions had the greatest effect on the behavior of the people evaluated, with the aspect of family and work relationships being of primary importance; followed by the health factor and finally the digestion factor. This scientific study included an analysis of three principal aspects, being first the daily food as a nutrition action, followed a chemical analysis of ionic substances of the human body of the 10 persons evaluated. In addition, the third aspect evaluated was the emotional state of the people and a clinic with the urine analysis were considered to indicate the pH, temperature and oxygen level of each person, with which the main chemical elements of the ionic substances that can circulate through the human body were obtained, as part of the food intake. and drinks, emotional factor and digestion. This scientific study was made from March to May of 2023

Intracellular cross talk and physical interaction between two classes of neurotransmitter-gated channels

Fast chemical communications in the nervous system are mediated by several classes of receptor channels believed to be independent functionally and physically. We show here that concurrent activation of P2X 2 ATP-gated channels and 5-HT 3 serotonin-gated channels leads to functional interaction and nonadditive currents (47-73% of the predicted sum) in mammalian myenteric neurons as well as in Xenopus oocytes or transfected human embryonic kidney (HEK) 293 cell heterologous systems. We also show that these two cation channels coimmunoprecipitate constitutively and are associated in clusters. In heterologous systems, the inhibitory cross talk between P2X 2 and 5-HT 3 receptors is disrupted when the intracellular C-terminal domain of the P2X 2 receptor subunit is deleted and when minigenes coding for P2X 2 or 5-HT 3 A receptor subunit cytoplasmic domains are overexpressed. Injection of fusion proteins containing the C-terminal domain of P2X 2 receptors in myenteric neurons also disrupts the functional interaction between native P2X 2 and 5-HT 3 receptors. Therefore, activity-dependent intracellular coupling of distinct receptor channels underlies ionotropic cross talks that may significantly contribute to the regulation of neuronal excitability and synaptic plasticity

Oligometástasis en cáncer de mama: estrategias y perspectivas para el control local del tumor primario y de las metástasis

El cáncer de mama metastásico, identificado en el momento del diagnóstico o desarrollado tras transcurrir cierto tiempo desde la aparición de la enfermedad primaria, presenta una naturaleza heterogénea. Los resultados obtenidos gracias a los avances farmacológicos nos motivan a explorar la suplementación del tratamiento empleando técnicas de abordaje local. Esta revisión está dirigida a analizar la información disponible en la literatura sobre dos aspectos fundamentales en el cáncer de mama. Por un lado, el control del tumor primario, tanto en la mama como en los ganglios linfáticos locorregionales, y por otro, el control local de las metástasis en función de su localización en los casos de enfermedad oligometastásica. Las principales estrategias para llevar a cabo dicho control local son la cirugía, la radioterapia, incluyendo la radioterapia estereotáctica corporal o la radioterapia de haz externo, y la ablación por radiofrecuencia. Las evidencias discutidas señalan que, a la espera de más resultados procedentes de ensayos controlados aleatorios y de estudios específicos de la enfermedad, las pacientes con oligometástasis deben ser evaluadas por un equipo multidisciplinar. Las metástasis únicas podrían ser candidatas para tratamiento local, cada vez más eficiente, y esto, en combinación con los avances en la terapia sistémica, podría resultar en un mejor control de la enfermedad. Todas estas alternativas deberían presentarse a las pacientes con la finalidad de seleccionar un tratamiento personalizado, con base en la evidencia científica y en las características propias de su enfermedad, que presuponga un resultado más eficaz.Metastatic breast cancer, identified at the time of diagnosis or developed after a certain period since the onset of the primary disease, presents a heterogeneous nature. The results obtained through pharmacological advances encourage us to explore supplementing the treatment using local management techniques. This review aims to analyze the available literature on two fundamental aspects of breast cancer. On the one hand, the control of the primary tumor, both in the breast and in the locoregional lymph nodes, and on the other hand, the local control of metastases depending on their location in cases of oligometastatic disease. The main strategies for carrying out such local control are surgery, radiotherapy, including stereotactic body radiotherapy or external beam radiotherapy, and radiofrequency ablation. The evidence discussed indicates that, pending further results from randomized controlled trials and disease-specific studies, patients with oligometastasis should be evaluated by a multidisciplinary team. Single metastases could be candidates for local treatment, increasingly efficient, and this, in combination with advances in systemic therapy, could result in better disease control. All these alternatives should be presented to patients with the purpose of selecting a personalized treatment, based on scientific evidence and the unique characteristics of their disease, which presupposes a more effective outcome.AstraZenecaLillyPfizerRoch

Fuentes, síntomas y estrategias de afrontamiento al estrés-competitivo en nadadores

La presente investigación de tipo descriptivo transversal tuvo como objetivo caracterizar el estrés precompetitivo de 123 nadadores mexicanos de categoría master. La edad de los participantes osciló entre los 36 y 92 años de edad. El instrumento utilizado para recoger la información fue el cuestionario FUSIES (fuentes, síntomas y estrategias de afrontamiento al estrés), este se aplicó antes de iniciar una competencia nacional perteneciente al serial master de natación. El instrumento midió la percepción del estrés, bajo una escala tipo Likert de 1= nunca y 5 = extremo, con alfa de Cronbach de .95. Entre los principales resultados se observó un nivel normal bajo de estrés (M = 2.307 ± .5) en los nadadores; las fuentes que generan mayor estrés son la injusticia de autoridades (M = 3.70 ± 1.2), mucho tráfico (M = 3.48 ± 1.1) y no tener dinero (M = 3.28 ± 1.2). A su vez, los síntomas de estrés con mayor puntaje en los nadadores es la preocupación (M = 2.96 ± 1.08), la tensión en la espalda (M = 2.62 ± 1.2) y el tartamudeo (M = 2.34 ± 1.3). En lo relativo a las estrategias de afrontamiento que aplican con mayor frecuencia los nadadores son: ejercitarse (M = 3.59 ± 1.35), buscar la solución del problema (M = 3.51 ± 1.35) y pensar positivamente (M = 3.51 ± 1.31). Concluyendo que el pensar positivamente, les permite reducir sus niveles de preocupación, inseguridad y desesperación pre competitiva, por lo que se asume que los niveles de estrés percibidos se encuentran en un nivel moderado.This transversal descriptive research aimed to characterize the stress-precompetitive 123 swimmer's category Mexican master. The age of participants ranged between 36 and 92 years old. The instrument used to collect information was the questionnaire FUSIES (sources, symptoms and stress coping strategies), this was applied before starting a master serial belonging to national swimming competition. The instrument measures perceived stress, under a Likert scale from 1 = never and 5 = extreme, with Cronbach's alpha of .95. Among the main results normal low stress (M = 2,307 ± 0.5) was observed in swimmers; sources that generate greater stress are the injustice of authorities (M = 3.70 ± 1.2), a lot of traffic (M = 3.48 ± 1.1) and no money (M= 3.28 ± 1.2). In turn, symptoms of stress with the highest score in swimmers is Concern (M= 2.96 ± 1.08), the back strain (M= 2.62 ± 1.2) and stuttering (M= 2.34 ± 1.3). Regarding coping strategies most frequently applied swimmers are: exercise (M= 3.59 ± 1.35), finding the solution (M = 3.51 ± 1.35) and think positively (M = 3.51 ± 1.31). Think positively concluding that allows them to reduce their levels of concern, insecurity and desperation pre-competitive, so it is assumed that levels of perceived stress are at a moderate level.Esta pesquisa descritiva transversal objetivou caracterizar a 123 nadadores o estresse pré-competitiva na natação master mexicana. A idade dos participantes variou entre 36 e 92 anos de idade. O instrumento utilizado para coleta de informações foi o FUSIES (fontes, sintomas e estratégias de confronto do estresse), este foi aplicado antes de iniciar um serial master da competição nacional de natação. O instrumento mediu o estresse percebido com a escala de Likert de 1 = nunca e 5 = sempre, com alfa de Cronbach 0,95. Entre os principais resultados o nível normail-baixo de estresse (M = 2,307 ± 0,5) foi observada nos nadadores; fontes que geram uma maior estresse são a injustiça das autoridades (M = 3,70 ± 1,2), tráfego (M = 3,48 ± 1,1) e não ter dinheiro (M = 3,28 ± 1,2). Por sua vez, sintomas de estresse com o maior número de pontos em nadadores é a preocupação (M = 2,96 ± 1,08), a tensão nas costas (M = 2,62 ± 1,2) e tartamudez (M = 2,34 ± 1,3). No que diz respeito as estratégias de confronto mais frequentemente aplicada pelos nadadores são fazer exercício (M = 3,59 ± 1,35), procurar a solução do problema (M = 3,51 ± 1,35) e pensamento positivo (M = 3,51 ± 1,31). Concluindo que o pensamento positivo, permite-lhes reduzir os seus níveis de preocupação, insegurança e desespero pré competitivo, por isso, assumese que os níveis de estresse percebido estão em um nível moderado