Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice

Acid-sensing ion channels (ASIC) open in response to extracellular acidosis. ASIC1a, a particular subtype of these channels, has been described to have a postsynaptic distribution in the brain, being involved not only in ischemia and epilepsy, but also in fear and psychiatric pathologies. High-frequency stimulation of skeletal motor nerve terminals (MNTs) can induce presynaptic pH changes in combination with an acidification of the synaptic cleft, known to contribute to muscle fatigue. Here, we studied the role of ASIC1a channels on neuromuscular transmission. We combined a behavioral wire hanging test with electrophysiology, pharmacological, and immunofluorescence techniques to compare wild-type and ASIC1a lacking mice (ASIC1a −/− knockout). Our results showed that 1) ASIC1a −/− female mice were weaker than wild type, presenting shorter times during the wire hanging test; 2) spontaneous neurotransmitter release was reduced by ASIC1a activation, suggesting a presynaptic location of these channels at individual MNTs; 3) ASIC1a-mediated effects were emulated by extracellular local application of acid saline solutions (pH = 6.0; HEPES/MES-based solution); and 4) immunofluorescence techniques revealed the presence of ASIC1a antigens on MNTs. These results suggest that ASIC1a channels might be involved in controlling neuromuscular transmission, muscle contraction and fatigue in female mice.Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Lino, Noelia Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: González Inchauspe, Carlota María Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Gonzalez, Laura Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Wunsch, Amanda M.. University of Iowa; Estados UnidosFil: Wemmie, John A.. University of Iowa; Estados UnidosFil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

An investigation to enhance understanding of the stimulation of weed seedling emergence by soil disturbance

Enhanced understanding of soil disturbance effects on weed seedling recruitment will help guide improved management approaches. Field experiments were conducted at 16 site-years at 10 research farms across Europe and North America to (i) quantify superficial soil disturbance (SSD) effects onChenopodium album emergence and (ii) clarify adaptive emergence behaviour in frequently disturbed environments. Each site-year contained factorial combinations of two seed populations (local and common, with the common population studied at all site-years) and six SSD timings [0, 50, 100, 150, 200 day-degrees (d°C, base temperature 3°C) after first emergence from undisturbed soil]. Analytical units in this study were emergence flushes. Flush magnitudes (maximum weekly emergence per count flush) and flush frequencies (flushes year−1) were compared between disturbed and undisturbed seedbanks. One year after burial, SSD promoted seedling emergence relative to undisturbed seedbanks by increasing flush magnitude rather than increasing flush frequency. Two years after burial, SSD promoted emergence through increased flush magnitude and flush frequency. The promotional effects of SSD on emergence were strongest within 500 d°C following SSD; however, low levels of SSD-induced emergence were detected as late as 3000 d°C following SSD. Accordingly, stale seedbed practices that eliminate weed seedlings should occur within 500 d°C of disturbance, because few seedlings emerge after this time. However, implementation of stale seedbed practices will probably cause slight increases in weed population densities throughout the year. Compared with the common population, local populations exhibited reduced variance in total emergence measured within sites and across SSD treatments, suggesting thatC. albumadaptation to local pedo-climatic conditions involves increased consistency in SSD-induced emergence

Desenlaces clínicos de los pacientes con diabetes e hiperglucemia de estrés que presentaron infección por SARS-CoV-2

Introduction. Diabetes and stress hyperglycemia (SH) have been related with poorer clinical outcomes in patients infected by SARS-CoV-2 and at risk for severe disease.Objective. To evaluate clinical outcomes in three groups of patients (with diabetes, without diabetes and stress hyperglycemia [SH]) with SARS-CoV-2 infection.Materials and methods. A retrospective cohort study was conducted in Cali-Colombia. Patients aged ≥18 years with a diagnosis of SARS-CoV-2 infection managed in the emergency room, hospitalization or intensive care unit (ICU) between March 2020 and December 2021 were included. Immunocompromised patients and pregnant women were excluded. Patients were classified in three groups: without diabetes, with diabetes and SH. A comparison between the groups was performed. Results. A total of 945 patients were included (59.6% without diabetes, 27% with diabetes and 13.4% with SH). Fifty-five-point three percent required ICU management, with a higher need in patients with SH (89.8%) and diabetes (67.1%), with no difference between these groups (p=0.249). A higher chance of death was seen in SH vs. without diabetes (adjOR= 8.12, 95% CI 5.12-12.88, p<0.01). Frequency of acute respiratory distress syndrome, need for invasive mechanical ventilation, use of vasopressors and inotropes, the need for de novo renal replacement therapy and mortality was higher in patients with metabolic alterations (diabetes and SH). Conclusions. Diabetes and SH are associated to worse clinical outcomes and mortality in patients with COVID-19. These patients should be identified early and considered as high risk at moment of COVID-19 diagnosis that allow to mitigate adverse outcomes.Introducción. La diabetes y la hiperglucemia de estrés (HE) se han relacionado con peores desenlaces clínicos en pacientes infectados por SARS-CoV-2 y con riesgo de enfermedad grave. Objetivo. Evaluar los resultados clínicos en tres grupos de pacientes (con diabetes, sin diabetes e hiperglucemia de estrés [SH]) con infección por SARS-CoV-2.Materiales y métodos. Se realizó un estudio de cohorte retrospectivo en Cali-Colombia. Se incluyeron pacientes ≥18 años con diagnóstico de infección por SARS-CoV-2 atendidos en urgencias, hospitalización o unidad de cuidados intensivos (UCI) entre marzo de 2020 y diciembre de 2021. Se excluyeron pacientes inmunocomprometidos y mujeres embarazadas. Los pacientes fueron clasificados en tres grupos: sin diabetes, con diabetes e HE. Se realizó una comparación entre los grupos.Resultados. Se incluyeron un total de 945 pacientes (59,6% sin diabetes, 27% con diabetes y 13,4% con HE). El 55,3% requirió manejo en UCI, con mayor necesidad en pacientes con HE (89,8%) y diabetes (67,1%), sin diferencia entre estos grupos (p=0,249). Se observó una mayor probabilidad de muerte en HE vs. sin diabetes (adjOR= 8,12, 95% IC 5,12-12,88, p<0,01). La frecuencia de síndrome de distrés respiratorio agudo, necesidad de ventilación mecánica invasiva, uso de vasopresores e inotrópicos, necesidad de terapia de reemplazo renal de novo y la mortalidad fue mayor en pacientes con alteraciones metabólicas (diabetes e HE).Conclusiones. La diabetes y la HE se asociaron a peores resultados clínicos y mortalidad en pacientes con COVID-19. Estos pacientes deben ser identificados tempranamente y considerados de alto riesgo al momento del diagnóstico de COVID-19 que permitan mitigar los desenlaces adversos

Most worrysome weeds in Spain

Se presentan los resultados de una encuesta realizada durante el periodo de junio a octubre de 2014, y en la que participaron 315 técnicos de campo de toda España. Los datos están disponibles en Internet y su análisis permite concluir que a) las malas hierbas preocupan tanto como las plagas y enfermedades; b) respecto a los métodos de control, el control químico con herbicidas es el más usado y el considerado más eficaz; se han detectado las malas hierbas más preocupantes en una serie de cultivos, incluyendo el motivo de la preocupación. En cultivos leñosos, destaca “Conyza” por su dificultad de control, en arroz destacan “Echinochloa” y “Cyperus”; en algodón y maíz preocupan “Abutilon”, “Chenopodium”, “Cyperus”, Echinochloa y Sorghum; en cultivos extensivos de secano, la preocupación no está tan concentrada en pocas especies, destacando malas hierbas gramíneas en trigo y cebada junto con Centaurea, que es considerada preocupante adicionalmente en el cultivo del girasol. Finalmente, se seleccionan arvenses de preocupación creciente, entre las que destacan “Abutilon”, “Centaurea”, “Chenopodium” y “Sorghum”.Since June to October 2014, 315 Spanish field advisors participated in a survey. Data is available on internet and results show that a) weeds are as worrying as other pests and diseases; b) chemical control is the most used weed control method and is considered to be the most efficient one; c) knowledge transfer in weed management is largely dependant on herbicide industry; d) most worrying weeds have been identified for several crops, as well as the reasons why they are considered worrysome. In permanent crops, “Conyza” is refered to be by far the worst weed, mainly because it is difficult to control; in rice, the worst weeds are “Echinochloa” and “Cyperus”; in corn and cotton “Abutilon”, “Chenopodium”, “Cyperus”, “Echinochloa” and “Sorghum”; in annual dryland crops weed problems are less focused, being the most worrying weeds annual grasses in wheat and barley, besides “Centaurea”, which is also considered to be a problem in sunflower. Finally, there are weeds of increasing threat like “Abutilon”, “Centaurea”, “Chenopodium” and “Sorghum”

Análisis de sistemas bucoadhesivos

Objetivo: El objetivo de este estudio es el diseño de un parche bucoadhesivo para la administración transbucal de clorhidrato de doxepina utilizando diferentes polímeros así como la caracterización de dichos sistemas en cuanto al análisis calorimétrico y la capacidad de hinchamiento. Materiales y métodos: Se ha utilizado clorhidrato de doxepina y diferentes polímeros, carboximetilcelulosa sódica, hidroxipropilmetilcelulosa y chitosan. La calorimetría diferencial de barrido (DSC) se ha realizado en un dispositivo Mettler FP 80 equipado con un horno FP 85 y la capacidad de hinchamiento utilizando placas de agar. Resultados: Se obtienen termogramas de los parches y las mezclas físicas donde se observan transiciones endotérmicas entre 30 y 120º C y el pico endotérmico del principio activo en las mezclas físicas binarias. La entalpía de deshidratación es similar en los polímeros de carboximetilcelulosa sódica y chitosan (281 J/g) siendo menor en la película de hidroxipropilmetilcelulosa (251 J/g), al igual que el porcentaje de hidratación donde se demuestra que los parches elaborados con hidroxipropilmetilcelulosa presenta menor tendencia a captar agua (55,91 %) frente al 67,04 % y 67,30 % de la carboximetilcelulosa sódica y chitosan, respectivamente. Conclusión: Los resultados obtenidos muestran que existe compatibilidad entre los componentes de la formulación y los datos de entalpía se correlacionan con los datos obtenidos en el ensayo de hinchamiento.Aim: The aim of this study is to design a bucoadhesive patch for the transbuccal administration of doxepin hydrochloride using different polymers as well as the characterization of these systems for calorimetric analysis and the swelling capacity. Materials and methods: Doxepin hydrochloride was used as well as various polymers; carboxymethylcellulose sodium, hydroxypropylmethyl cellulose and chitosan. Differential scanning calorimetry (DSC) was carried out using a Mettler FP 80 device equipped with a FP 85 oven and the swelling capacity using agar plates. Results: Thermograms obtained patches and physical mixtures where there are endothermic transitions between 30 and 120º C and the endothermic peak of the active principle in binary physical mixtures. Dehydration enthalpy is similar in polymers of carboxymethylcellulose sodium and chitosan (281 J/g), the film having less hydroxypropylmethylcellulose (251 J/g), the percentage of moisture shows that the patches prepared with hydroxypropylmethylcellulose have less tendency to collect water (55.91 %) compared to 67.04 % and 67.30 % with sodium carboxymethylcellulose and chitosan, respectively. Conclusion: The results show that there is compatibility between the components of the formulation and the enthalpy data correlate with the data obtained in the swelling test

Aplastic anemia and severe pancytopenia during treatment with peg-interferon, ribavirin and telaprevir for chronic hepatitis C

Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin. Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe hematological abnormalities or aplastic anemia (AA) have not been described. We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011. Among 142 cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were identified and three were consistent with the diagnosis of AA. Mean age was 59 years, five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation. Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy. Three patients had pre-treatment hematological abnormalities related to splenomegaly. In six patients, antiviral treatment was interrupted at the onset of hematological abnormalities. Two patients died due to septic complications and one patient due to acute alveolar hemorrhage. The remaining patients recovered. Severe pancytopenia and especially AA, are not rare during triple therapy with telaprevir in patients with advanced liver disease. Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications

Weight-length relationships, weight conversion factors and condition factor trends for two stocks of black anglerfish (Lophius budegassa) in southern Bay of Biscay, Galician waters and northern Atlantic areas from a decade

The weight-length relationship has a wide application in fish biology and fisheries management, such as for predicting weight from length data, or for the calculation of production and biomass of a fish stock. Weight-length relationship, weight conversion factors and condition factor are presented from a decade (2006 to 2015) for both stocks of black anglerfish (Lophius budegassa) in southern Bay of Biscay and Galician waters (ICES Div. VIIIc-IXa, southern stock) and in Celtic Seas (ICES Div. VIIb,c,h,j,k, northern stock). A total of 2035 and 1263 specimens were sampled respectively in each stock from commercial landings and research surveys. Total length [Lt (cm)], total weight [Wt (g)], “commercial” weight (gutted with liver) [Wgl (g)] and “scientific” weight (gutted without liver) [Wg (g)] were obtained. The weight-length relationships for the combined sexes were: Lt = 0.020 Wt2.916; Lt = 0.017 Wgl2.929; Lt = 0.017 Wg2.922 in Div. VIIIc-IXa, and Lt = 0.025 Wt2.841; Lt = 0.013 Wgl2.984; Lt = 0.013 Wg2.971 in Div. VIIb,c,h,j,k. These updated values can be used in the annual assessment of the state of both stocks in the ICES working group, replacing those previous estimated more than a decade ago. The conversion factor (total weight - gutted weight) here estimated is also useful in fisheries management due to the commercial landings of this species are available in gutted weight. The evolution of the condition factor along the year, indicator of nutritional status evolution, is estimated and can be a proxy for estimating the spawning season. Its evolution is studied throughout the year for immature and mature individuals of each sex. The results are similar to the previously estimated in other studies