Preoperative pregabalin prevents succinylcholine-induced fasciculation and myalgia: A meta-analysis of randomized trials.

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction; however, its use is associated with fasciculation and myalgia. We performed a systematic review and meta-analysis of randomized controlled clinical trials comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included with a total of 481 patients - 241 in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR = 0.69, 95% CI 0.56-0.84, P < .001), which remained statistically significant for pregabalin (RR = 0.71, 95% CI 0.54-0.93, P = .013) and gabapentin (RR = 0.61, 95% CI 0.45-0.82, P = .001) separately. There was no difference in fasciculations between the groups (RR = 0.92, 95% CI 0.82-1.03, P = .148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24 h of surgery.

Patient-reported outcomes in RA patients treated with tofacitinib or bDMARDs in real-life conditions in two Latin American countries.

OBJECTIVE: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. METHODS: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). RESULTS: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients' mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (-2.55[.30] vs. -2.52[.26]), HAQ-DI score (-.56[.07] vs. -.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (-2.37[.22] vs. -2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported. CONCLUSION: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs. CLINICAL TRIAL NUMBER: NCT03073109.

Factores asociados al consumo de sustancias psicoactivas de un grupo de pacientes con diagnóstico de esquizofrenia de una institución de salud mental de Medellín, Antioquia / Factors associated with the consumption of psychoactive substances in a group of patients diagnosed with schizophrenia from a mental health institution in Medellín, Antioquia / Fatores associados ao consumo de substâncias psicoativas em um grupo de pacientes com diagnóstico de esquizofrenia de uma instituição de saúde mental de Medellín, Colômbia

Objetivo: establecer la relación entre factores sociodemográficos y clínicos con el con­sumo de sustancias psicoactivas (SPA) en un grupo de pacientes con diagnóstico de esquizofrenia, atendidos en una institución de salud mental de la ciudad de Medellín, Colombia. Metodología: estudio observacional, retrospectivo de intención analítica, de un grupo de 268 pacientes atendidos en una institución de salud mental de Medellín, en los últi­mos seis meses del año 2021. Se identificaron factores sociodemográficos, de consumo de SPA y clínicos como tipo de medicamentos, reingresos hospitalarios y adherencia al tratamiento farmacológico. Se consideraron valores de Odds Ratio con intervalo de confianza (IC95%) y se identificaron factores asociados al consumo por medio de un modelo de regresión logística. Resultados: se identificó que el 34.7% de la muestra reporta consumo de SPA; variables clínicas asociadas, tipo de medicamentos, número de ingresos hospitalarios y adherencia al tratamiento. Se encontraron diferencias significativas en la edad entre el grupo de consumidores y no consumidores, con una mediana de edad menor para el grupo de consumidores. Se determinó que ser hombre, tener una mediana de edad de 27 años y estar desempleado representa un riesgo mayor para el consumo de SPA. Finalmente se establece que la edad, el sexo, la ocupación y la adherencia al tratamiento, podrían predecir el consumo en un 34%. Conclusiones: los pacientes jóvenes, en su mayoría hombres, con diagnóstico de es­quizofrenia, tienen mayor riesgo de consumo de SPA, lo que implica mayor riesgo de recaídas y menor adherencia al tratamiento farmacológico.

Objective: to establish the relationship between sociodemographic and clinical factors with the consumption of psychoactive substances (PAS) in a group of patients diagnosed with schizophrenia, treated at a mental health institution in the city of Medellín, Colombia. Methodology: observational, retrospective study with analytical intent, of a group of 268 patients treated at a mental health institution in Medellín, in the last six months of 2021. Sociodemographic, SPA consumption, and clinical factors such as the type of medication, hospital readmissions and adherence to drug treatment were identified. Odds Ratio values with confidence interval (95% CI) were considered and factors associated with consumption were identified by means of a logistic regression model. Results: it was shown that 34.7% of the sample reports PAS consumption, associated clinical variables, type of medication, number of hospital admissions, and adherence to treatment. Significant differences in age were found between the group of users and non-users, with a lower median age for the group of users. It was determined that being a man, having a median age of 27 years and being unemployed represent a greater risk for the consumption of PAS. Finally, it is established that age, sex, occupation, and adherence to treatment could predict consumption by 34%. Conclusions: young patients, mostly men, with a diagnosis of schizophrenia, have a higher risk of PAS consumption, which implies a higher risk of relapse and lower adherence to drug treatment.

Objetivo: estabelecer a relação entre fatores sociodemográficos e clínicos com o consumo de substâncias psicoativas (SPA) em um grupo de pacientes diagnosticados com esquizofrenia, atendidos em uma instituição de saúde mental na cidade de Medellín, Colômbia. Metodologia:estudo observacional, retrospectivo com intenção analítica, de um grupo de 268 pacientes atendidos em uma instituição de saúde mental em Medellín, nos últimos seis meses de 2021. Foram identificados fatores sociodemográficos, consumo de SPA e clínicos quanto ao tipo de medicamento, readmissões hospitalares e adesão ao tratamento medicamentoso. Valores de Odds Ratio com intervalo de confiança (IC95%) foram considerados e fatores associados ao consumo foram identificados por meio de um modelo de regressão logística. Resultados: identificou-se que 34,7% da amostra relata consumo de SPA; variáveis clínicas associadas, tipo de medicamento, número de internações e adesão ao tratamento. Foram encontradas diferenças significativas de idade entre o grupo de usuários e não usuários, com menor mediana de idade para o grupo de usuários. Foi determinado que ser homem, ter idade mediana de 27 anos e estar desempregado representa maior risco para o consumo de SPA. Por fim, estabelece-se que idade, sexo, ocupação e adesão ao tratamento poderiam predizer o consumo em 34%. Conclusões: pacientes jovens, em sua maioria homens, com diagnóstico de esquizofrenia, apresentam maior risco de consumo de SPA, o que implica maior risco de recaída e menor adesão ao tratamento medicamentoso

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Work productivity in rheumatoid arthritis patients from two Latin American countries treated with tofacitinib or biological DMARDs.

OBJECTIVE: To evaluate work productivity of adult Latin American patients with rheumatoid arthritis (RA) treated with tofacitinib and biological disease-modifying anti-rheumatic drugs (bDMARDs) measured by the Work Productivity and Activity Impairment (WPAI) in RA questionnaire at 0- and 6-month follow-up. METHODS: This non-interventional study was performed in Colombia and Peru. Evaluated the effects of tofacitinib and bDMARDs in patients with RA after failure of conventional DMARDs. The WPAI-RA questionnaire was administered at baseline and at the 6-month (±1 month) follow-up. The results are expressed as least squares means (LSMs), and standard errors (SEs). RESULTS: One hundred patients treated with tofacitinib and 70 patients treated with bDMARDs were recruited. Twenty-eight percent of patients from the tofacitinib group and 40.0% from the bDMARDs group were working for pay at baseline. At month 6, the changes in absenteeism, presenteeism, and work impairment due to health were -18.3% (SE 7.7), -34.8% (SE 5.9), and -11.0% (SE 16.5), respectively, in the tofacitinib group and -19.4% (SE 8.0), -34.8% (SE 6.2), and -15.9% (SE 15.0), for the bDMARD group. CONCLUSION: For patients who reported working, there were improvements in presenteeism, absenteeism, and work impairment due to health in both groups. TRIAL REGISTRATION: NCT03073109.

[Quantitative and qualitative analysis of the influence of confinement by COVID-19 in fracture patients entered in a traumatology service at a third level hospital]. / Análisis cuantitativo y cualitativo de la influencia del confinamiento por COVID-19 en los pacientes con fractura ingresados en un servicio de traumatología en un hospital de tercer nivel.

INTRODUCTION: The COVID-19 pandemic has led to the confinement of approximately one third of the world population, causing a drastic change in the activities of daily life with many repercussions at the health, economic and social levels. OBJECTIVES: The objective of the present work is to present the epidemiological variations in the production of fractures in the period of mandatory confinement in our reference population. METHODS: Analytical retrospective comparative study of two groups of patients: Group A: patients admitted before the state of alarm that forced confinement in the period from January 13 to March 13 compared to Group B: patients admitted in the two months of confinement, until the de-escalation period began, March 13-May 13. Epidemiological variables including age, personal history, type of fracture, mechanism of injury, outpatient rate, and hospital stay were recorded. RESULTS: A total of 190 patients were included. 112 in the pre-confinement period and 78 in the confinement (30% decrease). The mean age (p = 0.007) and falls at home (p < 0.001) were higher in the confinement group. The postoperative (p = 0.006) and overall (p < 0.001) hospital stay were significantly less in the confinement group. No differences were found in the anatomical location of the lesion, sex, comorbidities, mechanism of injury, outpatient rate, or death. CONCLUSIONS: Based on the results of our study, the period of forced confinement due to the COVID-19 pandemic has produced a drastic decrease in the total number of fractures admitted to the traumatology service of a third level hospital. On the other hand, osteoporotic hip fractures have not varied in their incidence and a decrease in the average postoperative and overall stay has been observed.

Surgically treated calcaneal joint fractures: what does postoperative computed tomography give us? / Fracturas intraarticulares de calcáneo tratadas quirúrgicamente: ¿qué nos aporta la tomografía computarizada postoperatoria?

INTRODUCTION: There is currently great controversy about the ideal treatment of intraarticular calcaneal fractures. The objective of this study is to determine the usefulness of postoperative computed tomography (CT). PATIENTS AND METHODS: We conducted a retrospective descriptive study of patients operated on in the period 2007 to 2015 in our center. Epidemiological variables, specific fracture data, surgical intervention as well as results and complications were collected. The radiological evaluation was performed using simple radiology (Böhler angle) and coronal CT (congruence of posterior subtalar joint). For the functional results we use the AOFAS hindfoot scale and the EVA scale for the level of pain. RESULTS: We included 46 fractures in 43 patients (three bilateral). Thirty-five were male and eight female, with an average age of 42 years (18-79) and an average follow-up of 57.39 months (33-129). Preoperative CT was performed in all cases, of which 11 were Sanders ii, 23 type iii and 12 type iv. Postoperative CT was only performed in 17 cases. The subsequent subtalar reduction measured by CT was satisfactory (articular step < 2 mm) in 12 cases. The average presurgical Böhler angle was 6.45 ± 10.21 ([-22]-25) and the post-surgical angle of 20.46 ± 7.09 (4-38). Subtalar osteoarthritis developed in 19 cases (symptomatic in 12) and calcaneo-cuboid osteoarthritis in six cases (only one symptomatic). The AOFAS was 74.28 ± 18.98 (27-100) and the EVA was 4.14 ± 2.98 (2-9). A CT scan with a step of less than 2 mm was statistically significant, with a higher result on the AOFAS scale (77.17 average points) as well as lower EVA on average (2.83) (p = 0.002). Regarding the Böhler, it was statistically significant the relationship of an angle > 20° post-surgical with higher AOFAS (80.82) and lower VAS (3.18) (p = 0.001). The literature search obtained a total of 117 articles that met the search criteria, of which only 29 requested postoperative CT. CONCLUSIONS: The indication of postoperative CT in patients operated by intraarticular calcaneal fracture is the best technique to corroborate the correct reduction of the subtalar joint surface, although it is not universally accepted, according to the literature.

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk.

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a-/- mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling.

Experience using the «Shetty test¼ for initial foot and ankle fracture screening in the Emergency Department. / Experiencia con la aplicación del test de Shetty para el despistaje inicial de fracturas del pie y tobillo en el área de Urgencias.

OBJECTIVE: The indiscriminate practice of radiographs for foot and ankle injuries is not justified and numerous studies have corroborated the usefulness of clinical screening tests such as the Ottawa Ankle Rules. The aim of our study is to clinically validate the so-called Shetty Test in our area. MATERIAL AND METHOD: A cross-sectional observational study by applying the Shetty test to patients seen in the Emergency Department. RESULTS: We enrolled 100 patients with an average age of 39.25 (16-86). The Shetty test was positive on 14 occasions. Subsequent radiography revealed a fracture in 10 cases: 4 were false positives. The test was negative in the remaining 86 patients and radiography confirmed the absence of fracture (with sensitivity of 100% and specificity of 95.56%, positive predictive value of 71.40%, and negative predictive value of 100%). CONCLUSIONS: The Shetty test is a valid clinical screening tool to decide whether simple radiography is indicated for foot and ankle injuries. It is a simple, quick and reproducible test.

Biotransformation of magnetic nanoparticles as a function of coating in a rat model.

Long-term in vivo studies in murine models have shown that DMSA-coated nanoparticles accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected. During that time, nanoparticles undergo a process of biotransformation either by reducing the size or the particle aggregation or both. Using a rat model, we have evaluated the transformations of magnetic nanoparticles injected at low doses. Particles with two different coatings, dimercaptosuccinic acid (NP-DMSA) and polyethylene glycol (NP-PEG-(NH2)2) have been administered to animals, to evaluate the role of coating in the degradation of the particles. We have found that low doses of magnetic nanoparticles are quickly metabolized by the animals. In fact, using a nanoparticle dose four times lower than in previous experiments, NP-DMSA were not observed 24 h after the administration either in the liver or in the lungs. Interestingly, an increased amount of ferritin, the iron storage protein, was observed in liver tissues from rats that were treated with the low dose of NP-DMSA in comparison with the control ones, suggesting a rapid metabolization of the particles into ferritin iron. On the other side we have found that, NP-PEG-(NH2)2 are still detectable in several organs 24 h after their administration at low doses. Probably, due to the longer circulation times of the NP-PEG-(NH2)2, there is a delay in the arrival of the particles to the tissue and this is the reason why we are able to see the particles 24 h post-administration. PEG coating could also be protecting the nanoparticles from rapid degradation of the reticuloendothelial system. Knowledge on the biodistribution, circulation time and degradation processes is required to gain a better understanding of the safety evaluation of this kind of nanomaterial for biomedical applications.

Ab initio studies of the electronic structure of L-cysteine adsorbed on Ag(111).

We have performed ab initio calculations for the adsorption of L-cysteine on Ag(111) using density functional theory. We have focused on two possible adsorbed species: the L-cysteine radical (•S-CH(2)-CH-NH(2)-COOH) adsorbed almost flat at a bridge site, slightly displaced toward an fcc location, and the zwitterionic radical Z-cysteine (•S-CH(2)-CH-NH(3)(+)-COO(-)) adsorbed at a bridge site, shifted to a hcp site forming a (4 × 4) unit cell (θ = 0.06) and a (√3 × âˆš3) R 30° unit cell (θ = 0.33), respectively. Special attention has been paid to the electronic structure of the system. The adsorbate-silver bond formation has been exhaustively investigated by analyzing the density of states projected onto the different atoms of the molecule, and by charge density difference calculations. A complicated interplay between sp and d states of silver in the formation of bonds between the adsorbates and the surface has been found. The role of the carboxyl group in the interaction with the surface has been also analyzed.

Optimization of the crossflow microfiltration of arazá juice (Eugenia stipitata) under different operation modes / Optimización del proceso de microfiltración tangencial de jugo dearazá (Eugenia stipitata) a diferentes modos de operación

This study analyzed the effects of temperature and transmembrane pressure on the crossflow microfiltration process of arazá (Eugenia stipitata) juice treated with a commercial pectic enzyme preparation, thus finding the appropriate operation values of the process. Clarified arazá juice was obtained with a crossflow microfiltration pilot plant equipped with ceramic membranes with a 0.48 m2 total effective filtration area and mean pore diameter of 0.2 µm. The juice was evaluated at transmembrane pressures 1.5,3.0 and 4.5 bar, and at temperatures of 30, 35 and 40ºC at different volumetric reduction factors. The tests were carried out using three systems (total recirculation, concentration, and continuous mode). In total recirculation, it was found that the most influential variable was the transmembrane pressures, and that the partial enzymatic liquefaction of the arazá juice, prior to microfiltration, produced an unusual pattern of permeate flux, characterized by an increase following an abrupt decrease at 4.5 bar and 6.5 m/s. In this case, the highest values of the flux were obtained when compared with those obtained during the crossflow microfiltration in concentration mode. After reaching the value of volumetric reduction factor (3.2), during the crossflow microfiltration in continuous mode, it was not necessary to stop the process as the volumetric reduction factor remained constant for the continuous removal of retained, achieving a high permeate fluxin a short period of time 319 L/(h m2), thus adding to the economic viability of the process.

En este trabajo se analizaron los efectos de la temperatura y la presión transmembrana sobre el proceso de microfiltración tangencial de jugo de arazá (Eugenia stipitata) tratado con una preparación comercial de enzimas pectolíticas, encontrando los valores adecuados de operación. Se obtuvo un jugo clarificado de arazá con un equipo piloto de microfiltración tangencial provisto de membranas cerámicas de 0,48 m2 de área total efectiva de filtración, diámetro promedio de poro de 0,2 µm, evaluado a diferentes presionestransmembrana de 1,5; 3,0 y 4,5 bar y temperaturas de 30, 35 y 40ºC, a diferentes factores de reducciónvolumétrica. Las pruebas fueron llevadas a cabo utilizando tres modos de operación: recirculación total,concentración y continuo. En recirculación total, se encontró que la variable más influyente sobre el proceso fue la presión transmembrana y que la licuefacción enzimática parcial realizada al jugo de arazá, previo a la microfiltración, produjo un patrón inusual del flux de permeado, caracterizado por un incremento después de una disminución abrupta cuando se trabajó a 4,5 bar y 6,5 m/s. En este caso se encontraron los valores más altos del flux al compararse con los obtenidos durante la microfiltración tangencial en modo de concentración. Una vez alcanzado el valor de factor de reducción volumétrica (3,2) durantela microfiltración tangencial en modo continuo no fue necesario detener el proceso, ya que el factor de reducción volumétrica se mantuvo constante durante la eliminación continua de retenido, lográndose altos flujos de permeado en corto tiempo (319 L/(h m2)), facilitando la viabilidad económica del proceso.

The Caenorhabditis elegans genome: a multifractal analysis.

The Caenorhabditis elegans genome has several regular and irregular characteristics in its nucleotide composition; these are observed within and between chromosomes. To study these particularities, we carried out a multifractal analysis, which requires a large number of exponents to characterize scaling properties. We looked for a relationship between the genetic information content of the chromosomes and multifractal parameters and found less multifractality compared to the human genome. Differences in multifractality among chromosomes and in regions of chromosomes, and two group averages of chromosome regions were observed. All these differences were mainly dependent on differences in the contents of repetitive DNA. Based on these properties, we propose a nonlinear model for the structure of the C. elegans genome, with some biological implications. These results suggest that examining differences in multifractality is a viable approach for measuring local variations of genomic information contents along chromosomes. This approach could be extended to other genomes in order to characterize structural and functional regions of chromosomes.

Highly conserved regions in the 5' region of human olfactory receptor genes.

Regulation of human olfactory receptor (hOR) genes is a complex process of control and signalization with various structures and functions that are not clearly understood. To date, nearly 390 functional hOR genes and 462 pseudogenes have been discovered in the human genome. Enhancer models and trans-acting elements for the regulation of different hOR genes are among the few examples of our knowledge concerning regulation of these genes. We looked for upstream control elements that might help explain these complex control mechanisms. To analyze the human olfactory gene family, we looked for functional genes and pseudogenes common to all hOR genes obtained from public databases. Subsequently, we analyzed sequences upstream of the transcription start sites with data mining and bioinformatics tools. We found two highly conserved regions, which we called HCR I and HCR II, upstream of the transcription start sites in 77 hOR genes and 87 pseudogenes. These regions showed possible enhancer functions common to both genes and pseudogenes, an intriguing feature that may be associated with the expression of pseudogenes. Based on these HCRs, we propose a structural model of gene regulation for the olfactory gene family.

First principles calculations of mechanical properties of 4,4'-bipyridine attached to Au nanowires.

A first attempt is made to calculate the forces involved in the breaking of nanowires consisting of a molecule attached to nanosized metallic pieces. As a model system, we consider different Au nanowires connected by a 4,4(')-bipyridine or pyrazine molecule, for which density functional calculations were performed at different elongations. The geometry of the system was optimized for different forces applied. In all cases the calculated maximum forces were close to 1 nN, which is of the order of the experimental values, and smaller than the corresponding to the rupture of the Au-Au chain (1.5-1.6 nN). When 4,4(')-bipyridine is attached to Au monoatomic nanowire, the maximum force required to break the Au-Au bond may be lowered to values close to that obtain to break the Au-N bond, but when 4,4(')-bipyridine is attached to small Au clusters, the breaking of the nanowire takes place at the Au-N bond only.

Valores de referencia para el control de calidad de plantas medicinales como materia prima para fines terapéuticos en Colombia / Reference values for quality control of medicinal plants as raw materials for therapeutic purposes in Colombia

Se presentan los valores obtenidos, en el proceso de evaluación y desarrollo de métodos, para el control de calidad de 11 de las plantas medicinales aprobadas en Colombia: Semillas de anís (Pimpinella anisum), bulbos de ajo (Allium sativum), corteza de canela (Cinnamomum zeylanicum.), semillas de cardamomo (Elettaria cardamomum), flores de caléndula (Calendula officinalis), raíces de genciana (Gentiana lutea), hojas de hamamelis (Hammamelis virginiana), semillas de lino (Linum usitatissimum), semillas entera de trigo (Triticum aestivum), rizomas y raíces de valeriana (Valeriana officinalis) y flores de manzanilla (Matricaria chamomilla). Los análisis realizados a cada planta medicinal comprenden: La descripción morfológica macro- y microscópica, la cuantificación de cenizas totales, el contenido de sustancias extraíbles, la pérdida de peso por secado, el contenido de aceites esenciales y la identificación por cromatografía de capa fina de marcadores taxonómicos

Differential Ca2+ and Sr2+ regulation of intracellular divalent cations release in ventricular myocytes.

The regulation of the Ca2+ -induced Ca2+ release (CICR) from intracellular stores is a critical step in the cardiac cycle. The inherent positive feedback of CICR should make it a self-regenerating process. It is accepted that CICR must be governed by some negative control, but its nature is still debated. We explore here the importance of the Ca2+ released from sarcoplasmic reticulum (SR) on the mechanisms that may control CICR. Specifically, we compared the effect of replacing Ca2+ with Sr2+ on intracellular Ca2+ signaling in intact cardiac myocytes as well as on the function of single ryanodine receptor (RyR) Ca2+ release channels in panar bilayers. In cells, both CICR and Sr2+ -induced Sr2+ release (SISR) were observed. Action potential induced Ca2+ -transients and spontaneous Ca2+ waves were considerably faster than their Sr2+ -mediated counterparts. However, the kinetics of Ca2+ and Sr2+ sparks was similar. At the single RyR channel level, the affinities of Ca2+ and Sr2+ activation were different but the affinities of Ca2+ and Sr2+ inactivation were similar. Fast Ca2+ and Sr2+ stimuli activated RyR channels equally fast but adaptation (a spontaneous slow transition back to steady-state activity levels) was not observed in the Sr2+ case. Together, these results suggest that regulation of the RyR channel by cytosolic Ca2+ is not involved in turning off the Ca2+ spark. In contrast, cytosolic Ca2+ is important in the propagation global Ca2+ release events and in this regard single RyR channel sensitivity to cytosolic Ca2+ activation, not low-affinity cytosolic Ca2+ inactivation, is a key factor. This suggests that the kinetics of local and global RyR-mediated Ca2+ release signals are affected in a distinct way by different divalent cations in cardiac muscle cells.

[Effect of tobramycin with topical diclofenac on arachidonic acid in endotoxin-induced uveitis]. / Efecto de tobramicina más diclofenaco tópico sobre el ácido araquidónico en la uveítis inducida por endotoxina.

PURPOSE: We studied if tobramycin associated to sodium diclofenac modifies the drug effect of the latter on arachidonic acid metabolism in an endotoxin induced uveitis (EIU) model in albino rabbits. METHODS: Experimental uveitis was induced by intravitreal injection of a 10 ng lipopolysaccharide A Salmonella typhimurium endotoxin dissolved in 5 microl saline solution in the right eye of experimental animals. We have used 48 animals (4 groups of 12 animals each). The control group (G-I) was injected with saline solution (5 microl); the endotoxin group (G-II) was injected with 5 microl of ET; group III and IV were injected with the same amount of ET and treated with topical sodium diclofenac (1%) (Group III) and tobramycin and sodium diclofenac (0.3%) (Group IV) two hours before the administration of endotoxin and then every two hours until 24 hours, when we determined E2 prostaglandin and B4 leukotriene concentration in aqueous humor obtained by paracentesis of the anterior chamber. RESULTS: We observed how the E2 prostaglandin concentration was reduced in the two treatment groups compared with the endotoxin group (p<0.01). However, there were no differences between groups III and IV (p>0.01). There was a mild increase of B4 leukotriene in both treatment groups, which was not significant in relationship to the endotoxin group (p>0.01). No differences were found between the two treatment groups (p>0.01). CONCLUSION: Using the association of tobramycin does not affect the action of sodium diclofenac in arachidonic acid metabolism in endotoxin induced uveitis.

A functional assay for paralytic shellfish toxins that uses recombinant sodium channels.

Saxitoxin (STX) and its derivatives are highly toxic natural compounds produced by dinoflagellates commonly present in marine phytoplankton. During algal blooms ("red tides"), shellfish accumulate saxitoxins leading to paralytic shellfish poisoning (PSP) in human consumers. PSP is a consequence of the high-affinity block of voltage-dependent Na channels in neuronal and muscle cells. PSP poses a significant public health threat and an enormous economic challenge to the shellfish industry worldwide. The standard screening method for marine toxins is the mouse mortality bioassay that is ethically problematic, costly and time-consuming. We report here an alternative, functional assay based on electrical recordings in cultured cells stably expressing a PSP target molecule, the STX-sensitive skeletal muscle Na channel. STX-equivalent concentration in the extracts was calibrated by comparison with purified STX, yielding a highly significant correlation (R=0.95; N=30) between electrophysiological determinations and the values obtained by conventional methods. This simple, economical, and reproducible assay obviates the need to sacrifice millions of animals in mandatory paralytic shellfish toxin screening programs.