The Cloning and Characterization of a Three-Finger Toxin Homolog (NXH8) from the Coralsnake Micrurus corallinus That Interacts with Skeletal Muscle Nicotinic Acetylcholine Receptors.

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve-diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions.

Analysis of the role of perfusion, mechanical, and electrical stimulation in bioreactors for cardiac tissue engineering.

Since cardiovascular diseases (CVDs) are globally one of the leading causes of death, of which myocardial infarction (MI) can cause irreversible damage and decrease survivors' quality of life, novel therapeutics are needed. Current approaches such as organ transplantation do not fully restore cardiac function or are limited. As a valuable strategy, tissue engineering seeks to obtain constructs that resemble myocardial tissue, vessels, and heart valves using cells, biomaterials as scaffolds, biochemical and physical stimuli. The latter can be induced using a bioreactor mimicking the heart's physiological environment. An extensive review of bioreactors providing perfusion, mechanical and electrical stimulation, as well as the combination of them is provided. An analysis of the stimulations' mechanisms and modes that best suit cardiac construct culture is developed. Finally, we provide insights into bioreactor configuration and culture assessment properties that need to be elucidated for its clinical translation.

Transport-controlled growth decoupling for self-induced protein expression with a glycerol-repressible genetic circuit.

Decoupling cell formation from recombinant protein synthesis is a potent strategy to intensify bioprocesses. Escherichia coli strains with mutations in the glucose uptake components lack catabolite repression, display low growth rate, no overflow metabolism, and high recombinant protein yields. Fast growth rates were promoted by the simultaneous consumption of glucose and glycerol, and this was followed by a phase of slow growth, when only glucose remained in the medium. A glycerol-repressible genetic circuit was designed to autonomously induce recombinant protein expression. The engineered strain bearing the genetic circuit was cultured in 3.9 g L-1 glycerol + 18 g L-1 glucose in microbioreactors with online oxygen transfer rate monitoring. The growth was fast during the simultaneous consumption of both carbon sources (C-sources), while expression of the recombinant protein was low. When glycerol was depleted, the growth rate decreased, and the specific fluorescence reached values 17% higher than those obtained with a strong constitutive promoter. Despite the relatively high amount of C-source used, no oxygen limitation was observed. The proposed approach eliminates the need for the substrate feeding or inducers addition and is set as a simple batch culture while mimicking fed-batch performance.

Effects of PM10 Airborne Particles from Different Regions of a Megacity on In Vitro Secretion of Cytokines by a Monocyte Line during Different Seasons.

Several epidemiological studies have demonstrated that particulate matter (PM) in air pollution can be involved in the genesis or aggravation of different cardiovascular, respiratory, perinatal, and cancer diseases. This study assessed the in vitro effects of PM10 on the secretion of cytokines by a human monocytic cell line (THP-1). We compared the chemotactic, pro-inflammatory, and anti-inflammatory cytokines induced by PM10 collected for two years during three different seasons in five different Mexico City locations. MIP-1α, IP-10, MCP-1, TNF-α, and VEGF were the main secretion products after stimulation with 80 µg/mL of PM10 for 24 h. The THP-1 cells showed a differential response to PM10 obtained in the different sites of Mexico City. The PM10 from the north and the central city areas induced a higher pro-inflammatory cytokine response than those from the south. Seasonal pro-inflammatory cytokine secretion always exceeded anti-inflammatory secretion. The rainy-season-derived particles caused the lowest pro-inflammatory effects. We concluded that toxicological assessment of airborne particles provides evidence supporting their potential role in the chronic exacerbation of local or systemic inflammatory responses that may worsen the evolution of some chronic diseases.

Recombinant protein expression in proteome-reduced cells under aerobic and oxygen-limited regimes.

Industrial cultures are hindered by the physiological complexity of the host and the limited mass transfer capacity of conventional bioreactors. In this study, a minimal cell approach was combined with genetic devices to overcome such issues. A flavin mononucleotide-based fluorescent protein (FbFP) was expressed in a proteome-reduced Escherichia coli (PR). When FbFP was expressed from a constitutive protein generator (CPG), the PR strain produced 47% and 35% more FbFP than its wild type (WT), in aerobic or oxygen-limited regimes, respectively. Metabolic and expression models predicted more efficient biomass formation at higher fluxes to FbFP, in agreement with these results. A microaerobic protein generator (MPG) and a microaerobic transcriptional cascade (MTC) were designed to induce FbFP expression upon oxygen depletion. The FbFP fluorescence using the MTC in the PR strain was 9% higher than that of the WT bearing the CPG under oxygen limitation. To further improve the PR strain, the pyruvate dehydrogenase complex regulator gene was deleted, and the Vitreoscilla hemoglobin was expressed. Compared to oxygen-limited cultures of the WT, the engineered strains increased the FbFP expression more than 50% using the MTC. Therefore, the designed expression systems can be a valuable alternative for industrial cultivations.

Increasing the Pentose Phosphate Pathway Flux to Improve Plasmid DNA Production in Engineered E. coli.

The demand of plasmid DNA (pDNA) as a key element for gene therapy products, as well as mRNA and DNA vaccines, is increasing together with the need for more efficient production processes. An engineered E. coli strain lacking the phosphotransferase system and the pyruvate kinase A gene has been shown to produce more pDNA than its parental strain. With the aim of improving pDNA production in the engineered strain, several strategies to increase the flux to the pentose phosphate pathway (PPP) were evaluated. The simultaneous consumption of glucose and glycerol was a simple way to increase the growth rate, pDNA production rate, and supercoiled fraction (SCF). The overexpression of key genes from the PPP also improved pDNA production in glucose, but not in mixtures of glucose and glycerol. Particularly, the gene coding for the glucose 6-phosphate dehydrogenase (G6PDH) strongly improved the SCF, growth rate, and pDNA production rate. A linear relationship between the G6PDH activity and pDNA yield was found. A higher flux through the PPP was confirmed by flux balance analysis, which also estimates relevant differences in fluxes of the tricarboxylic acid cycle. These results are useful for developing further cell engineering strategies to increase pDNA production and quality.

Clinical Significance of SOX10 Expression in Human Pathology.

The embryonic development of neural crest cells and subsequent tissue differentiation are intricately regulated by specific transcription factors. Among these, SOX10, a member of the SOX gene family, stands out. Located on chromosome 22q13, the SOX10 gene encodes a transcription factor crucial for the differentiation, migration, and maintenance of tissues derived from neural crest cells. It plays a pivotal role in developing various tissues, including the central and peripheral nervous systems, melanocytes, chondrocytes, and odontoblasts. Mutations in SOX10 have been associated with congenital disorders such as Waardenburg-Shah Syndrome, PCWH syndrome, and Kallman syndrome, underscoring its clinical significance. Furthermore, SOX10 is implicated in neural and neuroectodermal tumors, such as melanoma, malignant peripheral nerve sheath tumors (MPNSTs), and schwannomas, influencing processes like proliferation, migration, and differentiation. In mesenchymal tumors, SOX10 expression serves as a valuable marker for distinguishing between different tumor types. Additionally, SOX10 has been identified in various epithelial neoplasms, including breast, ovarian, salivary gland, nasopharyngeal, and bladder cancers, presenting itself as a potential diagnostic and prognostic marker. However, despite these associations, further research is imperative to elucidate its precise role in these malignancies.

Design of microaerobically inducible miniR1 plasmids.

Plasmid DNA manufacture is an essential step to produce gene therapy agents and next-generation vaccines. However, little attention has been paid toward developing alternative replicons that can be coupled with large-scale production conditions. Our results demonstrate that the miniR1 replicon can be efficiently induced by oxygen limitation when a copy of the regulatory protein RepA under control of a microaerobic promoter is used. The results are potentially attractive for industrial applications.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

Purpose Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. Methods Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007–2013 and 2014–2020. Results Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0–6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. Conclusions The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain (AU)

Cerebrospinal fluid: history, collection techniques, indications, contraindications and complications / Líquido cefalorraquidiano: história, técnicas de coleta, indicações, contraindicações e complicações

ABSTRACT This article is based on a historical review of the medical literature with the purpose of acknowledging the historical stages and anatomical findings over the years, which led gradually to performance of the first lumbar puncture by Quincke, as well as collection techniques and analyses, allowing it to be an irreplaceable diagnostic tool in daily clinical practice. Cerebrospinal fluid analyses have continued to develop and nowadays play a major role in diagnosing and understanding the physiopathology of a great variety of neurological conditions. Biomarkers and genetic sequencing have recently been the target of multiple studies and are implicated as promising diagnostic tools of a large range of diseases.

RESUMEN Este artículo se basa en una revisión histórica de la literatura médica cuyo objetivo fue reconocer las fases y los hallazgos anatómicos a lo largo de los años que condujo gradualmente a la primera punción lumbar por Quincke, así como las técnicas y los análisis de recolección; esa punción se ha convertido en una herramienta insustituible de diagnóstico en la práctica clínica diaria. Los análisis del líquido cefalorraquídeo se desarrollaron y hoy tienen un papel importante en el diagnóstico y en la comprensión de la fisiopatología de varias condiciones neurológicas. Recientemente, los biomarcadores y la secuenciación genética fueron objeto de varios estudios y son considerados técnicas de diagnóstico prometedoras para muchas enfermedades.

RESUMO Este artigo se baseia em uma revisão histórica da literatura médica cujo objetivo foi reconhecer as etapas e os achados anatômicos ao longo dos anos do desempenho de Quincke - desde a primeira punção lombar -, bem como as técnicas e as análises de coleta que permitiram que essa punção se tornasse uma ferramenta insubstituível na prática clínica diária. As análises do líquido cefalorraquidiano continuaram se desenvolvendo e hoje desempenham um papel importante no diagnóstico e na compreensão da fisiopatologia de diversas condições neurológicas. Recentemente, biomarcadores e sequenciamento genético foram objeto de vários estudos e são considerados técnicas de diagnóstico promissoras para uma grande variedade de doenças.

Fiabilidad en la evaluación radiológica de la calcificación aórtica abdominal mediante la escala de 24 puntos / Reliability of radiologic evaluation of abdominal aortic calcification using the 24-point scale

Objetivo. La calcificación de la aorta abdominal se asocia a un incremento en el riesgo de morbilidad cardiovascular, y disponer de un método de cuantificación de la misma es clínicamente trascendente. La escala de 24 puntos (AAC-24) es el método estándar para su evaluación en la radiología simple lateral de columna lumbar. El objetivo del estudio ha sido conocer el nivel de acuerdo intra e interobservador que aporta esta escala, teniendo en cuenta la heterogeneidad de la distribución de las calcificaciones en el diseño del análisis estadístico. Material y métodos. Se analizó la concordancia intraobservador (sobre radiografías de 81 pacientes, con una separación de 4 años) y la concordancia interobservador (sobre radiografías de 100 pacientes, con tres evaluadores), utilizando simultáneamente la correlación intraclase y el método gráfico de Bland-Altman. Resultados. El coeficiente de correlación intraclase fue de 0,93 (intervalo de confianza al 95% [IC95%]: 0,6-0,9) y 0,91 (IC95%: 0,8-0,9), intra e interobservador, respectivamente, con un incremento del coeficiente en el tercil de mayor discrepancia. La diferencia de medias osciló entre 0,3 y-1,2 puntos. La amplitud entre los límites de acuerdo, entre 4,7 y 9,4 puntos. Se observó un aumento significativo de las diferencias en relación con el aumento progresivo de la calcificación. Conclusiones. La valoración de la calcificación de la aorta abdominal en radiología simple lateral de columna lumbar mediante la escala AAC-24 es un método fiable y reproducible, observándose un mayor grado de concordancia intra e interobservador en las fases iniciales de la calcificación (AU)

Objective. Calcification of the abdominal aorta is associated with increased cardiovascular morbidity, so a reliable method to quantify it is clinically transcendent. The 24-point scale (AAC-24) is the standard method for assessing abdominal aortic calcification on lateral plain films of the lumbar spine. The aim of this study was to determine the intraobserver and interobserver agreements for the AAC-24, taking into account the heterogeneity of the distribution of the calcifications in the design of the statistical analysis. Material and methods. We analyzed the intraobserver agreement (in plain films from 81 patients, with a four-year separation between observations) and the interobserver agreement (in plain films from 100 patients, with three observers), using both intraclass correlation and Bland-Altman plots. Results. The intraobserver intraclass correlation coefficient was 0.93 (95% confidence interval [CI95%]: 0.6-0.9), and the interobserver intraclass correlation coefficient was 0.91 (CI95%: 0.8-0.9) with an increase in the coefficient in the tercile with the greatest discrepancy. The difference in means ranged from 0.3 to 1.2 points, and the distance between the limits of agreement ranged from 4.7 to 9.4 points. These differences increased significantly as the calcification progressed. Conclusions. Using the AAC-24 on lateral plain films of the lumbar spine is a reliable and reproducible method of assessing calcification of the abdominal aorta; both intraobserver and interobserver agreement are higher during the initial phases of calcification (AU)

Evaluation of cardiopulmonary parameters and recovery from anesthesia in cougars (Puma concolor) anesthetized with detomidine/ketamine and isoflurane or sevoflurane / Avaliação de parâmetros cardiorrespiratórios e recuperação da anestesia em pumas (Puma concolor) anestesiados com detomidina/cetamina e isoflurano ou sevoflurano

The aim of this study was to assess the cardiopulmonary effects, the onset time after the administration of a detomidine/ketamine combination, and the recovery from anesthesia of cougars (Puma concolor) anesthetized with detomidine/ketamine and isoflurane or sevoflurane for abdominal ultrasound imaging. Fourteen animals were randomly allocated into two experimental groups: GISO (n=7) and GSEVO (n=7). Chemical restraint was performed using 0.15mg/kg detomidine combined with 5mg/kg ketamine intramuscularly; anesthesia induction was achieved using 2mg/kg propofol intravenously and maintenance with isoflurane (GISO) or sevoflurane (GSEVO). The following parameters were assessed: heart rate, respiratory rate, systolic and diastolic arterial blood pressure, mean arterial blood pressure, oxyhemoglobin saturation, rectal temperature, central venous pressure, and end-tidal carbon dioxide. The time to sternal recumbency (TSR) and time to standing position (TSP) were also determined. There was not statistically significant difference for the cardiopulmonary variables or TSP whereas TSR was significantly shorter in GSEVO. The time to onset of anesthesia was 11.1±1.2 minutes and 11.3±1.8 minutes for GISO and GSEVO, respectively. The anesthesia of cougars with detomidine/ketamine and isoflurane or sevoflurane was conducted with safety, cardiopulmonary stability, and increased time to sternal recumbency in the GISO group.

O objetivo do presente estudo foi avaliar os efeitos cardiorrespiratórios e a recuperação anestésica de onças-pardas (Puma concolor) submetidas à anestesia com detomidina/cetamina e isofluorano ou sevofluorano para avaliação ultrassonográfica abdominal. Para isso, foram utilizados 14 animais divididos aleatoriamente em dois grupos experimentais GISO (n=7) e GSEVO (n=7). Foram submetidos à contenção química com detomidina 0,15mg/kg associada à cetamina 5mg/kg pela via intramuscular, induzidos com propofol 2mg/kg pela via intravenosa e mantidos com isofluorano (GISO) ou sevofluorano. Foram avaliados os parâmetros: frequência cardíaca e respiratória, pressão arterial sistólica, média e diastólica saturação de oxihemoglobina, temperatura retal, pressão venosa central e fração expirada de dióxido de carbono. O tempo para adoção de decúbito esternal e posição quadrupedal também foram avaliados. Não houve diferença estatística para as variáveis cardiorrespiratórias e no tempo para adoção da posição quadrupedal. O tempo para adoção de decúbito esternal foi significativamente menor no GSEVO em relação ao GISO. Concluiu-se que a anestesia de onças pardas com detomidina/cetamina e isoflurano ou sevoflurano foi realizada de maneira segura, com estabilidade cardiorrespiratória e com aumento no tempo para adoção de decúbito esternal no GISO.

Cambios sintomáticos en policías con estrés postraumático y psicoterapia de grupo / Symptomatic changes in police officers with post-traumatic stress and group psychotherapy

El artículo muestra los cambios sintomáticos que tuvieron Policías colombianos (7 hombres y una mujer con edades entre los 18 y 45) que presentaban estrés postraumático después de un proceso de intervención psico-terapéutica grupal de orientación psicoanalítica. El proceso psicoterapéutico duró 3 meses con una frecuencia de 2 sesiones por semana y una duración de 1.30 hora por sesión. Los cambios sintomáticos fueron evaluados a través de "Escala administrada por el clínico" (Clinician-Administered PTSD Scale, CAPS; Blake, Weathers, Nagy, Kaloupek, Charney y Keane, 1995) y de entrevistas clínicas individuales. Se encontró que en los policías algunos síntomas asociados a los Criterios B, C, D, F, de la escala, se disminuyeron, otros se incrementaron, y en otros no hubo modificaciones.

The article shows the changes that were symptomatic among Colombian Police officers (7 men and one woman aged between 18 and 45) who had post-traumatic stress after an intervention process psychoanalytically oriented group psychotherapy. The psychotherapeutic process lasted 3 months with a frequency of 2 sessions per week and a duration of 1.30 hours per session. Symptomatic changes were assessed by Scale administered by the clinician (Clinician-Administered PTSD Scale, CAPS, Blake, Weathers, Nagy, Kaloupek, Charney and Keane, 1995) and individual clinical interviews. We found that in Police officers, some symptoms associated with Criterion B, C, D, and of the F scale, decreased, in others increased, and there were no other changes.

Grelina, alimentação e exercício físico: os efeitos sobre o controle do apetite / Ghrelin, food intake and physical exercise: the effects about the appetite of control

A obesidade se tornou uma epidemia mundial nos últimos anos e vem trazendo preocupação aos órgãos de saúde pública do mundo todo. Sabe-se que os fatores que levam à obesidade são muitos e que seu tratamento deve ser acompanhado por uma equipe multidisciplinar para obter-se o melhor resultado possível na redução dos efeitos desta doença. É evidenciado que diversos hormônios compõem os mecanismos que regulam o metabolismo energético e o apetite. Muitos deles estão relacionados a aspectos que promovem o surgimento da obesidade, a qual tem relação proporcional ao comprometimento metabólico que acaba refletindo em diversas complicações para a saúde. A inibição ou a estimulação do apetite é componente importante no estudo da obesidade. A descoberta da grelina desencadeou uma cascata de estudos nas áreas de endocrinologia, nutrição e fisiologia do exercício. Muitos destes trabalhos foram desenvolvidos com sujeitos de diferentes composições corporais, gêneros, estados alimentares e com exercícios em diferentes intensidades de esforço. Dessa forma, o objetivo deste trabalho é sintetizar os principais trabalhos que envolvam o hormônio grelina em uma revisão que permita discutir os resultados sobre os efeitos deste hormônio nos diversos tecidos e sua participação na fisiologia humana com intenção de melhor compreensão sobre o assunto.

Evaluación de resultados quirúrgicos de la miectomía como tratamiento de la miocardiopatía hipertrófica obstructiva: experiencia de un centro en Uruguay / Evaluation of surgical results of myectomy in the treatment of hypertrophic obstructive cardiomyopathy: experience of a single center in Uruguay

Introducción: la miectomía quirúrgica del septum interventricular es el gold standard en el tratamiento de la miocardiopatía hipertrófica (MH) que requiere cirugía para alivio sintomático. No se encontró publicada ninguna serie de pacientes tratados mediante miectomía en Uruguay, lo que motivó analizar una serie de nuestro centro, valorando variables para su comparación con series de referencia. Material y método: se incluyeron todos los pacientes con miectomía entre enero de 2001 y enero de 2008. Se consignaron variables demográficas, ecocardiográficas y sobrevida a los 18 y 72 meses. Resultados: se incluyeron 23 pacientes, 14 mujeres. Edad promedio 59 años. Siete presentaban familiar de primer grado con MH. Seis presentaban lesiones coronarias significativas. El promedio del gradiente intraventricular máximo fue 96,32 mmHg, SIVD 21,4 mm y FEVI 66%. 17 tenían SAM, y de ellos, 15 presentaban insuficiencia mitral severa. En el preoperatorio, 14 presentaban CF NYHA III y nueve CF IV; 20 recibieron algún procedimiento asociado. La mortalidad operatoria fue de 8,7% (dos pacientes). El gradiente máximo postoperatorio promedio fue 12 mmHg, SIVD 16,65 mm y FEVI 64%. A los 18 meses, 20 estaban vivos y en CF I. La sobrevida actuarial a seis años fue 76,7%. Conclusiones: en 20 de los 23 pacientes se asoció otro procedimiento, mayormente sustitución valvular mitral. La miectomía redujo significativamente los gradientes intraventriculares, el espesor del SIVD y los síntomas en todos los pacientes (p < 0,0001). La mortalidad operatoria fue de 8,7% (dos pacientes) y la sobrevida actuarial a seis años de 76,7%. Estos resultados se equiparan a series de referencia.

Introduction: surgical septum myectomy remains the gold standard for the treatment of obstructive hypertrophic cardiomyopathy requiring surgery forsymptomatic relief. Wasn’t found in the literature, any series of patients underwent myectomy in Uruguay.Our objetive was the analysis of our center series, assessing variables for comparison with reference series.Materials and methods: were included all patients with myectomy from january 2001 to 2008. Demographicsand ultrasonographics variables, and survival at 18 and 72 months were consignated. Results: Were included 23 patients, 14 women. Mean age 59 years. Seven with a first grade relativeaffected of hypertrophic cardiomyopathy (HM). Six with coronary lessions. The mean maximum intraventricular gradient was 96,32 mmHg, dyastolic interventricular septum wide 21,4 mm, EF 66%. 17with systolic anterior motion, 15 with severe mitral insufficience. Before surgery, 14 shows NYHA functionalclass (FC) III, and 9 FCIV. 20 with one additional surgical procedure. Operative mortality was 8,7% (two patients). The mean maximum intraventriculargradient after surgery was 12 mmHg, dyastolic interventricular septum wide 16,65mmand EF 64%. At 18 months, survival was 20 patients, all in FC I. Actuarial survival at 6 years was 76,7%. Conclussions: 20 of 23 patients with an additional procedure, mainly mitral valve substitution. Myectomyimproved intraventricular gradients, DIVS wide and symptoms in all patients (p<0,0001). Operative mortality was 8,7% (two patients), and actuarialsurvival at 6 years was 76,7%. This results are comparable with reference series.

Transcriptome analysis of the Amazonian viper Bothrops atrox venomgland using expressed sequence tags (ESTs)

Bothrops atrox is a highly dangerous pit viper in the Brazilian Amazon region.We produced a global catalogue of gene transcripts to identify the main toxin and other protein families present in the B. atrox venom gland. We prepared a directional cDNA library, from which a set of 610 high quality expressed sequence tags (ESTs) were generated by bioinformatics processing. Our data indicated a predominance of transcripts encoding mainly metalloproteinases(59% of the toxins). The expression pattern of the B. atrox venom was similar to Bothrops insularis, Bothrops jararaca and Bothrops jararacussu in terms of toxin type, although some differences were observed. B. atrox showed a higher amount of the PIII classof metalloproteinases which correlates well with the observed intense hemorrhagic action of its toxin. Also, the PLA2 content was the second highest in this sample compared to theother three Bothrops transcriptomes. To our knowledge, this work is the first transcriptome analysis of an Amazonian rain forest pit viper and it will contribute to the body of knowledge regarding the gene diversity of the venom gland of members of the Bothropsgenus. Moreover, our results can be used for future studies with other snake species from the Amazon region to investigate differences in gene patterns or phylogenetic relationships.

Níveis de beta-endorfina em resposta ao exercício e no sobretreinamento: [revisão] / Levels of beta-endorphin in response to exercise and overtraining: [review]

O sobretreinamento (ST) é um fenômeno esportivo complexo e multifatorial; e atualmente não existe nenhum marcador independente que possa diagnosticá-lo. Interessantemente, alguns sintomas do ST apresentam relação com os efeitos da b-endorfina (b-end1-31). Alguns de seus efeitos são importantes para o treinamento, como analgesia, maior tolerância ao lactato e euforia do exercício. Esses efeitos podem ser revertidos por destreinamento ou por ST, ocasionando diminuição no desempenho, redução da tolerância à carga e depressão. O exercício físico é o principal estímulo da b-end1-31, pois sua secreção é volume/intensidade dependente, tanto para exercícios aeróbios quanto anaeróbios. No entanto, o treinamento excessivo pode diminuir suas concentrações, alterando assim seus efeitos benéficos para o treinamento. Portanto, a b-end1-31 poderia ser utilizada como um marcador adicional de ST, principalmente porque seus efeitos apresentam extensa relação com os sintomas do ST.

Overtraining (OT) is a complex and multifactorial sport phenomenon, and there is no independent marker that can diagnose OT. Interestingly, some symptoms of OT are related to b-endorphin (b-end1-31) effects. Some of its effects, such as analgesia, increasing lactate tolerance, and exercise-induced euphoria, are important for training. These effects can be reverted by detraining or OT, which may cause decrease in performance, reduced load tolerance, and depression. The main stimulus for b-end1-31 secretion is to exercise because its secretion is volume/intensity dependent for both aerobic and anaerobic exercise. Excess training, however, may reduce b-end1-31 concentrations, thus altering its beneficial effects. Therefore, b-end1-31 could be used as an additional OT marker, mainly because its effects are strongly related to OT symptoms.

Unidades de Cuidados Intermedios. Consecuencias asistenciales en un hospital de referencia / Intermediate care units. Health careconsequences in a reference hospital

Introducción. Las Unidades de Cuidados Intermedios constituyen formas de prestación asistencial a pacientes potencialmente críticos que permiten mejorar la relación coste-beneficio de la asistencia ofertada por los Servicios de Medicina Intensiva (SMI). Objetivo. Analizar la repercusión asistencial que en un centro docente de referencia ha tenido la apertura estable de una Unidad de este tipo. Diseño. Prospectivo. Período. Desde el inicio de 2003 a finales de 2005. Ámbito. Servicio de Medicina Intensiva, con acreditación docente, dotado de 15 camas de Unidad de Cuidados Intensivos (UCI) convencional y 4 camas de cuidados intermedios. Pacientes y método. Análisis, en 3.392 ingresos consecutivos en el SMI de datos demográficos (sexo y edad, tipo de paciente y procedencia del ingreso), de gravedad (SAPS 2), pronóstico (MPM II 0 y SAPS 2) y carga asistencial (NEMS). Análisis específico de la estancia y de la mortalidad (intra y post UCI). Resultados. La apertura estable de una Unidad de Cuidados Intermedios se asocia con un incremento de pacientes atendidos por el SMI, y permite identificar claramente dos tipos distintos de pacientes conforme la ubicación ligada a la causa de ingreso. Los pacientes atendidos en la Unidad de Cuidados Intermedios tienen una menor estancia, una menor gravedad, un mejor pronóstico de supervivencia y una menor carga asistencial. Sin embargo, la puesta en marcha de esta prestación no disminuye el intervalo de mortalidad total (intra + post UCI). Conclusión. La puesta en marcha de una Unidad de Cuidados Intermedios dependiente de un SMI incrementa la capacidad asistencial del mismo y del centro al que presta servicio sin afectar a la mortalidad global

Introduction. Intermediate Care Units are forms to provide health care services to potentially critical patients that allow for improved cost-benefit ratio of the care offered by Intensive Medicine Departments. Objective. Analyze heart care repercussion that the permanent opening of this type of unit had in a reference teaching center. Design. Prospective. Period. From the beginning of 2003 to the end of 2005. Scope. Intensive Medicine Department (IMD), with teaching accreditation, which has 15 conventional ICU beds and 4 intermediate care beds. Patients and methods. Analysis of demographic data (gender and age, type of patient, and origin or admission), of severity (SAPS 2), prognosis (MPM II 0 and SAPS2) and health care burden (NEMS) in 3,392 consecutive admissions to IMD. Specific analysis of the stay and mortality (intra- and post ICU). Results. Permanent opening of an intermediate care unit is associated with an increase of patients seen by the IMD and makes it possible to clearly identify two different types of patients according to the site linked to the cause of the admission. The patients seen in the Intermediate Care Unit have a shorter stay, less seriousness, greater survival prognosis and less care burden. However, the initiation of this service does not decrease the interval of total mortality (intra + post- ICU). Conclusion. Initiating an intermediate care unit depending on an IMD increases its health care capacity and that of the center it gives service to without affecting global mortality