Cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage I seminoma treated with a risk-adapted strategy: a Spanish single-centre retrospective analysis.

PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.

Christofredo Jakob, los cimientos de la neurociencia argentina / Christofredo Jakob, the foundations of argentine neuroscience

El presente artículo es una reseña biográfica de la vida del Dr. Christofredo Jakob, desde su formación en Alemania, las personalidades que acompañaron su desarrollo y las publicaciones científicas en suelo germano. Luego llegarían los inicios de su trabajo en la Argentina y los principales alcances de sus investigaciones. A través de esta reseña recorremos los comienzos del estudio sistemático del sistema nervioso en el país y recordamos el Día del Neurocientífico argentino. (AU)

This article is a biographical review of the life of Dr. Christofredo Jakob, from his training in Germany, the personalities who accompanied his development and the scientific publications on German soil. Then came the beginnings of his work in Argentina and the main achievements of his research. Through this review, we retrace the beginnings of the systematic study of the nervous system in the country and we remember the Day of the Argentine Neuroscientist. (AU)

Transcriptomic and proteomic analyses reveal the first occurrence of diverse toxin groups in Millepora alcicornis.

Millepora alcicornis is a reef-forming cnidarian widely distributed in the Mexican Caribbean. Millepora species or "fire corals" inflict a painful stinging reaction in humans when touched. Even though hundreds of organic and polypeptide toxins have been characterized from sea anemones and jellyfish, there are few reports regarding the diversity of toxins synthesized by fire corals. Here, based on transcriptomic analysis of M. alcicornis, several predicted proteins that show amino acid sequence similarity to toxins were identified, including neurotoxins, metalloproteases, hemostasis-impairing toxins, serin proteases, cysteine-rich venom proteins, phospholipases, complement system-impairing toxins, phosphodiesterases, pore-forming toxins, and L-aminoacid oxidases. The soluble nematocyst proteome of this organism was shown to induce hemolytic, proteolytic, and phospholipase A2 effects by gel zymography. Protein bands or spots on 1D- and 2D-PAGE gels corresponding to zones of hemolytic and enzymatic activities were excised, subjected to in-gel digestion with trypsin, and analyzed by mass spectrometry. These proteins exhibited sequence homology to PLA2s, metalloproteinases, pore-forming toxins, and neurotoxins, such as actitoxins and CrTX-A. The complex array of venom-related transcripts that were identified in M. alcicornis, some of which are first reported in "fire corals", provide novel insight into the structural richness of Cnidarian toxins and their distribution among species. SIGNIFICANCE: Marine organisms are a promising source of bioactive compounds with valuable contributions in diverse fields such as human health, pharmaceuticals, and industrial application. Currently, not much attention has been paid to the study of fire corals, which possess a variety of molecules that exhibit diverse toxic effects and therefore have great pharmaceutical and biotechnological potential. The isolation and identification of novel marine-derived toxins by classical approaches are time-consuming and have low yields. Thus, next-generation strategies, like base-'omics technologies, are essential for the high-throughput characterization of venom compounds such as those synthesized by fire corals. This study moves the field forward because it provides new insights regarding the first occurrence of diverse toxin groups in Millepora alcicornis. The findings presented here will contribute to the current understanding of the mechanisms of action of Millepora toxins. This research also reveals important information related to the potential role of toxins in the defense and capture of prey mechanisms and for designing appropriate treatments for fire coral envenomation. Moreover, due to the lack of information on the taxonomic identification of Millepora, the insights presented here can advise the taxonomic classification of the species of this genus.

Anestesia en un caso de estenosis traqueal secuela de COVID-19, para un procedimiento de traqueoplastía / Anesthesia in a case of tracheal stenosis sequelae of COVID-19, to a tracheoplasty procedure

Resumen: Introducción: La pandemia por COVID-19 es una enfermedad de predominio respiratorio que ha afectado a nivel mundial y ha dejado más de 151 millones de casos, los cuales suelen requerir un manejo de ventilación mecánica con la intensión de controlar las vías aéreas superiores para la adecuada oxigenación de las personas con COVID-19, y que se reduzca así el riesgo de contagio para el personal médico. Objetivo: Describir el abordaje anestésico para la inducción y mantenimiento de una traqueoplastía derivado a estenosis traqueal secundaria por COVID-19. Material y métodos: Se aborda la descripción de un caso y los lineamientos que se han dado para el manejo de la estenosis traqueal. Conclusiones: El control oportuno anestésico y la instalación de férula laríngea son apropiados para el manejo de la estenosis traqueal secundaria al proceso de intubación mecánica prolongada por COVID-19.

Abstract: Introduction: The COVID-19 pandemic is a predominantly respiratory disease that has affected worldwide and has left more than 151 million cases, which usually require mechanical ventilation management with the intention of managing the upper airways for ventilation adequate oxygenation of people with COVID-19 and that reduces the risk of contagion for medical personnel. Objective: To describe the anesthetic approach for the induction and maintenance of a tracheoplasty derived from tracheal stenosis secondary to COVID-19. Material and methods: The description of a case and the guidelines that have been given for the management of tracheal stenosis are addressed. Conclusions: Timely anesthetic management and installation of a laryngeal splint is appropriate for the management of tracheal stenosis secondary to the process of prolonged mechanical intubation due to COVID-19.

Infarto cerebeloso bilateral agudo en territorio de la arteria cerebelosa posterior inferior: reporte de caso / Acute bilateral cerebellar infarction in territory of the posterior inferior cerebellar artery: a case report

Antecedentes: Los infartos cerebelosos suponen una entidad rara con una incidencia baja del total de ictus isquémicos. El territorio más prevalente de los infartos cerebelosos son los de la arteria cerebelosa posterior inferior (PICA). Cuando los infartos se limitan al cerebelo, los pacientes típicamente experimentan síntomas no específicos, esto hace considerar otros diagnósticos de forma errónea. Descripción del caso clínico: paciente femenina de 54 años, con antecedente de hipertensión arterial, quien presentaba cefalea insidiosa y progresiva acompañado de vértigo, alteración en la marcha y deterioro progresivo del estado de conciencia. Se realizó imagen de Resonancia Magnética Cerebral (IRM), la cual reveló zonas hiper intensas bilaterales en región cerebelosa que delimitaban territorio vascular de la arteria cerebelosa posterior inferior además dilatación moderada del sistema ventricular. Fue intervenida quirúrgicamente, realizándose craniectomía suboccipital descompresiva; posterior a la cirugía presentó mejoría clínica. Conclusiones: El ictus isquémico cerebeloso bilateral es una forma infrecuente de ictus y su presentación clínica es muy diversa. El desarrollo de las neuroimágenes, juegan un papel importante para ayudar a los médicos a seleccionar el tratamiento adecuado. Alrededor de la mitad de los pacientes con infartos cerebelosos que presentan deterioro neurológico progresivo y son tratados con craniectomía suboccipital descompresiva tienen buenos resultados. El pilar fundamental de este caso fue el hacer un diagnóstico temprano de esta entidad, ya que permitió prevenir las posibles complicaciones graves asociadas al infarto cerebeloso, las cuales ocurren durante la primera semana del ictus y, por lo tanto, asegurar un pronóstico favorable para el paciente...(AU)

circRNA Regulates Dopaminergic Synapse, MAPK, and Long-term Depression Pathways in Huntington Disease.

Huntington disease (HD) is the most common neurogenetic disorder caused by expansion of the CAG repeat in the HTT gene; nevertheless, the molecular bases of the disease are not fully understood. Non-coding RNAs have demonstrated to be involved in the physiopathology of HD. However, the role of circRNAs has not been investigated. The aim of this study was to identify the circRNAs with differential expression in a murine cell line model of HD and to identify the biological pathways regulated by the differentially expressed circRNAs. CircRNA expression was analyzed through a microarray, which specifically detects circular species of RNA. The expression patterns between a murine cell line expressing mutant Huntingtin and cells expressing wild-type Huntingtin were compared. We predicted the miRNAs with binding sites for the differentially expressed circRNAs and the corresponding target genes for those miRNAs. Using the target genes, we performed a function enrichment analysis. We identified 23 circRNAs differentially expressed, 19 downregulated and four upregulated. Most of the downregulated circRNAs derive from the Rere gene. The dopaminergic synapse, MAPK, and long-term depression pathways were significantly enriched. The three identified pathways have been previously associated with the physiopathology of HD. The understanding of the circRNA-miRNA-mRNA network involved in the molecular mechanisms driving HD can lead us to identify novel biomarkers and potential therapeutic targets. To the best of our knowledge, this is the first study analyzing circRNAs in a model of Huntington disease.

Vasodilation Elicited by Isoxsuprine, Identified by High-Throughput Virtual Screening of Compound Libraries, Involves Activation of the NO/cGMP and H2S/KATP Pathways and Blockade of α1-Adrenoceptors and Calcium Channels.

Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H2S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of this study was to identify hits with high binding affinity for the triterpene binding-allosteric sites of eNOS and CSE and to evaluate their vasodilator effect. Additionally, the mechanism of action of the most potent compound was explored. A high-throughput virtual screening (HTVS) of 107,373 compounds, obtained from four ZINC database libraries, was performed employing the crystallographic structures of eNOS and CSE. Among the nine top-scoring ligands, isoxsuprine showed the most potent vasodilator effect. Pharmacological evaluation, employing the rat aorta model, indicated that the vasodilation produced by this compound involved activation of the NO/cGMP and H2S/KATP signaling pathways and blockade of α1-adrenoceptors and L-type voltage-dependent Ca2+ channels. Incubation of aorta homogenates in the presence of isoxsuprine caused 2-fold greater levels of H2S, which supported our preliminary in silico data. This study provides evidence to propose that the vasodilator effect of isoxsuprine involves various mechanisms, which highlights its potential to treat a wide variety of cardiovascular diseases.

Inter-observer agreement of the Wagner, University of Texas and PEDIS classification systems for the diabetic foot syndrome.

BACKGROUND: The aim of this cohort study was to assess the inter-observer agreement of three diabetic foot classification systems: the Wagner, the University of Texas and the PEDIS. METHODS: We included 250 consecutive patients diagnosed of diabetic foot syndrome in 2009-2013. Wound scores were recorded at admission and a reevaluation was performed simultaneously or 24h later by a different evaluator. Demographical, laboratory data and associated risk factors were obtained from the patients' medical records. RESULTS: The Kappa coefficient showed a moderate inter-observer agreement between the first evaluation and the reevaluation for Wagner scale (Kappa=0.55; 95% CI: 0.507-0.593), University of Texas scale (Kappa=0.513; 95% CI: 0.463-0.563) and for PEDIS scale (Kappa=0.574; 95% CI: 0.522-0.626). CONCLUSIONS: This moderate agreement shows that these scales should not be used alone for management decisions regarding diabetic foot syndrome and should, therefore, be integrated with other clinical data to ensure an adequate handover.

A solar radiation database for Chile.

Chile hosts some of the sunniest places on earth, which has led to a growing solar energy industry in recent years. However, the lack of high resolution measurements of solar irradiance becomes a critical obstacle for both financing and design of solar installations. Besides the Atacama Desert, Chile displays a large array of "solar climates" due to large latitude and altitude variations, and so provides a useful testbed for the development of solar irradiance maps. Here a new public database for surface solar irradiance over Chile is presented. This database includes hourly irradiance from 2004 to 2016 at 90 m horizontal resolution over continental Chile. Our results are based on global reanalysis data to force a radiative transfer model for clear sky solar irradiance and an empirical model based on geostationary satellite data for cloudy conditions. The results have been validated using 140 surface solar irradiance stations throughout the country. Model mean percentage error in hourly time series of global horizontal irradiance is only 0.73%, considering both clear and cloudy days. The simplicity and accuracy of the model over a wide range of solar conditions provides confidence that the model can be easily generalized to other regions of the world.

Infarto talámico bilateral por compromiso de la arteria de percheron / Bilateral Thalamic Infarct by Commitment of the Artery of Percheron

Introduccion: La arteria de Percheron se origina de un solo tronco arterial talamoperforante que proporciona suministro bilateral a los tálamos paramedianos y al mesencéfalo rostral. Esta es una variante anatómica que permite la irrigación bilateral de los tálamos, a partir de un tronco común de origen asimétrico en la arteria cerebral posterior. Las lesiones en esta área dan origen a una variedad de manifestaciones clínicas. Caso clínico: Presentamos el caso de una paciente femenina blanca de 89 años, quien fue admitida en el Hospital Virgen de los Lirios de Alcoy, diagnosticada con Infarto talámico bilateral de la arteria de Percherón. Discusión: Son muchos los factores por el cual este infarto es infradiagnosticado, entre ellos, la baja estimación de la frecuencia de este infarto junto con la gran heterogeneidad clínica y además la baja sensibilidad de la Tomografía computarizada en la fase hiperaguda. En general el pronóstico a largo plazo es bueno, este varía con respecto a los patrones radiológicos encontrados, siendo más afectados los casos en los que involucra mesencefalo...(AU)

Affinin (Spilanthol), Isolated from Heliopsis longipes, Induces Vasodilation via Activation of Gasotransmitters and Prostacyclin Signaling Pathways.

Heliopsis longipes roots have been widely used in Mexican traditional medicine to relieve pain, mainly, toothaches. Previous studies have shown that affinin, the major alkamide of these roots, induces potent antinociceptive and anti-inflammatory activities. However, the effect of H. longipes root extracts and affinin on the cardiovascular system have not been investigated so far. In the present study, we demonstrated that the dichloromethane and ethanolic extracts of H. longipes roots, and affinin, isolated from these roots, produce a concentration-dependent vasodilation of rat aorta. Affinin-induced vasorelaxation was partly dependent on the presence of endothelium and was significantly blocked in the presence of inhibitors of NO, H2S, and CO synthesis (NG-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (PAG), and chromium mesoporphyrin (CrMP), respectively); K⁺ channel blockers (glibenclamide (Gli) and tetraethyl ammonium (TEA)), and guanylate cyclase and cyclooxygenase inhibitors (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and indomethacin (INDO), respectively). Our results demonstrate, for the first time, that affinin induces vasodilation by mechanisms that involve gasotransmitters, and prostacyclin signaling pathways. These findings indicate that this natural alkamide has therapeutic potential in the treatment of cardiovascular diseases.

Trombosis de un ictus isquemico en el Hospita Escuela Universitario, Tegucigalpa, Honduras / Ischemic stroke thrombolysis in the University School Hospital, Tegucigalpa, Honduras

Hipócrates padre de la medicina, reconoció la enfermedad cerebrovascular hace más de 2 400 años y utilizó el término apoplejía. En Estados Unidos esta enfermedad es la principal causa de discapacidad, así como la tercera causa de muerte. En Honduras se ha observado que en los últimos años la incidencia hospitalaria del evento cerebrovascular se ha elevado notablemente, lo que constituye la primera causa de morbilidad y mortalidad no traumática en la población adulta y refleja el impacto que la enfermedad tiene en la población. Objetivo: realizar un análisis del primer caso de trombólisis en enfermedad cerebrovascular isquémica en el Hospital Escuela Universitario, Tegucigalpa, Honduras. Caso clínico: paciente femenina de 79 años, quien 40 minutos previos a su ingreso a emergencia de Medicina Interna del Hospital Escuela Universitario, presentó abruptamente afasia neurológica se encontró afasia motora, hemiparesia faciobraquiocrural derecha, con afectación sensitiva superficial ipsilateral y Babinski derecho. La tomografía cerebral simple no fluente y disminución de la fuerza en hemicuerpo derecho. En la evaluación no demostró anormalidades, por lo que cumplió los criterios establecidos y se decide trombolizar. Se logró disminuir el puntaje en la Escala del Instituto Nacional de Salud de 18 a 7 puntos y en la Escala de Rankin Modificada de 4 a 1. Conclusión: la paciente ingresó con déficit motor hemicorporal con afectación del lenguaje; tras la intervención se rescató el área de penumbra y egresó con leve déficit secuelar del lenguaje en la comprensión, sin déficit motor, ni pérdida de la fluidez del lenguaje. El uso de activador recombinante tisular de plasminógeno para ictus isquémico, con tres horas o menos de evolución, aumenta los beneficios del paciente ya que disminuyen las secuelas y reduce los gastos del sistema de salud. Portal razón es catalogado como evidencia clase A...(AU)

Reporte de familia: distrofia muscular oculofaríngea / Family report: Muscular Dystrophy Oculopharyngeal

Antecedentes: La Distrofia Muscular Oculofaríngea es un trastorno hereditario de rara ocurrencia. Este síndrome se caracteriza fundamentalmente por ptosis palpebral progresiva, disfagia y debilidad proximal de las extremidades. Casos Clínicos: Se presenta una familia en la cual se encontraron dos casos afectados, en la confección del árbol genealógico se encontró consanguineidad entre los padres apoyando la existencia de un posible patrón hereditario para esta alteración. Conclusión: El conocimiento de esta entidad es fundamental para sospecharla, por lo infrecuente de esta condición y las pocas publicaciones en la literatura latinoamericana de estos casos se presenta la siguiente revisión...(AU)

Role of Nitric Oxide and Hydrogen Sulfide in the Vasodilator Effect of Ursolic Acid and Uvaol from Black Cherry Prunus serotina Fruits.

The present research aimed to isolate the non-polar secondary metabolites that produce the vasodilator effects induced by the dichloromethane extract of Prunus serotina (P. serotina) fruits and to determine whether the NO/cGMP and the H2S/KATP channel pathways are involved in their mechanism of action. A bioactivity-directed fractionation of the dichloromethane extract of P. serotina fruits led to the isolation of ursolic acid and uvaol as the main non-polar vasodilator compounds. These compounds showed significant relaxant effect on rat aortic rings in an endothelium- and concentration-dependent manner, which was inhibited by NG-nitro-L-arginine methyl ester (L-NAME), DL-propargylglycine (PAG) and glibenclamide (Gli). Additionally, both triterpenes increased NO and H2S production in aortic tissue. Molecular docking studies showed that ursolic acid and uvaol are able to bind to endothelial NOS and CSE with high affinity for residues that form the oligomeric interface of both enzymes. These results suggest that the vasodilator effect produced by ursolic acid and uvaol contained in P. serotina fruits, involves activation of the NO/cGMP and H2S/KATP channel pathways, possibly through direct activation of NOS and CSE.

Composition and biological activities of the aqueous extracts of three scleractinian corals from the Mexican Caribbean: Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea

Background: Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea, three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Methods: Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A2 (PLA2), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Results: Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. Conclusion: This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.(AU)

Composition and biological activities of the aqueous extracts of three scleractinian corals from the Mexican Caribbean: Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea

Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea, three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Methods: Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A2 (PLA2), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Results: Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. Conclusion: This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.

Cytolytic and systemic toxic effects induced by the aqueous extract of the fire coral Millepora alcicornis collected in the Mexican Caribbean and detection of two types of cytolisins

Background Millepora alcicornis is a branching hydrocoral common throughout the Caribbean Sea. Like other members of this genus, this species is capable of inducing skin eruptions and blisters with severe pain after contact. In the present study, we investigated the toxicity of theM. alcicornis aqueous extract on several animal models. Considering that some cnidarian hemolysins have been associated to local tissue damage, since they also induce lysis of other cell types, we also made a partial characterization of the hemolytic activity of M. alcicornis aqueous extract. This information is important for understanding the defense mechanisms of the "fire corals".Methods The effects of pH, temperature, and some divalent cations on the hemolytic activity of the extract were assayed, followed by a zymogram analysis to detect the cytolysins and determine their approximate molecular weight. The toxicity of the aqueous extract was assayed in mice, by intravenous administration, and histopathological changes on several tissues were analyzed by light microscopy. The toxicity of the extract was also tested inArtemia salina nauplii, and the damages caused on the crustaceans were analyzed by transmission and scanning electron microscopy.Results The hemolytic activity of the hydrocoral extract was enhanced in the presence of Ca 2+ (≥2 mM), Mg 2+ (≥6 mM), and Ba2+ (≥0.1 mM); however, it was reduced in the presence of Cu2+(≥0.1 mM), Zn 2+ (≥6 mM), and EDTA (≥0.34 mM). Differences in the pH did not affect the hemolytic activity, but it was temperature-sensitive, since preincubation at ≥ 50 °C sharply reduced hemolysis. The zymogram showed the presence of two types of hemolysins: ~ 28-30 kDa proteins with phospholipase A 2 activity and ~ 200 kDa proteins that do not elicit enzymatic activity. The aqueous extract of this cnidarian was lethal to mice (LD 50 = 17 μg protein/g), and induced kidney, liver, and lung damages. Under denaturing conditions, the aqueous extract completely lost its toxic and hemolytic activities.Conclusions The results showed that the M. alcicornis aqueous extract contains two types of thermolabile hemolysins: proteins of approximately 28-30 kDa with PLA 2 activity, while the others are larger proteins of approximately 200 kDa, which do not possess PLA 2activity. Those thermolabile cytolysins, which are stable to pH changes and whose activity is calcium dependent, are capable of inducing damage in lung, kidney and liver tissues, resulting in a slow death of mice. M. alcicorniscytolysins also provoke tissue dissociation inArtemia salina nauplii that might be attributed to pore forming mechanisms.(AU)

Cytolytic and systemic toxic effects induced by the aqueous extract of the fire coral Millepora alcicornis collected in the Mexican Caribbean and detection of two types of cytolisins

Background Millepora alcicornis is a branching hydrocoral common throughout the Caribbean Sea. Like other members of this genus, this species is capable of inducing skin eruptions and blisters with severe pain after contact. In the present study, we investigated the toxicity of theM. alcicornis aqueous extract on several animal models. Considering that some cnidarian hemolysins have been associated to local tissue damage, since they also induce lysis of other cell types, we also made a partial characterization of the hemolytic activity of M. alcicornis aqueous extract. This information is important for understanding the defense mechanisms of the fire corals.Methods The effects of pH, temperature, and some divalent cations on the hemolytic activity of the extract were assayed, followed by a zymogram analysis to detect the cytolysins and determine their approximate molecular weight. The toxicity of the aqueous extract was assayed in mice, by intravenous administration, and histopathological changes on several tissues were analyzed by light microscopy. The toxicity of the extract was also tested inArtemia salina nauplii, and the damages caused on the crustaceans were analyzed by transmission and scanning electron microscopy.Results The hemolytic activity of the hydrocoral extract was enhanced in the presence of Ca 2+ (2 mM), Mg 2+ (6 mM), and Ba2+ (0.1 mM); however, it was reduced in the presence of Cu2+(0.1 mM), Zn 2+ (6 mM), and EDTA (0.34 mM). Differences in the pH did not affect the hemolytic activity, but it was temperature-sensitive, since preincubation at 50 °C sharply reduced hemolysis. The zymogram showed the presence of two types of hemolysins: ~ 2830 kDa proteins with phospholipase A 2 activity and ~ 200 kDa proteins that do not elicit enzymatic activity. The aqueous extract of this cnidarian was lethal to mice (LD 50 = 17 g protein/g), and induced kidney, liver, and lung damages. Under denaturing conditions, the aqueous extract completely lost its toxic and hemolytic activities.Conclusions The results showed that the M. alcicornis aqueous extract contains two types of thermolabile hemolysins: proteins of approximately 2830 kDa with PLA 2 activity, while the others are larger proteins of approximately 200 kDa, which do not possess PLA 2activity. Those thermolabile cytolysins, which are stable to pH changes and whose activity is calcium dependent, are capable of inducing damage in lung, kidney and liver tissues, resulting in a slow death of mice. M. alcicorniscytolysins also provoke tissue dissociation inArtemia salina nauplii that might be attributed to pore forming mechanisms.

Nutraceutical value of black cherry Prunus serotina Ehrh. fruits: antioxidant and antihypertensive properties.

In Mexico black cherry (Prunus serotina Ehrh.) fruits are consumed fresh, dried or prepared in jam. Considering the evidence that has linked intake of fruits and vegetables rich in polyphenols to cardiovascular risk reduction, the aim of this study was to characterize the phenolic profile of black cherry fruits and to determine their antioxidant, vasorelaxant and antihypertensive effects. The proximate composition and mineral contents of these fruits were also assessed. Black cherry fruits possess a high content of phenolic compounds and display a significant antioxidant capacity. High-performance liquid chromatography/mass spectrometric analysis indicated that hyperoside, anthocyanins and chlorogenic acid were the main phenolic compounds found in these fruits. The black cherry aqueous extract elicited a concentration-dependent relaxation of aortic rings and induced a significant reduction on systolic blood pressure in L-NAME induced hypertensive rats after four weeks of treatment. Proximate analysis showed that black cherry fruits have high sugar, protein, and potassium contents. The results derived from this study indicate that black cherry fruits contain phenolic compounds which elicit significant antioxidant and antihypertensive effects. These findings suggest that these fruits might be considered as functional foods useful for the prevention and treatment of cardiovascular diseases.