18ß-Glycyrrhetinic Acid Improves Cardiac Diastolic Function by Attenuating Intracellular Calcium Overload.

Ranolazine, a late sodium current inhibitor, has been demonstrated to be effective on heart failure. 18ß-glycyrrhetinic acid (18ß-GA) has the similar inhibitory effect on late sodium currents. However, its effect on diastolic function is still unknown. This study aimed to determine whether 18ß-GA can improve the diastolic function and to explore the underlying mechanisms. Eighty male Sprague Dawley (SD) rats of Langendorff model were randomly divided into the following groups: group A, normal cardiac perfusion group; group B, ischemia-reperfusion group; group C, ischemia-reperfusion with anemoniasulcata toxin II (ATX-II); group D, ranolazine group; and group E, 18ß-GA group with four different concentrations. Furthermore, a pressure-overloaded rat model induced by trans-aortic constriction (TAC) was established. Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC. Changes of free intracellular calcium (Ca2+) concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents. With the intervention of ATX-II on ischemia reperfusion injury group, 5 µmol/L ranolazine, and 5, 10, 20, 40 µmol/L 18ß-GA could improve ATX-II-induced cardiac diastolic dysfunction. 630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats. 18ß-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes. The study demonstrates that 18ß-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats. The mechanism may be attributed to the inhibition of enhanced late sodium currents.

Modulatory Activities of Plant Extracts on Jellyfish Cytotoxicity.

INTRODUCTION: The potential efficacy of selected plant extracts to counteract the dermal toxicity of jellyfish envenomation was investigated using an in vitro cell culture model. METHODS: We studied plant extracts from Carica papaya, Ananas comosus, and Bouvardia ternifolia, known for their antivenom properties, in pairwise combinations with tissue homogenates of the jellyfish Pelagia noctiluca, Phyllorhiza punctata, and Cassiopea andromeda, to evaluate modulations of jellyfish cytotoxic effects. L929 mouse fibroblasts were incubated with pairwise jellyfish/plant extract combinations and examined by MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). RESULTS: C papaya and A comosus significantly lowered the cytotoxicity of P noctiluca and P punctata but induced a slight worsening of C andromeda cytotoxicity. Conversely, B ternifolia was protective against P punctata, ineffective against P noctiluca, and worsened C andromeda cytotoxicity. CONCLUSIONS: Data showed species-specific and contrasting effects of plant extracts, suggesting that those containing protease activities, namely A comosus and C papaya, are more effective in lowering the cytotoxicity of jellyfish venom containing toxic peptidic factors such as phospholipase A. However, all examined plants require further investigation in vivo to evaluate their ability to counteract jellyfish injury to the skin.

Cnidarian Jellyfish: Ecological Aspects, Nematocyst Isolation, and Treatment Methods of Sting.

Cnidarians play an important role in ecosystem functioning, in the competition among species, and for possible utilization of several active compounds against cardiovascular, nervous, endocrine, immune, infective, and inflammatory disorders or having antitumoral properties, which have been extracted from these organisms. Nevertheless, notwithstanding these promising features, the main reason for which cnidarians are known is due to their venomousness as they have a serious impact on public health as well as in economy being able to affect some human activities. For this reason a preeminent subject of the research about cnidarians is the organization of proper systems and methods of care and treatment of stinging. This chapter aims to present the data about the morphological, ecological, toxicological, epidemiological, and therapeutic aspects regarding cnidarians with the purpose to summarize the existing knowledge and to stimulate future perspectives in the research on these organisms.

Delayed Allergic Reactions to Jellyfish Stings: Usefulness of Ultrasonographic Evaluation.

Jellyfish stings often cause immediate local skin reactions, and, less frequently, the affected individuals may develop delayed allergic reactions days or months after the sting. Here, we present 4 such cases. In all cases, color Doppler ultrasonography was performed at the time of diagnosis, and in 3 of the cases, clinical follow-ups with ultrasonographic evaluations were performed. Ultrasonography initially showed dermal thickening with decreased echogenicity that progressively normalized during follow-up. Ultrasonography was useful in quantifying inflammation by measuring the thickness of the dermis and was more precise than standard clinical follow-up of cutaneous lesions in these cases.

[Contact with jellyfish led to intermittent severe hypertension].

Jellyfish is the number one cause of human pathologies due to contact with marine organisms. Jellyfish stings can cause a vast number of symptoms in humans like contact derma-titis, itching, pain, cardiovascular problems, anaphylaxis, and even death. This case report is about a 72-year-old woman with intermittent severe hypertension after being stung by jellyfish. Because of tourism and jellyfish migration the prevalence of patients with symptoms after jellyfish stings is increasing.

Drug-Induced QT Prolongation and Torsades de Pointes: An All-Exclusive Relationship or Time for an Amicable Separation?

QT prolongation was perceived as a major antiarrhythmic mechanism, but soon became a surrogate for torsades de pointes (TdP) instead. Drugs that prolong the QT interval range from having potent torsadogenic activity to no proarrhythmic action and even antiarrhythmic effects. Blockade of hERG channels is the primary cause of TdP, but blockade/activation of other channels can also be torsadogenic. TdP is primarily caused by disturbances of TRIaD, but disturbance of wavelength can also contribute to TdP (where TRIaD is triangulation, reverse use dependence, instability and dispersion, and wavelength equals conduction velocity times effective refractory period). The above proarrhythmic parameters do not only result in TdP, but can also lead to ventricular tachycardia (VT) and ventricular fibrillation (VF). Note that QT prolongation (not listed as a causal factor) yields many false positives (potentially depriving patients from much needed drugs) and false negatives (potentially exposing patients to lethal arrhythmias). Thus, drug-induced QT prolongation is a bad surrogate for TdP, VT or VF; it is high time to move away from an oversimplified and erroneous surrogate.

Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom

Background Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis. Methods The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. Results P. caribaeorum venom produced hemolytic and PLA2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. Conclusion These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.

Urticaria induced by ingestion of anemonia sulcata

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Assessing the Efficacy of First-Aid Measures in Physalia sp. Envenomation, Using Solution- and Blood Agarose-Based Models.

Stings from the hydrozoan species in the genus Physalia cause intense, immediate skin pain and elicit serious systemic effects. There has been much scientific debate about the most appropriate first aid for these stings, particularly with regard to whether vinegar use is appropriate (most current recommendations recommend against vinegar). We found that only a small percentage (≤1.0%) of tentacle cnidae discharge during a sting event using an ex vivo tissue model which elicits spontaneous stinging from live cnidarian tentacles. We then tested a variety of rinse solutions on both Atlantic and Pacific Physalia species to determine if they elicit cnidae discharge, further investigating any that did not cause immediate significant discharge to determine if they are able to inhibit cnidae discharge in response to chemical and physical stimuli. We found commercially available vinegars, as well as the recently developed Sting No More® Spray, were the most effective rinse solutions, as they irreversibly inhibited cnidae discharge. However, even slight dilution of vinegar reduced its protective effects. Alcohols and folk remedies, such as urine, baking soda and shaving cream, caused varying amounts of immediate cnidae discharge and failed to inhibit further discharge, and thus likely worsen stings.

Review article: Role of magnesium sulphate in the management of Irukandji syndrome: A systematic review.

Signs of Irukandji syndrome (IS) suggest an underlying catecholamine storm with research demonstrating that Carukia barnesi venom causes a significant rise in adrenaline/noradrenaline serum levels. A systematic review was undertaken to ascertain the current evidence in treating IS with magnesium salts. A literature search was conducted using Scopus, Medline and ScienceDirect. Further articles were discarded via title description and/or abstract details. The remaining were read in full, and those identified as not having sufficient information regarding magnesium and patient outcomes were removed. Nine articles were identified. One article was a randomised controlled trial, which concluded that there appears to be no beneficial difference between those patients who received the magnesium sulphate (MgSO4 ) and those who received the placebo and recommended against the use of MgSO4 in IS. Of the remaining eight, one reported the failure of MgSO4 and the remaining seven were case series reporting varying success in its use. This systematic review found insufficient evidence to support any clear recommendation regarding the use of magnesium, but nor was there clear evidence to recommend against its use in IS. Two case series describe significant reduction in key symptoms and hypertension but are a non-randomised albeit prospective series with the limitations accompanying this. The reporting of recrudescence of symptoms with reduction of dose does suggest a dose-response relationship. The evidence for the use of MgSO4 is at best anecdotal, and further research is required to either confirm its benefit or confirm the randomised controlled trial.

Dermoscopic Findings of Jellyfish Stings Caused by Pelagia noctiluca / Dermatoscopia de las picaduras de medusa causadas por Pelagia noctiluca

BACKGROUND AND OBJECTIVES: Jellyfish are free-living members of the phylum Cnidaria who share a specialized stinging cell, the cnidocyte. Pelagia noctiluca is the most frequent and toxic jellyfish species found in the Balearic beaches and cnidocytes are arranged in pigmented clusters called 'warts'. Dermoscopy continues to expand its use much beyond the pigmentary lesions and to date, there is no data regarding dermoscopic findings in jellyfish stings. The aim of the present work was to study the dermoscopic findings of jellyfish stings in the island of Mallorca. PATIENTS AND METHODS: We retrospectively reviewed the clinical and dermoscopic images of 25 episodes of jellyfish stings caused by P. noctiluca that occurred between 2009 and 2015. RESULTS: Overall, the following dermoscopic features were found: brown dots (84%), pinkish hue (56%), pinpoint brown crusts (44%), scale-crust (40%), brown 'Chinese characters pattern' (32%), 'serpentine' ulceration (28%), linear purpura (20%), and whitish-yellow crusts (15%). Vessels were mainly dotted (36%) or reticular (16%). Scale-crust, serpentine ulceration and pinkish hue were significantly more frequent in lesions older than 2 days. Conclusions and limitations: Our study identifies 4 dermoscopic features that may represent the contact with P. noctilucacnidocytes: brown dots, brown 'Chinese characters pattern', pinpoint brown crusts and whitish-yellow crusts. A peculiar finding of 'serpentine ulceration' with brown dots would be very suggestive of P. noctiluca sting. We believe dermoscopy is a valuable tool in the diagnosis of jellyfish stings when a clear history of contact is lacking. Further studies are needed to validate our findings in other jellyfish species

INTRODUCCIÓN Y OBJETIVOS: Las medusas son miembros del phylum Cnidaria que comparten una célula urticante especializada, el cnidiocito. En Baleares, Pelagia noctiluca es la medusa más frecuente y tóxica. En ella los cnidiocitos se encuentran en agrupaciones pigmentadas llamadas 'verrugas'. La dermatoscopia continúa ampliando su uso más allá de las lesiones pigmentadas, pero hasta la fecha no se ha utilizado en el diagnóstico de las picaduras de medusa. El objetivo del presente trabajo es estudiar los hallazgos dermatoscópicos en esta patología en la isla de Mallorca. PACIENTES Y MÉTODOS: Revisamos retrospectivamente las imágenes clínicas y dermatoscópicas de 25 episodios de picaduras de medusa por P. noctiluca entre 2009 y 2015. RESULTADOS: Se encontraron las siguientes imágenes: puntos marrones (84%), tono rosado (56%), costras marrones puntiformes (44%), escamocostra (40%), patrón en 'letras chinas' marrones (32%), ulceración 'en serpentina' (28%), púrpura lineal (20%) y costras blancoamarillentas (15%). Los vasos fueron puntiformes (36%) o reticulares (16%). La escamocostra, la ulceración en serpentina y el tono rosado fueron significativamente más frecuentes en las lesiones de más de 2días de duración. Conclusiones y limitaciones: Nuestro estudio identificó 4 imágenes dermatoscópicas debidas al contacto con los cnidiocitos: puntos marrones, patrón en 'letras chinas' marrones, costras marrones puntiformes y costras blancoamarillentas. La combinación de ulceración 'en serpentina' y puntos marrones sería muy sugestiva de picadura por P. noctiluca. La dermatoscopia es una herramienta útil en el diagnóstico de las picaduras de medusas, en ausencia del antecedente de contacto con ellas. Se necesitan más estudios para validar estos hallazgos en picaduras por otras especies de medusa