Mucormycosis: A sweet enemy, case series / Mucormicosis: un dulce enemigo, serie de casos.

Mucormycosis is a rare fungal infection caused by fungi of the Mucorales order that occurs in immunocompromised individuals or with loss of skin or mucosa barrier integrity. This report presents four cases of rhinocerebral mucormycosis attended at a third-level hospital in Cali (Colombia) during a period of three years. All patients had different case histories and times of evolution. All four had a previous or de novo diagnosis of type 2 diabetes mellitus, with glycated hemoglobin higher than 10% on admission. We ruled out other possible pathologies that could explain their immunocompromised condition. Mucormycosis diagnosis was made with direct visualization of hyaline coenocytic hyphae on biopsies. The basis of treatment was liposomal amphotericin B and surgical debridement. Two patients presented bacterial coinfection. One asked for voluntary discharge without having completed the treatment, and another one died. The remaining two have attended controls and had an adequate evolution.

La mucormicosis es una infección fúngica poco frecuente causada por hongos del orden Mucorales, la cual se presenta en individuos inmunocomprometidos o con pérdida de la integridad de la barrera de piel o mucosas. Se reportan cuatro casos de mucormicosis rinocerebral atendidos en un hospital de tercer nivel de Cali (Colombia) durante un periodo de tres años. Los cuatro pacientes presentaron diferentes cuadros clínicos y tiempos de evolución. Todos tenían diagnóstico de diabetes mellitus de tipo 2, de novo o previo, con una hemoglobina glucosilada de ingreso mayor del 10 % y en todos se descartaron otras enfermedades que explicaran su compromiso inmunitario. La mucormicosis se diagnosticó por la visualización directa de hifas hialinas sincitiales (coenocytic) en las biopsias tomadas. El pilar del tratamiento fue la anfotericina B liposómica junto con el desbridamiento quirúrgico. Dos pacientes presentaron coinfección bacteriana. De los cuatro, uno firmó su egreso voluntario sin completar el tratamiento y otro falleció. Los dos pacientes restantes han asistido a los controles y han mostrado una adecuada evolución.

A Case Report of Hemolytic Hyponatremia.

Hereditary spherocytosis/elliptocytosis is a non-immune hemolytic anemia caused by an alteration in the erythrocyte membrane that predisposes the cell to its lysis. This report presents a case of a 42-year-old woman with a history of spontaneous abortion, associated with postpartum bleeding, chronic anemia, and premature menopause. After five years, she consulted due to alterations in the state of consciousness and severe symptomatic hyponatremia, with a diagnosis of hypopituitarism, explained by a late Sheehan syndrome. During hospitalization, she developed non-immune hemolytic anemia associated with a positive osmotic fragility test. A diagnosis of hereditary spherocytosis/elliptocytosis was made. We correlate blood hypoosmolarity as a trigger with the in vitro hypotonic solution of the osmotic fragility test for the diagnosis of this disease. This association is not reported in the literature; in our case, we show the concomitant improvement of anemia with the increase in sodium levels and hormonal replacement.

Identification of the NA+/K+-ATPase α-Isoforms in Six Species of Poison Dart Frogs and their Sensitivity to Cardiotonic Steroids.

Cardiotonic steroids (CTS) are a group of compounds known to be toxic due to their ability to inhibit the Na+/K+-ATPase (NKA), which is essential to maintain the balance of ions in animal cells. An evolutionary strategy of molecular adaptation to avoid self-intoxication acquired by CTS defended organisms and their predators is the structural modification of their NKA where specific amino acid substitutions confer resistant phenotypes. Several lineages of poison dart frogs (Dendrobatidae) are well known to sequester a wide variety of lipophilic alkaloids from their arthropod diet, however there is no evidence of CTS-sequestration or dietary exposure. Interestingly this study identified the presence of α-NKA isoforms (α1 and α2) with amino acid substitutions indicative of CTS-resistant phenotypes in skeletal muscle transcriptomes obtained from six species of dendrobatids: Phyllobates aurotaenia, Oophaga anchicayensis, Epipedobates boulengeri, Andinobates bombetes, Andinobates minutus, and Leucostethus brachistriatus, collected in the Valle del Cauca (Colombia). P. aurotaenia, A. minutus, and E. boulengeri presented two variants for α1-NKA, with one of them having these substitutions. In contrast, O. anchicayensis and A. bombetes have only one α1-NKA isoform with an amino acid sequence indicative of CTS susceptibility and an α2-NKA with one substitution that could confer a reduced affinity for CTS. The α1 and α2 isoforms of L. brachistriatus do not contain substitutions imparting CTS resistance. Our findings indicate that poison dart frogs express α-NKA isoforms with different affinities for CTS and the pattern of this expression might be influenced by factors related to evolutionary, physiological, ecological, and geographical burdens.

Colombian Scorpion Centruroides margaritatus: Purification and Characterization of a Gamma Potassium Toxin with Full-Block Activity on the hERG1 Channel.

The Colombian scorpion Centruroides margaritatus produces a venom considered of low toxicity. Nevertheless, there are known cases of envenomation resulting in cardiovascular disorders, probably due to venom components that target ion channels. Among them, the humanether-à-go-go-Related gene (hERG1) potassium channels are critical for cardiac action potential repolarization and alteration in its functionality are associated with cardiac disorders. This work describes the purification and electrophysiological characterization of a Centruroides margaritatus venom component acting on hERG1 channels, the CmERG1 toxin. This novel peptide is composed of 42 amino acids with a MW of 4792.88 Da, folded by four disulfide bonds and it is classified as member number 10 of the γ-KTx1 toxin family. CmERG1 inhibits hERG1 currents with an IC50 of 3.4 ± 0.2 nM. Despite its 90.5% identity with toxin É£-KTx1.1, isolated from Centruroides noxius, CmERG1 completely blocks hERG1 current, suggesting a more stable plug of the hERG channel, compared to that formed by other É£-KTx.

Estudio de utilización de fármacos antigotosos en población colombiana, 2016 / Patterns of anti-gout drug use in a Colombian population: 2016

RESUMEN Objetivo: Identificar las características clínicas de los pacientes con gota y la forma de utilización de los medicamentos antigotosos en Colombia. Métodos: Estudio de corte transversal en el que se analizaron 310 historias clínicas de pacientes atendidos en el último trimestre del 2016 y que recibieron un medicamento antigotoso. Se identificaron variables sociodemográficas, clínicas, farmacológicas, comorbilidades y paraclínicas. Para cada medicamento antigotoso se determinó si el uso fue según las recomendaciones aprobadas por la Federal Drug Administration (FDA). Se realizaron análisis descriptivos, bivariados y multivariados. Resultados: Se evaluaron pacientes de 14 diferentes ciudades de Colombia, con un predominio masculino del 70,3% (n = 218) y una mediana de edad de 64 arios (RIC: 26-94 arios). El antigotoso más frecuentemente utilizado fue alopurinol (n = 255; 82,3%), seguido de colchicina (n = 54; 17,4%). Los diagnósticos hallados como indicación fueron: hiperuricemia (n = 181; 58,4%), gota (n = 34; 11%), artritis gotosa (n = 28; 9%). El 74,5% (n = 231) de las prescripciones tenía un uso aprobado según la FDA, especialmente alopurinol en el manejo de gota e hiperuricemias, mientras que colchicina se encontró siendo utilizada en indicaciones no aprobadas (n = 44; 81,4%). Las comorbilidades más frecuentes fueron hipertensión (68,4%) y dislipidemia (55,8%). Conclusiones: Los pacientes con gota en tratamiento farmacológico tienen una elevada frecuencia de comorbilidades cardiovasculares, y están siendo tratados con alopurinol para la prevención a largo plazo, mientras que una menor proporción recibe colchicina que comúnmente es utilizada para indicaciones no aprobadas por las agencias reguladoras.

ABSTRACT Objective: To identify the clinical characteristics of patients with gout, and the prescription patterns of anti-gout medications in Colombia. Methods: Cross-sectional study, that analysed the data from 310 medical records of patients treated in the last quarter of 2016, and who received an anti-gout medication. Sociodemographic, clinical, pharmacological, comorbidities, and paraclinical variables were identified. For each anti-gout drug used, it was determined whether the use was in accordance with Federal Drug Administration (FDA) approved recommendations. Descriptive, bivariate and multivariate analyses were performed. Results: Patients from 14 different cities in Colombia were evaluated, with a male predominance of 70.3% (n = 218) and a median age of 64 years (RIC: 26-94 years). The most frequently used anti-gout medication was allopurinol (n = 255; 82.3%), followed by colchicine (n = 54; 17.4%). The main diagnoses found as an indication were: hyperuricaemia (n=181, 58.4%), gout (n = 34; 11.0%), and gouty arthritis (n = 28; 9.0%). Almost three-quarters (74.5%; n = 231) of the prescriptions had an approved use according to the FDA, especially allopurinol in the management of gout and hyperuricaemia, while colchicine was found to be used in unapproved indications (n = 44, 81.4%). The most frequent comorbidities were hypertension (68.4%) and dyslipidaemia (55.8%). Conclusions: Patients with gout who are under pharmacological treatment have a high frequency of cardiovascular comorbidities. They were being treated with allopurinol for long-term prevention, while a smaller proportion received colchicine, which is often used for indications not approved by regulatory agencies.

Identification of Na+/K+-ATPase α/ß isoforms in Rhinella marina tissues by RNAseq and a molecular docking approach at the protein level to evaluate α isoform affinities for bufadienolides.

Na+/K+-ATPase (NKA) function is inhibited by Bufadienolides (BD), a group of cardiotonic steroids (CTS) primarily produced by anurans of the Bufonidae family, such as Rhinella marina. This study characterized the presence of α and ß NKA subunit isoforms in R. marina via RNAseq in four tissues: oocytes, skin, heart, and skeletal muscle. Transcripts encoding three α-like isoforms (α1, α2, α3) and three ß-like isoforms (ß1, ß2, ß4) were identified. The amino acid sequence of α1-like isoform shared 99.4% identity with the α1 isoform previously published for R. marina. Sequences for α2, α3, and ß4 from R. marina were previously unavailable. The first extracellular loop in the α2-like isoform in R. marina showed similar substitutions to those found in their susceptible homologues in other taxa (L/Q111T and S119T); in contrast, this same loop in α3-like isoform showed similar substitutions (Q111L and G120R) to those reported for toad-eating animals such as snakes, which suggests relatively lower affinity for CTS. Docking results showed that all three α-like isoforms identified in R. marina transcriptomes have low affinity to CTS compared to the susceptible α1 isoform of Sus scrofa (pig), with α1-like isoform being the most resistant. The tissue-specific RNAseq results showed the following expression of NKA α-like and ß-like subunit isoforms: Oocytes expressed α1 and ß1; skin α1, ß1, and low levels of ß2; heart α1, α3, and ß1; skeletal muscle α1, ß4, with low levels of α2, α3, and ß1. R. marina could be used as an important model for future structural, functional and pharmacological studies of NKA and its isoforms.

Snake venomics, experimental toxic activities and clinical characteristics of human envenomation by Bothrocophias myersi (Serpentes: Viperidae) from Colombia.

Venoms of the viperid genus Bothrocophias, restricted to Colombia and Ecuador, are poorly known. Only a proteomic analysis of B. campbelli venom has been described. In this work we present a proteomic study of B. myersi venom, its biological activities, and describe the clinical characteristics of a patient bitten by this species. B. myersi venom mainly consists of phospholipases A2 (54.0%) and metalloproteinases (21.5%), among proteins of twelve different families. This venom exhibited proteolytic, phospholipase A2, myotoxic, edema-forming, and lethal activities. Enzymatic activities did not show statistically significant differences in comparison to Bothrops asper venom, but B. myersi venom displayed weaker hemorrhagic and coagulant activities. Polyvalent Viperidae antivenoms produced in Costa Rica and Colombia cross-recognized B. myersi venom by ELISA, however only the latter neutralized its lethal activity in mice when tested at a ratio of 3 mg venom/mL antivenom, suggesting it should be useful to treat envenomings inflicted by this species. A patient bitten by B. myersi developed edema and myotoxicity, evidenced by an increased creatine kinase activity in plasma. A good correlation was found between experimental biological activities of Bothrocophias myersi venom and the clinical features of an envenoming provoked by this species. SIGNIFICANCE: The proteomic characterization, toxicity, immunorecognition and neutralization of Bothrocophias myersi venom have been determined for the first time. The distribution of this pit viper is restricted to Colombia and Ecuador, and its venom contains a high proportion of phospholipases A2 and metalloproteinases. The polyvalent antivenom produced in Colombia neutralized the lethal activity of this venom in vivo, and therefore should be effective in the treatment of envenomings by this snake.

Caracterización entomológica del dengue en el departamento de Risaralda, Colombia, 2011-2012 / Entomological characterization of Dengue at the Departament Risalda, Colombia, 2011 - 2011

Introducción: El dengue es una enfermedad metaxénica, endemoepidémica en diferentes regiones de Colombia. Sin embargo pocos estudios entomológicos se realizan, por lo cual es importante la caracterización del vector por diferentes indicadores. Materiales y métodos: Se realizó un estudio observacional evaluando la presencia de larvas y/o pupas de Aedes aegypti y los índices aédico, de depósitos, de Bretau, en barrios de los municipios de Risaralda, Colombia, en 2011-2012. Resultados: Se evaluó un total de 2420 barrios, en los 14 municipios (14,8% La Virginia; 12,7% Santuario y 9,7% Marsella). Se inspeccionaron 57352 casas (mediana 12/barrio, mínimo 1-máximo 324), de las cuales 2.645 fueron positivas (4,6% índice aédico crudo). Se evaluaron 70657 depósitos (mediana 17/barrio, 0-399) de los cuales 2987 fueron positivos (4,2% índice de depósitos crudo; 5,2% índice de Bretau crudo). Para Pereira (capital) se tuvo un índice aédico promedio de 11,76% (9,13% depósitos y 23,24% Bretau), seguido por La Virginia (municipio parte de la zona metropolitana de Risaralda) con 9,76% (8,24% depósitos y 11,1% Bretau) y Belén de Umbría con 6,72% (4,66% depósitos y 6,76% Bretau). Conclusiones: Como se esperaba los mayores índices correspondieron a las zonas más urbanas (Pereira y La Virginia). Esto concuerda con lo que reportan otros estudios a nivel epidemiológico donde dichas zonas muestran las mayores tasas de incidencia del dengue, por lo cual se desprende la importancia de relacionar las tasas entomológicas con las epidemiológicas para evaluar su importancia en términos de la transmisión vectorial en la región, así comootras variables ecológicas y sociales de importancia en dicho comportamiento.

Estudio epidemiológico sobre juegos de azar y factores asociados en poblacion universitariade la universidad de Manizales, Colombia, 2010 / Epidemiological study of gambling games and associated factors in the university population, of Manizales University, Colombia 2010

Antecedentes: Los juegos de azar se definen como toda actividad que consista en poner en riesgo un objeto de valor con la esperanza de obtener otro de mayor cuantía. El juego patológico constituye actualmente un importante problema de salud mental que acarrea un gran número de problemas a nivel personal, familiar y social. Materiales y métodos: En el presente estudio se analiza la frecuencia de práctica de juegos de azar y factores relacionados en estudiantes de pregrado de la universidad de Manizales en el año 2010, en una muestra seleccionada de 305 estudiantes en donde se analizaron variables como género, edad, programa, estrato socioeconómico, ingreso semanal, tipo de juego y su frecuencia, consumo de alcohol, cigarrillo, drogas, función familiar entre otras. Se utilizó para la evaluación del tipo de jugador el cuestionario de F.A.J.E.R (No jugador, Jugador con riesgo, Jugador dependiente). Resultados: Los resultados indican que 53,3% practican algun juego de azar. Según el cuestionario de F.A.J.E.R, un 7,6% y se clasificaron como jugadores dependientes, 13,6% jugadores en riesgo. Se encontró asociación significativa entre tipo de jugador y genero (p=0,000), programa (p=0,017), antecedentes de familiares de juego patológico(p=0,000), consumo de alcohol (p=0,000), funcionalidad familiar (p=0,011), consumo de sustancias psicoactivas (p=0,020), tabaquismo (p=0,042). Conclusiones: Existe una importante frecuencia de la práctica de juegos de azar en la población estudiada y el juego patológico merece más atención desde la perspectiva de la salud...

Ganglioside GD1a increases the excitability of voltage-dependent sodium channels.

The effect of the negatively charged ganglioside GD1a, one of the major brain gangliosides [H. Beitinger, W. Probst, R. Hilbig, H. Rahmann, Seasonal variability of sialo-glycoconjugates in the brain of the Djungarian hamster (Phodopus sungorus). Comp. Biochem. Physiol., B 86 (1987) 377-384] on the function of brain derived BTX-modified voltage-dependent sodium channel was studied using the planar lipid bilayer system. Bilayers were formed either with a mixture of neutral phospholipids (4 phosphoethanolamine (PE):1 phosphocholine (PC)) alone or with one containing 6% of the disialoganglioside GD1a. The permeation and activation properties of the channels were measured in the presence of symmetrical 200 mM NaCl. We found that the single channel conductance was not affected by GD1a, whereas the steady-state activation curve displayed a hyperpolarizing shift in the presence of GD1a. Since the lipid distribution in these membranes is symmetrical, then the GD1a effect on sodium channels may result either from an induction of channel conformational changes or from an asymmetrical interaction between the channel (extracellular vs. intracellular channel aspect) and GD1a. Regardless of the mechanism, the data indicate that differences in ganglioside content in neuronal cells may contribute to the previously observed sodium channel functional variability within (soma, dentritic, axon hillock) and between neuronal cells as well as to excitability changes in those physiological and pathological conditions where changes in the neuronal ganglioside content occur.