Acute kidney injury and electrolyte disorders in COVID-19.

Acute kidney injury (AKI) and electrolyte disorders are important complications of hospitalized coronavirus disease 2019 (COVID-19) patients. AKI is thought to occur due to multiple pathophysiological mechanisms, such as multiple organ dysfunction (mainly cardiac and respiratory), direct viral entry in the renal tubules, and cytokine release syndrome. AKI is present in approximately one in every ten hospitalized COVID-19 patients. The incidence rates of AKI increase in patients who are admitted to the intensive care unit (ICU), with levels higher than 50%. Additionally, renal replacement therapy (RRT) is used in 7% of all AKI cases, but in nearly 20% of patients admitted to an ICU. COVID-19 patients with AKI are considered moderate-to-severe cases and are managed with multiple interdisciplinary conducts. AKI acts as a risk factor for mortality in severe acute respiratory syndrome coronavirus 2 infection, especially when RRT is needed. Electrolyte disorders are also common manifestations in hospitalized COVID-19 patients, mainly hyponatremia, hypokalemia, and hypocalcemia. Hyponatremia occurs due to a combination of syndrome of inappropriate secretion of antidiuretic hormone and gastrointestinal fluid loss from vomiting and diarrhea. When it comes to hypokalemia, its mechanism is not fully understood but may derive from hyperaldosteronism due to renin angiotensin aldosterone system overstimulation and gastrointestinal fluid loss as well. The clinical features of hypokalemia in COVID-19 are similar to those in other conditions. Hypocalcemia is the most common electrolyte disorder in COVID-19 and seems to occur because of vitamin D deficiency and parathyroid imbalance. It is also highly associated with longer hospital and ICU stay.

Polimorfismo de los genes C677T de la enzima metil-n-tetrahidrofolato reductasa, A2756G de la enzima metionina sintasa y A66G de la enzima metionina sintasa reductasa y su relación con la homocisteína en pacientes con enfermedades cardiovasculares / C677T gene polymorphism of the enzyme-n-methyl-tetrahydrofolate reductase, A2756G gene polymorphism of the enzyme methionine synthase and A66G gene polymorphism of methionine synthase reductase and its relationship with homocysteine in patients with cardiovascular disease

La Hiperhomociteinemia (HHcy) se considera como un factor de riesgo idenpendiente para el desarrollo de aterosclerosis y de enfermedad arterial coronaria (EAC). Los polimorfismos en encimas involucradas en la regulación del metabolismo de la Hcy como la metiltetrahidrofolato reductasa (MTHFR), metionina sintasa (MTR), y la metionina sintasa reductasa (MTRR) pueden contribuir a la variación de los niveles de homocisteína en plasma (Hcy). En este estudio investigamos la asociación de los polimorfismos genéticos de las enzimas involucradas en la remetilación de la homocisteínia: metionina sintasa (MTR), metil N-tetrahidrofolato reductasa (MTHFR) y metionina sintasa reductasa (MTRR), con los niveles de Hcy en pacientes con EAC y sujetos sanos. Población 136 individuos de los cuales 90 presentaron diagnóstico de enfermedad cardiovascular (IAM y ACV) y 46 eran aparentemente sanos (controles). La concentración de Hcy fue significativamente más alta en pacientes con ECV que en los sujetos control (P<0,001). HHcy (>15 µmol/L) confirió un RR de IAM de 2.52 (95% IC: 1.4-4.4, P<0,001) y de ACV de 1.88 (95% IC: 1.0-3-5, P<0,05). Los niveles de vitamina B12 y folato se encontraba en el rango de los valores de referencia en el 86% de los individuos. La frecuencia del alelo T para C677T de MTHFR, del alelo G para A66G de MTRR y del alelo G para A2756G de MTR fueron 0.31, 0.30, 0.22 respectivamente para los sujetos casos. Los polimorfismos C677T, A66G y A276G de los genes MTHFR, MTRR y MTR no tuvieron diferencia estadísticamente significativa entre el grupo de casos con respecto al grupo control. Los polimorfismos estudiados no se relacionaron estadísticamente con la HHcy en los individuos en estudio. Sugerimos que HHcy confiere riesgo para ECV. En nuestro estudio encontramos evidencia de que la regulación de Hcy es poligénica.

The Hiperhomocysteinemia (HHcy) is considered an independent risk factor for developing atherosclerosis and cardiovascular arterial disease (CAD). The polymorphisms of the enzymes involved in the regulation of homocysteine (Hcy) metabolism as the methyltetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) may contribute to the elevation of Hcy in plasma. The main aim of the this study was to investigate the association of genetic polymorphisms of the enzymes involved in remethylation of homocysteine: methionine synthase (MTR), N-methyl tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), with levels of Hcy in patients with CHF and healthy subjects. Population: 136 subjects of whom 90 had a diagnosis of cardiovascular disease (heart failure and stroke) and 46 were apparently healthy (controls). The concentration of Hcy was significantly higher in patients with cardiovascular disease than compare with the control group (P<0.001). HHcy (>15 mmol/L) conferred a relative risk (RR) of heart failure of 2.52 (95% CI: 1.4-4.4, P <0.001) and stroke, RR of 1.88 (95% CI: 1.0-3.5, P <0.05). The levels of vitamin B12 and folate was in the range of reference values in 86% of subjects. The frequency of the T allele of MTHFR C677T was 0,31, for the G allele of MTRR A66G was 0,30 and for the G allelwe for MTR A2756G was 0.22 for the subjects with heart failure and stroke referred as case. C677T polymorphism, A66G and A2756G of the genes MTHFR, MTRR and MTR had no associated statistically with HHcy in the subjects of the study. We suggest that HHcy confers risk for CVD. In our study we found evidence that the regulation of Hcy is polygenic.

Frecuencia de sensibilización alimentos y aero-alergenos en pacientes recibidos en el laboratorio de Corpodiagnostica C.A. durante el periodo 2010-2011 / Frequency of sensitization for food and aero-allergens in patients reciived in a Venezuelan laboratory during 2010-2011 period

La alergia tipo I se ha definido como una reacción inmunológica adversa mediada por IgE que se produce después de una exposición repetida al alérgeno. La prevalencia de las alergias ha aumentado considerablemente en los últimos 20 años, lo que aumenta la necesidad del estudio de la respuesta a varios alérgenos. El objetivo fue evaluar la frecuencia de sensibilización a alimentos y aero-alérgenos en los pacientes referidos al Laboratorio de Corpodiagnostica C.A. durante el periodo 2010-2011. Se determinó niveles de IgE específica a 2445 pacientes, usando el método inmunoblot in vitro RIDA Allergy-screen (r-Biopharm, Alemania). La tasa de sensibilización total medida por IgE específica a alimentos fue de 30,43%, donde los alimentos más comunes fueron Leche, Queso, Trigo, Maíz y Cerdo; mientras que la tasa de sensibilización para aero-alérgenos fue de 46,16%; de los cuales los más comunes fueron los ácaros mayores y B. tropicalis. Este estudio provee de una herramienta importante para la identificación de los alérgenos alimentarios y respiratorios de mayor prevalencia en la población venezolana.

Type I allergy had been defined as an adverse immunologic reaction mediated by IgE that occurs after a repeated exposure to the allergen. The prevalence of the allergies has increased considerably in the last 20 years, thus increasing the need of study the response to several allergens. The objective was to evaluate the frecuency of foods and respiratory allerges sensitization in patients referred to Corpodiagnostica Laboratory (Caracas, Venezuela, ISO 9001:2008 certified laboratory) in the period that correspond from January 2010 to July 2011. We determinated specific IgE levels to 2445 patients, by the in vitro RIDA® Allergy-screen immunoblot method (r-biopharm®, Germany). The total sensitization rate mediated by specific IgE to food allergen was 30,43% where the foods most common were milk, cheese, wheat flour, corn and pork; while the sensitization for aero-allerges was 46,16%; the most common were the major mites and B. tropicalis. This study provides an important tool for the identification of food and aero-allergens with major prevalence in the Venezuelan population.

Metabotropic receptor-activated calcium increases and store-operated calcium influx in mouse Müller cells.

PURPOSE: Metabotropic receptor agonists that signal through G(q)-coupled pathways increase Ca(2+) in mammalian Müller cells by release from intracellular stores and Ca(2+) influx pathways that have not been well described. The authors examined the involvement of voltage-dependent and non-voltage-dependent Ca(2+) channels in metabotropic muscarinic receptor-activated Ca(2+) increases and store-operated Ca(2+) influx in cultured mouse Müller cells. METHODS: Intracellular Ca(2+) was measured using fluorescence imaging with the ratiometric dye fura-2. Currents were recorded using the whole-cell patch-clamp recording method: mRNA and protein were identified using reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemical approaches. RESULTS: The muscarinic receptor agonist carbachol (3-20 microM) produced increases in Ca(2+) that were blocked by the muscarinic receptor antagonists atropine and pirenzepine. RT-PCR confirmed mRNA for metabotropic M1 muscarinic receptors. Depletion of Ca(2+) stores by the sarcoplasmic/endoplasmic Ca(2+) ATPase (SERCA) inhibitors thapsigargin and cyclopiazonic acid or the inhibition of phospholipase C occluded the carbachol-activated increase in Ca(2+). Carbachol-activated Ca(2+) increases in Müller cells were enhanced by the diacylglycerol derivative 1-oleyl-2-acetyl-sn-glycerol and were blocked by transient receptor potential (TRP) channel blockers Gd(3+), La(3+), 2-APB, and flufenamic acid. Both muscarinic receptor activation and thapsigargin treatment depleted Ca(2+) stores and produced Ca(2+) entry that was attenuated by La(3+), 2-APB, Gd(3+), and flufenamic acid. mRNA and protein for TRPC1 and TRPC6 were present in mouse Müller cells, and carbachol activated a Gd(3+)-sensitive, TRP-like cation channel. CONCLUSIONS: Metabotropic muscarinic receptor-activated Ca(2+) increases in mouse Müller cells require the release of Ca(2+) from intracellular stores and the activation of Ca(2+) entry that involves TRP-like cation channels but is independent of voltage-dependent Ca(2+) channels.

Sensibilidad de la IgE vs. IgE específica en contra alérgenos de ácaros y hongos para el despistaje de alergias tipo I en una población de trabajadores / Total IgE sensitivity against specific IgE against mites and molds in Workers for the screening of type I allergy

Las alergias mediadas por IgE (tipo 1) son enfermedades crónicas que afectan a más del 20% de la población en algunos países. Se analizaron muestras de un grupo de 55 trabajadores del IUPOLC, Caracas, Venezuela, que manifestaron presentar síntomas relacionados con Alergias tipo I, mediante el uso de un cuestionario especialmente diseñado para tal fin. En ichas muestras se determinó la IgE Total Sérica por ELISA (Dr. Fooke Laboratorien, Alemania) y simultaneamente se ensayó un panel de IgE específica compuesto por ácaros y hongos de conocida prevalencia local por la técnica de Allergy Screen® (r-biopharm, Alemania), en aras de calcular la sensibilidad diagnósticada de la IgE Total sérica como marcador para el diagnóstico de Alergias Tipo I ante el hallazgo de valores significativos de IgE Específica para los alergenos seleccionados. Se escogieron los valores de referencia de IgE Total utilizados en la mayoría de los laboratorios clínicos de Venezuela. El valor de sensibilidad diagnóstica obtenido en el estudio para la IgE Total sérica fue de 66,67%, con una especificada de 100%. Valor Predictivo VPP de 100%. Valor Predicitivo Negativo 61,29%. Se discutió la posibilidad de que este valor de sensibilidad pudiese ser incluso menor con la inclusión de mayor número de alergenos y/o pruebas de piel. En conclusión, la utilización de la IgE Total sérica como herramienta diagnóstica de primera instancia (tamizaje y/o screening) de alergia tipo I, debe estar acompañada de la historia clínica del paciente y la prescripción de otros ensayos como la IgE específica. Los laboratorios clínicos locales deben procurar la utilización de mejores esquemas de interpretación (valores de referencia) de la IgE Total sérica que contribuyan a un mejor diagnóstico de esta patología.

IgE mediated allergies (Type I)are chronic diseases that effect more than 20% the population in some countries. We analyzed 55 blood samples from workers of Universitary Institute of Scientific Police, IUPOLC Caracas, Venezuela, that presented Allergies related symptyoms at the moment ofthe study. We used a specially designed survey to register that information. We tested serum Total IgE by ELISA method and a specific IgE using an immunoblott nitrocellulose paner composed with mites and molds allergens of well know local prevalence, in order to calculate the diagnostic sensitivity of serum Total IgE as a marker for screening Type I Allergies compared with allergen sensitivities detected on the individuals. We selected the most common reference values for serum Total IgE used in Venezuela. The sensitivity obtained for serum Total IgE was 66,67% specificity 100%, Positive Predictive Value 100%, and Negative Predictive Value 61,29%. We discussed the possibility that the sensitivity obtained for Total IgE could be oven lower if more number of allergens and skin tests were included on the study. We conclude that the use of Total IgE as screening diagnostic tool for allergies must be used together with clinical history of the patient and other assays like i.e. Specific IgE. Local Clinical Laboratories should promote of better interpretation schemes (reference values) for Total IgE that actually helps to a better diagnosis of this disease.

Prevalencia de sensibilización hacía ácaros y hongos en trabajadores con alergia tipo I / Prevalence of sensibilization to mites and moulds on workers with allergy tipe I

Empleados de oficinas que actualmente trabajan dentro de edificaciones con sistemas cerrados de aire acondicionado, pudiesen estar expuestos a hongos y ácaros en su lugar de trabajo. Las condiciones pudiesen ser peores si estos sistemas no son mantienen de forma apropiada. El Instituto Universitario de Policía Científica de Caracas” (IUPOLC, Venezuela), pudiese ser un ejemplo de esta situación. Analizar la prevalencia de los niveles de IgE Específica en contra de ácaros (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia Tropicalis) y hongos ambientales (Penicillium notatum, Cladosporium herbarum, Aspergillus fumigatus, Alternaria tenuis/alternata) en una población que reporta sintomatología relacionadas con Alergias tipo I (Mediadas por IgE), y que labora en Instituto Universitario de Policía Científica de Caracas, IUPOLC. De la totalidad de trabajadores del edificio del IUPOLC, actualmente 47 empleados reportaron poseer síntomas asociados con Alergias Tipo I al momento de la toma de la muestra para este estudio. Se evaluó los niveles de IgE específica en contra de ácaros y hongos utilizando el sistema de Allergy Screen® de r-biopharm, (Actualmente utilizado en más de 70 países), el cual es un método de fase solida de nitro celulosa. El laboratorio que realizó el estudio está suscrito al esquema de control de calidad externo UK NEQA) (Reino Unido) y además organiza el único sistema disponible para tal fin en Venezuela. 82.98% de los pacientes estudiados presentaron sensibilizaciones en contra de ácaro y/o hongos. 53,19% mostraron valores significativos hacía ácaros; Dentro de ellos el más frecuente fue Blomia tropicalis, (25 casos), seguido Dermatophagoides pteronissynus por Dermatophagoides farinae. Dentro de los hongos los más frecuentes resultaron Cladosporium herbarum (10 casos), Aspergillus fumigatus, (9 casos) Penicillium notatum (4 casos) y Alternaria alternata (1 caso)...

Office employees that actually work inside buildings with air-conditioned closed systems are well known to be exposed to fungi and storage mites in their workplace. The conditions could be worst when those systems aren’t properly maintained. The “Instituto Universitario de Policía Científica de Caracas” (IUPOLC, Venezuela) could be an example for that situation. AIM: To evaluate the prevalence of sensitization to moulds and mites though Specific IgE levels determinations, on workers of the IUPOLC that presented clinical symptoms associated with allergy type I at the moment of the study. From the total population of workers of the IPUOLC facility, actually 47 employees of IUPOLC presented one or more clinical symptoms associated with allergy at the moment of the study. The level of serum-specific IgE to mites and moulds were evaluated, using the Allergy Screen® r-biopharm methodology enzymatic solid phase method in nitro-cellulose in all subjects (Actually used in more than 70 countries). The Laboratory that performed the tests is actually subscribed to the UK NEQAS (United Kingdom National External Quality Assessment Service), and also they organize the only Allergy External Quality Scheme available in Venezuela. 82.98% of the patients analyzed presented one or more increased values for mites or molds. 53,2% resulted with positive values for Mites; the most frequent mites involved on the population were Blomia tropicalis, (with 25 cases), Dermatophagoides pteronissynus and Dermatophagoides farinae. On molds the most frequent sensibilizations resulted on Cladosporium herbarum (10 cases), Aspergillus fumigatus, (9 cases) Penicillium notatum (4 cases) and last Alternaria alternata (1 case). This study suggests an important role of fungi and mites as occupational allergens for IUPOLC workers. The prevalence of allergic symptoms among employees of IUPOLC was relatively high...

Prevalencia de norovirus en muestras de heces procedenes del laboratotio del Hospital José Gregorio Hernández / The prebalence of the norovirus in fecal samples which originated at the laboratory of the Hospital José Gregorio Hernandez. Catia, Caracas

La gastroenteritis en Venezuela es la principal causa de muerte y morbilidad en la población infantil. La falta de adecuadas metodologías diagnósticas en el laboratorio de rutina impide identificar todos los posibles microorganismos causantes de gastroenteritis enfocando el diagnóstico al estudio de parásitos protozoarios o helmintos, bacterias aeróbicas y en menos grado virus y hongos. Basado en esto, decidimos determinar si el norovirus es el agente causal de gastroenteritis en nuestro país, determinar las condiciones ambientales y sanitarias en la comunidad en estudio y analizar los esquemas y técnicas diagnósticas actualmente utilizadas en los centros de salud. Se evaluaron 173 muestras de heces de pacientes que asistieron al laboratorio del Hospital Magallanes de Catia. Se utilizó un kit de inmunoensayo enzimático, ELISA RIDASCREEN norovirus de r-biopharm AG, alemania, el cual permite el diagnóstico in vitro e identificación cualitativa de los norovirus genogrupo I y II en muestras de heces. De las 173 muestras de heces analizadas 29 (16,76%) resultaron positivas, 144 (83,32%) fueron negativas. Cuando se evaluaron por grupo etario, el grupo de niños de 6-13 años se obtuvo el mayor número de muestras positivas (8) seguido del grupo de niños 0 - 5 años con 7 muestras positivas. Se encontró mayor frecuencia de norovirus en muestras con aspecto heterogéneo, color marrón y verde de consistencia blanda y alcalina, así mismo 19,08% de las muestras fueron positivas para algún parásito (Protozoario o Helmintos) visibles en el examen microscópico directo. Se demostró que 16,76% de las diarreas en le grupo evaluado fueron por norovirus, siendo importante su determinación para el diagnóstico de gastroenteritis.

Gastroenteritis is the main cause of death and morbidity among children in Venezuela. The lack of adequate diagnostic methodologies in the laboratory reduce the identification of all possible microorganisms that cause gastroenteritis, since they focus the diagnosis on the study of parasites, protozoa or helminthes, aerobic bacteria and, to a lesser degree, on viruses and fungi. Based on this, we decided to determine if the norovirus is the causal agent of gastroenteritis in our country; to determine the environmental and sanitary conditions in the community under study; and, to analyze the diagnostic framework and techniques currently used in healthcare centers. 173 fecal samples of patients that visited the laboratory of the Hospital Magallanes in Catia were evaluated. An enzymatic immunoassay kit, ELISA RIDASCREEN norovirus of r-biopharm AG, Germany, was used since it permits the in vitro diagnosis and the qualitative identification of the norovirus genogroups I and II in fecal samples. Of the 173 stool samples analyzed, 29 (16.76%) tested positive, 144 (83.32%) tested negative. When evaluated by age group, the group of children between 6-13 years old presented the greatest number of positive samples (8), followed by the group of children between 0-5 with 7 positive samples. The highest frequency of norovirus was found in samples of heterogeneous appearance, brown-green color, soft and alkaline consistency; also, 19.08% of the samples tested positive for some type of parasite (Protozoa or Helminthes), visible with direct microscopic examination. So, we can conclude that it was shown that 16.76% of the diarrheas in the evaluation group were due to norovirus, its determination being important for the diagnosis of gastroenteritis.

Proton-mediated feedback inhibition of presynaptic calcium channels at the cone photoreceptor synapse.

Generation of center-surround antagonistic receptive fields in the outer retina occurs via inhibitory feedback modulation of presynaptic voltage-gated calcium channels in cone photoreceptor synaptic terminals. Both conventional and unconventional neurotransmitters, as well as an ephaptic effect, have been proposed, but the intercellular messaging that mediates the inhibitory feedback signal from postsynaptic horizontal cells (HCs) to cones remains unknown. We examined the possibility that proton concentration in the synaptic cleft is regulated by HCs and that it carries the feedback signal to cones. In isolated, dark-adapted goldfish retina, we assessed feedback in the responses of HCs to light and found that strengthened pH buffering reduced both rollback and the depolarization to red light. In zebrafish retinal slices loaded with Fluo-4, depolarization with elevated K(+) increased Ca signals in the synaptic terminals of cone photoreceptors. Kainic acid, which depolarizes HCs but has no direct effect on cones, depressed the K(+)-induced Ca signal, whereas CNQX, which hyperpolarizes HCs, increased the Ca signals, suggesting that polarization of HCs alters inhibitory feedback to cones. We found that these feedback signals were blocked by elevated extracellular pH buffering, as well as amiloride and divalent cations. Voltage clamp of isolated HCs revealed an amiloride-sensitive conductance that could mediate modulation of cleft pH dependent on the membrane potential of these postsynaptic cells.

Light-regulated subcellular translocation of Drosophila TRPL channels induces long-term adaptation and modifies the light-induced current.

Drosophila phototransduction results in the opening of two classes of cation channels, composed of the channel subunits transient receptor potential (TRP), TRP-like (TRPL), and TRPgamma. Here, we report that one of these subunits, TRPL, is translocated back and forth between the signaling membrane and an intracellular compartment by a light-regulated mechanism. A high level of rhabdomeral TRPL, characteristic of dark-raised flies, is functionally manifested in the properties of the light-induced current. These flies are more sensitive than flies with no or reduced TRPL level to dim background lights, and they respond to a wider range of light intensities, which fit them to function better in darkness or dim background illumination. Thus, TRPL translocation represents a novel mechanism to fine tune visual responses.