Biomineral crystallographic preferred orientation in Solenogastres molluscs (Aplacophora) is controlled by organic templating.

Aplacophoran molluscs are shell-less and have a worm-like body which is covered by biomineralized sclerites. We investigated sclerite crystallography and the sclerite mosaic of the Solenogastres species Dorymenia sarsii, Anamenia gorgonophila, and Simrothiella margaritacea with electron-backscattered-diffraction (EBSD), laser-confocal-microscopy and FE-SEM imaging. The soft tissue of the molluscs is covered by spicule-shaped, aragonitic sclerites. These are sub-parallel to the soft body of the organism. We find, for all three species, that individual sclerites are untwinned aragonite single crystals. For individual sclerites, aragonite c-axis is parallel to the morphological, long axis of the sclerite. Aragonite a- and b-axes are perpendicular to sclerite aragonite c-axis. For the scleritomes of the investigated species we find different sclerite and aragonite crystal arrangement patterns. For the A. gorgonophila scleritome, sclerite assembly is disordered such that sclerites with their morphological, long axis (always the aragonite c-axis) are pointing in many different directions, being, more or less, tangential to cuticle surface. For D. sarsii, the sclerite axes (equal to aragonite c-axes) show a stronger tendency to parallel arrangement, while for S. margaritacea, sclerite and aragonite organization is strongly structured into sequential rows of orthogonally alternating sclerite directions. The different arrangements are well reflected in the structured orientational distributions of aragonite a-, b-, c-axes across the EBSD-mapped parts of the scleritomes. We discuss that morphological and crystallographic preferred orientation (texture) is not generated by competitive growth selection (the crystals are not in contact), but is determined by templating on organic matter of the sclerite-secreting epithelial cells and associated papillae.

Effect of FeCl3 concentration in chemically enhanced primary treatment on the performance of a conventional wastewater treatment plant. A case study.

The effect of coagulant dosage in a chemically enhanced primary treatment (CEPT) on the performance of a conventional wastewater treatment plant (WWTP) has been investigated. Lab-scale experiments simulations were carried out in order to evaluate the effect of coagulant addition on the primary settling performance. In these experiments, FeCl3 was used as coagulant. Later, the WWTP was theoretically simulated using a commercial software (WEST®) to evaluate the effect of coagulation/flocculation on the global system, based on the results obtained at lab-scale. According to these results, the CEPT modifies the organic matter balance in the WWTP, decreasing the contribution of readily (SS) and slowly (XS) biodegradable fractions of COD to the aerobic biological process up to 27.3% and 80.8%, respectively, for a dosage of FeCl3 of 24 mg L-1. Consequently, total suspended solids in the aerobic reactor and the secondary purged sludge decreased up to 33% and 13%, respectively. However, the influence on effluent quality was negligible. On the contrary, suspended solids concentration in the sludge to be treated by anaerobic digestion increased, mainly regarding the Ss and Xs fractions, which caused an 8.1% increase in biogas production potential, with approximately 60% of CH4 concentration.

Guinea fowl eggshell structural analysis at different scales reveals how organic matrix induces microstructural shifts that enhance its mechanical properties.

Guinea fowl eggshells have an unusual structural arrangement that is different from that of most birds, consisting of two distinct layers with different microstructures. This bilayered organization, and distinct microstructural characteristics, provides it with exceptional mechanical properties. The inner layer, constituting about one third of the eggshell thickness, contains columnar calcite crystal units arranged vertically as in most bird shells. However, the thicker outer layer has a more complex microstructural arrangement formed by a switch to smaller calcite domains with diffuse/interlocking boundaries, partly resembling the interfaces seen in mollusk shell nacre. The switching process that leads to this remarkable second-layer microstructure is unknown. Our results indicate that the microstructural switching is triggered by changes in the inter- and intracrystalline organic matrix. During production of the outer microcrystalline layer in the later stages of eggshell formation, the interactions of organic matter with mineral induce an accumulation of defects that increase crystal mosaicity, instill anisotropic lattice distortions in the calcite structure, interrupt epitaxial growth, reduce crystallite size, and induce nucleation events which increase crystal misorientation. These structural changes, together with the transition between the layers and each layer having different microstructures, enhance the overall mechanical strength of the Guinea fowl eggshell. Additionally, our findings provide new insights into how biogenic calcite growth may be regulated to impart unique functional properties. STATEMENT OF SIGNIFICANCE: Avian eggshells are mineralized to protect the embryo and to provide calcium for embryonic chick skeletal development. Their thickness, structure and mechanical properties have evolved to resist external forces throughout brooding, yet ultimately allow them to crack open during chick hatching. One particular eggshell, that of the Guinea fowl, has structural features very different from other galliform birds - it is bilayered, with an inner columnar mineral structure (like in most birds), but it also has an outer layer with a complex microstructure which contributes to its superior mechanical properties. This work provides novel and new fundamental information about the processes and mechanisms that control and change crystal growth during the switch to microcrystalline domains when the second outer layer forms.

The unique fibrilar to platy nano- and microstructure of twinned rotaliid foraminiferal shell calcite.

Diversification of biocrystal arrangements, incorporation of biopolymers at many scale levels and hierarchical architectures are keys for biomaterial optimization. The planktonic rotaliid foraminifer Pulleniatina obliquiloculata displays in its shell a new kind of mesocrystal architecture. Shell formation starts with crystallization of a rhizopodial network, the primary organic sheet (POS). On one side of the POS, crystals consist of blocky domains of 1 µm. On the other side of the POS crystals have dendritic-fractal morphologies, interdigitate and reach sizes of tens of micrometers. The dendritic-fractal crystals are twinned. At the site of nucleation, twinned crystals consist of minute fibrils. With distance away from the nucleation-site, fibrils evolve to bundles of crystallographically well co-oriented nanofibrils and to, twinned, platy-blade-shaped crystals that seam outer shell surfaces. The morphological nanofibril axis is the crystallographic c-axis, both are perpendicular to shell vault. The nanofibrillar calcite is polysynthetically twinned according to the 60°/[100] (= m/{001}) twin law. We demonstrate for the twinned, fractal-dendritic, crystals formation at high supersaturation and growth through crystal competition. We show also that c-axis-alignment is already induced by biopolymers of the POS and is not simply a consequence of growth competition. We discuss determinants that lead to rotaliid calcite formation.

Patterns of crystal organization and calcite twin formation in planktonic, rotaliid, foraminifera shells and spines.

The foraminiferal order Rotaliida represents one third of the extant genera of foraminifers. The shells of these organisms are extensively used to decipher characteristics of marine ecosystems and global climate events. It was shown that shell calcite of benthic Rotaliida is twinned. We extend our previous work on microstructure and texture characterization of benthic Rotaliida and investigate shell calcite organization for planktonic rotaliid species. Based on results gained from electron backscattered diffraction (EBSD) and field emission electron microscopy (FESEM) imaging of chemically etched/fixed shell surfaces we show for the planktonic species Globigerinoides sacculifer, Pulleniatina obliquiloculata, Orbulina universa (belonging to the two main planktonic, the globigerinid and globorotaliid, clades): very extensive 60°-{001}-twinning of the calcite and describe a new and specific microstructure for the twinned crystals. We address twin and crystal morphology development from nucleation within a biopolymer template (POS) to outermost shell surfaces. We demonstrate that the calcite of the investigated planktonic Rotaliida forms through competitive growth. We complement the structural knowledge gained on the clade 1 and clade 2 species with EBSD results of Globigerinita glutinata and Candeina nitida shells (clade 3 planktonic species). The latter are significantly less twinned and have a different shell calcite microstructure. We demonstrate that the calcite of all rotaliid species is twinned, however, to different degrees. We discuss for the species of the three planktonic clades characteristics of the twinned calcite and of other systematic misorientations. We address the strong functionalization of foraminiferal calcite and indicate how the twinning affects biocalcite material properties.

Regulation of cardiac ion channels by transcription factors: Looking for new opportunities of druggable targets for the treatment of arrhythmias.

Cardiac electrical activity is governed by different ion channels that generate action potentials. Acquired or inherited abnormalities in the expression and/or function of ion channels usually result in electrophysiological changes that can cause cardiac arrhythmias. Transcription factors (TFs) control gene transcription by binding to specific DNA sequences adjacent to target genes. Linkage analysis, candidate-gene screening within families, and genome-wide association studies have linked rare and common genetic variants in the genes encoding TFs with genetically-determined cardiac arrhythmias. Besides its critical role in cardiac development, recent data demonstrated that they control cardiac electrical activity through the direct regulation of the expression and function of cardiac ion channels in adult hearts. This narrative review summarizes some studies showing functional data on regulation of the main human atrial and ventricular Na+, Ca2+, and K+ channels by cardiac TFs such as Pitx2c, Tbx20, Tbx5, Zfhx3, among others. The results have improved our understanding of the mechanisms regulating cardiac electrical activity and may open new avenues for therapeutic interventions in cardiac acquired or inherited arrhythmias through the identification of TFs as potential drug targets. Even though TFs have for a long time been considered as 'undruggable' targets, advances in structural biology have led to the identification of unique pockets in TFs amenable to be targeted with small-molecule drugs or peptides that are emerging as novel therapeutic drugs.

Calcite crystal orientation patterns in the bilayers of laminated shells of benthic rotaliid foraminifera.

Shells of calcifying foraminifera play a major role in marine biogeochemical cycles; fossil shells form important archives for paleoenvironment reconstruction. Despite their importance in many Earth science disciplines, there is still little consensus on foraminiferal shell mineralization. Geochemical, biochemical, and physiological studies showed that foraminiferal shell formation might take place through various and diverse mineralization mechanisms. In this study, we contribute to benthic foraminiferal shell calcification through deciphering crystallite organization within the shells. We base our conclusions on results gained from electron backscattered diffraction (EBSD) measurements and describe microstructure/texture characteristics within the laminated shell walls of the benthic, symbiontic foraminifera: Ammonia tepida, Amphistegina lobifera, Amphistegina lessonii. We highlight crystallite assembly patterns obtained on differently oriented cuts and discuss crystallite sizes, morphologies, interlinkages, orientations, and co-orientation strengths. We show that: (i) crystals within benthic foraminiferal shells are mesocrystals, (ii) have dendritic-fractal morphologies and (iii) interdigitate strongly. Based on crystal size, we (iv) differentiate between the two layers that comprise the shells and demonstrate that (v) crystals in the septa have different assemblies relative to those in the shell walls. We highlight that (vi) at junctions of different shell elements the axis of crystal orientation jumps abruptly such that their assembly in EBSD maps has a bimodal distribution. We prove (vii) extensive twin-formation within foraminiferal calcite; we demonstrate (viii) the presence of two twin modes: 60°/[001] and 77°/~[6 -6 1] and visualize their distributions within the shells. In a broader perspective, we draw conclusions on processes that lead to the observed microstructure/texture patterns.

Adscripción del farmacéutico a cuidados intensivos: generando sinergias / Pharmacist Adscription To Intensive Care: Generating Synergies

OBJETIVO: Evaluar la incorporación de un farmacéutico de hospital a la actividad habitual de una unidad de cuidados intensivos (UCI). DISEÑO: Estudio observacional prospectivo para evaluar las intervenciones farmacéuticas, realizadas por un farmacéutico adscrito temporalmente a una UCI, sobre las prescripciones médicas. Ámbito: UCI médico-quirúrgica con 21 camas. PACIENTES: Se incluyeron los pacientes con al menos una estancia en UCI y se excluyeron los pacientes con ingreso y alta en periodos en los que no se contó con la presencia física del farmacéutico. INTERVENCIONES: Se realizaban tras la revisión diaria de las prescripciones y se comunicaban de forma verbal o escrita al médico responsable. Variables principales: Intervenciones realizadas, grupo terapéutico de los medicamentos implicados, forma de realización de la intervención y el grado de aceptación. RESULTADOS: Se realizaron 194 intervenciones en 62 pacientes. La mayoría estaban relacionadas con aspectos de seguridad (33%) y optimización de la terapia (32%). Las más frecuentes se dirigieron a la administración de medicamentos por sonda nasogástrica (19%) y a la monitorización farmacocinética (14,4%). Los grupos de medicamentos más implicados fueron los antiinfecciosos en un 33% de los casos y los del aparato digestivo en un 27%. El 56,2% de las intervenciones se realizaron verbalmente y el 80% fueron aceptadas. CONCLUSIONES: La adscripción de un farmacéutico a una UCI y la realización de intervenciones sobre las prescripciones han permitido mejorar la seguridad y optimizar la farmacoterapia en más de la mitad de los pacientes. La alta tasa de aceptación de las mismas apoyaría la implementación de este tipo de programas en las unidades de críticos

OBJECTIVE: To evaluate incorporation of the hospital pharmacist to the routine activity of an Intensive Care Unit (ICU). DESIGN: A prospective observational study was carried out to evaluate the impact of pharmacist interventions, made by a pharmacist temporarily assigned to the ICU, upon medical prescriptions. SETTING: A medical and surgical ICU with 21 beds. PATIENTS: Patients with at least one ICU stay were included, while patients with admission and discharge in periods when the pharmacist was not present were excluded. INTERVENTIONS: The interventions were made after daily review of the prescriptions, and were communicated verbally or in writing to the supervising physician. MAIN VARIABLES: Number of interventions, therapeutic group of the drugs involved, type of intervention and degree of acceptance. RESULTS: A total of 194 interventions were made in 62 patients. The majority were related to safety aspects (33%) and the optimization of therapy (32%). The most frequent interventions were the administration of drugs via the nasogastric tube (19%) and pharmacokinetic monitoring (14.4%). The most frequently involved groups of drugs were anti-infectious agents (33%) and digestive system medications (27%). A total of 56.2% of the interventions were made verbally, and 80% were accepted. CONCLUSIONS: Pharmacist adscription to an ICU and the implementation of interventions on prescriptions have allowed improvement of safety and the optimization of pharmacotherapy in more than 50% of the patients. The high rate of acceptance of these interventions would support the implementation of such programs in critical care units

Arginase inhibition improves endothelial function in patients with type 2 diabetes mellitus despite intensive glucose-lowering therapy.

BACKGROUND: Arginase is implicated in the pathogenesis behind endothelial dysfunction in type 2 diabetes mellitus (T2DM) by its inhibition of nitric oxide formation. Strict glycaemic control is not sufficient to improve endothelial function or cardiovascular outcomes in patients with T2DM, thus other treatment strategies are needed. We hypothesized that arginase inhibition improves endothelial function beyond glucose-lowering therapy following glucose optimization in patients with poorly controlled T2DM. METHODS AND RESULTS: Endothelial function was evaluated in 16 patients with poorly controlled T2DM (visit 1) and 16 age-matched controls using venous occlusion plethysmography. T2DM patients were re-evaluated (visit 2) after intensive glucose-lowering regimen. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatations were evaluated before and after 120 min intra-arterial infusion of the arginase inhibitor N(ω)-hydroxy-nor-L-arginine (nor-NOHA). HbA1c was reduced from 87 ± 17 (visit 1) to 65 ± 11 mmol mol-1 (visit 2, P < 0.001). Basal EDV, but not EIDV, was significantly lower in patients with T2DM than in healthy subjects (P < 0.05). EDV and EIDV were unaffected by glucose-lowering regimen in patients with T2DM. Arginase inhibition enhanced EDV in T2DM patients both at visit 1 and visit 2 (P < 0.01). There was no difference in improvement in EDV between the two occasions. EIDV was unaltered by nor-NOHA in T2DM at visit 1, but was slightly improved at visit 2. CONCLUSIONS: Arginase inhibition improves endothelial function in patients with poorly controlled T2DM, which is maintained following glucose optimization. Thus, arginase inhibition is a promising therapeutic target beyond glucose lowering for improving endothelial function in T2DM patients.

Pharmacist Adscription To Intensive Care: Generating Synergies. / Adscripción del farmacéutico a cuidados intensivos: generando sinergias.

OBJECTIVE: To evaluate incorporation of the hospital pharmacist to the routine activity of an Intensive Care Unit (ICU). DESIGN: A prospective observational study was carried out to evaluate the impact of pharmacist interventions, made by a pharmacist temporarily assigned to the ICU, upon medical prescriptions. SETTING: A medical and surgical ICU with 21 beds. PATIENTS: Patients with at least one ICU stay were included, while patients with admission and discharge in periods when the pharmacist was not present were excluded. INTERVENTIONS: The interventions were made after daily review of the prescriptions, and were communicated verbally or in writing to the supervising physician. MAIN VARIABLES: Number of interventions, therapeutic group of the drugs involved, type of intervention and degree of acceptance. RESULTS: A total of 194 interventions were made in 62 patients. The majority were related to safety aspects (33%) and the optimization of therapy (32%). The most frequent interventions were the administration of drugs via the nasogastric tube (19%) and pharmacokinetic monitoring (14.4%). The most frequently involved groups of drugs were anti-infectious agents (33%) and digestive system medications (27%). A total of 56.2% of the interventions were made verbally, and 80% were accepted. CONCLUSIONS: Pharmacist adscription to an ICU and the implementation of interventions on prescriptions have allowed improvement of safety and the optimization of pharmacotherapy in more than 50% of the patients. The high rate of acceptance of these interventions would support the implementation of such programs in critical care units.

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C16:0- and C24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

Estudio de prevalencia del trastorno por déficit de atención e hiperactividad en niños en régimen de acogimiento residencial / Prevalence study of attention deficit hyperactivity disorder in children in residential care

INTRODUCCIÓN: Los niños que se encuentran en régimen de acogimiento residencial constituyen un colectivo de riesgo en el que los problemas médicos pueden alcanzar altas tasas, especialmente aquellos relacionados con la esfera psicológica, donde el trastorno por déficit de atención e hiperactividad (TDAH) es una de las alteraciones del neurodesarrollo más frecuentes. OBJETIVO: El propósito de este estudio fue determinar la prevalencia de TDAH en los niños de un centro de acogida en Albuñol (Granada) en 2016. Material y Métodos. En este estudio transversal se incluyeron los 106 niños de edades comprendidas entre los 5 y los 17 años del Centro Hogar "Cristo Rey". La evaluación psicométrica se basó en la Escala de Vanderbilt de TDAH. Las funciones ejecutivas se evaluaron mediante el Behavior Rating Inventory of Executive Function (BRIEF) en aquellos participantes que cumplieron los criterios de Vanderbilt, y también se aplicaron los criterios del DSM-5 en la entrevista clínica para reforzar el diagnóstico de TDAH. RESULTADOS: La prevalencia de TDAH fue del 17.9% en nuestro grupo, siendo el subtipo inatento el más frecuente. CONCLUSIONES: La prevalencia de TDAH en el centro de acogida "Cristo Rey" fue notablemente elevada en comparación con la prevalencia en niños de la población general. Es necesario seguir investigando acerca de las comorbilidades relacionadas con el TDAH en niños en régimen de acogimiento residencial. Deberían instaurarse programas de detección e intervención en centros de acogida por las repercusiones que puede llegar a tener el TDAH

INTRODUCTION: Children in residential care constitute a risk group in which medical problems can reach high rates, especially those concerned to the psychological sphere, including attention deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders. OBJECTIVE: The purpose of this study was to determine the prevalence of ADHD in children in a foster care institution in Albuñol (Granada) in 2016. MATERIALS AND METHODS: This cross-sectional descriptive study included 106 children aged 5 to 17 years from "Cristo Rey" foster care institution. Psychometric evaluation was based on Vanderbilt ADHD Diagnostic Rating Scale. Executive functions were tested using the Behavior Rating Inventory of Executive Function (BRIEF) in participants who met Vandebilt criteria, as well Diagnostic and DSM- 5 criteria were applied in a clinical interview to strengthen ADHD diagnosis. RESULTS: The prevalence of ADHD was determined to be 17.9 % in our group, with innatentional subtype being the most important. CONCLUSION: Prevalence of ADHD in "Cristo Rey" foster care institution was visibly high in comparison with estimated prevalence in children general population. Research is needed to identify comorbidities in children in residential care suffering from ADHD. ADHD detection and intervention programmes in residential care must be developed because of its repercussion

In vitro evaluation of new possible cell engraftment enhancers for cell transplantation.

Orthotopic liver transplantation (OLT) is the best treatment to restore liver function in liver failure. The low availability of organs has focused interest on the use of cell transplantation to restore liver function. However, this technique is limited because cells can not bind to liver parenchyma and die soon after perfusion. Pretransplant treatment with engraftment enhancers (EE) to increase vascular permeability may increase cell attachment. Using an endothelial cell culture to measure the loss of intercellular endothelial adhesion as a screening test, we evaluated the capacity of 15 monoclonal antibodies against adhesion molecules expressed on endothelial cells to act as EE showing that 3 antibodies (anti-CD54, efalizumab, and abciximab) act as EE by producing disruptions in the cell layer.

Sobredosis de metformina secundaria a insuficienciarenal aguda. A propósito de 6 observaciones / Overdose of metformin secondary to acute renal insufficiency: a report of six cases

La metformina es una biguanida utilizada en el tratamiento de pacientes adultos obesos afectos de una diabetes mellitus tipo 2 que reduce un 36% la mortalidad cuando se compara con el tratamiento convencional. Su administración tiene determinadas contraindicaciones que limitan su utilización y, cuando se hace caso omiso de ellas, especialmente la insuficiencia renal aguda, la metformina se acumula y aparece una acidosis láctica que puede ser fatal. Se presentan 6 pacientes con insuficiencia renal aguda que tuvieron una acidosis metabólica aguda extrema (pH < 6,90 y bicarbonato < 5 mEq/l) e hiato aniónico aumentado mientras recibían tratamiento antidiabético con metformina. El ácido láctico sérico, analizado solamente en los 4 pacientes que sobrevivieron, estuvo elevado. Dos pacientes fallecieron tras presentar una parada cardíaca evitable. En conclusión, la acidosis láctica que aparece durante el tratamiento antidiabético con metformina exige un rápido diagnóstico y tratamiento que permitan retirar el fármaco e iniciar rápidamente una hemofiltración continua o hemodiálisis prolongadas con bicarbonato

Metformin is a biguanide used in the treatment of obese adults with type 2 diabetes mellitus; metformin decreases mortality by 36% in comparison to conventional treatment. Metformin administration has certain contraindications that, when ignored, especially in the case of acute renal insufficiency, leads to the accumulation of the drug and consequent lactic acidosis that can be fatal. We present 6 patients with acute renal insufficiency that experienced extreme acute metabolic acidosis (pH < 6.90 and bicarbonate < 5 mEq/l) and increased anion gap while receiving metformin for the treatment of diabetes. Serum lactic acid, only evaluated in the 4 patients that survived, was high. Two patients died after cardiac arrest that could have been avoided. In conclusion, lactic acidosis appearing during metformin treatment for diabetes requires rapid diagnosis and treatment to enable the drug to be withdrawn and prolonged continuous hemofiltration or hemodialysis with bicarbonate to be initiated

[Overdose of metformin secondary to acute renal insufficiency: a report of six cases]. / Sobredosis de metformina secundaria a insuficiencia renal aguda. A propósito de 6 observaciones.

Metformin is a biguanide used in the treatment of obese adults with type 2 diabetes mellitus; metformin decreases mortality by 36% in comparison to conventional treatment. Metformin administration has certain contraindications that, when ignored, especially in the case of acute renal insufficiency, leads to the accumulation of the drug and consequent lactic acidosis that can be fatal. We present 6 patients with acute renal insufficiency that experienced extreme acute metabolic acidosis (pH <6.90 and bicarbonate <5 mEq/l) and increased anion gap while receiving metformin for the treatment of diabetes. Serum lactic acid, only evaluated in the 4 patients that survived, was high. Two patients died after cardiac arrest that could have been avoided. In conclusion, lactic acidosis appearing during metformin treatment for diabetes requires rapid diagnosis and treatment to enable the drug to be withdrawn and prolonged continuous hemofiltration or hemodialysis with bicarbonate to be initiated.