Cost-effective fibrinolytic enzyme production by microalga Dunaliella tertiolecta using medium supplemented with corn steep liquor.

A fibrinolytic enzyme from the microalga Dunaliella tertiolecta was produced under mixotrophic conditions using different corn steep liquor (CSL) concentrations ( 0 ≤ CLS ≤ 0.75%), purified using a combination of salting out and ion-exchange chromatography, and then biochemical characterized. Cultivation of this microalga using 0.5% CSL led to the highest maximum cell concentration (1.960±0.010 mg L-1) and cell productivity (0.140g L-1 day-1), besides a high fibrinolytic activity of the extract obtained by the homogenization method (102 ±1 U mL-1). The enzyme extracted from the microalgal biomass was 5-fold purified with a 20% yield and was found to have a specific activity of 670 U mg-1. The enzyme, whose molecular weight determined by fibrin zymography was 10 kDa, was shown to be stable at pH 3.0-9.0 and up to 70°C with optimal pH and temperature values of 8.0 and 50°C, respectively. When compared to other fibrinolytic enzymes, this protease stood out for its high fibrinolytic activity, which was enhanced by Fe2+, inhibited by Zn2+, Cu2+, Mg2+, and Ca2+, and strongly inhibited by phenylmethylsulfonyl fluoride, suggesting that it belongs to the serine metalloprotease family. Moreover, thanks to its thermal stability, the enzyme may be easily preserved and activated under high-temperature conditions.

Histomorphometric analysis of the lung of Swiss mice treated with a fibrinolytic protease.

Fibrinolytic enzymes are considered promising alternative in the treatment of cardiovascular diseases by preventing fibrin clots. A protease from Mucor subtilissimus UCP 1262 was obtained by solid state fermentation and purified by ion exchange chromatography. The purified extract was administered at an acute dose of 2000 mg/mL to evaluate its toxic effects to the lungs of mice. After 14 days of treatment, a histomorphometric study was performed by the type 1 and 2 pneumocyte count and the evaluation of the lung area. As result, the experimental group showed a significant decrease of type 2 pneumocyte and although a decrease in the alveolar area was observed in relation to the control group, no significant pulmonary toxicity, emphysema, and fibrosis characteristics were detected. The in vitro tests suggest possible clinical applications for the enzyme.

A novel collagenolytic protease from Mucor subtilissimus UCP 1262: Comparative analysis of production and extraction in submerged and stated-solid fermentation.

This work aimed to compare the production of collagenolytic proteases produced by M. subtilissimus UCP1262 in submerged fermentation (SF) and solid-state fermentation (SSF) as well as extracting in aqueous two-phase system (ATPS). Collagenolytic protease production was performed in using MS-2 culture medium (SF) and soybean bran as substrate (SSF). Subsequently, the fermented liquid from both fermentations were used for the extraction of enzyme by ATPS, it was verified the influence of different variables from a factorial design 23. In SSF the highest protease and collagenolytic activities were achieved with 362.66 U/mL and 179.81 U/mL, respectively. When compared with SF (26.33 and 18.70 U/mL) higher values were obtained in the activities. The protease partitioning from SF and SSF in ATPS showed a similar profile showing higher affinity for the polymer rich phase. The highest value for the response variable purification factor (3.49) was obtained in the system using SSF. Thus, SSF shows promise as a bioprocess for extracellular production of collagenolytic proteases, using of soybean bran as substrate had used sustainable raw material, aiming application this possible enzyme in the treatment of burns and postoperative scarring.

Purification and characterization of fibrinolytic protease from Streptomyces parvulus by polyethylene glycol-phosphate aqueous two-phase system.

Fibrinolytic proteases are a promising alternative in the pharmaceutical industry, they are used in the treatment of cardiovascular diseases, especially thrombosis. Microorganisms are the most interesting source of fibrinolytic proteases. The aim of this study was the production of fibrinolytic protease from Streptomyces parvulus DPUA 1573, the recovery of the protease by aqueous two-phase system and partial biochemical characterization of the enzyme. The aqueous two-phase system was performed according to a 24-full factorial design using polyethylene glycol molar mass, polyethylene glycol concentration, citrate concentration and pH as independent variables. It was analyzed the effect of different ions, surfactants, inhibitors, pH and temperature on enzyme activity. The best conditions for purifying the enzyme were 17.5% polyethylene glycol 8,000, 15% Phosphate and pH 8.0, it was obtained a partition coefficient of 7.33, a yield of 57.49% and a purification factor of 2.10-fold. There was an increase in enzyme activity in the presence of Fe2+ and a decrease in the presence of $\beta$-Mercaptoethanol, phenylmethylsulfonyl fluoride and Iodoacetic acid. The optimum pH was 7.0 and the optimum temperature was 40 ºC. The purified protease exhibited a molecular mass of 41 kDa. The fibrinolytic protease from Streptomyces parvulus proved to be a viable option for the development of a possible drug with fibrinolytic action.

Purification and characterization of a protease from Aspergillus sydowii URM5774: Coffee ground residue for protease production by solid state fermentation.

Solid state fermentation is a promising technology largely used in biotechnology process and is a suitable strategy for producing low-cost enzymatic products. At the present study, a novel enzyme obtained through solid state fermentation using Aspergillus sydowii was herein purified and characterized. The fermentations used coffee ground residue as substrate and the crude enzyme was submitted through further purification steps of: acetonic precipitation, DEAE-Sephadex and Superdex G-75 column. Both crude and purified enzymes were submitted to biochemical characterization of their thermostability, optimal temperature and pH, effects of inhibitors and metal ions. A purified protease was obtained with yield of 5.9-fold and 53% recovery, with maximal proteolytic activity of 352.0 U/mL. SDS-PAGE revealed a band of protein at 47.0 kDa. The enzyme activity was abolished in the presence of phenyl-methyl sulfonyl fluoride and partially inhibited against Triton X-100 (78.0%). The optimal activity was found in pH 8.0 at 45°C of temperature. Besides, the enzyme showed stability between 35°C and 50°C. It was possible to determine appropriate conditions to the obtainment of thermostable proteases with biotechnological interest associated with a method that concomitantly shows excellent production levels and recovery waste raw material in a very profitable process.

Ultrasound-Assisted Enzyme-Catalyzed Hydrolysis of Collagen to Produce Peptides With Biomedical Potential: Collagenase From Aspergillus terreus UCP1276.

Ultrasound has been applied for varied purposes as it provides additional mechanical energy to a system, and is still profitable and straightforward, which are advantages for industrial applications. In this work, ultrasonic treatments were applied to purified collagenase fractions from a fermented extract by Aspergillus terreus UCP 1276 aiming to evaluate the potential effect on collagen hydrolysis. The physical agent was evaluated as an inductor of collagen degradation and consequently as a producer of peptides with anticoagulant activity. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis analyses were also carried out to compare the hydrolysis techniques. The ultrasound (40 kHz, 47.4 W/L) processing was conducted under the same conditions of pH and temperature at different times. The ultrasound-assisted reaction was accelerated in relation to conventional processing. Collagenolytic activity was enhanced and tested in the presence of phenylmethanesulfonyl fluoride inhibitor. Underexposure, the activity was enhanced, reaching more than 72.0% of improvement in relation to the non-exposed enzyme. A period of 30 min of incubation under ultrasound exposure was enough to efficiently produce peptides with biological activity, including anticoagulation and effect on prothrombin time at about 60%. The results indicate that low-frequency ultrasound is an enzymatic inducer with likely commercial applicability accelerating the enzymatic reaction. Bioelectromagnetics. 2020;41:113-120. © 2019 Bioelectromagnetics Society.

CgTI, a novel thermostable Kunitz trypsin-inhibitor purified from Cassia grandis seeds: Purification, characterization and termiticidal activity.

Cassia grandis trypsin inhibitor (CgTI) is a novel plant serine proteinase inhibitor. This study sets out to purify a thermostable inhibitor from the seeds of Cassia grandis and to provide biochemical information about a novel peptide belonging to the Kunitz family. Moreover, toxicity assays against Artemia, Aedes aegypti larvae-L4 and Nasutitermes corniger are evaluated. The purification process was performed using acetone precipitation, Trypsin-Sepharose-CL4B and Superdex-G75. The inhibitor showed an apparent molecular mass of around 19.8 kDa on Superdex-G75 gel filtration, and a mass of around 19.0 kDa visualized by SDS-PAGE under reducing conditions, and it also showed the protein consists of two polypeptide chains. N-terminal sequencing by Edman's degradation of 16 residues revealed a sequence of amino acids SVVLDTSGEPIRNGGG. 2D-electrophoresis identified a pI value of 6.3 and a 1:1 stoichiometric ratio was noted during CgTI-trypsin complex formation. The inhibitor retained the inhibitory activity over a broad range of pH (5-10) and showed thermostable activity at temperatures 30-80 °C. Furthermore, in vivo assays showed no lethality effect against Artemia and Aedes aegypti larvae, but mortality against Nasutitermes corniger with termiticidal activity LC50 of 0.685 mg/mL on workers and 0.765 mg/mL on soldiers. Preliminary investigations of CgTI revealed it to be a promising biotechnological and biomedical candidate.

Can γ-radiation modulate hemagglutinating and anticoagulant activities of PpyLL, a lectin from Phthirusa pyrifolia?

Blood coagulation and platelet-dependent primary homeostasis are important defense mechanisms against bleeding and novel inhibitors have been researched to obtain pharmacological and clinical applications. In this work, the PpyLL, a lectin obtained from Phthirusa pyrifolia, was characterized in terms of its molecular structure and biological functions (anticoagulant, antiplatelet agreggation and hemagglutinating activities) in presence or absence of Gamma radiation exposure. Results revealed a lectin with secondary-structure content by approximately 49% of ß-sheet, 20% of ß-turn and 31% of disordered structure. Irradiation effect demonstrated possible different sites of function by lectin on anticoagulant and hemagglutinating activities, once a decrease about 80% was observed when compared the activities under 0.5kGy of exposition to gamma radiation. An emphatic discussion about the use of gamma radiation as a possible modulator of the lectin activity was made, and once the ionizing radiation affected differently the anticoagulation and hemagglutinating activities, we speculated that the results are determined by selective molecular damages in different binding sites. PpyLL biological activities and gamma radiation modulation could be considered for future researches in biomedical field aiming possible medical applications.

Evaluation of Chitosan-Based Films Containing Gelatin, Chondroitin 4-Sulfate and ZnO for Wound Healing.

In this work, chitosan-based films containing gelatin and chondroitin-4-sulfate (C4S) with and without ZnO particles were produced and tested in vitro to investigate their potential wound healing properties. Chitosans were produced from shrimp-head processing waste by alkaline deacetylation of chitin to obtain chitosans differing in molecular weight and degree of deacetylation (80 ± 0.5%). The film-forming solutions (chitosan, C4S and gelatin) and ZnO suspension showed no toxicity towards fibroblasts or keratinocytes. Chitosan was able to agglutinate red blood cells, and film-forming solutions induced no hemolysis. Film components were released into solution when incubated in PBS as demonstrated by protein and sugar determination. These data suggest that a stable, chitosan-based film with low toxicity and an ability to release components would be able to establish a biocompatible microenvironment for cell growth. Chitosan-based films significantly increased the percentage of wound healing (wound contraction from 65 to 86%) in skin with full-thickness excision when compared with control (51%), after 6 days. Moreover, histological analysis showed increased granulation tissue in chitosan and chitosan/gelatin/C4S/ZnO films. Chitosan-based biopolymer composites could be used for improved biomedical applications such as wound dressings, giving them enhanced properties.

Deshidratación hipernatrémica asociada a la alimentación con lactancia materna en el periodo neonatal / Hypernatremic dehydration associated with breast-feeding in the neonatal period

Introducción: La deshidratación hipernatrémica en el neonato se asocia de forma característica a la alimentación con lactancia materna exclusiva en madres primigestas por una mala técnica de amamantamiento. Pese a los avances en los cuidados perinatológicos, continúa siendo una patología habitual en nuestros días. Población y métodos: Estudio descriptivo retrospectivo de los neonatos alimentados con lactancia materna exclusiva y natremia ≥150 mmol/L, que precisaron ingreso en el Hospital Universitario Central de Asturias en los últimos 14 años. Resultados: Serie de 26 casos (0,54 por cada 1.000 recién nacidos vivos). La pérdida media de peso hasta el ingreso fue del 17,9%, con una natremia media de 162 mmol/L. Se observó una relación lineal entre el sodio sérico y la pérdida de peso. El 73% de las madres eran primigestas. El 34% de los casos procedían de la maternidad de nuestro hospital, el 34% habían acudido al servicio de urgencias de nuestro centro y el 30,6% acudían remitidos por sus pediatras de referencia. Todos los casos evolucionaron satisfactoriamente. Se constató un aumento de la incidencia en los últimos años. Conclusiones: La deshidratación hipernatrémica asociada a la lactancia materna exclusiva aparece, en la mayoría de los casos, en madres primigestas. La formación del personal sanitario, la intensificación de los cuidados del neonato durante su estancia en la maternidad y el control precoz del mismo tras el alta hospitalaria pueden considerarse medidas útiles para evitar esta patología, cuya existencia pone de manifiesto una carencia en el sistema sanitario (AU)

Introduction: Hypernatremic dehydration in newborns is associated to exclusive breastfeeding in primiparous mothers with wrong breastfeeding technique. Despite advances in perinatological care, hypernatremic dehydration remains common today. Subjects and methods: Retrospective study of exclusive breastfeeding neonates with serum sodium concentrations equal to or greater than 150 mmol/L requiring admission in the Hospital Universitario Central de Asturias in the last 14 years. Results: Twenty-six newborn were included in the study (0.54 per 1,000 live births). At admission, the mean percentage of weight loss was 17.9% and mean serum sodium value 162 mmol/L. A linear relationship between serum sodium and weight loss was observed. 73% of the mothers were primiparous. 34% of the sample were admitted directly from the maternity, 34% came from the emergency department and 30,6% were referred to the hospital by their reference pediatrician. All cases evolved satisfactorily. An increase in incidence in recent years was objectively. Conclusions: Hypernatremic dehydration in exclusively breastfed neonates appears in most cases in primiparous. Breastfeeding training for health professionals, to intensify the care of the newborn during their stay in the maternity and to implement an early visit after postnatal discharge may be considered useful measures to prevent this pathology. Nowadays, this disease reflects a lack of support for breast-feeding mothers in health system (AU)

Cambios en la presentación y evolución de la atresia esofágica en los últimos 20 años / Changes in the presentation and evolution of esophageal atresia in the last 20 years

Objetivo: Conocer los cambios ocurridos en las dos últimas décadas en las formas de presentación clínica, malformaciones asociadas, tratamiento y evolución de la atresia esofágica, comparando una serie actual con otra histórica de nuestro mismo centro. Métodos: Estudio descriptivo retrospectivo. Revisión de las historias clínicas de todos los casos codificados como atresia de esófago al alta desde 1/1/2003 a 31/12/2013. Comparación con la serie histórica de nuestro centro de 1/1/1980 a 31/12/1990 publicada en 1992. Resultados: Al comparar la serie ya publicada con la revisión actual no encontramos diferencias estadísticamente significativas en la incidencia de atresia esofágica (2,29 frente a 2,61 casos por cada 10.000 neonatos vivos), ni en el porcentaje de prematuridad (25,9 frente a 45%), ni en el porcentaje de casos con ecografía intraútero patológica (65 frente a 50%), ni en el porcentaje de casos con otras malformaciones asociadas (59,2 frente a 68,1%). Encontramos diferencias estadísticamente significativas en el porcentaje de cirugía en el primer día de vida (40,7 frente a 9%), en el porcentaje de sepsis nosocomial postquirúrgica (44,4 frente a 86%) y en la mortalidad (40,7 frente a 4,5%). Conclusiones: La atresia de esófago es una patología con una importante morbilidad asociada. En los últimos veinte años no hemos encontrado diferencias en su forma de presentación, pero si en su evolución, con un descenso muy importante en la mortalidad

Objective: To know the changes in the last two decades in clinical presentation, associated malformations, treatment and outcome of esophageal atresia, comparing this current series with another historical of our own hospital. Methods: A retrospective descriptive study. Review of medical records of all cases coded as esophageal atresia at discharge from 1/1/2003 to 12/31/2013. Comparison with our historical series from 1/1/1980 to 12/31/1990, published in 1992. Results: No statistically significant differences in the incidence of esophageal atresia (2.29 versus 2.61 cases per 10,000 live infants), or the percentage of prematurity (25.9 vs. 45%), or the percentage of cases with pathological intrauterine ultrasound (65 vs. 50%), or the percentage of cases with associated malformations (59.2 vs. 68.1%). Found significant differences in percentage of surgery on the first day of life (40.7 vs. 9%), the percentage of nosocomial postsurgical sepsis (44.4 vs. 86%) and mortality (40.7 vs 4.5%). Conclusions: Esophageal atresia is a condition associated with significant morbidity. In the last twenty years we have not found differences in their presentation, but we had found differences in its evolution, with a significant decrease in mortality

Acute neonatal appendicitis: a diagnosis to consider in abdominal sepsis.

Appendicitis in the neonatal period is extremely rare. Its low incidence together with non-specific clinical symptoms often mean the diagnosis is delayed, leading to increased rates of peritonitis and mortality. We report the case of a 33-week premature infant, small for gestational age (1180 g at birth), clinically stable and receiving exclusive enteral feeding, who presented clinical manifestations of necrotizing enterocolitis at 14 days of life. Acute phase reactants were elevated and abdominal radiography showed pneumoperitoneum. Laparotomy revealed acute perforated appendicitis without intestinal involvement and purulent fluid in the peritoneum, for which appendectomy was performed. Neonatal acute appendicitis should be considered in the differential diagnosis of abdominal sepsis since early diagnosis and treatment significantly reduce associated morbidity and mortality.

Prevalencia de anquiloglosia en recién nacidos en el Principado de Asturias / Prevalence of ankyloglossia in newborns In Asturias (Spain)

INTRODUCCIÓN: La prevalencia de anquiloglosia ha sido estimada alrededor del 4% de los recién nacidos vivos. Se desconoce la situación a nivel nacional. MATERIAL Y MÉTODOS: Estudio multicéntrico, observacional, prospectivo en el que participaron 6 hospitales asturianos. Durante 3 meses se exploró a todos los recién nacidos los días domingo, martes y jueves. Para el diagnóstico de anquiloglosia se utilizaron los criterios de Coryllos y Hazelbaker. RESULTADOS: Se exploró a 667 recién nacidos. La prevalencia de anquiloglosia fue del 12,11% (IC 95%: 9,58-14,64). El 62% eran varones. Uno de cada 4 niños con anquiloglosia tenía antecedentes familiares de frenillo lingual corto. Según la clasificación de Coryllos el tipo II fue el más frecuente (54%). CONCLUSIONES: La prevalencia de anquiloglosia en Asturias fue 2 o 3 veces superior a la esperada. Es necesario unificar los criterios diagnósticos, así como realizar estudios para conocer su asociación con dificultades en la lactancia u otros problemas posteriores

INTRODUCTION: The prevalence of ankyloglossia has been estimated at around 4% of live births. Its prevalence at national level is unknown. MATERIAL AND METHODS: Multicenter, prospective observational study. Six hospitals in Asturias took part. All newborns were examined on Sundays, Tuesdays and Thursdays for 3 months. Coryllos and Hazelbaker criteria were used to diagnose ankyloglossia. RESULTS: The prevalence in the 667 newborns examined was 12.11% (95% CI: 9.58 to 14.64), of whom 62% were male. One in 4 children with ankyloglossia had a family history. According to Coryllos' classification, type II was the most common (54%). CONCLUSIONS: The prevalence of ankyloglossia in Asturias was 2 to t3 times higher than expected. The diagnostic criteria for ankyloglossia needs to be unified, and further studies are required to determine the association with breastfeeding difficulties and other health problems

Periviabilidad: el límite de la prematuridad en un hospital regional de referencia durante los últimos 10 años / Peri-viability: limits of prematurity in a regional hospital in the last 10 years

OBJETIVO: Conocer la viabilidad de prematuros de 22-25 semanas gestacionales en nuestro centro durante últimos 10 años. PACIENTES Y MÉTODOS: Estudio retrospectivo descriptivo. Neonatos nacidos en nuestro hospital entre 1-1-2002 y 31-12-2011, de 22 a 25 semanas gestacionales. RESULTADOS: De 121 neonatos, 45 (37%) eran mortinatos y 76 (63%) nacidos vivos (16 fallecieron en partos y 60 ingresaron en cuidados intensivos neonatales). De los 60 ingresados, 34 fallecieron antes del alta y 26 sobrevivieron (21% del total, 34% de nacidos vivos y 43% de ingresados en cuidados intensivos neonatales). Causas de fallecimiento: 16, limitación del esfuerzo terapéutico en partos; 8, limitación del esfuerzo terapéutico en neonatología; 7, sepsis nosocomiales; 7, enterocolitis necrosantes; 4, problemas respiratorios, y 8, causa desconocida. No sobrevivió ningún menor de 24 semanas. De los 26 supervivientes, 4 presentaron alteraciones neurológicas importantes y 11, normalidad neurológica aparente. No encontramos diferencias estadísticamente significativas en cuanto a mortalidad entre los 2 quinquenios analizados. CONCLUSIONES: La periviabilidad presenta importantes problemas clínicos y éticos a los neonatólogos

AIM: To determine the preterm viability between 22 and 25 gestational weeks in our hospital in last 10 years. PATIENTS AND METHODS: A descriptive retrospective study was conducted on preterms between22-25 gestational weeks born between 1-1-2002 and 12-31-2011. RESULTS: There were 121 newborns, 45 (37%) stillbirths and 76 (63%) live births (16 died indelivery room, and 60 admitted to neonatal intensive unit). Among the 60 admitted, 34 died before hospital discharge, and 26 survived (21% of total, 34% of live births and 43% of those admitted to neonatal intensive unit). The causes of death were: 16 therapeutic effort limitation in delivery room, 8 therapeutic effort limitation in neonatal ward, 7 nosocomial sepsis, 7 NEC,4 respiratory problems, and 8 of unknown cause. There were no survivors below 24 gestational weeks. Of the 26 survivors, 4 had major neurological disorders, and 11 with a normal neurological outcome. No significant statistical differences were found in the mortality between the two five-year periods analysed. CONCLUSIONS: The peri-viability has important clinical and ethical problems for neonatologist

[Prevalence of ankyloglossia in newborns in Asturias (Spain)]. / Prevalencia de anquiloglosia en recién nacidos en el Principado de Asturias.

INTRODUCTION: The prevalence of ankyloglossia has been estimated at around 4% of live births. Its prevalence at national level is unknown. MATERIAL AND METHODS: Multicenter, prospective observational study. Six hospitals in Asturias took part. All newborns were examined on Sundays, Tuesdays and Thursdays for 3 months. Coryllos and Hazelbaker criteria were used to diagnose ankyloglossia. RESULTS: The prevalence in the 667 newborns examined was 12.11% (95% CI: 9.58 to 14.64), of whom 62% were male. One in 4 children with ankyloglossia had a family history. According to Coryllos' classification, type II was the most common (54%). CONCLUSIONS: The prevalence of ankyloglossia in Asturias was 2 to t3 times higher than expected. The diagnostic criteria for ankyloglossia needs to be unified, and further studies are required to determine the association with breastfeeding difficulties and other health problems.

[Peri-viability: limits of prematurity in a regional hospital in the last 10 years]. / Periviabilidad: el límite de la prematuridad en un hospital regional de referencia durante los últimos 10 años.

AIM: To determine the preterm viability between 22 and 25 gestational weeks in our hospital in last 10 years. PATIENTS AND METHODS: A descriptive retrospective study was conducted on preterms between 22-25 gestational weeks born between 1-1-2002 and 12-31-2011. RESULTS: There were 121 newborns, 45 (37%) stillbirths and 76 (63%) live births (16 died in delivery room, and 60 admitted to neonatal intensive unit). Among the 60 admitted, 34 died before hospital discharge, and 26 survived (21% of total, 34% of live births and 43% of those admitted to neonatal intensive unit). The causes of death were: 16 therapeutic effort limitation in delivery room, 8 therapeutic effort limitation in neonatal ward, 7 nosocomial sepsis, 7 NEC, 4 respiratory problems, and 8 of unknown cause. There were no survivors below 24 gestational weeks. Of the 26 survivors, 4 had major neurological disorders, and 11 with a normal neurological outcome. No significant statistical differences were found in the mortality between the two five-year periods analysed. CONCLUSIONS: The peri-viability has important clinical and ethical problems for neonatologist.

Intoxicación por cafeína en un recién nacido prematuro / Caffeine intoxication in a premature newborn

El citrato de cafeína se usa en Neonatología como tratamiento de primera línea para tratar o prevenir la apnea de la prematuridad. Describimos un caso de intoxicación accidental por cafeína (140mg/kg) en un prematuro de 36 horas de vida. El paciente presentó alteraciones neurológicas y cardiacas, con hiperglucemia, elevación de la creatininfosfo-quinasa y de la troponina T. En sangre la cifra máxima de cafeína fue de 127 µg/ml. La evolución fue favorable con tratamiento conservador. El análisis de los errores en la seguridad de los pacientes debe ser un punto esencial en la educación pediátrica (AU)

Caffeine citrate is used as first-line therapy in neonates to treat or prevent apnea of prematurity. We describe a caffeine intoxication (140 mg/kg) in a 36 hours-old preterm neonate. Patient showed neurological and cardiac alterations, with hyperglycemia, elevated creatine kinase and troponin and peak caffeine plasma level of 127 µg/ml. Clinical evolution was favorable with conservative support. Analysis of patient safety errors must be essential point in paediatric education (AU)

Marcadores biológicos de infección neonatal / Biological markers of neonatal infection

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