Determining Structural Changes for Ligand Recognition between Human and Rat Phosphorylated BACE1 in Silico and Its Phosphorylation by GSK3ß at Thr252 by in Vitro Studies.

Alzheimer's disease (AD) is a neurodegenerative disease affecting older adults. AD pathogenesis involves the production of the highly neurotoxic amyloid-ß peptide 1-42 (Aß1-42) from ß-site amyloid precursor protein cleaving enzyme 1 (BACE1). The phosphorylation of BACE1 at Thr252 increases its enzymatic activity. This study examined the phosphorylation of BACE1 from human and rat BACE1 in silico through phosphorylation predictors. Besides, we explored how phosphorylation at various sites affected the BACE1 structure and its affinity with amyloid precursor protein (APP) and six BACE1 inhibitors. Additionally, we evaluated the phosphorylation of Thr252-BACE1 by glycogen synthase kinase 3 ß (GSK3ß) in vitro. The phosphorylation predictors showed that Thr252, Ser59, Tyr76, Ser71, and Ser83 could be phosphorylated. Also, Ser127 in rat BACE1 can be phosphorylated, but human BACE1 has a Gly at this position. Molecular dynamics simulations showed that Ser127 plays an important role in the open and closed BACE1 conformational structures. Docking studies and the molecular mechanics generalized Born surface area (MMGBSA) approach showed that human BACE1 phosphorylated at Thr252 and rat BACE1 phosphorylated at Ser71 have the best binding and free energy with APP, forming hydrogen bonds with Asp672. Importantly, inhibitors have a higher affinity for the phosphorylated rat BACE1 than for its human counterpart, which could explain their failure during clinical trials. Finally, in vitro experiments showed that GSK3ß could phosphorylate BACE1. In conclusion, BACE1 phosphorylation influences the BACE1 conformation and its recognition of ligands and substrates. Thus, these features should be carefully considered in the design of BACE1 inhibitors.

Simultaneous selection of nanobodies for accessible epitopes on immune cells in the tumor microenvironment.

In the rapidly advancing field of synthetic biology, there exists a critical need for technology to discover targeting moieties for therapeutic biologics. Here we present INSPIRE-seq, an approach that utilizes a nanobody library and next-generation sequencing to identify nanobodies selected for complex environments. INSPIRE-seq enables the parallel enrichment of immune cell-binding nanobodies that penetrate the tumor microenvironment. Clone enrichment and specificity vary across immune cell subtypes in the tumor, lymph node, and spleen. INSPIRE-seq identifies a dendritic cell binding clone that binds PHB2. Single-cell RNA sequencing reveals a connection with cDC1s, and immunofluorescence confirms nanobody-PHB2 colocalization along cell membranes. Structural modeling and docking studies assist binding predictions and will guide nanobody selection. In this work, we demonstrate that INSPIRE-seq offers an unbiased approach to examine complex microenvironments and assist in the development of nanobodies, which could serve as active drugs, modified to become drugs, or used as targeting moieties.

Optimization and characterization of reinforced biodegradable cellulose-based aerogels via polylactic acid/polyhydroxybutyrate coating.

Vine shoots (VS) and waste eucalyptus paperboard (EP) have been used as cellulose sources (in the form of cellulose nanocrystals -CNCs- and cellulosic fibers respectively) for developing cellulose-based aerogels. Two different parameters including cellulose concentration (0.5 % and 2 % w/v) and freezing temperatures (-20 °C and -80 °C) were tested to evaluate differences in the porosity of the aerogels via Brunauer-Emmett-Teller (BET) and thermal conductivity analyses. In addition, a supplementary coating was applied to the raw aerogels by means of dipping the materials in either polylactic acid (PLA) or polyhydroxybutyrate (PHB) solutions (1 % w/v). Their microstructure was observed via SEM and the reinforcing capacity provided by the coating was measured by means of mechanical compressive tests (~10-fold improvement) and water resistance (contact angle >100°). Finally, aerogels' biodegradability was also confirmed according to the standard ISO 20200 thus providing a sustainable and high-performance alternative to conventional materials also following circular economy principles.

The Phytoestrogenic Effect of Hibiscus sabdariffa Involves Estrogen Receptor α in Ovariectomized Wistar Rats.

The calyxes of Hibiscus sabdariffa present multiple pharmacological effects primarily attributed to their high anthocyanin content; however, little is known about their phytoestrogenic effect. Ovarian hypofunction (OH) is a process characterized by the rapid detention of the production of ovarian hormones, which compromises reproductive and cognitive functions. Hormone replacement therapy (HRT) efficiently compensates for OH; nevertheless, questions have been raised on its secondary effects and safety. One of the alternatives to tackling OH involves using phytoestrogens such as anthocyanins for their structural similarity to natural estrogens. In a Wistar rat model of ovariectomy (OVX), we recently reported the beneficial properties of an anthocyanin-rich extract prepared from the calyces of H. sabdariffa (HSE) in hindering the adverse effects of OH on memory performance and highlighted a possible phytoestrogenic impact through the modulation of estrogen receptor (ER) expression. We now report that HSE and estradiol differentially affected the expression of ERα and ERß. ERα was more sensitive to HSE; meanwhile, estradiol preferentially modulated ERß. Thus, our study leads to further research on using H. sabdariffa as a nutrition-based alternative to HRT.

Physicochemical, calorimetric and texture profile characteristics of various gluten-free flours.

It is important to understand how the composition and structure of proteins from other flours differ from proteins in wheat, in order to have a better option to substitute gluten products with gluten-free food products. The aim of this study was the characterization of gluten-free flours and comparison of their rheological and calorimetric properties against wheat flour, for its use as gluten-free alternative. Chemical composition analysis, water solubility index (WSI), water absorption index (WAI), texture and calorimetric profile were determined. The closest WAI to wheat flour (1.45 g gel/g sample) was corn flour (2.41 g gel/g sample), while the WSI of chickpea flour was 5.51% approaching that of wheat flour of 5.88%. The hardness and adhesiveness values closest to wheat (1.65 kgf and 0.03 mJ) were amaranth flour with 0.85 kgf and 0.01 mJ, respectively. The phenolic content and antioxidant capacity were higher in the corn and bean flours with 244.4 mg GAE/100 g, 148 mg GAE/100 g and 190 mg AAE/100 g and 170 mg AAE/100 g, respectively. The combination of these non-conventional flours can be an innovative source of gluten-free formulas.

Aloe Vera and Nopal mucilage on the reduction of agglomeration during spray drying and storage of blackberry and raspberry extracts.

The objective of this investigation was to evaluate the influence of two carrier agents, Nopal and Aloe Vera mucilage on the physicochemical properties and stability of blackberry and raspberry powders obtained by spray drying. A pilot scale spray dryer with a feed flow of 20 L/h and an atomization speed of 28,000 rpm was used. The inlet and outlet air temperatures were from 180 to 80°C, respectively. Yield, moisture content, water activity, hygroscopicity index, solubility time, volumetric density, stability diagrams, micrographs, and particle temperature were evaluated. The highest yields for blackberry extract were 75% with a concentration of 2.5% (w/v) Nopal mucilage, while raspberry extract yielded 65% with a concentration of 5% (w/v) Nopal mucilage. The increase in the concentration of the carrier agent presented an increase in the values of humidity, water activity, volumetric density, and solubility when Nopal mucilage was used as a carrier agent in both blackberry and raspberry extracts. Furthermore, when Aloe Vera mucilage was used as a carrier agent, these same values decreased with increasing concentration. The storage conditions of the powders obtained should be stored at temperatures below 20°C and water activities below 0.4. In addition, the stability diagrams show the particle conditions that should not be exceeded during spray drying.

Effects of High Temperature Exposure on the Wingate Test Performance in Male University Students.

It has been suggested that heat exposure prior to exercise could induce changes in anaerobic exercise. Therefore, the purpose of this study was to observe the effects of high temperature heat exposure prior to an anaerobic test. Twenty-one men (age: 19.76 ± 1.22 years; height: 1.69 ± 0.12 m; weight: 67.89 ± 11.78 kg) voluntarily participated in this investigation. All of them performed two Wingate tests, vertical jump and macronutrient intake control. On the first day, the test was performed under normal environmental conditions. On the second day, it was performed in a similar way, but with previous exposure to heat at high sauna temperatures (15 min; 100 ± 2 °C). There were no differences in the vertical jump and macronutrient intake. However, the results showed an improvement in power (W) (p < 0.05), relative power (W/kg) (p < 0.01) and revolutions per minute (p < 0.05) 10 s after the start of the test. There was also an increase in thigh (p < 0.01) and skin temperature (p < 0.01) with pre-heat exposure. The results obtained suggest that this pre-exercise protocol could improve power in short and intensive actions.

Effects of Hibiscus sabdariffa calyces on spatial memory and hippocampal expression of BDNF in ovariectomized rats.

Ovarian hypofunction is characterized by decay in brain-derived neurotrophic factor (BDNF), a neurotrophin associated with cognitive and memory function. Hormone replacement therapy is the most common treatment to counteract the negative effects of ovarian insufficiency; however, this therapy may increase the odds of endometrial cancer, blood clots, stroke, and breast cancer. Therefore, a safer alternative to synthetic estrogens is needed. One possible candidate may be phytoestrogens. Hibiscus sabdariffa L. (Malvaceae) is a source of natural food colorants; the calyces and leaves of the plant are consumed in drinks and culinary preparations and are recognized for several health benefits related to their high content of anthocyanins. In the present study, we used an ovariectomized rat model to assess the phytoestrogenic effect of H. sabdariffa, and evaluated spatial memory and BDNF expression. Ninety-day-old female Wistar rats were randomly separated into six groups. Rats from four groups were ovariectomized and injected with a physiological dose of estradiol, or given, in drinking water, an extract prepared from calyces of H. sabdariffa at doses of 50 or 100 mg/kg body weight. Both Intact and Sham groups were included as controls. At day 42, short- and long-term memories were assessed by the Barnes maze test, and hippocampal BDNF expression was evaluated by RT-qPCR and Western blot. Ovariectomy significantly decreased memory performance and BDNF expression, compared with controls. However, administration of H. sabdariffa extract reversed the negative effect of ovariectomy on short- and long-term memory parameters and BDNF expression. A stronger effect was observed at a lower dose of the extract. In conclusion, the extract from H. sabdariffa acted as a phytoestrogen in ovariectomized rats, improving spatial memory performance and hippocampal BDNF expression. Based on these promising results, further clinical experimentation is recommended to study the benefits of H. sabdariffa as an alternative hormonal therapy in patients with ovarian hypofunction.

Multifunctional cellulosic aerogels from Posidonia oceanica waste biomass with antioxidant properties for meat preservation.

Posidonia oceanica waste biomass has been valorized to develop bioactive multifunctional cellulosic aerogels (HCAG) by simpler and greener protocols. Hydrophobization of cellulosic aerogels was achieved through PLA coating, while bioactivity was imparted by the incorporation of hydrophilic (E2) and hydrophobic extracts (E3) produced from the same biomass. The incorporation of extracts led to denser aerogels, with less porous structures. These aerogels showed outstanding water and oil sorption capacities (1500-1900%), being able to release the adsorbed liquid almost completely after 7 days. Interestingly, all the aerogels showed a positive inhibition effect (23-91%) on the ß-carotene bleaching assay. Moreover, the aerogels loaded with extracts, especially when combining E2 and E3, were able to reduce the oxidation of lipids and oxymyoglobin in red meat after 10 days of storage. This evidences the potential of these multifunctional aerogels as bioactive adsorbing pads to preserve the quality of fresh packaged foods.

Evaluación in silico del efecto de compuestos fenólicos de Pleurotus ostreatus sobre la enzima 5-lipoxigenasa (5- LOX) / In silico evaluation of the effect of Pleurotus ostreatus phenolic compounds on the enzyme 5-lipoxygenase (5-LOX)

Introducción: Los hongos comestibles, en particular Pleurotus ostreatus, representan una importante fuente de metabolitos bioactivos con propiedades inmunomoduladoras, antioxidantes y antiinflamatorias. Trabajos recientes han demostrado que extractos y compuestos purificados a partir de esta seta, entre ellos, la fracción rica en fenoles, inhiben el factor nuclear kappa B(NF-κB), la cicloxigenasa (COX) y modulan cascadas de señalización relacionadas con el balance redox. De acuerdo con estos antecedentes, dichos compuestos podrían actuar, además, como inhibidores de la enzima 5- lipoxigenasa (5-LOX). Objetivo: Evaluar el efecto in silico de trece compuestos fenólicos presentes en la especie Pleurotus ostreatus sobre la enzima 5-LOX, al utilizar como compuesto de referencia la mangiferina. Métodos: El acoplamiento se llevó a cabo a través del programa AutoDock 4.2 (http://autodock.scripps.edu) y la estructura de 5 LOX se obtuvo con la base de datos de proteínas, PDB (www.wwpdb.org). Se estimaron la energía libre (ΔG), la constante de disociación (Ki) y la eficiencia de ligando (LE). Se obtuvieron los parámetros de similitud a un fármaco y los relacionados con la absorción, distribución, metabolismo, excreción y toxicidad (ADME/T) de los mejores modelos de acoplamiento. Resultados: Los mejores indicadores de ΔG y Ki, correspondieron a los ácidos homogentísico, clorogénico y gentísico, con valores de ΔG (-11,81; -12,28 y -11,67 kcal/moL) y Ki (2,19 10-9; 9,99 10-10, 2,79 10-9 M), respectivamente. La eficiencia de ligando alcanzó valores adecuados para estos tres compuestos fenólicos. El modelo de acoplamiento del ácido homogentísico mostró los mejores resultados en cuanto a la similitud a un fármaco y pruebas ADME/T. Conclusiones: El estudio in silico reveló las potencialidades de la fracción rica en fenoles de P. ostreatus, y en particular, del ácido homogentísico como inhibidor de la enzima 5 -LOX, y justifica el desarrollo de ensayos confirmativos in vitro/ in vivo que corroboren sus efectos antioxidantes y antinflamatorios(AU)

Introduction: Edible mushrooms, Pleurotus ostreatus in particular, are an important source of bioactive metabolites with immunomodulatory, antioxidant and anti-inflammatory properties. Recent studies have shown that extracts and compounds purified from this mushroom, among them the phenol-rich fraction, inhibit nuclear factor kappa B (NF-κB), cyclooxygenase (COX), and modulate signaling cascades related to redox balance. According to these antecedents, such compounds could also act as inhibitors of the enzyme 5-lipoxygenase (5-LOX). Objective: Evaluate the in silico effect of 13 phenolic compounds present in the species Pleurotus ostreatus on the enzyme 5-LOX using mangiferin as reference compound. Methods: Docking was carried out with the software AutoDock 4.2 (http://autodock.scripps.edu) and the 5-LOX structure was obtained with the protein database PDB (www.wwpdb.org). Estimation was performed of free energy (ΔG), dissociation constant (Kd) and ligand efficiency (LE). Drug-likeness parameters were obtained, as well as those related to absorption, distribution, metabolism, excretion and toxicity (ADMET) of the best docking models. Results: The best ΔG and Kd indicators were homogentisic, chlorogenic and gentisic acids, with ΔG and Kd values of -11.81, -12.28, -11.67 kcal/mol, and 2.19 10-9, 9.99 10-10, 2.79 10-9 M, respectively. Ligand efficiency achieved adequate values for these three phenolic compounds. The docking model for homogentisic acid showed the best results in terms of drug likeness and ADMET tests. Conclusions: The in silico study revealed the potential of the phenol-rich fraction of P. ostreatus, homogentisic acid in particular, as an enzyme 5-LOX inhibitor, and justifies the development of confirmatory in vitro / in vivo assays to corroborate its antioxidant and anti-inflammatory effects(AU)

Valorisation of vine shoots for the development of cellulose-based biocomposite films with improved performance and bioactivity.

This work reports on the valorization of Tempranillo vine shoots for the development of bio-based packaging materials. Cellulose (F3) and nanocellulose (NANO F3) were produced by the conventional method, while less purified cellulosic fractions (F2A) and nanocrystals (NANO F2A) were extracted by simplified protocols (omitting Soxhlet and alkaline treatments) to reduce production costs and environmental impact and evaluate the potential added functionalities of these less purified materials. Although most of the hemicelluloses in F2A were digested upon acid hydrolysis, a small fraction remained in NANO F2A. On the other hand, the presence of a minor xylan fraction in F3 limited the access of sulphuric acid towards the cellulose microfibrils, hindering hydrolysis and producing heterogeneous fibrillar structures in NANO F3. The obtained materials were used to produce cellulosic films, as well as blends with agar, and their performance properties were evaluated. Overall, NANO F2A films showed the best compromise between performance and sustainability and presented additional antioxidant capacity. The properties of the films could be adjusted by the incorporation of agar, improving their ductility and water permeability.

In-Depth Characterization of Bioactive Extracts from Posidonia oceanica Waste Biomass.

Posidonia oceanica waste biomass has been valorised to produce extracts by means of different methodologies and their bioactive properties have been evaluated. Water-based extracts were produced using ultrasound-assisted and hot water methods and classified according to their ethanol-affinity (E1: ethanol soluble; E2: non-soluble). Moreover, a conventional protocol with organic solvents was applied, yielding E3 extracts. Compositional and structural characterization confirmed that while E1 and E3 extracts were mainly composed of minerals and lipids, respectively, E2 extracts were a mixture of minerals, proteins and carbohydrates. All the extracts showed remarkably high antioxidant capacity, which was not only related to phenolic compounds but also to the presence of proteins and polysaccharides. All E2 and E3 extracts inhibited the growth of several foodborne fungi, while only E3 extracts decreased substantially the infectivity of feline calicivirus and murine norovirus. These results show the potential of P. oceanica waste biomass for the production of bioactive extracts.

High-performance starch biocomposites with celullose from waste biomass: Film properties and retrogradation behaviour.

In this work, the effects of relative humidity (RH) pre-conditioning (53% vs. 85% RH) and incorporation of cellulose fillers (from Posidonia waste biomass) on the properties and retrogradation of melt compounded starch biocomposites were investigated. Pre-conditioning at 85% RH promoted starch gelatinization during processing, leading to more amorphous materials with reduced stiffness but better barrier properties. Furthermore, these films were less stable upon storage due to greater starch retrogradation. Cellulose incorporation improved significantly the mechanical and water barrier performance, especially in the films pre-conditioned at 85% RH due to enhanced filler dispersion. Although incomplete gelatinization of the starch pre-conditioned at 53% RH led to films with bigger cellulose aggregates, their mechanical and water barrier properties were better, outperforming starch-cellulose biocomposites typically reported in the literature. Moreover, the presence of cellulose limited the degree of starch retrogradation upon storage, highlighting the potential of Posidonia biomass as a cheap source of high-performance fillers.

Potential of lignocellulosic fractions from Posidonia oceanica to improve barrier and mechanical properties of bio-based packaging materials.

This work reports on the valorization of residues from Posidonia oceanica leaves for the purpose of obtaining lignocellulosic fractions of interest for the development of bio-based materials for food packaging. The lignocellulosic fractions were characterized, thereby confirming the purification of cellulose and showing increases in crystallinity and thermal stability after the consecutive extraction steps. Subsequently, pure lignocellulosic films were obtained and characterized and the pure cellulose film showed the best properties in terms of mechanical performance and water vapor permeability. Finally, composite starch films containing lignocellulosic fractions were developed by melt compounding and characterized. Although the film containing the pure cellulose additive showed the optimum improvement in terms of mechanical properties (with an increase of 85% in the elastic modulus and 38% in the tensile strength), similar water vapor permeability reduction (~40%) was achieved with the least purified fractions, explained by their effect on starch gelatinization, as evidenced by SAXS/WAXS.

Tectonic DSAEK for the Management of Impending Corneal Perforation.

Purpose. To report a case of severe corneal thinning secondary to dry eye treated with a tectonic Descemet stripping automated lamellar keratoplasty (DSAEK) and amniotic membrane graft. Methods. A 72-year-old man with a history of long standing diabetes mellitus type 2 and dry eye presented with 80% corneal thinning and edema on the right eye and no signs of infectious disease, initially managed with topical unpreserved lubrication and 20% autologous serum drops. Eight weeks after, the defect advanced in size and depth until Descemetocele was formed. Thereafter, he underwent DSAEK for tectonic purposes. One month after the procedure, the posterior lamellar graft was well adhered but a 4 mm epithelial defect was still present. A multilayered amniotic membrane graft was then performed. Results. Ocular surface healed quickly and reepithelization occurred over a 2-week period. Eight months after, the ocular surface remained stable and structurally adequate. Conclusion. Tectonic DSAEK in conjunction with multilayered amniotic graft may not only provide structural support and avoid corneal perforation, but may also promote reepithelization and ocular surface healing and decrease concomitant inflammation.

Effect of the temperature on the spray drying of Roselle extracts (Hibiscus sabdariffa L.).

The effect of the drying temperature on the volatile components and sensory acceptance of the Roselle (Hibiscus sabdariffa) extract in powder was investigated. The Roselle extraction was carried out by maceration with 7 L of 30% ethanol (v/v), 560 g of fresh Roselle calyces for 168 h. The Roselle extracts were spray dried at different temperatures 150, 160, 170, 180, 190, 200 and 210 degrees C, giving different outlet values about yield and final moisture. The volatile compounds in Roselle extract and dried samples were performed using needles of solid phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS HP-5890). Twenty volatile compounds were identified in the extracts among them terpenoids, esters, hydrocarbons and aldehydes. Fourteen volatile compounds were identified in the powder sample, but only ten were present in the Roselle extract. This indicates that some compounds were lost and some others were generated due to a degradation process. An acceptability sensory analysis showed that the best powder sample was the Roselle extract dehydrated using temperature between 190 degrees C and 200 degrees C (p<0.05). There was not statistically significant difference in the pH of Roselle extracts ranging from 3.4 to 3.9. It was concluded that the spray drying temperature of the Roselle extracts has an effect on the volatile compounds losses.

A prospective randomized blinded study of the effect of intravenous fluid therapy on postoperative nausea and vomiting in children undergoing strabismus surgery.

BACKGROUND: Nausea and vomiting is a common postoperative complication that often necessitates the use of antiemetic agents. METHODS: In a prospective, randomized, double blind trial, the effect of perioperative fluid administration on postoperative adverse outcomes following anesthesia was studied. One hundred children undergoing strabismus repair were randomly assigned to receive 10 ml x kg(-1) x h(-1) (control group) or 30 ml x kg(-1) x h(-1) (superhydration group) of lactated Ringer's solution during the operation. During the first 24 h postoperatively, nausea and vomiting, thirst, pain, and fever were evaluated. RESULTS: Groups were similar with respect to demographic data, surgical procedures and baseline hemodynamic variables. In the first 24 h postoperatively, nausea and vomiting occurred in 27 patients (54%) of the control group and 11 (22%) of patients in the superhydration group (P = 0.001). Comparison of the superhydration group with the control group also showed a statistically significant benefit of superhydration on postoperative thirst (P = 0.0002) and fever (P = 0.02). The differences in nausea and vomiting, thirst, and fever remained significant after adjustment for age, gender, weight, and duration of surgery. There was no significant difference between the two groups in postoperative pain. CONCLUSIONS: Intravenous superhydration administration is an inexpensive and safe therapy for reducing postoperative nausea and vomiting and discomfort.

Alteraciones de los mecanismos hemostáticos en niños operados del corazón / Alterations of hemosthasis in children operated of heart

Se estudiaron 20 niños postoperados del corazón, bajo circulación extracorpórea, que habían tenido pruebas de coagulación preoperatoria normales. Al ingresar a terapia intensiva, y 24 horas después, se les hicieron las siguientes determinaciones: hemoglobina (Hb), tiempo de protrombina (TP), tiempo parcial de tromboplastina (TPT), tiempo de trombina (TT), fibrinógeno, factores V, VIII y VIII/Von Willebrand, productos líticos de fibrina (PLF), cuenta y adhesividad plaquetaria, lisis de euglobulinas, plasminógeno y antitrombina III (ATIII). La Hb, FV y VIII, fibrinógeno, plaquetas, plasminógeno ATIII y adhesividad plaquetaria; el TP, TPT y TT, inicialmente alargados, se acortaron a las 24 horas, pero sin significación estadística. Los PLF fueron negativos en las dos ocasiones. En algunos pacientes se utilizó paquete globular, plasma frasco, vitamina K y concentrados plaquetarios. La prolongación del TP, TPT, y la disminución de la Hb, el fibrinógeno, el FV y la ATIII en el primer estudio fueron secundarios a la hemodilución, las plaquetas además disminuyen por daño físico. La adhesividad plaquetaria disminuida favorece el sangrado anormal. No se observó coagulación intravascular diseminada

Evolución de la coagulación intravascular diseminada con microdosis de heparina / Course of disseminated intravascular coagulation with low doses of heparin

A 34 lactantes infectados graves se les midió tiempo de protrombina (TP), tiempo de tromboplastina parcial (TTP), plaquetas, fibrinógeno y productos líticos de fibrina (PLF). Todos se consideraron portadores de coagulación intravascular diseminada (CID). Se clasificaron en tres grupos: grupo I (6 pacientes) con fibrinógeno alto, plaquetas normales o altas y PLF elevados (considerado en fase de hipercoagulabilidad); grupo II (16 pacientes) con fibrinógeno normal, plaquetas bajas o normales y PLF elevados (en fase de compensación o "encubrimiento") y grupo III (12 pacientes) con fibrinógeno bajo, plaquetas bajas y PLF elevados (en fase de consumo). Después del tratamiento de fondo y utilización de heparina a 100 U/kg/24h, en infusión continua, se observó que en el grupo I el fibrinógeno, plaquetas y PLF disminuyeron a cifras normales; en el grupo II, el fibrinógeno y las plaquetas se mantuvieron normales y los PLF disminuyeron y en el grupo III, el fibrinógeno y las plaquetas se elevaron y los PLF disminuyeron. En los tres grupos el TP y TTP presentaron cambios sin importancia. Se concluye que la heparina en microdosis y a infusión continua frena la CID en cualquiera de las tres fases de evolución