Synergism of small molecules targeting VDAC with sorafenib, regorafenib or lenvatinib on hepatocarcinoma cell proliferation and survival.

Voltage dependent anion channels (VDAC) in the outer mitochondrial membrane regulate the influx of metabolites that sustain mitochondrial metabolism and the efflux of ATP to the cytosol. Free tubulin and NADH close VDAC. The VDAC-binding small molecules X1 and SC18 modulate mitochondrial metabolism. X1 antagonizes the inhibitory effect of tubulin on VDAC. SC18 occupies an NADH-binding pocket in the inner wall of all VDAC isoforms. Here, we hypothesized that X1 and SC18 have a synergistic effect with sorafenib, regorafenib or lenvatinib to arrest proliferation and induce death in hepatocarcinoma cells. We used colony formation assays to determine cell proliferation, and a combination of calcein/propidium iodide, and trypan blue exclusion to assess cell death in the well differentiated Huh7 and the poorly differentiated SNU-449 cells. Synergism was assessed using the Chou-Talalay method. The inhibitory effect of X1, SC18, sorafenib, regorafenib and lenvatinib was concentration and time dependent. IC50s calculated from the inhibition of clonogenic capacity were lower than those determined from cell survival. At IC50s that inhibited cell proliferation, SC18 arrested cells in G0/G1. SC18 at 0.25-2 IC50s had a synergistic effect with sorafenib on clonogenic inhibition in Huh7 and SNU-449 cells, and with regorafenib or lenvatinib in SNU-449 cells. X1 or SC18 also had synergistic effects with sorafenib on promoting cell death at 0.5-2 IC50s for SC18 in Huh7 and SNU-449 cells. These results suggest that small molecules targeting VDAC represent a potential new class of drugs to treat liver cancer.

Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

Bilateral facial palsy with paresthesias, variant of Guillain-Barré syndrome following COVID-19 vaccine: A case series of 9 patients.

Several cases of Guillain-Barré Syndrome (GBS) associated with COVID-19 vaccination have been reported, including the rare subtype known as Bilateral Facial Palsy with paresthesias (BFP). To date, it is not known whether a causal relationship may exist between the two. We report 9 cases of BFP in patients vaccinated against COVID-19 in the previous month. Nerve conduction studies revealed demyelinating polyneuropathy in 4 patients, and 5 presented bilateral, focal facial nerve involvement, exclusively. Ganglioside antibody panel was positive in 4 patients (anti-GM1=2, anti-GD1a=1 and anti-sulfatide=1). Seven patients received intravenous immunoglobulin treatment, one plasma exchange, and one patient died from sudden cardiac arrest following arrhythmia before treatment could be administered. Rates of BFP following COVID-19 vaccination, did not differ from those reported in previous series. Epidemiological studies are essential to determine whether a causal relationship may exist between this rare form of GBS and COVID-19 vaccination.

Honduras: estudiantes universitarios en situación de discapacidad durante la COVID-19 / Honduras: University students with disabilities during COVID-19

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Fast acetone tissue processing of human organs provides tissue characteristics equal to conventional processing.

Routine preparation of paraffin embedded tissue for histopathological diagnosis, here termed conventional histological technique (CT), whether performed manually or using an automated system, requires approximately 12 h. We developed earlier a rapid acetone dehydration technique (AT) for processing biopsies of nervous tissue that meets requirements for preserving tissue morphology and staining properties, and reduces processing time to 3.3 h. We compared the morphology and staining properties of human organ biopsies including adrenal gland, liver, ovary, pancreas, prostate, testis and thyroid prepared using both AT and CT. Following fixation with 10% formaldehyde and processing by either AT or CT, sections were stained using routine and special staining, and immunohistochemical methods. We evaluated nuclear and cytoplasmic staining, staining intensity, sharpness of images and presence of artifacts such as cracking and folding. AT preserved the morphology and staining properties of the tissues as well as CT. Consequently, the rapid AT procedure is a promising alternative technique for tissue processing.

Tratamento tardio de fratura do complexo zigomático-orbitário com uso de fixação interna rígida / Late treatment of the zygomatic-orbital complex fracture with rigid internal fixation

RESUMO: As fraturas do complexo zigomático-orbitário são bastante frequentes devido a sua localização e projeção na face, podendo gerar grandes transtornos funcionais e estéticos ao paciente. O osso zigomático é essencial na configuração da face, sendo a principal estrutura formadora do terço médio dela. Os traumas que mais frequentemente provocam fraturas do complexo zigomático-orbitário são agressões físicas, acidentes de trânsito e esportivos. O tipo de fratura, tempo decorrido, a severidade e o envolvimento de outras estruturas faciais influenciam a modalidade de tratamento a ser empregado. O presente trabalho apresenta um caso clínico de fratura do complexo zigomático-orbitário esquerdo, diagnosticada tardiamente, e tratada por meio de osteotomia, redução e fixação em três pontos com placas e parafusos do sistema 1.5, e reconstrução do assoalho orbitário com tela de titânio. (AU)

ABSTRACT: Fractures of the zygomatic-orbital complex are quite frequent due to their location and projection on the face, which can cause major functional and aesthetic disorders to the patient. The zygomatic bone is essential in the configuration of the face, being the main forming structure of the middle third of it. The traumas that most often cause fractures of the zygomatic-orbital complex are physical aggression, traffic accidents, and sports. The type of fracture, elapsed time, severity, and the involvement of other facial structures influence the type of treatment to be employed. The present work presents a clinical case of fracture of the left zygomatic-orbital complex, diagnosed late, and treated by osteotomy, reduction, and fixation in three points with 1.5 system plates and screws, and reconstruction of the orbital floor with titanium mesh. (AU)

Efecto de gas de formalina sobre el recuento de mesófilos en nailon comercial destinado a procedimientos quirúrgicos / Effect of formaline gas on the counting of mesophiles in commercial nylon destined to surgical procedures

RESUMEN La investigación se realizó a fin de evaluar el efecto del gas de formalina sobre el recuento de mesófilos en nailon comercial (poliamida) destinado a procedimientos quirúrgicos. En primer lugar, se evaluó la contaminación de una muestra del material comercial de 1 g expuesta al ambiente de quirófano por 72 horas, a través de la técnica de recuento en placa para mesófilos; se obtuvieron 850 UFC/g. Una vez comprobada la contaminación de la poliamida comercial, esta se sometió a gases de formalina en comprimidos. Se colocaron 5 muestras (n=5) de nailon de 1 g cada una en 5 recipientes herméticos de 1 litro con 1 gramo de formalina cada uno; estos recipientes se almacenaron en un mueble en sala de esterilización a un metro de altura del piso y posteriormente, fueron abiertos y cultivados a través de la técnica de recuento en placa para mesófilos, uno por día a lo largo de 5 días a intervalos de 24 horas. Los resultados obtenidos no registraron crecimientos de microorganismos a partir de las 24 horas y durante los 5 días posteriores y se encontraron diferencias estadísticamente significativas (p < 0,05). Se concluye que bajo las condiciones del presente estudio el tiempo de esterilización de la formalina sobre nailon comercial es de 24 horas.

ABSTRACT Hie present research work was carried out with the purpose of evaluating the effect of formalin gas on the count of mesophiles in commercial nylon (polyamide) destined to surgical procedures. Firstly, the contamination of a 1 g commercial nylon sample, exposed to the operating room environment for 72 hours, was evaluated through the plate counting technique for mesophiles; it yielded a result of 850 CFU / gram. Once the contamination of the commercial polyamide was checked, it was subjected to formalin gases in tablets. Five nylon samples (n=5) of 1 gram each were placed in 5 1 liter airtight containers containing 1 gram of formalin; Hese containers were stored in a cabinet in the sterilization room one meter above the floor, and later opened and cultivated through the plate counting technique for mesophiles, one per day for 5 days at 24 hour intervals. The results obtained after being exposed to formalin gases in tablets did not register growths of microorganisms after 24 hours and during the 5 days after the study, finding statistically significant differences (p < 0.05) in relation to the studied times concluding under the conditions of the present study that the sterilization time of the formalin on commercial nylon is equal to 24 hours.

JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells.

The multikinase inhibitor sorafenib, and opening of voltage dependent anion channels (VDAC) by the erastin-like compound X1 promotes oxidative stress and mitochondrial dysfunction in hepatocarcinoma cells. Here, we hypothesized that X1 and sorafenib induce mitochondrial dysfunction by increasing reactive oxygen species (ROS) formation and activating c-Jun N-terminal kinases (JNKs), leading to translocation of activated JNK to mitochondria. Both X1 and sorafenib increased production of ROS and activated JNK. X1 and sorafenib caused a drop in mitochondrial membrane potential (ΔΨ), a readout of mitochondrial metabolism, after 60 min. Mitochondrial depolarization after X1 and sorafenib occurred in parallel with JNK activation, increased superoxide (O2•-) production, decreased basal and oligomycin sensitive respiration, and decreased maximal respiratory capacity. Increased production of O2•- after X1 or sorafenib was abrogated by JNK inhibition and antioxidants. S3QEL 2, a specific inhibitor of site IIIQo, at Complex III, prevented depolarization induced by X1. JNK inhibition by JNK inhibitors VIII and SP600125 also prevented mitochondrial depolarization. After X1, activated JNK translocated to mitochondria as assessed by proximity ligation assays. Tat-Sab KIM1, a peptide selectively preventing the binding of JNK to the outer mitochondrial membrane protein Sab, blocked the depolarization induced by X1 and sorafenib. X1 promoted cell death mostly by necroptosis that was partially prevented by JNK inhibition. These results indicate that JNK activation and translocation to mitochondria is a common mechanism of mitochondrial dysfunction induced by both VDAC opening and sorafenib.

El estado metabólico y su asociación con la actividad ósea en la mujer posmenopáusica / Metabolic status and its association with bone activity in post-menopausal women

Antecedentes y objetivo: En la posmenopausia se presentan alteraciones en el metabolismo de los lípidos, sensibilidad a la insulina e incremento del tejido adiposo visceral, lo que se asocia a un aumento del riesgo cardiometabólico. La osteocalcina (OCN) es una proteína de remodelación ósea, que recientemente se ha observado que participa en la regulación del metabolismo de la glucosa, lípidos y del tejido adiposo. Son limitados los estudios de OCN en la etapa posmenopáusica. El objetivo de este trabajo fue investigar la relación de la concentración de OCN con la obesidad y el síndrome metabólico (SM) en mujeres pre y posmenopáusicas. Métodos: Estudio transversal que incluyó a 261 participantes de 45 a 60 años, quienes fueron evaluadas clínicamente y se les midió glucosa y perfil de lípidos. La OCN sérica y la insulina se determinaron por quimioluminiscencia. Resultados: De las participantes, 128 fueron premenopáusicas y 133 posmenopáusicas; el 33% de las participantes presentaban SM. En las mujeres posmenopáusicas, la concentración de OCN fue superior en comparación a las premenopáusicas (7,2±4,0 vs. 5,5±6,4 ng/mL, p<0,019). La concentración de OCN en la mujer posmenopáusica con SM fue más elevada en comparación al grupo control (8,4±5,1 vs. 6,3±2,8 ng/mL, p=0,003). Conclusión: En la posmenopausia, el déficit de estrógenos y la resistencia a la insulina se asocian a un incremento de la concentración de OCN

Introduction and objective: Changes in lipid metabolism, insulin sensitivity, and visceral adipose tissue increase cardio-metabolic risk. Recent evidence suggests that osteocalcin (OCN) may play a role in metabolism. However, little is known about the OCN in post-menopausal women. The aim of this study was to investigate the relationship between the concentration of OCN with obesity and metabolic syndrome (MS) in pre-and post-menopausal women. Methods: A cross-sectional study was conducted that included 261 participants who were reviewed clinically and underwent laboratory studies, including the determination of serum OCN and insulin by chemiluminescence. Results: Of the participants, 128 were pre-menopausal, 133 post-menopausal, and 33% had MS. OCN concentration was higher in post-menopausal women than in pre-menopausal (7.7±5.7 vs. 5.3 + 2.6 ng/mL, P<.001). OCN levels in post-menopausal women with MS were greater than those without MS (8.4±5.1 vs 6.3±2.8 ng/mL, P.003). Conclusion: Oestrogen deficiency and insulin resistance are associated with increased OCN during the stage of post-menopausal stage

Performance of butanol separation from ABE mixtures by pervaporation using silicone-coated ionic liquid gel membranes.

This work aims at the separation of n-butanol from aqueous solutions by means of pervaporation using membranes based on gelled ionic liquids (IL). These membranes were mechanically stabilized with a double silicone coating using two polydimethylsiloxane (PDMS) films. The first step of the membrane preparation considered the formation of a gelled ionic liquid layer, which was formed using two different imidazolium-based ionic liquids: [omim][Tf2N] and [bmim][Tf2N], and two different phosphonium-based ionic liquids: [P6,6,6,14][Tf2N] and [P6,6,6,14][DCA]. The gelation procedure was carried out on a porous paper support using a low molecular weight gelator. The membranes obtained from this method were tested in pervaporation assays to separate butanol from model ABE (Acetone-Butanol-Ethanol) fermentation solutions. These assays were done in an experimental setup especially built for this purpose. The pervaporation performance of these ionic liquid-based membranes was compared to that obtained with a single PDMS layer membrane. From these experimental results, butanol/water selectivity for [P6,6,6,14][Tf2N]-based membranes reached a value equal to 892, which is 150 times higher than the value obtained for a single PDMS layer membrane. Simultaneously, for the same IL, the transmembrane fluxes (kg h-1 m-2) of butanol and water were 37% and 99.6% lower than the values obtained using a single PDMS layer membrane, respectively. The hydrophobic character of the selected ionic liquid and its relatively high values for the transport parameters can explain this experimental response.

Structural and histological differences between connective tissue grafts harvested from the lateral palatal mucosa or from the tuberosity area.

Tuberosity grafts had a greater percentage of lamina propria and lower percentage of submucosa when compared to lateral palate grafts. OBJECTIVE: The study aims to understand the differences in the structural composition of soft tissue autografts harvested from the lateral palate or the tuberosity. MATERIAL AND METHODS: Patients were randomly allocated to receive autografts harvested either from palatal or tuberosity sites to augment horizontal volume deficiencies around single-tooth implants. Tissue biopsies were analyzed for histological and histo-morphometric analysis. Picro-sirius red stain was used to evaluate collagen 1 and 3. Also, immuno-histochemical analysis was performed against MMP1, MMP2, cytokeratin-10, cytokeratin-13, and lysine hydroxylase-2. RESULTS: Twenty specimens were harvested from 9 subjects in the lateral palate group (PG) and 11 subjects in the tuberosity group (TG). The percentage of lamina propria represented 51.08% in the PG group and 72.79% in the TG group, while the area of submucosa was minimal in the TG group representing 4.89% of the total sample vs 25.75% in the PG. The total area of COL-1 and 3 in the TG was 1.19 ± 0.57 and 0.72 ± 0.44 mm2, respectively, while in the PG, the corresponding values were 1.4 ± 0.7 and 1.04 ± 0.5 mm2. The immuno-histochemical analysis generally showed a higher expression of LLH-2, MMP2, CYT-10, and CYT-13 in the TG when compared with the PG. CONCLUSION: Tuberosity grafts had a greater percentage of lamina propria and lower percentage of submucosa. The collagen content in the lamina propria was similar for both groups while the immuno-histochemical profile showed differences in the antibody expression of the epithelial cells. CLINICAL RELEVANCE: Tuberosity grafts had more lamina propria and less submocusa, which may be beneficial for volume augmentation.

mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development.

Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments. The mechanism responsible for these changes remains unknown. Here, we show that the pro-inflammatory cytokine IFNγ contributes to the inhibition of epithelial cell proliferation in intestinal epithelial cells (IECs) by inducing the activation of mTORC1. Activation of mTORC1 in response to IFNγ was detected in IECs present along the crypt axis and in colonic macrophages. mTORC1 inhibition enhances cell proliferation, increases DNA damage in IEC. In macrophages, mTORC1 inhibition strongly reduces the expression of pro-inflammatory markers. As a consequence, mTORC1 inhibition exacerbated disease activity, increased mucosal damage, enhanced ulceration, augmented cell infiltration, decreased survival and stimulated tumor formation in a model of colorectal cancer CRC associated to colitis. Thus, our findings suggest that mTORC1 signaling downstream of IFNγ prevents epithelial DNA damage and cancer development during colitis.

Rhabdomyolysis during envenomation by Physalia sp envenomation in New Caldonia.

We report the first case of rhabdomyolysis following envenomation by a Physalia sp in New Caledonia. Systemic envenomation by this marine hydrozoan is well known, including myalgia as a commonly reported clinical feature. Nonetheless, a related increase in muscle enzymes, featuring rhabdomyolysis, has not previously been described. In this case report, we describe a patient with rhabdomyolysis and acute renal failure. Rhabdomyolysis should be checked in case of systemic physalia envenomation.

Comparación entre Células Troncales Mesenquimales obtenidas de Médula Ósea, Tejido Adiposo y Gelatina de Wharton en base a los Criterios de la ISCT / Comparison between Mesenchymal Stem Cells obtained from Bone Marrow, Adipose Tissue and Wharton Gelatin according to the ISCT Criteria

RESUMEN: Las células troncales mesenquimales (CTM) representan una población heterogénea con capacidad para auto-renovarse y diferenciarse a distintos tipos celulares. Estas fueron descritas en un inicio en médula ósea (MO) a mediados del siglo pasado, desde entonces este tejido se ha convertido en el estándar de oro para la obtención y caracterización de CTM. Actualmente se sabe que este tipo de células se encuentran alojadas en nichos distribuidos por todo el organismo, donde contribuyen a los procesos de regeneración del tejido donde se localizan. No obstante, encontrar una fuente alterna de CTM con las mismas características que las de MO, pero que su extracción no suponga riesgo para el donador es fundamental para su utilización con fines terapéuticos. En este trabajo se aislaron células troncales de médula ósea, y se compararon con tejido adiposo y gelatina de Wharton y caracterizaron de acuerdo a los criterios de la Sociedad Internacional para la Terapia Celular (ISCT). Los resultados mostraron que la morfología, diferenciación osteogénica y adipogénica, así como la expresión de los antígenos de superficie CD90, CD73 y CD105 cumplen con los estándares, señalando a las provenientes de gelatina de Wharton como mejor opción.

ABSTRACT: Mesenchymal stem cells (MSC) represent a heterogeneous population with the capacity to self-renew and differentiate into different cell types. At the middle of the last century these cells initially were described in bone marrow (BM), thence this tissue has become the gold standard for obtaining and characterization of MSC. It is known that these cells are housed in specific areas called niches distributed throughout all body, where they contribute to tissue regeneration processes of self-tissue were they are located. However, finding an alternative source of CTM with the same characteristics that have showed in MO, but its obtention no represent a risk since the donor is essential to their use for therapeutic purposes. In this study we isolated mesenchymal stem cells from bone marrow, adipose tissue and Wharton's jelly and they were compared in their characteristics in according to the standards of the International Society for Cellular Therapy (ISCT). The results showed that the morphology as well as adipogenic and osteogenic differentiation and also the expression of surface antigens (CD90, CD73, and CD105) from all tissues accomplished the standards, although Wharton's jelly represented the best option.

Coagulation factors, anticoagulant proteins, and plasminogen in Mexican older adults.

INTRODUCTION: Hemostasis protects upon the occurrence of vascular endothelial damage, with involving of different factors. The interaction of these factors in older adults is poorly known, and has been associated with different disorders. Therefore, we determined the activity of coagulation factors (CF), anticoagulant proteins (AP), and plasminogen (Plg), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican older adults (OA). METHODS: CF (I, II, V, VII, VIII, IX, X, and XI y XII), AP [protein C (PC), protein S (PS), and antithrombin (AT)], and Plg were determined from 244 plasma samples of OA using commercial kits in a coagulometer ACL Elite Pro. RESULTS: A total of 139 women and 105 men were under study. They were divided into age range groups (50-59, 60-69, 70-79, and ˃80 years). Activity of CF, AP, and Plg was determined. Frequencies of CF, AP, and Plg activity values were obtained for each age group according to gender. Differences were found between both frequencies for each protein. CONCLUSION: Significant differences were found, so it is recommended to establish reference values (RV) for the activity of fibrinogen and FX by decade and gender, FVII and FXII by gender, FII, FV, FVIII, PC, PS, and Plg by decade, whereas for FIX, FXI, and AT, they are not modified by age or gender, so the RV described for adult Mexican population can be used. It is important to integrate these results into established diagnostic algorithms, which can be taken into account to provide an accurate diagnosis and treatment for patients with suspected hemorrhagic or thrombotic processes, as well as suggest those habits that improve their quality of life, to maintain optimal health and prevent thrombotic and hemorrhagic events.

The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants.

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.

The prothrombotic state associated with obesity-induced hypertension is reduced by cocoa and its main flavanols.

BACKGROUND: Little is known about the effects of cocoa and its main flavanols on the prothrombotic state associated with the development of hypertension in diet-induced obesity models. PURPOSE: To evaluate the effects of cocoa powder, cocoa extract and their main flavanols on plasma biomarkers related to impaired coagulation and fibrinolysis and its association with hypertension and obesity-related metabolic disorders in rats fed a hypercaloric diet. METHODS: Male Wistar rats were randomly assigned to 7 treatment groups (n = 7): normal diet (ND); hypercaloric diet control group (HCD); HCD + cocoa powder (CO); HCD + cocoa extract (CO-EX); HCD + (-)-epicatechin (EPI); HCD + (+)-catechin (CAT); and HCD + procyanidin B2 (PB2). Blood pressure was measured using the tail-cuff method (week 7). At the end of the experimental period (week 8), rats were sacrificed and blood samples were collected immediately for coagulation and biochemical analyses. RESULTS: Oral administration of CO, CO-EX and their main flavanols significantly decreased plasma biomarkers related to impaired coagulation and fibrinolysis (vWF, FVIII, fibrinogen and PAI-1) in rats fed a hypercaloric diet. These effects were associated with decreased systolic and diastolic blood pressure, aortic oxidative stress (MDA levels) and improvement of dyslipidemia, insulin resistance and circulating markers of inflammation (TNF-α, IL-6 and CRP) compared to the HCD group. CONCLUSION: Our results showed that cocoa and its main flavanols may improve endothelial dysfunction and exert their antihypertensive effects by decreasing the prothrombotic state in rats fed a hypercaloric diet. Moreover, improvement of obesity-related metabolic disorders may also contribute to their BP-lowering effect.