(-)-Epicatechin and colonic metabolite 2,3-dihydroxybenzoic acid, alone or in combination with metformin, protect cardiomyocytes from high glucose/high palmitic acid-induced damage by regulating redox status, apoptosis and autophagy.

(-)-Epicatechin (EC) and a main colonic phenolic acid derived from flavonoid intake, 2,3-dihydroxybenzoic acid (DHBA), display antioxidant and antidiabetic activities. Diabetic cardiomyopathy (DCM) is one of the main causes of mortality in patients with diabetes, lacking a suitable treatment. Hyperglycaemia and dyslipidaemia are mainly responsible for oxidative stress and altered apoptosis and autophagy in cardiomyocytes during DCM. In this context, phenolic compounds could be suitable candidates for alleviating DCM, but have scarcely been investigated or their use in combination with antidiabetic drugs. This study evaluates the effects of EC, DHBA and antidiabetic drug metformin (MET), alone or all combined (MIX), on redox status, autophagy and apoptosis in H9c2 cardiomyocytes challenged with high concentrations of glucose (HG) and palmitic acid (PA). Under HG + PA conditions, EC, DHBA, MET and MIX equally improved redox status, reduced apoptosis induction and ameliorated autophagy inhibition. Mechanistically, all treatments alleviated HG + PA-induced oxidative stress by reinforcing antioxidant defences (∼40% increase in glutathione, ∼30% diminution in GPx activity and ∼15% increase in SOD activity) and reducing ROS generation (∼20%), protein oxidation (∼35%) and JNK phosphorylation (∼200%). Additionally, all treatments mitigated HG + PA-induced apoptosis and activated autophagy by decreasing Bax (∼15-25%), caspase-3 (∼20-40%) and p62 (∼20-40%), and increasing Bcl-2, beclin-1 and LC3-II/LC3-I (∼40-60%, ∼15-20%, and ∼25-30%, respectively). JNK inhibition improved protective changes to redox status, apoptosis and autophagy that were observed in EC-, DHBA- and MIX-mediated protection. Despite no additive or synergistic effects being detected when phenolic compounds and MET were combined, these results provide the first evidence for the benefits of EC and DHBA, comparable to those of MET alone, to ameliorate cardiomyocyte damage, that involve an improvement in antioxidant competence, autophagy and apoptosis, these effects being mediated at least by targeting JNK.

Dietary Supplementation with a Cocoa-Carob Blend Modulates Gut Microbiota and Prevents Intestinal Oxidative Stress and Barrier Dysfunction in Zucker Diabetic Rats.

We have recently developed a cocoa-carob blend (CCB) rich in polyphenols with antidiabetic properties. In this study, we investigated whether its benefits could be related to gut health and gut microbiota (GM) composition and the likely phenolic metabolites involved. Zucker diabetic fatty rats were fed on a standard or a CCB-rich diet for 12 weeks. Intestinal barrier structure and oxidative and inflammatory biomarkers were analyzed in colonic samples. GM composition and phenolic metabolites were evaluated from feces. The results show that CCB improved mucin and tight-junction proteins and counteracted gut oxidative stress and inflammation by regulating sirtuin-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) levels. CCB also modulated the composition of the GM, showing increases in Akkermansia and Bacteroides and decreases in Ruminococcus genera. Correlation analysis strengthened the associations between these genera and improved pathological variables in diabetic animals. Moreover, 12 phenolic metabolites were identified in CCB feces, being2,3-dihydroxybenzoic and 3,4,5-trihydroxybenzoic acids significantly associated with increased levels of Akkermansia and Oscillospira genera. Our findings support the potential use of CCB to prevent intestinal damage and dysbiosis in T2D, which would help to delay the progression of this pathology.

Single-Use Versus Reusable Cystoscope for Ureteral Stent Removal: A Comparative Study of Perceived Pain and Procedure Times.

INTRODUCTION: The aim of this study was to compare the IsirisTM cystoscope with a common reusable flexible cystoscope in terms of patient perceived pain and endoscopy time in the ureteral stent removal setting. MATERIALS AND METHODS: A non-randomized prospective study comparing the IsirisTM single-use cystoscope with a reusable flexible cystoscope. A visual analogue scale (VAS) was used for pain assessment and endoscopy time was recorded in seconds. Univariate and multivariate analyses were performed to assess the correlation between endoscope type and clinical variables with VAS score and endoscopy time. RESULTS: A total of 85 patients were included in the study: 53 in the disposable cystoscope group and 32 in the reusable cystoscope group. Ureteral stent extraction was successful in all cases. The mean VAS score was similar between groups (single-use group was 2.09 +/- 2.53 vs 2.53 +/- 2.14 in the reusable cystoscope group) (p = 0.13). Same was observed endoscopy time (74.92 +/- 74.45 s. in the single-use group vs 98.87 +/- 153.33 s. in the reusable group) (p = 0.07). Age (coefficient ß = -0.36, p < 0.04) and body mass index (BMI) (coefficient ß = -0.22, p < 0.02) were inversely correlated with perceived pain during ureteral stent removal, measured by VAS score. CONCLUSIONS: Ureteral catheter removal with a flexible cystoscope is a well-tolerated procedure in patients. Older age and high BMI are associated with better intervention tolerance. Use of a single-use flexible cystoscope is comparable to that of a common flexible cystoscope in terms of pain and endoscopy time.

Single-Use Versus Reusable Cystoscope for Ureteral Stent Removal: A Comparative Study of Perceived Pain and Procedure Times

Introduction: The aim of this study was to compare the IsirisTM cystoscope with a common reusable flexible cystoscope in terms of patient perceived pain and endoscopy time in the ureteral stent removal setting. Materials and Methods: A non-randomized prospective study comparing the IsirisTM single-use cystoscope with a reusable flexible cystoscope. A visual analogue scale (VAS) was used for pain assessment and endoscopy time was recorded in seconds. Univariate and multivariate analyses were performed to assess the correlation between endoscope type and clinical variables with VAS score and endoscopy time. Results: A total of 85 patients were included in the study: 53 in the disposable cystoscope group and 32 in the reusable cystoscope group. Ureteral stent extraction was successful in all cases. The mean VAS score was similar between groups (single-use group was 2.09 +/– 2.53 vs 2.53 +/– 2.14 in the reusable cystoscope group) (p = 0.13). Same was observed endoscopy time (74.92 +/– 74.45 s. in the single-use group vs 98.87 +/– 153.33 s. in the reusable group) (p = 0.07). Age (coefficient β = –0.36, p < 0.04) and body mass index (BMI) (coefficient β = –0.22, p < 0.02) were inversely correlated with perceived pain during ureteral stent removal, measured by VAS score. Conclusions: Ureteral catheter removal with a flexible cystoscope is a well-tolerated procedure in patients. Older age and high BMI are associated with better intervention tolerance. Use of a single-use flexible cystoscope is comparable to that of a common flexible cystoscope in terms of pain and endoscopy time (AU)

Metabolic regulation of (-)-epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid on the glucose uptake, lipid accumulation and insulin signalling in cardiac H9c2 cells.

Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake have been suggested to exert healthful effects, although their mechanism of action remains unknown. Heart damage is highly prevalent in metabolic diseases, and the failure of this organ is a major cause of death worldwide. In this study, the modulation of the energy metabolism and insulin signalling by the mentioned compounds in cardiac H9c2 cells was evaluated. Incubation of cells with EC (1-20 µM) and 2,3-dihydroxybenzoic acid (DHBA, 10 µM) reduced glucose uptake, and both compounds decreased lipid accumulation at concentrations higher than 0.5 µM. EC and DHBA also increased the tyrosine phosphorylated and total insulin receptor (IR) levels, and activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in cardiac H9c2 cells. Interestingly, EC and DHBA did not modify glucose transporters (SGLT-1 and GLUT-1) levels, and increased GLUT-4 values. In addition, EC and DHBA decreased cluster of differentiation 36 (CD36) and fatty acid synthase (FAS) values, and enhanced carnitine palmitoyl transferase 1 (CPT1) and proliferator activated receptor α (PPARα) levels. By using specific inhibitors of AKT and 5'-AMP-activated protein kinase (AMPK), the participation of both proteins in EC- and DHBA-mediated regulation on glucose uptake and lipid accumulation was shown. Taken together, EC and DHBA modulate glucose uptake and lipid accumulation via AKT and AMPK, and reinforce the insulin signalling by activating key proteins of this pathway in H9c2 cells.

Supplementation with a Cocoa-Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats.

Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa-carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM.

Acute supplementation with grapes in obese subjects did not affect postprandial metabolism: a randomized, double-blind, crossover clinical trial.

PURPOSE: The aim of this study was to determine whether grape polyphenols have a "second-meal effect", modulating glucose and lipid elevations in the postprandial period after two successive meals in subjects with obesity. METHODS: A randomized, double-blind, placebo-controlled, acute clinical trial was conducted. Twenty-five obese subjects (BMI = ≥ 30 and < 40 kg/m2) were randomly divided into two groups. At an initial visit, blood was collected in a fasting state and the subjects received breakfast and 46 g of either grape powder (equivalent to 252 g fresh grapes) or placebo, both solved in water. Lunch was provided 5 h later and then blood was collected after 0, 30, 60, 120, 180, 240, 300, 330, 360, and 420 min since arrival. Two weeks later, at a second visit, the subjects received the other powder. The following were determined: glucose, insulin, triglycerides, uric acid, blood count, hemoglobin, viscosity, antioxidant capacity, and satiety perception. RESULTS: Postprandial increases were observed as expected in, for example, glucose and triglycerides after breakfast and lunch. The grape powder supplementation did not cause any significant modification compared to placebo, in these parameters; nor did it significantly modify plasma antioxidant capacity in the 6 h postprandial period. DISCUSSION: Single grape powder supplementation did not modify postprandial responses in obese subjects, probably because the polyphenol dose was insufficient to induce such an effect. The result of a combination of grape with other polyphenol-rich products or chronic supplementation with grape powder on postprandial responses remains to be elucidated. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov , NCT03741218.

Calcificación arterial generalizada idiopática de la infancia: a propósito de un caso / Generalized arterial calcification in childhood: a case report

INTRODUCCIÓN: La calcificación arterial de la infancia es una enfermedad rara, autosómica recesiva, potencialmente letal, caracterizada por la calcificación de la lámina elástica interna de arterias de tamaño grande y mediano con engrosamiento intimal. CASO CLÍNICO: Presentamos el caso de una autopsia clínica de un recién nacido varón pre-término que muestra al nacimiento hidrops fetal y cianosis generalizada. El estudio macroscópico reveló cardiomegalia secundaria a oclusión arterial por calcificación. DISCUSIÓN: Se realiza correlación clínico-histológica de la entidad con hallazgos macro y microscópicos relevantes y actualización de diagnóstico genético

INTRODUCTION: Arterial calcification of infancy is a rare autosomal recessive genetic disorder with extremely poor prognosis characterized by extensive calcification of internal elastic lamina and thickened of intimal tissue of large and medium sized arteries. CASE REPORT: We present the case of a newborn necropsy with hydrops and widespread cyanosis. The internal examination revealed heart enlargement due to occlusive calcification of the arteries. DISCUSSION: The aim of the present report is to provide a correlation of clinical and pathological features. An update of genetic diagnosis is provided

[Generalized arterial calcification in childhood: A case report]. / Calcificación arterial generalizada idiopática de la infancia: a propósito de un caso.

INTRODUCTION: Arterial calcification of infancy is a rare autosomal recessive genetic disorder with extremely poor prognosis characterized by extensive calcification of internal elastic lamina and thickened of intimal tissue of large and medium sized arteries. CASE REPORT: We present the case of a newborn necropsy with hydrops and widespread cyanosis. The internal examination revealed heart enlargement due to occlusive calcification of the arteries. DISCUSSION: The aim of the present report is to provide a correlation of clinical and pathological features. An update of genetic diagnosis is provided.

Factores asociados a la presencia de valores alterados de calprotectina fecal en pacientes con estudio endoscópico panentérico normal / No disponible

INTRODUCCIÓN: la calprotectina fecal es un parámetro útil a la hora de decidir si un paciente se puede beneficiar de la realización de estudios endoscópicos. No obstante, cierto número de individuos sintomáticos y con cifras elevadas de este marcador no tendrán lesiones endoscópicas. El objetivo de este estudio es determinar qué factores se asocian a cifras alteradas de calprotectina fecal en pacientes con estudios endoscópicos de intestino delgado y colon normales. MÉTODOS: estudio prospectivo y observacional de pacientes con síntomas digestivos. Se ha analizado la asociación de diferentes variables con cifras alteradas de calprotectina y estudios endoscópicos (cápsula de intestino delgado y colonoscopia) negativos. RESULTADOS: se incluyen 143 pacientes (98 mujeres - 68,5 %), con una edad media 40,06 ± 16,42 (15-82) años. El consumo de tabaco y la toma de antiinflamatorios no esteroideos se asoció a la presencia de cifras alteradas de calprotectina y estudios endoscópicos negativos (p: 0,029 y p: 0,006). Los valores medios de calprotectina fecal fueron significativamente mayores entre los fumadores, consumidores de antiinflamatorios y pacientes con test positivo de sobrecrecimiento bacteriano de intestino delgado. El tabaquismo (OR: 3,505; p: 0,028), la toma de antiinflamatorios (OR: 3,473; p: 0,021) y el sobrecrecimiento bacteriano (OR: 3,172; p: 0,013) son factores de riesgo independientes para presentar una calprotectina alterada sin lesiones endoscópicas. No se obtuvo asociación con ninguna otra variable. CONCLUSIONES: el consumo de tabaco y de antiinflamatorios no esteroideos tiene una fuerte asociación con la presencia de valores elevados de calprotectina en ausencia de lesiones endoscópicas. Se ha observado también asociación con el sobrecrecimiento bacteriano de intestino delgado

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Factors associated with the presence of abnormal levels of fecal calprotectin in patients with negative panenteric studies.

BACKGROUND: fecal calprotectin is a selection tool prior to endoscopic studies in patients with gastrointestinal symptoms. However, some symptomatic patients with altered fecal calprotectin will not have any endoscopic lesions. The aim of the study was to determine the factors associated with the presence of altered fecal calprotectin in patients with negative endoscopic studies of the colon and small bowel. METHODS: this was an observational, prospective study of patients with digestive symptoms. The association of different clinical factors with elevated fecal calprotectin in the absence of endoscopic lesions of the colon and small bowel were analyzed. RESULTS: 143 patients were included in the study, 98 were female (68.5 %) and the mean age was 40.06 ± 16.42 (15-82) years. Smoking and non-steroidal anti-inflammatory drug intake were associated with altered fecal calprotectin in patients with a negative endoscopy of the colon and small bowel (p = 0.029 and p = 0.006). The mean values of fecal calprotectin were significantly higher in smokers, users of non-steroidal anti-inflammatory drugs and patients with small intestine bacterial overgrowth. Smoking (OR: 3.505; p = 0.028), non-steroidal anti-inflammatory drugs intake (OR: 3.473; p = 0.021) and small intestine bacterial overgrowth (OR: 3.172; p = 0.013) were independent risk factors for altered fecal calprotectin in the absence of endoscopic lesions. No association was found for any of the other variables. CONCLUSIONS: smoking and the use of non-steroidal anti-inflammatory drugs are strongly associated with elevated levels of fecal calprotectin in symptomatic patients with a negative colonoscopy and capsule endoscopy of the small bowel. Small intestine bacterial overgrowth is also associated.

Retención sintomática de cápsula degradable Agile(R) / Symptomatic retention of the Agile(R) patency capsule

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Symptomatic retention of the Agile® patency capsule.

The Agile® capsule has shown to be useful when evaluating the patency of the small bowel in patients prior to capsule endoscopy studies. It is a safe tool and a low rate of complications have been reported, highlighting symptomatic retention, although references in literature are scarce and it is only observed in 1.2% of the procedures. We present the case of a symptomatic retention of this device in a patient with previously known colonic Crohn's disease in who a small bowel study was indicated and was sent for prior patency test.

Gastric schwannoma presenting as a casual ultrasonographic findings.

We present the case of a patient under study due to ascites in which a mass located on the gastric wall was observed during ultrasonography. Further studies (upper endoscopy and computed tomography) confirmed this finding. After an ultrasound-guided percutaneous biopsy, diagnosis of gastric schwannoma was made as intense S-100 expression was found. Surgery was rejected due to the bad clinical situation of the patient and because the mass was an asymptomatic benign tumor.

Schwannoma gástrico como hallazgo ecográfico casual / Gastric schwannoma presenting as a casual ultrasonographic findings

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Fibrolamellar hepatocellular carcinoma: a rare entity diagnosed by abdominal ultrasound.

We present the case of a young man with a hepatic mass in which ultrasound gives great and immediate support for diferential diagnosis.

Carcinoma hepatocelular fibrolamelar, una entidad infrecuente diagnosticada por ecografía abdominal / Fibrolamellar hepatocellular carcinoma: a rare entity diagnosed by abdominal ultrasound

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Hipertensión portal e ictericia colestásica como forma de presentación de una amiloidosis sistémica / Portal hypertension and cholestatic jaundice as a form of presentation of systemic amyloidosis

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