Search

Background: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown., Objectives: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension., Materials: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion., Results: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test)., Conclusions: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT 1 ). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase in the heat shock protein 70 (Hsp70)-an antioxidant factor. We aim to determine the mechanisms involved in melatonin (Mel) prevention of kidney damage and arrhythmogenic heart remodeling. Unilateral ureteral-obstruction (UUO) and sham-operated rats were treated with either melatonin (4 mg/kg/day) or vehicle for 15 days. Hearts and kidneys from obstructed rats showed a reduction in VDR and Hsp70. Associated with AT 1 up-regulation in the kidneys and the heart of UUO rats also increased oxidative stress, fibrosis, apoptosis, mitochondrial edema, and dilated crests. Melatonin prevented these changes and ventricular fibrillation during reperfusion. The action potential lengthened and hyperpolarized in melatonin-treated rats throughout the experiment. We conclude that melatonin prevents renal damage and arrhythmogenic myocardial remodeling during unilateral ureteral obstruction due to a decrease in oxidative stress/fibrosis/apoptosis associated with AT 1 reduction and Hsp70-VDR increase., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Bowel reconstruction techniques after right hemicolectomy has currently been objective of review, due to the high rate of anastomotic leak. The aim of this study is to analyse our results of the mechanical reinforced terminolateral ileo-transverse anastomosis., Materials and Methods: A prospective and descriptive study of a consecutive series of right colonic cancer cases that underwent right hemicolectomy. Mechanical reinforced terminolateral ileo-transverse anastomosis technique was carried out in all patients. Demographics, emergency or elective surgery, surgical management, postoperative complications, rate of anastomotic leak, need for surgical procedure after complication, average stay, and mortality were analysed., Results: A total of 452 patients underwent surgery between 2010 and 2017. Of those, 40.6% were female and 59.4% were male. The average age and body mass index (BMI) was 72±11.3 years old, and 26±7.1, respectively. Elective surgery was carried out in 405 (89.6%) patients. Laparoscopic approach was used in 250 patients (61.7%) and 6% needed conversion. Only 41 patients (10.6%) had major complications (Clavien-Dindo III-IV). The rate of postoperative paralytic ileus reach was up to 13.9%. Reintervention was needed in five patients (1.1%) due to anastomotic leak and three (0.7%) of them from the elective surgery subgroup. There were 10 patients (2.2%) with postoperative gastrointestinal bleeding. The average stay was 8.2±2.8 days and late postoperative mortality in the first 30 days was 2%., Conclusions: Mechanical reinforced terminolateral ileo-colic anastomosis is a safe technique with a low anastomotic leak rate. Although our results using this approach seem promising, postoperative paralytic ileus is still a high-rate complication.

Heart failure (HF) is a growing medical problem and it is of interest to study new biomarkers for better characterisation. In this sense, nitric oxide, reactive oxygen species (ROS), NADPH, and superoxide dismutase (SOD) were evaluated, along with their possible predictive value in patients with HF. An analysis was also performed on the potential differences between patients with and without secondary pulmonary hypertension (SPH), considered to have a worse prognosis. A significant decrease of nitric oxide and SOD was noted in HF, whereas ROS and NADPH were increased. These results agree with the pathophysiological changes characteristic of HF. It was also demonstrated that in patients with HF and SPH that nitric oxide and SOD were decreased when compared to HF without SPH, whereas ROS and NADPH were increased. Therefore, our results suggest that nitric oxide, ROS, NADPH, and SOD, could be considered as possible markers in HF, and could also characterise patients with SPH., (Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Hypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic factors, such as Wilms' tumor 1 transcription factor (WT-1), could contribute to the development of hypertension. The aim of this paper is to evaluate the expression of WT-1 and related genes in the nephrogenic process in connection with the development of hypertension as well as the corresponding anatomical and functional correlation., Methods: Male spontaneously hypertensive and control rats were evaluated weekly from birth until week 8 of life. Their blood pressure was taken weekly using the tail-cuff blood pressure system. Weekly, 5 rats per group were sacrificed with a lethal injection of pentobarbital, and their kidneys were removed, decapsulated and weighed. The serum was collected for measuring biochemical parameters. The results were assessed using one-way analysis of variance for comparisons between groups., Results: The relationship between renal weight/total body weights was established, without significantly different values. These data were compared with apoptosis, fibrosis, number and size of the glomeruli. The elevation of systolic blood pressure was significant since week 6. Biochemical values differed slightly. Histology showed a slight increase in deposits of collagen fibers since week 4. Additionally, in kidney cortices, the expression of WT-1, heat shock protein 70 (Hsp70) and vitamin D receptors (VDR) decreased since week 4. Finally, we demonstrated ultrastructural damage to mitochondria since week 4., Conclusions: Our results would suggest an unprecedented link, possibly a regulatory mechanism, between WT-1 on nephrogenic alteration processes and their relationship with hypertension. Moreover, and previous to the increase in blood pressure, we demonstrated low expressions of WT-1, VDR and Hsp70 in kidneys from neonatal SHRs. If so, this may suggest that deregulation in the expression of WT-1 and its impact on nephrogenesis induction could be crucial in understanding the development and maintenance of hypertension.

Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours., Competing Interests: The authors declare no conflicts of interest with respect to the authorship, research and/or publication of this article, (© 2015 John Wiley & Sons Ltd.)

A 6-year-old boy presented with neovascular glaucoma secondary to total retinal detachment. Magnetic resonance imaging findings suggested diffuse infiltrating retinoblastoma. Enucleation was subsequently performed and led to a final histopathological diagnosis of advanced Coats' disease. Diffuse infiltrating retinoblastoma and advanced Coats' disease can be indistinguishable from each other on magnetic resonance imaging., (Copyright 2010, SLACK Incorporated.)

Werner syndrome (WS) is a premature aging and cancer-prone disease caused by loss of the RecQ helicase WRN protein. Cultured WS fibroblasts display high genomic instability and senesce prematurely. Epigenetic inactivation of the WRN gene occurs in numerous tumor types, in which WRN demonstrates tumor suppressor-like activity (Agrelo et al., 2006). However, the role of WRN in tumors that express WRN protein is unknown. Here we report that the inhibition of WRN expression strongly impairs growth of 12 out of 15 cancer cell lines tested. For those cell lines in which WRN depletion induced high cell death, the majority of the surviving proliferative clones exhibited WRN expression. Growth arrest induced by WRN depletion was characterized by an accumulation of cells in the G2/M cell cycle phases and an increase in DNA damage. Importantly, WRN depletion inhibited tumor growth in vivo in SCID mouse xenograft models. Altogether, these findings support a dual role for WRN in tumorigenesis; tumor suppressor-like activity in tumors with WRN inactivation and the promotion of proliferation and survival in tumors that express WRN. These findings suggest a possible therapeutic role for WRN as an anti-cancer target, and highlight the importance of WRN protein status for tumorigenesis and clinical treatments of patients.