Methylglyoxal chronic administration promotes diabetes-like cardiac ischaemia disease in Wistar normal rats

Background and aimsThe influence of lifestyle is well documented, especially the diet regime, in the development of type 2 diabetes (T2D) and associated cardiovascular diseases. Diabetic patients have increased risk of suffering cardiac ischemia and impaired response to such accidents. Methylglyoxal (MG) circulates at high concentration in diabetics' blood and is linked to the development of diabetes chronic complications. We propose that besides promoting the cardiovascular disease, MG may also negatively regulate the endogenous cardioprotection pathways after ischemia.Methods and resultsWe performed a comparative study between three animal groups: normal Wistar (W), type 2 diabetic non-obese Goto-Kakizaki (GK) and normal rats submitted to MG chronic administration (3months) with gradually enhanced concentration, up to 75 mg/Kg (WMG). Hearts were submitted to different experimental conditions: control, ischemia and ischemia-reperfusion. Levels of oxidative stress markers, advanced glycation end-products (AGEs) and their receptors (RAGEs) were evaluated. The serine/threonine protein kinase Akt (Akt), crucial for cardiomyocytes recovery after ischemia, and apoptosis markers were also assessed.Levels of MG, systemic and cardiac oxidative stress markers, AGEs and RAGEs were similar in GK and WMG groups. Akt protein was negatively regulated by MG, leading to impaired apoptotic markers.ConclusionChronic MG administration to normal rodents mimicked most diabetic alterations, being associated with the development of cardiovascular disease and the impairment of survival pathways. Our results demonstrate the negative effect of MG rich diet in healthy animals and suggest the potential of methylglyoxal as a therapeutic target in diabetes.     

Fetal Wound Healing Biomarkers

Fetal skin has the intrinsic capacity for wound healing, which is not correlated with the intrauterine environment. This intrinsic ability requires biochemical signals, which start at the cellular level and lead to secretion of transforming factors and expression of receptors, and specific markers that promote wound healing without scar formation. The mechanisms and molecular pathways of wound healing still need to be elucidated to achieve a complete understanding of this remodeling system. The aim of this paper is to discuss the main biomarkers involved in fetal skin wound healing as well as their respective mechanisms of action.     

Evaluation of Schistosomiasis Mansoni Morbidity by Hepatic and Splenic Elastography

In patients with Mansoni schistosomiasis, it is fundamental to evaluate the disease morbidity, which is reflected by the severity of periportal fibrosis (PPF) and parameters of portal hypertension, as analyzed by ultrasonography (US). This study aimed to evaluate the morbidity of schistosomiasis by hepatic and splenic point shear-wave elastography (pSWE) and relate this to US parameters. The PPF pattern, the diameter of the portal and splenic veins and the size of the spleen were evaluated by US. Then, liver and spleen pSWEs were assessed in 74 patients using the same equipment. As the PPF pattern progressed, the splenic pSWE values significantly increased. Significant correlations between splenic pSWE, the longitudinal and transverse lengths of the spleen and the diameters of the portal and splenic veins were observed. These findings, however, were not observed through hepatic pSWE. In conclusion, the splenic pSWE has the potential for assessing morbidity in schistosomiasis mansoni.     

Revisiting colorectal cancer animal model – An improved metastatic model for distal rectosigmoid colon carcinoma

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model.We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1?×?10⁷ cells/animal) in RNU rats (n?=?55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, β-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (^99mTc-MIBI).Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake.With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.     

Biomechanical simulation of temporomandibular joint replacement (TMJR) devices: a scoping review of the finite element method

The aim of this study was to perform a literature review on the use of finite element modeling (FEM) for the evaluation of the biomechanical behavior of temporomandibular joint replacement (TMJR) devices. An electronic search of online medical and scientific literature database was conducted using selected search terms. The search identified 307 studies, of which 19 were considered relevant to this study. Of the 19 selected studies, 10 (52.6%) investigated the influence of geometry and fixation methods, while two (10.5%) evaluated the behavior of artificial condyle–fossa structures. The TMJR devices assessed in these studies included TMJ Inc. (aka Christensen; 63.2%), Zimmer Biomet (15.7%), Stryker (10.5%), and a theoretical intramedullary condylar component (5.3%); 26.3% of the studies evaluated custom TMJR devices. Such studies provided important data on the distribution of strain and stress through TMJR structural components and surrounding bone by using different software systems and methods. The mean stress values were lower on a custom TMJR condyle–ramus component and the supporting bone than on the stock device. FEM proved to be an accurate and valuable biomechanical simulation tool for studying the current TMJR devices and should be considered a useful tool for the improvement and development of future joint replacement devices.     

Autosomal dominant polycystic kidney disease and coronary artery dissection or aneurysm: a systematic review

Importance Autosomal dominant polycystic kidney disease (ADPKD) has been associated with cardiovascular abnormalities such as intracranial and aortic aneurysms. Objective To systematically review the case reports and case series of ADPKD patients with coronary artery dissection or aneurysm. Evidence review Systematic review registration number: CRD42015015723. Data sources: MEDLINE, Web of Science and OpenGrey, reference lists of studies. Study selection: Published case reports and case series. Data extraction: Two parties analyzed the studies. Disagreements were solved by consensus or by a third party. Funding: none. Findings The reports of 23 patients (22 from 17 studies – six with coronary artery dissection and 16 with coronary artery aneurysm – and one with coronary dissection) were analyzed and reported here. Most patients were symptomatic. Coronary dissection showed female and left descending anterior artery predominance, features similar to non-ADPKD patients, but a median diagnostic age below expected (41 vs. 50 years old). Coronary aneurysms had male and right coronary artery predominance but lower median diagnostic age (44 years old) and higher rate of multiple vessel affection than reported for non-ADPKD patients. Conclusion and relevance Clinical disparities may suggest a different mechanism of aneurysm formation compared to the population without ADPKD. Nevertheless, lack of access to data of one patient and text of one article limited our conclusions. Coronary aneurysms and dissections represent a source of coronary syndromes and death in ADPKD. Mutation of ADPKD-related genes may predispose to coronary abnormalities, especially aneurysms. Further analysis regarding this association is necessary.