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Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired glucose homeostasis, insulin resistance and hyperglycemia. Among its serious multisystemic complications is diabetic retinopathy (DR), which develops slowly and often insidiously. This disorder-the most common cause of vision loss in working-age adults-is characterized by functional and morphological changes in the retina. It results from the exacerbation of ischemic and inflammatory conditions prompted by alterations in the blood vessels, such as the development of leukostasis, thickening of the basement membrane, retinal neovascularization and fibrovascular tissue formation at the vitreoretinal interface. The pathogenic alterations are usually triggered at the biochemical level, involving a greater activity in 4 pathways: the polyol pathway, the hexosamine pathway, the formation of advanced glycation end-products and the activation of protein kinase C isoforms. When acting together, these pathways give rise to increased levels of reactive oxygen species and decreased levels of endogenous antioxidant agents, thus generating oxidative stress. All current therapies are aimed at the later stages of DR, and their application implies side effects. One possible strategy for preventing the complications of DM is to counteract the elevated superoxide production stemming from a high level of blood glucose. Accordingly, some treatments are under study for their capacity to reduce vascular leakage and avoid retinal ischemia, retinal neovascularization and macular edema. The present review summarizes the biochemical aspects of DR and the main approaches for treating it., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Arsenic, a metalloid and naturally occurring element, is one of the most abundant elements in the earth's crust. Water is contaminated by arsenic through natural sources (underground water, minerals and geothermal processes) and anthropogenic sources such as mining, industrial processes, and the production and use of pesticides. Humans are exposed to arsenic mainly by drinking contaminated water, and secondarily through inhalation and skin contact. Arsenic exposure is associated with the development of vascular disease, including stroke, ischemic heart disease and peripheral vascular disease. Also, arsenic increases the risk of tumors of bladder, lungs, kidneys and liver, according to the International Agency for Research on Cancer and the Food and Drug Administration. Once ingested, an estimated 70-90% of inorganic arsenic is absorbed by the gastrointestinal tract and widely distributed through the blood to different organs, primarily to the liver, kidneys, lungs and bladder and secondarily to muscle and nerve tissue. Arsenic accumulates in the organs, especially in the liver. Its excretion mostly takes place through urination. The toxicokinetics of arsenic depends on the duration of exposure, pathway of ingestion, physicochemical characteristics of the compound, and affected biological species. The present review outlines of arsenic toxic effects focusing on different cancer types whit highest prevalence's by exposure to this metalloid and signaling pathways of carcinogenesis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Type 2 diabetes (T2D), which causes many adverse effects such as endothelial dysfunction and cardiovascular disease, affects approximately 425 million people worldwide. However, about half have not yet been diagnosed. For what is recommended the use of screening tools to identify individuals at risk for T2D or in the early stages of the disease in order to impement preventive strategies or early treatment. According to a widely used survey, the FINDRISC scale, a hereditary family history of T2D (FH-T2D) is as important a risk factor as having had high glucose levels. The aim of the present study was to carry out non-probabilistic sampling in a Mexican population to evaluate key factors in the development of diabetes. The participants were divided into three groups: with and without FH-T2D and diagnosed with T2D. A comparison of the groups with and without FH-T2D revealed higher values in the former for body mass index (BMI: 24.5 vs 21.9 kg/m 2 ), glycosylated hemoglobin [Hb1Ac: 5.775% (39 mmol/mol) vs 4.825% (29 mmol/mol)] and triglycerides (164.18 vs 68.12 mg/dL), and a lower value for the BH 4 /BH 2 index (0.7846 vs 1.6117). These results indicate significant metabolic alterations and endothelial dysfunction for the FH-T2D group. This strongly suggests the need to screen individuals with a family history of inherited T2D based on their level of HbA1c, triglycerides and BH 4 ., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO • to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH 4 ), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion ([Formula: see text]). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress ([Formula: see text]) and endothelial function (BH4). There were significantly lower levels of [Formula: see text] and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.

The present review summarizes the methods most used in drug search and design, which may help to keep pace with the growing antibiotic resistance among pathogens. The rate of reduction in the effectiveness of many antimicrobial medications, caused by this resistance, is faster than new drug development, thereby creating a worldwide public health threat. Among the scientific community, the urgency of finding new drugs is peaking interest in the use of in silico studies to explore the interaction of compounds with target receptors. With this approach, small molecules (designed or retrieved from data bases) are tested with computer-aided molecular simulation to explore their efficacy. That is, ligand-protein complexes are constructed and evaluated via virtual screening (VS), molecular dynamics (MD), and docking simulations with the data from the physical, chemical and pharmacological properties of such molecules. Additionally, the application of quantitative structure-activity relationship (QSAR), multi-target quantitative structure-activity relationship (mt- QSAR), and multi-tasking quantitative structure-biological effect (mtk-QSBER) can be enhanced by principal component analysis and systematic workflows. These types of studies aid in selecting a group of promising molecules with high potency and selectivity as well as low toxicity, thus making in vitro and in vivo (animal model) testing more efficient. Since knowledge of the receptor topography and receptor-ligand interactions has yielded promising compounds and effective drugs, there is now no doubt that the use of in silico tools can lead to more rapid validation of new potential drugs for preclinical studies and clinical trials.

An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.