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Advanced glycation end products (AGEs) are a diverse group of compounds that are formed as a result of the non-enzymatic reaction between a reducing sugar such as glucose and the free NH2 groups of an amino acid in a protein or other biomolecule. The chemical reaction, by which these products are generated, is known as the Maillard reaction and occurs as a part of the body’s normal metabolism. Such a reaction is enhanced during diabetes due to hyperglycemia, but it can also occur during the preparation, processing, and preservation of certain foods. Therefore, AGEs can also be obtained from the diet (d-AGE) and contribute to an increase of the total serum pool of these compounds. They have been implicated in a wide variety of pathological processes, mainly because of their ability to induce inflammatory responses and oxidative stress increase. They are extensively accumulated as a part of the normal aging, especially in tissues rich in long half-life proteins, which can compromise the physiology of these tissues. d-AGEs are abundant in diets rich in processed fats and sugars. This review is addressed to the current knowledge on these products and their impact on the immunomodulation of various mechanisms that may contribute to exacerbation of the diabetes pathophysiology.

Cardiovascular complications are the main cause of mortality and morbidity in the diabetic patients, in whom changes in myocardial structure and function have been described. Numerous molecular mechanisms have been proposed that could contribute to the development of a cardiac damage. In this regard, angiotensin II (Ang II), a proinflammatory peptide that constitutes the main effector of the renin-angiotensin system (RAS) has taken a relevant role. The aim of this review was to analyze the role of Ang II in the different biochemical pathways that could be involved in the development of cardiovascular damage during diabetes. We performed an exhaustive review in the main databases, using the following terms: angiotensin II, cardiovascular damage, renin angiotensin system, inflammation, and diabetes mellitus. Classically, the RAS has been defined as a complex system of enzymes, receptors, and peptides that help control the blood pressure and the fluid homeostasis. However, in recent years, this concept has undergone substantial changes. Although this system has been known for decades, recent discoveries in cellular and molecular biology, as well as cardiovascular physiology, have introduced a better understanding of its function and relationship to the development of the diabetic cardiomyopathy.

We evaluated the use of BCG and Mitomicin C instillations administered with Electromotive Drug Administration (EMDA) in patients with nonmuscle invasive bladder cancer in whom Bacillus Calmette-Guerin (BCG) therapy had failed, in order to provide bladder preservation for these patients. We evaluated the oncological outcomes and tolerability in a long follow up This treatment seems to be safe and to provide good responses in well selected patients, without a high progression rate. Background: Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed.Objectives: To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. Material and Methods: We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC + EMDA, BCG, BCG, MMC + EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. Results: Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. Conclusion: Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases. [ABSTRACT FROM AUTHOR]