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Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have proven to delay diabetic kidney disease (DKD) progression on top of the standard of care with the renin-angiotensin system (RAS) blockade. The molecular mechanisms underlying the synergistic effect of SGLT2i and RAS blockers is poorly understood. We gave a SGLT2i (empagliflozin), an angiotensin-converting enzyme inhibitor (ramipril), or a combination of both drugs for 8 weeks to diabetic (db/db) mice. Vehicle-treated db/db and db/m mice were used as controls. At the end of the experiment, mice were killed, and the kidneys were saved to perform a differential high-throughput proteomic analysis by mass spectrometry using isobaric tandem mass tags (TMT labeling) that allow relative quantification of the identified proteins. The differential proteomic analysis revealed 203 proteins differentially expressed in one or more experimental groups (false discovery rate < 0.05 and Log2 fold change ≥ ±1). Fourteen were differentially expressed in the kidneys from the db/db mice treated with empagliflozin with ramipril. Among them, MAP17 was up-regulated. These findings were subsequently validated by Western blot. The combined therapy of empagliflozin and ramipril up-regulated MAP17 in the kidney of a diabetic mice model. MAP17 is a major scaffolding protein of the proximal tubular cells that places transporters together, namely SGLT2 and NHE3. Our results suggest that SGLT2i on top of RAS blockade may protect the kidney by boosting the inactivation of NHE3 via the up-regulation of key scaffolder proteins such as MAP17., (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Objective: To develop a tool that measures levels of adherence to antiretroviral treatment (ART) in resource-poor settings, based on a combination of four methods for measuring adherence., Methods: Retrospective review of 500 medical records of people living with HIV, randomly selected from October 2017 to January 2020. Adherence to ART was measured by combining four measurement methods (coverage of prescribed ART, ART picked up at pharmacies, viral load, and self-reported adherence). Chi-squared tests were performed with p<0.05 for statistically significant differences and logistic binary regression to identify the probability of optimal and suboptimal adherence. Spearman tests were performed for correlation of categories, and Cronbach's alpha was used to measure the internal consistency of the tool., Results: We obtained 497 adherence scores. Of these, 307 (61.8%) users qualified as adherent, 141 (28.4%) as semi-adherent, and 49 (9.8%) as non-adherent. A higher probability of optimal adherence was found in groups aged 60 years and older (odds ratio [OR]: 1.6; CI95%: 0.8-3.5), with no difference between men and women (OR: 0.9; CI95%: 0.7-1.4). Spearman's test reported a relationship (r = 0.8) between viral load levels and final score, and Cronbach's alpha yielded modest internal consistency (α = 0.7)., Conclusions: A tool was developed to measure adherence to ART in a resource-poor environment. The tool shows modest levels of internal consistency and a strong correlation between viral load and adherence.

Treatments with sodium-glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin-angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagliflozin alone or combined significantly decreased blood glucose compared to vehicle-treated db/db. The dual and triple therapies achieved significantly greater reductions in diastolic blood pressure than ramipril alone. Compared to vehicle-treated db/db, empagliflozin combined with ramipril or in triple therapy significantly prevented GFR increase, but only the triple combination exerted greater protection against podocyte loss. In the heart, empagliflozin alone or combined reduced cardiac isovolumetric relaxation time (IVRT) and left atrium (LA) diameter as compared to vehicle-treated db/db. However, only the triple therapy was able to reduce cardiomyocyte area. Importantly, the add-on triple therapy further enhanced the intrarenal ACE2/Ang(1-7)/Mas protective arm of the RAS. These data suggest that triple therapy with empagliflozin, atrasentan and ramipril show synergistic cardiorenal protective effects in a type 2 diabetic mouse model.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19). The main organ affected in this infection is the lung and the virus uses the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the target cells. In this context, a controversy raised regarding the use of renin-angiotensin system (RAAS) blockers, as these drugs might increase ACE2 expression in some tissues and potentially increase the risk for SARS-CoV-2 infection. This is specially concerning in diabetic patients as diabetes is a risk factor for COVID-19., Methods: 12-week old diabetic mice (db/db) were treated with ramipril, or vehicle control for 8 weeks. Non-diabetic db/m mice were included as controls. ACE2 expression and activity were studied in lung, kidney and heart of these animals., Results: Kidney ACE2 activity was increased in the db/db mice as compared to the db/m (143.2% ± 23% vs 100% ± 22.3%, p = 0.004), whereas ramipril had no significant effect. In the lung, no differences were found in ACE2 when comparing db/db mice to db/m and ramipril also had no significant effect. In the heart, diabetes decreased ACE2 activity (83% ± 16.8%, vs 100% ± 23.1% p = 0.02), and ramipril increased ACE2 significantly (83% ± 16.8% vs 98.2% ± 15%, p = 0.04)., Conclusions: In a mouse model of type 2 diabetes, ramipril had no significant effect on ACE2 activity in either kidneys or in the lungs. Therefore, it is unlikely that RAAS blockers or at least angiotensin-converting enzyme inhibitors increase the risk of SARS-CoV-2 infection through increasing ACE2., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Pigmented lesions on acral sites are common; clinical differentiation of nevi and early melanoma can be challenging. In these cases, dermoscopy can provide a more accurate diagnosis. Most dermoscopic patterns on acral skin have been described in Asian and European populations, while there are few studies in Latin American populations, Objectives: To determine the frequency of pigmented lesions in volar skin and their dermoscopic patterns in a Mexican population. Methods: An observational, descriptive, cross-sectional study was performed in Hispanic patients with the presence of at least one pigmented lesion on acral skin. Clinical and dermoscopic images were obtained. These were subsequently evaluated independently by two dermatologists trained and experienced in dermoscopy, Results: A total of 582 pigmented lesions on volar skin were diagnosed in 321 patients. Overall, prevalence of acral pigmented lesions on volar skin was 6.8%. For both observers, parallel furrows were the most frequent pattern described, but for observer 2, a lattice-like pattern was prevalent on the toes and a homogeneous pattern on the sides of the feet. There was lower inter-observer agreement, with a kappa index of 0.144, Study Limitations: The lesions were not biopsied, so clinical-histological correlation could not be performed. The study did not correlate dermoscopic patterns with age, Conclusions: As previously reported by other authors, parallel furrows were the most frequently found dermoscopic pattern on palmoplantar skin