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Resumen La terapia basada en incretinas lleva al control glucemico de una manera dependiente de glucosa con un bajo riesgo de hipoglucemia, por lo que resulta atractiva para su uso hospitalario. El objetivo de esta revision sistematica fue evaluar los beneficios de la terapia basada en incretinas en pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos. Se buscaron estudios publicados hasta agosto de 2021 en las bases de datos PubMed y Scopus. Se seleccionaron los ensayos clinicos que comparaban la terapia basada en incretinas (sola o en combinacion con insulina) versus el regimen con insulina. Los resultados de los estudios incluidos mostraron que la terapia basada en incretinas registro un promedio de glucosa sanguinea, un porcentaje de registros dentro de meta terapeutica y un porcentaje de falla al tratamiento similar al manejo con insulina, particularmente en pacientes con hiperglucemia leve a moderada. Ademas, el tratamiento basado en incretinas se asocio con una menor dosis total de insulina y una menor incidencia de hipoglucemia. En conclusion, la terapia basada en incretinas logro un control glucemico similar al tratamiento con insulina en los pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos, con la ventaja de disminuir el requerimiento insulinico y con menor riesgo de hipoglucemia.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a "cytokine storm" and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.

Diabetes mellitus is a disease that is characterized by the chronic presence of blood glucose levels caused by a defect in the secretion of insulin or in the action of this hormone in the body which must be treated integrally with a multidisciplinary approach. The natural treatment of this disease is a common practice around the world, especially in Latin America, there are several clinical studies, in vivo or in vitro assays that focus on assessing the hypoglycemic capacity of various natural products used empirically by the population for years for the phytotherapeutic treatment of the disease as well as the chemicals related to the mechanism of action that produces the hypoglycaemic effect. In the present article, a brief review of the evidence of the hypoglycemic capacity of some natural products for the alternative treatment of diabetes mellitus 2

Asthma is a chronic disease whose main anatomical–functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.

AIM To examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats. METHODS Wistar rats weighing 170-200 g were divided into groups as follows: (1) Control groups; and (2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations: (1) Group of males or females with a consumption of a solution of alcohol at 40%; and (2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy. RESULTS In all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocellular disorganization CONCLUSION The results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.

Background: Exercise training induces adaptive physiological and morphological modifications in the entire organism, however, excessive loads of training may increase damage in tissues. The purpose of this study was to evaluate the effect of silymarin in lung and liver histological changes in rats subjected to exercise training (ET). Methods: Male Wistar rats were subjected to an 8-week ET treadmill program 5 days per week, 60 min/session, and were previously administered 100 mg ascorbic acid or 100 mg of silymarin. Results: Silymarin increased alveolar and bronchial muscle size, improve vascularization, and reduced tissue inflammation. In liver, silymarin promoted the reduction of lipid content. Conclusion: Silymarin supplementation may improve inflammation in pulmonary tissue after 8 weeks of the ET treadmill program, improve cell recovery, and reduce intrahepatic lipid content.

Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful nuclear transcription factor that coordinates an antioxidant cytoprotector system complex stimulated by the increase in inoxidative stress (OS). In the present manuscript, we conduct a review on the evidence that shows the effect different modalities of physical exercise exert on the antioxidant metabolic response directed by Nrf2. During physical exercise, the reactive oxygen species (ROS) are increased; therefore, if the endogenous and exogenous antioxidant defenses are unable to control the elevation of ROS, the resulting OS triggers the activation of the transcriptional factor Nrf2 to induce the antioxidant response. On a molecular basis related to physical exercise, hormesis maintenance (exercise preconditioning) and adaptative changes in training are supported by a growing body of evidence, which is important for detailing the health benefits that involve greater resistance to environmental aggressions, better tolerance to constant changes, and increasing the regenerative capacity of the cells in such a way that it may be used as a tool to support the prevention or treatment of diseases. This may have clinical implications for future investigations regarding physical exercise in terms of understanding adaptations in high-performance athletes but also as a therapeutic model in several diseases.

Diabetes mellitus is the most common chronic disease worldwide that causes numerous complications, including male infertility. The prevalence of DM is 451 million people and estimated that would increase to 693 million in 2045. Fluorosis caused by drinking water contaminated with inorganic fluoride is a public health problem in many areas around the world. Previous studies have shown that fluoride exposure damages the male reproductive function. This study aimed to evaluate the fluoride sub-chronic exposure on the spermatozoa function in streptozotocin (STZ)-induced diabetic mice. After confirming diabetes by measuring blood glucose levels, the male mice received 45.2 ppm of fluoride added or deionized water. We evaluated several parameters in diabetic mice exposed to fluoride: standard quality analysis, the mitochondrial transmembrane potential (ψm), the caspase activity in spermatozoa, urinary fluoride excretion, and histological evaluation in the testes. After 60 days of fluoride-exposure, diabetic mice, significantly decreased sperm quality (motility, viability, and concentration). Spermatozoa from fluoride-exposure in diabetic mice presented a significant decrease in ψm and a significant increase in activity caspase 3/7. Urinary fluoride excretion was decreased in diabetic mice exposed to fluoride. Subchronic fluoride exposure of mice with STZ-induced diabetes aggravated testicular damage and the spermatozoa function.

The aim of this study is to characterize bone erosions in metatarsal heads (MTH) in rheumatoid arthritis (RA) and gout by grayscale ultrasound. In a descriptive, cross-sectional study, we evaluated 40 patients with RA and 40 with gout, both diagnosed according to the American College of Rheumatology/European League Against Rheumatism criteria, respectively. All patients had bone erosion demonstrated by ultrasound, which was used, following OMERACT criteria, to describe the shape, size, number, border definition, overhanging margin, topography (intra- or extra-articular), and distribution (over dorsal, medial, lateral, or plantar aspect) of the lesions in the MTH. Descriptive statistics were used and a concordance exercise between two ultrasonographers blinded to the diagnosis was performed. Bone erosions in RA were observed most frequently at the plantar and lateral aspect of the fifth MTH, round in 96 %, small-sized (2.43 ± 0.9 mm), intra-articular (100 %), and single (75 %). Few bone erosions had a well-defined border an overhanging margin while in gout were found most frequently in the medial and dorsal aspect of the first MTH, single in 71 %, intra-articular in 100 %, and of median size (4.0 ± 2.3). For shape, 51 % was round and 49 % was oval. A well-defined border was present in 39 %, and an overhanging margin in 62 %. Inter-rater reliability kappa was excellent (0.81, 95 % CI 0.56-1.00). Some characteristics of bone erosions in RA, including shape, size, ill-defined border, and localization in the fifth MTH could distinguish the lesions from gout. Grayscale US has excellent reliability to describe bone erosions in RA and gout.

(1) Background: Regular exercise induces physiological and morphological changes in the organisms, but excessive training loads may induce damage and impair recovery or muscle growth. The purpose of the study was to evaluate the impact of Silymarin (SM) consumption on endurance capacity, muscle/cardiac histological changes, bodyweight, and food intake in rats subjected to 60 min of regular exercise training (RET) five days per week. (2) Methods: Male Wistar rats were subjected to an eight-week RET treadmill program and were previously administered SM and vitamin C. Bodyweight and food consumption were measured and registered. The maximal endurance capacity (MEC) test was performed at weeks one and eight. After the last training session, the animals were sacrificed, and samples of quadriceps/gastrocnemius and cardiac tissue were obtained and process for histological analyzes. (3) Results: SM consumption improved muscle recovery, inflammation, and damaged tissue, and promoted hypertrophy, vascularization, and muscle fiber shape/appearance. MEC increased after eight weeks of RET in all trained groups, moreover, the SM-treated group was enhanced more than the group with vitamin C. There were no significant changes in bodyweight and in food and nutrient consumption along the study. (5) Conclusion: SM supplementation may enhance physical performance, recovery, and muscle hypertrophy during the eight-week RET program.

Background: The need to advance and achieve success is deeply ingrained in human evolution. As a species, humans developed instincts that allowed them to survive and transmit their genes along generations. The will to win is an instinct that has been maintained in the species for millions of years. Sport is an activity as old as humans themselves and is subject to rules; Objective: The proposal of this work is to explore some of the most recurrent practices to achieve the athletes’ goals, and the origins and historical use of methods or substances to improve performance and its regulation, as well as to review the impact of new technologies on achieving better results and to make a proposal of what actions should be takenin order to prevent bad practices; Methods: A narrative literature review of ethical sports issues and decision-making was performed in the English language; Results: Practically all behavior with regards to the theme of sports is regulated by ethical codes that must be followed by sportspersons, as well as by everyone involved in the athlete’s healthcare and in the athlete’s administrative, marketing, and business aspects. Notwithstanding this, winning and reaping glory implies a reward far greater than fame and fortune, which can lead to poor ethical practices in athletes, as well as in interested parties who detract from the intrinsic value of the spirit of sports. The will to win could exceed the limits of what is permitted in fair-play, like the use of prohibited methods or substances; Conclusions: In this work, we review some of the bioethical aspects ofsports. Additionally, recommendations are offered for good practices and to prevent falling into poor ethical behavior.

Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with daily chemical administration. In the first, we administered the antidepressant once to groups of 5 mice by the intragastric (i.g.) route (2, 20, and 200 mg/kg) and performed the analysis at 24, 48, and 72 h postadministration. A control group administered i.g. distilled water was included in the assay, as well as another treated with the micronuclei-inducing chemical daunorubicin (2.5 mg/kg, injected intraperitoneally (i.p.)). In this assay, we found significant damage induced by duloxetine starting from the first time evaluated, showing the highest MNPE increase at the end of the assay. We observed a saturation effect as well, suggested by a decreasing relative efficiency with respect to each tested dose. In a second assay, we administered the antidepressant i.g. every day for 5 weeks (2, 6, and 12 mg/kg), and micronuclei analysis was performed at the end of each week. In this study, we also found a significant increase in both MNPEs and MNNEs which was clear by the second week of administration. Our results suggest that short-term as well as cumulative damage is produced by duloxetine. Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.

Duloxetine is an antidepressant which has showed valuable results, particularly in patients with major depression. This type of drugs is known to require genotoxic studies as part of their preclinical safety evaluation. In the case of duloxetine, however, there have been controversial results. Therefore, we considered it worthwhile to extend studies on the matter in an attempt to reach a conclusion. The present assay was made in mouse bone marrow to evaluate the capacity of the drug to induce sister chromatid exchanges (SCE), as well as to modify the proliferation kinetics and the mitotic index. Three doses of the antidepressant were tested (2, 20, and 200 mg/kg), besides the control mice were administered with purified water, and the positive treated animals administered with 1 mg/kg of doxorubicin. The results indicated a moderate but significant increase of SCE with the three tested doses, no effect regarding the mitotic index and a small reduction in the proliferation kinetics. Although in our assay the drug showed a lower effect, the present study agreed with a previous report that analyzed the amount of micronuclei in mouse peripheral blood, and it confirmed the relevance of evaluating the genotoxic effect of antidepressants, specifically duloxetine by applying diverse tests.

Background Autonomic dysfunction, smooth muscle fibrosis and vascular damage lead to small intestinal bacterial overgrowth (SIBO) in Systemic Sclerosis (SSc). SIBO is characterized by diarrhea, abdominal pain, bloating, malabsorption and malnutrition. Objectives To evaluate by NIH PROMIS® gastrointestinal symptoms scales and SIBO by hydrogen breath test (HBT) in patients with SSc. Methods We include 68 patients with SSc (ACR-EULAR 2015) who signed informed consent. NIH PROMIS®questionarie was applied to evaluated gastrointestinal symptoms and classified in not symptomatic, least, mildy, moderately and most symptomatic. Glucose HBT was applied after 14 hours fast, oral hygiene and 30 days free of antibiotics. Patients who has a negative HBT with symptoms associated to glucose ingestion we repeat test with lactulose. Results We applied questionnaire to 58 SSc patients, age 52 (26–75)years, 65 (96%) female and 3 (4%) males, disease duration 13 (1–40) years, limited SSc 41 (59%) and diffuse 27 (41%), body mass index 24 (12–39). They are using prednisone (28%), micofenolate (14%), methotrexate (19%), azatioprin (5%), amlodipine or nifedipine (33%). Patients had continuous and very high increase of parts per millon (ppm) of exhaled Hydrogen: min0: 13 ppm (5–21), min15:17 ppm (5–43), min30:17 (3–49), min45:18ppm (7–103), min 60:22ppm (8–145), min90:18ppm (2–250), min120:25ppm (3–212), min150:71ppm (3–235). Normal values: Frequency of gastrointestinal symptoms were flatulence (87.5vs81.2%), nausea/vomiting (72.7vs37.6%), constipation (65.6vs40%), diarrhea (45.2vs33.4%), abdominal pain %) and incontinence (39.4vs31.3%) respectively between SCB (+) positive and negative. Hyperproduction of hydrogen in breath had a direct correlation to severity of their symptoms (p≤0.05). The severity of diarrhea was in close relation to the severity of its rectal incontinence (r=0.73,p=0.001), and greater abdominal pain with flatulence (r=72, p=0.001). Conclusions Gastrointestinal symptoms are common in SSc regardless of whether they have SIBO. However, a higher Row Score SGI or moderate severe status (NIH PROMIS) correlates with high H scores from the 30th minute, therefore, the questionnaire is useful within the SSc assessment. Disclosure of Interest None declared

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Depression is a common disease that may cause severe damage to human health. Imipramine (IMI) and desipramine (DES) are medicaments used for treatment, yet studies on their genotoxic potential have given controversial results. Therefore, we designed the present assay to determine their effect as inducers of micronucleated polychromatic erythrocytes (MNPE) and micronucleated normochromatic erythrocytes (MNNE) in mice. The study was carried out in animals administered daily with the compounds for 4 weeks, and the determination of micronuclei was done each week. We also evaluated the bone marrow cytotoxicity induced by the chemicals. Besides, the same determinations were carried out in the following 4 consecutive weeks, but in this period the animals were not treated with the tested compounds. Our results showed a significant increase in both MNPE and MNNE induced by both compounds from the first week of administration. At the fourth week, IMI increased three times the control level, while the effect of DES was about seven times such level. In the second, 4-week phase, we observed a reduction in the rate of micronuclei approaching the control level. We also detected a bone marrow-mitotic division decrease by the evaluated chemicals. Our results point to the need for cautiousness in the clinical use of the compounds as well as for testing the effect in patients under treatment.

Infection with Helicobacter pylori has been shown to be at the origin of various gastric pathologies. However, it has not yet been established whether the etiology of such diseases, particularly of gastric cancer, is related to the production of free radicals or to mutagenesis. The aim of this study was to determine whether a six-month infection with Helicobacter pylori increased the amount of lipid peroxidation, nitric oxide, and DNA damage in Mongolian gerbils (Meriones unguiculatus). H. pylori was characterized genotypically and administered orally to the animals. Four tests were applied to identify the presence of bacteria at one, two, four, and six months after the inoculation, namely, isolation and identification in culture, the urease test, the ELISA assay, and immunohistochemical staining of gastric biopsies. The infection was considered to be successful when three of the above-mentioned tests were positive. The infection occurred in 30% of the animals in the first month after the H. pylori inoculation and in 60-70% of the animals in the later stages. Levels of malondialdehyde, nitric oxide, and DNA damage (using the "comet" assay) were determined in the gastric tissue of the animals at one, two, four, and six months. We found statistically significant increases in malondialdehyde and nitric oxide levels from the second month on. The comet assay in animals infected with H. pylori showed a significant increase in the mean tail length throughout the observation period. We conclude that our results support the assumption that oxidative damage and DNA breakage produced by the infection with H. pylori are some of the initial alterations occurring in the development of gastric diseases.

The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum, Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum, which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.