Fine Particulate Matter (PM2.5) Air Pollution and Type 2 Diabetes Mellitus (T2DM): When Experimental Data Explains Epidemiological Facts

Epidemiologic and experimental studies suggest that environmental exposures to air pollutants can increase prevalence of metabolic and cardiorespiratory diseases. Among the risk factors, many studies have shown that air pollution, especially by fine particulate matter (PM2.5), can lead to the development of type 2 diabetes mellitus (T2DM) or make diabetics more susceptible to other health complications. This chapter aimed to discuss the pathophysiologic mechanisms evolved in susceptibility to cardiorespiratory PM2.5 effects in T2DM subjects, as well as the enhancing effect of PM2.5 exposure on development of T2DM. We discussed the pathophysiologic mechanisms of PM2.5 exposure and T2DM based on pro−/anti-inflammatory balance, metabolic regulation, redox status, and heat shock response, reinforcing the complex nature of T2DM etiology and highlighting the PM2.5 air pollution as a critical health problem

Lifestyle and Aging Effects in the Development of Insulin Resistance — Activating the Muscle as Strategy Against Insulin Resistance by Modulating Cytokines and HSP70

This chapter discusses about subclinical processes related to insulin resistance development that worsen the muscle metabolic functions, generated by factors such as lifestyle (bad quality food intake and sedentary behavior) and aging. Also discussed are the effects of regular physical exercise as a strategy to prevent the metabolic impairment in organisms, approaching since muscle subclinical molecular processes to the whole body’s integrative physiology. Insulin resistance development includes modification in the pattern of inflammatory cytokines, heat shock proteins, tissue- specific defects in insulin action and signaling, oxidative stress and ectopic lipid deposition. The exercise is a known modulator of all parameters listed above and has important role in the regulation of “immune-metabolic” homeostasis from the muscle to the whole body. This chapter aims to present a new molecular approach related to the control of metabolism and encourage scientists and students to propose new strategies against insulin resistance and diabetes type 2 developments

Environmental Particulate Air Pollution Exposure and the Oxidative Stress Responses: A Brief Review of the Impact on the Organism and Animal Models of Research

Particulate matter (PM) is a mixture of solid particles and liquid droplets found in the air, and it is one of the most harmful air pollutants. When inhaled, it affects the pulmonary system, cardiovascular systems, and other tissues. The size, composition, and deposition of PM, mainly related to fine and ultrafine particulate matter, are factors that determine the harmful effects of exposure to particles. Among the main effects is the inducer of ROS production, and consequently oxidative tissue damage in target organs and other responses, mediated by inflammatory cytokines and cellular stress response. The main pathway through which particles are potent mediators of oxidative stress is the damage caused to DNA and lipid molecules, whereas the pro-inflammatory response involves an immune response against PM, which in turn, it is related to cell stress responses observed by heat shock proteins (HSPs) expression and release. Thus, the ability of an organism to respond to PM inhalation requires anti-oxidative, anti-inflammatory, and cellular stress defenses that can be impaired in susceptible subjects as people with chronic diseases as diabetes and obesity. In this chapter, we discuss the mechanistic aspects of PM effects on health and present some animal research models in particle inhalation studies

Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients : lessons from basic research (inclusive bats), light on conceivable therapies

The major risk factors to fatal outcome in COVID-19 patients, i.e., elderliness and pre-existing metabolic and cardiovascular diseases (CVD), share in common the characteristic of being chronic degenerative diseases of inflammatory nature associated with defective heat shock response (HSR). The molecular components of the HSR, the principal metabolic pathway leading to the physiological resolution of inflammation, is an anti-inflammatory biochemical pathway that involves molecular chaperones of the heat shock protein (HSP) family during homeostasis-threatening stressful situations (e.g., thermal, oxidative and metabolic stresses). The entry of SARS coronaviruses in target cells, on the other hand, aggravates the already-jeopardized HSR of this specific group of patients. In addition, cellular counterattack against virus involves interferon (IFN)-mediated inflammatory responses. Therefore, individuals with impaired HSR cannot resolve virus-induced inflammatory burst physiologically, being susceptible to exacerbated forms of inflammation, which leads to a fatal “cytokine storm”. Interestingly, some species of bats that are natural reservoirs of zoonotic viruses, including SARS-CoV-2, possess an IFN-based antiviral inflammatory response perpetually activated but do not show any sign of disease or cytokine storm. This is possible because bats present a constitutive HSR that is by far (hundreds of times) more intense and rapid than that of human, being associated with a high core temperature. Similarly in humans, fever is a physiological inducer of HSR while antipyretics, which block the initial phase of inflammation, impair the resolution phase of inflammation through the HSR. These findings offer a rationale for the reevaluation of patient care and fever reduction in SARS, including COVID-19

Diet and Inflammation: Effects of Macronutrients and Dietary Patterns

Cardiovascular disease (CVD) has already been demonstrated to be related to a chronic and complex inflammatory process, in which the loss of endothelial protective properties - the so-called endothelial dysfunction - plays a central role. A number of different approaches, both pharmacological and non-pharmacological, have been tested with inconclusive results so far. One field of special interest is the impact of the different macronutrients and dietary patterns in the inflammatory response that, ultimately, leads to endothelial dysfunction and increased cardio-metabolic risk. Although apparently simple, interventions regarding dietary habits have complex implications and involve a number of covariates that may interfere in the final results. To date, results about the protective effects of diet - in general - regarding cardio-metabolic risk remain to be fully proven

Effects of Physical Activity on The Inflammatory Process Related to Insulin Resistance and Obesity

Atherosclerosis, the pathophysiological substrate for cardiovascular disease (CVD), is the final stage of an inflammatory cascade. During the process, endothelial dysfunction ensues and the inflammatory state is perpetuated. A number of traditional risk factors, as obesity and insulin resistance/type 2 diabetes, are characterized by a proinflammatory state as well, with increased levels of cytokines, interleukins, vasoactive peptides and enhanced expression of specific cellular receptors. The anti-inflammatory properties of physical exercise and its positive effects as a strategy for obesity and insulin resistance have already been shown in terms of cardiovascular protection and survival

Efeitos do tratamento com glutamina via enteral em modelo animal de sepse

The aim of study was to evaluate the effects of enteral glutamine treatment on clinical parameters in an animal model of sepsis. Were used 24 mice (B6129SF2/J) in two experiments: First 11 mice were divided into three groups to evaluate the animal model better to simulate the sepsis. Animals received saline (control) or faecal solution 10 or 20% (i.p), and were evaluated glycaemia and rectal temperature for 24h. Second 13 mice were divided into: Control, Sepsis, Glutamine and Sepsis+Glutamine. Glutamine was administered by gavage (1 g/kg) each 4h for 47h. Glycaemia, rectal temperature, leukocyte count and body weight was evaluated. Results: The administration of 20% faecal solution induced hypodynamic phase of sepsis with hypothermia, hypoglycaemia and low leukocyte count. The treatment with glutamine avoids the decrease in leukocyte. Conclusion: Since the immune response is essential in sepsis, the use of glutamine can be useful as adjuvant therapy in sepsis. Objetivo: Avaliar o tratamento enteral com L-glutamina nos parâmetros clínicos em modelo experimental de sepse. Métodos: Foram utilizados 24 camundongos B6129SF2/J: Primeiramente, 11 camundongos foram divididos em três grupos para avaliar o modelo experimental que mimetize a fase hipodinâmica na sepse. Os animais receberam solução fisiológica ou solução fecal a 10% ou 20% (i.p.), sendo avaliados glicemia e temperatura corporal em 24h. Avaliamos o efeito do tratamento de L-glutamina por 48h na glicemia, temperatura retal, contagem de leucócitos e peso corporal em 13 animais nos grupos: Controle, Sepse, Glutamina e Sepse+Glutamina. Resultados: A solução fecal 20% induziu a sepse, evidenciando hipotermia, hipoglicemia e leucopenia. O tratamento com L-glutamina evitou a leucopenia. Conclusão: O tratamento com L-glutamina previne a leucopenia no modelo experimental de sepse, sem melhorar outros parâmetros clínicos. Sendo a resposta imune essencial na sepse, o uso de glutamina pode ser útil como terapia adjuvante na sepse.

COVID-19: From Pathophysiology to Treatment

The new coronavirus first appeared in December 2019 in Wuhan, China, being officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (ICTV), as well as the name of the disease has been described as COVID-19 (coronavirus disease 2019). In March 2020, the disease was considered a global pandemic, with currently more than 514 million cases worldwide, with 6.4 million deaths. Severe cases of COVID-19 progress to acute respiratory distress syndrome (ARDS), on average about 8–9 days after the onset of symptoms. It is also worth mentioning that the severity of the disease in patients is not only due to the viral infection but also due to the host response. This phase, called a cytokine storm, reflects a state of systemic immune activation, with high levels of cytokines, such as IL-6, IL-1b, IL-2, IL-12, IL-18, TNF, and interferon gamma (IFN-γ). In this sense, the management of the disease largely depends on symptomatic and supportive treatments. For severely or critically ill patients with acute respiratory distress syndrome (ARDS) and sepsis, in addition to supplemental oxygen, mechanical ventilation, and ARDS-specific therapies, antiviral and antibiotic treatments should also be considered. Thus, the purpose of this chapter is to describe the pathophysiology and treatment of SARS-CoV-2 infection

L-GLUTAMINE SUPPLEMENTATION ASSOCIATED WITH MODERATE AEROBIC TRAINING IMPROVES BIOMETRIC, GLYCEMIC PROFILE AND THE ANTIOXIDANT DEFENSE

Introduction: L-glutamine is a non-essential amino acid, whose intrinsic pool of appears to be depleted during catabolic conditions, such as intense or high duration exercise, and to avoid the exercise- related benefits. Therefore, its supplementation could provide an additional source of L-glutamine and prevent these effects. However, the oral intake of its free form has been discouraged, despites of some evidences reporting positive effects. Objective: to verify whether the L-glutamine supplementation (in its free form) could provide an additional improvement in biometric, glycemic and redox parameters, in animals undergoing moderate aerobic training (MAT). Methods: 28 Swiss male mice were divided into four groups: Cont (n=7), Ex (n=7), Glut (n=8), and Ex+Glut (n=6). Glut and Ex+Glut received gastric gavage of L-glutamine (1g/kg), while Cont and Ex groups received 100 µL of PBS one hour before exercising, five days/week, six weeks. Ex and Ex+Glut underwent moderate swimming, while Cont and Glut remained sedentary, for the same period. Mice started swimming with 2% of body weight attached to the tail during 20 min, and ended the experiment with 4% during 60 min. Results: L-glutamine supplementation increased the gastrocnemius mass and improved the glucose tolerance in animals submitted to MAT. It improved the antioxidant status in gastrocnemius, liver and pancreas, and declined it in adipose tissue in animals undergoing MAT. The drop of adipose antioxidant defense was associated with adiposity, while pancreas antioxidant activity was inversely associated with the glucose intolerance. Conclusion: L-glutamine (free form) improves biometric and glucose parameters, and enhances antioxidant activities