Insulin infusion sets associated with adverse events: strategies for improved diabetes education.

Introduction: Insulin Infusion Sets (IIS) play a crucial role in ensuring the safe delivery of insulin through a Continuous Subcutaneous Insulin Infusion (CSII) for individuals with Type 1 Diabetes (T1D). Recent advancements in therapy have highlighted the need to address issues such as unexplained hyperglycemia and IIS occlusion. Objective: To investigate the adverse events (AEs) associated with IIS that impact the treatment of T1D, with a specific focus on promoting effective educational practices. Methods: One hundred and eighteen patients under treatment at the Diabetes Center Insulin Pump Ambulatory, Federal University of São Paulo responded to a semi-structured questionnaire. Over 6 months, a nurse researcher interviewed them via video calls. Results: Catheter-related adverse events (AEs) included catheter knots, folding, and accidental traction. AEs associated with cannula use were mainly related to cannula fixation adhesive, insulin leakage, bleeding episodes, and skin problems. The cannula patch tends to detach easily in hot conditions or when used for more than 3 days, leading to local itching. Adhesive glue can cause redness and pain. Insulin leakage typically occurs after the catheter disconnects from the cannula, accidental cannula traction, or beneath the cannula patch. Bleeding has been reported inside the cannula or at the insertion site, resulting in local pain and, in some cases, obstruction of insulin flow. When accidental cannula traction occurs, it is recommended to replace the entire IIS system. In situations involving bleeding, leakage, insulin odor, or unsuccessful attempts to correct hyperglycemic episodes with a "bolus" of insulin, it is advisable to change the IIS system and evaluate appropriate techniques for handling and infusing the device. Moreover, regular inspections of the device and reservoir/cartridge are essential. Conclusion: Serious AEs can occur even in cases where the occlusion alarm is not activated, leading to interruptions in insulin flow. Conversely, in less severe situations, alarm activation can occur even in the absence of insulin flow interruption. Accidental catheter traction and catheter bending are commonly encountered in everyday situations, while issues related to the cannula directly affect blood glucose levels. AEs related to the IIS cannula often involve insulin leakage into the skin, bleeding, and skin events attributed to adhesive issues with the cannula.

Automatic Classification of Emotions Based on Cardiac Signals: A Systematic Literature Review.

Emotions play a pivotal role in human cognition, exerting influence across diverse domains of individuals' lives. The widespread adoption of artificial intelligence and machine learning has spurred interest in systems capable of automatically recognizing and classifying emotions and affective states. However, the accurate identification of human emotions remains a formidable challenge, as they are influenced by various factors and accompanied by physiological changes. Numerous solutions have emerged to enable emotion recognition, leveraging the characterization of biological signals, including the utilization of cardiac signals acquired from low-cost and wearable sensors. The objective of this work was to comprehensively investigate the current trends in the field by conducting a Systematic Literature Review (SLR) that focuses specifically on the detection, recognition, and classification of emotions based on cardiac signals, to gain insights into the prevailing techniques employed for signal acquisition, the extracted features, the elicitation process, and the classification methods employed in these studies. A SLR was conducted using four research databases, and articles were assessed concerning the proposed research questions. Twenty seven articles met the selection criteria and were assessed for the feasibility of using cardiac signals, acquired from low-cost and wearable devices, for emotion recognition. Several emotional elicitation methods were found in the literature, including the algorithms applied for automatic classification, as well as the key challenges associated with emotion recognition relying solely on cardiac signals. This study extends the current body of knowledge and enables future research by providing insights into suitable techniques for designing automatic emotion recognition applications. It emphasizes the importance of utilizing low-cost, wearable, and unobtrusive devices to acquire cardiac signals for accurate and accessible emotion recognition.

Advances in Non-Invasive Neuromodulation: Designing Closed-Loop Devices for Respiratory-Controlled Transcutaneous Vagus Nerve Stimulation.

Studies suggest non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a potential therapeutic option for various pathological conditions, such as epilepsy and depression. Exhalation-controlled taVNS, which synchronizes stimulation with internal body rhythms, holds promise for enhanced neuromodulation, but there is no closed-loop system in the literature capable of performing such integration in real time. In this context, the objective was to develop real-time signal processing techniques and an integrated closed-loop device with sensors to acquire physiological data. After a conditioning stage, the signal is processed and delivers synchronized electrical stimulation during the patient's expiratory phase. Additional modules were designed for processing, software-controlled selectors, remote and autonomous operation, improved analysis, and graphical visualization. The signal processing method effectively extracted respiratory cycles and successfully attenuated signal noise. Heart rate variability was assessed in real time, using linear statistical evaluation. The prototype feedback stimulator device was physically constructed. Respiratory peak detection achieved an accuracy of 90%, and the real-time processing resulted in a small delay of up to 150 ms in the detection of the expiratory phase. Thus, preliminary results show promising accuracy, indicating the need for additional tests to optimize real-time processing and the application of the prototype in clinical studies.

The Relationship Between Different Bench Test Methodologies and Accuracy of Insulin Infusion Pumps: A Systematic Literature Review.

Diabetes technology has rapidly evolved, and insulin infusion pumps (IIPs) have gained worldwide acceptance in diabetes care. The safety of medical equipment is highly discussed, imposing complex challenges in its use. The accuracy of IIPs can be determined through laboratory tests, generally following the IEC 60601-2-24 protocol. Studies have evaluated the accuracy and precision of IIPs, and there are discrepant results. So, we conducted a Systematic Literature Review to assess the methodologies used to evaluate the accuracy of IIPs, organizing the findings in a compiled perspective. The methodology was based on Kitchenham and Biolchini guidelines, and when possible it was carried out the Bayesian meta-analyses to compare the accuracy of IIPs. Most studies used the microgravimetric technique to evaluate the device accuracy, and some proposed adaptations for the standard protocol. The variation of results was recurrent, and the establishment of a protocol, especially to evaluate patch pumps, is necessary. The present study gives enough data to understand the scenario of the IIPs evaluation, as well as the different protocols that can be explored for its evaluation. This highlights the need for a reliable, practical, and low-cost methodology to assist the evaluation of IIPs.

Stress-induced cardiometabolic perturbations, increased oxidative stress and ACE/ACE2 imbalance are improved by endurance training in rats.

AIMS: To investigate the effects of endurance training on stress-induced cardiometabolic perturbations given the elevated release of stress hormones and subsequent glucose homeostasis perturbations. MATERIALS AND METHODS: Rats were randomized into non-trained rats, rats submitted to endurance training, non-trained rats submitted to stress, and trained rats submitted to stress. Endurance training was applied for 8 weeks, while chronic stress was applied at the 4th, 5th, and 6th weeks of the training period. Two weeks after the last stressor stimuli, rats were euthanized, and blood and heart were collected for biochemical tests. KEY FINDINGS: Exacerbated corticosterone levels were observed in both stressed groups, and chronic stress per se impaired glucose tolerance and insulin sensitivity. Training reduced circulating adrenaline, even though noradrenaline levels were elevated in the blood and heart of trained rats. While stress-induced high circulating serotonin levels were further increased by endurance training, cardiac serotonin levels were attenuated in trained rats. Endurance training mitigated the stress-induced higher circulating lipids. Cardiac TBARs and GPx activity increased in trained rats while CAT and GPx were reduced in response to chronic stress. Endurance training not only attenuated the stress-induced higher circulating ACE/ACE2 ratio but also reduced ACE/ACE2 balance in the heart. Glucose intolerance, insulin resistance, and altered stress hormones release were linked to impairment of cardiometabolic responses, elevated oxidative stress, and dysregulation of ACE/ACE2 ratio. SIGNIFICANCE: Endurance training mitigated the stress-related pathophysiological responses, which could be related to improvements in the antioxidant capacity and the balance of ACE/ACE2 activity.

Insulin Pump-Associated Adverse Events in a Brazilian Reference Center for the Treatment of Diabetes Mellitus: Proposal for a Taxonomy of Device Failures in Adults, Adolescents, and Children.

BACKGROUND: Since the introduction of continuous subcutaneous insulin infusion (CSII), the benefits have been numerous. However, adverse events (AEs) are experienced by up to 40% of users per year, exposing them to potentially fatal risks. The available evidence on the variables that trigger AEs associated with CSII remains limited, indicating the importance of studies on the subject. AIM: To propose a taxonomy based on the prevalent AEs experienced by patients from a reference diabetes mellitus (DM) center in Brazil using different CSII devices. METHODS: 118 patients participated in an online interview and answered the questions of the data collection instrument. Identifying categories and subcategories of analysis contributed to constructing the AEs taxonomy. RESULTS: The five analysis categories identified were: CSII User Interface (n = 45), CSII Alert System (n = 13), CSII Software and Connection (n = 11), CSII Durability (n = 30), and Electrical and Mechanical System of CSII (n = 60) A total of 159 AEs were identified, including conflicting alert messages and error/warning notification failures, errors resulting from engine malfunctions, data loss, patient interface deficiencies, button problems, and battery failure. CONCLUSIONS: The study describes in a taxonomic format the AEs directly associated with the use of modern CSIIs that may contribute with additional information to the Food and Drug Administration (FDA) Medical Device Report (MDR) adverse event codes. In addition to guiding educational actions in the treatment of DM and providing information for health professionals and medical device developers, prospective studies examining the frequency of such problems, including the potential psychosocial impact of this technologically advanced therapy, are needed.

Saccharomyces boulardii exerts renoprotection by modulating oxidative stress, renin angiotensin system and uropathogenic microbiota in a murine model of diabetes.

AIMS: We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice. MAIN METHODS: Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed. KEY FINDINGS: Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers. SIGNIFICANCE: Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes.

Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes / A produção de catecolaminas pelo tecido renal e a cultura de células mesangiais é modulada diferencialmente pelo diabetes

Abstract Introduction: According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro. Methods: Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture. Results: diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group. Conclusion: The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

Resumo Introdução: Segundo a Federação Internacional de Diabetes, o número de pessoas com diabetes mellitus pode chegar a 700 milhões em 2045. As catecolaminas estão envolvidas na regulação de várias funções renais. Este estudo investiga os efeitos da hiperglicemia no metabolismo das catecolaminas no tecido renal de ratos controle, diabéticos e diabéticos tratados com insulina, tanto in vivo como in vitro. Métodos: Os ratos Wistar-Hannover machos foram randomizados em: grupos controle, diabéticos e diabéticos tratados com insulina. O diabetes foi induzido por uma única injeção de estreptozotocina, e o grupo diabético tratado também recebeu insulina. Após 60 dias, sangue e tecido renal dos grupos foram coletados para quantificação de catecolaminas e cultura de células mesangiais. Resultados: ratos diabéticos apresentaram peso corporal mais baixo, hiperglicemia, e aumento da ingestão de água e diurese. Ademais, o diabetes promoveu uma redução acentuada na depuração de creatinina comparado com o grupo controle. Quanto aos extratos de rim total, ambos os grupos diabéticos (tratados/não tratados) tiveram redução significativa na concentração de noradrenalina. Na cultura de células mesangiais, a concentração de catecolaminas foi menor no meio de cultura do que no compartimento intracelular para todos os grupos. Níveis médios de noradrenalina, adrenalina e dopamina estavam aumentados no grupo diabético. Conclusão: O principal achado deste estudo foi que 8 semanas de indução de diabetes alteraram o sistema catecolaminérgico renal de maneira muito específica, já que a produção de catecolaminas no tecido renal excisado de ratos diabéticos foi modulada diferencialmente comparada com produção e secreção por células mesangiais cultivadas.

Resistance exercise shifts the balance of renin-angiotensin system toward ACE2/Ang 1-7 axis and reduces inflammation in the kidney of diabetic rats.

AIMS: We aimed to determine whether resistance training (RT) regulates renal renin-angiotensin system (RAS) components and inflammatory mediators in diabetic rats. MAIN METHODS: Male Wistar rats (3 months old) were randomly assigned into four groups: non-trained (NT), trained (T), non-trained + diabetes (NTD) and trained +diabetes (TD). Diabetes was induced by streptozotocin (50 mg/kg, Sigma Chemical Co., St. Louis, MO, USA), before RT protocol. Trained rats performed RT protocol on a 110-cm ladder (8 ladder climbs, once/day, 5 days/week, 8 weeks), carrying a load corresponding to 50-80% of maximum carrying capacity. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7), inflammatory markers, and also the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined. KEY FINDINGS: Blood glucose and urinary volume were elevated in diabetic animals, and RT decreased albuminuria, renal Ang I and Ang II levels in diabetic rats. RT shifted the balance of renal RAS toward ACE2/Ang 1-7 axis in TD group, and mitigated the high levels of interleukin (IL)-10, IL-1ß and cytokine-induced neutrophil chemoattractant 1 (CINC) in the context of diabetes. Strong positive correlations were found between albuminuria and Ang II, IL-10 and IL-1ß. On the other hand, intrarenal Ang 1-7 levels were negatively correlated with IL-10 and IL-1ß levels. SIGNIFICANCE: RT improved kidney function by modulating intrarenal RAS toward ACE2/Ang 1-7 axis and inflammatory cytokines. RT represents a reasonable strategy to improve the renal complications induced by diabetes, counteracting nephropathy-associated maladaptive responses.

Nandrolone combined with strenuous resistance training impairs myocardial proteome profile of rats.

We aimed to investigate the effects of high doses of nandrolone decanoate and resistance training (RT) on the proteomic profile of the left ventricle (LV) of rats, using a label-free quantitative approach. Male rats were randomized into four groups: untrained vehicle (UTV), trained vehicle (TV), untrained nandrolone (UTN), and trained nandrolone (TN). Rats were familiarized with the exercise training protocol (jump exercise) for one week. Jump-exercise was performed five days a week for 6 weeks, with 30 s of inter-set rest intervals. Nandrolone was administrated for 6 weeks (5 mg/kg, twice a week, via intramuscular). Systolic and diastolic arterial pressure and heart rate were measured 48 h post-training. LV was isolated and collagen content was measured. The expression of cardiac proteins was analyzed by ultra-efficiency liquid chromatography with mass spectrometry high / low collision energy (UPLC/MSE). Nandrolone and RT led to cardiac hypertrophy, even though high doses of nandrolone counteracted the RT-induced arterial pressures lowering. Nandrolone also affected the proteome profile negatively in LV of rats, including critical proteins related to biological processes (metabolism, oxidative stress, inflammation), structural function and membrane transporters. Our findings show physiological relevance since high doses of nandrolone induced detrimental effects on the proteome profile of heart tissue and hemodynamic parameters of rats. Furthermore, as nandrolone abuse has become increasingly common among recreational athletes and casual fitness enthusiasts, we consider that our findings have clinical relevance as well.

Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes.

INTRODUCTION: According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro. METHODS: Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture. RESULTS: diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group. CONCLUSION: The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

Accuracy of a Low-Cost Continuous Subcutaneous Insulin Infusion Pump Prototype: In Vitro Study Using Combined Methodologies.

Considering that infusion devices are safety-critical systems, the main goal of this paper is to evaluate the infusion accuracy and precision of a low-cost insulin infusion pump prototype, using two different methodologies. The first one used a microgravimetric method adapted from IEC60601-2-24, and the second estimated the displacement of the syringe plunger in response to programmed infusions. The low-cost prototype resulted in a compact and functional device with good accuracy. The prototype infused the programmed fluid doses with an average error of 2.2%. The percentage of infusions within ± 5% accuracy was 42.50 and of 84.17% for the ± 15% limit. The developed miniaturized mechanical system presented functionality, precision, and accuracy when coupled to the electronic system, responded well to repeatability tests. Additionally, the results from in vitro tests demonstrated that the performance of the device is satisfactory and comparable to commercial continuous insulin infusion pumps. This study presents a low-cost prototype as a candidate to be used by type 1 diabetic patients in Brazil and developing countries, especially in the context of public health.

Modulatory action of environmental enrichment on hormonal and behavioral responses induced by chronic stress in rats: Hypothalamic renin-angiotensin system components.

Environmental enrichment (EE) has been studied as a protocol that can improve brain plasticity and may protect against negative insults such as chronic stress. The aim of this study was to evaluate the effects of EE on the hormonal and behavioral responses induced by chronic mild unpredictable stress (CMS) in rats, considering the involvement of the renin-angiotensin system. Male adult rats were divided into 4 groups: control, CMS, EE, and CMS + EE, and the experimental protocol lasted for 7 weeks. EE was performed during 7 weeks, 5 days per week, 2 h per day. CMS was applied during weeks 3, 4, and 5. After the CMS (week 6), depression-like behavior was evaluated by forced swimming and sucrose consumption tests, anxiety level was evaluated using the elevated plus-maze test, and memory was evaluated using the Y-maze test. On week 7, the animals were euthanized and basal plasma levels of corticosterone and catecholamines were determined. The hypothalamus was isolated and tissue levels of angiotensin peptides were evaluated. CMS increased plasma corticosterone, norepinephrine, and epinephrine basal concentrations, induced depression-like behaviors, impaired memory, and increased hypothalamic angiotensin I, II, and IV concentrations. EE decreased stress hormones secretion, depression-like behaviors, memory impairment, and hypothalamic angiotensin II induced by stress. Reductions of anxiety-like behavior and norepinephrine secretion were observed in both stressed and unstressed groups. The results indicated that EE seemed to protect adult rats against hormonal and behavioral CMS effects, and that the reduction of angiotensin II could contribute to these effects.

Recreational training improves cardiovascular adaptations, metabolic profile and mental health of elderly women with type-2 diabetes mellitus.

We investigated the effects of a recreational training (RET) protocol in elderly women with type-2 diabetes mellitus (T2DM). We hypothesized that non-conventional physical activities of RET protocol might improve clinical outcomes regarding cardiovascular function, metabolic profile and mental health as participants keep the adherence to the protocol during the 3-month follow-up. Cardiovascular parameters (heart rate, systolic and diastolic blood pressure), circulating biomarkers (glucose and lipids) and salivary cortisol were attenuated in response to exercise. RET also reduced anxiety and depression indexes. RET protocol constitutes a potential therapeutic approach for managing T2DM in elderly women.

Tactile stimulation of adult rats modulates hormonal responses, depression-like behaviors, and memory impairment induced by chronic mild stress: Role of angiotensin II.

Physical touch can help to decrease the effects of stress. The aim of this study was to evaluate the influence of tactile stimulation on the hormonal and behavioral responses of young adult rats submitted to chronic mild unpredictable stress (CMS), considering the role of angiotensin II (Ang II). In Experiment 1, male rats were divided into 4 groups: control, stress, tactile stimulation (TS), and stress + TS. CMS was applied for three weeks. Tactile stimulation was applied for seven weeks, five days a week. After the CMS protocol, depression-like behaviors were evaluated by forced swimming and sucrose consumption tests. Learning and memory were evaluated using the Y-maze test. Fifteen days after the CMS procedure, the animals were euthanized and the levels of stress hormones were determined. The hypothalamus was isolated for determination of the Ang II concentration. In Experiment 2, control and stressed rats, with or without treatment using losartan (angiotensin II type 1 receptor blocker), were evaluated using the same behavioral tests and the hypothalamus Ang II concentration was also determined. CMS increased plasma corticosterone, norepinephrine, and epinephrine concentrations, induced depression-like behaviors, impaired learning and memory, and increased the Ang II concentration in the hypothalamus. Tactile stimulation attenuated these stress-induced effects. Losartan treatment effectively prevented increase of the hypothalamic Ang II concentration and the development of depression-like behavior, and also reduced the impairment of learning and memory in the stressed animals. The results indicated that tactile stimulation seemed to protect adult rats against hormonal and behavioral chronic stress effects, and that Ang II could be involved in the CMS effects.

Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

Nandrolone combined with strenuous resistance training reduces vascular nitric oxide bioavailability and impairs endothelium-dependent vasodilation.

Anabolic Androgenic Steroids (AASs) misuse has increased among adolescents and recreational athletes due to their potential effects on muscle hypertrophy. On the other hand, AAS might induce alterations on cardiovascular system, although some controversies regarding AAS on vascular properties remain unknown. To address this question, we aimed to investigate the effects of high doses of nandrolone combined with strenuous resistance training (RT) on function and structure of thoracic aorta. Rats were randomized into four groups: non-trained vehicle (NTV), trained vehicle (TV), non-trained nandrolone (NTN), and trained nandrolone (TN), and submitted to 6 weeks of treatment with nandrolone (5 mg/kg, twice a week) and/or resistance training. In vitro response of thoracic aorta to acetylcholine (ACh) was analyzed. Vascular nitric oxide (NO) and reactive oxygen species (ROS) synthesis were evaluated using 4,5-diaminofluorescein diacetate (DAF-2) and hydroethidine fluorescent techniques, respectively. Thoracic aorta was processed for microscopy analyses and tunica media thickness was measured. ACh-mediated relaxation response was impaired in endothelium intact aortic rings isolated from trained rats (TV and TN) as compared with their matched non-trained groups. TN rats showed reduced ACh-mediated vasodilatation than NTN rats. NO production and bioavailability decreased in thoracic aorta of nandrolone-treated rats in relation to their matched non-trained group (NTN vs. NTV; TN vs. TV). ROS production and tunica media thickness were increased in TN rats when compared with TV rats. These findings indicate that high doses of nandrolone combined with strenuous RT affect NO bioavailability and might induce endothelial dysfunction and arterial morphological alterations.

Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia.

Sepsis is an uncontrolled systemic inflammatory response against an infection and a major public health issue worldwide. This condition affects several organs, and, when caused by Gram-negative bacteria, kidneys are particularly damaged. Due to the importance of renin-angiotensin system (RAS) in regulating renal function, in the present study, we aimed to investigate the effects of endotoxemia over the renal RAS. Wistar rats were injected with Escherichia coli lipopolysaccharide (LPS) (4 mg/kg), mimicking the endotoxemia induced by Gram-negative bacteria. Three days after treatment, body mass, blood pressure, and plasma nitric oxide (NO) were reduced, indicating that endotoxemia triggered cardiovascular and metabolic consequences and that hypotension was maintained by NO-independent mechanisms. Regarding the effects in renal tissue, inducible NO synthase (iNOS) was diminished, but no changes in the renal level of NO were detected. RAS was also highly affected by endotoxemia, since renin, angiotensin-converting enzyme (ACE), and ACE2 activities were altered in renal tissue. Although these enzymes were modulated, only angiotensin (ANG) II was augmented in kidneys; ANG I and ANG 1-7 levels were not influenced by LPS. Cathepsin G and chymase activities were increased in the endotoxemia group, suggesting alternative pathways for ANG II formation. Taken together, our data suggest the activation of noncanonical pathways for ANG II production and the presence of renal vasoconstriction and tissue damage in our animal model. In summary, the systemic administration of LPS affects renal RAS, what may contribute for several deleterious effects of endotoxemia over kidneys.

Unraveling the role of high-intensity resistance training on left ventricle proteome: Is there a shift towards maladaptation?

High-intensity resistance training (RT) induces adaptations that improve physiological function. However, high intensity, volume and/or frequency may lead to injury and other health issues such as adverse cardiac effects. The aim of this study was to evaluate the effect of RT on left ventricle proteome, and to identify the pathways involved on the harmful adaptations induced by this protocol. Male Wistar rats were randomized into 2 groups: Trained (T) and Sedentary (S). Animals from T group were trained for 6weeks, and then all the animals were sacrificed and left ventricle was isolated for analysis. We identified 955 proteins, and 93 proteins were considered; 36 were expressed exclusively in T group, and 4 in S group. Based on quantitative analysis, 42 proteins were found overexpressed and 11 underexpressed in T group compared with S group. Using the Gene Ontology to relate the biological processes in which these proteins are involved, we conclude that RT protocol promotes changes similar to those found in the initial phase of heart failure, but we also observed a concomitant increased expression of protective proteins, suggesting the activation of pathways to avoid major damages on left ventricle and delay the onset of pathological hypertrophy. STATEMENT OF SIGNIFICANCE OF THE STUDY: Our study shows that high-intensity RT protocol changes left ventricle proteome, modifying metabolic profile of heart tissue and inducing the expression of proteins that acts against cardiac injury. We hypothesize that these adaptations occur to prevent the onset of cardiac dysfunction. Despite highly significant, it remains to be determined whether these adaptations are sufficient to further keep left ventricle function and exert cardioprotection, and whether this panel will be shifted towards maladaptation, and heart failure.

Relationship among stress, depression, cardiovascular and metabolic changes and physical exercise / Relação entre estresse, depressão, alterações cardiometabólicas e exercício físico

Abstract Introduction: Stress is considered one of the most significant health problems in modern society. It can be characterized as any changes in the homeostasis of an individual that require an adaptive response. An imbalance in the secretion of the primary stress mediators may be responsible for the onset and development of several diseases. Thus, chronic stress has been recognized as a risk factor for depression as well as cardiovascular and metabolic diseases. Given the pathophysiological mechanisms associated with chronic stress and related cardiovascular and metabolic changes, it is necessary to implement measures to prevent, control and/or avoid their development. Physical exercise is a non-pharmacological resource that is widely used for this purpose. Its beneficial effects include the improvement of the emotional state as well as lipid and glycemic control. Objective: The aim of this review is to discuss the relationship between stress, depression, cardiovascular and metabolic changes, and highlight the importance of physical exercise in the prevention and treatment of resulting disorders. Materials and Methods: We searched MEDLINE and SCIELO from 2000 through 2012, using the terms chronic stress, mood disorders, depression, cardiovascular and metabolic changes, and exercise. Results: Most of the studies found in our literature search have shown that exercise can attenuate and/or reverse the deleterious effects of chronic stress. Conclusion: Regular physical exercise is useful for maintaining health, especially with respect to improving mood and mental stress.

Resumo Introdução: O estresse é um dos mais significativos problemas de saúde na sociedade moderna, podendo ser caracterizado como qualquer mudança na homeostase do indivíduo que requer uma resposta adaptativa. O desequilíbrio na produção dos mediadores primários do estresse pode ser responsável pelo surgimento e desenvolvimento de várias doenças. Dessa forma, o estresse crônico tem sido reconhecido como fator de risco para a depressão e doenças cardiometabólicas. Frente aos mecanismos fisiopatológicos associados ao estresse crônico e às alterações cardiometabólicas correlatas, torna-se necessário encontrar medidas adequadas para preveni-las, controlá-las e/ou evitá-las. Sabe-se que o exercício físico é um recurso não-farmacológico amplamente utilizado para essa finalidade e os efeitos benéficos desencadeados incluem melhora do estado emocional e controle lipídico e glicêmico. Objetivo: O objetivo desta revisão foi discutir a relação entre os mecanismos fisiopatológicos do estresse, depressão, alterações cardiometabólicas e a importância da utilização do exercício físico na prevenção e tratamento destas disfunções desencadeadas. Materiais e Métodos: Para esta revisão foram consultadas as bases de dados MEDLINE e SCIELO e inclusos no campo de pesquisa os termos estresse crônico, alterações de humor, depressão, alterações cardíacas e metabólicas e o exercício físico. Como limite de busca, foi definida a pesquisa de artigos publicados entre os anos de 2000 e 2012. Resultados: A maior parte dos estudos mostrou que o exercício é capaz de atenuar e/ou reverter os efeitos deletérios do estresse crônico. Conclusão: A prática regular do exercício físico tem grande utilidade para a manutenção da saúde, sobretudo com relação à melhora do humor e do estresse mental.