VDR, SOD-2, and CYP24A1 Gene Expression in Different Genotypes of BsmI SNP of the Vitamin D Receptor Gene in Individuals with Hypovitaminosis.

BACKGROUND: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of cellular tissues, and it is expressed through the vitamin D receptor (VDR) gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. OBJECTIVE: To evaluate the effect of the genotypes of BsmI single nucleotide polymorphism (SNP) of the VDR gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. METHODS: This was a cross-sectional analytical study. After signing the informed consent form, individuals were invited to participate and answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p < 0.05. RESULTS: 98 individuals with vitamin D ≤ 20 ng/dL were evaluated, and the BsmI SNP of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. CONCLUSION: BsmI SNP of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

Air pollution combined with high-fat feeding aggravates metabolic and cardiovascular diseases: A dangerous, oxidative, and immune-inflammatory association.

Obesity and particulate air pollutant (PM2.5) are important risk factors for cardiometabolic diseases. PM2.5 exacerbates insulin resistance and lipid ectopic deposition in obese animals. The inorganic fraction of PM2.5, the Residual Oil Fly Ash (ROFA), is related to cardiovascular events, by enhancing the generation of reactive species, inflammatory cytokines, and leukocyte activation. However, the synergistic effects of ROFA and a high-fat diet (HFD) are still poorly described, and the studies were mainly conducted with males. AIMS: To investigate if ROFA could potentiate the cardiometabolic effects of diet-induced obesity in female rats. MATERIAL AND METHODS: Wistar female rats were divided into four groups: Control (n = 6), Polluted (n = 6), HFD (n = 6), and HFD + Polluted (n = 6). HFD and HFD + Polluted received a high-fat diet (HFD) (58.3 % as fats), whilst Control and Polluted groups received a standard diet (Nuvilab CR-1). In addition, Polluted and HFD + Polluted groups received intranasal instillation of ROFA (250 µg/50 µL), while Control and HFD groups received saline solution (50 µL) daily, five days per week. Both interventions occurred 24 weeks after the animals were euthanized. KEY FINDINGS: HFD combined with ROFA exposure impaired lipid profile challenged systemic and cardiac antioxidant defense, and presented a synergistic effect in inducing an immune-inflammatory condition. We found that the lipid profile disturbance is associated with HFD-induced hepatic, but not cardiac, deposition of triglycerides in female animals. SIGNIFICANCE: Our results support the hypothesis that ROFA exposure combined with bad feeding can exacerbate metabolic and cardiovascular diseases.

Increased eHSP70-to-iHSP70 ratio in prediabetic and diabetic postmenopausal women: a biomarker of cardiometabolic risk.

Decreased estrogen levels in menopause are associated with anthropometric, metabolic, and inflammatory impairments, predisposing women to cardiometabolic risk factors such as diabetes. Menopause and type two diabetes (DM2) are marked by altered heat shock response (HSR), shown by decreased expression of the 70-kDa heat shock protein in the intracellular milieu (iHSP70). While iHSP70 plays an anti-inflammatory role, extracellular HSP70 (eHSP70) may mediate pro-inflammatory pathways and has been associated with insulin resistance in DM2. Considering the roles of these proteins according to localization, the eHSP70-to-iHSP70 ratio (H-index) has been proposed as a biomarker for HSR. We, therefore, evaluated whether this biomarker is associated with glycemic and inflammatory status in postmenopausal women. In this transversal study, 36 postmenopausal women were grouped according to fasting glycemia status as either the control group (normoglycemic, ≤ 99 mg/dL) or DM2 (prediabetic and diabetic, glycemia ≥ 100 mg/dL). DM2 group showed higher triglyceride/glucose (TyG) index and plasma atherogenic index (PAI), both of which are indicators of cardiometabolic risk. In addition, we found that the eHSP70-to-iHSP70 ratio (plasma/peripheral blood mononuclear cells-PBMC ratio) was higher in the DM2 group, compared with the control group. Furthermore, blood leukocyte and glycemia levels were positively correlated with the eHSP70-to-iHSP70 ratio in women that presented H-index values above 1.0 (a.u.). Taken together, our results highlight the eHSP70-to-iHSP70 ratio as a biomarker of altered HSR in DM2 postmenopausal women.

Adapted Murine Sepsis Score: Improving the Research in Experimental Sepsis Mouse Model.

The Murine Sepsis Score (MSS) is used to assess the severity of sepsis in rats and mice based on observational characteristics. The quantitative variables of glycemia, body weight, and temperature are predictors of severity in experimental models of sepsis. Therefore, our study sought to adapt the MSS with the same variables to indicate earlier the severity of the disease in murine models of the disease. Sepsis mice presented hypoglycemia, weight loss, and hypothermia. Therefore, these variables were included in the Adapted Murine Sepsis Score (A-MSS). The A-MASS presented 100% specificity and 87.5% sensibility been able to differentiate the early sepsis symptoms and its severity. The A-MSS allows an early and more complete diagnosis of sepsis in mice and might be considered as a procedure to improve the analysis of systemic sepsis dysfunction in murine experimental models.

Oxidative and Cellular Stress Markers in Postmenopause Women with Diabetes: The Impact of Years of Menopause.

Women live approximately one-third of their lives in postmenopause. Among postmenopausal women, type 2 diabetes mellitus (DM2) is one of the most prevalent chronic diseases. These conditions promote alterations in the oxidative, metabolic, and immune-inflammatory profiles marked by higher extracellular 72 kDa-heat shock protein (eHSP72). Here, we investigated whether the time of menopause is associated with oxidative cellular stress marker levels in postmenopausal women with DM2. Sixty-four women were recruited (56.7 ± 12.6 years old) in the pre- (n = 22) and postmenopause (n = 42) period, with (n = 19) or without DM2 (n = 45), and a fasting blood collection was made for the evaluation of metabolic, oxidative, and inflammatory markers. We found that menopause and DM2 influenced metabolic and oxidative parameters and presented synergistic effects on the plasma lipoperoxidation levels. Also, postmenopausal women had the highest eHSP72 concentration levels associated with the years in postmenopause. We conclude that the time of menopause impacts the markers of cellular stress and increases the risk of oxidative stress, mainly when it is associated with DM2.

Effects of aerobic and resistance exercise training associated with carnosine precursor supplementation on maximal strength and V̇O2max in rats with heart failure.

BACKGROUND: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was to test whether CET associated with supplementing carnosine precursors could present better responses in the functional capacity and biochemical variables of rats with HF. METHODS: Twenty-one male Wistar rats were subjected to myocardial infarction and allocated to three groups: sedentary (SED, n = 7), CET supplemented with placebo (CETP, n = 7), and CET with HF supplemented with ß-alanine and L-histidine (CETS, n = 7). The trained animals were submitted to a strength protocol three times per week. Aerobic training was conducted twice per week. The supplemented group received ß-alanine and L-histidine orally (250 mg/kg per day). RESULTS: Maximum oxygen uptake, running distance, time to exhaustion and maximum strength were higher in the CET-P group than that in the SED group and even higher in the CET-S group than that in the CET-P group (P < 0.01). CET-S showed lower oxidative stress and inflammation markers and higher heat shock protein 72 kDa content and mRNA expression for calcium transporters in the skeletal muscle compared to SED. CONCLUSION: CET together with ß-alanine and L-histidine supplementation in rats with HF can elicit adaptations in both maximum oxygen uptake, running distance, time to exhaustion, maximum strength, oxidative stress, inflammation and mRNA expression. Carnosine may influence beneficial adjustments in the cell stress response in the skeletal muscle and upregulate the mRNA expression of calcium transporters.

Salivary cortisol concentrations in hematogy/oncology nurses on working days and days off.

OBJECTIVE: to assess salivary cortisol concentrations in hematology/oncology nurses on working days and days off. METHODS: a cross-sectional study carried out with 28 nurses from a university hospital. A sociodemographic, employment and health profile questionnaire was applied. For saliva collection, Salivette® tubes were used. Descriptive and analytical analysis was used. RESULTS: there was no significant difference in cortisol concentrations between working days and days off (p>0.05). The high cortisol concentration was associated with not having children (0.621±0.340; p=0.046), not using medication (0.623±0.133; p=0.017) and birth control pills (0.556 ± 0.228; p=0.047) and intention to leave work (0.951±0.154; p=0.001). A positive correlation was identified between cortisol and absence from work due to health issues (0.72; p=0.05) and weight gain (0.935; p=0.02). CONCLUSION: in general, cortisol concentration is within the reference parameters, with no significant difference in its secretion on working days and days off.

Insufficient social distancing may contribute to COVID-19 outbreak: The case of Ijuí city in Brazil.

The coronavirus disease that emerged in 2019 (COVID-19) is highly contagious and has given way to a global pandemic. A present COVID-19 has high transmission rates worldwide, including in small Brazilian cities such as Ijuí. Located in the northwest part of the state of Rio Grande do Sul (RS) and with a population of 83,475, Ijuí was selected as the site of a population-based survey involving 2,222 subjects, from April to June 2020. Subjects were tested for the presence of antibodies against coronavirus (SARS-CoV-2) and answered questions regarding social distance adherence (SDA), daily preventive routines (DPR), comorbidities, and sociodemographic characteristics. In parallel, the local government registered the official COVID-19 cases in Ijuí, as well as the mobile social distancing index (MSDI). In this study, we demonstrate that there was a decrease in the levels of SDA, DPR and MSDI before the beginning of COVID-19 community transmission in Ijuí. Furthermore, we provide predictions for the number of COVID-19 cases, hospitalizations, and deaths in the city. We conclude that insufficient social distancing, as evidenced by different methods, may be related to the rapid increase of COVID-19 cases in Ijuí. Our study predicts an approaching outbreak of COVID-19 in Ijuí through community spread, which could be avoided or attenuated with increased levels of social distancing among the population.

Ovariectomy enhances female rats' susceptibility to metabolic, oxidative, and heat shock response effects induced by a high-fat diet and fine particulate matter.

Obesity and exposure to fine particulate matter (air pollutant PM2.5) are important risk factors for metabolic and cardiovascular diseases. They are also related to early menopause. The reduction of 17ß-estradiol (E2) levels during female climacteric, marked by menopause, is of significant concern because of its imminent influence on metabolism, redox and inflammatory status. This complex homeostasis-threatening scenario may induce a heat shock response (HSR) in cells, enhancing the expression of the 70 kDa heat shock protein (HSP70). A failure in this mechanism could predispose women to cardiovascular diseases. In this study, we evaluated if the climacteric could represent an additional risk among obese rats exposed to PM2.5 by worsening lipid, oxidative, and inflammatory parameters and HSP70 in cardiac tissue. We induced obesity in female Wistar rats using a high-fat diet (HFD) (58.3% as fats) and exposed them to 50 µL of saline 0.9% (control, n = 15) or 250 µg residual oil fly ash (ROFA, the inorganic portion of PM2.5) (polluted, n = 15) by intranasal instillation, 5 days/w for 12 weeks. At the 12th week, we subdivided these animals into four groups: control (n = 6), OVX (n = 9), polluted (n = 6) and polluted + OVX (n = 9). OVX and polluted + OVX were submitted to a bilateral ovariectomy (OVX), a surgical model for menopause, while control and polluted received a false surgery (sham). ROFA exposure and HFD consumption were continued for 12 additional weeks, after which the animals were euthanized. ROFA enhanced the susceptibility to ovariectomy-induced dyslipidemia, while ovariectomy predisposed female rats to the ROFA-induced decrease of cardiac iHSP70 expression. Ovariectomy also decreased the IL-6 levels and IL-6/IL-10 in obese animals, reinforcing a metabolic impairment and a failure to respond to unfavorable conditions. Our results support the hypothesis that obese ovariectomized animals are predisposed to a metabolic worsening under polluted conditions and are at higher risk of cardiovascular diseases.

Salivary cortisol concentrations in hematogy/oncology nurses on working days and days off / Concentración de cortisol salival en enfermeras de hemato-oncología en días laborales y días libres / Concentração de cortisol salivar de enfermeiros de hemato-oncologia nos dias de trabalho e folga

ABSTRACT Objective: to assess salivary cortisol concentrations in hematology/oncology nurses on working days and days off. Methods: a cross-sectional study carried out with 28 nurses from a university hospital. A sociodemographic, employment and health profile questionnaire was applied. For saliva collection, Salivette® tubes were used. Descriptive and analytical analysis was used. Results: there was no significant difference in cortisol concentrations between working days and days off (p>0.05). The high cortisol concentration was associated with not having children (0.621±0.340; p=0.046), not using medication (0.623±0.133; p=0.017) and birth control pills (0.556 ± 0.228; p=0.047) and intention to leave work (0.951±0.154; p=0.001). A positive correlation was identified between cortisol and absence from work due to health issues (0.72; p=0.05) and weight gain (0.935; p=0.02). Conclusion: in general, cortisol concentration is within the reference parameters, with no significant difference in its secretion on working days and days off.

RESUMEN Objetivo: evaluar la concentración de cortisol salival en enfermeras de Hemato-Oncología en días laborales y días libres. Métodos: estudio transversal realizado con 28 enfermeras de un hospital universitario. Se aplicó un cuestionario de perfil sociodemográfico, laboral y de salud. Para la recolección de saliva se utilizaron tubos Salivette ®. Se utilizó análisis descriptivo y analítico. Resultados: no hubo diferencia significativa en la concentración de cortisol entre los días laborables y los días libres (p> 0.05). La alta concentración de cortisol se asoció con no tener hijos (0.621±0.340; p=0.046), no usar medicación (0.623±0.133; p=0.017) y anticonceptivos orales (0.556±0.228; p=0.047) y tener la intención de dejar el trabajo (0.951±0,154; p=0.001). Se identificó una correlación positiva entre cortisol y absentismo laboral por problemas de salud (0.72; p=0.05) y aumento de peso (0.935; p=0.02). Conclusión: en general, la concentración de cortisol se encuentra dentro de los parámetros de referencia, sin diferencia significativa en su secreción el día de trabajo y tiempo libre.

RESUMO Objetivo: avaliar a concentração de cortisol salivar em enfermeiros de Hemato-Oncologia nos dias de trabalho e de folga. Métodos: estudo transversal, realizado com 28 enfermeiros de um hospital universitário. Aplicou-se questionário sociodemográfico, laboral e perfil de saúde. Para coleta de saliva, foram utilizados tubos Salivette®. Empregou-se análise descritiva e analítica. Resultados: não houve diferença significativa na concentração de cortisol entre os dias de trabalho e de folga (p>0,05). A concentração de cortisol elevada esteve associada a não possuir filhos (0,621±0,340; p=0,046), não fazer uso de medicação (0,623±0,133; p=0,017) e de anticoncepcional oral (0,556±0,228; p=0,047) e ter a intenção de deixar o trabalho (0,951±0,154; p=0,001). Identificou-se correlação positiva entre cortisol e afastamento do trabalho por problemas de saúde (0,72; p=0,05) e aumento de peso (0,935; p=0,02). Conclusão: em geral, a concentração de cortisol está dentro dos parâmetros de referência, não apresentando diferença significativa na sua secreção no dia de trabalho e folga.

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.

A single dose of eHSP72 attenuates sepsis severity in mice.

High levels of extracellular 72 kDa heat shock protein (eHSP72) can be detected in the serum of septic patients and are associated with increased oxidative profiles and elevated rates of mortality among these patients. However, a possible immunomodulatory role for this protein, resulting in tissue protection during sepsis, has never been assessed. In this study, we investigated whether eHSP72 administration could attenuate the severity of sepsis in a mouse peritonitis model. Animals (90-day-old male C57BL/6J mice) were divided into Sepsis (n = 8) and Sepsis + eHSP72 (n = 9) groups, which both received injections of 20% fecal solution [1 mg/g body weight (wt), intraperitoneal (i.p.)], to trigger peritonitis induced-sepsis, whereas a Control group (n = 7) received a saline injection. eHSP72 was administered (1.33 ng/g body wt) to the Sepsis+eHSP72 group, 12 h after sepsis induction. All animals were evaluated for murine sepsis score (MSS), hemogram, core temperature, and glycemia (before and 4, 12, and 24 h after sepsis induction). Treatment with eHSP72 promoted reduced sepsis severity 24 h after sepsis induction, based on MSS scores (Control = 1.14 ± 1.02; Sepsis = 11.07 ± 7.24, and Sepsis + eHSP72 = 5.62 ± 1.72, P < 0.001) and core temperatures (°C; Control = 37.48 ± 0.58; Sepsis = 35.17 ± 2.88, and Sepsis + eHSP72 = 36.94 ± 2.02; P = 0.006). eHSP72 treatment also limited the oxidative profile and respiratory dysfunction in mice with sepsis. Although sepsis modified glycemic levels and white and red blood cell counts, these variables were not influenced by eHSP72 treatment (P > 0.05). Finally, eHSP72 improved the survival rate after sepsis (P = 0.0371). Together, our results indicated that eHSP72 may ameliorate sepsis severity and possibly improve some sepsis indices in mice.

Reduction of functional cardiovascular reserve in the stages of chronic kidney disease.

OBJECTIVE: Patients with chronic kidney disease (CKD) present reduced oxygen consumption at peak exercise (VO2 peak). No studies have evaluated objective measures of the cardiovascular reserve, besides VO2 peak and VO2 at the anaerobic threshold (VO2 AT), and compared these measures among ckd patients at different stages of the disease. METHODS: Fifty-eight patients [pre-dialysis group (PD)=26, hemodialysis group (HD)=20, and post-kidney transplant group (KT)=12] were included. The following measures of cardiovascular reserve were obtained: 1) peak heart rate (HR); 2) peak systolic blood pressure (SBP); 3) VO2 peak and % predicted; 4) VO2 AT and % of predicted VO2; 5) peak circulatory power; 6) ventilatory efficiency for the production of carbon dioxide (VE/VCO2 slope); 7) oxygen uptake efficiency slope (OUES); and 8) recovery of gas exchange. RESULTS: The VO2 peak and VO2 AT in the PD, HD, and KT groups were reduced to 86% and 69%, 70% and 57%, and 79% and 64% of the predicted value, respectively. Patients in the HD group had lower VO2 peak (17.5±5.9 vs. 23.2±8.2 [p-value=0.036]) and VO2 AT (14.0±5.2 vs. 18.3±4.7 [p-value=0.039]) compared to patients in the KT group. OUES was significantly lower in the HD group compared to the KT group (p-value=0.034). Age in the PD, HD, and KT groups and sedentary lifestyle in the KT group were predictors of VO2 peak. CONCLUSIONS: CKD patients presented a reduction in cardiovascular reserve regardless of the stage of the disease. However, hemodialysis patients presented a greater reduction of cardiovascular reserve when compared to post-kidney transplant patients.

The association of subchronic exposure to low concentration of PM2.5 and high-fat diet potentiates glucose intolerance development, by impairing adipose tissue antioxidant defense and eHSP72 levels.

The subchronic exposure to fine particulate matter (PM2.5) and high-fat diet (HFD) consumption lead to glucose intolerance by different mechanisms involving oxidative stress and inflammation. Under stressful conditions, the cells exert a heat shock response (HSR), by releasing the 72-kDa heat shock proteins (eHSP72), fundamental chaperones. The depletion of the HSR can exacerbate the chronic inflammation. However, there are few studies about the early effects of the association of HFD consumption and exposure to low concentrations of PM2.5 in the oxidative stress and HSR, in the genesis of glucose intolerance. Thus, we divided 23 male B6129SF2/J mice into control (n = 6), polluted (n = 6), HFD (n = 6), and high-fat diet + polluted (HFD + polluted) (n = 5) groups. Control and polluted received a standard diet (11.4% of fats), while HFD and HFD + polluted received HFD (58.3% of fats). Simultaneously, polluted and HFD + polluted received 5 µg/10 µL of PM2.5, daily, 7×/week, while control and HFD were exposed to 10 µL of saline solution 0.9% for 12 weeks. At the 12th week, animals were euthanized. We collected the metabolic tissues to analyze oxidative parameters, total blood to the hematological parameters, and plasma to eHSP72 measurement. The association of HFD and PM2.5 impaired glucose tolerance in the 12th week. Besides, it triggered an antioxidant defense by the adipose tissue, which was negatively correlated with eHSP72 levels. In conclusion, a low concentration of PM2.5 exposure associated with HFD consumption leads to glucose intolerance, by impairing adipose tissue antioxidant defense and systemic eHSP72 levels.

Chronic heat treatment positively impacts metabolic profile of ovariectomized rats: association with heat shock response pathways.

Low estrogen levels may predispose women to increased bodyweight and dyslipidemia. Previous studies from our laboratory suggest an involvement of depressed heat shock response (HSR) in this scenario because estrogen potently stimulates HSR. As heat treatment induces the expression of the anti-inflammatory heat shock proteins of the 70-kDa family (HSP70) and its accompanying HSR, we aimed to investigate whether chronic heat treatment promotes beneficial effects on biometric, lipid profile, oxidative stress, and HSR in ovariectomized rats. Wistar adult female rats (n = 32) were divided into four groups: control (C, n = 7), ovariectomized (OVX, n = 9), heat-treated (HT, n = 9), and heat-treated ovariectomized rats (OVX+HT, n = 7). HT and OVX+HT rats were anesthetized and submitted to heat treatment (once a week for 12 weeks) in a water bath (41 °C) to increase rats' rectal temperature up to 41 °C for 15 min, while C and OVX animals were submitted to a 36 °C water bath. HT attenuated the weight gain induced by OVX and increased HDL cholesterol and triglyceride serum levels. Also, OVX rats showed increased total cholesterol and LDL cholesterol levels that were not influenced by HT. Interestingly, it was found that an overall trend for HT to decrease tissue catalase and superoxide dismutase antioxidant activities was paralleled by a decrease in malondialdehyde levels (indicative of lower lipoperoxidation), especially in the skeletal muscle. Surprisingly, OVX was not able to depress intracellular HSP70 expression in the skeletal muscle, as expected, and this remained unchanged with HT. However, chronic HT did enhance intracellular HSP70 contents in white adipose tissue of OVX animals. As both glucose and insulin tolerance tests were not affected by OVX, which was not modified by HT, we suppose that estrogen absence alone is not sufficient to determine a state of insulin resistance associated with low intramuscular HSP70 content.

Reduction of functional cardiovascular reserve in the stages of chronic kidney disease

SUMMARY OBJECTIVE Patients with chronic kidney disease (CKD) present reduced oxygen consumption at peak exercise (VO2 peak). No studies have evaluated objective measures of the cardiovascular reserve, besides VO2 peak and VO2 at the anaerobic threshold (VO2 AT), and compared these measures among ckd patients at different stages of the disease. METHODS Fifty-eight patients [pre-dialysis group (PD)=26, hemodialysis group (HD)=20, and post-kidney transplant group (KT)=12] were included. The following measures of cardiovascular reserve were obtained: 1) peak heart rate (HR); 2) peak systolic blood pressure (SBP); 3) VO2 peak and % predicted; 4) VO2 AT and % of predicted VO2; 5) peak circulatory power; 6) ventilatory efficiency for the production of carbon dioxide (VE/VCO2 slope); 7) oxygen uptake efficiency slope (OUES); and 8) recovery of gas exchange. RESULTS The VO2 peak and VO2 AT in the PD, HD, and KT groups were reduced to 86% and 69%, 70% and 57%, and 79% and 64% of the predicted value, respectively. Patients in the HD group had lower VO2 peak (17.5±5.9 vs. 23.2±8.2 [p-value=0.036]) and VO2 AT (14.0±5.2 vs. 18.3±4.7 [p-value=0.039]) compared to patients in the KT group. OUES was significantly lower in the HD group compared to the KT group (p-value=0.034). Age in the PD, HD, and KT groups and sedentary lifestyle in the KT group were predictors of VO2 peak. CONCLUSIONS CKD patients presented a reduction in cardiovascular reserve regardless of the stage of the disease. However, hemodialysis patients presented a greater reduction of cardiovascular reserve when compared to post-kidney transplant patients.

RESUMO OBJETIVO Pacientes com doença renal crônica (DRC) apresentam redução no consumo de oxigênio no pico do exercício (VO2 pico). Nenhum estudo avaliou medidas objetivas da reserva cardiovascular, além do VO2 pico e do VO2 no limiar anaeróbio (LA), e comparou essas medidas entre pacientes com DRC nos diferentes estágios da doença. MÉTODOS Cinquenta e oito pacientes [grupo pré-diálise (PD)=26, grupo hemodiálise (HD)=20 e grupo pós-transplante (PT)=12] foram incluídos. As seguintes medidas da reserva cardiovascular foram obtidas: 1) frequência cardíaca (FC) pico; 2) pressão arterial sistólica (PAS) pico; 3) VO2 pico e % do predito; 4) VO2 LA e % do VO2 predito; 5) potência circulatória pico; 6) eficiência ventilatória para a produção de dióxido de carbono (VE/VCO2 slope); 7) eficiência ventilatória para o consumo de oxigênio (Oues); 8) recuperação das trocas gasosas. RESULTADOS O VO2 pico e o VO2 LA nos grupos PD, HD e PT foram reduzidos para 86% e 69%, 70% e 57%, e 79% e 64% do valor previsto, respectivamente. Pacientes do grupo HD obtiveram VO2 pico (17,5±5,9 vs. 23,2±8,2 [p=0,036]) e VO2 LA (14,0±5,2 vs. 18,3±4,7 [p=0,039]) mais baixo, comparado aos pacientes PT. A Oues foi significativamente menor no grupo HD comparado ao grupo PT (p=0,034). Idade nos grupos PD, HD e PT, e sedentarismo no grupo PT foram preditores do VO2 pico. CONCLUSÃO Pacientes com DRC apresentam redução da reserva cardiovascular independentemente do estágio da doença. No entanto, pacientes em hemodiálise apresentam uma redução mais acentuada da reserva cardiovascular quando comparados aos pacientes pós-transplante.

Ovariectomy predisposes female rats to fine particulate matter exposure's effects by altering metabolic, oxidative, pro-inflammatory, and heat-shock protein levels.

The reduction of estrogen levels, as a result of menopause, is associated with the development of metabolic diseases caused by alterations in oxidative stress (OS), inflammatory biomarkers, and 70-kDa heat-shock protein (HSP70) expression. Additionally, exposure to fine particulate matter air pollution modifies liver OS levels and predisposes organisms to metabolic diseases, such as type 2 diabetes (T2DM). We investigated whether ovariectomy affects hepatic tissue and alters glucose metabolism in female rats exposed to particulate air pollution. First, 24 female Wistar rats received an intranasal instillation of saline or particles suspended in saline 5 times per week for 12 weeks. The animals then received either bilateral ovariectomy (OVX) or false surgery (sham) and continued to receive saline or particles for 12 additional weeks, comprising four groups: CTRL, Polluted, OVX, and Polluted+OVX. Ovariectomy increased body weight and adiposity and promoted edema in hepatic tissue, hypercholesterolemia, glucose intolerance, and a pro-inflammatory profile (reduced IL-10 levels and increased IL-6/IL-10 ratio levels), independent of particle exposure. The Polluted+OVX group showed an increase in neutrophils and neutrophil/lymphocyte ratios, decreased antioxidant defense (SOD activity), and increased liver iHSP70 levels. In conclusion, alterations in the reproductive system predispose female organisms to particulate matter air pollution effects by affecting metabolic, oxidative, pro-inflammatory, and heat-shock protein expression.

Effects of High-Fat Diet on eHSP72 and Extra-to-Intracellular HSP70 Levels in Mice Submitted to Exercise under Exposure to Fine Particulate Matter.

Obesity, air pollution, and exercise induce alterations in the heat shock response (HSR), in both intracellular 70 kDa heat shock proteins (iHSP70) and the plasmatic extracellular form (eHSP72). Extra-to-intracellular HSP70 ratio (H-index = eHSP70/iHSP70 ratio) represents a candidate biomarker of subclinical health status. This study investigated the effects of moderate- and high-intensity exercise in the HSR and oxidative stress parameters, in obese mice exposed to fine particulate matter (PM2.5). Thirty-day-old male isogenic B6129F2/J mice were maintained for 16 weeks on standard chow or high-fat diet (HFD). Then, mice were exposed to either saline or 50 µg of PM2.5 by intranasal instillation and subsequently maintained at rest or subjected to moderate- or high-intensity swimming exercise. HFD mice exhibited high adiposity and glucose intolerance at week 16th. HFD mice submitted to moderate- or high-intensity exercise were not able to complete the exercise session and showed lower levels of eHSP70 and H-index, when compared to controls. PM2.5 exposure modified the glycaemic response to exercise and modified hematological responses in HFD mice. Our study suggests that obesity is a critical health condition for exercise prescription under PM2.5 exposure.

Detectable levels of eHSP72 in plasma are associated with physical activity and antioxidant enzyme activity levels in hypertensive subjects.

Previous studies reported that extracellular HSP72 (eHSP72) correlates with poor prognosis, markers of vascular dysfunction, and the severity of cardiovascular diseases, associated with a systemic oxidative and inflammatory profile. On the other hand, eHSP72 may represent immune-regulatory signaling that is related to exercise benefits, but the association between physical activity levels and eHSP72 levels is not established. Thus, since regular physical activity may avoid oxidative stress and inflammation, we investigate whether detectable levels of eHSP72 in plasma are associated with physical activity and antioxidant enzyme activity levels in hypertensive subjects. Physical activity levels of hypertensive subjects (n = 140) were measured by tri-axial movement sensor pedometer for 24 h during 5 consecutive days. One day after, blood was collected into heparinized tubes for oxidative stress analyses (catalase-CAT and superoxide dismutase-SOD activities and malondialdehyde levels) or in disodium EDTA tubes for eHSP72 assays. Thus, hypertensive subjects were classified as physically inactive (< 10,000 footsteps/day) or active (> than 10,000 footsteps/day) and according detectable or not detectable eHSP72 levels in plasma, performing the inactive/eHSP72-, active/eHSP72-, inactive/eHSP72+, and active/eHSP72+ groups. We found that detectable levels of eHSP72 in plasma were associated with physical activity levels and low oxidative stress profile (Higher CAT and SOD activities and low malondialdehyde levels). eHSP72 levels can be used as a biomarker of the amount of physical activity necessary to improve antioxidant defense and thus cardiovascular health in hypertensive subjects.

Resistance training and L-arginine supplementation are determinant in genomic stability, cardiac contractility and muscle mass development in rats.

L-arginine supplementation has been related to increased maximum strength and improvement of hemodynamic parameters in several diseases. The aim of our study was to evaluate the effect of L-arginine supplementation and resistance training on muscle mass, hemodynamic function and DNA damage in healthy rats subjected to a low-arginine concentration diet. Twenty three Wistar rats (290-320g) were divided into 4 groups: Sedentary (SED-Arg, n = 6), Sedentary+Arg (SED+Arg, n = 6), Resistance Training (RT-Arg, n = 5), Resistance Training+Arg (RT+Arg, n = 6). Trained animals performed resistance training protocol in a squat apparatus adapted for rats (4 sets of 10-12 repetitions, 90s of interval, 4x/week, 65-75% of One Maximum Repetition, for 8 weeks). Comet assay was performed to measure DNA damage in leukocytes. The resistance training induced higher muscle mass in trained groups. The L-arginine supplementation increased both gastrocnemius and left ventricle to body mass ratio and increased left ventricle contractility without changing hemodynamic variables. The SED+Arg group showed higher concentration of extracellular heat shock protein 72 (eHSP72) and total testosterone, as well as lower uric acid concentration in blood versus SED-Arg group. The administration of isolated L-arginine supplementation and its association with resistance training promoted less damage in leukocytes DNA. In conclusion, the L-arginine supplementation showed synergistic effect with resistance training regarding leukocyte genomic stability in a low-L-arginine diet scenario.