Functional analysis of airway remodeling is related with fibrotic mediators in asthmatic children.

BACKGROUND: Asthmatic children present variable degrees of airway inflammation, remodeling, and resistance, which correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. OBJECTIVE: To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways. METHODS: 39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses. RESULTS: Asthmatic children showed an increased number of blood eosinophils (p < 0.04), basophils (p < 0.04), monocytes (p < 0.002) and lymphocytes (p < 0.03). In addition, asthmatic children showed impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p < 0.0001) and in the serum (p < 0.0001); TGF-beta in the BC (p < 0.0001) and in the serum (p < 0.004); IL-5 in the BC (p < 0.02) and in the serum (p < 0.01); IL-4 in the serum (p < 0.0002). CONCLUSIONS: Impulse oscillometry is a sensitive method to detect airway resistance in persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 µg/mL and 10 µg/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 × 105 cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and tumor necrosis factor (TNF) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 µg/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01), while only the 10 µg/mL dose of vitamin C induced the release of Klotho (10 µg/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.

Impact of social distancing from the COVID-19 pandemic on the immuno-inflammatory response of older adults.

BACKGROUND: Older adults, as the population considered at increased risk for severe COVID-19, were the most impacted by social isolation. Thus, this study aimed to assess the salivary immune/inflammatory response of older adults before and during the COVID-19 pandemic. METHODS: A cohort of 11 older adults (mean age 66.8 ± 6.1) was followed at three different time points: before (S1) and after 6 (S2) and 20 months (S3) of the beginning of the COVID-19 pandemic in Brazil. Unstimulated saliva samples were obtained to assess the levels of antibodies (secretory IgA, IgG and IgM) by ELISA and cytokines (IL-2, IL-5, IL-6, IL-8 and IL-10, TSLP, IFN-γ, TNF-α) by multiplex analysis. Significant differences were evaluated using the Kruskal-Wallis test with Dunn's post-test. RESULTS: None volunteer presented periodontal disease or caries. All volunteers received at least two doses of the COVID-19 vaccines after S2 and before S3. A tendency to increase salivary levels of SIgA and IgM at S2 and of IgG at S3 were observed compared to the values found at S1 and S2. Significantly decreased levels of IL-2 and IL-5 were found at S2 and S3 (p < 0.001) time points. Lower levels of IFN-γ were found at S2 as compared to the values observed at S1 (p < 0.01). A significant decrease in the IFN-γ/IL-10 ratio was found at S2 (p < 0.01). When assessing the Th1/Th2 ratios, a significant decrease was found in the IFN-γ/TSLP ratio at S2 (p < 0.001) and S3 (p < 0.001) when compared to the values at S1. In addition, a significant increase was observed in the TNF-α/IL-5 ratio at S2 (p < 0.001) and S3 (p < 0.001) in comparison to the values at S1. In a similar way, an increase in the TNF-α/IL-6 ratio (Fig. 5E) was observed at S3 (p < 0.001) when compared to the values at S1. CONCLUSIONS: Overall, this study provides valuable insights into the impact of COVID-19-induced social isolation on immune/inflammatory responses in the upper airway mucosa, particularly those present in oral cavity, of older adults. It demonstrates that a controlled shift in Th1 and Th2 immune responses, both during infection and post-vaccination, can create favorable conditions to combat viral infections without exacerbating the immune response or worsening the pathology.

Regular Practice of Physical Activity Improves Cholesterol Transfers to High-Density Lipoprotein (HDL) and Other HDL Metabolic Parameters in Older Adults.

The effects of regular physical activity on two important anti-atherosclerosis functions of high-density lipoprotein (HDL), namely its capacity to receive both forms of cholesterol and its anti-oxidant function, were investigated in this study comparing older adults with young individuals. One-hundred and eight healthy adult individuals were enrolled and separated into the following groups: active older (60-80 yrs, n = 24); inactive older (60-79 yrs, n = 21); active young (20-34 yrs, n = 39); and inactive young (20-35 yrs, n = 24). All performed cardiopulmonary tests. Blood samples were collected in order to assess the following measures: lipid profile, HDL anti-oxidant capacity, paraoxonase-1 activity, HDL subfractions, and lipid transfer to HDL. Comparing active older and active young groups with inactive older and inactive young groups, respectively, the active groups presented higher HDL-C levels (p < 0.01 for both comparisons), unesterified cholesterol transfer (p < 0.01, p < 0.05), and intermediate and larger HDL subfractions (p < 0.001, p < 0.01) than the respective inactive groups. In addition, the active young group showed higher esterified cholesterol transfer than the inactive young group (p < 0.05). As expected, the two active groups had higher VO2peak than the inactive groups; VO2peak was higher in the two younger than in the two older groups (p < 0.05). No differences in unesterified and esterified cholesterol transfers and HDL subfractions were found between active young and active older groups. HDL anti-oxidant capacity and paraoxonase-1 activity were equal in all four study groups. Our data highlight and strengthen the benefits of regular practice of physical activity on an important HDL function, the capacity of HDL to receive cholesterol, despite the age-dependent decrease in VO2peak.

Empowering frail older adults: multicomponent elastic-band exercises and BCAA supplementation unleash physical health and preserve haematological biomarkers.

The effectiveness of Branched Chain Amino Acids (BCAAs) supplementation on enhancing exercise performance in both young and older adults remains a topic of debate. Recent research suggests that BCAAs combined with regular exercise might have an impact on human erythropoiesis, blood dynamics, and iron homeostasis. Given the increasing longevity of the global population, it is crucial to investigate the potential benefits of BCAA supplementation and regular exercise as non-pharmacological interventions for improving the overall health of frail older adults. To assess the influence of a 40-week multicomponent exercise intervention (MEP) combined BCCA supplementation on the haematological indicators of frail older adults (83-93 years old) residing in nursing homes. A prospective, naturalistic, controlled clinical trial employing an intervention-washout-intervention was conducted for this purpose. The study included four experimental groups: MEP plus BCAA supplementation (MEP + BCAA, n = 8), MEP only (n = 7), BCAA supplementation only (n = 7), and control group non exercising (CG, n = 13). Fried's physical frailty (PF) protocol was employed to stratify the participants. Additionally, the assessment included the evaluation of nutritional status, comorbidities, and anthropometric measurements. Among the several haematological markers examined, only mean cellular Haemoglobin Concentration (MCH) [F = 4.09; p < 0.03] and Mean Cell haemoglobin Concentration (MCHC) [F = 10, 323; p < 0,0001] showed significant effects of time group. Our findings demonstrate that a long-term intervention with BCAA plus MEP did not lead to significant alterations in the haematological profile. An 8-week withdrawal from interventions did not affect the frailty status in the MEP and MEP + BCAA groups, whereas the control group exhibited an increase in PF status. The findings, demonstrating the potential pro-immune effect and maintenance of MCH and MCHC levels, highlight the relevance of incorporating exercise and nutritional strategies to promote healthy aging. This study contributes to the achievement of the United Nations Sustainable Development Goals 3 (good health and well-being) and 10 (reduced Inequalities) for all.

Roux-en-Y Gastric Bypass Improves Adiponectin to Leptin Ratio and Inflammatory Profile in Severely Obese Women with and without Metabolic Syndrome: A Randomized Controlled Trial.

Obesity is a troubling public health problem as it increases risks of sleep disorders, respiratory complications, systemic arterial hypertension, cardiovascular diseases, type 2 diabetes mellitus, and metabolic syndrome (MetS). As a measure to counteract comorbidities associated with severe obesity, bariatric surgery stands out. This study aimed to investigate the adiponectin/leptin ratio in women with severe obesity with and without MetS who had undergone Roux-en-Y gastric bypass (RYGB) and to characterize the biochemical, glucose, and inflammatory parameters of blood in women with severe obesity before and after RYGB. Were enrolled females with severe obesity undergoing RYGP with MetS (n = 11) and without (n = 39). Anthropometric data and circulating levels of glucose, total cholesterol, high-density lipoprotein (HDL), non-HDL total cholesterol, low-density lipoprotein (LDL), adiponectin, and leptin were assessed before and 6 months after RYGB. Significant reductions in weight, body mass index, and glucose, total cholesterol, LDL, and leptin were observed after surgery, with higher levels of HDL, adiponectin, and adiponectin/leptin ratio being observed after surgery compared to the preoperative values of those. This study demonstrated that weight loss induced by RYGB in patients with severe obesity with or without MetS improved biochemical and systemic inflammatory parameters, particularly the adiponectin/leptin ratio.

Effects of Roux-en-Y gastric bypass on the metabolic profile and systemic inflammatory status of women with metabolic syndrome: randomized controlled clinical trial.

BACKGROUND: Obesity remains a public health problem worldwide. The high prevalence of this condition in the population raises further concerns, considering that comorbidities are often associated with obesity. Among the comorbidities closely associated with obesity, metabolic syndrome (MS) is particularly important, which potentially increases the risk of manifestation of other disorders, such as the prothrombotic and systemic pro-inflammatory states. METHODS: A randomized, controlled clinical trial was performed involving female patients (n = 32) aged between 18 and 65 years, with a clinical diagnosis of MS, with severe obesity undergoing Roux-en-Y gastric bypass (RYGB). The study design followed the Consolidated Standards of Reporting Trials statement (CONSORT). Lipid profile, blood glucose and adipokines (adiponectin, leptin, and resistin) and (cytokines IL-1ß, IL-6, IL-17, IL-23, and TNF-α) in blood plasma samples were evaluated before and six months after RYGB. RESULTS: Patients undergoing RYGB (BSG) showed a significant improvement from preoperative grade III obesity to postoperative grade I obesity. The results showed that while HDL levels increased, the other parameters showed a significant reduction in their postoperative values when compared not only to the values observed before surgery in the BSG group, but also to the values obtained in the control group (CG). As for systemic inflammatory markers adiponectin, leptin, resistin, IL-1ß, IL-6, IL-17, IL-23 and TNF- α it was observed that the levels of resistin and IL-17 in the second evaluation increased significantly when compared to the levels observed in the first evaluation in the CG. In the BSG group, while the levels of adiponectin increased, the levels of the other markers showed significant reductions in the postoperative period, in relation to the respective preoperative levels. The analysis of Spearman's correlation coefficient showed a significant positive correlation between IL-17 and IL-23 in the preoperative period, significant positive correlations between TNF-α and IL-6, TNF-α and IL-17, IL-6 and IL-17, and IL-17 and IL-23 were observed postoperatively. CONCLUSIONS: According to our results, the reduction of anthropometric measurements induced by RYGB, significantly improves not only the plasma biochemical parameters (lipid profile and glycemia), but also the systemic inflammatory status of severely obese patients with MS. Trials registration NCT02409160.

From Young to Older, the 4 Phases Method Is Efficient in Promoting Quick Weight, BMI, and Waist Circumference Reductions.

Background: Investigate the effectiveness of the scientific 4 Phases Method, a methodology developed by EMAGRECENTRO, which is based on a ketogenic approach (total carbohydrate intake <40 g/day; including fibers) associated with health coach assistance, in promoting reductions in body weight, body mass index (BMI), and waist circumference after 5 weeks of methodology application. Methods: Record files from 354 individuals, both sexes, aged between 18 and 67, who took part in the 4 Phases Method were used to develop this study. Age, sex, weight, height, BMI, waist circumference measurement, and the presence of ketone bodies in the urine were evaluated before (baseline) and after 5 weeks of the 4 Phases application. Results: In general, a significant reduction in body weight (−7.8 ± 1.2 kg, p < 0.0001), BMI (−2.8 ± 0.4 kg/m2, p < 0.0001), and waist circumference measurement (−7.6 ± 0.4 cm, p < 0.0001) was found after the application of the 4 Phases Method, regardless of age, gender, and BMI. Conclusions: Taken together, our results demonstrated that the 4 Phases Method was able to promote significant body weight, BMI, and waist circumference reductions in the short term, particularly by associating a ketogenic intake strategy with a regular close follow-up weekly consultation with a health coach assistance.

Salivary Proteome, Inflammatory, and NETosis Biomarkers in Older Adult Practitioners and Nonpractitioners of Physical Exercise.

Since aging has been associated with increased production of inflammatory biomarkers, the ability to monitor older adults repeatedly is highly desirable, and saliva is an interesting biofluid for the search of biomarkers, as it is easily accessible in a noninvasive manner. However, given the incipient knowledge of salivary biomarkers in aging and its relationship to physical exercise, the present study is aimed at evaluating the protein expression and the levels of inflammatory and NETosis biomarkers in the saliva of practitioners (PE) and nonpractitioners (NPE) of physical exercise older adults. Six (6) practitioner and 4 nonpractitioner older adults were enrolled in this study. Unstimulated whole saliva was collected for analysis of the proteome by label-free mass spectrometry, as well as of the inflammatory status by evaluation of C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and cytokines (TNF-α, interleukin- (IL-) 1ß, and IL-8), while NETosis was assessed by myeloperoxidase (MPO) and neutrophil elastase. Regarding oral health, the decayed, missing, and filled teeth (DMF-T) index, bleeding on probing, suppuration, and probing depth measurement (mm) were evaluated. In addition, functional capacity was investigated using the General Physical Fitness Index (GPFI). In relation to the proteome analysis, 93 and 143 proteins were found exclusively in the PE and NPE groups, respectively; 224 proteins were common to both groups. Among these proteins, 10 proteins showed statistical difference (p < 0.05) between the groups: alpha-2-macroglobulin, component 3 of the complement, serotransferrin, and protein soluble in brain acid 1 were less expressed, while lactotransferrin, alpha-amylase 1, S100-A8, S100-A9, lactoperoxidase, and galectin-3 binding protein were more expressed in the PE group. No differences between groups were observed in the analysis of inflammatory and NETosis biomarkers. This study shows the potential utility of saliva for detecting protein biomarkers in a noninvasive biological sample of the elderly population.

Vertical Jump Tests: A Safe Instrument to Improve the Accuracy of the Functional Capacity Assessment in Robust Older Women.

Age-related decreases in muscle function lead to disabilities and are associated with negative health outcomes in older people. Although several physical tests can be used to assess physical performance, muscle strength, and power, their interpretation can be hampered by the ceiling effect of some of them. The aim of this study was to assess whether vertical jump tests are safe in terms of physical integrity and whether they are useful in assessing physical performance in forty-one robust older women. The investigation entailed an assessment of anthropometric characteristics, physical functioning tests (Short Physical Performance Battery (SPPB), sit-to-up 5 times and sit-to-up 30 s, gait speed, time-up-to-go test (TUGT)), and tests evaluating muscle strength and power (handgrip, lower limb isokinetic tests, and vertical jumping tests). Significant negative correlations were found between vertical jumping tests and BMI, body fat percentage, sit-to-up 5 times and TUGT. In addition, significant positive correlations were observed between vertical jumping tests and SPPB, gait speed, handgrip, and concentric isokinetic tests of knee muscles. No adverse events in volunteers' physical integrity were reported during and after the performance of all physical tests. Thus, the study results showed that vertical jumping tests are safe and accurate for assessing physical performance and are useful for monitoring age-related loss of muscle performance in robust older women.

Better Response to Influenza Virus Vaccination in Physically Trained Older Adults Is Associated With Reductions of Cytomegalovirus-Specific Immunoglobulins as Well as Improvements in the Inflammatory and CD8+ T-Cell Profiles.

Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups-non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)-for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p < 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p < 0.05) and CET (p < 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p < 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p < 0.05 and p < 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p < 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p < 0.05) and increased IL-10 levels post-vaccination (p < 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.

l-Glutamine supplementation enhances glutathione peroxidase and paraoxonase-1 activities in HDL of exercising older individuals.

BACKGROUND: Oxidative stress is an important factor in the formation of atherosclerotic plaques. High-density lipoprotein (HDL) harbors paraoxonase-1 (PON-1) and glutathione peroxidase (GPx), key enzymes in the protection against the harmful effects of oxidative stress. Although exercise training can increase both HDL-c content and its antioxidant action, and glutamine (Gln) intake also promotes GPx-based defenses, the association between exercise training and Gln in the regulation of PON-1 activity was not explored. Therefore, the objective of this study was to investigate the effects of Gln supplementation on the redox balance and on the total HDL antioxidant capacity by evaluation of the activity of PON-1 and GPx enzymes in physically exercised elderly individuals compared to non-exercised ones. METHODS: Fifty-one practitioners of a combined exercise training program (CET, age: 71.9 ± 5.7 years) and 32 non-practitioners (NP, age: 73 ± 6.3 years) participated in the study. CET and NP groups were separated into 2 subgroups according to the supplementation: Gln, 0.3 g/kg/day + 10 g maltodextrin (CET-Gln, n = 26; and NP-Gln, n = 16) or placebo, 10 g maltodextrin (CET-PL, n = 25; and NP-PL, n = 16). Blood samples were drawn at baseline and after 30 days after commencement of the supplementation for biochemical and enzyme activity analyses. RESULTS: Increased HDL-c, total peroxidase (PRx), and GPx activities were found in both CET-Gln and NP-Gln after the supplementation period, compared to baseline, in opposition to CET-PL and NP-PL groups. PON-1 activity increased only in CET-Gln. In both CET-Gln and NP-Gln groups, there was a reduction of the total peroxides/PRx, iron/PRx, and total peroxides/GPX ratios after supplementation. In CET-Gln, thiobarbituric acid-reactive substances (TBARS)/PRx and TBARS/GPx ratios were also lower after supplementation. CET-Gln and CET-PL subgroups had lower glycemia than NP-Gln and NP-PL, either at baseline or after the supplementation periods. The other parameters were unchanged after supplementation [total cholesterol, LDL-c, triglycerides, non-HDL cholesterol, total peroxides, TBARS, iron serum, Trolox-equivalent antioxidant capacity (TEAC), and uric acid]. CONCLUSIONS: Gln supplementation can increase glutathione peroxidase activity regardless the individuals were physically active or sedentary, but the PON-1 activity only increased in physically active individuals. These results show the potential of Gln supplementation in the maintenance of the vascular redox balance, with potential implications for atherogenesis protection.

Effect of Training-Detraining Phases of Multicomponent Exercises and BCAA Supplementation on Inflammatory Markers and Albumin Levels in Frail Older Persons.

Nowadays, it is accepted that the regular practice of exercise and branched-chain amino acids supplementation (BCAAs) can benefit the immune responses in older persons, prevent the occurrence of physical frailty (PF), cognitive decline, and aging-related comorbidities. However, the impact of their combination (as non-pharmacological interventions) in albumin and the inflammatory markers is not fully understood. Therefore, we investigated the effect of a 40-week multifactorial intervention [MIP, multicomponent exercise (ME) associated or not with BCAAs] on plasma levels of inflammatory markers and albumin in frail older persons (≥75 years old) living at residential care homes (RCH). This study consisted of a prospective, naturalistic, controlled clinical trial with four arms of multifactorial and experimental (interventions-wahshout-interventions) design. The intervention groups were ME + BCAAs (n = 8), ME (n = 7), BCAAs (n = 7), and control group (n = 13). Lower limb muscle-strength, cognitive profile, and PF tests were concomitantly evaluated with plasma levels of albumin, anti- and pro-inflammatory cytokines [Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) respectively], TNF-α/IL-10 ratio, and myeloperoxidase (MPO) activity at four different time-points: Baseline (T1), after 16 weeks of multifactorial intervention (T2), then after a subsequent 8 weeks washout period (T3) and finally, after an additional 16 weeks of multifactorial intervention (T4). Improvement of cognitive profile and muscle strength-related albumin levels, as well as reduction in the TNF-α levels were found particularly in ME plus BCAAs group. No significant variations were observed over time for TNF-α/IL-10 ratio or MPO activity. Overall, the study showed that MIP triggered slight alterations in the inflammatory and physical function of the frail older participants, which could provide independence and higher quality of life for this population.

L-Glutamine Supplementation Enhances Strength and Power of Knee Muscles and Improves Glycemia Control and Plasma Redox Balance in Exercising Elderly Women.

We investigated the effects of oral L-glutamine (Gln) supplementation, associated or not with physical exercises, in control of glycemia, oxidative stress, and strength/power of knee muscles in elderly women. Physically active (n = 21) and sedentary (n = 23) elderly women aged 60 to 80 years were enrolled in the study. Plasma levels of D-fructosamine, insulin, reduced (GSH) and oxidized (GSSG) glutathione, iron, uric acid, and thiobarbituric acid-reactive substances (TBARs) (lipoperoxidation product), as well as knee extensor/flexor muscle torque peak and average power (isokinetic test), were assessed pre- and post-supplementation with Gln or placebo (30 days). Higher plasma D-fructosamine, insulin, and iron levels, and lower strength/power of knee muscles were found pre-supplementation in the NPE group than in the PE group. Post-supplementation, Gln subgroups showed higher levels of GSH, GSSG, and torque peak, besides lower D-fructosamine than pre-supplementation values. Higher muscle average power and plasma uric acid levels were reported in the PE + Gln group, whereas lower insulin levels were found in the NPE + Gln than pre-supplementation values. TBARs levels were diminished post-supplementation in all groups. Gln supplementation, mainly when associated with physical exercises, improves strength and power of knee muscles and glycemia control, besides boosting plasma antioxidant capacity of elderly women.

Elderly Subjects Supplemented with L-Glutamine Shows an Improvement of Mucosal Immunity in the Upper Airways in Response to Influenza Virus Vaccination.

BACKGROUND: Although glutamine is able to improve the immune response, its action in the upper airway immunity against the influenza virus vaccine remains unclear. Therefore, we aimed to evaluate the L-glutamine supplementation effect on the mucosal immune/inflammatory response of elderly subjects vaccinated against the influenza virus. METHODS: Saliva sampling from 83 physically active elderly volunteers were collected pre- and 30 days after influenza virus vaccination and supplementation with L-glutamine (Gln, n = 42) or placebo (PL, n = 41). RESULTS: Gln group showed higher salivary levels of interleukin (IL)-17, total secretory immunoglobulin A (SIgA), and specific-SIgA post-vaccination than values found pre-vaccination and in the PL group post-vaccination. Whereas higher salivary levels of IL-6 and IL-10 were observed post-vaccination in the Gln group, IL-37 levels were lower post-vaccination in both groups than the values pre-vaccination. Tumor necrosis factor (TNF)-α levels were unchanged. Positive correlations between IL-6 and IL-10 were found in all volunteer groups pre- and post-vaccination and also between IL-17 and IL-6 or IL-10 in the Gln group post-vaccination. A negative correlation between IL-37 and IL-10 was found pre- and post-vaccination in the PL group. CONCLUSION: Gln supplementation was able to modulate salivary cytokine profile and increase SIgA levels, both total and specific to the influenza virus vaccine, in physically active elderly subjects.

Combined Exercise Training and l-Glutamine Supplementation Enhances Both Humoral and Cellular Immune Responses after Influenza Virus Vaccination in Elderly Subjects.

BACKGROUND: Since aging affects the immune responses against vaccination, the present study evaluated the effects of L-glutamine (Gln) supplementation in the humoral and cellular immune responses in elderly subjects, practitioners or not, of physical exercise training. METHODS: Eighty-four elderly people (aged 72.6 ± 6.1), non-practitioners (NP, n = 31), and practitioners of combined-exercise training (CET, n = 53) were submitted to Influenza virus vaccination and supplemented with Gln (0.3 g/kg of weight + 10 g of maltodextrin, groups: NP-Gln (n = 14), and CET-Gln (n = 26)), or placebo (10 g of maltodextrin, groups: NP-PL (n = 17), and CET-PL (n = 27)). Blood samples were collected pre (baseline) and 30 days post-vaccination and supplementation. RESULTS: Comparing with the baseline values, whereas the NP-Gln and CET-PL groups showed higher specific-IgM levels, the CET-Gln group showed higher specific-IgM and IgA levels post-vaccination. The titer rate of hemagglutination inhibition was higher in the CET-Gln, NP-PL, and NP-Gln groups post-vaccination than baseline values. The absolute number of naive and effector CD4+ T cells was higher especially in the NP-Gln and CET-Gln groups, whilst activated CD4+ T cells were higher in CET subgroups post-vaccination. CONCLUSION: Our results showed that both l-glutamine supplementation and combined-exercise training can improve the immune responses to the Influenza virus vaccine in elderly subjects.

Chronic alteration of circadian rhythm is related to impaired lung function and immune response.

BACKGROUND: Alterations of the circadian rhythm negatively impact several aspects of the health, including the lung function. Chronic shiftwork scale classically induces alterations in the circadian rhythm. However, its effects on pulmonary immune response are unknown. AIMS: To evaluate the impact of chronic alteration of circadian rhythm on pulmonary function and immune response. METHODS: In this context, a 12 × 24 hours and 12 × 48 hours work scale in shiftwork scale policemen (n = 25; 38.73 ± 6.92 years old) were compared with fixed work scale (8 h/d) civil men (n = 25; 34.00 ± 9.60 years old) who were evaluated for perceived stress, sleepiness, physical activity levels, anthropometric characteristics, lung function, pulmonary and systemic cellular and humoral immune response. RESULTS: Policemen presented increased levels of perceived stress (P < .0008), impaired sleepiness (P < .04) and lung function as demonstrated by reduced forced vital capacity (FVC) (P < .053) and FEV1 (P < .043) when compared with civil men. In addition, increased levels of exhaled nitric oxide (P < .037) and of IL-2 (P < .0046) in the breath condensate revealed that policemen presented chronic lung inflammation compared with civil men. Although the whole blood analysis did not showed any differences between the two groups concerning the number of leucocytes, the humoral response revealed that policemen presented increased levels of IL-2 (P < .002) and lower levels of IL-10 (P < .001), clearly displaying a clinical status of low-grade inflammation. CONCLUSIONS: Chronic alteration of circadian rhythm in shiftwork scale policemen results in impaired lung function, beyond to impair pulmonary and systemic immune function.

L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals.

Although regular combined aerobic-resistance exercises can ameliorate the inflammatory status and redox balance in elderly population, it is unclear whether protein or specific amino acid supplementation could improve such benefits. Therefore, we aimed to evaluate the inflammatory status and redox indexes through of the saliva of 34 elderly subject nonpractitioners (NP group, 73.3 ± 6.6 years) and 49 elderly subject practitioners of a combined-exercise training in moderate intensity (CET group, 71.9 ± 5.8 years) before (pre) and after (post) 30 days of supplementation with L-glutamine (Gln) or placebo (PL). Our results showed that, both in pre- and postsupplementation, the salivary levels of nitric oxide (NO·) and TNF-α were lower, whereas the levels of uric acid and IL-10 (as well as IL-10/TNF-α ratio) were higher in the CET groups than in the NP groups. In postsupplementation, both groups supplemented with Gln (NP-Gln and CET-Gln) showed higher salivary uric acid levels compared to baseline. In addition, lower NO· levels were found in the CET-Gln group postsupplementation than presupplementation values. Whereas the CET-Gln group showed lower GSH levels postsupplementation, NP-Gln subjects showed lower GSSG levels at the same time point, both compared to baseline. Interestingly, salivary peroxidase activity was lower only in NP groups (NP-PL and NP-Gln) postsupplementation than baseline values. A positive significant correlation between salivary peroxidase activity and GSH levels, and also between salivary peroxidase activity and uric acid levels were observed in the CET-Gln group both pre- and postsupplementation. No differences were found in albumin, total antioxidant activity (TEAC), and reducing power analysis between groups, pre- or postsupplementation. In conclusion, the elderly subjects from the CET group showed a better inflammatory response and redox balance and, for the first time, it was shown that daily supplementation with Gln for 30 days can improve these benefits with putative association with a healthy aging.

New Insights on the Effect of TNF Alpha Blockade by Gene Silencing in Noise-Induced Hearing Loss.

Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor α (TNFα) was involved in this context. The effect of Tnfα gene silencing on the expression profile related to the TNFα metabolic pathway in an experimental model of noise-induced hearing loss had not previously been studied. METHODS: Single ears of Wistar rats were pretreated with Tnfα small interfering RNA (siRNA) by trans-tympanic administration 24 h before they were exposed to white noise (120 dBSPL for three hours). After 24 h of noise exposure, we analyzed the electrophysiological threshold and the amplitude of waves I, II, III, and IV in the auditory brain response click. In addition, qRT-PCR was performed to evaluate the TNFα metabolic pathway in the ears submitted or not to gene silencing. RESULTS: Preservation of the electrophysiological threshold and the amplitude of waves was observed in the ears submitted to gene silencing compared to the ears not treated. Increased anti-apoptotic gene expression and decreased pro-apoptotic gene expression were found in the treated ears. CONCLUSION: Our results allow us to suggest that the blockade of TNFα by gene silencing was useful to prevent noise-induced hearing loss.

Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis.

Cardiovascular benefits for the general population of combined aerobic-resistance exercise training are well-known, but the impact of this exercise training modality on the plasma lipid, inflammatory, and antioxidant status in elderly women that are exposed to a great risk of developing ischemic cardio- and cerebrovascular diseases has not been well investigated. So, we aimed to evaluate the plasma lipids, oxidative stress, and inflammatory cytokines in 27 elderly women (TRAINED group, 69.1 ± 8.1 yrs) that were performing moderate intensity combined aerobic-resistance exercise training (3 times/week for at least 18 months) and in 27 sedentary elderly women (SED group, 72.0 ± 6.4 yrs), not submitted to exercise training for at least 5 yrs. Our results showed that BMI was lower in the TRAINED group than in the SED group (25.1 ± 3.2 vs. 28.7 ± 5.1, p < 0.05). The TRAINED group had lower glycemia (92 ± 3 vs. 118 ± 12, p < 0.05), glycated hemoglobin (5.9 ± 0.1 vs. 6.4 ± 0.2, p < 0.05), and triglycerides (98 (75-122) vs. 139 (109-214), p < 0.01); equal total cholesterol (199 (175-230) vs. 194 (165-220)), LDL-cholesterol (108 (83-133) vs. 109 (98-136)), and non-HDL-cholesterol (54 (30-74) vs. 62 (26-80)); and also higher HDL-cholesterol (64 (52-77) vs. 52 (44-63), p < 0.01) and LDL-C/oxLDL ratio (13378 ± 2570 vs. 11639 ± 3113, p < 0.05) compared to the SED group. Proinflammatory cytokines as IL-1ß (11.31 ± 2.4 vs. 28.01 ± 4.7, p < 0.05), IL-6 (26.25 ± 7.4 vs. 49.41 ± 17.8, p < 0.05), and TNF-α (25.72 ± 2.8 vs. 51.73 ± 4.2, p < 0.05) were lower in the TRAINED group than in the SED group. The TRAINED group had lower total peroxides (26.3 ± 7.4 vs. 49.0 ± 17.8, p < 0.05) and oxidized LDL (1551 ± 50.33 vs. 1773 ± 74, p < 0.02) and higher total antioxidant capacity (26.25 ± 7.4 vs. 49.41 ± 17.8, p < 0.001) compared to the SED group. In conclusion, in TRAINED women, BMI was lower, plasma lipid profile was better, plasma oxidative stress was diminished, and there was less expression of proinflammatory interleukins than in SED, suggesting that combined aerobic-resistance exercise training may promote the protection against the complications of ischemic cardio- and cerebrovascular disease in elderly women.