A phytotherapic blend immunity-6™ inhibits myeloid leukemic cells 2 activation involving purinergic signaling.

Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.

Therapeutic use of intravenous selenium in respiratory and immunological diseases: evidence based on reviews focused on clinical trials.

The oxidative stress caused by systemic inflammatory response syndrome (SIRS), septic shock, and sepsis, is a risk factor triggering an increase in mortality in patients diagnosed with these pathologies. Selenium (Se) is an essential mineral that has antioxidant and cytoprotective functions, being strongly associated with the proper functioning of intracellular metabolic processes. In this context, the present study aims to investigate de therapeutic effects of intravenous selenium use considering pathologies such as SIRS, septic shock, sepsis, acute respiratory distress syndrome (ARDS), ventilator associated pneumonia (VAP), and coronavirus disease (COVID-19). This is an narrative literature review in which six main articles found in databases of SciELO, PubMed, and Google Scholar, were selected and analyzed. As a result, articles were found evidencing the benefit of Se in the inflammatory response, increasing the GPx-3 activity and decreasing the inflammatory cytokines, in addition to generating a lower risk of VAP, shortening the hospitalization time, and mortality. Thus, Se supplementation has beneficial evidence for acute respiratory diseases and should be considered as a viable option as adjuvant therapy.

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.

The use of a pre-workout supplement containing an amphetamine derivative and its effects on physical performance / Uso de suplemento pre-entrenamiento que contiene un derivado anfetamínico y sus efectos sobre el desempeño físico / Uso de suplemento pré-treino que contém um derivado anfetaminico e seus efeitos sobre o desempenho físico

ABSTRACT Introduction: The quest for better sports performance or simply for esthetic ends has led individuals to seek ergogenic resources indiscriminately to attain their goals. It is believed that nutritional supplements promote better strength, power, focus and better reaction time. Nutritional supplements are used to delay fatigue and increase athletic performance. Also, the anorectics, drugs derived from amphetamines and commonly sought for weight loss, act on the central nervous system by releasing substances that transmit the sensation of not being hungry. Supplements that promise quick solutions to these goals may have compounds in their formulas that compromise health. Objectives: In this study, the potential of creatine and Jack 3D® to boost physical performance and delay muscle fatigue was evaluated in animals that were given the supplements. Methods: The animals underwent 10 weeks of swim training at 80% of the maximum load and received creatine and/or Jack 3D. The muscle contractions were recorded by an electrophysiograph for analysis of muscle fatigue. Results: It was observed that the SED+CR group had significantly different values compared to the SED group and NAT+CR group showed significant differences between groups for the SED, SED+JACK, JACK, NAT and NAT+JACK groups (p <0.05). For the two last parameters, the SED group showed a significant difference in relation to the SED+CR, NAT and NAT+CR groups (p <0.05). Conclusions: These results demonstrate a possible positive influence of physical exercise associated with the use of creatine, delaying muscle fatigue and making an increase in sports performance possible. Level of Evidence III; Development of diagnostic criteria in consecutive patients (with "gold" reference standard applied) .

RESUMEN Introducción: La búsqueda por el mejor desempeño deportivo o simplemente para fines estéticos ha inducido a los individuos a buscar indiscriminadamente recursos ergogénicos para alcanzar el éxito. Se cree que la ingestión de suplementos nutricionales puede proporcionar mayor resistencia, potencia, enfoque y mejor tiempo de reacción. Los suplementos nutricionales son empleados para retardar el surgimiento de la fatiga y aumentar el desempeño atlético. También comúnmente buscados para adelgazamiento están los anorexígenos, medicamentos a base de drogas anfetamínicas, que actúan sobre el sistema nervioso central liberando sustancias que transmiten la sensación de ausencia de hambre. Los suplementos que prometen soluciones rápidas para estos objetivos pueden presentar en sus fórmulas, compuestos que comprometen la salud. Objetivo: En este estudio fue evaluado el potencial de la creatina y del Jack3D® para el desempeño físico y la fatiga muscular de los animales que recibieron la suplementación. Métodos: Los animales fueron sometidos a 10 semanas de entrenamiento de natación a 80% de la carga máxima y recibieron creatina y/o Jack3D. Las contracciones musculares fueron registradas por un electrofisiógrafo para análisis de la fatiga muscular. Resultados: Se observó que el grupo SED+CR presentó valores significativamente diferentes en comparación con el grupo SED y el grupo NAT+CR presentó diferencias significativas con relación a los grupos SED, SED+JACK, NAT y NAT+JACK (p < 0,05). En los dos últimos parámetros, el grupo SED presentó diferencia significativa con relación a los grupos SED+CR, NAT y NAT+CR (p < 0,05). Conclusión: Esos resultados demuestran una posible influencia positiva del ejercicio físico asociado al uso de la creatina, retardando la fatiga muscular y posibilitando un aumento en el desempeño deportivo. Nivel de evidencia III; Desarrollo de criterios diagnósticos en pacientes consecutivos (con estándar de referencia "oro" aplicado) .

RESUMO Introdução: A busca pelo melhor rendimento esportivo ou simplesmente para fins estéticos tem induzido indivíduos a procurarem indiscriminadamente recursos ergogênicos para atingir o êxito. Acredita-se que a ingestão de suplementos nutricionais pode proporcionar maior resistência, potência, foco e melhor tempo de reação. Os suplementos nutricionais são empregados afim de retardar o surgimento da fadiga e aumentar o desempenho atlético. Também comumente procuradas para emagrecimento estão os anorexígenos, medicamentos à base de drogas anfetamínicas, que agem sobre o sistema nervoso central liberando substâncias que transmitem a sensação de ausência de fome. Suplementos que prometem soluções rápidas para estes objetivos podem conter em suas fórmulas compostos que comprometem a saúde. Objetivos: Neste estudo foi avaliado o potencial da creatina e do Jack 3D®para o desempenho físico e fadiga muscular dos animais que receberam a suplementação. Métodos: Os animais foram submetidos a 10 semanas de treinamento de natação a 80% da carga máxima e receberam creatina e/ou Jack 3D. As contrações musculares foram registradas por um eletrofisiógrafo para análise da fadiga muscular. Resultados: Observou-se que o grupo SED+CR apresentou valores significativamente diferentes em comparação com o Grupo SED e o Grupo NAT+CR apresentou diferenças significativas com relação aos grupos SED, SED+JACK, NAT e NAT+JACK (p < 0,05). Nos dois últimos parâmetros, o Grupo SED apresentou diferença significativa com relação aos grupos SED+CR, NAT e NAT+CR (p < 0,05). Conclusão: Esses resultados demonstram uma possível influência positiva do exercício físico associado ao uso da creatina, retardando a fadiga muscular e possibilitando um aumento no desempenho esportivo. Nível de Evidência III; Desenvolvimento de critérios diagnósticos em pacientes consecutivos (com padrão de referência "ouro" aplicado) .

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.

Creatine Supply Attenuates Ischemia-Reperfusion Injury in Lung Transplantation in Rats.

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

Anti-Inflammatory Activity of Miodesin™: Modulation of Inflammatory Markers and Epigenetic Evidence.

PURPOSE: To investigate the effects of a combined herbal medicine Miodesin™ on the inflammatory response of key cells involved in the acute and chronic inflammatory processes as well as the possible epigenetic involvement. METHODS: After the establishment of the IC50 dose, the chondrocyte, keratinocyte, and macrophage cell lines were pretreated for 2 hours with Miodesin™ (200 µg/mL) and stimulated with LPS (1 µg/mL) for 24 hours. The supernatant was used to measure the levels of cytokines (IL-1ß, IL-6, IL-8, and TNF-α) and chemokines (CCL2, CCL3, and CCL5), and the cells were used to extract the mRNA for the transcription factor (NF-κß), inflammatory enzymes (COX-1, COX-2, PLA2, and iNOS), and chemokines (CCL2, CCL3, and CCL5). RESULTS: Miodesin™ inhibited the release of LPS-induced cytokines (IL-1ß, IL-6, IL-8, and TNF-α; p < 0.01) and chemokines (CCL2, CCL3, and CCL5; p < 0.01) and the expression of the transcription factor (NF-κß; p < 0.01), inflammatory enzymes (COX-1, COX-2, PLA2, iNOS; p < 0.01), and chemokines (CCL2, CCL3, and CCL5; p < 0.01). In addition, the evaluation of epigenetic mechanism revealed that Miodesin™ did not induce changes in DNA methylation, assuring the genetic safeness of the compound in terms of the inflammatory response. CONCLUSIONS: Miodesin™ presents anti-inflammatory properties, inhibiting hyperactivation of chondrocytes, keratinocytes, and macrophages, involving epigenetics in such effects.

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.

A Mixture of Polyunsaturated Fatty Acids ω-3 and ω-6 Reduces Melanoma Growth by Inhibiting Inflammatory Mediators in the Murine Tumor Microenvironment.

BACKGROUND: Although it has been previously demonstrated that acute inflammation can promote the tumor growth of a sub-tumorigenic dose of melanoma cells through of 5-lipoxygenase inflammatory pathway and its product leukotriene B4, and also that the peritumoral treatment with eicosapentaenoic acid and its product, leukotriene B5, reduces the tumor development, the effect of the treatment by gavage with omega-3 and omega-6 in the tumor microenvironment favorable to melanoma growth associated with acute inflammation has never been studied. METHODS: C57BL/6 mice were coinjected with 1 × 106 apoptotic cells plus 1 × 103 viable melanoma cells into the subcutaneous tissue and treated by gavage with omega-3-rich fish oil or omega-6-rich soybean oil or a mixture of these oils (1:1 ratio) during five consecutive days. RESULTS: The treatment by gavage with a mixture of fish and soybean oils (1:1 ratio) both reduced the melanoma growth and the levels of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), PGE2/prostaglandin E3 (PGE3) ratio, and CXC ligand 1 (CXCL1) and increased the levels of interleukin 10 (IL-10) to IL-10/CXCL1 ratio in the melanoma microenvironment. CONCLUSION: The oral administration of a 1:1 mixture of fish oil and soybean oil was able to alter the release of inflammatory mediators that are essential for a microenvironment favorable to the melanoma growth in mice, whereas fish oil or soybean oil alone was ineffective.

Creatine supplementation impairs airway inflammation in an experimental model of asthma involving P2 × 7 receptor.

Creatine (Cr) is a substrate for adenosine triphosphate synthesis, and it is the most used dietary supplement among professional and recreative athletes and sportsmen. Creatine supplementation may increase allergic airway response, but the cellular and molecular mechanisms are unknown. We used murine model of OVA-induced chronic asthma and showed that Cr supplementation increased total proteins, ATP level, lymphocytes, macrophages, and IL-5 levels in BALF, as well as IL-5 in the supernatant of re-stimulated mediastinal lymph nodes. IL-5 and IL-13 expression by epithelial cells and by peribronchial leukocytes were increased by Cr. Cr augmented the expression of P2 × 7 receptor by peribronchial leukocytes and by epithelial cells, and increased the accumulation of eosinophils in peribronchial space and of collagen fibers in airway wall. In human cells, while Cr induced a release of ATP, IL-6, and IL-8 from BEAS-2B cells, whole blood cells, such as eosinophils, and CD4+ T cells, P2 × 7 receptor inhibitor (A740003) reduced such effects, as denoted by reduced levels of ATP, IL-6, and IL-8. Therefore, Cr supplementation worsened asthma pathology due to activation of airway epithelial cells and peribronchial leukocytes, involving purinergic signaling.

Acute Effects Using Light-Emitting Diode Therapy (LEDT) for Muscle Function during Isometric Exercise in Asthma Patients: A Pilot Study.

The aim of this study was to evaluate the effectiveness of acute application of LEDT in improving peripheral muscle performance during isometric exercise in patients with asthma. Eleven patients, with a mean age 38 ± 10, underwent a single LEDT and sham application in the femoral quadriceps' dominant member (cluster with 50 LED λ = 850 nm, 50 mW, 15 s; 37.5 J), 48 h apart in a randomized crossover design. Before and after LEDT and sham application, the patients were submitted an isometric endurance test (60% of the maximum isometric voluntary contraction), up to the limit of tolerance simultaneous recording of surface electromyography. There were no statistically significant differences between groups at the time of contraction (before 41±14 versus 44±16; after 46±12 versus 45±20 s) during the isometric contraction test and inflammatory markers before and after a single LEDT application. A single application of LEDT in the parameters and dose according to the equipment used in the study were not able to promote differences in the time of contraction and the fatigue response in asthmatic patients. However, the chronic effects of LEDT application for improving muscle performance in these patients are unknown and may present different responses during applications for a long time.

Low-Level Laser Therapy Reduces Lung Inflammation in an Experimental Model of Chronic Obstructive Pulmonary Disease Involving P2X7 Receptor.

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible airflow limitation, airway inflammation and remodeling, and enlargement of alveolar spaces. COPD is in the top five leading causes of deaths worldwide and presents a high economic cost. However, there are some preventive measures to lower the risk of developing COPD. Low-level laser therapy (LLLT) is a new effective therapy, with very low cost and no side effects. So, our objective was to investigate if LLLT reduces pulmonary alterations in an experimental model of COPD. C57BL/6 mice were submitted to cigarette smoke for 75 days (2x/day). After 60 days to smoke exposure, the treated group was submitted to LLLT (diode laser, 660 nm, 30 mW, and 3 J/cm2) for 15 days and euthanized for morphologic and functional analysis of the lungs. Our results showed that LLLT significantly reduced the number of inflammatory cells and the proinflammatory cytokine secretion such as IL-1ß, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF). We also observed that LLLT decreased collagen deposition as well as the expression of purinergic P2X7 receptor. On the other hand, LLLT increased the IL-10 release. Thus, LLLT can be pointed as a promising therapeutic approach for lung inflammatory diseases as COPD.

Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimental model of lung fibrosis in mice.

Lung fibrosis (LF) is a chronic and progressive lung disease characterized by pulmonary parenchyma progressive lesion, inflammatory infiltration, and interstitial fibrosis. It is developed by excessive collagen deposition and other cellular matrix components, resulting in severe changes in the alveolar architecture. Considering the absence of effective treatment, the aim of this study was to investigate the effect of photobiomodulation therapy (PBMT) on the development of PF. For this purpose, we used C57BL6 mice subjected to induction of LF by bleomycin administration (1.5 U/kg) by orotracheal route and, after 14 days of the induction, mice were treated with PBMT applied to the thorax 1×/day for 8 days (wavelength 660 ± 20 nm, power 100 mW, radiant exposure 5 J/cm2, irradiance 33.3 mW/cm2, spot size 2.8cm2, total energy 15 J, time of irradiation: 150 s) and inflammatory and fibrotic parameters were evaluated with or without PBMT. Our results showed that PBMT significantly reduced the number of inflammatory cells in the alveolar space, collagen production, interstitial thickening, and static and dynamic pulmonary elastance. In addition, we observed reduced levels of IL-6 e CXCL1/KC released by pneumocytes in culture as well as reduced level of CXCL1/KC released by fibroblasts in culture. We can conclude that the PBMT improves both inflammatory and fibrotic parameters showing a promising therapy which is economical and has no side effects.

Bilateral Vertebral Artery Dissection after a Chiropractic Therapy Session

Vertebral artery dissection (VAD) is a rare and sometimes unrecognized cause of stroke in patients younger than 45 years. Herein, we describe a very rare case of bilateral vertebral artery dissection after a session of cervical therapy manipulation (chiropractic).

Vertebral artery dissection (VAD) is a rare and sometimes unrecognized cause of stroke in patients younger than 45 years. Herein, we describe a very rare case of bilateral vertebral artery dissection after a session of cervical therapy manipulation (chiropractic).

Effect of photobiomodulation on endothelial cell exposed to Bothrops jararaca venom.

Bleeding is a common feature in envenoming caused by Bothrops snake venom due to extensive damage to capillaries and venules, producing alterations in capillary endothelial cell morphology. It has been demonstrated, in vivo, that photobiomodulation (PBM) decreases hemorrhage after venom inoculation; however, the mechanism is unknown. Thus, the objective was to investigate the effects of PBM on a murine endothelial cell line (tEnd) exposed to Bothrops jararaca venom (BjV). Cells were exposed to BjV and irradiated once with either 660- or 780-nm wavelength laser light at energy densities of 4 and 5 J/cm(2), respectively, and irradiation time of 10 s. Cell integrity was analyzed by crystal violet and cell viability/mitochondrial metabolism by MTT assay. The release of lactic dehydrogenase (LDH) was quantified as a measure of cell damage. In addition, cytokine IL1-ß levels were measured in the supernatant. PBM at 660 and 780 nm wavelength was able to increase cellular viability and decrease the release of LDH and the loss of cellular integrity. In addition, the concentration of pro-inflammatory cytokine IL1-ß was reduced after PBM by both wavelengths. The data reported herein indicates that irradiation with red or near-infrared laser resulted in protection on endothelial cells after exposure to Bothrops venom and could be, at least in part, a reasonable explanation by the beneficial effects of PBM inhibiting the local effects induced by Bothrops venoms, in vivo.

Photobiomodulation Protects and Promotes Differentiation of C2C12 Myoblast Cells Exposed to Snake Venom.

BACKGROUND: Snakebites is a neglected disease and in Brazil is considered a serious health problem, with the majority of the snakebites caused by the genus Bothrops. Antivenom therapy and other first-aid treatments do not reverse local myonecrose which is the main sequel caused by the envenomation. Several studies have shown the effectiveness of low level laser (LLL) therapy in reducing local myonecrosis induced by Bothropic venoms, however the mechanism involved in this effect is unknown. In this in vitro study, we aimed to analyze the effect of LLL irradiation against cytotoxicity induced by Bothrops jararacussu venom on myoblast C2C12 cells. METHODOLOGY: C2C12 were utilized as a model target and were incubated with B. jararacussu venom (12.5 µg/mL) and immediately irradiated with LLL at wavelength of red 685 nm or infrared 830 nm with energy density of 2.0, 4.6 and 7.0 J/cm2. Effects of LLL on cellular responses of venom-induced cytotoxicity were examined, including cell viability, measurement of cell damage and intra and extracellular ATP levels, expression of myogenic regulatory factors, as well as cellular differentiation. RESULTS: In non-irradiated cells, the venom caused a decrease in cell viability and a massive release of LDH and CK levels indicating myonecrosis. Infrared and red laser at all energy densities were able to considerably decrease venom-induced cytotoxicity. Laser irradiation induced myoblasts to differentiate into myotubes and this effect was accompanied by up regulation of MyoD and specially myogenin. Moreover, LLL was able to reduce the extracellular while increased the intracellular ATP content after venom exposure. In addition, no difference in the intensity of cytotoxicity was shown by non-irradiated and irradiated venom. CONCLUSION: LLL irradiation caused a protective effect on C2C12 cells against the cytotoxicity caused by B. jararacussu venom and promotes differentiation of these cells by up regulation of myogenic factors. A modulatory effect of ATP synthesis may be suggested as a possible mechanism mediating cytoprotection observed under laser irradiation.

Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury.

BACKGROUND: Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage. This study evaluated the effects of Cr supplementation in a model of lung I/R. METHODS: Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response. RESULTS: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleukin-1ß (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized. Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001). CONCLUSIONS: Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and anti-oxidant properties of Cr and modulation of TLRs.

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1ß, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients.