Inhaled molecular hydrogen reduces hippocampal neuroinflammation, glial reactivity and ameliorates memory impairment during systemic inflammation.

Sepsis is associated with numerous physiological and biochemical abnormalities that result in a life-threatening condition. The involvement of the Central Nervous System (CNS) during sepsis has received considerable attention, especially the hippocampus which plays a key role in the learning and memory processes. The increased interest in this limbic region during systemic inflammation (SI) is related to the number of sepsis survivor patients who have cognitive impairments. A single injection of lipopolysaccharide (LPS)-induced systemic inflammation is the most commonly used murine endotoxemia model because it replicates several pathophysiological changes observed in severe sepsis. Molecular hydrogen (H2) has been used as an anti-inflammatory therapeutic strategy to prevent neuroinflammation. However, the mechanisms by which inhaled H2 mitigate memory loss during SI remains unknown. To understand how H2 acts in the hippocampus, the current study focused on specific mechanisms that may be involved in reducing neuroinflammation in rats during SI. We hypothesized that inhaled H2 decreases LPS-induced hippocampal pro-inflammatory cytokines surges and this effect is associated with reduced memory loss. Using different and integrative approaches, i.e., from hippocampal cells electrophysiology to animal behavior, we report that inhaled H2 decreased LPS-induced peripheral and hippocampal inflammation, decreased microglial and astrocytic activation, lessen memory loss without affecting long-term potentiation (LTP). To our knowledge, this is the first evidence showing that inhaled H2 reduces hippocampal microglial and glial cells inflammation, which may be associated with a reduced memory impairment induced by SI.

Inflammatory markers in the hippocampus after audiogenic kindling.

Here, we investigated the participation of pro and anti-inflammatory cytokines in the spread of repeated audiogenic seizures from brainstem auditory structures to limbic areas, including the hippocampus. We used Wistar Audiogenic Rats (WARs) and Wistars submitted to the audiogenic kindling protocol with a loud broad-band noise. We measured pro and anti-inflammatory cytokines and nitrate levels in the hippocampus of stimulated animals. Our results show that all WARs developed audiogenic seizures that evolved to limbic seizures whereas seizure-resistant controls did not present any seizures. However, regardless of seizure severity, we did not observe differences in the pro inflammatory cytokines IL-1ß, IL-6, TNF-α and IFN-α or in the anti-inflammatory IL-10 in the hippocampi of audiogenic and resistant animals. We also did not find any differences in nitrate content. Our data indicate that the spread of seizures during the audiogenic kindling is not dependent on hippocampal release of cytokines or oxidative stress, but the severity of brainstem seizures will be higher in animals with higher levels of cytokines and the oxidative stress marker, nitrate.

Evaluation of clinical and radiographic measures and reliability of the quadriceps angle measurement in elderly women with knee osteoarthritis / Avaliação das medidas radiográficas e clínicas e confiabilidade do ângulo do quadríceps em idosas com osteoartrite de joelhos

Introduction Knees osteoarthritis (OA) is a complex degenerative disease with intra-articular changes affecting the amplitude of the quadriceps angle (Q). To measure this variable, it is necessary to use reliable protocols aiming at methodological reproducibility. The objective was to evaluate the intra-examiner and inter-examiner reliability of clinical and radiographic measures of the Q angle and to investigate the relationship between the degree of OA and the magnitude of this angle in the elderly. Materials and methods 23 volunteers had the Q angle measured by two evaluators at 48-h interval. Clinical measurements were collected by using the universal goniometer in the same position adopted in the radiographic examination. Results The intra-examiner reliability was good (0.722 to 0.763) for radiographic measurements and low (0.518 to 0.574) for clinical assessment, while inter-examiner reliability was moderate (0.634) for radiographic measurements and low (0.499) to the clinics. The correlation analysis between the radiographic values with the OA classification showed no correlation between them (p = 0.824 and r = -0.024). Conclusion Clinically, it is suggested that the radiographic examination is preferable to evaluate the Q angle of elderly women with knee osteoarthritis. Moreover, the magnitude of this angle did not correlate with the degree of impairment of OA in this population.

Introdução A osteoartrite (OA) de joelhos é uma doença degenerativa complexa com alterações intra-articulares que comprometem a amplitude do ângulo do quadríceps (Q). Para mensuração dessa variável, é necessária a utilização de protocolos que apresentem confiabilidade, visando reprodutibilidade metodológica. Objetivo Avaliar a confiabilidade intra e interexaminadores das medidas clínicas e radiográficas do ângulo Q e verificar se existe relação entre o grau de OA e a magnitude deste ângulo em idosas. Materiais e métodos 23 voluntárias, tiveram o ângulo Q mensurado por 2 avaliadores, com intervalo de 48 horas. As medidas clínicas foram coletadas por meio do goniômetro universal na mesma posição adotada no exame radiográfico. Resultados A confiabilidade intraexaminador foi boa (0,722–0,763) nas medidas radiográficas e baixa (0,518–0,574) nas medidas clínicas, enquanto a confiabilidade interexaminadores foi moderada (0,634) nas medidas radiográficas e baixa (0,499) nas clínicas. A análise da correlação entre os valores radiográficos com a classificação da OA não demonstrou correlação entre os mesmos (p = 0,824 e r = -0,024). Conclusão Clinicamente, sugere-se que o exame radiográfico seja preferível para avaliação do ângulo Q de idosas com OA de joelhos. Além disto, a magnitude deste ângulo não se relacionou com o grau de acometimento da OA nesta população.

Association between inflammatory biomarkers in plasma, radiological severity, and duration of exposure in patients with silicosis.

OBJECTIVE: To evaluate the plasma levels of CCL2, CCL3, CCL11, CCL24, tumor necrosis factor alpha, sTNFR1, and sTNFR2 in subjects exposed to silica (SES) with and without silicosis compared with unexposed reference control group, and their associations with the radiological severity and duration of exposure to silica. METHODS: Fifty-seven SES; 36 with silicosis and 22 subjects in control group, were included in the study. RESULTS: CCL3, CCL24, sTNFR1, and sTNFR2 were increased in SES and in SES with silicosis than in controls. There were no differences in the levels of CCL2, CCL11, or tumor necrosis factor alpha. The sTNFR2 level was greater in SES with silicosis than in SES without silicosis. There was a positive correlation between sTNFR1 and sTNFR2 and the radiological severity and time of exposure to silica. sTNFR2 was associated with all categories of radiological severity. CONCLUSION: sTNFR2 is associated with silicosis severity and early exposure to silica.

Biomarcadores inflamatórios na silicose pulmonar / Inflammatory biomarkers in pulmonary silicosis

A silicose representa um importante problema de saúde pública em todo o mundo, sobretudo nos países em desenvolvimento, sendo a principal causa de invalidez entre as doenças respiratórias ocupacionais. É uma pneumoconiose fibrótica, irreversível e potencialmente fatal, causada pela inalação de poeira contendo sílica cristalina. O diagnóstico é estabelecido através da história clínica e ocupacional de exposição à sílica, na presença de alterações radiológicas. Estudos experimentais e clínicos sugerem que a inalação da poeira da sílica está associada a um processo inflamatório pulmonar e sistêmico, mesmo em indivíduos que não desenvolveram silicose. Até o momento não existem exames laboratoriais específicos para o diagnóstico da doença, de modo que o conhecimento de marcadores biológicos associados à imunopatologia da silicose pode ser importante na detecção precoce da instalação e desenvolvimento da doença. O presente artigo traz uma revisão de estudos que investigaram os possíveis biomarcadores inflamatórios da doença no sangue e no lavado bronco-alveolar de humanos e de modelos experimentais.

Silicosis is an important public health problem worldwide, especially in developing countries and is the leading cause of disability among occupational respiratory diseases. It is a fibrotic disease irreversible and potentially fatal caused by inhaling dust containing crystalline silica, the most frequent type of pneumoconiosis. Diagnosis is established by clinical and occupational history of exposure to silica, in the presence of radiological changes. Experimental and clinical studies suggest that inhalation of silica dust is associated with pulmonary and systemic inflammation even in patients who did not develop silicosis. There are no specific tests for the routine laboratory diagnosis of the disease and the study of biological markers associated with the immunopathology of silicosis is important to understanding the establishment and development of silicosis. This article presents a review of studies investigating the possible inflammatory biomarkers of disease in blood and bronchoalveolar lavage from humans and experimental models.

Effect of aerobic training on plasma cytokines and soluble receptors in elderly women with knee osteoarthritis, in response to acute exercise.

The aim of this study was to evaluate levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and soluble forms of the TNF-α receptor (sTNFR1 and sTNFR2) from plasma taken from the peripheral blood of elderly individuals presenting with osteoarthritis (OA) of the knee. These patients underwent aerobic treatment through the use of physical exercises. The study consisted of a longitudinal analysis of older individuals presenting clinical and radiographic diagnosis of knee OA that were submitted to 12 weeks of aerobic treatment. The individuals were evaluated during acute exercise or after chronic exercise. During acute exercise (walking slowly on the mat), blood samples of the patients were collected before, immediately after, and 30 min following the end of training. After chronic exercise (aerobic walking training, three times/week for 12 weeks), patient blood samples were obtained for comparison. Additionally, clinical and functional assessments (WOMAC test and 6-min walk) were performed at the end of all physical exercises. Plasma concentrations of cytokines and soluble receptors were measured by ELISA. Aerobic training increased the plasma concentration of sTNR1; however, it decreased the plasma concentration of sTNFR2, when compared with levels of resting patients. Acute exercise differentially affects the levels of sTNFR1 dependent on when the samples were taken, before and after aerobic training. However, the levels of sTNFR2 were not affected by training. For the population studied, we observed differences in the levels of sTNFR1 and sTNFR2 following acute and chronic exercise. Other additional factors, like the level of inactivity of the individual and the type of physical exercise that patients are exposed to, need to be considered as well. The variation in the levels of soluble receptors correlated with functional improvement; however, the inflammatory osteoarthritis markers (IL-6 and TNF-α) were unaffected by the walking exercises.

Confiabilidade do limiar de lactato identificada pelo método visual / Reliability of identifying lactate threshold by use of visual method

O limiar de lactato (LL) é utilizado como um marcador da acidose metabólica e representa o momento durante o exercício em que o lactato sanguíneo começa aumentar de forma exponencial. Este LL tem sido utilizado como medidor de condicionamento físico, indicador sensível do estado do treinamento aeróbico em sujeitos saudáveis e doentes, além disso, auxilia na identificação do estímulo de treinamento ideal e na prescrição da intensidade de treinamento. O objetivo do presente estudo foi avaliar a confiabilidade intra e interexaminadores das medidas do LL obtidas através do método de detecção visual. Para isso, 31 voluntárias do sexo feminino (67,50 ± 4,41 anos; 1,52 ± 0,07 m; 64,55 ± 11,46 kg), aparentemente saudáveis e no período pós-menopausa, participaram do estudo. O LL foi determinado a partir de um teste realizado na esteira ergométrica até a fadiga, que consistiu de estágios com carga progressiva (variação da velocidade e/ou inclinação). Amostras de sangue foram coletadas por meio de uma punção na polpa digital do dedo médio a cada 3 minutos durante o teste. Em seguida, foram construídos os gráficos do método de detecção visual (software Prisma5) a partir da concentração de lactato sanguíneo coletado a cada estágio do exercício (intervalo de 3 minutos) em função da taxa de trabalho correspondente ao consumo de oxigênio (VO2) estimado durante o teste na esteira. A análise estatística foi realizada através do Coeficiente de Correlação Intraclasse (CCI). A confiabilidade intraexaminador foi excelente (0,950 - 0,952) e a confiabilidade interexaminadores foi boa (0,789 - 0,770). Dessa forma,sugere-se que o método de detecção visual é uma forma segura e confiável para detectar o LL na prática clínica e em pesquisas.

The lactate threshold (LT) is used as a marker for metabolic acidosis and represents the time during the exercise in which blood lactate begins to increase exponentially. LT has been used as a measurer of physical capacity,a sensitive indicator of the state of aerobic training in healthy and sickpatients, in addition, assists in identifying the optimal training stimulus and the prescription of training intensity. The aim of this study was to evaluate the reliability, intra and interrater, of the LT obtained by a visual detection method. For this, 31 female volunteers (67.50 ± 4.41 years, 1.52± 0.07 m, 64.55 ± 11.46 kg), apparently healthy and postmenopausal, participated in the study. The LT was determined from a test performed on a treadmill, which consisted of stages with progressive workload(variation of speed and/or incline), until the patient experienced fatigue. Blood samples were collected from a finger prick of the middle finger every 3 minutes during the test. Next, the visual detection method graphics were constructed (software Prisma5) from the blood lactate concentration collected at each stage of exercise (3 minute intervals) depending on the work rate corresponding to oxygen consumption (VO2) estimated during the treadmill test. Statistical analysis was performed by the intraclass correlation coefficient (ICC). Intrarater reliability was excellent (0.950- 0.952) and interrater reliability was good (0.789 - 0.770). Thus, it has been determined that the visual detection method is a safe and reliable way to detect the LT in clinical practice and research.