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.

Effects of a Kinect-based physical training program on body composition, functional fitness and depression in institutionalized older adults.

Exergames have already been used as therapeutic tools to enhance both physical and cognitive functions in older adults. AIM: To evaluate the effects of a Kinect-based physical activity program on the quality of life, depression, functional fitness and body composition in institutionalized older adults. METHODS: A total of 50 older adults aged >60 years were selected and randomized to a control and video game group. Body composition was determined by means of anthropometric measurements. Quality of life was assessed using the WHOQOL-BREF questionnaire, and depression was classified using the Beck Depression inventory. Functional fitness was assessed using the Arm Curl, Chair Stand, 8-foot up-and-go, sit and reach, and the aerobic endurance test. RESULTS: After 12 weeks of protocol, we observed a significant improvement in all functional fitness parameters. CONCLUSIONS: Our findings suggest that a Kinect-based physical activity program seems to positively impact the three domains related to quality of life and directly associated with age (physical, social and psychological domains), and to promote a more active lifestyle in institutions housing older individuals. Geriatr Gerontol Int 2020; ••: ••-••.

Blood lactate increases with the progression of mitral valve disease in dogs / Aumento de lactato sanguíneo com progressão de valvopatia mitral em cães

In dogs with congestive heart failure, the upregulated sympathetic tone causes vasoconstriction that impairs peripheral blood supply, therefore causing the accumulation of lactate. In this prospective cross-sectional study with a longitudinal component, blood lactate was quantified in 10 healthy and 34 myxomatous mitral valve disease (MMVD) dogs to investigate its potential use as a diagnostic and prognostic biomarker. While there were no differences in lactate concentration between control animals and stages B1 (3.31±0.62mmol/L) and B2 (3.32±0.46mmol/L) dogs, significant differences were found between healthy (2.50±0.69mmol/L) and both C (3.99±0.47mmol/L) and D (6.97±1.23mmol/L) animals. When a cut-off of 3.35mmol/L was used, lactate was able to distinguish dogs with normal and remodeled hearts with a sensitivity of 78.2% and specificity of 63.6%. Also, significant correlations existed between lactate and indicators of cardiac remodeling. Finally, animals with blood lactate <3.5mmol/L carried a better prognosis when compared with dogs in which lactate was >5.0mmol/L. Our results suggest that the progression of MMVD results in accumulation of lactate within the bloodstream, which is likely attributable to the impaired peripheral tissue perfusion. In MMVD dogs, blood lactate may be used as a surrogate for cardiac remodeling, and an increased concentration is associated with a worse prognosis regarding the time to evolve into congestive heart failure.(AU)

Em cães com insuficiência cardíaca congestiva, o tônus simpático hiperregulado causa vasoconstrição e interfere com o suprimento sanguíneo periférico, resultando no acúmulo de lactato. Neste estudo prospectivo transversal com um componente longitudinal, o lactato sanguíneo foi quantificado em 10 cães saudáveis e 34 cães com doença mixomatosa da valva mitral (DMVM) para investigar seu potencial como biomarcador diagnóstico e prognóstico. Embora não tenham sido identificadas diferenças na concentração de lactato entre animais controle e cães com DMVM nos estágios B1 (3,31±0,62mmol/L) e B2 (3,32±0,46mmol/L), diferenças significativas foram constatadas entre os cães saudáveis (2,50±0,69mmol/L) e cães com DMVM estágio C (3,99±0,47mmol/L) ou D (6,97±1,23mmol/L). Quando utilizado o valor de corte de 3,35mmol/L, o lactato foi capaz de diferenciar cães com corações normais daqueles com corações remodelados com sensibilidade de 78,2% e especificidade de 63,6%. Além disso, correlações significativas foram encontradas entre o lactato e os indicadores de remodelamento cardíaco. Por fim, os animais com lactato sanguíneo <3,5mmol/L tiveram prognóstico melhor comparativamente aos cães com concentrações >5,0mmol/L. Nossos resultados sugerem que a progressão da DMVM resulta no acúmulo de lactato na corrente sanguínea, fato que é provavelmente atribuído à perfusão periférica prejudicada. Em cães com DMVM, o lactato sanguíneo pode ser utilizado como indicador de remodelamento cardíaco, cuja concentração elevada está associada com pior prognóstico relativo ao tempo para evoluir para insuficiência cardíaca congestiva.(AU)

Matrix metalloproteinases 2 and 9 in rabbits with doxorubicin-induced cardiomyopathy / Metaloproteinases de matriz 2 e 9 em coelhos com cardiomiopatia induzida pela doxorrubicina

Some studies have shown the role played by matrix metalloproteinases and their inhibitors in doxorubicin cardiotoxicity. In this study, we sought to investigate how plasma and myocardial MMP 2 and 9 perform in rabbits with doxorubicin-induced cardiomyopathy, searching for a correlation between the activity of these collagenases and cardiac remodeling. Cardiomyopathy was induced by doxorubicin given intravenously twice a week for six consecutive weeks. Plasma MMP activity and the echocardiogram were assessed at baseline, and at 15 and 45 days after first injection of doxorubicin. The myocardial activity of these enzymes was solely evaluated in nine rabbits at 45 days, and results were compared with nine healthy controls. We only identified the full-length forms of both MMP 2 and 9 throughout the study. The plasma pro-MMP 2 reduced along the deterioration of cardiac function, while the pro-MMP 9 increased significantly at T45 as compared to baseline and T15. A negative significant correlation was found to exist between the plasma activity of pro-MMP 2 and mitral E-to-mitral septal annular early diastolic velocity ratio, which is an estimate of mean left atrial pressure and congestion. Only pro-MMP 2 was found in myocardial samples, and mean activity of such enzyme was statistically lower than that recorded for healthy controls. Although no active form was documented for either collagenase, the duration of the treatment with doxorubicin played a role in the alteration of plasma pro-forms activity. However, these changes could not be associated with most echocardiographic parameters that are supportive of cardiac remodeling.(AU)

Alguns estudos já demonstraram o papel exercido pelas metaloproteinases de matriz e seus inibidores na cardiotoxicidade promovida pela doxorrubicina. Assim, este estudo teve como objetivo investigar o comportamento das MMPs 2 e 9 plasmáticas e miocárdicas em coelhos com cardiomiopatia induzida pela doxorrubicina, buscando determinar se há correlação entre a atividade dessas colagenases e o remodelamento cardíaco. A cardiomiopatia foi induzida pela doxorrubicina aplicada por via intravenosa duas vezes por semana ao longo de seis semanas consecutivas. A atividade plasmática das MMPs e o ecocardiograma foram avaliados no momento basal e aos 15 e 45 dias após a primeira aplicação da doxorrubicina. A atividade miocárdica dessas enzimas foi quantificada em apenas nove coelhos aos 45 dias e os resultados comparados com outros nove controles saudáveis. Foram identificadas apenas as formas inativas das MMPs 2 e 9 durante todo o estudo. A pro-MMP 2 plasmática reduziu à medida que a função cardiaca se deteriorou, enquanto a pro-MMP 9 aumentou significativamente em T45 quando comparada aos momentos basal e T15. Houve correlação negativa significativa entre a atividade plasmática da pro-MMP 2 e a relação entre E mitral e a velocidade anular mitral no início da diástole, um parâmetro que permite estimar a pressão atrial esquerda média e a congestão. Apenas a pro-MMP 2 foi documentada nas amostras miocárdicas dos coelhos com cardiomiopatia e atividade media dessa enzima foi estatisticamente menor que aquela observada nos controles saudáveis. Embora a forma ativa de ambas as colagenases não tenha sido identificada, o tempo de tratamento com doxorrubicina interferiu na atividade das formas inativas plasmáticas. Contudo, essas alterações não se associaram com a maioria dos parâmetros ecocardiográficos que indicam remodelamento cardíaco.(AU)

Systemic Sympathoexcitation Was Associated with Paraventricular Hypothalamic Phosphorylation of Synaptic CaMKIIα and MAPK/ErK.

Systemic administration of adrenergic agonist (Isoproterenol; ISOP) is known to facilitate cardiovascular changes associated with heart failure through an upregulation of cardiac toll-like receptor 4 (TLR4). Furthermore, previous studies have shown that cardiac tissue-specific deletion of TLR4 protects the heart against such damage. Since the autonomic regulation of systemic cardiovascular function originates from pre-autonomic sympathetic centers in the brain, it is unclear how a systemically driven sympathetic change may affect the pre-autonomic paraventricular hypothalamic nuclei (PVN) TLR4 expression. Here, we examined how change in PVN TLR4 was associated with alterations in the neurochemical cytoarchitecture of the PVN in systemic adrenergic activation. After 48 h of intraperitoneal 150 mg/kg ISOP treatment, there was a change in PVN CaMKIIα and MAPK/ErK expression, and an increase in TLR4 in expression. This was seen as an increase in p-MAPK/ErK, and a decrease in synaptic CaMKIIα expression in the PVN (p < 0.01) of ISOP treated mice. Furthermore, there was an upregulation of vesicular glutamate transporter (VGLUT 2; p < 0.01) and a decreased expression of GABA in the PVN of Isoproterenol (ISOP) treated WT mice (p < 0.01). However, after a PVN-specific knockdown of TLR4, the effect of systemic administration of ISOP was attenuated, as indicated by a decrease in p-MAPK/ErK (p < 0.01) and upregulation of CaMKIIα (p < 0.05). Additionally, loss of inhibitory function was averted while VGLUT2 expression decreased when compared with the ISOP treated wild type mice and the control. Taken together, the outcome of this study showed that systemic adrenergic activation may alter the expression, and phosphorylation of preautonomic MAPK/ErK and CaMKIIα downstream of TLR4. As such, by outlining the roles of these kinases in synaptic function, we have identified the significance of neural TLR4 in the progression, and attenuation of synaptic changes in the pre-autonomic sympathetic centers.