Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma

AbstractAsthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.</jats:p

Experience with tacrolimus in children with steroid-resistant nephrotic syndrome

Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-β immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-β tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels

Large vessel vasculitis

Takayasu arteritis is a chronic granulomatous disease of the aorta and its major branches that usually affects women during the second and third decades of life, but it has been reported in young children. This review details the clinical, pathological and radiological features, differential diagnoses and management of the condition, focusing chiefly on the disease in children. The recent definition of Takayasu arteritis is discussed. The condition should be considered in patients with unexplained arterial hypertension or unexplained inflammatory syndromes without signs of localization. Since the disease may be life-threatening and progressive, early recognition is necessary to initiate appropriate therapy. Patients with persistent ischaemic symptoms including hypertension might benefit from revascularization procedures

Climate change and freshwater zooplankton: what does it boil down to?

Recently, major advances in the climate–zooplankton interface have been made some of which appeared to receive much attention in a broader audience of ecologists as well. In contrast to the marine realm, however, we still lack a more holistic summary of recent knowledge in freshwater. We discuss climate change-related variation in physical and biological attributes of lakes and running waters, high-order ecological functions, and subsequent alteration in zooplankton abundance, phenology, distribution, body size, community structure, life history parameters, and behavior by focusing on community level responses. The adequacy of large-scale climatic indices in ecology has received considerable support and provided a framework for the interpretation of community and species level responses in freshwater zooplankton. Modeling perspectives deserve particular consideration, since this promising stream of ecology is of particular applicability in climate change research owing to the inherently predictive nature of this field. In the future, ecologists should expand their research on species beyond daphnids, should address questions as to how different intrinsic and extrinsic drivers interact, should move beyond correlative approaches toward more mechanistic explanations, and last but not least, should facilitate transfer of biological data both across space and time

Quantitative assessment of alterations in regional left ventricular contractility with color-coded tissue Doppler echocardiography: Comparison with sonomicrometry and pressure-volume relations

Background: Tissue Doppler imaging (TDI) is a novel method of color- coding myocardial velocity on-line. The objective of the present study was to evaluate endocardial velocity with TDI as a method of objectively quantifying alterations in regional contractility over a wide range induced by inotropic modulation. Methods and Results: Myocardial length crystals were used to simultaneously assess regional left ventricular (LV) function, and high- fidelity pressure and conductance catheters were used to assess global LV contractility by pressure-volume relations in nine open-chest dogs. Mid-LV M- mode and two-dimensional color TDI images were recorded during control and inotropic modulation stages with dobutamine and esmolol. Predicted significant increases in TDI indices occurred with dobutamine: peak systolic velocity of 4.41±1.07 to 6.67±1.07 cm/s*, systolic time-velocity integral (TVI) of 0.43±0.12 to 0.62±0.10 cm*, and diastolic TVI of 0.49±0.11 to 0.71±0.17 cm*. Opposing significant decreases occurred with esmolol: peak systolic velocity of 4.46±0.94 to 2.31±0.81 cm/s*, systolic TVI of 0.47±0.12 to 0.19±0.11 cm*, and diastolic TVI of 0.55±0.11 to 0.33±0.11 cm* (*all P<.001 versus control). Changes in TDI peak systolic velocity were correlated with changes in fractional shortening (r=.88) and shortening velocity (r=.87) by sonomicrometry. Changes in TDI peak velocity from multiple mid-LV sites also correlated significantly with maximal elastance (r=.85±.04) from pressure-volume relations. Conclusions: TDI measures reflect directional and incremental alterations in regional and global LV contractility and have the potential to quantify regional LV function