Normal right- and left ventricular volumes and myocardial mass in children measured by steady state free precession cardiovascular magnetic resonance

BACKGROUND: Quantification of ventricular volume by steady state free precession (SSFP) cardiovascular magnetic resonance is accurate and reproducible. Normal values exist for adults, but are lacking for children.We sought to establish normal values for left and right ventricular volumes, mass and function in healthy children by using SSFP. METHODS AND RESULTS: Fifty children (27 females, 23 males) without cardiovascular disease were evaluated. Median age was 11 years (range 7 months - 18 years), weight 35 kg (range 7-77 kg), height 146 cm (range 66-181 cm). Thirty-six examinations were performed with breath holding, 14 in freely breathing sedated children.Ventricular volumes and mass were measured in the end systolic and end diastolic phase on SSFP cine images acquired in a short axis plane as a stack of 12 contiguous slices covering full length of both ventricles. Regression analysis showed an exponential relationship between body surface area (BSA) and ventricular volumes and mass (normal value = a*BSAb). Normative curves for males and females are presented in relation to BSA for the end-diastolic volume, end-systolic volume and mass of both ventricles. Intra- and interobserver variability of the measurements was within the limits of 2% and 7% respectively, except for right ventricular mass (10%). CONCLUSION: The exponential equation for calculation of normal values for each ventricular parameter and graphical display of normative curves for data acquired in healthy children by SSFP cardiovascular magnetic resonance are provided

Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

BACKGROUND: Investigations on pulmonary macrophages (MΦ) mostly focus on alveolar MΦ (AM) as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. METHODS: Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. RESULTS: IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6.CONCLUSION: AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response

Loureirin B, an essential component of Sanguis Draxonis, inhibits Kv1.3 channel and suppresses cytokine release from Jurkat T cells

Sanguis draxonis (SD), also known as “Dragon’s Blood”, is a traditional herb medicine that has been used to treat a variety of complications with unknown mechanisms. Recent studies show that SD displays immunosuppressive activities and improves symptoms of type I diabetes in animal models. However, the mechanisms underlying SD’s immunosuppressive actions are not completely understood. The voltage-gated Kv1.3 channel plays a critical role in the pathogenesis of autoimmune diseases by regulating the functions of both T cells and B cells. Here we investigated the effect of SD and one of its active components loureirin B (LrB) on Kv1.3. Both SD and LrB inhibited Kv1.3-mediated currents, produced a membrane depolarization, and reduced Ca(2+) influx in Jurkat T cells. In addition, application of LrB inhibited phytohemagglutinin (PHA)-induced IL-2 release from activated Jurkat T cells. Furthermore, point mutations in the selective filter region significantly reduced the inhibitory effect of LrB on Kv1.3. The results of these experiments provide evidence that LrB is a channel blocker of Kv1.3 by interacting with amino acid residues in its selective filter region. Direct inhibition of Kv1.3 in T cells by SD and LrB might be the cellular and molecular basis of SD-mediated immunosuppression

Effects of thermal water inhalation in chronic upper respiratory tract infections in elderly and young patients

Background: Chronic upper respiratory tract infections (cURTI) are very frequent illnesses which occur at any age of life. In elderly, cURTI are complicated by immunosenescence, with involvement of lung immune responsiveness. Results: In the present study, 51 elderly (age range: 66-86) and 51 young (age range 24-58) cURTI patients underwent a single cycle (two weeks) of inhalatory therapy with salt-bromide-iodine thermal water in the thermal station "Margherita di Savoia" (Margherita di Savoia, BAT, Italy). Peripheral blood serum cytokines and clinical assessment were performed before therapy (T0) and after six months (T1) and 12 months (T2) from inhalatory treatment. In both elderly and young patients, at baseline an increased release of T helper (h)1-related cytokines [interleukin (IL)-2 and interferon-γ] and of Th2-related cytokine (IL-4) was documented. Inhalatory treatment reduced the excessive secretion of all the above-cited cytokines. IL-10 values were above normality at all times considered in both groups of patients. In addition, an increase in IL-17 and IL-21 serum levels following therapy was observed in both groups of patients. Pro-inflammatory cytokine (IL-1β, IL-6, IL-8 and tumor necrosis factor-α) baseline values were lower than normal values at T0 in both elderly and young cURTI patients. Their levels increased following inhalatory treatment. Clinically, at T2 a dramatic reduction of frequency of upper respiratory tract infections was recorded in both groups of patients. Conclusion: Thermal water inhalation is able to modulate systemic immune response in elderly and young cURTI patients, thus reducing excessive production of Th1 and Th2-related cytokines, on the one hand. On the other hand, increased levels of IL-21 (an inducer of Th17 cells) and of IL-17 may be interpreted as a protective mechanism, which likely leads to neutrophil recruitment in cURTI patients. Also restoration of pro-inflammatory cytokine release following inhalatory therapy may result in microbe eradication. Quite importantly, the maintenance of high levels of IL-10 during the follow-up would suggest a consistent regulatory role of this cytokine in attenuating the pro-inflammatory arm of the immune response

Evidence-based guidelines for use of probiotics in preterm neonates

<p>Abstract</p> <p>Background</p> <p>Current evidence indicates that probiotic supplementation significantly reduces all-cause mortality and definite necrotising enterocolitis without significant adverse effects in preterm neonates. As the debate about the pros and cons of routine probiotic supplementation continues, many institutions are satisfied with the current evidence and wish to use probiotics routinely. Because of the lack of detail on many practical aspects of probiotic supplementation, clinician-friendly guidelines are urgently needed to optimise use of probiotics in preterm neonates.</p> <p>Aim</p> <p>To develop evidence-based guidelines for probiotic supplementation in preterm neonates.</p> <p>Methods</p> <p>To develop core guidelines on use of probiotics, including strain selection, dose and duration of supplementation, we primarily used the data from our recent updated systematic review of randomised controlled trials. For equally important issues including strain identification, monitoring for adverse effects, product format, storage and transport, and regulatory hurdles, a comprehensive literature search, covering the period 1966-2010 without restriction on the study design, was conducted, using the databases PubMed and EMBASE, and the proceedings of scientific conferences; these data were used in our updated systematic review.</p> <p>Results</p> <p>In this review, we present guidelines, including level of evidence, for the practical aspects (for example, strain selection, dose, duration, clinical and laboratory surveillance) of probiotic supplementation, and for dealing with non-clinical but important issues (for example, regulatory requirements, product format). Evidence was inadequate in some areas, and these should be a target for further research.</p> <p>Conclusion</p> <p>We hope that these evidence-based guidelines will help to optimise the use of probiotics in preterm neonates. Continued research is essential to provide answers to the current gaps in knowledge about probiotics.</p

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.