Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children’s Hospital (Rotterdam, the Netherlands), but as more ...benign infections in others such as the Geneva Children’s Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994–5) and retrospectively (1993–4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v23.9%), the rate of admission to the intensive care unit (3.6v 28.1%), mechanical ventilation (0 v7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.
In contrast to endogenous opioids, the highly addictive drug morphine activates the μ-opioid receptor without causing its
rapid endocytosis. It has recently been reported that coapplication of low ...concentrations of d -Ala 2 , N -Me-Phe 4 ,Gly 5 -ol-enkephalin (DAMGO) facilitates the ability of morphine to stimulate μ-opioid receptor endocytosis and prevents the development
of morphine tolerance in rats. To investigate the clinical relevance of this finding for analgesic therapy, the endocytotic
efficacies of a series of clinically used opioids were determined, and the effect of a combination of these drugs with morphine
on the μ-opioid receptor endocytosis in receptor-expressing human embryonic kidney (HEK) 293 cells was quantified. The combination
of morphine and opioid drugs with high endocytotic efficacies (e.g., DAMGO, etonitazene, sufentanil, β-endorphin, piritramide,
or methadone) did not result in a facilitation of morphine-mediated endocytosis but rather in a decrease of the receptor endocytosis
mediated by the tested opioid drugs. These findings demonstrate a partial agonistic effect of morphine on the agonist-induced
receptor endocytosis. Moreover, we demonstrated that the endocytotic potencies of opioid drugs are negatively correlated with
their ability to cause receptor desensitization and opioid tolerance in HEK 293 cells. These results strongly support the
hypothesis that μ-opioid receptor endocytosis counteracts receptor desensitization and opioid tolerance by inducing fast receptor
reactivation and recycling. In addition, it is shown that agonist-induced receptor endocytosis facilitates the compensatory
up-regulation of the cAMP pathway, a cellular hallmark of opioid withdrawal. Our findings suggest that opioids with high endocytotic
efficacies might cause reduced opioid tolerance but can facilitate compensatory mechanisms, resulting in an enhanced opioid
dependence.
The relationship between clinical severity of respiratory syncytial virus (RSV) infection and distribution of subtype A or B was investigated. The data of 232 children, who were admitted with RSV ...infection or diagnosed in the outpatient department of the Sophia Children's Hospital, Rotterdam between 1992 and 1995, were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence assay. Subtyping was performed by an indirect immunofluorescence assay using specific monoclonal antibodies. Gender, age at diagnosis, gestational age and birth weight, the presence of underlying diseases, feeding difficulties, the presence of wheezing and retractions, respiratory rate, temperature, clinical diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical ventilation were observed. Analysis was performed on data from all patients diagnosed with RSV infection in the period between 1992 and 1995 spanning three RSV seasons, and separately on the RSV season 1993-4. The outcome of the three year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and 24 (39.3%) subtype B isolates. None of the variables observed in the season 1993-4 differed significantly between RSV subtype A and B. Similar results were obtained from the analysis in the period 1992 until 1995, with the exception of PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more retractions were noted in patients with subtype A, p = 0.03). After correcting for possible confounders using regression analysis, these differences were not significant anymore. The data indicate that there is no relationship between clinical severity of RSV infection and subtype.
Aims Fetuin-A has been identified as a potent circulating inhibitor of ectopic calcification. We investigated the relationship between baseline fetuin-A serum levels and the rate of progression of ...aortic valve calcification (AVC) in non-dialyzed patients with aortic valve disease (AVD). Methods and results Seventy-seven patients (mean age 70 ± 8 years) with echocardiographically proven AVD were collected. In all patients, serum fetuin-A levels, creatinine, calcium, lipid parameters, and C-reactive protein were measured at baseline. For quantification of AVC progression, all patients underwent multislice spiral computed tomography examinations at baseline and after a mean follow-up of 12.6 ± 1.4 months (range 7–18 months). In a multifactorial analysis of covariance including fetuin-A levels, baseline AVC score, the covariables sex, age, body mass index, C-reactive protein, glomerular filtration rate, serum lipids, diabetes, smoking status, and hypertension, only serum fetuin-A levels significantly predict the progression of AVC (P < 0.001). Post hoc analysis demonstrated that patients with baseline fetuin-A levels lower than the median of the cohort (0.72 g/L) showed a significantly higher increase of AVC scores (34.6 ± 31.4%) than patients with fetuin-A levels larger than the median (10.0 ± 11.2%, P < 0.001) despite comparable baseline AVC scores. In addition, fetuin-A levels were associated with major adverse clinical events (MACE; P = 0.03). Conclusion Serum levels of the calcification inhibitor fetuin-A are associated with the progression of AVC and MACE, independent of the renal function and inflammation.
Abstract Background Enteroviruses (EV) and parechoviruses (HPeV) are the most common causes of aseptic meningitis, encephalitis and sepsis-like syndrome in neonates. Detection by nucleic acid ...amplification methods improves patient management. Objective Development of a real-time PCR assay on a LightCycler for simultaneous detection of EV, HPeV and an internal control to monitor inhibition. Study design We investigated the value of the new assay, prospectively, in a variety of samples from patients suspected of having viral meningitis or sepsis-like syndrome. Results The assay detected 64 EV serotypes and HPeV types 1–4. Of 186 patients, 63 (33.9%) were EV positive and 18 (9.7%) HPeV positive in one or more samples. In 43 of 159 feces and 6 of 57 throat samples viral culture and PCR were positive. With real-time PCR 27 extra EV and 19 HPeV positives were found. Blood and CSF were present from 33 patients. In 19 patients blood and CSF were positive, one was only positive in CSF, two were only positive in blood, 11 were negative. From 96 patients CSF and/or blood samples were tested and compared to results in throat and/or feces samples. Forty patients were EV-PCR and 14 HPeV-PCR positive in blood and/or CSF. All of these were confirmed by a positive PCR for the respective virus in feces and/or throat. Conclusions Simultaneous detection of EV and HPeV with this two-step real-time PCR is specific, faster and more sensitive than viral culture. All systemic infections (blood or CSF positive) were confirmed in feces. Culture is no longer necessary for clinical diagnosis and should only be performed on PCR-positive samples to obtain isolates for typing purposes. Application of this assay is an important improvement for patient management since the outcome of the analysis is available within the time frame of clinical decision-making.
The Global Solar Dynamo Cameron, R. H.; Dikpati, M.; Brandenburg, A.
Space science reviews,
09/2017, Letnik:
210, Številka:
1-4
Journal Article
Recenzirano
Odprti dostop
A brief summary of the various observations and constraints that underlie solar dynamo research are presented. The arguments that indicate that the solar dynamo is an alpha-omega dynamo of the ...Babcock-Leighton type are then shortly reviewed. The main open questions that remain are concerned with the subsurface dynamics, including why sunspots emerge at preferred latitudes as seen in the familiar butterfly wings, why the cycle is about 11 years long, and why the sunspot groups emerge tilted with respect to the equator (Joy’s law). Next, we turn to magnetic helicity, whose conservation property has been identified with the decline of large-scale magnetic fields found in direct numerical simulations at large magnetic Reynolds numbers. However, magnetic helicity fluxes through the solar surface can alleviate this problem and connect theory with observations, as will be discussed.
The effect of osmotic shock, enzymatic incubation, pulsed electric field, and high shear homogenization on the release of water-soluble proteins and carbohydrates from the green alga
Ulva lactuca
was ...investigated in this screening study. For osmotic shock, both temperature and incubation time had a significant influence on the release with an optimum at 30 °C for 24 h of incubation. For enzymatic incubation, pectinase demonstrated being the most promising enzyme for both protein and carbohydrate release. Pulsed electric field treatment was most optimal at an electric field strength of 7.5 kV cm
−1
with 0.05 ms pulses and a specific energy input relative to the released protein as low as 6.6 kWh kg
prot
−1
. Regarding literature, this study reported the highest protein (~ 39%) and carbohydrate (~ 51%) yields of the four technologies using high shear homogenization. Additionally, an energy reduction up to 86% was achieved by applying a novel two-phase (macrostructure size reduction and cell disintegration) technique.
Cigarette smoking, the major cause of chronic obstructive pulmonary disease (COPD), induces aberrant airway epithelial structure and function. The underlying mechanisms are unresolved so far. We ...studied effects of cigarette smoke extract (CSE) on epithelial barrier function and wound regeneration in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBECs) from COPD patients, nonsmokers and healthy smokers. We demonstrate that CSE rapidly and transiently impairs 16HBE barrier function, largely due to disruption of cell-cell contacts. CSE induced a similar, but stronger and more sustained, defect in PBECs. Application of the specific epidermal growth factor receptor (EGFR) inhibitor AG1478 showed that EGFR activation contributes to the CSE-induced defects in both 16HBE cells and PBECs. Furthermore, our data indicate that the endogenous protease calpain mediates these defects through tight junction protein degradation. CSE also delayed the reconstitution of 16HBE intercellular contacts during wound healing and attenuated PBEC barrier function upon wound regeneration. These findings were comparable between PBECs from smokers, healthy smokers and COPD patients. In conclusion, we demonstrate for the first time that CSE reduces epithelial integrity, probably by EGFR and calpain-dependent disruption of intercellular contacts. This may increase susceptibility to environmental insults, e.g. inhaled pathogens. Thus, EGFR may be a promising target for therapeutic strategies to improve mucosal barrier function in cigarette smoking-related disease.
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