Molecular Mass Characteristics of (2‐Benzothiazolon‐3‐yl)acetic Acid–Telechelic Poly(ethylene oxide)s Determined by MALDI‐TOF Mass Spectrometry and SEC

(2‐benzothiazolon‐3‐yl)acetic acid–telechelic poly(ethylene oxide)s (1 100–4 440 Da) with narrow molecular mass distributions (MMD) were analysed by matrix‐assisted laser desorption‐ionisation time‐of‐flight mass spectrometry (MALDI‐TOF MS) and size exclusion chromatography (SEC). The average molecular masses (M̄_n and M̄_w) determined by both methods were compared and a good agreement established. The cutting of the low molecular part of the initial poly(ethylene glycol) MMD during purification and isolation of the produced telechelic poly(ethylene oxide)s was proved. For this reason, the degree of esterification (x) of poly(ethylene glycol) (PEG) with (2‐benzothiazolon‐3‐yl)acetic acid was calculated by MALDI‐TOF MS and SEC, using additional UV data. The two series of x values derived from the M̄_n‐values, determined by the two methods, are very close. All of them are less than unity and the differences between the two types of x values decrease with the PEG molecular mass growth.     

Nonfibrillar Abeta 1-42 inhibits glutamate uptake and phosphorylates p38 in human fibroblasts

Alzheimer disease (AD) is the most prevalent neurodegenerative disease, characterized by an increased deposition of β-amyloid (Abeta) within the central nervous system, leading to neuronal death. The availability of effective models, in which confirming novel pathogenic hypotheses and developing therapeutic targets, represents a very important goal for the field of AD. Fibroblasts from these patients may be relevant models in which addressing these issues, as they display biochemical alterations mirroring SNC ones. In this work, fibroblasts obtained from controls were studied after exposure to nonfibrillar Abeta 1-42, showing decreased glutamate uptake, similar to that observed in AD cells, in absence of transporters modifications. Nonfibrillar Abeta 1-42 was able to induce in control cells mitochondrial alterations and p38-phosphorylation, mirroring similar alterations found in AD fibroblasts. Under our experimental conditions, this treatment induced neither apoptosis nor necrosis. To investigate a putative role of p38-modulation in mediating nonfibrillar Abeta 1-42 toxicity, fibroblasts from controls were pretreated with retinoic-acid, and SB203580, a p38-inhibitor. These pretreatments prevented both p38-phosphorylation and glutamate uptake inhibition. Our results suggest that nonfibrillar Abeta 1-42 downregulates glutamate transporters activity interfering with p38-activation and mitochondrial stress. Thus, modulating complex kinase signaling pathway might represent a future therapeutic target in AD.     

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.     

Variations in the prevalence across countries of chronic bronchitis and smoking habits in young adults.

The present work aims to assess the international variation in the prevalence of chronic bronchitis and its main risk factor, smoking habits, in young adults of 35 centres from 16 countries. Respiratory symptoms and pulmonary function were assessed in 17,966 subjects (20-44 yrs), randomly selected from the general population, in the frame of the European Community Respiratory Health Survey. The median prevalence of chronic bronchitis was 2.6%, with wide variations across countries (p<0.001; 0.7-9.7%). The prevalence of current smokers ranged 20.1-56.9%, (p<0.001) with a median value of 40%. Current smoking was the major risk factor for chronic bronchitis, especially in males. Its effect increased according to number of pack-yrs: in males, the odds ratio of chronic bronchitis was 3.51 (95% confidence interval (CI) 2.31-5.32) in 1-14 pack-yrs smokers and increased to 17.32 (9.97-30.11) in > or = 45 pack-yrs smokers with respect to nonsmokers. Only 30% of the geographical variability in prevalence could be explained by differences in smoking habits, suggesting that other environmental and/or genetic factors may play an important role. In conclusion, chronic bronchitis is a substantial health problem even in young adults. The impressive prevalence in current smokers in most countries highlights the need to improve the quality of prevention.     

Reference values of maximal respiratory mouth pressures: a population-based study.

The aim of our study was to measure values of maximal inspiratory (MIP) and expiratory (MEP) mouth pressures in 625 (266 male, 359 female) clinically and functionally normal subjects drawn out of a sample representative of the general population. MEP (near TLC and FRC) was found to be significantly higher when compared with MIP (near RV and FRC), and pressures in male subjects were significantly higher than those in female subjects. MEP values at TLC and FRC were found to be closely related, as were values of MIP near RV and near FRC. Among the tested body-size variables, body surface area (BSA) for all parameters had the highest degree of correlation. Stepwise linear regression analysis was performed to define the equation of normality for all four parameters, employing BSA, sex, age, and relative interaction terms. R2 values, although the variables employed for the equations were highly significant, were relatively low and didn't fully explain the source of variability. The influence of age was smaller than the influence of BSA, although age did reduce the unexplained variance in MEP and MIP. These results confirm that the most useful employment of MIP and MEP is to monitor their changes in each patient, but they point out, however, the usefulness of reliable reference equations.