Airway responsiveness to beta-adrenergic agonist (salbutamol) in asthma.

Despite the controversy of airway responsiveness to beta2-agonist drugs in asthma, in a previous study we showed increased responsiveness of asthmatic airways to isoprenaline. Therefore, in the present study of airway sensitivity to other beta2-agonists, salbutamol and its relationship to histamine responsiveness was reexamined. The threshold bronchodilator concentrations of inhaled salbutamol required for a 20% increase in forced expiratory flow in 1 sec (FEV1), (PC20) was measured in 20 normal and 19 asthmatic adults. Airway responsiveness to histamine, as the concentration that caused a 20% decrease in FEV1, was also measured in 11 normal and 12 asthmatic subjects; and the correlation between PC20 salbutamol and PC20 histamine was evaluated. Sensitivity to salbutamol was greater in asthmatics (PC20 = 7.24 mg/L) than in non-asthmatics (PC20 = 124.25 mg/L, p < 0.001). Airway responsiveness to histamine in asthmatics (PC20 = 0.18 g/L) was also significantly greater than in normal subjects (PC20 = 19.46 g/L, p < 0.001). There was a significant correlation between PC20 salbutamol and histamine (Rs = 0.6052, p < 0.005). Maximum response to both salbutamol and histamine and slope of concentration-response curves of both agents were significantly greater in patients with asthma than in normal subjects (p < 0.001 and p < 0.005 for maximum response and slope, respectively). The increased sensitivity of asthmatics to inhaled salbutamol suggests that they also may be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways.     

Five-Year Breast Surgeon Experience in LYMPHA at Time of ALND for Treatment of Clinical T1–4N1–3M0 Breast Cancer

Annals of Surgical Oncology - Breast cancer-related lymphedema (BCRL) is a source of postoperative morbidity for breast cancer survivors. Lymphatic microsurgical preventive healing approach...     

Oxidative stress in patients with asthma and its relation to uncontrolled asthma

This study aims to evaluate markers of oxidative stress in Tunisian asthmatic patients and investigate whether their markers are correlated with uncontrolled asthma.This prospective cohort study was conducted on 48 healthy subjects and 60 patients with asthma (34 patients with controlled asthma and 26 patients with uncontrolled asthma). The levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP), and glutathione (GSH), as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), were estimated in plasma by spectrophotometry.Asthmatic patients have significantly higher plasmatic levels of MDA and AOPP than healthy controls (p < 0.001). Lower GSH level and GPx activity were found in patients with asthma compared to controls (p < 0.001). In contrast, higher SOD activity was noted in asthmatic patients (p < 0.001).The comparison among the patients with controlled asthma and uncontrolled asthma revealed increased MDA and AOPP levels and SOD activity (p < 0.001) as well as a decreased GSH level and GPx activity (p = 0.004, p = 0.019) in patients with uncontrolled asthma. Spirometry level was significantly correlated with SOD activity (r = 0.447; p = 0.010), whereas no significant correlations were found with the other parameters (MDA, AOPP, GSH, and GPx).Asthmatic patients, especially those with uncontrolled asthma, suffer a high degree of reactive oxygen species (ROS) formation causing considerable oxidative stress. Increased MDA level and SOD activity and reduced GPx activity were predictors of poorly controlled asthma.     

Solvation in protein (un)folding of melittin tetramer–monomer transition

Protein structural integrity and flexibility are intimately tied to solvation. Here, we examine the effect that changes in bulk and local solvent properties have on protein structure and stability. We observe the change in solvation of an unfolding of the protein model, melittin, in the presence of a denaturant, trifluoroethanol. The peptide system displays a well defined transition in that the tetramer unfolds without disrupting the secondary or tertiary structure. In the absence of local structural perturbation, we are able to reveal exclusively the role of solvation dynamics in protein structure stabilization and the (un)folding pathway. A sudden retardation in solvent dynamics, which is coupled to the change in protein structure, is observed at a critical trifluoroethanol concentration. The large amplitude conformational changes are regulated by the local solvent hydrophobicity and bulk solvent viscosity.     

New Innovations in the Treatment of PJI and Biofilms—Clinical and Preclinical Topics

Purpose of Review

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement. A main source for antibiotic tolerance and treatment failure is bacterial production of biofilm—a resilient barrier against antibiotics, immune system, and mechanical debridement. The purpose of this review is to explore some novel approaches to treat PJI and biofilm-related infections.

Recent Findings

Innovative treatment strategies of bacterial and biofilm infections revolve around (a) augmenting current therapies, such as improving the delivery and efficiency of conventional antibiotics and enhancing the efficacy of antiseptics and (b) administrating completely new therapeutic modalities, such as using immunotherapy, nanoparticles, lytic bacteriophages, photodynamic therapy, novel antibiotics, and antimicrobial peptides.

Summary

Several promising treatment strategies for PJI are available to be tested further. The next requirement for most of the novel treatments is reproducing their effects in clinically representative animal models of PJI against clinical isolates of relevant bacteria.