Serum Albumin: A Multifaced Enzyme

Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrier of fatty acids, recognizes metal ions, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays esterase, enolase, glucuronidase, and peroxidase (pseudo)-enzymatic activities. HSA-based catalysis is physiologically relevant, affecting the metabolism of endogenous and exogenous compounds including proteins, lipids, cholesterol, reactive oxygen species (ROS), and drugs. Catalytic properties of HSA are modulated by allosteric effectors, competitive inhibitors, chemical modifications, pathological conditions, and aging. HSA displays anti-oxidant properties and is critical for plasma detoxification from toxic agents and for pro-drugs activation. The enzymatic properties of HSA can be also exploited by chemical industries as a scaffold to produce libraries of catalysts with improved proficiency and stereoselectivity for water decontamination from poisonous agents and environmental contaminants, in the so called “green chemistry” field. Here, an overview of the intrinsic and metal dependent (pseudo-)enzymatic properties of HSA is reported to highlight the roles played by this multifaced protein.

Association between Body Composition and Dysphagia in Patients with Amyotrophic Lateral Sclerosis

The influence of changes in body composition on swallowing in patients with Amyotrophic Lateral Sclerosis (ALS) is unknown. Understanding the interrelation between body compartments and dysphagia may establish specific treatments related to both nutritional aspects as to myofunctional ones designed to delay swallowing loss. Aim: The aim of the study was to evaluate the relationship between body composition and dysphagia during the course of the disease. Methods: The protocol of this study included assessments carried out quarterly for one year and included: analysis of body composition by multi-frequency segmental bioimpedance, nutritional diagnosis, maximum strength test of the tongue and lips, analysis of swallowing using the Functional Oral Intake Score (FOIS) and Swallowing Rating Scale of the American Speech-Language-Hearing Association (ASHA), speech intelligibility and analysis of disease severity. To measure the degree of relationship between quantitative variables, Spearman’s correlation was used. Results: Thirty-four patients were evaluated, 28 Spinal Group and 6 Bulbar Group. The results did not show any significant differences in the analysis of body composition between the groups. Positive associations were found between body compartments and swallowing analysis. The phase angle showed a strong correlation between the FOIS scales (r = 0.74, p < 0.01), ASHA (r = 0.77, p < 0.01) and tongue (r = 0.66, p < 0.01). Conclusions: Changes in body compartments were related to swallowing functionality and speech intelligibility in ALS patients, emphasizing the importance of analyzing body compartments for decision making by the interdisciplinary team. Although these preliminary data were collected in a small sample size, they serve to motivate future studies in this area.

Fate and transformation of silver nanoparticles in different biological conditions

The exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall application. Despite their wide use and significant amount of scientific data on their effects on biological systems, detailed insight into their in vivo fate is still lacking. This study aimed to elucidate the biotransformation patterns of AgNPs following oral administration. Colloidal stability, biochemical transformation, dissolution, and degradation behaviour of different types of AgNPs were evaluated in systems modelled to represent biological environments relevant for oral administration, as well as in cell culture media and tissue compartments obtained from animal models. A multimethod approach was employed by implementing light scattering (dynamic and electrophoretic) techniques, spectroscopy (UV–vis, atomic absorption, nuclear magnetic resonance) and transmission electron microscopy. The obtained results demonstrated that AgNPs may transform very quickly during their journey through different biological conditions. They are able to degrade to an ionic form and again reconstruct to a nanoparticulate form, depending on the biological environment determined by specific body compartments. As suggested for other inorganic nanoparticles by other research groups, AgNPs fail to preserve their specific integrity in in vivo settings.

Circulating Metabolites Associated with Body Fat and Lean Mass in Adults with Overweight/Obesity

The interplay between fat mass and lean mass within human metabolism is not completely understood. We aimed to identify specific circulating metabolomic profiles associated with these body composition compartments. Cross-sectional analyses were conducted over 236 adults with overweight/obesity from the Satiety Innovation (SATIN) study. Body composition was assessed by dual-energy X-ray absorptiometry. A targeted multiplatform metabolite profiling approach was applied. Associations between 168 circulating metabolites and the body composition measures were assessed using elastic net regression analyses. The accuracy of the multimetabolite weighted models was evaluated using a 10-fold cross-validation approach and the Pearson’s correlation coefficients between metabolomic profiles and body compartments were estimated. Two different profiles including 86 and 65 metabolites were selected for % body fat and lean mass. These metabolites mainly consisted of lipids (sphingomyelins, phosphatidylcholines, lysophosphatidylcholines), acylcarnitines, and amino acids. Several metabolites overlapped between these body composition measures but none of them towards the same direction. The Pearson correlation coefficients between the metabolomic profiles and % body fat or lean mass were 0.80 and 0.79, respectively. Our findings suggest alterations in lipid metabolism, fatty acid oxidation, and protein degradation with increased adiposity and decreased lean body mass. These findings could help us to better understand the interplay between body composition compartments with human metabolic processes.

Biomarkers in Progressive Fibrosing Interstitial Lung Disease: Optimizing Diagnosis, Prognosis, and Treatment Response

Interstitial lung disease (ILD) comprises a heterogenous group of diffuse lung disorders that commonly result in irreversible pulmonary fibrosis. While idiopathic pulmonary fibrosis (IPF) is the prototypical progressive fibrosing ILD (PF-ILD), a high proportion of patients with other ILD subtypes develop a PF-ILD phenotype. Evidence exists for shared pathobiology leading to progressive fibrosis, suggesting that biomarkers of disease activity may prove informative across the wide spectrum of ILDs. Biomarker investigation to date has identified a number of molecular markers that predict relevant ILD endpoints, including disease presence, prognosis, and/or treatment response. In this review, we provide an overview of potentially informative biomarkers in patients with ILD, including those suggestive of a PF-ILD phenotype. We highlight the recent genomic, transcriptomic, and proteomic investigations that identified these biomarkers and discuss the body compartments in which they are found, including the peripheral blood, airway, and lung parenchyma. Finally, we identify critical gaps in knowledge within the field of ILD biomarker research and propose steps to advance the field toward biomarker implementation.

Pneumomediastinum, Pneumoretroperitoneum, Pneumoperitoneum and Subcutaneous Emphysema Secondary to a Penetrating Anal Injury

Simultaneous occurrence of pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum and subcutaneous emphysema is rare. The most reported mechanisms are barotrauma, thermal injury and instrument puncture caused by colonoscopy. Ectopic air may travel into different body compartments through distinct anatomical fascial planes. Definite curative treatment involves surgical repair of the bowel wall defect. Conservative treatment is available in selected patients. Here, we present a case of traumatic penetrating rectal injury leading to developing air in the peritoneum, retroperitoneum, mediastinum, and subcutaneous space with good recovery under conservative treatment.

Body composition by computed tomography vs. dual energy x-ray absorptiometry: Long-term prediction of all-cause mortality in the Health ABC cohort

Background Body composition assessment by computed tomography (CT) predicts health outcomes in diverse populations. However, its performance in predicting mortality has not been directly compared to dual-energy-X-ray-absorptiometry (DXA). Additionally, the association between different body compartments and mortality, acknowledging the compositional nature of human body, is not well-studied. Compositional Data Analysis, that is applied to multivariate proportion-type dataset, may help to account for the inter-relationships of body compartments by constructing log-ratios of components. Here, we determined the associations of baseline CT-based measures of mid-thigh cross-sectional areas vs. DXA measures of body composition with all-cause mortality in Health ABC cohort, using both traditional (individual body compartments) and Compositional Data Analysis (using ratios of body compartments) approaches. Methods The Health ABC study assessed body composition in 2911 older adults in 1996-97. We investigated the individual and ratios of (by Compositional Analysis) body compartments assessed by DXA (lean, fat, and bone-mass) and CT (muscle, subcutaneous fat area, intermuscular fat (IMF), and bone) on mortality, using Cox proportional hazard models. Results Lower baseline muscle area by CT (HRmen=0.56 [95%CI: 0.48-0.67], HRwomen=0.60 [0.48-0.74]), fat-mass by DXA (HRmen=0.48 [0.24-0.95]) were predictors of mortality in traditional Cox-regression analysis. Consistently, Compositional Data Analysis revealed that lower muscle area vs. IMF, muscle area vs. bone area, and lower fat-mass vs. lean-mass were associated with higher mortality in both sexes. Conclusion Both CT measure of muscle area and DXA fat-mass (either individually or relative to other body compartments) were strong predictors of mortality in both sexes in a community research setting.

Making the choice between bioelectrical impedance measures for body hydration status assessment

Situational or persistent body fluid deficit (i.e., de- or hypo-hydration) is considered a significant health risk factor. Bioimpedance analysis (BIA) has been suggested as an alternative to less reliable subjective and biochemical indicators of hydration status. The present study aimed to compare various BIA models in the prediction of direct measures of body compartments associated with hydration/osmolality. Fish (n = 20) was selected as a biological model for physicochemically measuring proximate body compartments associated with hydration such as water, dissolved proteins, and non-osseous minerals as the references or criterion points. Whole-body and segmental/local impedance measures were used to investigate a pool of BIA models, which were compared by Akaike Information Criterion in their ability to accurately predict the body components. Statistical models showed that ‘volumetric-based’ BIA measures obtained in parallel, such as distance2/Rp, could be the best approach in predicting percent of body moisture, proteins, and minerals in the whole-body schema. However, serially-obtained BIA measures, such as the ratio of the reactance to resistance and the resistance adjusted for distance between electrodes, were the best fitting in predicting the compartments in the segmental schema. Validity of these results should be confirmed on humans before implementation in practice.

Circulation of Fluorescently Labelled Phage in a Murine Model

Interactions between bacteriophages and mammals strongly affect possible applications of bacteriophages. This has created a need for tools that facilitate studies of phage circulation and deposition in tissues. Here, we propose red fluorescent protein (RFP)-labelled E. coli lytic phages as a new tool for the investigation of phage interactions with cells and tissues. The interaction of RFP-labelled phages with living eukaryotic cells (macrophages) was visualized after 20 min of co-incubation. RFP-labeled phages were applied in a murine model of phage circulation in vivo. Phages administered by three different routes (intravenously, orally, rectally) were detected through the course of time. The intravenous route of administration was the most efficient for phage delivery to multiple body compartments: 20 min after administration, virions were detected in lymph nodes, lungs, and liver; 30 min after administration, they were detectable in muscles; and 1 h after administration, phages were detected in spleen and lymph nodes. Oral and rectal administration of RFP-labelled phages allowed for their detection in the gastrointestinal (GI) tract only.