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The Follow-Up Metabolic Medicine Hospital Consultation
Published in Michael M. Rothkopf, Jennifer C. Johnson, Optimizing Metabolic Status for the Hospitalized Patient, 2023
Michael M. Rothkopf, Jennifer C. Johnson
However, it is important to understand that PN can be a plasma expanding solution. This is particularly true if it contains a significant amount of sodium. Understanding this relates to the distribution of administered fluids throughout body compartments and the concept of “free water”. As we have discussed previously, the body is divided into intracellular and extracellular compartments. The relationship is roughly ⅔ intracellular fluid (ICF) and ⅓ extracellular fluid (ECF). The extracellular space is further subdivided into intravascular and interstitial spaces. The relationship here is ¾ interstitial versus ¼ intravascular (see Figure 13.2).
Water Balance, Electrolyte Balance, and Hydration
Published in Charles Paul Lambert, Physiology and Nutrition for Amateur Wrestling, 2020
For the 70 kg male (154 lbs) the total amount of body water is ~60% of bodyweight or ~42 kgs. The intracellular space contains the most water at about ~67% of total body water or ~28 kg. The extracellular space contains about ~23% of total body water at ~14 kg. The extracellular space can be further broken down into the intravascular space (fluid in the blood vessels and lymph vessels) and the interstitial space. Plasma volume is typically 3.5 L or 3.5 kg or ~8.3% of total body water and therefore represents the intravascular space while 14.8% or 6.2 kg are in the interstitial space or the space between cells. It must be remembered that a kg of water or sweat is equal to a L of water or sweat (Table 18.1).
Shock
Published in Lauren A. Plante, Expecting Trouble, 2018
Cellular hypoxia occurs as a result of impaired or reduced tissue oxygenation; this is secondary to either reduced oxygen-carrying capacity or delivery in the setting of increased oxygen consumption. This results in the physical characteristics of shock. Cellular hypoxia can cause intracellular edema, which, in turn, can lead to cell wall membrane pump dysfunction and leakage of intracellular contents into the extracellular space (1,2). When these biochemical processes remain unchecked, the result is acidosis, pH imbalance, release of proinflammatory cytokines that can worsen shock, and humoral processes that can impair regional blood flow (3). This microcirculatory derangement causes increased microvascular permeability, interstitial edema formation, and viscosity alterations (1,3–5).
Stimuli-sensitive nano-drug delivery with programmable size changes to enhance accumulation of therapeutic agents in tumors
Published in Drug Delivery, 2023
Mohammad Souri, Mohammad Kiani Shahvandi, Mohsen Chiani, Farshad Moradi Kashkooli, Ali Farhangi, Mohammad Reza Mehrabi, Arman Rahmim, Van M. Savage, M. Soltani
Due to the distribution of oxygen in tumor tissue, which depends on the cell density, regions of the tumor that are further away from the microvascular have a higher level of acidity, so secondary nanoparticles in the extracellular space have different release rates depending on their location (Figure 16). The released drug can gain more penetration over time if not used by cancer cells (Supplementary Video 2). Another part of the free drug, which is located near the microvascular, enters the bloodstream. The drug released from the 1 nm secondary nanoparticles is expected to enter the bloodstream more due to its higher concentration in the tissue (Supplementary file, Figure S3). In general, the results show that reducing the size of secondary nanoparticles and increasing the circulation time by reducing the size of primary nanoparticles improves the bioavailability of free drugs or in other words increases the area under curve (AUC) of the free drug in the extracellular space (Figure 17). Improving bioavailability increases cell death. Increasing the injection concentration also increases the concentration of free drugs in the extracellular space. Therefore, cancer cells are exposed to higher concentrations of the drug, so cell death increases (Supplementary file, Figure S4), although injectable dose limits should be considered.
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity
Published in Gut Microbes, 2021
Miguel S. Marques, Ana C. Costa, Hugo Osório, Marta L. Pinto, Sandra Relvas, Mário Dinis-Ribeiro, Fátima Carneiro, Marina Leite, Ceu Figueiredo
That PqqE cleaves the cytoplasmic domain of JAM-A independently of the T4SS raises the question of how the bacterial protease reaches the inside of the host cell. Bioinformatics predictions and direct mass spectrometry-based methods identified a signal sequence in PqqE proposing its targeting to the outer membrane or secretion.38,39 PqqE was reported in the extracellular proteome of H. pylori.40 Analysis of the composition of the H. pylori exoproteome at multiple phases of bacterial growth identified PqqE as enriched in the culture supernatant compared to subcellular fractions derived from intact bacteria. This suggests the selective release of these proteins into the extracellular space. In fact, PqqE was the second-highest enriched protein in the supernatant after HtrA.39 PqqE can also be found in the proteome of outer membrane vesicles (OMVs) of H. pylori.41H. pylori OMVs can be uptaken by gastric cells by clathrin-dependent and -independent endocytic pathways, depending on the lipid composition and receptor clustering in the host cell membrane.42 These vesicles can deliver bacterial components into host cells, including peptidoglycan and the CagA virulence factor.43,44 Although the fate of H. pylori OMVs inside the host cells is largely unknown, one may speculate they may function as delivery vehicles of the PqqE protease into the host cell cytoplasm, where PqqE is able to access the C-terminus of JAM-A leading to its cleavage.
Which path to follow? Utilizing proteomics to improve therapy choices for breast cancer patients
Published in Expert Review of Proteomics, 2020
Aurora S. Blucher, Gordon B. Mills, Yiu Huen Tsang
In addition, RNA profiling as well as analysis of 50 breast cancer-associated genes (the PAM50 assay) revealed 5 breast tumor intrinsic subtypes including luminal A, luminal B, HER2-enriched, basal-like and normal-like breast cancer [18]. The PAM50 classification allows allocation of patients into subsets for more precise prediction of recurrence risk and survival. For patients with early luminal breast cancers, multigene expression-based predictors such as MammaPrint, Oncotype DX, and Prosigna can recognize low-risk patients who do not require or benefit from chemotherapy [19]. However, these assays do display potential misclassification for a subset of patients [20] and do not fully reflect the tumor functional heterogeneity as they are a ‘grind and bind’ approach that homogenizes the tumor by mixing tumor and stroma cells as well as destroying cellular architecture and heterogeneity. Furthermore, protein levels and even more importantly, protein function are poorly reflected in DNA and RNA levels. Recent advances in proteomic technologies permit deep functional profiling of clinical samples to address potential mRNA-directed subtype misclassification caused by 1) variations in transcript-protein abundance correlations, 2) inability to recapitulate post-translation modifications (e.g. protein phosphorylation, methylation, and acetylation) induced by ligand-mediated interplay between tumor and stroma, 3) the lack of characterization of extracellular space and 4) poor characterization of other cells such as lymphocytes in the tumor ecosystem.