Neural Therapy
W. John Diamond in The Clinical Practice of Complementary, Alternative, and Western Medicine, 2017
This is the most popular, but least understood theory, concerning the matrix of the extracellular space as described by Pischinger.46 The extracellular space is a soup of nerve endings, fibroblasts, arterioles and capillaries, lymphatics and venules, cell membranes, and a sol-gel matrix of glycoproteins and proteoglycans. This space is where all interaction, whether electrical, ionic, or osmotic is happening. These regulating properties can be changed by manipulation of any of the physical, anatomical, or humeral properites of the space. This ground system has a very interesting property, in that a small change in one area causes a full phase shift in the whole system throughout the body (sounds pretty much like nonlinear dynamics and chaos to me.). The matrix is probably a liquid crystal, with different properties depending on its phase of existence, injecting novocaine or lidocaine into this matrix at an appropriate focus or point, will cause a phase shift in the entire system, with resolution of the symptoms that the previous phase was causing.
Imaging of Intracellular Targets
George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos in Handbook of Small Animal Imaging, 2018
Once the imaging agent survives the physiological barriers, specific targeting can begin. In oncologic applications, the first targeting step is usually achieved by enhanced perfusion and retention (EPR) where the imaging probes will extravasate into the tumor stroma through the fenestrations of the angiogenic vasculature. Once in the extracellular space, they can target specific features of the tumor cell. However, this is further complicated in brain malignancies where the tight junctions between epithelial cells of the blood-brain barrier prevent EPR. Nevertheless, EPR enhancement strategies, such as the administration of Bradykinin, have been reported and mathematical formulations have recently become available to optimize EPR properties of imaging probes (Wu et al. 1998; Dellian et al. 2000; Decuzzi et al. 2005; Ferrari 2005).
Diffusion-Weighted Imaging in Stroke
Andrei I. Holodny in Functional Neuroimaging, 2019
With acute ischemia, ATP concentrations fall and Na+/K+ ATPase and other ionic pumps fail (4–6). There is a net transfer of ions from the extracellular space to the intracellular space. Water follows the ions by osmosis, resulting in cellular swelling or cytotoxic edema. Several reasons have been proposed to explain the restriction of diffusion [decrease in the apparent diffusion coefficient (ADC)] that is observed in cytotoxic edema. The first is related to the difference in ADC that exists between the intracellular and extracellular spaces. In the intracellular space, cellular organelles, cytoskeletal macromolecules, and other subcellular structures serve as barriers to the random motion of water molecules. In an acute gray matter infarct, cytotoxic edema increases the fraction of water molecules that are in the intracellular space, where diffusion is relatively restricted, from approximately 80% to approximately 95%. Furthermore, cellular swelling leads to a reduction in the extracellular space volume and a consequential increase in the tortuosity of extracellular space pathways (7,8). In addition, ischemic rat brains demonstrate significant reductions in intracellular metabolite ADCs (8–11). Proposed explanations include an increased intracellular viscosity due to dissociation of microtubules and fragmentation of other cellular components due to collapse of the energy-dependent cytoskeleton, increased tortuosity of the intracellular space, and decreased cytoplasmic mobility. Temperature decreases and cell membrane permeability may also play a minor role in explaining ADC reduction in acutely ischemic tissue (11–13).
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.
An update on gene therapy for lysosomal storage disorders
Published in Expert Opinion on Biological Therapy, 2019
Murtaza S. Nagree, Simone Scalia, William M. McKillop, Jeffrey A. Medin
Many lysosomal enzymes are transported into the lysosome by the mannose-6-phosphate receptor (M6PR) pathway [2]. Terminal mannose residues phosphorylated in the cis-Golgi interact with M6PR. Protein-M6PR complexes then traffic to the lysosome via vesicular transport [3]. Lysosomal enzymes can be secreted into the extracellular space, though it is unclear if this is a consequence of mis-sorting or an active process. M6PR is expressed on the surface of many cell types; this can serve to scavenge extracellular enzyme back to the lysosome [4]. Incidentally, the secretion of some lysosomal enzymes is dramatically increased when overexpressed, and a significant proportion of secreted enzyme is appropriately modified for uptake and transport to lysosomes [5]. Standard-of-care for some LSDs is treatment with enzyme therapy (ET; commonly referred to as Enzyme Replacement Therapy; ERT). In ET, enzyme purified ex vivo is infused and subsequently taken up by M6PR-expressing cells [6].
Physical analysis of temperature-dependent effects of amplitude-modulated electromagnetic hyperthermia
Published in International Journal of Hyperthermia, 2019
Peter Wust, Pirus Ghadjar, Jacek Nadobny, Marcus Beck, David Kaul, Lukas Winter, Sebastian Zschaeck
Table 1 summarizes the electrical properties of the intracellular and extracellular spaces used in the model of Figure 2, which are assumed as constant from direct current (DC) until 100 MHz [21,22]. The extracellular space is an electrolytic fluid similar to a 0.9%-NaCl solution with frequency-independent high electrical conductivity σe = 1.2 S/m. The lower electrical conductivity σi = 0.3 S/m of the cytoplasm is due to water bounded by proteins and may vary according to cell type [19]. For a cell membrane (index ‘m’) of 5–10 nm thickness, low dielectric values and extremely low electrical conductivities σm have been reported for frequencies <1 MHz with increasing σm above 1 MHz [22].
Related Knowledge Centers
- Metabolite
- Multicellular Organism
- Protein
- Cell Membrane
- Neurotransmitter
- Receptor
- Cell
- Intracellular Space
- Ion
- Hormone