scholarly journals Exofocal changes in experimental focal cerebral ischemia: an experimental approach and its clinical correlation.

1969 ◽  
Vol 39 (3 Supl 3) ◽  
pp. 85-94
Author(s):  
César A. Arango Dávila ◽  
Martha Isabel Escobar ◽  
Efraín Buriticá ◽  
Hernán Pimienta

Introduction: The brain is an extraordinarily dynamic structure specially its physiology in response to pathological events. This response include several mechanisms such as changes in cell metabolism, genes expression and possible modifications in cell phenotype and in connectivity that reflect activation of processes like neurogenesis, neuritogenesis and synaptogenesis. Several aspects related with neuroplasticity has been proposed as part of the pathophysiological bases to understand brain ischemia and its exofocal phenomena. Progress in understanding of the pathophysiology of brain lesion has required the use of experimental models to evaluate cellular events that occur immediately after the lesion or later, to associate this changes with clinical observations and to propose pharmacological neuroprotection therapies. Objective: The purpose of the present work is to compile the advances in understanding of plasticity after brain lesion, mainly related with exofocal areas to a core lesion. Discussion and conclusions: The present work shows recent advances in neuroplasticity based on experimental approaches, and preclinical findings related with the exofocal ischemic phenomena: changes in areas not completely ischemic, changes in no ischemic areas affected by chemical or electrical signals, changes in the pattern of connectivity and adaptative changes in remote areas to the ischemic core. Finally, we discuss clinical aspects associated with this changes, experimental strategies and clinical pharmacological interventions.

Author(s):  
Anna Sobiepanek ◽  
Alessio Paone ◽  
Francesca Cutruzzolà ◽  
Tomasz Kobiela

AbstractMelanoma is the most fatal form of skin cancer, with increasing prevalence worldwide. The most common melanoma genetic driver is mutation of the proto-oncogene serine/threonine kinase BRAF; thus, the inhibition of its MAP kinase pathway by specific inhibitors is a commonly applied therapy. However, many patients are resistant, or develop resistance to this type of monotherapy, and therefore combined therapies which target other signaling pathways through various molecular mechanisms are required. A possible strategy may involve targeting cellular energy metabolism, which has been recognized as crucial for cancer development and progression and which connects through glycolysis to cell surface glycan biosynthetic pathways. Protein glycosylation is a hallmark of more than 50% of the human proteome and it has been recognized that altered glycosylation occurs during the metastatic progression of melanoma cells which, in turn facilitates their migration. This review provides a description of recent advances in the search for factors able to remodel cell metabolism between glycolysis and oxidative phosphorylation, and of changes in specific markers and in the biophysical properties of cells during melanoma development from a nevus to metastasis. This development is accompanied by changes in the expression of surface glycans, with corresponding changes in ligand-receptor affinity, giving rise to structural features and viscoelastic parameters particularly well suited to study by label-free biophysical methods.


Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 119-131
Author(s):  
Jana Palmowski ◽  
Kristina Gebhardt ◽  
Thomas Reichel ◽  
Torsten Frech ◽  
Robert Ringseis ◽  
...  

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.


2019 ◽  
Vol 56 (3) ◽  
pp. 605-610
Author(s):  
Ioan Sarbu ◽  
Cristian Adrian Dinu ◽  
Cristian Constantin Budacu ◽  
Mihaela Gabriela Luca ◽  
constantin Mihai ◽  
...  

Materials used in additive techniques are initially in a plastic state to be inserted into different cavities or easily molded (a blunt, for example), after which they pass into a rigid phase. This process is carried out by various methods depending on the material nature. The process can be purely physical (solidifying the alloy melt, the termoplasticized macromolecular compounds), modification and rearrangement of the internal structure (sintering of ceramic masses, crystallization of glasses, amalgam intake), a process of evaporation of some components (lacquers, plasticizing polymers) or a chemical process. This latter process can be an acid-base reaction between two inorganic substances (PCZ, CIS cements), a chelating reaction (ZOE cements) between a phenolic range (organic compound, usually eugenol or orthoethoxybenzoic acid) and an inorganic powder (ZnO) or a reaction in which a macromolecular compound is formed. After the type of the reaction, the macromolecules are classified into polymers (the formation reaction is called polymerization, the compounds of which are obtained by monomers, the main chain is formed by the carbon atom only), polycondensates (the formation reaction is called polycondensation, the chain also formed from heteroatom-ON, depending on the type of material) or substances that are obtained by polyaddition ( a repeated addition, the mechanism being different from the polymerization. Our study was conducted in the Dental Clinic and comprises a total of 17 patients. The group was represented by patients aged 50-85 years. Clinical observations have been made on cases of fracture of acrylic bases, with the analysis and assessment of some clinical aspects with increased risk of fracture (jaw / mandible, median / paramedian fracture line, etc.), which increase the risk to and fracture when associated. Clinical observations have shown the presence of the risk of fracture in acrylic prostheses, with the need first of all for the proper design and realization of mobile prostheses, but also for the use of inserts.


2021 ◽  
Vol 20 (4) ◽  
pp. 63-68
Author(s):  
Daria L. Tsyba ◽  
Olga V. Kirik ◽  
Dmitrii E. Korzhevskii

The relevance of this work is determined by the high prevalence and social significance of cerebrovascular diseases and the need to develop effective methods for verifying neuronal damage due to cerebral ischemia in experimental models. The aim of this study was to assess the possibility of immunohistochemical revealing of neurofilaments to detect axonal injury in cerebral ischemia models. Materials and methods. A model of transient focal cerebral ischemia by the left middle cerebral artery occlusion was reproduced in male Wistar, SHR and WKY rats. Axonal injury was assessed by immunohistochemical reactions for neurofilament proteins using SMI-32 and 2F11 antibodies. Results. In cerebral ischemia, damage to nerve fibers occurs, manifested by thickening of axons, their varicose expansion and segmental accumulation of neurofilament proteins. These changes are more noticeable with an immunohistochemical reaction to the SMI-32 marker of neurofilament heavy chain. Conclusions. The use of antibodies to the non-phosphorylated neurofilament heavy chain makes it easy to identify degenerating nerve fibers and can be recommended as an alternative method for detecting axonal injury.


1989 ◽  
Vol 71 (5) ◽  
pp. 727-731 ◽  
Author(s):  
Hans-Göran Hårdemark ◽  
Nils Ericsson ◽  
Zbigniew Kotwica ◽  
Gerd Rundström ◽  
Ib Mendel-Hartvig ◽  
...  

✓ Cerebrospinal fluid (CSF) markers of brain damage are potentially capable of providing quantitative information about the extent of certain neurological injury. The presence of such markers in CSF after brain damage is transient and it is essential to understand their kinetics if they are to be used in clinical practice. In the present study, the CSF concentrations of two neurospecific proteins, S-100 protein and neuron-specific enolase (NSE), were determined in rats before and repeatedly after one of two types of experimental brain damage: traumatic cortical injury and focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. The two types of experimental brain damage resulted in significant differences in the kinetics of S-100 and NSE concentrations in CSF. Cortical contusion was followed by a rapid increase in both S-100 and NSE and a peak occurred in both after about 7½ hours, at which time the values declined toward normal. A second, smaller peak was seen after about 1½ days. The increase and decrease in S-100 and NSE levels in CSF was slower after MCA occlusion; a peak was seen after 2 to 4 days. Furthermore, S-100 was generally higher than NSE after trauma, whereas after MCA occlusion the NSE concentration was slightly higher than the S-100 value. These results support the use of CSF markers for estimation of the extent of brain damage in experimental models and forms a basis for the understanding of their kinetics, which is important for their use in clinical practice.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22056-e22056
Author(s):  
A. Fusi ◽  
A. Busse ◽  
S. Ochsenreither ◽  
A. Rietz ◽  
U. Keilholz

e22056 Background: Within circulating tumor cells there may be a subset of cell with stem cell (tumor initiating) characteristics able to develop distant metastasis. Several markers including nestin and CD133 have been found to be possible candidates to identify such a kind of subpopulation in other experimental models. We evaluated the presence of melanoma cells bearing stem cell phenotype in the bloodstream of patients with cutaneous or uveal melanoma after depletion of the leukocytes fraction. Methods: Between 50 and 100 ml of peripheral blood were collected from 12 melanoma patients with various tumor burden as well as three healthy volunteers. Blood samples were enriched for tumour cells by CD45 depletion of the leukocyte fraction using magnetic beads separation (EasySep, Stem Cell Technologies. Inc.). The remaining material was stained with antibodies for the markers Melan-A/Mart-1 (Dako) and HMB45 (Dako), CD133 (Miltenyi Biotec) and nestin (R&D System) and analysed by flow cytometry (BD FACSCalibur). Ten ml of blood were further processed and CD133, nestin, Melan-A/Mart-1 transcripts were quantified by Real Time RT-PCR (LightCycler, Roche Diagnostic). Results: CD45-depleted fractions in healthy controls were negative for melanoma markers. Melan-A/Mart-1 and/or HMB45 positive cells were detectable in 11 out of 12 melanoma patients. The absolute number of melanoma cells identified ranged from 6 to 176 per 10 ml of blood. Nestin expressing cells were more represented compared to CD133 expressing cells (median 27.4%, range 0.3% to 65.1% vs. median 9.3%, range 0.1% to 16.8%) within the melanoma fraction of cells positive for Melan-A/Mart-1 and/or HMB45. In one patient two different melanoma cell populations were detectable. The population of cells with lower expression of the melanoma markers showed at the same time higher expression of nestin and CD133 (5.9% vs. 1.3% and 10.2% vs. 6.7% respectively). Nestin results were in good accordance to the FACS data (nestin: r=0.55; CD133: r=0.23; Pearson test). Conclusions: The novel negative separation technique allows reliable isolation of melanoma cells from peripheral blood of patients with metastatic disease. A significant fraction of melanoma cells in peripheral blood bears a stem cell phenotype. No significant financial relationships to disclose.


2006 ◽  
Vol 290 (5) ◽  
pp. F975-F984 ◽  
Author(s):  
Peter A. Friedman ◽  
William G. Goodman

This review considers many new basic and clinical aspects of parathyroid hormone (PTH). We focus especially on the identification of PTH fragments and how they may relate to renal failure, diagnosis, and treatment of secondary hyperparathyroidism and renal osteodystrophy. The biosynthesis and metabolism of PTH, measurement of circulating forms of PTH, the effects of PTH on receptor activation and turnover, the relationship between PTH levels and bone turnover in renal failure in humans, and the involvement of PTH in experimental models of renal failure are discussed. Despite these developments in understanding the etiology of renal failure and the availability of new assays for bioactive PTH, no adequate surrogate for bone biopsy and quantitative bone histomorphometry has been developed.


2003 ◽  
Vol 994 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Jeong Hyun Lee ◽  
Yong-Kyu Lee ◽  
Makoto Ishikawa ◽  
Keiko Koga ◽  
Mari Fukunaga ◽  
...  

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