0000000000854386
AUTHOR
Rosario Salvador
Radioprotection and Radiomitigation: From the Bench to Clinical Practice.
The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by …
Oxidative stress and antioxidants in the pathophysiology of malignant melanoma.
Abstract The high number of somatic mutations in the melanoma genome associated with cumulative ultra violet (UV) exposure has rendered it one of the most difficult of cancers to treat. With new treatment approaches based on targeted and immune therapies, drug resistance has appeared as a consistent problem. Redox biology, including reactive oxygen and nitrogen species (ROS and RNS), plays a central role in all aspects of melanoma pathophysiology, from initiation to progression and to metastatic cells. The involvement of melanin production and UV radiation in ROS/RNS generation has rendered the melanocytic lineage a unique system for studying redox biology. Overall, an elevated oxidative st…
Infrared thermal imaging in the diagnosis of musculoskeletal injuries: a systematic review and meta-analysis.
OBJECTIVE. Musculoskeletal injuries occur frequently. Diagnostic tests using ionizing radiation can lead to problems for patients, and infrared thermal imaging could be useful when diagnosing these injuries. CONCLUSION. A systematic review was performed to determine the diagnostic accuracy of infrared thermal imaging in patients with musculoskeletal injuries. A meta-analysis of three studies evaluating stress fractures was performed and found a lack of support for the usefulness of infrared thermal imaging in musculoskeletal injuries diagnosis.
Melanoma in the liver: Oxidative stress and the mechanisms of metastatic cell survival.
Abstract Metastatic melanoma is a fatal disease with a rapid systemic dissemination. The most frequent target sites are the liver, bone, and brain. Melanoma metastases represent a heterogeneous cell population, which associates with genomic instability and resistance to therapy. Interaction of melanoma cells with the hepatic sinusoidal endothelium initiates a signaling cascade involving cytokines, growth factors, bioactive lipids, and reactive oxygen and nitrogen species produced by the cancer cell, the endothelium, and also by different immune cells. Endothelial cell-derived NO and H2O2 and the action of immune cells cause the death of most melanoma cells that reach the hepatic microvascul…
Speckle correlation technique to determine roughness in the dermatologic interval.
A non-invasive method is proposed to determine human skin roughness. The technique is based on measurement of the correlation between two field distributions scattered by a metallised triafol (cellulose acetate foil) replica of the epidermal area to be analysed. The two speckle patterns are produced from the same rough surface illuminated by two coherent plane waves (He-Ne laser) under two slightly different angles. The accuracy of the method is highlighted by measurements made on a set of standard samples with roughnesses previously determined by mechanical profilometry. Analysis of the results indicates a precision of around 10%, and an applicability within the interest range of very roug…
Young's modulus measurement of the radius bone using a shearing interferometer with carrier fringes
Abstract A technique for measuring Young's modulus of the radius bone by using electronic speckle-shearing pattern interferometry is proposed. The technique is based on the introduction of carrier fringes and the use of a phase unwrapping algorithm to obtain a phase map corresponding to the out-of-plane displacements of a radius bone without sign ambiguities. The carrier fringes are obtained by the correlation algorithm of two consecutive speckle fields with a translation of the illuminating beam between each recording, then the spatial synchronous detection (SSD), an unwrapping phase algorithm and integration process along shear direction are successfully applied for obtaining a displaceme…
Abstract 1390: A combination of natural polyphenols, a NAD+ booster, and a Toll-like receptor 2/6 agonist exerts high radioprotection in normal tissues without interfering with the anticancer efficacy of ionizing radiations
Abstract Ionizing radiation damages cells via direct ionization of DNA and other cellular targets as well as by indirect effects through reactive oxygen species. The response to radiation exposure depends on the cell type and dose of radiation, inherent tissue sensitivity and repair, and modulating intracellular factors that include cell cycle status, O2 pressure, and levels of thiols and other antioxidants. Potentially protective agents against exposure to harmful radiation have been investigated for decades. However, no ideal radioprotector is currently available. A wide range of phytochemicals are antioxidants and, thus, potentially radioprotective. Topical administration of Pterostilben…
Polyphenolic Phytochemicals in Cancer Prevention and Therapy: Bioavailability versus Bioefficacy
Natural polyphenols are organic chemicals which contain phenol units in their structures. They show antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Still, definitively demonstrating the human benefits of isolated polyphenolic compounds (alone or in combination) using modern scientific methodology has proved challenging. The most common discrepancy between experimental and clinical observations is the use of nonphysiologically relevant concentrations of polyphenols in mechanistic studies. Thus, it remains highly controversial how applicable underlying mechanisms are with bioavailable concentrations and biological half-li…
Determination of the object surface function by structured light: application to the study of spinal deformities.
The projection of structured light is a technique frequently used to determine the surface shape of an object. In this paper, a new procedure is described that efficiently resolves the correspondence between the knots of the projected grid and those obtained on the object when the projection is made. The method is based on the use of three images of the projected grid. In two of them the grid is projected over a flat surface placed, respectively, before and behind the object; both images are used for calibration. In the third image the grid is projected over the object. It is not reliant on accurate determination of the camera and projector pair relative to the grid and object. Once the met…
Synchronization of Two Photoelastic Light Modulators to Obtain Müeller Matrix
We report a method for the temporal synchronization of two photoelastic light modulators. For synchronizing, we used the transistor-transistor logic output signals from each modulator, which contain the information on the light polarization. These signals were introduced in a phase-detector circuit, which provided the phase difference value between both modulators. Three optical devices were used to test the synchronization method proposed: a polarizer, a half-wave, and a quarter-wave retarder plate. The value of each of the elements of the Mueller matrix for these devices was obtained using the method of the 36 measurements. The results show a high correlation between the theoretical and e…
Abstract 2810: Pterostilbene, a natural phytoalexin, weakens the antioxidant defenses of aggressive cancer cells in vivo: a pituitary gland- and Nrf2-dependent mechanism
Abstract Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies lack of correlation to the bioavailable concentrations is a critical issue. We studied the underlying mechanisms using different human melanomas (A2058, MeWo and MelJuso) and pancreatic cancers (AsPC-1 and BxPC-3) (with genetic backgrounds correlating with most tumors in patients), growing in nude mice as xenografts, and pterostilbene (Pter, 3’,5’-dimethoxy-4-stilbenol; abundant in e.g. blueberries and a natural dimethoxylated analog of resveratrol). RESULTS: Intravenous administration of Pter decreased human melanoma and pancreatic cancer growth (an effect associated with lower rates of tumor c…
Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron (MN) disease. Its primary cause remains elusive, although a combination of different causal factors cannot be ruled out. There is no cure, and prognosis is poor. Most patients with ALS die due to disease-related complications, such as respiratory failure, within three years of diagnosis. While the underlying mechanisms are unclear, different cell types (microglia, astrocytes, macrophages and T cell subsets) appear to play key roles in the pathophysiology of the disease. Neuroinflammation and oxidative stress pave the way leading to neurodegeneration and MN death. ALS-associated mitochondrial dysfunction occurs at different le…
Glucocorticoid receptor antagonism overcomes resistance to BRAF inhibition in BRAF(V600E)-mutated metastatic melanoma
Clinical applications of glucocorticoids (GC) in Oncology are dependent on their pro-apoptotic action to treat lymphoproliferative cancers, and to alleviate side effects induced by chemotherapy and/or radiotherapy. However, the mechanism(s) by which GC may also promote tumor progression remains unclear. GC receptor (GR) knockdown decreases the antioxidant protection of highly metastatic B16-F10 melanoma cells. We hypothesize that a GR antagonist (RU486, mifepristone) could increase the efficacy of BRAF-related therapy in BRAF(V600E)-mutated metastatic melanoma. In vivo formed spontaneous skin tumors were reinoculated into nude mice to expand the metastases of different human BRAF(V600E) mel…
Infrared Thermography Protocol for the Diagnosis and Monitoring of the Diabetic Foot: Preliminary Results
The diabetic foot, according to the International Consensus on the Diabetic Foot, is an infection, ulceration or destruction of the deep tissues related to neurological alterations and peripheral vascular disease in the lower limbs [1]. This pathology represents an important problem of public health because the affected patients can suffer amputations and even the death [2].
Efficacy and tolerability of EH301 for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled human pilot study
Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Our objective was to evaluate the efficacy and tolerability of Elysium Health's candidate drug EH301 in people with ALS (PALS). Methods: This was a single-center, prospective, double-blind, randomized, placebo-controlled pilot study. Thirty-two PALS we…
Automatic analysis of speckle photography fringes
Speckle interferometry is a technique adequate to metrological problems such as the measurement of object deformation. An automatic system of analysis of such measurements is given; it consists of a motorized x-y plate positioner controlled by computer, a CCD video camera, and software for image analysis. A fringe-recognition algorithm determines the spacing and orientation of the fringes and permits the calculation of the magnitude and direction of the displacement of the analyzed object point in images with variable degrees of illumination. For a 256 x 256 pixel image resolution, the procedure allows one to analyze from three fringes to a number of fringes that corresponds to 3 pixels/fri…
Effects of endodontic treatment on apparent Young’s modulus of human teeth: in vitro study using speckle interferometry
The introduction of new techniques for endodontic procedures requires the analysis of the biomechanical behavior of dental structures. Digital speckle shearing pattern interferometry (DSSPI) is a nondestructive optical measuring technique that allows one to directly quantify deformations in teeth that are subjected to stress. DSSPI technique was applied to measure small deformations caused by flexion in different types of teeth. The test was carried out both before and after endodontic treatment with the ProTaper method in order to evaluate the variation of dental elasticity, taking into the account the type of tooth and the endodontic treatment. The results obtained show that dental elasti…
Efficacy and tolerability of EH301 for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled human pilot study
Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Our objective was to evaluate the efficacy and tolerability of Elysium Health’s candidate drug EH301 in people with ALS (PALS). Methods: This was a single-center, prospective, double-blind, randomized, placebo-controlled pilot study. Thirty-two PALS we…