Ultrasound absorption and entropy production in biological tissue: a novel approach to anticancer therapy

The entropy production of tumorous cells is higher than that of normal cells, and entropy flow is therefore directed from tumorous toward healthy cells. This results in information concerning the cancer propagating into the surrounding normal tissue. However, ultrasound absorption results in additional entropy production in tissues. The entropy mechanism possibly provides a basis for a novel approach to anticancer therapy through the use of ultrasound irradiation. Through the calculation of ultrasound-induced entropy production and comparison of the theoretical results with the experimental data on ultrasound absorption in biological tissues, we have demonstrated that ultrasound absorption will increase the entropy in normal tissue more efficiently than in tumorous tissue due to the more acidic nature of the latter. Consequently, the direction of entropy flow between these two kinds of cells may be reversed on exposure to ultrasound. The higher entropy accumulation of normal cells during ultrasound irradiation may possibly lead to a change in the original direction of entropy flow and avoid the propagation of information on the cancer into the normal tissues. We suggest that low-intensity, low-frequency ultrasound irradiation may be an efficient tool for the therapy of solid tumors

Hydrothermal processes related to Triassic and Jurassic submarine basaltic complexes in northeastern Hungary and in the Dinarides and Hellenides

Comparative studies on hydrothermal alteration of submarine peperitic basalt occurrences related to the Triassic early rifting of the Neotethys were carried out in various parts of the Dinarides and Hellenides. The study areas included the displaced fragments of the Dinarides in the Darnó Unit, NE Hungary, the Kalnik Mts in Croatia and the Vares-Šmreka area in Bosnia and Herzegovina. In the Hellenides, similar environments were studied in the Stragopetra Mts., Greece. Jurassic pillow basalts formed in a back-arc-basin of the Neotethys were also studied (in the Szarvaskő Unit, NE Hungary, which also represents a displaced unit of Dinaridic origin). Within the submarine basaltic lava flows, six volcanic facies were distinguished. The hydrothermal alteration was characterized according to those facies. The first process was the albitization of the rock-forming plagioclase at ~300°C temperature in all localities. During the higher temperature stage of the subsequent cooling, chloritization in the ground mass is typical for all types of basalts, however chlorite and rarely quartz formed in the fractures and amygdales of the Triassic basalts, while chlorite, quartz and prehnite precipitated in the fractures of the Jurassic rocks. At lower temperatures of this cooling-related process, calcite is a common mineral filling up the larger amygdales, jig-saw type fractures and other open spaces, but some epidote, pumpellyite, prehnite and laumontite also occur in the Triassic basalts. The late stage alteration (happened at the lowest temperature) is characterized by argillitization at every locality. The observed hydrothermal alteration patterns also show slight differences according to the volcanic facies as a function of the distal/proximal setting in relation to the eruptive centers and the presence/absence of water-saturated and unconsolidated carbonate or siliciclastic sediments at the time of the emplacement of lava flows. The study revealed that the most important factors influencing mineralogy and zoning of hydrothermal alteration in these short living local hydrothermal systems are the rapid cooling of the hydrothermal fluid, the dominance of the not much evolved seawater as the source of hydrothermal fluid and the local, i.e. effective water/rock ratio, determined by the degree of fracturing in the rock. The mineralogical-textural peculiarities of the highly localized hydrothermal fluid/rock interaction in the studied submarine sea-mount type volcanoes are clearly different from the products of the large-scaled hydrothermal processes occurring at mid-oceanic ridges. Recognition of these differences is important in the evaluation of ore potential of Neotethyan realm or other areas with occurrences of submarine basaltic unit

Inhibitors of bacterial efflux pumps that also inhibit efflux pumps of cancer cells

Bacteria and cancer cells frequently increase their resistance to chemotherapeutics as a consequence of therapy. Whenever studied, refractory response to chemotherapy is due to the over-expression of efflux pumps that render the bacterium or cancer cell resistant not only to the agent used for therapy, but to many, if not all other agents as well. Control over the efflux pump that bestows multidrug resistance has been a goal of research during the past decade. As a consequence of this search for inhibitors of efflux pumps, it has been noted that many agents which affect the efflux pump system of bacteria also have similar activity against efflux pumps of drug-resistant cancer cells. This review aims to identify such agents

Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis

Background: Hydantoin derivatives are very promising candidates to improve the efficacy of anticancer chemotherapy. Previously, we demonstrated that eight hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T-lymphoma cells, as well as acting synergistically with the anticancer drug doxorubicin. Materials and Methods: The activity of the hydantoin derivatives were investigated in another MDR cancer model, namely Colo 205/S sensitive and Colo 320/R resistant colon carcinoma cells respectively, having normal or overexpressed ABCB1 systems. Results: Among the hydantoin derivatives evaluated, BS-1, MN-3 and JH-63 were the most effective ABCB1 transporter inhibitors at the concentration of 4 mg/l on the Colo 320/R cells, compared to the positive control, verapamil. Conclusion: The derivatives did not induce apoptosis of Colo 320/R resistant colon carcinoma cells, indicating that these hydantoin compounds are potent efflux pump inhibitors (EPI) without affecting the signalling pathways that regulate apoptosis

Psychiatric symptoms of patients with primary mitochondrial DNA disorders

<p>Abstract</p> <p>Background</p> <p>The aim of our study was to assess psychiatric symptoms in patients with genetically proven primary mutation of the mitochondrial DNA.</p> <p>Methods</p> <p>19 adults with known mitochondrial mutation (MT) have been assessed with the Stanford Health Assessment Questionnaire 20-item Disability Index (HAQ-DI), the Symptom Check List-90-Revised (SCL-90-R), the Beck Depression Inventory-Short Form (BDI-SF), the Hamilton Depression Rating Scale (HDRS) and the clinical version of the Structured Clinical Interview for the the DSM-IV (SCID-I and SCID-II) As control, 10 patients with hereditary sensorimotor neuropathy (HN), harboring the peripheral myelin protein-22 (PMP22) mutation were examined with the same tools.</p> <p>Results</p> <p>The two groups did not differ significantly in gender, age or education. Mean HAQ-DI score was 0.82 in the MT (range: 0-1.625) and 0.71 in the HN group (range: 0-1.625). Level of disability between the two groups did not differ significantly (<it>p </it>= 0.6076). MT patients scored significantly higher on the BDI-SF and HDRS than HN patients (12.85 versus 4.40, <it>p </it>= 0.031, and 15.62 vs 7.30, <it>p </it>= 0.043, respectively). The Global Severity Index (GSI) of SCL-90-R also showed significant difference (1.44 vs 0.46, <it>p </it>= 0.013) as well as the subscales except for somatization. SCID-I interview yielded a variety of mood disorders in both groups. Eight MT patient (42%) had past, 6 (31%) had current, 5 (26%) had both past and current psychiatric diagnosis, yielding a lifetime prevalence of 9/19 (47%) in the MT group. In the HN group, 3 patients had both past and current diagnosis showing a lifetime prevalence of 3/10 (30%) in this group. SCID-II detected personality disorder in 8 MT cases (42%), yielding 3 avoidant, 2 obsessive-compulsive and 3 personality disorder not otherwise specified (NOS) diagnosis. No personality disorder was identified in the HN group.</p> <p>Conclusions</p> <p>Clinicians should be aware of the high prevalence of psychiatric symptoms in patients with mitochondrial mutation which has both etiologic and therapeutic relevance.</p

Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke

<p>Abstract</p> <p>Background</p> <p>A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined.</p> <p>Methods</p> <p>Sera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay.</p> <p>Results</p> <p>Concentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100β, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the effects of low ficolin-3 and high CRP were independent.</p> <p>Conclusions</p> <p>Our findings indicate that ficolin-mediated lectin pathways of complement activation contribute to the pathogenesis of ischemic stroke and may be additive to complement-independent inflammatory processes.</p

Physicochemical attack against solid tumors based on the reversal of direction of entropy flow: an attempt to introduce thermodynamics in anticancer therapy

BACKGROUND: There are many differences between healthy tissue and growing tumor tissue, including metabolic, structural and thermodynamic differences. Both structural and thermodynamic differences can be used to follow the entropy differences in cancerous and normal tissue. Entropy production is a bilinear form of the rates of irreversible processes and the corresponding "generalized forces". Entropy production due to various dissipation mechanisms based on temperature differences, chemical potential gradient, chemical affinity, viscous stress and exerted force is a promising tool for calculations relating to potential targets for tumor isolation and demarcation. METHODS: The relative importance of five forms of entropy production was assessed through mathematical estimation. Using our mathematical model we demonstrated that the rate of entropy production by a cancerous cell is always higher than that of a healthy cell apart from the case of the application of external energy. Different rates of entropy production by two kinds of cells influence the direction of entropy flow between the cells. Entropy flow from a cancerous cell to a healthy cell transfers information regarding the cancerous cell and propagates its invasive action to the healthy tissues. To change the direction of entropy flow, in addition to designing certain biochemical pathways to reduce the rate of entropy production by cancerous cells, we suggest supplying external energy to the tumor area, changing the relative rate of entropy production by the two kinds of cells and leading to a higher entropy accumulation in the surrounding normal cells than in the tumorous cells. CONCLUSION: Through the use of mathematical models it was quantitatively demonstrated that when no external force field is applied, the rate of entropy production of cancerous cells is always higher than that of healthy cells. However, when the external energy of square wave electric pulses is applied to tissues, the rate of entropy production of normal cells may exceed that of cancerous cells. Consequently, the application of external energy to the body can reverse the direction of the entropy current. The harmful effect brought about by the entropy flow from cancerous to healthy tissue can be blocked by the reversed direction of entropy current from the irradiated normal tissue around the tumor

A Sequence of Phase Transformations and Phases in NiCoFeCrGa High Entropy Alloy

The present investigation is directed to phase transitions in the equimolar NiCoFeCrGa high entropy alloy, which is a mixture of face-centered cubic (FCC) and body-centered cubic (BCC) crystalline phases. The microstructure of the samples was investigated by using scanning electron microscopy (SEM), time-of-flight secondary ion mass spectroscopy (TOF-SIMS), transmission electron microscopy-based energy-dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS), as well as X-ray diffraction (XRD) measurements. Based on the phases observed in different temperature ranges, a sequence of the phase transitions can be established, showing that in a realistic process, when freely cooling the sample with the furnace from high to room temperature, a microstructure having spinodal-like decomposition can also be expected. The elemental mapping and magnetic behaviors of this decomposed structure are also studied

A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver

Background Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice. Results We exploit the fumarylacetoacetate hydrolase (Fah) gene correction-induced regeneration in Fah-deficient livers, to demonstrate that such approach stabilizes luciferase expression more than 5000-fold above the level detected in WT animals, following plasmid DNA introduction complemented by transposon-mediated chromosomal gene transfer. Building on this advancement, we created a versatile technology platform for performing gene function analysis in vivo in the mouse liver. Our technology allows the tag-free expression of proteins of interest and silencing of any arbitrary gene in the mouse genome. This was achieved by applying the HADHA/B endogenous bidirectional promoter capable of driving well-balanced bidirectional expression and by optimizing in vivo intronic artificial microRNA-based gene silencing. We demonstrated the particular usefulness of the technology in cancer research by creating a p53-silenced and hRas G12V-overexpressing tumor model. Conclusions We developed a versatile technology platform for in vivo somatic genome editing in the mouse liver, which meets multiple requirements for long-lasting high-level transgene expression. We believe that this technology will contribute to the development of a more accurate new generation of tools for gene function analysis in mice.Peer reviewe