On the interaction of non-thermal atmospheric pressure plasma with tissues

Biomolecules & therapeutics, 2014

Non-thermal atmospheric-pressure plasma, also named cold plasma, is defined as a partly ionized gas. Therefore, it cannot be equated with plasma from blood; it is not biological in nature. Non-thermal atmospheric-pressure plasma is a new innovative approach in medicine not only for the treatment of wounds, but with a wide-range of other applications, as e.g. topical treatment of other skin diseases with microbial involvement or treatment of cancer diseases. This review emphasizes plasma effects on wound healing. Non-thermal atmospheric-pressure plasma can support wound healing by its antiseptic effects, by stimulation of proliferation and migration of wound relating skin cells, by activation or inhibition of integrin receptors on the cell surface or by its pro-angiogenic effect. We summarize the effects of plasma on eukaryotic cells, especially on keratinocytes in terms of viability, proliferation, DNA, adhesion molecules and angiogenesis together with the role of reactive oxygen sp...

2008

This study aimed to evaluate the effects of micron sized non-thermal atmospheric pressure plasma inside the animal body on breast cancer tumor. The μ-plasma jet consists of micron sized hollow tube in which pure helium gas is ionized by high voltage (4 kV) and high frequency (6 kHz). The efficiency of the plasma treatment in killing cancer cells was first investigated by cell viability measurements of treated 4T1 cells using flow cytometry and cell cycle analysis. For exploration of the in vivo effects of the plasma treatment, the BALB/c mice inoculated by 4T1 cell lines were exposed subcutaneously to plasma for 3 minutes. In addition, H&E staining, TUNEL and Western blotting assays were performed in order to observed the effects of the non-thermal plasma on the tumor cells. The results showed that the efficiency of the plasma in suppression of the tumor growth is comparable to that of a typical chemotherapy drug. Moreover, the results indicated that the plasma induces apoptosis in the tumor tissue and increases the ratio of the apoptotic to anti-apoptotic protein expression. We believe that these findings presented herein may extend our knowledge of the mechanisms by which the plasma exerts its promising anti-cancer effects. The cancer treatment by non-thermal atmospheric pressure plasma has attracted considerable attentions to the field of cancer therapy by using cold plasma 1–5. The conventional cancer therapy techniques are associated with many issues such as the normal tissue damage, time consuming treatment procedure and expensive therapies 6. The non-thermal plasma treatment has been introduced as a cost effective, rapid and low damage treatment which may represent an alternative for the conventional methods. Plasma contains the reactive species 7,8 , free radicals 9 , energetic ions 10 and also the transient electric fields inherent with plasma delivery 11,12 which are formed in the atmospheric room temperature medium and interact with the cells and other living organisms. It was shown that the plasma induced the apoptotic cell death in cancer cells while it had no adverse effect on the normal cell lines in the appropriate dosage 13,14. The results also indicated that by exposing the free radicals to cancer cells, the cells could produce the intracellular reactive oxygen species (ROS) which could cause apoptotic cell death 15. In addition, the role of nitric oxide (NO) generated by plasma is considerable 16,17. Moreover many other studies tried to figure out the mechanism of the cell death in cancer cells treated by the non-thermal plasma such as the cell signals activation induced by the reactive agents 18–21. Meanwhile, few studies have presented the effect of non-thermal plasma on the in-vivo tumor models 22,23. The reports have shown the tumor suppression with different dosage of the plasma treatment 23. The researchers also tried to figure out the mechanism of the plasma tumor interaction 23,24. One of the benefits of the plasma treatment in the in-vivo model is that the plasma has low harm effects on the normal tissue in the appropriated dosages 25 .

This study aimed to evaluate the effects of micron sized non-thermal atmospheric pressure plasma inside the animal body on breast cancer tumor. The μ-plasma jet consists of micron sized hollow tube in which pure helium gas is ionized by high voltage (4 kV) and high frequency (6 kHz). The efficiency of the plasma treatment in killing cancer cells was first investigated by cell viability measurements of treated 4T1 cells using flow cytometry and cell cycle analysis. For exploration of the in vivo effects of the plasma treatment, the BALB/c mice inoculated by 4T1 cell lines were exposed subcutaneously to plasma for 3 minutes. In addition, H&E staining, TUNEL and Western blotting assays were performed in order to observed the effects of the non-thermal plasma on the tumor cells. The results showed that the efficiency of the plasma in suppression of the tumor growth is comparable to that of a typical chemotherapy drug. Moreover, the results indicated that the plasma induces apoptosis in the tumor tissue and increases the ratio of the apoptotic to anti-apoptotic protein expression. We believe that these findings presented herein may extend our knowledge of the mechanisms by which the plasma exerts its promising anti-cancer effects. The cancer treatment by non-thermal atmospheric pressure plasma has attracted considerable attentions to the field of cancer therapy by using cold plasma 1–5. The conventional cancer therapy techniques are associated with many issues such as the normal tissue damage, time consuming treatment procedure and expensive therapies 6. The non-thermal plasma treatment has been introduced as a cost effective, rapid and low damage treatment which may represent an alternative for the conventional methods. Plasma contains the reactive species 7,8 , free radicals 9 , energetic ions 10 and also the transient electric fields inherent with plasma delivery 11,12 which are formed in the atmospheric room temperature medium and interact with the cells and other living organisms. It was shown that the plasma induced the apoptotic cell death in cancer cells while it had no adverse effect on the normal cell lines in the appropriate dosage 13,14. The results also indicated that by exposing the free radicals to cancer cells, the cells could produce the intracellular reactive oxygen species (ROS) which could cause apoptotic cell death 15. In addition, the role of nitric oxide (NO) generated by plasma is considerable 16,17. Moreover many other studies tried to figure out the mechanism of the cell death in cancer cells treated by the non-thermal plasma such as the cell signals activation induced by the reactive agents 18–21. Meanwhile, few studies have presented the effect of non-thermal plasma on the in-vivo tumor models 22,23. The reports have shown the tumor suppression with different dosage of the plasma treatment 23. The researchers also tried to figure out the mechanism of the plasma tumor interaction 23,24. One of the benefits of the plasma treatment in the in-vivo model is that the plasma has low harm effects on the normal tissue in the appropriated dosages 25 .

PLOS One, 2011

2009

Summary form only given: The number of potential applications of non-equilibrium nonthermal atmospheric pressure discharges in biology and medicine has grown significantly in the recent years. The plasma science community is looking closely at medical applications of various plasma systems. For example, use of plasma in treatment of dental cavities, sterilization of various surfaces, treatment of skin diseases, delicate surgeries, and many other applications. It is now clear that these plasmas can have not only physical (i.e. burning the tissue), but a medically relevant therapeutic effect- plasmas can trigger a complex sequence of biological responses in tissues and cells. To move ahead in further development of actual commercial tools that will enter the hospital, and in finding novel, and perhaps even unexpected, uses of these plasmas and understanding of mechanisms of interaction of non-equilibrium gas discharge with living organisms becomes essential. It is our goal to attempt an understanding of mechanisms of interaction of plasma with living tissues and cells. Clearly, these mechanisms depend on the way the plasma is generated, the way it is delivered, and the organism it is delivered to; i.e. radiofrequency discharge in helium will likely have somewhat different mechanisms of interaction than afterglow from a nitrogen arc. We attempt to classify different types of species created in plasma and assess their importance in achieving desirable effect. As the system readily available to us is the floating electrode dielectric barrier discharge (FE-DBD), we will use it as example plasma; however, we will attempt to be more general in our task of understanding the mechanisms. We will present different types of plasmas we use for treatment of living tissues and cells followed by discussion of physical and then biological mechanisms of interaction.

2010

Thermal plasmas and lasers have been widely used in medicine to cut, ablate and cauterize tissues through heating; in contrast, non-thermal plasma produces various highly active molecules and atoms without heat. As a result, its effects on living cells and tissues could be selective and tunable. This makes non-thermal plasma very attractive for medical applications. However, despite several interesting demonstrations of non-thermal plasma in blood coagulation and tissue sterilization, the biological and physical mechanisms of its interaction with living cells are still poorly understood impeding further development of non-thermal plasma as a clinical tool. Although several possible mechanisms of interaction have been suggested, no systematic experimental work has been performed to verify these hypotheses. Using cells in culture, it is shown in this work that non-thermal plasma created by dielectric barrier discharge (DBD) has dose-dependent effects ranging from increasing cell proliferation to inducing apoptosis which are consistent with the effects of oxidative stress. DNA damage is chosen as a marker to assess the effects of oxidative stress in a quantitative manner. It is demonstrated here that plasma induced DNA damage as well as other effects ranging from cell proliferation to apoptosis are indeed due to production of intracellular reactive oxygen species (ROS). We found that DNA damage is initiated primarily by plasma generated active neutral species which cannot be attributed to ozone alone. Moreover, it is found that extracellular media and its components play a critical role in the transfer of the non-thermal plasma initiated oxidative stress into cells. Specifically, it is found that the peroxidation efficiency of amino acids is the sole predictor of the ability of the medium to transfer the oxidative stress induced by non-thermal plasma. Phosphorylation of H2AX, a DNA damage marker, following plasma treatment is found to be ATR dependent and ATM independent, suggesting that non-thermal plasma may induce formation of bulky lesions unlike ionizing radiation (IR) or H2O2 which primarily produce DNA double strand breaks. Moreover, it is found that the pathway by which plasma generated oxidative stress is transferred across cellular membranes does not involve lipid peroxidation by-products, although lipid peroxidation does occur.

2009

Non-thermal atmospheric pressure dielectric barrier discharge plasma applied directly to living tissues is now being widely considered for various clinical applications. One of the key questions that arise in this type of topical treatment is if the skin remains undamaged after non-thermal plasma treatment. The results from the previous rodent model provided strong evidence for the ability of non-thermal plasma to sterilize the surface of the tissue without any thermal damage to the tissue. It is well established that porcine (pig) skin closely resembles human skin; hence we evaluated the potential toxic effects of non-thermal plasma treatment on underlying skin cells and tissue on porcine skin. In a Yorkshire pig model, the intact skin and wounded tissue treatment was carried out at varying doses to locate the damaging power/time (dose) combination and the resulting skin damage was analyzed. In this paper we study the possible short term and long term toxic effects of the non-thermal plasma treatment on intact living tissue. Non-thermal plasma has been shown to sterilize intact tissue without visible or microscopic damage, and our goal was to identify the boundaries of skin toxicity after treatment.

Arheologie Moldovei, 2023

In this issue of the chronicle we publish the Medieval coins, which are kept in the collection of the "Constantin Mihai" Museum, from the "Ion Neculce" Theoretical High School in Târgu Frumos. The coins have been discovered over time in the localities around the town of Târgu Frumos (Iași County): Principality of Moldavia (1 pc.): Ștefan I, gros, 1433-1435; Ottoman Empire (2 pcs.): Mehmed II, akçe, 1451-1461; Mustafa III, para, 1764/1765; Kingdom of Hungary (2 pcs.): Hunyadi Mátyás, denár, 1471-1481 (1), 1479-1485 (1); Polish-Lithuanian Commonwealth: Polish Crown (3 pcs.): Zygmunt I Stary, grosz, 1548 (1); Zygmunt III Waza, szeląg, 1626 (1), trojak, 1599 (1); Lithuania (7 pcs.): Aleksander I Jagiellończyk, pólgrosz, 1501-1506; Zygmunt II August, pólgrosz, 1557 (1), 1558 (1), 1560 (1), 1561 (2), 1565 (1); Ryga (city) (1 pc.): Zygmunt III Waza, trojak, 1593; Gdańsk (1 pc.): Zygmunt III Waza, ort, 1626; Holy Roman Empire: Kingdom of Hungary (4 pc.): Ferdinand I, denar, 1553; Maximilian II, denar, 1578; Rudolf II, denar, 1589; Ferdinand II, denar, 1629; Branderburg-Prussia (1 pc.): Georg Wilhelm, Schilling, 1626; Kampen (imperial city) (1 pc.): Leeuwendaalder, 1649; Swedish Empire (1 pcs.): Ryga (city): Krystyna, Schilling, 1637; Austrian Empire (1 pc.): Franz I, 3 Kreuzer, 1815.