Manjula Balasubramanian

Mechanism of Blood Coagulation by Nonthermal Atmospheric Pressure Dielectric Barrier Discharge Plasma

Mechanisms of blood coagulation by direct contact of nonthermal atmospheric pressure dielectric barrier discharge (DBD) plasma are investigated. This paper shows that no significant changes occur in the pH or Ca2+ concentration of blood during discharge treatment. Thermal effects and electric field effects are also shown to be negligible. Investigating the hypothesis that the discharge treatment acts directly on blood protein factors involved in coagulation, we demonstrate aggregation of fibrinogen, an important coagulation factor, with no effect on albumin. We conclude that direct DBD treatment triggers selective natural mechanisms of blood coagulation.

Bio-Medical Applications of Non-Thermal Atmospheric Pressure Plasma

Non-Thermal Floating Electrode Dielectric Barrier Discharge (FE-DBD) Plasma in Direct Contact with Living Tissue The focus of this work is direct application of non-thermal atmospheric pressure plasma to human tissue, where this tissue serves as a second active electrode. Such use has significant advantages over the existing technologies. Ultra Violet (UV) radiation, especially high energy Vacuum UV (VUV), does not have good penetration depth in air and VUV exists only in the discharge area. Short-lived active species and radicals (like OH, NO, O2( + Δ g 1 ) and other electronically excited species, atomic Oxygen, etc.) do not,

Use of Non-Thermal Atmospheric Pressure Plasma Discharge for Coagulation and Sterilization of Surface Wounds

Summary form only given. Atmospheric pressure plasma discharges have recently gained interest of the medical community. Such systems have been used for sterilization of surfaces, for biochemical surface functionalization, and for many other applications. Specifically, thermal plasma discharges are applied in the field of tissue sterilization and blood coagulation as a faster alternative to normal biochemical coagulation. However, the use of thermal plasma is limited for two reasons: (a) the extremely high temperatures (2000 K up to 10000 K) cause severe tissue damage and (b) the necessity of general anesthesia makes it inconvenient for wide-spread patient use, apart from the hospital setting. Our research team has developed a novel method using non-thermal dielectric barrier discharge plasma (DBD plasma) to coagulate blood and sterilize tissues without causing thermal damage. This treatment would be safe to patients because no exposed electrodes are involved and high frequency current (about 10 KHz) is kept below milli-ampere. Our experiments have shown that such plasma treatment hastens blood coagulation and causes simultaneous wound sterilization. We suppose that these processes are stimulated by a large concentration of chemically active species in plasma that are ions, radicals (O, OH, N) and electronically-excited atoms and molecules. This novel plasma technology can find many applications in the medical field. Within the hospital setting, this technology may prove useful in the operating room for patients suffering from bleeding not amenable to other methods of coagulation (hemophilia cases, for example). Because of simultaneous sterilization, this device could also help prevent intra-operative infections. Sterilization effects of non-thermal plasma are well-known and were confirmed, for example, in our previous studies. We have determined relative time and power for blood coagulation by plasma without tissue damage as confirmed by gross and microscopic examination, and tissue cultures

Applications of Non Thermal Atmospheric Pressure Plasma in Medicine

Non-thermal atmospheric pressure plasma is now being developed for use in various medical applications. Over the past few years a lot of clinical applications of non-thermal plasma have been tested and the results show promising potential for Plasma Medicine. In this paper we present a review of various applications of non-thermal plasma in medicine like non-thermal plasma assisted blood coagulation and skin sterilization, melanoma skin cancer treatment and treatment of cornea lesions.

Classical Hodgkin lymphoma concurrently evolving in a patient with marginal zone B-cell lymphoma of the spleen

Combination of the splenic marginal zone B-cell lymphoma (SMZL) and classical Hodgkin lymphoma (cHL) is extremely rare. We report a unique case with concurrent SMZL and cHL. The patient was a 63-year-old man who presented with fatigue and anemia, showing a splenomegaly and retroperitoneal lymphadenopathy. A splenectomy revealed monotonous marginal zone lymphocytic infiltrates and numerous large Reed-Sternberg-like cells. Flow cytometry revealed a kappa light-chain-restricted CD5 (-), CD23 (-) B-cell population. DNA polymerase chain reaction analysis confirmed the presence of clonal rearrangement of the immunoglobulin heavy-chain gene. Immunohistochemical studies revealed that the large atypical cells were CD30 (+), CD15 (weakly +), CD20 (-), CD45 (-), Pax5 (weakly +), BOB.1 (-), and Oct2 (-), indicating the coexistence of SMZL with cHL. After the chemotherapy, the patient achieved a clinical/radiologic remission, whereas cHL was detected in liver and bone marrow subsequently. The case indicates that both components of lymphoma can present concurrently as a composite form of lymphoma and both need to be treated adequately.

Sterilization of Living Human and Animal Tissue by Non-Thermal Atmospheric Pressure Dielectric Barrier Discharge Plasma

Summary form only given. Sterilization prior to a medical procedure (pre-operative), during, or following such a procedure has always been an issue at a hospital. Sterilization by liquid chemistry (alcohol, or Betadinetrade) has been available for a long time; however, such a procedure becomes difficult if not impossible when attempting to sterilize an open wound, a diabetic sore, or a burn site. Thus, controllable and targeted sterilization of living tissue without contact with or damage to this tissue is needed. Non-thermal atmospheric pressure plasmas have long been used in sterilization of various surfaces without damage to such surfaces and offer a good solution for skin sterilization as well. Presented is a method of sterilization of living tissue using a floating electrode dielectric barrier discharge (FF-DBD), based on a conventional DBD. Here plasma is bounded by quartz dielectric on one side and tissue of a living animal or human on the other side. Complete sterilization (> 7-log reduction in viable colony forming units) is shown from common bacteria abundant on human skin (Streptococcus staphylococcus, and yeast), and from model bacteria such as Escherichia coli, Bacillus subtilis spores, etc. Sterilization is normally achieved, depending on initial microorganism concentration, in 2 to 6 seconds of treatment (up to 15 seconds in some special cases), while no damage is observed during such treatment either visually or microscopically. Microscopic tissue damage assessment is carried out via tissue collection, sectioning, Haematoxylin and Eosin stain (H&E), and microscopic analysis. Mechanisms of this interaction and plasma selectivity to killing bacteria without damaging skin will be discussed. Data from a differential skin toxicity trial on SKIII hairless mice will be presented. During this trial, plasma doses are escalated until damage to animal skin is observed. Plasma-chemical effects are separated from thermal damage by use of FE-DBD plasma in non-thermal (microfilament temperature ~300 K +/-30 K) or thermal (~500-700 K) regimes. Non-thermal plasma regimes are shown to be less damaging while achieving nearly the same sterilization efficiency.

Toxicity analysis of direct nonthermal plasma treatment of living tissue

Non-thermal dielectric barrier discharge plasma produced at normal atmospheric pressure and applied directly to living tissues is now being widely considered for various applications in medicine, viz; skin sterilization, wound treatment, treatment in malignant tissues and many others. One of the key questions that arise in this type of topical treatment is whether the skin remains undamaged after non-thermal plasma treatment. In this paper we study the possible short term and long term toxic effects of the non-thermal plasma treatment on intact living tissue. 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 visible or microscopic damage to the tissue. We evaluated the potential toxic effects of non-thermal plasma treatment on underlying skin cells and tissue on intact porcine skin, since it is well established that porcine (pig) skin closely resembles human skin. Based on prior knowledge that non-thermal plasma has non-damaging and damaging regimes, an experimental protocol based on the pig model was constructed. In a Yorkshire pig model, the intact skin treatment was carried out at varying doses to locate the damaging power/time (dose) combination and the resulting skin damage was analyzed. Once the dose where damage occurred was located, the treatment was stopped recording the power level and time of application. Then successively lower power levels were applied on different patches to find a dose (power/time) which was non-damaging for prolonged treatment times. The pig was kept alive for one day post treatment and the tissue samples were sectioned before euthanizing the animal. From the experiments we determined that a dose of 15 mins at a low power of 0.2 Watt/cm2 caused no visible or microscopic damage to the tissue while a dose of 3 mins at high power of 1.0 Watt/cm2 caused a second degree burn. These results were confirmed by histology staining. Of note is that sterilization is achieved in about 5 sec at a low power treatment of 0.2 Watt/cm2. Detailed analysis of any biochemical changes and inflammatory response initiation in the treated tissue will be carried out. In this paper we show that low power plasma treatment is non-toxic to intact pig skin.

Toxicity of direct non-thermal atmospheric pressure plasma treatment of living tissue

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.

Mechanism of Blood Coagulation by Non-Thermal Atmospheric Pressure Dielectric Barrier Discharge

Mechanisms of blood coagulation by direct contact of non-thermal atmospheric pressure dielectric barrier discharge plasma are investigated. This study shows that no significant changes occur in pH or Ca2+ concentration of blood during discharge treatment. Thermal effects and electric field effects are also shown to be negligible. Investigating the hypothesis that the discharge treatment acts directly on blood protein factors involved in coagulation, we demonstrate aggregation of fibrinogen, an important coagulation factor, with no effect on albumin. We conclude that direct dielectric barrier discharge treatment triggers selective natural mechanisms of blood coagulation.

Non-Equilibrium Dielectric Barrier Discharge Plasma Promoting Apoptotic Behavior in Melanoma Skin Cancer Cells

Summary form only given. Initiation of programmed cell death, or apoptosis, is an important issue in cancer treatment as cancer cells frequently have acquired the ability to block apoptosis and thus are more resistant to chemotherapeutic drugs. Targeted and perhaps selective initiation of apoptosis in cancerous tissue is desirable for many reasons, ranging from the enhancement of or aid to current medical methods to problems currently lacking a solution, i.e. lung cancer. Inactivation (killing) of human Melanoma skin cancer cell lines in vitro by Floating Electrode Dielectric Barrier Discharge (FE-DBD) plasma was tested.