Myoblast Sheet Transplantation for Treatment of Heart Failure after Myocardial Infarction

Heart failure is a common, severe, and progressive condition associated with high mortality and morbidity. Because of population-aging in the coming decades, heart failure is estimated to reach epidemic proportions. Current medical and surgical treatments have reduced mortality, but the prognosis for patients has remained poor. Transplantation of skeletal myoblasts has raised hope of regenerating the failing heart and compensating for lost cardiac contractile tissue. In the present work, we studied epicardial transplantation of tissue-engineered myoblast sheets for treatment of heart failure. We employed a rat model of myocardial infarction-induced acute and chronic heart failure by left anterior descending coronary artery ligation. We then transplanted myoblast sheets genetically modified to resist cell death after transplantation by expressing antiapoptotic gene bcl2. In addition, we evaluated the regenerative capacity of myoblast sheets expressing the cardioprotective cytokine hepatocyte growth factor in a rat chronic heart failure model. Furthermore, we utilized in vitro cardiomyocyte and endothelial cell culture models as well as microarray gene expression analysis to elucidate molecular mechanisms mediating the therapeutic effects of myoblast sheet transplantation. Our results demonstrate that Bcl2-expression prolonged myoblast sheet survival in rat hearts after transplantation and induced secretion of cardioprotective, proangiogenic cytokines. After acute myocardial infarction, these sheets attenuated left ventricular dysfunction and myocardial damage, and they induced therapeutic angiogenesis. In the chronic heart failure model, inhibition of graft apoptosis by Bcl-2 improved cardiac function, supported survival of cardiomyocytes in the infarcted area, and induced angiogenesis in a vascular endothelial growth factor receptor 1- and 2-dependent mechanism. Hepatocyte growth factor-secreting myoblast sheets further enhanced the angiogenic efficacy of myoblast sheet therapy. Moreover, myoblast-secreted paracrine factors protected cardiomyocytes against oxidative stress in an epidermal growth factor receptor- and c-Met dependent manner. This protection was associated with induction of antioxidative genes and activation of the unfolded protein response. Our results provide evidence that inhibiting myoblast sheet apoptosis can enhance the sheets efficacy for treating heart failure after acute and chronic myocardial infarction. Furthermore, we show that myoblast sheets can serve as vehicles for delivery of growth factors, and induce therapeutic angiogenesis in the chronically ischemic heart. Finally, myoblasts induce, in a paracine manner, a cardiomyocyte-protective response against oxidative stress. Our study elucidates novel mechanisms of myoblast transplantation therapy, and suggests effective means to improve this therapy for the benefit of the heart failure patient.

Role of lipid peroxidation in impairment of mitochondrial function at complex I by methyl isocyanate treatment of rats in vivo

The subcutaneous administration of methyl isocyanate (MIC) in 1.0 LD50 dose in rats caused a significant effect on hepatic mitochondrial function only at complex I region of the respiratory chain. MIC administration at 1.0 LD50 dose also resulted in significant increases in malondialdehyde and ferrous ion concentration in liver mitochondria. It is suggested that the augmented lipid peroxidation in hepatic mitochondria, catalyzed by iron, possibly mobilized from intracellular stores leads to the inhibition of enzymes of mitochondrial respiration at complex I region, in vivo, in rats receiving a lethal dose of MIC subcutaneously.

Effective drug dosage design for treatment of infectious diseases using dynamic inversion

A generic nonlinear mathematical model describing the human immunological dynamics is used to design an effective automatic drug administration scheme. Even though the model describes the effects of various drugs on the dynamic system, this work is confined to the drugs that kill the invading pathogen and heal the affected organ. From a system theoretic point of view, the drug inputs can be interpreted as control inputs, which can be designed based on control theoretic concepts. The controller is designed based on the principle of dynamic inversion and is found to be effective in curing the �nominal model patient� by killing the invading microbes and healing the damaged organ. A major advantage of this technique is that it leads to a closed-form state feedback form of control. It is also proved from a rigorous mathematical analysis that the internal dynamics of the system remains stable when the proposed controller is applied. A robustness study is also carried out for testing the effectiveness of the drug administration scheme for parameter uncertainties. It is observed from simulation studies that the technique has adequate robustness for many �realistic model patients� having off-nominal parameter values as well.

Self-consistent microscopic treatment of the effects of self-motion of the probe on ionic and dipolar solvation dynamics

A simple but self-consistent microscopic theory for the time dependent solvation energy of both ions and dipoles is presented which includes, for the first time, the details of the self-motion of the probe on its own solvation dynamics. The theory leads to several interesting predictions. The most important of them is that, for dipolar solvation, both the rotational and the translational motions of the dipolar solute probe can significantly accelerate the rate of solvation. In addition, the rotational self-motion of the solute can also give rise to an additional mechanism of nonexponentiality in solvation time correlation functions in otherwise slow liquids. A comparison between the present theoretical predictions and the recent experimental studies of Maroncelli et al. on solvation dynamics of aniline in l-propanol seems to indicate that the said experiments have missed the initial solvent response up to about 45 ps. After mapping the experimental results on the redefined time scale, the theoretical results can explain the experimental results for solvation of aniline in 1-propanol very well. For ionic solvation, the translational motion is significant for light solutes only. For example, for Li+ in water, translational motion speeds up the solvation by about 20%. The present theory demonstrates that in dipolar solvation the partial quenching of the self-motion due to the presence of specific solute-solvent interactions (such as H-bonding) may lead to a much slower solvation than that when the self-motion is present. This point has been discussed. In addition, we present the theoretical results for solvation of aniline in propylene carbonate, Here, the solvation is predicted to be complete within 15-20 ps.

Treatment of electroplating effluent through emulsion-free liquid embrane

Separation of dissolved heavy metals such-as Cr(VI) and Cu(II) from electroplating effluents using a new technique of emulsion-free liquid membrane (EFLM) has been studied. Experimental results show that nearly 95% extraction is obtained resulting in stripping phase enrichment up to 50 times relative to feed. It is also found that emulsion-free liquid membranes are highly efficient and superior to other types of liquid membranes.

Angiotensin converting enzyme inhibitors in the treatment of hypertension

Angiotensin converting enzyme (ACE) catalyses the conversion of angiotensin I (Ang I) to angiotensin II (Ang II). The ACE activity directly related to hypertension as Ang II is the blood pressure regulating hormone. Therefore, ACE inhibitors are a major class of antihypertensive drugs. Captopril, chemical name, was the first orally active ACE inhibitory antihypertensive drug, discovered in 1977. Since then, a number of such drugs have been synthesized. Enzyme-inhibitor bound crystal structural studies reveal a great deal of understanding about the interactions of the inhibitors at the active site of ACE. This can be helpful in the rational design of ACE inhibitors. With the advancement of the combination therapy, it is known that ACE inhibitors having antioxidant activity can be beneficial for the treatment of hypertension. This study describes the development of ACE inhibitors in the treatment of hypertension. Importance of ACE inhibitors having antioxidant activity is also described.

Toward More Precise Radiotherapy Treatment of Lung Tumors

A computational framework for modeling the respiratory motion of lung tumors provides a 4D parametric representation that tracks, analyzes, and models movement to provide more accurate guidance in the planning and delivery of lung tumor radiotherapy.

Pulsed plasma treatment of polluted gas using wet/low temperature corona reactors

pplication of pulsed plasma for gas cleaning is gaining prominence in recent years mainly from the energy consideration point of view. Normally, gas treatment is carried out, at or above room temperature, by a conventional dry type corona reactor. However, this treatment is still inadequate in the removal of certain stable gases present in the exhaust/flue gas mixture. The authors report some interesting results of the treatment of such stable gases with pulsed plasma at very low ambient temperature. Also reported in the paper is an improvement in DeNO/DeNOx efficiency using unconventional wet-type reactors, designed and fabricated by the authors, operating at different ambient temperatures. Apart from laboratory tests on simulated gas mixtures, field tests were also carried out on the exhaust gas of a 8 kW diesel engine. Further, an attempt was made to test the feasibility of a helical wire as a corona electrode in place of the conventional straight wire electrode. A comparative analysis of the various tests is presented together with a note on the energy consideration

Treatment of NOx from Diesel Engine Exhaust by Dielectric Barrier Discharge Method

This paper reports improved performance of discharge plasma in filtered engine exhaust treatment. Our paper deals about the removal of NOX emissions from the diesel exhaust by electric discharge plasma. For the treatment of diesel exhaust a new type of reactor referred to as crossflow dielectric barrier discharge reactor has been used, where the gas flow is perpendicular to the corona electrode. Experiments were conducted at different flow rates ranging from 2 l/min to 10 l/min. The discharge plasma assisted barrier discharge reactor has shown promising results in NOX removal at high flow rates.

Pulsed plasma treatment of polluted gas using wet/low temperature corona reactors

Application of pulsed plasma for gas cleaning is gaining prominence in recent years mainly from the energy consideration point of view. Normally, gas treatment is carried out, at or above room temperature, by a conventional dry type corona reactor. However, this treatment is still inadequate in the removal of certain stable gases present in the exhaust/flue gas mixture. The authors report some interesting results of the treatment of such stable gases with pulsed plasma at very low ambient temperature. Also reported in the paper is an improvement in DeNO/DeNOx efficiency using unconventional wet-type reactors, designed and fabricated by the authors, operating at different ambient temperatures. Apart from laboratory tests on simulated gas mixtures, field tests were also carried out on the exhaust gas of a 8 kW diesel engine. Further, an attempt was made to test the feasibility of a helical wire as a corona electrode in place of the conventional straight wire electrode. A comparative analysis of the various tests is presented together with a note on the energy consideration

Treatment of NOx from Diesel Engine Exhaust by Dielectric Barrier Discharge Method

This paper reports improved performance of advantages when compared to its counterpart as it is cost discharge plasma in filtered engine exhaust treatment. Our effective, low capital and operation costs, salable by- paper deals about the removal of NOX emissions from the diesel products, and integration with the existing systems. In this exhaust by electric discharge plasma. For the treatment of diesel paper we describe an alternate reactor geometry referred to exhaust a new type of reactor referred to as cross-flow dielectric as cross-flow DBD reactor, where the exhaust gas flow barrier discharge reactor has been used, where the gas flow is perpendicular to the wire-cylinder reaction chamber. This perpendicular to the corona electrode. Experiments were reactor is used to treat the actual exhaust of a 3.75 kW diesel- conducted at different flow rates ranging from 2 l/min to 10 l/ generator set. The main emphasis is laid on the NOX treatment min. The discharge plasma assisted barrier discharge reactor of diesel engine exhaust. Experiments were carried out at has shown promising results in NOX removal at high flow rates.

Herbal medicines used in the treatment of diabetes mellitus in Arunachal Himalaya, northeast, India

Ethnopharmacological relevance: Medicinal plants have played an important role in treating and preventing a variety of diseases throughout the world. Khampti tribal people living in the far-flung Lohit district of the Eastern Arunachal Himalaya, India still depend on medicinal plants and most of them have a general knowledge of medicinal plants which are used for treating a variety of ailments. This survey was undertaken in Lohit district in order to inventory the medicinal plants used in folk medicine to treat diabetes mellitus. Materials and methods: Field investigations were conducted in seventeen remote villages of Lohit district starting from April 2002 to May 2004 through interviews among 251 key informants who were selected randomly during our household survey. To elucidate community domains and determine differences in indigenous traditional knowledge of medicinal plants with anti-diabetic efficacy, we repeated our field survey starting from April 2008 to May 2010 with one hundred traditional healers locally called as ``Chau ya'' in Khampti of Lohit district. ``Chau ya'' traditional healers who know and use medicinal plants for treating diabetes mellitus were interviewed using a semi-structured questionnaire. Results: This study reports an ethnobotanical survey of medicinal plants in Lohit district of Arunachal Pradesh reputed for the treatment of diabetes mellitus. Forty-six plant species were identified in the study area to treat diabetes mellitus by the Khamptis ``Chau ya'' traditional healers. Comparative published literature survey analysis of this study with other ethnobotanical surveys of plants used traditionally in treating diabetes mellitus suggests that eleven plant species make claims of new reports on antidiabetic efficacy. These plant species are Begonia roxburghii, Calamus tenuis, Callicarpa arborea, Cuscuta reflexa, Dillenia indica, Diplazium esculentum, Lectuca gracilis, Millingtonia hortensis, Oxalis griffithii, Saccharum spontaneum, and Solanum viarum. Some of the plants reported in this study have an antidiabetic effect on rodent models but none have sufficient clinical evidence of effectiveness. Conclusions: The wide variety of medicinal plants that are used to treat diabetes mellitus in this area supports the importance of plants in the primary healthcare system of the rural people of Lohit district of Arunachal Pradesh. The finding of new plant uses in the current study reveals the importance of the documentation of such ethnobotanical knowledge. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Combination of single walled carbon nanotubes/graphene oxide with paclitaxel: a reactive oxygen species mediated synergism for treatment of lung cancer

Heterogeneity in tumors has led to the development of combination therapies that enable enhanced cell death. Previously explored combination therapies mostly involved the use of bioactive molecules. In this work, we explored a non-conventional strategy of using carbon nanostructures (CNs) single walled carbon nanotube (SWNT) and graphene oxide (GO)] for potentiating the efficacy of a bioactive molecule paclitaxel (Tx)] for the treatment of lung cancer. The results demonstrated enhanced cell death following combination treatment of SWNT/GO and Tx indicating a synergistic effect. In addition, synergism was abrogated in the presence of an anti-oxidant, N-acetyl cysteine (NAC), and was therefore shown to be reactive oxygen species (ROS) dependent. It was further demonstrated using bromodeoxyuridine (BrdU) incorporation assay that treatment with CNs was associated with enhanced mitogen associated protein kinase (MAPK) activation that was ROS mediated. Hence, these results for the first time demonstrated the potential of SWNT/GO as co-therapeutic agents with Tx for the treatment of lung cancer.