Ajay Kumar

Proton-conducting polymer electrolyte. I. The polyethylene oxide+NH4ClO4 system

Proton transport in solution-cast films of polyethylene oxide (PEO) complexed with ammonium perchlorate (NH4ClO4) has been established using optical microscopy, XRD, DTA, IR, coulometry, transient ionic current and electrical conductivity studies. The solubility of NH4ClO4 in PEO is found to be limited to a maximum concentration NH4+/EO ratio of 0.167. The highest conductivity ( approximately 1.05*10-5 S cm-1) is for the film with NH4+/EO=0.02-0.1. The H+ ion transference number, tH+, and mobility, mu H+, are 0.85 and 1.7*10-4 cm2 V-1 s-1, respectively. The movement of ClO4- ions also contributes slightly to the overall charge transport.

Thoracic reconstruction with the omentum: Indications, complications, and results

This study provides a retrospective analysis of 60 patients who underwent thoracic reconstruction with the omentum. Patients were identified by searching several databases to determine demographics, indications for surgery, operative technique, and postoperative course, including donor and recipient site morbidity. From January 1975 to May 2000, the authors harvested and transferred the omentum successfully (57 pedicled, 3 free) in 60 patients (mean age, 60 years; age range, 21–86 years) for sternal wound infections (N = 34), chest wall resections (N = 17), pectus deformities (N = 2), intrathoracic defects (N = 4), and breast reconstruction (N = 3). The omentum was used as a primary flap in 39 patients and as a salvage flap in 21 patients. Average operative time was 3.9 hours and average hospital stay was 34.3 days. Partial flap loss occurred in 7 patients, with no total flap failures. Morbidity included six abdominal wound infections and seven epigastric hernias. Mortality was 11.7%. The omentum can be harvested safely and used reliably to reconstruct varying thoracic wounds and defects. Specific indications from this series include osteoradionecrosis, chest wall tumors, massive sternal wounds, and refractory mediastinitis.

Omental free flap reconstruction in complex head and neck deformities

Microvascular free flaps continue to revolutionize coverage options in head and neck reconstruction. This article reviews our 25‐year experience with omental free tissue transfers.

Tumor growth retardation and chemosensitizing action of fatty acid synthase inhibitor orlistat on T cell lymphoma: implication of reconstituted tumor microenvironment and multidrug resistance phenotype.

BACKGROUND Orlistat, a fatty acid synthase (FASN) inhibitor, has been demonstrated to inhibit tumor cell survival. However, the mechanism(s) of its tumor growth retarding action against malignancies of hematological origin remains unclear. It is also not understood if the antitumor action of orlistat implicates modulated susceptibility of tumor cell to anticancer drugs. Therefore, the present investigation focuses to study the antitumor and chemosensitizing action of orlistat in a murine host bearing a progressively growing T cell lymphoma. METHODS Tumor-bearing mice were administered with vehicle alone or containing orlistat followed by administration of PBS with or without cisplatin. Tumor progression and survival of tumor-bearing host were monitored along with analysis of tumor cell survival and apoptosis. Tumor ascitic fluid was examined for pH, NO and cytokines. Expression of genes and proteins was investigated by RT-PCR and western blot respectively. ROS was analyzed by DCFDA staining and FASN activity by spectrophotometry. RESULTS Orlistat administration to tumor-bearing mice resulted in tumor growth retardation, prolonged life span, declined tumor cell survival and chemosensitization to cisplatin. It was accompanied by increased osmotic fragility, modulated acidosis, expression of ROS, NO, cytokines, MCT-1 and VH(+) ATPase, Bcl2, Caspase-3, P53, inhibited FASN activity and declined expression of MDR and MRP-1 proteins. CONCLUSION Orlistat manifests antitumor and chemosensitizing action implicating modulated regulation of cell survival, reconstituted-tumor microenvironment and altered MDR phenotype. GENERAL SIGNIFICANCE These observations indicate that orlistat could be utilized as an adjunct regimen for improving antitumor efficacy of cisplatin.

Fatty acid synthase inhibitor orlistat induces apoptosis in T cell lymphoma: role of cell survival regulatory molecules.

BACKGROUND De novo fatty acid synthesis catalyzed by fatty acid synthase (FASN) is crucial for tumor cell survival. Thus therapeutic targeting of FASN is considered as a novel antineoplastic strategy. However, little is understood in this respect regarding malignancies of hematological origin. The present investigation was therefore, undertaken to study the molecular mechanisms of the antitumor action of FASN inhibitor orlistat (tetrahydrolipstatin) using a murine model of a T cell lymphoma. METHODS The antitumor efficacy of orlistat was investigated in vitro by estimating cell survival by MTT assay and apoptosis by Wright Giemsa, TUNEL, Annexin-V/PI staining and % DNA fragmentation. Generation of reactive oxygen species (ROS) in tumor cells was studied using fluorescence microscopy. Expression of genes and proteins was carried out by RT-PCR and western blot analyses respectively. FASN and CPT-1 activity was estimated by spectrophotometer. Cytokines expression was analyzed by ELISA. RESULTS We report that inhibition of FASN with its specific inhibitor orlistat manifests tumor-specific inhibition of cell survival, accompanied by induction of apoptosis. Orlistat-treated tumor cells showed an altered ROS generation, shift in cytokine balance and modulated expression of cell survival regulatory molecules like HSP70, Bcl2, p53, PUMA, Caspase-3 and CAD. It was observed that IFN-γ mediates orlistat-dependent modulation of FASN expression. CONCLUSION AND GENERAL SIGNIFICANCE In this study, we report some of the so far unexplored novel aspects underlying the molecular mechanisms associated with orlistat-dependent modulation of tumor cell survival. These observations will help in designing antineoplastic therapeutic protocols using orlistat against malignancies of hematological origin.

Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: a role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation.

Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Daltons lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications.

Cyanobacteria, pesticides and rice interaction

Abstract Cyanobacteria (blue-green algae) are widely distributed in tropical wet land rice fields where they play important role in building soil fertility. Due to their ability to photosynthesize and fixing atmospheric nitrogen, these are used as inoculants in rice fields to obtain additional benefits. The fertilizers and pesticides are being extensively used and therefore, it is necessary to find out effects of agrochemicals particularly pesticides on non target organisms like cyanobacteria. In the present investigation interaction of pesticides and cyanobacteria has been studied at different stages of rice crop. It was observed that application of herbicide butachlor decreased growth and N2-fixation of both native and inoculated cyanobacteria whereas insecticide metacid application was found to increase these attributes. The interaction of algal inoculation and both the biocides application were superior than algal inoculation with the herbicide application on both algae and rice. It is concluded from this study that herbicides application affected adversely cyanobacteria but insecticide application was favorable to them and application of both biocides was better than herbicide alone. Therefore judicious use of these chemicals and cyanobacteria in rice fields are suggested.

Cataract surgery under topical anesthesia: Gender-based study of pain experience.

Background: Pain perception, expression, tolerance, and the healthcare provider’s evaluation and management of pain are affected by the gender of the patient. To the best of our knowledge, there is lack of gender-based evaluation of pain during cataract surgery under topical anesthesia. Aims: This study has been initiated to evaluate and determine pain experience during cataract surgery under topical anesthesia and to study the gender-based differences of the same. Settings and Design: Hospital-based study involving cataract surgery under topical anesthesia using standard cataract surgery. It was an interventional comparative case series. Materials and Methods: One hundred and sixty patients were included in four groups, according to the gender and choice of surgery. Patients underwent either phacoemulsification with foldable intra ocular lens (IOL) or manual small incision cataract surgery with rigid IOL under topical anesthesia. Patients ranked their pain experience on VAS scale after the surgery and the surgeon recorded the ease/difficulty accordingly using a questionnaire. Statistical Analysis Used: MedCalc version 10.2.0.0 (www.medcalc.be) for windows was used to analyze the results. Analysis of variance (ANOVA) test and Kruskal-Walis test were used to analyze the data. Results: The overall visual analog scale (VAS) score was 0.8 (SD 1.3 range 0-8), with no statistical difference among the groups (P=0.5). The average surgeon’s score was 3.3 (SD 0.71 range 3-7), with no statistical difference between the groups (P=0.37).There were no sight threatening complications during the surgery in any group. Conclusions: The outcome of the study demonstrates that the patients undergoing cataract surgery under topical anesthesia perceive comparable pain and discomfort irrespective of their gender.

Proton conduction in some solid hydrates and KDP-ferroelectric family materials

Abstract Proton conduction in solid hydrates and KDP-ferroelectric family materials is briefly reviewed with emphasis on the materials studied in our laboratory. Typical experimental studies like coulometry, IR, transient ionuc current for mobility and σ versus 1 T on APT·5H 2 O, KDP and ADP materials have been specifically discussed. A mechanism for proton transport in KDP and ADP has been proposed, in which it is suggested that H…O…H bridge gets electrolysed on the application of dc electric field resulting in H + and OH − ions as mobile ionic species.

Diverse roles of LPA signaling in the intestinal epithelium

Lysophosphatidic acid (LPA) is a lipid mediator that modulates a wide variety of cellular functions. Elevated LPA signaling has been reported in patients with colorectal cancer or inflammatory bowel diseases, and the tumorigenic role of LPA has been demonstrated in experimental models of colon cancer. However, emerging evidence indicates the importance of LPA signaling in epithelial wound healing and regulation of intestinal electrolyte transport. Here, we briefly review current knowledge of the biological roles of LPA signaling in the intestinal tract.