POTENTIAL PROTECTIVE EFFECT OF APOCYNIN IN ETHYLENE GLYCOL-INDUCED HEPATIC DAMAGE BY ATTENUATION OF MITOCHONDRIAL OXIDATIVE STRESS

ABSTRACTObjective: The present study was carried out to investigate the protective role of apocynin (APO), an nicotinamide adenine dinucleotide phosphateoxidase inhibitor, against ethylene glycol (EG)-induced hepatotoxicity in rats.Methods: Male Sprague-Dawley rats were divided into three groups with six animals in each group. Control group; EG group, in which hyperoxaluriawas induced by 0.4% EG in drinking water for 9 days; and EG+APO group, 0.4% EG in drinking water for 9 days along with APO at a dosage of200 mg/kg body weight/day, intraperitoneal. All the experimental animals were sacrificed on day 10. Serum and the liver homogenates were analyzedfor various biochemical parameters. Mitochondria from liver were isolated by differential centrifugation and were diagnosed for vital biochemicalparameters.Results: Hyperoxaluric animals have shown significantly increased levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvictransaminase, alkaline phosphatase, and lactate dehydrogenase, thus suggesting liver dysfunction. Declined activities of respiratory chain enzymesshowed mitochondrial dysfunction in EG treated rats. In addition, mitochondrial oxidative stress was evident by decreased levels of superoxidedismutase, reduced glutathione, and an increased lipid peroxidation (LPO). APO (200 mg/kg/day), significantly decreased EG-induced oxidativestress by reducing LPO and restoring antioxidant enzymes activities in liver tissue. Also, reduction in the impairment of liver mitochondria functioningwas detected in APO treated rats. Histological analysis depicted that APO treatment decreased liver epithelial damage, increased Kupffer cells, andrestored normal hepatocyte morphology.Conclusion: The results demonstrated the potential beneficial effects of APO in reducing EG-induced liver damage that might be through attenuationof mitochondrial oxidative stress.Keywords: Ethylene glycol, Liver, Oxidative stress, Mitochondrion, Apocynin, Antioxidant

Energy Management in Wireless Sensor Network Using PEGASIS

AbstractThe area of Wireless Sensor Network is one of the fastest growing fields in the communication and engineering world. The main objective of WSN is to sense the crucial information from the environment depending on the type of application for which it is deployed and send this information to its Base Station(BS) so that it can take corrective action. These Sensor Nodes ommunicate with each other through various protocols. The problem of the conventional method is, during gathering of sensed data each node transmits its sensed data directly to the base station for which it will deplete its power quickly. In this project, we propose PEGASIS(Power-Efficient Gathering in Sensor Information System),a near optimal chain-based protocol for extending the lifetime of network. In PEGASIS, each node communicates only with a close neighbour, performing a chain, elect a leader from the chain who collects the data from the neighbours to be transmitted to the base station. As a result the average energy spend by each node per round is reduced and to lower the bandwidth requirement. By using certain algorithm we can propose the shortest path of transmission of data to the base station. As a result less power consumption can be achieved to increase efficiency and life time of the network

TRAF2, an innate immune sensor, reciprocally regulates mitophagy and inflammation to maintain cardiac myocyte homeostasis

Mitochondria are essential for cardiac myocyte function, but damaged mitochondria trigger cardiac myocyte death. Although mitophagy, a lysosomal degradative pathway to remove damaged mitochondria, is robustly active in cardiac myocytes in the unstressed heart, its mechanisms and physiological role remain poorly defined. We discovered a critical role for TRAF2, an innate immunity effector protein with E3 ubiquitin ligase activity, in facilitating physiological cardiac myocyte mitophagy in the adult heart, to prevent inflammation and cell death, and maintain myocardial homeostasis

MHC II cell-based immunotherapy for non-small cell lung cancer in the presence of immune suppression.

Lung cancer is the leading cause of cancer deaths in the United States. Despite the existing treatments of surgery, radiotherapy, chemotherapy, and multimodal therapies, the long term survival of patients remains low. Activation of tumor-specific CD4+ T helper and cytotoxic CD8+ T cells offers a promising approach for the treatment of cancer patients. My project focuses on developing a novel vaccine (MHC II vaccines) designed to activate tumor-reactive CD4+ T cells. MHC II vaccines are lung cancer cells transfected with costimulatory molecules and MHC II alleles syngeneic to the prospective recipient. We hypothesize that because the vaccine cells do not express invariant chain (Ii), they preferentially present tumor-encoded peptides, rather than exogenously synthesized peptides, and thereby activate tumor-reactive T cells. Because active immunotherapies will only be effective if recipients are immuno-competent, we have tested if the vaccines activate CD4+ T cells from patients who have elevated levels of myeloid-derived suppressor cells (MDSC), a suppressor cell population that is present in many patients with cancer, and which inhibit both innate and adaptive immune system. The results described in Chapter 2 demonstrate that lung cancer MHC II vaccines activate tumor specific CD4+ T cells from the blood of healthy donors and lung cancer patients despite the presence of immune suppressive cells. Further, MHC II vaccines prime and boost CD4+ T cells that cross react with other subtypes of lung cancer cells but do not react with non-lung tumor cells or with normal lung fibroblast cells (Chapter 3).Various mechanisms of immune suppression have been attributed to MDSC, including arginine depletion by arginase production, iNOS production, however since MDSC is an emerging new field many more mechanisms are under their way. I have found a new mechanism through which MDSC also block T cell proliferation by sequestering cysteine, which is an essential amino acid for T cell (Chapter 4). T cells require cysteine because they lack the enzyme cystathionase which converts methionine to cysteine, and because they do not have an intact xc- transporter and therefore cannot import cystine and reduce it to cysteine. Therefore, T cells depend on macrophages and dendritic cells to export cysteine via their ASC neutral amino acid transporter. MDSC express the xc- transporter and import cystine; however, they do not express the ASC transporter and do not export cysteine. Since the import rate of cystine by MDSC is similar to that of macrophages and dendritic cells, but MDSC do not release cysteine, MDSC compete with macrophages and DC for the available extracellular cystine, but do not contribute to the extracellular pool of cysteine necessary for T cell proliferation. Therefore, in the presence of MDSC, T cells are deprived of the cysteine they need to proliferate and their activation is blocked. In summary, MHC II lung cancer vaccines may be used to treat immune suppressed advanced stage lung cancer patients. Furthermore, provision of stable form of cysteine along with MHC II lung cancer vaccine could further enhance the effectiveness of these vaccines

Clinico-microbiological profile of healthcare associated pneumonia in critically ill patients at level-I trauma centre of India

INTRODUCTION: Device-associated infections constitute the majority of health-care infections in Intensive Care Units (ICUs). Trauma patients are more prone to acquire such infections; ventilator-associated pneumonia (VAP) being the most common Health care associated infections (HAI) in ICU has serious implications such as increased morbidity, prolonged hospital stay, and mortality. This study aims to compare the clinicomicrobiological profile of VAP and non-VAP trauma patients at Level I trauma center. MATERIALS AND METHODS: A 4-year retrospective study of prospectively maintained database was conducted at Level 1 trauma center from January 2013 to December 2016. The patients were classified into two groups named VAP and non-VAP patients. VAP patients were defined according to the criteria of the Centers for Disease Control and Prevention. The data were compiled and analyzed. Statistical data were analyzed using SPSS version 21 software. RESULTS: During the study period, 134 (13%) cases of VAP and 909 (87%) non-VAP cases were observed in our study. The total number of ventilator days for VAP patients was 5128 days, which ranged from 2 to 82 days (median 42 days). The length of hospital stay in non-VAP category ranged from 1 to 390 days (median 195.5 days). Inhospital mortality was observed in 62 (46%) patients with VAP. Three hundred and eighteen (35%) non-VAP patients had also had a fatal outcome. Gram-negative organisms, most commonly Acinetobacter spp. (13, 21%), were reported in the fatal VAP patients. CONCLUSION AND DISCUSSION: Higher rate of mortality was observed in patients with VAP in comparison to non-VAP patients, both being on mechanical ventilation. Early recognition of VAP, implementation of proper VAP preventive bundle strategies, and stringent infection control practices are essential mandates to prevent VAP

A 5-year surveillance on antimicrobial resistance of Acinetobacter isolates at a level-I trauma centre of India

INTRODUCTION: Acinetobacter spp. has emerged as a major cause of nosocomial outbreaks. Multiple antibiotic resistance is an important problem in Acinetobacter isolates in recent years. The aim of this study was to evaluate the rate of antimicrobial resistance and changes in resistance pattern over a period of 5 years (2012–2016) in Acinetobacter spp. isolated from trauma patients. MATERIALS AND METHODS: Acinetobacter spp. was identified by VITEK 2 and antibiotic susceptibility of isolates was investigated by disc-diffusion method and VITEK 2 automated system. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute guidelines. RESULTS: Out of the total 16,210 isolates obtained throughout the period of 5 years, Acinetobacter spp. accounted for 3744 (28.9%). Out of which, the species which was maximally isolated was Acinetobacter baumannii (98.5%), followed by Acinetobacter lwoffii (1.4%) and Acinetobacter hemolyticus (0.1%). The highest number of clinical isolates of Acinetobacter were recovered from neurosurgical ward (n = 1210), followed by the neurosurgical intensive care unit (ICU) (n = 1000) and surgical ICU (n = 948) and the most common sample of Acinetobacter isolation was from tracheal aspirate (37.1%), followed by wound swab (18.8%). The highest level of resistance was observed against ciprofloxacin (96%), followed by cefepime (95%), ceftazidime (95%), piperacillin (95%), and amikacin (92%). The trend of antibiotic resistance was found to be statistically significant (P < 0.001) for most of the antibiotics being tested such as amikacin and carbapenems. CONCLUSION: The high rate of antibiotic resistance of the Acinetobacter strains indicated that there is an urgent need for controlled antibiotic usage and appliance of hospital infection control measures

Pattern of antimicrobial resistance of Gram-negative bacilli in surgical site infections in in-patients and out-patients at an apex trauma Center: 2013–2016

INTRODUCTION: Antimicrobial resistance is an increasing problem worldwide especially among the surgical site infections (SSIs). SSI is becoming more serious due to hospital-acquired infections/nosocomial infections, which further leads to the overuse of broad-spectrum antibiotics. To investigate the antimicrobial resistance patterns among Gram-negative bacteria in SSI in in- and out-patients the present study was designed. METHODOLOGY: During the 4 years (January 2013–December 2016), the antimicrobial resistant pattern was studied in the admitted patients and in the patients who were followed up to the outpatients department (OPD) after discharge. Antimicrobial resistance pattern testing was done by the disk diffusion method on Mueller-Hinton agar and by E-test for ten antibiotics according to The Clinical and Laboratory Standards Institute guidelines for Gram-negative bacilli. RESULTS: A total of 2,447 strains were isolated from the studied population on over the period of 4 years. Of 2447, 1996 (81%) were isolated from patients who had SSI during the hospital stay, and 451 (18%) were from patients who attended the OPD after discharge. In the outpatients, who followed up in the OPD for the SSI, Escherichia coli (148), and Pseudomonas aeruginosa (93), whereas in the patients who develop SSI during their hospital stay, Acinetobacter baumannii (622), E. coli (424), and Klebsiella pneumoniae (315) were found to be common. A very high resistance pattern was observed in both the studied groups; however, a higher resistance pattern was seen in in-patients as compared to outpatients. CONCLUSION: In our study, we have reported resistance pattern in Gram-negative bacteria isolated from the patients who were came for the follow as well as in the inpatients. For the outpatients, it can be concluded that it could be a community-acquired infection which is also an alarming condition for our society

Symbiotic Fungi for Eco-friendly Environment: <i>A Perspective</i>

396-400Increasing interest in commercial cultivation of medicinal and economically important plants on large scale has necessitated development of various tissue culture techniques for their early growth and improvement in yield. But sometimes micropropagated plants do not acclimatize due to lack of eco-friendly microorganisms in the rhizosphere zones. The relevance of mycorrhiza for the acclimatization, success of micropropagated plantlets has gained importance in the recent past, because most of the forest trees are obligatory dependent upon the mycorrhizal symbiosis. The influence of early mycorrhizal symbiosis under controlled conditions and their resistance to environmental stresses had been reported earlier. Since Arbuscular mycorrhizal fungi do not grow like any other fungi apart from their living hosts, an axenically cultivable mycorrhiza-like-fungus named, Piriformospora indica was discovered. The utilization of this fungus in acclimatization of selected economically and medicinally important plants has been discussed in this paper for further exploration