STUDIES ON FACTORS INFLUENCING HIGH-DENSITY LIPOPROTEIN FUNCTIONALITY AND REVERSE CHOLESTEROL TRANSPORT

Coronary artery disease (CAD) in dyslipidemic and diabetic subjects remains the leading cause of death in the Western society. Current therapeutic strategies to prevent cardiovascular diseases are primarily based on the use of statins, which inhibit key enzyme in the cholesterol synthesis, HMG-CoA reductase. Another prominent risk factor for developing premature atherosclerosis is the low levels of high-density lipoprotein cholesterol (HDL-C). Despite documented benefits of statins a good proportion of individuals still remain at a higher risk of developing CAD. Therefore, focus has shifted on HDL-raising therapeutics to further improve the CV outcome. While Niacin and fenofibrate have not shown clinical benefits in two separate trials, results from CETP inhibitors, Torcetrapib and Dalcetrapib, in phase 3 clinical studies have been disappointing despite substantial increase in HDL-C. One of the challenges encountered with measuring plasma HDL as a biomarker for cardiovascular risk is the fact that the antiinflammatory HDL becomes pro-inflammatory after it undergoes oxidative modification in diabetics. Pro-inflammatory states have also been shown to reduce HDL functionality. Thus, the lack of translatability of animal results to humans has further added challenges in the HDL therapeutics area. These findings necessitated rethinking about HDL therapeutics leading to transition in HDL therapy concept that seems to focus more around HDL functionality rather than HDL level. This PhD dissertation focuses on factors that influence HDL functionality and analyzes a correlation between HDL functionality and aortic lipid deposition. Several agents that raise HDL levels have been utilized to dissect HDL functionality. In addition, animal model of diabetes and atherosclerosis was employed to establish a correlation between HDL functionality, hyperglycemia and inflammation. Through a series of studies, it is shown that HDL function correlates with beneficial effects, and diabetes and inflammation dampens HDL functionality leading to increased accumulation of aortic lesion formation. Agents that attenuate hyperlipidemia, glycemic index and proinflammatory state improved HDL functionality leading to reductions in atherosclerotic burden

Correlation of clinical, biochemical and radiological characteristics with histopathology of ovarian masses: hospital based descriptive study

Background: Ovarian cancer is an important cause of morbidity and mortality in the middle aged women. A systematic study of all ovarian tumours encountered in a large institute over a period of years is more likely to produce a significant amount of useful data regarding the clinical manifestations, the incidence of various types of ovarian tumours and the type of treatment offered. In this study we correlate various clinical presentations, ultrasound features, and various tumour marker levels with histopathology of ovarian masses.Methods: The study was conducted in the department of obstetrics and gynaecology in collaboration with department of radiology and pathology and lab medicine, Deen Dayal Upadhyay hospital from April 2015 to December 2016.Results: In the present study, 97 ovarian masses have been operated out of total 708 gynaecological surgeries in the obstetrics and gynaecology department of Deen Dayal Upadhyay hospital over the stipulated period. Prevalence of ovarian masses was 13.7%. Most of the ovarian masses were prevalent in the reproductive age group i.e. 21-40 years of age group in the present study though malignant masses were commonest in post-menopausal age group in the present study. 2 out 11 malignant ovarian masses were in the age group of 10-20 years which were dysgerminoma and immature teratoma respectively. Intra-operative findings like presence of mural nodule, haemorrhage and necrosis, ascites, papillary excrescences and omental caking were also found to have strong correlation with malignancy.Conclusions: A detailed preoperative workup and a simple tool loke RMI can differentiate between benign and malignant masses pre-operatively especially in post-menopausal women

Lack of Correlation of Plasma HDL With Fecal Cholesterol and Plasma Cholesterol Efflux Capacity Suggests Importance of HDL Functionality in Attenuation of Atherosclerosis

A number of clinical findings suggested HDL-raising as a plausible approach to treat residual risk of CVD. However, lack of CVD risk reduction by elevated HDL cholesterol (HDL-C) through cholesterol ester transfer protein (CETP) inhibition and enhanced risk reduction in apolipoprotein A-I Milano (apoAI-M) individuals with low HDL-C shifted the focus from HDL-C level to HDL function. In the present study, we investigated correlations between HDL-C, HDL function, fecal cholesterol excretion, and ex vivo plasma cholesterol efflux capacity (CEC) in animal models using two HDL modulators, LXR and PPAR-α agonists. In C57Bl mice, LXR agonist, T1317, raised HDL-C by 30%, while PPAR-α agonist, fenofibrate, reduced HDL-C by 30%, but fecal cholesterol showed twofold increase in both cases. CEC showed a 30–40% increase. Combination of LXR and PPAR-α agonists showed no changes in HDL-C, but, interestingly, fecal cholesterol increased by 4.5-fold, and CEC by 40%, suggesting existence of additional pathway for fecal cholesterol excretion. Regression analysis showed a lack of correlation between HDL-C and fecal cholesterol and CEC, while fecal cholesterol showed significant correlation with CEC, a measure of HDL function. ABCA1 and G1, the two important players in RCT showed greater induction with LXR agonist than PPAR-α agonist. HDL-C increased by 40 and 80% in LXR and PPAR-α treated apoA-I transgenic mice, respectively, with 80% increase in fecal cholesterol. A fivefold increase in fecal cholesterol with no correlation with either plasma HDL-C or CEC following co-treatment with LXR and PPAR-α agonists suggested existence of an HDL-independent pathway for body cholesterol elimination. In hyperlipidemic diabetic ob/ob mice also combination of LXR and PPAR-α agonists showed marked increases in fecal cholesterol content (10–20-fold), while HDL-C rise was only 40%, further suggesting HDL-independent elimination of body cholesterol in mice treated with combination of LXR and PPAR-α agonists. Atherosclerosis attenuation by LXR and PPAR-α agonists in LDLr-deficient mice was associated with increased fecal cholesterol, but not HDL-C. However, fecal cholesterol counts showed inverse correlation with aortic cholesteryl ester content. These data suggest: (a) lack of correlation between HDL-C and fecal or aortic cholesterol content; (b) HDL function (CEC) correlated with fecal cholesterol content; (c) association of reduced aortic lipids in LDLr−/− mice with increased fecal cholesterol, but not with HDL-C, and (d) existence of an HDL-independent pathway for fecal cholesterol excretion following co-treatment with LXR and PPAR-α agonists

Screening of efficient arbuscular mycorrhizal fungi for Azadirachta indica under nursery condition: a step towards afforestation of semi-arid region of western India

To optimize nursery practices for efficient plant production procedures and to keep up to the ever growing demand of seedlings, identification of the most suitable species of arbuscular mycorrhizal fungi (AMF), specific for a given tree species, is clearly a necessary task. Sixty days old seedlings of Neem (Azadirachta indica A. Juss) raised in root trainers were inoculated with six species of AMF and a mixed inoculum (consortia) and kept in green house. Performances of the treatments on this tree species were evaluated in terms of growth parameters like plant height shoot collar diameter, biomass and phosphorous uptake capabilities. Significant and varied increase in the growth parameters and phosphorous uptake was observed for most of the AMF species against control. Consortia culture was found to be the best suited AMF treatment for A.indica, while Glomus intraradices and Glomus mosseae were the best performing single species cultures. It is the first time in the state of Gujarat that a wide variety of AMF species, isolated from the typical semi-arid region of western India, were tested for the best growth performance with one of the most important tree species for the concerned region