Design, Synthesis, Characterization, and Crystal Structure Studies of Nrf2 Modulators for Inhibiting Cancer Cell Growth In Vitro and In Vivo.

Nrf2 is one of the important therapeutic targets studied extensively in several cancers including the carcinomas of the colon and rectum. However, to date, not many Nrf2 inhibitors showed promising results for retarding the growth of colorectal cancers (CRCs). Therefore, in this study, first, we have demonstrated the therapeutic effect of siRNA-mediated downmodulation of Nrf2 on the proliferation rate of CRC cell lines. Next, we have designed, synthesized, characterized, and determined the crystal structures for a series of tetrahydrocarbazoles (THCs) and assessed their potential to modulate the activity of Nrf2 target gene NAD(P)H:quinone oxidoreductase (NQO1) activity by treating colorectal carcinoma cell line HCT-116. Later, the cytotoxic potential of compounds was assessed against cell lines expressing varying amounts of Nrf2, viz., breast cancer cell lines MDA-MB-231 and T47D (low functionally active Nrf2), HCT-116 (moderately active Nrf2), and lung cancer cell line A549 (highly active Nrf2), and the lead compound 5b was tested for its effect on cell cycle progression in vitro and for retarding the growth of Ehrlich ascites carcinomas (EACs) in mice. Data from our study demonstrated that among various compounds 5b exhibited better therapeutic index and retarded the growth of EAC cells in mice. Therefore, compound 5b is recommended for further development to target cancers.

Study of Aetiology and Outcome in Acute Febrile Illness Patients with Multiple Organ Dysfunction Syndrome.

INTRODUCTION: Acute febrile illness with Multi Organ Dysfunction Syndrome (MODS) carries significant morbidity and mortality despite standard therapy in intensive care settings. Infections are the most common cause of MODS followed by polytrauma. Present study was undertaken in medical intensive care units of a tertiary hospital to study the aetiology and outcome among patients with acute febrile illness developing MODS. AIM: 1) To study the aetiology of acute febrile illness in patients developing MODS. 2) To study the final outcome among these patients. MATERIALS AND METHODS: The present study was conducted at a tertiary care hospital in Mysuru, Karnataka, India, over a period of 6 months from July 2013 to December 2013. The Institutional Ethics Committee Approval (IEC) was obtained before the commencement of the study. A total of 213 cases admitted in intensive care unit with acute febrile illness with two or more organ dysfunction were screened for the inclusion and exclusion criterias. RESULTS: A total of 213 cases of acute febrile illness with one or more organ dysfunction were screened. Of the screened patients 75 patients were finally included in the study out of which 46 (61.3%) patients were males and 29 (38.7%) patients were females. Aetiology for acute febrile illness with MODS could be established in 49 (65.3%) patients and it was obscure in 26 (34.7%) patients despite repeated investigations. Dengue infection (29.3%) was the commonest cause of febrile illness with MODS followed by leptospirosis (22.7%). Majority of these patients had haematological derangements (78.7%) and liver function test abnormalities (68%). Out of these 75 cases, 54 (72%) patients recovered completely and 21 (28%) patients died. Among males (N=46), 35 (76.1%) patients recovered and 11 (23.9%) patients died where as among females (N=29), 19 (65.5%) patients recovered and 10 (34.5%) patients died. Mortality was proportionate with the number of organ dysfunction, especially Central Nervous System (CNS) involvement. CONCLUSION: Incidence of febrile illness with MODS is more prevalent in males but the outcome appears poorer among females. The diagnosis remained obscure in a sizable proportion of these patients. Prognosis was inversely dependent on the number of organs involved especially with CNS manifestations.

Basic Risk Factors Awareness in Non-Communicable Diseases (BRAND) Study Among People Visiting Tertiary Care Centre in Mysuru, Karnataka.

INTRODUCTION: Non Communicable Diseases (NCDs) are the major causes of mortality and morbidity globally. Awareness about NCDs and their risk factors has an important role in prevention and management strategies of these NCDs. AIM: 1) To assess the awareness of risk factors contributing to NCDs among the patients visiting tertiary care hospital in Mysuru district; 2) To compare the difference in awareness of risk factors for NCDs among the urban and rural patients with/ without NCD visiting the tertiary care hospital. MATERIALS AND METHODS: A cross- sectional study was conducted in a tertiary care centre- JSS Hospital, Mysuru, Karnataka from March 2013 - August 2013. The patients visiting Medicine OPD during the period were the study subjects. The subjects were allocated into 4 groups: Urban without any NCD, Urban with atleast one NCD, rural without NCD, rural with atleast one NCD. A pretested questionnaire regarding awareness of risk factors for NCDs was used in the study and frequency and proportions were used to analyse the data. RESULTS: A total of 400 subjects, 100 subjects in each group were included in the study. Out of these subjects about 65% of the urban group and 42% of the rural group subjects were aware of the NCDs and their risk factors. Least awareness was observed among the rural subjects without any NCDs (35%). CONCLUSION: The awareness of risk factors of NCDs and knowledge regarding prevention of NCDs was not satisfactory. The results highlighted the need and scope for health education and interventions to improve the awareness about NCDs and their risk factors.