GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains unclear. Crystal structures of Plasmodium falciparum GMPS in conjunction with mutational and enzyme kinetic studies reported here provide evidence that an 85° rotation of the GATase domain is required for ammonia channelling and thus for the catalytic activity of this two-domain enzyme. We suggest that conformational changes in helix 371–375 holding catalytic residues and in loop 376–401 along the rotation trajectory trigger the different steps of catalysis, and establish the central role of Glu374 in allostery and inter-domain crosstalk. These studies reveal the mechanism of domain rotation and inter-domain communication, providing a molecular framework for the function of all single polypeptide GMPSs and form a solid basis for rational drug design targeting this therapeutically important enzyme.

Morinda citrifolia (Noni) is a medicinal plant widely distributed in the tropical regions of India, Indonesia and Malaysia and has a long history of treating a wide variety of diseases such as cancer, atherosclerosis and diabetes. The present investigation was designed to evaluate blood biochemical parameters and antioxidant effects in calves fed with M. citrifolia. A total of eight calves were divided into two groups as control (n = 4) and treatment (n = 4). The calves of treatment group were fed with fresh minced raw fruit (100 g/calf/day) and the calves in control group were fed with placebo. Blood samples were collected at weekly intervals for four weeks for estimation of biochemical parameters and to determine antioxidant activity. The crude extract of noni fruits significantly (P < .01) decreased the concentrations of serum total cholesterol, triglycerides, serum glucose and also decreased (P < .05) serum creatinine and urea. There was a reduction in lipid peroxidation (LPO) than control; however, superoxide dismutase (SOD) and catalase levels were dramatically increased (P < .01) in morinda-fed calves. The results of present preliminary study demonstrated hypolipidemic, hypoglycaemic and antioxidant effect of M. citrifolia in calves. The findings of this study could be exploited for stress amelioration and management of metabolic diseases in calves and cattle without adverse effects.

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Background: Lung cancer is one of the leading causes of cancer related morbidity and mortality among both the sexes. It accounts for 13% of all new cancer cases and 19% of cancer related deaths worldwide. In India, lung cancer constitutes 6.9% of all new cancer cases and 9.3% of all cancer related deaths in both sexes. Majority of them present in advanced disease. Aim: This study aims to identify the contributing factors for delays in lung cancer diagnosis and treatment. Methods: This is a retrospective cross-sectional observational study which was conducted at Department of Oncology, Mysore Medical College and Research Institute, India. Records of the all histologically confirmed lung cancer patients from the year 2011 to 2016 were reviewed. Results: A total of 133 patients were identified with lung cancer and their records were evaluated. Out of these 133 patients, 60% of the cases were males. The median age was 63 years with the youngest being 37 and the eldest was 83 years. Majority of patients were in stage III (59%) and IV (36%). About 89% of the patients were smokers. Non–small cell lung cancer accounted 83% (squamous cell 66.5%, adenocarcinoma 30.5%, large cell 1.5% and neuroendocrine 1.5%) and small cell lung cancer was 17%. A total of 17% (26) of patient were on empirical antitubercular treatment (ATT) since the onset of current symptoms. While analyzing delay with independent T test showed mean delay of 25.01 days (± SD 6.17) in patient without ATT and with ATT delay was 57.09 days (± SD 8.05) ( P ≤ 0.01). Thirty five percentage (46) of patient received treatment within 1 month from the first hospital visit, 28% (37) within two months and 37% (50) within 3-4 months of the first hospital visit. The delay to hospital visit was shorter in advanced cancer and small cell cancer maybe because of the acute presenting symptoms. Conclusion: Various factors contributing for the delays are lag time from symptom onset to first visit with primary physician, delay due to investigation and symptomatic treatment under primary physician care, delay further aggravated by empirical but inappropriate ATT, further delay due to diagnostic procedure to establish the cancer diagnosis. Thus proper and timely referral to the specialist from primary physician will reduce these delays and help to avoid situation where curable disease become incurable and significantly alters the prognosis.

e21670 Background: Olanzapine has been shown to be a safe and effective agent for the prevention of CINV. This study aims to compare olanzapine with aprepitant in the prevention of CINV. Methods: This study included breast cancer patients receiving doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 chemotherapy. Female patient; age, ≥ 18; chemotherapy naïve; no nausea/ vomiting in the past 24 hours were included. Patients with seizure disorder, brain metastasis, prior use of antipsychotic agents and hypersensitivity to olanzapine were excluded. Patients were randomized into two groups. Olanzapine group received tab olanzapine 10 mg on day 1 to 3. Aprepitant group received tab.aprepitant 125mg on day 1 and 80mg on days 2-3. Both groups received inj palnosteron 0.25mg, inj dexamethasone 8mg on day 1. Use of rescue therapy for nausea or vomiting was permitted. The primary end point of the study was complete response (CR) for nausea that is no nausea in the acute (within 24 hours), delayed (days 2-5), and overall periods (0-120 hours). Secondary endpoint was CR for vomiting and no use of rescue drugs in all periods. Beginning with the first day of chemotherapy and daily through day 5, patients were asked to record daily episodes of nausea using a visual analogue scale from 0 to 10, with 0 indicating no nausea and 10 indicating a maximal level of nausea. They were asked to record daily episodes of vomiting (number and time) and the utilization of rescue therapy. Results: A total of 84 patients (42 in each arm) were evaluated and consented for the study. The median age 48 years; range 29-80; ECOG PS - 0, 1. CR for nausea was 84% for the acute period , 58% for the delayed period and 56% for the overall period for the olanzapine group. CR for nausea in aprepitant group was 69% acute period, 55% delayed period, and 55% for the overall period. CR for vomiting was 91% acute; 74% delayed; 70% overall period for olanzapine group. CR for vomiting in aprepitant group was 91% acute; 83% delayed; 83% overall period. There were no Grade 3 /4 toxicities. Conclusions: Olanzapine is better in the prevention of nausea. However aprepitant is better in the prevention of vomiting. Combination of these two agents needs to be studied in future studies.

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