Chylomicron marker metabolism in health and disease.

In this thesis, chylomicron (CM) and CM-remnant (CM-R) metabolism in humans was studied by the application of unique markers which label these lipoprotein particles from the stage of production by the enterocyte until, removal by hepatic receptor mediated processes. Retinyl palmitate (RP) is a vitamin A ester, which labels the CM/CM-R by behaving like the cholesterol ester (CE) which is carried in the core of these particles. Development of a mono-specific antibody to apolipoprotein (apo) B-48 and application of an enzyme linked immunosorbant assay (ELISA) enabled quantification of this apolipoprotein which is specifically located on the surface of CM/CM-R. The postprandial lipaemic response for all parameters were determined by the area under the time response curve (AUC). Plasma was separated by flotation ultracentrifugation, overlayered with saline (d=1.006 g/ml), to separate the triacylglycerol-rich lipoprotein (TRL) and infranatant fractions. To examine the effects of habitual low intensity exercise on the postprandial CM response to meals of varying fat contents, triacylglycerol (TAG), apo B-48 and RP were measured in the TRL fraction. 14 young men were recruited and divided into two groups, active and inactive, depending on their habitual activity level. Active subjects were defined as those who undertook aerobic activity for at least 3 sessions a week and the inactive group took no regular exercise. In response to meals of 20 g, 40 g and 80 g fat content, the active subjects showed lower postprandial CM response as assessed by the TRL-apo B-48 AUC, by 35%, 58% and 66% (p < 0.05), respectively. The TRL-RP response to these meals was also lower by 67%, 54% and 49% (p < 0.01 in each case), in the active subjects. Plasma lipoprotein lipase (LPL) activity was 50% (p < 0.05) higher in the active group following the 80 g fat meal. The metabolism of CM/CM-R in the postprandial state was studied in 9 middle aged men with non-insulin dependent diabetes mellitus (NIDDM) and in 6 matched controls. The subjects were given a standardised meal containing 50 g fat, followed by a 12 hr postprandial study. NIDDM subjects, compared with the controls, showed exaggerated plasma postprandial responses of apo B-48, TAG and RP of 3696 vs 1796 ug.ml-1.min (p < 0.005), 2525 vs 1243 mmol.L-1.min (p < 0.05), and 3957 vs 2923 umol.L-1.min (p < 0.05), respectively. In the TRL fraction, apo B-48, TAG and RP AUCs were 1021 vs 473 ug.ml-1.min (p < 0.05), 1307 vs 527 mmol.L-1.min (p < 0.05), and 2707 vs 2158 umol.L-1.min (NS = not significant), respectively. There was no significant difference in plasma lipoprotein lipase (LPL) activity, between the groups. The effect of bezafibrate on postprandial lipoprotein metabolism was investigated in a 6-week placebo controlled, cross-over trial in the same 9 NIDDM subjects. Bezafibrate reduced the AUC for plasma apo B-48, TAG and RP by 45% (p , 0.005), 30% (p < 0.005) and 46% (p < 0.01). The corresponding reduction following bezafibrate therapy in TRL apo B-48, TAG and RP were 62% (p < 0.005), 54% ( p < 0.005) and 49% (p < 0.05), respectively. Plasma LPL activity was increased after bezafibrate therapy (p < 0.005). The effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors on postprandial lipoprotein metabolism, and in particular, CM-R metabolism, were investigated in 20 middle-aged subjects with primary hypercholesterolaemia. Subjects were given a high fat meal and the CM/CM-R markers, apo B-48 and RP, were measured in various fractions of plasma, obtained by cumulative flotation ultracentrifugation, using a linear salt gradient. The Sf 20-400 fraction of plasma, containing the majority of plasma CM-R was isolated. Reductions in TAG, CE, retinyl ester (RE) and apo B-48 AUC, in this fraction, following 4 weeks of HMG CoA reductase therapy, were 61% (p < 0.01), 20% (p < 0.01), 13 % (NS) and 23% (p < 0.01), respectively. Additionally, the smaller, potentially atherogenic CM-R, as measured by apo B-48 AUC in the Sf 60-100 and Sf 20-60 fractions of plasma were reduced by 15% (p < 0.05) and 22% (p < 0.05), respectively, following HMG CoA therapy. These studies have established that measurement of apo B-48 and RP are useful in the study of the metabolism of CM/CM-R in health and disease

Haemoglobin measurement by point-of-care devices- a need of the hour: study conducted on antenatal females

Background: Haemoglobin measurement in antenatal care can help in timely detection and treatment of anaemia, which is a major contributory factor to maternal mortality in developing countries. The transport of samples for haemoglobin assessment may delay the treatment, resulting in preventable deaths. Haemoglobin measurement by point of care testing (POCT) devices is easy, quick and less invasive. There are very few studies which compare the capillary blood haemoglobin using point of care devices with venous blood samples. This study was conducted to compare capillary blood haemoglobin using POCT device with venous blood haemoglobin using haematology analysers in antenatal Indian females.Methods: One hundred pregnant women were recruited during their first trimester antenatal visits. Hemoglobin by finger prick capillary sample (POCT) was compared with haemoglobin of venous sample analysed by the haematology analyser (Beckman coulter) which was considered as gold standard. Intraclass correlation co-efficient based on Bland Altman analysis was computed using SPSS v21. A p value less than 0.05 was considered statistically significant.Results: The intraclass correlation coefficient of 0.97 was recorded with central laboratory reference standard, with a mean difference of -0.481 gm% and -0.482 gm% by capillary and venous blood samples, respectively (p&lt;0.0001).Conclusions: A good agreement between capillary blood haemoglobin (POCT device) and venous blood (haematology analyser) was achieved

A Note on Low-Dimensional String Compactifications

We study supersymmetric compactifications of type II strings on eightfolds to two dimensions. It is demonstrated that the type IIB string on an eightfold is free of gravitational anomalies. T-duality requires that this theory when further compactified on a circle must have a vacuum momentum; this is explicitly shown to be present and to have the right value. A subtlety in the relation of IIB compactifications and M-Theory orientifolds to two dimensions is pointed out.Comment: 12 pages Tex file, no figure

Antiulcer Potential of the Ethanolic Extract of Aerva Persica Merrill Root in Rats

AbstractThe ethanol extract of the roots of Aerva persica (Burm f) Merrill (Amaranthaceae) was investigated to determine its antiulcer and in vivo antioxidant activities in albino Wistar rats. Ulcers were induced by ethanol and pylorus ligation. The extract was administered at the dose of 200mg/kg orally, p.o. for 15 consecutive days. The ulcer index of the ethanol extract was found to be significantly reduced compared with control animals. The effect was also assessed by determining the free acidity, pepsin activity, total carbohydrate (TC), and protein content (PK) in control, standard, and test group animals. The in vivo antioxidant activity was evaluated by determining the reduced glutathione level (GSH) and malondialdehyde (MDA) level in the tissue homogenates. The results reveal the significant reduction in the level of malondialdehyde and the increase in the level of reduced glutathione in the rats that received the ethanolic extract. Furthermore, histopathological studies have shown that pretreatment with the ethanolic extract of the roots of A persica reduces (100%) ethanol- and pylorus ligation-induced hemorrhagic necrosis in rats

Brucellosis: An underdiagnosed infection in children

Brucellosis, which is believed and categorized as an animal disease, can, surprisingly, be found in humans also. We report a 5-year boy presenting to us with prolonged (5 months) unexplained fever, non-tender discrete lymphadenopathy, and hepatosplenomegaly and finally proved to be a case of brucellosis, which was treated appropriately. Brucellosis should be considered as one of the differential diagnoses causing prolonged fever in children

M2-branes on M-folds

We argue that the moduli space for the Bagger-Lambert A_4 theory at level k is (R^8 \times R^8)/D_{2k}, where D_{2k} is the dihedral group of order 4k. We conjecture that the theory describes two M2-branes on a Z_{2k} ``M-fold'', in which a geometrical action of Z_{2k} is combined with an action on the branes. For k=1, this arises as the strong coupling limit of two D2-branes on an O2^- orientifold, whose worldvolume theory is the maximally supersymmetric SO(4) gauge theory. Finally, in an appropriate large-k limit we show that one recovers compactified M-theory and the M2-branes reduce to D2-branes.Comment: 16 pages, LaTeX, v2: typos corrected, included appendices on Chern-Simons level quantization and monopole charge quantizatio

Role of Fluorescent In Situ Hybridization, Cholangioscopic Biopsies, and EUS‐FNA in the Evaluation of Biliary Strictures

Background and Aims: Our goal was to compare the diagnostic accuracy of FISH in the detection of malignancy compared with other standard diagnostic modalities, including brush cytology and biopsy specimens over a 10-year period of prospective data collection. Methods: We conducted a review of all consecutive biliary strictures evaluated between 2006 and 2016. Patients with a final pathologic diagnosis or conclusive follow-up were included. We evaluated the performance of FISH polysomy (CEP 3, 7, and 17) and 9p21 deletion as well as cholangioscopic biopsy (CBx) and EUS-FNA. Statistical analysis was performed with the Mann–Whitney U and Fisher’s exact tests. Results: Of 382 patients with indeterminate strictures, 281 met inclusion criteria. Forty-nine percent were malignant. Cytology, FISH polysomy, and FISH polysomy/9p21 showed a specificity of 99.3%. FISH polysomy/9p21 as a single modality was the most sensitive at 56% (p < 0.001). The sensitivity of FISH polysomy/9p21 and cytology was significantly higher than cytology alone at 63 versus 35% (p < 0.05). EUS-FNA for distal strictures and CBx for proximal strictures increased sensitivity from 33 to 93% (p < 0.001) and 48–76% (p = 0.05) in cytology-negative strictures. Conclusions: The high specificity of FISH polysomy/9p21 suggests that a positive result is sufficient for diagnosing malignancy in indeterminate strictures. The significantly higher sensitivity of FISH polysomy/9p21 compared to cytology supports the use of FISH in all non-diagnostic cases. Although both EUS-FNA and CBx were complimentary, our results suggest that distal strictures should be evaluated by EUS initially. Proximal strictures may be evaluated by FISH first and then by CBx if inconclusive

Air pollution in Delhi: A review of past and current policy approaches

Delhi National Capital Region (Delhi NCR) is facing serious challenges linked to worrying levels of air pollution (mainly NO2, PM10 and PM2.5). The CADTIME prject (Clean Air in Delhi through Implementation, Mitigation and Engagement) aims to understand what is required to deliver significant reductions in levels of air pollution. This paper presents the results of the first stage of the project: it firstly contextualises the challenges of air quality management in Delhi within the broader evolution of environmental policies and governance in India, with particular consideration to the tensions between environmental protection and the country's development objectives. Secondly, it sets out how CADTIME will combine multiple source qualitative and quantitative data to develop an air quality action plan and an implementation strategy. In particular, through two workshops with local and national experts and stakeholders, and two rounds of focus groups with citizens of Delhi we will contrast stakeholders' priorities and preferences for existing and potential solutions to air pollution with citizens' lived experiences, thus assessing the political/technical feasibility and public acceptability of current and proposed measures. Furthermore, we will complement the primary qualitative data with a critical review examining the successes and failures of UK and European policies to draw lessons that can be relevant for Delhi and to avoid ineffective policies and achieve cost-effective solutions for the city in the shortest possible time

Increasing Trends of Leptospirosis in Northern India: A Clinico-Epidemiological Study

Leptospirosis is often not suspected by physicians in patients with acute febrile illnesses reporting from supposedly “non-endemic areas,” including north India. Clinical manifestations are protean, and complications can affect most organ systems, including liver, kidneys, lungs, and the central nervous system. Timely diagnosis and specific therapy can reduce severity of illness and, in turn, mortality. In this study conducted at a tertiary care center in north India, we find how a much-neglected disease entity has emerged as a major cause of acute febrile illness in a so called “non-endemic area.” Incidence is increasing yearly. The majority of patients were from a rural background, and were farmers or farm labourers. Poor hygiene, contact with animals, rat infestation of houses, and contact with stagnant dirty water are the major determinants of disease. Apart from the usual symptoms of intermittent fever with chill and rigor, hepatosplenomegaly, renal decompensation, muscle pain and tenderness, and conjunctival suffusion, signs and symptoms indicating involvement of the respiratory and central nervous systems were also commonly observed. Severe complications resulting in mortality do occur and is especially due to late suspicion among primary level physicians, and the resulting inappropriate therapy