ANTIOXIDANT AND ANTIBACTERIAL ACTIVITIES OF LEAVES, SKIN, FLESH AND SEEDS OF SRI LANKAN VARIETY OF CUCURBITA MOSCHATA

Reactive oxygen species are continuously produced by normal physiological activities of the human body and these cause damage to the cell membrane and biomolecules and thereby resulting chronic diseases. Antioxidants are scavengers of such free radicals and could combat oxidative stress. In spite of the advances in modern medicine, plant based remedies are increasingly sort after due to their lesser side effects. The antioxidants capacity and antimicrobial properties of ethyl acetate, acetone and methanol extracts of seeds, leaves, flesh and skin of the Sri Lankan variety of Cucerbita moschata were investigate. The ethyl acetate extracts of leaves gave the highest rate of change of reducing power with concentration (0.1625 ml/mg) in Fe3+ reducing power assay and the highest hydroxyl radical activity (72.8±3.8%). The acetone extract of leaves gave the highest rate of change of radical scavenging activity with concentration (7.016 ml/mg) during DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. Ethyl acetate extract of leaves also showed the highest phenolic content (42.4±2.4 mg (PGE/g)) and highest flavonoid content (40.2±0.6 mg (QE)/g). All extracts of skin and seeds as well as the methanol extract of leaves and acetone extract of flesh showed antibacterial activity against Bacillus subtilis. The three extracts of skin and the acetone extract of leaves showed antibacterial activity against the Escherichia coli

AN INVESTIGATION OF SOME PHENOLOGICAL EVENTS IN THREE MANGROVE GENERA WITH REFERENCE TO SELECTED CLIMATIC FACTORS IN NEGOMBO LAGOON

Mangroves consist of ICw tree species which are adapted to grow under tidal conditions.Studies on the phenology of mangroves is scarce. The main objective of this research wasto study major phenological cycles of some overexploited species and to compare thesewith previous observations on the same species samples from three other lagoons.Phenological cycles of leafing. flowering and fruiting of R hizophora apiculata, R.Mucronata, Bru.guicra gvmnorhi:a. B. Sexangula and Ccriops taga! were studies for aperiod of 24 months at selected sites in Negombo lagoon which is located in the wet zoneof Sri Lanka. Phenological cycles were followed and phenological indices were calculated.Thcse d;lla were compared with monthly variations in rain fall. temperature and humidityof the study area.Leal production showed two distinct maxima per year in all species. Rainfall seemed toexert a great influence on leaf rcflushing. Peaks of leaf rcflushing coincided with lulls ofIluwcriru; and fruiting. Annual bimodality was observed for flowering fruiting in allspecies. These species showed unimodal pattern of some of these events when they weregrowing in dry zonePhenological cycles constructed using data obtained show no intraspecific variation in thetime required to complete a single flowering-fruiting cycle, Similarly. intragcncricvariation was absent in the life time of leafing cyclesIn Rh izophora species. leaf bud jut emerged took I - 1,5 yrs to complete a single cyclewhere as in Bruguicra species this period was 2 - 2,5 yrs, In CeriOI)S tagal, it was 1,5 - 2yrs. Similarly. a flower bud of Rhizophora species took 1,5 - 2.5 yrs, Brugcciera species Iyr and C tagu! about 1,5 yrs to form a mature hypocotyl.A comparison of these observations with findings of the previous study proves thatphenological cycles in studies species are environmentally dependent and not speciesspecific,Unimodality of floral phenology in dry zone species may he due to the seasonal variation inground water salinity,

Prior exposure of graphic editing, video editing and animation software among new medical entrants at Faculty of Medicine, University of Kelaniya

Introduction: The use of graphic related educational materials is common in modern medicaleducation.Objectives: This study assesses the familiarity of graphic editing software (GES), video editingsoftware (VES) and animation software (AS) among new medical entrants.Methods: Moodle based self-administered questionnaire was given to new medical students who joinedthe Faculty of Medicine, University of Kelaniya in 2017.Results: There were 155 students in the batch where 66 (43%) were males. Thirty-nine percent (n=60)had used GES before entering to the faculty, among them 20% used GES at least once a month and55% reported to have at least an average skill level. Twenty-one percent (n=32) had used VES, amongthem 20% used it at least once and 24 % reported to have at least an average skill level. Ten percent(n=15) had used AS, among them 13% used it at least once and 11% reported to have at least an averageskill level. Students had used GES more than VES (P<0.01) and AS (P<0.01), and VES more than AS(P=0.01) before entering to the faculty.Conclusions: The majority of students had not used GES, VES and AS before entering to the facultyand it would be beneficial to teach this software to medical students. Self-assessment of skill level canunderestimate or overestimate the actual skill level of the student and can be identified as a limitationof the study

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1-42 toxicity in astrocytes

Neurodegeneration in Alzheimer’s disease (AD) is extensively studied, and the involvement of astrocytes and other cell types in this process has been described. However, the responses of astrocytes themselves to amyloid peptides ((A; the widely accepted major toxic factor in AD) is less well understood. Here, we show that A(1-42) is toxic to primary cultures of astrocytes. Toxicity does not involve disruption of astrocyte Ca2+ homeostasis, but instead occurs via formation of the toxic reactive species, peroxynitrite. Thus, A(1-42) raises peroxynitrite levels in astrocytes, and A(1-42) toxicity can be inhibited by antioxidants, or by inhibition of nitric oxide (NO) formation (reactive oxygen species (ROS) and NO combine to form peroxynitrite), or by a scavenger of peroxynitrite. Increased ROS levels observed following A(1-42) application were derived from NADPH oxidase. Induction of heme oxygenase-1 (HO-1) protected astrocytes from A(1-42) toxicity, and this protective effect was mimicked by application of the carbon monoxide (CO) releasing molecule CORM-2, suggesting HO-1 protection was attributable to its formation of CO. CO suppressed the rise of NADPH oxidase-derived ROS caused by A(1-42). Under hypoxic conditions (0.5% O2, 48h) HO-1 was induced in astrocytes and A(1-42) toxicity was significantly reduced, an effect which was reversed by the specific HO-1 inhibitor, QC-15. Our data suggest that A(1-42) is toxic to astrocytes, but that induction of HO-1 affords protection against this toxicity due to formation of CO. HO-1 induction, or CO donors, would appear to present attractive possible approaches to provide protection of both neuronal and non-neuronal cell types from the degenerative effects of AD in the central nervous system

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1-42 toxicity in astrocytes

Neurodegeneration in Alzheimer’s disease (AD) is extensively studied, and the involvement of astrocytes and other cell types in this process has been described. However, the responses of astrocytes themselves to amyloid β peptides ((Aβ; the widely accepted major toxic factor in AD) is less well understood. Here, we show that Aβ(1-42) is toxic to primary cultures of astrocytes. Toxicity does not involve disruption of astrocyte Ca2+ homeostasis, but instead occurs via formation of the toxic reactive species, peroxynitrite. Thus, Aβ(1-42) raises peroxynitrite levels in astrocytes, and Aβ(1-42) toxicity can be inhibited by antioxidants, or by inhibition of nitric oxide (NO) formation (reactive oxygen species (ROS) and NO combine to form peroxynitrite), or by a scavenger of peroxynitrite. Increased ROS levels observed following Aβ(1-42) application were derived from NADPH oxidase. Induction of heme oxygenase-1 (HO-1) protected astrocytes from Aβ(1-42) toxicity, and this protective effect was mimicked by application of the carbon monoxide (CO) releasing molecule CORM-2, suggesting HO-1 protection was attributable to its formation of CO. CO suppressed the rise of NADPH oxidase-derived ROS caused by Aβ(1-42). Under hypoxic conditions (0.5% O2, 48h) HO-1 was induced in astrocytes and Aβ(1-42) toxicity was significantly reduced, an effect which was reversed by the specific HO-1 inhibitor, QC-15. Our data suggest that Aβ(1-42) is toxic to astrocytes, but that induction of HO-1 affords protection against this toxicity due to formation of CO. HO-1 induction, or CO donors, would appear to present attractive possible approaches to provide protection of both neuronal and non-neuronal cell types from the degenerative effects of AD in the central nervous system

Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. The prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) pathway is a key mammalian oxygen sensing pathway and is frequently perturbed by pathological states including infection and inflammation. We discovered a significant upregulation of hypoxia regulated gene transcripts in patients with chronic hepatitis B (CHB) in the absence of liver cirrhosis. We used state-of-the-art in vitro and in vivo HBV infection models to evaluate a role for HBV infection and the viral regulatory protein HBx to drive HIF-signalling. HBx had no significant impact on HIF expression or associated transcriptional activity under normoxic or hypoxic conditions. Furthermore, we found no evidence of hypoxia gene expression in HBV de novo infection, HBV infected human liver chimeric mice or transgenic mice with integrated HBV genome. Collectively, our data show clear evidence of hypoxia gene induction in CHB that is not recapitulated in existing models for acute HBV infection, suggesting a role for inflammatory mediators in promoting hypoxia gene expression

Omeprazole Inhibits Proliferation and Modulates Autophagy in Pancreatic Cancer Cells

BACKGROUND: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. CONCLUSIONS: We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of pancreatic cancer. Since omeprazole use has already been established in clinical practice these results could lead to new clinical applications

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially