EVALUATION OF POLLUTION DAMAGE COST IN BELLANWILA A.TTIDIYA WETLAND

Management of waste, both liquid and solid has become a critical environmental concernparticularly in the more urbanized areas ill 'Sri Lanka and this problem is most severe inthe densely populated areas of Western province. Bellanwila Attidiya wetland is also one ofthe places, which is used as open dumpsites. It has bad effects on the health, air quality, biodiversity water, and land.The main objective of the present study was to evaluate the pollution damage cost of thewetland. In addition peoples views were also obtained on possibility of recreation in thewetland.In the present study the Contingent Valuation Method was used to evaluate the pollutiondamage cost of the wetland. Data was derived from a Contingent Valuation survey carriedout among the residents of the area and commuters who travel along the road which passesthrough the wetland. The results were consistent with theory and an aggregate cost ofwetland pollution was estimated to be 2870 00 million rupees per year. People expressedtheir willingness for proposals of developing the wet land as a recreation site.The valuation may be useful in cost benefit analysis of wetland management and otherrelated policy and planning programmes related to wetlands. This could be used as aninstrument to get the local and international attention and draw funds for the wetlandconservation.

AWARENESS OF USAGE OF SUNSCREENS AMONG SCHOOL CHILDREN IN KANDY, SRI LANKA

Objective: The objective of this research was to evaluate the awareness of usage of sunscreens among school children in Kandy, Sri Lanka.Methods: School children (138) who do outdoor sports were recruited from six schools. Knowledge and attitudes towards the usage and application of sunscreens were assessed using a researcher administered questionnaire. Statistical analyses were done using Statistical Package for the Social Science (SPSS version-16).Results: Among the school children who do outdoor sports, 71 (51.4%) of participants used sunscreens and 67 (48.6%) of participants did not use sunscreens.Conclusion: According to the results most of the school children have a lack of knowledge, attitudes and practice towards the usage of sunscreens

Formation primaquine-5, 6-orthoquinone, the putative active and toxic metabolite of primaquine via direct oxidation in human erythrocytes

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics Short precorneal residence time and poor transocular membrane permeability are the major challenges associated with topical ocular drug delivery. In the present research, the efficiency of the electrolyte-triggered sol-to-gel-forming system of natamycin (NT) transfersomes was investigated for enhanced and prolonged ophthalmic delivery. Transfersomes were optimized by varying the molar ratios of phospholipid, sorbitan monostearate (Span) and tocopheryl polyethylene glycol succinate (TPGS). NT transfersome formulations (FNs) prepared with a 1:1 molar ratio of phospholipid-to-Span and low levels of TPGS showed optimal morphometric properties, and were thus selected to fabricate the in situ gelling system. Gellan gum-based (0.3% w/v) FN-loaded formulations (FNGs) immediately formed an in situ gel in the simulated tear fluid, with considerable viscoelastic characteristics. In vitro cytotoxicity in corneal epithelial cells and corneal histology studies demonstrated the ocular safety and cytocom-patibility of these optimized formulations. Transcorneal permeability of NT from these formulations was significantly higher than in the control suspension. Moreover, the ocular disposition studies of NT, from the FNs and FNGs, in New Zealand male albino rabbits demonstrated the superiority of the electrolyte-sensitive FNGs in terms of NT delivery to the ocular tissues

Enantioselective metabolism of primaquine by human CYP2D6

BACKGROUND: Primaquine, currently the only approved drug for the treatment and radical cure of Plasmodium vivax malaria, is still used as a racemic mixture. Clinical use of primaquine has been limited due to haemolytic toxicity in individuals with genetic deficiency in glucose-6-phosphate dehydrogenase. Earlier studies have linked its therapeutic effects to CYP2D6-generated metabolites. The aim of the current study was to investigate the differential generation of the CYP2D6 metabolites by racemic primaquine and its individual enantiomers. METHODS: Stable isotope (13)C-labelled primaquine and its two enantiomers were incubated with recombinant cytochrome-P450 supersomes containing CYP2D6 under optimized conditions. Metabolite identification and time-point quantitative analysis were performed using LC-MS/MS. UHPLC retention time, twin peaks with a mass difference of 6, MS-MS fragmentation pattern, and relative peak area with respect to parent compound were used for phenotyping and quantitative analysis of metabolites. RESULTS: The rate of metabolism of (+)-(S)-primaquine was significantly higher (50% depletion of 20 μM in 120 min) compared to (−)-(R)-primaquine (30% depletion) when incubated with CYP2D6. The estimated V(max) (μmol/min/mg) were 0.75, 0.98 and 0.42, with K(m) (μM) of 24.2, 33.1 and 21.6 for (±)-primaquine, (+)-primaquine and (−)-primaquine, respectively. Three stable mono-hydroxylated metabolites, namely, 2-, 3- and 4-hydroxyprimaquine (2-OH-PQ, 3-OH-PQ, and 4-OH-PQ), were identified and quantified. 2-OH-PQ was preferentially formed from (+)-primaquine in a ratio of 4:1 compared to (−)-primaquine. The racemic (±)-primaquine showed a pattern similar to the (−)-primaquine; 2-OH-PQ accounted for about 15–17% of total CYP2D6-mediated conversion of (+)-primaquine. In contrast, 4-OH-PQ was preferentially formed with (−)-primaquine (5:1), accounting for 22% of the total (−)-primaquine conversion. 3-OH-PQ was generated from both enantiomers and racemate. 5-hydroxyprimaquine was unstable. Its orthoquinone degradation product (twice as abundant in (+)-primaquine compared to (−)-primaquine) was identified and accounted for 18–20% of the CYP2D6-mediated conversion of (+)-primaquine. Other minor metabolites included dihydroxyprimaquine species, two quinone-imine products of dihydroxylated primaquine, and a primaquine terminal alcohol with variable generation from the individual enantiomers. CONCLUSION: The metabolism of primaquine by human CYP2D6 and the generation of its metabolites display enantio-selectivity regarding formation of hydroxylated product profiles. This may partly explain differential pharmacologic and toxicologic properties of primaquine enantiomers

Differential kinetic profiles and metabolism of primaquine enantiomers by human hepatocytes

BACKGROUND: The clinical utility of primaquine (PQ), used as a racemic mixture of two enantiomers, is limited due to metabolism-linked hemolytic toxicity in individuals with genetic deficiency in glucose-6-phosphate dehydrogenase. The current study investigated differential metabolism of PQ enantiomers in light of the suggestions that toxicity and efficacy might be largely enantioselective. METHODS: Stable isotope (13)C-labelled primaquine and its two enantiomers (+)-PQ, (−)-PQ were separately incubated with cryopreserved human hepatocytes. Time-tracked substrate depletion and metabolite production were monitored via UHPLC–MS/MS. RESULTS: The initial half-life of 217 and 65 min; elimination rate constants (λ) of 0.19 and 0.64 h(−1); intrinsic clearance (Cl(int)) of 2.55 and 8.49 (µL/min)/million cells, which when up-scaled yielded Cl(int) of 6.49 and 21.6 (mL/min)/kg body mass was obtained respectively for (+)- and (−)-PQ. The extrapolation of in vitro intrinsic clearance to in vivo human hepatic blood clearance, performed using the well-stirred liver model, showed that the rate of hepatic clearance of (+)-PQ was only 45 % that of (−)-PQ. Two major primary routes of metabolism were observed—oxidative deamination of the terminal amine and hydroxylations on the quinoline moiety of PQ. The major deaminated metabolite, carboxyprimaquine (CPQ) was preferentially generated from the (−)-PQ. Other deaminated metabolites including PQ terminal alcohol (m/z 261), a cyclized side chain derivative from the aldehyde (m/z 241), cyclized carboxylic acid derivative (m/z 257), a quinone-imine product of hydroxylated CPQ (m/z 289), CPQ glucuronide (m/z 451) and the glucuronide of PQ alcohol (m/z 437) were all preferentially generated from the (−)-PQ. The major quinoline oxidation product (m/z 274) was preferentially generated from (+)-PQ. In addition to the products of the two metabolic pathways, two other major metabolites were observed: a prominent glycosylated conjugate of PQ on the terminal amine (m/z 422), peaking by 30 min and preferentially generated by (+)-PQ; and the carbamoyl glucuronide of PQ (m/z 480) exclusively generated from (+)-PQ. CONCLUSION: Metabolism of PQ showed enantioselectivity. These findings may provide important information in establishing clinical differences in PQ enantiomers

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signaling

Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1435/1449 and LPS1690 appear responsible for tissue specific immune signalingpathways activation and increased virulence. The modification of lipid A to tetra-acylated1435/1449 and/or penta-acylated1690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1435/1449 and LPS1690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR 2 and TLR 4 activation. This enabless P. gingivalis to select the conditions for its entry, survival and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. Thismini review describes a number of effects that LPS1435/1449 and LPS1690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production and adverse effects on pregnancy outcome. The ability to change its LPS1435/1449 and/or LPS1690 composition may enables P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue

A model of online protection to reduce children's online risk exposure: empirical evidence from Asia

Children are surrounded by a variety of digital media and are exposed to potential risks that come with such easy accessibility. Learning how to be safe online is an important consideration for both children and their caregivers. The present study proposes an integrated model of online safety based on constructs from protection motivation theory and the health belief model, namely perceived severity of (and susceptibility to) risk, online self-efficacy, online privacy concern, and digital literacy. The study comprised a survey conducted among 420 schoolchildren aged 9–16 years. Using partial least squares-structural equation modelling, the results illustrated the presence of a negative effect of ‘perceived severity of online risk’ toward online risks, whereas the effect of ‘digital literacy’ was found to be positive. Children whose perception of online risks was more severe were less exposed to online risks if they had higher ‘online privacy concerns’ than the children with higher ‘digital literacy’ who are more exposed to online risk. Results of the study show that engaging in safe online behaviour requires children to have a high perception regarding severity of online risks as well as knowledge of online privacy concerns. Online risks and opportunities occur in parallel. Consequently, the factors that increase or decrease risk may also increase or decrease the benefits