Ahmad, G. | Search bioRxiv

bioRxiv2020

The role of sodium thiocyanate supplementation during dextran sodium sulphate-stimulated experimental colitis

Ulcerative colitis is a condition characterised by the infiltration of leukocytes into the gastrointestinal wall. Leukocyte-MPO catalyses hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) formation from chloride (Cl-) and thiocyanous (SCN-) anions, respectively. While HOCl indiscriminately oxidises biomolecules, HOSCN primarily targets low-molecular weight protein thiols. Oxidative damage mediated by HOSCN may be reversible, potentially decreasing MPO-associated host tissue destruction. This study investigated the effect of SCN- supplementation in a model of acute colitis. Female mice were supplemented dextran sodium sulphate (DSS, 3% w/v) in the presence of 10 mM Cl- or SCN- in drinking water ad libitum, or with salts (NaCl and NaSCN only) or water only (controls). Behavioural studies showed mice tolerated NaSCN and NaCl-treated water with water-seeking frequency. Ion-exchange chromatography showed increased fecal and plasma SCN- levels in thiocyanate supplemented mice; plasma SCN- reached similar fold-increase for smokers. Overall there was no difference in weight loss and clinical score, mucin levels, crypt integrity and extent of cellular infiltration between DSS/SCN- and DSS/Cl- groups. Neutrophil recruitment remained unchanged in DSS-treated mice, as assessed by fecal calprotectin levels. Total thiol and tyrosine phosphatase activity remained unchanged between DSS/Cl- and DSS/SCN- groups, however, colonic tissue showed a trend in decreased 3-chlorotyrosine (1.5-fold reduction, p<0.051) and marked increase in colonic GCLC, the rate-limiting enzyme in glutathione synthesis. These data suggest that SCN- administration can modulate MPO activity towards a HOSCN-specific pathway, however, this does not alter the development of colitis within a DSS murine model.HighlightsSodium thiocyanate (SCN-) supplementation increased plasma and fecal SCN- level.Thiocyanate supplementation diverted HOCl-mediated oxidative damage in mice colon.Thiocyanate supplementation stimulated thiol synthesis in the DSS colitis model.Thiocyanate provides no protection in an acute experimental model of UC.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsCDCrohn’s Disease3-Cl-Tyr3-chlorotyrosineDSSDextran Sodium SulphateGAPDHGlyceraldehyde 3-phosphate dehydrogenaseGCLCGlutamate-Cysteine Ligase Catalytic SubunitGIGastrointestinalGSHGlutathioneGSSGGlutathione DisulfideHOBrHypobromous AcidHOClHypochlorous AcidHCN-Hydrogen; CyanideHOSCNHypothiocyanous AcidIBDInflammatory Bowel DiseaseMPOMyeloperoxidaseNrf2Nuclear factor erythroid 2-related Factor 2PMNsPolymorphonuclear NeutrophilsPTPProtein Tyrosine PhosphatasesROSReactive Oxygen SpeciesSCN-ThiocyanateUCUlcerative ColitisView Full Text

pathology↗

bioRxiv2017

The elephant in the room- Universal coverage for Costly treatments in an upper middle income country

BackgroundUpper middle income countries have made substantial progress towards universal health coverage. We investigated whether the coverage extended to diseases that incur catastrophic health spending, the contribution of pooled financing and the factors driving it in Malaysia.\n\nMethodsWe adapted the WHO definition of catastrophic health spending to define costly treatment as one that cost, at prevailing market price, more than 10% of the median annual household income in Malaysia. Coverage is defined as the proportion of patients in a year who were in need of a treatment and who received it. Data to estimate coverage and financing were extracted from the published and grey literature, as well as secondary data sources available on disease epidemiology and healthcare in Malaysia.\n\nResultsWe found coverage varies from universal for dialysis, cataract surgery, medicines for organ transplant and CML, to practically none for HCV, stroke, psoriasis and epilepsy surgery. Coverage of targeted therapies for solid cancers, knee replacement surgery, anti-TNF for arthritis and coagulation factors for haemophilia were poor while iron chelation for thalassemia, coronary revacularization, epoetin and anti-retrovirals were barely adequate. Coverage correlates negatively (r=-0.82) with health benefits foregone, and is entirely driven by the contribution of pooled financing (r=0.99 p<0.0001). The relative effectiveness of a treatment, its budget impact, media coverage and political influence of the disease area have little influence on financing. Only effectiveness of the leadership representing the therapy area is influential; an increase in one point on the leadership effectiveness scale is associated with 30% increase in the contribution of pooled financing.\n\nConclusionCoverage for catastrophically costly treatments is uneven and inequitable in Malaysia, despite most of these are affordable. Decisions on coverage are driven by political-economic consideration.

epidemiology↗