Biological Activity of Different Forms of Oxidized Parathyroid Hormone

Preclinical studies have shown that parathyroid hormone (PTH) loses its biological effects through oxidation. PTH can be oxidized at methionines 8 and 18. Three possible variations of oxidized PTH (oxPTH) exist: Met8(ox)PTH, Met18(ox)PTH, and Met8, Met18(di-ox)PTH. A recent study showed that Met18(ox)PTH retained biological activity and was able to upregulate Fgf23 gene expression, whereas Met8(ox)PTH and Met8, Met18(di-ox)PTH showed less or no biological activity. An earlier study likewise showed that the oxidation of Met18 has minor effects on the secondary structure of PTH, whereas the oxidation of Met8 causes substantial structural changes, consistent with another study showing that oxidization just at Met8 blocks the generation of the second messenger cAMP, whereas the effect of the oxidation of Met18 is much less potent in inhibiting cAMP formation. A considerable percentage of circulating PTH in chronic kidney disease (CKD) patients is oxidized. However, we do not know the relative amounts of the different forms of oxPTH with agonistic, partial agonistic, or even antagonistic biological actions in different CKD populations. This might explain different clinical findings in the different CKD populations analyzed so far. The currently available method that was used in these clinical studies just distinguishes between oxPTH and noxPTH without being able to differentiate between different forms of oxPTH. Only methods of PTH measurement that are able to differentiate between PTH forms (noxPTH, Met8(ox)PTH, Met18(ox)PTH, and Met8, Met18(di-ox)PTH) have the potential to improve patient care, because only these methods will definitively separate bioactive from non-bioactive PTH forms. Such methods need to be developed, validated, and used in prospective randomized clinical trials to define the potential value of bioactive PTH forms as a predictor of cardiovascular events, mortality, and bone turnover

Sustainability of Scientific Journals in the Developing World With Special Reference to Bangladesh

The study explores sustainability of scientific journal publication in Bangladesh. Forty-three journal editors were interviewed, and 66 current journals were physically examined for production quality, regularity of publication, and availability at concerned libraries. Findings revealed that 68% of the journals were published late, 30% had inconsistencies in typesetting, and 14% were indexed. Most journals were found either excellent or of good quality in terms of printing (85%), binding (77%), paper (92%), and graphic reproduction (76%). Most journals were not available in major libraries under study. Of the 43 editors, 28 (35%) reported a cost recovery of 1-45% from subscriptions, advertisements, and sales. About 74.4% of the editors did not consider their journals at risk. Although 86% of the editors were confident that their journals would be sustained in the long run, 37.3% could not give any convincing logic in support of their statement. Major problems include lack of skilled staff, finance, quality articles and institutional support, and lengthy peer review process. Only one journal editor was found to be a full-time editor having training in editing and publication. One-half (51%) of the editors reported have training in editing, while four had publication training. Most editors (79%) were interested in acquiring training in editing and publication. Institutional support and backup, enthusiasm and zeal of editors, unmet need for standard local journals, constant flow of funds and articles, and skilled manpower are instrumental for sustainability of science journals in Bangladesh

Inverse correlation of intact PTH, oxidized PTH as well as non-oxidized PTH with 25-hydroxyvitamin D3 in kidney transplant recipients

Background 25-hydroxyvitamin D (25(OH)D) and potentially also 1,25-dihydroxyvitamin D (1,25(OH)2D) inhibits the synthesis of parathyroid hormone (PTH) in the chief cells of the parathyroid gland. Clinical studies showing a negative correlation between (25(OH)D and PTH are in good agreement with these findings in basic science studies. However, PTH was measured in these studies with the currently clinically used 2nd or 3rd generation intact PTH (iPTH) assay systems. iPTH assays cannot distinguish between oxidized forms of PTH and non-oxidized PTH. Oxidized forms of PTH are the by far most abundant form of PTH in the circulation of patients with impaired kidney function. Oxidation of PTH causes a loss of function of PTH. Given that the clinical studies done so far were performed with an PTH assay systems that mainly detect oxidized forms of PTH, the real relationship between bioactive non-oxidized PTH and 25(OH)D as well as 1,25(OH)2D is still unknown. Methods To address this topic, we compared for the first time the relationship between 25(OH)D as well as 1,25(OH)2D and iPTH, oxPTH as well as fully bioactive n-oxPTH in 531 stable kidney transplant recipients in the central clinical laboratories of the Charité. Samples were assessed either directly (iPTH) or after oxPTH (n-oxPTH) was removed using a column that used anti-human oxPTH monoclonal antibodies, a monoclonal rat/mouse parathyroid hormone antibody (MAB) was immobilized onto a column with 500 liters of plasma samples. Spearman correlation analysis and Multivariate linear regression were used to evaluate the correlations between the variables. Results There was an inverse correlation between 25(OH)D and all forms of PTH, including oxPTH (iPTH: r=-0.197, p<0.0001; oxPTH: r=-0.203, p<0.0001; n-oxPTH: r=-0.146, p=0.001). No significant correlation was observed between 1,25(OH)2D and all forms of PTH. Multiple linear regression analysis considering age, PTH (iPTH, oxPTH and n-oxPTH), serum calcium, serum phosphor, serum creatinine, fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), albumin, and sclerostin as confounding factors confirmed these findings. Subgroup analysis showed that our results are not affected by sex and age. Conclusion In our study, all forms of PTH are inversely correlated with 25-hydroxyvitamin D (25(OH)D). This finding would be in line with an inhibition of the synthesis of all forms of PTH (bioactive n-oxPTH and oxidized forms of PTH with minor or no bioactivity) in the chief cells of the parathyroid glad

Gas-Phase Synthesis of Triphenylene (C18 H12 ).

For the last decades, the hydrogen-abstraction-acetylene-addition (HACA) mechanism has been widely invoked to rationalize the high-temperature synthesis of PAHs as detected in carbonaceous meteorites (CM) and proposed to exist in the interstellar medium (ISM). By unravelling the chemistry of the 9-phenanthrenyl radical ([C14 H9 ]. ) with vinylacetylene (C4 H4 ), we present the first compelling evidence of a barrier-less pathway leading to a prototype tetracyclic PAH - triphenylene (C18 H12 ) - via an unconventional hydrogen abstraction-vinylacetylene addition (HAVA) mechanism operational at temperatures as low as 10 K. The barrier-less, exoergic nature of the reaction reveals HAVA as a versatile reaction mechanism that may drive molecular mass growth processes to PAHs and even two-dimensional, graphene-type nanostructures in cold environments in deep space thus leading to a better understanding of the carbon chemistry in our universe through the untangling of elementary reactions on the most fundamental level

Pro-poor intervention strategies in irrigated agriculture in Asia: poverty in irrigated agriculture: issues and options: Bangladesh

Irrigated farming / Poverty / Irrigation management / Water resource management / Policy / Planning / Institutions / Organizations / Local government / Non-governmental organizations / Legislation / Water users / Participatory management / Public sector / Water allocation / Cost recovery / Households / Income / Expenditure / Irrigation canals / Bangladesh

C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival

Background Increased fibroblast growth factor 23 (FGF23) is a risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease. Limited data exist comparing the association of either c-terminal FGF23 (cFGF23) or intact FGF23 (iFGF23) in kidney transplant recipients (KTRs) with overall (all-cause) graft loss. Methods We conducted a prospective observational cohort study in 562 stable kidney transplant recipients. Patients were followed for graft loss and all-cause mortality for a median follow-up of 48 months. Results During a median follow-up of 48 months, 94 patients had overall graft loss (primary graft loss or death with functioning graft). Both cFGF23 and iFGF23 concentrations were significantly higher in patients with overall graft loss than those without (24.59 [11.43–87.82] versus 10.67 [5.99–22.73] pg/ml; p < 0.0001 and 45.24 [18.63–159.00] versus 29.04 [15.23–60.65] pg/ml; p = 0.002 for cFGF23 and iFGF23, respectively). Time-dependent ROC analysis showed that cFGF23 concentrations had a better discriminatory ability than iFGF23 concentrations in predicting overall (all-cause) graft loss. Cox regression analyses adjusted for risk factors showed that cFGF23 (HR for one unit increase of log transformed cFGF23: 1.35; 95% CI, 1.01–1.79; p = 0.043) but not iFGF23 (HR for one unit increase of log transformed iFGF23: 0.97; 95% CI, 0.75–1.25; p = 0.794) was associated with the overall graft loss. Conclusion Elevated cFGF23 concentrations at baseline are independently associated with an increased risk of overall graft loss. iFGF23 measurements were not independently associated with overall graft loss. The cFGF23 ELISA might detect bioactive FGF23 fragments that are not detected by the iFGF23 ELISA

Excision of choledochal cyst in children by Roux-en-Y hepaticojejunostomy

The aim of this study was to review our experience of total excision with Roux-en-Y hepatico-jejunostomy for the surgical management of type I and type IVa choledochal cysts in 30 children. Among them, 22 were in type I and 8 in type IVa choledochal cysts. All had complete excision and Roux-en-Y hepaticojejunostomy with no morality. Morbidity consisted of prolong drainage (n=2) and late onset cholangitis/pancreatitis (n=4). Choledochal cyst generally has an excellent prognosis with early complete excision and Roux-en-Y hepaticojejunostomy

Low-Cost Aquifer Storage and Recovery: Implications for Improving Drinking Water Access for Rural Communities in Coastal Bangladesh

Fresh water resources are scarce in rural communities in the southern deltaic plains of Bangladesh where both shallow and deep groundwater is frequently brackish, and fresh water ponds have been increasingly salinized by inundation during storm surges and brackish-water aquaculture. Low-cost aquifer storage and recovery (ASR) schemes were constructed at 13 villages in three coastal districts by developing storage in shallow confined fine to medium sand aquifers overlain by variable thicknesses of silt and clay. A typical ASR scheme consisted of a double-chambered graded sand filtration tank with a volume of 19.5  m3 that feeds filtered pond water to four to six large diameter (d=30.5 or 56 cm) infiltration wells through PVC pipes fitted with stop valves and flow meters. The infiltration wells were completed at 18–31 m below ground and filled with well-sorted gravel capped with a thin layer of fine sand that acts as a second stage filter. Infiltration rates at 13 sites averaged 3  m3/day (range: 3–6  m3/day) over one year of operation. At 11 sites where water was abstracted, the recovery rate ranged from 5 to 40%. The source pond source water frequently had turbidity values of ≥100  NTU. After sand filtration, the turbidity is typically 5 NTU. Despite this, clogging management involving frequent (monthly to weekly) manual washing to remove fine materials deposited in the sand filtration tank and the infiltration wells is found to be necessary and effective, with post-manual-washing operational infiltration rates restored to annual average values. E. coli counts in recovered water are greatly reduced compared to raw pond water, although E. coli is still detected in about half of the samples. Arsenic in recovered water was detected to be at level of > 100  μg/L repeatedly at three sites, suggesting that As risks must be carefully managed and require further investigation