Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.     

Antifolate Agents Against Wild and Mutant Strains of Plasmodium falciparum

Plasmodium falciparum dihydrofolate reductase is an important target for antimalarial chemotherapy. The emergence of resistance has significantly reduced the efficacy of the classic antifolate drugs cycloguanil and pyrimethamine. In this paper we report new dihydrofolate reductase inhibitors identified using molecular modelling principles with the goal of designing new antifolate agents active against both wild and tetramutant dihydrofolate reductase strains three series of trimethoprim analogues were designed, synthesised and tested for biological activity. Pyrimethamine and cycloguanil have been reported to loose efficacy because of steric repulsion in the active site pocket produced due to mutation in Plasmodium falciparum dihydrofolate reductase. The synthesised molecules have sufficient flexibility to withstand this steric repulsion to counteract the resistance. The molecules have been synthesised by conventional techniques and fully characterised by spectroscopic methods. The potency of these molecules was evaluated by in vitro enzyme specific assays. Some of the molecules were active in micromolar concentrations and can easily be optimised to improve binding and activity.     

An In Vitro Stereomicroscopic Evaluation of Bioactivity between Neo MTA Plus,Pro Root MTA,BIODENTINE & Glass Ionomer Cement Using Dye Penetration Method

The ideal root end filling material should form a tight seal in the root canal by adhering to the cavity walls. Several materials have been used for root end filling. The present study aims to find out and compare the bioactivity of Neo MTA Plus, Pro Root MTA White, BIODENTINE & glass ionomer cement as root end filling materials using 1% methylene blue as tracer. Materials and methods: 80 extracted human permanent maxillary anterior teeth were used in the study. They were divided into four groups. Specimens were sectioned transversely in the cervical area to separate the crown from the root. The root canal was obturated with gutta percha and zinc oxide eugenol sealers. Thereafter, each sample was resected apically by removing 3 mm of the apex and filled with different materials. Samples were kept in buffering solution at 37 °C until the recommended evaluation periods. The specimens were then suspended in 1% methylene blue for 24 h, prior to the analysis. The teeth were then sectioned, and dye penetration was examined, photographed, and evaluated under a stereomicroscope. Results: Vertical dye penetration showed significant differences across different groups. The minimum dye penetration was seen in Neo MTA plus followed by BIODENTINE, Pro Root MTA and maximum in GIC. There was no significant difference in dye penetration between Neo MTA plus and BIODENTINE both at fifteen days and one-month intervals. Conclusion: The present study suggests Neo MTA plus and BIODENTINE should be the preferred material for root end filling.     

Re-visiting pH-adjusted potassium to avoid hypokalemic crisis during management of diabetic ketoacidosis: A conceptual framework

Background and aimsDiabetic ketoacidosis (DKA) treatment guidelines recommend to initiate potassium-replacement when serum potassium (S_K) drops within normal range, and to withhold insulin if S_K is below normal. Despite strict recommendations, hypokalemia is frequently observed in DKA.MethodsScientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia.ResultsAcidosis affects S_K and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing S_K level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated.ConclusionIn light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge.