The effect of synovial fluid proteins in the degradation of hyaluronic acid induced by ascorbic acid

The degradation of hyaluronic acid induced by ascorbic acid and the effect of synovial fluid proteins, such as ceruloplasmin, transferrin, and albumin, were investigated on the basis of the elution volume and the molecular weight of hyaluronic acid using high-performance gel permeation chromatography. Hyaluronic acid was degraded to less than one-third of the original molecular weight in the range of the physiological concentrations of ascorbic acid. Synovial fluid proteins protected against the ascorbate-dependent degradation of hyaluronic acid at their physiological concentrations. It is suggested that the inhibitory activity of ceruloplasmin mainly depends on the ferroxidase activity and that of transferrin is probably due to iron binding property.     

Effect of tryptophol on pentylenetetrazol and picrotoxin induced convulsion in mice.

The effect of treatment of mice with tryptophol (TOL), a neutral metabolite of tryptophan, on drug-induced convulsion was studied. TOL effectively suppressed both pentylenetetrazol and picrotoxin induced convulsion. Diphenylhydantoin (DPH), a potent inhibitor of brain aldehyde reductase, significantly reduced the anticonvulsant effect of TOL, however, TOL level in brain of DPH-treated mice was rather higher than that of control one. These results strongly suggest that the manifestation of the anticonvulsant effect of TOL requires the conversion of TOL to its active metabolite, indoleacetaldehyde.     

Cost-Effectiveness of Empagliflozin and Metformin Combination Versus Standard Care as First-Line Therapy in Patients With Type 2 Diabetes Mellitus

ObjectiveSodium-glucose cotransporter 2 inhibitors have been shown to reduce cardiovascular events but are currently not used as the first-line therapy. This study was conducted to evaluate the cost-effectiveness of first-line empagliflozin plus metformin versus metformin monotherapy among Australians with type 2 diabetes mellitus (T2DM) and existing cardiovascular disease (CVD).MethodsA Markov model with 1-year cycles and a 5-year time horizon was constructed to simulate the occurrence of recurrent cardiovascular events among Australians aged 50 to 84 years with T2DM and CVD. Efficacy results were derived from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose trial. Costs and utilities were drawn from published sources. The evaluation adopted both health care and societal perspectives, with the latter ascribing the Australian government’s “value of statistical life year” (A$213 000) to each year lived by a person. Future outcomes were discounted at 5% annually. Sensitivity analyses were conducted to enhance the robustness of conclusions.ResultsCompared with metformin monotherapy, first-line empagliflozin plus metformin reduced overall cardiovascular events by 0.82% and overall deaths by 7.72% over 5 years. There were 0.2 years of life saved per person and 0.16 quality-adjusted life years gained, at a net health care cost of A$4408. These equated to incremental cost-effectiveness ratios of A$22 076 per year of life saved and A$28 244 per quality-adjusted life year gained. The gains in the value of statistical life year equated to A$42 530 per person, meaning that from a societal perspective, the intervention was cost-saving.ConclusionFirst-line empagliflozin plus metformin may represent a cost-effective strategy for the management of T2DM and CVD in Australia.     

Polymorphism and Liquid‐Liquid Demixing in Supersaturated Drug Solution

In the field of pharmaceutical compound crystallization, one of the challenging tasks is to control the nucleation and the polymorphism. With these objectives, it becomes clear that an important stage is the phase diagram determination of the considered substance. We have investigated the phase diagram of a pharmaceutical compound in a mixture of ethanol/water. We have observed and characterized, in this phase diagram, a solid‐solid (polymorphism) and a liquid‐liquid phase separation as a function of temperature and drug substance concentration.