AIM OF THE STUDY: Endothelial barrier dysfunction is a pathological hallmark of many diseases and can be caused by lipopolysaccharides (LPS) stimulation. Therefore, this study aims to investigate the possible barrier protective effects of tHGA upon LPS-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs).
MATERIALS AND METHODS: HUVECs were pretreated with tHGA prior to LPS stimulation, where inflammatory parameters including permeability, monocyte adhesion and migration, and release of pro-inflammatory mediators were examined. Additionally, the effect of tHGA on F-actin rearrangement and adhesion protein expression of LPS-stimulated HUVECs was evaluated.
RESULTS: It was found that pretreatment with tHGA inhibited monocyte adhesion and transendothelial migration, reduced endothelial hyperpermeability and secretion of prostaglandin E2 (PGE2). Additionally, tHGA inhibited cytoskeletal rearrangement and adhesion protein expression on LPS-stimulated HUVECs.
CONCLUSION: As the regulation of endothelial barrier dysfunction can be one of the therapeutic strategies to improve the outcome of inflammation, tHGA may be able to preserve vascular barrier integrity of endothelial cells following LPS-stimulated dysfunction, thereby endorsing its potential usefulness in vascular inflammatory diseases.
Method: The health utilities of hypoglycaemia event were measured using Visual Analogue Scale (VAS) and Time Trade-Off (TTO) methods among conveniently sampled consenting adults (>18 years and literate in either English or Malay language), which were then divided into two groups: those in the general population (GP) and those with Type 2 Diabetes Mellitus (T2DM). Each respondent was required to value 13 different health states, including frequencies of daytime hypoglycaemia and nocturnal hypoglycaemia, each depending on its severity (non-severe or severe).
Results: 256 respondents from the GP and 99 respondents with T2DM completed the survey. The T2DM group gave higher VAS-values compared to the GP group. The highest mean VAS-utility value for non-severe nocturnal hypoglycaemia occurring once monthly was 0.543 (SD 0.161), and for severe daytime hypoglycaemia occurring once quarterly was 0.293 (SD 0.162) which was the lowest utility value compared to other health states. However, non-severe nocturnal hypoglycaemia occurring once quarterly was 0.537 (SD 0.284) and has the highest TTO-utility value. Severe nocturnal hypoglycaemia occurring once quarterly has the lowest utility value which was -0.104 (SD 0.380). Daytime hypoglycaemia has lower utility value compared to nocturnal hypoglycaemia. Severe hypoglycaemia has a greater disutility compared with the non-severe hypoglycaemia in both studied groups.
Conclusion: The findings show that as a health utility, hypoglycaemia has a substantial impact on utility with severe hypoglycaemia having a greater negative impact compared to non-severe events across the board. This highlights the importance of preventing development of severe hypoglycaemia in patients with Type 2 Diabetes Mellitus at any time of the day.