Empagliflozin on top of metformin treatment improves arterial function in patients with type 1 diabetes mellitus

Background

Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We explored the possible effects of empagliflozin’s effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients.

Methods

Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function [brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI)], arterial stiffness [pulse wave velocity (PWV) and common carotid artery stiffness (β-stiffness)]. For statistical analysis one-way analysis of variance with Bonferroni post-test was used.

Results

Empagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD [2.6-fold (P?<?0.001) vs. 1.8-fold (P?<?0.05)] and RHI [1.4-fold (P?<?0.01) vs. 1.3-fold (P?<?0.05)]. Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and β-stiffness compared to metformin [by 15.8% (P?<?0.01) and by 36.6% (P?<?0.05), respectively]. Metformin alone did not influence arterial stiffness.

Conclusion

Empagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies.Trial registration Clinical trial registration: NCT03639545

     

Experiences from the implementation of a biosafety system in Slovenia

The development and implementation of an effective national biosafety system is important for several key reasons: to ensure safe access to products of modern biotechnology, to build public confidence, to encourage the growth of domestic modern biotechnology, and to comply with international standards and agreements. There is no single best approach in the development and implementation of a national biosafety system and each country is faced with unique challenges. Slovenia is a small country and a new EU Member State. However, it has developed and implemented an efficient national biosafety system. The key elements of this system are administrative procedure, risk assessment, enforcement, and public participation and information.     

Voltametric monitoring of enzyme-mediated indigo reduction in the presence of various fibre materials

A comparative study of enzyme-mediated indigo reduction is presented as an environmentally-friendly alternative to alkaline sodium dithionite reduction. The effect of the mediator 1,8-dihydroxy-9,10-anthraquinone in enzymatic reduction was studied by means of voltammetry, both in the presence and absence of different textile materials (polyamide 6, polyamide 6,6 and cotton), and compared to chemically reduced indigo. It was observed that bio-catalytic formation of leuco indigo and its exhaustion on substrates is inversely proportional to the pH within the range of 7–11. Additionally, substrate coloration was strongly influenced by the mediator, resulting in in situ formation of leuco indigo. This effect was most pronounced for polyamide substrates. The reuse of an enzyme-mediated reduction bath for dyeing was assessed showing that the levelness of the obtained shade was either excellent or good at pH 9 and 11, respectively. The wash, perspiration, and light color fastness properties of all textile materials dyed with enzymatically-reduced indigo were comparable or even better than those obtained with chemically reduced indigo. The use of enzyme-mediated reduction of indigo combined with potential reuse of the reduction bath represents a cost effective and environmentally-friendly dyeing process that can be applied for the dyeing of natural cellulosic and synthetic polyamide fibres.     

Interaction Between Equally Charged Membrane Surfaces Mediated by Positively and Negatively Charged Macro-Ions

In biological systems, charged membrane surfaces are surrounded by charged molecules such as electrolyte ions and proteins. Our recent experiments in the systems of giant phospholipid vesicles indicated that some of the blood plasma proteins (macro-ions) may promote adhesion between equally charged membrane surfaces. In this work, theory was put forward to describe an IgG antibody-mediated attractive interaction between negatively charged membrane surfaces which was observed in experiments on giant phospholipid vesicles with cardiolipin-containing membranes. The attractive interactions between negatively charged membrane surfaces in the presence of negatively and positively charged spherical macro-ions are explained using functional density theory and Monte Carlo simulations. Both, the rigorous solution of the variational problem within the functional density theory and the Monte Carlo simulations show that spatial and orientational ordering of macro-ions may give rise to an attractive interaction between negatively charged membrane surfaces. It is also shown that the distinctive spatial distribution of the charge within the macro-ions (proteins) is essential in this process.     

Environmental changes affect ecosystem services of the intermittent Lake Cerknica

Lake Cerknica is an intermittent wetland with seasonal water level fluctuations. This paper discusses the possible changes of ecosystem services due to altered ecosystem functions caused by regional climate change. For this purpose, the lake's water regime was analysed and biomass production of common reed (Phragmites australis), the prevailing species, was related to ambient temperatures and water level. The effect of the latter was also examined for reed transpiration rate and plant diversity. The results revealed a gradual loss of seasonality of floods and droughts. High water level in winter months and temperatures at the beginning as well as the end of vegetation period were found to have a significant influence on reed biomass. The plant diversity research in six subsequent years in three different aquatic habitats revealed trends of a decrease due to increased water depth during the vegetation period. The complexity of the system and consequently ecosystem services might also be affected due to changes of other processes, which revealed to be related to water level; namely transpiration rate, plant mycorrhizal colonisation and soil mineralisation.     

Scarless excision of an insertion sequence restores capsule production and virulence in Acinetobacter baumannii

We identify a new mechanism mediating capsule production and virulence in the WHO and CDC priority ESKAPE pathogen Acinetobacter baumannii. Non-capsulated and avirulent bacteria can revert into a capsulated and virulent state upon scarless excision of an ISAba13 insertion sequence under stress conditions. Reversion events fully restore capsule production and in vivo virulence. This increases our knowledge about A. baumannii genome dynamics, and the regulation of capsule production, virulence and resistance.Subject terms: Bacterial genetics, Bacterial pathogenesis     

Cross-presentation of Listeria-derived CD8 T cell epitopes requires unstable bacterial translation products

Presentation of bacteria-derived CD8 T cell epitopes by dendritic cells (DC) requires either their direct infection or that DC acquire and cross-present Ags from other infected cells. We found that cross-presentation of Listeria monocytogenes-derived CD8 T cell epitopes was much stronger than direct Ag presentation by infected murine DC. Cross-presentation of Listeria-derived CD8 T cell epitopes showed unique physiological requirements. It was dependent upon the delivery of unstable bacterial translation products by infected, but still viable, Ag donor cells. Cross-presentation was enhanced both when unstable translation products in infected Ag donor cells were protected from proteasomal degradation and when the production of misfolded bacterial proteins was increased. The requirement of unstable translation products for cross-presentation may represent a novel pathway that functions to focus the CD8 T cell response toward epitopes derived from newly synthesized proteins.     

Sequence polymorphisms within the pMGA genes and pMGA antigenic variants in Mycoplasma gallisepticum

Antigenic variants of Mycoplasma gallisepticum major surface lipoprotein, pMGA, are encoded by a large gene family. In this study sequence analyses of the PCR-amplified pMGA genes showed two types of sequences similar to the pMGA1.2 gene in M. gallisepticum strains. They differed in the sequence encoding a proline-rich region (PRR) at the N-terminus of the pMGA protein. The type A genes had sequences similar to the published pMGA1.2 gene sequence of strain S6, whereas the type B genes lacked the second repetitive segment encoding PTPN sequence within PRR and were similar to the published sequence of PG31 strain. Low in vitro passages of M. gallisepticum strains isolated recently in Slovenia from four avian species showed very different expression patterns of pMGA1.2 and pMGA1.9 genes. Among isogenic populations of S6(B) and IHB1 strains a high frequency of pMGA antigenic variants lacking an epitope for monoclonal antibody (mAb) 71 was found. Strain IHB1 clones, which synthesized pMGA recognized by mAb 71, transcribed pMGA genes whose partial sequence encoded the amino acid sequence (262)TNGDEPRSVS of the mAb 71 epitope. Other IHB1 clones synthesized pMGA variants with different isoelectric points, lacking the epitope for mAb 71, but expressing downstream epitopes for other mAbs. Our study suggests that a molecular basis for pMGA antigenic variation lies in the corresponding changes at the DNA level.