Parameters influencing renal response to SGLT2 inhibitors and GLP1 receptor agonists in type 2 diabetes patients with preserved renal function: a comparative, prospective study.

PURPOSE: SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1-RA) protect the kidney in type 2 diabetes (T2DM) subjects. The role of patient's phenotype years before starting the treatment in determining the kidney response to these drugs has never been evaluated. SUBJECTS AND METHODS: Clinical and biochemical parameters were collected in 92 T2DM patients with preserved kidney function from year -4 (T-4) to year +3 (T+3) from the introduction of semaglutide or empagliflozin (T0). Glomerular filtration rate (eGFR) slopes were evaluated to identify eGFR changes (ΔGFR) and predictors of treatment response. Urinary markers of kidney impairment were measured at T0, including KIM-1, TNFR1 and L-FABP. RESULTS: Characteristics of patients on semaglutide (n = 46) or empagliflozin (n = 37) were similar at T-4 and T0. ΔGFR from T0 to T+3 was -5.5 [-10.0; -0.7] vs -2.6 [-102.4] ml/min/1.73 m2 for GLP1-RA and SGLT2i, respectively (p = ns). Compared with patients with a slower eGFR decline, those with ΔGFR > 5 ml/min/1.73 m2 from T0 to T+3 (49%) or ΔGFR > 10 ml/min/1.73 m2 from T-4 to T+3 (25%) had similar characteristics and urinary markers at T-4 and T0. The latter group showed greater eGFR decline from T-3 to T0, which tended to be delayed more by SGLT2i than GLP1-RA (p = 0.09). CONCLUSION: In our cohort, subjects with T2DM and preserved renal function show similar eGFR response to treatment with GLP1-RA or SGLT2i. Baseline urinary biomarkers or prior phenotyping do not predict treatment response. An early eGFR decline identifies patients prone to lose more eGFR over time, who may benefit more from SGLT2i treatment.

Gallium-rich Pd-Ga phases as supported liquid metal catalysts.

A strategy to develop improved catalysts is to create systems that merge the advantages of heterogeneous and molecular catalysis. One such system involves supported liquid-phase catalysts, which feature a molecularly defined, catalytically active liquid film/droplet layer adsorbed on a porous solid support. In the past decade, this concept has also been extended to supported ionic liquid-phase catalysts. Here we develop this idea further and describe supported catalytically active liquid metal solutions (SCALMS). We report a liquid mixture of gallium and palladium deposited on porous glass that forms an active catalyst for alkane dehydrogenation that is resistant to coke formation and is thus highly stable. X-ray diffraction and X-ray photoelectron spectroscopy, supported by theoretical calculations, confirm the liquid state of the catalytic phase under the reaction conditions. Unlike traditional heterogeneous catalysts, the supported liquid metal reported here is highly dynamic and catalysis does not proceed at the surface of the metal nanoparticles, but presumably at homogeneously distributed metal atoms at the surface of a liquid metallic phase.

Characterization of maize chitinase-A, a tough allergenic molecule.

Food allergies are recognized as an increasing health concern. Proteins commonly identified as food allergens tend to have one of about 30 different biochemical activities. This leads to the assumption that food allergens must have specific structural features which causes their allergenicity. But these structural features are not completely understood. Uncovering the structural basis of allergenicity would allow improved diagnosis and therapy of allergies and would provide insights for safer food production. The availability of recombinant food allergens can accelerate their structural analysis and benefit specific studies in allergology. Plant chitinases are an example of food allergenic proteins for which structural analysis of allergenicity has only partially been reported. The recombinant maize chitinase, rChiA, was purified from Pichia pastoris extracellular medium by differential precipitation and cation exchange chromatography. Enzyme activity was evaluated by halo-assays and microcalorimetric procedures. rChiA modeling was performed by a two-step procedure, using the Swiss-Model server and Modeller software. Allergenicity of rChiA was verified by immunoblot assays with sera from allergic subjects. rChiA is active in the hydrolysis of glycol chitin and tetra-N-acetylchitotetraose and maintains its activity at high temperatures (70°C) and low pH (pH 3). The molecule is also reactive with IgE from sera of maize-allergic subjects. rChiA is a valuable molecule for further studies on structure-allergenicity relationships and as a tool for diagnosing allergies.

Probiotics and refractory chronic spontaneous urticaria.

Background. In chronic spontaneous urticaria (CSU) first-line therapy with an antihistamine-based regimen may not achieve satisfactory control in patients. Thus, a continuing need exists for effective and safe treatments for refractory CSU. Aim. To evaluate the clinical efficacy and safety of an intake of a combination of 2 probiotics (Lactobacillus salivarius LS01 and Bifidobacterium breve BR03) in patients with CSU who remain symptomatic despite concomitant H1-antihistamine therapy. Methods. This report analyzes the effects of therapy with two probiotic strains on the clinical progress of 52 unselected patients with difficulty to treat CSU underwent to medical examination in two Italian specialist urticaria Clinics between September 2013 and September 2014. A mixture of Lactobacillus LS01 and Bifidobacterium BR03 were administered in each patient twice daily for 8 weeks. To evaluate patients' improvement with probiotics, urticaria activity score over 7 days (UAS7) was used at baseline and at week 8 in addition to a 5-question urticaria quality of life questionnaire. Results. Fifty-two patients with CSU were included in this study (10 male and 42 female, age range 19-72 years). Mean disease duration was 1.5 years. Fourteen patients discontinued treatment, so evaluable population consisted of 38 patients. Nine of the 38 patients experienced mild clinical improvement during probiotic treatment (23.7%); one patient reported significant clinical improvement (2.6%) and one patient had complete remission of urticaria (2.6%). Twenty-seven patients did not have improvement in symptoms (71.1%). No side effects during the course of therapy were reported. Conclusions. A combination of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 administered twice daily for 8 weeks might reduce the symptoms scores and improve quality of life scores in a part of patients with CSU who remained symptomatic despite treatment with H1 antihistamine mostly in subjects with allergic rhinitis.

Electrophoretic Deposition of α-Fe2O3/Chitosan Nanocomposite Coatings for Functional and Biomedical Applications.

Promising composite coatings based on hematite (α-Fe2O3) mesocrystals of size 110 nm and chitosan (CHT) molecules for different biotechnological applications have been successfully obtained by electrophoretic deposition (EPD). Homogeneous and reproducible coatings have been obtained by studying and controlling the chemical interactions between both phases (α-Fe2O3 and CHT). A voltage of 25 V and a deposition time of 5 min were chosen as best deposition conditions, which resulted in highly homogeneous coatings with well-distributed α-Fe2O3 particles. According to TGA measurements, the content of α-Fe2O3 and chitosan in the final composite coating were found to be 74 and 26 wt%, respectively. The presence of both phases in the composite coating was determined by XRD analysis and the coatings microstructure was observed by SEM.

Investigation of the size-property relationship in CuInS2 quantum dots.

In this work we investigated fundamental properties of CuInS2 quantum dots in dependence of the particle size distribution (PSD). Size-selective precipitation (SSP) with acetone as poor solvent was performed as an adequate post-processing step. Our results provide deep insight into the correlation between particle size and various optical characteristics as bandgap energy, absorption and emission features and the broadness of the emission signal. These structure-property relationships are only achieved due to the unique combination of different analytical techniques. Our study reveals that the removal of 10 wt% of smallest particles from the feed results in an enhancement of the emission signal. This improvement is ascribed to a decreased quenching of the emission in larger particles. Our results reveal the impact of PSDs on the properties and the performance of an ensemble of multicomponent QDs and anticipate the high potential of controlling PSDs by well-developed post-processing.

Defibrotide blunts the prothrombotic effect of thalidomide on endothelial cells.

Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy has been identified to increase this risk. Defibrotide (DF), a polydisperse oligonucleotide, showed previously to counteract the alterations in endothelial cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis induced by thalidomide. In this in vitro study, MM by itself alters the profibrinolytic potential of ECs decreasing the tissue plasminogen activator (t-PA) and increasing the plasminogen activator inhibitor 1 (PAI-1) levels which is potentiated by thalidomide. Defibrotide was able to counteract these effects. Additionally, DF upregulated the t-PA and downregulated PAI-1 gene expression modulated by thalidomide. Defibrotide also protects ECs from thalidomide-mediated cell death without interfering with its antitumor effects. These findings support DF clinical use for the prevention of DVT induced by immunomodulatory drugs.

Long-term tolerability of etoricoxib in patients with previous reactions to non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs frequently cause adverse reactions. This retrospective study was based on analysis of the data obtained from interviews conducted with 173 patients, who underwent and tolerated a challenge test with etoricoxib (a selective cyclooxigenase 2 enzyme inhibitor). Only one of 82 patients who were treated with etoricoxib reported reactions. We can conclude that etoricoxib shows a high long-term tolerability in patients with non-steroidal anti-inflammatory drug hypersensitivity.