More patients reach glycaemic control with a fixed‐ratio combination of insulin glargine and lixisenatide (iGlarLixi) than with basal insulin at 12 weeks of treatment: A post hoc time‐to‐control analysis of LixiLan‐O and LixiLan‐L

The present post hoc analysis of two 30‐week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan‐O trial) or basal insulin (LixiLan‐L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) ≤7.2 mmol/L, was estimated using the Kaplan–Meier method. In the LixiLan‐O and LixiLan‐L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan‐O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan‐L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time‐to‐target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points.     

Inhibition of Taq polymerase as a method for screening heparin for oversulfated contaminants

Heparin and low molecular heparins are extensively used in the treatment of a wide range of diseases in addition to their classic anticoagulant activity and can be found coating medical devices such as catheters, stents and filters. Early in 2008, a sharp increase in heparin-associated severe adverse events, including over 80 deaths, was linked to the presence of a contaminant identified as hypersulfated chondroitin sulfate (OS-CS). OS-CS is one of several oversulfated glycosaminoglycans (GAGs) of different origins that can potentially cause similar clinical problems underscoring the need to develop robust screening methods for contaminants in existing and future lots of heparin. This study demonstrates that oversulfated GAGs block the activity of Taq polymerase used for real time PCR. Based on this finding we developed a simple, rapid, sensitive and high throughput screening method to detect and quantify oversulfated chondroitin sulfate (OS-CS) and other potential oversulfated contaminants in commercial lots of heparin. This method requires less than 100 miliUnits (mU) of heparin as starting material, therefore avoiding the need to lyophilize and concentrate samples, and has a limit of detection of <1 ng for all oversulfated GAGs tested.     

Analgesic, anti-inflammatory and oxy-radical scavenger activity of imidazole and imidazole derivatives

The author describes the recent work of his laboratory on imidazole. It increased the analgesic effects of morphine, and rivalled acetylsalicylic acid as an analgesic antipyretic agent. At 160 mg/kg, imidazole protected rats against indomethacin-induced gastric ulcers. It was equal to acetylsalicylic acid in reducing carrageenan inflammation, and was superior to it as anti-arthritic drug. Imidazole 2-hydroxybenzoate caused 36% inhibition of synovial fluid depolymerization.     

Two new single-nucleotide polymorphisms in the COL1A1 upstream regulatory region and their relationship to bone mineral density.

Single-nucleotide polymorphisms (SNPs) in regulatory regions of candidate genes may determine variability in bone mineral density (BMD) because they may be responsible for differences in levels of a gene product in response to external signals. Under this hypothesis, we scanned an 800-base pair (bp) region within the COL1A1 promoter, known to harbor cis elements important for in vivo expression, and we found two new polymorphisms: -1663indelT and -1997 G/T. The G to T transversion at -1997 was associated with lumbar spine BMD (p = 0.015) when tested in a cohort of 256 postmenopausal women after adjusting by age, body weight, and years since menopause; a lower degree of association was detected also for femoral neck BMD in a subgroup of 146 women in univariate analysis and after adjusting by age (p = 0.044). The polymorphism -1663indelT, which corresponds to a deletion of a T in a tract of eight T residues (-1670 to -1663), did not show significant association with BMD. Interestingly, -1663indelT is in strong linkage disequilibrium (LD) with the previously described Sp1 polymorphism of intron 1, which in this study did not show association with BMD either. Significant interaction between -1997 G/T and -1663indelT (p = 0.019), and between -1997 G/T and Sp1 (p = 0.045) was observed also. Individuals heterozygous for the three polymorphisms showed the highest mean BMD value. Gel retardation assays showed that oligonucleotides containing either the -1663 or the -1997 polymorphic sites specifically bind primary osteoblast nuclear proteins. We named these binding sites as PCOL1 and PCOL2, respectively. In summary, this study describes two new SNPs in the COL1A1 promoter, which may affect bone mass determination.