Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study

Background and aimsCholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM.Methods and results57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA.A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP.ConclusionExogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.     

Prevalence of Toxoplasma gondii infection in cats from Olsztyn city

17 serum samples from cats after surgery operations in one of veterinary clinic in Olsztyn have been examined. The study on anti-Toxoplasma gondii immunoglobulin IgG presence was carried out by direct agglutination method using the Toxo-Screen DA test. 70.6% positive samples in 1:40 titration, 58.8% in 1:4000 titration and 5.9% questionable result in both dilutions were obtained.     

Drug safety evaluation of lenvatinib for thyroid cancer

Introduction: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor of VEGFR1,2,3,4, FGFR1,2,3,4, PDGFR-α as well as RET and KIT signaling network. Its activity against radioiodine-resistant differentiated thyroid cancer (DTC) has been recently demonstrated. Patients, who were given lenvatinib, showed significantly longer median progression free survival than placebo group, 18.3 vs 3.6 months, respectively. This review is focused on lenvatinib safety profile in patients treated due to DTC and medullary thyroid carcinoma. Among the most frequent lenvatinib-related adverse events (AEs) were hypertension, proteinuria, diarrhea, appetite decrease, weight loss, nausea and stomatitis. Although a lot of them were manageable, in 35–68% of patients dose reduction was required. Nevertheless, only 15% of subjects withdrew the drug due to its toxicity.Areas covered: published results of clinical trials phase II and III investigating both safety and efficacy of lenvatinib in thyroid cancer.Expert opinion: Lenvatinib shows acceptable safety profile in patients with thyroid carcinoma. Treatment-related side effects are usually manageable by dose modifications or by concomitant non-pharmacological and pharmacological treatment. However, the early recognition of any potential drug toxicity is crucial to avoid serious complications as well as to keep a patient on drug as long as the treatment is beneficial.     

Association Between Self-reported Physical Activity and Skin Autofluorescence,a Marker of Tissue Accumulation of Advanced Glycation End Products in Adults With Type 1 Diabetes: A Cross-sectional Study

Purpose

The accumulation of advanced glycation end products (AGEs) in local tissue is an important cause of low-grade inflammation and oxidative stress and is linked to late diabetic complications. Physical activity has various beneficial cardiometabolic effects in type 1 diabetes (T1D) and is associated with lower frequency of chronic complications of diabetes, although the specific mechanisms still remain unclear. The present study determines the association between self-reported physical activity and skin autofluorescence (AF), a marker of tissue accumulation of AGEs in adults with T1D.

Mechanical dispersion is associated with poor outcome in heart failure with a severely depressed left ventricular function and bundle branch blocks

Objectives: Bundle branch blocks (BBB)-related mechanical dyssynchrony and dispersion may improve patient selection for device therapy, but their effect on the natural history of this patient population is unknown.

Methods: A total of 155 patients with LVEF?≤?35% and BBB, not treated with device therapy, were included. Mechanical dyssynchrony was defined as the presence of either septal flash or apical rocking. Contraction duration was assessed as time interval from the electrocardiographic R-(Q-)wave to peak longitudinal strain in each of 17 left ventricular segments. Mechanical dispersion was defined as either the standard deviation of all time intervals (dispersion_SD) or as the difference between the longest and shortest time intervals (dispersion_delta). Patients were followed for cardiac mortality during a median period of 33 months.

Results: Mechanical dyssynchrony was not associated with survival. More pronounced mechanical dispersion_delta was found in patients with dyssynchrony than in those without. In the multivariate regression analysis, patients’ functional class, diabetes mellitus and dispersion_delta were independently associated with mortality.

Conclusions: Mechanical dispersion, but not dyssynchrony, was independently associated with mortality and it may be useful for risk stratification of patients with heart failure (HF) and BBB.

• Key Messages

• Mechanical dispersion, measured by strain echocardiography, is associated with poor outcome in heart failure with a severely depressed left ventricular function and bundle branch blocks.

• Mechanical dispersion may be useful for risk stratification of patients with heart failure and bundle branch blocks.

     

Quantitative ADME Proteomics – CYP and UGT Enzymes in the Beagle Dog Liver and Intestine

Pharmaceutical Research - Beagle dogs are used to study oral pharmacokinetics and guide development of drug formulations for human use. Since mechanistic insight into species differences is needed...     

Quantitative Myocardial Perfusion Imaging Versus Visual Analysis in Diagnosing Myocardial Ischemia: A CE-MARC Substudy

Objectives

This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography.