Undetected and undiagnosed comorbidity in patients with obesity undergoing bariatric surgery-Results from the Berlin Bariatric Cohort study.

The quality of general obesity management before bariatric surgery (BS) is rarely investigated. Inadequate information regarding undetected and undiagnosed comorbidities (UUCs) in individuals with obesity may influence the penetration, risks, and outcomes of BS. We conducted a cohort study involving a pre-specified medical check-up in a cooperation between a BS department and an outpatient medical centre.

Paternal eNOS deficiency in mice affects glucose homeostasis and liver glycogen in male offspring without inheritance of eNOS deficiency itself.

Aims/hypothesis: It was shown that maternal endothelial nitric oxide synthase (eNOS) deficiency causes fatty liver disease and numerically lower fasting glucose in female wild-type offspring, suggesting that parental genetic variants may influence the offspring's phenotype via epigenetic modifications in the offspring despite the absence of a primary genetic defect. The aim of the current study was to analyse whether paternal eNOS deficiency may cause the same phenotype as seen with maternal eNOS deficiency.

Methods: Heterozygous (+/-) male eNOS (Nos3) knockout mice or wild-type male mice were bred with female wild-type mice.

Free vitamin D is independently associated with systolic blood pressure in diabetic patients with impaired kidney function.

Vitamin D contributes to blood pressure (BP) regulation. We compared the association of BP in diabetic patients with either total vitamin D - the standard way of analyzing the vitamin D status - or free vitamin D, because only free vitamin D passes the cell membrane and interacts with the nuclear vitamin D receptor (VDR). An analytical cross-sectional study was conducted with 178 diabetic patients with impaired kidney function.

Relationship Between Vitamin D and Hormones Important for Human Fertility in Reproductive-Aged Women.

Vitamin D deficiency is very common in women of reproductive age. Studies in animals suggests a link between vitamin D and reproductive hormone biosynthesis. A systematic analysis of the correlation of reproductive hormones in reproductive-aged women with both total and free vitamin D was, however, not done so far.

Opposite correlation of 25-hydroxy-vitamin D- and 1,25-dihydroxy-vitamin D-metabolites with gestational age, bone- and lipid-biomarkers in pregnant women.

25-Hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)D) need to be bound to carrier proteins to be transported to their target cells. The majority of either 25OHD or 1,25(OH)D is bound to vitamin D-binding protein (DBP), a smaller fraction is bound to albumin and only very small amounts of 25OHD or 1,25(OH)D are free. Albumin-bound 25OHD or 1,25(OH)D is relatively easily available after dissociation from albumin.

Linagliptin and telmisartan induced effects on renal and urinary exosomal miRNA expression in rats with 5/6 nephrectomy.

Dipeptidyl peptidase 4 inhibitors and angiotensin II receptor blockers attenuate chronic kidney disease progression in experimental diabetic and non-diabetic nephropathy in a blood pressure and glucose independent manner, but the exact molecular mechanisms remain unclear. MicroRNAs (miRNAs) are short, non-coding RNA species that are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of nephropathy. miRNAs are present in urine in a remarkably stable form, packaged in extracellular vesicles.

Mechanisms of GLP-1 receptor-independent renoprotective effects of the dipeptidyl peptidase type 4 inhibitor linagliptin in GLP-1 receptor knockout mice with 5/6 nephrectomy.

Dipeptidyl peptidase type 4 (DPP-4) inhibitors were reported to have beneficial effects in experimental models of chronic kidney disease. The underlying mechanisms are not completely understood. However, these effects could be mediated via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP1R) pathway.

Comparison of free and total 25-hydroxyvitamin D in normal human pregnancy.

Vitamin D status correct monitoring during pregnancy is critically important for both maternal and fetal health. 25-Hydroxyvitamin D (25(OH)D) - a prohormone of a biologically active 1,25-dihydroxyvitamin D (1,25(OH)D), despite the lack of biological activity, during the past decades has been routinely used as a main biomarker characterizing vitamin D status. About 85% of 25(OH)D in the bloodstream is bound to its specific carrier - vitamin D-binding protein (DBP), the remaining 15% are loosely bound to albumin, and only less than 0.

Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet.

Aims/hypothesis: Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy.

Methods: Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating.

Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium.

Background: The use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11-12% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate.

Reference intervals for measured and calculated free 25-hydroxyvitamin D in normal pregnancy.

The determination of free 25-hydroxyvitamin D (25(OH)D) as compared to the analysis of total 25-hydroxyvitamin D might reflect better the vitamin D status during pregnancy, since vitamin D-binding protein (DBP) concentrations increase throughout pregnancy and the vast majority of 25(OH)D is tightly bound to DBP thus strongly influencing total 25(OH)D. The concentration of the biologically active free 25(OH)D - on the other hand - is much less dependent on the DBP concentrations. The study was conducted in May-June 2016 in 368 Caucasian pregnant healthy women - residents of Northeastern Germany.

Why should we measure free 25(OH) vitamin D?

Vitamin D, either in its D or D form, is essential for normal human development during intrauterine life, kidney function and bone health. Vitamin D deficiency has also been linked to cancer development and some autoimmune diseases. Given this huge impact of vitamin D on human health, it is important for daily clinical practice and clinical research to have reliable tools to judge on the vitamin D status.

Impact of vitamin D on pregnancy-related disorders and on offspring outcome.

Observational studies from all over the world continue to find high prevalence rates of vitamin D insufficiency and deficiency in many populations, including pregnant women. Beyond its classical function as a regulator of calcium and phosphate metabolism, vitamin D elicits numerous effects in the human body. Current evidence highlights a vital role of vitamin D in mammalian gestation.

Pre-Interventional Kynurenine Predicts Medium-Term Outcome after Contrast Media Exposure Due to Coronary Angiography.

Background/aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application.

Head-to-head comparison of structurally unrelated dipeptidyl peptidase 4 inhibitors in the setting of renal ischemia reperfusion injury.

Background And Purpose: Results regarding protective effects of dipeptidyl peptidase 4 (DPP4) inhibitors in renal ischaemia-reperfusion injury (IRI) are conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a model of renal IRI.

Experimental Approach: IRI was induced in uninephrectomized male rats by renal artery clamping for 30 min.

Global Overexpression of ET-1 Decreases Blood Pressure - A Systematic Review and Meta-Analysis of ET-1 Transgenic Mice.

Background/aims: ET-1 has independent effects on blood pressure regulation in vivo, it is involved in tubular water and salt excretion, promotes constriction of smooth muscle cells, modulates sympathetic nerve activity, and activates the liberation of nitric oxide. To determine the net effect of these partially counteracting mechanisms on blood pressure, a systematic meta-analysis was performed.

Methods: Based on the principles of Cochrane systematic reviews, we searched in major literature databases - MEDLINE (PubMed), Embase, Google Scholar, and the China Biological Medicine Database (CBM-disc) - for articles relevant to the topic of the blood pressure phenotype of endothelin-1 transgenic (ET-1+/+) mice from January 1, 1988 to March 31, 2016.

Paternal programming of offspring cardiometabolic diseases in later life.

Early - intrauterine - environmental factors are linked to the development of cardiovascular disease in later life. Traditionally, these factors are considered to be maternal factors such as maternal under and overnutrition, exposure to toxins, lack of micronutrients, and stress during pregnancy. However, in the recent years, it became obvious that also paternal environmental factors before conception and during sperm development determine the health of the offspring in later life.

Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner.

Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice.

The dipeptidyl peptidase inhibitor linagliptin and the angiotensin II receptor blocker telmisartan show renal benefit by different pathways in rats with 5/6 nephrectomy.

Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan.

Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography.

Background: Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss.

Endothelin-1 Overexpression Improves Renal Function in eNOS Knockout Mice.

Background/aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice.

Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics.

Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension.

Dealing with large sample sizes: comparison of a new one spot dot blot method to western blot.

Background: Western blot is the gold standard method to determine individual protein expression levels. However, western blot is technically difficult to perform in large sample sizes because it is a time consuming and labor intensive process. Dot blot is often used instead when dealing with large sample sizes, but the main disadvantage of the existing dot blot techniques, is the absence of signal normalization to a housekeeping protein.

Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy.

Background: Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear.

Method: This study examined the long-term renoprotective effects of DPP-4 inhibitor linagliptin in db/db mice, a model of type 2 diabetes. Results were compared with the known beneficial effects of renin-angiotensin system blockade by enalapril.

Endothelin receptor antagonists in clinical research--lessons learned from preclinical and clinical kidney studies.

Endothelin receptor antagonists (ETRAs) are approved for the treatment of pulmonary hypertension and scleroderma-related digital ulcers. The efforts to approve this class of drugs for renal indications, however, failed so far. Preclinical studies were promising.