A Novel Strategy for the Mechanical Subpulmonary Support in Failing Fontan Patients.

Background: The number of single ventricle patients undergoing Fontan palliation and surviving to adulthood worldwide has steadily increased in recent years. Nevertheless, the Fontan circulation is destined to fail. Ultimately, heart transplantation (HTx) remains the definitive treatment option.

An in vitro system to silence mitochondrial gene expression.

The human mitochondrial genome encodes thirteen core subunits of the oxidative phosphorylation system, and defects in mitochondrial gene expression lead to severe neuromuscular disorders. However, the mechanisms of mitochondrial gene expression remain poorly understood due to a lack of experimental approaches to analyze these processes. Here, we present an in vitro system to silence translation in purified mitochondria.

MitoRibo-Tag Mice Provide a Tool for In Vivo Studies of Mitoribosome Composition.

Mitochondria harbor specialized ribosomes (mitoribosomes) necessary for the synthesis of key membrane proteins of the oxidative phosphorylation (OXPHOS) machinery located in the mitochondrial inner membrane. To date, no animal model exists to study mitoribosome composition and mitochondrial translation coordination in mammals in vivo. Here, we create MitoRibo-Tag mice as a tool enabling affinity purification and proteomics analyses of mitoribosomes and their interactome in different tissues.

PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly.

The regulation of mitochondrial RNA life cycles and their roles in ribosome biogenesis and energy metabolism are not fully understood. We used CRISPR/Cas9 to generate heart- and skeletal-muscle-specific knockout mice of the pentatricopeptide repeat domain protein 1, PTCD1, and show that its loss leads to severe cardiomyopathy and premature death. Our detailed transcriptome-wide and functional analyses of these mice enabled us to identify the molecular role of PTCD1 as a 16S rRNA-binding protein essential for its stability, pseudouridylation, and correct biogenesis of the mitochondrial large ribosomal subunit.

Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer.

Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival.

Pilot study for the evaluation of morphological and functional changes in retinal blood flow in patients with insulin resistance and/or type 2 diabetes mellitus.

Background: The aim of this study was to investigate early morphological and functional pathology in the retinal micro-circulation in patients with insulin resistance and/or type 2 diabetes mellitus (T2DM).

Methods: Fifty-four subjects, without features of retinopathy under ophthalmological investigation, were recruited for study participation and were classified into three study groups according to their metabolic staging: (1) Group C comprised nondiabetic, insulin-sensitive subjects with a BMI <28 kg/m(2); (2) Group IR comprised nondiabetic, insulin-resistant, obese subjects with a BMI ≥28 kg/m(2); and (3) Group DM comprised patients with manifested T2DM. Retinal microvascular blood flow was assessed using scanning laser doppler flowmetry (Heidelberg Retina Flowmeter) before and after flicker light stimulation (10 Hz; Photo Stimulater 750).

Combination of a MDR1-targeted replicative adenovirus and chemotherapy for the therapy of pretreated ovarian cancer.

Purpose: Targeted oncolytic adenoviruses capable of replication selectively in cancer cells are an appealing approach for the treatment of various cancer types refractory to conventional therapies. The aim of this study was to evaluate the effect of Ad5/3MDR1E1, a multidrug resistance gene 1 (MDR1)-targeted fiber-modified replication-competent adenovirus for the therapy of platinum-pretreated ovarian cancer in combination with cytostatic agents.

Methods: MDR1-specific tumor cell killing of Ad5/3MDR1E1 was systematically evaluated in chemotherapy naïve and pretreated ovarian cancer cells in vitro.

Hysteroscopic management of residual trophoblastic tissue is superior to ultrasound-guided curettage.

Study Objective: The aim of this study was to estimate the rate of intrauterine adhesions and subsequent pregnancy outcome in patients with residual trophoblastic tissue treated with hysteroscopic resection versus ultrasound-guided dilation and evacuation (D&E).

Design: Cohort study from 2 centers (Canadian Task Force classification II-2).

Setting: Two surgical teams at the University of Duesseldorf Medical Center and the PAN Clinic in Cologne, Germany.

The fixed combination of pioglitazone and metformin improves biomarkers of platelet function and chronic inflammation in type 2 diabetes patients: results from the PIOfix study.

Background: Type 2 diabetes mellitus (T2DM) is characterized by a proinflammatory and procoagulant condition. This study investigates the impact of a pioglitazone plus metformin therapy on biomarkers of inflammation and platelet activation in comparison to a treatment with glimepiride plus metformin.

Methods: The study was designed as a multicenter, randomized, double-blinded two-arm trial.

PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with glimepiride on diabetic dyslipidemia.

Objective: Dyslipidemia in patients with type 2 diabetes is characterized by elevated triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol, and a predominance of small dense low-density lipoprotein (LDL) particles. Also, patients suffer from β-cell dysfunction, chronic systemic inflammation, increased hormonal visceral adipose tissue activity, and an increased risk of cardiovascular events. The aim of our study was to investigate the effect of a fixed pioglitazone + metformin (PM) combination (vs.

High-sensitivity C-reactive protein predicts cardiovascular risk in diabetic and nondiabetic patients: effects of insulin-sensitizing treatment with pioglitazone.

Systemic inflammatory activity has turned out to play a key pathogenic role in vascular atherosclerosis, insulin resistance, and type 2 diabetes mellitus. Inflammatory biomarkers may therefore be a valuable tool for risk evaluation. Among them, the best evidence to date supports the use of high-sensitivity C-reactive protein (hs-CRP) to monitor insulin resistance and cardiovascular risk in diabetic and nondiabetic individuals.

Combined pioglitazone and metformin treatment maintains the beneficial effect of short-term insulin infusion in patients with type 2 diabetes: results from a pilot study.

Background: The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application.

Methods: This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 +/- 2 years; body mass index 29 +/- 3.2 kg/m(2); hemoglobin A1c [HbA1c] 7.

Time-action profile and patient assessment of inhaled insulin via the Exubera device in comparison with subcutaneously injected insulin aspart via the FlexPen device.

Background: The goal of our investigation was to compare the pharmacokinetics/pharmacodynamics properties of and patient preference for insulin aspart applied with the FlexPen (Novo Nordisk, Bagsvaerd, Denmark) (IAFP) with pulmonary human insulin applied with the Exubera (Pfizer, New York, NY) device (HIEX).

Methods: Twelve patients with diabetes (six with type 1 and six with type 2; eight men, four women; age, 54.5 +/- 11.

The IRIS V study: pioglitazone improves systemic chronic inflammation in patients with type 2 diabetes under daily routine conditions.

Background: The peroxisome proliferator-activated receptor-gamma agonist pioglitazone is established as a drug to treat patients with type 2 diabetes mellitus. In addition to lowering blood glucose levels, one of the favorable effects of pioglitazone is improvement of systemic chronic inflammation particularly affecting vessel walls. The effect can be monitored by the measurement of the biomarker C-reactive protein in the range of 0-10 mg/L (high-sensitivity C-reactive protein [hsCRP]).

Effect of insulin glulisine on microvascular blood flow and endothelial function in the postprandial state.

Objective: To investigate the effect of insulin glulisine on postprandial microvascular blood flow in type 2 diabetes.

Research Design And Methods: A total of 15 patients with type 2 diabetes received insulin glulisine or human insulin before a liquid meal test. Thereafter, skin microvascular blood flow was measured by laser Doppler fluxmetry and blood samples were taken for measurement of plasma levels of glucose, insulin, intact proinsulin, asymmetric dimethylarginine, nitrotyrosine, interleukin-18, matrix metalloproteinase-9, oxidized LDL, and free fatty acids.

Relaxin expression correlates significantly with serum fibrinogen variation in response to antidiabetic treatment in women with type 2 diabetes mellitus.

Aim: Diabetes is associated with aberrant coagulation. Relaxin, an insulin-like peptide hormone, is a candidate to be involved in the underlying molecular mechanisms. Therefore, the present study investigated the correlation of relaxin expression with fibrinogen levels in diabetes patients undergoing oral antidiabetic treatment.

Relaxin expression correlates significantly with serum changes in VEGF in response to antidiabetic treatment in male patients with type 2 diabetes mellitus.

Recent studies indicate that relaxin as well as VEGF possess cardioprotective properties. This study aimed to determine the association of relaxin with VEGF in patients with type 2 diabetes. We therefore analyzed samples from a recent study showing the benefits of anti-diabetic treatment on cardiovascular risk markers independently from glycemic control.

Self-monitoring of blood glucose levels requires intensive training for use of meters to obtain reliable and clinically relevant measurements.

Background: Anecdotal reports from pediatric sites have indicated that some blood glucose meters may display wrong and misleading numbers rather than error indications, when operated in deviation from the instructions for use (IFU), eg by manipulating the strip during the count-down phase.

Methods: This study was performed with 60 patients with diabetes (32 female, 28 male, 21 type 1, 39 type 2, age (mean+/-SD): 56+/-11 years) who measured their blood glucose levels twice with five different blood glucose meters (Precision(R) Xceed [Abbott Medisense], Freestyle Mini [Abbott Medisense], Accu-Chek Comfort [Roche Diagnostics], Accu-Chek Aviva [Roche Diagnostics], and Ascensia Contour [Bayer Vital]). The first measurement was performed in accordance with the IFU, and the second by manipulating the test strip using a standardised inflexion/release procedure during the count-down phase.

Anticancer drugs induce mdr1 gene expression in recurrent ovarian cancer.

Ovarian cancer is currently the most lethal gynecologic malignancy in Europe and the US. Platin analogues and paclitaxel demonstrate high remission rates, but unfortunately the efficacy of cytostatic agents is limited by the development of multidrug resistance (mdr). Clinical paclitaxel resistance is often associated with mdr1 overexpression.

Association of high-sensitive C-reactive protein with advanced stage beta-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus is associated with increased cardiovascular risk. One laboratory marker for cardiovascular risk assessment is high-sensitivity C-reactive protein (hsCRP).

Methods: This cross-sectional study attempted to analyze the association of hsCRP levels with insulin resistance, beta-cell dysfunction and macrovascular disease in 4270 non-insulin-treated patients with type 2 diabetes [2146 male, 2124 female; mean age +/-SD, 63.

Impact of rosiglitazone on beta-cell function, insulin resistance, and adiponectin concentrations: results from a double-blind oral combination study with glimepiride.

Addition of rosiglitazone to sulfonylurea has been shown to improve glycemic control in patients with type 2 diabetes previously treated with sulfonylurea monotherapy alone. This investigation was performed to assess the specific impact of rosiglitazone on insulin resistance, beta-cell function, cardiovascular risk markers, and adiponectin secretion in this treatment concept. One hundred two patients from a double-blind, 3-arm comparator trial (group 0, glimepiride + placebo, n = 30; group 4, glimepiride + 4 mg rosiglitazone, n = 31; group 8, glimepiride + 8 mg rosiglitazone, n = 41; 48 women, 54 men; age [mean +/- SD], 62.

Biological background and role of adiponectin as marker for insulin resistance and cardiovascular risk.

Adiponectin is a serum protein secreted by adipocytes and accounts for approximately 0.01% of total plasma protein. In healthy patient populations adiponectin can be found in concentrations of 7-12 mg/l.