Effects of hyperglycemia, hyperinsulinemia, and hyperosmolarity on neutrophil apoptosis

BACKGROUND: Hyperglycemia is an independent risk factor for increased mortality of critically ill surgical patients, but despite the recognized clinical benefits of early insulin treatment, there is a lack of understanding of the cellular and molecular mechanisms behind this phenomenon. We hypothesized that polymorphonuclear neutrophils, the first line of the innate immune defense system, suffer from altered apoptotic turnover when exposed to hyperglycemic conditions, ultimately decreasing the number of viable cells active at a site of infection. METHODS: Venous blood samples were drawn from 10 volunteers and incubated for 0.5 or 24 h in a 1:10 dilution with RPMI 1640 medium at various glucose and insulin concentrations. Mannitol was used to control for increased osmolarity. In addition, all samples were incubated either with low-dose lipopolysaccharide (LPS) (1 ng/mL) or without LPS. Neutrophils were extracted using Ficoll-Hypaque density centrifugation and stained with annexin V and propidium iodide. Fluorescence was detected by flow cytometry and analyzed using CellQuest software. RESULTS: The mean percentage of apoptotic neutrophils after 24 h of incubation at physiologic glucose concentrations (100 mg/dL) was 42.2 +/- 4.1%; exposure to low-dose LPS decreased this number to 18.4 +/- 2.5% (p < 0.01). Neither the exposure to low (10 mg/dL) nor increasingly high (200 or 400 mg/dL) glucose concentrations altered these percentages significantly. Exposing whole blood to increasing osmolarity (addition of 5.5 mM and 16.5 mM mannitol to simulate 200 and 400 mg/dL glucose) led to a mean absolute reduction of the percentage of apoptotic neutrophils to 34.6 +/- 3.6% (+5.5 mOsm; p < 0.05) and 32.3 +/- 4.5% (16.5 mOsm; p < 0.01), respectively. CONCLUSIONS: The ability of neutrophils to enter their apoptotic program in cultured whole blood withstands short-term changes in glucose and insulin concentrations. Neither hyperglycemia nor hypoglycemia led to a significant alteration of the apoptotic turnover of these cells, suggesting that the increased rate of infectious complications in short-term hyperglycemic critically ill patients may not be traced to increased apoptosis of neutrophils. However, isolated hyperosmolarity reduces neutrophil apoptosis, an observation that may warrant future investigation.     

Biomaterials as Scaffold for Bone Tissue Engineering

Abstract Almost 20 years after the invention of tissue engineering, autogenous bone grafting has remained the favored strategy for the treatment of bone defects. As an alternative, a vast variety of bone substitutes has been developed and is available for clinical use. The ongoing search for bone substitutes, however, reflects the limitations imposed to both autogenous and allogenous bone grafts as well as to bone substitute materials. The concept of tissue engineering holds great promise for the future treatment of osseous defects. Research in this interdisciplinary field is carried out to find a way of producing biologic substitutes as functional tissue replacement. For this, functionally active cells are applied on supporting scaffolds under controlled stimulation with growth factors. Scaffolds are temporary matrices for bone growth and provide a specific environment and architecture for tissue development. Ideally, scaffolds favor cellular attachment, growth and differentiation in vitro and in vivo. Especially ceramics and biodegradable polymers are widely used and have been tested in various animal studies. Yet, to allow for precise production of specific custom-made scaffolds, rapid prototyping (RP) techniques have recently drawn a lot of attention. Using these methods scaffolds with a predefined, well-controlled internal and external architecture mimicking the structure of natural bone can be generated. Although biocompatibility of the materials used in the process and the structural resolution that can be technically achieved so far limit the range of use, rapid manufacturing techniques do offer great opportunities to generate suitable scaffolds for bone tissue engineering in the near future.     

Pulmonary surfactant dysfunction in pediatric cystic fibrosis: Mechanisms and reversal with a lipid-sequestering drug

Background

Airway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation.

Age‐ and Sex‐Dependent Changes of Intra‐articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis

The objective of this cross‐sectional study was to define normal sex‐ and age‐dependent values of intra‐articular bone mass and microstructures in the metacarpal heads of healthy individuals by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra‐articular bone. Healthy individuals of different sex and age categories and RA patients with similar age and sex distribution received HR‐pQCT scans of the second metacarpal head and the radius. Total, cortical, and trabecular bone densities as well as microstructural parameters were compared between 1) the different ages and sexes in healthy individuals; 2) between metacarpal heads and the radius; and 3) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra‐articular (intracapsular) bone margins. These data were applied in measuring intra‐articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra‐articular and radial bone parameters were good (r = 0.51 to 0.62, p < 0.001). In contrast to radial bone, intra‐articular bone remained stable until age 60 years (between 297 and 312 mg HA/cm³) but decreased significantly (p < 0.001) in women thereafter (237.5 ± 44.3) with loss of both cortical and trabecular bone. Similarly, RA patients showed significant (p < 0.001) loss of intra‐articular total (263.0 ± 44.8), trabecular (171.2 ± 35.6), and cortical bone (610.2 ± 62.0) compared with sex‐ and age‐adjusted controls. Standard sex‐ and age‐dependent values for physiological intra‐articular bone were defined. Postmenopausal state and RA led to significant decrease of intra‐articular bone. © 2016 American Society for Bone and Mineral Research.     

Anästhesiologische Risikoevaluation und rechtssichere Aufklärung per Telemedizin – Sind wir bereit für einen Paradigmenwechsel?

Die Anaesthesiologie - In Deutschland werden pro Jahr 17 Millionen Narkosen und damit auch ungefähr so viele Narkosevorgespräche durchgeführt. Bis dato finden diese praktisch...     

The DGAI CPR registry - the datasets "hospital care" and "long-term process"

After several years of preparation the German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für An?sthesiologie und Intensivmedizin--DGAI) has, during its annual conference 2007, officially launched the DGAI CPR registry. After implementation of the dataset "primary care" in 2004, the datasets "definite care" and "long-term process" have now been released. The completed, internet based database is open for any interested person or institution as a tool for quality management. Data may be recorded online, and basic analyses be performed immediately. Beyond that benchmarks with other institutions are possible, by including the well accepted Utstein style on international level too.     

Surgical treatment of AO type C distal humeral fractures: internal fixation with a Y-shaped reconstruction (Lambda) plate

Although surgical repair is considered the standard treatment for intraarticular distal humeral fractures, most investigators have assessed its results using dual-plate fixation in 2 planes. The purpose of this study was to determine the functional outcome of open reduction and internal fixation of these complex fractures using Y-shaped reconstruction plates. We identified 17 patients who had operative treatment for Arbeitsgemeinschaft Für Osteosynthesefragen (AO) type 1, 3-C fractures using a Y-shaped Lambda plate (Zimmer, Warsaw, IN). Patients were recalled for follow-up that included recording of a complete history, physical examination, radiographic evaluation, and completion of a limb-specific questionnaire. The mean duration of follow-up was 37.3 months. The average loss of extension was 13 degrees , and the average arc of flexion-extension was 112 degrees . As determined by the Mayo Elbow Performance Index, 6 were graded excellent; 8, good; 3, fair; and none, poor. Surgical repair of intraarticular distal humeral fractures by open reduction and internal fixation with a Lambda plate is an effective procedure that allows for stable osteosynthesis without loss of reduction or fixation as a basis for good functional outcome.