Herbal Extracts of Ginseng and Maqui Berry Show Only Minimal Effects on an In Vitro Model of Early Fracture Repair of Smokers.

Smoking is a major risk factor for delayed fracture healing, affecting several aspects of early fracture repair, including inflammation, osteogenesis, and angiogenesis. Panax ginseng (GE) and maqui berry extract (MBE) were shown in our previous studies to reduce smoke-induced cellular damage in late bone-healing in vitro models. We aimed here to analyze their effects on the early fracture repair of smokers in a 3D co-culture model of fracture hematomas and endothelial cells. Both extracts did not alter the cellular viability at concentrations of up to 100 µg/mL. In early fracture repair in vitro, they were unable to reduce smoking-induced inflammation and induce osteo- or chondrogenicity. Regarding angiogenesis, smoking-induced stress in HUVECs could not be counteracted by both extracts. Furthermore, smoking-impaired tube formation was not restored by GE but was harmed by MBE. However, GE promoted angiogenesis initiation under smoking conditions via the Angpt/Tie2 axis. To summarize, cigarette smoking strikingly affected early fracture healing processes in vitro, but herbal extracts at the applied doses had only a limited effect. Since both extracts were shown before to be very effective in later stages of fracture healing, our data suggest that their early use immediately after fracture does not appear to negatively impact later beneficial effects.

Febrile-Range Hyperthermia Can Prevent Toxic Effects of Neutrophil Extracellular Traps on Mesenchymal Stem Cells.

Fracture healing is characterized by an inflammatory phase directly after fracture which has a strong impact on the healing outcome. Neutrophils are strong contributors here and can release neutrophil extracellular traps (NETs). NETs are found after trauma, originally thought to capture pathogens. However, they can lead to tissue damage and impede wound healing processes. Their role in fracture healing remains unclear. In this study, the effect of isolated NETs on the function of bone-forming mesenchymal stem cells (SCP-1 cells) was examined. NETs were isolated from stimulated healthy neutrophils and viability, migration, and differentiation of SCP-1 cells were analyzed after the addition of NETs. NETs severely impaired the viability of SCP-1 cells, induced necrosis and already nontoxic concentrations reduced migration significantly. Short-term incubation with NETs had a persistent negative effect on osteogenic differentiation, as measured by AP activity and matrix formation. The addition of DNase or protease inhibitors failed to reverse the negative effect of NETs, whereas a short febrile-range temperature treatment successfully reduced the toxicity and membrane destruction. Thus, the possible modification of the negative effects of NETs in fracture hematomas could be an interesting new target to improve bone healing, particularly in patients with chronic diseases such as diabetes.

Preoperative Ascorbic Acid Levels in Proximal Femur Fracture Patients Have No Postoperative Clinical Impact, While Ascorbic Acid Levels upon Discharge Have a Major Effect on Postoperative Outcome.

Proximal femur fractures show a high prevalence in elderly patients and are associated with an elevated risk of multimorbidity and early mortality. Recovery is impaired by malnutrition and oxidative stress, which is affected by antioxidants such as ascorbic acid (AA). This study monitored AA levels during hospitalization of patients with a proximal femur to investigate the influence of AA status to the clinical outcome. AA levels of 25 elderly patients with a proximal femur fracture were measured during hospitalization using high performance liquid chromatography. Plasma samples were collected preoperatively, on the first day after surgery, on the third day after surgery and on the day of discharge. Nutritional Risk Screening 2002 (NRS) and Mini Nutritional Assessment (MNA) were assessed to evaluate the nutritional status. In patients with proximal femoral fractures, preoperative AA concentrations were significantly lower compared to elderly patients without an acute fracture. A significant decrease of 33.8% in AA plasma level was measured on the day after surgery with a significant recovery up to the time of discharge. The preoperative AA status did not have any significant effect on clinical outcome. However, inadequate AA levels (<50 µmol/L) upon discharge significantly increased the incidence and the severity of postoperative complications. These results indicate that the AA status upon discharge has a greater impact on clinical outcome than assumed, and therefore, AA supplementation during hospitalization should be considered.

Crucial Role of Vitamin D in the Musculoskeletal System.

Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D's central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported.

Therapeutic peritoneal lavage with warm saline solution as an option for a critical hypothermic trauma patient.

INTRODUCTION: In this paper, we present the case of a 63-year-old woman, who was found in her flat lying unconscious on the floor for an unknown time. At the time of admission, her core temperature was 24 °C and ventricular fibrillation was detected on the electrocardiogram (ECG). Because of the unstable conditions, the persistent nonperfusing cardiac rhythm and the dramatically inhibited coagulation cascade, a peritoneal lavage connected to a rapid infuser was performed for rewarming, instead of using a transportable heart-lung machine and a haemodialysis device. After a prolonged cardiopulmonary resuscitation (CPR), the patient could be transferred to the intensive care unit (ICU) in a stable condition. After 40 days in the ICU, recovery was fast, and another month of treatment later, she could be discharged back home without any discomfort. CONCLUSION: This report illustrates the successful use of the peritoneal lavage for rewarming a severely hypothermic patient without any extracorporeal rewarming device. Furthermore, it can be used in nearly every hospital if the necessary equipment is affordable. It is demonstrated that this technique is able to provide good outcomes for all victims of accidental hypothermia.

Green tea protects human osteoblasts from cigarette smoke-induced injury: possible clinical implication.

PURPOSE: Recent reports discuss the altered bone homeostasis in cigarette smokers, being a risk factor for osteoporosis and negatively influencing fracture healing. Cigarette smoke is known to induce oxidative stress in the body via an increased production of reactive oxygen species (ROS). These increases in ROS are thought to damage the bone-forming osteoblasts. Naturally occurring polyphenols contained in green tea extract (GTE), e.g., catechins, are known to have anti-oxidative properties. Therefore, the aim of this study was to investigate whether GTE and especially catechins protect primary human osteoblasts from cigarette smoke-induced damage and to identify the underlying mechanisms. METHODS: Primary human osteoblasts were isolated from patients' femur heads. Cigarette smoke medium (CSM) was obtained using a gas-washing bottle and standardized by its optical density (OD(320)) at λ = 320 nm. ROS formation was measured using 2'7'dichlorofluorescein diacetate, and osteoblasts' viability was detected by resazurin conversion. RESULTS: Co-, pre-, and post-incubation with GTE and catechins significantly reduced ROS formation and thus improved the viability of CSM-treated osteoblasts. Besides GTE's direct radical scavenging properties, pre-incubation with both GTE and catechins protected osteoblasts from CSM-induced damage. Inhibition of the anti-oxidative enzyme HO-1 significantly reduced the protective effect of GTE and catechins emphasizing the key role of this enzyme in GTE anti-oxidative effect. CONCLUSIONS: Our data suggest possible beneficial effects on bone homeostasis, fracture healing, and bone mineral density following a GTE-rich diet or supplementation.

Quercetin protects primary human osteoblasts exposed to cigarette smoke through activation of the antioxidative enzymes HO-1 and SOD-1.

Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS). The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM) rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers.