Fetuin-A Induces Cytokine Expression and Suppresses Adiponectin Production

BACKGROUND: The secreted liver protein fetuin-A (AHSG) is up-regulated in hepatic steatosis and the metabolic syndrome. These states are strongly associated with low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that fetuin-A may play a role in the regulation of cytokine expression, the modulation of adipose tissue expression and plasma concentration of the insulin-sensitizing and atheroprotective adipokine adiponectin. METHODOLOGY AND PRINCIPAL FINDINGS: Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding inflammatory cytokines and the adipokine adiponectin (ADIPOQ) was assessed by real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05). Treatment of mice with fetuin-A, analogously, resulted in a marked increase in adipose tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively). These effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression and lower circulating adiponectin levels (p<0.05, both). Furthermore, fetuin-A repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes (p<0.02) and induced inflammatory cytokine expression. In humans in plasma, fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker of subclinical inflammation (r = 0.26, p = 0.01), and negatively with total- (r = -0.28, p = 0.02) and, particularly, high molecular weight adiponectin (r = -0.36, p = 0.01). CONCLUSIONS AND SIGNIFICANCE: We provide novel evidence that the secreted liver protein fetuin-A induces low-grade inflammation and represses adiponectin production in animals and in humans. These data suggest an important role of fatty liver in the pathophysiology of insulin resistance and atherosclerosis

Patient Motion Using a Computerized Leg Brace in Everyday Locomotion Tasks

Exoskeletal systems are becoming a rehabilitation standard of care for persons with lower limb paralysis. As muscular dysfunctions affect a heterogeneous patient group, each individual develops their own strategy to negotiate everyday locomotion challenges. This paper introduces a microprocessor controlled orthotic system that passively supports people with lower limb paralyses in their everyday locomotion tasks while incorporating the user as the highest control entity. A clinical study with seven patients with a range of leg pareses investigated the functionality and usage of the system while capturing the mechanical stress on the device. Data from the knee joint was recorded in locomotion tasks including level walking, ramp, and stair negotiation. For all patients, the measurements demonstrate that the motion for level walking was close to the motion of healthy individuals. In other tasks, variations between the patients were large with respect to motion kinematics, power, and torque requirements. As the control concept supported individualized motion patterns, patients perceived the system functionality as intuitive. The mechanically most demanding task was stair descent with a peak torque of 1.47 Nm/kg and peak dissipative power up to 2.67 W/kg. Intra-subject variability makes prediction of movements and loads challenging

Energy Recuperation at the Hip Joint for Paraplegic Walking: Interaction Between Patient and Supportive Device

For patients with lower limb paralysis, wearable robotic systems are becoming increasingly important for regaining mobility. The actuation of these systems is challenging because of the necessity to deliver high power within very limited space. However, not all patients need full support, as many patients have residual muscle function that can be applied for locomotion. This work introduces a microprocessor-controlled leg (hip-knee-ankle-foot) orthosis (mpLeg) with energy recuperation capabilities at the hip joint. The system redistributes motion energy generated by the patient during walking. In stance phase of walking, energy is stored in an elastic element at the hip joint. This energy can be released by computer control later in the gait phase, to support swing phase motion. This work aims at investigating the influence of the elastic element in the orthotic hip joint on a patient’s motion. Experiments conducted with a patient suffering from incomplete paraplegia demonstrated that the motion pattern during walking improved with activated energy recuperation. This observation was made over a wide range of system parameters. The patient used the energy recuperation capabilities of the mpLeg with up to 4.1 J recuperated energy per step, which resulted in a more natural swing phase motion during walking. Therefore energy recuperation at the hip joint is a feasible technology for future supportive devices

Activities with a Microprocessor-Controlled Leg Brace for Patients with Lower Limb Paralysis: A Series of Case Studies

Lower limb paralysis often leads to depreciation in mobility of the affected individuals. Computer-controlled leg brace systems open up new possibilities for these patients, by improving the safety of mobility tasks in everyday life, especially when walking on uneven terrain, inclined surfaces, steps and stairs. This paper introduces such a system. To investigate the use of device functionalities in the patient’s everyday environment, the knee joint of the brace was configured to store data of various sensors, measuring motion with a high temporal resolution over several weeks of home use. Results from a clinical trial including 8 patients with different pathologies show that the system was used by the patients for more than 10 hours per day on average, taking more than 2,100 steps per day. Maximum use time was more than 20.24 hours with 12,609 steps per day. An implemented yielding function to support walking down slopes or stairs was used by all patients. This function can also catch the user in case of stumbling, which on average happened 3 times per day. Seven out of eight patients reported improvements in quality and safety of many activities in daily life using the novel system, compared to their previous device