Enhanced Survival and Neuronal Differentiation of Adrenal Chromaffin Cells Cografted into the Striatum with NGF-producing Fibroblasts

Although adrenal medullary chromaffin cells have been used extensively for intracerebral grafting, their survival has generally been poor. Improved survival of the implanted cells has been achieved by exposing the chromaffin cells to NGF in vivo. Culture studies have shown, however, that chromaffin cells are converted into sympathetic neurons when NGF is included in the medium. The degree to which such a transdifferentiation may occur in vivo has not been determined. We assessed the effects of cografting chromaffin cells with primary fibroblasts genetically engineered to express NGF. Chromaffin cells from 10 d old rats were implanted with NGF-producing or beta- galactosidase-producing primary fibroblasts (control fibroblasts) into the striatum of 6-hydroxydopamine treated adult rats of the same strain. Eight weeks postgrafting, chromaffin cells cografted with NGF- producing fibroblasts displayed many of the features of mature sympathetic neurons such as large somata, long processes, transmitter vesicles similar to those found in neurons, and positive immunolabeling for the neuronal markers neurofilament, MAP2 and SCG10. Chromaffin- derived neuron number was also significantly enhanced in the presence of NGF-producing fibroblasts. While control fibroblasts were also found to increase chromaffin cell number above that of chromaffin cells grafted alone, the control fibroblasts did not induce neuronal transdifferentiation. These results demonstrate that chromaffin cells cografted with NGF-producing fibroblasts undergo transdifferentiation in vivo and express many characteristics of mature sympathetic neurons. The consequences of this transdifferentiation on the long term survival and function of the transplanted cells in vivo remain to be clarified

Sock-Type Wearable Sensor for Estimating Lower Leg Muscle Activity Using Distal EMG Signals

Lower leg muscle activity contributes to body control; thus, monitoring lower leg muscle activity is beneficial to understand the body condition and prevent accidents such as falls. Amplitude features such as the mean absolute values of electromyography (EMG) are used widely for monitoring muscle activity. Garment-type EMG measurement systems use electrodes and they enable us to monitor muscle activity in daily life without any specific knowledge and the installation for electrode placement. However, garment-type measurement systems require a high compression area around the electrodes to prevent electrode displacement. This makes it difficult for users to wear such measurement systems. A less restraining wearable system, wherein the electrodes are placed around the ankle, is realized for target muscles widely distributed around the shank. The signals obtained from around the ankle are propagated biosignals from several muscles, and are referred to as distal EMG signals. Our objective is to develop a sock-type wearable sensor for estimating lower leg muscle activity using distal EMG signals. We propose a signal processing method based on multiple bandpass filters from the perspectives of noise separation and feature augmentation. We conducted an experiment for designing the hardware configuration, and three other experiments for evaluating the estimation accuracy and dependability of muscle activity analysis. Compared to the baseline based on a 20-500 Hz bandpass filter, the results indicated that the proposed system estimates muscle activity with higher accuracy. Experimental results suggest that lower leg muscle activity can be estimated using distal EMG signals

Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs

Soluble guanylate cyclase (sGC) stimulator riociguat is a relatively novel therapeutic agent for pulmonary hypertension (PH) in human medicine. Riociguat induces endothelium-independent pulmonary artery (PA) relaxation by directly activating the sGC-cyclic guanosine-3′,5′-monophosphate (cGMP) pathway in muscle cells. Although riociguat may be effective in the treatment of dogs with refractory PH, basic studies on its clinical application in veterinary medicine are lacking. The present study aimed to explore the effects of riociguat on the contractility of an isolated canine PA and the hemodynamics of dogs with acute PH. In an isolated endothelium-denuded canine PA, the effects of riociguat on endothelin (ET)-1-induced contraction and cGMP levels were investigated using the Magnus method and ELISA, respectively. The effect of riociguat on the hemodynamics of the thromboxane A2 analog U46619-induced PH model dog was examined by invasive catheterization. Riociguat increased cGMP levels and reduced ET-1-induced contraction of the isolated PA. Riociguat inhibited the U46619-induced elevation of PA pressure and pulmonary vascular resistance and increased cardiac output, but it had no effect on basal systemic blood pressure. These results demonstrate for the first time that riociguat can inhibit the elevation of PA pressure through PA relaxation via an endothelium-independent increase in cGMP in dogs with PH