Effects of conditioned medium obtained from human adipose-derived stem cells on skin inflammation.

Introduction: Cell therapy using adipose-derived mesenchymal stem cells (ASCs) is a promising avenue of regenerative medicine for the treatment of various diseases. It has been considered that ASCs exert their therapeutic effects through the secretion of multiple factors that are critical for tissue remodeling or the suppression of inflammation. Recently, conditioned medium (CM) from ASCs that contains a complex of secreted factors has received attention as a cost-effective alternative to cell therapy. Methods: We investigated the effects of CM obtained from ASCs (ASCs-CM) using human dermal fibroblasts (hDFs) and human epidermal keratinocytes with or without interleukin (IL)-1ß and examined mRNA levels of marker genes. We also examined alterations in cell proliferation and morphology of hDFs following treatment with ASCs-CM. We further investigated the effects of ASCs-CM treatment on prevention of skin inflammation using a mouse model. Results: In hDFs and human epidermal keratinocytes, the ASCs-CM treatment suppressed pro-inflammatory factors and enhanced regenerative and remodeling factors with or without interleukin (IL)-1ß exposure. The ASCs-CM treatment also enhanced cell proliferation of hDFs and prevented morphological changes in response to IL-1ß exposure. Furthermore, in a mouse model of skin inflammation, treatment with ASCs-CM reduced the inflammatory reactions, including redness and thickness. Conclusions: CM from ASCs may represent a potential alternative to ASC therapy for the treatment of inflammatory skin conditions.

Surgical Procedures Based on the Arthrographic Findings of the Fifth MTP Joint With Proximal Phalanx Duplication in Postaxial Polydactyly of the Foot.

Radiographic findings in several atypical cases of postaxial polydactyly of the foot do not provide sufficient information to assess the cartilaginous structures or duplicated digit connections at the MTP joint. The purpose of this study was to demonstrate the surgical procedures using arthrography for the cartilaginous structures of the MTP joint in postaxial polydactyly of the foot. We performed arthrography in 7 feet of 7 patients with postaxial polydactyly of the foot in which duplication of the proximal phalanx was observed at the fifth MTP joint on the basis of radiographic evaluation. The average age at surgery was 13.5 months and average duration of postsurgical follow-up was 36 months. Individual surgical procedures were confirmed or modified during the operation by reference to the arthrographic findings. Radiographic and arthrographic findings were assessed in relation to the findings from direct observation of the cartilaginous structures at surgery. Postoperative malalignment, functional disturbance and pain in the reconstructed toe were evaluated. The arthrographic findings provided different forms of cartilaginous structures that could be categorized in 4 types, and reflected the cartilaginous connection visualized at surgery that could not be detected on radiographs in each case. No cases revealed any deformities, functional disturbance, or pain in the reconstructed toe after surgery. The parents' evaluation in each case was "very satisfied" or "satisfied." The arthrographic findings provided additional information regarding variations in the cartilaginous structures of the fifth MTP joint and for determining individual surgical procedure for postaxial polydactyly of the foot.

Role of intra-ventricular vortex in left ventricular ejection elucidated by echo-dynamography.

PURPOSE: From the correlation between the blood flow dynamics and wall dynamics in the left ventriocle (LV) analyzed using echo-dynamography, the ejection mechanisms and role of the intra-ventricular vortex in the LV were elucidated in detail during the pre-ejection transitional period (pre-ETP), the very short period preceding LV ejection. METHODS: The study included 10 healthy volunteers. Flow structure was analyzed using echo-dynamography, and LV wall dynamics were measured using both high-frame-rate two-dimensional echocardiography and a phase difference tracking method we developed. RESULTS: A large accelerated vortex occurred at the central basal area of the LV during this period. The main flow axis velocity line of the LV showed a linearly increasing pattern. The slope of the velocity pattern reflected the deformity of the flow route induced by LV contraction during the pre-ETP. The centrifugal force of the vortex at its junction with the main outflow created a stepwise increase of about 50% of the ejection velocity. CONCLUSION: Ejection of blood from the LV was accomplished by the extruding action of the ventricular wall and the centrifugal force of the accelerated vortex during this period. During ejection, acceralated outflow was considered to create a spiral flow in the aorta with help from the spherical structure of the Valsalva sinus.

Left Ventricular Blood Flow Dynamics In Aortic Stenosis Before And After Aortic Valve Replacement.

Surgical intervention for aortic valve stenosis (AS) has been established; however its diagnosis based on echocardiographic assessment is still limited by aortic valvular velocity, aortic valvular pressure gradients, and color Doppler imaging. Echo-dynamography (EDG) is a method to determine intracardiac flow dynamics, such as two-dimensional blood flow velocity, vortex, and dynamic pressure. These flow dynamics may be influenced by left ventricular (LV) wall motion and the resistance in LV outflow caused by AS. The objective of the present study was to assess the changes and differences in LV vortices and vorticity before and after AS surgery. Five patients who underwent aortic valve replacement surgery for AS and five control patients were included. Besides routine echocardiographic measurement, EDG was applied to determine the two-dimensional blood flow vector and vorticity. The LV vortex flow in the isovolumetric contraction phase had multiple formations in preoperative cases. The clockwise vortex was found in all cases postoperatively; the vortex formation showed no significant difference between postoperative and normal control groups. EDG may serve important information on LV flow dynamics, non-invasively.

Deformability of the pulsating left ventricular wall: A new aspect elucidated by high resolution ultrasonic methods.

BACKGROUND: Although the deformability of the left ventricular (LV) wall appears to be important in maintaining effective cardiac performance, this has not been debated by anyone, probably owing to the difficulties of the investigation. OBJECTIVES: This study applies a new technology to demonstrate how the LV wall deforms so as to adjust for optimum cardiac performance. SUBJECTS AND METHODS: Ten healthy volunteers were the subjects. Using echo-dynamography, an analysis at the "microscopic" (muscle fiber) level was done by measuring the myocardial axial strain rate (aSR), while the "macroscopic" (muscle layer) level contraction-relaxation/extension (C-R/E) properties of the LV wall were analyzed using high frame rate 2D echocardiography. RESULTS: Deformability of the LV was classified into three types depending on the non-uniformity of both the C-R/E properties and the aSR distribution. "Basic" deformation (macroscopic): The apical posterior wall (PW) thickness change was concentric and monophasic, whereas it was eccentric and biphasic in the basal part. This deformation was large in the PW, but small in the interventricular septum (IVS). The elongation of the mitral ring diameter and the downward movement of its posterior part were shown to be concomitant with the anterior extrusion of the PW. "Combined" deformation (macroscopic and microscopic): This was observed when the basic deformation was coupled with the spatial aSR distribution. Three patterns were observed: (a) peristaltic; (b) bellows-like; and (c) pouch-like. "Integrated" deformation: This was the time serial aSR distribution coupled with the combined deformation, illustrating the rotary pump-like function. The deformability of the LV assigned to the apical part the control of pressure and to the basal part, flow volume. The IVS and the PW exhibited independent behavior. CONCLUSIONS: The non-uniformity of both the aSR distribution and the macroscopic C-R/E property were the basic determinants of LV deformation. The apical and basal deformability was shared in LV mechanical function.

Non-uniform distribution of the contraction/extension (C-E) in the left ventricular myocardium related to the myocardial function.

OBJECTIVE: We attempted to disclose the microscopic characteristics of the non-uniform distribution of the contraction and extension (C-E) of the left ventricular (LV) myocardium using a new methodology (echo-dynamography). METHODS: The distributions of the "axial strain rate" (aSR) and the intra-mural velocity in the local areas of the free wall including the posterior wall (PW) and interventricular septum (IVS) were microscopically obtained using echo-dynamography with a high accuracy of 821 µm in the spatial resolution. The results were shown by the color M-mode echocardiogram or curvilinear graph. Subjects were 10 presumably normal volunteers. RESULTS: (1) Both the C-E in the pulsating LV wall showed non-uniformity spatially and time-sequentially. (2) The C-E property was better evaluated by the aSR distribution method rather than the intra-mural velocity distribution method. (3) Two types of non-uniformity of the aSR distribution were observed: i.e. (i) the difference of its (+)SR (contraction: C) or (−)SR (extension: E) was solely the "magnitude"; (ii) the coexistence of both the (+) SR and (−)SR at the same time. (4) The aSR distribution during systole was either "spotted," or "multi-layered," or "toned" distribution, whereas "stratified," "toned," or "alternating" distributions were observed during diastole. (5) The aSR distribution in the longitudinal section plane was varied in the individual areas of the wall even during the same timing. (6) To the mechanical function of the LV, there was a different behavior between the IVS and PW. . CONCLUSIONS: The aSR and its distribution were the major determinants of the C-E property of the LV myocardium. Spatial as well as time-sequential uniformity of either contraction or extension did not exist. The myocardial function changed depending on the assemblage of the aSR distribution, and by the synergistic effect of (+)SR and (-)SR, the non-uniformity itself potentially served to hold the smooth LV mechanical function.

New concept of the contraction-extension property of the left ventricular myocardium.

OBJECTIVES: Using newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction-extension (C-E) property, which has an important relationship to LV function. METHODS: Strain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821µm in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30-50 years). RESULTS: The time course of the SR distribution disclosed the characteristic C-E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function. The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions. CONCLUSION: The newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C-E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV.

Validation of Echo-Dynamography by virtual color doppler echocardiography generated from phase contrast magnetic resonance angiography datasets.

Echo-Dynamography (EDG) is a smart visualization technique in echocardiography in which two-dimensional distribution of blood flow vectors in cardiovascular system is deduced by applying fluid dynamics theories into Doppler velocity datasets. Previous validation studies such as numerical simulation of free jet model or model circulation were too simple to reproduce unstable and asymmetrical flow in left ventricle. In the present study, virtual color Doppler echocardiography is generated from PC-MRA (phase contrast magnetic resonance angiography) datasets. EDG is applied on virtual Doppler data and the blood flow vectors are compared with those of the original PC-MRA data. EDG-derived blood flow vectors showed similar pattern as the original PC-MRA data when blood flow velocity had high value. The errors were caused from underestimating the magnitude of vortex flow component in the flow field near the boundary of the left ventricular wall. The results also indicated that apical long axis view had small error compared with parasternal long axis view. Despite EDG method causes small errors, it provides important information on blood flow dynamics in most parts.

Evaluation of vortex flow in left ventricle by echo-dynamography and phase contrast magnetic resonance angiography.

Echo-dynamography (EDG) is a method for visualizing left ventricular (LV) blood flow based on cardiac Doppler measurement in which blood flow component perpendicular to the ultrasonic beam is deduced by applying fluid dynamics theories to two-dimensional (2D) distribution of blood flow component along the ultrasonic beam. EDG has been validated by numerical simulation and particle image velocimetry of model circulation. However, these validations were too simple to reproduce unstable and asymmetrical flow in a beating heart. In the present study, EDG is compared with three-directional (3D) blood flow distribution on the same plane obtained with phase contrast magnetic resonance angiography (PCMRA) for clinical validation. Moreover, the location and vorticity of the vortex flow in LV are measured quantitatively and the relation to echocardiographic parameters of systolic and diastolic functions is discussed. 3D components of blood flow on a plane were obtained with triple scans of the same plane with ECG trigger and breath holding; 1) phase encode (x-axis), 2) read out (y-axis) and 3) slice selection (z-axis). After the acquisition of MRA dataset, color Doppler dataset of the same plane was acquired and 2D velocity distribution was obtained with EDG in MATLAB programs. EDG and PCMRA showed similar velocity vector distribution and formation of LV vortex flow. The vortex at mid diastolic phase was strongly affected by early diastolic filling while the vortex at isometric contraction was affected by atrial filling. EDG gained a new insight on systolic-diastolic coupling from the view point of LV blood flow such as LV vortex formation.