The nature of the spreading effects occasioned by hyaluronidase in subcutaneous connective tissue.
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OBJECTIVE: To determine whether changes in subcutaneous adipose tissue plasminogen activator inhibitor-1 (PAI-1) expression influence plasma PAI-1 level during weight loss in obese humans. DESIGN: Study of the variations of PAI-1 levels both in plasma and in subcutaneous abdominal adipose tissue in 15 volunteer non-diabetic obese subjects, body mass index (BMI) 40.4.+/-1.9 kg/m2, aged 48+/-3 y, before and after a 3 week very low calorie diet (VLCD) programme (3.9+/-0.1 MJ/day). MEASUREMENTS: Plasma and adipose tissue PAI-1 protein levels were measured by enzyme-linked immunosorbent assay and PAI-1 mRNA levels were quantified by quantitative RT-competitive PCR. RESULTS: VLCD induced weight loss (5.8+/-0.8 kg) and decreased plasma PAI-1 concentration (-26% (P<0. 01)). Surprisingly, PAI-1 mRNA and protein abundance in subcutaneous adipose tissue increased by 87% (P<0.05) and by 44% (P<0.01), respectively. CONCLUSION: These data indicate thus that changes in subcutaneous adipose tissue PAI-1 expression are not involved in the decrease of plasma PAI-1 levels during VLCD in obese subjects. International Journal of Obesity (2000)24, 70-74
UNLABELLED: The risk of wound infections is inversely related to subcutaneous tissue oxygen tension. General anesthesia increases local blood flow by direct vasodilation and central inhibition of thermoregulatory vasoconstriction. Epidural anesthesia can increase perfusion in blocked regions by decreasing sympathetic tone. We therefore tested the hypothesis that epidural anesthesia increases tissue oxygen tension in awake and anesthetized subjects. Fifteen healthy volunteers underwent epidural, general, and combined epidural and general anesthesia. Subcutaneous tissue oxygen tension was measured using tonometers in the lateral upper arm and the lateral thigh. Epidural anesthesia to a T10 level was maintained with 0.75% mepivacaine. General anesthesia was maintained with 1.5% sevoflurane in 30% oxygen; 30% inspired oxygen was given via a sealed facemask during baseline and epidural anesthesia. Baseline subcutaneous tissue oxygen tensions for arm and thigh were 57 +/- 11 and 54 +/- 8 mm Hg, respectively. Epidural anesthesia significantly increased tissue oxygenation in the thigh by 9 mm Hg, to 63 +/- 7 mm Hg, without increasing arm oxygenation. Tissue oxygenation in the arm and thigh were similar during general anesthesia alone, 58 +/- 11 and 63 +/- 12 mm Hg. Arm oxygenation remained unchanged with the addition of epidural anesthesia; however, thigh subcutaneous oxygen partial pressure increased 8 +/- 3 mm Hg, from 63 +/- 12 to 71 +/- 9 mm Hg. Although epidural anesthesia increased tissue oxygenation significantly with and without general anesthesia, the magnitude of this increase might be of marginal clinical importance in regard to surgical wound infections. IMPLICATIONS: Epidural anesthesia significantly increased subcutaneous tissue oxygenation in the thigh both with and without general anesthesia. Although each increase was statistically significant, previous work suggests that the magnitude of these changes is unlikely to markedly reduce the risk of surgical wound infection.
Men with noninsulin-dependent diabetes mellitus (type 2 DM) provide a different subcutaneous body fat distribution and a concentration of fatness on the upper trunk compared with healthy subjects. However, subcutaneous fat distribution is always measured in an inaccurate and/or very simplified way (e.g., by caliper), and to date, there exists no study reporting on the exact and complete subcutaneous adipose tissue distribution of type 2 DM men. A new optical device, the LIPOMETER, enables the nonivasive, quick, and safe determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Tops of 21 men with clinically proven type 2 DM (mean age of 57.5 +/- 6.7 years) and 111 healthy controls of similar age (mean age 59.0 +/- 5.4 years) were measured. In this paper, we describe the precise SAT-Top differences of these two groups and we present the multidimensional SAT-Top information condensed in a two-dimensional factor value plot. In type 2 DM men, especially in the upper trunk, SAT-Top is significantly increased (up to +50.7% at the neck) compared with their healthy controls. One hundred eleven of the 132 individuals (84.1%) are correctly classified (healthy or type 2 DM) by their subcutaneous fat pattern by stepwise discriminant analysis.
The LIPOMETER is an optical device for measuring the thickness of a subcutaneous adipose tissue layer. It illuminates the interesting layer, measures the backscattered light signals and from these, it computes absolute values of subcutaneous adipose tissue layer thickness (in mm). Previously, these light pattern values were fitted by nonlinear regression analysis to absolute values provided by computed tomography. Nonlinear regression analysis might provide slight limitations for our problem: a selected curve type cannot be changed afterwards during the application of the measurement device. Artificial neural networks yield a more flexible approach to this fitting problem and might be able to refine the fitting results. In the present paper we compare nonlinear regression analysis with the behaviour of different architectures of multilayer feed forward neural networks trained by error back propagation. Specifically, we are interested whether neural networks are able to yield a better fit of the LIPOMETER light patterns to absolute subcutaneous adipose tissue layer thicknesses than the nonlinear regression techniques. Different architectures of these networks are able to surpass the best result of regression analysis in training and test, providing higher correlation coefficients, regression lines with absolute values obtained from computed tomography closer to the line of identity, decreased sums of absolute and squared deviations, and higher measurement agreement.
Steady state expression of lipoprotein lipase was compared in abdominal and gluteal subcutaneous adipose tissue of nonobese men and women. In both regions enzyme activity and lipoprotein lipase mRNA levels were significantly higher in women than in men. In men the enzyme activity was higher in abdominal than in gluteal adipose tissue (P less than 0.01) whereas the opposite was observed in women (P less than 0.05). In both sexes, however, lipoprotein lipase mRNA levels were threefold higher in the abdominal as compared to the gluteal site, whether they were determined in isolated fat cells or in fat segments (P less than 0.01). This regional difference persisted when the mRNA values were expressed as a function of the mRNA concentration for beta-actin. There was a correlation between the two adipose tissue regions as regards the values for enzyme activity and mRNA level (r = 0.6-0.8). Northern blot analysis revealed two mRNA species of 3.5 and 3.7 kilobases, respectively. It is concluded that there are regional variations in the steady state expression of lipoprotein lipase in human subcutaneous adipose tissue. This involves site variations in gene expression as well as posttranslational modification of lipoprotein lipase enzyme activity and may contribute to the characteristic variations in adipose tissue mass and distribution between men and women.
Magnetic resonance imaging (MRI) was used in the diagnosis of various conditions giving rise to leg oedema, with special attention to the oedema after femoro-distal vascular reconstruction for obliterative atherosclerosis (n = 14). Patients with deep venous thrombosis (n = 6), chronic lymphoedema (n = 6) and closed muscular compartment syndrome (n = 2) were also investigated. Leg volume increase was measured according to the formula of a truncated cone. Interstitial fluid hydrostatic pressure (Pif) was recorded with the wick-in-needle technique. Spin echo series with 10 mm transverse slices were obtained with MRI. Following vascular reconstructions, leg volume increased 26% on the operated side. In the operated leg, no gradient in Pif was found between the posterior muscular compartment and the subcutaneous tissue. However, there was a significantly higher Pif in the subcutaneous tissue compared to the anterior muscular compartment (p less than 0.05). In the operated group, MRI revealed oedema around the entire circumference of the leg, mainly restricted to the subcutaneous tissue. In contrast, oedema of the leg muscles, particularly in the posterior compartments, was typical for patients having deep venous thrombosis. The group with chronic lymphoedema showed circumferential subcutaneous oedema alone or in combination with a fibrotic honeycomb pattern. Oedema of the affected muscular compartment was easily observed in patients who had a closed compartment syndrome. In conclusion, the use of MRI is promising in the investigation of conditions giving rise to leg oedema. It is likely that the formation of post-reconstructive oedema is taking place in the subcutaneous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Between 1990 and 1994 a study was carried out of 32 patients who had degloving injuries of the limbs. There were three types of injuries: type I, nine patients with severely damaged skin and subcutaneous tissue; type II, 13 patients whose skin and subcutaneous tissue were moderately damaged, but subcutaneous veins were still identifiable; and type III, 10 patients whose skin and subcutaneous tissue were moderately damaged and venous back flow was observed. The patients in type I were treated by extensive debridement and the flaps were used for free full and split thickness skin grafting. In type II, arterialization of the venous system of the flaps was performed and successful perfusion was observed in nine patients. In type III, venous anastomoses were performed and all had good results. Revascularization of the flaps in types II and III degloving injuries of the limbs gave good results. The raw surface which needed skin grafting was minimized and the course of treatment and morbidity were decreased.
OBJECTIVE: To investigate the enhancement of the transverse rectus abdominis musculocutaneous (TRAM) flap survival in local ischemic area by recombinant adenovirus mediated vascular endothelial growth factor 165 gene (Ad-VEGF165). METHODS: The vascular pedicle TRAM flaps were made in the right abdomen of 30 SD rats and they were randomly divided into 5 groups. The Ad-VEGF165 was injected into the subcutaneous tissue of epigastria(group 1), the subcutaneous tissue of epigastria and rectus abdominis muscle (group 2), and the rectus abdominis muscle (group 3); Adenovirus mediated green fluorescent protein (Ad-GFP) and DMEM were injected into the subcutaneous tissue of epigastria and rectus abdominis muscle as auto-control (group 4) and blank control (group 5), respectively. The survival areas of TRAM flap was measured after 7 days of operation. The microvascular density (MVD) and the integral optical density (IOD) were tested with anti-rat CD34 and with VEGF immunohistochemistry and in situ hybridization histochemistry (ISHH), respectively. RESULTS: The survival areas of TRAM flap in groups 1, 2 and 3 (14.19 +/- 2.77, 15.18 +/- 2.18 and 8.30 +/- 1.28 cm2) were higher than those in groups 4 and 5(4.12 +/- 1.86 and 3.60 +/- 1.95 cm2), being significant differences (P < 0.05). The CD34 MVD of the TRAM flap in groups 1, 2 and 3 was higher than that in groups 4 and 5; the positive expression for VEGF and ISHH were shown in groups 1, 2 and 3 and there was significant difference when compared with groups 4 and 5 (P < 0.05). CONCLUSION: Treatment by recombinant Ad-VEGF165 gene is an effective option for enhancement of the TRAM flap survival in the local ischemic area.
Subcutaneous adipose tissue development was studied in Yorkshire (lean) and Ossabaw (obese) pigs. Three pigs of each breed were slaughtered at 1 to 2 (group 1), 14 to 20 (group 2), 56 to 70 (group 3) and 180 (group 4) days of age. Formalin and(or) Bouin's fixed paraffin sections were analyzed by various staining procedures. Fresh frozen sections were tested for lipid, esterase activity and glycogen. Fat cell size increased with age in the Ossabaw pigs. Fat cell size was similar for group 1 and 2 Yorkshire pigs. Transitional cells between spindle-shaped. basophilic cells and multilocular adipocytes were present in group 1 Yorkshire pigs. The transition was characterized by a loss of cytoplasmic basophilia and a change in nuclei size and shape. The nuclei of presumptive preadipocytes and small multilocular adipocytes contained one to three prominent nucleoli surrounded by an evenly dispersed, pale staining chromatin material. Cells with identical nuclear morphologies and little apparent cytoplasm were observed in adipose tissue of Ossabaw and Yorkshire pigs of all age groups. The frequency of multilocular adipocytes (percentage of the total adipocytes that were multilocular) decreased during the first 2 weeks of life in both breeds. In age group 3, multilocular adipocytes were more numerous in Ossabaw pigs than in Yorkshire pigs (20 vs less than 1%). Capillary histological and histochemical changes were associated with adipocyte hypertrophy in the younger pigs of both breeds.
PURPOSE: Our goal was to describe the MR findings of volume overload (VO) in the lower extremities. METHOD: Fifteen individuals were studied, including eight healthy controls and seven patients with VO (four cardiac, three renal). MR evaluation included various SE techniques. Edema detection, localization, and symmetry were assessed subjectively. Relaxation time estimates were also made of the subcutaneous tissue, marrow, and three muscles. RESULTS: Subcutaneous tissue was markedly edematous in seven of seven patients and asymmetric in four of seven, whereas marrow was normal in all patients. Muscle edema was mild and asymmetric in six and two of seven patients, respectively. Perifascial fluid collections were identified in six of seven patients. CONCLUSION: Subcutaneous tissue edema is the dominant feature of VO in the lower extremities. Perifascial fluid is common but does not necessarily distribute symmetrically. Muscle edema is relatively mild. These findings should aid in identifying VO as the potential cause of swelling in patients with swollen legs.
The basis of the chronic lipolytic effect of somatotropin on adipose tissue was investigated in sheep. Lipolytic rate was assessed in subcutaneous adipose tissue both in vivo, by microdialysis, and in vitro. Somatotropin treatment resulted in a small increase in basal (unstimulated) lipolysis and also in the maximum lipolytic rate observed in the presence of catecholamines both in vivo and in vitro. There was a small increase in the number of beta-adrenergic receptors but no change in the amount of the two isoforms of the stimulatory GTP-binding protein, Gs. Treatment with somatotropin decreased the response to antilipolytic agents such as the adenosine analog N6-phenylisopropyladenosine and prostaglandin E1. There was, however, no change in the number of adenosine receptors or amounts of the inhibitory GTP-binding proteins (Gi-1 plus Gi-2). Somatotropin also decreased prostaglandin E2 production by subcutaneous adipose tissue in vivo. Somatotropin treatment thus alters lipolytic regulation in sheep and this is characterized by changes in a number of proteins involved in this process.
The present study addressed the ability of moxifloxacin to penetrate into healthy and inflamed subcutaneous adipose tissues in 12 patients with soft tissue infections (STIs). Penetration of moxifloxacin into the interstitial space fluid of healthy and inflamed subcutaneous adipose tissues was measured by use of in vivo microdialysis following administration of a single intravenous dosage of 400 mg in six diabetic and six nondiabetic patients with STIs. For the entire study population, the mean time-concentration profile of free moxifloxacin in plasma was identical to the time-concentration profile of free moxifloxacin in tissue (P was not significant). For healthy and inflamed adipose tissues for the diabetic subgroup, the mean moxifloxacin areas under the concentration-time curves (AUCs) from 0 to 8 h (AUC(0-8)s) were 8.1 +/- 7.1 and 3.7 +/- 1.9 mg.h/liter, respectively (P was not significant). The ratios of the mean AUC(0-8) for inflamed tissue/AUC(0-8) for free moxifloxacin in plasma were 0.5 +/- 0.4 for diabetic patients and 1.2 +/- 0.8 for nondiabetic patients (P was not significant). The ratios of the AUCs from 0 to 24 h for free moxifloxacin in plasma/MIC at which 90% of isolates are inhibited were >58 and 121 h for Streptococcus species and methicillin-sensitive Staphylococcus aureus, respectively. Concentrations of moxifloxacin effective against clinically relevant bacterial strains are reached in plasma and in inflamed and healthy adipose tissues. Thus, the pharmacokinetics of moxifloxacin in tissue and plasma support its use for the treatment of STIs in diabetic and nondiabetic patients.
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OBJECTIVE: The objective was to develop a microdialysis set-up to measure the concentration-time course of scopolamine in the interstitium of subcutaneous adipose tissue. MATERIALS AND METHODS: Six healthy male volunteers were eligible for data analysis. Subjects received 0.5 mg scopolamine as a 15-minute intravenous infusion. Microdialysis samples from interstitial space fluid of subcutaneous adipose tissue and blood samples were taken at predefined intervals over a period of 360 minutes. Scopolamine concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). RESULTS: High inter-individual variability was observed in all pharmacokinetic parameters. The mean peak serum concentration (C(max)) of 6.5 +/- 3.9 ng/ml (data in mean +/- SD) was attained after 15 +/- 3 minutes (t(max)), whereas in dialysate, a mean peak concentration of 2.7 +/- 1.7 ng/ml was measured after 27 +/- 8 minutes. The ratio of the area under the concentration versus time curve from 0-360 min for interstitium (AUC(interstitium 0-360 min0) to the AUC for serum (AUC(serum 0-360 min)) was 0.96 +/- 0.7. The elimination half-life of scopolamine was 121 +/- 85 minutes in serum and 166 +/- 117 minutes in dialysate. Values for total clearance and volume of distribution in serum were 99.1 +/- 35.0 1/h and 188 +/- 76 1, respectively. CONCLUSIONS: In the present study, we were able to define a microdialysis set-up, which allows for the measurement of scopolamine concentrations in target tissues. In addition, we demonstrated that the concentrations of scopolamine in subcutaneous adipose tissue resemble closely the concentration-time course in serum of healthy volunteers.
BACKGROUND: Little is still known concerning subcutaneous adipose tissue and cellulite, and controversial questions are still under discussion. AIMS: Magnetic resonance imaging and spectroscopy were used to address two unresolved questions relating to the anatomy and physiology of subcutaneous adipose tissue. METHODS: Using high spatial resolution magnetic resonance imaging we characterized the topography of the dermo- hypodermal junction, and the three-dimensional architecture of the subcutaneous fibrous septae. Using proton spectroscopy, we measured water and lipid fractions within a fat lobule, and T1 and T2 values of the detected compounds. All these data were analysed according to sex and presence of cellulite. RESULTS: MR imaging quantified deeper indentations of adipose tissue into the dermis, and evidenced for the first time a great increase in the thickness of the inner fat layer in women with cellulite. Moreover, 3D reconstruction of the fibrous septae network showed a higher percentage of septae in a direction perpendicular to the skin surface in women with cellulite; but our study also depicted the tortuous aspect of this network. MR proton spectroscopy could not show any differences related to sex or presence of cellulite concerning T1 and T2 relaxation times of the detected compounds within a fat lobule, neither the unsaturated lipid fraction, the saturated lipid fraction, nor the water fraction. CONCLUSIONS: Magnetic resonance imaging showed that the 3D architecture of fibrous septae couldn't be modelled simply as perpendicular planes for women and tilted planes at 45 degrees for men. MR spectroscopy did not confirm the hypothesis of increased water content in the adipose tissue of women with cellulite as suggested by others, except if such water would be located in the connective septae.
The effect of head-up tilt upon subcutaneous and skeletal muscle blood flow in the crus was studied before and during epidural blockade in 10 subjects. Relative changes in blood flow were estimated by the local 133Xe washout technique. In subcutaneous tissue head-up tilt induced a decrease in blood flow of about 40% and there was no difference in the vascular response to head-up tilt before and during epidural blockade. In skeletal muscle tissue essentially the same was found as head-up tilt decreased blood flow by about 26% the response being uninfluenced by epidural blockade. In 3 patients local nervous blockade was induced by Lidocaine in 133Xe labelled subcutaneous tissue on one side. During epidural blockade and tilt blood flow increased by 12% whereas blood flow decreased by 30% on the control side. Thus epidural blockade had no influence on the vasoconstrictor response in subcutaneous tissue and skeletal muscle to head-up tilt whereas local blockade was able to prevent the response. Local mechanisms including the local veno-arteriolar reflex appear to play an important role for the observed maintenance of arterial blood pressure in the tilted position during central sympathetic blockade.