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Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis.

OBJECTIVES: Ertapenem is FDA approved for the treatment of skin and skin-structure infections (SSSI), but its in vivo penetration into the interstitial space of soft tissues is unknown. The present microdialysis study was conducted to measure free, protein-unbound ertapenem concentrations in muscle and subcutaneous tissue. VOLUNTEERS AND METHODS: In a single-centre, prospective, open-label study six healthy volunteers (three females, 22-37 years) were treated with 1 g ertapenem given as a single intravenous dose. Microdialysis and plasma samples were collected before and at different time points up to 12 h after medication. Drug concentrations were determined by a validated LC-MS-MS method. RESULTS: No serious or microdialysis-associated adverse events were observed. Ertapenem concentrations in plasma reached a maximum (C(max)) of 103.3 +/- 26.3 mg/L, a terminal elimination half-life (t(1/2)) of 3.8 +/- 0.6 h and an AUC(0-infinity) of 359.7 +/- 66.5 mg.h/L. Mean peak concentrations of free, protein-unbound ertapenem in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were much lower (C(max) = 6.7 +/- 4.1 and 4.0 +/- 1.6 mg/L, respectively). This degree of tissue distribution is consistent with high concentration-dependent plasma protein binding of ertapenem (84-96%). AUC(0-infinity) values for both muscle and adipose tissue were lower as well (39.7 +/- 24.8 and 18.6 +/- 4.6 mg.h/L). However, unbound interstitial fluid concentrations exceeded MIC(90) values for the important SSSI pathogens for 7 (subcutis) and 10 h (muscle) after dosing. CONCLUSIONS: These results support the previously observed clinical efficacy of ertapenem in the treatment of SSSI.

Adult↗

Open-flow microperfusion of subcutaneous adipose tissue for on-line continuous ex vivo measurement of glucose concentration.

OBJECTIVE: To evaluate a novel technique for on-line continuous glucose measurement in subcutaneous adipose tissue, and to investigate its accuracy for detection of hypoglycemia. RESEARCH DESIGN AND METHODS: The method combined an open-flow microperfusion of subcutaneous adipose tissue using a double lumen catheter and an extracorporeal sensor cell. An isotonic ion-free solution was perfused through the inner lumen of the catheter, equilibrated with the subcutaneous tissue fluid, and sampled through the outer lumen. The recovery was continuously monitored as the ratio between the measured sampled fluid conductivity and the subcutaneous tissue fluid conductivity (assumed to have a constant value of 1.28 S/m at 25 degrees C). Glucose concentration was calculated on-line from the measured glucose in the sampled fluid and the measured recovery in healthy volunteers during hyperglycemic glucose loads (n = 8), hypoglycemic hyperinsulinemic clamp (n = 6), and a 24-h monitoring period (n = 7). RESULTS: Subcutaneous glucose concentrations in the fasting state were 94% of the plasma glucose concentrations in arterialized venous samples. According to the error grid analysis, 96.9% of the on-line measured subcutaneous glucose concentrations during hyperglycemia and 96.3% during hypoglycemia were in accurate or acceptable zones. The mean differences between the measured subcutaneous glucose and the actual plasma glucose concentration were -0.06-3.3 mmol/l (hyperglycemia), and -0.6-1.1 mmol/l (hypoglycemia). CONCLUSIONS: By combining open-flow microperfusion, glucose sensor, and conductivity measurement, glucose concentration in the subcutaneous adipose tissue can be monitored on-line, extracorporeally, and continuously without any in vivo calibration, and gives accurate measurements during hyper- and hypoglycemia.

Adipose Tissue↗

The double isotope technique for in vivo determination of the tissue-to-blood partition coefficient for xenon in human subcutaneous adipose tissue--an evaluation.

Local subcutaneous 133xenon (133Xe) elimination was registered in the human forefoot in 34 patients. The tissue/blood partition coefficient for Xe was estimated individually by simultaneous registration of 133Xe and [131I]antipyrine ([131I]AP) washout from the same local depot. When measured in this way, an average partition coefficient for Xe was found to be 4.3 +/- 1.23 ml g-1. This value is significantly lower than the partition coefficient found in a previous in vitro study in which a Xe partition coefficient of 7.5 +/- 1.57 ml g-1 was found. Thus, if the local blood flow is calculated using the partition coefficient found by the double isotope technique, significantly lower values are obtained than if the in vitro determined coefficient is used. This difference is explained mainly by local dilution when injecting xenon subcutaneously. In short-term studies, utilization of the double isotope technique reduces the coefficient of variation on average flow determinations, thus an improvement in accuracy of local blood flow estimation can be obtained compared to the method in which an average partition coefficient is used. For long-term studies a partition coefficient of 7.5 ml g-1 seems valid.

Adipose Tissue↗

Myringoplasty using a subcutaneous soft tissue graft.

A retrospective study was performed on patients who underwent myringoplasty using an autologous subcutaneous soft tissue graft over a 5-year period. Details including age, site and size of perforation, grade of surgeon, surgical approach, postoperative dressings, overnight stay, complications and outcome were recorded and analysed. Fifty-two patients underwent myringoplasty using a subcutaneous soft tissue graft. Their ages ranged from 4 to 78 years (median = 36 years). The mean follow-up period was 19 months. Successful closure to give an intact tympanic membrane was obtained in 82.7% of patients. Thresholds improved on pure tone audiometry in 57.1% and deteriorated in only one patient. There was no case of dead ear as a result of surgery. Subcutaneous tissue graft has comparable outcomes with temporalis fascia graft with additional advantages of a smaller incision, minimum dissection and a lower risk of bleeding.

Adolescent↗

Comparison of two methods to assess the tissue/blood partition coefficient for xenon in subcutaneous adipose tissue in man.

A new method to calculate the tissue/blood partition coefficient (lambda) for xenon in studies on the subcutaneous adipose tissue blood flow was compared with a previously reported method based on local skinfold thickness (lambda LST). The former method included needle biopsies from the abdominal and femoral subcutaneous adipose tissue, and the mean fat cell diameter was measured (lambda ECT). The extracellular tissue fraction in subcutaneous tissue was then estimated from a diagram. The tissue lipid content was approximated to equal the relative intracellular volume and Ostwald's solubility coefficients for 133Xe, based on the distribution of xenon in lipid, albumin and 0.9% saline were applied. Estimated lambda-values based on needle biopsies from the abdominal site were: 8.6 +/- 0.1 versus 9.9 +/- 0.4 ml g-1 (mean +/- SE) (P < 0.05) and from the femoral site: 9.1 +/- 0.1 versus 9.6 +/- 0.2 in lean (n = 10) and obese subjects (n = 10), respectively. The corresponding lambda-values obtained from skinfold measurements were: 6.2 +/- 0.5 versus 11.0 +/- 0.4 (P < 0.001) and 6.9 +/- 0.3 versus 11.4 +/- 0.4 (P < 0.001) in lean and obese subjects, respectively. Pooled lambda LST-values correlated positively with estimated adipose tissue blood flow (ATBF) (r: 0.34, P < 0.05, n = 40) whereas no such correlation was found for lambda ECT-values. In conclusion, a new method is presented which may allow an accurate determination of, and which may lead to reliable data on, subcutaneous ATBF in both lean and obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Body compartment and subcutaneous adipose tissue distribution--risk factor patterns in obese subjects.

The purpose of this study was to investigate whether upper body obesity and/or visceral obesity are related to cardiovascular risk factors among severely obese subjects, phenomena that have previously been reported in more heterogeneous body weight distributions. 2450 severely obese men and women aged 37 to 59 years, with a body mass index of 39 +/- 4.5 kg/m2 (mean +/- SD) were examined cross-sectionally. Eight cardiovascular risk factors were studied in relation to the following body composition indicators: four trunk and three limb circumferences, along with weight, height and sagittal trunk diameter. From the latter three measurements lean body mass (LBM, i.e., the non-adipose tissue mass) and the masses of subcutaneous and visceral adipose tissue were estimated by using sex-specific prediction equations previously calibrated by computed tomography. Two risk factor patterns could be distinguished: 1. One body compartment-risk factor pattern in which the subcutaneous adipose tissue (AT) mass and, in particular, the visceral AT mass were positively related to most risk factors while the lean body mass was negatively related to some risk factors. 2. One subcutaneous adipose tissue distribution- risk factor pattern in which the neck circumference was positively and the thigh circumference negatively related to several risk factors. It is concluded that lean body mass (LBM), visceral and subcutaneous adipose tissue masses as well as neck and thigh circumferences, used as indices of subcutaneous adipose tissue distribution, are independently related to cardiovascular risk factors in severely obese men and women.

Adipose Tissue↗

Total and segmental subcutaneous adipose tissue volume measured by ultrasound.

Total and segmental subcutaneous adipose tissue volumes (SATV) were estimated and compared in 13 healthy young women with a mean age of 21.4 yr. Total and segmental (head and neck, forearm, upper arm, trunk, thigh, and lower leg) SATV were estimated from subcutaneous adipose tissue layer thickness and the body surface area; the former by B-mode ultrasound and the latter by direct measurement. Consecutive magnetic resonance images (MRI) were obtained from head to toe (10 mm thickness), from which adipose tissue areas as well as total and regional SATV were determined. SATV of the upper arm and thigh estimated by ultrasound was significantly lower compared to that of MRI-measured SATV; however, there were no significant differences found in the other four segments. As a result, total estimated SATV obtained was on average 5.5% lower with ultrasound than with MRI-measured total SATV; however, there were no statistically significant differences between the two values. Significant strong correlations were observed between MRI-measured total and segmental SATV, and SATV estimated by ultrasound (r = 0.79-0.95) for all segments except head and neck. These results show the effectiveness of the ultrasound method for estimating SATV; however, the quantitative analysis tissue volumes would require correction.

Adipose Tissue↗

Regional differences of PCB and PCQ concentrations in the blood and subcutaneous fat tissue of residents of Nagasaki.

In this study, we analyzed PCB and PCQ concentrations in the subcutaneous fat tissue of residents of Nagasaki Prefecture, and compared these levels between the blood and subcutaneous fat tissue of people living in various parts of the prefecture. Seventy-one inhabitants were examined. In the blood, PCB concentrations in Tamanoura and Fukue were significantly higher than those in Nagasaki City. The CB% ratio in Tamanoura was significantly higher than that in Nagasaki and Isahaya. PCQ concentrations were below detection level except in one case. PCB concentrations in fishery areas showed higher levels than urban or agricultural areas. PCB concentration in the subcutaneous fat tissue was 100 times higher than that in the blood. PCQs could be detected in almost all of the subcutaneous tissues, but there was no regional difference in the PCQ concentration.

Adipose Tissue↗

[Polychlorinated dibenzo-p-dioxins in the subcutaneous adipose tissue of yusho patients].

The abdominal subcutaneous adipose tissues, the mother milk, and the blood samples of yusho patients were collected between 1986 and 1988, and analyzed for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) by high resolution gas chromatography/high resolution mass spectrometry in selected ion monitoring mode. PCDDs and PCDFs were found all of the samples examined.: 1,2,3,7,8-Pentachlorodibenzo-p-dioxin (pentaCDD), 1,2,3,6,7,8-hexaCDD, octaCDD, 2,3,4,7,8-pentachlorodibenzofuran (pentaCDF), and 1,2,3,4,7,8- and 1,2,3,6,7,8-hexaCDF were detected. The levels of PCDDs was several times lower than those of PCDFs in all samples. The concentrations of PCDDs and PCDFs found in the fat of the mother milk were similar to those of the adipose tissues. On the other hand, the levels of PCDDs and PCDFs in the blood samples were several hundred times less than those of the adipose tissues.

Adipose Tissue↗

Ultrasound measurement in defining the regional distribution of subcutaneous fat tissue.

The aim of this research is to determine the significance of ultrasound diagnostics in measuring the thickness of subcutaneous fat tissue as well as to point out sex and age differences in regional distribution of subcutaneous fat tissue. The research included 37 men and 33 women with different body mass indexes. Ultrasound measuring of subcutaneous fat tissue was conducted on 16 measuring points. The thickness of subcutaneous fat tissue measured by ultrasound and estimated proportion of fat tissue obtained by comparative methods coincided mostly on the back side of the upper arm, lower abdominal region in interspinal line and the front side of the forearm. Analysis of the subcutaneous fat tissue distribution indicates that there is more equal accumulation of fat tissue in women than in men. BMI limit value for obesity is not the same for men and women because the point at which abdominal region becomes the main storage of subcutaneous fat in body depends on sex. That BMI value represents the physiological beginning of obesity since it marks the change in distribution pattern of subcutaneous fat tissue in different body regions.

Adipose Tissue↗

[Subcutaneous fatty tissue].

Up until now, subcutaneous fat has been considered to be a distinct entity. Recent studies have demonstrated chemical and metabolic differences between 2 kinds of fat, mobile fat and fixed fat. The main aim of this article is to show that these differences also have histological, embryological and anatomical implications. Their surgical consequences are important for plastic surgery and lipoplasty procedures.

Adipose Tissue↗

Softness and fatty acid composition of subcutaneous adipose tissue, and methylmalonic acid concentrations in the plasma of intensively reared lambs.

The aim of the present work was to study the relationships between lamb growth performance, soft adipose tissue and fatty acid composition of subcutaneous adipose tissue of intensively reared lambs, and to determine if the occurrence of soft fat, and of odd numbered (Odd FA) and methyl-branched-chain fatty acids in subcutaneous adipose tissue was related to plasma concentrations of methylmalonic acid (MMA). For this purpose, a sensitive gas chromatography assay to measure low plasma concentrations of MMA was developed and validated. In all, 49 male lambs were reared from 23.6 to 41.0kg. They were fed ad libitum with hay and pelleted concentrates containing either cereals (80%, C) or sugar beet pulp (70%, BP). Plasma concentrations of MMA were measured 12 days before slaughter. Softness score and fatty acid compositions of caudal adipose tissue were determined after slaughter. At the end of the trial, 75% of the carcasses had soft adipose tissue. The occurrence of soft fat appears to be related to high metabolisable energy intake per kg body weight. Soft fat was characterised by a higher water content, a lower proportion of saturated even-numbered fatty acids and higher proportions of Odd FA and methyl-branched-chain fatty acids in caudal adipose tissue, compared to firm fat. Despite high proportions of Odd FA and branched-chain fatty acids in caudal adipose tissue, plasma concentrations of MMA were low (2.02+/-1.98&mgr;mol/l). No clear relationships between MMA concentrations and soft fat or the proportions of branched-chain fatty acids other than the Iso and Anteiso acids was observed. It was concluded that the present study does not support the hypothesis that the liver's capacity to metabolise MMA was exceeded.

Journal Article↗

Expression of murine renin genes in subcutaneous connective tissue.

A renin promoter-large tumor antigen (T antigen) fusion gene was constructed to provide a reporter function for renin expression in transgenic mice. These transgenic mice gave rise to tumors in subcutaneous soft tissue, which was attributed to transgene expression at this site. An immunohistochemical analysis of transgenic fetuses from several independent lines revealed scattered T-antigen-containing mesenchymal cells and fibroblasts in the subcutaneous layer of the skin between the panniculus carnosus muscle of the skin and the skeletal muscle of the body wall. This localization is consistent with the location of overt tumorigenesis in adult mice. This pattern was specific for the renin-T antigen fusion gene as no immunohistochemical staining was observed in transgenic fetuses containing a heterologous promoter-T antigen fusion gene. Northern blot analysis of tumor RNA indicated that most of the tumors expressed both T antigen and the endogenous renin gene Ren-1c. In addition, when multiple renin genes were introduced by crossing transgenic mice with nontransgenic DBA/2J mice, which contain another allele of the Ren-1 locus as well as the duplicated locus Ren-2, the resultant tumors expressed the Ren-2 gene. Northern blots were then used to analyze renin expression in the subcutaneous tissue of normal mice. Fully processed renin mRNA was detected in eviscerated 15.5-day postcoitus fetal and newborn carcasses and in newborn skin. Our data indicate that there is a renin-expressing cell population in fetal and newborn subcutaneous tissue.

Animals↗

[Dynamics of oxygen tension in the brain and subcutaneous adipose tissue of newborn rats during anoxia and reoxygenation].

The oxygen tension (pO2) in the brain and subcutaneous tissue of newborn rats was studied during anoxia and reoxygenation with hyperoxic gas mixtures. The level of pO2 in both tissues during anoxia fell from 10-30 mm Hg to 0 mm Hg. When newborn rats were reoxygenated with 50% or 100% O2, the oxygen tension in the brain and subcutaneous first increased and then decreased in spite of the hyperoxic inhalation. The decrease of pO2 in the subcutaneous during hyperoxia was more pronounced than that in the brain. Data obtained are discussed.

Adipose Tissue↗

Microdialysis of subcutaneous adipose tissue in vivo for continuous glucose monitoring in man.

Subcutaneous adipose tissue extracellular glucose was investigated in vivo in man with a microdialysis technique. A small dialysis probe (4 or 10 x 0.5 mm) was implanted subcutaneously, and was perfused continuously with a micro-infusion pump. Dialysate samples were collected in 15-min periods. A transient yield of ATP was recorded immediately after insertion of the probe; thereafter ATP was almost undetectable. During steady-state conditions the tissue dialysate glucose concentration remained constant for at least 2 h, which indicated that there was no drainage of glucose from the interstitial fluid to the tissue dialysate. Simultaneous dialysis of venous blood and subcutaneous fat in rats showed that the recovery of glucose from the adipose tissue interstitial fluid to the dialysate was only 20% of that from blood. However, in vivo dialysis of human adipose tissue with glucose-containing solutions produced an equilibrium with the extracellular space at a glucose concentration that was similar to the blood glucose concentration. After oral glucose ingestion and following i.v. insulin and glucose administration the relative variations in subcutaneous glucose closely resembled those in blood glucose. It is concluded that the subcutaneous implantation of the presently used small dialysis device causes only minor and transient traumatic effects. The dialysis recovery of glucose is lower in adipose tissue than in blood. However, the relative kinetics of subcutaneous tissue dialysate glucose are closely related to variations in the blood glucose concentration, and thus may be used for monitoring of glycaemic control in man.

Adipose Tissue↗

Omental and subcutaneous adipose tissue steroid levels in obese men.

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.

Abdominal Fat↗

Anatomical study of subcutaneous adipofascial tissue: a concept of the protective adipofascial system (PAFS) and lubricant adipofascial system (LAFS).

The subcutaneous adipofascial tissue over the entire body was radiographically and macroscopically investigated in 20 fresh and embalmed cadavers. The subcutaneous adipofascial tissue was made up of two adipofascial layers. Because the superficial layer forms a solid structure and is thought to protect against external forces, the adipofascial system formed by the solid structure was named the "protective adipofascial system (PAFS)". Because the deep layer forms a mobile layer and is thought to lubricate musculoskeletal movement, the adipofascial system formed by the mobile structure was named "lubricant adipofascial system (LAFS)". By classifying subcutaneous adipofascial tissue by its functional characteristics, we found we could understand the subcutaneous adipofascial structure over the entire body well.

Adipose Tissue↗