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PubMedDate not supplied

Inference of blood glucose concentrations from subcutaneous glucose concentrations: applications to glucose biosensors.

An approach for inference of blood glucose concentrations in real time is considered. First, a model that predicts the subcutaneous glucose concentration from the blood glucose concentration is presented. The model includes diffusive transport from the blood to the subcutaneous tissue and reactive-like cellular uptake of glucose. Next, the Phillips-Tikhonov regularization method is considered to solve the real-time input estimation problem that determines the blood glucose concentration given the subcutaneous glucose concentration. The inverse problem is regularized by imposing a smoothing condition to obtain a stable solution. Three different penalization functionals were considered in evaluating the regularization method using a synthetic function that approximates the subcutaneous glucose response to an oral glucose tolerance test in a human subject. Various levels of either white noise or time-correlated noise were superimposed onto the synthetic response to evaluate the sensitivity of the inverse to measurement error. For inversion assuming only diffusive transport, the optimal time interval of integration of previous subcutaneous measurements was found to be about 1.5/alpha, where alpha(-1) is the dominant time constant for the exchange of glucose between the blood and subcutaneous tissue. The optimal sampling rate was found to be 54alpha. Linear regularizations based on minimization of first or second derivatives of the blood glucose concentration were found to be satisfactory, each yielding a minimum error that was about 50% greater than the measurement error. Including nonlinear, reactive-like uptake of glucose was found to decrease the error magnification factor slightly. Both the model and the inverse method relating blood and subcutaneous glucose concentrations are successfully applied to experimental measurements using glucose biosensors reported by Schmidtke et al. (Proc. Natl. Acad. Sci. USA 95:294-299, 1998).

Algorithms↗

PubMed1990

Subcutaneous adipose tissue: a source of lactate production after glucose ingestion in humans.

The in vivo kinetics of lactate and pyruvate in the extracellular space of subcutaneous adipose tissue after glucose ingestion were investigated in healthy volunteers by the use of a microdialysis sampling technique. Comparison was made with the metabolite levels in venous plasma. The absolute subcutaneous tissue concentrations of lactate and pyruvate were estimated in the fasting state by perfusion with varying lactate- and pyruvate-containing solutions. An equilibrium with the surrounding extracellular fluid was found for both lactate and pyruvate in concentrations similar to those in venous plasma. After glucose ingestion there was an increase in the circulating levels of glucose, lactate, and pyruvate, which returned to base-line values within 3 h. There was a more marked increase in lactate in subcutaneous adipose tissue than in venous blood, and the adipose tissue lactate remained elevated for at least 3 h. In contrast, pyruvate levels increased much less in subcutaneous fat than in venous blood. The addition of isoproterenol (which inhibits adipose tissue glucose metabolism) to the tissue perfusate lowered the subcutaneous tissue lactate levels significantly but did not affect the subcutaneous pyruvate levels. These data suggest that human subcutaneous adipose tissue is a source of in vivo lactate production after glucose ingestion. Since lactate is thought to be a major substrate for glycogen synthesis in the liver, the present findings may provide evidence of a new and important role of the adipose tissue metabolism in the regulation of whole body glucose homeostasis in humans.

Adipose Tissue↗

PubMed2001

In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue.

We studied eight normal-weight male subjects to examine whether the lipolytic rate of deep subcutaneous and preperitoneal adipose tissues differs from that of superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the superficial anterior and deep posterior subcutaneous abdominal adipose tissues and in the preperitoneal adipose tissue in the round ligament were measured by microdialysis and (133)Xe washout under basal, postabsorptive conditions and during intravenous epinephrine infusion (0.15 nmol. kg(-1). min(-1)). Both in the basal state and during epinephrine stimulation, the superficial subcutaneous adipose tissue had higher interstitial glycerol concentrations than the two other depots. Similarly, the calculated glycerol outputs from the superficial depot were significantly higher than those from the deep subcutaneous and the preperitoneal depots. Thus, it is concluded that the lipolytic rate of the superficial subcutaneous adipose tissue on the anterior abdominal wall is higher than that of the deep subcutaneous adipose tissue on the posterior abdominal wall and that of the preperitoneal adipose tissue in the round ligament.

Abdomen↗

PubMed2002

Differences of subcutaneous adipose tissue topography between type-2 diabetic men and healthy controls.

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.

Adipose Tissue↗

PubMed2003

Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran: a population model analysis.

OBJECTIVE: Ximelagatran, an oral direct thrombin inhibitor, is rapidly bioconverted to melagatran, its active form. The objective of this population analysis was to characterise the pharmacokinetics of melagatran and its effect on activated partial thromboplastin time (APTT), an ex vivo measure of coagulation time, in orthopaedic surgery patients sequentially receiving subcutaneous melagatran and oral ximelagatran as prophylaxis for venous thromboembolism. To support the design of a pivotal dose-finding study, the impact of individualised dosage based on bodyweight and calculated creatinine clearance was examined. DESIGN AND METHODS: Pooled data obtained in three small dose-guiding studies were analysed. The patients received twice-daily administration, with either subcutaneous melagatran alone or a sequential regimen of subcutaneous melagatran followed by oral ximelagatran, for 8-11 days starting just before initiation of surgery. Nonlinear mixed-effects modelling was used to evaluate rich data of melagatran pharmacokinetics (3326 observations) and the pharmacodynamic effect on APTT (2319 observations) in samples from 216 patients collected in the three dose-guiding trials. The pharmacokinetic and pharmacodynamic models were validated using sparse data collected in a subgroup of 319 patients enrolled in the pivotal dose-finding trial. The impact of individualised dosage on pharmacokinetic and pharmacodynamic variability was evaluated by simulations of the pharmacokinetic-pharmacodynamic model. RESULTS: The pharmacokinetics of melagatran were well described by a one-compartment model with first-order absorption after both subcutaneous melagatran and oral ximelagatran. Melagatran clearance was correlated with renal function, assessed as calculated creatinine clearance. The median population clearance (creatinine clearance 70 mL/min) was 5.3 and 22.9 L/h for the subcutaneous and oral formulations, respectively. The bioavailability of melagatran after oral ximelagatran relative to subcutaneous melagatran was 23%. The volume of distribution was influenced by bodyweight. For a patient with a bodyweight of 75kg, the median population estimates were 15.5 and 159L for the subcutaneous and oral formulations, respectively. The relationship between APTT and melagatran plasma concentration was well described by a power function, with a steeper slope during and early after surgery but no influence by any covariates. Simulations demonstrated that individualised dosage based on creatinine clearance or bodyweight had no clinically relevant impact on the variability in melagatran pharmacokinetics or on the effect on APTT. CONCLUSIONS: The relatively low impact of individualised dosage on the pharmacokinetic and pharmacodynamic variability of melagatran supported the use of a fixed-dose regimen in the studied population of orthopaedic surgery patients, including those with mild to moderate renal impairment.

Administration, Cutaneous↗

PubMed2003

Therapeutic approaches to subcutaneous mycoses.

Subcutaneous mycoses, which are much less common than superficial fungal infections, are characterized by a heterogeneous group of infections that often result from direct penetration of the fungus into the dermis and subcutaneous tissue through traumatic injury. The fungus spreads by local deep tissue invasion from the inoculation site. The disease usually remains localized and then slowly spreads to adjacent tissue and eventually to the lymphatics. More rarely, hematogenous dissemination is observed. There are usually various clinical features and thus a broad range of differential diagnoses. The common subcutaneous mycoses are sporotrichosis, chromoblastomycosis, phaeohyphomycosis, eumycotic mycetoma, and hyalohyphomycosis. Many subcutaneous mycoses are confined to the tropical and subtropical regions, but some, such as sporotrichosis, are also prevalent in temperate regions. Subcutaneous mycoses can occur in healthy individuals. In immunocompromised individuals, these infections can disseminate widely. Treatment usually involves use of antifungal agents and/or surgical excision. Treatment of some serious subcutaneous mycoses remains unresolved, and there have been reports of relapses or progression during therapy and problems with lack of tolerability of antifungal drugs. Identification of the etiologic agent by culture is essential for prognostic and management considerations, since some fungi are more frequently associated with dissemination. Results of antifungal susceptibility tests may provide valuable information for deciding the appropriate method of treatment. Development of new antifungal agents and combination therapies may result in improvement in the management of subcutaneous mycoses in the future.

Antifungal Agents↗

PubMed2005

Continuous glucose monitoring in interstitial subcutaneous adipose tissue and skeletal muscle reflects excursions in cerebral cortex.

Continuous glucose monitoring (CGM) is being explored using several types of glucose sensors. Some are designed for subcutaneous adipose tissue. It is important to determine to which extent these glucose fluctuations in different tissues reflect changes taking place in the central nervous system, where glucose sensing is thought to occur. We studied the ability of subcutaneous adipose interstitial fluid measurements to parallel glucose propagations in blood, muscle, and central nervous system (CNS) during hyper- and hypoglycemia. A subcutaneous CGM system was applied in the CNS, subcutaneous adipose tissue, and skeletal muscle of nine Vietnamese potbellied pigs, and data were compared with frequent sampling in blood. Alterations in glucose levels were induced with intravenous glucose and insulin. During hyperglycemia, no difference was detected in delay between blood and interstitial glucose levels in subcutaneous adipose tissue (18.0 +/- 0.8 min), muscle (18.0 +/- 0.9 min), and CNS (20.3 +/- 1.2 min), respectively. During hypoglycemia, we found no time difference between interstitial parameters in the three tissues. However, the amplitude of glucose changes varied considerably, with a smaller magnitude of glucose change taking place in the brain. The timing of glucose excursions in subcutaneous adipose tissue and muscle reflect excursions in CNS. The reduced magnitude of glucose excursions in the brain suggests that different mechanisms of glucose transport are operative in CNS compared with subcutaneous adipose tissue and muscle.

Adipose Tissue↗

PubMed2006

Insulin signaling in human visceral and subcutaneous adipose tissue in vivo.

In this study, we evaluated the activation of various insulin signaling molecules in human fat in vivo and compared signaling reactions in visceral and subcutaneous fat depots. Paired abdominal omental and subcutaneous fat biopsies were obtained from nonobese subjects with normal insulin sensitivity under basal conditions and 6 and 30 min following administration of intravenous insulin. Insulin receptor phosphorylation was more intense and rapid and insulin receptor protein content was greater in omental than in subcutaneous adipose tissue (P < 0.05). Insulin-induced phosphorylation of Akt also occurred to a greater extent and earlier in omental than in subcutaneous fat (P < 0.05) in the absence of significant changes in Akt protein content. Accordingly, phosphorylation of the Akt substrate glycogen synthase kinase-3 was more responsive to insulin stimulation in omental fat. Protein content of extracellular signal-regulated kinase (ERK)-1/2 was threefold higher in omental than in subcutaneous fat (P < 0.05), and ERK phosphorylation showed an early 6-min peak in omental fat, in contrast with a more gradual increase observed in subcutaneous fat. In conclusion, the adipocyte insulin signaling system of omental fat shows greater and earlier responses to insulin than that of subcutaneous fat. These findings may contribute to explain the biological diversity of the two fat depots.

3T3 Cells↗

PubMed1994

Development of a miniaturized glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method. Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients.

OBJECTIVE: To develop a reliable and practical glucose monitoring system by combining a needle-type glucose sensor with a microdialysis sampling technique for long-term subcutaneous tissue glucose measurements. RESEARCH DESIGN AND METHODS: A microdialysis Cuprophan hollow-fiber probe (inner diameter, 0.20 mm; length, 15 mm) was perfused with isotonic saline solution (120 microliters/h) and glucose concentrations in the dialysate were measured by a needle-type glucose sensor extracorporeally. This system was tested both in vitro and in vivo. Subcutaneous tissue glucose concentrations were then monitored continuously in 5 healthy and 8 diabetic volunteers for 7 to 8 days. A hollow-fiber probe was inserted into the abdominal subcutaneous tissue. RESULTS: This monitoring system achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to > 27.8 mM glucose, with a time delay of 6.9 +/- 1.2 min associated with a rise in glucose and 8.8 +/- 1.6 min with a fall in the glucose level (means +/- SE). The overall correlation between subcutaneous tissue (Y) and blood (X) glucose concentration was Y = 1.08X + 0.19 (r = 0.99). The subcutaneous tissue glucose concentration could be monitored precisely for 4 days without any in vivo calibrations and for 7 days by introducing in vivo calibrations. CONCLUSIONS: Glycemic excursions could be monitored precisely in the subcutaneous tissue by this microdialysis sampling method with a needle-type glucose sensor in ambulatory diabetic patients.

Adult↗

PubMed2002

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↗

PubMed2003

Development of centrality indices of subcutaneous fat during growth.

Changes of fat distribution were followed up in Czech and Slovak children from 1.5 to 15 years of age, using centrality indices, which relate the values of skinfolds on the trunk to the skinfolds on the extremities, head and neck. Up to 5 years of age, subcutaneous fat was deposited relatively more on the extremities, head and neck than on the trunk, which was expressed by lower values of the centrality indices. After the age of 5 years, the accumulation of subcutaneous fat was greater on the trunk, which was also expressed by higher values of the centrality indices. The comparison of the individual indices revealed in both genders a relatively higher amount of subcutaneous fat on the trunk in boys until 12 years of age. During puberty subcutaneous fat over triceps and on the forearm was reduced. In girls the deposition of the subcutaneous fat was relatively greater at different sites of the trunk than in boys, with the exception of the age of 14-15 years. The deposition of subcutaneous fat was greater on the trunk than on the head (cheek) and on the extremities in Czech compared to Slovak children, except for 12-year-old girls. During the period between the fifties and the seventies of the last century, in Czech children, especially in girls, the deposition of subcutaneous fat on the trunk was relatively smaller than on other parts of the body surface, which was expressed by the reduction of the centrality indices. Index 12 was therefore considered as the most valuable for the characterization of fat distribution on the body surface.

Adipose Tissue↗

PubMed2004

[Establishment of in vivo adriamycin-induced multidrug resistance models of subcutaneous and hepatic transplanted human liver cancer in nude mice].

BACKGROUND & OBJECTIVE: Multidrug resistance (MDR) phenotype is the obstacle of chemotherapy in tumors and inspired research interesting. This study was to establish multidrug resistance (MDR) models induced with adriamycin in vivo of subcutaneous or in situ hepatic transplanted human liver cancer in nude mice (BALB/C nu/nu), and explore the biological characteristics and mechanism of multidrug resistance, which can provide an ideal animal model for the basic,and clinical study of MDR. METHODS: After successful performing either subcutaneous or hepatic transplantation in nude mice with liver cancer cell line HepG2, adriamycin (ADM) was injected into abdominal cavity to induce multidrug resistance. The chemosensitivity of HepG2 and ADM-cultured HepG2 cells was determined by MTT assay. P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), and cell pump-efflux to Rhodamine 123 (R123) were determined by flow cytometry. The mRNA expression of P-gp, MRP, and LRP was assessed with reverse transcriptase polymerase chain reaction(RT-PCR). RESULTS: Most biological characteristics of either subcutaneous or hepatic transplanted HepG2 liver cancer in nude mice like the parent HepG2 liver cancer. Both of them showed significant multidrug resistance. Among them, the resistance index of ADM was 26.4 times in hepatic transplanted group, and 24.6 times in subcutaneous transplanted group higher than that of parent cell line HepG2. In subcutaneous,and hepatic transplanted ADM-cultured groups, P-gp [(77.3+/-2.1)%, and (78.1+/-1.9)%], MRP [(72.1+/-4.3)%, and (72.7+/-5.0)%], and LRP [(31.1+/-1.0)%, and (32.2+/-1.4)%] positive cells increased significantly, their mRNA positive expression increased also, and the cell pump-efflux to R123 strengthened. However, no significant difference of above data was observed between subcutaneous,and hepatic transplanted tumor group (P >0.05). CONCLUSION: Both MDR subcutaneous and hepatic HepG2 transplanted models induced by in vivo injection of adriamycin in nude mice have the same biological characteristics as parent HepG2 liver cancer. These 2 animal models could be used as in vivo MDR models to explore the mechanism of MDR and reversing therapeutic methods.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

[Lipolytic and lipoprotein lipase activity of subcutaneous and visceral adipose tissue in Cushing's syndrome].

Cushing's syndrome has been recently compared to visceral-type obesity, since it is characterised by the accumulation of adipose tissue at a deep abdominal site, to the detriment of the subcutaneous adipose panniculus, and is associated with insulin-resistance and hyperlipemia. The aim of the present study was to evaluate the influence of glucocorticoid hormones on lipolytic activity (index of FFA mobilisation) and on lipoproteinlipase (LPL) activity (an index of the accumulation of triglycerides) in subcutaneous and perirenal adipose tissue in order to clarify the mechanisms involved in this type of accumulation in Cushing's syndrome. Five patients (4 F and 1 M) were included in the study, mean age 27.8 +/- 3.7 years and BMI 21.3 +/- 1.2 kg/m2; patients were hospitalised in the 2nd Surgical Clinic at the University of Padua and underwent surgery for secondary corticosurrenal hyperplasia with ACTH secreting hypophysial adenoma. Lipolytic activity in subcutaneous adipose tissue in these patients was significantly lower (p less than 0.05) than in control subjects, in particular after noradrenalin stimulation (p less than 0.01). No significant difference was observed when lipolytic activity in subcutaneous adipose tissue was compared to that one in perirenal tissue. LPL activity in subcutaneous adipose tissue did not reveal statistically significant differences compared to control subjects, although values were lower. A further decrease in LPL activity, which was not however significant, was observed in perirenal tissue in comparison to subcutaneous tissues in the same patients. The mean weight of adipocytes (ug) was slightly lower in subcutaneous adipose tissue compared to control subjects and even lower in perineal tissue in comparison to the subcutis in the same patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1988

[Results of the UFT sensitivity test using human urogenital cancers transplanted subcutaneously and under the subrenal capsule of nude mice].

Experimental chemotherapy with UFT was performed against human urogenital cancers, transplanted subcutaneously and under the subrenal capsule (SRC) of nude mice. The tumor take with subcutaneous assay was confirmed in 21 cell lines of human neoplasms, which consisted of 9 renal cell carcinomas, 5 renal pelvic carcinomas, 1 ureteral carcinoma, 3 carcinomas of the urinary bladder, 2 prostatic carcinomas and 1 testicular tumor. On the other hand, the tumor take with subrenal capsule assay was confirmed in 17 of the neoplasm, which consisted of 7 renal cell carcinomas, 4 renal pelvic carcinomas, 4 carcinomas of urinary bladder, 1 prostatic carcinoma and 1 testicular tumor. UFT was administered, starting on Day 14 for subcutaneous transplantation and starting on Day 0 for SRC assay. The dose of UFT was the same as clinical dose for both subcutaneous transplantation and subrenal capsule assays. Treatment with UFT was performed for 6 weeks in subcutaneous transplantation assay and for 4 weeks in subrenal capsule assay. Effect of UFT was evaluated by the inhibition rate (IR) calculated by the mean tumor weights of both treated and untreated groups. Responses to the treatment in subcutaneous transplantation and subrenal capsule assays were judged as effective when the IR were higher than 58% and 20%, respectively. Responses rates of UFT in subcutaneous transplantation and subrenal capsule assays were 43% and 82%, respectively.

Animals↗

PubMedDate not supplied

Distribution of [3H]dexamethasone in rat subcutaneous tissue after delivery from osmotic pumps.

Inflammation surrounding implantable glucose sensors may be controlled through local release of dexamethasone at the site of implantation. In the present study, we evaluated the distribution of dexamethasone in rat subcutaneous tissue during the first 2.5 days after local release. Osmotic pumps containing [3H]dexamethasone were implanted into the subcutaneous tissue of rats. Digital autoradiography was used to measure the distribution of the [3H]dexamethasone within the subcutaneous tissue at 6, 24, and 60 h after implantation. Measured concentration profiles, near the catheter tip through which the agent was released, were compared to mathematical models of drug diffusion and elimination. The results demonstrate that the majority of the [3H]dexamethasone delivered into the subcutaneous tissue was found within a 3 mm region surrounding the catheter tip. There was good agreement between the experimental data and the mathematical model. The diffusion coefficient for dexamethasone in subcutaneous tissue was found to be D = 4.11 +/- 1.77 x 10(-10) m2/s, and the elimination rate constant was found to be k = 3.65 +/- 2.24 x 10(-5) s(-1). The diffusion coefficient and elimination rate constants for dexamethasone in subcutaneous tissue have not been previously reported. The use of a mathematical model may be useful in predicting the effectiveness of local delivery of dexamethasone around implantable glucose sensors.

Animals↗

PubMed1997

Human prostate tumor angiogenesis in nude mice: metalloprotease and plasminogen activator activities during tumor growth and neovascularization of subcutaneously injected matrigel impregnated with human prostate tumor cells.

BACKGROUND: A critical aspect for growth of solid tumors is the development of a blood supply. Our objective was to establish a model for the study of angiogenesis of human prostate tumors by examining the growth of microvessels into Matrigel containing human prostate tumor cells implanted subcutaneously in nude mice. METHODS: Human prostate tumor cell lines PC-3 and LNCaP were injected in Matrigel under the abdominal skin of nude mice and were harvested at 4, 8, and 14 days post-injection. The growth of tumor cells and blood vessels was examined histologically and by immunohistochemical localization of von Willibrand Factor VIII (vWF). Since plasminogen activators and matrix metalloproteases are associated with angiogenesis, the activities and molecular forms of these proteases were determined in Matrigel control and Matrigel-tumor cell subcutaneous implants. RESULTS: Blood vessel formation in the Matrigel implants containing LNCaP and PC-3 cells was demonstrable at 8 days post-injection. However, the pattern of blood vessel formation by the two tumor cell lines was different; PC-3 tumors showed a more invasive phenotype and smaller diameter blood vessels, whereas LNCaP tumors grew as large cellular spheroids surrounded by large, dilated blood vessels. Many blood vessels of PC-3 tumors expressed vWF by day 14 of growth, whereas most blood vessels in LNCaP tumors were immunohistochemically negative for this antigen. Mouse skin blood vessels in the same PC-3 and LNCaP tumor histological sections were positive for vWF. Matrigel contained both plasminogen activator and metalloprotease activities. The plasminogen activator activity in Matrigel control implants was totally inhibited by 4 days post-injection, indicating the presence of an inhibitor provided by the host mouse. LNCaP tumor cells injected did not have appreciable plasminogen activator activity, nor did LNCaP tumors develop plasminogen activator activity with tumor growth post-injection. PC-3 cells did have plasminogen activator activities, which were partially negated after subcutaneous injection (4 days), but then increased again by 8 days post-injection. This increase in plasminogen activator activity was due to urokinase (about 54 kDa) produced by the tumor and not by the mouse host (mouse urine urokinase about 44 kDa). Matrigel alone demonstrated gelatinase B (about 95 kDa) activity in zymograms, and gained considerable gelatinase A (about 70 and 74 kDa) activity after subcutaneous implantation. No metalloprotease activity from the tumor cells could be distinguished over that contributed by the mouse host cells in the Matrigel. Matrigel also contains caseinolytic activities of approximately 56, 80, 85, and 89 kDa. After subcutaneous injection of Matrigel, the 89 kDa form increases considerably in activity and the others are diminished. This pattern is also observed in LNCaP and PC-3 tumors post-injection, except the PC-3 tumors demonstrate increased 56 kDa activity. CONCLUSION: The subcutaneous growth of LNCaP and PC-3 prostate tumor cells in Matrigel in nude mice can be used to study tumor-induced angiogenesis. However, the organization of LNCaP and PC-3 tumor growth and the pattern of microvessels associated with each tumor are different in this system, implying that each tumor has unique influences on the pattern of microvessel development. The mode of action by which this is brought about is not known, but may be due to specific factors produced/ released by the tumor cells.

Animals↗

PubMed2006

Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans.

OBJECTIVE: Mesenchymal stem cells from synovium have a greater proliferation and chondrogenic potential than do those from bone marrow, periosteum, fat, and muscle. This study was undertaken to compare fibrous synovium and adipose synovium (components of the synovium with subsynovium) to determine which is a more suitable source for mesenchymal stem cells, especially for cartilage regeneration, and to examine the features of adipose synovium-derived cells, fibrous synovium-derived cells, and subcutaneous fat-derived cells to determine their similarities. METHODS: Human fibrous synovium, adipose synovium, and subcutaneous fat were harvested from 4 young donors and 4 elderly donors. After digestion, the nucleated cells were plated at a density considered proper to expand at a maximum rate without colony-to-colony contact. The surface epitopes, proliferative capacity, cloning efficiency, and chondrogenic, osteogenic, and adipogenic differentiation potentials of the cells were compared. RESULTS: Fibrous synovium- and adipose synovium-derived cells were higher in STRO-1 and CD106 and lower in CD10 compared with subcutaneous fat-derived cells. Cells derived from fibrous and adipose synovium had higher proliferative potential and colony-forming efficiency compared with subcutaneous fat-derived cells, both in mixed-population and in single-cell-derived cultures. In chondrogenic assays, pellets from fibrous synovium- and adipose synovium-derived cells produced more cartilage matrix than did cell pellets from subcutaneous fat. Osteogenic ability was also higher in fibrous synovium- and adipose synovium-derived cells, whereas adipogenic potential was nearly indistinguishable among the 3 populations. Differentiation potential of the cells was similar between young and elderly donors. CONCLUSION: Cells derived from the fibrous synovium and from the adipose synovium demonstrate comparable chondrogenic potential. Adipose synovium-derived cells are more similar to fibrous synovium-derived cells than to subcutaneous fat-derived cells.

Adolescent↗

PubMedDate not supplied

Effect of indole-3-acetic acid administration by gavage and by subcutaneous injection on rat leukocytes.

This study was done to investigate the effect of indole-3-acetic acid (IAA) administered subcutaneously and by gavage on neutrophil function and cytotoxicity in neutrophils and lymphocytes. A gavage administration resulted in an increase in phagocytic capacity in neutrophils in a dose depended manner for 1 mg, 2 mg, 18 mg, and 40 mg of IAA per kg of body mass, respectively, compared with the control. Similarly, subcutaneous administration of IAA at 2, 18, and 40 mg per kg of body mass promoted a significant rise in phagocytosis by neutrophils. H2O2 production in neutrophils from treated rats by gavage was similar to those receiving subcutaneous IAA treatment, and did not show a significant difference between treatments and control. IAA treatment, whether by gavage or subcutaneous, did not produce an alteration in antioxidant enzyme activities or in glucose-6-phosphate dehydrogenase activity of either neutrophils or lymph nodes. Subcutaneous IAA administration did not alter the neutrophil and lymphocyte death as deduced by unaltered membrane integrity, DNA fragmentation and mitochondrial transmembrane potential, compared with controls. In conclusion, IAA administration either subcutaneously or by gavage could increase the phagocytic capacity by neutrophils and this acid administration did not have prooxidant effects or cytotoxic effects on neutrophils and lymphocytes.

Administration, Oral↗