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  • BLOOD  (7)
  • 1
    Keywords: AGENTS ; BLOOD ; Germany ; PERFUSION ; QUANTIFICATION ; VOLUME ; BLOOD-FLOW ; FLOW ; SIGNAL ; PARAMETERS ; RECRUITMENT ; KINETICS ; BODY ; SONOGRAPHY ; OXYGEN ; POWER DOPPLER SONOGRAPHY ; VASCULARIZATION ; ULTRASOUND-INDUCED DESTRUCTION ; exercise ; RE ; WEIGHT ; HEALTHY-VOLUNTEERS ; replenishment kinetics ; TUMOR PERFUSION ; muscle perfusion ; replenishment kinetics of microbubbles ; CAPILLARIES ; microvascular density ; contrast-enhanced sonography
    Abstract: Objective. The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. Methods. Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL - min(-1) - kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1 - Hkt = PVF) in which the microbubbles can distribute. Results. Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO2max (r= 0.59; P 〈.01). Among CEUS parameters, B showed the closest correlation to CFC (r = 0.53; P 〈.01). When CFC was normalized for PVF, correlation of B to CFC was r = 0.64 (P 〈.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] similar to mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] similar to mL - min(-1) - 100 g tissue(-1)). Conclusions. B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification
    Type of Publication: Journal article published
    PubMed ID: 16632781
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  • 2
    Keywords: CELLS ; EXPRESSION ; GROWTH ; BLOOD ; Germany ; RISK ; RNA ; RISK-FACTORS ; LESIONS ; PLASMA ; risk factors ; smoking ; LDL ; OVEREXPRESSION ; PERIPHERAL-BLOOD ; COX-2 ; LIPOPROTEINS ; N-ACETYL-CYSTEINE ; inflammation ; HYPERCHOLESTEROLEMIA ; SERUM ; ELISA ; free radicals ; MATRIX METALLOPROTEINASES ; ATHEROSCLEROTIC LESIONS ; GLUTAMATE LEVELS ; hyperlipoproteinemia ; NITRIC-OXIDE-SYNTHASE ; OXIDIZED LOW-DENSITY
    Abstract: Cyclooxygenase (COX)-2 is expressed in macrophages of arteriosclerotic lesions and promotes inflammation. We investigated whether COX-2 is already expressed in peripheral blood mononuclear cells (PBMCs) of subjects possessing risk-related factors, such as in smokers and hyperlipidemics. PBMCs were isolated from the venous blood of normolipidemic nonsmokers (NL-NSM; n = 15), normolipidemic smokers (NL-SM; n = 12), hyperlipidemic nonsmokers (HL-NSM; n = 10), and hyperlipidemic smokers (HL-SM; n = 10). RNA from PBMCs was used for RT-PCR. Plasma concentrations of oxidized low-density lipoproteins (oxLDL) were rneasured by ELISA, those of glutamate and cystine by HPLC. The results show that COX-2 expression in PBMCs was significantly increased in the groups with cardiovascular risk factors (NL-SM, HL-SM, HL-NSM) compared with NL-NSM. COX-2 expression in PBMCs was positively Correlated with concentrations of total serum cholesterol, oxLDL, glutamate, or cystine. We suggest that the elevated COX-2 expression indicates a priming of PBMCs as a response to a systemic pro-oxidative and proinflammatory shift in subjects with cardiovascular risk factors, which might also contribute to growth and instability of arteriosclerotic lesions. (C) 2004 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15607906
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  • 3
    Keywords: BLOOD ; Germany ; IN-VIVO ; PERFUSION ; VIVO ; imaging ; SYSTEM ; METABOLISM ; BLOOD-FLOW ; FLOW ; MAGNETIC-RESONANCE ; MAGNETIC-RESONANCE-SPECTROSCOPY ; METABOLITES ; SPECTROSCOPY ; magnetic resonance imaging ; resistance ; ENERGY ; AGE ; SKELETAL-MUSCLE ; KINETICS ; exercise ; methods ; SIZE ; contrast-enhanced ultrasonography ; magnetic resonance spectroscopy ; contrast-enhanced ultrasound ; Skeletal muscle ; INTRAMYOCELLULAR LIPIDS ; AREA ; ADAPTATIONS ; Concentric resistance training ; ENDURANCE
    Abstract: Purpose: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 +/- 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results: The significant (P〈0.001) increase in CSA (60 +/- 16 before vs. 64 +/- 15 cm(2) after training) and in absolute muscle strength (isometric, 146 +/- 44 vs. 174 +/- 50 Nm; isokinetic, 151 +/- 53 vs. 174 +/- 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 +/- 75 vs. 326 +/- 62) nor ultra-sonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 +/- 1.2 vs. 1.1 +/- 1.1 ml/min/100 g; blood flow velocity, 0.49 +/- 0.44 vs. 0.52 +/- 0.74 mm s(-1)). Also, the intensities of high-energy phosphates phosphocreatine and beta-adenosintriphosphate were not different after training within the skeletal muscle at rest (beta-ATP/phosphocreatine, 0.29 +/- 0.06 vs. 0.28 +/- 0.04). Conclusion: The significant increase in muscle size and strength in response to concentric isokinetic and isometric resistance training occurs without an increase in the in vivo microcirculation of the skeletal muscles at rest. (C) 2008 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19144482
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  • 4
    Keywords: APOPTOSIS ; CELLS ; IN-VITRO ; BLOOD ; CELL ; Germany ; INHIBITION ; DISEASE ; HEART ; PATIENT ; MACROPHAGES ; SERA ; treatment ; ACID ; GLUTATHIONE ; PLASMA ; DECREASE ; cholesterol ; LDL ; LIPOPROTEIN ; PERIPHERAL-BLOOD ; OXIDATION ; cysteine ; arteriosclerosis,risk factors in hyperlipidemia,glutathione in atherosclerosis,redox status as a ris ; CORONARY-ARTERY DISEASE ; HEART-DISEASE ; N-ACETYL-CYSTEINE ; SERUM LEVELS
    Abstract: Treatment of hyperlipidemic patients with the thiol compound N-acetyleysteine (NAC) was previously shown to cause a significant dose-related increase in the high-density lipoprotein (HDL) -cholesterol serum level, suggesting the possibility that its disease-related decrease may result from a diminished thiol concentration and/or thiol/disulfide redox status (REDST) in the plasma. We therefore investigated plasma thiol levels and REDST in normo-/byperlipidemic subjects with and without coronary heart disease (CHD). The thiol level, REDST, and amino acid concentrations in the plasma and intracellular REDST of peripheral blood mononuclear cells (PBMC) have been determined in 62 normo- and hyperlipidemic subjects. Thirty-three of these subjects underwent coronary angiography, because of clinical symptoms of CHD. All groups of hyperlipidemic patients under test and those normolipidemic individuals with documented coronary stenoses showed a marked decrease in plasma thiol concentrations, plasma and intracellular REDST of PBMCs, and a marked increase in plasma taurine levels. Individual plasma thiol concentrations and plasma REDST were strongly negatively correlated with the serum LDL-cholesterol and positively correlated with the serum HDL-cholesterol level. Together with the earlier report about the effect of NAC on the HDL-cholesterol serum level, our findings suggest strongly that lower HDL-cholesterol serum levels may result from a decrease in plasma thiol level and/or REDST possibly through an excessive cysteine, catabolism into taurine. (C) 2003 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 14607527
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  • 5
    Keywords: AGENTS ; BLOOD ; Germany ; PERFUSION ; DIAGNOSIS ; QUANTIFICATION ; VOLUME ; DISEASE ; TISSUE ; BLOOD-FLOW ; CONTRAST ; SKIN ; blood flow ; CONTRAST AGENT ; FLOW ; PARAMETERS ; SKELETAL-MUSCLE ; KINETICS ; HEALTHY ; SONOGRAPHY ; BOLUS ; POWER DOPPLER SONOGRAPHY ; VASCULARIZATION ; ULTRASOUND-INDUCED DESTRUCTION ; AGENT ; RE ; monitoring ; HEALTHY-VOLUNTEERS ; MICROBUBBLE CONTRAST ; replenishment kinetics ; TUMOR PERFUSION ; PRINCIPLES ; POWER ; contrast-enhanced ; contrast-enhanced ultrasonography ; muscle perfusion ; replenishment kinetics of microbubbles ; venous occlusion plethysmography
    Abstract: Objective. The purpose of this study was to develop a clinically applicable examination method to assess per-fusion of the skeletal muscle using contrast-enhanced ultrasonography (CEUS) analyzing replenishment kinetics of microbubbles. Methods. Power Doppler sonography (7 MHz) after intravenous bolus injection of 10 mL of a microbubble contrast agent was used to repeatedly examine the perfusion of the right biceps muscle at rest and after defined exercise in 10 healthy volunteers. Parameters of perfusion, such as local blood volume, blood flow velocity, and perfusion, were calculated by a modified analysis of replenishment kinetics. For validation, CEUS was correlated with venous occlusion plethysmography (VOP) examining the right forearm flexor muscles at rest and after defined exercise. Results. The CEUS examination was easily feasible and was able to depict the physiologic large variability of the right biceps muscle perfusion at rest (mean +/- SID, 3.0 +/- 2.3 [similar to mL/s (.) 100 mg]) compared with the results after exercise (22.9 +/- 11.0 [similar to mL/s (.) 100 mg]). The perfusion calculated with VOP significantly correlated with the CEUS parameters perfusion (r = 0.81; P 〈 .001) and blood volume (r = 0.82; P 〈 .001). The calculated mean blood flow velocity in the right forearm flexor muscles raised from 0.41 +/- 0.24 mm/s at rest to 0.64 +/- 0.39 mm/s after exercise, showing a significant correlation with the CEUS perfusion (r = 0.72; P 〈 .001). Conclusions. Muscle perfusion can be easily and quantitatively assessed with CEUS. Compared with VOP, CEUS allows for a separate analysis of different muscle groups, unaffected by skin perfusion. Its application may be of particular interest in the diagnosis and monitoring of pathologic microvascularization in myositis or diabetic obstructive disease
    Type of Publication: Journal article published
    PubMed ID: 15784761
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  • 6
    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; BLOOD ; Germany ; SYSTEM ; GENE-EXPRESSION ; microarray ; TUMORS ; LINES ; PATIENT ; DNA ; MECHANISM ; prognosis ; CELL-LINES ; cytokines ; antibodies ; antibody ; immunohistochemistry ; DESIGN ; OBESITY ; LINE ; SKELETAL-MUSCLE ; adenocarcinoma ; MICROARRAY ANALYSIS ; OVEREXPRESSION ; PERIPHERAL-BLOOD ; cell lines ; pancreatic cancer ; THYROID-HORMONE ; SERUM ; ELISA ; PANCREATIC-CANCER ; CAPACITY ; DUCTAL ADENOCARCINOMA ; INTERLEUKIN-6 ; INFLAMMATORY CYTOKINES ; SCREEN ; ABILITY ; DNA-MICROARRAY ; ACUTE-PHASE RESPONSE ; ANOREXIA ; cachexia ; NEUROPEPTIDE-Y ; UNCOUPLING PROTEIN-3
    Abstract: Background and Purpose: The mechanism behind aggressive development of cachexia in patients suffering from pancreatic cancer is not well understood. In this study, we investigated which factors are associated with the cachectic status of the patients and evaluated cachexia-promoting capacity of cancer and inflammatory cells. Experimental Design: DNA microarray analysis and quantitative reverse transcription-PCR were used to screen for cachexia-associated factors in pancreatic specimens obtained from non-cachectic and cachetic patients diagnosed with pancreatic ductal adenocarcinoma. The expression pattern of the most prominently altered cachexia-associated factor, interleukin-6 (IL-6), was further analyzed in patients sera by ELISA, in pancreatic specimens by immunohistochemistry, and in a coculture system by quantitative reverse transcription-PCR using pancreatic cancer cell lines T3M4 (IL-6 positive) and Panc-1 (IL-6 negative) and peripheral blood mononuclear cells (PBMC) obtained from donors and noncachectic and cachectic patients. Results: Among numerous analyzed factors, IL-6 was significantly overexpressed in pancreatic specimens and elevated in serum of cachectic patients. The coculture system revealed that pancreatic cancer T3M4 cells but not Panc-1 cells were able to stimulate IL-6 exclusively in cachectic PBMC (by 14-fold) and this triggering was reduced by half in the presence of IL-6-neutralizing antibodies. Conclusion: IL-6 represents a prominent cachexia-associated factor in pancreatic cancer. IL-6 overexpression in cachectic patients is related to the ability of certain tumors to sensitize PBMC and induce cytokine expression in cachectic PBMC
    Type of Publication: Journal article published
    PubMed ID: 16115919
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  • 7
    Keywords: CELLS ; EXPRESSION ; tumor ; BLOOD ; CELL ; Germany ; SYSTEM ; GENE ; GENE-EXPRESSION ; GENES ; DIFFERENTIATION ; TIME ; PATIENT ; TUMOR-NECROSIS-FACTOR ; RESPONSES ; MACROPHAGES ; IMMUNE-RESPONSES ; gene expression ; PLASMA ; PCR ; LYMPHOCYTES ; ADHESION ; PARAMETERS ; POLYMERASE-CHAIN-REACTION ; cholesterol ; LOW-DENSITY-LIPOPROTEIN ; immune response ; CENTRAL-NERVOUS-SYSTEM ; PERIPHERAL-BLOOD ; MONOCYTE ; CD40 LIGAND ; development ; CEREBRAL-ISCHEMIA ; ELEVATED EXPRESSION ; ONSET ; macrophage ; NECROSIS ; HUMAN ENDOTHELIAL-CELLS ; MONOCYTES ; traumatic brain injury ; POLYMERASE ; PBMC ; WELL ; MONONUCLEAR CELLS ; ACTIVATED PARENCHYMAL MICROGLIA/MACROPHAGES ; lymphopenia ; MANGANESE SUPEROXIDE-DISMUTASE ; oxLDL ; PLASMA OXIDIZED LDL
    Abstract: Peripheral blood mononuclear cells (PBMCs), i.e. lymphocytes, monocytes and macrophages are key players in the development of innate and adaptive immune responses. However, little is known about their properties in patients with acute stroke. Experimental procedures: We presently characterized the early time course of PBMC subpopulations in 19 patients with acute ischemic stroke and symptom onset below 6 h compared to 19 age-matched healthy subjects. Immediately after acute ischemic stroke, as well as 1 and 3 days thereafter, PBMC subpopulations (cluster of differentiation [CD]3+, CD14+, CD19+, CD68+) were isolated by magnetic bead system and the expression of proinflammatory (CD40, tumor necrosis factor-alpha [TNF alpha]), proapoptotic (caspase-3 [CPP32], poly(ADP-ribose) polymerase [PARP]) and adhesion relevant (CD38) genes was measured by quantitative polymerase chain reaction (PCR). Furthermore, besides routine parameters, plasma levels of oxidized low-density lipoproteins (oxLDL) were studied. Results: In comparison to healthy subjects, patients revealed (i) twofold elevated plasma oxLDL concentrations, (ii) decreased (15%) blood cholesterol levels, and (iii) a 40% decrease in total number of lymphocytes. Furthermore, the majority of PBMC subpopulations revealed an increased expression of proinflammatory, proapoptotic or adhesion-relevant genes. Significant positive correlations were observed between expression of most of these genes in PBMCs and individual plasma oxLDL concentrations. Conclusion: Elevated expression of proinflammatory, proapoptotic and adhesion genes in subsets of PBMCs after ischemic stroke may contribute to an immunodepressive syndrome, possibly due to increased plasma oxLDL levels. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19258025
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