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Biomedical subjects

S Klaus

Publications and source records attributed to S Klaus.

At least 37 records · Page 2Linked to original sources
PubMed2001

Metabolic and hemodynamic response of adipose tissue to angiotensin II.

OBJECTIVE: Recent studies have revealed the presence of a local renin-angiotensin system in adipose tissue. To examine the possible role of this system in adipose tissue, we performed microdialysis studies on the effect of angiotensin II (Ang II) on blood flow and metabolism in abdominal subcutaneous adipose tissue (aSAT) and femoral subcutaneous adipose tissue (fSAT) in young healthy men. RESEARCH METHODS AND PROCEDURES: Using the microdialysis technique, two different protocols were run perfusion with Ringer's solution + 50 mM ethanol with the subsequent addition of 125, 250, and 500 microg/liter Ang II (n = 8) and Ringers's solution + 50 mM ethanol with the subsequent addition of isoproterenol (1 microM) alone and in combination with 500 microg/liter Ang II (n = 6). Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured for estimating blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. RESULTS: Perfusion with Ang II resulted in a dose-dependent decrease in blood flow (fSAT > aSAT), lipolysis (fSAT > aSAT), and glucose uptake (fSAT = aSAT). Isoproterenol increased blood flow and lipolysis at both sites and those effects could be returned to baseline values by the addition of Ang II in aSAT but not fSAT. DISCUSSION: In conclusion, our data indicate that in addition to its well-known vasoconstricting effect, Ang II inhibits lipolysis in adipose tissue, whereby femoral fat depots seem to be more sensitive to this effect than abdominal depots.

Adipose Tissue↗
PubMed2001

Assessment of hemolysis related quantities in a microaxial blood pump by computational fluid dynamics.

A computational assessment or even quantification of shear induced hemolysis in the predesign phase of artificial organs (e.g., cardiac assist devices) would largely decrease efforts and costs of design and development. In this article, a general approach of hemolysis analysis by means of computational fluid dynamics (CFD) is discussed. A validated computational model of a microaxial blood pump is used for detailed analysis of shear stress distribution. Several methods are presented that allow for a qualitative assessment of shear stress distribution and related exposure times using a Lagrangian approach and mass distribution in combination with shear stress analysis. The results show that CFD offers a convenient tool for the general assessment of shear-induced hemolysis. The determination of critical regions and an estimation of the amount of blood subject to potential damage in relation to the total mass flow are shown to be feasible. However, awareness of limitations and potential flaws in CFD based hemolysis assessments is crucial.

Computational Biology↗
PubMed2001

In situ metabolic and hemodynamic response to dexfenfluramine in white adipose tissue of rats.

Serotonergic neurons are included in the regulation of eating behavior and energy metabolism. Dexfenfluramine (DF), a serotonin releaser and reuptake inhibitor, is known to reduce food intake and body weight and to improve the metabolic profile of obese subjects with and without metabolic complications such as type 2 diabetes. Due to cases of valvular heart diseases, DF was withdrawn from the market in 1997. However, serotonergic drugs are still used in clinical practice. We studied the hemodynamic and metabolic changes induced by in situ perfusion of inguinal subcutaneous adipose tissue (SAT) of normal-weight rats with either 1 microM isoproterenol (IP) or 5 microM DF using the microdialysis technique. Perfusion of SAT with IP resulted in an increase in blood flow (+25%) and lipolysis (+35%) when compared to baseline. In contrast to that, perfusion of SAT with DF resulted in a decrease in blood flow (-25%) and lipolysis (-35%). Additionally, dialysate glucose was decreased and dialysate lactate was increased during perfusion with DF, indicating stimulation of glucose uptake and the glycolytic pathway. It is concluded that DF reduces blood flow and lipolysis whereas it stimulates the glycolytic pathway in SAT and that this could contribute to the positive metabolic outcome, i.e., lowered blood lipids and fat mass of DF-treated obese subjects.

Adipose Tissue↗
PubMed2001

Effects of angiotensin II and the AT(1) receptor antagonist losartan on the renal excretion of urodilatin.

BACKGROUND: The precise mechanisms regulating the natriuretic peptide urodilatin (ANP-95-126) remain to be defined. Renal excretion of urodilatin (U(URO)V) has been shown to be modified by variations in plasma sodium and renal perfusion pressure. This suggests a relationship between urodilatin and the renin-angiotensin system. METHODS: We investigated the effects of angiotensin II (AII, 0.1 nmol/l) and the AT(1) receptor antagonist losartan (LS, 1 micromol/l) on U(URO)V and renal function in isolated rat kidneys perfused for 180 min in a closed circuit system. A further series employing a vasoconstricting concentration of endothelin-1 (ET-1, 0.01 nmol/l) was performed to explore the effects of vasoconstriction and glomerular filtration rate (GFR) on U(URO)V. RESULTS: Urine flow (UV) and urinary sodium excretion (U(Na)V) decreased and renal vascular resistance (RVR) increased after treatment with AII (n = 5) in comparison with a control group (n = 6; p < 0.05). Treatment with LS (n = 5) and AII+LS (n = 5) had no significant effect on these parameters. GFR decreased after AII (p < 0.05) and was not significantly altered by other interventions. U(URO)V decreased after AII (p < 0.05) and was comparable to the control group after LS and AII+LS. ET-1 (n = 5) induced a significant increase in RVR and decreased UV and U(Na)V (p < 0.05). Point-to-point analysis revealed that the ET-1-induced vasoconstriction and the subsequent decrease in GFR had no effect on U(URO)V. CONCLUSIONS: This suggests that vasoconstrictory concentrations of AII decrease U(URO)V in the isolated perfused rat kidney. The lack of effect of ET-1 on U(URO)V suggests that the AII-induced alterations in urodilatin excretion cannot be explained by vasoconstriction per se.

Angiotensin II↗
PubMed2001

Effects of posture and positive airway pressure on plasma atrial natriuretic peptide and renal urodilatin excretion.

AIMS: To determine whether a coupling of plasma atrial natriuretic peptide (ANP) and renal excretion of urodilatin (U(URO)V)--recently observed during supraphysiological concentrations of ANP--may also be detected during moderate changes in ANP levels, i.e. if ANP is increased by supine positioning and decreased by applying continuous positive airway pressure (CPAP). MATERIAL AND METHODS: We investigated 10 healthy male volunteers, orally hydrated with 200 ml water/h, in a randomized crossover study for periods of 1 hour following 2 protocols. Protocol 1: sitting and supine position. Protocol 2: sitting with and without a CPAP of 8 cm H2O. RESULTS: ANP increased ongoing from the sitting to the supine position (SIT-1: 13.2 +/- 4.7; SUP: 27.9 +/- 21.9 pg x ml(-1); p < 0.01) during protocol 1 and decreased after the onset of CPAP in seated subjects (SIT-2: 16.9 +/- 7.9; SIT-CPAP: 13.9 +/- 6.5 pg x ml(-1); p < 0.05) during protocol 2. U(URO)V decreased slightly, but not significantly, during protocol I (SIT-1: 63.9 +/- 21.7; SUP: 49.9 +/- 13.2 fmol x min(-1)) and remained unchanged after institution of CPAP in the sitting position (SIT-2: 68.5 +/- 25.2; SIT-CPAP: 68.5 +/- 50.2 fmol x min(-1)). Correlation analysis revealed no relationship between plasma ANP and U(URO)V. CONCLUSIONS: Moderate variations in the levels of ANP in water-loaded volunteers do not induce parallel changes in the urinary excretion of urodilatin.

Adult↗
PubMed2001

[Microdialysis for metabolic monitoring during septicemia].

Currently, metabolic changes in ICU patients in critical states are determined mainly by indirect laboratory parameters (e.g. blood lactate). Microdialysis is a new means of performing metabolic monitoring that permits organ-specific objectification on the basis of interstitial fluid samples. Continuous endotoxin infusion was administered to 10 female pigs and, in addition to hemodynamic monitoring, lactate and glycerol in the subcutaneous, intramuscular and hepatic tissue were measured by microdialysis. The interstitial concentrations of lactate and glycerol rose significantly under endotoxaemia and showed an earlier increase than blood lactate levels. Microdialysis is simple to apply, appears to be a suitable means of obtaining important information about cellular metabolic changes in different tissues of the critically ill patient, and can detect subtle changes that laboratory parameters can identify only later and incompletely.

Animals↗
PubMed2000

Pentoxifylline improves circulatory and metabolic recovery after cardiopulmonary resuscitation.

BACKGROUND: To evaluate the effectiveness of a bolus application of pentoxifylline (PTXF) at the beginning of CPR in a standardized resuscitation animal model. METHODS AND RESULTS: In a laboratory model of cardiac arrest, 12 Wistar rats (382-413 g) were randomized into two groups. Both groups underwent 4 min of cardiopulmonary arrest induced by a transthoracic application of a fibrillating current of 10 mA. At the beginning of CPR, group one (n=6) received a bolus injection of 10 mg kg(-1) body weight PTXF versus sodium chloride in group two (controls: n=6). All animals developed a severe lactate acidosis during and after CPR but in PTXF treated animals acid-base values returned to baseline pattern. During return of spontaneous circulation (ROSC) in the PTXF group lactate concentration decreased from 13.4+/-2.1 to 1.9+/-0.7 mmol l(-1) within 60 min (P<0.01). In control animals, lactate values remained high (10.8+/-3.5 by 60 min, P<0.01). After bolus injection of PTXF pH increased from 6.93+/-0.06 to 7.29+/-0.13 within 60 min of ROSC versus 6.85+/-0.05 to 6.97+/-0.23 in sodium chloride treated animals (P<0.01). Within 5 min of ROSC, PTXF treated animals achieved higher oxygenation values (PTXF P(a)O(2)=216.9+/-62.5 mmHg, control 132. 2+/-15.1 mmHg, P<0.01). CONCLUSIONS: Administration of PTXF at the beginning of CPR improved macrocirculation, acid-base status and arterial oxygenation.

Acid-Base Imbalance↗
PubMed2000

Kinetic analysis of the thermic effect of food and its relationship to body composition in humans.

The course of energy expenditure after a meal can vary widely with regard to the slope of onset, amplitude, and duration of the thermic effect. The aim of the present study was to explore the relationship between the thermic effect of food (TEF), as characterized by kinetic analysis of postprandial energy expenditure, body composition, and variables related to the metabolic syndrome including central obesity, hypertension, and glucose tolerance. A total of 181 men and women (body mass index [BMI] range, 19.4 to 52.2 kg/m2) were characterized for body composition, blood pressure, oral glucose tolerance, and energy expenditure after a test meal. Energy expenditure, as measured by indirect calorimetry, was analyzed over a 6-hour period by 3-parameter curve fitting using equations derived from kinetics describing a biphasic reaction involving 2 consecutive first-order reactions (A-->B-->C). Apart from total thermic effect of food (TEFk), the curve also provided an estimate of time of peak (Tp) and amplitude of peak (Ap) for each subject. Multiple stepwise regression analysis with TEFk, Ap, and Tp as dependent variables showed significant effects of sex, age, body weight, body fat, beta-blockade, and body composition on TEF curve parameters. Cluster analysis based on Tp shown 2 distinct clusters with significant differences in age and body fat mass. This study shows that kinetic analysis of postprandial energy expenditure can be used to examine the determinants of the time course of the thermic effect of food in man.

Adult↗
PubMed2000

Changes of interstitial fluid volume in superficial tissues detected by a miniature ultrasound device.

We evaluated the changes of tissue layer thickness in circumscribed superficial tissue areas with a 10-MHz A-mode and a 20-MHz B-mode ultrasound device under alterations in body posture and plasma volume to detect fluid shifts between the different compartments. In 20 male volunteers, we measured tissue thickness by A mode and corium and subcutis thickness by B mode at the forehead before and 30 min after three procedures: change from upright to supine position (P1); change from upright to 30 degrees head-down-tilt position (P2); infusion of 10 ml/kg body wt of Ringer solution (P3). We found a significant correlation between baseline tissue thickness and the sum of corium and subcutis thicknesses (r = 0.75, P < 0.01). The changes of body posture and plasma volume resulted in significant increases of tissue thickness (P1, 2.9%; P2, 11.6%; P3, 5.8%) and corium thickness (P1, 4.7%; P2, 8.1%; P3, 9.1%) but not of the sum of chorium and subcutis thicknesses. We conclude that fluid shifts from the intravascular to the extravascular compartment are detectable by evaluating corium thickness with a B-mode, or more easily tissue thickness with an A-mode, ultrasound device.

Adult↗
PubMed2000

Resting metabolic rate and substrate use in obesity hypertension.

There is substantial evidence that obesity is a prime risk factor for the development of hypertension. Although hyperinsulinemia and an increased activity of the sympathetic nervous system have been implicated in the pathogenesis of "obesity hypertension," their effects on energy metabolism have not been studied thus far. In the present study, we therefore examined resting metabolic rate (RMR) and basal substrate oxidation in subjects with obesity and obesity-related hypertension. A total of 166 subjects were characterized for RMR and basal substrate use through indirect calorimetry. Blood pressure was measured at rest and with 24-hour ambulatory monitoring. Blood samples were collected for the measurement of plasma catecholamines, leptin, and the insulin response to an oral glucose load. In our study population, 116 subjects were defined as hypertensive and 91 were defined as obese. Hypertensive patients under beta-adrenergic blockade (n=42) had a significantly lower RMR than did patients without beta-blockade (P<0. 05) and were therefore excluded from further analyses. Univariate regression analysis revealed a significant relationship between RMR and body fat mass, as well as body fat-free mass, in both groups. Compared with obese normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels, and an increased insulin response to oral glucose (P<0.01). Together, these findings are compatible with the idea that chronic neurogenic and metabolic adaptations related to obesity may play a role in the development of obesity hypertension in susceptible individuals.

Adult↗
PubMed1998

DNA sequence and muscle-specific expression of human sarcosin transcripts.

We have characterized two abundant human cDNAs which, through Northern hybridization analysis, are selectively expressed in human sarcomeric muscle. DNA sequencing was performed and the two cDNAs were found to share sequence identity, with the exception of a 3' UTR extension present on the longer transcript. Our data suggest that the two transcripts are generated through alternative use of two poly(A) addition signals. The cDNAs encode a large open reading frame encompassing at least 435 codons. Through sequence comparisons, both at the DNA and predicted amino acid sequence level, we have been unable to find significant sequence similarity to any other characterized sequence. Consequently, we have termed this novel human sequence sarcosin. Although novel, Southern hybridization analysis demonstrated that the sarcosin sequence has been conserved in several mammalian species.

Amino Acid Sequence↗
PubMed1998

Hemodynamics of stroke patients under therapy with low molecular weight hydroxyethyl starch.

In stroke penumbra perfusion depends passively on hemodynamics. So far hemodynamic effects of low molecular weight hydroxyethylstarch (HES) has not been investigated. Ten stroke patients received hypervolemic HES therapy. Cardiac output and heart rate were monitored using the bioimpedance method, blood pressure by conventional measurement. The Scandinavian Stroke Scale assessed clinical outcome. Circadian cardiac output changes were measured in 20 controls. Patients' cardiac output increased after the loading dose (5.3 +/- 1.4 l min(-1) to 6.5 +/- 1.7 l min(-1), p < 0.01), fluctuating then between 5 and 7 l min(-1) without nocturnal decrease. Beside an initial increase, the heart rate showed, like blood pressure, no remarkable changes. The Scandinavian Stroke Scale score did not change significantly. The controls showed a circadian cardiac output fluctuation (2.00 am, 5.3 +/- 0.3 l min(-1); 8.30 am, 8.1 +/- 0.6 l min(-1). Our patients showed a hemodynamic and clinical stabilization under therapy with low molecular weight HES. The physiological nocturnal decrease of cardiac output and blood, which might cause clinical deterioration in stroke patients, was avoided.

Adult↗
PubMed1998

Efficacious topical treatment for murine cutaneous leishmaniasis with ethanolic formulations of amphotericin B.

The goal of the present study was to evaluate the antileishmanial effects of topically applied lipid-based formulations containing amphotericin B (AmB) in CBA mice as a model for human cutaneous leishmaniasis. Such treatment, if efficacious, is expected to be superior to systemic treatments since, by acting in a localized manner, it will require lower, and therefore less toxic, drug dosages. Three preparations of AmB complexed to polar lipids were tested: Fungizone (mixed micelles composed of AmB and deoxycholate), Amphocil (AmB and cholesteryl sulfate complex), and ABPLC (AmB and phospholipid complex). All these formulations killed parasites in vitro with similar efficacies but were ineffective when they were applied topically. However, Amphocil and ABPLC, but not Fungizone, when dispersed in an aqueous solution containing 5 to 25% ethanol, induced a statistically significant improvement in lesion size from week 2 or 3 onward (a total of 15 mg of AmB per kg of body weight was applied over 3 weeks). AmB biodistribution measurements following topical application of Amphocil, determined by high-pressure liquid chromatography, showed that AmB was detectable in the skin but not in the internal organs. Application of at least 10 times more drug was necessary to obtain detectable levels of AmB in the internal organs. After application of therapeutic doses of ABPLC, very low levels of AmB were detected in the internal organs. These experiments show for the first time that AmB administered topically as a complex either with cholesteryl sulfate or with phospholipids and in the presence of ethanol can penetrate the skin and kill sensitive organisms in a localized manner by using very low total drug concentrations.

Administration, Topical↗
PubMed1998

Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature.

We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and development of obesity and insulin resistance (Lowell, B. B., S. V. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. Kozak, and J. S. Flier. Nature 366: 740-742, 1994). In adult UCP-DTA mice, we measured food intake and food assimilation, locomotor activity, metabolic rate, and body temperature in comparison to control animals. No differences could be observed in food intake or assimilation and locomotor activity. Weight-specific metabolic rates at temperatures between 20 and 37 degrees C, however, were consistently lower in transgenic mice. Continuous telemetric recording of core body temperature showed that transgenic mice displayed a downshift in body temperature levels of approximately 0.9 degree C. In summary, we provide evidence that attenuated body temperature levels alone can be responsible for development of obesity and that BAT thermogenesis is a major determinant of body temperature levels in rodents.

Absorption↗
PubMed1997

Physiological approach to maturation of brown adipocytes in primary cell culture.

Molecular and metabolic aspects of differentiation of brown adipocytes of the Djungarian hamster (Phodopus sungorus) were studied in primary culture. Expression of uncoupling protein and lipoprotein lipase were investigated by Western and Northern blotting and indirect immuno-fluorescence microscopy. The activity of 5'-deiodinase type II was determined by a radioactive enzyme assay. Activity of cytochrome-c-oxidase and cell respiration rates were measured with a Clark electrode. We evaluated functional differences of developmental stages by measuring the reaction to beta-adrenergic stimulation throughout the differentiation process. The results show that differentiation of hamster brown adipocytes is an at least two-step development with physiologically discriminable cell types. Generation of triiodothyronine (T3) from thyroxine by activation of the 5'deiodinase occurs in immature brown adipocytes and is mediated primarily by beta1- rather than beta3-adrenergic receptors. The thermogenic capacity is subsequently increased in mature brown adipocytes. beta-Adrenergic receptor stimulation increases UCP expression of mature adipocytes but is not able to recruit new brown adipocytes.

Adipocytes↗
PubMed1997

Functional differentiation of white and brown adipocytes.

Adipose tissue plays an important role in mammalian energy equilibrium not only as a lipid-dissipating, i.e. energy-storing, tissue (white adipose tissue), but also as an energy-dissipating one (brown adipose tissue). Brown adipocytes have the ability of facultative heat production due to a unique mitochondrial protein, the uncoupling protein (UCP). Differentiation of white and (to a lesser extent) brown adipocytes has been studied in different cell culture systems, which has led to the identification of external inducers, second messenger pathways and transcription factors involved in adipocyte differentiation. Functional differentiation of white adipocytes implies adipose conversion, whereas in brown adipocytes it insinuates additionally the development of a thermogenic function. This review discusses recent advances in the elucidation of the pathways responsible for, and the molecular bases of, adipose conversion on the one hand and development of the thermogenic properties of brown adipocytes on the other.

Adipocytes↗
PubMed1996

Short photoperiod reduces leptin gene expression in white and brown adipose tissue of Djungarian hamsters.

Leptin gene expression in white (WAT) and brown adipose tissue (BAT) of the Djungarian hamster (Phodopus sungorus) was analyzed during seasonal acclimatization. Leptin gene expression in WAT was markedly reduced during winter, independent of changes in environmental temperature. Exposure to artificial short photoperiod also decreased leptin gene expression in WATas well as in BAT. Although specific leptin gene expression was lower in BAT, total depot expression was as high as in WAT depots, due to higher RNA content of BAT. Our results indicate that there is significant leptin synthesis in brown fat and that leptin might be involved in photoperiod mediated seasonal adaptations of mammals independent of food deprivation or overfeeding.

Adipose Tissue↗