Biomedical subjects

S Klaus

Publications and source records attributed to S Klaus.

At least 19 recordsLinked to original sources

PubMed2006

Focussing cellular function. Metabolic monitoring in perioperative and Intensive Care Medicine.

In the clinical field microdialysis today is a routine technique for monitoring the chemistry of tissues and organs in physiological and pharmacological research on animals. In more than 10.000 papers on microdialysis research it is used to uncover physiological mechanisms and the influence of drugs in almost every organ of the body. Since the first papers describing microdialysis in the human brain microdialysis has become a technique for routine monitoring of energy metabolism especially in neurointensive care. This paper gives an account of the microdialysis technique describing its practical use and interpretation in monitoring energy metabolism and ischemia in different organs with respect to the field of perioperative and intensive care medicine. This article gives an overview over current results of clinical studies using microdialysis in critical care medicine and tries to focus on possible indications for clinical biochemical monitoring. However, despite numerous publications available microdialysis has not been shown to improve outcome of the patients yet.

Biomarkers↗

PubMed2006

Tyramine in the assessment of regional adrenergic function.

Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue with microdialysis probes in normal subjects. We measured glycerol concentrations to follow changes in lipolysis and monitored tissue perfusion with ethanol dilution. During perfusion with tyramine, dialysate glycerol concentration increased dose-dependently from 83+/-8 microM at baseline to 181+/-18 microM at 3.5 mM tyramine (p<0.001) followed by a fall down to 121+/-9 microM at 35 mM tyramine (p<0.001). Propranolol almost completely blocked this response. A similar lipolytic response was not observed in isolated human adipocytes. Dopamine <35 microM did not replicate the tyramine-induced lipolysis; however, dopamine >35 microM potently inhibited lipolysis. We conclude that tyramine-induced lipolysis is explained by a pre-synaptic mechanism. Tyramine applied through a microdialysis probe in concentrations up to 3.5 mM can be used to assess pre- and post-synaptic mechanisms regulating lipid mobilization.

Adipocytes↗

PubMed2006

High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.

Maternal low-protein diet during pregnancy is a risk factor for cardiovascular disease of the offspring in later life. The impact of high-protein diet during pregnancy on the cardiovascular phenotype of the offspring, however, is still unknown. We examined the influence of a high-protein diet during pregnancy and lactation on the renal, hemodynamic, and metabolic phenotype of the F1 generation. Female Wistar rats were either fed a normal protein diet (20% protein: NP) or an isocaloric high-protein diet (40% protein: HP) throughout pregnancy and lactation. At weaning, the offspring were fed with standard diet, and they were allocated according to sex and maternal diet to four groups: normal-protein male (NPm, n = 25), normal-protein female (NPf, n = 19), high-protein male (HPm, n = 24), high-protein female (HPf, n = 29). During the experiment (22 wk), the animals were characterized by repeated measurement of body weight, food intake, blood pressure, glucose tolerance, energy expenditure, and kidney function. At the end of the study period histomorphological analyses of the kidneys and weight measurement of reproductive fat pads were conducted. There were no differences in birth weight between the study groups. No influence of maternal diet on energy expenditure, glucose tolerance, and plasma lipid levels was detected. Blood pressure and glomerulosclerosis were elevated in male offspring only, whereas female offspring were characterized by an increased food efficiency, higher body weight, and increased fat pads. Our study demonstrates that a high-protein diet during pregnancy and lactation in rats programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.

Adaptation, Physiological↗

PubMed2005

Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation.

OBJECTIVE: To examine the antiobesity effect of epigallocatechin gallate (EGCG), a green tea bioactive polyphenol in a mouse model of diet-induced obesity. METHODS: Obesity was induced in male New Zealand black mice by feeding of a high-fat diet. EGCG purified from green tea (TEAVIGO) was supplemented in the diet (0.5 and 1%). Body composition (quantitative magnetic resonance), food intake, and food digestibility were recorded over a 4-week period. Animals were killed and mRNA levels of uncoupling proteins (UCP1-3), leptin, malic enzyme (ME), stearoyl-CoA desaturase-1 (SCD1), glucokinase (GK), and pyruvate kinase (PK) were analysed in different tissues. Also investigated were acute effects of orally administered EGCG (500 mg/kg) on body temperature, activity (transponders), and energy expenditure (indirect calorimetry). RESULTS: Dietary supplementation of EGCG resulted in a dose-dependent attenuation of body fat accumulation. Food intake was not affected but faeces energy content was slightly increased by EGCG, indicating a reduced food digestibility and thus reduced long-term energy absorption. Leptin and SCD1 gene expression in white fat was reduced but SCD1 and UCP1 expression in brown fat was not changed. In liver, gene expression of SCD1, ME, and GK was reduced and that of UCP2 increased. Acute oral administration of EGCG over 3 days had no effect on body temperature, activity, and energy expenditure, whereas respiratory quotient during night (activity phase) was decreased, supportive of a decreased lipogenesis and increased fat oxidation. CONCLUSIONS: Dietary EGCG attenuated diet-induced body fat accretion in mice. EGCG apparently promoted fat oxidation, but its fat-reducing effect could be entirely explained by its effect in reducing diet digestibility.

Animals↗

PubMed2005

PYY3-36 as an anti-obesity drug target.

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Animals↗

PubMed2005

Metabolic stress during hypoglycaemia clamp assessed by microdialysis.

AIM: Microdialysis allows the biochemical analysis of interstitial fluids as a bedside procedure. This technique is of interest to evaluate the glucose dependent metabolism in hypoglycaemic patients. It was the aim to perform subcutaneous and blood microdialysis during hypoglycaemic clamp experiments in 12 healthy young men to reveal basis data for critical care microdialysis practice. METHODS: The hyperinsulinaemic clamp was induced with a continuous infusion of 1.5 mU min(-1) kg(-1) insulin (H-insulin, Hoechst, Frankfurt, Germany). A 20% dextrose solution simultaneously was infused at a variable rate to control blood glucose levels. For hypoglycaemia blood glucose levels were reduced to 40 mg/dL for a 30 min period. Glucose, lactate, pyruvate and glycerol concentrations were semicontinuously measured. RESULTS: The absolute concentrations of glucose and glycerol in blood vs subcutaneous microdialysate were significant different during observation. Until the end of hypoglycaemia, glucose concentration in both compartments declined in parallel, followed by an increase thereafter. During the clamp the subcutaneous glycerol increased threefold, whereas blood glycerol rose with a delay of 15 min and increased only twofold. After the clamp in both compartments glycerol values normalized. The lactate-pyruvate-ratio persisted in normal range throughout the examination. CONCLUSIONS: In our experiment subcutaneous lipolysis increased faster and more profound than blood microdialysis. We propose the microdialysis technique as an additional monitoring tool in hypoglycaemia patients.

Adult↗

PubMed2005

High myocardial lactate concentration is associated with poor myocardial function prior to cardiopulmonary bypass.

AIM: This study was designed to analyse the relationship between myocardial lactate--determined by microdialysis--and hemodynamics during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: Twenty consecutive patients with coronary artery disease were enrolled for this prospective, observational study. Microdialysis measurements were performed in the apical region of the heart during periods of 15 to 20 min before, during, and after CPB; hemodynamics and plasma lactate concentrations were determined correspondingly. Correlation analysis revealed a relationship between myocardial lactate concentration and right ventricular ejection fraction at baseline (Spearman's r: 0.6; P=0.02). Patients were thus grouped according to the myocardial lactate concentration at baseline into a high-lactate group (2.5+/-0.7 mmol.l(-1), n=10) and low-lactate group (0.9+/-0.5 mmol.l(-1), n=10). RESULTS: Preoperative left ventricular ejection fraction was not different between the groups (high-lactate group: 53+/-16%; low-lactate group: 57+/-15%; P=n.s.) Patients in the high-lactate-group had a lower stroke volume index (P=0.005) and right ventricular ejection fraction (P=0.04) before, and higher central venous and pulmonary artery pressures (P<0.01) after CPB. Plasma lactate was significantly higher during CPB in the high-lactate-group (P<0.05). No correlation was observed between myocardial and plasma lactate. Six patients in the high-lactate but none in the low-lactate-group needed inotropic support after weaning from CPB (P=0.01). CONCLUSIONS: These data are suggestive of an association between subtle myocardial ischemia--detected by microdialysis--and perioperative myocardial dysfunction in patients undergoing CABG. The microdialysis technique may be a valuable adjunct for monitoring myocardial metabolism during cardiac surgery.

Aged↗

PubMed2004

Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

Animals↗

PubMed2003

Metabolic changes detected by microdialysis during endotoxin shock and after endotoxin preconditioning.

OBJECTIVE: Preconditioning with low doses of endotoxin has been shown to induce endotoxin hyporesponsiveness. The present study was designed to assess the metabolic response of various tissues during endotoxemia and after pretreatment with endotoxin. DESIGN: Controlled experimental animal study. SETTING: Research laboratory of a university hospital. MEASUREMENTS AND RESULTS: Ten pigs were randomly assigned to a control ( n = 5) or a treatment group ( n = 5), the latter receiving incremental doses of endotoxin 5-2 days prior the experiments. Apart from hemodynamics and oxygen transport variables, lactate, glucose, and glycerol were measured in muscle, subcutaneous fat, and hepatic tissue using microdialysis. Endotoxin was infused (1 micro g.kg.h) until the animals died. A significant increase in tissue lactate (eightfold) and glycerol (fivefold) was observed in the control animals. This effect was almost completely abolished in the endotoxin pretreated group. Endotoxin pretreatment had no significant effects on mean arterial pressure [56 (range 34-89) mmHg vs 70 (47-88) mmHg, n.s.] or cardiac output [4.8 (3.0-5.9) l/min vs 3.2 (2.1-4.2) l/min, n.s.], but significantly improved arterial pO(2) and pH ( P<0.05). Increase of oxygen extraction was higher in control animals [from 34% (range 24-47%) to 72% (range 61-79%)] compared to the pretreatment group [from 30% (range 22-42%) to 44% (range 34-50%), P<0.05]. Endotoxin pretreatment increased survival time from 5.3 h (5.0-5.8) to 8.0 h (7.0-8.5) ( P<0.05), respectively. CONCLUSIONS: Microdialysis monitoring revealed that endotoxin preconditioning ameliorates the increase in tissue metabolism during endotoxemia, accompanied by decreased systemic oxygen demand despite unchanged global hemodynamics.

Animals↗

PubMed2003

Application of Taylor vortices in hemocompatibility investigations.

BACKGROUND: Artificial organs, implants and extracorporeal circulation affect the physiological flow characteristics of blood as a liquid organ. These artificial systems consist of a wide variety of biomaterials with different geometries and, therefore, with their own flow properties. Secondary flow also occurs in extra--as well as in intracorporeal circulation. METHODS: In order to investigate the influence of vortical flow conditions a modified Taylor-Couette system was introduced. It consisted of two coaxial cylinders whose surfaces were the target of investigation. The annular gap was filled with donor blood shear and secondary flows were produced by rotating the inner cylinder. Platelet activation and protein adsorption were investigated as markers for thrombogenicity. RESULTS: At shear rates high enough to establish stable Taylor vortices (G > or = 550 s(-1)) significant differences between vortical Taylor flow and steady laminar flow were detected. At shear rates of G > or = 550 s(-1) laminar flow caused a significantly higher platelet drop and PF4 release when compared to Taylor vortex flow. Also protein adsorption per square unit was significantly higher for laminar flow. CONCLUSIONS: Based on the present data we conclude that vortical flow patterns lead to an accumulation of platelets and plasma proteins in the vortex center and therefore to a decreased probability of contact between platelets and material surfaces. It can be concluded that a preactivation of the platelets circulating in extracorporeal circuits can be manifested downstream in other geometrical configurations and flow conditions.

Adsorption↗

PubMed2003

Clinical biochemical tissue monitoring during ischaemia and reperfusion in major vascular surgery.

BACKGROUND: Major vascular surgery with aortic cross-clamping is associated with temporary ischaemia of the lower limb due to lack of tissue blood flow. The present study was designed to determine if the short-term changes in cellular metabolism occurring during this situation can be detected by subcutaneous microdialysis. It was also hoped to ascertain if this new technique is useful in the continuous bedside monitoring of metabolism during aortic surgery. METHODS: In a controlled clinical study 20 patients undergoing elective aortic surgery were monitored using microdialysis probes that were inserted in the subcutaneous tissue of the left lower limb and a non-ischaemic region (shoulder). Interstitial fluid was obtained and the concentrations of glucose and lactate during lower limb ischaemia and during reperfusion were measured and compared with concentrations observed in fluid obtained from the non-ischaemic control tissue. RESULTS: Circulatory occlusion caused an immediate and significant decrease in the glucose/lactate ratio from 3.1+/-1.3 to 0.48+/-0.5 (P<0.05) that returned to preocclusion values within 2 h of commencing reperfusion. CONCLUSION: We suggest that microdialysis may be used both to assess acute changes in tissue metabolism during ischaemic periods and also to act as an additional tool for the detection of peri-operative acute variations in limb blood flow.

Aged↗

PubMed2002

Habitual fat intake and basal fat oxidation in obese and non-obese Caucasians.

OBJECTIVE: To examine the relationship between habitual fat intake and basal fat oxidation in obese and non-obese Caucasian men and women. METHODS: Habitual fat intake was assessed by 7-day weighed dietary records and resting fat oxidation was determined after an overnight fast in 132 weight stable non-diabetic subjects (38 males, 94 females). All subjects were characterized for weight, height, waist-to-hip ratio, physical activity, plasma glucose and insulin response to an oral glucose load, plasma catecholamine and leptin levels. Under-reporters, defined according to plausibility of the relationship between energy expenditure and energy intake, were excluded from the analyses. RESULTS: The mean age was 53.1+/-10.6 y (19-72 y) and mean body mass index (BMI) was 30.7+/-5.8 kg/m(2) (19.4-45.8 kg/m(2)). Sixty-eight subjects were obese (BMI>30 kg/m(2)). Univariate regression analysis revealed a significant, albeit modest, relationship between absolute fat intake and BMI (r(2)=0.06; P<or=0.05) but not between fat intake and fat mass (r(2)=0.026; P=0.08). However, multiple regression analysis revealed significant effects of body fat mass (FM) and sex on basal fat oxidation (bFO) explaining 33% of the variation of bFO (P<or=0.0001; radical s.e.=18.0 g/24 h). In univariate regression analysis, habitual fat intake was significantly related to adjusted fat oxidation, explaining 12% of the variation (P<or=0.0001; radical s.e.=11.7 g/24 h). CONCLUSION: Habitual fat intake has a significant, albeit modest, effect on basal fat oxidation, even when adjusted for sex and body FM. The rather modest effect of habitual fat intake on fat oxidation may in part explain the increased propensity to gain FM on a high-fat diet.

Adult↗

PubMed2002

In vitro blood damage by high shear flow: human versus porcine blood.

Devices for modern heart support are minimized to reduce priming blood volume and contact area with foreign surfaces. Their flow fields are partly governed by very high velocity gradients. In order to investigate blood damage, porcine and human blood was passed through a narrow Couette type shear gap applying defined high shear rates within the typical range for devices such as blood pumps or artificial heart valves (gamma = 1800/s to 110,000/s for 400 ms). Traumatization profiles of both blood species were recorded in terms of hemolysis and platelet count. Sublethal damage in terms of platelet (PF4) and complement activation (C5a) was additionally measured for human blood. Results for porcine and human blood were very similar. Hemolysis was not started until critical shear rates of about 80,000/s. Impact on platelets was severe with drops in cell count of up to 65% (at gamma = 55,000/s to 110,000/s) likely to set stronger limits to the design layout of devices than hemolysis. Concentrations of PF4 and C5a clearly increased with shear rate exhibiting stronger gradients where hemolysis started. Due to the similar results of porcine and human blood for hemolysis and platelet drop, porcine blood seems to be suitable for device testing. Selection of blood species would thus depend on handling, availability and analysis demands.

Animals↗

PubMed2001

Differential gene expression in white and brown preadipocytes.

White (WAT) and brown (BAT) adipose tissue are tissues of energy storage and energy dissipation, respectively. Experimental evidence suggests that brown and white preadipocytes are differentially determined, but so far not much is known about the genetic control of this determination process. The aim of this study was to identify differentially expressed genes involved in brown and white preadipocyte development. Using representational difference analysis (cDNA RDA) and DNA microarray screening, we identified four genes with higher expression in white preadipocytes (three different complement factors and delta-6 fatty acid desaturase) and seven genes with higher expression levels in brown preadipocytes, of which three are structural genes implicated in cell adhesion and cytoskeleton organization (fibronectin, alpha-actinin-4, metargidin) and four that might function in gene transcription and protein synthesis (vigilin, necdin, snRNP polypeptide A, and a homolog to human hepatocellular carcinoma-associated protein). The expression profile of these genes was analyzed during preadipocyte differentiation, upon beta-adrenergic stimulation, and in WAT and BAT tissue in vivo compared with references genes such as peroxisome proliferator-activated receptor-gamma (PPARgamma), uncoupling protein 1 (UCP1), cytochrome c oxidase.

Adipocytes↗

PubMed2001

Effect of the beta(3)-adrenergic agonist Cl316,243 on functional differentiation of white and brown adipocytes in primary cell culture.

We investigated the effect of the specific beta(3)-adrenergic receptor agonist CL 316,243 (CL) on proliferation and functional differentiation of the Siberian hamster (Phodopus sungorus) white and brown preadipocytes in primary cell culture. Proliferation of both white and brown preadipocytes was stimulated by a general beta-adrenergic agonist (isoproterenol) but not by CL. Lipolysis of differentiated white and brown adipocytes was stimulated similarly by CL with maximum effect at 10 nM. Thermogenic properties of cells were assessed by immunodetection of UCP-1, the brown adipocyte specific uncoupling protein, and measurement of cytochrome c oxidase (COx) activity as an index of mitochondrial capacity. UCP-1 content was largely increased by CL in BAT but not in WAT cultures. Basal UCP-2 mRNA levels were similar in WAT and BAT cultures and increased by both CL and isoproterenol. COx activity of BAT cultures was twice as high as that of WAT cultures but in neither cell culture system could it be increased by beta-adrenergic stimulation. We suggest (i) that white and brown preadipocyte proliferation is increased in vitro via beta1 or beta(2), but not beta(3)-adrenergic pathways, (ii) that white and brown preadipocytes represent different cell types, and (iii) that in vitro beta-adrenergic stimulation it is not sufficient to induce complete thermogenic adaptation of brown adipocytes.

Adipocytes↗

PubMed2001

Leptin-induced nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei involved in body weight regulation.

Leptin is involved in the hypothalamic control of food intake and body weight. Fos immunohistochemistry has been used to functionally map leptin target neurons involved in these regulatory processes. However, only a subset of hypothalamic neurons expressing the long form of the leptin receptor (Ob-Rb) also coexpress the neuronal activation marker Fos after leptin stimulation. To functionally map all leptin target neurons, regardless of whether leptin-mediated neuronal activation or inhibition occurs, we immunohistochemically investigated the leptin-induced nuclear translocation of the signal transducer and activator of transcription molecule STAT3, which represents a crucial step in the regulation of leptin-dependent gene expression. As proven by colocalization studies with the nuclear 4',6-diamidino-2-phenylindole dilactate stain, intracerebroventricular leptin treatment, but not intracerebroventricular application of pyrogen-free saline, induced a time-dependent nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei, with strong nuclear STAT3 signals detectable in the arcuate nucleus, the lateral hypothalamus, and the ventromedial and dorsomedial hypothalamic nuclei. This leptin-induced STAT3 translocation pattern proved to be distinct from that induced by interleukin-6, another cytokine using STAT3 in its signaling pathway. Combined immunohistochemical STAT3 and Fos detection after leptin treatment revealed a higher number of STAT3-positive than Fos-positive cell nuclei in the aforementioned hypothalamic structures and showed that Fos immunoreactivity colocalized only in a subset of all leptin-responsive STAT3 nuclei. These results suggest that the detection of nuclear STAT3 immunoreactivity represents a new neuroanatomical tool to functionally map central leptin actions. They further support the importance of ventrally located caudal hypothalamic structures representing the main leptin targets involved in body weight regulation.

Animals↗

PubMed2001

Historical biogeography and a mitochondrial DNA phylogeny of grouse and ptarmigan.

We sequenced 2690 nucleotides of mitochondrial DNA (mtDNA) including the entire control region (CR), partial 12S and 16S ribosomal RNAs, NADH dehydrogenase subunit 2, and cytochrome b genes from representatives of all the 17 living species of grouse and ptarmigan (Aves; Galliformes; subfamily Tetraoninae). Substitution rates and phylogenetic signals were variable among genes, with the CR being more informative than protein-coding and rRNA genes. Phylogenetic trees, computed with the CR or the concatenated sequences, indicate that: (1) genus Bonasa is monophyletic and basal within the subfamily, (2) all the other currently recognized genera of Tetraoninae are monophyletic, except Dendragapus; (3) D. obscurus is related to Centrocercus urophasianus and divergent from former D. canadensis and D. falcipennis, which, accordingly, may be ascribed to the distinct genus Falcipennis; (4) Tympanuchus, Dendragapus, and Centrocercus form a clade comprising taxa distributed exclusively in North America; and (5) the North American species of Bonasa (B. umbellus) and Lagopus (L. leucurus) are basal to their Eurasian and Holarctic congeneric species. These findings, and a dispersal-vicariance analysis, support a North American origin of the subfamily and of all the genera of Tetraoninae, with the possible exception of Tetrao. Present species distributions might have been attained by at least three dispersal events from North America to Eurasia, involving the ancestors to Palearctic Bonasa, the ancestors to circumpolar Lagopus mutus/L. lagopus, and the clade leading to Tetrao/Falcipennis. According to a "standard calibration" of the mtDNA molecular clock (2% sequence divergence per million years), Bonasa split about 5-6 million years ago, the other genera diverged during the upper Pliocene, and most of the congeneric species with North American and Eurasian distributions (Bonasa, Lagopus, and Falcipennis) originated during the lower Pleistocene, well before the last interruption of the Beringian land bridge.

Animals↗

PubMed2001

Early postoperative thrombolytic therapy after laparotomy.

Early postoperative pulmonary embolism due to deep venous thrombosis has been reported to be associated with a mortality rate of approximately 46%. Administration of thrombolytic drugs is relatively contraindicated during this period so that conservative or surgical treatment can be considered as a therapeutical intervention. We report the case of a 68-year-old male patient who was subjected to systemic thrombolytic therapy due to pulmonary embolism on the first day after laparatomy.

Aged↗