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Biomedical subjects

M Stohrer

Publications and source records attributed to M Stohrer.

12 recordsLinked to original sources
PubMed2004

Effect of exercise on the mobilization of retinol and retinyl esters in plasma of sled dogs.

Fasting dogs do transport vitamin A (VA) in plasma not only as retinol but predominantly as retinyl esters. Contrary to retinol, nothing is known concerning the effects of athletic performance on plasma retinyl ester concentrations. The aim of this study was therefore to examine whether physical stress because of exercise and modification of the oxidative stress by supplementation of alpha-tocopherol influences the concentrations of retinol and retinyl esters in plasma of sled dogs. The study was carried out on 41 trained adult sled dogs, which were randomly assigned into two groups. One group (19 dogs) was daily substituted with 50 mg dl-alpha-tocopheryl acetate per kilogram body weight and the control group (22 dogs) was maintained on a basal diet during 3 months prior to exercise. The plasma concentrations of retinol, retinyl esters, alpha-tocopherol and triglycerides were measured immediately before, directly after and 24 h after exercise. The supplementation of alpha-tocopheryl acetate had no effect on plasma retinol and retinyl ester concentrations at any measurement time point. However, retinyl ester levels doubled in the non-supplemented group immediately after the race (p < 0.001), whereas in the supplemented group similar high levels were observed not until 24 h post-racing (p < 0.001). The high levels of retinyl esters were paralleled to some extent by an increase in plasma triglyceride concentrations, which were significantly higher 24 h post-racing than immediately before (p < 0.001) and after exercise (p < 0.001) in both groups. The increase in retinyl ester concentrations might be indicative of their mobilization from liver and adipose tissue. Whether plasma retinyl esters can be used as an indicator for the extent of nutrient mobilization during and post-exercise in sled dogs remains to be elucidated.

Adipose Tissue↗
PubMed2001

Computer prediction of human thermoregulatory and temperature responses to a wide range of environmental conditions.

A mathematical model for predicting human thermal and regulatory responses in cold, cool, neutral, warm, and hot environments has been developed and validated. The multi-segmental passive system, which models the dynamic heat transport within the body and the heat exchange between body parts and the environment, is discussed elsewhere. This paper is concerned with the development of the active system, which simulates the regulatory responses of shivering, sweating, and peripheral vasomotion of unacclimatised subjects. Following a comprehensive literature review, 26 independent experiments were selected that were designed to provoke each of these responses in different circumstances. Regression analysis revealed that skin and head core temperature affect regulatory responses in a nonlinear fashion. A further signal, i.e. the rate of change of the mean skin temperature weighted by the skin temperature error signal, was identified as governing the dynamics of thermoregulatory processes in the cold. Verification and validation work was carried out using experimental data obtained from 90 exposures covering a range of steady and transient ambient temperatures between 5 degrees C and 50 degrees C and exercise intensities between 46 W/m2 and 600 W/m2. Good general agreement with measured data was obtained for regulatory responses, internal temperatures, and the mean and local skin temperatures of unacclimatised humans for the whole spectrum of climatic conditions and for different activity levels.

Acclimatization↗
PubMed2000

Oncotic pressure in solid tumors is elevated.

Oncotic and hydrostatic pressure differences control the movement of fluid and large molecules across the microvascular wall of normal and tumor tissues. Recent studies have shown that the interstitial fluid pressure in tumors is elevated and is approximately equal to the microvascular pressure. Whereas oncotic pressure in blood plasma of various species is known, no data are available on the oncotic pressure in the interstitial space of tumors. We hypothesize that because of the leaky nature of tumor vessels, oncotic pressure in tumor interstitium should be close to that in plasma. To this end, we first developed a chronic wick method for the direct measurement of oncotic pressures in the interstitial fluid of tumors grown in mice. We found interstitial oncotic pressures in four human tumor xenografts to be higher than in s.c. tissue and comparable to that in plasma [rhabdomyosarcoma (RD), 24.2+/-4.7; squamous cell carcinoma (FaDu), 19.9+/-1.9; small cell lung carcinoma (54A), 21.1+/-2.8; colon adenocarcinoma (LIS174T), 16.7+/-3.0 mm Hg; s.c. tissue, 8.2+/-2.3; plasma, 20.0+/-1.6 mm Hg]. These results support our hypothesis that the oncotic pressure difference across the tumor microvascular wall is low. The high oncotic pressure in tumors is consistent with the elevated interstitial fluid pressure, and it contributes to the suboptimal delivery of large therapeutic agents to neoplastic cells.

Animals↗
PubMed1999

A computer model of human thermoregulation for a wide range of environmental conditions: the passive system.

A dynamic model predicting human thermal responses in cold, cool, neutral, warm, and hot environments is presented in a two-part study. This, the first paper, is concerned with aspects of the passive system: 1) modeling the human body, 2) modeling heat-transport mechanisms within the body and at its periphery, and 3) the numerical procedure. A paper in preparation will describe the active system and compare the model predictions with experimental data and the predictions by other models. Here, emphasis is given to a detailed modeling of the heat exchange with the environment: local variations of surface convection, directional radiation exchange, evaporation and moisture collection at the skin, and the nonuniformity of clothing ensembles. Other thermal effects are also modeled: the impact of activity level on work efficacy and the change of the effective radiant body area with posture. A stable and accurate hybrid numerical scheme was used to solve the set of differential equations. Predictions of the passive system model are compared with available analytic solutions for cylinders and spheres and show good agreement and stable numerical behavior even for large time steps.

Algorithms↗
PubMed1992

Laser Doppler flux and tissue oxygenation of experimental tumours upon local hyperthermia and/or hyperglycaemia.

Laser Doppler fluxmetry and oxygen partial pressure (pO2) histography have been applied to investigate the acute effects of hyperthermia (HT) and/or hyperglycaemia (HG) on microcirculatory function and tissue oxygenation of subcutaneous rat tumours growing on the dorsum of the hind foot. The experiments were performed to test whether, and to what extent, the two adjunct treatment modalities applied alone or in combination can modify these therapeutically relevant parameters. Local HT was performed in a saline bath (44 degrees C) for 2 h; HG was induced by i.v. infusion of 40% glucose solution for 2.5 h (blood glucose levels: 35-40 mM during heating). Laser Doppler flux (LDF) in superficial tumour tissue regions was recorded over the entire treatment period; tumour pO2 distribution was evaluated immediately after termination of the treatment. HG alone reduced the average LDF signal to 18% of the baseline reading before treatment, but did not influence the tumour oxygenation status and the proportion of pO2 readings occurring in the radiobiologically hypoxic class (pO2 = O-2.5 mm Hg). This phenomenon is most probably due to the occurrence of the Crabtree effect (reduction of the O2 consumption rate when excess glucose is available within a malignant tumour). Hyperthermia alone reduced LDF to approximately the same extent, and led to a rise in the number of pO2 readings in the hypoxic range with only minor changes in the average pO2. The combined treatment (HT/HG) neither increased the fraction of "hypoxic" pO2 readings nor intensified the flow drop already present at the end of the tumour heating. It is thus concluded that under hyperglycaemia the oxygenation status of normothermic and heated tumours is maintained. It may therefore be hypothesized that hyperthermia in conjunction with hyperglycaemia might be a better "radiosensitizer" than hyperthermia alone.

Animals↗
PubMed1991

Acute changes of systemic parameters in tumour-bearing rats, and of tumour glucose, lactate, and ATP levels upon local hyperthermia and/or hyperglycaemia.

Arterial blood pressure and relevant parameters of the arterial blood (O2 and CO2 tensions, pH, haematocrit, serum electrolytes and osmolality) were determined in tumour-bearing rats upon local hyperthermia (HT) and/or hyperglycaemia (HG). Tumour heating was performed in a saline bath (44 degrees C) for 120 min; hyperglycaemia was induced by i.v. infusion of 40% glucose solution for 150 min [blood glucose levels: 35-40 mM during heating; total amount of glucose: 1.19 g/100 g body wt.; infusion rates: 0.31 ml (100 g body wt.)-1 min-1 for 2 min, 0.02 ml (100 g body wt.)-1 min-1 for 88 min, and 0.01 ml (100 g body wt.)-1 min-1 for 60 min]. Immediately after treatment, glucose, lactate and ATP levels were determined in tumour and muscle specimens and compared to these values under normothermic (NT) and/or normoglycaemic (NG) conditions. In all groups (NT/NG, NT/HG, HT/NG, HT/HG) there were only minor but characteristic changes in blood parameters, which were mainly due to the volume and type of the infused fluids (glucose solution, saline). During hyperglycaemia, tumour glucose levels rose 13- to 17-fold, whereas muscle glucose concentrations exhibited only a 3- to 5-fold increase; lactate levels were 1.9-2.5 times higher in tumours than in muscle, indicating an increase in the metabolic differences between normal and malignant tissues. Despite an increased glucose availability, tumours did not show an improved energy status and, thus, would not be expected to develop a decrease in thermal sensitivity or stimulation in growth rate. The good systemic tolerability of the combined treatment (HT/HG) and the differential changes in malignant and normal tissue occurring under these conditions, support further attempts to manipulate tumour metabolic environment by glucose in order to achieve better therapeutic results.

Adenosine Triphosphate↗
PubMed1989

Tumor blood flow: the principal modulator of oxidative and glycolytic metabolism, and of the metabolic micromilieu of human tumor xenografts in vivo.

We have investigated therapeutically relevant pathophysiological parameters of human breast and lung cancer xenografts in nude rats. All lung cancers and one breast cancer exhibited rapid growth and high blood flow values paralleled by high metabolic rates. The tissue of these tumors was well oxygenated up to very advanced growth stages. Xenografts from other breast cancer cell lines grew much more slowly, were poorly perfused, and exhibited low metabolic rates. Here, tumor hypoxia and tissue acidosis were evident. These results indicate that significant differences in the metabolic micromilieu can be detected in human tumors; these are due to varying perfusion rates and may be partly responsible for failure to obtain tumor control in individual patients.

Animals↗
PubMed1989

Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts.

Better understanding of the micromilieu of human tumors in situ is mandatory for further improvement of diagnostic and therapeutic interventions. Since investigations of untreated tumors of a wide size range are precluded in humans for ethical reasons, size-dependent changes in the pathophysiology of primary and metastatic human tumors were studied using "tissue-isolated" xenografts in nude rats. Tumor types included lung and breast cancers, ovarian and thyroid carcinomas, uterus tumors, and melanomas. A 10-fold variation in weight-adjusted tumor perfusion indicated large variations in angiogenesis which were unrelated to tumor type. Flow values obtained were consistent with data from clinical observations and were comparable to that in isografted rodent tumors. Using actual consumption and supply rates, maximum oxygen and glucose uptake rates were calculated for each tumor type. The capacity to consume oxygen and glucose varied 9-fold and 4-fold, respectively. However, considering actual consumption rates, blood flow was the principal modulator of substrate supply and tumor metabolism in these human tumor xenografts. Consequently, therapeutically relevant parameters of the metabolic micromilieu largely depended on the efficacy of the tumor circulation. Hereby, high metabolic rates concomitant with high flow values coincided with rapid tumor growth. Thus, in order to design the best individualized therapy, flow-related data should supplement histological classification and clinical staging and grading. Further development of relatively noninvasive technologies (magnetic resonance imaging, magnetic resonance spectroscopy, or positron emission tomography) might permit such monitoring.

Animals↗
PubMed1984

Metabolites of nucleic acids in bovine milk.

To investigate metabolites of nucleic acids in milk as by-products of protein biosynthesis, a method for determination of pyrimidine and purine compounds by reversed-phase high-pressure liquid chromatography was developed. Reproducibility of the measured compounds was 2%. Recovery of the main constituents averaged about 99%. In addition to orotic acid, allantoin, and uric acid, the free bases hypoxanthine, xanthine, and guanine, the ribonucleosides uridine, cytidine, and pseudouridine, and the ribonucleotides, guanosine 5'-monophosphate and cytidine 5'-monophosphate, were quantified in milk samples of Holstein-Friesian cows. Milk production from days 45 to 65 of lactation influenced concentrations of individual metabolites differently. Concentrations of orotic acid, allantoin, and uric acid decreased with increasing milk production, whereas concentrations of uridine, cytidine, pseudouridine, hypoxanthine, xanthine, and guanine remained unchanged. The results allowed conclusions on rate limiting steps of catabolic pathways of pyrimidines and purines and indicated relationships with protein biosynthesis. A possible role of metabolites of nucleic acids as taste factors and as substrates for milk microbes is suggested.

Allantoin↗
PubMedDate not supplied

Protective effect of vitamin E in a rat model of focal cerebral ischemia.

Under certain pathological conditions such as cerebral ischemia and reperfusion the occurrence of free radicals is remarkably increased. However, only very little information is available on their quantitative relevance for the pathophysiology and final outcome of diseases. The aim of the present study was to evaluate the contribution of oxygen radicals in the pathogenesis of a stroke. For this purpose a rat model for stroke was used. Two of three vitamin E deficient groups were repleted with different dosages of DL-alpha-tocopherylacetate. No signs of vitamin E deficiency could be observed. However, the weight gain during repletion was increased in the vitamin E repleted groups. Brain infarction was created by occlusion of the right middle cerebral artery (MCAO) for two hours. After 24 hours the measurements of infarct volumes were taken. The infarct volume of the group with the highest repletion dosage was significantly reduced by 81%. This was also expressed in a higher rate of gait disturbances after MCAO of the deficient animals. The control of vitamin E status exhibited a similar repletion-dependent level in plasma and brain. These results strongly support the hypothesis that the generation of oxygen radicals occurring during reperfusion is an important aspect of the pathophysiological mechanism in brain infarction.

Animals↗