Impact of therapeutically induced reactive oxygen species and radical scavenging by α-tocopherol on tumor cell adhesion

Many tumor treatment modalities such as ionizing radiation or some chemotherapy induce reactive oxygen species (ROS) resulting in therapeutic cell damage. The aim of this study was to analyze whether such ROS induction may affect the mechanical stability of solid tumor tissue by degradation of the extracellular matrix proteins or by a loss of cell adhesion molecules. Additionally, the protective impact of alpha-tocopherol treatment on these processes was studied. Experimental DS-sarcomas in rats were treated with a combination of localized 44 degrees C hyperthermia, inspiratory hyperoxia and xanthine oxidase in order to induce pronounced oxidative stress. A second group of animals were pret…

Begleitende Inhaltsstoffe in 22 OTC-Fischöl- und Lebertranpräparaten: Cholesterin, Schwermetalle und Vitamin A

Fischolkapseln werden von selbstmedizierenden Patienten in zunehmendem Mase eingenommen. Hier wurde der Frage nachgegangen, ob 22 kommerziell erhaltliche Fischol- und Lebertranzubereitungen Begleitsubstanzen enthalten, deren Menge unter Umstanden nachteilig fur den Patienten sein konnten. Gemessen wurden: Cholesterin mit der Gaschromatographie, Schwermetalle mittels Atomabsorption und Vitamin A mit der hochauflosenden Flussigkeitschromatographie (HPLC). Sowohl der Cholesterin-als auch der Schwermetallgehalt lagen in unbedenklichen Bereichen. Der Vitamin-A-Gehalt von Lebertrankapseln wurde jedoch in Mengen gefunden, bei denen schwangere Frauen die Dosierungsempfehlungen der Hersteller nicht …

Zum Aufbau der Epiphysenfuge im chronischen Vitamin-A-Mangel — eine histologische und morphometrische Studie an der proximalen Tibiaepiphyse

Vitamin A und analoge Substanzen (Retinoide) uben auf Wachstum und Differenzierung des Bewegungsapparates einen wesentlichen Einflus aus. In zahlreichen in vitro-Untersuchungen konnte gezeigt werden, das der Metabolismus von Chondrozyten und Osteoklasten durch toxische Vitamin A-Konzentrationen in komplexer Weise beeinflust wird [1]. Hingegen ist der physiologische Wirkungsmechanismus von Retinol bei der Wachstumsregulation des Knochens noch weitgehend unklar. Das Ziel der vorliegenden in vivo-Untersuchung war deshalb die morphologische Analyse der Epiphysenfuge an Ratten, wobei Tiere im chronischen Vitamin A-Mangel mit Kontrollen verglichen wurden.

A Computerised System for Electrocochleographic (ECOG) Measurement

To study the influence of vitamin A on hearing we choose to examine ECoGs induced by an audible stimulus.The basis of this project is a suitable experimental equipment for inducing and recording inner ear electrical responses in guinea pigs. The problem to be studied asks for a high number of animals and measurements within one animal; furthermore the ECoGs of each animal have to be examined over a long period of time. This calls for a simple and automated measurement and evaluation procedure. In contrats to most ECoG experiments we do not study the influence of special oto — toxic agents (noise,drugs etc) but examine the variation of ECoG signals as caused by different metabolic states of …

?-Carotene Supplements Cannot Meet All Vitamin A Requirements of Vitamin A-Deficient Rats

Crystalloid lysozyme inclusions in Paneth cells of vitamin A-deficient rats.

The effect of vitamin A-deficiency on jejunal Paneth cells in rats was investigated. Crystalloid particles were observed in secretion granules of Paneth cells from 6 out of 8 rats with vitamin A-deficiency. The particles were similar to those found in Paneth cells under other experimental conditions. Using an immuno-electron-microscopic technique we demonstrated a clear lysozyme immunoreactivity of these particles. In 2 vitamin A-deficient rats tubular structures have been detected in addition to the crystalloid particles. Crystalloid particles or tubular structures were not detectable in a control group of 8 vitamin A-supplemented rats. The morphological alterations of Paneth cells may be …

Crystalloid Lysozyme Inclusions in Paneth Cells of Vitamin A-Deficient Rats

The effect of vitamin A-deficiency on jejunal Paneth cells in rats was investigated. Crystalloid particles were observed in secretion granules of Paneth cells from 6 out of 8 rats with vitamin A-deficiency. The particles were similar to those found in Paneth cells under other experimental conditions. Using an immuno-electron-microscopic technique we demonstrated a clear lysozyme immunoreactivity of these particles. In 2 vitamin A-deficient rats tubular structures have been detected in addition to the crystalloid particles. Crystalloid particles or tubular structures were not detectable in a control group of 8 vitamin A-supplemented rats. The morphological alterations of Paneth cells may be …

Biochemical, morphological, and functional aspects of systemic and local vitamin A deficiency in the respiratory tract.

Consensus meeting: monosodium glutamate – an update

Update of the Hohenheim consensus on monosodium glutamate from 1997: Summary and evaluation of recent knowledge with respect to physiology and safety of monosodium glutamate.Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic.University of Hohenheim, Stuttgart, Germany.The experts met and discussed the questions and arrived at a consensus.Total intake of glutamate from food in European countries is generally stable and ranged from 5 to 12 g/day (free: ca. 1 g, protein-bound: ca. 10 g, added as flavor: ca. 0.4 g). L-Glutamate (GLU) from all sources is mainly used as energy fuel in enterocytes. A maximum intake of 6.000 [c…

Uptake and Metabolism of ?-Carotene Isomers in Rats

Serum-Vitamin-A-Bestimmungen und ihre Aussagekraft zum Vitamin-A-Status

Wie viele Arbeiten uber den Vitamin-A-Metabolismus und Retinol-Serumhomoostase zeigten, unterliegt die Retinol-Serum-Konzentration im physiologischen Bereich der Leberreserven (20–300 Μg/g Leber) einer strengen Regulation. Daher gibt der Serumspiegel nur bei einem extremen Mangel oder bei ubersattigung mit Vitamin A Auskunft uber die Speichervorkommen. Im Grenzbereich, dem marginalen Mangel, kommt es aber schon zur Schadigung peripherer Gewebe, bevor sich der Retinol-Serumspiegel verandert. Auch bei beginnender Hypervitaminose A zeigen sich Veranderungen im Serumspiegel erst zu einem spateren Zeitpunkt. Daher ist die Bestimmung des Vitamin-A-Serumspiegels kein guter Indikator fur den Vitami…

Long-Term Administration of High Dose Vitamin A to Rats Does Not Cause Fetal Malformations: Macroscopic, Skeletal and Physicochemical Finds

A rat model was used to investigate whether high oral doses of vitamin A lead to fetal malformations and to what extent retinyl esters (RES) are transferred from the mother to the fetuses. Retinol and RES concentrations in plasma behave similarly in rats and humans. When high concentrations of vitamin A are administered, plasma retinol concentrations remain relatively constant, whereas plasma RES increased in parallel with the dose. To achieve an elevation from approximately 150 to > 1525 nmol x L(-1) in the experimental group before mating, female Ibm: RORO (spf) rats were fed a maintenance diet enriched with 15.2 x 10(3) retinol equivalents (RE) x kg(-1) at the start and increased stepwis…

Aufnahme und Verteilung von14C-Retinylacetat in Organe und Sinnesgewebe (Innenohr) des Meerschweinchens

Es wird uber die Aufnahme und chemische Identifizierung von14C-Retinylacetat in das Innenohr des Meerschweinchens nach per oraler Verabreichung berichtet. Die Untersuchung wurde aus methodischen Grunden bei Vitamin-A-mangelernahrten Tieren durchgefuhrt. Es findet sich eine zeitabhangige Verteilung in den Sinnesgeweben, die der anderer Organe gleicht. Die chemische Identifizierung zeigt, das das als Retinylacetat verabreichte markierte Vitamin A in den membranosen Strukturen des Innenohres in Form des Retinylpalmitats zu finden ist. Dies mag ein Hinweis sein auf die Fahigkeit des Innenohrgewebes, die Transportform des Vitamins A, das Retinol, zu verestern und eventuell auch zu speichern.

Expression patterns of complex glycoconjugates and endogenous lectins during fetal development of the viscerocranium

Summary Experimental evidence suggests that carbohydrates and their corresponding receptors (endogenous lectins) decode biological information. Therefore, the expression of complex oligosaccharides — the potential ligand part of this recognition system — during chondrogenesis and osteogenesis was determined in the viscerocranium of fetal rats by mapping the staining patterns of exogenous lectins. Results were compared with the expression of bone- and/or cartilage-specific core proteins and the binding profiles of neoglycoconjugates. These synthetic tools make possible the localization of sugar-ligand-binding sites. The spatial and temporal distribution patterns of glycoconjugates were highl…

Computer Aided Evaluation of HPLC (High Pressure Liquid Chromatography) with Fluorometric Detection

A program system for automated HPLC measurements of vitamin A concentration is reported. This system provides for guidance of operators, for control of apparatus and for supervision of quality measurements.

Aktuelle Ergebnisse der Adipositasforschung

Distribution patterns in glycoconjugate expression during the development of the rat palate.

The distribution of complex carbohydrate structures during the embryonic development of the rat palate was analysed by examining lectin-binding patterns in serial paraffin and cryostat sections. With few exceptions, the binding patterns showed a general increase in lectin receptors in the more developed stages of palatogenesis. High mannose oligosaccharides were especially amplified during development. Terminal fucose molecules were not expressed. In contrast, terminal sialic acid molecules were ubiquitously distributed in epithelial and mesenchymal tissues. Non-sialylated terminal N-acetylglucosamine was specifically restricted to evolving bone matrix. Before palatal fusion, quantitative b…

Vitamin A deficiency increases noise susceptibility in guinea pigs.

The effect of vitamin A deficiency in guinea pigs on noise-induced temporary threshold shift (TTS) was evaluated after short (15 min) acoustic overstimulation with a moderate (90 dB) broad-band white noise. Some guinea pigs were fed ad libitum a purified diet deficient in vitamin A (VAD group) until biochemical signs of deficiency occurred. A second, control group (VA group) received the same diet as well as 100 IU vitamin A daily by pharyngeal tube. Cochlear potentials were recorded by special computerized equipment using implanted electrodes. Before acoustic stimulation, a baseline value was determined with a test stimulus [90 dBA (A-filter according to usual DIN instructions)] correspond…

HPLC-Bestimmung von Retinol, Retinal und Retinylestern sowie ihren isomeren Konfigurationen in biologischen Proben

Die HPLC-Bestimmung von Retinol, Retinal, Retinylestern und ihren isomeren Konfigurationen erfolgt mit Hilfe von zwei Detektoren bei verschiedenen Wellenlangen. Der reine Retentionszeiten- und Spektrenvergleich bringt keine hinreichende Genauigkeit.

Vitamin A und Hörorgan Literaturübersicht

Seit der Entdeckung des Vitamin A und ersten Beschreibung seiner Wirkung wird dieses auch in der Otorhinolaryngologie als Therapeutikum bei den unterschiedlichsten Formen von Horstorungen eingesetzt und seine Wirkungsweise am Innenohr erforscht. So wurden sowohl tierexperimentelle als auch klinische Studien durchgefuhrt, um die Bedeutung des Vitamins fur die Funktion des Hororgans zu klaren. Daneben wurden eine Reihe von Beobachtungen mitgeteilt, die einen Zusammenhang zwischen Storungen des Vitamin-A-Stoffwechsels und gleichzeitig auftretenden Horstorungen beschrieben. Neuere Untersuchungen haben ergeben, das Vitamin A in hohen Konzentrationen im Innenohr vorkommt und dort auch gespeichert…

Characterization of glycoconjugate expression during development of Meckel's cartilage in the rat

The staining patterns of 24 biotinylated lectins were analyzed in serial sections of the mandible of 13- to 21-day-old rat embryos by means of the avidin-biotin-peroxidase method. A ubiquitous distribution of binding sites was demonstrated after incubation with Con A (Canavalia ensiformis), DSL (Datura stramonium; except bone matrix), and WGA (Triticum vulgare). ECL (Erythrina cristagalli), GSL I (Griffonia simplicifolia), SJA (Saphora japonica), VVL (Vicia villosa), DBA (Dolichus biflorus), UEA I (Ulex europeus), and LTA (Lotus tetragonobolus) were constantly negative. In early stages of development, GSL II (Griffonia simplicifolia II) was a selective marker of prechondral blastema. In con…

Intensified oxidative and nitrosative stress following combined ALA-based photodynamic therapy and local hyperthermia in rat tumors.

Oxidative stress-related changes in tumors upon localized hyperthermia (HT), 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and their combination (ALA+HT) were examined after the observation that the antitumor effects of ALA-PDT could be significantly enhanced upon simultaneous application of HT. Rats bearing s.c. DS-sarcomas (0.6–1.0 ml) on the hind foot dorsum were anesthetized and underwent one of the following treatments: (i) ALA-PDT (375 mg/kg 5-ALA i.v.); (ii) localized HT, 43°C for 60 min; (iii) combined ALA-PDT and HT [=ALA+HT]. Appropriate control experiments were also performed. After treatment, tumors were excised and rapidly frozen for later analysis of nitrosative s…

Fetal calf serum and retinoic acid affect proliferation and terminal differentiation of a rat rhabdomyosarcoma cell line (BA-HAN-1C)

We report on the establishment of a model for differentiation induction in sarcomas, using the clonal rhabdomyosarcoma cell line BA-HAN-1C. This rhabdomyosarcoma cell line is composed of morphologically undifferentiated mononuclear stem cells, some of which spontaneously fuse to form terminally differentiated multinuclear myotube-like giant cells. The deprivation of fetal calf serum (FCS) or the exposure to retinoic acid, respectively, resulted in a significant inhibition of proliferation (P less than 0.001) and a marked increase in cellular differentiation as shown by a significant increase in the number of myotube-like giant cells (P less than 0.001) and in the creatine kinase activity (P…

The Phenomenon of a High Triglyceride Response to an Oral Lipid Load in Healthy Subjects and Its Link to the Metabolic Syndrome

Excessive postprandial triglyceride (TG) responses despite normal fasting TG levels have been described in single cases within small groups of healthy subjects and in patients with obesity or precocious atherosclerosis, known to be associated with high insulin fasting levels. To clarify this association, fasting and postprandial TG and insulin levels were studied in 113 healthy young (25.7 +/- 2.6 years), normal weight (body mass index 20.8 +/- 2.3 kg/m2) male subjects who were selected from among 117 subjects on the basis of TG fasting levels200 mg/dl. After a 12-hour fast a standardized liquid lipid load was administered containing 58 g mainly saturated fat and 1,017 kcal energy. Both fas…

Sensitive Analysis of Retinyl Esters by Isocratic Adsorption Chromatography

A sensitive method for the determination of retinyl esters, including their geometric isomers, by isocratic adsorption HPLC is described. The development of a special recycling system allows the separation of all-trans-, 13-cis, 11-cis- and 9-cis-retinyl palmitate, -stearate, -oleate, -palmitoleate and -linoleate with short retention times and high sensitivity. Extraction of the retinyl esters from various organs with mobile phase avoids additional evaporation steps. The method was evaluated by the determination of retinyl esters in small tissue samples such as tongue, trachea and inner ear. This is the first report of the detection of retinyl esters in these tissues, which are known to dep…

Vitamin A and ciliated cells I. Respiratory epithelia

To estimate the role of vitamin A on ciliated cells we investigated whether ciliated cells undergo any alteration during vitamin A deficiency. The epithelia examined include the ciliated cells of the respiratory tract and the ciliated sensory cells of the inner ear, the tongue, and the olfactory cells. This part of the paper will describe the ciliated epithelium of the tracheobronchial tract and its relation to vitamin A status. During vitamin A deficiency a partial loss of ciliae can be observed before any squamous metaplasia (which usually occurs during longer lasting vitamin A deficiency) develops. The scanning electron microscopic data illustrate the altered surface of the epithelium du…

Impact of Reactive Oxygen Species on the Expression of Adhesion Molecules in Vivo

Many non-surgical tumor treatments induce reactive oxygen species (ROS) which result in cell damage. This study investigated the impact of ROS induction on the expression of adhesion molecules and whether alpha-tocopherol pre-treatment could have a protective effect. Experimental rat DS-sarcomas were treated with a combination of localized 44 degrees C-hyperthermia, inspiratory hyperoxia and xanthine oxidase which together lead to a pronounced ROS induction. Further animals were pre-treated with alpha-tocopherol. The in vivo expression of E- and N-cadherin, alpha-catenin, integrins alpha v, beta 3 and beta 5 as well as of the integrin dimer alpha v beta 3 was assessed by flow cytometry. The…

Vitamin A deficiency. New knowledge on diagnosis, consequences and therapy

Due to the rapid development of biochemical analyses in the last 10 years different substances like vitamin A, with an apparent clarified metabolism and action, were re-estimated. As a result, new knowledge was presented which could be essential for human health. Some details and consequences are reviewed in this paper. Marginal deficiency, which also may occur in industrialized nations, cannot be determined with certainty by usual blood analyses. The reasons for marginal deficiency are either different diseases or unbalanced nutrition. From epidemiological research it is argued that low vitamin A intake is associated with a higher incidence of cancer in different tissues. However, vitamin …

Vitamin A in parenteral nutrition: uptake and distribution of retinyl esters after intravenous application.

Short-term parenteral application of vitamin A was examined in rats. Retinyl margarinate, which is chemically similar to physiological retinyl esters, was used in vitamin A-depleted rats to study uptake, distribution, and storage of retinyl esters in tissues. Vitamin A-depleted and Vitamin A-sufficient rats were infused with a micellar suspension of retinyl margarinate for 7 h and then killed at different times. Retinyl margarinate was directly taken up by all tissues examined. It appears that infusion of retinyl esters in micellar form provides a direct way to supply vitamin A to peripheral, vitamin A-dependent tissues. Therefore, a short-term infusion of retinyl esters with an emulsifier …

An ex vivo model of the rat trachea to study the effect of inhalable toxic compounds

Different cell culture and organ systems are used to evaluate the physiological responses of the airways to the effects of carcinogenic [e.g., benzo(a)pyrene] and anticarcinogenic (e.g., retinoids) compounds on cellular growth and differentiation. However, in contrast to in vivo conditions dissociated epithelial cells or tracheal ring cultures are covered with medium. Therefore, we developed an ex vivo perfusion model enabling evaluation of morphology and metabolism of different compounds under near-physiological conditions. The trachea was surrounded with culture medium and perfused with air by means of a small animal respirator. To test the viability of the system under various experiment…

Comparative assessment of the toxicology of vitamin A and retinoids in man.

As the title implies, any assessment of the toxic effects of vitamin A derivatives must distinguish between vitamin A in the truest sense, i.e. retinol, and retinoic acid and its synthetic derivatives. Just as no single description is universally applicable to the mode of action of vitamin A derivatives, so too do their toxic effects defy generalization. The recommendation made in 1982 by IUPAC [Eur. J. Biochem., 129 (1989) 1] to designate all derivatives with the typical structure of the vitamin as being retinoids may be chemically logical and correct but, when it comes to describing the effects and side-effects of vitamin A derivatives, it leads to misunderstandings. Retinol, which is fre…