An innovative approach to the determination of safety for a dietary ingredient derived from a new source: case study using a crystalline lutein product.

Lutein and zeaxanthin are antioxidant carotenoids that occur naturally in the diet. A new source of these carotenoids, a crystalline lutein product, is an extract from the marigold flower (Tagetes erecta) that contains approximately 86% by weight of the carotenoids lutein and zeaxanthin. The safety of consumption of a crystalline lutein product used as an ingredient in food is determined by evaluating the safety of ingestion of the whole product, as well as safety of ingestion of the major constituents, lutein and zeaxanthin. The approach to evaluating the safety of increased lutein and zeaxanthin intake from consumption of crystalline lutein product is based on an evaluation of the incremental increase this ingestion will produce in lutein and zeaxanthin and in total carotenoids, compared to background exposure. In addition, bioavailability of lutein+zeaxanthin from crystalline lutein product, when added to food, is determined and used to adjust the estimated daily intake of lutein and zeaxanthin from this new source and standardize it to the bioavailable dose of these carotenoids from food sources. The proposed level of ingestion of lutein and zeaxanthin from the crystalline lutein product would increase intake of lutein zeaxanthin in the generally vegetable-poor American diet to a level comparable to the mean intake of individuals consuming the recommended number of servings of vegetables per day and is therefore determined to be both prudent and safe. Safety of consumption of the whole product is determined by evaluating the source of the product, production process, nature and quantity of impurities, and product specifications. Corroboration of safety is provided by animal toxicology studies of the crystalline lutein product, as well as human and epidemiologic studies of lutein and zeaxanthin intake. It can be concluded that crystalline lutein is a safe and GRAS source of lutein for its proposed uses in food.

Hazard identification by methods of animal-based toxicology.

This paper is one of several prepared under the project "Food Safety In Europe: Risk Assessment of Chemicals in Food and Diet" (FOSIE), a European Commission Concerted Action Programme, organised by the International Life Sciences Institute, Europe (ILSI). The aim of the FOSIE project is to review the current state of the science of risk assessment of chemicals in food and diet, by consideration of the four stages of risk assessment, that is, hazard identification, hazard characterisation, exposure assessment and risk characterisation. The contribution of animal-based methods in toxicology to hazard identification of chemicals in food and diet is discussed. The importance of first applying existing technical and chemical knowledge to the design of safety testing programs for food chemicals is emphasised. There is consideration of the presently available and commonly used toxicity testing approaches and methodologies, including acute and repeated dose toxicity, reproductive and developmental toxicity, neurotoxicity, genotoxicity, carcinogenicity, immunotoxicity and food allergy. They are considered from the perspective of whether they are appropriate for assessing food chemicals and whether they are adequate to detect currently known or anticipated hazards from food. Gaps in knowledge and future research needs are identified; research on these could lead to improvements in the methods of hazard identification for food chemicals. The potential impact of some emerging techniques and toxicological issues on hazard identification for food chemicals, such as new measurement techniques, the use of transgenic animals, assessment of hormone balance and the possibilities for conducting studies in which common human diseases have been modelled, is also considered.

Rhegmatogenous retinal detachment in a hypertensive dog.

A 4-year-old dog of the Appenzeller strain with experimentally induced renal hypertension presented with apparently longstanding retinal changes, including hemorrhage, detachment, tears/holes, and anemia, in one eye and intravitreal hemorrhage in the other. The retinal tears/holes probably occurred following constant vitreous traction due to retinal hemorrhage and subsequent exsanguination of most of the retinal vasculature. This animal was reexamined six months later and most of these changes had persisted. Photodocumentation is presented.

Fatal legionellosis in patients with malignant hematologic diseases.

Pneumonia was present in 70/157 (44.6%) autopsied patients with malignant hematologic diseases. In 16/70 patients (22.9%), legionellae were found to be the causative agents by screening lung tissue specimens with the direct fluorescent antibody method. In 5/16 patients with Legionella pneumonia, in whom legionellosis had been suspected clinically, the diagnosis had already been established by serology, urinary Legionella antigen detection, and culture. These results provide evidence that legionellosis is an important pneumonia etiology in patients with malignant hematological diseases. Thus, Legionella diagnostics should be applied routinely, and antibiotics effective in the treatment of legionellosis should be added to the usual therapy in patients with etiologically unexplained pneumonias. In view of the common occurrence of relapses of Legionella pneumonia, antibiotic therapy should be continued for an extended period.

[Morphologic studies of the pathogenesis of ligneous conjunctivitis]. / Morphologische Untersuchungen zur Pathogenese der Conjunctivitis lignosa.

The cases of ligneous conjunctivitis published since 1964 are presented in a review of the literature. A total of 84 cases have been described. The predominance of this disease in women is lower than was previously thought. Ligneous conjunctivitis tends to occur more frequently in children. However, it is not a "disease of little girls". Two cases are described in the present paper, including pathomorphological studies. In both cases, neutrophilic granulocytes were studied by electron microscopy. The results are compared with a control case and with corresponding reports in the literature. The number of granules in the neutrophilic granulocytes was significantly reduced in both cases. In one of the cases studied the granules were increased in size. These findings support the hypothesis that ligneous conjunctivitis could be the result of a lowered resistance associated with a disturbance of wound healing.

Histopathological diagnosis of brain tumours with the help of a computer: mathematical fundaments and practical application.

With the help of a personal computer we have subjected 1684 tumours of the central and peripheral nervous systems to a discriminant analysis to test whether the different brain tumours can be classified. By ascribing a coefficient value which belongs to a linear function to the objective criteria for each tumour these can be ordered in groups, and a classification is then possible. This has been termed discriminant analysis. Fifty histological characteristics were the criteria taken into consideration for each tumour. By using Bayes' formula with a correction for binomial distribution we obtained a correct diagnosis in 98% of the cases studied. The differential diagnosis with its percentage of probabilities is given by the computer. The mathematical fundaments are given. The valuability and precision of this method are discussed.

What's new in lung physiology? Pulmonary vessel regulation/non-respiratory metabolic lung functions.

Whereas in the last few decades respiratory functions of the lung occupied a central role in research activity, current interests are concentrating more and more on non-respiratory functions. The present small overview concerns itself with vasoregulation and metabolic operations of the lung. A series of important review articles on this topic convey extensive information.

Perfluorocarbone (FDA 20) and extracorporeal circuit of isolated extremity perfusion.

The applicability of Fluosol DA 20 as a perfusion fluid was investigated in the isolated limb perfusion of 14 mongrel dogs and its performance compared with that of diluted blood. Control of perfusion parameters permitted a direct comparison of the two perfusion liquids. Muscle tissue, blood and perfusate were analyzed for pH, pO2, pCO2, O2 content, lactate, pyruvate, ATP and creatine phosphate. Due to given experimental conditions, the pH values of the perfusion liquid and muscle tissue were in a slightly acidic range. The oxygen uptake of the perfusion liquids and the oxygenation of tissue was satisfactory, the metabolism of the muscle tissue was not disrupted.

[Mesenteric lipodystrophy: differential diagnosis of a benign abdominal tumor]. / Mesenteriale Lipodystrophie: Differentialdiagnostik eines gutartigen abdominellen Tumors.

In a clinical presentation of a patient with mesenteric lipodystrophy the usefulness of the two imaging procedures ultrasound and computeromography is firstly demonstrated. Both methods have proven as good means in early diagnosis and patients follow up. Combination of ultrasound and guided tumor puncture is able to establish diagnosis avoiding laparotomy. For the follow up of these patients ultrasound and computertomography are valuable.

Histologic abnormalities in routine biopsies of patients with esophagitis and different gastric acid secretion.

Intraepithelial eosinophilic granulocytes were previously reported to evidence prolonged acid reflux in patients with reflux esophagitis. The following study was performed to investigate whether or not these histologic abnormalities are specific to patients with esophagitis and high H+ ion activity of the gastric juice. Esophagitis was proved endoscopically in all patients. Biopsy specimens were obtained during endoscopy by forceps biopsy from the area involved. Afterwards an acid secretion test to determine basal and pentagastrin-stimulated H+ ion activity and a Bernstein test were performed. Histologic findings were correlated with the results of the acid secretion test. In this study, the occurrence of intraepithelial eosinophils was similar in patients with high and with low gastric acid output, but was overall low in these patients and has not proved to be a specific diagnostic criterion for reflux.

[Stroma-free hemoglobin solution and perfusion of isolated extremities]. / Stromafreie Hämoglobinlösung und isolierte Extremitätenperfusion.

Pyridoxylated stroma-free hemoglobin solution was compared to hemodiluted blood in extremity perfusion of mongrel dogs. pH-values in tissue and in perfusate as well as oxygen tension showed no significant difference, and oxygen supply to the periphery was sufficient. Measurement of lactate, pyruvate, ATP and CP demonstrated domination of aerobic metabolism. We proved that stroma-free hemoglobin solution ( SFHb -PLP) can substitute hemodiluted blood (Hk 18) in isolated extremity perfusion. Metabolic results were confirmed by histological examination where no tissue alterations could be found in the perfused extremity or the whole body system.

Long-term observation of PFC storage in organs of rats after various dosages.

The study reports long term observations concerning the proliferation of connective tissue and histological changes in the liver, spleen and lung of Wistar rats after intravenous injection of fluorocarbons (Fluosol-DA 20% and 35%). No elevated connective tissue values were observed after a single injection of 2.3-3.1 g fluorocarbons per kg body weight with F-DA 20% or 4.1-5.1 g/kg body weight with F-DA 35% at determination of the stroma using the hydroxyproline method. After repeated intravenous injections of F-DA 20% (up to 22 g fluorocarbons/kg body weight) and F-DA 35% (up to 31 g/kg body weight), elevated levels of hydroxyproline were found in the liver as proof of proliferation of connective tissue. When F-DA 20% was injected, normal levels of hydroxyproline were found even after one year. In neither case were quantitative changes in the connective tissue of the lungs observed. Representative results for the spleen could not be reported because of methodological reasons. Histological changes were demonstrated and discussed. Since the given doses of F-DA 35% were significantly higher than those normally used, we can assume that the connective tissue proliferation occurs only after a very high limit is exceeded.

[Morphological findings in the rabbit cornea after tear gas cauterization (author's transl)]. / Morphologische Befunde an der Kaninchencornea nach Tränengasverätzung.

Solutions of various concentrations of chloracetophenone (dissolved in 1, 1, 1, trichlorethane) were trickled on the corneas of rabbits. The substance was either applied to the center or to the limbus, or simultaneously to the center and limbus of the cornea. After surgical removal of the cornea on day 21, the alterations were examined by a light microscope. When chloractephenone was applied to the middle of the cornea, signs of intensified epithelial regeneration were observed, even to the point of a severe granulating and necrotic infection with ulceration. The severity of these changes depended on the concentration used and showed that repair of a corneal defect had been attempted. The same changes were observed when the same concentrations of chloracetophenone were applied to the limbus, but with greater severity. Some of these alterations led to perforation of the cornea when the substance was applied to center and limbus. These results are discussed in reference to the correlation of the changes seen in animal tests to those in the human eye.

Problems of assessment in the surgery of renal adenomas.

We report 6 cases of renal adenomas in which difficulties were encountered in the determination of malignancy. The clinical and anatomical data are discussed, particularly the difficulties with the histological frozen section diagnosis of such tumors, together with the therapeutic outcome. The objective of a differentiating procedure is to increase the number of operations with organ conservation, while avoiding metastasis that could be derived from apparently benign renal adenomas.

[Ultrastructural studies of fluorocarbon excretion and uptake in the lung (author's transl)]. / Elektronenoptische Untersuchungen zur Fluorocarbon-Ausscheidung und Aufnahme in der Lunge.

Certain fluorochemicals are under discussion as synthetic substitutes for erythrocytes because of their high binding capacity for blood gases. The excretion of fluorocarbons occurs predominately in the lungs. As a part of this process of excretion, active cellular transport can be demonstrated by ultrastructural examination. Chronic organ defects, especially lung fibrosis, were not detected.