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Biomedical subjects

U Heinrich

Publications and source records attributed to U Heinrich.

At least 19 recordsLinked to original sources

Influence of applied quantity of sunscreen products on the sun protection factor--a multicenter study organized by the DGK Task Force Sun Protection.

It is often debated that the protection against solar-induced erythema under real conditions is dependent upon the amount of sunscreen applied. It is believed that when too little is applied a lower sun protection than indicated on the label will result. The aim of this study was to quantify this effect. In this multicenter study, the influence of three different amounts (0.5, 1.0, 2.0 mg/cm(2)) of three commercial sunscreen products in three reliable test centers was investigated according to the test protocol of The International Sun Protection Factor Test Method. The main result was a linear dependence of the SPF on the quantity applied. Taking into consideration the volunteer-specific variations, an exponential dependence of confidence interval of the in vivo SPF and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was linked to the lowest confidence intervals. Thus, from the point of view of producing reliable and reproducible in vivo results under laboratory conditions, the recommendation of this multicenter study is an application quantity of 2.0 mg/cm(2).

Confidence Intervals↗

Antioxidant supplements improve parameters related to skin structure in humans.

In the present study we investigated the influence of two different antioxidant supplements composed of carotenoids, vitamin E and selenium on parameters related to skin health and skin aging. Thirty-nine volunteers with healthy, normal skin of skin type 2 were divided into 3 groups (n = 13) and supplemented for a period of 12 weeks. Group 1 received a mixture of lycopene (3 mg/day), lutein (3 mg/day), beta-carotene (4.8 mg/day), alpha-tocopherol (10 mg/day) and selenium (75 microg/day). Group 2 was supplemented with a mixture of lycopene (6 mg/day), beta-carotene (4.8 mg/day), alpha-tocopherol (10 mg/day) and selenium (75 microg/day). Group 3 was the placebo control. Upon supplementation serum levels of selected carotenoids increased in both verum groups. Skin density and thickness were determined by ultrasound measurements. A significant increase for both parameters was determined in the verum groups. Roughness, scaling, smoothness and wrinkling of the skin were determined by Surface Evaluation of Living Skin (Visioscan). Roughness and scaling were improved by the supplementation with antioxidant micronutrients. In the placebo group no changes were found for any of the parameters.

Adolescent↗

Proof of partial imbalances 6q and 11q due to maternal complex balanced translocation analyzed by microdissection of multicolor labeled chromosomes (FISH-MD) in a patient with Dandy-Walker variant.

We report on a family in which a daughter is described with mental retardation, as well as malformations of the heart, and of the brain (Dandy-Walker variant). The patient's phenotype suggests a chromosomal rearrangement. However, her karyotype was unremarkable by conventional cytogenetic analysis. In order to detect chromosome rearrangements overseen by this method, the subtelomere regions of suspicious chromosomes were verified by fluorescence in situ hybridization (FISH). A rearranged derivative chromosome 6 was identified. Further examinations by FISH-microdissection (FISH-MD) revealed a maternal complex balanced translocation. The patient inherited the derivative chromosome 6 from her mother and therefore carries a partial monosomy 6q26-->qter and a partial trisomy 11q23.3-->qter.

Allelic Imbalance↗

Methodological scheme for designing the monitoring of genetically modified crops at the regional scale.

According to EC regulations the deliberate release of genetically modified (GM) crops into the agro-environment needs to be accompanied by environmental monitoring to detect potential adverse effects, e.g. unacceptable levels of gene flow from GM to non-GM crops, or adverse effects on single species or species groups thus reducing biodiversity. There is, however, considerable scientific and public debate on how GM crops should be monitored with sufficient accuracy, discussing questions of potential adverse effects, agro-environmental variables or indicators to be monitored and respective detection methods; Another basic component, the appropriate number and location of monitoring sites, is hardly considered. Currently, no consistent GM crop monitoring approach combines these components systematically. This study focuses on and integrates spatial agro-environmental aspects at a landscape level in order to design monitoring networks. Based on examples of environmental variables associated with the cropping of Bt-Maize (Zea maize L.), herbicide-tolerant (HT) winter oilseed rape (Brassica napus L.), HT sugar beet (Beta vulgaris L.), and starch-modified potato (Solanum tuberosum L.), we develop a transferable framework and assessment scheme that comprises anticipated adverse environmental effects, variables to be measured and monitoring methods. These we integrate with a rule-based GIS (geographic information system) analysis, applying widely available spatial area and point information from existing environmental networks. This is used to develop scenarios with optimised regional GM crop monitoring networks.

Beta vulgaris↗

Transport of insulin-like growth factor-I across endothelial cell monolayers and its binding to the subendothelial matrix.

Cultured human umbilical vein endothelial cells (HUVEC) were used as a model to study transendothelial IGF-I transport, and its deposition into the extracellular matrix (ECM). Specific binding of (125)I-IGF-I to HUVEC monolayers was demonstrated, which was inhibited by aIR-3, a specific antibody directed against the IGF-I receptor. ECM-associated (125)I-IGF-I was approximately 10% of cell-bound IGF-I at 22 degrees C, and increased 4.5-fold at 37 degrees C, indicating that endothelial metabolism is required for the transport. However, neither monensin and cytochalasin B, both of which block endocytosis, nor aIR-3 did inhibit transport of (125)I-IGF-I into the ECM. In order to characterize IGF-I binding to the subendothelial ECM, HUVEC were removed nonenzymatically by treatment with Triton X-100 and ammonia. Specific, saturable binding of (125)I-IGF-I to the isolated ECM was observed, which was protease-sensitive. Antibodies directed against vitronectin inhibited IGF-I binding to the matrix by 35%, while antibodies directed against other ECM proteins had no significant influence on IGF-I binding. Using radioimmunoassays the IGF binding protein-2 was detected in the ECM, while IGFBP-1 and IGFBP-3 were below the detection limits. In order to evaluate functional aspects of IGF-I binding to the matrix, HUVEC were incubated under serum-free conditions in the absence and presence of IGF-I. Under serum-free conditions 48% of cells rounded up and started to detach after 2 hours incubation, while only 23% of the cells started to detach in the presence of IGF-I. These data indicate that IGF-I is transported via a paracellular route across endothelial cells, and becomes bound to the subendothelial ECM. Vitronection seems to be involved in binding of IGF-I to the ECM. ECM-associated IGF-I might play a role in endothelial cell survival and stability.

Ammonia↗

Dietary tomato paste protects against ultraviolet light-induced erythema in humans.

Carotenoids are efficient antioxidants capable of scavenging reactive oxygen species generated under conditions of photooxidative stress. It has been shown that supplementation with high doses of beta-carotene protects skin against UV-induced erythema. This study was designed to investigate whether intervention with a natural dietary source rich in lycopene protects against UV-induced erythema in humans. Tomato paste (40 g), providing approximately 16 mg/d of lycopene, was ingested with 10 g of olive oil over a period of 10 wk by 9 volunteers. Controls (n = 10) received olive oil only. Erythema was induced by illumination of dorsal skin (scapular region) with a solar simulator at the beginning of the study, after 4 wk and after 10 wk. Intensity of erythema was measured by chromatometry; the a-value was determined directly before and 24 h after irradiation. Serum carotenoid levels were measured by HPLC. At the beginning of the study, carotenoid levels did not differ between the two groups. Serum levels of lycopene increased in supplemented subjects; the other carotenoids did not change significantly, and no change in serum carotenoids was observed in the control group. At wk 10, dorsal erythema formation was 40% lower in the group that consumed tomato paste compared with controls (P = 0.02; Wilcoxon-Mann-Whitney test). No significant difference between groups was found at wk 4 of treatment. The data demonstrate that it is feasible to achieve protection against UV light-induced erythema by ingestion of a commonly consumed dietary source of lycopene.

Adult↗

Clinical and endocrine characteristics in atypical and classical growth hormone insensitivity syndrome.

OBJECTIVE: Classical growth hormone insensitivity syndrome (GHIS) comprises a dysmorphic phenotype, extreme short stature (height SDS < 3), normal GH and low IGF-I and IGFBP-3. Wide clinical variation is recognised with classical and atypical forms. We aimed to delineate features of the milder "atypical" GHIS phenotype, and to determine whether this correlates with milder auxological and biochemical features. METHODS: Fifty-nine patients from a European series of 82 patients with GHIS, with strict diagnostic criteria of GHIS, were studied and assigned to classical or atypical GHIS groups according to facial phenotype, i.e. "classical" required 2 of 3 recognized GHIS features (frontal bossing, mid-facial hypoplasia and depressed nasal bridge), "atypical" required 0 or 1 of these facial features. Classical and atypical GHIS groups were compared in terms of (1) phenotypic features, including high-pitched voice, sparse hair, blue sclera, hypoglycaemia, microphallus, (2) birth length, height SDS, and (3) basal IGF-I, IGF-II, IGFBP-1, IGFBP-3, GHBP and increase in IGF-I on IGF-I generation testing. RESULTS: Fifty patients [24 males, 26 females, aged 8.6 +/- 4.6 years (mean +/- SD)] had "classical GHIS", 9 patients (7 males, 2 females, aged 7.8 +/- 4.1 years) had "atypical GHIS", 7 with normal facies. Atypical GHIS patients had lesser height deficit (Ht SDS -4.0 +/- 1.4) compared to classical GHIS (-6.7 +/- 1.4), less reduction in IGFBP-3 SDS (atypical -5.5 +/- 3.3; classical -8.6 +/- 2.4), and more had normal GHBP (>10% binding). Other variables were also less frequent in atypical GHIS patients: high-pitched voice 11% (70% classical), sparse hair 11% (42% classical), blue sclera 0% (38% classical), hypoglycaemia 11% (42% classical), and microphallus 14% (1 of 7 males), compared to 79% of classical (19 of 24 males). CONCLUSIONS: Atypical GHIS patients, with relatively normal facial appearance, demonstrate less height defect and biochemical abnormalities compared to classical patients. GH insensitivity may be present in children with short stature and an otherwise normal appearance.

Body Height↗

Immuno-electron microscopic localization of the alpha(1) and beta(1)-subunits of soluble guanylyl cyclase in the guinea pig organ of corti.

Guanylyl cyclases (GC) catalyze the formation of the intracellular signal molecule cyclic GMP from GTP. For some years it has been known that the heme-containing soluble guanylyl cyclase (sGC) is stimulated by NO and NO-containing compounds. The sGC enzyme consists of two subunits (alpha(1) and beta(1)). In the present study, the alpha(1) and beta(1)-subunits were identified in the guinea pig cochlea at the electron microscopic level using a post-embedding immuno-labeling procedure. Ultrathin sections of LR White embedded specimens were incubated with various concentrations of two rabbit polyclonal antibodies to the alpha(1)- and beta(1)-subunit, respectively. The immunoreactivity was visualized by a gold-labeled secondary antibody in an energy-filtering transmission electron microscope (EFTEM). Marked immunoreactivity for both antibodies was found in the inner and outer hair cells, with numerous gold particles at the border of the cuticular plates, associated with the cell nuclei or attached to electron-dense parts of the cytoplasm. In the pillar cells and apical Deiters cells, soluble guanylyl cyclase immunoreactivity was located at the rim of the cuticular plates and between the microtubuli bundles. Together with the recently identified nitric oxide synthase isoforms [Eur. Arch. Otorhinolaryngol. 254 (1997) 396; Eur. Arch. Otorhinolaryngol. 255 (1998) 483], the soluble guanylyl cyclase may be involved in signalling processes in the organ of Corti.

Animals↗

Role of inflammation in chemical-induced lung cancer.

Chemical-induced carcinogenesis has been in the focus of toxicological research for many decades. However, the mechanisms leading to tumor formation are only understood with certain substances. The intake of potential carcinogens by inhalation is a major route of exposure. Chemical-induced lung tumors are the final manifestation of a multistep pathway, resulting in an imbalance between cell proliferation and cell death by apoptosis. The impact of certain confounding factors e.g. extent of inflammatory response, type of genotoxic event, antagonizing principles and genetic background are discussed in this article. Finally, methods to assess the inflammatory potential of chemicals are referred to.

Administration, Inhalation↗

Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans.

BACKGROUND: Carotenoids and tocopherols, known to be efficient antioxidants and capable of scavenging reactive oxygen species generated during photooxidative stress, may protect the skin from ultraviolet light-induced erythema. beta-Carotene is widely used as an oral sun protectant but studies on its protective effects are scarce. OBJECTIVE: The objective of this study was to investigate the protective effects of oral supplementation with carotenoids and a combination of carotenoids and vitamin E against the development of erythema in humans. DESIGN: A carotenoid supplement (25 mg total carotenoids/d) and a combination of the carotenoid supplement and vitamin E [335 mg (500 IU) RRR-alpha-tocopherol/d] were given for 12 wk to healthy volunteers. Erythema was induced by illumination with a blue-light solar simulator. Serum beta-carotene and alpha-tocopherol concentrations and skin carotenoid levels were assessed by HPLC and reflection photometry. RESULTS: Serum beta-carotene and alpha-tocopherol concentrations increased with supplementation. Erythema on dorsal skin (back) was significantly diminished (P < 0.01) after week 8, and erythema suppression was greater with the combination of carotenoids and vitamin E than with carotenoids alone. CONCLUSION: The antioxidants used in this study provided protection against erythema in humans and may be useful for diminishing sensitivity to ultraviolet light.

Adult↗

Bioavailability of fine dispersed platinum as emitted from automotive catalytic converters: a model study.

Automobile exhaust catalytic converters emit fine dispersed elemental platinum, Pt (0), in the nanometer range coated on larger aluminium oxide carrier particles. A pre-requisite for a potential systemic toxic effect of the emitted platinum is its bioavailability which was investigated using laboratory animals. To this end, a model substance was synthesised which consisted of aluminium oxide particles < or = 5 microns onto which platinum particles > or = 4 nm were deposited by a calcination process. These particles closely resemble those emitted from automobile exhaust converters. This model substance was applied to female Lewis rats in two doses by intratracheal instillation; the animals were killed after 1, 7, 28 and 90 days. In addition, the model substance was also applied during a 90-day inhalation study. After microwave digestion of the tissues, the platinum was determined in all organs and body fluids by inductively coupled plasma/mass spectrometry (ICP/MS). Platinum was found in the blood, urine and faeces and all important organs (liver, spleen, kidneys, adrenals, stomach, femur). Based on the platinum content determined in the body fluids and all organs (except the lung and the faeces) it was calculated that up to 16% of the platinum was retained in the lung 1 day after intratracheal instillation and up to 30% of the fine dispersed platinum deposited on an average during 90 days inhalation in the lung was bioavailable. Using size exclusion chromatography (SEC) in combination with ICP/MS, it was shown that > or = 90% of the bioavailable platinum was bound to high molecular weight compounds (approximately 80-800 kDa), most likely proteins.

Administration, Inhalation↗

Effect of iodine supply on neonatal thyroid volume and TSH.

A cross-sectional study was performed to prove the correlation between iodine intake and neonatal thyroid volume in a randomized group of 100 mother/newborn pairs. Thyroid volume and iodine excretion were measured by ultrasound and urinary iodine excretion, respectively. Iodine intake and, nutritional and smoking habits were estimated by questionnaire. In 89 mother/child-pairs the data were complete for all parameters and have been analyzed: 32 mothers substituted with iodine tablets, average dose 175 microg K-Iodide/day. Iodine excretion of prenatally iodine-substituted newborns increased by 62% whereas neonatal thyroid volume was reduced by 18% compared with the non-iodine-supplemented group. Smoker's newborns (n = 8) had a thyroid volume 20% larger than that of newborns of non-smokers. Neonatal TSH-screening values remained within normal limits.

Cross-Sectional Studies↗

Norditropin SimpleXx: a liquid human growth hormone formulation, a pen system and an auto-insertion device.

Patient compliance is of vital importance for the outcome of any medical therapy. Compliance is especially a problem in long-term treatment of non-life threatening diseases, such as growth retardation in children. Until recently, all human growth hormone (hGH) products required a reconstitution process. Norditropin((R)) SimpleXx(TM) is a liquid formulation of the biosynthetic hGH product Norditropin((R)), and, together with an improved NovoPen((R)) 1.5, NordiPen(TM), and an auto-insertion device, PenMate(TM)/NordiPenMate(TM), it has been developed in order to ease the injection process for patients. A randomized, open, multicentre, crossover trial compared Norditropin((R)) SimpleXx(TM)/improved NovoPen((R)) 1.5 with freeze-dried Norditropin((R)) PenSet((R))/Nordiject((R)). A total of 67 children with GH deficiency, aged 5-18 years, were treated with either Norditropin((R)) SimpleXx(TM) for 6 weeks followed by Norditropin((R)) for 6 weeks or the opposite (sequences I and II, respectively). Acceptability/convenience and pain perception were evaluated by questionnaire after each period. The function and handling of the PenMate(TM) were evaluated in a Dutch trial by 27 GH-treated children with intrauterine growth retardation, aged 4-16 years, and their parents. All children were accustomed to using the Nordiject((R)) pen. The evaluation of the PenMate(TM) was based on a questionnaire. A similar trial was conducted in England, in which the NordiPen(TM) and the NordiPenMate(TM) were evaluated by 25 GH-treated children and their parents. Norditropin((R)) SimpleXx(TM) was found to be easier to inject by 64% of the children, and 98% of the children found the system easier to use overall. There was no difference in pain perception between the two administration systems, as judged by questionnaires and visual analogue scale score. Three out of four patients preferred to continue treatment with Norditropin((R)) SimpleXx(TM). The safety profiles of the two systems were similar. In the Dutch trial, the PenMate(TM) was found to be easy and safe to handle, even for very young children (aged 4-5 years). Of patients who took a long time to get used to the injections, 73% found that the new pen would help. A total of 88% of the children would prefer to use the PenMate(TM) in the future. Positive results of the handling tests were also reported in the British trial. The use of Norditropin((R)) SimpleXx(TM) and the auto-insertion device may improve patient compliance.

Adolescent↗

Bioavailability of platinum emitted from automobile exhaust.

A model substance was used which is similar in respect to platinum content of exhaust particles emitted from a three-way-catalytic converter equipped engine. The bioavailability of platinum from such exhaust particles and the kind of platinum species formed in vivo were assessed. An in vitro solubility test showed a solubility of approximately 10 percent of platinum content of the model substance in physiological sodium chloride solution. Two short-term animal studies (8 days) were performed. In all examined rat tissues and body fluids platinum could be detected. In addition, the contribution of the overall bioavailability caused by swallowing a certain amount of the intratracheally applied platinum was evaluated by oral application. It was very low. An analytical method was developed to determine platinum species. Synthetic samples (matrix with a platinum standard solution) were analysed. In rat bronchoalveolar lavage spiked with a platinum standard solution only low molecular complexed platinum was found whereas in rat blood plasma all platinum was bound to proteins. In ongoing studies, the model substance is being tested in a three month rat inhalation study.

Animals↗

Increased dermal carotenoid levels assessed by noninvasive reflection spectrophotometry correlate with serum levels in women ingesting Betatene.

beta-Carotene is being used as an oral sun protectant, and evidence indicates that carotenoids may protect human skin from light-induced lesions. However, limited information is available on the distribution and accumulation of beta-carotene in skin, especially with respect to various skin regions. With the use of reflection spectroscopy, we investigated the accumulation of total carotenoids in human skin after repeated supplementation of 12 women with beta-carotene from a natural source Betatene, an algal extract. After daily ingestion of 24 mg beta-carotene (in Betatene) for 12 wk, an increase in carotenoid skin levels was observed. Highest basal values were measured in skin of the forehead, palm of the hand and dorsal skin, with lower levels measured in skin of the arm and back of the hand. Upon treatment, increases in carotenoid skin levels were found in all areas as follows: 2.4-fold in forehead, 0.7-fold in dorsal skin, 2.2-fold in the palm of the hand, 17-fold on the back of the hand and 1.7-fold on the inside of the arm. After cessation of treatment, the carotenoid levels decreased in all skin areas. Serum beta-carotene levels were elevated upon treatment and correlated with carotenoid skin levels. Correlations for serum vs. skin from the palm of the hand (r = 0.94) and skin from the forehead (r = 0.89) were calculated, indicating that serum levels appeared to be a suitable indicator for carotenoid accumulation in specific regions of the skin. With doses of approximately 20-25 mg carotenoids/d, it is possible to raise dermal carotenoid levels.

Adult↗