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Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 109 records · Page 6Linked to original sources

Skin irritation from air-oxidized ethoxylated surfactants.

Surfactants are known to be skin irritants, but change in their irritant potential due to change in composition during handling and storage has not previously been investigated. The aim of this study was to investigate the influence of oxidation products on the irritant potential of a non-ionic ethoxylated alcohol, C12E5. Pure and oxidized C12E5 were tested, using 2 different patch test procedures; 1 with a single 24 h exposure and 1 with repeated exposures. 18 healthy volunteers participated in each of these studies. Evaluations were made by visual scoring and by measurement of transepidermal water loss and skin blood flow. In the single exposure study, no significant difference in skin irritation was observed between pure C12E5 and a sample of oxidized C12E5 at the concentrations tested (1, 3, 9 and 27%). After repeated exposures, however, the oxidized C12E5 was significantly more irritant than pure C12E5 at the concentrations 9% and 27% (p<0.05). Non-ionic ethoxylated surfactants are known for their weak skin irritant effect and are, due to this, often included in products with prolonged contact with the skin, i.e., skin care products. An increased irritant potential after oxidation might be of importance due to the conditions of use.

Adult↗

Dental erosion in Cuban children associated with excessive consumption of oranges.

Marked erosion at the mesial edges of upper front teeth was observed during an examination of Cuban children. The preferential erosion of mesial edges produced characteristic V-shaped defects on upper central incisors, and the aim of the present study, carried out on 12-yr-old children (N = 1010) in 10 communities in the Province of Havana was to establish the frequency of dental erosion and explain its occurrence. The symmetrical erosion of teeth 11 and 21 (excluding crown injuries and attrition) were clinically classified into four grades: 0.5 = objectionable; 1 = abnormal mesial shortening of incisal edges; 2 = V-shaped defect of cutting edges; 3 = exposure of dentine and extension of the erosive defect to the lateral incisors. In four of the communities, children did not show or rarely showed incisal erosion. In the other six communities, the frequency was surprisingly high (16.6-40.9%). Overall, 17.4% of children exhibited erosion, and the occurrence was significantly higher in girls (20.7%) than in boys (15.0%). The typical V-shaped pattern of erosion seems to be a consequence of the manner in which citrus fruits are eaten. There was also a positive correlation between the frequency of dental erosion and the proximity of citrus plantations, which presumably related to the extent of (daily) orange consumption.

Adolescent↗

T helper 1-type cytokine transcription in peripheral blood mononuclear cells of pseudorabies virus (Suid herpesvirus 1)-primed swine indicates efficient immunization.

The induction of porcine cytokines, which are believed to be important for the regulation of T helper (Th)1- and Th2-specific immune responses of pigs, was analysed after in vitro restimulation with a herpesvirus, Suid herpes 1 (pseudorabies virus [PRV]), in peripheral blood mononuclear cells (PBMC). To this end, quantitative, competitive reverse transcription-polymerase chain reaction (RT-qcPCR) was established using constructed heterologous DNA MIMICS, which contain cytokine- or glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-specific primer-binding sites. This is a simple method that allows reliable determination of the differing regulation of cytokine mRNAs specific for porcine interleukin (IL)-2, -4 and -10, interferon gamma (IFN-gamma) and the housekeeping gene, GAPDH, as an endogenous control. PBMC derived from naive (innate response) and PRV-primed (memory response) outbred swine were analysed comparatively. The results demonstrated that restimulation with PRV significantly enhanced the transcription of Th1-type cytokines (IL-2 and IFN-gamma) but not of Th2-type cytokines (IL-4 and IL-10). This virus-specific cytokine response was only found with PBMC from swine protected against lethal PRV challenge infection, but not with naive PBMC or with PBMC from pigs immunized with plasmid DNA encoding PRV glycoprotein gC. Notably, PBMC derived from immune and naive pigs constitutively produced relatively high amounts of IL-10-specific mRNA, exceeding that of GAPDH mRNA, independently of the addition of viral antigen or the mitogen concanavalin A (Con A). The results of this work should help to provide a better understanding of the effector cell/cytokine network response to infection with, or vaccination against, PRV. Additionally, the simple, reliable and sensitive RT-qcPCR, when used to determine the porcine cytokine pattern, might be of prognostic value for the induction of protective immunity.

Animals↗

Vascular reactivity in patients with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome.

OBJECTIVE: Early structural and functional changes in the systemic vasculature have been proposed to play a major pathogenetic role in preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. The aim of the study was to determine vascular reactivity in patients with preeclampsia with and without HELLP syndrome with respect to those in healthy pregnant control subjects. STUDY DESIGN: Forearm blood flow was measured by strain gauge plethysmography with the venous occlusion technique in 12 hypertensive patients with HELLP syndrome, in 8 patients with preeclampsia without HELLP syndrome, and in 8 healthy normotensive pregnant control subjects. To determine vascular reactivity the forearm blood flow was measured at baseline and after forearm occlusion for a period of 5 minutes (reactive hyperemia). The investigations were repeated 4 to 6 months post partum. Forearm vascular resistance was calculated as the ratio of mean arterial pressure to forearm blood flow. RESULTS: Mean arterial pressure at rest was elevated in patients with preeclampsia (116 +/- 20 mm Hg) and in patients with HELLP syndrome (110 +/- 16 mm Hg) with respect to healthy pregnant control subjects (86 +/- 10 mm Hg; P <.05). Forearm blood flow at rest was not statistically different in patients with preeclampsia (5.1 +/- 2.6 mL/min per 100 mL) and with HELLP syndrome (4.7 +/- 1.5 mL/min per 100 mL) with respect to pregnant control subjects (5.9 +/- 3.1 mL/min per 100 mL); however, forearm vascular resistance at rest was elevated in patients with preeclampsia (25.9 +/- 9.5 units; P <.05) and in patients with HELLP syndrome(24.6 +/- 6.9 units; P <.05) with respect to healthy control subjects (17.0 +/- 6.1 units). During reactive hyperemia the peak forearm blood flow, which is an indicator of maximal vasodilatory capacity, was impaired in patients with preeclampsia (21.9 +/- 8.2 mL/min per 100 mL; P <.05) but not in patients with HELLP syndrome (37.4 +/- 17.5 mL/min per 100 mL) and healthy control subjects (44.9 +/- 15.0 mL/min per 100 mL). Consequently, minimum forearm vascular resistance was higher in women with preeclampsia (6.1 +/- 1.9 units) than in both women with HELLP syndrome (3.5 +/- 1.6 units) and the control subjects (2.8 +/- 2.4 units). CONCLUSION: Despite similarly elevated forearm vascular resistances at rest in patients with HELLP syndrome and in patients with preeclampsia, forearm vascular resistance during reactive hyperemia did not differ significantly from that in healthy control subjects in the women with HELLP syndrome but was increased in women with preeclampsia. Vasodilatory reactivity thus is reduced in preeclampsia but not in HELLP syndrome, which suggests different alterations of the vasculature.

Adult↗

Metabolic activity of fresh and cryopreserved cynomolgus monkey (Macaca fascicularis) hepatocytes.

1. The effect of cryopreservation on the metabolic capacity of monkey hepatocytes over 4 h in suspension and 24 h in culture was determined. Hepatocytes were diluted in a buffer containing 10% DMSO and frozen in a computer-controlled chamber. 2. Initial ethoxyresorufin and ethoxycoumarin O-deethylase (ECOD) activities were the same in fresh and cryopreserved (CP) hepatocytes. ECOD activity in suspensions declined over 4 h but was the same in fresh and CP hepatocytes. 3. The formation of testosterone hydroxy (OHT) metabolites (namely 6beta-OHT, 2beta-OHT, 16beta-OHT, 16alpha-OHT, 15beta-OHT, 2alpha-OHT and 6beta-OHT) was unaffected by cryopreservation. The loss of OHT activities over 4 h in CP and fresh whole cell suspensions was attributed to a loss of cofactor. CP hepatocyte cultures had equivalent OHT activities to freshly isolated hepatocytes. 4. Initial UDP-glucuronyltransferase (UGT) activities, using the substrates 4-methylumbelliferone, ethoxycoumarin and hydroxycoumarin, were equivalent in fresh and CP whole hepatocytes. At later times, UGT activity was lower in CP than fresh hepatocytes but this was due to a loss of UDPGA. Initial sulphotransferase (SULT) activities, using the substrates 2-naphthol, ethoxycoumarin and hydroxycoumarin, were equivalent in fresh and CP hepatocytes. SULT activities were less stable than UGT activities but were the same in fresh and CP hepatocytes throughout the 4-h incubation. 5. Initial glutathione S-transferase activities (using 1-chloro-2,4-dinitrobenzene) were the same in fresh and CP hepatocytes and both did not decrease over 4 h. 6. CP monkey hepatocytes are a useful model for metabolic and cytotoxicity studies. These cells can be can be used either in suspension or in culture.

Animals↗

Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction.

The use of primary hepatocytes is now well established for both studies of drug metabolism and enzyme induction. Cryopreservation of primary hepatocytes decreases the need for fresh liver tissue. This is especially important for research with human hepatocytes because availability of human liver tissue is limited. In this review, we summarize our research on optimization and validation of cryopreservation techniques. The critical elements for successful cryopreservation of hepatocytes are (1) the freezing protocol, (2) the concentration of the cryoprotectant [10% dimethyl-sulfoxide (DMSO)], (3) slow addition and removal of DMSO, (4) carbogen equilibration during isolation of hepatocytes and before cryopreservation, and (5) removal of unvital hepatocytes by Percoll centrifugation after thawing. Hepatocytes of human, monkey, dog, rat, and mouse isolated and cryopreserved by our standard procedure have a viability > or = 80%. Metabolic capacity of cryopreserved hepatocytes determined by testosterone hydroxylation, 7-ethoxyresorufin-O-de-ethylase (EROD), 7-ethoxycoumarin-O-deethylase (ECOD), glutathione S-transferase, UDP-glucuronosyl transferase, sulfotransferase, and epoxide hydrolase activities is > or = 60% of freshly isolated cells. Cryopreserved hepatocytes in suspension were successfully applied in short-term metabolism studies and as a metabolizing system in mutagenicity investigations. For instance, the complex pattern of benzo[a]pyrene metabolites including phase II metabolites formed by freshly isolated and cryopreserved hepatocytes was almost identical. For the study of enzyme induction, a longer time period and therefore cryopreserved hepatocyte cultures are required. We present a technique with cryopreserved hepatocytes that allows the induction of testosterone metabolism with similar induction factors as for fresh cultures. However, enzyme activities of induced hepatocytes and solvent controls were smaller in the cryopreserved cells. In conclusion, cryopreserved hepatocytes held in suspension can be recommended for short-term metabolism or toxicity studies. Systems with cryopreserved hepatocyte cultures that could be applied for studies of enzyme induction are already in a state allowing practical application, but may be further optimized.

Animals↗

Persistent Legionella infection in a patient after bone marrow transplantation.

We report on a patient who developed Legionella pneumonia after bone marrow transplantation. Despite appropriate antibiotic treatment, disease progressed. The patient developed a lung abscess from which Legionella and Prevotella were isolated. Cure was achieved by surgical resection. The resected material was sterile, but 16S ribosomal DNA analysis revealed Legionella DNA.

Bone Marrow Transplantation↗

Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis- cellularity correlates with the degree of enhancement detected by magnetic resonance imaging.

OBJECTIVE: Sacroiliitis is a hallmark of the spondyloarthropathies (SpA). The degree of inflammation can be quantified by magnetic resonance imaging (MRI). The aim of this study was to further elucidate the pathogenesis of SpA by quantitative cellular analysis of immunostained sacroiliac biopsy specimens and to compare these findings with the degree of enhancement in the sacroiliac joints (SJ) as detected by dynamic MRI. METHODS: The degree of acute sacroiliitis detected by MRI after intravenous administration of gadolinium-DTPA was quantitatively assessed by calculating the enhancement observed in the SJ and chronic changes were graded as described in 32 patients with ankylosing spondylitis (n=18), undifferentiated SpA (n=12) and psoriatic arthritis (n=2). Back pain was graded on a visual analogue scale (VAS, 0-10) and disease duration (DD) was assessed. Shortly after MRI, SJ of patients with VAS > 5 were biopsied guided by computed tomography. Immunohistological examination was performed using the APAAP technique; only whole sections > 3 mm were counted. RESULTS: By MRI, chronic changes </= grade II were detected in nine patients (group I, DD 2.5 (SD 2.9) years) and > II in 13 patients (group II, DD 7.3 (SD 4.8) years), while enhancement < 70% was found in eight (group A, DD 5.6 (SD 3.3) years) and > 70% in 12 patients (group B, DD 4.7 (SD 5.8) years). The relative percentage of cartilage (78-93%), bone (7-18%) and proliferating connective tissue (1-4%) was comparable between the groups (range). There were more inflammatory cells in group I compared with group II (mean (SD) 26.7(20.1) versus 5.3 (5. 2), p=0.04) and group A compared with B (21.8 (17.3) versus 6.0 (5. 6), p=0.05) cells/10 mm(2)), T cells (10.9 (8.5)) being slightly more frequent than macrophages (9.6 (16.8/10 mm(2))). Clusters of proliferating fibroblasts were seen in three and new vessel formation in seven cases. CONCLUSION: This study shows that T cells and macrophages are the most frequent cells in early and active sacroiliitis in SpA. The correlation of cellularity and MRI enhancement provides further evidence for the role of dynamic MRI to detect early sacroiliitis.

Acute Disease↗

The regulator of G protein signaling family.

Regulator of G protein signaling (RGS) proteins are responsible for the rapid turnoff of G protein-coupled receptor signaling pathways. The major mechanism whereby RGS proteins negatively regulate G proteins is via the GTPase activating protein activity of their RGS domain. Structural and mutational analyses have characterized the RGS/G alpha interaction in detail, explaining the molecular mechanisms of the GTPase activating protein activity of RGS proteins. More than 20 RGS proteins have been isolated, and there are indications that specific RGS proteins regulate specific G protein-coupled receptor pathways. This specificity is probably created by a combination of cell type-specific expression, tissue distribution, intracellular localization, posttranslational modifications, and domains other than the RGS domain that link them to other signaling pathways. In this review we discuss what has been learned so far about the role of RGS proteins in regulating G protein-coupled receptor signaling and point out areas that may be fruitful for future research.

Amino Acid Sequence↗

Angiotensin II receptor subtypes determine induced NO production in rat glomerular mesangial cells.

Angiotensin II (ANG II) and nitric oxide (NO) have contrasting vascular effects, yet both sustain inflammatory responses. We investigated the impact of ANG II on lipopolysaccharide (LPS)/interferon-gamma (IFN)-induced NO production in cultured rat mesangial cells (MCs). LPS/IFN-induced nitrite production, the inducible form of nitric oxide synthase (NOS-2) mRNA, and protein expression were dose dependently inhibited by ANG II on coincubation, which was abolished on ANG II type 2 (AT(2)) receptor blockade by PD-123319. Homology-based RT-PCR verified the presence of AT(1A), AT(1B), and AT(2) receptors. To shift the AT receptor expression toward the type 1 receptor, two sets of experiments were performed: LPS/IFN preincubation for 24 h was followed by 8-h coincubation with ANG II; or during 24-h coincubation of LPS/IFN and ANG II, dexamethasone was added for the last 6-h period. Both led to an amplified overall expression of NOS-2 protein and NO production that was inhibitable by actinomycin D in the first setup. Induced NO production was enhanced via the AT(1) receptor; however, it was diminished via the AT(2) receptor. In conclusion, induced NO production is negatively controlled by the AT(2), whereas AT(1) receptor stimulation enhanced NO synthesis in MCs. The overall NO availability depended on the onset of the inflammatory stimuli with respect to ANG II exposure and the available AT receptors.

Angiotensin II↗

TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II.

The present study was conducted to explore the possible contribution of a recently described leak K+ channel, TASK (TWIK-related acid-sensitive K+ channel), to the high resting K+ conductance of adrenal glomerulosa cells. Northern blot analysis showed the strongest TASK message in adrenal glomerulosa (capsular) tissue among the examined tissues including heart and brain. Single-cell PCR demonstrated TASK expression in glomerulosa cells. In patch-clamp experiments performed on isolated glomerulosa cells the inward current at -100 mV in 30 mM [K+] (reflecting mainly potassium conductance) was pH sensitive (17+/-2% reduction when the pH changed from 7.4 to 6.7). In Xenopus oocytes injected with mRNA prepared from adrenal glomerulosa tissue the expressed K+ current at -100 mV was virtually insensitive to tetraethylammonium (3 mM) and 4-aminopyridine (3 mM). Ba2+ (300 microM) and Cs+ (3 mM) induced voltage-dependent block. Lidocaine (1 mM) and extracellular acidification from pH 7.5 to 6.7 inhibited the current (by 28% and 16%, respectively). This inhibitory profile is similar (although it is not identical) to that of TASK expressed by injecting its cRNA. In oocytes injected with adrenal glomerulosa mRNA, TASK antisense oligonucleotide reduced significantly the expression of K+ current at -100 mV, while the sense oligonucleotide failed to have inhibitory effect. Application of angiotensin II (10 nM) both in isolated glomerulosa cells and in oocytes injected with adrenal glomerulosa mRNA inhibited the K+ current at -100 mV. Similarly, in oocytes coexpressing TASK and ATla angiotensin II receptor, angiotensin II inhibited the TASK current. These data together indicate that TASK contributes to the generation of high resting potassium permeability of glomerulosa cells, and this background K+ channel may be a target of hormonal regulation.

4-Aminopyridine↗

The effect of continuous treatment with sodium nitroprusside on the serum kinetics of the brain marker protein S-100beta in neonates undergoing corrective cardiac surgery by means of hypothermic cardiopulmonary bypass.

Neonates who undergo cardiac surgery of d-transposition of the great arteries by means of hypothermic cardiopulmonary bypass (CPB) represent a group at increased risk to develop brain injury and altered psychomotor development in early life. Measurement of protein S-100beta, an astrocytic calcium binding protein, in serum may provide information on transient astroglial cell activation and disintegration of the related blood-brain barrier due to oxidative stress during and after CPB. Conflicting results have been reported that concern the neuroprotective effect of the NO liberator sodium nitroprusside (SNP) in vitro. We evaluated the effect of continuous treatment with SNP on the serum kinetics of S-100beta in infants and children after corrective cardiac surgery. The data on 25 neonates treated intraoperatively and postoperatively and 28 without treatment were analyzed. SNP was infused (1-5 microg/kg body weight/minute depending on the haemodynamic status) after the induction of anesthesia, and during and after the termination of CPB for 2 days. Serum concentrations of S-100beta were analyzed by the use of a commercially available immunoluminometric kit (Byk-Sangtec, Dietzenbach, Germany). There were no significant differences in the bypass data between the SNP-treated and non-treated group. In comparison to the pre-bypass values, a similar increase in the concentration of protein S-100beta was found 2 hours after the termination of CPB in the SNP-treated and non-treated neonates, which decreased over the subsequent 48 postoperative hours. However, significantly lower post-bypass serum levels of S-100beta were found in the SNP-treated group after 24 hours (p = 0.0009) and 48 hours (p = 0.04) of treatment. In conclusion, the significant elevation of serum levels of protein S-100beta may indicate increased astroglial cell reactivity and increased passage into the blood stream. Longer-lasting treatment with NO liberator SNP seemed to decrease the release of S-100beta into the blood stream and may have delayed protection on the astroglial cells. The neurological significance of such an observation, however, should be evaluated in further follow-up studies, which need to include additional neurophysiological and neurodevelopmental tests.

Biomarkers↗

Effect of corticosteroids on HELLP syndrome: a case report.

The HELLP syndrome is associated with a high rate of prematurity, which is the major cause of neonatal morbidity and mortality. Several studies have demonstrated the feasibility of prolongation of pregnancies complicated by HELLP syndrome. Until now the role of an additive pharmacological regimen, and particularly the role of corticosteroids, is still not clear. We report a case of a successful prolongation of a pregnancy complicated by HELLP syndrome and note a direct relationship with application and withdrawal of corticosteroids. A 26-year old primigravida was admitted with HELLP syndrome in the 25th week of gestation. We commenced a therapy with 40 mg methylprednisolone i.v. once daily, with clinical symptoms and biochemical parameters improving within two days. On day 6 we discontinued steroid medication with a consecutive deterioration of all biochemical data and clinical symptoms. Corticosteroids were recommenced and within two hours an improvement of all symptoms and laboratory data was observed. Overall we were able to prolong the pregnancy for 33 days. This case report underlines the beneficial effect of corticosteroids in patients with HELLP syndrome. Thus steroids might be helpful for postponing deliveries in very preterm gestation and for stabilizing the maternal status.

Adult↗

A gelatin sponge implantation model in swine for the determination of local immune reactions.

For in vivo determination of innate and memory immune reactions we have implanted sterile gelatin sponges subcutaneously in swine for the monitoring of the following immunological parameters: 1. Analysis of local cell population phenotypes after vascularization of the gelatin sponges using flow cytometry. 2. Comparative analysis of sponge-infiltrating cells after loading with viral antigen in primed as well as naive animals. 3. Performance of reverse transcription quantitative competitive PCR (RT-qcPCR) for the detection of porcine cytokine mRNA indicative for IFN-gamma, IL-2, IL-4, IL-8 and IL-10. The in vitro analysis, e.g. by re-exposure to viral antigens, allows the determination of cytokine reaction patterns of sponge derived cells, draining lymph node cells as well as PBMC of the same individual. Studies of innate reactions and modulation of cellular infiltration in transplanted gelatin sponges are possible. Functional assays, e.g. cell-mediated cytotoxicity, antigen specific cell proliferation, using sponge-derived cells will provide additional information about the suitability of the model for example in vaccine potency tests.

Animals↗

Workers' dermal exposure to UV-curable acrylates in the furniture and Parquet industry.

The use of ultraviolet radiation-curable coatings (UV-coatings) has increased rapidly in the parquet and furniture industry. Work with UV-coatings involves risk from skin exposure to chemically reactive, concentrated acrylates that are known skin contact irritants and sensitizers. Yet, the methods and tools for measuring and quantifying dermal exposure from hazardous chemicals directly on the skin are limited and methods to measure skin exposure to UV-coatings in occupational or environmental settings have been lacking. Skin exposure to UV-coatings was measured employing a quantitative tape stripping method that we have developed for this purpose. A pilot study was performed at three workplaces. In the main study, workers' skin exposure to uncured UV-coatings was measured at seven workplaces and on two separate workdays (rounds 1 and 2) within a six-month period to determine exposure variation. Skin exposure was measured at four standardized sites on the hand, 3-4 times per work shift. The forehead was sampled once. A questionnaire was carried out with the workers in both rounds to find out factors that can affect skin exposure to UV-coatings. The pilot study indicated that both skin and surface contamination to TPGDA-containing UV-coatings were common and varied up to 2110 microgram on the sampling area of 10cm(2). In the main study skin contamination due to TPGDA was found on 16 of 23 workers, at 6 out of the 7 workplaces, and from 36 (5. 4%) of the 664 samples. In round one 8.6% (n=383) of the samples contained TPGDA and in round two 1.1 % (n=281). The average TPGDA mass on all the positive samples (n=36) was 30.4+/-77.0 microgram for the first and second rounds alone this mass was 30.6+/-80 (n=33) and 28.3+/-16.5 microgram (n=3), respectively. Despite the limited sampling area and sampling sites, we could find residues of TPGDA at all sampling times, even at the beginning of the work shift. This may be due to transfer of UV-coatings through contaminated equipment, shoes and surfaces. Our study indicates that there is a risk of harmful skin exposure to UV-coatings in the furniture and parquet industry.

Acrylates↗

[Comparative epidemiologic study of caries in German and Hungarian adolescents].

The aim of the study was to assess the trend of caries prevalence in German and Hungarian population sample. The authors examined 15-16-year-old Hungarian adolescents in Debrecen and Budapest in 1997 (451 persons), then re-examined them in 1999 (377 persons). These data were compared to those of 15-16 and 17-18-year-old adolescents examined in the Eastern part of Germany (Plauen) in 1991 (668 persons) and in 1995 (586 persons). The results showed significant caries reduction in Germany. The DMFT values of 17-18-year-old adolescents were nearly half in Germany (x = 5.2) compared to those of Hungary (x = 9.0). This fact suggests the necessity of introduction of effective preventive programs including salt fluoridation in Hungary.

Adolescent↗

Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtaline (AHTN).

Synthetic musks are present in fine fragrances, cosmetics, soaps and laundry detergents. One of the most important synthetic musks is 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline+ ++ (AHTN; annual production: about 1500 metric tons). An increasing number of studies show that AHTN accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. In the present report it is shown that a single high dose of AHTN leads to acute hepatic damage in rats, characterized by single cell necrosis, inflammation, swelling of liver parenchymal cells, and the presence of cytoplasmic condensations in the hepatocytes, while at the ultrastructural level disorganization of the rough endoplasmic reticulum and mitochondria as well as focal cytolysis is evident. Furthermore, evidence is presented that AHTN is not genotoxic, does not induce peroxisome proliferation, and does not lead to the induction of drug-metabolizing enzymes as phenobarbital and 3-methylcholanthrene do.

Animals↗