Efficacy of the stannous ion and a biopolymer in toothpastes on enamel erosion/abrasion.

OBJECTIVES: Sn(2+) has promising erosion-inhibiting properties in solutions, but little is known about respective effects in toothpastes. In addition, biopolymers might have protecting potential. Aim of this study was to investigate the effects of Sn(2+) in toothpastes and of a biopolymer (chitosan) added to a Sn(2+) formulation on erosion/abrasion. METHODS: Enamel samples were subjected to cyclic erosion procedures (10 days; 0.50% citric acid, pH 2.5; 6× 2 min/day), and brushing (2× 15s/day, load 200 g) during immersion in slurries (2 min). The toothpastes were NaF formulations (NaF/1, NaF/2, NaF/3) and Sn(2+) formulations (NaF/SnCl(2), AmF/SnF(2), AmF/NaF/SnCl(2)) and AmF/NaF/SnCl(2)+0.5% chitosan. Declared concentrations of active ingredients in toothpastes were 1400-1450 µg/g F(-) and 3280-3500 µg/g Sn(2+). Negative controls were erosion only and placebo, positive control was a SnF(2) gel. Tissue loss was quantified profilometrically, Sn on enamel surfaces was measured by energy dispersive X-ray spectroscopy. RESULTS: Loss values (µm) for erosion only and placebo were 14.4 ± 4.5 and 20.2 ± 3.8, respectively, and 4.6 ± 1.9 for the positive control (p ≤ 0.001 each compared to erosion only). The other loss values were: NaF/1 16.5 ± 3.0, NaF/2 14.0 ± 2.7, NaF/3 12.6 ± 3.9, NaF/SnCl(2) 14.7 ± 5.1, AmF/SnF(2) 13.5 ± 4.8, AmF/NaF/SnCl(2) 12.4 ± 4.2, AmF/NaF/SnCl(2)+chitosan 6.6 ± 3.5 (except NaF/1 all p ≤ 0.01 compared to placebo). AmF/NaF/SnCl(2)/chitosan was more effective than all other toothpastes (p ≤ 0.01 each). Sn on the enamel surface ranged between 1.3 ± 0.3 and 2.8 ± 0.04 wt.% with no obvious relationship with efficacy. CONCLUSIONS: The NaF and Sn(2+) toothpastes without chitosan exhibited similar anti-erosion and abrasion-prevention effects. The experimental Sn(2+) formulation with chitosan revealed promising results similar to those of the positive control. CLINICAL SIGNIFICANCE: NaF toothpastes offer a degree of protection against erosion/abrasion, which is likely sufficient for most subjects with average acid exposures. For patients with initial erosive lesions, however, more effective toothpaste is desirable. The combination of Sn(2+) and a biopolymer appears promising in this context.

Bioequivalence of subcutaneous and intravenous body-weight-independent high-dose low-molecular-weight heparin Certoparin on anti-Xa, Heptest, and tissue factor pathway inhibitor activity in volunteers.

The objective of the study was to demonstrate the bioequivalence of subcutaneously (s.c.) and intravenously (i.v.) administered fixed, high-dose low-molecular-weight heparin (LMWH) on anti-activated factor X activity (anti-FXa). Secondary objectives were the analysis of the pharmacodynamic effects on Heptest, thrombin inhibition, tissue factor pathway inhibitor (TFPI), and the urinary excretion of LMWH in the randomized cross-over study following i.v. and s.c. application of 8000 anti-FXa units LMWH Certoparin in 18 healthy subjects. The bioequivalence following s.c. administration was demonstrated from the antilog of the point estimator for the application differences (s.c. minus i.v.) by an area under the activity-time curve (0-24 h) of 101% (range, 93-110%). LMWH was bioequivalent also on Heptest and TFPI, and was 50% on thrombin inhibition. The urinary excretion of biologically active material was 4.1 and 3.6% following i.v. and s.c. administration, respectively. Differences in the pharmacodynamic parameters of the assays indicate specific biological actions of high and low molecular sacharide chains of the LMWH.

Reduction in thrombus extension and clinical end points in patients after initial treatment for deep vein thrombosis with the fixed-dose body weight-independent low molecular weight heparin certoparin.

Low molecular weight heparin (LMWH) is effective in the treatment of acute deep vein thrombosis (DVT) in adults. This has not been demonstrated for one LMWH alone. The relationship between venographic changes due to LMWH therapy and clinical outcome in the initial treatment period has not been reported. A pooled analysis of two clinical trials was performed. The trials compared a fixed-dose, body weight-independent, subcutaneous LMWH, certoparin (8000 antifactor Xa [aXa] U twice a day [b.i.d.]), with an adjusted-dose intravenous unfractionated heparin (UFH) with respect to venographic changes expressed as Marder score and occurrence of recurrent venous thromboembolism, major bleeding, and mortality. The Marder score was 23.2 +/- 8.4 in patients randomized to LMWH (n = 299 paired phlebograms) and 23.9 +/- 8.9 in patients allocated to UFH (n = 297 paired phlebograms) at entry (2p = 0.23) and 18.9 +/- 9.7 and 20.5 +/- 9.9 at the end of the initial therapy (2p = 0.04), respectively. The composite outcome of recurrent venous thromboembolism, major bleeding, and mortality occurred less frequently during treatment with LMWH (n = 393) than it did with UFH (n = 404, 1.3% versus 5.0%, risk reduction [RR] 0.26, 95% confidence interval [CI] 0.11 to 0.63, 2p = 0.004). Single events of recurrent thromboembolism (2p = 0.12), major bleeding (2p = 0.03), and mortality (2p = 0.12) were observed less frequently with LMWH. A trend toward a lack of regression of thrombus size was observed in recurrent venous thromboembolism (2p = 0.08). Body weight-independent LMWH significantly reduces thrombus size and the incidence of composite outcome during the initial treatment of acute proximal venous thrombosis compared with adjusted dose intravenous UFH. The data indicate a relation between an unimproved Marder score and a recurrent venous thromboembolism.

Crystal-like high frequency phonons in the amorphous phases of solid water.

The high frequency dynamics of low-density (LDA) and high-density (HDA) amorphous ice and of cubic ice ( I(c)) has been measured by inelastic x-ray scattering in the 1-15 nm(-1) momentum transfer ( Q) range. Sharp phononlike excitations are observed, and the longitudinal acoustic branch is identified up to Q = 8 nm(-1) in LDA and I(c) and up to 5 nm(-1) in HDA. The narrow width of these excitations is in sharp contrast to the broad features observed in all amorphous systems studied so far. The "crystal-like" behavior of amorphous ices, therefore, implies a considerable reduction in the number of decay channels available to soundlike excitations which is interpreted as a sign of low local disorder.

Ice XII in its second regime of metastability

We present neutron powder diffraction results which give unambiguous evidence for the formation of the recently identified new crystalline ice phase [2], labeled ice XII, in completely different conditions. Ice XII is produced here by compressing hexagonal ice I(h) at T = 77, 100, 140, and 160 K up to 1.8 GPa. It can be maintained at ambient pressure in the temperature range 1.5

Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators.

BACKGROUND: Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism. METHODS: Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee. RESULTS: The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02). CONCLUSION: Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.

No evidence for involvement of the leptin gene in anorexia nervosa, bulimia nervosa, underweight or early onset extreme obesity: identification of two novel mutations in the coding sequence and a novel polymorphism in the leptin gene linked upstream region.

Mutations in the leptin gene can result in profound obesity in both rodents and humans. In humans, serum leptin levels correlate with body mass index (BMI: kg m(-2)). However, in patients with anorexia nervosa (AN) leptin levels are lower than in BMI-matched healthy controls. We had previously argued that genes involved in weight regulation should be considered as candidate genes for AN. To investigate this hypothesis we screened the coding region of the leptin gene and part of the leptin gene linked upstream region (LEGLUR) in 49 patients with AN and 315 children and adolescents with extreme obesity. Two novel mutations in the coding region (Ser-91-Ser; Glu-126-Gln), each found in a single proband, and a novel polymorphism in the LEGLUR (position -1387 G/A; frequency of both alleles approximately 0.50) were identified. Tests for association of LEGLUR polymorphism alleles were negative by comparing allele frequencies between 115 AN patients, 71 bulimia nervosa patients, 315 extremely obese children and adolescents, 141 healthy underweights and 50 controls that were not selected for body weight. Tests for transmission disequilibrium were also negative. Hence, an influence of variations in the leptin gene on eating disorders or extreme early onset obesity could not be detected.

Effect of hyperoxia on the composition of the alveolar surfactant and the turnover of surfactant phospholipids, cholesterol, plasmalogens and vitamin E.

Experimental and clinical studies have provided evidence for the involvement of oxygen free radicals in development of acute and chronic lung diseases. Hyperoxia is very often an indispensable therapeutic intervention which seems to impose oxidative stress on lung tissue. We measured the effect of hyperoxia (80% O2 for 20 h) (1) on the lipid composition of pulmonary surfactant treated in vitro, (2) on surfactant lipid synthesis and secretion of type II pneumocytes in primary culture, (3) on the lipid composition and on the SP-A content of rat lung lavages and (4) on the turnover of phospholipids, cholesterol, plasmalogens and vitamin E in type II pneumocytes, lamellar bodies and lavages of adult rat lungs. (1) Hyperoxia of lung lavages in vitro reduces the vitamin E content significantly but does not change the relative proportion of PUFA or the content of plasmalogens. (2) Hyperoxia does not affect the biosynthesis or secretion of surfactant lipids and plasmalogens by type pneumocytes in primary culture. (3) Hyperoxic treatment of rats increases the SP-A content and reduces the vitamin E content significantly but does not change the concentration of other lipid components of lung lavage. (4) The vitamin E turnover, measured in type II pneumocytes, lamellar bodies and lung lavages, is increased 2-fold in these fractions. In contrast, the turnover of surfactant cholesterol and surfactant lipids does not change. (5) Hyperoxia caused an increase of the vitamin E uptake by type II pneumocytes resulting in a vitamin E enrichment of lamellar bodies. From these results we conclude that type II pneumocytes are able to regulate the turnover of lipophilic constituents of the alveolar surfactant independently of each other. Hyperoxia caused type II pneumocytes to increase the vitamin E content of lamellar bodies. The lipid and SP-A content of alveolar fluid can be regulated independently each other.

[The history of veterinary medicine at the Georgia Augusta University of Göttingen]. / Zur Geschichte der Tiermedizin an der Georgia Augusta zu Göttingen.

225 years ago at the university of Göttingen J. C. P. ERXLEBEN has founded veterinary medicine as an academic science in Germany. Epochs and changes of this discipline at the oldest university veterinary institution in Germany are described-exemplified with personalities who represented this scientific field at the Georgia Augusta.

Production of monoclonal antibodies to rotavirus suitable for detection of rotavirus in stool samples by one-step EIA.

Two stable hybridoma cell clones producing high amounts of monoclonal antibodies (MAb) to rotavirus have been selected. The MAbs were shown to recognize different epitopes of the major inner capsid rotavirus protein VP 6. The two types of MAb in question cross-reacted with human and animal group A rotaviruses. Due to their high affinity and good binding capacity to microtiter plates a simultaneous EIA was developed for detection of rotavirus in stool samples. The sensitivity and specificity of MAb one-step EIA was compared with an approved polyclonal sandwich EIA by testing 1309 stool samples.

[Occurrence and identification of enterotoxin-producing E. coli strains in milk and dairy products]. / Vorkommen und Nachweis von Enterotoxin-bildenden E. coli-Stämmen in Milch und Milchprodukten.

Enteric diseases caused by enterotoxigenic E. coli strains (ETEC) become more and more important all over the world. Frequently food is implicated as a vector. --From this the necessity arises to identify ETEC strains and/or their heatlabile (LT) and heat-stable enterotoxins (ST). The examinations carried out for the presented paper showed the following results: Detection of LT by coagglutination is a simple and rapid test and may be helpful for screening. Most suitable, however, is the application of ELISA which enables the detection of 1 ng/ml LT with a good reproducibility. For identification of ST the suckling mouse assay (SMA) yields reliable results. ELISA and SMA have proved to be useful in practice for examination of food samples. By means of these methods 157 E. coli strains predominantly isolated from milk and milk products were examined. Hereby, five ETEC strains could be identified (3.2%). For the purpose of food examination a procedure was developed which ensures a reliable and efficient identification of E. coli enterotoxin. The essential steps are enrichment in E.E.-broth, subcultivation in CAYE-2-broth, identification of LT by ELISA resp. coagglutination and the detection of ST with aid of the SMA. So, isolation of single colonies can be omitted, which is an essential advantage.

[Results from the Central Laboratory for Streptococci Research in Kiel from 1965 to 1977 - a survey (author's transl)]. / Ergebnisse aus der Streptokokken-Zentrale in Kiel von 1965 bis 1977 - ein Uberblick.

At the Central Laboratory for Streptococci Research at the Institute for Hygiene of the Federal Dairy Research Centre in Kiel a data bank has been established which comprises as well bibliographical data (until now more than 8000 titles out of the international literature concerning streptococci) as laboratory data of all strains which have been identified since 1965. For this present publication as a survey the total material covering 34,935 strains was analyzed and interpreted. Besides a short introduction describing the general examination procedure for streptococci and the encoding of results for the data bank the material is condensed in different tables considering the incidence of pathogenic species occuring mainly in man and animals. In addition findings of enterococci and lactic streptococci are presented. 41.8% of the strains examined were isolated from human specimens, 46.7% from cattle and the remaining ones from pigs, horses, dogs, laboratory animals and others. Only 2.0% of all cultures could not be identified as one of the known species. Remarkable observations are - the high incidence of group B-Streptococci in man - the unexpected frequency of typical "human" streptococci as those of group F and G and also Sc. milleri and Sc. MG in different animals - the possible interrelation of group L- and P-streptococci in pigs and cattle - the overlap of Sc. faecalis and Sc. faecium in man and animals showing no typical distribution as it is postulated in the literature - the high percentage of unidentifiable streptococci from pigs and laboratory animals as an eventual indication for some new species. In consecuting papers some problems emerging from the presented material and own experiments will be discussed as - interrelation of group B-Streptococci in man and cattle - incidence and importance of enterococci in humans, animals and foodstuffs and - classification of species not to identify by serological grouping.

[Residues of chlorinated hydrocarbons in milk and milk products - situation and evaluation (author's transl)]. / Rückstände chlorierter Kohlenwasserstoffe in Milch und Milchprodukten - Situation und Bewertung

Residues of the most varied chemical substances can be found in milk and in milk products. For the transfer into milk such factors as fat solubility, persistance with respect to metabolic processes and accumulation capacity in certain organic systems are of particular importance. For the description of the situation with respect to residues of chlorinated insectides the results of analyses obtained in 20 supply areas of the German Federal Republic are presented and interpreted. In 1974 the following mean values were found (fat basis): alpha-HCH 0.04, gamma-HCH 0.072, heptachloro-epoxide 0.024, dieldrin 0.021 and DDT 0.20 ppm. These mean values are far below the max. quantities legally permissible and in no way constitute a toxicological risk (referred to ADI). In the German Federal Republic the concentrations of hexachlorobenzene in some cases reach the permissible max. quantity of 0.5 ppm on a fat basis. There is reason to assume that this substance finds its way into the milk not only via its application as a fungicide but probably also via a number of other, in part unknown, sources of contamination in or on vegetable products. With PCB (polychlorinated biphenyls) average concentrations from 0.2 to 0.3 ppm must be expected to be present in milk and milk products (fat basis). At present a toxicological interpretation of the values found is hardly possible.