Inhibitory effect of dairy products on the mutagenicities of chemicals and dietary mutagens

The antimutagenic effects of uninoculated milk and milks cultured with Bifidobacterium or Lactobacillus strains towards the mutagenicity induced by two direct mutagens, 4-nitroquinoline N-oxide and 2-nitrofluorene, and three dietary indirect mutagens, aflatoxin B1, benzo(a)pyrene and quercetin, were investigated using the in vitro Salmonella typhimurium test. Each cultured milk sample and control milk had a significant antimutagenic effect, to an extent varying with the mutagen used. Uninoculated milk had a greater inhibitory effect than cultured milks towards dietary indirect mutagens.     

Effect of airborne particulate extracts on monocyte oxidative metabolism

The present study was designed to examine the effects of metyrapone in vitro on the activities of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2, the two intracellular enzymes responsible for the metabolism of glucocorticoids. Enzymatic activities of 11beta-HSD1 and 2 were determined by a radiometric conversion assay using cortisol and cortisone as physiological substrates. The enzyme activity assays were carried out in the absence and presence of metyrapone using sheep liver and kidney microsomes as the source of 11beta-HSD1 and 2, respectively. It was found that metyrapone inhibited the reductase activity of 11beta-HSD1 in a dose-dependent manner with an apparent Ki of 30 microM. Moreover, this inhibition was competitive because the Km for cortisone was increased in the presence of metyrapone. In contrast, metyrapone showed biphasic effects on the dehydrogenase activity of 11beta-HSD1, in that it increased the activity at concentrations lower than 100 microM but decreased it at higher concentrations. However, under similar conditions, metyrapone had little effect on the unidirectional dehydrogenase activity of 11beta-HSD2. In conclusion, the present results provide the first direct evidence that metyrapone is a competitive inhibitor of 11beta-HSD1 reductase, and that it also exerts biphasic effects on 11beta-HSD1 dehydrogenase activity. These findings indicate that metyrapone influences peripheral glucocorticoid metabolism through its regulation of 11beta-HSD1 activity, in addition to its classic inhibitory effects on adrenal steroid biosynthesis. It is therefore imperative that this novel extra-adrenal effect of metyrapone be considered when this drug is used in the diagnosis and treatment of adrenocorticoid-related diseases.     

Processing of refractory materials using various magnesium sources derived from Zinelbulak talc-magnesite

Magnesia(MgO)is widely used in the production of refractory materials due to its high melting point,high thermal shock,and excellent slag resistance.The properties of refractory materials depend upon magnesia sources and processing parameters.In this work,three different magnesium sources,namely,magnesium hydroxide concentrate,magnesium carbonate concentrate,and intermediate flotation concentrate,were obtained from the Zinelbulak talc-magnesite,Uzbekistan,by causticization-hydration and flotation processes,respectively.A series of refractory materials were prepared on the basis of these magnesium sources,and their effects on physico-mechanical properties and microstructures were investigated as a function of sintering temperature,molding pressure,and the particle size of magnesium sources.The experimental results showed that a refractory material obtained from the magnesium hydroxide concentrate at 16000C for 4 h demonstrated favorable parameters due mainly to a higher degree of contact among fine particles.The results obtained from X-ray diffraction and optical microscopy confirmed the presence of periclase and forsterite as the predominant phases in refractory specimens.The prepared refractory materials meet the requirements of the State Standards(Nos.4689-94 and 14832-96)for magnesia and forsterite refractories,respectively.It is,therefore,suggested herein that the use of different magnesium sources derived from the Zinelbulak talc-magnesite will offer the potential to provide economic benefits in the refractory industry.     

Micronucleus test and erythropoiesis: effect of cobalt on the induction of micronuclei by mutagens

The Children Act focuses attention on meeting the assessed needs of children with disabilities. General practitioners (GPs) and Community Child Health (CCH) doctors in one health district were asked by postal questionnaire who it was who currently assessed such needs and who would do so in the future. The involvement of GPs (15) varied from none (1) to regular reassessment (3). Nearly all (14) treated acute illnesses but educational assessments were assigned to CCH doctors. Community doctors (9) had a clearer idea of their role including regular reassessment (9), education assessment (9) and interagency liaison (3). Both groups complained of poor communication with each other and with hospital services. To fulfil the requirements of the Children Act, community child health services, family health services authorities and district health authorities will have to specify how and by whom children with disabilities are identified and assessed. Arrangements will vary according to local service development. These arrangements, and the resulting liaison with other agencies, should be specified in National Health Service contracts, thus improving communication and cooperation.     

Peptides derived from collagen: new biochemical markers of bone metabolism]

OBJECTIVE: To study a possible association of the Helicobacter pylori seroprevalence with ABO(H) and Lewis (a,b) blood group phenotypes in blood donors. DESIGN: A cross-sectional study of blood donors using ABO(H) and Lewis (a,b) blood group phenotype as predictors. METHODS: ABO(H) and Lewis (a,b) blood group phenotyping was performed with monoclonal antibody. The H. pylori immunoglobulin G (IgG) antibody relative activity was evaluated by enzyme-linked immunosorbent assay (ELISA) using acid glycine extract from H. pylori. SUBJECTS: One hundred and fifty-nine randomly selected blood transfusion donors. RESULTS: The individuals with Lewis (a+b-)/non-secretor phenotype showed a significantly higher proportion of the H. pylori-seronegative subjects and a lower IgG immune response to H. pylori antigens as compared with the individuals of Lewis (a-b+)/secretor phenotype. CONCLUSION: The Lewis (a,b) histo-blood group antigens are implicated in the mechanisms of naturally occurring resistance to H. pylori infection.     

Microbiological activity of whole and fractionated crude extracts of tea (Camellia sinensis), and of tea components

Aqueous extracts of teas (Camellia sinensis) of different types and from various sources inhibited a wide range of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus. Tea extracts were bactericidal to staphylococci and Yersinia enterocolitica at well below 'cup of tea' concentrations. Activity was confined to one of four fractions obtained from a green tea extract by partition chromatography. Testing of pure tea compounds and closely related chemicals suggested that the antibacterial activity of extracts of green tea can be explained by its content of epigallocatechin, epigallocatechin gallate and epicatechin gallate. In black tea extracts, theaflavin and its gallates are additional antibacterially active components.     

The effect of specimen geometry on the accuracy of the constitutive equation derived from the hot torsion test

A rigid-viscoplastic FE code has been used to simulate the isothermal hot torsion of specimens used in tests designed for determining the relationship governing constitutive behaviour. For a given constitutive equation, the torque-rotation data were derived from the FE analysis of specimens of various geometries. Subsequently, based on these data, the constitutive equation was regenerated using an existing analytical relationship relating torque and twist in a cylindrical specimen. The effect of geometry of hot torsion specimens on the accuracy of the constitutive equation derived from the analytical relationship was investigated. Recommendations on the preferred geometry of hot torsion specimens for high deformations were made.     

Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions

We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.     

The effect of sulphasalazine on neutrophil superoxide generation in rheumatoid arthritis

Sensorineural hearing loss related to autoimmune disease is a well-recognized condition, although the exact pathophysiologic mechanisms remain unclear. One current theory postulates immune complex-induced interference with blood-labyrinth barrier integrity in the stria vascularis. The C3H/lpr autoimmune mouse was chosen to study the permeability of capillaries in the stria vascularis because this mouse model has demonstrated abnormalities of the stria vascularis and shifts in the auditory brain stem response threshold during active disease. C3H/lpr mice with active disease were compared with younger mice without disease, as well as age-matched C3H/HeJ control mice. The mice were injected with the tracer ferritin and examined by transmission electron microscopy to evaluate the integrity of the capillary tight junctions in the stria vascularis. Four of five mice with active disease were noted to have extensive leakage of ferritin into the perivascular tissues. Neither the young, disease-free autoimmune mice nor the nonautoimmune control mice demonstrated vessel leakage. Thickening of the basement membrane was also noted in the diseased animals. The results imply that active disease leads to a breakdown in the blood-endolymph barrier, which could underlie the hearing loss accompanying autoimmune and other immune diseases.     

Scavenging effect of silipide, a new silybin-phospholipid complex, on ethanol-derived free radicals

Ethanol metabolism by cytochrome P4502E1 (CYP2E1) produces free radical intermediates, identified as hydroxyethyl radicals. We have observed that in vitro addition or in vivo pretreatment of rats with Silipide, a new 1:1 complex of silybin with phosphatidyl-choline, is able to decrease the spin trapping of hydroxyethyl radicals in microsomes from chronic alcohol-fed rats. This effect is not due to an interference with the metabolism of ethanol by CYP2E1, but is rather related to the capacity of the silybin molecule to scavenge hydroxyethyl radicals. However, such an effect is lost when pure silybin in amounts comparable to those present in Silipide is administered instead, due to the low bioavailability of uncomplexed flavonoid. Further experiments in vivo have shown that Silipide administration also decreases hydroxyethyl radical signals detectable in the bile of rats acutely treated with ethanol. The ability of Silipide to scavenge ethanol-derived radicals along with its antioxidant activity suggests that this drug might be potentially useful in counteracting free radical-mediated injuries involved in the development of liver damage caused by alcohol abuse.     

The effect of various factors on the strength of hard-alloy balls

Conclusions The compressive strength of hard-alloy balls depends mainly on the peening regimes; it is therefore necessary to inspect the products thoroughly at the given production stage.The mechanical strength of hard-alloy balls with a hole depends substantially on the orientation of the hole relative to the axis of loading: when the hole is oriented parallel to the axis of load application, the compressive strength of the balls is about 3.5 times higher than that of balls with arbitrary orientation of the holes.Additional heat treatment of specimens increases their mechanical strength on an average by 12–18%.The strength of the balls depends to a considerable extent on their surface roughness.Translated from Poroshkovaya Metallurgiya, No. 10 (346), pp. 101–103, October, 1991.     

Structure and metabolism of collagens in various pathologies

Collagen constitutes approximately one third of the body's proteins; it has different functions, and changes in its metabolism and structure accompany almost every pathologic process. This article reviews basic knowledge of the alterations and defects in collagen metabolism and structure which give rise to a number of heritable and acquired diseases, their causes and consequences.     

OH-radical-type reactive oxygen species derived from superoxide and nitric oxide: a sensitive method for their determination and differentiation

Reactive oxygen species are involved in many diseases where the radical species OH, peroxynitrite and the non-radical, hypochlorous acid, play an outstanding role. The formation of OH-type oxidants is essentially confined to a few types of reactions. The most prominent ones are the one-electron reduction of hydrogen peroxide by F2+ or Cu+ -ions (Fenton-type reactions), reaction of hypochlorite with superoxide and finally formation and decay of peroxynitrite (ONOOH), formed from superoxide and NO. In this communication we wish to report on a simple model system allowing to differentiate between these ROS: ethene formation from ACC is only detectable in the presence of hypochlorite (v. Kruedener et al, 1995) and not detectable with Fenton-type oxidants or SIN-1 (3-morpholinosydonimine, a peroxynitrite generator by releasing sequentially superoxide and NO) at 10 microM concentrations. On the other hand, ethene formation from KMB is negligible in the presence of hypochlorite but proceeds rapidly with Fenton-type oxidants (4 microM H2O2; 4 microM Fe2+) as well as with 1 microM SIN-1. Stimulation of Fenton-type oxidants and not of SIN-1 by EDTA and characteristic patterns of inhibition by SOD, catalases, hemoglobin and uric acid allow a differentiation between these two potential precursors of OH-radicals. Synthetic ONOOH shows different reaction kinetics as compared to SIN-1. Inhibition of ONOOH-dependent ethene formation by different compounds occurs more or less "random" indicating an unspecific influence of proteins and also small molecules. Comparison of the individual inhibition types of several selected compounds allows a differential analysis as to the generation pathway of the final oxidants, OH- radical or peroxynitrite.     

Phospholipid pool, lipid peroxidation, and superoxide dismutase activity under various types of oxidative stress of the brain and the effect of low-energy infrared laser irradiation

The effect of low-energy infrared laser irradiation on the phospholipid pool, lipid peroxidation, and superoxide dismutase activity in the brain of white rats was studied in experimental ischemia, reperfusion, and acute edema. These models are characterized by oxidative stress; the contents of tri- and diphosphoinositides and sphingomyelins were lowered, whereas the levels of phosphatidylserine and phosphatidylethanolamine did not change, and the amount of phosphatidylcholine was increased. In acute brain edema, the contents of hydroperoxides and malonic dialdehyde in enzymatic and nonenzymic lipid peroxidation systems were increased in mitochondrial and microsomal fractions and the level of arachidonic acid was significantly elevated. Infrared laser irradiation contributes to the correction of the changes in the phospholipid pool; laser irradiation lowered the increased levels of hydroperoxides and malonic dialdehyde and elevated superoxide dismutase activity in the brain during ischemia, reperfusion, and acute edema of the brain. The data suggest that low-energy infrared laser irradiation has certain neuroprotective activity in various types of oxidative stress including ischemia, reperfusion, and acute edema of the brain.     

The involvement of medullary reticular formation in the hypotensive effect of extracts from seeds of Cassia tora

In pentobarbital anesthetized rats, the medial portion of the medullary reticular formation has been identified to be directly involved in the hypotensive effect of extracts from the seeds of Cassia tora. This conclusion was drawn from the observed decrease in arterial blood pressure following local injection of extracts of this herb into this reticular site and from its inability to promote hypotension when the same reticular site has been electrolytically lesioned. The role of the medullary reticular formation in the Cassia tora-induced hypotension was suggested to be one which modulates the basic cardiovascular reflexes, favoring a decrease in vasomotor tone.     

The effect of various forms of heparin on the release of immune complexes from the surface of cultured mesangial cells

Heparin is capable of enhancing the rate of release of antigen from nephritic rat kidneys. It also interferes with the binding of immune complexes by cultured glomerular mesangial cells. Postulating that these two effects might be related, we sought to determine what basic aspects of the molecular structure of heparin are responsible for the interference with binding in vitro. After cultured mesangial cells had bound radiolabelled synthetic immune complexes, heparin or a variety of structurally related molecules were added to the supernatant. De-N-sulphated heparin, heparan sulphate, low molecular weight heparin, and low molecular weight dextran sulphate had no effect on immune complex binding. High molecular weight dextran sulphate was able, like heparin, to dislodge immune complexes from mesangial cells, suggesting that high molecular weight and high sulphation are required. These results differ from previous findings in vivo, suggesting that the effect of heparin in vivo is not due to interaction at the mesangial cell surface. Alternative explanations for the effect of heparin in the intact animal include destabilization of the immune complex structure or, more probably, an effect at the boundary between the immune complex deposit and the basement membrane.     

Applicability of cultured hepatocytes derived from goat, sheep and cattle in comparative drug metabolism studies

1. Using trimethoprim (TMP), scoparone (SCOP), ethylmorphine (EtM), 1-naphthol (1-N) and phenol red (PhR) as test substrates, biotransformation activities were investigated in cultured hepatocytes from male and female rat, male and female goat, and female sheep and cattle. 2. As compared with rat hepatocytes, the total culture cytochrome P450 content was relatively well maintained in ruminant hepatocytes. In 72 h, it decreased to approximately half the initial content, whereas in rat hepatocytes only 30% was maintained. In ruminant hepatocytes, sulphation of 1-N remained fairly stable, glucuronidation of PhR decreased gradually, and glucuronidation of 1-N increased during the 72-h culture period. 3. Oxidative metabolism of TMP was rapid in goat and sheep hepatocytes, as compared with rat hepatocytes, reflecting species differences in TMP pharmacokinetics in vivo. In contrast with rat hepatocytes, 6-O-demethylation was by far the major pathway of scoparone metabolism in ruminant hepatocytes. The glucuronidation and sulphation activities were similar among the species. 4. In goat liver cells, sex differences in some oxidative biotransformations were observed, females being more active than males. In rat hepatocytes, a reverse sex difference was observed. 5. In conclusion, cultured hepatocytes from agricultural target species appear a useful in vitro model to study comparative metabolism of veterinary drugs and other xenobiotics. Comparing rat and ruminant, sex and species differences and similarities in drug metabolism can be observed that reflect the in vivo situation.