A SHORTCUT FORMULA FOR THE 230-MeV PROTON-INDUCED NEUTRON DOSE EQUIVALENT IN CONCRETE AFTER A METAL SHIELD, DERIVED FROM MONTE CARLO SIMULATIONS WITH MCNPX.

Monte Carlo simulations were performed with MCNPX to determine the neutron dose equivalent in thick concrete after a metal shield, a double-layered shielding configuration. In the simulations, a 230-MeV proton beam impinging on a copper target was used to produce the neutrons. For forward angles up to 30° with respect to the proton beam, it is found that the neutron dose equivalent in thick concrete after a metal layer can be expressed in a single formula. This single formula being the neutron dose equivalent formula for a single thick concrete shield enhanced with an additional exponential term. The exponent of this additional exponential term is related to the relative macroscopic neutron removal cross section of the metal with respect to the concrete. The single formula found fits MCNPX data for the neutron dose equivalent in thick concrete after layers of metal ranging from beryllium to lead. First attempts were made to make this shortcut formula applicable to alloys and compounds of metals.

Normal variability of children's scaled scores on subtests of the Dutch Wechsler Preschool and Primary scale of Intelligence - third edition.

Intelligence tests are included in millions of assessments of children and adults each year (Watkins, Glutting, & Lei, 2007a , Applied Neuropsychology, 14, 13). Clinicians often interpret large amounts of subtest scatter, or large differences between the highest and lowest scaled subtest scores, on an intelligence test battery as an index for abnormality or cognitive impairment. The purpose of the present study is to characterize "normal" patterns of variability among subtests of the Dutch Wechsler Preschool and Primary Scale of Intelligence - Third Edition (WPPSI-III-NL; Wechsler, 2010 ). Therefore, the frequencies of WPPSI-III-NL scaled subtest scatter were reported for 1039 healthy children aged 4:0-7:11 years. Results indicated that large differences between highest and lowest scaled subtest scores (or subtest scatter) were common in this sample. Furthermore, degree of subtest scatter was related to: (a) the magnitude of the highest scaled subtest score, i.e., more scatter was seen in children with the highest WPPSI-III-NL scaled subtest scores, (b) Full Scale IQ (FSIQ) scores, i.e., higher FSIQ scores were associated with an increase in subtest scatter, and (c) sex differences, with boys showing a tendency to display more scatter than girls. In conclusion, viewing subtest scatter as an index for abnormality in WPPSI-III-NL scores is an oversimplification as this fails to recognize disparate subtest heterogeneity that occurs within a population of healthy children aged 4:0-7:11 years.

Severity of bulimia nervosa. Measurement and classification into health or pathology.

AIMS: In order to identify the most important components of the severity of bulimia nervosa (as well as identifying clinical cases), we explored the relation between dimensional and categorical assessment. This was achieved by studying the performance of variables from standard instruments (measuring specific and general psychopathology) in predicting an expert rating of overall syndrome severity. METHOD: In total, 213 cases were selected (across the whole range of severity). We applied regression with optimal scaling to model nonlinear relations in the data, and the lasso method with bootstrapping for predictor selection. The best model contained 2 scales of the Eating Disorders Inventory ('bulimia' and 'drive for thinness') and the frequency of the binges. The sensitivity and specificity of case classification using the obtained model was determined. RESULTS: The model can predict the probability of being a clinical case at a rate of 88%. The presented statistical methods are innovative and promising approaches that can help researchers and clinicians to better define sets of variables for treatment evaluation and outcome studies. CONCLUSION: The results indicate that severity and outcome in bulimia nervosa should be determined by measuring both cognitive and behavioral aspects of the symptoms.

Pollution of the Begej Canal sediment--metals, radioactivity and toxicity assessment.

The Begej Canal is one among a large number of canals in Vojvodina (Northern Province of Serbia and Montenegro). The paper describes a study of metal and radioactivity contamination of the Begej Canal sediment. It is also concerned with the evaluation of sediment acute toxicity based on standard test species Daphnia magna and simultaneously extracted metals and acid volatile sulfides. The quality of sediment was assessed according to Dutch standards, but the results were also compared with some Canadian and USEPA (United States Environmental Protection Agency) guidelines for sediment quality. The results showed severe pollution with chromium, copper, cadmium and zinc, whereby the anthropogenic origin of these contaminants was indicated. The tests of toxicity of sediment pore water to D. magna, gave no indication of the presence of substances in acutely toxic concentrations to this species. It can be speculated that, despite of high metal contents, the observed toxicity was low because of the high contents of clay and iron, as well as sulphide. Also, based on a comparison with the Danube sediment and Vojvodina soil in general, the data of the Begej sediment contamination with 238U and 137Cs. The 137Cs data were used for approximate dating of the sediment. No traces of contamination by nuclear power plants in the region were found, while the presence of technologically enhanced naturally occurring radioactive materials (TENORM) was proved. Conclusions based on different criteria for sediment quality assessment were in some cases contradictory. Study also showed that radioactivity aspects can be useful in sediment quality surveys. The obtained results will be invaluable for the future activities regarding integrated water management based on EC Water Framework Directive (2000/60/EC) in the Danube basin, and particularly in the region of crossborder water body of the Begej Canal.

Effect of vegetable and carotenoid consumption on aberrant crypt multiplicity, a surrogate end-point marker for colorectal cancer in azoxymethane-induced rats.

Epidemiological studies indicate that increased vegetable consumption reduces the risk of colorectal cancer mortality. In the present study we have investigated the effect of consumption of standard diets supplemented with freeze-dried vegetables (peas, spinach, sprouts and broccoli) and carotenoids (all-trans beta-carotene and palm oil carotenoid extract) on surrogate end-point markers for colorectal cancer in an azoxymethane-induced rat model. Mean aberrant crypt multiplicity was reduced (19%) by the pea-supplemented diet only (P < 0.05). The vegetable-induced effect was more apparent in aberrant crypt foci with higher multiplicity. Intervention with diets supplemented with peas, spinach, sprouts and a mix of all vegetables reduced the number of foci with >2 aberrant crypts/focus by 37, 26, 23 and 26%, respectively (P < 0.05). Even more pronounced effects were observed in foci with >3 aberrant crypts/focus, with reductions of approximately 50% in the pea and spinach intervention groups. All-trans beta-carotene and palm oil-derived carotenoids, supplied at similar doses to those expected in the vegetable diets, inhibited ACM only marginally. Aberrant crypt foci formation in groups fed a sprout-supplemented diet prior to or following azoxymethane treatment was similar, indicating that this effect is due to inhibition of promotion rather than initiation of colorectal carcinogenesis. Vegetable and carotenoid consumption did not affect in situ proliferation of colonic crypt cells, as assessed by semi-automated image analysis of bromodeoxyuridine (BrdU)-positive nuclei. BrdU-negative nuclei of colonic crypt cells were reduced slightly in the combined vegetable groups, as compared with the control (P < 0.05). These data: (i) are in line with epidemiological evidence regarding beneficial effects of vegetable consumption on colorectal carcinogenesis; (ii) indicate that consumption of several types of vegetables inhibits early post-initiation events in colorectal carcinogenesis; (iii) suggest that the vegetable-induced effect is more pronounced in advanced lesions; (iv) indicate that the carotenoid content of the vegetables (alpha- and beta-carotene) contributes only marginally to the vegetable-induced effects.

The association of increasing dietary concentrations of fish oil with hepatotoxic effects and a higher degree of aorta atherosclerosis in the ad lib.-fed rabbit.

The long-term effects of consumption of marine long-chain n-3 polyunsaturated fatty acids (PUFA) on atherosclerosis in the rabbit were examined. Female Dutch rabbits were fed purified diets, containing 40 energy% total fat, for a period of 2.5 years. To study the dose response relationship between fish oil intake and atherosclerosis, four diets were formulated with fish oil levels being 0, 1, 10 and 20 energy%. A fifth and sixth group were fed an alpha-linolenic acid-(C18:3, n-3) and linoleic acid-(C18:2, n-6) rich diet, respectively. Every 6 weeks, blood samples were taken for determination of clinical chemical parameters, triacylglycerol and total cholesterol levels. Feeding 10 and 20 energy% fish oil containing diets, resulted in an increase of liver enzymes (AST, ALT and ALP). Histological evaluation of the liver also revealed adverse effects of fish oil containing diets. Triacylglycerol blood levels were similar in all groups, and remained constant throughout the study. Total cholesterol levels in blood was significantly lower in the animals fed a linoleic acid-rich diet, as compared with the other five groups. An n-3 long-chain PUFA concentration dependent increase in aorta plaque surface area was observed in the fish oil groups. A significant positive relationship was found between the group mean score for severity of liver pathology and the aorta plaque surface area. These results indicate that the long-chain n-3 polyunsaturated fatty acids in fish oil may be hepatotoxic to the herbivorous rabbit, which may interfere with the outcome of atherosclerosis studies. This finding necessitates the exclusion of liver pathology in experimental studies on atherosclerosis in animal models.

Cyclin A, cyclin B and stringlike are regulated separately in cell cycle arrested trochoblasts of Patella vulgata embryos.

Trochoblasts are the first cells to differentiate during the development of spiralian embryos. Differentiation is accompanied by a cell division arrest. In embryos of the limpet Patella vulgata, the participation of cell cycle-regulating factors in trochoblast arrest was analysed as a first step to unravel its cause. We determined the cell cycle phase in which the trochoblasts are arrested by analysing the subcellular locations of mitotic cyclins. The results show that the trochoblasts are most likely arrested in the G2 phase. This was supported by measurement of the DNA content in trochoblast nuclei after the last division. Trochoblasts complete their final division at the sixth mitotic cycle. This mitotic cycle resembles the first postblastoderm cell cycle of Drosophila, in which mitotic activity is controlled by expression of the string gene. As failure of string expression results in cell cycle arrest in the G2 phase, negative regulation of a Patella string homolog could be responsible for trochoblast arrest. Although Stl messengers disappeared from trochoblasts during their final division, expression was observed again 20 min later. Messengers remained present in all trochoblasts at low levels during further development. Thus, expression of the stringlike gene allows the cell cycle arrest of these cells, whereas in Drosophila cells arrested in division lack string messengers.

Rat odontogenic tumors associated with disturbed tooth eruption.

Most odontogenic tumors occurring in rats have the appearance of immature or mature odontomas. The present brief paper describes two spontaneously occurring odontogenic lesions in rats; both had the appearance of complex odontomas. One was associated with a lesion that had the appearance of an odontogenic fibroma; the other occurred concomitant with a lesion that had the appearance of a cementoblastoma. Their possible relationship with disturbed eruption due to malocclusion is discussed.

The stringlike genes of the limpet Patella vulgata.

As a first step in analyzing the function of a cdc25 homolog during the embryonic development of Patella vulgata (Pv), genomic clones encoding these stringlike proteins (Stl) were isolated and characterized. These clones belong to four groups which are derived from different regions of the Pv genome. As the sequences of Stl genes from two of these groups are almost identical, we suggest that these genes represent copies of the same gene. The Stl3 gene, which has been analyzed in detail, consists of four exons separated by three introns. Its sequence encodes a 250-amino-acid protein with a calculated weight of 28 kDa. The Stl protein contains regions conserved in all other cdc25 proteins. Stl messengers are not stored maternally in Pv oocytes and Stl transcription only starts after the first embryonic cleavages.

Review article. The rat incisor in toxicologic pathology.

Microscopic examination of the incisors of rats and mice may reveal toxicologically significant changes. First, the incisor morphology reflects the nutritional status of the animal: fluctuations of mineral metabolism and vitamin availability are disclosed by the rodent incisors, because the incisors continue to grow during life. Similarly, direct or indirect changes of mineral metabolism by a test substance are reflected in the morphological appearance of the incisor dentin. In addition, hormonal disturbances may give rise to typical structural alterations of the incisor in the test animal. Certain chemicals may have deleterious effects upon the odontogenic tissues, resulting in tooth malformation and malocclusion and eventually in odontomas. Apparent nasal tumors may turn out to be of dental origin. Nasal luminal masses that are discussed within this scope are dental malformation, dental callus, and true odontogenic tumors. According to our experience, odontogenic tumors might possibly develop within the scope of a reaction to mechanical tooth trauma as well. In carcinogenicity studies, this consideration deserves attention when evaluating treatment-related putative odontogenic tumors.

Quantitative in situ analysis of xanthine oxidoreductase activity in rat liver.

The tetrazolium salt method previously developed for the detection of xanthine oxidoreductase activity in unfixed cryostat sections has been validated for quantitative purposes. The specificity of the enzyme reaction was studied by incubating unfixed cryostat sections of rat liver in test medium containing the substrate hypoxanthine, in control medium that lacked the substrate, and in medium containing substrate and allopurinol, a specific inhibitor of xanthine oxidoreductase activity. The specific reaction rate was determined cytophotometrically by subtracting the amount of final reaction product generated in the control reaction from that formed in the test reaction. Highest specific enzyme activity in rat liver was found when the incubation medium contained 18% (w/v) polyvinyl alcohol, 100 mM phosphate buffer, pH 7.8, 0.45 mM 1-methoxyphenazine methosulfate, 5 mM tetranitro BT, and 0.5 mM hypoxanthine. Enzyme activity was present in liver parenchymal cells and in sinusoidal cells (endothelial and Kupffer cells) and was completely inhibited by allopurinol. A linear relationship was observed between the specific amount of final reaction product generated at 37 degrees C and incubation time at least up to 21 min, as well as section thickness up to 12 microns. Xanthine oxidoreductase activity, expressed as mumoles substrate converted per cm3 tissue/min, was 1.61 +/- 0.34 in pericentral areas and 1.24 +/- 0.16 in periportal areas. These values are similar to biochemical data reported in the literature. In conclusion, the tetrazolium method to detect xanthine oxidoreductase activity in unfixed cryostat sections of rat liver gives a reliable reflection of in situ activity.

Localization and quantification of cyclin A and B mRNA during the embryonic development of Patella vulgata.

As the first five cleavages of the Patella vulgata embryo are synchronous, they are well suited to determine the mRNA level of cyclin A and B genes in an embryo. During the third and fourth cleavage cycle the quantity of A and B mRNA is regulated in a cell-cycle-dependent way, reaching a high level between cleavages and a lower level just after mitosis. This implies that transcription of the cyclin genes occurs before the overall transcription increases directly after the fifth cleavage. During the first cleavages cyclin A and B mRNA is localized in distinct parts of the cytoplasm. Between two successive cell devisions it is found as a crescent-shaped domain at the peripheral side of the nucleus. At cytokinesis it is present between two separating nuclei and at newly formed cell membranes. At the fifth cleavage this localization disappears. Changes in the expression pattern of cyclin A and B may be expected after the fifth cleavage, when the first cells become arrested in cell division and differentiate. The mechanism causing cell division arrest of these primary trochoblasts is still unknown. Cell division arrest caused by the absence of cyclin A and/or B mRNA could be conditional for further differentiation. However, a decrease in cyclin A and B mRNA level in the trochoblasts is not detectable until 4 h after their last division. Later in development no cyclin A and B mRNA can be detected in these cells, whereas cyclin A and B mRNA is present in other cells of the embryo. Thus, the absence of cyclin A and B mRNA in primary trochoblasts, and in the later differentiating secondary and accessory trochoblasts is not obligatory for cell division arrest or cell differentiation.

A re-evaluation of the tissue distribution and physiology of xanthine oxidoreductase.

Xanthine oxidoreductase is an enzyme which has the unusual property that it can exist in a dehydrogenase form which uses NAD+ and an oxidase form which uses oxygen as electron acceptor. Both forms have a high affinity for hypoxanthine and xanthine as substrates. In addition, conversion of one form to the other may occur under different conditions. The exact function of the enzyme is still unknown but it seems to play a role in purine catabolism, detoxification of xenobiotics and antioxidant capacity by producing urate. The oxidase form produces reactive oxygen species and, therefore, the enzyme is thought to be involved in various pathological processes such as tissue injury due to ischaemia followed by reperfusion, but its role is still a matter of debate. The present review summarizes information that has become available about the enzyme. Interpretations of contradictory findings are presented in order to reduce confusion that still exists with respect to the role of this enzyme in physiology and pathology.

Conversion of xanthine dehydrogenase into xanthine oxidase in rat liver and plasma at the onset of reperfusion after ischemia.

The aim of this study was to test whether conversion of xanthine dehydrogenase into xanthine oxidase as induced by fasting, ischemia of the liver or both is an in vivo process or only occurs in vitro in homogenates. For this purpose, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied in liver homogenates obtained from rats after normal feeding or 24 hr of fasting followed or not by 2 hr of ischemia of the liver. In fed rats, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied as well in liver homogenates after different periods of reperfusion after 2 hr of ischemia. Homogenization was carried out under strictly controlled conditions, after which the supernatants were incubated at 37 degrees C in buffer for 0 to 5 hr. Enzyme activities were assayed spectrophotometrically by measuring urate production at 295 nm. Conversion started only after 2 to 3 hr of incubation of supernatants of control fed livers, whereas conversion started immediately after 24 hr of fasting. The percentage oxidase activity of total xanthine oxidoreductase activity in ischemic livers from fed animals was slightly higher (26.7% +/- 1.7%; p < 0.05) than in control livers (19.3% +/- 1.4%), whereas the percent oxidase activity in ischemic livers from fasted animals (16.7% +/- 1.0%) was not different from that in control animals (16.8% +/- 1.1%). Ischemia for 2 hr caused in vitro a substantial increase in the conversion rate in supernatants of livers of fed and fasted rats as compared with their controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of storage on the retention of enzyme activity in cryostat sections. A quantitative histochemical study on rat liver.

The effect of storage of unfixed cryostat sections from rat liver for 4 h, 24 h, 3 days and 7 days at -25 degrees C was studied on the activities of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, xanthine oxidoreductase, glutamate dehydrogenase, succinate dehydrogenase (all demonstrated with tetrazolium salt procedures), glucose-6-phosphatase (cerium-diaminobenzidine method), 5'-nucleotidase (lead salt method), dipeptidyl peptidase II, acid phosphatase (both simultaneous azo coupling methods), D-amino acid oxidase (cerium-diaminobenzidine-cobalt-hydrogen peroxide procedure) and catalase (diaminobenzidine method). The effect of drying of the cryostat sections at room temperature for 5 and 60 min was investigated as well. The enzyme activities were quantified by cytophotometric measurements of test and control reactions. The test minus control reaction was taken as a measure for specific enzyme activity. It was found that the activities of all the enzymes investigated, with one exception, were affected neither by storage of the cryostat sections at -25 degrees C for up to 7 days, nor by drying of the sections at room temperature for up to 60 min. The exception was xanthine oxidoreductase, whose activity was reduced by 20% after 5 min drying of sections or after 4 h storage. Therefore, only incubations for xanthine oxidoreductase activity have to be performed immediately after cutting cryostat sections, whereas for the other enzymes a considerable margin appears to exist.

The effect of ischaemia on xanthine oxidase activity in rat intestine and liver.

Effects of 60 and 120 minutes of in-vitro ischaemia on the localization of xanthine oxidase activity were studied in rat intestine and liver. A histochemical method was applied on unfixed cryostat sections using a semipermeable membrane. The incubation medium contained hypoxanthine as substrate, cerium ions which capture the enzyme product, hydrogen peroxide, and sodium azide to inhibit catalase and peroxidase activities. In a second step reaction diaminobenzidine was polymerized in the presence of cobalt ions and hydrogen peroxide by decomposition of cerium perhydroxide. Large amounts of final reaction product were found in the cytoplasm of enterocytes and goblet cells of control small intestine. When the incubation was performed in the absence of substrate or in the presence of substrate and allopurinol, a specific inhibitor of xanthine oxidase activity, no reaction product was found. After 60 and 120 minutes of storage of tissue blocks at 37 degrees C enzyme activity was significantly reduced in the apical region of epithelial cells, whereas a high activity was present in the basal region of these cells. A very low xanthine oxidase activity was found in rat liver. Highest activity was present in endothelial cells, whereas in liver parenchymal cells, a more pronounced activity was found in pericentral than in periportal hepatocytes. Ischaemia up to 120 minutes did not affect the enzyme activity in livers. It was concluded that increased xanthine oxidase activity during ischaemia may not be responsible for cell damage during reperfusion in contrast with assumptions in the literature.

Distribution of xanthine oxidoreductase activity in human tissues--a histochemical and biochemical study.

Localization of the activity of both the dehydrogenase and oxidase forms of xanthine oxidoreductase were studied in biopsy and postmortem specimens of various human tissues with a recently developed histochemical method using unfixed cryostat sections, poly-(vinyl alcohol) as tissue stabilizator, 1-methoxyphenazine methosulphate as intermediate electron acceptor and Tetranitro BT as final electron acceptor. High enzyme activity was found only in the liver and jejunum, whereas all the other organs studied showed no activity. In the liver, enzyme activity was found in sinusoidal cells and both in periportal and pericentral hepatocytes. In the jejunum, enterocytes and goblet cells, as well as the lamina propria beneath the basement membrane showed activity. The oxidase activity and total dehydrogenase and oxidase activity of xanthine oxidoreductase, as determined biochemically, were found in the liver and jejunum, but not in the kidney and spleen. This confirmed the histochemical results for these organs. Autolytic rat livers several hours after death were studied to exclude artefacts due to postmortem changes in the human material. These showed loss of activity both histochemically and biochemically. However, the percentage activity of xanthine oxidase did not change significantly in these livers compared with controls. The findings are discussed with respect to the possible function of the enzyme. Furthermore, the low conversion rate of xanthine dehydrogenase into xanthine oxidase during autolysis is discussed in relation to ischemia-reperfusion injury.

High levels of xanthine oxidoreductase in rat endothelial, epithelial and connective tissue cells. A relation between localization and function?

The localization of xanthine oxidoreductase activity was investigated in unfixed cryostat sections of various rat tissues by an enzyme histochemical method which specifically demonstrates both the dehydrogenase and oxidase forms of xanthine oxidoreductase. High activity was found in epithelial cells from skin, vagina, uterus, penis, liver, oral and nasal cavities, tongue, esophagus, fore-stomach and small intestine. In addition activity was demonstrated in sinusoidal cells of liver and adrenal cortex, endothelial cells in various organs and connective tissue fibroblasts. Xanthine oxidoreductase produces urate which is a scavenger of oxygen-derived radicals. Because the enzyme is found in epithelial and endothelial cells which are subject to relatively high oxidant stress, it is postulated that in these cells xanthine oxidoreductase is involved in the antioxidant enzyme defense system. In addition, a possible role for the enzyme in proliferation and differentiation processes is discussed.

Longitudinal dispersion in model of central airways during high-frequency ventilation.

We have measured the longitudinal dispersion of boluses of helium, acetylene and sulphur hexafluoride in a plastic model of the human airways--generations zero through six--during high frequency ventilation (HFV). HFV was maintained by a piston pump. Frequency f and tidal volume VT ranged from 2.5 to 25 Hz and from 5 to 20 ml, respectively. Boluses were injected near the entrance of the zeroth generation (trachea), and the dispersion curves were measured by mass spectrometry at the end of the sixth airway generation. The shapes of the bolus dispersion curves could be well described with Gaussian distribution functions. With the exception of the HFV-conditions with VT = 5 ml, the effective dispersion coefficient DDISP appeared to be independent of the molecular diffusion coefficient. This independency was also found by other investigators in studies with dogs and human subjects. The measured results for DDISP for different f and VT could be satisfactorily described with the empirical equation DDISP = 0.0617 f0.8VT1.38 [cm2S-1]. Application of this equation to f and VT values normally applied in man resulted in DDISP values which should be considered to be too small for maintaining eucapnic ventilation in vivo. On the basis of this result we believe that during HFV in intubated subjects gas transport by longitudinal dispersion will be limited to the instrumental dead space--the endotracheal tube inclusive--and a few generations of large bronchi.