bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytochemical analysis and gastroprotective activity of an olive leaf extract
Authors: Dekanski Dragana , Janicijevic-Hudomal Snezana , Tadic Vanja , Markovic Goran , Arsic Ivana , Mitrovic Dusan
Published: April 2009

Some medicinal features of olive leaf have been known for centuries. It has been traditionally used as an antimicrobial and to prevent and treat diabetes mellitus and heart disease. Whether olive leaf, a natural antioxidant, influences the gastric defense mechanism and exhibits gastroprotection against experimentally-induced gastric lesions remains unknown. In this study, the content of total phenols, total flavonoids and tannins in olive leaf extract (OLE) were determined. Seven phenolic compounds were identified and quantified (oleuropein, caffeic acid, luteolin, luteolin-7-O-glucoside, apigenin-7-O-glucoside, quercetin, and chryseriol). Furthermore, the protective activity of the OLE in gastric mucosal injury induced by a corrosive concentration of ethanol was investigated. In relation to the control group, pretreatment with OLE (40, 80 and 120 mg kg-1) significantly (p < 0.001) attenuated the gastric lesions induced by absolute ethanol. The protective effect of the OLE was similar to that obtained with a reference drug, ranitidine. The results obtained indicate that OLE possesses significant gastroprotective activity, and that the presence of compounds with antioxidative properties would probably explain this effect.
Electrochemical and molecular simulation studies on the corrosion inhibition of L-glutamine monolayers on an iron surface
Authors: Zhang Zhe , Chen Shenhao , Feng Yuanyuan , Ding Yunqiao , Zhou Juanjuan , Jia Henglei
Published: April 2009

L-Glutamine was used to form monolayers for the inhibition of the corrosion of iron in 0.50 mol dm-3 H2SO4. The protection ability of the films was examined by electrochemical impedance spectroscopy. The mechanism of adsorption is discussed using quantum chemical calculations and molecular simulations. Scanning electron microscopy was applied to confirm the formation of L-glutamine monolayers and the inhibitive effect. The results indicate that the molecules of L-glutamine are able to form films on the surface of iron and longer immersion time of the iron electrode in the solution results in a stronger inhibition ability of the films. The films are formed spontaneously by the adsorption of L-glutamine with a specific affinity of its head-group to the iron surface, hence, the densely and ordered monolayers can be considered as self-assembled.
Local heat transfer coefficients during the evaporation of 1,1,1,2-tetrafluoroethane (R-134a) in a plate heat exchanger
Authors: Zivkovic Emila , Kabelac Stephan , Serbanovic Slobodan
Published: April 2009

The evaporation heat transfer coefficient of the refrigerant R-134a in a vertical plate heat exchanger was investigated experimentally. The area of the plate was divided into several segments along the vertical axis. For each of the segments, the local value of the heat transfer coefficient was calculated and presented as a function of the mean vapor quality in the segment. Owing to the thermocouples installed along the plate surface, it was possible to determine the temperature distribution and vapor quality profile inside the plate. The influences of the mass flux, heat flux, pressure of system and the flow configuration on the heat transfer coefficient were also taken into account and a comparison with literature data was performed.
Drax's Reading in Neverwinter Nights: With a Tutor as Henchman
Authors: Commeyras Michelle
Published: April 2009

This is an account of what a teacher educator learned from using the video game Neverwinter Nights with Drax, a high school student whose reading is like that of an elementary school student. Neverwinter Nights is a role-playing adventure game that requires reading print along with other meaningful signs such as sounds, artefacts, color, maps, etc. Using examples from eight hours of transcribed play, the author details the ways in which print matters to game play. Drax read walkthroughs which led to reading dialogues calling for practice with word recognition, which in turn led to acquiring new vocabulary. He also used strategies such as thinking aloud, rereading, and attending to details. Based on these findings, the author argues that it is worthwhile to explore and research opportunities for reading development within video games with print.
Visualization of Expert Chat Development in a World of Warcraft Player Group
Authors: Chen Mark
Published: April 2009

This article describes expertise development in a player group in the massively multiplayer online game World of Warcraft using visualization of chat log data. Charts were created to get a general sense of chat trends in a specific player group engaged in ‘high-end raiding’, a 40-person collaborative activity. These charts helped identify patterns in the frequency of chat over time during two specific gaming sessions. The sessions represented significant moments in the raid group's history: the first time a particular monster, Ragnaros, was fought and one of the first times he was defeated. Differences between the two cases show differences in the raiding practice and are evidence of learned expertise. Based on this analysis, it is clear that this visualization process is a useful analysis tool within ethnographic accounts of expertise development.
Hypothalamic Reactive Oxygen Species Are Required for Insulin-Induced Food Intake Inhibition
Authors: Jaillard Tristan , Roger Michael , Galinier Anne , Guillou Pascale , Benani Alexandre , Leloup Corinne , Casteilla Louis , Pénicaud Luc , Lorsignol Anne
Published: April 2009

OBJECTIVE

Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin.

RESEARCH DESIGN AND METHODS

We first measured hypothalamic ROS levels and food intake after acute intracerebroventricular injection of insulin. Second, effect of pretreatment with a ROS scavenger or an NADPH oxidase inhibitor was evaluated. Third, we examined the consequences of two nutritional conditions of central insulin unresponsiveness (fasting or short-term high-fat diet) on the ability of insulin to modify ROS level and food intake.

RESULTS

In normal chow-fed mice, insulin inhibited food intake. At the same dose, insulin rapidly and transiently increased hypothalamic ROS levels by 36%. The pharmacological suppression of this insulin-stimulated ROS elevation, either by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic effect of insulin. Finally, in fasted and short-term high-fat diet–fed mice, insulin did not promote elevation of ROS level and food intake inhibition, likely because of an increase in hypothalamic diet-induced antioxidant defense systems.

CONCLUSIONS

A hypothalamic ROS increase through NADPH oxidase is required for the anorexigenic effect of insulin.
Linkage Disequilibrium Mapping of the Replicated Type 2 Diabetes Linkage Signal on Chromosome 1q
Authors: Prokopenko Inga , Zeggini Eleftheria , Hanson Robert L. , Mitchell Braxton D. , Rayner N. William , Akan Pelin , Baier Leslie , Das Swapan K. , Elliott Katherine S. , Fu Mao , Frayling Timothy M. , Groves Christopher J. , Gwilliam Rhian , Scott Laura J. , Voight Benjamin F. , Hattersley Andrew T. , Hu Cheng , Morris Andrew D. , Ng Maggie , Palmer Colin N.A. , Tello-Ruiz Marcela , Vaxillaire Martine , Wang Cong-rong , Stein Lincoln , Chan Juliana , Jia Weiping , Froguel Philippe , Elbein Steven C. , Deloukas Panos , Bogardus Clifton , Shuldiner Alan R. , McCarthy Mark I. ,   for the International Type 2 Diabetes 1q Consortium
Published: April 2009

OBJECTIVE

Linkage of the chromosome 1q21–25 region to type 2 diabetes has been demonstrated in multiple ethnic groups. We performed common variant fine-mapping across a 23-Mb interval in a multiethnic sample to search for variants responsible for this linkage signal.

RESEARCH DESIGN AND METHODS

In all, 5,290 single nucleotide polymorphisms (SNPs) were successfully genotyped in 3,179 type 2 diabetes case and control subjects from eight populations with evidence of 1q linkage. Samples were ascertained using strategies designed to enhance power to detect variants causal for 1q linkage. After imputation, we estimate ∼80% coverage of common variation across the region (r 2 > 0.8, Europeans). Association signals of interest were evaluated through in silico replication and de novo genotyping in ∼8,500 case subjects and 12,400 control subjects.

RESULTS

Association mapping of the 23-Mb region identified two strong signals, both of which were restricted to the subset of European-descent samples. The first mapped to the NOS1AP (CAPON) gene region (lead SNP: rs7538490, odds ratio 1.38 [95% CI 1.21–1.57], P = 1.4 × 10−6, in 999 case subjects and 1,190 control subjects); the second mapped within an extensive region of linkage disequilibrium that includes the ASH1L and PKLR genes (lead SNP: rs11264371, odds ratio 1.48 [1.18–1.76], P = 1.0 × 10−5, under a dominant model). However, there was no evidence for association at either signal on replication, and, across all data (>24,000 subjects), there was no indication that these variants were causally related to type 2 diabetes status.

CONCLUSIONS

Detailed fine-mapping of the 23-Mb region of replicated linkage has failed to identify common variant signals contributing to the observed signal. Future studies should focus on identification of causal alleles of lower frequency and higher penetrance.
Longitudinal Analysis of Depressive Symptoms and Glycemic Control in Type 2 Diabetes
Authors: Aikens James E. , Perkins Denise White , Lipton Bonnie , Piette John D.
Published: April 2009

OBJECTIVE

To compare whether depressive symptoms are more strongly related to subsequent or prior glycemic control in type 2 diabetes and to test whether patient characteristics modify these longitudinal associations.

RESEARCH DESIGN AND METHODS

On two occasions separated by 6 months, depressive symptoms and glycemic control were assessed in 253 adults with type 2 diabetes. Regression analyses examined depressive symptoms as both a predictor and outcome of glycemic control and tested whether medication regimen (e.g., insulin versus oral drugs) was an effect modifier before and after adjusting for baseline levels of the outcome being predicted.

RESULTS

Depressive symptom severity predicted poor glycemic control 6 months later (P = 0.018) but not after baseline glycemic control was taken into account (P = 0.361). Although baseline glycemic control did not generally predict depressive symptoms 6 months later (P = 0.558), it significantly interacted with regimen (P = 0.008). Specifically, glycemic control predicted depressive symptoms among patients prescribed insulin (β = 0.31, P = 0.002) but not among those prescribed oral medication alone (β = −0.10, P = 0.210). Classifying depression dichotomously produced similar but weaker findings.

CONCLUSIONS

Depressive symptoms do not necessarily lead to worsened glycemic control. In contrast, insulin-treated patients in poor glycemic control are at moderate risk for worsening of depressive symptoms. These patients should be carefully monitored to determine whether depression treatment should be initiated or intensified.
Abdominal Visceral Adiposity in the First Trimester Predicts Glucose Intolerance in Later Pregnancy
Authors: Martin Aisling Mary , Berger Howard , Nisenbaum Rosane , Lausman Andrea Y. , MacGarvie Sharon , Crerar Carrie , Ray Joel G.
Published: April 2009

OBJECTIVE

To assess whether abdominal adiposity in early pregnancy is associated with a higher risk of glucose intolerance at a later gestational stage.

RESEARCH DESIGN AND METHODS

Subcutaneous and visceral fat was measured with ultrasonography at ∼12 weeks' gestation. A 50-g glucose challenge test (GCT) was performed between 24 and 28 weeks' gestation. The risk of having a positive GCT (≥7.8 mmol/l) was determined in association with subcutaneous and visceral adipose tissue depths above their respective upper-quartile values relative to their bottom three quartile values.

RESULTS

Sixty-two women underwent GCTs. A visceral adipose tissue depth above the upper quartile value was significantly associated with a positive GCT in later pregnancy (adjusted odds ratio 16.9 [95% CI 1.5–194.6]). No associations were seen for subcutaneous adipose tissue.

CONCLUSIONS

Measurement of visceral adipose tissue depth in early pregnancy may be associated with glucose intolerance later in pregnancy.
Synthesis of Co3O4 nanoparticles by oxidation-reduction method and its magnetic characterization
Authors: Ozkaya T. , Baykal A. , Koseoğlu Y. , Kavas H.
Published: April 2009

Without any surfactant, antiferromagnetic Co3O4 nanoparticles were synthesized successfully for the first time by means of an oxidation-reduction method with cobalt sulfate as starting material, which was oxidized to cobalt salt by NaNO3 after alkalinizing with NaOH. Morphological, structural, spectroscopic and magnetic characterization of the product were done by SEM, TEM, XRD, and VSM, respectively. The average crystallite size (on the base of line profile fitting method), D and σ, is estimated as 30 ± 6 nm. Some anomalous magnetic properties and their enhanced effect have been observed in Co3O4 antiferromagnetic nanocrystallites, including a bias field, coercivity, permanent magnetic moments and an open loop. These phenomena are attributed to the unidirectional anisotropy which is caused by the exchange coupling between AFM and FM layers, the existence of the spin glass like surface spins of Co3O4 nanoparticles due to size effects and surface-area effect.
Endogenous stages of Choleoeimeria baltrocki (Daszak et Ball, 1991) n. comb. infecting the gall bladder of gold skink, Eumeces schneiderii Daudin, 1802 from Egypt
Authors: Abdel-Baki Abdel-Azeem , El-Fayomi Huda , Sakran Thabet , Abdel-Haleem Heba
Published: April 2009

Examination of 98 gold skink, Eumeces schneiderii Daudin, 1802 from Alexandria and Marsa-matroh Governorates, Egypt revealed oocysts of Choleoeimeria baltrocki (Daszak et Ball, 1991) n. comb. in the gall bladder and faeces. The prevalence of the infection was 40.8%. Sporulated oocysts were found in the faeces and the gall bladder contents. Sporulated oocysts were tetrasporocystic, cylindrical, reaching a mean of 38.7 (36–42) × 19.9 (17–25) μm with bilayered smooth and colourless wall. The dizoic sporocysts were subspherical and measuring 10.8 (9.5–13) × 9.3 (8–10.5) μm with a large globular sporocyst residuum. Sporocyst wall was bilayered joined by meridional suture. Sporozoites were crescent-shaped, blunt at one end and slightly tapered at the other. Endogenous stages (meronts, gamonts, gametes and young oocysts) were confined to the gall bladder epithelium and the infected cells were hypertrophied. Based on the morphological features of the exogenous stages and endogenous development of the present parasite, its generic affiliation was revised and placed into the genus Choleoeimeria.
Isolation and biological characterisation of a new isolate of Neospora caninum from an asymptomatic calf in Brazil
Authors: García-Melo Debora , Regidor-Cerrillo Javier , Ortega-Mora Luis , Collantes-Fernández Esther , Oliveira Vanessa , Oliveira Milton , Silva Andrea
Published: April 2009

Neospora caninum is a tissue-cyst forming parasite that has been recognized worldwide as a cause of abortion in cattle. Despite the ubiquitous distribution of this parasite and its broad range of hosts, the number of N. caninum isolates obtained to date is limited. In addition, the majority of isolates have been obtained from clinically affected hosts, therefore potentially biasing this population towards more virulent isolates. This report describes the isolation and biological characterisation of a new N. caninum isolate, Nc-Goiás 1, obtained from an asymptomatic, naturally infected calf from Brazil. This new isolate was identified as a member of the N. caninum species by polymerase chain reaction (PCR) using specific primers based on the N. caninum internal transcribed spacer 1 (ITS-1) sequence, and was genetically identified at multiple loci using microsatellite analysis. Finally, a pathogenicity study was conducted in a BALB/c mice model. All Nc-Goiás 1-infected mice survived without exhibiting any clinical signs. Further pathogenic characterisation of this isolate suggested that Nc-Goiás 1 is less virulent than other N. caninum isolates (Nc-Liv and Nc-1) studied in this mouse model. This is the first report of the isolation and biological characterisation of N. caninum from an infected but clinically healthy calf in South America.
Dendromonocotyle urogymni sp. nov. (Monogenea, Monocotylidae) from Urogymnus asperrimus (Elasmobranchii, Dasyatidae) off eastern Australia
Authors: Chisholm Leslie , Whittington Ian
Published: April 2009

Dendromonocotyle urogymni sp. nov. is described from the dorsal surface of the porcupine ray, Urogymnus asperrimus, kept at Cairns Marine Aquarium Fish in Cairns, Queensland, Australia. Dendromonocotyle urogymni can be distinguished most readily from the other 15 species in the genus by the male copulatory organ which has a distinct spherical inflation mid-way along its length. This is the first monocotylid to be described from U. asperrimus.
Records of cysticercoids of Fimbriarioides tadornae Maksimova, 1976 and Branchiopodataenia gvozdevi (Maksimova, 1988) (Cyclophyllidea, Hymenolepididae) from brine shrimps at the Mediterranean coasts of Spain and France, with a key to cestodes from Artemia spp. from the Western Mediterranean
Authors: Vasileva Gergana , Redón Stella , Amat Francisco , Nikolov Pavel , Sánchez Marta , Lenormand Thomas , Georgiev Boyko
Published: April 2009

Cysticercoids of two cestode species isolated from brine shrimps from the Mediterranean coasts of Spain and France are described. Fimbriarioides tadornae Maksimova, 1976 (adults known as parasites of Tadorna tadorna) was recorded from Artemia parthenogenetica and A. franciscana from Spain (Bras del Port and River Ebro Delta, respectively), and from A. franciscana from Aigues-Mortes, France (new geographical record). Branchiopodataenia gvozdevi (Maksimova, 1988) (adults known as parasites of Larus genei) was recorded from A. parthenogenetica (Bras del Port, Spain), A. salina (San Pedro del Pinatar, Spain) and A. franciscana (River Ebro Delta, Spain); this is the first record of the species in Europe. An illustrated key to cysticercoids of 12 cestode species from Artemia spp. from the Western Mediterranean is proposed.
Nematode assemblages from Mountain Pine (Pinus mugo Turra) communities in Pirin Mountain, Bulgaria
Authors: Mincheva Y. , Lazarova S. , Peneva V.
Published: April 2009

The structural and functional diversity of nematode communities from Pinus mugo sites in Pirin Mountain was assessed. The sampling plots represent different levels of disturbance — next to and outside ski runs. Nematode assemblages from this habitat can be characterised with high diversity (in total, 104 taxa and richness ranging from 41 to 65 genera per site). In general, the trophic structure was dominated by omnivorous and bacterial feeders coupled with low proportion of plant feeding nematodes. The high values of Maturity indices and the results from faunal analysis indicate relatively stable environment and undisturbed conditions for all sites. No clear correlation between the nematode assemblages’ characteristics and the level of disturbance (position of the site in relation to ski runs) was revealed.
Sex and Age Differences in the Distribution of 14C-Sterigmatocystin in Immature and Mature Rats
Authors: Walkow J. , Sullivan G. , Maness D. , Yakatan G. J.
Published: April 2009

Sterigmatocystin, a mycotoxin produced by several fungi, is carcinogenic when injected subcutaneously in rats. The potential of sterigmatocystin as a contaminant to human foodstuffs makes understanding its absorption, distribution, metabolism, and excretion characteristics desirable. Single doses (8 mg/kg) of 14C-sterigmatocystin were dissolved in wheat germ oil and administered orally to immature (50–150 g) and mature (200–300 g) rats of both sexes. Five rats of each sex and age group were sacrificed at 3, 6, 12, 48, and 96 hours after dosing. Biological specimens were collected and analyzed for total radioactivity. The differences in tissue levels of 14C-sterigmatocystin due to age and sex were examined using Tukey's paired comparison procedure for the mean area under the tissue level vs. time curves. Statistically significant differences in the gastrointestinal tract tissue levels were observed in 70% or more of these tissues when comparing mature males vs. mature females and immature females vs. mature females. Age and sex differences were also observed in 30% or less of the organ tissues in the other comparisons made. The sterigmatocystin plasma levels vs. time curves for each group have at least two distinct peaks that may be indicative of enterohepatic recirculation. The plasma levels obtained in the male rats are consistently higher than those in the females.
Phenotypic Reversion of Cultured Mouse Adenocarcinoma Cells: Mediation by Cell Density and Chemical Exposure
Authors: Bempong M. A. , Myers J. A.
Published: April 2009

Reversions of mouse adenocarcinoma (MAC/10T3) cells from fibroblastic, high-tumorigenic to epithelioid, low-tumorigenic phenotype was obtained by either seeding MAC/10T3 cells at low cell density or by exposing them to varying concentrations of IQ-1 or IQ-2 compounds. Clonal isolation was carried out by the ring isolation technique, and the various cloned revertant types were characterized by their cell morphology, saturation density, and tumorigenicity. Most of the revertants isolated 11 to 15 days after seeding at low cell density eventually returned to the fibroblastic, high-tumorigenic (HT) phenotype when serially passed at high cell density. In contrast, 25 to 36.3% of the slow-growing revertants isolated between 21 and 28 days after seeding at low cell density maintained the parental epithelioid morphology when subsequently seeded at high cell density. The observation of a possible temporal relationship between the low density seeding and the occurrence of stable revertants, and the observed differential cellular proliferation at low or high cell density, may suggest that reversion from a less tumorigenic phenotype to a highly tumorigenic state may involve a multistep process with a stringent requirement for active cell cycle.
A Teratological Evaluation and Postnatal Behavioral Screen of KF-868 In Rats
Authors: Hoberman A. M. , Weatherholtz W. M. , Durloo R. S.
Published: April 2009

The effects of a new experimental drug, KF-868, were investigated after administration to pregnant Sprague-Dawley rats at 0(vehicle), 0.1, 2.0, and 40.0 mg/kg per day during Days 7 through 17 of gestation by examination of term fetuses and naturally delivered offspring. Pregnant rats administered 0.1, 2.0, and 40.0 mg/kg per day gained significantly more weight during the dosage period than did the vehicle control group. Treatment-related physical signs, bloody crust on nose and stains on fur, were observed in the high dosage group. Fetal viability was significantly increased, and resorptions were significantly decreased for the mid and high dosage groups, when compared with the control group. Average fetal body weights for cesarean-delivered fetuses were less for the 40.0 mg/kg per day dosage groups than for the vehicle control group. Visceral and skeletal evaluations of fetuses revealed no difference between the control and test groups. Percent survival of pups was significantly less for the high dosage group than for the control group. Average rat body weights prior to mating for the high dosage group were generally less than for the control group. All physical and functional developmental values were comparable among the control and test groups. Evaluation of postweaning parameters of pups revealed no significant difference in sex maturation, behavior (open-field and water maze), and reproductive capacity. Average body weight gains during the 9-week growth period before mating were significantly less for the 40.0 mg/kg per day dosage group F1 generation female rats. Toxicity in fetuses and offspring was observed only at the highest dosage level. Dosage-dependent, significant increases in maternal body weight gain, as compared with control values, occurred for doses in the 3 KF-868-administered groups. These results indicate that 0.1 and 2.0 mg/kg per day dosages of KF-868 were not lethal and did not produce any adverse effects on the morphological or functional development of offspring. Toxicity was evident in offspring and fetuses of dams administered 40.0 mg/kg per day KF-868, 40,000 times as high as the daily therapeutic dose.
Evaluation of a New Reproductive Toxicology Protocol Using Diethylstilbestrol (DES) as a Positive Control Compound
Authors: Reel J. R. , Lawton A. D. , Wolkowski-Tyl R. , Davis G. W. , Lamb J. C.
Published: April 2009

A new National Toxicology Program (NTP) reproductive toxicology assay designated Fertility Assessment by Continuous Breeding was evaluated using trans-diethylstilbestrol (DES) as a positive control compound. The testing scheme employs young adult CD-1 male and female mice and is comprised of 5 possible tasks: task 1, 14-day dose-finding (repeated or continuous dosing); task 2, continuous breeding; task 3, determination of affected sex; task 4, offspring assessment; task 5, hormone patterns. Only tasks 2 and 3 were performed in the present study. Task 2 employed dietary levels of 0, 1, 10, and 50 ppb DES (99% pure). Task 3 used the control and high dose parental mice from task 2 in a crossover mating trial (control x treated) to determine whether one or both sexes in the F0 generation were adversely affected. Continuous exposure of F0 mice to 50 ppb DES in the diet during task 2 significantly decreased (P < 0.01) the proportion of pairs that produced at least 1 litter as compared to pairs continuously exposed to dietary levels of 0, 1, and 10 ppb DES. In addition, continuous exposure to 50 ppb DES in the diet had a cumulative adverse effect on the production and viability of litters. Thus, the pairs fed 50 ppb DES produced significantly fewer litters (P < 0.01), had fewer live pups per litter (P < 0.01), and tended toward a lower proportion of pups born alive per litter than did pairs in the 0, 1, and 10 ppb DES groups. In the crossover mating trial (task 3) the proportion of F0 females that mated (number with copulatory plugs/number cohabited) and that were fecund (number delivering litters/number with copulatory plugs) did not differ significantly among the 3 different combinations of paired mice. It was noted, however, that the proportion of cohabited F0 females delivering litters (number delivering litters/number cohabited) was significantly reduced (P < 0.05) in the control male x 50 ppb DES female group vs. the control male x control female group. The proportion of cohabited F0 females delivering litters in the 50 ppb DES male x control female group did not differ significantly from either of the above groups. Further, the number of live pups per litter and the proportion of pups born alive were significantly lower (P < 0.01) in the F0 control male x 50 ppb DES female group than in the other 2 groups. The proportion of male pups born alive (males/total) and the live pup weights, however, did not differ significantly among the 3 combinations of paired mice. Collectively, these results indicated that DES interfered with ovulation, conception, pre- and postimplantational processes in female mice. Thus, this new assay readily discriminated DES as a reproductive toxicant in CD-1 mice.
Measurement of Viability and Aryl Hydrocarbon Hydroxylase Activity in Cryopreserved Baboon Peripheral Blood Lymphocytes and Pulmonary Alveolar Macrophages
Authors: McLemore T. L. , Kuehl T. J.
Published: April 2009

Pulmonary alveolar macrophages (PAMs) and peripheral blood lymphocytes obtained from healthy nonsmoking baboons were evaluated for the ability to retain viability and aryl hydrocarbon hydroxylase (AHH) activity following cryopreservation for 2, 4, 6, 8, and 12 week intervals. Viability was measured (by trypan blue dye exclusion) in lymphocytes following 2, 4, 6, 8, and 12 weeks of cryopreservation. No significant decrease in viability was observed (P > 0.05 for all comparisons; nonpaired 2-tailed, t-test; n = 22), with lymphocytes retaining 88% of their original viability following 12 weeks of cryopreservation. Similarly, a slight, but insignificant decrease in PAM viability was observed following cryopreservation for 2, 4, 6, and 8 week intervals (P > 0.05 in all instances), with PAMs retaining 93.5% of the original 0 time viability. AHH activity was also evaluated in PAMs and lymphocytes following cryopreservation. Lymphocyte noninduced and BA-induced AHH activities were slightly but not significantly decreased after 2, 4, 6, 8, and 12 week cryopreservation intervals (P > 0.05 for all comparisons). Similarly, AHH activity in cultured PAMs was not significantly decreased following cryopreservation for 2, 4, 6, and 8 week intervals (P > 0.05 for all noninduced and BA-induced AHH levels assayed at the various time intervals; n = 8). Even following cryopreservation periods, for 8 or 12 week intervals, PAMs and lymphocytes retained 91% and 90%, respectively, of the original BA-induced AHH activity. These data demonstrate that baboon PAMs and lymphocytes are capable of undergoing cryopreservation while maintaining viability and AHH activity.
In Vitro Induction of Aryl Hydrocarbon Hydroxylase in Baboon Pulmonary Alveolar Macrophages and Peripheral Blood Lymphocytes
Authors: McLemore T. L. , Kuehl T. J.
Published: April 2009

Aryl hydrocarbon hydroxylase (AHH) activity was measured in cultured pulmonary alveolar macrophages (PAMs) (n = 12) and peripheral blood lymphocytes (n = 72) from unrelated baboons. It was determined that optional AHH induction was observed in PAMs when cells were cultured for 24 or 48 hours in the presence of a 15 μM concentration of the inducer, benzanthracene (BA). Maximal enzyme activity was observed in mitogen-activated lymphocytes when cells were cultured for 96 or 120 hours in the presence of 10 μM BA concentration. Additionally, there were no differences in PAM or lymphocyte AHH induction when cells were cultured in different types of culture medium (P > 0.10 in all instances, using paired, 2-tailed, Student's t-test). Similarly, no differences were observed between PAM AHH activity when human AB serum or autologous baboon serum was used in the culture medium (P > 0.30). However, slightly higher BA-induced AHH levels were noted in lymphocytes cultured in the presence of autologous baboon serum as compared with human AB serum (P < 0.02). Using optimal culture conditions for PAMs and lymphocytes from individual baboons a 6.5-fold interindividual variation in PAM and a 30-fold variation in lymphocyte BA-induced AHH levels were observed (n = 8 and 64, respectively). These studies document that AHH is measurable in cultured baboon PAMs and lymphocytes and that there is wide interindividual variation in BA-induced AHH levels. The distribution of AHH activity appears to be similar to that observed in the human population.
Effects of Nitrogen Dioxide on Resistance to Klebsiella pneumoniae in Mice
Authors: McGrath J.J. , Oyervides J.
Published: April 2009

We studied the effects of nitrogen dioxide (NO2) exposure on host resistance in mice. Mice were exposed continuously in inhalation chambers to 0.5, 1.0, or 1.5 ppm NO2 for 3 months or to 5 ppm NO2 for 3 days. Chamber NO2 concentrations were monitored continuously by a Thermoelectron chemiluminescent analyzer verified by the Saltzman procedure in accordance with Federal Register procedures. After the NO2 exposure, the mice were placed in an infectivity chamber and exposed to aerosolized cultures of Klebsiella pneumoniae for 15 minutes. Chamber clouds contained 55.2 ± 9.3 organisms (1–3 μ in size) per liter of air. The animals were removed from the infectivity chamber and observed for 15 days, after which percent mortalities and relative mean survival times (RMST) were determined. Control mice and mice exposed to 0.5, 1.0, or 1.5 ppm NO2 for 3 months did not differ significantly in mortality or RMST. In mice exposed to 5 ppm NO2 for 3 days, percent mortality was significantly higher and RMST was significantly lower. Lung index (lung weight/body weight) and body weight did not differ significantly after exposure to 0.5, 1.0, and 1.5 ppm NO2 for 3 months or to 5 ppm NO2 for 3 days. These results indicate that inhalation of 5 ppm NO2 for 3 days depresses host resistance to K. pneumoniae, whereas inhalation of 1.5 ppm NO2 for up to 3 months does not.
Subchronic and Chronic Toxicity Studies of 2,4-Dinitrotoluene. Part I. Beagle Dogs
Authors: Ellis H.V. , Hong C.B. , Lee C.C. , Dacre J.C. , Glennon J.P.
Published: April 2009

Subchronic and chronic toxicities of 2,4-dinitrotoluene (2,4-DNT) were studied in beagle dogs. The major adverse effect of 2,4-DNT in dogs was a neuropathy, characterized by incoordination and paralysis. There were vacuolation, endothelial proliferation, and gliosis of the cerebellums of some affected dogs. These effects were seen in 1 dog given 1.5 mg/kg per day for 2 years, in all dogs given 10 mg/kg per day within 6 months, and in all dogs given 25 mg/kg per day within 2 months. There was great variation between individuals in onset and severity of adverse effects. Some dogs progressed to a complete paralysis, leading to death. Methemoglobin and its sequelae were common, but not life threatening. Heinz bodies were a useful indicator of this effect. Less important adverse effects seen included testicular degeneration and biliary tract hyperplasia. No changes were found in tumor incidence, immunoglobin E and cytogenetic assays, and other routine hematologic and clinical laboratory tests.
Subchronic and Chronic Toxicity Studies of 2,4-Dinitrotoluene. Part II. CD® Rats
Authors: Lee C.C. , Hong C.B. , Ellis H.V. , Dacre J.C. , Glennon J.P.
Published: April 2009

Subchronic and chronic toxicities of 2,4-dinitrotoluene were studied in CD® rats. Feeding of 2,4-dinitrotoluene for 13 weeks at a low dose of 34 mg/kg per day in males and 38 mg/kg per day in females caused depressed weight gain. The middle dose of 93 and 108 mg/kg per day, respectively, was toxic, caused reticulocytosis and splenic hemosiderosis, and decreased spermatogenesis. The high dose of 266 and 145 mg/kg per day, respectively, was more toxic and lethal. Some rats had widespread and stiff-legged gaits and demyelination in the cerebellum and brain stem. After feeding up to 2 years, the low dose (0.57 and 0.71 mg/kg per day, respectively) caused no apparent toxic effects. The middle dose (3.9 and 5.1 mg/kg per day, respectively) was toxic; the high dose (34 and 45 mg/kg per day) was more toxic and shortened the life span. Target organs included the blood (toxic anemia), the liver (hepatocellular carcinoma), the testis (atrophy and depression of spermatogenesis), the connective tissue in males (fibromas), the mammary tissue in females (fibroadenomas), and the neuromuscular system in some rats.
A Selected Review of Risk Models: One Hit, Multihit, Multistage, Probit, Weibull, and Pharmacokinetic
Authors: Hanes B. , Wedel T.
Published: April 2009

This paper provides some of the underlying mathematical derivations for the one-hit, multihit, multistage, Weibull, and pharmacokinetic risk models. Our purposes are to remove for the nonmathematician some of the mystery as to the derivation of the formulas for each particular risk model and to discuss some of the assumptions contained in the risk models. Confidence limits and maximum likelihood estimates of the model parameters are not discussed, since they are not pertinent to our objectives. Rai and Van Ryzin(1) have outlined these procedures in sufficient detail.
Pattern of Response of Intact Drosophila to Known Teratogens
Authors: Schuler R.L. , Radike M.A. , Hardin B.D. , Niemeier R.W.
Published: April 2009

Drosophila, as the test organism, was used to assess 17 chemicals. The teratogenic potential of 15 of these chemicals is well established from animal studies or human epidemiology. The test involves examination of adult flies following treatment during larval stages of development. Flies are examined for abnormal external morphology. The incidence of abnormalities in treated and control populations is compared using the Chi-square test. All 17 chemicals were active to varying degrees in the test system. Most chemicals produced a unique response yielding individual patterns of abnormalities. These results suggest that Drosophila may have the potential to become a valuable teratogen screen, but further, more rigorous examination–particularly with nonteratogens–is required.
GLP Trends Today and Tomorrow
Authors: Baldwin J.K. , Hoover B.K.
Published: April 2009

The definition of the scope and application of GLPs vs. glps is discussed. Current concepts and future trends, such as the 2-tiered approach, data hardness, data quality indicators, and professional ethics, are examined.
Pathways of Selenium Metabolism Including Respiratory Excretory Products
Authors: Ganther H.E.
Published: April 2009

Selenium occurs in a variety of different chemical forms in plants and animals. Plants take up inorganic forms of selenium and make numerous selenium analogs of sulfur compounds. Exclusion of selenium from proteins is characteristic of plant species able to tolerate high concentrations of selenium. Animals metabolize both inorganic and organic forms of selenium into biologically active compounds, including selenocysteine in glutathione peroxidase. Intermediary metabolism of selenium in animals characteristically involves reduction and methylation, resulting in the excretion of urinary or respiratory metabolites that include the trimethylselenonium ion and dimethylselenide. Some mechanisms for reduction and methylation of selenium in animals are discussed, as well as the effects of methylation on toxicity.
Proposed Supplemental Dosages of Selenium for a Phase I Trial Based on Dietary and Supplemental Selenium Intakes and Episodes of Chronic Selenosis
Authors: Chen J. , Clark L.C.
Published: April 2009

Phase I trials are needed to identify the maximum safe dose of both inorganic and organic selenium (Se) compounds that could be used under medical supervision for patients at extremely high risk of cancer. Based on naturally occurring episodes of chronic selenosis and experience with Se supplementation trials, we recommend a range of doses for inorganic and organic Se compounds that should be investigated in a Phase I trial in order to identify the maximum tolerated dose for these compounds.
Teratogen-induced Decrements of Postnatal Functional Capacity
Authors: Newman L. M. , Johnson E. M.
Published: April 2009

Differences in response to pharmacologic or other exogenous agents occur when they are applied to individuals of different ages. The present report presents a discussion of the relative vulnerabilities of various early stages in the life cycle. Various published results, using several systems, including lung, kidney, gastrointestinal tract, and immune system, have clearly established that unique developmental events take place not just in embryonic development but also during fetal development and that the latter period may be highly vulnerable to perturbation by a teratogenic agent. Defects may be manifest in subtle ways and result in neonates that, although they may appear to be normal, in fact lack physiologic reserves or capabilities beyond those necessary for simply surviving. In the clinical world, it is possible that a prenatal insult often undetected by routine types of clinical evaluation could put an individual at jeopardy or increase its postnatal vulnerability to an insult tolerated by unaltered off spring.
The Setting of Particulate Exposure Levels for Chronic Inhalation Toxicity Studies
Authors: Morrow P. E.
Published: April 2009

This paper briefly reviews the development of regulatory agency guidelines for toxicity testing and the impact of the maximum tolerated dose (MTD) concept on chronic study designs within and outside of the regulatory arena. From the orientation of an inhalation toxicologist, the MTD is viewed as a difficult and costly concept to implement and one that is generally inappropriate as a general basis for setting dust exposure levels in sub-chronic and chronic inhalation toxicity studies. Two possible alternatives are discussed, especially in the context of accumulating evidence that most dusts, even the most innocuous, when presented in excessive amounts produce a spectrum of pulmonary responses that cannot be dissociated from injury.
Psychotic Reactions Following the Naive Ingestion of an Anorectic, Phenylpropanolamine, in Psychiatric Patients
Authors: Scavullo B. C. , Dementi B.
Published: April 2009

Two clinical case histories are presented that indicate that naive ingestion of the anorectic, phenylpropanolamine, may induce psychotic reactions in patients with preexisting diagnosed psychiatric disturbance. These clinical observations and concerns are buttressed by a review of the scientific literature relevant to the psychotic inducing effects of phenylpropanolamine and structurally similar sympathomimetic derivatives of β-phenylethylamine, such as amphetamine and ephedrine.
Critical Toxicity Reference System I. An Approach for Managing Quantitative Toxicity Data
Authors: Smolko E. D. , Mckee D. J. , Menzel D. B.
Published: April 2009

The Critical Toxicity Reference (CTR) system is an approach for managing quantitative toxicity data. The essential components of this system include a thorough search of available literature, abstraction of information from selected references, entry of information into a computerized database, searching the database for specific types of studies, and reporting data in a form usable for direct analysis. The CTR system was developed in response to the need for quantitative use of data from animal studies in setting National Ambient Air Quality Standards (NAAQS), and the first application was the criteria pollutant ozone. Animal toxicity studies provide most information on health effects of ozone exposure. However, the data have been used only qualitatively for setting the NAAQS. A primary reason for this limited utilization is the lack of a method for combining results from different studies to present a comprehensive analysis of any given health effect observed upon ozone exposure. The CTR system deals with this problem and was specifically designed for retrieval on the basis of qualitative or quantitative comparisons. The method extends beyond conventional bibliographic methods by allowing integration with dosimetry and risk analysis modeling methods. This approach is generally applicable to any toxicant.
Identification and Ranking of Chemical Hazards for the Railroad Industry
Authors: Karch N. J. , Golden R. J. , Lowenbach W. A. , Yost L. J. , Weiss A. L.
Published: April 2009

This paper describes a unique system for the systematic evaluation of volatile chemicals that may be released to the atmosphere in large quantities. Chemicals were ranked for their potential to cause death or serious injury in a surrounding community in the event of a large release following a rail accident. Two parameters were scored in the risk model: (1) toxicity and (2) exposure. Toxicity evaluations were based on data on acute lethality and serious sublethal effects. The decision rules used to score the chemicals and the assumptions relied on in the selection of the underlying data are detailed. The potential for exposure was evaluated using a simplified model based on vapor pressure and molecular diffusion. The rankings based on these scores and the overall risk scores were compared to rankings based on two other sophisticated exposure models: Mackay, an empirical model of evaporation, and SPILLS, a Gaussian puff dispersion model in use by the Association of American Railroads. The rank orders predicted by each model of a chemical's propensity to evaporate were in excellent agreement with one another. Because the process of evaluation and review of the underlying data for ranking is still underway, the ranking is confidential.
The History of the Use of Animals in Research and the Development of the Animal Welfare Concept
Authors: Goeke J. E.
Published: April 2009

The ideological underpinning of the animal welfare/animal rights movement is not a recent development, but rather the result of a revolutionary change in Western man's perception of the natural world between 1500 and 1800. In 1500, these basic perceptions were as follows: (1) the world was created for man's sake and all other species were subordinate to his wishes, (2) man's stance toward other species was essentially that of subjugation or conquest, (3) humans were absolutely unique and separate from the rest of creation. By 1800, these basic perceptions had been fundamentally altered to reflect the following: (1) the world did not exist for nor was it created for man alone, (2) man's stance toward the natural world and especially toward other animals was that of stewardship, and animals were within the sphere of moral concern, (3) man was a superior animal, although the basis for this superiority was not entirely clear, and was related to all other animals through physiologic similarities and the powers of feeling and sensation.
Review Procedures of Animal Research and the Veterinarian's Role
Authors: Ewald B. H.
Published: April 2009

Government and accrediting agencies have mandated the establishment of an Institutional Animal Care and Use Committee (IACUC) with slightly different functional and membership requirements. The committee has two primary functions, including protocol review and observation of facilities and procedures. The committee's mission is to reduce, replace, or refine animal use without interfering with research. Procedures for establishment of the committee and methods of review are presented. The veterinarian assumes a quality assurance role that includes disease prevention, consultation, establishment of standards, and training. Scientists, veterinarians, and committee members cooperatively can reduce unnecessary animal use, pain, and distress.
GLP: A Global Basis
Authors: Friedman I.
Published: April 2009

This paper addresses four questions related to worldwide GLP regulations: (1) How global are GLP regulations? (2) How and why did they become global? (3) What is their present global status? (4) What might we predict about the future?
Unique Aspects of GLP Pathology
Authors: Farrow M. G.
Published: April 2009

This paper is based in large part on my experiences visiting or reviewing data from over 24 laboratories in the past 18 months and discusses major problems that I have encountered in GLP pathology.
Japanese GLP Requirements
Authors: McKAY D.
Published: April 2009

Japanese GLP were developed and published some time after their counterparts in the US. It is, therefore, interesting to see in which way the Japanese authorities decided to make changes in the light of experience in the U.S. Facility petition for confirmation is an example of a different approach. With this procedure, whereby information in great detail must be submitted, the Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF) has taken on an ongoing task of some magnitude. For now Japanese sponsors and contract laboratories, there are many possibilities for misunderstandings. These include language, culture, differing corporate/organization structures, differing job titles. We must realize, however, that it is also difficult for the Japanese authorities, who are faced with the same problems in reverse. It appears that bilateral arrangements are the answer, but these are slow to materialize.