Sample records for previous studies rats

  1. Effect of Previous Irradiation on Vascular Thrombosis of Microsurgical Anastomosis: A Preclinical Study in Rats.

    Barrera-Ochoa, Sergi; Gallardo-Calero, Irene; López-Fernández, Alba; Romagosa, Cleofe; Vergés, Ramona; Aguirre-Canyadell, Marius; Soldado, Francisco; Velez, Roberto


    The objective of the present investigation was to compare the effect of neoadjuvant irradiation on the microvascular anastomosis in cervical bundle using an experimental model in rats. One hundred forty male Sprague-Dawley rats were allocated into 4 groups: group I, control, arterial microanastomosis; group II, control, venous microanastomosis; group III, arterial microanastomosis with previous irradiation (20 Gy); and group IV, venous microanastomosis with previous irradiation (20 Gy). Clinical parameters, technical values of anastomosis, patency, and histopathological parameters were evaluated. Irradiated groups (III and IV) and vein anastomosis groups (II and IV) showed significantly increased technical difficulties. Group IV showed significantly reduced patency rates (7/35) when compared with the control group (0/35). Radiotherapy significantly decreased the patency rates of the vein (7/35) when compared with the artery (1/35). Groups III and IV showed significantly reduced number of endothelial cells and also showed the presence of intimal thickening and adventitial fibrosis as compared with the control group. Neoadjuvant radiotherapy reduces the viability of the venous anastomosis in a preclinical rat model with a significant increase in the incidence of vein thrombosis.

  2. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats

    Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara EF; Dutra, Bárbara A; Oliveira, Márcio V; de Magalhães, Amélia CM; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M


    This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. PMID:26490345

  3. Computed tomography in the evaluation of abdominal fat distribution associated with a hyperlipidic diet in previously undernourished rats

    Costa, Carlos Alberto Soares da [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Faculdade de Ciencias Medicas. Program of Post-graduation in Clinical and Experimental Physiopathology; Alves, Erika Gomes; Gonzalez, Gabriele Paula; Barbosa, Thais Barcellos Cortez; Lima, Veronica Demarco; Nascimento, Renata; Moura, Egberto Gaspar de; Saba, Celly Cristina Alves do Nascimento [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. of Physiological Sciences]. E-mail:; Monteiro, Alexandra Maria Vieira [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Faculdade de Ciencias Medicas


    Objective: To study, by means of computed tomography, the repercussion of post-weaning dietary supplementation with soy oil or canola oil on the abdominal fat distribution in previously undernourished rats. Materials and methods: Dams submitted to 50% food restriction (FR) compared with dams receiving a standard diet (C). After weaning, undernourished rats received a diet supplemented with 19% soy oil (19% FR-soy) or 19% canola oil (19% FR-canola). Rats in the control group received a diet with 7% soy oil (7% C-soy) until the end of the experimental period. At the age of 60 days old, the rats were submitted to computed tomography for evaluation of total abdominal and visceral fat area. The rats' length and body mass were evaluated and, after their sacrifice, the abdominal fat depots were excised weighted. The data are reported as mean {+-} mean standard error, with p < 0.05 considered as significance level. Results: Rats in the group 19% FR presented similar length, body weight and visceral fat mass. As a whole, the evaluations have shower results significantly lower in relation to the control group (7% C-soy). However, computed tomography has found significant differences in abdominal fat distribution for the groups 19% FR-soy and 19% FR-canola. Conclusion: Computed tomography has demonstrated that the abdominal fat distribution may be dependent on the type of vegetable oil included in the diet. (author)

  4. Previous Cocaine Exposure Makes Rats Hypersensitive to Both Delay and Reward Magnitude

    Roesch, Matthew R.; Takahashi, Yuji; Gugsa, Nishan; Bissonette, Gregory B.; Schoenbaum, Geoffrey


    Animals prefer an immediate over a delayed reward, just as they prefer a large over a small reward. Exposure to psychostimulants causes long-lasting changes in structures critical for this behavior and might disrupt normal time-discounting performance. To test this hypothesis, we exposed rats to cocaine daily for 2 weeks (30 mg/kg, i.p.). Approximately 6 weeks later, we tested them on a variant of a time-discounting task, in which the rats responded to one of two locations to obtain reward while we independently manipulated the delay to reward and reward magnitude. Performance did not differ between cocaine-treated and saline-treated (control) rats when delay lengths and reward magnitudes were equal at the two locations. However, cocaine-treated rats were significantly more likely to shift their responding when we increased the delay or reward size asymmetrically. Furthermore, they were slower to respond and made more errors when forced to the side associated with the lower value. We conclude that previous exposure to cocaine makes choice behavior hypersensitive to differences in the time to and size of available rewards, consistent with a general effect of cocaine exposure on reward valuation mechanisms. PMID:17202492

  5. Previous studies underestimate BMAA concentrations in cycad flour.

    Cheng, Ran; Banack, Sandra Anne


    The traditional diet of the Chamorro people of Guam has high concentrations of the neurotoxin BMAA, beta-methyl-amino-L-alanine, in cycad tortillas and from animals that feed on cycad seeds. We measured BMAA concentration in washed cycad flour and compared different extraction methods used by previous researchers in order to determine how much BMAA may have been unaccounted for in prior research. Samples were analyzed with AQC precolumn derivatization using HPLC-FD detection and verified with UPLC-UV, UPLC-MS, and triple quadrupole LC/MS/MS. Although previous workers had studied only the free amino acid component of BMAA in washed cycad flour, we detected significant levels of protein-associated BMAA in washed cycad flour. These data support a link between ALS/PDC and exposure to BMAA.

  6. Effects of previous aeroionization on consecutive waking and sleeping phases in rats

    Lambert, J. F.; Olivereau, J. M.


    The investigation showed that positive and negative air ions have opposite general effects on the structure of sleep in rats. When submitted to positive air ions, the animals consecutively exhibited during sleep an EEG with increased amplitude and lowered frequency. This decrease in vigilance level is nevertheless accompanied by obvious signs of a disturbed sleep, that is: more polyphasic sleep and decrease of slow wave sleep which is the most efficient for physical restoration. The generally opposite action of negative air ions is consistent with their effects described by other authors who have studied human sleep after aeroionotherapy. The general paradigm of air ion action on sleep is in agreement with implications of recent sleep theories.

  7. Study of cystic artery by arteriography. Importance of previous cholecystography

    Machado, G.O.

    An oral cholecystography previously to celiac and mesenteric arteriography is performed, in order to identify the cystic artery, in 42 patients with pancreatitis, according Seldinger technique. The cystic artery was identified in all the cases, the pattern being the outlet of the cystic artery from the right hepatic artery. Infusion pump and seriography were not used.

  8. The Impact of Previous Physical Training on Redox Signaling after Traumatic Brain Injury in Rats: A Behavioral and Neurochemical Approach.

    da Silva Fiorin, Fernando; de Oliveira Ferreira, Ana P; Ribeiro, Leandro R; Silva, Luiz F A; de Castro, Mauro R T; da Silva, Luís R H; da Silveira, Mauro E P; Zemolin, Ana P P; Dobrachinski, Fernando; Marchesan de Oliveira, Sara; Franco, Jeferson L; Soares, Félix A; Furian, Ana F; Oliveira, Mauro S; Fighera, Michele R; Freire Royes, Luiz F


    Throughout the world, traumatic brain injury (TBI) is one of the major causes of disability, which can include deficits in motor function and memory, as well as acquired epilepsy. Although some studies have shown the beneficial effects of physical exercise after TBI, the prophylactic effects are poorly understood. In the current study, we demonstrated that TBI induced by fluid percussion injury (FPI) in adult male Wistar rats caused early motor impairment (24 h), learning deficit (15 days), spontaneous epileptiform events (SEE), and hilar cell loss in the hippocampus (35 days) after TBI. The hippocampal alterations in the redox status, which were characterized by dichlorofluorescein diacetate oxidation and superoxide dismutase (SOD) activity inhibition, led to the impairment of protein function (Na(+), K(+)-adenosine triphosphatase [ATPase] activity inhibition) and glutamate uptake inhibition 24 h after neuronal injury. The molecular adaptations elicited by previous swim training protected against the glutamate uptake inhibition, oxidative stress, and inhibition of selected targets for free radicals (e.g., Na(+), K(+)-ATPase) 24 h after neuronal injury. Our data indicate that this protocol of exercise protected against FPI-induced motor impairment, learning deficits, and SEE. In addition, the enhancement of the hippocampal phosphorylated nuclear factor erythroid 2-related factor (P-Nrf2)/Nrf2, heat shock protein 70, and brain-derived neurotrophic factor immune content in the trained injured rats suggests that protein expression modulation associated with an antioxidant defense elicited by previous physical exercise can prevent toxicity induced by TBI, which is characterized by cell loss in the dentate gyrus hilus at 35 days after TBI. Therefore, this report suggests that previous physical exercise can decrease lesion progression in this model of brain damage.

  9. New study reveals twice as many asteroids as previously believed


    The ISO satellite Credits: ESA ISO An artist's impression of the ISO spacecraft. The ISO Deep Asteroid Search indicates that there are between 1.1 million and 1.9 million 'space rocks' larger than 1 kilometre in diameter in the so-called 'main asteroid belt', about twice as many as previously believed. However, astronomers think it is premature to revise current assessments of the risk of the Earth being hit by an asteroid. Despite being in our own Solar System, asteroids can be more difficult to study than very distant galaxies. With sizes of up to one thousand kilometres in diameter, the brightness of these rocky objects may vary considerably in just a few minutes. They move very quickly with respect to the stars - they have been dubbed 'vermin of the sky' because they often appear as trails on long exposure images. This elusiveness explains why their actual number and size distribution remains uncertain. Most of the almost 40,000 asteroids catalogued so far (1) orbit the Sun forming the 'main asteroid belt', between Mars and Jupiter, too far to pose any threat to Earth. However, space-watchers do keep a closer eye on another category of asteroids, the 'Near Earth Asteroids' or 'NEAs', which are those whose orbits cross, or are likely to cross, that of our planet. The ISO Deep Asteroid Search (IDAS), the first systematic search for these objects performed in infrared light, focused on main belt asteroids. Because it is impossible to simply point the telescope at the whole main belt and count, astronomers choose selected regions of the belt and then use a theoretical model to extrapolate the data to the whole belt. Edward Tedesco (TerraSystems, Inc., New Hampshire, United States) and François-Xavier Desert (Observatoire de Grenoble, France) observed their main belt selected areas in 1996 and 1997 with ESA's ISO. They found that in the middle region of the belt the density of asteroids was 160 asteroids larger than 1 kilometre per square degree - an area of the

  10. Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation

    Bendre, M; Comasco, E; Nylander, I; Nilsson, K W


    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse. PMID:26645625

  11. Spreading depression is facilitated in adult rats previously submitted to short episodes of malnutrition during the lactation period

    Rocha-de-Melo A.P.


    Full Text Available Lactating rat dams were submitted to short episodes (1, 2 or 3 weeks of nutritional restriction by receiving the "regional basic diet" (RBD, with 8% protein of low-income human populations of Northeast Brazil. Their pups were then studied regarding the developmental effects on body and brain weights. When the rats reached adulthood, cortical susceptibility to the phenomenon of spreading depression (SD was evaluated by performing electrophysiological recordings on the surface of the cerebral cortex. SD was elicited at 20-min intervals by applying 2% KCl for 1 min to a site on the frontal cortex and its occurrence was monitored at 2 sites in the parietal region by recording the electrocorticogram and the slow potential change of SD. When compared to control rats fed a commercial diet with 23% protein, early malnourished rats showed deficits in body and brain weights (10% to 60% and 3% to 15%, respectively, as well as increases in velocity of SD propagation (10% to 20%. These effects were directly related to the duration of maternal dietary restriction, with pups malnourished for 2 or 3 weeks presenting more intense weight and SD changes than those malnourished for 1 week. The effects of 1-week restrictions on SD were less evident in the pups malnourished during the second week of lactation and were more evident in pups receiving the RBD during the third week. The results indicate that short episodes of early malnutrition during the suckling period can affect body and brain development, as well as the cortical susceptibility to SD during adulthood. The data also suggest that the third week of lactation is the period during which the brain is most sensitive to malnutrition, concerning the effects on SD

  12. Effects of previous physical exercise to chronic stress on long-term aversive memory and oxidative stress in amygdala and hippocampus of rats.

    Dos Santos, Tiago Marcon; Kolling, Janaína; Siebert, Cassiana; Biasibetti, Helena; Bertó, Carolina Gessinger; Grun, Lucas Kich; Dalmaz, Carla; Barbé-Tuana, Florencia María; Wyse, Angela T S


    Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na(+), K(+)-ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised+stressed). The animals were subjected to controlled exercise treadmill for 20min,three times a week, for two months prior to submission to the CVS (40days). Results show that CVS impaired performance in inhibitory avoidance at 24h and 7days after training session. CVS induced oxidative stress, increasing reactive species, lipoperoxidation and protein damage, and decreasing the activity of antioxidant enzymes. The activity of Na(+), K(+)-ATPase was decreased, but the immunocontents and gene expression of catalytic subunits were not altered. The previous physical exercise was able to improve performance in inhibitory avoidance at 24h after training; additionally, exercise prevented oxidative damage, but was unable to reverse completely the changes observed on the enzymatic activities. Our findings suggest that physical exercise during the developmental period may protect against aversive memory impairment and brain oxidative damage caused by chronic stress exposure later in life. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  13. Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine apparently increases brain serotoninergic activity in the rat: no influence of previous chronic immobilization stress.

    Pol, O; Campmany, L; Armario, A


    The functional relationship between brain catecholamines and serotoninergic function was studied in stress-naive and chronically immobilized rats after blockade of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha MpT). The levels of noradrenaline (NA), serotonin, and 5-hydroxyindole acetic acid (5-HIAA) in pons plus medulla, brainstem, hypothalamus, hippocampus, and frontal cortex, and those of 3-methoxy, 4-hydroxyphenile-tileneglicol sulphate (MHPG-SO4) in the hypothalamus were measured by HPLC. Chronic immobilization (IMO) resulted in higher NA levels in pons plus medulla and hypothalamus, the latter area (the only one in which the NA metabolite was determined) also showing slightly elevated MHPG-SO4 levels as compared to stress-naive rats. Chronic IMO did not alter either serotonin or 5-HIAA levels, but acute stress consistently increased 5-HIAA levels in all areas, independently of previous chronic stress. Administration of alpha-MpT drastically reduced NA and increased 5-HIAA levels in all brain regions excepting the frontal cortex. The effect of the drug on serotoninergic function was not altered by previous chronic exposure to IMO. These data suggest that the noradrenergic system appears to exert a tonic inhibitory effect on serotoninergic activity in the brain, with the intensity of the effect depending on the brain area studied. In addition, chronic stress does not appear to alter the functional relationship between noradrenergic and serotoninergic activities, although interactions might exist in more restricted brain areas; this deserves further study.

  14. Effect of previous strength training episode and retraining on facilitation of skeletal muscle hypertrophy and contractile properties after long-term detraining in rats.

    Lee, Sukho; Hong, Kwang-Seok; Kim, Kijeong


    In the present study, we investigated the effects of previous strength training and retraining following long-term cessation of exercise on muscle mass and contractile properties. Female Sprague-Dawley rats (n=24) aged eight weeks were randomly assigned one of the four groups: control (CON), detraining (DT), training (TR), and retraining (RT). The training regimen consisted of climbing ladder 5×3 sets, once every third day for eight weeks with weight attached to the tail. The weight carried during each training session was initially 50% of body weight and progressively increased by 10% per session. The rats in DT were detained for 20 weeks followed by eight weeks strength training. The rats in the both TR and RT groups underwent eight weeks training. DT was age matched new training group while RT was retraining group after 20 weeks of detraining. Soleus, gastrocnemius, tibialis anterior, and flexor hallucis longus (FHL) muscles were harvested in order to measure the weight, and in situ contractile properties of FHL were measured including specific twitch tension (Spt) and specific tetanic tension (Spo). TR showed significant increase in muscle mass compared to CON (Pstrength training facilitates retraining-induced muscle hypertrophy following long-term cessation of exercise.

  15. Summary of Previous Chamber or Controlled Anthrax Studies and Recommendations for Possible Additional Studies

    Piepel, Gregory F.; Amidan, Brett G.; Morrow, Jayne B.


    This report and an associated Excel file(a) summarizes the investigations and results of previous chamber and controlled studies(b) to characterize the performance of methods for collecting, storing and/or transporting, extracting, and analyzing samples from surfaces contaminated by Bacillus anthracis (BA) or related simulants. This report and the Excel are the joint work of the Pacific Northwest National Laboratory (PNNL) and the National Institute of Standards and Technology (NIST) for the Department of Homeland Security, Science and Technology Directorate. The report was originally released as PNNL-SA-69338, Rev. 0 in November 2009 with limited distribution, but was subsequently cleared for release with unlimited distribution in this Rev. 1. Only minor changes were made to Rev. 0 to yield Rev. 1. A more substantial update (including summarizing data from other studies and more condensed summary tables of data) is underway

  16. The impact of previous traumatic brain injury on health and functioning: a TRACK-TBI study.

    Dams-O'Connor, Kristen; Spielman, Lisa; Singh, Ayushi; Gordon, Wayne A; Lingsma, Hester F; Maas, Andrew I R; Manley, Geoffrey T; Mukherjee, Pratik; Okonkwo, David O; Puccio, Ava M; Schnyer, David M; Valadka, Alex B; Yue, John K; Yuh, Esther L


    The idea that multiple traumatic brain injury (TBI) can have a cumulative detrimental effect on functioning is widely accepted. Most research supporting this idea comes from athlete samples, and it is not known whether remote history of previous TBI affects functioning after subsequent TBI in community-based samples. This study investigates whether a previous history of TBI with loss of consciousness (LOC) is associated with worse health and functioning in a sample of individuals who require emergency department care for current TBI. Twenty-three percent of the 586 individuals with current TBI in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study reported having sustained a previous TBI with LOC. Individuals with previous TBI were more likely to be unemployed (χ(2)=17.86; p=0.000), report a variety of chronic medical and psychiatric conditions (4.75≤χ(2)≥24.16; pTBI history. Those with a previous TBI had less-severe acute injuries, but experienced worse outcomes at 6-month follow-up. Results of a series of regression analyses controlling for demographics and acute injury severity indicated that individuals with previous TBI reported more mood symptoms, more postconcussive symptoms, lower life satisfaction, and had slower processing speed and poorer verbal learning, compared to those with no previous TBI history. These findings suggest that history of TBI with LOC may have important implications for health and psychological functioning after TBI in community-based samples.

  17. Matched cohort study of external cephalic version in women with previous cesarean delivery.

    Keepanasseril, Anish; Anand, Keerthana; Soundara Raghavan, Subrahmanian


    To evaluate the efficacy and safety of external cephalic version (ECV) among women with previous cesarean delivery. A retrospective study was conducted using data for women with previous cesarean delivery and breech presentation who underwent ECV at or after 36 weeks of pregnancy during 2011-2016. For every case, two multiparous women without previous cesarean delivery who underwent ECV and were matched for age and pregnancy duration were included. Characteristics and outcomes were compared between groups. ECV was successful for 32 (84.2%) of 38 women with previous cesarean delivery and 62 (81.6%) in the control group (P=0.728). Multivariate regression analysis confirmed that previous cesarean was not associated with ECV success (odds ratio 1.89, 95% confidence interval 0.19-18.47; P=0.244). Successful vaginal delivery after successful ECV was reported for 19 (59.4%) women in the previous cesarean delivery group and 52 (83.9%) in the control group (Pcesarean delivery. To avoid a repeat cesarean delivery, ECV can be offered to women with breech presentation and previous cesarean delivery who are otherwise eligible for a trial of labor. © 2017 International Federation of Gynecology and Obstetrics.

  18. Selection of bacteria originating from a human intestinal microbiota in the gut of previously germ-free rats

    Licht, Tine Rask; Madsen, Bodil; Wilcks, Andrea


    Denaturing gradient gel electrophoresis (DGGE) was applied to separate PCR-amplified 16S rRNA genes originating from human microbiota associated (HMA) rat faeces as well as from the human faecal sample used for inoculation of the animals. Subsequently, a total of 15 dominant bands were excised fr...

  19. Previous history of chronic stress changes the transcriptional response to glucocorticoid challenge in the dentate gyrus region of the male rat hippocampus.

    Datson, Nicole A; van den Oever, Jessica M E; Korobko, Oksana B; Magarinos, Ana Maria; de Kloet, E Ronald; McEwen, Bruce S


    Chronic stress is a risk factor for several neuropsychiatric diseases, such as depression and psychosis. In response to stress glucocorticoids (GCs) are secreted that bind to mineralocorticoid and glucocorticoid receptors, ligand-activated transcription factors that regulate the transcription of gene networks in the brain necessary for coping with stress, recovery, and adaptation. Chronic stress particularly affects the dentate gyrus (DG) subregion of the hippocampus, causing several functional and morphological changes with consequences for learning and memory, which are likely adaptive but at the same time make DG neurons more vulnerable to subsequent challenges. The aim of this study was to investigate the transcriptional response of DG neurons to a GC challenge in male rats previously exposed to chronic restraint stress (CRS). An intriguing finding of the current study was that having a history of CRS had profound consequences for the subsequent response to acute GC challenge, differentially affecting the expression of several hundreds of genes in the DG compared with challenged nonstressed control animals. This enduring effect of previous stress exposure suggests that epigenetic processes may be involved. In line with this, CRS indeed affected the expression of several genes involved in chromatin structure and epigenetic processes, including Asf1, Ash1l, Hist1h3f, and Tp63. The data presented here indicate that CRS alters the transcriptional response to a subsequent GC injection. We propose that this altered transcriptional potential forms part of the molecular mechanism underlying the enhanced vulnerability for stress-related disorders like depression caused by chronic stress.

  20. Teratology studies in the rat.

    Leroy, Mariline; Allais, Linda


    The rat is the rodent species of choice for the regulatory safety testing of xenobiotics, such as medicinal products, food additives, and other chemicals. Many decades of experience and extensive data have accumulated for both general and developmental toxicology investigations in this species. The high fertility and large litter size of the rat are advantages for teratogenicity testing. The study designs are well defined in the regulatory guidelines and are relatively standardized between testing laboratories across the world. Teratology studies address maternal- and embryo-toxicity following exposure during the period of organogenesis. This chapter describes the design and conduct of a teratology study in the rat in compliance with the regulatory guidelines. The procedures for the handling and housing of the pregnant animals, the caesarean examinations and the sampling of fetuses for morphological examinations are described. The utility and design of preliminary studies and the inclusion of satellite animals in the main study for toxicokinetic sampling are discussed.

  1. Developing Reading Comprehension through Metacognitive Strategies: A Review of Previous Studies

    Channa, Mansoor Ahmed; Nordin, Zaimuariffudin Shukri; Siming, Insaf Ali; Chandio, Ali Asgher; Koondher, Mansoor Ali


    This paper has reviewed the previous studies on metacognitive strategies based on planning, monitoring, and evaluating in order to develop reading comprehension. The main purpose of this review in metacognition, and reading domain is to help readers to enhance their capabilities and power reading through these strategies. The researchers reviewed…

  2. Sourcing quality-of-life weights obtained from previous studies: theory and reality in Korea.

    Bae, SeungJin; Bae, Eun Young; Lim, Sang Hee


    The quality-of-life weights obtained in previous studies are frequently used in cost-utility analyses. The purpose of this study is to describe how the values obtained in previous studies are incorporated into the industry submissions requesting listing at the Korean National Health Insurance (NHI), focusing on the issues discussed in theoretical studies and national guidelines. The industry submissions requesting listing at the Korean NHI from January 2007 until December 2009 were evaluated by two independent researchers at the Health Insurance Review and Assessment Service (HIRA). Specifically, we observed the methods that were used to pool, predict joint health state utilities, and retain consistency within submissions in terms of the issues discussed in methodological research papers and recommendations from national guidelines. More than half of the submissions used QALY as an outcome measure, and most of these submissions were sourced from prior studies. Heterogeneous methodologies were frequently used within a submission, with the inconsistent use of upper and lower anchors being prevalent. Assumptions behind measuring joint health state utilities or pooling multiple values for single health states were omitted in all submissions. Most national guidelines were rather vague regarding how to predict joint health states, how to select the best available value, how to maintain consistency within a submission, and how to generalize values obtained from prior studies. Previously-generated values were commonly sourced, but this practice was frequently related to inconsistencies within and among submissions. Attention should be paid to the consistency and transparency of the value, especially if the value is sourced from prior studies.

  3. Vibrations of twisted cantilevered plates - Summary of previous and current studies

    Leissa, A. W.; Macbain, J. C.; Kielb, R. E.


    This work summarizes a comprehensive study made of the free vibrations of twisted, cantilevered plates of rectangular planform. Numerous theoretical and experimental investigations previously made by others have resulted in frequency results which disagree considerably. To clarify the problem a joint industry/government/university research effort was initiated to obtain comprehensive theoretical and experimental results for models having useful ranges of aspect ratios, thickness ratios and twist angles. Theoretical data came from 19 independent computer analyses, including finite element, shell theory and beam theory idealizations. Two independent sets of experimental data were also obtained. The theoretical and experimental results are summarized and compared.

  4. Neonatal taurine and alanine modulate anxiety-like behavior and decelerate cortical spreading depression in rats previously suckled under different litter sizes.

    Francisco, Elian da Silva; Guedes, Rubem Carlos Araújo


    The amino acids taurine and alanine play a role in several physiological processes, including behavior and the electrical activity of the brain. In this study, we investigated the effect of treatment with taurine or alanine on anxiety-like behavior and the excitability-dependent phenomenon known as cortical spreading depression (CSD), using rats suckled in litters with 9 and 15 pups (groups L9 and L15). From postnatal days 7 to 27, the animals received per gavage 300 mg/kg/day of taurine or alanine or both. At 28 days, we tested the animals in the elevated plus maze, and at 33-35 days, we recorded CSD and analyzed its velocity of propagation, amplitude, and duration. Compared with water-treated controls, the L9 groups treated with taurine or alanine displayed anxiolytic behavior (higher number of entries in the open arms; p taurine, alanine, or both) treated at adulthood (90-110 days). The L15 condition resulted in smaller durations and higher CSD velocities compared with the L9 condition. Besides reinforcing previous evidence of behavioral modulation by taurine and alanine, our data are the first confirmation that treatment with these amino acids decelerates CSD regardless of lactation conditions (normal versus unfavorable lactation) or age at amino acid administration (young versus adult). The results suggest a modulating role for both amino acids on anxiety behavior and neuronal electrical activity.


    Gurpreet Kaur


    Full Text Available Previous caesarean section sparks an area of controversy in Obstetrics. The management of women with previous caesarean section regarding the mode of delivery whether to opt for repeat caesarean section or vaginal delivery, is an area of debate. Very often the decision on management is not made on Principle of sound reasoning and many who choose the elective repeat caesarean section do so to circumvent the anxious moment that arise during conduct ion of labour. AIMS AND OBJECTIVE: To determine the maternal and fetal outcome in relation to type of delivery . MATERIALS AND METHOD S: A 18 month prospective observational study was conducted where in 150 patients who had a term pregnancy with a history of prior LSCS were included after obtaining their consent for participation. The obstetric and fetal outcomes of these patients in the present pregnancy were analyzed by Z test. RESULTS: Out of the 150 subjects 78 ( 52% were in age group of 26 - 30 years, 106 ( 70.67% patients belonged to the urban population, 116 ( 77.33% were booked patie nts, 107 ( 71.33% were housewives, 122 ( 81.33% belonged to middle class and 22 ( 14.67% were from high socio economic status. 67 ( 44.67% were second gravid, 112 ( 74.67% were para 1. Out of total 134 patients 29 ( 21.64% had elective caesarean section and 5 ( 3 .73% patients came as emergency admission and underwent caesarean section. Out of 134 patients, with one previous caesarean section. 32 had spontaneous onset of labour. Out of which 20 ( 68.97% had vaginal delivery and 9 ( 31.03% had repeat caesarean section. 13 patients had augmentation, 11 ( 84.62% had vaginal delivery and 2 ( 15.38% had caesarean section. In 58 patients labour was induced 29 ( 50% had section. 14 patients out of 50 who had previous 2 caesarean section only 1 ( 7.69% patient had spontane ous onset of labour and had caesarean section. 3 ( 92.86% patients had elective caesarean section. There were only 2 patients with previous 3 caesarean

  6. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    Moreno Victor


    Full Text Available Abstract Background Colorectal cancer (CRC is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive, rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive, rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant, and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive. In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1

  7. A longitudinal study of plasma insulin and glucagon in women with previous gestational diabetes

    Damm, P; Kühl, C; Hornnes, P


    OBJECTIVE: To investigate whether plasma insulin or glucagon predicts later development of diabetes in women with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The subjects studied were 91 women with diet-treated GDM and 33 healthy women. Plasma insulin and glucagon during a 50......-g oral glucose tolerance test (OGTT) were measured during pregnancy, postpartum, and at follow-up 5-11 years later. At follow-up, the women were also examined with a 75-g OGTT or an intravenous glucagon test. RESULTS: Twenty-seven (30%) of the women with previous GDM had abnormal glucose tolerance...... response) at all time points investigated; this was also found when only nonobese glucose-tolerant women were examined. Low insulin secretion during pregnancy together with a high fasting plasma glucose level at the diagnostic OGTT in pregnancy and hyperglycemia during the postpartum OGTT were predictive...

  8. A study about the interest and previous contact of high school students with Astronomy

    Carvalho, C. L.; Zanitti, M. H. R.; Felicidade, B. L.; Gomes, A. D. T.; Dias, E. W.; Coelho, F. O.


    The currently problems in Astronomy teaching in Brazilian Basic Education contrast with the space, and the popularity that astronomical themes have in various media in the country. In this work, we present the results of a study about the interest, and previous contact of high school students from a public school in the city of "São João del-Rei"/MG with topics related to Astronomy. The study and the pedagogical intervention were carried out by students of the PIBID/CAPES/UFSJ. The intervention was performed through an oral exposition with the students' participation, followed by the use of the Stellarium program. The results suggest the majority of students surveyed are interested in Astronomy, and have had some contact with the area. However, some inconsistencies in their responses were identified and examined. The implications for research and for Astronomy Education are discussed. We also make some considerations about relationship between the lack of specific knowledge and the misinformation as one possible reason for the little interest of students in various areas of Science.

  9. Religious Identity in Iranian Society: A Systematic Review of Previous Studies (2001-2013


    literature on identity, evidence suggests that the role of religion in shaping individuals' and group's identity is widely ignored. However, a growing number of studies have begun to take into consideration the key role of religion (Arweck & Nesbitt 2010, King and Boyatzis 2004, Peek 2005. This article has attempted to review systematically previous research and conceptualizations on the religious identity based on national studies and surveys and academic dissertations.     Materials and Methods   As mentioned, the purpose of this study was to review the results of some influential researches in the field of religious identity. To get this purpose, one of the best known methods for reviewing previous studies, a systematic review, was applied. Systematic review deals with establishing and synthesizing of researches and evidences with focus on a specific question. This occurs through the organized, transparent, formal, clear and flexible procedures and processes. A systematic review of research is not limited to review the history and this overview and review can be used in different levels, fields and goals. During the first phase of the study, terms of "religious identity", "Islamic identity", "Iranian identity" and "religious identity" was searched at libraries and research centers and in databases such as Center for Scientific Information Database (SID, a database of Iranian journals and magazines (Magiran, Noor specialized journals database, and Science and Information Technology Institute (IrnaDoc. After reviewing the gathered documents and specifying its relationship with the object and purpose of the study, a total of 47 documents were selected. Documents based on the five major parameter were summarized and reviewed: 1-general information, 2-goals and research questions, 3-research methodology, 4-variables, 5-findings     Discussion of Results and Conclusion   Findings show that in the highest percentage (38.2% of researches, religious identity has been

  10. Phase II study of pegylated liposomal doxorubicin plus vinorelbine in breast cancer with previous anthracycline exposure.

    Martin, Miguel; García-Donas, Jesus; Casado, Antonio; de la Gándara, Isabel; Pérez-Segura, Pedro; García-Saenz, Jose-Angel; Ibáñez, Gabriel; Loboff, Belen; García-Ledo, Gemma; Moreno, Fernando; Grande, Enrique; Diaz-Rubio, Eduardo


    Thirty-five patients with metastatic breast cancer (MBC) entered a phase II study of pegylated liposomal doxorubicin 35 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 30 mg/m2 i.v. on day 1 every 4 weeks. Patients were required to have measurable disease, previous chemotherapy with an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Thirty-four patients were assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 35% (12 of 34; 95% CI, 20%-54%). One complete response and 11 partial responses were noted. In addition, 14 patients (41%) had stable disease of > 4 months duration, and 7 patients (20.5%) had disease progression. The response rates to the combination when it was used as first- and second-line chemotherapy were 31% (4 of 13) and 38% (8 of 21), respectively. Median time to disease progression was 7 months (range, 1-35 months) and median overall survival was 13 months (range, 2 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 44% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 6%) and mucositis (15%). Late alopecia was seen in 53% of patients (grade 1 in 41%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Three patients presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and 2 of these patients recovered normal values after cessation of therapy. The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population.

  11. The biomechanics of running in athletes with previous hamstring injury: A case-control study.

    Daly, C; Persson, U McCarthy; Twycross-Lewis, R; Woledge, R C; Morrissey, D


    Hamstring injury is prevalent with persistently high reinjury rates. We aim to inform hamstring rehabilitation by exploring the electromyographic and kinematic characteristics of running in athletes with previous hamstring injury. Nine elite male Gaelic games athletes who had returned to sport after hamstring injury and eight closely matched controls sprinted while lower limb kinematics and muscle activity of the previously injured biceps femoris, bilateral gluteus maximus, lumbar erector spinae, rectus femoris, and external oblique were recorded. Intergroup comparisons of muscle activation ratios and kinematics were performed. Previously injured athletes demonstrated significantly reduced biceps femoris muscle activation ratios with respect to ipsilateral gluteus maximus (maximum difference -12.5%, P = 0.03), ipsilateral erector spinae (maximum difference -12.5%, P = 0.01), ipsilateral external oblique (maximum difference -23%, P = 0.01), and contralateral rectus femoris (maximum difference -22%, P = 0.02) in the late swing phase. We also detected sagittal asymmetry in hip flexion (maximum 8°, P = 0.01), pelvic tilt (maximum 4°, P = 0.02), and medial rotation of the knee (maximum 6°, P = 0.03) effectively putting the hamstrings in a lengthened position just before heel strike. Previous hamstring injury is associated with altered biceps femoris associated muscle activity and potentially injurious kinematics. These deficits should be considered and addressed during rehabilitation.

  12. Rancidity inhibition study in frozen whole mackerel (scomber scombrus by a previous plant extract treatment.

    Aubourg, Santiago P.


    Full Text Available The effect of flaxseeds (Linum usitatissimum on rancidity development in frozen whole mackerel (Scomber scombrus was studied. For it, fresh mackerel were dipped in flaxseeds aqueous extract during 60 min, frozen at –80 ºC during 24 hours and kept frozen (–20 ºC up to 12 months. Sampling was carried out on the initial material and at months 1, 3, 5, 7, 9 and 12 of frozen storage at –20 ºC. A parallel experiment with non treated fish was carried out in the same conditions. Rancidity development was measured by several biochemical indices (free fatty acids, peroxides, conjugated dienes and trienes, secondary oxidation products and lipoxygenase activity and complemented by the sensory analysis (skin, flesh odour, consistency and flesh appearance. As a result of the previous antioxidant treatment, peroxides showed to breakdown faster (pSe ha estudiado el efecto del lino (Linum usitatissimum en el desarrollo de rancidez en caballa entera congelada (Scomber scombrus. Para ello, caballas frescas fueron sumergidas en extractos acuosos de semillas de lino durante 60 min, congeladas a -80 ºC durante 24 h y mantenidas congeladas ( -20 ºC durante 12 meses. Se tomaron muestras del material inicial y tras 1, 3, 5, 7, 9 y 12 meses de congelación a -20 ºC . Un experimento paralelo con pescado no tratado fue llevado acabo en las mismas condiciones. El desarrollo de la rancidez fue medido por varios índices bioquímicos (ácidos grasos libres, peróxidos, dienos y trienos conjugados, productos secundarios de oxidación y actividad lipoxigenasa y completado con análisis sensorial (piel, olor de la carne, consistencia y apariencia de la carne. Como resultado del tratamiento antioxidante, los peróxidos se degradaron más rápidos (p < 0.05 después del mes 7, y por tanto, contenidos mayores (p < 0.05 de dienos y trienos conjugados pudieron ser detectados en el pescado tratado. El tratamiento antioxidante también condujo a un

  13. Effects of a single high dose of Chlorpyrifos in long-term feeding, ethanol consumption and ethanol preference in male Wistar rats with a previous history of continued ethanol drinking.

    Carvajal, Francisca; Sanchez-Amate, Maria Del Carmen; Lerma-Cabrera, José Manuel; Cubero, Inmaculada


    Chlorpyrifos (CPF) is an organophosphate compound that is slowly delivered in the organism after subcutaneous injection, keeping acetylcholinesterase (AChE) activity mildly inhibited for weeks. We have previously reported reduced voluntary ethanol drinking 8 weeks post-CPF administration in Wistar rats when AChE activity was almost completely recovered. Additionally, the OPs disrupt the functioning of certain neurochemical systems and modify the formation and/or degradation of some neuropeptides with a known role in regulating voluntary consumption of alcohol. Moreover, chronic ethanol intake significantly alters the regional expression of some of these neurochemical systems. Thus, the present study explored whether a previous history with ethanol consumption modify the disturbance in the voluntary ethanol consumption induced by CPF administration. For this aim, we measured ethanol consumption in increasing concentrations (8%, 15% and 20% w/v) from 4 days to 8 weeks following a single dose of CPF. Two experiments were carried out; experiment 1 was conducted in ethanol-naïve rats and experiment 2, in animals with a previous history of ethanol drinking before CPF administration. Additionally, food and body weight measures were collected. We report here a significant increase in ethanol consumption and preference at high ethanol concentrations (15% and 20%) in CPF-treated animals with a previous history of ethanol consumption (experiment 1) and a long-lasting increase in food intake both in ethanol-exposed (experiment 1) and ethanol-naïve CPF-treated rats (experiment 2). Present data are discussed under the interesting idea that CPF targets neurobiological pathways critically involved with ethanol consumption. Additionally, we conclude that CPF effects on voluntary ethanol consumption are ethanol-experience dependent.

  14. Previous exercise training increases levels of PPAR-α in long-term post-myocardial infarction in rats, which is correlated with better inflammatory response

    Marília Harumi Higuchi Santos


    Full Text Available OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1 or 4 weeks (EI4 or SI4 of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%, without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35% and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82 in infarcted areas (both p=0.001. Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001 in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02, in contrast to SI4 (r=0.05, p=0.87. CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis

  15. Renal Function and Hemodynamic Study in Obese Zucker Rats

    Park, Sung Kwang; Kang, Sung Kyew


    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies w...

  16. Convergence in the Bilingual Lexicon: A Pre-registered Replication of Previous Studies

    White, Anne; Malt, Barbara C.; Storms, Gert


    Naming patterns of bilinguals have been found to converge and form a new intermediate language system from elements of both the bilinguals’ languages. This converged naming pattern differs from the monolingual naming patterns of both a bilingual’s languages. We conducted a pre-registered replication study of experiments addressing the question whether there is a convergence between a bilingual’s both lexicons. The replication used an enlarged set of stimuli of common household containers, providing generalizability, and more reliable representations of the semantic domain. Both an analysis at the group-level and at the individual level of the correlations between naming patterns reject the two-pattern hypothesis that poses that bilinguals use two monolingual-like naming patterns, one for each of their two languages. However, the results of the original study and the replication comply with the one-pattern hypothesis, which poses that bilinguals converge the naming patterns of their two languages and form a compromise. Since this convergence is only partial the naming pattern in bilinguals corresponds to a moderate version of the one-pattern hypothesis. These findings are further confirmed by a representation of the semantic domain in a multidimensional space and the finding of shorter distances between bilingual category centers than monolingual category centers in this multidimensional space both in the original and in the replication study. PMID:28167921

  17. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.

    Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P


    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at as #NCT01414205.




    Full Text Available With the world - wide rising trend of caesarean delivery (CD, modern obstetric practice deals with a new group of mothers carrying reproductive performance upon a scarred uterus with obvious risk in feto - maternal outcome. AIMS: (1 To analyse the maternal & neonatal outcome in post - caesarean pregnancy. (2 To evaluate the factors influencing outcome in such cases. Design : Observational analytical study. MATERIALS & METHODS: The present study was carried out over two years (2010 - 11 taking consecutive 100 p ost - caesarean cases as admitted on my admission days & delivered in BR Singh Hospital. Data collection was done by interview technique along with hospital records. ANALYSIS USED: Percentage analysis was most often done. Categorical variables were compared with chi - square test; P value was calculated with 2012 Graphpad Software. Relative risk (RR & Odd ratio (OR were calculated with 1993 - 2012 Medcalc Software bvba (Version 12.3.0. All statistical tests were evaluated at the 0.05 significance level. RESULT S: Post - caesarean pregnancy rate was 26.02%. Vaginal birth after caesarean (VBAC incidence was 22% whereas VBAC success on trial of labour was 55%. VBAC gave best morbidity outcome (18.18% & 27.27%. But failed VBAC cases result more significant maternal morbidity (RR=3.97, P=0.0037 & NICU admission was also found highest in failed VBAC cases (38.89%. Maternal and neonatal morbidity were significantly high when scar integrity was lost; also significantly co - related with elderly mothers (>35 yrs., un - boo ked cases & non - admitted cases undergone repeat CD. CONCLUSIONS: Post - caesarean cases need meticulous antenatal check - up & mandatory institutional delivery with proper selection of mode of confinement to have a better maternal & neonatal outcome

  19. Life cycle impact assessment of ammonia production in Algeria: A comparison with previous studies

    Makhlouf, Ali, E-mail:; Serradj, Tayeb; Cheniti, Hamza


    In this paper, a Life Cycle Analysis (LCA) from “cradle to gate” of one anhydrous ton of ammonia with a purity of 99% was achieved. Particularly, the energy and environmental performance of the product (ammonia) were evaluated. The eco-profile of the product and the share of each stage of the Life Cycle on the whole environmental impacts have been evaluated. The flows of material and energy for each phase of the life cycle were counted and the associated environmental problems were identified. Evaluation of the impact was achieved using GEMIS 4.7 software. The primary data collection was executed at the production installations located in Algeria (Annaba locality). The analysis was conducted according to the LCA standards ISO 14040 series. The results show that Cumulative Energy Requirement (CER) is of 51.945 × 10{sup 3} MJ/t of ammonia, which is higher than the global average. Global Warming Potential (GWP) is of 1.44 t CO{sub 2} eq/t of ammonia; this value is lower than the world average. Tropospheric ozone precursor and Acidification are also studied in this article, their values are: 549.3 × 10{sup −6} t NMVOC eq and 259.3 × 10{sup −6} t SO{sub 2} eq respectively.

  20. Experimental bluetongue virus infection of sheep; effect of previous vaccination: clinical and immunologic studies.

    Mahrt, C R; Osburn, B I


    Clinical and immunologic responses of sheep to vaccination and subsequent bluetongue virus (BTV) challenge exposure were studied and compared with those of non-vaccinated sheep. Sheep were vaccinated with inactivated BTV administered with aluminum hydroxide and cimetidine or levamisole. After sheep were vaccinated, precipitating group-specific antibodies to BTV were detected, but serotype-specific neutralizing antibodies were not detected. Cellular immune responses (lymphocyte blastogenesis) to BTV were not detected. After virulent BTV challenge exposure, vaccinated and nonvaccinated sheep developed acute clinical disease of similar severity. Clinical signs included hyperemia and petechiae of oral mucosa and coronary bands of the feet, excess salivation, nasal discharge with crusting, ulceration of the muzzle, and edema of lips and intermandibular space. Marked increases in serum creatine kinase activity were associated with stiff gait, reluctance to move, and vomiting. Fever and leukopenia were detected in most of the challenge-exposed sheep. Viremia and neutralizing antibodies were detected in vaccinated and nonvaccinated sheep after challenge exposure. Bluetongue virus-specific reaginic antibodies were not detected in sera from any of the sheep when the passive cutaneous anaphylaxis test was used.

  1. Phase III Randomized Study of Bendamustine Compared With Chlorambucil in Previously Untreated Patients With Chronic Lymphocytic Leukemia

    Wolfgang U. Knauf; Toshko Lissichkov; Ali Aldaoud; Anna Liberati; Javier Loscertales; Raoul Herbrecht; Gunnar Juliusson; Gerhard Postner; Liana Gercheva; Stefan Goranov; Martin Becker; Hans-Joerg Fricke; Francoise Huguet; Ilaria Del Giudice; Peter Klein; Lothar Tremmel; Karlheinz Merkle; Marco Montillo


    This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C...

  2. Multigeneration reproduction study of isomalt in rats.

    Waalkens-Berendsen, D H; Koëter, H B; Sinkeldam, E J


    The sugar replacer isomalt was fed to Wistar rats of both sexes throughout three successive generations at concentrations of 0, 2.5, 5 and 10% in the diet. A group of rats fed a diet containing 10% sucrose served as an additional control group. The initial mating was of 100 rats of each sex in each group. For subsequent matings 20 rats of each sex from each group were used. For each generation two litters were reared until they were at least 3 wk old. Feeding isomalt to rats for three successive generations did not induce any adverse effects on fertility, reproductive performance or development compared with control animals fed diets containing maize starch and sucrose instead of isomalt. The second litter of third-generation rats was given detailed gross and microscopic examinations 4 wk after weaning. A marked treatment-related change was an increase in the relative weight of the caecum (filled and empty), 4 wk after weaning in the second litter of third-generation rats fed 10% isomalt. There was also an increase in the relative weight of the filled caecum in males of the 5% isomalt group. These findings were not accompanied by diarrhoea or histological changes in the caecum. The results of the present study did not demonstrate any deleterious effects on the reproduction, maternal performance or development of rats fed isomalt at dietary levels of up to 10% over three successive generations.

  3. Effective Teaching and Learning Environments and Principal Self-Efficacy in Oklahoma: Replication of a Previous Study

    Berry, Kathryn


    The purpose of this study was to replicate a previous study by Smith et al. (2006) that explored principal self-efficacy beliefs for facilitating effective instructional environments at their schools. There has been limited research conducted on principal's self-efficacy, and the studies that have been completed on the topic have not been…

  4. Maternal and perinatal outcomes of delivery after a previous Cesarean section in Enugu, Southeast Nigeria: a prospective observational study.

    Ugwu, George O; Iyoke, Chukwuemeka A; Onah, Hyacinth E; Egwuatu, Vincent E; Ezugwu, Frank O


    Obstetricians in developing countries appear generally reluctant to conduct vaginal delivery in women with a previous Cesarean because of lack of adequate facilities for optimal fetomaternal monitoring. To describe delivery outcomes among women with one previous Cesarean section at a tertiary hospital in Southeast Nigeria. This was a prospective observational study to determine maternal and perinatal outcomes of attempted vaginal birth after Cesarean sections (VBAC) following one previous Cesarean section. Analysis was done with SPSS statistical software version 17.0 for Windows using descriptive and inferential statistics at 95% level of confidence. Two thousand six hundred and ten women delivered in the center during the study period, of whom 395 had one previous Cesarean section. A total of 370 women with one previous Cesarean section had nonrecurrent indications, of whom 355 consenting pregnant women with one previous Cesarean section were studied. A majority of the women (320/355, 90.1%) preferred to have vaginal delivery despite the one previous Cesarean section. However, only approximately 54% (190/355) were found suitable for trial of VBAC, out of whom 50% (95/190 had successful VBAC. Ninety-five women (50.0%) had failed attempt at VBAC and were delivered by emergency Cesarean section while 35 women (9.8%) had emergency Cesarean section for other obstetric indications (apart from failed VBAC). There was no case of uterine rupture or neonatal and maternal deaths recorded in any group. Apgar scores of less than 7 in the first minute were significantly more frequent amongst women who had vaginal delivery when compared to those who had elective repeat Cesarean section (P=0.03). Most women who had one previous Cesarean delivery chose to undergo trial of VBAC, although only about half were considered suitable for VBAC. The maternal and fetal outcomes of trial of VBAC in selected women with one previous Cesarean delivery for non-recurrent indications were good

  5. Estimating the effect of current, previous and never use of drugs in studies based on prescription registries

    Nielsen, Lars Hougaard; Løkkegaard, Ellen; Andreasen, Anne Helms;


    PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do not ca...... with Hazard Ratios ranging from 1.68 to 1.78 for current use compared to never use. CONCLUSIONS: The findings suggest that it is possible to estimate the effect of never, current and previous use of HT on breast cancer using prescription data.......PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do...... not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance...

  6. An fMRI study of neuronal activation in schizophrenia patients with and without previous cannabis use

    Else-Marie eLøberg


    Full Text Available Previous studies have mostly shown positive effects of cannabis use on cognition in patients with schizophrenia, which could reflect lower neurocognitive vulnerability. There are however no studies comparing whether such cognitive differences have neuronal correlates. Thus, the aim of the present study was to compare whether patients with previous cannabis use differ in brain activation from patients who has never used cannabis. The patients groups were compared on the ability to up-regulate an effort mode network during a cognitive task and down-regulate activation in the same network during a task-absent condition. Task-present and task-absent brain activation was measured by functional magnetic resonance neuroimaging (fMRI. Twenty-six patients with a DSM-IV and ICD-10 diagnosis of schizophrenia were grouped into a previous cannabis user group and a no-cannabis group. An auditory dichotic listening task with instructions of attention focus on either the right or left ear stimulus was used to tap verbal processing, attention and cognitive control, calculated as an aggregate score. When comparing the two groups, there were remaining activations in the task-present condition for the cannabis group, not seen in the no-cannabis group, while there was remaining activation in the task-absent condition for the no-cannabis group, not seen in the cannabis group. Thus, the patients with previous cannabis use showed increased activation in an effort mode network and decreased activation in the default mode network as compared to the no-cannabis group. It is concluded that the present study show some differences in brain activation to a cognitively challenging task between previous cannabis and no-cannabis schizophrenia patients.

  7. Factors Associated with Unfavorable Treatment Outcomes in New and Previously Treated TB Patients in Uzbekistan: A Five Year Countrywide Study.

    Jamshid Gadoev

    Full Text Available TB is one of the main health priorities in Uzbekistan and relatively high rates of unfavorable treatment outcomes have recently been reported. This requires closer analysis to explain the reasons and recommend interventions to improve the situation. Thus, by using countrywide data this study sought to determine trends in unfavorable outcomes (lost-to-follow-ups, deaths and treatment failures and describe their associations with socio-demographic and clinical factors.A countrywide retrospective cohort study of all new and previously treated TB patients registered in the National Tuberculosis programme between January 2006 and December 2010.Among 107,380 registered patients, 67% were adults, with smaller proportions of children (10%, adolescents (4% and elderly patients (19%. Sixty per cent were male, 66% lived in rural areas, 1% were HIV-infected and 1% had a history of imprisonment. Pulmonary TB (PTB was present in 77%, of which 43% were smear-positive and 53% were smear-negative. Overall, 83% of patients were successfully treated, 6% died, 6% were lost-to-follow-up, 3% failed treatment and 2% transferred out. Factors associated with death included being above 55 years of age, HIV-positive, sputum smear positive, previously treated, jobless and living in certain provinces. Factors associated with lost-to-follow-up were being male, previously treated, jobless, living in an urban area, and living in certain provinces. Having smear-positive PTB, being an adolescent, being urban population, being HIV-negative, previously treated, jobless and residing in particular provinces were associated with treatment failure.Overall, 83% treatment success rate was achieved. However, our study findings highlight the need to improve TB services for certain vulnerable groups and in specific areas of the country. They also emphasize the need to develop unified monitoring and evaluation tools for drug-susceptible and drug-resistant TB, and call for better TB

  8. Assessment of empathy in first-episode psychosis and meta-analytic comparison with previous studies in schizophrenia.

    Achim, Amelie M; Ouellet, Rosalie; Roy, Marc-André; Jackson, Philip L


    Empathy is a multidimensional construct that relies on affective and cognitive component processes. A few studies have reported impairments of both cognitive and affective empathy components in patients with schizophrenia. It is, however, not known whether these difficulties are already present at psychosis onset. The affective and cognitive components of empathy were thus assessed in 31 patients with first-episode psychosis (FEP) and 31 matched healthy controls using the Interpersonal Reactivity Index (IRI). Our results were then compared to previous studies of empathy in patients with more chronic schizophrenia via a meta-analysis. In addition, we also assessed the relationship between empathy ratings, Mentalizing performance and clinical symptoms. Contrary to what has been reported in people with more chronic schizophrenia, the IRI ratings did not significantly differ between FEP and controls in our study, though a trend was observed for the Personal distress scale. For the Perspective taking scale, our meta-analysis revealed a significantly lower effect size in this study with FEP patients relative to previous schizophrenia studies. In the FEP group, the IRI ratings were not related to positive, negative or general psychopathology symptoms, but a significant relationship emerged between the Liebowitz Social Anxiety Scale and Perspective taking (negative correlation). In addition, a significant positive correlation was observed between the Empathic concern subscale and our theory of mind task. This study supports the idea that the cognitive component of empathy is less affected in patients with first-episode psychosis relative to patients with more chronic schizophrenia, and the impairments reported in previous reports with more chronic populations should be interpreted in light of a possible deterioration of this cognitive skill. The findings also provide some insight into the relationship between empathy and clinical symptoms such as social anxiety.

  9. Psychotic illness in first-time mothers with no previous psychiatric hospitalizations: a population-based study.

    Unnur Valdimarsdóttir


    Full Text Available BACKGROUND: Psychotic illness following childbirth is a relatively rare but severe condition with unexplained etiology. The aim of this study was to investigate the impact of maternal background characteristics and obstetric factors on the risk of postpartum psychosis, specifically among mothers with no previous psychiatric hospitalizations. METHODS AND FINDINGS: We investigated incidence rates and potential maternal and obstetric risk factors of psychoses after childbirth in a national cohort of women who were first-time mothers from 1983 through 2000 (n = 745,596. Proportional hazard regression models were used to estimate relative risks of psychoses during and after the first 90 d postpartum, among mothers without any previous psychiatric hospitalization and among all mothers. Within 90 d after delivery, 892 women (1.2 per 1,000 births; 4.84 per 1,000 person-years were hospitalized due to psychoses and 436 of these (0.6 per 1,000 births; 2.38 per 1,000 person-years had not previously been hospitalized for any psychiatric disorder. During follow-up after the 90 d postpartum period, the corresponding incidence rates per 1,000 person-years were reduced to 0.65 for all women and 0.49 for women not previously hospitalized. During (but not after the first 90 d postpartum the risk of psychoses among women without any previous psychiatric hospitalization was independently affected by: maternal age (35 y or older versus 19 y or younger; hazard ratio 2.4, 95% confidence interval [CI] 1.2 to 4.7; high birth weight (> or = 4,500 g; hazard ratio 0.3, 95% CI 0.1 to 1.0; and diabetes (hazard ratio 0. CONCLUSIONS: The incidence of psychotic illness peaks immediately following a first childbirth, and almost 50% of the cases are women without any previous psychiatric hospitalization. High maternal age increases the risk while diabetes and high birth weight are associated with reduced risk of first-onset psychoses, distinctly during the postpartum period.

  10. A multicenter phase II study of irinotecan in patients with advanced colorectal cancer previously treated with 5-fluorouracil.

    Méndez, Miguel; Salut, Antonieta; García-Girón, Carlos; Navalon, Marta; Diz, Pilar; García López, Maria José; España, Pilar; de la Torre, Ascensión; Martínez del Prado, Purificación; Duarte, Isabel; Pujol, Eduardo; Arizcun, Alberto; Cruz, Juan Jesús


    This multicenter, open-label, phase II study was performed to assess the efficacy and toxicity of irinotecan 350 mg/m2 intravenously every 3 weeks in patients with advanced colorectal cancer (CRC) previously treated with 5-fluorouracil (5-FU). The study enrolled 115 patients and a total of 558 cycles (median, 6 per patient) were administered. The overall objective response rate on an intent-to-treat basis was 18% (with 1 complete response and 20 partial responses), whereas 42 patients (37%) showed stable disease. Median time to progression was 4.8 months and median survival was 13.6 months. Grade 3/4 toxicities included delayed diarrhea (19.1%), nausea/vomiting (10.4%), and neutropenia (8.7%). There were 2 toxic deaths, 1 from delayed diarrhea and 1 from hemorrhage and grade 4 mucositis. In conclusion, the present study confirms the antitumor efficacy of irinotecan monotherapy in patients with CRC pretreated with 5-FU.

  11. Outcomes of induction of labour in women with previous caesarean delivery: a retrospective cohort study using a population database.

    Sarah J Stock

    Full Text Available BACKGROUND: There is evidence that induction of labour (IOL around term reduces perinatal mortality and caesarean delivery rates when compared to expectant management of pregnancy (allowing the pregnancy to continue to await spontaneous labour or definitive indication for delivery. However, it is not clear whether IOL in women with a previous caesarean section confers the same benefits. The aim of this study was to describe outcomes of IOL at 39-41 weeks in women with one previous caesarean delivery and to compare outcomes of IOL or planned caesarean delivery to those of expectant management. METHODS AND FINDINGS: We performed a population-based retrospective cohort study of singleton births greater than 39 weeks gestation, in women with one previous caesarean delivery, in Scotland, UK 1981-2007 (n = 46,176. Outcomes included mode of delivery, perinatal mortality, neonatal unit admission, postpartum hemorrhage and uterine rupture. 40.1% (2,969/7,401 of women who underwent IOL 39-41 weeks were ultimately delivered by caesarean. When compared to expectant management IOL was associated with lower odds of caesarean delivery (adjusted odds ratio [AOR] after IOL at 39 weeks of 0.81 [95% CI 0.71-0.91]. There was no significant effect on the odds of perinatal mortality but greater odds of neonatal unit admission (AOR after IOL at 39 weeks of 1.29 [95% CI 1.08-1.55]. In contrast, when compared with expectant management, elective repeat caesarean delivery was associated with lower perinatal mortality (AOR after planned caesarean at 39 weeks of 0.23 [95% CI 0.07-0.75] and, depending on gestation, the same or lower neonatal unit admission (AOR after planned caesarean at 39 weeks of 0.98 [0.90-1.07] at 40 weeks of 1.08 [0.94-1.23] and at 41 weeks of 0.77 [0.60-1.00]. CONCLUSIONS: A more liberal policy of IOL in women with previous caesarean delivery may reduce repeat caesarean delivery, but increases the risks of neonatal complications.

  12. Birth outcome in women with previously treated breast cancer--a population-based cohort study from Sweden.

    Kristina Dalberg


    Full Text Available BACKGROUND: Data on birth outcome and offspring health after the appearance of breast cancer are limited. The aim of this study was to assess the risk of adverse birth outcomes in women previously treated for invasive breast cancer compared with the general population of mothers. METHODS AND FINDINGS: Of all 2,870,932 singleton births registered in the Swedish Medical Birth Registry during 1973-2002, 331 first births following breast cancer surgery--with a mean time to pregnancy of 37 mo (range 7-163--were identified using linkage with the Swedish Cancer Registry. Logistic regression analysis was used. The estimates were adjusted for maternal age, parity, and year of delivery. Odds ratios (ORs and 95% confidence intervals (CIs were used to estimate infant health and mortality, delivery complications, the risk of preterm birth, and the rates of instrumental delivery and cesarean section. The large majority of births from women previously treated for breast cancer had no adverse events. However, births by women exposed to breast cancer were associated with an increased risk of delivery complications (OR 1.5, 95% CI 1.2-1.9, cesarean section (OR 1.3, 95% CI 1.0-1.7, very preterm birth (<32 wk (OR 3.2, 95% CI 1.7-6.0, and low birth weight (<1500 g (OR 2.9, 95% CI 1.4-5.8. A tendency towards an increased risk of malformations among the infants was seen especially in the later time period (1988-2002 (OR 2.1, 95% CI 1.2-3.7. CONCLUSIONS: It is reassuring that births overall were without adverse events, but our findings indicate that pregnancies in previously treated breast cancer patients should possibly be regarded as higher risk pregnancies, with consequences for their surveillance and management.

  13. Does the previous diagnosis of arterial hypertension affect one´s daily life? Pró-Saúde Study

    Gilberto Senechal de Goffredo Filho


    Full Text Available In addition to damaging several target organs, arterial hypertension may negatively impact patients' activities of daily living. Biological and behavioral mechanisms underlying such limitations have yet to be clarified. The objectives of this study were to investigate whether having been previously told of a hypertension diagnosis is associated with the frequency and duration of temporary limitations in activities of daily living, and whether these relationships differ by gender, age, or socioeconomic position. We analyzed sectional data from 2,666 participants (56% women; 55% with high school or lower schooling at the baseline phase (1999 - 2001 of a longitudinal investigation of university employees in Rio de Janeiro, Brazil (Pró-Saúde Study, asking participants whether they had ever been diagnosed with hypertension by a health professional, if they had been unable to perform any activities of daily living due to a health problem in the previous 2 weeks, and for how many days that had occurred. Multinomial logistic regression models were fitted for the overall study population and for age, gender, educational level, and per capita household income strata. Associations between hypertension diagnosis and temporary limitations were not observed in the overall study population and in gender, education and income strata. However, there were higher odds of temporary limitations among participants aged 55 years old or more with hypertension diagnosis (adjusted OR = 9.5; 95%CI 1.5 - 58.6, regardless of blood pressure levels and use of antihypertensive medication. Elderly people may keep an attitude of higher vigilance regarding conditions or events potentially worsening their health status.

  14. Exposure to a predator scent induces chronic behavioral changes in rats previously exposed to low-level blast: Implications for the relationship of blast-related TBI to PTSD

    Georgina Perez-Garcia


    Full Text Available Blast-related mild traumatic brain injury (mTBI has been unfortunately common in veterans who served in the recent conflicts in Iraq and Afghanistan. The postconcussion syndrome associated with these mTBIs has frequently appeared in combination with post-traumatic stress disorder (PTSD. The presence of PTSD has complicated diagnosis since clinically PTSD and the postconcussion syndrome of mTBI have many overlapping symptoms. In particular establishing how much of the symptom complex can be attributed to the psychological trauma associated with PTSD in contrast to the physical injury of TBI has proven difficult. Indeed some have suggested that much of what is now being called blast-related postconcussion syndrome is better explained by PTSD. The relationship between the postconcussion syndrome of mTBI and PTSD is complex. Association of the two disorders might be viewed as additive effects of independent psychological and physical traumas suffered in a war zone. However we previously found that rats exposed to repetitive low-level blast exposure in the absence of a psychological stressor developed a variety of anxiety and PTSD-related behavioral traits that were present months following the last blast exposure. Here we show that a single predator scent challenge delivered 8 months after the last blast exposure induces chronic anxiety related changes in blast-exposed rats that are still present 45 days later. These observations suggest that in addition to independently inducing PTSD-related traits, blast exposure sensitizes the brain to react abnormally to a subsequent psychological stressor. These studies have implications for conceptualizing the relationship between blast-related mTBI and PTSD and suggest that blast-related mTBI in humans may predispose to the later development of PTSD in reaction to subsequent psychological stressors.

  15. Predicting DUI recidivism of male drunken driving: a prospective study of the impact of alcohol markers and previous drunken driving.

    Portman, M; Penttilä, A; Haukka, J; Eriksson, P; Alho, H; Kuoppasalmi, K


    The aim of the present study was to determine whether the alcohol biomarkers CDT, GGT, the biomarker gamma-CDT index and previous drunken driving contributed significantly to the prediction of DUI recidivism. The subjects consisted of two different samples of drivers, viz. drivers who were found to have a positive breath alcohol concentration during random breath testing surveys (n=237), and drunken drivers who were apprehended during ordinary police work (n=193). The drunken driving events were monitored using a data-base both retrospectively and prospectively. It was found that the biomarker index, gamma-CDT, emerged as a notable predictor of recidivism in the group of random breath tested drivers. Measurement of gamma-CDT and its impact on DUI recidivism has not to our knowledge been applied to random breath tested drivers before. The apprehended drunken drivers, on the other hand, did not show a significant relationship between gamma-CDT and DUI recidivism. However, in both groups of drivers it was found that a previous conviction for drunken driving strongly predicted DUI recidivism. More attention should be paid by both physicians and the police to the high risk of recidivism among those convicted of drunken driving.

  16. The suitability of XRF analysis for compositional classification of archaeological ceramic fabric: A comparison with a previous NAA study

    Padilla, R. [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear (CEADEN), Laboratorio de Analisis Quimico, Calle 30 no. 502, Playa, Ciudad Habana (Cuba)]. E-mail:; Espen, P. van [University of Antwerp (Belgium); Torres, P.P. Godo [Centro de Antropologia, Havana (Cuba)


    The main drawbacks of EDXRF techniques, restricting its more frequent use for the specific purpose of compositional analysis of archaeological ceramic fabric, have been the insufficient sensitivity to determine some important elements (like Cr, REE, among others), a somewhat worse precision and the inability to perform standard-less quantitative procedures in the absence of suitable certified reference materials (CRM) for ceramic fabric. This paper presents the advantages of combining two energy dispersive X-ray fluorescence methods for fast and non-destructive analysis of ceramic fabric with increased sensitivity. Selective polarized excitation using secondary targets (EDPXRF) and radioisotope excitation (R-XRF) using a {sup 241}Am source. The analytical performance of the methods was evaluated by analyzing several CRM of sediment type, and the fitness for the purpose of compositional classification was compared with that obtained by using Instrumental Neutron Activation Analysis in a previous study of Cuban aborigine pottery.

  17. Evaluation of questionnaire-based information on previous physical work loads. Stockholm MUSIC 1 Study Group. Musculoskeletal Intervention Center.

    Torgén, M; Winkel, J; Alfredsson, L; Kilbom, A


    The principal aim of the present study was to evaluate questionnaire-based information on past physical work loads (6-year recall). Effects of memory difficulties on reproducibility were evaluated for 82 subjects by comparing previously reported results on current work loads (test-retest procedure) with the same items recalled 6 years later. Validity was assessed by comparing self-reports in 1995, regarding work loads in 1989, with worksite measurements performed in 1989. Six-year reproducibility, calculated as weighted kappa coefficients (k(w)), varied between 0.36 and 0.86, with the highest values for proportion of the workday spent sitting and for perceived general exertion and the lowest values for trunk and neck flexion. The six-year reproducibility results were similar to previously reported test-retest results for these items; this finding indicates that memory difficulties was a minor problem. The validity of the questionnaire responses, expressed as rank correlations (r(s)) between the questionnaire responses and workplace measurements, varied between -0.16 and 0.78. The highest values were obtained for the items sitting and repetitive work, and the lowest and "unacceptable" values were for head rotation and neck flexion. Misclassification of exposure did not appear to be differential with regard to musculoskeletal symptom status, as judged by the calculated risk estimates. The validity of some of these self-administered questionnaire items appears sufficient for a crude assessment of physical work loads in the past in epidemiologic studies of the general population with predominantly low levels of exposure.

  18. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study.

    Le Page, Emmanuelle; Deburghgraeve, Véronique; Lester, Marie-Antoinette; Cardiet, Isabelle; Leray, Emmanuelle; Edan, Gilles


    Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1-10]. Mean age at alemtuzumab start was 40 years [26-49] for 8 Secondary Progressive (SP) and 30 years [26-35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (± 3) and 8.3 (± 4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2-30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1-7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1-4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave's disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX.


    STEEN, H; MEIJER, DKF; Merema, M.T.


    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation tri-n-butylmethylam

  20. [Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats].

    Nai, Gisele Alborghetti; de Oliveira, Mariliza Casanova; de Oliveira Tavares, Graziela; Pereira, Laís Fabrício Fonseca; Soares, Nádia Derli Salvador Lemes; Silva, Patrícia Gatti


    Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0mg/kg); group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (plocal anaesthetic groups (p=0.0001), but not between the negative control group and the local anaesthetic groups (p>0.05). No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  1. Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats

    Gisele Alborghetti Nai


    Full Text Available BACKGROUND AND OBJECTIVE: Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. METHODS: 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0 mg/kg; group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. RESULTS: The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (p 0.05. CONCLUSION: No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated.

  2. A phase I study of imatinib mesylate in combination with chlorambucil in previously treated chronic lymphocytic leukemia patients.

    Hebb, Jonathan; Assouline, Sarit; Rousseau, Caroline; Desjardins, Pierre; Caplan, Stephen; Egorin, Merrill J; Amrein, Lilian; Aloyz, Raquel; Panasci, Lawrence


    The tyrosine kinase inhibitor, imatinib, has the potential to indirectly inhibit DNA repair. This mechanism of action has been shown to mediate sensitization to chlorambucil in chronic lymphocytic leukemia (CLL). To evaluate this effect in vivo, we performed a phase I study of chlorambucil combined with imatinib in relapsed CLL patients. The three dose levels studied included imatinib at 300, 400, or 600 mg/day. Imatinib was given on days 1-10, and chlorambucil (8 mg/m(2) daily) was given on days 3-7 of a 28-day cycle (up to 6 cycles). Eleven patients participated in this study. Low-grade gastrointestinal toxicities were observed in a dose-dependent manner. Forty-five percent of patients responded (two unconfirmed CRs and three PRs). Two responding patients were fludarabine refractory. The in vitro IC(50) of chlorambucil alone or in the presence of 5 μM imatinib in CLL lymphocytes correlated with the decrease in lymphocyte counts on day 15. Imatinib plasma concentrations achieved in patients were in the range of those effective in in vitro sensitization studies. The combination of chlorambucil and imatinib in patients with previously treated CLL was well tolerated and showed evidence of clinical efficacy. Based on our results, we recommend the 400 mg daily dose of imatinib on days 1-10 with 8 mg/m(3) chlorambucil on days 3-7 every 28 days as the phase II dose. This represents the first clinical trial examining the potential synergy between a tyrosine kinase inhibitor and a conventional alkylating agent for the treatment of CLL.

  3. Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

    Griffis, L C; Twerdok, L E; Francke-Carroll, S; Biles, R W; Schroeder, R E; Bolte, H; Faust, H; Hall, W C; Rojko, J


    Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to

  4. A Two-Year Ecological Study of Norway Rats (Rattus norvegicus) in a Brazilian Urban Slum.

    Panti-May, Jesús A; Carvalho-Pereira, Ticiana S A; Serrano, Soledad; Pedra, Gabriel G; Taylor, Josh; Pertile, Arsinoê C; Minter, Amanda; Airam, Vladimir; Carvalho, Mayara; Júnior, Nivison N; Rodrigues, Gorete; Reis, Mitermayer G; Ko, Albert I; Childs, James E; Begon, Mike; Costa, Federico


    The Norway or brown rat (Rattus norvegicus) is among the most ubiquitous of rodents. However, the lack of studies describing Norway rat populations from tropical areas have limited our understanding regarding their demography and seasonal dynamics. In this study, we describe seasonal pattern in the abundance, reproductive parameters, and morphometrics of Norway rat populations in Salvador, Brazil. Rodents were trapped over four seasonal trapping periods (2013-2014) from three valleys. A total of 802 Norway rats were trapped over the course of the study over 7653 trap-nights. Norway rat abundance was high, but there was no significant differences between seasons. The reproductive parameters (e.g. frequency of pregnant and lactating females) did not show statistical differences between seasons. Female rats collected in the rainy season were heavier and older than females from the dry season. Salvador rats had a high incidence of pregnancy and birth rate (estimated birth rate of 79 young per year) compared to previous studies. The information generated is critical for the understanding of the ecology of Norway rat, the main reservoir of Leptospira in Salvador. However, future studies examining the effect of rodent control programs aimed at reducing populations, and determining rates of recovery, will further clarify our understanding of population dynamics.

  5. Patterns and Determinants of Treatment Seeking among Previously Untreated Psychotic Patients in Aceh Province, Indonesia: A Qualitative Study

    Marthoenis Marthoenis


    Full Text Available Immediate treatment of first-episode psychosis is essential in order to achieve a positive outcome. However, Indonesian psychiatric patients often delay accessing health services, the reason for which is not yet fully understood. The current study aimed to understand patterns of treatment seeking and to reveal determinants of the delay in accessing psychiatric care among first-time user psychotic patients. Qualitative interviews were conducted with sixteen family members who accompanied the patients to a psychiatric hospital. Many families expressed beliefs that mental illness appertains to village sickness and not hospital sickness; therefore, they usually take the patients to traditional or religious healers before taking them to a health professional. They also identified various factors that potentially delay accessing psychiatric treatment: low literacy and beliefs about the cause of the illness, stigmatisation, the role of extended family, financial problems, and long distance to the psychiatric hospital. On the other hand, the family mentioned various factors related to timely help seeking, including being a well-educated family, living closer to health facilities, previous experience of successful psychotic therapy, and having more positive symptoms of psychosis. The findings call for mental health awareness campaigns in the community.

  6. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia.

    Knauf, Wolfgang U; Lissichkov, Toshko; Aldaoud, Ali; Liberati, Anna; Loscertales, Javier; Herbrecht, Raoul; Juliusson, Gunnar; Postner, Gerhard; Gercheva, Liana; Goranov, Stefan; Becker, Martin; Fricke, Hans-Joerg; Huguet, Francoise; Del Giudice, Ilaria; Klein, Peter; Tremmel, Lothar; Merkle, Karlheinz; Montillo, Marco


    This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL). Patients (chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee. A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients. Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.

  7. Integrating Sonography Training Into Undergraduate Medical Education: A Study of the Previous Exposure of One Institution's Incoming Residents.

    Day, James; Davis, Joshua; Riesenberg, Lee Ann; Heil, Daniel; Berg, Katherine; Davis, Robyn; Berg, Dale


    Sonography is a crucial and versatile tool within the field of medicine. Recent advancements in technology have led to increased use of point-of-care sonography. We designed a survey to assess prior point-of-care sonography training among incoming interns at an academic teaching hospital. In 2012 and 2013, we surveyed incoming interns (n = 154 and 145, respectively) regarding point-of-care sonography training received during medical school. The survey questions included formal didactic sessions, bedside instruction, and the use of simulation technology. One-fourth (26.3% in 2012 and 23.4% in 2013) of responding interns reported having never done an ultrasound scan at the bedside. In 2012 and 2013, 55.0% and 55.6% of respondents reported never having done an ultrasound scan in a simulation center, respectively. Interns agreed that sonography education should be provided during medical school. On average, interns disagreed with the statement that sonography should be taught in residency only. There was no significant difference in the sex or general previous experience with sonography across both intern classes. Point-of-care sonography is inconsistently taught in medical school. The interns in our study also thought that sonography education should begin in medical school, and sonography should be taught by using simulation and at the bedside. © 2015 by the American Institute of Ultrasound in Medicine.

  8. Pilot Study of an Individualised Early Postpartum Intervention to Increase Physical Activity in Women with Previous Gestational Diabetes

    Harold David McIntyre


    Full Text Available Optimal strategies to prevent progression towards overt diabetes in women with recent gestational diabetes remain ill defined. We report a pilot study of a convenient, home based exercise program with telephone support, suited to the early post-partum period. Twenty eight women with recent gestational diabetes were enrolled at six weeks post-partum into a 12 week randomised controlled trial of Usual Care (n=13 versus Supported Care (individualised exercise program with regular telephone support; n=15. Baseline characteristics (Mean ± SD were: Age  33±4  years; Weight 80 ± 20 kg and Body Mass Index (BMI 30.0±9.7 kg/m2. The primary outcome, planned physical activity {Median (Range}, increased by 60 (0–540 mins/week in the SC group versus 0 (0–580 mins/week in the UC group (P=0.234. Walking was the predominant physical activity. Body weight, BMI, waist circumference, % body fat, fasting glucose and insulin did not change significantly over time in either group. This intervention designed to increase physical activity in post-partum women with previous gestational diabetes proved feasible. However, no measurable improvement in metabolic or biometric parameters was observed over a three month period.

  9. Risk factors and therapeutic coverage at 6 years in patients with previous myocardial infarction: the CASTUO study

    Félix-Redondo, Francisco Javier; Lozano Mera, Luis; Consuegra-Sánchez, Luciano; Giménez Sáez, Fernando; Garcipérez de Vargas, Francisco Javier; Castellano Vázquez, José María; Fernández-Bergés, Daniel


    Objectives To determine the degree of risk factor control, the clinical symptoms and the therapeutic management of patients with a history of previous myocardial infarction. Methods Cross-sectional study at 6 years of a first episode of acute myocardial infarction between 2000 and 2009, admitted at a hospital in the region of Extremadura (Spain). Of 2177 patients with this diagnosis, 1365 remained alive and therefore were included in the study. Results We conducted a person-to-person survey in 666 (48.8%) individuals and telephone survey in 437 (31.9%) individuals. The former are analysed. 130 were female (19.5%). The mean age was 67.4 years and the median time since the event was 5.8 (IQR 3.6–8.2) years. Active smokers made up 13.8%, low-density lipoprotein (LDL) cholesterol was ≥70 mg/dL: 82%, blood pressure ≥140/90 mm Hg (≥140/85 in diabetics): 49.8%, fasting glucose ≥126 mg/dL: 26%, heart rate 50–59 bpm: 60.7%, and obesity: 45.9%. Patients reported presenting angina comprised 22.4% and those with dyspnoea, 29.3%. Drug coverage was: 88.0% antiplatelet drugs, 86.5% statins, 75.6% β-blockers and 65.8% blockers of the renin-angiotensin system. Patients receiving all four types of drugs made up 41.9%, with only 3.0% having jointly controlled cholesterol, blood pressure, heart rate and glycaemia. Conclusions LDL cholesterol, heart rate and blood pressure were risk factors with less control. More than 1/5 of patients had angina and more than 1/4, dyspnoea. Risk factor control and the clinical condition were far from optimal, as was drug coverage, although to a lesser degree. PMID:27127637

  10. Renal Function and Hemodynamic Study in Obese Zucker Rats

    Park, Sung Kwang; Kang, Sung Kyew


    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies were performed in these rats. Results Functional studies showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese Zucker, 1.23±.07)ml/min; lean Zucker, 0.93±.03ml/min). Micropuncture studies revealed that the increase in GFR in obese Zucker rats was attributable to the increases in the single nephron plasma flow rate and glomerular transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was the same in both groups. Morphologic studies revealed that the increase in GFR in obese Zucker rats was associated with an increase in glomerular volume. Conclusions These results suggest that obesity and hyperinsulinemia, which are the characteristics of type II diabetes, can be associated with glomerular hyperfiltration and glomerular capillary hypertension. PMID:7626557

  11. Persistence of cardiovascular risk factors in women with previous preeclampsia: a long-term follow-up study.

    Aykas, Fatma; Solak, Yalcin; Erden, Abdulsamet; Bulut, Kadir; Dogan, Selcuk; Sarli, Bahadr; Acmaz, Gokhan; Afsar, Baris; Siriopol, Dimitrie; Covic, Adrian; Sharma, Shailendra; Johnson, Richard J; Kanbay, Mehmet


    Preeclampsia is a cardiovascular (CV) disease risk factor, and lifestyle modifications are recommended. It was suggested that preeclampsia may increase the prevalence of various CV disease risk factors such as metabolic syndrome, hypertension, insulin resistance, microalbuminuria, and endothelial dysfunction, among others. Here, we investigate the role of serum uric acid in preeclampsia in the development of CV complications. This was an observational case-control study that compared women with history of preeclampsia (n = 25) with age-matched controls with uncomplicated pregnancies (n = 20) who were followed for at least 5 years. Measurements included clinical and ambulatory blood pressure monitoring, ultrasound-measured flow-mediated dilatation (FMD), microalbuminuria, carotid intima-media thickness (CIMT) and serum uric acid, as well as clinical and demographic features. Cardiovascular disease risk factors were compared in women with and without previous preeclampsia. At the time of index gestation, preeclamptic women had higher serum uric acid values (4.36 ± 0.61 vs 2.27 ± 0.38 mg/dL, P preeclampsia were more likely to have hypertension and had higher serum uric acid levels, higher microalbuminuria and CIMT levels, and lower FMD values than did the patients who did not have preeclampsia. The 2 groups were similar with regard to various ambulatory blood pressure parameters. Univariate associates of FMD were history of preeclampsia and the current hypertension status. Microalbuminuria correlated with gestational uric acid levels (coefficient of correlation of 0.40, P = 0.01 for FMD and coefficient of correlation of 0.37, P = 0.01 for CIMT, respectively). Preeclampsia might be a risk factor for the development of cardiovascular risk factors at least 5 years after index pregnancy. Serum uric acid and microalbuminuria may be mechanistic mediators of heightened risk, along with impaired endothelial function in preeclampsia.

  12. Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year study evaluation.

    Derosa, Giuseppe; Ragonesi, Pietro Dario; Fogari, Elena; Cicero, Arrigo Francesco Giuseppe; Bianchi, Lucio; Bonaventura, Aldo; Romano, Davide; Maffioli, Pamela


    The aim of this study was to evaluate whether the positive effects of sitagliptin on glycemic control and insulin resistance were maintained also after 2 years of therapy and whether sitagliptin could be effective also in improving lipid profile. In this randomized, double-blind, placebo-controlled trial, 205 patients with type 2 diabetes in therapy with different antidiabetic drugs were randomized to add sitagliptin 100 mg once a day or placebo to their current therapy. We evaluated at the baseline and after 6, 12, 18, and 24 months the following parameters: body mass index, glycated hemoglobin (HbA1c ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg). Sitagliptin, added to previously taken antidiabetic agents, proved to be effective in improving glycemic profile, reducing HbA1c by -17.5%, FPG by -12.7%, PPG by -20.5%. Regarding insulin resistance, sitagliptin decreased FPI by -8.3% and HOMA-IR by -20.0%, confirming that what have been already reported in short-term studies can be applied also after 2 years of treatment. Sitagliptin also reduced body weight by -4.3%. Our study also showed the positive effect of sitagliptin on lipid profile; in particular, sitagliptin decreased TC by -13.3%, LDL-C by -20.4%, and Tg by -32.3%, and also increased HDL-C by + 13.6%. Sitagliptin proved to be effective on glycemic profile and insulin resistance even after 2 years of therapy and to be effective in improving body weight and lipid profile. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  13. Central Arctic atmospheric summer conditions during the Arctic Summer Cloud Ocean Study (ASCOS: contrasting to previous expeditions

    M. Tjernström


    Full Text Available Understanding the rapidly changing climate in the Arctic is limited by a lack of understanding of underlying strong feedback mechanisms that are specific to the Arctic. Progress in this field can only be obtained by process-level observations; this is the motivation for intensive ice-breaker-based campaigns such as that described in this paper: the Arctic Summer Cloud-Ocean Study (ASCOS. However, detailed field observations also have to be put in the context of the larger-scale meteorology, and short field campaigns have to be analysed within the context of the underlying climate state and temporal anomalies from this.

    To aid in the analysis of other parameters or processes observed during this campaign, this paper provides an overview of the synoptic-scale meteorology and its climatic anomaly during the ASCOS field deployment. It also provides a statistical analysis of key features during the campaign, such as some key meteorological variables, the vertical structure of the lower troposphere and clouds, and energy fluxes at the surface. In order to assess the representativity of the ASCOS results, we also compare these features to similar observations obtained during three earlier summer experiments in the Arctic Ocean, the AOE-96, SHEBA and AOE-2001 expeditions.

    We find that these expeditions share many key features of the summertime lower troposphere. Taking ASCOS and the previous expeditions together, a common picture emerges with a large amount of low-level cloud in a well-mixed shallow boundary layer, capped by a weak to moderately strong inversion where moisture, and sometimes also cloud top, penetrate into the lower parts of the inversion. Much of the boundary-layer mixing is due to cloud-top cooling and subsequent buoyant overturning of the cloud. The cloud layer may, or may not, be connected with surface processes depending on the depths of the cloud and surface-based boundary layers and on the relative strengths of

  14. Discussion on further studies to measure and evaluate fitness and motor performance for preschool children; summary and previous studies in Japan and future consideratin

    Murase, Tomohiko; Demura, Shinichi


    This article discusses and summarizes previous studies dealing with fitness and motor performance in preschool children from the viewpoint of measurement and evaluation, and determines topics for further studies. The studies reviewed in this article were mainly published in the “Japan Journal of Physical Education, Health and Sport Sciences” (edited by the Japan Society of Physical Education, Health and Sport Sciences), and the “Japanese Journal of Physical Fitness and Sports Medicine” (edite...

  15. Two-year carcinogenicity study of acrylamide in Wistar Han rats with in utero exposure.

    Maronpot, R R; Thoolen, R J M M; Hansen, B


    Acrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a 'probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin.

  16. Methylphenidate (Ritalin): behavioral studies in the rat.

    Askenasy, Erik P; Taber, Katherine H; Yang, Pamela B; Dafny, Nachum


    Attention Deficit Hyperactivity Disorder (ADHD) is a neuropsychiatric syndrome with an onset in childhood characterized by an inability to remain focused or to concentrate for prolonged periods of time. Children suffering from this disease are many times described as either inattentive or as hyperactive-impulsive depending on what form of the disease they manifest. Methylphenidate is the preferred treatment for this behavioral disorder and is used for long term disease management. Much still remains unknown concerning this stimulant and its effects on behavior and future abuse potential are pertinent questions. Since animal models are used to study the mechanism of drug action and rats are used often in drug studies, the objective of this review is to summarize the research reports that mainly have used rats as the model to investigate the action of methylphenidate. Topics discussed in this review include: (1) What effect does a single dose of methylphenidate have on locomotion activity; (2) Does repeated administration of methylphenidate result in tolerance or sensitization; and (3) Does methylphenidate have rewarding properties as measured by the self-administration and condition placed preference paradigms.

  17. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma.

    Kumar, Shaji; Flinn, Ian; Richardson, Paul G; Hari, Parameswaran; Callander, Natalie; Noga, Stephen J; Stewart, A Keith; Turturro, Francesco; Rifkin, Robert; Wolf, Jeffrey; Estevam, Jose; Mulligan, George; Shi, Hongliang; Webb, Iain J; Rajkumar, S Vincent


    Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms)≥very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at (NCT00507442).

  18. Respective Role of the Dorsal Hippocampus and the Entorhinal Cortex during the Recombination of Previously Learned Olfactory-Tactile Associations in the Rat

    Boisselier, Lise; Ferry, Barbara; Gervais, Rémi


    The hippocampal formation has been extensively described as a key component for object recognition in conjunction with place and context. The present study aimed at describing neural mechanisms in the hippocampal formation that support olfactory-tactile (OT) object discrimination in a task where space and context were not taken into account. The…

  19. Studies of aluminum in rat brain

    Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.


    The effects of high aluminum concentrations in rat brains were studied using /sup 14/C autoradiography to measure the uptake of /sup 14/C 2-deoxy-D-glucose (/sup 14/C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The /sup 14/C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of /sup 14/C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10/sup 9/ Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab.

  20. Chronic study on BHT in rats

    Würtzen, G.; Olsen, P.


    Groups of 40, 29, 39 and 44 F0 rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated, and groups of 100, 80, 80 and 100 F1 rats of each sex were...... formed. After weaning, the highest dose of BHT was lowered to 250 mg/kg/day for the F1 rats. At weaning the BHT-treated F1 rats, especially the males, had lower body weights than the controls and the effect was dose related. The survival of the BHT-treated rats of both sexes was higher than...

  1. Patient acceptance and clinical impact of Bravo monitoring in patients with previous failed catheter-based studies.

    Sweis, R; Fox, M; Anggiansah, R; Anggiansah, A; Basavaraju, K; Canavan, R; Wong, T


    Standard pH monitoring is performed over 24 h with a naso-oesophageal catheter (C-pH). Limitations include naso-pharyngeal discomfort, nausea and social embarrassment resulting in reduced reflux-provoking activities. Recently a catheter-free pH-monitoring technique has become available. The tolerability and diagnostic yield of this system in patients who failed standard monitoring remain unknown. To examine the tolerability and diagnostic outcome of catheter-free pH-monitoring technique in patients who failed standard monitoring. Patients referred for C-pH and catheter-free pH monitoring completed a tolerability questionnaire. Acid exposure in the distal oesophagus and symptom index (SI) were reviewed. Over 4 years, 883/1751 (50%) of patients with typical reflux symptoms referred for C-pH were diagnosed with gastro-oesophageal reflux disease (GERD) based on a pathological percentage time acid exposure (%time pH patients failed C-pH and, of these, 129 successfully completed 2-day catheter-free pH monitoring. Ninety-eight (76%) of these patients had a pathological percentage pH patients (P patients who had previously failed C-pH; catheter-free pH monitoring assists the definitive diagnosis of GERD in this group.

  2. A Study of the Relationship between Previous Exposure to Education and Practice-Teaching Performance at the University of Ife.

    Olatunji, S. A.


    A study to identify relationships between the amount of exposure students have to education (as a discipline) and their student teaching performances is reported. Students attending the University of Ife from 1973-1976 were studied. A positive relationship was discovered, but other factors need to be researched further. (MLW)

  3. Reproducibility discrepancies following reanalysis of raw data for a previously published study on diisononyl phthalate (DINP in rats

    Min Chen


    Full Text Available A 2011 publication by Boberg et al. entitled “Reproductive and behavioral effects of diisononyl phthalate (DINP in perinatally exposed rats” [1] reported statistically significant changes in sperm parameters, testicular histopathology, anogenital distance and retained nipples in developing males. Using the statistical methods as reported by Boberg et al. (2011 [1], we reanalyzed the publically available raw data ([dataset] US EPA (United States Environmental Protection Agency, 2016 [2]. The output of our reanalysis and the discordances with the data as published in Boberg et al. (2011 [1] are highlighted herein. Further discussion of the basis for the replication discordances and the insufficiency of the Boberg et al. (2011 [1] response to address them can be found in a companion letter of correspondence (doi: 10.1016/j.reprotox.2017.03.013.; (Morfeld et al., 2011 [3].

  4. Marine fouling community in the Eastern harbour of Alexandria, Egypt compared with four decades of previous studies



    Full Text Available The aim of the present study is to compare the fouling communities between the years 1960 and 1999 in the Eastern harbour of Alexandria, Egypt and to study the main factors that may be controlling these communities. This comparison is based on monthly durations of panel immersion. By using roughened white polystyrene test panels (12.5x12.5 cm, monthly samples of marine fouling were collected from the harbour from October 1998 through September 1999. It is clear that a remarkable variation in number and diversity of fouling communities throughout the last four decades is evident. The minimum diversities were recorded during the studies of 1960 and 1970 (19 and 20 species respectively, while the maximum diversity (35 species was achieved during the 1991 study. Moreover, a small shift among the four dominant groups (Polychaeta, Cirripedia, Bryozoa and Amphipoda was noted during the four decades of the studies. The present comparison indicated that many factors may contribute to this variation, of which nutrient enrichment is the most important and the nature of the applied test panel is lees so.

  5. Biokinetic study of radionuclides in rats after feeding a chitosan diet

    Nishimura, Y.; Kim, H.S.; Watanabe, Y.; Yukawa, M.; Imai, K.; Watari, K. [National Inst. of Radiological Sciences, Chiba (Japan); Yan, A.; Inaba, J.


    Chitosan is derived from chitin, which is a cellulose-like biopolymer distributed widely in nature, especially in crustaceans, insects, fungi and yeast. Chitin and chitosan are known to be one of the naturals chelating agents. We already reported that the whole-body retention of orally administered {sup 85}Sr in rats decreased remarkably after feeding a chitosan diet when comparing them with controls. The present study was to investigate whether chitosan can be applied to the animal and human bodies in order to reduce the bioavailability of radionuclides in food. Wistar strain male rats were used in this experiment. These rats were fed with different diets in order to observe the removal of ingested radio-iron and zinc by chitosan. The whole-body retention of radio-iron was slightly lower in the 5%-chitosan diet group than non-chitosan diet group. In tissue distribution study, rats were sacrificed 14 days after administration. The relative concentration of iron in the blood and spleen was found to be lower in the 5%-chitosan diet group. The whole-body retention of {sup 65}Zn decreased sharply in the rats given 3% phytate water in advance of {sup 65}Zn administration when compared with the control rats. The rats given 5% chitosan and 1% phytate water also showed a significant reduction in radio-zinc. However, 5% chitosan diet on it's own did not have a significant effect on accelerating the removal of radio-zinc in the rats. Previous studies have shown that the administration of 1% phytate water is also not effective in reducing radio-zinc in rats. These results suggest that the effectiveness of phytate and chitosan in reducing the bioavailability of radio-zinc depend on their concentration. (author)

  6. A cross-sectional study of personality traits in women previously treated or untreated for alcohol use disorders

    Sundh Valter


    Full Text Available Abstract Background A better understanding of the relationship between treatment-seeking for alcohol problems and personality traits could give useful insight in factors promoting or hindering treatment for alcohol use disorders (AUD. The aim of this study was to analyze the associations between treatment-seeking for AUD, personality traits, and psychiatric co-morbidity in women. The study was based on pooled cross-sectional data from three population based samples and one clinical sample (n = 1,339. Comparisons were made between treated and untreated women with AUD, and between those with resolved and unresolved AUD. Results A stepwise logistic regression model showed that treatment-seeking for AUD was not associated with personality traits. Among women with lifetime AUD (n = 217, those who had been treated (n = 42 had significantly higher scores than untreated women (n = 175 on three personality traits of the Karolinska Scales of Personality (KSP; somatic anxiety, muscular tension, and guilt. Women with resolved AUD, who had received treatment (n = 23 had significantly higher scores on scales measuring somatic anxiety, psychic anxiety, muscular tension, irritability, and guilt than untreated women with resolved AUD. The latter group resembled women without AUD on most personality traits. There were no differences in occurrence of lifetime psychiatric disorders between the treated and the untreated women, whereas treated women with current AUD had increased risk of lifetime anxiety (OR: 3.1, 95% CI: 1.1–8.7. Conclusion Treatment-seeking was not associated with personality traits in this study. Still, it can be concluded that women with resolved AUD who had received treatment had high scores on the KSP-scales measuring psychic and somatic anxiety, tension, irritability, and feelings of guilt. This suggests that personality assessment might be a useful tool in tailoring individual treatment programs for women with AUD. Future studies need to

  7. Chemical Processes with Supercritical CO2 in Engineered Geologic Systems: Significance, Previous Study, and Path Forward (Invited)

    Xu, T.; Pruess, K.


    Chemical reactions with dissolved CO2 in the aqueous phase have long been considered in fundamental geosciences and practical applications. Recently, studies on geologic carbon sequestration and enhanced geothermal systems using CO2 as heat transmission fluid have brought new interests in chemical reaction processes directly with supercritical CO2 (scCO2, or gas phase). In the vicinity of a CO2 injection well, the aqueous fluid initially present in a geological formation would be quickly removed by dissolution (evaporation) into the flowing gas stream and by immiscible displacement by the scCO2, creating a gas phase dominant zone. In this zone, the water evaporation could cause formation dry-out and precipitation of salt near the injection well, reducing formation porosity, permeability, and injectivity. The scCO2 may directly attack well construction materials such as cement. Over time, the gas phase will tend to migrate upwards towards the caprock because the density of the scCO2 is lower than that of the aqueous phase. In the upper portions of the reservoir, the scCO2 will directly react with caprock minerals and alter the hydrological properties and mechanical strength. On the other hand, the scCO2 phase will maintain the dissolution into the aqueous phase, lowering pH, inducing mineral dissolution, complexing with dissolved cations, increasing CO2 solubility, increasing the density of the aqueous phase, and promoting “convective mixing”. Chemical processes are quite different in the scCO2 dominant geologic systems. The absence of an aqueous phase poses unique questions, as little is presently known about the chemistry of non-aqueous systems. Additional issues arise from the reactivity of water that is dissolved in the ScCO2 phase. In this presentation, the author will discuss the importance, state of the studies performed, and future research directions.

  8. Warfarin dosing after bariatric surgery: a retrospective study of 10 patients previously stable on chronic warfarin therapy.

    Schullo-Feulner, A M; Stoecker, Z; Brown, G A; Schneider, J; Jones, T A; Burnett, B


    Many changes associated with bariatric surgery have the potential to affect warfarin dosing; yet current literature includes little data describing this phenomenon. Investigating this relationship may allow for determination of post-bariatric surgery warfarin dosing using stable pre-operative dosing levels. A retrospective chart review was completed for 10 patients stabilized on chronic warfarin therapy who underwent bariatric surgery. Data collection consisted of the following: warfarin requirement in mg/week, time in target range (TTR), creatinine, liver function, diarrhoea, medication changes, diet, and signs of bleeding and/or thrombosis. Three study patients underwent laparoscopic adjustable gastric banding procedures and seven patients underwent Roux-en-Y gastric bypass. The average (standard deviation) weekly warfarin dose required in the immediate post-operative interval was 64% (25%) of baseline dosing, corresponding to a TTR of 48%. At 6 months, patients required 85% (19%) of baseline weekly dosing, with TTR of 53.4%. At 1 year, dosing was 90% (16%) of baseline with TTR of 63.5%. Patients underwent medication changes as well as transient bouts of diarrhoea. Two patients suffered unspecified haemorrhages of the gastrointestinal tract (international normalized ratio [INR] = 2.3 and 9.8). This patient set demonstrated an initial drop in warfarin requirement, followed by escalating dosing trends that became more predictable as patients were farther out from procedure.


    Kevin M. Kostelnik; James H. Clarke; Jerry L. Harbour


    Environmental remediation efforts that are underway at hundreds of contaminated sites in the United States will not be able to remediate large portions of those sites to conditions that would permit unrestricted access. Rather, large volumes of waste materials, contaminated soils and cleanup residuals will have to be isolated either in place or in new, often on-site, disposal cells with long term monitoring, maintenance and institutional control needs. The challenge continues to be to provide engineering systems and controls that can ensure the protection of public health and the environment over very long time horizons (hundreds to perhaps thousands of years) with minimal intervention. Effective long term management of legacy hazardous and nuclear waste requires an integrated approach that addresses both the engineered containment and control system itself and the institutional controls and other responsibilities that are needed. Decisions concerning system design, monitoring and maintenance, and the institutional controls that will be employed are best done through a "risk-nformed, performance-based" approach. Such an approach should incorporate an analysis of potential "failure" modes and consequences for all important system features, together with lessons learned from experience with systems already in place. The authors will present the preliminary results of a case study approach that included several sites where contamination isolation systems including institutional controls have been implemented. The results are being used together with failure trees and logic diagrams that have been developed for both the engineered barriers and the institutional controls. The use of these analytical tools to evaluate the potential for different levels of failure and associated consequences will be discussed. Of special interest is the robustness of different approaches to providing long-term protection through redundancy and defense in depth.

  10. Variations of the accessory nerve: anatomical study including previously undocumented findings-expanding our misunderstanding of this nerve.

    Tubbs, R Shane; Ajayi, Olaide O; Fries, Fabian N; Spinner, Robert J; Oskouian, Rod J


    The anatomy of the accessory nerve has been well described but continued new clinical and anatomical findings exemplify our lack of a full understanding of the course of this nerve. Therefore, this study aimed to expand on our knowledge of the course of the 11th cranial nerve via anatomical dissections. Fifty-six cadavers (112 sides) underwent dissection of the accessory nerve from its cranial and spinal origins to its emergence into the posterior cervical triangle. Immunohistochemistry was performed when appropriate. Our findings included two cases (1.8%) where the nerve was duplicated, one intracranially and one extracranially. One accessory nerve (0.9%) was found to enter its own dural compartment within the jugular foramen. The majority of sides (80%) were found to have a cranial root of the accessory nerve. Thirty-one sides (28%) had connections to cervical dorsal roots medially and three sides (2.7%) laterally. Medial connections were most common with the C1 nerve. Medial components of these dorsal root connections were all sensory in nature. However, lateral components were motor on two sides (1.8%). Nerves traveled anterior to the internal jugular vein on 88% of sides. One (0.9%) left side nerve joined an interneural anastomosis between the dorsal rootlets. Macroganglia were found on the spinal part of the intracranial nerve on 13% of sides. The lesser occipital nerve arose directly from the accessory nerve on two sides (1.8%) and communicated with the accessory nerve on 5.4% of sides. One side (0.9%) was found to communicate with the facial nerve with both nerves innervating the sternocleidomastoid muscle. Additional anatomical knowledge of the variants of the accessory nerve may benefit patient care when this nerve is pathologically involved.

  11. Cardiac Muscle Studies with Rat Ventricular Strips

    Whitten, Bert K.; Faleschini, Richard J.


    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  12. Missing osteoconductive effect of a resorbable PEO/PBT copolymer in human bone defects: a clinically relevant pilot study with contrary results to previous animal studies.

    Roessler, M; Wilke, A; Griss, P; Kienapfel, H


    PEO/PBT 70/30 (POLYACTIVE(R) 70/30), a degradable porous copolymer with elastic properties, was found to be osteoconductive in many animal studies. The aim of this study was to determine the osteoconductive effect in a human paired control iliac defect model. In seven patients undergoing anterior spinal interbody fusion surgery, two bicortical iliac defects for autograft harvesting were created. The defect size was identical for both defects measuring about 40 x 15 mm (group I). One defect was filled with the degradable implants, whereas the remaining one was left untreated as a control. The defect site for treatment was chosen randomly. In three further patients, only one defect measuring about 40 x 35 mm was created (group II). All patients were examined clinically and radiologically by spiral-CT after 1, 6, 12, 24, and 52 weeks. Three-dimensional reconstructions as well as CT-volumetric measurements using 1 mm sections were used as evaluation methods. In group I, a two-tailed paired t-test showed that the treated defects had significantly less formation of new bone than the untreated ones (p < 0.05 after 12 weeks, p < 0.01 after 52 weeks). Also, in group II, not much bone ingrowth could be observed. The histological evaluation of one patient in group I revealed no bone within the pores, and a fibrous layer between bone and implant was always present. Therefore, PEO/PBT 70/30 cannot be recommended as a bone substitute for clinical use. Differences in bone regeneration between humans and certain animal species as well as inapplicable defect models in previous animal studies are discussed as possible reasons for the failure.

  13. Quantifying the influence of previously burned areas on suppression effectiveness and avoided exposure: A case study of the Las Conchas Fire

    Matthew P. Thompson; Patrick Freeborn; Jon D. Rieck; Dave Calkin; Julie W. Gilbertson-Day; Mark A. Cochrane; Michael S. Hand


    We present a case study of the Las Conchas Fire (2011) to explore the role of previously burned areas (wildfires and prescribed fires) on suppression effectiveness and avoided exposure. Methodological innovations include characterisation of the joint dynamics of fire growth and suppression activities, development of a fire line effectiveness framework, and...

  14. Study of some physical aspects previous to design of an exponential experiment; Estudio de algunos aspectos fisicos previos al diseno de una experiencia exponencial

    Caro, R.; Francisco, J. L. de


    This report presents the theoretical study of some physical aspects previous to the design of an exponential facility. The are: Fast and slow flux distribution in the multiplicative medium and in the thermal column, slowing down in the thermal column, geometrical distribution and minimum needed intensity of sources access channels and perturbations produced by possible variations in its position and intensity. (Author) 4 refs.

  15. Phase II study of reintroduction of oxaliplatin for advanced colorectal cancer in patients previously treated with oxaliplatin and irinotecan: RE-OPEN study

    Suenaga M


    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Toshiharu Yamaguchi21Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, JapanBackground: The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin. Methods: Eligible patients had received prior chemotherapy including oxaliplatin and irinotecan that achieved a response or stable disease followed by confirmed disease progression ≥6 months previously during prior oxaliplatin-based therapy. The primary endpoint was the disease control rate (DCR after 12 weeks of treatment starting. The DCR was defined as the sum of patients with complete response, partial response, and stable disease. Results: Thirty-three patients were enrolled. The median age was 62 (range: 35–77 years and the male/female ratio was 19/14. Eastern Cooperative Oncology Group performance status was 0 in 84.8%. Fourteen primary tumors were in the colon and 19 were in the rectum. All patients received modified FOLFOX6 as the protocol treatment. After 12 weeks of treatment starting, the DCR was 39.4% (95% confidence interval 21.8–57.0 and the response rate (complete response and partial response was 6.1%. The median number of chemotherapy cycles was five and the median total dose of oxaliplatin was 425 mg/m2. Median progression-free survival time was 98 days and median overall survival was 300 days. The incidence of grade ≥1 and grade ≥3 allergic reactions was 28.1% and 3.1%, respectively. The incidence of grade ≥1 and grade ≥3 peripheral sensory neuropathy was 53.1% and 0%, respectively. There were no other severe adverse events and no treatment

  16. Tomografia computadorizada na avaliação da distribuição do tecido adiposo abdominal de ratos alimentados com rações hiperlipídicas após desnutrição neonatal Computed tomography in the evaluation of abdominal fat distribution associated with a hyperlipidic diet in previously undernourished rats

    Carlos Alberto Soares da Costa


    Full Text Available OBJETIVO: Descrever repercussões da ração suplementada com óleo de soja ou óleo de canola, por meio da tomografia computadorizada, na distribuição do tecido adiposo abdominal, após desmame de ratos desnutridos durante a lactação. MATERIAIS E MÉTODOS: Ratas lactantes submetidas a restrição alimentar (RA em 50%, de acordo com o consumo das lactantes controles (C. Após o desmame, filhotes desnutridos receberam ração contendo 19% de óleo de soja (RA-soja 19% ou óleo de canola (RA-canola 19%. Os filhotes do grupo controle receberam ração contendo 7% de óleo de soja (C-soja 7%. Aos 60 dias de idade, foram realizadas medidas corporais e das áreas de tecido adiposo abdominal por meio de tomografia computadorizada. Após sacrifício, tecido adiposo abdominal foi excisado e pesado. Os dados foram expressos como média ± erro-padrão da média, considerando o nível de significância de p OBJECTIVE: To study, by means of computed tomography, the repercussion of post-weaning dietary supplementation with soy oil or canola oil on the abdominal fat distribution in previously undernourished rats. MATERIALS AND METHODS: Dams submitted to 50% food restriction (FR compared with dams receiving a standard diet (C. After weaning, undernourished rats received a diet supplemented with 19% soy oil (19% FR-soy or 19% canola oil (19% FR-canola. Rats in the control group received a diet with 7% soy oil (7% C-soy until the end of the experimental period. At the age of 60 days old, the rats were submitted to computed tomography for evaluation of total abdominal and visceral fat area. The rats' length and body mass were evaluated and, after their sacrifice, the abdominal fat depots were excised weighted. The data are reported as mean ± mean standard error, with p < 0.05 considered as significance level. RESULTS: Rats in the group 19% FR presented similar length, body weight and visceral fat mass. As a whole, the evaluations have shower results

  17. Autoradiographic studies of the rat renotropic system.

    Castillo, O; Robertson, D; Goldin, H; Preuss, H G


    Rat sera, 10-30 h after unilateral nephrectomy (UNI), enhance 3H-thymidine ("3H-Tdr) incorporation into DNA of incubating renal tissue from control rats. Stimulation is even greater when extracts from remaining growing kidneys 20 h after UNI are combined with sera from rats after UNI. UNI extracts, i.e., extracts from the kidney remaining after uninephrectomy, are nonstimulatory alone. UNI sera and UNI sera plus UNI extracts could theoretically augment 3H-Tdr incorporation into renal DNA via dilutional means rather than enhanced DNA synthesis. To determine if our results were secondary to enhanced DNA synthesis, we performed our in vitro assay using the labelling of nuclei via autoradiography as another index. The addition of UNI sera compared to sera from sham-operated rats (SHAM) in seven paired experiments enhanced incorporation of 3H-Tdr into DNA by 30% (p less than 0.02) and the addition of both UNI sera and UNI extracts compared to SHAM sera and SHAM extracts enhanced incorporation by 48% (p less than 0.001). Unlike a dilutional effect, nuclear labelling also increased in these same seven experiments: UNI sera versus SHAM sera increased 25% (p less than 0.05) and UNI sera + UNI extracts versus SHAM sera + SHAM extracts increased 37% (p less than 0.01). We conclude that UNI sera and UNI sera + UNI extracts enhance 3H-Tdr incorporation into DNA by augmenting DNA synthesis, driving cells into the "S" phase. The use of 3H-Tdr incorporation into DNA in our assay does estimate DNA synthesis.

  18. Oral teratogenicity studies of methyl bromide in rats and rabbits.

    Kaneda, M; Hojo, H; Teramoto, S; Maita, K


    Teratogenicity studies of methyl bromide, a widely used fumigant, were conducted in rats and rabbits. Methyl bromide was dissolved in corn oil and administered orally to groups of 24 copulated female Crj:CD (SD) rats at dose levels of 0 (corn oil), 3, 10 or 30 mg/kg/day on days 6-15 of gestation and to groups of 18 artificially inseminated female Kbl:JW rabbits at 0, 1, 3 or 10 mg/kg/day on days 6-18 of gestation. Maternal rats and rabbits were euthanized on respective days 20 and 27 of gestation. Foetuses were examined for survival, growth and teratological alterations. Maternal toxicity was evident in the high-dose groups for both species. In these groups, maternal body weight gains and food consumption were significantly decreased during the dosing and post-dosing periods. Necropsy of maternal rats also revealed erosive lesions in the stomach and the surrounding organs. However, no treatment-related adverse effects were found in foetuses of the treated groups for both rat and rabbit studies. These results led to the conclusion that methyl bromide was not foetotoxic or teratogenic to rat and rabbit foetuses up to dose levels of 30 and 10 mg/kg/day, respectively, at which maternal toxicity was evident for both species.

  19. ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by International Association of Diabetes in Pregnancy Study Groups criteria.

    Noctor, Eoin; Crowe, Catherine; Carmody, Louise A; Kirwan, Breda; O'Dea, Angela; Glynn, Liam G; McGuire, Brian E; O'Shea, Paula M; Dunne, Fidelma P


    Women with previous gestational diabetes (GDM) are a high-risk group for future development of diabetes, metabolic syndrome, and cardiovascular disease. The new International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria significantly increase the number of women diagnosed with GDM. The long-term metabolic outcome in these women is unknown. We set out to determine the prevalence of metabolic syndrome, using adult treatment panel-III criteria; and insulin resistance, using HOMA2-IR, in white European women with previous GDM. Using a cohort design, we invited women meeting IADPSG GDM criteria across four Irish antenatal centres between 2007 and 2010 to participate. Two hundred and sixty-five women with previous values meeting IADPSG criteria for GDM participated (44 % of the population eligible for participation). Mean age was 36.7 years (SD 5.0). These women were compared with a randomly selected control group of 378 women (mean age 37.6 years, SD 5.1) known to have normal glucose tolerance (NGT) in pregnancy during the same period. A total of 25.3 % of women with previous IADPSG-defined GDM met metabolic syndrome criteria, compared to 6.6 % of women with NGT [at 2.6 (SD 1.0) vs. 3.3 years (SD 0.7) post-partum]. The prevalence of HOMA2-IR >1.8 was higher in women with previous IADPSG-defined GDM (33.6 vs. 9.1 % with NGT, p Women with previous GDM by IADPSG criteria demonstrate a greater than threefold prevalence of metabolic syndrome compared to women with NGT in pregnancy. Efforts to prevent projected long-term consequences of this should focus on interventions both in the preconception and post-partum periods.

  20. Methodological model of chronic stress associated with ligature-induced periodontitis in rats: a radiographic study

    Alex Semenoff Segundo


    Full Text Available This study evaluated the time efficiency of stress associated with ligature-induced periodontitis in rats. Sixty adult Wistar rats, housed in temperature-controlled rooms and receiving water and food ad libitum, were randomly separated into stress (n = 30 or control groups (n = 30. All animals were anesthetized, and nylon ligatures were placed at the gingival margin level of the maxillary right second molars. After the induction of periodontitis, rats in the stress group were subjected to physical restraint for 12 hours daily. The animals were euthanized after 7, 15 and 30 days by anesthetic overdose (10 animals per group per period. The right hemimaxillae were stored in formalin solution for 48 hours. Parallel radiographic images of the hemimaxillae were taken and processed following standard procedures. Radiographic examination was performed by a blinded and previously calibrated investigator. Bone height level was measured, and data were submitted to analysis of variance and post hoc Bonferroni tests (p 0.05. Restraint stress modulates the short-term progression of periodontal disease in rats. Therefore, the 12-hour daily physical restraint stress model in rats applied for up to 15 days is suitable for the investigation of the combined effect of ligation and restraint stress on periodontal degradation.

  1. Prevention and health promotion in undergraduate medical education: Preferences, attitudes and previous knowledge of medical students - a cross-sectional study

    Klement, Andreas; Bretschneider, Kristin; Lautenschläger, Christine; Stang, Andreas; Herrmann, Markus; Haerting, Johannes


    Objective: The interdisciplinary topic "prevention and health promotion" (Q10) was introduced into the medical training in Germany by the new medical licensing regulations in 2004. For the conception of an effective curriculum, it is helpful to know student preferences concerning teaching-formats, attitudes and self-estimated previous knowledge. Little is known concerning student perception of “prevention and health promotion” in Germany. Thus, this explorative cross-sectional study aims to p...

  2. Continous controversy about radiation oncologists' choice of treatment regimens for bone metatases: should we blame doctors, canser-related features, or design of previous clinical studies

    Nieder, Carsten; Pawinski, Adam; Dalhaug, Astrid


    Recent studies from Italy, Japan and Norway have confirmed previous reports, which found that a large variety of palliative radiotherapy regimens are used for painful bone metastases. Routine use of single fraction treatment might or might not be the preferred institutional approach. It is not entirely clear why inter-physician and inter-institution differences continue to persist despite numerous randomized trials, meta-analyses and guidelines, which recommend against more costly and inconve...

  3. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

    Sukach A. N.


    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  4. Influence of dietary melatonin on photoreceptor survival in the rat retina: an ocular toxicity study.

    Wiechmann, Allan F; Chignell, Colin F; Roberts, Joan E


    Previous studies have shown that melatonin treatment increases the susceptibility of retinal photoreceptors to light-induced cell death. The purpose of this study was to evaluate under various conditions the potential toxicity of dietary melatonin on retinal photoreceptors. Male and female Fischer 344 (non-pigmented) and Long-Evans (pigmented) rats were treated with daily single doses of melatonin by gavage for a period of 14 days early in the light period or early in the dark period. In another group, rats were treated 3 times per week with melatonin early in the light period, and then exposed to high intensity illumination (1000-1500 lx; HII) for 2h, and then returned to the normal cyclic lighting regime. At the end of the treatment periods, morphometric measurements of outer nuclear layer thickness (ONL; the layer containing the photoreceptor cell nuclei) were made at specific loci throughout the retinas. In male and female non-pigmented Fischer rats, melatonin administration increased the degree of photoreceptor cell death when administered during the nighttime and during the day when followed by exposure to HII. There were some modest effects of melatonin on photoreceptor cell death when administered to Fischer rats during the day or night without exposure to HII. Melatonin treatment caused increases in the degree of photoreceptor cell death when administered in the night to male pigmented Long-Evans rats, but melatonin administration during the day, either with or without exposure to HII, had little if any effect on photoreceptor cell survival. In pigmented female Long-Evans rats, melatonin administration did not appear to have significant effects on photoreceptor cell death in any treatment group. The results of this study confirm and extend previous reports that melatonin increases the susceptibility of photoreceptors to light-induced cell death in non-pigmented rats. It further suggests that during the dark period, melatonin administration alone (i.e., no

  5. Subchronic oral toxicity studies with y-cyclodextrin in rats

    Lina, B.A.R.; Bär, A.


    The toxicity of γ-cyclodextrin (γ-CD), a cyclic polymer of eight α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered

  6. The wild rat as sentinel animal in the environmental risk assessment of asbestos pollution: a pilot study.

    Ardizzone, Michele; Vizio, Carlotta; Bozzetta, Elena; Pezzolato, Marzia; Meistro, Serena; Dondo, Alessandro; Giorgi, Ilaria; Seghesio, Angelo; Mirabelli, Dario; Capella, Silvana; Vigliaturo, Ruggero; Belluso, Elena


    Asbestos has been banned in many countries, including Italy. However, sources of exposure may still exist, due to asbestos in-situ or past disposal of asbestos-containing waste. In an urban area with past high environmental exposure, like Casale Monferrato, the lung fiber burden in sentinel animals may be useful to identify such sources. A pilot study was conducted to assess the feasibility of its determination in wild rats, a suitable sentinel species never used before for environmental lung asbestos fiber burden studies. Within the framework of pest control campaigns, 11 adult animals from 3 sites in the urban area of Casale Monferrato and 3 control rats from a different, unexposed town were captured. Further, 3 positive and 3 negative control lung samples were obtained from laboratories involved in breeding programs and conducting experimental studies on rats. Tissue fiber concentration was measured by scanning electron microscopy with energy dispersive spectrometry. Asbestos (chrysotile and crocidolite) was identified in the lungs from rats from Casale Monferrato, but not in control rats and in negative control lung samples. Asbestos grunerite at high concentration was found in positive control lung samples. Measurement of the lung fiber burden in wild rats has proved feasible: it was possible not only to detect, but also to characterize asbestos fibers both qualitatively and quantitatively. The pilot study provides the rationale for using wild rats as sentinels of the soil contamination level in Casale Monferrato, to identify areas with the possible presence of previously unrecognized asbestos sources.

  7. Subchronic Toxicity Study on Soy Isoflavones in Rats1



    Objective To investigate the subchronic toxicity of soy isoflavones (SIF) in male rats. Method Fifty Sprague-Dawley rats were randomly divided into 5 groups,10 rats per group.SIF were given to rats in different groups by gavage at dose of 0,0.2,0.5,1.5,and 4.5 g/kg bw,respectively for 13 weeks.Clinical manifestations,body weight,and food consumption were observed weekly.At the end of the study,urinalysis,hematology,clinical chemistry,total testosterone,and follicle-stimulating hormone were tested,and histopathological examinations were performed. Results No mortality,ophthalmic abnormalities or treatment-related clinical signs were identified during the study.As compared with the control group,significantly lower body weights and food consumption were observed in 1.5 and 4.5 g/kg bw groups.In clinical chemistry tests,triglyceride was significantly decreased and high-density lipoprotein cholesterol was significantly increased in all SIF-treated groups.Total testosterone levels were significantly lower in 0.50,1.50,and 4.5 g/kg bw dose groups than in the control group.Microscopic examination showed that the mammary glands exhibited hyperplasia and excreted latex in rats of the 4.5 g/kg bw group.No changes attributable to treatment of SIF in other parameters were found. Conclusion SIF at high dosages caused significant endocrine disruption in male rats.The no observed adverse effect level (NOAEL) of SIF to male rats in this study is considered to be 0.20 g/kg bw.

  8. The impact of smoking and previous periodontal disease on peri-implant microbiota and health: a retrospective study up to 7-year follow-up.

    Quaranta, Alessandro; Assenza, Bartolomeo; D'Isidoro, Orlando; Profili, Fabia; Polimeni, Antonella; Vozza, Iole


    To evaluate the impact of smoking and previous periodontal disease on peri-implant microbiota and health in medium to long-term maintained patients. A retrospective evaluation of partial edentulous patients restored with dental implants and enrolled in a regular supportive therapy was performed. Inclusion criteria were: medium to long-term periodontal and implant maintenance (at least 5 years), a minimum of 2 implants placed in each patient, absence of systemic diseases that may affect osseointegration. 30 implants in 15 patients were included in the study. Subjects were divided in smokers or non-smokers and between patients previously affected by periodontal disease and periodontally healthy. Peri-implant and periodontal parameters were assessed (PD,BoP, mPI). Microbiological samples were collected around implant and an adjacent tooth. Real- Time Polymerase Chain Reaction (RT-PCR) analysis was performed. In all the three groups no differences in bacterial counts between dental and implant sites were observed. Non smoker, healthy patients: healthy clinical parameters, significant counts of spirochetes in isolated patients. Non smokers with previous periodontal disease: occasional positive BoP values, significant high counts of pathogenic bacteria. Smokers with previous periodontal disease: clinical signs of inflammation including deep pockets and slight bone resorption, significant counts of pathogenic bacteria. Over a follow-up of 5 to 7 years, it is possible to state that the absence of smoking habit and previous periodontal disease positively influences the peri-implant microbiological and clinical conditions in partial edentulous patients restored with dental implants and enrolled in a strict regular supportive therapy.

  9. Role of previous hospitalization in clinically-significant MRSA infection among HIV-infected inpatients: results of a case-control study

    Festa Anna


    Full Text Available Abstract Background HIV-infected subjects have high incidence rates of Staphylococcus aureus infections, with both methicillin-susceptible and methicillin-resistant (MRSA strains. Possible explanations could include the high burden of colonization, the behavioral risk factors, and the frequent exposures to health care facilities of HIV-infected patients. The purpose of the study was to assess the risk factors for clinically- significant methicillin-resistant Staphylococcus aureus (CS-MRSA infections in HIV-infected patients admitted to Infectious Diseases Units. Methods From January 1, 2002 to December 31, 2005, we conducted a retrospective case-control (1:2 study. We identified all the cases of CS-MRSA infections in HIV-infected patients admitted to the National Institute for Infectious Diseases (INMI "Lazzaro Spallanzani" in the 4-year study period. A conditional logistic regression model was used to identify risk factors for CS-MRSA infection. Results We found 27 CS-MRSA infections, i.e. 0.9 CS-MRSA infections per 100 HIV-infected individuals cared for in our Institute. At multivariate analysis, independent predictors of CS-MRSA infection were cumulative hospital stay, invasive procedures in the previous year, and low CD4 cell count. Particularly, the risk for CS-MRSA increased by 14% per an increase of 5 days hospitalization in the previous year. Finally, we identified a low frequency of community-acquired MRSA infections (only 1 of 27; 3.7% among HIV-infected patients. Conclusion Clinicians should be aware of the risk for CS-MRSA infection in the clinical management of HIV-infected patients, especially in those patients with a low CD4 cell count, longer previous hospital stay, and previous invasive procedures.

  10. Role of previous hospitalization in clinically-significant MRSA infection among HIV-infected inpatients: results of a case-control study

    Drapeau, Cecilia MJ; Angeletti, Claudio; Festa, Anna; Petrosillo, Nicola


    Background HIV-infected subjects have high incidence rates of Staphylococcus aureus infections, with both methicillin-susceptible and methicillin-resistant (MRSA) strains. Possible explanations could include the high burden of colonization, the behavioral risk factors, and the frequent exposures to health care facilities of HIV-infected patients. The purpose of the study was to assess the risk factors for clinically- significant methicillin-resistant Staphylococcus aureus (CS-MRSA) infections in HIV-infected patients admitted to Infectious Diseases Units. Methods From January 1, 2002 to December 31, 2005, we conducted a retrospective case-control (1:2) study. We identified all the cases of CS-MRSA infections in HIV-infected patients admitted to the National Institute for Infectious Diseases (INMI) "Lazzaro Spallanzani" in the 4-year study period. A conditional logistic regression model was used to identify risk factors for CS-MRSA infection. Results We found 27 CS-MRSA infections, i.e. 0.9 CS-MRSA infections per 100 HIV-infected individuals cared for in our Institute. At multivariate analysis, independent predictors of CS-MRSA infection were cumulative hospital stay, invasive procedures in the previous year, and low CD4 cell count. Particularly, the risk for CS-MRSA increased by 14% per an increase of 5 days hospitalization in the previous year. Finally, we identified a low frequency of community-acquired MRSA infections (only 1 of 27; 3.7%) among HIV-infected patients. Conclusion Clinicians should be aware of the risk for CS-MRSA infection in the clinical management of HIV-infected patients, especially in those patients with a low CD4 cell count, longer previous hospital stay, and previous invasive procedures. PMID:17470274

  11. Subchronic Inhalation Toxicity Study of n-pentane in Rats.

    Kim, Jong-Kyu; Cho, Hae-Won; Han, Jeong-Hee; Lee, Sung-Bae; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun


    This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).

  12. Study of corpus callosum in experimental hydrocephalic wistar rats

    Lopes Luiza da Silva


    Full Text Available PURPOSE: Hydrocephalus causes countless cerebral damages, especially on the structures around the ventricles. Hydrocephalic children present deficiencies in the nonverbal skills more than in the verbal skills, and not always revertible with an early treatment. As the corpus callosum has an important role in the nonverbal acquisition it is possible that the injuries in this structure are responsible for the cognitive dysfunctions of these children. This present study tries to establish the alterations caused by hydrocephalus on the corpus callosum of developing Wistar rats, induced by intracisternal injection of kaolin. METHODS : Seven, fourteen and twenty one days after the injection, the animals were killed, and the corpus callosum was dissected and prepared for the study of the axonal fibers. RESULTS AND CONCLUSION: The seven-day old rats in hydrocephalus development presented a delay in myelination in relation to the control rats. With the fourteen-day old rats in hydrocephalus development the corpus callosum showed a recovery of myelin, but with the twenty one-day old rats in hydrocephalus development the axonal fibers were damaged and reduced in number.

  13. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment

    Martinez-Trufero, J; Isla, D; Adansa, J C; Irigoyen, A; Hitt, R; Gil-Arnaiz, I; Lambea, J; Lecumberri, M J; Cruz, J J


    Background: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. Methods: Patients aged 18–75 years, with Eastern Cooperative Oncology Group performance status 0–2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m−2 BID) was administered on days 1–14 every 21 days for at least two cycles. Results: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1–9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). Conclusions: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules. PMID:20485287

  14. Risk for High Depressive Symptoms in Diagnosed and Previously Undetected Diabetes: 5-Year Follow-Up Results of the Heinz Nixdorf Recall Study

    Icks, Andrea; Albers, Bernd; Haastert, Burkhard; Pechlivanis, Sonali; Pundt, Noreen; Slomiany, Uta; Erbel, Raimund; Jöckel, Karl-Heinz; Kruse, Johannes; Kulzer, Bernd; Nowotny, Bettina; Herder, Christian; Giani, Guido; Moebus, Susanne


    Objective The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany. Methods We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD) 59.1 (7.6) years, 7.0% diagnosed diabetes, 5.3% previously undetected diabetes) from the population-based Heinz Nixdorf Recall study. Diabetes was assessed by self-report, medication, and blood glucose. High depressive symptoms were assessed using CES-D. We calculated odds ratios and their corresponding 95% confidence interval, using multiple logistic regression analyses. Result Cumulative 5-year incidences (95% CI) of high depressive symptoms in participants with diagnosed, undetected, and without diabetes were 7.1 (4.2–10.9), 4.1 (1.8–8.0), and 6.5 (5.6–7.4), respectively. The age-sex-adjusted OR for developing high depressive symptoms was 1.22 (0.74–2.03) in participants with diagnosed compared to those without diabetes, and 1.00 (0.59–1.68) after adjustment for BMI, physical activity, education, stroke, and myocardial infarction. The age-sex adjusted OR for developing high depressive symptoms in participants with previously undetected diabetes compared to those without diabetes was 0.72; 0.35–1.48; and fully adjusted 0.62; 0.30–1.30. Conclusion We found no significant associations, maybe due to low power. However, our results are in line with a recent meta-analysis suggesting that risk of developing high depressive symptoms in patients with diagnosed diabetes may be moderately higher than in those without diabetes, and that comorbidity may explain in part this association. In participants with previously undetected diabetes, this first longitudinal study indicates that the risk is not

  15. Risk for high depressive symptoms in diagnosed and previously undetected diabetes: 5-year follow-up results of the Heinz Nixdorf Recall study.

    Andrea Icks

    Full Text Available OBJECTIVE: The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany. METHODS: We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD 59.1 (7.6 years, 7.0% diagnosed diabetes, 5.3% previously undetected diabetes from the population-based Heinz Nixdorf Recall study. Diabetes was assessed by self-report, medication, and blood glucose. High depressive symptoms were assessed using CES-D. We calculated odds ratios and their corresponding 95% confidence interval, using multiple logistic regression analyses. RESULT: Cumulative 5-year incidences (95% CI of high depressive symptoms in participants with diagnosed, undetected, and without diabetes were 7.1 (4.2-10.9, 4.1 (1.8-8.0, and 6.5 (5.6-7.4, respectively. The age-sex-adjusted OR for developing high depressive symptoms was 1.22 (0.74-2.03 in participants with diagnosed compared to those without diabetes, and 1.00 (0.59-1.68 after adjustment for BMI, physical activity, education, stroke, and myocardial infarction. The age-sex adjusted OR for developing high depressive symptoms in participants with previously undetected diabetes compared to those without diabetes was 0.72; 0.35-1.48; and fully adjusted 0.62; 0.30-1.30. CONCLUSION: We found no significant associations, maybe due to low power. However, our results are in line with a recent meta-analysis suggesting that risk of developing high depressive symptoms in patients with diagnosed diabetes may be moderately higher than in those without diabetes, and that comorbidity may explain in part this association. In participants with previously undetected diabetes, this first longitudinal study indicates that the risk is not

  16. Inhalation developmental toxicology studies: Gallium arsenide in mice and rats

    Mast, T.J.; Greenspan, B.J.; Dill, J.A.; Stoney, K.H.; Evanoff, J.J.; Rommereim, R.L.


    Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague- Dawley rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m{sup 3} gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and {approx}30 positively mated rats or {approx}24 positively mated mice. Mice were exposed on 4--17 days of gestation (dg), and rats on 4--19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg. 37 refs., 11 figs., 30 tabs.

  17. Shallow landslide susceptibility model for the Oria river basin, Gipuzkoa province (North of Spain). Application of the logistic regression and comparison with previous studies.

    Bornaetxea, Txomin; Antigüedad, Iñaki; Ormaetxea, Orbange


    In the Oria river basin (885 km2) shallow landslides are very frequent and they produce several roadblocks and damage in the infrastructure and properties, causing big economic loss every year. Considering that the zonification of the territory in different landslide susceptibility levels provides a useful tool for the territorial planning and natural risk management, this study has the objective of identifying the most prone landslide places applying an objective and reproducible methodology. To do so, a quantitative multivariate methodology, the logistic regression, has been used. Fieldwork landslide points and randomly selected stable points have been used along with Lithology, Land Use, Distance to the transport infrastructure, Altitude, Senoidal Slope and Normalized Difference Vegetation Index (NDVI) independent variables to carry out a landslide susceptibility map. The model has been validated by the prediction and success rate curves and their corresponding area under the curve (AUC). In addition, the result has been compared to those from two landslide susceptibility models, covering the study area previously applied in different scales, such as ELSUS1000 version 1 (2013) and Landslide Susceptibility Map of Gipuzkoa (2007). Validation results show an excellent prediction capacity of the proposed model (AUC 0,962), and comparisons highlight big differences with previous studies.

  18. Food intake during the previous 24 h as a percentage of usual intake: a marker of hypoxia in infants with bronchiolitis: an observational, prospective, multicenter study

    Corrard François


    Full Text Available Abstract Background Hypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24 hours (bottle and spoon feeding, as a percentage of usual intake (24h FI, as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs. Methods In this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea + dyspnea + cough + expiratory sounds. Infants with risk factors (history of prematurity, chronic heart or lung disorders, breast-fed infants, and infants having previously been treated for bronchial disorders were excluded. The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2 was recorded. Hypoxia was noted if SpO2 was below 95% and verified. Results 24h FI ≥ 50% was associated with a 96% likelihood of SpO2 ≥ 95% [95% CI, 91–99]. In univariate analysis, 24h FI  Conclusion In practice, the measure of 24 h FI may be useful in identifying hypoxia and deserves further study.

  19. Study of the Pharmacokinetic Changes of Tramadol in Diabetic Rats

    Lida Hakemi


    Full Text Available Background:Besides the pathological states, diabetes mellitus may also alter the hepatic biotransformation of pharmaceutical agents. It is advantageous to understand the effect of diabetes on the pharmacokinetic of drugs. The objective of this study was to define the pharmacokinetic changes of tramadol and its main metabolites after in vivo intraperitoneal administration and ex vivo perfused liver study in diabetic rat model.Tramadol (10 mg/kg was administered to rats (diabetic and control groups of six intraperitoneally and blood samples were collected at different time points up to 300 min. In a parallel study, isolated liver perfusion was done (in diabetic and control rats by Krebs-Henseleit buffer (containing 500 ng/ml tramadol. Perfusate samples were collected at 10 min intervals up to 180 min. Concentration of tramadol and its metabolites were determined by HPLC.Results:Tramadol reached higher concentrations after i.p. injection in diabetics (Cmax of 1607.5 ± 335.9 ng/ml compared with control group (Cmax of 561.6 ± 111.4. M1 plasma concentrations were also higher in diabetic rats compared with control group. M2 showed also higher concentrations in diabetic rats. Comparing the concentration levels of M1 in diabetic and control perfused livers, showed that in contrast to intact animals, the metabolic ratios of M1 and M5 (M/T were significantly higher in diabetic perfused liver compared to those of control group.Conclusions:The pharmacokinetic of tramadol and its three metabolites are influenced by diabetes. As far as M1 is produced by Cyp2D6, its higher concentration in diabetic rats could be a result of induction in Cyp2D6 activity, while higher concentrations of tramadol can be explained by lower volume of distribution.

  20. Study on sperm damage caused by trichloroethylene in male rats



    Objective To study in vitro sperm damage caused by trichloroethylene in male rats.Methods Sperms of Sprague-Dawley(SD)rats were collected 4 hours after being contaminated by trichloroethylene of 0,2,4,6,8,and 10 mmol/L in vitro.Giemsa staining was performed to observe the morphological changes of sperms,and flow cytometer was used to detect the changes in mitochondrial membrane potential.Results The sperm motilities in6,8,and 10 mmol/L trichloroethylene groups decreased significantly

  1. The effect of chemotherapy on rat brain PET: preliminary study

    Kim, Jin Su; Kim, Il Han; Yu, A Ram; Park, Ji Ae; Woo, Sang Keun; Kim, Jong Guk; Cheon, Gi Jeong; Kim, Byeong Il; Choi, Chang Woon; Lim, Sang Moo; Kim, Hee Joung; Kim, Kyeong Min [Korea Institute Radiological and Medical Science, Seoul (Korea, Republic of)


    Chemotherapy was widely used for the therapy of cancer patients. When chemotherapy was performed, transient cognitive memory problem was occurred. This cognitive problem in brain was called as chemobrain. In this study, we have developed rat model for chemobrain. Cerebral glucose metabolism after chemotherapy was assessed using animal PET and voxel based statistical analysis method

  2. Four-week oral toxicity study with erythritol in rats

    Til, H.P.; Modderman, J.


    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  3. Four-week oral toxicity study with erythritol in rats

    Til, H.P.; Modderman, J.


    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  4. Four Forensic Entomology Case Studies: Records and Behavioral Observations on Seldom Reported Cadaver Fauna With Notes on Relevant Previous Occurrences and Ecology.

    Lindgren, Natalie K; Sisson, Melissa S; Archambeault, Alan D; Rahlwes, Brent C; Willett, James R; Bucheli, Sibyl R


    A yearlong survey of insect taxa associated with human decomposition was conducted at the Southeast Texas Applied Forensic Science (STAFS) facility located in the Center for Biological Field Studies of Sam Houston State University in Huntsville, TX. During this study, four insect-cadaver interactions were observed that represent previously poorly documented yet forensically significant interactions: Syrphidae maggots colonized a corpse in an aquatic situation; Psychodidae adults mated and oviposited on an algal film that was present on a corpse that had been recently removed from water; several Panorpidae were the first insects to feed upon a freshly placed corpse in the autumn; and a noctuid caterpillar was found chewing and ingesting dried human skin. Baseline knowledge of insect-cadaver interactions is the foundation of forensic entomology, and unique observations have the potential to expand our understanding of decomposition ecology.

  5. Vitamin D deficiency in medical patients at a central hospital in Malawi: a comparison with TB patients from a previous study.

    Yamikani Mastala

    Full Text Available OBJECTIVES: To determine the prevalence of vitamin D deficiency (VDD in adult medical, non-tuberculous (non-TB patients. To investigate associations with VDD. To compare the results with a similar study in TB patients at the same hospital. DESIGN: Cross-sectional sample. SETTING: Central hospital in Malawi. PARTICIPANTS: Adult non-TB patients (n = 157, inpatients and outpatients. OUTCOME MEASURES: The primary outcome was the prevalence of VDD. Potentially causal associations sought included nutritional status, in/outpatient status, HIV status, anti-retroviral therapy (ART and, by comparison with a previous study, a diagnosis of tuberculosis (TB. RESULTS: Hypovitaminosis D (≤75 nmol/L occurred in 47.8% (75/157 of patients, 16.6% (26/157 of whom had VDD (≤50 nmol/L. None had severe VDD (≤25 nmol/L. VDD was found in 22.8% (23/101 of in-patients and 5.4% (3/56 of out-patients. In univariable analysis in-patient status, ART use and low dietary vitamin D were significant predictors of VDD. VDD was less prevalent than in previously studied TB patients in the same hospital (68/161 = 42%. In multivariate analysis of the combined data set from both studies, having TB (OR 3.61, 95%CI 2.02-6.43 and being an in-patient (OR 2.70, 95%CI 1.46-5.01 were significant independent predictors of VDD. CONCLUSIONS: About half of adult medical patients without TB have suboptimal vitamin D status, which is more common in in-patients. VDD is much more common in TB patients than non-TB patients, even when other variables are controlled for, suggesting that vitamin D deficiency is associated with TB.

  6. Myocardial adaptation to high-intensity (interval) training in previously untrained men with a longitudinal cardiovascular magnetic resonance imaging study (Running Study and Heart Trial).

    Scharf, Michael; Schmid, Axel; Kemmler, Wolfgang; von Stengel, Simon; May, Matthias S; Wuest, Wolfgang; Achenbach, Stephan; Uder, Michael; Lell, Michael M


    To prospectively evaluate whether short-term high-intensity (interval) training (HI(I)T) induces detectable morphological cardiac changes in previously untrained men in cardiovascular magnetic resonance imaging. Eighty-four untrained volunteers were randomly assigned to a HI(I)T group (n=42; 44.1±4.7 years) or an inactive control group (n=42; 42.3±5.6 years). HI(I)T focused on interval runs (intensity: 95%-105% of individually calculated heart rate at the anaerobic threshold). Before and after 16 weeks, all subjects underwent physiological examination, stepwise treadmill test with blood lactate analysis, and contrast-enhanced cardiovascular magnetic resonance imaging (cine, tagging, and delayed enhancement). Indexed left ventricular (LV) and right ventricular (RV) volume (LV, 77.1±8.5-83.9±8.6; RV, 80.5±8.5-86.6±8.1) and mass (LV, 58.2±6.4-63.4±8.1; RV, 14.8±1.7-16.1±2.1) significantly increased with HI(I)T. Changes in LV and RV morphological parameters with HI(I)T were highly correlated with an increase in maximal aerobic capacity (VO2max) and a decrease in blood lactate concentration at the anaerobic threshold. Mean LV and RV remodeling index of HI(I)T group did not alter with training (0.76 ±0.09 and 0.24±0.10 g/mL, respectively [P=0.97 and P=0.72]), indicating balanced cardiac adaptation. Myocardial circumferential strain decreased after HI(I)T within all 6 basal segments (anteroseptal, P=0.01 and anterolateral, PHeart Association, Inc.

  7. Biomechanical jumping differences among elite female handball players with and without previous anterior cruciate ligament reconstruction: a novel inertial sensor unit study.

    Setuain, Igor; Millor, Nora; González-Izal, Miriam; Gorostiaga, Esteban M; Gómez, Marisol; Alfaro-Adrián, Jesús; Maffiuletti, Nicola A; Izquierdo, Mikel


    Persistent biomechanical and jumping capacity alterations have been observed among female athletes who have sustained anterior cruciate ligament (ACL) injuries. The purpose of this study was to examine if biomechanical jumping differences persist among a cohort of elite female handball players with previous ACL reconstruction several years after return to top-level competition. In order to achieve this goal, a direct mechanics simplified analysis by using a single Inertial Sensor Unit (IU) was used. Twenty-one elite female (6 anterior cruciate ligament reconstructed and 15 uninjured control players) handball players were recruited and evaluated 6.0 ± 3.5 years after surgical anterior cruciate ligament reconstruction. Bilateral and unilateral vertical jumps were performed to evaluate the functional performance and a single inertial sensor unit was employed in order to collect 3D acceleration and 3D orientation data. Previously ACL-reconstructed analysed athletes demonstrated significant (p reconstruction. Identification of the encountered deficits through the use of an IU devise could provide clinicians with a new reliable tool for movement analysis in a clinical setting.

  8. Studies on the adrenomedullary dependence of kappa-opioid agonist-induced diuresis in conscious rats.

    Borkowski, K. R.


    1. The dependence of kappa-opioid agonist-induced diuresis, upon an intact and functional adrenal medulla in conscious rats, was investigated in order to test the hypothesis that the diuresis is mediated by a blood-borne 'diuretic factor', of adrenomedullary origin, released by kappa-opioid receptor stimulation. 2. Confirming previous observations, adrenal demedullation significantly attenuated diuretic responses to the kappa-opioid agonists U50488H, ethylketocyclazocine (EKC) and tifluadom, but did not affect basal urine output, furosemide-induced diuresis or the antidiuretic response to the mu-opioid agonist, buprenorphine. Naloxone abolished U50488H-induced diuresis, confirming an involvement of opioid receptors. 3. Transfusion studies established that blood, from intact rats treated with U50488H, induced diuresis in intact and demedullated recipient rats, whether or not the recipients had been pretreated with naloxone. However, blood from demedullated rats treated with U50448H was unable to induce diuresis when administered to intact or demedullated recipients. 4. It is concluded that kappa-opioid agonist-induced diuresis is dependent upon an intact and functional adrenal medulla and appears to be mediated by a blood-borne 'diuretic factor' of adrenomedullary origin. PMID:2558758

  9. A longitudinal study of relationships between previous academic achievement, emotional intelligence and personality traits with psychological health of medical students during stressful periods.

    Yusoff, Muhamad Saiful Bahri; Esa, Ab Rahman; Mat Pa, Mohamad Najib; Mey, See Ching; Aziz, Rosniza Abdul; Abdul Rahim, Ahmad Fuad


    There is considerable evidence that emotional intelligence, previous academic achievement (i.e. cumulative grade point average (GPA)) and personality are associated with success in various occupational settings. This study evaluated the relationships of these variables with psychological health of first year medical students during stressful periods. A 1-year prospective study was done with students accepted into the School of Medical Sciences, Universiti Sains Malaysia. Information on emotional intelligence, GPA and personality traits were obtained prior to admission. The validated Universiti Sains Malaysia Emotional Quotient Inventory and Universiti Sains Malaysia Personality Inventory were used to measure emotional intelligence and personality traits, respectively. Stress, anxiety and depression were measured by the 21-item Depression Anxiety Stress Scale during the end-of-course (time 1) and final (time 2) examinations. At the less stressful period (time 1), stress level was associated with agreeableness and the final GPA, anxiety level was associated with emotional control and emotional conscientiousness and depression level was associated with the final GPA and extraversion. At the more stressful period (time 2), neuroticism associated with stress level, anxiety level was associated with neuroticism and emotional expression, and depression level was associated with neuroticism. This study found that neuroticism was the strongest associated factor of psychological health of medical students during their most stressful testing period. Various personality traits, emotional intelligence and previous academic performance were associated factors of psychological health during a less stressful period. These data suggest that early identification of medical students who are vulnerable to the stressful environment of medical schools might help them maintain psychological well-being during medical training.

  10. Study on the Properties of TiN Coatings on Previously Ion-Implanted Pure Magnesium Surface by MEVVA Ion Implantation

    ZHOU Hai; CHEN Fei; WANG Jian-ping


    A metal vapor vacuum arc (MEVVA) is used in ion implantation for substrate preparation before the deposition process which would ensure the improvement of mechanical properties of the coating.Ti ion is implanted into pure magnesium surface by MEVVA implanter operated with a modified cathode.Implanting energy is kept at 45 keV and dose is set at 3×1017 cm-2.TiN coatings are deposited by magnetically filtered vacuum-arc plasma source on unimplanted and previously implanted substrates.Microstructure and phase composition are analysed using scanning electron microscopy (SEM) and X-ray diffraction (XRD).The property of corrosion resistance of TiN coatings was studied by CS300P electrochemistry-corrosion workstation,and the main impact factor of the corrosion resistance was also analyzed.

  11. Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease

    Sorensen, M.; Lassen, Ulrik Niels; Jensen, Peter Buhl;


    and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC......, adequate organ functions and performance status less than 3 were eligible. Topotecan (2.0 mg/m, intravenously) was administered on days 1 to 3 with cisplatin (50 mg/m, intravenously) on day 3 every 3 weeks for a total of six cycles. RESULTS: Forty-three patients received 219 cycles of chemotherapy. Median.......3-7.7), respectively. CONCLUSION: Three-day topotecan with cisplatin on day 3 is active and safe in extensive disease SCLC. An ongoing phase III randomized trial compares this combination to standard treatment Udgivelsesdato: 2008/8...


    Hausmann, Jennifer C; Wack, Allison N; Allender, Matthew C; Cranfield, Mike R; Murphy, Kevin J; Barrett, Kevin; Romero, Jennell L; Wellehan, James F X; Blum, Stella A; Zink, M Christine; Bronson, Ellen


    The Maryland Zoo in Baltimore experienced an outbreak of Frog virus-3 (FV3)-like ranavirus during the summer of 2011, during which 14 of 27 (52%) of its captive eastern box turtles (Terrapene carolina carolina) survived. To assess survival, immunity, and viral shedding, an experimental challenge study was performed in which the surviving, previously infected turtles were reinfected with the outbreak strain of FV3-like ranavirus. Seven turtles were inoculated with virus intramuscularly and four control turtles received saline intramuscularly. The turtles were monitored for 8 wk with blood and oral swabs collected for quantitative polymerase chain reaction (qPCR). During that time, one of seven (14%) inoculated turtles and none of the controls (0%) died; there was no significant difference in survival. Clinical signs of the inoculated turtles, except for the turtle that died, were mild compared to the original outbreak. Quantitative PCR for FV3-like ranavirus on blood and oral swabs was positive for all inoculated turtles and negative for all controls. The turtle that died had intracytoplasmic inclusion bodies in multiple organs. Three inoculated and two control turtles were euthanized at the end of the study. No inclusion bodies were present in any of the organs. Quantitative PCR detected FV3-like ranavirus in the spleen of a control turtle, which suggested persistence of the virus. The surviving five turtles were qPCR-negative for FV3-like ranavirus from blood and oral swabs after brumation. Quantitative PCR for Terrapene herpesvirus 1 found no association between ranavirus infection and herpesvirus loads. In conclusion, previously infected eastern box turtles can be reinfected with the same strain of FV3-like ranavirus and show mild to no clinical signs but can shed the virus from the oral cavity.

  13. Studies on orthocephalization. IV. Differential growth of the sphenooccipital synchondosis in the rat

    Vilmann, H; Kirkeby, S; Moss, M L


    for the posterior end of the basisphenoid bone, although to a less degree. These conclusions have been reached by studying the distribution of alkaline phosphatase reaction in the perichondrium covering the sphenooccipital synchondrosis. Extension of reaction to this enzyme in perichondria has previously been shown...... to be a measure of growth rate. Sections of the sphenooccipital synchondrosis from 10 rats 10 days ago, incubated for reactions to alkaline phosphatase have formed the basis of the study. Quantitative expressions of the extension of enzymatic reaction have been collected. Statistical treatment of these data have...

  14. Clinical evaluation of balloon occlusion of the lower abdominal aorta in patients with placenta previa and previous cesarean section: A retrospective study on 43 cases.

    Chen, Manru; Xie, Lan


    This study investigated the efficacy of balloon occlusion of the lower abdominal aorta in cesarean section surgery for the patients with placenta previa and previous cesarean section. The patients who had placenta previa and underwent cesarean section (CS) were evaluated. The patients treated with CS to terminate the pregnancy were used as control group (23 cases); the patients treated with the preset abdominal aorta balloon before CS was taken as study group (20 cases). The investigated indicators included the intraoperative blood loss, blood loss within postoperative 24 h, the transfusion amount of red cell suspension (RCS), hospital stay, incidence rate of disseminated intravascular coagulation (DIC), the asphyxia, premature delivery and the mortality of the newborns. The two groups are comparable. The intraoperative blood loss, blood loss within postoperative 24 h, the transfusion amount of RCS and the percentage of uterus resection in the study group were significantly lower (P < 0.05) than that in the control group. The percentage of uterine cavity filling with ribbon gauze in the study group was higher than the control group (P < 0.05). The balloon occlusion of lower abdominal aorta seems effective in reducing postpartum hemorrhage and the blood transfusion and decreasing the risk of hysterectomy without harming the newborns. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  15. Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

    Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O


    Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats.

  16. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer.

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A


    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] "top scoring pairs" polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3' untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible.

  17. Study on the Specific Gene Expression during Spermatogenesis of Rat

    吴燕婉; 王春梅; 黄海燕; 石心泉; 邢志军; 刘德瑜


    Objective To explore specific gene expression for regulating meiosis of germ cells during spermatogenesis of rat testis Materials & Methods Male SD rats, aged 1, 3 and 8 weeks, were observed in this study. The methods of morphological observation on testicular tissues embedded by resin and mRNA differential display (DDRT-PCR) were combined to obtain specific mRNA expression gene fragments during the testicular development. Reverse dot blot hybridization was operated to further screen the positive differential DNA fragments.The positive DNA segments were sub-cloned in pGEM-T-Easy vector and transformed into the competent E-coli 109 straint. Northern blot analysis and in situ hybridization were also carried out for identifying tissue-specific expression as well as cell-specific expression DNA fragments. To screen λ-ZAP-II rat testicular gene library was searched for the original gene.Results Eighty two differential cDNA fragments were obtained through primary DDRT-PCR, among which 40 differential cDNA fragments were selected for further screening with reverse dot blot hybridization. After the reverse dot blot hybridization,12 primary differential DNA fragments were obtained. The size of DNA fragments ranged from 250 to 500 bp. The in situ hybridization of the testicular tissue showed that a specific DNA fragment derived from 8-week old rat testis, named CG14, was hybridized in adult rat testicular section, in which the positive nucleic acid signals were distributed specifically in the primary spermatocytes. Another DNA fragment derived from 1-week old rat testis, named AA 1 1, was hybridized specifically in Sertoli cell of 1-week old rat testis. Northern blot hybridization with [α-32P] dCTP labeled CG 1 4 probe, including cardiac, liver, kidney, brain, testis, and epididymis tissue mRNAs of rat, showed that an mRNA specific hybridization band, size of 1. 258 kb, was found in testis tissue and size of 1. 531 kb of another hybridization band present in epididymis

  18. A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.

    Planchard, David; Yokoi, Takashi; McCleod, Michael J; Fischer, Jürgen R; Kim, Young-Chul; Ballas, Marc; Shi, Kelvin; Soria, Jean-Charles


    Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing.

  19. Study of Antiulcer Activity of Bauhinia racemosa lam in Rats

    V.I. Borikar


    Full Text Available An experiment was conducted to study the antiulcer effect of the dried fruit powder of the plant Bauhinia racemosa in Wistar albino rats. Thirty Wistar rats of either sex weighing between 150 - 200gm were selected and divided into five groups, each comprising of six rats. The rats were divided into 5 groups T1T2, T3, T4, and T5 and were given 0.5 ml normal saline, aqueous extract in the dose rate of100mg/kg body weight, 200mg/kg body weight, alcoholic extract @100mg/kg body weight and 200mg/kg body weight respectively. After one hour all the groups were administered Paracetamol at a dose rate of 200mg/kg body weight orally. After 24hrs, the number of ulcers, ulcer score, percent incidence, ulcer index and healing index were recorded. From the results obtained it was concluded that aqueous extract in the dose rate of 200mg/kg body weight and alcoholic extract (100mg/kg & 200mg/kg body weight could produce antiulcer activity. [Vet World 2009; 2(6.000: 217-218

  20. HPLC study of tissue distribution of loganin in rats.

    Li, Xiaona; Wang, Qiao; Zhang, Lantong; Xu, Lei; Yin, Wei


    A rapid, sensitive and selective high performance liquid chromatography (HPLC) method was developed and validated for determination of loganin in rat tissues. Samples were prepared based on a simple protein precipitation. Separation of loganin was achieved on a reversed-phase C(18) column (250 x 4.6 mm, 5 microm) with a mobile phase consisting of acetonitrile and water (16:84, v/v) at a flow rate of 1.0 mL/min. The detection wavelength was set at 236 nm and the temperature of the column was kept at 30 degrees C. The method was applied to study tissue distribution of loganin in rats after a single administration of loganin at a dose of 20 mg/kg. The highest level was observed in kidney, then in stomach, lung and small intestine. The lowest level was found in brain. The peak levels were attained at 90 min in most tissues. It was indicated that kidney was the major distribution tissue of loganin in rats, and that loganin had difficulty in crossing the blood-brain barrier. It was also found there was no long-term accumulation of loganin in rat tissues.

  1. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer.

    Rao, S; Cunningham, D; Hawkins, R E; Hill, M E; Smith, D; Daniel, F; Ross, P J; Oates, J; Norman, A R


    The purpose of this study was to determine whether epirubicin, cisplatin and infused 5FU (ECF) improves overall survival (OS) compared to 5FU, etoposide and leucovorin (FELV) in patients with previously untreated advanced biliary cancer in a prospective randomised study. Patients were randomly assigned to receive epirubicin, cisplatin and infused 5FU ECF or bolus 5FU etoposide and leucovorin (FELV). The primary end point was OS with secondary end points of objective response rate (ORR), failure-free survival (FFS), quality of life (QOL) and toxicity. In all, 54 patients were recruited with 27 randomly assigned to each arm. The median OS for ECF was 9.02 months (95% confidence interval (CI): 6.46-11.51) and FELV 12.03 months (95% CI: 9.3-14.7), P=0.2059. Objective response rates were similar for both arms: ECF 19.2% (95% CI: 6.55-39.3); FELV 15% (95% CI: 3.2-37.9), P=0.72. There was significantly increased grade 3/4 neutropenia with FELV vs ECF (53.8 vs 29.5%, respectively, P=0.020). Symptom resolution was impressive for both regimens. This is the largest reported randomised study to date in this setting. ECF did not improve OS compared to FELV, but was associated with less acute toxicity. These data suggest that chemotherapy can prolong OS and achieve good symptomatic relief in advanced biliary cancer.

  2. Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: a meta-analysis of observational studies.

    Malindu Eranga Fernando

    Full Text Available AIMS: Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. METHODS: Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP and pressure time integral (PTI were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310. RESULTS: Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290-0.811, p<0.001; and 0.762, 95% CI 0.303-1.221, p = 0.001, respectively. Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181- 0.753, p = 0.001. Statistical heterogeneity between studies was moderate. CONCLUSIONS: Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic

  3. The influence of previous infections and antichlamydia pneumoniae seropositivity on functional outcome in ischemic stroke patients: results from the IN2 study.

    Consoli, Domenico; Vidale, Simone; Aguglia, Umberto; Bassi, Pietro; Cavallini, Anna; Consoli, Arturo; Galati, Franco; Guidetti, Donata; Micieli, Giuseppe; Neri, Giuseppe; Rasura, Maurizia; Sterzi, Roberto; Toni, Danilo; Inzitari, Domenico


    Although a growing attention is being paid to acute ischemic stroke patients, the correlation between clinical outcome and infectious events in this population has been poorly investigated. 749 ischemic stroke (mean age 71 years old, males 56%) patients were enrolled in this prospective case-control study by 11 Italian Stroke Units. Demographic data, vascular risk factors, previous infections and post-stroke infections (PSIs) were recorded. Blood samples were collected and the enzyme-linked immunoassay was chosen to measure Chlamydia pneumoniae IgG and IgA plasma antibodies (antibody titers were classified with specific cut-off levels: IgA > 1:16 and IgG > 1:64). Early poor outcome was defined as mRS score >2 at discharge, while poor outcome at 6-month follow-up. Univariate and multivariate analyses were performed. Median NIHSS was 7, IgA and IgG antichlamydia pneumoniae seropositivities were observed in 308 (37.1%) and 207 (23.6%) patients, respectively. Multivariate analyses showed significant correlations between PSIs and NIHSS (RR: 1.06; 95% CI 1.02-1.09; p < 0.001) and PSIs and IgA antichlamydia pneumoniae seropositivity (RR: 3.84; 95% CI 2.53-5.84; p < 0.001). Significant disability was associated with baseline NIHSS (RR: 1.32; 95% CI 1.16-1.50; p < 0.001), IgA (RR: 2.67; 95% CI 1.06-6.70; p = 0.035) and IgG antichlamydia (RR: 5.75; 95% CI 1.83-18.03; p = 0.003) seropositivity and atrial fibrillation (RR: 2.58; 95% CI 1.81-3.67; p < 0.001). While previous infections were not associated with functional outcome, antichlamydia antibodies play a negative role in ischemic stroke patients. Preventive strategies may reduce the stroke burden and improve the clinical outcome.

  4. Metabolomic Study on the Preventive Effect of Patrinia scabiosaefolia Fisch on Multipathogen Induced Pelvic Inflammatory Disease in Rats

    Wei Zou


    Full Text Available Patrinia scabiosaefolia Fisch (PSF, a well-known traditional Chinese medicine (TCM, has been used as a “heat-clearing and detoxifying” agent. The present study was to illustrate the preventive effect of PSF on pelvic inflammatory disease (PID in rats. The PID model was constructed by multipathogen infection of the upper genital tract with reference to the method previously reported. Urine metabolomic analysis was conducted with a GC-MS coupled with derivatization method. In this study, PID rats showed obvious infiltration of inflammatory cells and elevated expression of cytokines (IL-1β and IL-6 in upper genital tract, compared with control rats. Sixteen differentiating metabolites contributed to the alteration of metabolic profile in PID rats, including two amino acids, three fat acids, nine organic acids, and two types of sugars. The rats, infected by multipathogen and administered with PSF, showed decreased infiltration of inflammatory cells and lowered expression of cytokines in upper genital tract, compared with PID rats. Meanwhile, PSF intervened in the PID-associated alterations in TCA cycle, sugar metabolism, amino acid metabolism, and other uncertain metabolic pathways. These results indicate that PSF has preventive effect on multipathogen induced PID and holistic interventional effect on disease-associated metabolomic change.

  5. A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.

    Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi-Khansari, Mahmoud


    Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system. Tramadol and metabolites concentrations were determined by HPLC-FL. The sharp increase in liver enzymes level in both BDL groups was observed and significant changes were also observed in liver weight and volume. Tramadol metabolites concentration significantly decreased compared with the control and sham group (Ptramadol and increase in the half-life of the elimination of tramadol in rats with BDL suggests that personalized treatment and the therapeutic drug monitoring (TDM) data examination are necessary for patients with bile duct diseases and the dose of tramadol should be accordingly adjusted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. A Retrospective Case-Control Study Evaluating the Role of Mifepristone for Induction of Labor in Women with Previous Cesarean Section.

    Sharma, Chanderdeep; Soni, Anjali; Soni, Pawan K; Verma, Suresh; Verma, Ashok; Gupta, Amit


    To investigate the role of "mifepristone" for induction of labor (IOL) in pregnant women with prior cesarean section (CS). In this retrospective study, all pregnant women with prior CS who received oral mifepristone (400 mg) for IOL (as per clear obstetric indications) [group 1] were compared with pregnant women with prior CS who had spontaneous onset of labor (SOL) [group 2], with respect to incidence of vaginal delivery, CS, duration of labor, and various maternal and fetal outcomes. During the study period, 72 women received mifepristone (group 1) for IOL and 346 had SOL (group 2). In group 1 after mifepristone administration, 40 (55.6 %) women had labor onset, and 24 (33.3 %) women had cervical ripening (Bishop Score ≥ 8) within 48 h. There were no statistically significant differences with respect to duration of labor (p value: 0.681), mode of delivery (i.e., normal delivery or CS-p value: 0.076 or 0.120, respectively), or maternal (blood loss or scar dehiscence/rupture uterus), or fetal outcomes (NICU admission) compared to women with previous CS with SOL (group 2). However, the need of oxytocin (p value 0.020) and dose of oxytocin requirement (p value 0.008) were more statistically significant in group 1. Mifepristone may be considered as an agent for IOL in women with prior CS.

  7. Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

    Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis


    In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes.

  8. ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study

    Daniel Podzamczer


    Full Text Available Introduction: Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART. The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients’ well-being, assessed by several validated measures. Methods: Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index, quality of life (EQ-5D, EUROQoL & MOS-HIV, adherence (SMAQ, preference of treatment and perceived ease of medication (ESTAR through 48 weeks were performed. Results: Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80% were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4% had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6% patients switched from a NNRTI (84.8% from EFV/FTC/TDF and 33 (26.4% from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%, CNS adverse events (40.8%, gastrointestinal (19.2% and metabolic disorders (19.2%. At the time of this analysis (week 16, four patients (3.2% discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2% were virologically suppressed (<50 copies/mL. The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55 to week 4 (10.89±12.36 & week 16 (10.81±12.62, p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1. Adherence to therapy significantly and progressively increased (SMAQ from

  9. Perturbation of lipids and glucose metabolism associated with previous 2,4-D exposure: a cross-sectional study of NHANES III data, 1988-1994

    Schreinemachers Dina M


    Full Text Available Abstract Background Results from previous population studies showed that mortality rates from acute myocardial infarction and type-2 diabetes during the 1980s and 1990s in rural, agricultural counties of Minnesota, Montana, North and South Dakota, were higher in counties with a higher level of spring wheat farming than in counties with lower levels of this crop. Spring wheat, one of the major field crops in these four states, was treated for 85% or more of its acreage with chlorophenoxy herbicides. In the current study NHANES III data were reviewed for associations of 2,4-dichlorophenoxy acetic acid (2,4-D exposure, one of the most frequently used chlorophenoxy herbicides, with risk factors that are linked to the pathogenesis of acute myocardial infarction and type-2 diabetes, such as dyslipidemia and impaired glucose metabolism. Methods To investigate the toxicity pattern of chlorophenoxy herbicides, effects of a previous 2,4-D exposure were assessed by comparing levels of lipids, glucose metabolism, and thyroid stimulating hormone in healthy adult NHANES III subjects with urinary 2,4-D above and below the level of detection, using linear regression analysis. The analyses were conducted for all available subjects and for two susceptible subpopulations characterized by high glycosylated hemoglobin (upper 50th percentile and low thyroxine (lower 50th percentile. Results Presence of urinary 2,4-D was associated with a decrease of HDL levels: 8.6% in the unadjusted data (p-value = 0.006, 4.8% in the adjusted data (p-value = 0.08, and 9% in the adjusted data for the susceptible subpopulation with low thyroxine (p-value = 0.02. An effect modification of the inverse triglycerides-HDL relation was observed in association with 2,4-D. Among subjects with low HDL, urinary 2,4-D was associated with increased levels of triglycerides, insulin, C-peptide, and thyroid stimulating hormone, especially in the susceptible subpopulations. In contrast, subjects with

  10. Late tamoxifen in patients previously operated for breast cancer without postoperative tamoxifen: 5-year results of a single institution randomised study

    Bidoli Ettore


    Full Text Available Abstract Background A population of breast cancer patients exists who, for various reasons, never received adjuvant post-operative tamoxifen (TAM. This study was aimed to evaluate the role of late TAM in these patients. Methods From 1997 to 2003, patients aged 35 to 75 years, operated more than 2 years previously for monolateral breast cancer without adjuvant TAM, with no signs of metastases and no contraindication to TAM were randomized to TAM 20 mg/day orally for 2 years or follow-up alone. Events were categorized as locoregional relapse, distant metastases, metachronous breast cancer, tumours other than breast cancer and death from any causes, whichever occurred first. The sample size (197 patients per arm, plus 10% allowance was based on the assumption of a 30% decrease in the number of events occurring at a rate of 5% annually in the 10 years following randomization. Four hundred and thirty-three patients were randomized in the study (TAM 217, follow-up 216. Patients characteristics (TAM/follow-up included: median age 55/55 years, median time from surgery 25/25 months (range, 25-288/25-294, in situ carcinoma 18/24, oestrogen receptor (ER positive in 75/68, negative in 70/57, unknown in 72/91 patients. Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients. Results Thirty-six patients prematurely discontinued TAM after a median of 1 month, mostly because of subjective intolerance. Eighty-three events (TAM 39, follow-up 44 occurred: locoregional relapse in 10/8, distant metastases in 14/16, metachronous breast cancer in 4/10, other tumours in 11/10 patients. Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients (1 vs 10, p = 0.005. Event-free survival was similar in both groups of patients. Conclusions This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically

  11. In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

    Rivero, Javier; Luzardo, Octavio P., E-mail:; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.


    Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

  12. Evaluation of the Widal tube agglutination test for the diagnosis of typhoid fever among children admitted to a rural hdospital in Tanzania and a comparison with previous studies

    Malahiyo Rajabu


    Full Text Available Abstract Background The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi. However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. Methods We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." Results We found that 16 (1% of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. Conclusion Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of ≥ 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable.

  13. Effects of testosterone replacement therapy on nocturia and quality of life in men with hypogonadism: a subanalysis of a previous prospective randomized controlled study in Japan.

    Shigehara, Kazuyoshi; Konaka, Hiroyuki; Koh, Eitetsu; Izumi, Koji; Kitagawa, Yasuhide; Mizokami, Atsushi; Nakashima, Takao; Shimamura, Masayoshi; Iwamoto, Teruaki; Namiki, Mikio


    We investigated the effects of testosterone replacement therapy (TRT) on nocturia and general health among men with hypogonadism and nocturia. From our previous EARTH study population, 64 patients with a clinical diagnosis of nocturia (two or more times per one night) and hypogonadism, comprising the TRT group (n = 31) and controls (n = 33), were included in this analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 6 months. All patients responded to the following questionnaires: International Prostatic Symptoms Score (IPSS), Aging Male Symptoms (AMS) score and Short Form-36 health survey at baseline and 6-month visit. These categories were compared based on changes from baseline to the 6-month visit between TRT and control groups. At the 6-month visit, the TRT group had a significant decrease in IPSS question no. 7 and AMS question no. 4, whereas no significant changes were observed in the control group. Additionally, role limitation because of health program, vitality and mental health domains were significantly improved in the TRT group. Six-month TRT may improve nocturia, sleep conditions and quality of life among men with hypogonadism and nocturia.

  14. Efficacy of confrontational counselling for smoking cessation in smokers with previously undiagnosed mild to moderate airflow limitation: study protocol of a randomized controlled trial

    Huibers Marcus JH


    Full Text Available Abstract Background The use of spirometry for early detection of chronic obstructive pulmonary disease (COPD is still an issue of debate, particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation. We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed "confrontational counselling"; a patient-centred approach which involves specific communication skills and elements of cognitive therapy. An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions. The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation. Methods/Design The study design is a randomized controlled trial comparing confrontational counselling delivered by a respiratory nurse combined with nortriptyline for smoking cessation (experimental group, health education and promotion delivered by a respiratory nurse combined with nortriptyline for smoking cessation (control group 1, and "care as usual" delivered by the GP (control group 2. Early detection of smokers with mild to moderate airflow limitation is achieved by means of a telephone interview in combination with spirometry. Due to a comparable baseline risk of airflow limitation and motivation to quit smoking, and because of the standardization of number, duration, and scheduling of counselling sessions between the experimental group and control group 1, the study enables to assess the "net" effect of confrontational counselling. The study has been ethically approved and registered. Discussion Ethical as well as methodological considerations of the study are discussed in this protocol. A

  15. Renal tubular and adrenal medullary tumors in the 2-year rat study with canagliflozin confirmed to be secondary to carbohydrate (glucose) malabsorption in the 15-month mechanistic rat study.

    De Jonghe, Sandra; Johnson, Mark D; Mamidi, Rao N V S; Vinken, Petra; Feyen, Bianca; Lammens, Godelieve; Proctor, Jim


    During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Experimental Studies on Intra-vas Device in Rats

    叶阳; 陈振文; 邢志军; 吴燕婉


    In the present study,male SD rats were used to evaluate the efficacy of a new vas occlusion device,intravas device(IVD) and long-term morphological change of both vas and IVD.After inserting IVD into bilateral vas,all rats(9)became sterilized as proved by mate test and the fact that no sperm was found in female vagina after mat-ing.Half a year later,there had been a large amount of sperm in vas lumen dilated and sperm granuloma was found in the proximal end of IVD.Scanning electron microscope studies showed that nylon threads in IVD were covered by protein like matter.There were some normal sperms between the nylon sutures.A few sperms with deformed structure were found in the distal end of IVD.Conclusion:our studies showed that IVD could be an effective device in SD rats.Fluid and some deformed sperms may pass through IVD,but these sperms have no fertility.The mechanism of IVD needs to be further investigated.

  17. Surgical Management of Multijoint Septic Arthritis due to Rat-Bite Fever in a Pediatric Patient: A Case Study

    Adam M. Wegner


    Full Text Available In the United States, rat-bite fever is a rare systemic illness principally caused by Streptobacillus moniliformis, an organism found in the nasopharyngeal flora of rodents. Infection through direct exposure to rat excreta such as saliva, urine, or feces can lead to fever, rash, and an asymmetric migratory polyarthritis. As rodents are becoming more popular as pets, more pediatric cases are being documented. We report a pediatric case of delayed onset septic arthritis in the left wrist and right knee due to S. moniliformis from a rat bite. Previously reported pediatric case studies of suppurative arthritis due to S. moniliformis have only involved the hip. This case study demonstrates the importance of a thorough exposure history and consideration of zoonotic infections as a cause of septic arthritis in a pediatric patient that requires antibiotics and surgical intervention.

  18. Ground-water quality in Geauga County, Ohio; review of previous studies, status in 1999, and comparison of 1986 and 1999 data

    Jagucki, Martha L.; Darner, Robert A.


    Most residents in Geauga County, Ohio, rely on ground water as their primary source of drinking water. With population growing at a steady rate, the possibility that human activity will affect ground-water quality becomes considerable. This report presents the results of a study by the U.S. Geological Survey (USGS), in cooperation with the Geauga County Planning Commission and Board of County Commissioners, to provide a brief synopsis of work previously done within the county, to assess the present (1999) ground-water quality, and to determine any changes in ground-water quality between 1986 and 1999. Previous studies of ground-water quality in the county have consistently reported that manganese and iron concentrations in ground water in Geauga County often exceed the U.S. Environmental Protection Agency (USEPA) Secondary Maximum Contaminant Level (SMCL). Road salt and, less commonly, oil-field brines and volatile organic compounds (VOCs) have been found in ground water at isolated locations. Nitrate has not been detected above the USEPA Maximum Contaminant Level (MCL) of 10 milligrams per liter as N; however, nitrate has been found in some locations at levels that may indicate the effects of fertilizer application or effluent from septic systems. Between June 7 and July 1, 1999, USGS personnel collected a total of 31 water-quality samples from wells completed in glacial deposits, the Pottsville Formation, the Cuyahoga Group, and the Berea Sandstone. All samples were analyzed for VOCs, sulfide, dissolved organic carbon, major ions, trace elements, alkalinity, total coliforms, and Escherichia coli bacteria. Fourteen of the samples also were analyzed for tritium. Water-quality data were used to determine (1) suitability of water for drinking, (2) age of ground water, (3) stratigraphic variation in water quality, (4) controls on water quality, and (5) temporal variation in water quality. Water from 16 of the 31 samples exceeded the Geauga County General Health

  19. Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: Analysis from the PREDICT and CHARIOT studies.

    Roberts, Stuart K; Mitchell, Joanne; Leung, Reynold; Booth, David; Bollipo, Steven; Ostapowicz, George; Sloss, Andrew; McCaughan, Geoffrey W; Dore, Gregory J; Thompson, Alexander; Crawford, Darrell Hg; Sievert, William; Weltman, Martin; Cheng, Wendy; George, Jacob


    The aim of this study was to examine the distribution of interferon lambda-3 (IFN-λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-λ3 genotype frequency among the different ethnic populations. This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN-λ3 single nucleotide polymorphisms were genotyped by the Applied Biosystems's Taqman single nucleotide polymorphism genotyping assay. Between May 2012 and June 2012, 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high-dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN-λ3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN-λ3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN-λ3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001). The distribution of IFN-λ3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self-reported Asians and Maori/Pacific Islanders than Caucasians, Aboriginals, and Mediterraneans. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty

  20. Chronic toxicity study of Hyptis suaveolens (L. Poit in rats

    Bunjong Chaorai


    Full Text Available The effect of water extract of Hyptis suaveolens (H. suaveolens was evaluated for 6-month chronic toxicity in Wistar rats. Control group received distilled water orally 10 ml/kg/day. The extract was orally given to five treatment groups at the doses of 5, 50, 250, 500 and 500 mg/kg/day for 6 months. The last group was served as the recovery group. Changes in the body weights, actual and relative organ weights were not significantly demonstrated in all groups throughout the study. The results of hematological, biochemical parameters and histopathological lesions showed that the extract did not produce any significant doserelated changes. Therefore, it may be concluded that the extract of H. suaveolens at the given doses did not produce any significant toxic effect in rats during 6-month period of the treatment.

  1. [Preliminary study on efficacy and mechanism of Atractylodes Macrocephelae Rhizoma extracts in metabolic hyperlipidemia rats].

    Tang, Qi-jing; Chen, Su-hong; Pan, Dan-dan; Li, Bo; Lv, Gui-yan


    Hyperlipidemia is a major factor causing coronary heart disease and atherosclerosis. The high-density lipoprotein cholesterol (HDL-C) is a major indicator for measuring lipid levels. However, there is no an effective medicine that can obviously increase HDL-C at present. According to previous laboratory studies, atractylodes macrocephalae extracts could significantly increase HDL-C level. In this study, the metabolic hyperlipidemia rat model was established by feeding high-sugar and fat diets and alcohol-drinking to explore the effect and mechanism of atractylodes macrocephalae extracts on hyperlipidemia rats. According to the findingins, different doses of atractylodes macrocephalae extracts could reduce the levels of TC, TG, LDL-C, ACAT and increase the contents of LCAT, HDL-C. Particularly, the atractylodes macrocephalae extracts (100 mg · kg(-1) group showed increase in HDL-C by about 50% and significant declines in HMG-CoA reductase, TC, TG. In conclusion, Atractylodes Macrocephelae Rhizoma extracts could effectively regulate the dyslipidemia of hyperlipidemia rats, especially on HDL-C. Its mechanism may be related to reduction in cholesterol synthesis by inhibiting HMG-CoA reductase in livers and increase in lipid metabolism and transport by regulating LCAT and ACAT levels.

  2. Experimental study on aortic remodeling in sinoaortic denervated rats

    MIAO Chao-yu; TAO Xia; GUAN Yun-feng; YANG You-cai; CHU Zheng-xu; SU Ding-feng


    Objective: To study the aortic remodeling produced by chronic sinoaortic denervation (SAD) and its time course, and to study the role of humoral factor in the SAD-induced aortic remodeling. Methods: In rats with chronic SAD or sham operation, the aortic structure was measured by computer-assisted image analysis, the aortic function by isolated artery preparation, and angiotensin Ⅱ concentration by radioimmunoassay. Results and Conclusion: The aortic structural remodeling developed progressively at 4, 8, 16 and 32 weeks after SAD. Aortic structural remodeling after SAD expressed mainly as aortic hypertrophy due to SMC growth and collagen accumulation. The aortic contraction elicited by norepinephrine (NE) was progressively increased 8, 16 and 32 weeks after SAD. The aortic relaxation elicited by acetylcholine (ACh) was depressed 8, 16 and 32 weeks after SAD. In addition, in 32-week SAD rats the NE-induced contraction was not increased by endothelial denudation. These indicated that the increased contraction and depressed relaxation after SAD were related to the change of endothelium and/or the change of interaction between endothelium and SMC. In 10-week SAD rats, plasma angiotensin Ⅱ concentration remained unchanged, whereas aortic angiotensin Ⅱ concentration was significantly increased, suggesting that activation of tissue renin-angiotensin system may be involved in SAD-induced aortic remodeling.

  3. Achilles tendinosis: a morphometrical study in a rat model.

    Silva, Rafael Duarte; Glazebrook, Mark Anthony; Campos, Vinicius Castro; Vasconcelos, Anilton Cesar


    This study addresses the morphopathogenesis of Achilles tendinosis, using a rat model and presenting quantitative analysis of time-dependent histological changes. Thirty Wistar rats were used, randomly split in experimental and control groups. Animals of the experimental group were submitted to a treadmill running scheme. Five animals of each group were euthanized at four, eight and sixteen weeks. Achilles tendons were collected and processed routinely for histopath sections. Slides were stained by Hematoxylin-Eosin, Picrosirius Red, Alcian Blue, AgNOR, TUNEL and evaluated morphometrically. Cellular density decreased slightly along the time and was higher in the experimental group than in controls at fourth, eighth and sixteenth weeks. Fiber microtearing, percentual of reticular fibers and glycosaminoglycans content increased along the time and were higher in experimental group than in controls at all-time intervals. AgNOR labeling here interpreted as a marker of transcription activity was higher in the experimental groups than in controls at all-time intervals. Apoptotic cells were more frequent and diffusely distributed in tendinosis samples than in control groups. These results suggest that as mechanical overload is becoming chronic, cellular turnover and matrix deposition increases leading to tendinosis. The combination of staining techniques and morphometry used here to describe the evolution of lesions occurring in a rat model system has proved to be suited for the study of induced Achilles tendinosis.

  4. A study of the mechanism of butachlor-associated gastric neoplasms in Sprague-Dawley rats.

    Thake, D C; Iatropoulos, M J; Hard, G C; Hotz, K J; Wang, C X; Williams, G M; Wilson, A G


    Long term administration of butachlor to Sprague-Dawley rats in a previous bioassay, resulted in the induction of gastric neoplasms which occurred only in the highest dose group (3000 ppm in the diet), primarily in females and specifically in the fundic region. The tumors were a composite of highly undifferentiated enterochromaffin-like (ECL) cells and mucus producing cells with morphologic characteristics unlike those previously described in the rat stomach. Mucosal atrophy of marked intensity was a consistent feature of the gastric mucosa in animals from the highest dose group. An additional long term study was conducted in female Sprague-Dawley rats at dietary levels of 0, 100, 1000 and 3000 ppm to explore the mechanism(s) involved in the formation of these neoplasms. Cell proliferation was evaluated in both fundic and pyloric regions of the stomachs of rats at multiple time periods from 14 days to 26 months. Mucosal thickness was determined in the fundic region at the same time intervals as were used for cell proliferation studies. Gastric pH and gastric acid production were measured after approximately 21 months of exposure. Serum gastrin levels were analyzed at 14, 60, and 120 days and at 6, 18 and 20 months. Cholecystokinin (CCK)/gastrin receptor binding studies were conducted on samples of four tumors and pooled fundic mucosa from five animals in the control group. Cell proliferation was increased in both the neck and base regions of the fundic mucosa at nearly all time points measured from 14 days to 26 months. The magnitude of the changes in the base region were substantially greater than those in the neck region. Fundic mucosal thickness was decreased beginning at the 30-day time point and continued at all intervals, being less than one half that of controls at 20 and 26 months. Gastric pH in rats from the highest dose was elevated to nearly twice control levels at 21 months. Gastric acid secretion was dramatically decreased in animals from the 3000 ppm

  5. Methylene chloride: two-generation inhalation reproductive study in rats

    Nitschke, K.D.; Eisenbrandt, D.L.; Lomax, L.G.; Rao, K.S.


    Reproductive parameters in Fischer 344 rats were evaluated following inhalation of methylene chloride (MeCl/sub 2/) for two successive generations. Thirty male and female rats were exposed to 0, 100, 500, or 1500 ppm MeCl/sub 2/ for 6 hr/day, 5 days/week for 14 weeks and then mated to produce f1 litters. After weaning, 30 randomly selected f1 pups/sex/group were exposed to MeCl/sub 2/ for 17 weeks and subsequently mated to produce f2 litters. Reproductive parameters examined included fertility, litter size and neonatal growth, and survival. All adults and selected weanlings were examined for grossly visible lesions. Tissues from selected weanlings were examined histopathologically. No adverse effects on reproductive parameters, neonatal survival, or neonatal growth were noted in animals exposed to methylene chloride in either the f0 or f1 generations. Similarly, there were no treatment-related gross pathologic observations in f0 or f1 adults or f1 and f2 weanlings. Histopathologic examination of tissues from f1 and f2 weanlings did not reveal any lesions attributed to methylene chloride. Thus, exposure of rats to concentrations as high as 1500 ppm methylene chloride, which has been shown in a 2-year study to produce treatment-related effects, did not affect any reproductive parameters.

  6. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats.

    Waalkens-Berendsen, D H; Kuilman-Wahls, M E M; Bär, A


    The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to be pregnant in the control, low-, mid-, and high-dose group, respectively. The NHDC treatment was well tolerated and all animals survived till the end of the study. Body weights (bw) and body weight gains did not differ between controls and NHDC treatment groups. The intake of NHDC was 0.8-0.9, 1.6-1.7, and 3.1-3.4 g/kg bw/day for the low-, mid-, and high-dose group, respectively. Except for cecal enlargement, there were no changes observed at necropsy which could be related to the NHDC treatment. All dams had viable fetuses. The fecundity and gestation index, the number of corpora lutea, implantation sites, live and dead fetuses, early and late resorptions, pre- and post-implantation losses, and sex-ratio were not affected by the treatment. There were no differences for the mean weight of the gravid and empty uterus, ovaries, and placenta between the NHDC treatment groups and the controls. Examination of the fetuses for external, visceral, and skeletal changes did not reveal any fetotoxic, embryotoxic or teratogenic effects of NHDC. In conclusion, no adverse effects were observed at NHDC levels of up to 5% of the diet, the highest dose level tested, at which the rats consumed about 3.3g/kg body weight/day. The observed cecal enlargement is a well-known physiological, adaptive response to the ingestion of high doses of a low-digestible substance and is generally accepted to lack toxicological relevance.

  7. The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study.

    Flendrie, M.; Creemers, M.C.W.; Welsing, P.M.J.; Riel, P.L.C.M. van


    OBJECTIVE: To investigate the influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in rheumatoid arthritis (RA) and to compare it to infliximab in combination with other disease-modifying anti-rheumatic drugs. METHODS: RA patients starting infliximab the

  8. Erlotinib dosing-to-rash: A phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer

    A. mita (Alain); K. Papadopoulos (K.); M.J.A. de Jonge (Maja); G. Schwartz (G.); J. Verweij (Jaap); A. Ricart (A.); Q.S.C. Chu (Q. S C); A.W. Tolcher (A. W.); L. Wood (Lori); S.W. McCarthy (Stanley); M. Hamilton; K.K. Iwata (Kenneth); B. Wacker; K. de Witte (Karel); E.K. Rowinsky (Eric Keith)


    textabstractBackground: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacok

  9. Phase I study of cisplatin, hyperthermia, and lapatinib in patients with recurrent carcinoma of the uterine cervix in a previously irradiated area

    E.V. Meerten (Esther Van); M. Franckena (Martine); E.A.C. Wiemer (Erik); L.V. Doorn (Lena Van); J. Kraan (Jaco); A.M. Westermann (Anneke); S. Sleijfer (Stefan)


    textabstractBackground. Patients with recurrent cervical cancer in a previously irradiated area might benefit from cisplatin combined with hyperthermia. Lapatinib inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and HER2. Overexpression of EGFR and

  10. Impact of previous percutaneous transluminal coronary angioplasty and/or stenting revascularization on outcomes after surgical revascularization : insights from the imagine study

    Chocron, Sidney; Baillot, Richard; Rouleau, Jean Lucien; Warnica, Wayne J.; Block, Pierre; Johnstone, David; Myers, Martin G.; Calciu, Cristina Dana; Nozza, Anna; Martineau, Pierre; van Gilst, Wiek H.


    Aim To determine the impact of previous coronary artery revascularization by percutaneous transluminal coronary angioplasty and/or stenting (PCI) on outcome after subsequent coronary artery bypass grafting (CABG). Methods and results The ischaemia management with Accupril post-bypass Graft via Inhib

  11. Behavioral and neurochemical changes in response to acute stressors: influence of previous chronic exposure to immobilization.

    Pol, O; Campmany, L; Gil, M; Armario, A


    The effect of daily (2 h) exposure to immobilization (IMO) for 15 days on the behavioral and neurochemical responses of adult male rats to acute stress caused by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic exposure to IMO did not alter noradrenaline (NA), 3-methoxy,4-hydroxyphenyletileneglycol-SO4 (MHPG-SO4), serotonin, or 5-hydroxindoleacetic acid (5-HIAA) concentrations in any brain area as measured approximately 20 h after the last exposure to IMO. Exposure to behavioral tests did not modify neurochemical variables except NA levels in the hypothalamus of nonchronically stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats. These decreases in response to the two acute stressors were not observed in chronically stressed rats. However, MHPG-SO4 levels increased to the same extent in control and chronically stressed rats after exposure to the acute stressors. Likewise, increased 5-HIAA concentrations observed in response to acute stressors were similar in control and chronically stressed rats. The inhibition of activity (areas crossed and rearing) in the holeboard caused by acute IMO was less marked in rats previously exposed to the same stressor than in control rats, but the response to shock was similar. In the forced swim test, acute IMO decreased struggling in control rats but tended to increase it in chronically stressed rats. The response to shock followed the same pattern as that to IMO, although it was slight.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Clinical evaluation of recombinant factor VIII preparation (Kogenate) in previously treated patients with hemophilia A: descriptive meta-analysis of post-marketing study data.

    Yoshioka, A; Fukutake, K; Takamatsu, J; Shirahata, A


    The safety and efficacy of Kogenate, a recombinant factor VIII (rFVIII) preparation for the treatment of bleeding episodes, were studied in a 123-patient meta-analysis population of previously treated patients (PTPs), including 15 enrolled in the registration Phase III trial (PTP-I group), 93 from the post-marketing special investigation (PTP-II group), and 15 from short-term special investigations in surgery or tooth extraction (SI group). These patients (82 severe, 31 moderate, 9 mild, and 1 unknown), aged 11 months to 72 years, were enrolled in 28 centers in Japan. Blood samples taken at the baseline and at 3, 6, 9, 12, 18, and 24 months after the introduction of Kogenate were evaluated for FVIII inhibitor antibodies, antibodies formed against trace proteins derived from the rFVIII production process, and for general changes in laboratory test results. Mean exposure to Kogenate was 1103 days in PTP-I, 86 days in PTP-II, 27 days in patients in surgery, and 2 days in patients with tooth extraction. Assessment of FVIII inhibitor activity was conducted in 115 of the 123 patients by means of the Bethesda assay. Twelve patients were found to have a low titer of FVIII inhibitor (0.5-3.0 BU/mL) prior to any administration of Kogenate, and 103 were inhibitor-negative at the baseline. Among this latter group, 3 patients (2.9%) tested inhibitor-positive, with titers ranging from 1.2 to 2.1 BU/mL, with 4 patients below 1.0 BU/mL. One patient in the 11 PTPs investigated (PTP-I) developed antibodies against baby hamster kidney protein and mouse immunoglobulin G, but these findings were transient and asymptomatic. Hemostasis was achieved (markedly effective or effective) in 3666 of the 3855 bleeding episodes (95.1%) observed in 108 patients. Only 1 infusion was necessary in 3790 (98.3%) of these episodes. These data indicate that Kogenate is safe and very effective for the treatment of bleeding in PTPs with hemophilia A.

  13. Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

    Philip M. Coan


    Full Text Available We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR and Wistar Kyoto (WKY rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the

  14. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    Rosanna Ghinai


    Full Text Available Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

  15. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W; Bailey, Robin L; Agana, Nsiire; Mabey, David C W; Chen, Cheng-Yen; Adu-Sarkodie, Yaw; Marks, Michael


    Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

  16. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study

    Schramm, Tina Ken; Gislason, Gunnar Hilmar; Vaag, Allan


    % confidence intervals): 1.32 (1.24-1.40), glibenclamide: 1.19 (1.11-1.28), glipizide: 1.27 (1.17-1.38), and tolbutamide: 1.28 (1.17-1.39) were associated with increased all-cause mortality in patients without previous MI. The corresponding results for patients with previous MI were as follows: glimepiride: 1.......30 (1.11-1.44), glibenclamide: 1.47 (1.22-1.76), glipizide: 1.53 (1.23-1.89), and tolbutamide: 1.47 (1.17-1.84). Results for gliclazide [1.05 (0.94-1.16) and 0.90 (0.68-1.20)] and repaglinide and [0.97 (0.81-1.15) and 1.29 (0.86-1.94)] were not statistically different from metformin in both patients...... without and with previous MI, respectively. Results were similar for cardiovascular mortality and for the composite endpoint. Conclusion Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular...

  17. Treinamento aeróbico prévio à compressão nervosa: análise da morfometria muscular de ratos Aerobic training previous to nerve compression: morphometry analysis of muscle in rats

    Elisangela Lourdes Artifon


    of sciatic pain concerning morphometric parameters of soleus muscles of rats. MATERIALS AND METHODS: 18 rats were divided into three groups: sham (dip, 30 seconds, regular exercise (swimming, 10 minutes daily and progressive aerobic training (swimming, progressive time from 10 to 60 minutes daily. After six weeks of exercise, rats were subjected to the experimental model of sciatic pain. On the third day after injury, they were killed and their soleus muscles were dissected, weighed and processed for histological analysis. The analyzed variables were: muscle weight, cross-sectional muscle area and mean diameter of muscle fibers. RESULTS: Statistically significant difference was observed for all groups when compared to control muscle and that submitted to sciatic injury. Intergroup analysis showed no statistically significant difference for any of the variables. CONCLUSION: Both regular physical exercise and aerobic training had no preventive or aggravating effects on the consequences of functional inactivity after sciatica.

  18. An automatic recording system for the study of escape from fear in rats.

    Li, Ming; He, Wei


    Escape from fear (EFF) is an active response to a conditioned stimulus (CS) previously paired with an unconditioned fearful stimulus (US), which typically leads to the termination of the CS. In this paradigm, animals acquire two distinct associations: S-S [CS-US] and R-O [response-outcome] through Pavlovian and instrumental conditioning, respectively. The present study describes a computer controlled automatic recording system that captures the development of EFF and allows the determination of the respective roles of S-S and R-O associations in this process. We validated this system by showing that only rats subjected to a simultaneous CS-US conditioning (i.e., CS and US occur together at the beginning of each trial) acquired EFF, not those subjected to an unpaired CS-US conditioning. Paired rats had a progressively increased number of EFF and significantly shorter escape latencies than unpaired rats across the 5-trial blocks on the test day. However, during the conditioning phase, the unpaired rats emitted more 22kHz ultrasonic vocalizations, a validated measure of conditioned reactive fear responses. Our results demonstrate that the acquisition of EFF is contingent upon pairing of the CS with the US, not simply the consequence of a high level of generalized fear. Because this commercially available system is capable of examining both conditioned active and reactive fear responses in a single setup, it could be used to determine the relative roles of S-S and R-O associations in EFF, the neurobiology of conditioned active fear response and neuropharmacology of psychotherapeutic drugs.

  19. Biochemical and morphological study on hepatotoxicity of azathioprine in rat.



    Full Text Available Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.

  20. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats

    Waalkens-Berendsen, D.H.; Kuilman-Wahls, M.E.M.; Bär, A.


    The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to

  1. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats

    Waalkens-Berendsen, D.H.; Kuilman-Wahls, M.E.M.; Bär, A.


    The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to

  2. Morphological studies on the healing process of tooth extraction wounds in whole body irradiated rats

    Hosokawa, Yoichiro (Hokkaido Univ., Sapporo (Japan). School of Dentistry)


    The present studies were performed to investigate the healing process of the tooth extraction wound in whole body irradiated rats and to clarify the effect of irradiation on bone metabolism. One hundred and seven Wistar rats of about 100 g body weight were used and divided into 3 groups. Whole body irradiated rats were given single exposure with a dose of 8 Gy. The region of the left upper molars of local irradiated rats as controls, was exposed to 8 Gy. On the 7th day after irradiation, the left upper first molar of each rat was extracted. The rats were sacrificed at intervals of 1 to 14 days after extraction. Non-irradiated rats were sacrificed at the same intervals after extraction. The maxillary bone including the extraction wound was evaluated, histologically, histometrically and ultrastructurally. From the histological and histometrical findings, the difference of the healing process between non-irradiated rats and locally irradiated rats is not significant. In whole body irradiated rats, the healing process especially in the socket was disturbed. The osteoblastic new bone formation following production of granulation tissue was interfered with. Ultrastructurally, the cytoplasmic organellae were poorly developed in the osteoblast and osteoid formation was reduced in the socket. But periosteal new bone formation was the same as that of the locally irradiated rats. In whole body irradiated rats, the osteoclasts in the interradicular alveolar bone were decreased and have smaller nuclei, compared with non-irradiated and locally irradiated rats. Histometrically, the amount of bone loss was decreased in whole body irradiated rats. Ultrastructurally, the cyoplasmic organellae and ruffled border were poorly developed in the osteoclasts of whole body irradiated rats. The findings suggested that irradiation induced cytological changes not only in osteoblasts but in osteoclasts and these changes resulted in the delayed healing of extraction wound. (author) 106 refs.

  3. Subacute toxicopathological studies of methotrexate in Wistar rats

    N. N. Patel


    Full Text Available Aim: A toxico-pathological study was undertaken to assess the effects of Methotrexate administration in Wistar rats by performing the hematology, serum biochemical analysis and associated histopathological changes in visceral organs. Materials and Methods: Rats in 4 treatment groups with 6 male and 6 female rats each were administered methotrexate (Group II to IV at the dose rate of 0.062, 0.125 and 0.250 mg/kg body weight respectively and distilled water (Group I as vehicle control for 28 days. Hematological parameters viz., total erythrocyte count, haemoglobin, packed cell volume, MCV, MCH and MCHC, total leukocyte count and differential leukocyte count and serum biochemical parameters viz., aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum creatinine, blood urea nitrogen, total protein, albumin, globulin (Calculated were estimated after 28 days. Necropsy examination was performed in all sacrificed animals and gross lesions were recorded. Tissue samples (lung, liver, kidney, intestine, testes and heart were collected in 10% formalin solution for histo-pathological examination. Results: The dose dependent reduction in body weight, feed consumption, RBCs count, packed cell volume, haemoglobin, total leucocyte count, neutrophil count, total protein and albumin was observed in animals of group II, III and IV along with significant increase in lymphocyte count, AST, ALT, AKP, creatinine and BUN in animals of methotrexate treated group IV followed by group III. No significant change in monocyte, eosinophil and basophil counts were observed in any treatment groups. All the rats exposed to methotrexate at three different dose levels revealed dose dependent pathological changes characterized by degeneration, necrosis, congestion, haemorrhage and vascular changes. The main target organs affected were liver, kidney, lungs and testes. Conclusion: It can be concluded from this study that sub-acute exposure to methotrexate

  4. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    Lopez-Saura Pedro


    Full Text Available Abstract Background Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC or squamous cell skin carcinomas (SCSC. Methods Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Results Sixteen elder (median 70 years-old patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination, 40% PR (>30% tumor reduction, and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. Conclusion The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Trial registration Current Controlled Trials RPCEC00000052.

  5. Postmortem acinar autolysis in rat sublingual gland: a morphometric study

    Leticia Rodrigues Nery


    Full Text Available ABSTRACT OBJECTIVE: To analyze and to quantify morphological acinar postmortem changes in rat sublingual glands (SLG. MATERIAL AND METHODSs: Fifty rats were divided into two groups of 25 animals each. Group I was used for morphological and morphometric evaluations and group II for the determination of gland density and processed gland volume. Acinar autolytic changes were studied at 0 (control group, 3, 6, 12 and 24 h postmortem periods. The morphometric analysis of the volume density (Vv and total volume (Vt of intact (ia and autolyzed (aa acini was performed under light microscopy using a Zeiss II integration grid with 100 symmetrically distributed points. RESULTS: Morphologically, temporal progressive nuclear alterations and gradual loss of the structural architecture of acinar cells were found. Regarding quantitative results, both the Vvaa and the Vvia showed statistically significant differences among all postmortem periods (p0.05, respectively. Vtaa increased from 0.18 mm³ at 0 h to 38.17 mm³ at 12 h, while Vtia showed a decrease from 33.47 mm³ to 0 mm³ between 3-24 h postmortem. Data concerning Vtaa were adjusted by two-variable linear regression, obtaining the equation: y=-3.54 + 3.38x (r²=0.90. The Vtaa growth rate calculated by this equation was 3.38 mm³/h between 0-12 h. CONCLUSION: Acinar autolysis on rat SLG demonstrated the most significant signs during the first 6 h postmortem and was widely spread through the gland at 12 h.

  6. Behaviour-toxicological studies in rats exposed to cadmium

    Wurms, F.


    Studies were carried out on a behaviour-toxicological animal model in order to find out whether Cd may induce a minimal cerebral dysfunction and whether this effect outlasts prenatal and neonatal exposure. For this purpose, pregnant Wistar rats were given daily s.c. injections of 0.15 mg Cd/kg for a period of 50 d until weaning of the young rats at the age of 4 weeks. The male offspring were either given no Cd until the age of 100 d when the tests were started (A-group), or they were given daily s.c. injections of the above dose (B-group). The third group consisted of NaCl-injected control animals of the same age. The behaviour-toxicological tests were carried out in a Lashley test bench, a swimming labyrinth, and an open field test under blind conditions. Cd concentrations measured in the brain, liver and kidneys at different times during the investigation showed that the placenta-brain barrier or blood-brain barrier was not fully efficient under the experimental conditions. Cd concentrations in neonates were 2.5 times higher in the brain and 5 times higher in the liver and kidneys than in control animals. In both Cd groups, visual discrimination was impaired. In the swimming labyrinth and open field test, significant changes were observed only in B-group rats. Impaired visual differentiation was observed in both groups. However, it is impossible at the present stage of investigation to decide whether the direct Cd lesions are the only cause of these behaviour-toxicological effects.

  7. Pharmacokinetic/pharmacodynamic studies on exenatide in diabetic rats

    Xin-gang LI; Liang LI; Xuan ZHOU; Ye CHEN; Yu-peng REN; Tian-yan ZHOU; Wei LU


    Aim:To quantitatively evaluate the blood glucose-lowering effect of exenatide in diabetic rats.Methods:Male Harlan-Sprague-Dawley rats were treated with high-fat diet/streptozotocin to induce type 2 diabetes.After subcutaneous administration of a single dose of exenatide (4.2,42,or 210 pg/kg),serum exenatide,insulin concentration and blood glucose were measured.The pharmacokinetics of exenatide was characterized by a two-compartment model with first-order absorption.Insulin turnover was characterized by an effect compartment and indirect response combined model.Glucose turnover was described using an indirect response model with insulin (in effect compartment) stimulating glucose disposition and insulin (in insulin compartment) inhibiting glucose production simultaneously.The model parameters were estimated using nonlinear mixed-effects model program.Visual predictive check and model evaluation were used to make assessments.Results:Exenatide exhibited rapid absorption with ka=4.45 h-1,and the two-compartment model well described its pharmacokinetic profile.For the pharmacodynamic model,exenatide increased insulin release with the estimated Sm1 of 0.822 and SC50 of 4.02 pg/L.It was demonstrated that insulin stimulated glucose dissipation (Sm2=0.0513) and inhibited the production of glucose (Im=0.0381).Visual predictive check and model evaluation study indicated that a credible model was developed.Conclusion:The glucose-lowering effect of exenatide in diabetic rats is reliably described and predicted by the combined effect compartment/indirect response model.

  8. Study on Application of Static Magnetic Field for Adjuvant Arthritis Rats

    Norimasa Taniguchi


    Full Text Available In order to examine the effectiveness of the application of static magnetic field (SMF on pain relief, we performed a study on rats with adjuvant arthritis (AA. Sixty female Sprague–Dawley (SD rats (age: 6 weeks, body weight: approximately 160 g were divided into three groups [SMF-treated AA rats (Group I, non-SMF-treated AA rats (Group II and control rats (Group III]. The SD rats were injected in the left hind leg with 0.6 mg/0.05 ml Mycobacterium butyrium to induce AA. The rats were bred for 6 months as chronic pain model. Thereafter, the AA rats were or were not exposed to SMF for 12 weeks. We assessed the changes in the tail surface temperature, locomotor activity, serum inflammatory marker and bone mineral density (BMD using thermography, a metabolism measuring system and the dual-energy X-ray absorptiometry (DEXA method, respectively. The tail surface temperature, locomotor activity and femoral BMD of the SMF-exposed AA rats were significantly higher than those of the non-SMF-exposed AA rats, and the serum inflammatory marker was significantly lower. These findings suggest that the pain relief effects are primarily due to the increased blood circulation caused by the rise in the tail surface temperature. Moreover, the pain relief effects increased with activity and BMD of the AA rats.

  9. [Teratogenicity study of sodium chlorite in rats by oral administration].

    Sakemi, K; Usami, M; Kurebayashi, H; Ohno, Y


    The teratogenicity of sodium chlorite (NaClO2) was assessed in Wistar rats (Crj: Wistar). Sodium chlorite dissolved in distilled water was given to pregnant Wistar rats by gavage once a day from day 6 through 15 of pregnancy at doses of 0, 25, 50 and 100 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy, and their fetuses were examined for malformations. Sodium chlorite caused decreased food consumption, anemia, sedation, hematuria, and death in the pregnant rats at 100 mg/kg, but no fetal effects, such as malformations or growth retardation, were observed even at 100 mg/kg. It was concluded that sodium chlorite has no teratogenicity in rats when administered orally. The no-observed-adverse-effect level was 50 mg/kg/day for pregnant rats and 100 mg/kg/day or more for rat fetuses.

  10. Keratoepithelioplasty in rat: development of a model and histological study.

    Amano, S; Sawa, M; Ishii, Y


    A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using this model. The entire corneal epithelium was removed mechanically and a 1.5-mm width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observations showed much less vascular invasion in the part of the cornea adjacent to the lenticule than in other parts of the cornea, and the cornea remained clear adjacent to the lenticule. Histologically, a few vessels were observed in the corneal stroma under the lenticule. Epithelial cells on the lenticule specimens showed histological characteristics of the corneal epithelium. These findings indicate that one of the functions of KEP is to block neovascularization in the newly developing corneal epithelium by transplanting the lenticule between the corneal epithelium and conjunctival vessels. The present study also confirmed that this model is useful in the research of the pathophysiological mechanism of KEP.

  11. [Echocardiographic study of left ventricular geometry in spontaneously hypertensive rats].

    Escudero, Eduardo M; Pinilla, Oscar A; Carranza, Verónica B


    The purpose of this study was to analyze by echocardiogram left ventricular (LV) geometry in spontaneously hypertensive rats (SHR). Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W). Left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume, and mid ventricular shortening were calculated with echocardiographic parameters. Normal LV was defined considering the mean plus 2 SD of LVMI and RWT in W. Patterns of abnormal LV geometry were: LV concentric remodeling, LVMI 0.71; eccentric, left ventricular hypertrophy (LVH), LVMI > 2.06 mg/g - RWT 2.06 mg/g - RWT > 0.71. Systolic blood pressure (SBP) and cardiac output (CO) were used to obtain total peripheral resistance (TPR). twelve % of SHR had normal LV geometry; 18% LV concentric remodeling; 33% concentric LVH and 37% eccentric LVH. LV concentric remodeling showed the smallest CO and highest TPR of any group. Eccentric LVH presented similar SBP as the other SHR groups and high CO with lower TPR. Our findings in SHR exhibit different patterns of LV geometry like in humans. These results strengthen the similarities between SHR and human essential hypertension.


    E. Souri.


    Full Text Available Stereoselectivity of mefloquine enantiomers were studied in rats after oral administration of a single 50mg/Kg dose of the racemate. Pharmacokinetic parameters of (+-(RS-MFQ in blood and plasma showed no significant difference. The concentration, AUC , CLIF and VdlF of (+-(RS-enantiomerin blood were significantly higher than those for the (--(SR-enantiomer. Tlie results obtained from this study showed a reverse stereoselectivity of MFQ as compared with what reported for human. A very low amount of enantiomers excreted in urine and the excretion was not stereoselective. A preliminary study in different blood fractions showed that the accumulation of MFQ enantiomers in blood cells is stereoselective with a tendency of ( + -(RS-enatiomer for leukocytes and (--(SR-enantiomer for erythrocytes.

  13. Social Interaction Test between a Rat and a Robot: A Pilot Study

    Rusalky del Angel Ortiz


    Full Text Available The social interaction test is based on spontaneous behaviour observed between pairs of animals, usually rodents. Commonly, the behaviour of one of the members in the dyad is related to the behaviour of its partner; therefore, making accurate predictions about behaviour is difficult, and the behaviour of the dyad cannot be controlled. In the present study, we programmed an e-puck robot with simple behavioural patterns, such as moving around a cage and following and approaching a rat. The results were analysed by comparing behaviour that was displayed by two groups of experimental rats towards different types of partners: (i in the first group of experimental rats, they interacted with another group of rats and (ii in the second group of experimental rats, they interacted with the e-puck robot. Our aim was to study the behaviour of experimental rats in the social interaction test when the interaction partner is a pre-programmed robot, in order to find out whether a rat is able to display social interaction activities in that context. Those activities were evaluated by a structured scheme of possible behaviours, quantified in categories according to currently well-accepted nomenclature and definitions. In order to achieve this goal, we compared the social and nonsocial behaviour displayed by the experimental rat in rat-rat and rat-robot interactions (such as approaching and following behaviour. We observed predominantly nonsocial behaviours, such as exploring the cage, when the experimental rats confronted either another rat or the robot. The experimental rats displayed similar periods of approaching, sniffing and crawling (social behaviour, exploring, being quiet, self-grooming and evading (nonsocial behaviour in encountering both the rat and the robot. However, in the presence of the robot, the experimental rats displayed long periods of time spent in following, in contrast to short periods of immobility. In the present study, we explored a

  14. A RAPD based study revealing a previously unreported wide range of mesophilic and thermophilic spore formers associated with milk powders in China.

    Sadiq, Faizan A; Li, Yun; Liu, TongJie; Flint, Steve; Zhang, Guohua; He, GuoQing


    Aerobic spore forming bacteria are potential milk powder contaminants and are viewed as indicators of poor quality. A total of 738 bacteria, including both mesophilic and thermophilic, isolated from twenty-five powdered milk samples representative of three types of milk powders in China were analyzed based on the random amplified polymorphic DNA (RAPD) protocol to provide insight into species diversity. Bacillus licheniformis was found to be the most prevalent bacterium with greatest diversity (~43% of the total isolates) followed by Geobacillus stearothermophilus (~21% of the total isolates). Anoxybacillus flavithermus represented only 8.5% of the total profiles. Interestingly, actinomycetes represented a major group of the isolates with the predominance of Laceyella sacchari followed by Thermoactinomyces vulgaris, altogether comprising of 7.3% of the total isolates. Out of the nineteen separate bacterial species (except five unidentified groups) recovered and identified from milk powders, twelve proved to belong to novel or previously unreported species in milk powders. Assessment and characterization of the harmful effects caused by this particular micro-flora on the quality and safety of milk powders will be worth doing in the future.

  15. Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants.

    Kroos, Marian; Hoogeveen-Westerveld, Marianne; Michelakakis, Helen; Pomponio, Robert; Van der Ploeg, Ans; Halley, Dicky; Reuser, Arnold


    Pompe disease is an autosomal recessive lysosomal glycogen storage disorder, characterized by progressive muscle weakness. Deficiency of acid α-glucosidase (EC; can be caused by numerous pathogenic variants in the GAA gene. The Pompe Disease Mutation Database at aims to list all variants and their effect. This update reports on 94 variants. We examined 35 novel and 34 known mutations by site-directed mutagenesis and transient expression in COS-7 cells or HEK293T cells. Each of these mutations was given a severity rating using a previously published system, based on the level of acid α-glucosidase activity in medium and transfected cells and on the quantity and quality of the different molecular mass species in the posttranslational modification and transport of acid α-glucosidase. This approach enabled to classify 55 missense mutations as pathogenic and 13 as likely nonpathogenic. Based on their nature and the use of in silico analysis (Alamut® software), 12 of the additional 25 novel mutations were predicted to be pathogenic including 4 splicing mutations, 6 mutations leading to frameshift, and 2 point mutations causing stop codons. Seven of the additional mutations were considered nonpathogenic (4 silent and 3 occurring in intron regions), and 6 are still under investigation.

  16. Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

    Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M


    Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

  17. A Study on the Effects of IL-10 in Anti-Thy 1-Induced Glomerulonephritis in Rats

    Rachmawati, H.; Beljaars, L.; Reker-Smit, C.; Bakker, H. I.; Van Loenen-Weemaes, A. M.; Poelstra, K.


    In the present study, we examined the effects of IL-10 after 24 h in a model of acute glomerulonephritis (GN). One hour after the anti-Thy I antibody administration, a single i.v. dose of IL-10 was administered to rats. Normal rats, control nephritic rats and nephritic rats treated with IL-10, were

  18. [Histological study of a model of keratoepithelioplasty in the rat].

    Amano, S; Sawa, M; Ishii, Y


    A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using the model. The entire corneal epithelium was removed using a spatula and a 1.5-mm-width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observation showed significantly less vascular invasion in the part of the cornea adjacent to the lenticule than in other part of cornea, and clear cornea was maintained in the cornea adjacent to the lenticule. Histologically only few vessels were recognized in the lenticule, and the epithelial cells on the lenticule showed histological characteristics of corneal epithelium. These results indicate that surgical function of KEP can be obtained because the lenticules keep distance between corneal epithelium and conjunctival vessels. And it is also confirmed that this model is useful in research on the pathophysiological mechanism of KEP.

  19. Histophysiological study of aluminum chloride effect on male rats

    K. H. Al-Mallah


    Full Text Available This study was designed to detect the effects of aluminum chloride AlCl3 on some pathophysiological features of adult male rats. Eighteen rats were divided to 3 groups of 6 animals each. These included untreated control and 2 treated groups received AlCl3 at the doses 40 and 80 mg/kg of body weight, orally and daily for 30 days. The following parameters were recorded: Body weight (weekly, central nervous system activity tests (weekly, hematological examinations at 15 and 30 days of experimentally and gross and histopathology for brain, liver, kidneys and heart at the day (30. The results showed a significant decrease in body weight mean of 3rd group (80 mg/kg at 4th week, a significant decrease in the activity associated with time progress in experiment by recording (moving onset, square crossed and rearing in 3 minutes, negative geotaxis tests, there were no significant differences between groups at pack cell volume and hemoglobin concentration with a significant decrease in total leukocyte count at 2nd group (40 mg/kg. Differential leukocyte count revealed significant increase in lymphocyte at day 30. Histopathological changes were neuronal vaculation and proliferation of microgelial cells in brain, vacular degeneration and lymphocytic infiltrations in hepatic parenchyma with mild portal fibrosis in liver, at kidneys there were cloudy swelling, coagulative necrosis to the renal tubular epithelium, more severely noticed at 3rd group, no pathological changes were noticed at myocardium and coronary arteries at both treated groups.

  20. Toxicological study of lufironil in rats and dogs

    ZhouYP; ChenSY


    The aim of this study is to verify the toxicity of lufironil(LF),a competitive inhibitor of prolyl hydroxylase by long term administration in animals.SD rats and Beagle dogs were administered orally with LF for 6 months.The daily dose were 0.05,0.35,2.5mg·kg-1 and 0.05,0.15,0.45mg·kg-1,respectively.The recovery after stopping treatments were observed for 1 month.Hydroxyproline(Hyp) assay in serum and tissues,such as liver,kidney,lung and skin were made besides routine examinations of growth rates,food consumption,hematology,clinical chemistry and histology.The results showed that LF reduced total protein and Alb in serum,increased BUN and the weight indexes of liver,kidney and lung in the rats at the highest dose.Hykp decreased only in serum and liver.No other significant changes were seen.All the tested parameters remained normal in the dogs.It is concluded that LF is a safe drug with high selectivity on prolyl hydroxylase and its toxicity occurs only at extremely high dosage and is reversible.

  1. Breast cancer study in rats by using Raman scattering

    Martinez E, J. C. [IPN, Unidad Profesional Interdisciplinaria de Ingenieria, Campus Guanajuato, Av. Mineral de Valenciana 200, Col. Fracc. Industrial Puerto Interior, 36275 Silao, Guanajuato (Mexico); Cordova F, T.; Roca Ch, J. M.; Hernandez R, A., E-mail: [Universidad de Guanajuato, Division de Ciencias e Ingenierias, Departamento de Ingenieria Fisica, Loma del Bosque 103, Col. Lomas del Campestre, 37150 Leon, Guanajuato (Mexico)


    Full text: The use of Raman scattering to differentiate the biochemistry and hence distinguish between normal and abnormal samples of breast cancer with induced stress was investigated. Twelve different rat serum samples (5 control samples and 7 breast cancer samples) were measured. 25 spectra per sample were acquired in a region of 50 X 50 microns. Three hundred spectra were recorded and the spectral diagnostic models were constructed by using multivariate statistical analysis on the spectral matrix to carry out the discrimination between the control samples and cancers samples with induced stress. The spectral recording was performed with Raman microscopy system Thermo Scientific XRD in the range from 200 to 2000 cm{sup -1} with a laser source of 780 nm, 24 m W of power and 50 s and exposure time were used for each spectrum. It is shown that the serum samples from rats with breast cancer and the control group can be discriminate when the multivariate analysis methods are applied to their Raman data set. The ratios were significant and correspond to proteins and phospholipids. The preliminary results suggest that the Raman spectroscopy could be an alternative technique to study the breast cancer in humans in a near future. (Author)

  2. No Previous Public Services Required

    Taylor, Kelley R.


    In 2007, the Supreme Court heard a case that involved the question of whether a school district could be required to reimburse parents who unilaterally placed their child in private school when the child had not previously received special education and related services in a public institution ("Board of Education v. Tom F."). The…

  3. Zonation of the action of ethanol on gluconeogenesis and ketogenesis studied in the bivascularly perfused rat liver.

    Lopez, Carlos Henrique; Suzuki-Kemmelmeier, Fumie; Constantin, Jorgete; Bracht, Adelar


    Zonation of the actions of ethanol on gluconeogenesis and ketogenesis from lactate were investigated in the bivascularly perfused rat liver. Livers from fasted rats were perfused bivascularly in the antegrade and retrograde modes. Ethanol and lactate were infused into the hepatic artery (antegrade and retrograde) and portal vein. A previously described quantitative analysis that takes into account the microcirculatory characteristics of the rat liver was extended to the analysis of zone-specific effects of inhibitors. Confirming previous reports, gluconeogenesis and the corresponding oxygen uptake increment due to saturable lactate infusions were more pronounced in the periportal region. Arterially infused ethanol inhibited gluconeogenesis more strongly in the periportal region (inhibition constant=3.99+/-0.22mM) when compared to downstream localized regions (inhibition constant=8.64+/-2.73mM). The decrease in oxygen uptake caused by ethanol was also more pronounced in the periportal zone. Lactate decreased ketogenesis dependent on endogenous substrates in both regions, periportal and perivenous, but more strongly in the former. Ethanol further inhibited ketogenesis, but only in the periportal zone. Stimulation was found for the perivenous zone. The predominance of most ethanol effects in the periportal region of the liver is probably related to the fact that its transformation is also clearly predominant in this region, as demonstrated in a previous study. The differential effect on ketogenesis, on the other hand, suggest that the net effects of ethanol are the consequence of a summation of several partial effects with different intensities along the hepatic acini.

  4. Providing Visions of a Different Life: Self-study Narrative Inquiry as an Instrument for Seeing Ourselves in Previously-Unimagined Places

    Carmen Shields


    Full Text Available In this paper, we share stories of coming to narrative self-study research in graduate studies, and the impact this choice has had on personal and professional directions in ways we could not have imagined when graduate studies were initially embarked upon. Central to self-study narrative inquiry is a focus on life experience as a tool for connection with our own storied pasts. There we find the roots of our present-day perspectives and actions that we can incorporate into our everyday meaning-making, using our emergent understanding to choose present and future possibilities in our relationships.

  5. [Safety evaluation of micronomicin. III. Teratogenicity studies in rats].

    Hara, T; Nishikawa, S; Miyazaki, H; Ohguro, Y


    Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by Nara et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Teratogenicity studies of MCR in rats were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 75 mg/kg). The results of studies are as follows. 1. Fetal malformation attributable to MCR was not observed at any dose. 2. Suppression of maternal weight gain was observed at the dose levels of 50 mg/kg and over. 3. There was no adverse effect on new borns at any dose.

  6. The change in motivating factors influencing commencement, adherence and retention to a supervised resistance training programme in previously sedentary post-menopausal women: a prospective cohort study.

    Viljoen, Janet Erica; Christie, Candice Jo-Anne


    Understanding motivators for exercise participation in post-menopausal women may impact retention to exercise programmes and inform intervention trial designs. The purpose of this investigation was to assess self-reported motivational factors influencing adherence and retention to a 24-week progressive resistance training programme. Post-menopausal females (n = 34) were passively recruited to undertake a 24-week progressive resistance training protocol, in small-group sessions, on three non-consecutive days of the week. Attendance was recorded by the researcher. Qualitative reports were sourced from the sample for four phases of the study: pre-study (prior to week 1), recruitment (week 1), during study (weeks 2 - 24), and post-intervention (beyond week 24). Responses were categorised according to ten descriptors: specific health index improvement, education, flexibility of time, social contact, conscience (loyalty to the researcher), wellness, weight management, organisation parameters (pertaining to the study programme) and enjoyment of the exercises. Of the initial sample, 76.5% (n = 26) met the specified ≥80% attendance criterion. The primary findings were that motivation to volunteer for the study was driven by a perceived need for a structured exercise programme (50% of respondents). A commitment to the researcher was the primary motivator for continued adherence to the study for 50% of participants. Social contact with other participants was cited by 60% of the sample as the primary reason for adherence for the full duration of 24 weeks. A desire to maintain the "wellness" derived from the programme was cited by 60% as a reason for continuing an exercise routine post-study. This study identified that routine and supervision initially attract women to exercise programmes, while social cohesion of the group setting contributes to retention over time. Understanding the changing nature of motivating factors may contribute to better overall adherence

  7. Rats

    Alexey Kondrashov


    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  8. Metabonomic study of rats exposed to cigarette sidestream smoke

    LIAN Wen-liu; SHI Xian-zhe; LUO Jia; REN Feng-lian


    A metabonomic approach was undertaken in order to detect urinary endogenous and exogenous metabolites and to evaluate the effects of passive exposure to cigarette sidestream smoke on rats. Urinary samples from three groups of rats were determined including control rats, rats treated with blended cigarettes (nonmenthol cigarettes) and rats treated with menthol cigarettes. The total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), total 1-hydroxypyrene (1-HOP) and 3-hydroxybenzo[a] pyrene (3-HOBaP) were determined for assessing exposure to cigarette sidestream smoke toxins. Urinary endogenous metabolites in the three groups of rats were also analyzed and the data were processed by chemometrics. Eleven endogenous metabolites were found and identified. Their relative levels were compared among the three groups. The results show that cigarette sidestream smoke has complex effect on rats. Blended cigarette group makes difference to menthol cigarette group in the rats' urinary metabolic changes. Menthol adding to cigarettes has positive and negative effects on rats, respectively. The urinary metabolic profiling of menthol cigarette group is closer to that of control group.

  9. Spirulina acceptability trials in rats. A study for the ``Melissa'' life-support system

    Tranquille, N.; Emeis, J. J.; de Chambure, D.; Binot, R.; Tamponnet, C.


    Groups of five rats were fed for sixteen weeks a slightly deficient diet, supplemented with 0-40% of a dried preparation of the blue-green alga Spirulina as a protein source. Control groups were fed a normal rat diet. No significant differences between groups were found in food intake, growth rate or carbon dioxide production. All animals remained apparently healthy, and had similar organ weights. The study suggests taht Spirulina may be used as a protein source in rat diets.

  10. Global metabolic profiling for the study of Rhizoma Paridis saponins-induced hepatotoxicity in rats.

    Man, Shuli; Qiu, Peiyu; Li, Jing; Zhang, Liming; Gao, Wenyuan


    Rhizoma Paridis saponins (RPS) is a traditional Chinese medicine (TCM) from the plant Paris polyphylla var. yunnanensis (Fr.) Hand.-Mazz. Despite its potentially clinical utility such as anticancer and anti-inflammation, it has slight side effects and toxicity as previous report. In this work, 90-day administration of RPS induced liver injury. (1) H-NMR- and GC/MS-based metabonomic analyses in conjunction with histopathological examinations, blood biochemistry and hepatic phase I and II enzymes assays were performed to evaluate the toxic mechanisms of RPS induced in rats. As a result, oral administration of RPS possessed certain liver toxicity in SD rats. (1) H-NMR and GC/MS data indicated that RPS inhibited the oxidation of fatty acids, glycolysis, and TCA cycle pathway, and disturbed glycine, serine, and threonine metabolism. Low expression of TG, T-CHO, and LDL-C and high levels of ALT and AST indicated that chronic exposure to RPS caused hepatocyte damage, synthesis dysfunction, and transportation failure of lipoproteins. In addition, RPS downregulated the mRNA levels of CYP1A2, CYP2E1, and UGTs. In conclusion, we used metabonomics approach to study the toxicity of RPS for the first time. This research demonstrated that metabonomics method was a promising tool to study and diagnose TCM-induced toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 99-108, 2017.

  11. A brief review of the estimated economic burden of sexually transmitted diseases in the United States: inflation-adjusted updates of previously published cost studies.

    Chesson, Harrell W; Gift, Thomas L; Owusu-Edusei, Kwame; Tao, Guoyu; Johnson, Ana P; Kent, Charlotte K


    We conducted a literature review of studies of the economic burden of sexually transmitted diseases in the United States. The annual direct medical cost of sexually transmitted diseases (including human immunodeficiency virus) has been estimated to be $16.9 billion (range: $13.9-$23.0 billion) in 2010 US dollars.

  12. Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study

    Forner, Lone; Hansen, Ole Hyldegaard; von Brockdorff, Annet Schack


    Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO...

  13. The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents:the Chinese cohort from SOL-VETM observational study



    Objective To evaluate the safety and effectiveness of initiating once-daily insulin detemir(Levemir) as add-on therapy in patients with type 2 diabetes mellitus(T2DM) who failed treatment of oral anti-diabetic drugs(OAD).Methods The present study was derived from the data of

  14. Oral (gavage) two-generation (one litter per generation) reproduction study of pentachlorophenol (penta) in rats.

    Bernard, Bruce K; Hoberman, Alan M; Brown, W Ray; Ranpuria, Anish K; Christian, Mildred S


    ) for both reproductive and general toxicity. These findings are consistent with results from previously conducted studies wherein reproductive/developmental toxicity was observed only at doses that also induced general toxicity. It differs from previous findings in that the NOAEL for general toxicity is two to three times higher for the more pure product than for products produced and tested previously. In addition, the results did not indicate bioaccumulation of penta. Thus, penta did not selectively affect reproduction or development of the offspring of rats at a dose of 10 mg/kg/day, a dose that is 7000 to 20,000 times higher than human exposure.

  15. Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.


    Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 positively mated rats or mice. Positively mated mice were exposed on days 6--17 of gestation (dg), and rats on 6--19 dg. The day of plug or sperm detection was designated as O dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

  16. Histomorphometric Study of Alveolar Bone Healing in Rats Fed a Boron-Deficient Diet

    Bone healing after tooth extraction in rats is a suitable experimental model to study bone formation. Thus, we performed a study to determine the effects of boron (B) deficiency on bone healing by using this model. Weanling Wistar rats were divided into two groups: control (+B; 3 mg B/kg diet), and ...

  17. Concentration-dependent neurotoxicity of articaine: an electrophysiological and stereological study of the rat sciatic nerve

    Hillerup, Søren; Bakke, Merete; Larsen, Jytte Overgaard;


    We performed this study to quantify the detrimental effect of intraneural injection of 50 μL of saline, articaine 2%, or articaine 4% in the rat sciatic nerve.......We performed this study to quantify the detrimental effect of intraneural injection of 50 μL of saline, articaine 2%, or articaine 4% in the rat sciatic nerve....

  18. [Ketanserin and random skin flaps. An experimental study in the rat].

    Achouche, J; Teisseire, B; Laccourreye, O; Hadjean, E


    This prospective randomised study in a rodent model was designed to analyse the value of a serotonin antagonist, ketanserin, on the survival of random skin flaps in Wistar rats. Our study demonstrates the statistical value of this molecule. The surface of skin necrosis was statistically lower in the group of rats treated with pre and post operative subcutaneous injection of ketanserin.

  19. Alfalfa (Medicago sativa L.) is tolerant to higher levels of salinity than previous guidelines indicated: Implications of field and greenhouse studies

    Putnam, Daniel H.; Benes, Sharon; Galdi, Giuliano; Hutmacher, Bob; Grattan, Steve


    Alfalfa (Medicago sativa L.) is the most widely grown leguminous forage crop in North America and is valued for high productivity, quality, economic value, and for dairy productivity. Alfalfa has historically been classified as moderately sensitive to saline conditions, with yield declines predicted at >2 dS/m in the saturated soil paste extract. However, greenhouse, sand tank, and field studies over the past five years have confirmed that alfalfa can be grown with limited negative effects at much higher salinity levels. A broad collection of alfalfa varieties has exhibited a range of resistance at irrigation water salinities >5 dS/m ECw in greenhouse trials, with significant variation due to variety. USDA-ARS sand tank studies indicated similar or greater tolerances closer to 8 dS/m in the soil water, in addition to confirmation of significant varietal differences. A three-year field study on clay loam soil with applications of 5-7 dS/m ECw irrigation water indicated normal yields and excellent stand survivability. A second field study in the same soil type with levels from 8-10 dS/m ECw showed yield reductions of 10-15% but economic yields were still achieved at those levels. Field and greenhouse studies were conducted with mixed salt saline sodic waters typical of the San Joaquin Valley of California. Field evaluation of variety performance was subject to greater variation due to secondary salinity-soil interactions including water infiltration and crusting problems, not only salinity per-se. Thus, adequate irrigation water availability to the crop may be as important as salinity in impacting yields under field conditions. Once established, the deep-rooted characteristics of alfalfa enable utilization of deeper subsurface moisture, even at moderate to high salinity levels, as documented by USDA lysimeter studies. Significant advantages to salinity-tolerant varieties have been observed. It will be important to consider specific management factors which may enable

  20. Role of micronized progesterone in prevention of preterm labour in women with previous history of one or more preterm births: a research study at a tertiary care hospital

    Rashmi Ahuja


    Conclusions: The study concluded that progesterone use was associated with 64.2% reduction in the incidence of preterm delivery (p=0.029.Antenatal administration of progesterone reduces the risk of preterm birth before 37 weeks and 34 weeks as well as the risk of a newborn being born with a birth weight of less than 2500 gms. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1176-1180

  1. Two-generation reproduction toxicity study in rats with methoxychlor.

    Aoyama, Hiroaki; Hojo, Hitoshi; Takahashi, Ken L; Shimizu-Endo, Naoko; Araki, Masayuki; Takeuchi-Kashimoto, Yukiko; Saka, Machiko; Teramoto, Shoji


    A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.

  2. A Retrospective Study of Capecitabine/Temozolomide (CAPTEM Regimen in the Treatment of Metastatic Pancreatic Neuroendocrine Tumors (pNETs after Failing Previous Therapy

    Muhammad Wasif Saif


    Full Text Available Context Pancreatic neuroendocrine tumors (pNETs are notoriously resistant to currently available chemotherapy agents.Preclinical data has suggested synergy between temozolomide and capecitabine. Objective To report a retrospective data on the efficacy and safety of capecitabine and temozolomide (CAPTEM regimen in patients with metastatic pancreaticneuroendocrine tumors (pNETs who have failed prior therapies. Methods We reviewed the medical records of 7 patientswith metastatic pNETs who had had progressive cancer prior to treatment despite therapy, including long-acting releaseoctreotide (60 mg/month, chemotherapy and hepatic chemoembolization. Capecitabine was administered at a flat dose of1,000 mg orally twice daily on days 1-14 and temozolomide 200 mg/m2 was given in two divided doses daily on days 10-14of a 28-day cycle. Tumor assessments were repeated every two cycles and serum tumor markers were measured every cycle. Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors (RECIST parameters, and toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 3.0. Results Among 7 patients treated, three patients achieved a partial response, and two patients had stable disease. Totalresponse rate was 43%, and clinical benefit (responders and stable disease was 71%. Median duration of response was 8months (range: 4-12 months. Grade 3 and 4 toxicities included grade 3 thrombocytopenia in one patient and grade 3 fatigue in one patient. The most common toxicities were grade 1 and 2 neutropenia, grade 1 fatigue, grade 1 and 2 hand-foot syndrome. Conclusions Our retrospective study showed that modified CAPTEM regimen was well-tolerated and produced comparable response to historical data in neuroendocrine tumors, including pNETs. Our study is unique as it only included patients with pNETs. Further prospective studies are warranted to evaluate the combination of

  3. A gender-medicine post hoc analysis (MetaGeM project to test sex differences in previous observational studies in different diseases: methodology

    Colombo D


    Full Text Available Delia Colombo,1 Gilberto Bellia,1 Donatella Vassellatti,1 Emanuela Zagni,1 Simona Sgarbi,2 Sara Rizzoli21Novartis Farma, Origgio, 2MediData, Modena, ltaly Abstract: Only recently has medical research begun to understand the importance of taking sex into account, recognizing that symptoms and responses to medical treatment may be very different between males and females. However, the analyses provided by the pharmaceutical industry to regulatory authorities often do not present safety and efficacy data by sex. Novartis has started a gender-medicine project called MetaGeM, which includes nine observational studies sponsored by Novartis Farma, Italy; conducted in Italy between 2002 and 2013 in a range of different clinical areas. The MetaGeM project aims to analyze and describe by means of post hoc analyses and meta-analyses, clinical outcomes, therapeutic approaches, and safety data of these studies, by sex: PSYCHAE; GENDER ATTENTION in psoriasis; Synergy in psoriatic arthritis; ICEBERG in HBsAg carriers; SURF and CETRA in liver- and renal transplanted patients, respectively; DEEP in Parkinson's disease; and EVOLUTION and AXEPT in Alzheimer's disease. The present paper describes the methodology of the MetaGeM project.Keywords: gender-medicine, MetaGeM project, methodology

  4. Effect of Common Vegetables on Thyroid Function in Rats-A Preliminary Study

    S. R. Sarkar


    Full Text Available Goitrogenic potency of some vegetables of Delhi were studied in rats. Adult male rats were fed separately on thiouracil, thiocyanate and extracts of carrot, cabbage and turnip procured from Delhi market for 26 days. Cabbage and turnip showed high thiocyanate contents while carrot did not show any measurable amount. Appreciable increase in thyroid weight to body weight ratio, plasma thiocyanate, plasma/sup 131/1 contents and protein bound/sup 131/ 1 or plasma were observed in all groups of experimental, rats, except carrot. Results indicated goitrogenic nature of cabbage and turnip in rats.

  5. A study of the presence of B. burgdorferi, Anaplasma (previously Ehrlichia) phagocytophilum, Rickettsia, and Babesia in Ixodes ricinus collected within the territory of Belluno, Italy.

    Piccolin, G; Benedetti, G; Doglioni, C; Lorenzato, C; Mancuso, S; Papa, N; Pitton, L; Ramon, M C; Zasio, C; Bertiato, G


    In the years 2000 and 2001, we sampled ticks in order to establish the distribution of Ixodes ricinus in the province of Belluno; 5987 tick samples from 244 sites throughout the province were gathered, by dragging for a 5-min period. In 40 sites, seasonal variations and cycle stages of the parasites were studied at monthly intervals from March to September. A polymerase chain reaction (PCR) technique was used to identify the tick-infected sites. Of 1931 individual ticks, 8.23% were positive for Borrelia burgdorferi, 4.4% were positive for Ehrlichia, 1.6% were positive for Rickettsia, and 1.6% were positive for Babesia. The co-presence of Borrelia and Ehrlichia (1.2%) and Babesia (0.5%), Borrelia, Ehrlichia and Rickettsia (0.1%) was also found.

  6. Performance of the new 2012 EULAR/ACR classification criteria for polymyalgia rheumatica: comparison with the previous criteria in a single-centre study.

    Macchioni, Pierluigi; Boiardi, Luigi; Catanoso, Mariagrazia; Pazzola, Giulia; Salvarani, Carlo


    To compare the performance of published classification/diagnostic criteria for polymyalgia rheumatica (PMR), including the new 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, in a single-centre study. We studied all consecutive patients with new-onset PMR seen in our centre over 6 years, whose diagnosis was confirmed during a prospective 12-month follow-up period. Subjects were classified by each of the seven different criteria. Sensitivity and specificity were compared. Control population consisted of all consecutive patients aged ≥50 years seen in a 4-year period in our early arthritis clinic who had a 12-month confirmation of a diagnosis of rheumatoid arthritis (RA) or other inflammatory articular diseases. Data were collected from 136 cases and 149 controls, including 94 patients with RA. The most sensitive criteria were the new 2012 EULAR/ACR classification criteria (92.6%). Adding ultrasound (US) specificity increased from 81.5% to 91.3% in total cases and from 79.7% to 89.9% in RA. Bird criteria had a sensitivity of 89.2% but the lowest specificity (40.2% in total cases and 72.5% in RA). Jones and Nobunaga criteria were the most specific criteria (96.7% and 97.8% in total cases and 98.6% and 99.5% in RA) but the less sensitive (63.1% and 58.2%) ones. Overall, discriminatory ability, as reflected by the area under the receiver operating characteristic curve, was better for the 2012 US EULAR/ACR criteria (0.920 in total cases and 0.910 in RA). The new EULAR/ACR criteria in new-onset PMR patients perform best in discriminating PMR from RA and other inflammatory articular diseases. Ultrasound further increases the specificity of the criteria.

  7. Chronic toxicity and carcinogenicity study of erythritol in rats

    Lina, B.A.R.; Bos-Kuijpers, M.H.M.; Til, H.P.; Bär, A.


    The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two

  8. Embryotoxicity and teratogenicity study with erythritol in rats

    Smits- Prooije, A.E. van; Waalkens-Berendsen, D.H.; Bär, A.


    The embryotoxicity/teratogenicity of erythritol, a low-calorie polyol sugar substitute, was examined in Wistar Crl:(WI) WU BR rats. Erythritol was fed at dietary concentrations of 0, 2.5, 5, and 10% to groups of 32 female rats from Day 0 to 21 of gestation. The treatment was generally well tolerated

  9. Two-generation reproduction study of erythritol in rats

    Waalkens-Berendsen, D.H.; Smits- Prooije, A.E. van; Wijnands, M.V.M.; Bär, A.


    Erythritol was fed at dietary concentrations of 0, 2.5, 5, or 10% to Crl:(WI) WU BR rats of both sexes through two successive generations (F0 and F1). Twenty-four rats of each sex were mated in each group. For each generation one litter was reared until the pups were 21 days old. In the 10%

  10. Two-generation reproduction study of erythritol in rats

    Waalkens-Berendsen, D.H.; Smits- Prooije, A.E. van; Wijnands, M.V.M.; Bär, A.


    Erythritol was fed at dietary concentrations of 0, 2.5, 5, or 10% to Crl:(WI) WU BR rats of both sexes through two successive generations (F0 and F1). Twenty-four rats of each sex were mated in each group. For each generation one litter was reared until the pups were 21 days old. In the 10% erythrit

  11. Embryotoxicity and teratogenicity study with α-cyclodextrin in rats

    Waalkens-Berendsen, D.H.; Bär, A.


    The embryotoxicity/teratogenicity of α-cyclodextrin (α-CD) was examined in Wistar Crl:(WI)WU BR rats. α-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The addition

  12. Embryotoxicity and teratogenicity study with α-cyclodextrin in rats

    Waalkens-Berendsen, D.H.; Bär, A.


    The embryotoxicity/teratogenicity of α-cyclodextrin (α-CD) was examined in Wistar Crl:(WI)WU BR rats. α-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The

  13. Hypoxic neuropathy versus diabetic neuropathy : an electrophysiological study in rats

    Gispen, W.H.; Hendriksen, P.H.; Oey, P.L.; Wieneke, G.H.; Huffelen, A.C. van


    In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypo

  14. Embryotoxicity and teratogenicity study with erythritol in rats

    Smits- Prooije, A.E. van; Waalkens-Berendsen, D.H.; Bär, A.


    The embryotoxicity/teratogenicity of erythritol, a low-calorie polyol sugar substitute, was examined in Wistar Crl:(WI) WU BR rats. Erythritol was fed at dietary concentrations of 0, 2.5, 5, and 10% to groups of 32 female rats from Day 0 to 21 of gestation. The treatment was generally well tolerated

  15. Embryotoxicity and teratogenicity study with γ-cyclodextrin in rats

    Waalkens-Berendsen, D.H.; Verhagen, F.J.J.; Bär, A.


    The embryotoxicity/teratogenicity of γ-cyclodextrin (γ-CD) was examined in Wistar Crl:(WI)WU BR rats. γ-CD was fed at dietary concentrations of 0, 1.5, 5, 10, and 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. A comparison group received a diet with 20% lactose. The addition

  16. [Study of impulsivity in rats under conditions of choice between food reinforcements of different values].

    Zaĭchenko, M I; Merzhanova, G Kh


    Rat behavior was studied under conditions "with the right to choose the values of reinforcements depending on the time delay of its receipt". Rats were placed in a chamber equipped with two retractable pedals, pressing one of which provided a small portion of food (1 pellet), and pressing the second pedal was followed by the delivery of more valuable food (4 pellets), but delayed reinforcement. Rats preferring small reinforcement without the delay were considered as "impulsive" and rats choosing more valuable delayed reinforcement were considered as "self-controlling". Influence of the delay duration and change in the level of motivation on the pedal pressing was studied in both groups of rats. Preference in the selection of the pedal, latency of pressing the pedal and the number of omitted reactions were estimated. It was found that "impulsive" animals more rapidly pressed the pedal and less frequently omitted trials than "self-controlling" rats. After the increase in the delay duration up to 7 seconds, rats stopped choosing the pedal with the delayed reinforcement. Increased food motivation shifted the behavior of rats to "self-control", whereas rats after feeding preferred less valuable immediate reinforcement.

  17. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

    Febo, Marcelo; Ferris, Craig F


    Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav.

  18. Phase II Study of Bortezomib as a Single Agent in Patients with Previously Untreated or Relapsed/Refractory Acute Myeloid Leukemia Ineligible for Intensive Therapy

    Chiara Sarlo


    Full Text Available We explored the safety and efficacy of bortezomib given as single agent in patients with untreated or relapsed/refractory acute myeloid leukemia (AML, unfit for conventional chemotherapy. Fourteen patients were treated with bortezomib 1.5 mg/m2 administered twice weekly for two weeks, every 3 weeks. Median age was 70 years (range 60–81 and the median number of cycles delivered was 2 (range 1–4. Of 13 evaluable patients, in 8 (61%, the administration of bortezomib resulted in an antileukemic effect as demonstrated by peripheral blood and/or bone marrow blast reduction. In 4 (50% of these 8, a decrease by 37% of transfusion requirement was also observed . Overall median survival was 4 months (range 0.25–10. Neurotoxicity was the most frequent adverse event with 7 of 13 (54% patients experiencing grades 3-4 peripheral neuropathy. Neurotoxicity led to treatment discontinuation in 4 (57% of 7. In conclusion, the observed anti-leukemic activity of bortezomib indicates that there is room for designing additional studies in which combination with other chemotherapeutic agents should be considered. Clinical registration no.: EUDRACT 2006-006923-38.

  19. Can a Repeated Sprint Ability Test Help Clear a Previously Injured Soccer Player for Fully Functional Return to Activity? A Pilot Study.

    Padulo, Johnny; Attene, Giuseppe; Ardigò, Luca P; Bragazzi, Nicola L; Maffulli, Nicola; Zagatto, Alessandro M; Dello Iacono, Antonio


    To investigate the effects of fatigue induced by a repeated sprint ability (RSA) test on the neuromuscular responses of soccer players with a recent history of lower limb injuries (CH) and a matched control group in good fitness condition (GH). This was a case-control study. Nine CH and 9 GH. Allocation to CH or GH. Each player was assessed for blood lactate concentration and jumping performance [squat jump (SJ) and countermovement jump (CMJ)] before/after RSA. Post-RSA rate of perceived exertion (RPE) was obtained. Receiver operating characteristic analysis was performed to calculate RSA sensitivity and specificity in distinguishing between CH and GH. Intraclass correlation coefficient was used to assess reliability. No baseline differences were found for any variable. ΔSJ before/after RSA was -14 ± 2% and -5 ± 2% in CH and GH, respectively (P Repeated sprint ability is a simple, low-cost field test potentially able to assist in clinical decision making for return to sport.

  20. Prevalence of pain in the head, back and feet in refugees previously exposed to torture: a ten-year follow-up study

    Olsen, Dorthe Reff; Montgomery, Edith; Bøjholm, Søren


    exposed to torture in their home country were interviewed at a Danish rehabilitation clinic on average 8 years after their final release from confinement and re-interviewed 10 years later. Interviews focused on history of exposure to physical and mental torture and on pain in the head, back and feet...... prevalent at study. RESULTS: The mean number of times imprisoned was 2.5 and the mean cumulative duration of imprisonment 19.4 months. The most frequent physical torture method reported was beating (95.0%) and the main mental torture method deprivation (88.5%). Pain reported at follow-up was strongly...... associated with pain reported at baseline, and the prevalence of pain increased considerably (pain in the head, 47.5% at baseline and 58.3% at follow-up; back, 48.2% and 75.5%; feet, 23.7% and 63.3%). Predictor patterns at baseline and at follow-up had common traits, so that pain in the head and pain...

  1. Effects of dopaminergic replacement therapy on motor speech disorders in Parkinson's disease: longitudinal follow-up study on previously untreated patients.

    Rusz, Jan; Tykalová, Tereza; Klempíř, Jiří; Čmejla, Roman; Růžička, Evžen


    Although speech disorders represent an early and common manifestation of Parkinson's disease (PD), little is known about their progression and relationship to dopaminergic replacement therapy. The aim of the current study was to examine longitudinal motor speech changes after the initiation of pharmacotherapy in PD. Fifteen newly-diagnosed, untreated PD patients and ten healthy controls of comparable age were investigated. PD patients were tested before the introduction of antiparkinsonian therapy and then twice within the following 6 years. Quantitative acoustic analyses of seven key speech dimensions of hypokinetic dysarthria were performed. At baseline, PD patients showed significantly altered speech including imprecise consonants, monopitch, inappropriate silences, decreased quality of voice, slow alternating motion rates, imprecise vowels and monoloudness. At follow-up assessment, preservation or slight improvement of speech performance was objectively observed in two-thirds of PD patients within the first 3-6 years of dopaminergic treatment, primarily associated with the improvement of stop consonant articulation. The extent of speech improvement correlated with L-dopa equivalent dose (r = 0.66, p = 0.008) as well as with reduction in principal motor manifestations based on the Unified Parkinson's Disease Rating Scale (r = -0.61, p = 0.02), particularly reflecting treatment-related changes in bradykinesia but not in rigidity, tremor, or axial motor manifestations. While speech disorders are frequently present in drug-naive PD patients, they tend to improve or remain relatively stable after the initiation of dopaminergic treatment and appear to be related to the dopaminergic responsiveness of bradykinesia.

  2. Comparative study of Hg xCd 1-xTe films grown on CdTe thin films previously deposited from two different techniques

    Ali, A.; Abbas Shah, N.; Maqsood, A.


    High quality cadmium telluride (CdTe) thin films were grown on glass substrates with two different techniques, two evaporation source (TES) and closed space sublimation (CSS). Further to the above mercury telluride (HgTe) was then deposited by using single source on both CdTe thin films for obtaining Hg xCd 1-xTe samples. The crystalline structure of the Hg xCd 1-xTe sample grown from CSS-CdTe showed the preferential (1 1 1) orientation with smoother and larger grain size than those of TES-CdTe. The optical transmission for TES-CdTe sample was above 90% in the 1000-1500 nm range whereas it was significantly below 80% for CSS-CdTe sample. The optical transmission for TES-Hg xCd 1-xTe and CSS-Hg xCd 1-xTe was ˜60%. The resistivity at room temperature of TES-CdTe and CSS-CdTe was ˜3.33×10 9 Ω cm and ˜2.20×10 8 Ω cm, respectively, while the resistivity of TES-Hg xCd 1-xTe and CSS-Hg xCd 1-xTe samples was ˜1.73 Ω cm and ˜5.34×10 5 Ω cm, respectively. The comparative study of ternary compound prepared with the above techniques has been carried out for the first time.

  3. Comprehensive toxicity study of safrole using a medium-term animal model with gpt delta rats.

    Jin, M; Kijima, A; Suzuki, Y; Hibi, D; Inoue, T; Ishii, Y; Nohmi, T; Nishikawa, A; Ogawa, K; Umemura, T


    In order to investigate a medium-term animal model using reporter gene transgenic rodents in which general toxicity, genotoxicity and carcinogenicity are evaluated, F344 gpt delta rats were given a diet containing 0.1% and 0.5% (a carcinogenic dose) safrole for 13 weeks. Serum biochemistry and histopathological examinations revealed overt hepatotoxicity of safrole, in line with previous reports. In the current study, safrole treatment possibly resulted in renal toxicity in male rats. In the in vivo mutation assays, an increase or a tendency to increase of the gpt mutant frequencies (MFs) was observed in both sexes at the carcinogenic dose. The number and area of foci of glutathione S-transferase placental form (GST-P) positive hepatocytes, ratio of proliferating cell nuclear antigen (PCNA)-positive hepatocytes and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA were significantly increased in both sexes of the 0.5% group. The overall data suggested that the present model might be a promising candidate for investigating comprehensive toxicities of the agents. In addition, data demonstrating the base modification and cell proliferation due to exposure to safrole could contribute to understanding safrole-induced hepatocarcinogenesis, which imply expanding in application of this model.

  4. Development of hibernomas in rats dosed with phentolamine mesylate during the 24-month carcinogenicity study.

    Poulet, Frederique M; Berardi, Mark R; Halliwell, William; Hartman, Barbara; Auletta, Carol; Bolte, Henry


    Phentolamine is a reversible competitive alpha-adrenergic antagonist with similar affinities for alphal and alpha2 receptors. It has a long history of safe clinical use, and was developed as a potential therapy for male erectile dysfunction because of its capacity to increase the arteriolar blood flow to the corpora cavernosa. Phentolamine mesylate was administered to rats by oral gavage at daily doses of 10, 50, and 150 mg/kg for 24 months. A dose-related increase in mortality, ascribed to an exaggerated pharmacologic effect, was seen at high doses. Systemic exposure as measured by plasma drug concentration increased with dose and duration of dosing and slight drug accumulation occurred, particularly in high-dose males. In the treated groups, 10 males and 1 female were diagnosed with hibernomas, neoplasms of brown adipose tissue, which appeared in the thoracic cavity or retroperitoneal area as circumscribed, tan to reddish-brown lobulated masses. Histologically, the masses were well circumscribed with variably sized lobules defined by a rich capillary network and consisted of closely apposed oval to polygonal cells with large amounts of cytoplasm and a centrally located nucleus. The cytoplasm's appearance varied from multivacuolated to univacuolated to granular eosinophilic. In a few cases, neoplastic emboli were observed in capsular vessels. Ultrastructurally, the neoplastic cells contained numerous mitochondria with transverse parallel cristae that occupied over 60% of the cytoplasm and lipid droplets. This study documents the previously unreported development of hibernomas in rats treated with phentolamine mesylate.

  5. A rat model for studying neural stem cell transplantation

    Xue-mei ZHOU; Jing-bo SUN; Hui-ping YUAN; Dong-lai WU; Xin-rong ZHOU; Da-wei SUN; Hong-yi LI; Zheng-bo SHAO; Zhi-ren ZHANG


    Aim: The goal of this project was to develop a rat model for neural stem cell (NSC) transplantation studies in which NSCs were modified with brain-derived neurotrophic factor (BDNF) genes that may permit extensive and reliable analysis of the transplants. Methods: NSCs were cultured and purified by limiting dilution assay in vitro and infected with recombinant retrovirus pLXSN-BDNF (BDNF-NSCs) and retrovirus pLXSN (p-NSCs). The expression of BDNF genes in transgenic and control NSC groups was measured by FQ-PCR and ELISA assays. NSCs were then transplanted into the subretinal space of normal rat retinas in four groups, which included NSCs alone, BDNF-NSCs, phosphate buffered saline (PBS) control, and normal control. Survival, migration, and differentiation of dono-cells in host retinas were observed with optical coherence tomography (OCT), Heidelberg retina angiograph (HRA), and immunohis-tochemistry, respectively.Results: The results obtained by FQ-PCR demonstrated that the copy numbers of BDNF gene templates from BDNF-NSCs were the highest among the four groups (P<0.05). Consistent with the results of FQ-PCR, BDNF protein level from the supernatant of the BDNF-NSCs group was much higher than that of the other two groups (P<0.05) as suggested by the ELISA assays. HRA and OCT showed that graft cells could successfully survive. Immunohistochemical analysis revealed that transplanted BDNF-NSCs could migrate in the host retinas and differentiate into glial cells and neurons three months after transplantation. Conclusion: BDNF promotes NSCs to migrate and differentiate into neural cells in the normal host retinas.

  6. Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma.

    Raje, Noopur S; Moreau, Philippe; Terpos, Evangelos; Benboubker, Lotfi; Grząśko, Norbert; Holstein, Sarah A; Oriol, Albert; Huang, Shang-Yi; Beksac, Meral; Kuliczkowski, Kazimierz; Tai, Datchen F; Wooldridge, James E; Conti, Ilaria; Kaiser, Christopher J; Nguyen, Tuan S; Cronier, Damien M; Palumbo, Antonio


    In this double-blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m(2) on a 21-day cycle. No significant intergroup differences were observed among primary (median progression-free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80-1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72-1·45], P = 0·884). The most commonly-reported treatment-emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut-off point (mPFS [95% CI] = 8·3 [7·0-9·3] months vs. 5·8 [3·7-6·6] months; HR [95% CI] = 1·59 [1·11-2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

  7. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study

    Canaud, Bernard; Mingardi, Giulio; Braun, Johann; Aljama, Pedro; Kerr, Peter G.; Locatelli, Francesco; Villa, Giuseppe; Van Vlem, Bruno; McMahon, Alan W.; Kerloëguen, Cécile; Beyer, Ulrich


    Background. Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life (∼130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis. Methods. STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within ± 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29–36). Results. Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (−0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated. Conclusions. Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA. PMID:18586762

  8. RapidArc, intensity modulated photon and proton techniques for recurrent prostate cancer in previously irradiated patients: a treatment planning comparison study

    Ratib Osman


    Full Text Available Abstract Background A study was performed comparing volumetric modulated arcs (RA and intensity modulation (with photons, IMRT, or protons, IMPT radiation therapy (RT for patients with recurrent prostate cancer after RT. Methods Plans for RA, IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14 fractions. The recurrent gross tumor volume (GTV was defined on 18F-fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning target volume with a dose > 50.4 Gy. A maximum dose (DMax of 61.6 Gy was allowed to 5% of the GTV. For the urethra, DMax was constrained to 37 Gy. Rectal DMedian was 90 parameters. Results Tumor coverage (GTV and PTV was improved with RA (V95% 92.6 ± 7.9 and 83.7 ± 3.3%, when compared to IMRT (V95% 88.6 ± 10.8 and 77.2 ± 2.2%. The corresponding values for IMPT were intermediate for the GTV (V95% 88.9 ± 10.5% and better for the PTV (V95%85.6 ± 5.0%. The percentages of rectal and urethral volumes receiving intermediate doses (35 Gy were significantly decreased with RA (5.1 ± 3.0 and 38.0 ± 25.3% and IMPT (3.9 ± 2.7 and 25.1 ± 21.1%, when compared to IMRT (9.8 ± 5.3 and 60.7 ± 41.7%. CI90 was 1.3 ± 0.1 for photons and 1.6 ± 0.2 for protons. Integral Dose was 1.1 ± 0.5 Gy*cm3 *105 for IMPT and about a factor three higher for all photon's techniques. Conclusion RA and IMPT showed improvements in conformal avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate cancer. IMPT showed further sparing of organs at risk.

  9. Comparative study of renal sodium transport between ouabain-hypertensive rats and ouabain-nonhypertensive rats

    GE Heng; Lü Zhuo-ren


    Objective: To compare renal sodium transport, using fractional excretions of lithium(FEii)as a marker of proximal tubule sodium reabsorption, between hypertensive and non-hypertensive ouabaintreated rats and further to elucidate the role of ouabain in pathogenesis of hypertension. Methods:Thirty male Sprague-Dawley rats weighting 180-200 g were randomly divided into normal control group and ouabain treated group. Rats were infused with 1 ml/kg · d normal saline or 27.8 μg/kg · d ouabain intraperitoneally once a day respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Rats were sacrificed 6 weeks after treatment. Blood and 24-hour urine sample were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated.Ouabain levels of plasma and renal tissue, plasma renin activity, angiotensin Ⅱ and aldosterone concentration were determined. Results: 65% of the ouabain-treated rats achieved significantly higher SBP after 4weeks, compared with that of the saline control groups or self baseline (P<0. 01). But in the other 35%of the ouabain-treated rats, their SBP was similar with control group during the experiment (P>0. 05).The body weight, heart rate and food intake between the 3 groups were no significant differences (P>0.05). FELi and FDRNa were significantly lower in ouabain-hypertensive group compared with ouabain-nonhypertensive group and control group(P<0.01 and P<0.05). The FELi and FDRNa of ouabain-nonhypertensive groups were similar with control group(P>0.05). Ccr and FENa were comparable between the 3 groups (P>0. 05). Plasma and renal tissue ouabain levels, plasma renin activity, angiotensin Ⅱ and aldosterone contents in ouabain-hypertensive rats were

  10. Prenatal developmental toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats

    Wolterbeek, A.P.M.; Roberts, A.; Korte, H.; Unkila, M.; Waalkens-Berendsen, D.H.


    Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium aceta



    Multiple injections of D-galactosamine induce liver fibrosis and cirrhosis in rats. The purpose of this immunopathological study was to correlate inflammation and hepatic extracellular matrix remodeling after repeated administration of galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and

  12. Immunocytochemical study on the intracellular localization of the type 2 glucocorticoid receptor in the rat brain

    Eekelen, J.A.M. van; Kiss, J.Z.; Westphal, H.M.; Kloet, E.R. de


    The localization of the glucocorticoid receptor (GR) (type 2) in the rat brain was studied with immunocytochemistry using a monoclonal antibody against the rat liver GR. Strong GR immunoreactivity (GR-ir) was observed in neurons of limbic and brainstem structures known to be associated with the stre

  13. Short-term toxicity studies with triphenyltin compounds in rats and guinea-pigs

    Verschuuren, H.G.; Kroes, R.; Vink, H.H.; Esch, G.J. van


    Short-term toxicity studies have been carried out in rats and guinea-pigs fed diets containing triphenyltin acetate (TPTA), triphenyltin hydroxide (TPTH) or triethyltin hydroxide (TETH) for 90 days at levels ranging from 0 to 50 ppm. The lowest dietary levels found to retard growth in rats and guin

  14. A semiautomated test apparatus for studying partner preference behavior in the rat

    J. Bakker (Julie); J. van Ophemert (J.); F. Eijskoot (F.); A.K. Slob (Koos)


    textabstractA semiautomated three-compartment box (3CB) for studying partner preference behavior of rats is decribed. This apparatus automatically records the rat's time spent in each compartment, as well as the locomotor activity (i.e., the number of visits an animal pays to each compartment). Soft

  15. Review of previous geophysical and geological studies

    Levchenko, O.V; Neprochnov, Y.P.; Rao, D; Subrahmanyam, C; Murthy, K.S.R

    stream_size 5 stream_content_type text/plain stream_name Mem_Geol_Soc_India_39_5.pdf.txt stream_source_info Mem_Geol_Soc_India_39_5.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 ...

  16. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

    Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.


    Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.

  17. Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.


    Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 31 refs., 6 figs., 19 tabs.

  18. Fibre type regionalisation in lower hindlimb muscles of rabbit, rat and mouse : a comparative study

    Wang, LC; Kernell, D


    The topographical distribution of different fibre types in muscles of the lower hindlimb in rabbits and mice was quantitatively determined. The results were compared to those previously obtained, using the same new quantification methods, in homologous muscles of the rat. Type I fibres ('slow') were

  19. A quantitative in-vivo MR imaging study of brain dehydration in diabetic rats and rats treated with peptide hormones.

    Haraldseth, O; Jones, R A; Skottner, A


    The main aim of the study was to evaluate the combination of quantitative diffusion, T2 and Magnetisation Transfer Imaging of brain water homeostasis using untreated diabetes as an animal model of brain dehydration. In addition, experimental groups of diabetic rats treated with insulin and insulin-like growth factor (IGF-I) and normal rats treated with IGF-I and growth hormone were studied using the same MR imaging protocol. Untreated diabetes caused weight reduction and an increase in water intake, indicating a general body dehydration linked to chronic blood hyperosmolarity. In the investigated cortical gray matter untreated diabetes caused a significant reduction in the apparent diffusion coefficient of water (ADC) and an increase in T2 relaxtivity (R2) when compared to a control group. No significant changes were observed for the calculated magnetisation transfer parameters Kfor and T1sat. Both ADC and R2 normalized after appropriate insulin treatment whereas only ADC was normalized after IGF-I treatment. IGF-I treatment of normal rats caused significantly higher rate of increase in body weight compared to normal controls. There were, however, no significant changes in ADC, R2 nor the magnetisation transfer parameters measured in the cortical gray matter of the IGF-I treated normal rats. In conclusion, we found that changes in brain water homeostasis during diabetes were detected by quantitative MR imaging, and that the dehydration induced by diabetes was normalized by insulin treatment but not by IGF-I.

  20. Effect of ethanol on hepatobiliary transport of cationic drugs. A study in the isolated perfused rat liver, rat hepatocytes and rat mitochondria

    Steen, H.; Merema, M.; Meijer, D.K.F. (Department of Pharmacology and Therapeutics, University Centre for Pharmacy, Groningen State Univrsity, Groningen (Netherlands))


    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation tri-n-butylmethylammonium was found to be markedly stimulated by ethanol in a concentration-dependent fashion. The uptake of tri-n-butylmethylammonium at 1 [mu]M was increased to 120% and 137% at 0.5% (v/v, (=87 mM)) and 1% (v/v, (=174 mM)) ethanol, respectively. At 25 [mu]M, tri-n-butylmethylamonium uptake was increased to 124% and 152% at 0.5% (v/v) and 1% (v/v) of ethanol, respectively. The uptake of the organic cations azidoprocainamide methoiodide, vecuronium, ORG 9426 and ORG 6368, the anionic compound taurocholate and the uncharge compound ouabain was not markedly increased at these ethanol concentrations. The mechanism of action of ethanol on the uptake of tri-n-butylmethylammonium was further studied. Competitive inhibitors for the type I organic cation uptake system, procainamide ethobromide and verapamil, almost completely blocked uptake of tri-n-butyl-methylammonium (1 [mu]M) in the presence of 1% (v/v) ethanol, indicating that carrier-mediated uptake is still involved and that additional passive diffusion is unlikely. Neither the plasma membrane potential nor the accumulation of the cation in mitochondria was altered after ethanol treatment, suggesting that potential driving forces for uptake and sequestration were not affected. The results of our study indicate that ethanol selectively stimulates the uptake of the aliphatic organic cation tri-n-butylmethylammonium rather than through generally alterated hepatobiliary transport processes. (EG) (28 refs.).

  1. Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in streptozotocin-induced diabetic rats.

    Prasath, Gopalan Sriram; Subramanian, Sorimuthu Pillai


    Chronic hyperglycemia in diabetes is associated with profound changes in lipid and lipoprotein metabolism, with resultant alterations in particle distribution within lipoprotein classes. In the present study, an attempt has been made to explore the antihyperlipidemic effect of fisetin in streptozotocin-induced experimental diabetes in rats. Upon fisetin treatment to diabetic rats, the levels of blood glucose were significantly reduced with an improvement in plasma insulin. The increased levels of lipid contents in serum, hepatic, and renal tissues observed in diabetic rats were normalized upon fisetin administration. Also, the decreased levels of high-density lipoprotein cholesterol, and increased levels of low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol in serum of diabetic rats were normalized. Oil Red O staining established a large number of intracellular lipid droplets accumulation in the diabetic rats. Fisetin treatment exacerbated the degree of lipid accumulation. The results of the present study exemplify the antihyperlipidemic property of the fisetin. © 2014 Wiley Periodicals, Inc.


    CHENWen-Jian; ZHANGLong-Sheng; YANGXin-Li; SHENGJi-Yun; ZHOUJie-Ling; WUXi-Rui


    In this paper, morphological studies of uterus and ovary during terminating early pregnancy with mifcpristonc Were reported. In the experimental studies, 24 hrs after inhering 10 mg / kg mifcpristonc to early pregnant rats, all embryos wcrc dead, with decidual cells

  3. Histomorphometric study of diazinon on growth plate of rat

    Mahdiye Bazmi


    Conclusion: Diazinon leads to reduction in the Epiphyseal growth plate width of immature male rats. Therefore it could be a factor in the impairment of bone longitudinal growth and premature closure of the growth plate.

  4. Spinal Cord Studies in the African Giant Rat (Cricetomys gambianus ...


    Keywords: African giant rat; spinal cord; spinal tract; nuclei; spinal segment; morphometry. ©Physiological Society .... cervical segment appeared as a vertical slit (Figure 3a), the second to the sixth ... Intermediomedial column. Lsg. Laminae of ...

  5. Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with levetiracetam: a preliminary study.

    Zalewska-Kaszubska, Jadwiga; Bajer, Bartosz; Czarnecka, Elżbieta; Dyr, Wanda; Gorska, Dorota


    Many recent researches have confirmed the effectiveness of antiepileptic drugs in preventing alcohol dependency, whereas our previous study showed that repeated treatment with topiramate, a new antiepileptic drug, was effective in increasing the plasma levels of beta-endorphin (an endogenous opioid peptide) in rats. It is well documented that in humans a genetic deficit of beta-endorphin is often associated with alcohol addiction as alcohol consumption elevates the level of this peptide. The aim of the present study is multifaceted: to investigate the effect of repeated treatment of levetiracetam (50 or 100mg/kg b.w., twice daily) on voluntary alcohol intake in alcohol preferring rats (Warsaw High Preferring; WHP) and to assess changes in plasma beta-endorphin levels while alcohol is available and when it is not available for an extended period of time. We observed a noticeable increase in the levels of beta-endorphin in rats with free access to alcohol whether in a prolonged levetiracetam-treated or vehicle-treated group. However, in the levetiracetam group, a voluntary intake of alcohol diminished in comparison with both the pretreatment period and in comparison with the vehicle-treated rats. A similar increase in the plasma beta-endorphin levels was observed in levetiracetam-treated rats that did not have access to ethanol. This finding lets us to believe that levetiracetam may be a promising medication in treatment of alcohol dependency as its application leads to the increase in the beta-endorphin concentration and ultimately results in reducing deficiency of this peptide.

  6. Brain activation in response to visceral stimulation in rats with amygdala implants of corticosterone: an FMRI study.

    Anthony C Johnson

    Full Text Available BACKGROUND: Although visceral pain of gastrointestinal (GI origin is the major complaint in patients with irritable bowel syndrome (IBS it remains poorly understood. Brain imaging studies suggest a defect in brain-gut communication in IBS with a greater activation of central arousal circuits including the amygdala. Previously, we found that stereotaxic implantation of corticosterone (CORT onto the amygdala in rats induced anxiety and colonic hypersensitivity. In the present study we used functional magnetic resonance imaging (fMRI to identify specific brain sites activated in a rat model characterized by anxiety and colonic hypersensitivity. METHODOLOGY/PRINCIPAL FINDINGS: Anesthetized male rats received micropellets (30 microg each of either CORT or cholesterol (CHOL, to serve as a control, implanted stereotaxically on the dorsal margin of each amygdala. Seven days later, rats were anesthetized and placed in the fMRI magnet (7T. A series of isobaric colorectal balloon distensions (CRD - 90s 'off', 30s 'on', 8 replicates at two pressures (40 and 60 mmHg were performed in a standard block-design. Cross correlation statistical analysis was used to determine significant differences between distended and non-distended states in CORT and CHOL-treated animals. Analysis of the imaging data demonstrated greater overall brain activation in response to CRD in rats with CORT implants compared to CHOL controls. Additionally, CORT implants produced significant positive bilateral increases in MRI signal in response to CRD in specific nuclei known as integration sites important in anxiety and pain perception. CONCLUSIONS AND SIGNIFICANCE: These data indicate that chronic exposure of the amygdala to elevated levels of CORT enhances overall brain activation in response to CRD, and identified other specific brain regions activated in response to mechanical distension of the colon. These results demonstrate the feasibility of performing fMRI imaging in a rodent

  7. Effect of Honey on Peridural Fibrosis Formation after Laminectomy in Rats: A Novel Experimental Study

    Majid Reza Farrokhi


    been focused on peridural fibrosis (PF, which may be responsible for recurrent pain after laminectomy or discectomy. Honey has been shown to exert anti-inflammatory effects on exposed tissues besides its well-known antibacterial properties. The aim of this study were to investigate the effects of honey on the prevention of postlaminectomy fibrosis formation in a rat model. A controlled blinded study was performed in 45 male adult white Sprague-Dawley rats that underwent laminectomy at the L5-L6 levels. They were divided into 3 groups (A, B, and C of 15 rats each. Group A (sham underwent laminectomy and group B was treated with normal saline at the laminectomy site. Rats in group C received 0.1 mL honey at the laminectomy site. All rats were killed 4 weeks after laminectomy. PF was found in 5 rats (33% of control groups A and B, and in 2 rats (10% in honey-treated laminectomy group C. The difference was not statistically significant. Wound healing was not affected, and there was no cerebrospinal fluid leakage. Although honey appears to be safe, it cannot cause a significant reduction of PF formation after lumbar laminectomy in rats.

  8. Enzyme histochemical studies of membrane proteases in rat subfornical organ.

    De Bault, L E; Mitro, A


    Localization of membrane proteases glutamyl aminopeptidase (EAP), microsomal alanyl aminopeptidase (mAAP), dipeptidyl peptidase IV (DPP IV) and gamma-glutamyl transpeptidase (gamma-GTP) were studied in vessels of the rat subfornical organ (SFO), ependyma which cover the surface of the SFO, and adjacent brain structures. Results of enzyme histochemical reactions showed strong activity for EAP, mAAP, and gamma-GTP, but absence of DPP IV in microvessels of SFO. The ependyma which cover the SFO was positive for gamma-GTP, but negative for other studied proteases. Our results showed that the spectrum of enzymes in the majority of the vessels of SFO is similar to that of the microvessels of the adjacent brain tissue which were positive for EAP, mAAP, and gamma-GTP, but negative for DPP IV. The relative intensity of the enzyme reactions in vessels varied from central to lateral locations in the SFO and the adjacent brain tissue. There was also a difference in the relative reaction intensity from one enzyme to the other. The presence and heterogeneous distribution of the enzymes are consistent with the hypothesis that membrane proteases of the microvascular endothelium constitute an enzyme-barrier between blood and parenchyma of the SFO and between blood and brain tissue, and may be involved in metabolism or modulation of various peptides when they contact the plasma membrane of the endothelial cells of the vessels.

  9. Experimental Study of Angeng Prescription for Climacteric Syndrome in Rats

    CHEN Da-shuai


    Full Text Available Objective: To observe the effect of Angeng Formula on climacteric syndrome in rats. Methods: The ovaries of female SD rats were removed for the establishment of menopausal syndrome rat models. After drug delivery for 30 d, serum sex hormone levels and indexes of uterus, adrenal gland and pituitary were detected. Meanwhile, the effects of drugs on the histopathology of uterus, adrenal gland and pituitary in rats were observed. Results: Angeng prescription could increase the level of estradiol (E2 in castrated rat (P<0.01 and had a tendency to increase the level of progestin (P, lower the level of luteinizing hormone (LH and follicle-stimulating hormone (FSH as well as increase the indexes of the uterus and adrenal gland. Moreover, Angeng prescription could improve the pathologic condition of the uterus, adrenal gland and pituitary in castrated rats. Conclusion: Angeng prescription has a therapeutic effect on climacteric syndrome, the mechanism of which might be related with the function of regulating sex hormone.

  10. Experimental Study on Angeng Formula for Climacteric Syndrome in Rats

    CHEN Da-shuai; LI Peng-li; TAN Hai-zhi


    Objective:To observe the effect of Angeng Formula on climacteric syndrome in rats. Methods:The ovaries of female SD rats were removed for the establishment of menopausal syndrome rat models. After drug delivery for 30 d, serum sex hormone levels and indexes of uterus, adrenal gland and pituitary were detected. Meanwhile, the effects of drugs on the histopathology of uterus, adrenal gland and pituitary in rats were observed. Results:Angeng Formula could increase the level of estradiol (E2) in castrated rat (P<0.01) and had a tendency to increase the level of progestin (P), lower the level of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as well as increase the indexes of the uterus and adrenal gland. Moreover, Angeng Formula could improve the pathologic condition of the uterus, adrenal gland and pituitary in castrated rats. Conclusion:Angeng Formula has a therapeutic effect on climacteric syndrome, the mechanism of which might be related with the function of regulating sex hormone.

  11. Structural studies of innervation on nonpregnant rat uterus.

    Garfield, R E


    Whole-mount preparations of the uterus and mesentery from nonpregnant rats were examined after staining with glyoxylic acid or acetylcholinesterase to demonstrate the innervation. Some uterine tissues were also evaluated by electron microscopy. Glyoxylic acid fluorescent nerves were present in the mesentery, mesometrium, and uterine wall exclusively around blood vessels. Acetylcholinesterase positive nerve fibers from Frankenhäuser's plexus (cervical ganglia) were associated with blood vessels and muscle in the uterine wall but not in the mesentery. Electron microscopy revealed nerve varicosities with granular vesicles associated with blood vessels and varicosities with agranular vesicles located near blood vessels and muscle cells. Treatment of animals for 3 days with 5- and 6-hydroxydopamine, respectively, increased granular size and damaged the varicosities with granular vesicles but did not change nerves with agranular vesicles or induce the presence of gap junctions. The results of this study suggest that blood vessels in the uterus are highly innervated by both adrenergic and other types of nerves that probably control blood flow. Nonadrenergic but not adrenergic nerves may also directly control myometrial contractility.

  12. A Biochemical and Morphological Study of Rat Liver Microsomes

    Moulé, Y.; Rouiller, C.; Chauveau, J.


    Microsomes isolated by differential centrifugation from a rat liver homogenate in 0.88 M sucrose solution have been studied from the biochemical and morphological point of view. 1. Under these experimental conditions, the "total microsome" fraction was obtained by centrifuging the cytoplasmic extract free of nuclei and mitochondria, for 3 hours at 145,000 g. Morphologically, the total microsomes consist mainly of "rough-surfaced membranes" and "smooth" ones. 2. The total microsomes have been divided into 2 subfractions so that the 1st microsomal fraction contains the "rough" vesicles (2 hours centrifugation at 40,000 g) while the 2nd microsomal fraction consists essentially of smooth vesicles, free particles, and ferritin (centrifugation of the supernatant at 145,000 g for 3 hours). 3. By the action of 0.4 per cent sodium deoxycholate in 0.88 M sucrose, it was possible to obtain a pellet for each of the 2 fractions which consisted of dense particles, rich in RNA, poor in lipids, and which represented about 50 to 60 percent of the RNA and 10 to 15 per cent of the proteins. The results have been discussed taking into consideration the hypothesis of the presence of RNA in the membranes of microsomal vesicles. PMID:14424705

  13. Diluted isoflurane as a suitable alternative for diethyl ether for rat anaesthesia in regular toxicology studies.

    Nagate, Toshiaki; Chino, Tomonobu; Nishiyama, Chizuru; Okuhara, Daisuke; Tahara, Toru; Maruyama, Yoshimasa; Kasahara, Hiroko; Takashima, Kayoko; Kobayashi, Sayaka; Motokawa, Yoshiyuki; Muto, Shin-ichi; Kuroda, Junji


    Despite its explosive properties and toxicity to both animals and humans, diethyl ether is an agent long used in Japan in the anaesthesia jar method of rat anaesthetises. However, in response to a recent report from the Science Council of Japan condemning diethyl ether as acceptable practice, we searched for an alternative rat anaesthesia method that provided data continuous with pre-existing regular toxicology studies already conducted under diethyl ether anaesthesia. For this, we examined two candidates; 30% isoflurane diluted with propylene glycol and pentobarbitone. Whereas isoflurane is considered to be one of the representatives of modern volatile anaesthetics, the method of propylene glycol-diluted 30% isoflurane used in this study was our modification of a recently reported method revealed to have several advantages as an inhalation anaesthesia. Intraperitoneal pentobarbitone has long been accepted as a humane method in laboratory animal anaesthesiology. These 2 modalities were scrutinized in terms of consistency of haematology and blood chemistry with previous results using ether. We found that pentobarbitone required a much longer induction time than diethyl ether, which is suspected to be the cause of fluctuations in several haematological and blood chemical results. Conversely, only calcium ion concentration showed a slight difference from traditional results in the case of 30% isoflurane. Additionally, serum prolactin and corticosterone levels indicated that 30% isoflurane induced less stress than ether, confirming that 30% isoflurane can both provide results consistent with diethyl ether, while at the same time remove its disadvantages. As such 30% isoflurane appears to be a strong alternative anaesthetic agent for future regular toxicology studies in Japan.

  14. Role of oxidative stress in ethanol induced germ cell apoptosis — An experimental study in rats

    Maneesh, M.; Jayalekshmi, H; Dutta, Sanjiba; Chakrabarti, Amit; Vasudevan, D. M.


    The study was undertaken to evaluate the possible involvement of oxidative stress in the pathogenesis of ethanol induced testicular atrophy in rats. Adult male rats were orally administered ethanol at a dose of 1.6 g/kg body weight/day for four weeks. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and weighed. Apoptosis was studied by using the Feulgen reaction on 5 μ thin paraffin sections of testis. Testicular homogenate was p...

  15. [Histochemical study of the digestive organs of rats after a flight on "Kosmos-605"].

    Shubich, M G; Goriacheva, L L; Dudetskiĭ, V I; Lutsenko, N M; Mogil'naia, G M


    The histochemical study of the stomach, small and large intestines and pancreas of rats flown aboard the biosatellite Cosmos-605 as well as of synchronous and vivarium controls demonstrated a significant decline in the mucine producing capacity of epithelial cells of the stomach of the flight rats on the R + 1 day. The study showed an increased content of sialo- and sulphosaccharides in goblet cells of cryptae of large intestine and a reduced content of free cation protein in the acinar cells of the pancreas of flight rats. The changes were transient and disappeared by the R + 26 day.

  16. [Morphological study of the adrenals of rats exposed on the Kosmos-690 satellite].

    Savina, E A; Alekseev, E I


    Adrenals of 12 rats flown aboard the biosatellite Cosmos-690 and 30 rats used in the ground-based experiments Control-1 and Control-2 were studied morphologically. The animals were sacrificed on the 2nd and 27th days after completion of the experiments (i. e., on the 12 and 37th days after irradiation at a total dose of 800 rad). A comparative study of morphological changes in the adrenals of flight and control rats did not show any distinct differences. It is therefore concluded that space flight factors did not produce a significant effect on the adrenal response to irradiation at a dose of 800 rad.

  17. Inhalation developmental toxicology studies: Acetonitrile in rats. Final report

    Mast, T.J.; Weigel, R.J.; Westerberg, R.B.; Boyd, P.J.; Hayden, B.K.; Evanoff, J.J.; Rommereim, R.L.


    The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppM acetonitrile, 6 hours/day, 7 days/week. Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppM group (2/33 pregnant females; 1/10 non-pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposure-correlated increase in the incidence of supernumerary ribs. Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppM acetonitrile ({approximately}2 {mu}g cyanide/g of blood).

  18. A genome-wide SNP panel for mapping and association studies in the rat

    Guryev Victor


    Full Text Available Abstract Background The laboratory rat (Rattus norvegicus is an important model for human disease, and is extensively used for studying complex traits for example in the physiological and pharmacological fields. To facilitate genetic studies like QTL mapping, genetic makers that can be easily typed, like SNPs, are essential. Results A genome-wide set of 820 SNP assays was designed for the KASPar genotyping platform, which uses a technique based on allele specific oligo extension and energy transfer-based detection. SNPs were chosen to be equally spread along all chromosomes except Y and to be polymorphic between Brown Norway and SS or Wistar rat strains based on data from the rat HapMap EU project. This panel was tested on 38 rats of 34 different strains and 3 wild rats to determine the level of polymorphism and to generate a phylogenetic network to show their genetic relationships. As a proof of principle we used this panel to map an obesity trait in Zucker rats and confirmed significant linkage (LOD 122 to chromosome 5: 119–129 Mb, where the leptin receptor gene (Lepr is located (chr5: 122 Mb. Conclusion We provide a fast and cost-effective platform for genome-wide SNP typing, which can be used for first-pass genetic mapping and association studies in a wide variety of rat strains.


    A.O. Eweka.


    Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the inferior colliculus (IC of adult Wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups. The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with growers' mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The inferior colliculus was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the inferior colliculus showed some cellular degenerative changes, cellular hypertrophy, and autophagic vacuoles with some intercellular vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections.These findings indicate that MSG consumption may have a deleterious effect on the neurons of the inferior colliculus (IC. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the IC of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

  20. Developmental Toxicity Studies with Atrazine and its Major Metabolites in Rats and Rabbits

    Scialli, Anthony R; DeSesso, John M; Breckenridge, Charles B


    Atrazine (ATR), hydroxyatrazine (OH-ATR), and the three chloro metabolites of ATR (deethylatrazine [DEA], deisopropylatrazine [DIA], diaminochlorotriazine [DACT]) were evaluated for developmental effects in rats and rabbits. Three developmental toxicity studies were conducted on ATR in rats (two studies) and rabbits and a developmental toxicity study was conducted in rats for each of the four ATR metabolites DEA, DIA, DACT, and OH-ATZ. ATR administration by gavage to pregnant rats and rabbits from implantation (gestation day [GD] 6 in rat, GD 7 in rabbit) through closure of the palate (GD 15 in rat and GD 19 in rabbit) did not statistically significantly alter the incidence of developmental abnormalities or malformations at dose levels up to 100 (rat) or 75 (rabbit) mg/kg bw/day. There were no effects on developmental toxicity parameters for DEA, DIA, DACT, or OH-ATR at oral dose levels up to 100, 100, 150, or 125 mg/kg bw/day, respectively, with the exception of reductions in fetal body weight by DACT and OH-ATR in the presence of decreased maternal body weight gain. ATR did not adversely affect developmental end points in a two-generation study conducted in rats exposed to dose levels up to 500 ppm (38.7 mg/kg/day) in the diet. The 500-ppm dose level resulted in significantly reduced maternal body weight gain. Overall, data show that neither ATR nor its metabolites statistically significantly affected rat or rabbit embryo-fetal development even at dose levels producing maternal toxicity. PMID:24797531

  1. Effect of a single dosis of 96% ethanol on rat gastric mucosa. Part II. Histoenzymological studies.

    Kotz, J; Knapik, Z; Lubczyńska-Kowalska, W; Houszka, M; Lapińska, J; Rybak, M


    The histoenzymological studies of ATPase and SDH enzymes in rats' gastric mucosa after a single 90 s administration of 96% ethanol proved considerable changes in the enzymes activity in course of injury and subsequent regeneration of mucosa.

  2. Chronic toxicity and carcinogenicity study of isomalt in rats and mice.

    Smits-Van Prooije, A E; De Groot, A P; Dreef-Van der Meulen, H C; Sinkeldam, E J


    The chronic toxicity and possible carcinogenicity of the sugar replacer isomalt was studied in Wistar rats and Swiss mice. Groups of 50 animals of each sex were fed 0, 2.5, 5 or 10% isomalt in the diet for nearly 2.5 yr (rats) or 2 yr (mice). Control groups received either basal diet with 10% maize starch or basal diet with 10% sucrose. Additional groups of ten rats/sex were fed the same diets and were killed after 1 yr. Isomalt and sucrose were included in the diet at the expense of maize starch. Administration of isomalt was started, in rats, in utero, and in mice, at weaning age. Feeding isomalt did not affect the appearance or behaviour of rats or mice, nor did it cause diarrhoea. Mortality rate was unaffected. Body weights of rats and mice fed 10% isomalt were generally slightly lower than those of controls. Periodic examinations of rats for haematological criteria, clinical chemistry of the blood, urine composition and kidney function did not reveal any changes of toxicological significance. Periodic haematological examinations of mice were likewise negative. Caecal enlargement was observed in rats and mice of the high-dose group, but the microscopic structure of the caecal wall was unaffected. An increased number of treated male and female rats showed hyperplasia of the urothelium in the renal pelvis accompanied by mineralization, whereas the number of females showing corticomedullary mineralization was decreased in the treated groups. The incidence, type or location of neoplasia provided no evidence of a carcinogenic potential of isomalt. Feeding 10% sucrose did not induce significant differences compared with the controls fed 10% maize starch, whereas isomalt at levels of up to 10% produced some of the changes that are common to rats fed high levels of poorly digestible carbohydrates.

  3. Study of rat neuronal genes with ordered differential display method

    KANG; Jiansheng; (


    [1]Wang, Y., Du, Z. W., eds., Neurobiology and Molecular Biology, Beijing: People's Medical Publishing House, 1997, 184-207, 244-248.[2]Liang, P., Pardee, A., Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction, Science, 1992, 257: 967-971.[3]Michiels, L., Van Leuven, F., van den Oord, J. J. et al., Representational difference analysis using minute quantities of DNA, Nucleic Acids Res., 1998, 26(15): 3608-3610.[4]Diatchenko, L., Lau, Y. F., Campbell, A. P. et al., Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries, Proc. Natl. Acad. Sci. USA, 1996, 93(12): 6025-6030.[5]Matz, M., Lukyanov, S., Different strategies of differential display: areas of application, Nucleic Acids Res., 1998, 26: 5537-5543.[6]Matz, M., Usman, N., Shagin, D. et al., Ordered differential display: a simple method for systematic comparison of gene expression profiles, Nucleic Acids Res, 1997, 25: 2541-2542.[7]Chen, X. X., Guan, L. C., Bao, S. M. et al., Comparison and study of memory and open field behavior of four different mouse strain, Psychological Science, 1994, 17(1): 39-41.[8]Chapman, C. R., Casey, K. L., Dubner, R. et al., Pain measurement: an overview, Pain, 1985, 22: 1-31.[9]Mitchell, .D., Hellon, R. F., Neuronal and behavioral responses in rats during noxious stimulation of the tail, Proc. R. Soc. Lond., 1977, 197: 169-194.[10]Shen, Y., Yan, Y. S., eds., Medical Statistics, Shanghai: Shanghai Medical University Press, 1999, 39-44.[11]Kang, J. S., Li, R. X., Du, Y. C., Ordered differential display, Chemistry of Life, 1999, 19(6): 282-283.[12]Mou, L., Miller, H., Li, J. et al., Improvements to the differential display method for gene analysis, Biochem. Biophys. Res. Commun., 1994, 199: 564-569.[13]Lee, H. N., Weinstock, K. G., Kirkness, E. F. et al., Comparative expressed-sequence-tag analysis of differential gene

  4. A new rat model for studies of hypokinesia and antiorthostasis

    Musacchia, X. J.; Deavers, D. R.


    A new rat model (suspension and immobilization) is described for induction of hypokinesia and orthostatic manipulations. Hypokinetic responses were comparable to those in prolonged bed rest and weightlessness in humans, body or limb casted and small cage restrained animals. Responses to antiorthostasis (15 to 20 deg head down tilt) in rats were similar to those in neutral bouyancy tests in humans and animals and to those in prolonged bed rest in humans. During seven days of hypokinesia there was an atrophy of the gastrocnemius and increased excretion of urinary nitrogeneous end products. The antiorthostatic (AOH) 15 to 20 deg head down tilt resulted in diuresis, natriuresis and kaliuresis. No comparable responses were observed in orthostatic hypokinetic (OH) rats. Readaptation from AOH and OH occurred during one week recovery in metabolic cage conditions.

  5. Lectin Histochemical Study of Vasculogenesis During Rat Pituitary Morphogenesis

    Ali Reza Ebrahimzadeh Bideskan


    Full Text Available Objective(s The aim of this study was to investigate glycoconjugates distribution patterns as well as their changes during the course of pituitary portal vasculogenesis and angiogenesis.Materials and MethodsFormalin fixed paraffin sections of 10 to 20 days of Sprague Dawly rat fetuses were processed for histochemical studies using four different horseradish peroxidase (HRP conjugated lectins. Orange peel fungus (OFA, Vicica villosa (VVA, Glycine max (SBA and Wistaria floribunda (WFA specific for α-L-Fucose, D-Gal, α, ß-D-GalNAc and D- GalNAc terminal sugars of glycoconjugates respectively.ResultsOur finding indicated that adenohypophysal cells reacted with OFA on gestational day 10 (E10 and increased progressively to E14. Staining intensity did not change from days 14 to17, then after increased following days to E20 significantly (P< 0.05. A few cells around Rathke’s pouch reacted with VVA on E13, increased to E14 and decreased significantly afterward (P< 0.05. Reaction of some cells around Rathke’s pouch reacted with SBA on E14. This visible reaction was the same as E18 and decreased later (P< 0.05. Many cells around Rathke’s pouch reacted with WFA on E13 and increased on E 14 and E15 and decreased thereafter (P< 0.05.ConclusionReactions of OFA and other tested lectins with endothelial cells around Rathke’s pouch and developing pars distalis were different. These results suggest that embryonic origin of hypophiseal pituitary portal (HPP system endothelial cells are not the same and our finding also indicated that glycoconjugates with terminal sugars α-L-Fucose, D-Gal, α, ß-D-GalNAc may play critical role(s in cell interactions and tissue differentiations such as vasculogensis and angiogenesis as well as other developmental precursors in formation of the pituitary gland.

  6. Proteomic study of periovarian adipose tissue in 17β-estradiol-treated and untreated ovariectomized rats.

    Amengual-Cladera, Emilia; Capllonch-Amer, Gabriela; Lladó, Isabel; Gianotti, Magdalena; Proenza, Ana M


    Taking into account the sexual dimorphism previously found in white adipose tissue (WAT) regarding mitochondrial function and biogenesis, as well as insulin sensitivity, the aim of this study was to go further into the role of sex hormones in this dimorphism. To achieve this objective, we used ovariectomized rats and performed a screening by means of proteomic analyses of the periovarian WAT, combined with a study of the protein levels of specific factors involved in mitochondrial function. Rats were ovariectomized at 5 weeks of age and subcutaneously injected every 48 h with corn-oil (OVX group) or with 17β-estradiol (E2, 10 μg/kg body mass; OVX + E2 group) for 4 weeks prior to sacrifice. Beside proteomic analysis, protein levels of Transcription Factor A, Mitochondrial (TFAM), cytochrome oxidase (COX)II, and COXIV were determined by Western blot, and mRNA levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, ERα, ERβ, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPARγ), and adiponectin were quantified by real-time PCR. Our results show that ovariectomy leads to an increase in anabolic processes and inflammatory protein levels as well as to a decrease in some of the markers of mitochondrial function, which are restored, at least in part, by E2 supplementation. Indeed, this E2 supplementation seems to be counteracted by a decline in ERα and in the ERα to ERβ ratio values that could be directed to avoid an over-stimulation of the E2 signaling pathway, given the possibility of an activation of extra-gonadal steroid biosynthetic pathways.

  7. Embryofetal development study of vismodegib, a hedgehog pathway inhibitor, in rats.

    Morinello, Eric; Pignatello, Michael; Villabruna, Loris; Goelzer, Petra; Bürgin, Heinrich


    Vismodegib (Erivedge) is a first-in-class small-molecule hedgehog pathway inhibitor for the treatment of adults with advanced basal-cell carcinoma. Because this pathway is known to play key roles in patterning and growth during vertebrate development, vismodegib was anticipated to be embryotoxic. To support marketing applications, an embryofetal development study was completed in which a limited number of pregnant rats (n = 6/group) was administered vismodegib by oral gavage on gestation days 6 to 17. When vismodegib was administered at ≥60 mg/kg/day, doses associated with evidence of pharmacologic activity in previous rat toxicity studies, all conceptuses were resorbed at an early embryonic stage in the absence of significant maternal toxicity. When administered at 10 mg/kg/day, corresponding to an exposure (AUC0-24h ) approximately 15% of the median in patients at steady state, a variety of malformations were observed, including absent/fused digits in the hindlimb of multiple fetuses, multiple craniofacial abnormalities in one fetus, and an anorectal defect in one fetus. In addition, the incidence of variations, including dilated renal pelvis or ureter and incompletely or unossified skeletal elements, was significantly greater when compared with the controls. These results confirmed that vismodegib is likely to be embryotoxic at clinically relevant maternal exposures, and doses ≥60 mg/kg/day resulted in a 100% incidence of embryolethality that likely resulted from severe defects in early embryonic development. In contrast, craniofacial defects typically associated with hedgehog pathway inhibition were only observed in one fetus at the low dose of 10 mg/kg/day, which likely reflected minimal or intermittent pathway inhibition at low exposures.

  8. [Pharmacological study on blood pressure in rats with bone disorders].

    Shamoto, T


    To evaluate the relationship between the elevation of blood pressure and altered bone metabolism, the changes of systolic blood pressure in six experimental models for bone disorders were investigated. Rats used were either parathyroidectomized, ovariectomized, fed with a calcium-deficient diet, fed with a vitamin D-deficient diet, treated with HEBP (1-Hydroxyethylidene-1, 1-bisphosphonate) or treated with streptozotocin. Hypertension developed in 5-week-old male rats fed with a calcium-deficient diet for 2 weeks, which evoked hypocalcemia and nutritional hyperparathyroidism. The blood pressure returned to normal when fed with a normal calcium diet. In parathyroidectomized rats receiving a normal calcium diet, the blood pressure did not rise, though the plasma calcium level decreased to an extent similar to the rats fed with the calcium-deficient diet. These findings seem to indicate that hyperparathyroidism, but not hypocalcemia, was involved in the elevation of blood pressure in rats fed with a calcium-deficient diet. Hypertension was not observed in rats fed with a vitamin D-deficient diet or treated with streptozotocin. These rats showed not only an increase in parathyroid hormone (PTH) but also a decrease in 1,25 (OH)2 D3. These results may suggest that the presence of 1,25 (OH)2D3 as well as the enhanced parathyroid function is necessary for the development of hypertension. The elevated blood pressure was reduced by a calcium antagonist, nifedipine, or by calcium supplementation, but not by an inhibitor of angiotensin-converting enzyme, captopril, or by calcitonin. This may indicate that hypertension due to nutritional hyperparathyroidism responds to the calcium antagonist nifedipine and to calcium supplementation, but does not depend on renin or salt. Furthermore, an acute hypotensive effect by human PTH (1-34) was not observed in the hypertension of calcium-deficient rats, suggesting the difference between acute and chronic effects of PTH. The hypertension

  9. An experimental study of the effects of Matricaria chamomilla extract on cutaneous burn wound healing in albino rats.

    Jarrahi, Morteza


    Previous studies conducted on the anti-inflammatory, antimicrobial and antioxidant effects of Matricaria chamomilla (chamomile) extract led us to study the effect of topical chamomile extract on burn wound healing in albino rats. Thirty male albino rats (250-300 g) were randomly divided into three groups, as control, vehicle, and treatment. Second-degree burning was induced in 20% of whole surface area of animal body by placing the back of animal into boiling water for 8s. Animals of control group received no treatment. Animals of vehicle and treatment groups were treated topically by olive oil and extract dissolved in olive oil twice a day respectively from the first day of burn induction to complete wound healing. The percentage of wound healing was calculated weekly. The results showed that there was significant difference (p < 0.05) between vehicle and treatment groups. So we concluded that the chamomile extract in the form of rubbing oil had a good potential for acceleration of burn wound healing in rats.

  10. Acute effects of various diuretics on lithium clearance. Studies in rats on medium and low sodium diet.

    Thomsen, K; Leyssac, P P


    Previous studies have shown that the clearance of lithium (CLi) is a quantitative measure of the delivery of tubular fluid to Henle's loop in rats given food with an ordinary or high sodium content, but not in rats given food with a low sodium content, because under these latter circumstances lithium is also reabsorbed to some extent in the distal nephron. The present study examines the effect of acetazolamide, hydrochlorothiazide, furosemide, and amiloride on the distal reabsorption of lithium in conscious rats with hereditary diabetes insipidus fed standard diets with medium (300 mmol Na/kg) and low (5 mmol Na/kg) sodium contents, respectively. Low sodium diet induced distal Li reabsorption, as apparent from the decrease in CLi and a fall in the urine/plasma lithium concentration ratio (U/P)Li, to below 1.0. Amiloride and furosemide abolished the distal Li reabsorption. Acetazolamide also abolished distal Li reabsorption and, in addition, it increased the fluid output from the proximal tubules. Hydrochlorothiazide was unable to abolish distal Li reabsorption.

  11. Hymenolepiosis in a group of albino rats (Rattus albus): a study.

    Sreedevi, C; Ravi Kumar, P; Jyothisree, Ch


    A study was carried out on adult albino Wistar laboratory rats to know the incidence of hymenolepiosis, a zoonotic disease which were brought for experiment purpose. Faecal samples of 95 rats examined for parasitic infection by simple floatation technique in which 32 were positive (33.68 %) for hymenolepiosis. Identification of species of Hymenolepis was done based on morphology of egg. The highest prevalence of Hymenolepis diminuta (23.15 %) was recorded followed by Hymenolepis nana (10.52 %). Heavy infection with Hymenolepis in rats draws attention in view of public health importance in contact persons.

  12. Experimental study of icariin on vascular dementia in rats induced by 2-VO method

    Rui-xiaXU; QinWU; Jing-shanSHI


    AIM: To study the effects of icariin (ICA) on the learning and memory of ischemic vascular dementia (VD) model of rats,and explore the protective mechanisms. METHODS: ICA was administered to the VD model rats induced by a permanent bilateral occlusion of both common carotids arteries(2-VO method) and by cerebral ischemia-reperfusion (I10-R 10-110 method). Morris water maze was used to examine the abilities of spatial learning and memory of VD model rats. The activity of SOD, level of

  13. Subsequent pregnancy outcome after previous foetal death

    Nijkamp, J. W.; Korteweg, F. J.; Holm, J. P.; Timmer, A.; Erwich, J. J. H. M.; van Pampus, M. G.


    Objective: A history of foetal death is a risk factor for complications and foetal death in subsequent pregnancies as most previous risk factors remain present and an underlying cause of death may recur. The purpose of this study was to evaluate subsequent pregnancy outcome after foetal death and to

  14. Behavioral and Neurochemical Studies in Stressed and Unstressed Rats Fed on Protein, Carbohydrate and Fat Rich Diet

    Samia Moin§, Saida Haider*, Saima Khaliq1, Saiqa Tabassum and Darakhshan J. Haleem


    Full Text Available Stress produces behavioral and neurochemical deficits. To study the relationship between adaptation to stress and macronutrient intake, the present study was designed to monitor the effects of different diets on feed intake, growth rate and serotonin (5-Hydroxytryptamine, 5-HT metabolism following exposure to restraint stress in rats. Rats were divided into four groups (n=12 as control, sugar, protein and fat rich diet fed rats. After 5 weeks of treatment animals of each group were divided into unrestrained and restrained animals (n=6. Rats of restrained group were given immobilization stress for 2 hours/day for 5 days. Food intake and growth rates of unrestrained and restrained rats were monitored daily. Rats were decapitated on 6th day to collect brain samples for neurochemical estimation. Results show that sugar diet fed rats produced adaptation to stress early as compared to normal diet fed rats. Food intake and growth rates of unrestrained and restrained rats were comparable on 3rd day in sugar diet fed rats and on 4th day in normal diet fed rats. Stress decreased food intake and growth rates of protein and fat treated rats. Repeated stress did not alter brain 5-HT and 5-HIAA levels of normal diet fed rats and sugar diet fed rats. Protein diet fed restrained rats showed elevated brain 5-HT levels. Fat diet fed restrained rats significantly decreased brain TRP and 5-HIAA levels. Finding suggested that carbohydrate diet might protect against stressful conditions. Study also showed that nutritional status could alter different behaviors in response to a stressful environment.

  15. Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces

    Jian-feng XING; Hai-sheng YOU; Ya-lin DONG; Jun LU; Si-ying CHEN; Hui-fang ZHU; Qian DONG; Mao-yi WANG; Wei-hua DONG


    Aim: To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron brevis-capus (Vant) Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats.Methods: HPLC method was developed for simultaneous detection of scutellarin and scutellarein (the aglycone of scutellarin) in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders. Results. After a single oral dose of scutellarin (400 mg/kg), the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, t and C for scutel-larin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin (400 mg/kg), the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t and CL value for scuteliarin in male rats was significantly higher than that in female rats.Conclusion: The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharma-cokinetic parameters of scutellarin and scutallarein are due to the higher CL and lower absorption in male rats.

  16. Identification of Site of Morphine Action in Pregnant Wistar Rat Placenta Tissue: A C14-Morphine Study

    Leila Dehghani


    Full Text Available Objective: In previous studies it has been emphasized that the site of morphine action may be either in the embryo or the placenta. In the present study, we attempt to identify the site of morphine action on the fetal section of Wistar rat placenta by using C14-morphine.Materials and Methods: In this study (experimental, female Wistar rats (weights: 170-200 g were mated with male rats and their coupling times recorded. Experimental groups received daily doses of 0.05 mg/ml of C14-morphine in their drinking water. On the 9th and14th embryonic days, the pregnant rats were anesthetized and the placenta and uterus surgically removed. Placentas were fixed in 10% formalin for two weeks, then processed, sectioned in 5 μm and 25 μm thicknesses, and fixed on glass slides for further evaluation. The 25 μm sections were delivered to black and white film for three days. Films were processed and evaluated with a digital inverse microscope for possible radiological impression. The 5 μm sections were processed for hematoxylin and eosin (H&E staining, and evaluated by light microscope and MOTIC software.Results: Our results indicated that the site of action of C14-morphine was possibly located on the blood plexus of the fetal portion of the placenta. In addition, oral morphine consumption was shown to inhibit fetal and maternal placental development in the experimental groups.Conclusion: We conclude that morphine’s effectiveness on the reduction of embryo growth and development may be via its effects on the blood plexus of the fetal section of the placenta.

  17. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    Jong-Kyu Kim


    Conclusion: The no-observable-adverse-effect level (NOAEL of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS.

  18. How physical exercise changes rat myotendinous junctions: an ultrastructural study

    D. Curzi


    Full Text Available Myotendinous junctions can be easily injured by overloading or trauma, and exercise training may be a way of increasing their resistance to mechanical stress. To this end, we examined herein the morphological changes induced by moderate exercise training in the myotendinous junctions of extensor digitorum longus and gastrocnemius muscles in rats. Twelve Sprague-Dawley rats were used in this investigation. Six of them were trained to run on a treadmill for 1 h/day, 3 days/week over 10 weeks in order for them to achieve a running rate of 25 m/min at the end of the training period. Six age-matched sedentary rats were used as controls. The rats were sacrificed 24 h after the final training session, and the extensor digitorum longum (EDL and the gastrocnemium were excised; the myotendinous junctions (MTJ were then prepared and observed with electron microscopy. Digitation branching was evaluated by counting the bifurcations in the MTJ protrusions. Our observations indicate that exercise does indeed induce changes in MTJ morphology. In both muscles the number of bifurcated interdigitations increased significantly, as well as, in gastrocnemius, the branching of the finger-like processes. It was demonstrated that the MTJ is able to adapt to an increase in tensile force by enlarging the muscle-tendon contact area and, consequently, mechanical resistance.

  19. [Experiments using rats on Kosmos biosatellites: morphologic and biochemical studies].

    Il'in, E A; Kaplanskiĭ, A S; Savina, E A


    Results of morphological and biochemical investigations of rats flown on Cosmos biosatellites are discussed. It is emphasized that most changes occurring during exposure to microgravity are directly or indirectly related to lower musculoskeletal loads which in turn produce deconditioning of different physiological systems and organism as a whole. It is concluded that this deconditioning is associated with both metabolic and structural changes.

  20. How physical exercise changes rat myotendinous junctions: an ultrastructural study.

    Curzi, D; Salucci, S; Marini, M; Esposito, F; Agnello, L; Veicsteinas, A; Burattini, S; Falcieri, E


    Myotendinous junctions can be easily injured by overloading or trauma, and exercise training may be a way of increasing their resistance to mechanical stress. To this end, we examined herein the morphological changes induced by moderate exercise training in the myotendinous junctions of extensor digitorum longus and gastrocnemius muscles in rats. Twelve Sprague-Dawley rats were used in this investigation. Six of them were trained to run on a treadmill for 1 h/day, 3 days/week over 10 weeks in order for them to achieve a running rate of 25 m/min at the end of the training period. Six age-matched sedentary rats were used as controls. The rats were sacrificed 24 h after the final training session, and the extensor digitorum longum (EDL) and the gastrocnemium were excised; the myotendinous junctions (MTJ) were then prepared and observed with electron microscopy. Digitation branching was evaluated by counting the bifurcations in the MTJ protrusions. Our observations indicate that exercise does indeed induce changes in MTJ morphology. In both muscles the number of bifurcated interdigitations increased significantly, as well as, in gastrocnemius, the branching of the finger-like processes. It was demonstrated that the MTJ is able to adapt to an increase in tensile force by enlarging the muscle-tendon contact area and, consequently, mechanical resistance.

  1. Effect of diazinon in male rats. Histopathological and biochemical studies.

    Dikshith, T S; Behari, J R; Datta, K K; Mathur, A K


    Mild structural and functional changes were observed in liver and testes of rats after a single intraperitoneal administration of diazinon (21.6 mg/kg). Kidney, however, showed no pathological lesion. Attempts are made to correlate the pathological changes in these organs with the activity of succinic dehydrogenase, adenosine triphosphatase and alkaline phosphatase.

  2. [Study on inhibitory effect of EGCG on Calcium oxalate nephrolithiasis in rats and its related mechanism].

    Zhou, Yong; Wang, Shuo; Tang, Chun-bo


    In the study, the inhibitory effect of epigallocatechin gallate (EGCG) on Calcium oxalate nephrolithiasis and its possible mechanism were investigated. The rat Calcium oxalate nephrolithiasis model was induced through the combined oral administration of ethylene glycol and ammonium chloride, which was intervened with EGCG. Rat blood samples were collected to detect blood creatinine (Cr), blood urea nitrogen (BUN) and blood calcium. Rat urine samples were collected to observe and compare 24-hour urine volume, oxalic acid (Ox) and calcium in urine. Renal samples were collected to prepare tissue slices and observe the pathological changes in Calcium oxalate nephrolithiasis. The expression of osteopontin (OPN) in renal tissues was evaluated by Real-time PCR and Western blot. According to the results, compared with normal rats, rats in the nephrolithiasis model showed significant increases in Cr, BUN, urine Calcium, urine Ox and renal OPN expression (P nephrolithiasis, those processed with EGCG revealed remarkable declines in Cr, BUN, urine Calcium and urine Ox (P nephrolithiasis rats showed significant pathological changes in Calcium oxalate calculus. After ECCG treatment, the renal pathological changes and OPN expression attenuated significantly in a concentration-dependent manner. The results showed that EGCG inhibits the formation of calcium oxalate nephrolithiasis in rats and shows a notable protective effect on renal functions.

  3. Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

    Mazen M. Jamil Al-Obaidi


    Full Text Available Objectives. To estimate the impact of ellagic acid (EA towards healing tooth socket in diabetic animals, after tooth extraction. Methods. Twenty-four Sprague Dawley male rats weighing 250–300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w. of freshly prepared streptozotocin (STZ, to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV. The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg orally. The maxilla tissue stained by eosin and hematoxylin (H&E was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2 and alkaline phosphatase (ALP were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction.


    Josiah O. Adjene


    Full Text Available Histological effects of red pepper commonly used as spice in food on the stomach of adult wistar rats were carefully investigated. The rats of both sexes (n=24, average weight of 200g were randomly assigned into two treatments (n=16 and control (n=6 groups. The rats in the treatments groups received 1g and 2g of red pepper thoroughly mixed with 20g of their feeds for 7 and 14 days, while the control rats received equal amounts of feeds without the red pepper added. The rats were fed with grower's mash purchased from Edo feeds and flour mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day eight and fifteen of the experiment respectively.The stomach was carefully dissected out and quickly fixed in 10% formol saline for routine histological procedure after H & E method.The histological findings after H&E methods indicated that the treated sections of the stomach showed some level of cellular hypertrophy, congestion of blood vessels degenerative changes disruption and distortion of the cytoarchitecture of the stomach.These findings indicate that red pepper may have some deleterious effects on the microanatomy of the stomach of adult wistar rat at higher doses. It is recommended that further studies aimed at corroborating these findings be carried out.

  5. Digital Joint Reconstruction with Osteotendinous Joint Allograft: Experimental Study in Rats.

    Iglesias, Martin; Cruz-Reyes, Ángel Uriel; Butrón, Patricia; Hernández-Agallo, Ricardo; de la Barrera, Víctor Antonio Torres; Reyes-Montero, Claudio; Durand-Carbajal, Marta; Torres-Villalobos, Gonzalo


    Fresh or frozen nonvascularized osteotendinous joint allografts (OTJA) have not been used previously, clinically or experimentally, for metacarpophalangeal joint reconstruction. Therefore, we evaluated the viability of OTJA for metatarsophalangeal joint (MTJ) reconstruction in rats. In the experimental group of 12 Lewis rats, we reconstructed the MTJ of the third digit of the hindlimb with a fresh, nonvascularized OTJA obtained from the same digit from 12 donor rats. In the control group of 6 Lewis rats, an autologous composite osteotendinous graft of the MTJ of the same digit was obtained and repositioned in situ as an auto-transplant. Weight, pain, edema, dehiscence, and wound infection were evaluated every 24 hours for 30 days postoperatively. At the end of 30 days, we evaluated digit position, flexion and extension, passive mobility, radiological bone healing, and histological grades of rejection. We found no statistically different changes in weight, edema, pain, digit position, or radiological bone healing in either group. No wound dehiscence or infection was seen in any of the rats. Ten degrees of flexion and extension mobility were lost in the control group; the experimental group lost up to 30 degrees (P = 0.009). Histologically, 9 of the experimental group rats (9/12, 75%) showed rejection reactions compared with none of the controls (0%) (P = 0.009). Fresh nonvascularized OTJA caused an immune reaction without exposure of the graft, but with bone resorption. However, the rats maintained digital form and alignment with decreased passive flexion and extension of 10-30 degrees.

  6. Teratological studies in defatted jojoba meal-supplemented rats.

    Cokelaere, M; Flo, G; Lievens, S; Van Boven, M; Vermaut, S; Decuypere, E


    To look for possible developmental effects in the offspring of jojoba meal-treated Wistar rats, and to distinguish between the effects of reduced food intake and the specific developmental effects of jojoba meal itself, mated female rats were divided into three groups of 20 rats. They received during gestation: (a) normal rodent food (control group); (b) normal rodent food supplemented with 3% defatted jojoba meal (jojoba group); or (c) normal rodent food pair-fed with the jojoba group (pair-fed group). The jojoba meal group showed approximately 30% inhibition of food intake. Ten rats from each group were killed on gestation day 21. Compared to the control group, foetal body weight was reduced in both the jojoba and pair-fed groups, with a greater reduction in the jojoba group. Skeletal ossification was retarded to the same extent in both the jojoba and pair-fed groups. The other 10 rats from each group were left to produce litters. Compared with controls, the body weight of the pups was lower in both the jojoba and pair-fed groups; the reduction was slightly greater in the jojoba group, but this difference disappeared after 1 week. The offspring showed no other abnormalities and reproduced normally. We conclude that, at the dose used, the retardation in foetal skeletal ossification, induced by jojoba meal supplementation during gestation, is due to food intake inhibition. Moreover, the lower birth weight of the young of jojoba-treated dams compared with the pair-fed group is merely due to a lower body weight gain during gestation.

  7. A rat liver foci promotion study with 50-Hz magnetic fields.

    Rannug, A; Holmberg, B; Mild, K H


    To investigate the possible tumor-promoting effect of magnetic fields (MF), we have performed two liver foci bioassays in rats which were exposed to MF at four flux density levels (0.5 microT, 5 microT, 0.05 mT, and 0.5 mT). The MF were generated in exposure equipment consisting of copper coils surrounding racks with animal cages and giving homogenous horizontal 50-Hz magnetic fields. Rats previously submitted to partial hepatectomy and diethylnitrosamine treatment were exposed to MF for 12 weeks. Exposed and control rats were kept in separate rooms. As a positive control phenobarbital (PB) was administered for 12 weeks. The number, area, and volume of foci expressing gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST-p) were evaluated. The body weight gains and relative liver weights of MF-exposed rats were not different as compared to control rats. There was a slight increase in GGT-staining foci, but not in GST-p-staining foci, in the groups exposed to flux densities of 0.5 microT and 0.05 mT compared to the control group in the first experiment. The number of both GGT- and GST-p-staining foci in the livers of all MF-exposed groups were, however, within the control range when the results of the two experiments were considered together.

  8. Food Neophobia in Wild Rats (Rattus norvegicus Inhabiting a Changeable Environment-A Field Study.

    Klaudia Modlinska

    Full Text Available Food neophobia is a reaction to novel food observed in many animal species, particularly omnivores, including Rattus norvegicus. A neophobic reaction is typically characterised by avoidance of novel food and the necessity to assess both its potential value and toxicity by the animal. It has been hypothesised that this reaction is not observed in rats inhabiting a changeable environment with a high level of variability with regard to food and food sources. This study was conducted in such changeable conditions and it aims to demonstrate the behaviour of wild rats R. norvegicus in their natural habitat. The rats were studied in a farm setting, and the experimental arena was demarcated by a specially constructed pen which was freely accessible to the rats. At regular intervals, the rats were given new flavour- and smell-altered foods, while their behaviour was video-recorded. The results obtained in the study seem to confirm the hypothesis that rats inhabiting a highly changeable environment do not exhibit food neophobia. The observed reaction to novel food may be connected with a reaction to a novel object to a larger extent than to food neophobia. The value of the results obtained lies primarily in the fact that the study was conducted in the animals' natural habitat, and that it investigated their spontaneous behaviours.

  9. Food Neophobia in Wild Rats (Rattus norvegicus) Inhabiting a Changeable Environment—A Field Study

    Modlinska, Klaudia; Stryjek, Rafał


    Food neophobia is a reaction to novel food observed in many animal species, particularly omnivores, including Rattus norvegicus. A neophobic reaction is typically characterised by avoidance of novel food and the necessity to assess both its potential value and toxicity by the animal. It has been hypothesised that this reaction is not observed in rats inhabiting a changeable environment with a high level of variability with regard to food and food sources. This study was conducted in such changeable conditions and it aims to demonstrate the behaviour of wild rats R. norvegicus in their natural habitat. The rats were studied in a farm setting, and the experimental arena was demarcated by a specially constructed pen which was freely accessible to the rats. At regular intervals, the rats were given new flavour- and smell-altered foods, while their behaviour was video-recorded. The results obtained in the study seem to confirm the hypothesis that rats inhabiting a highly changeable environment do not exhibit food neophobia. The observed reaction to novel food may be connected with a reaction to a novel object to a larger extent than to food neophobia. The value of the results obtained lies primarily in the fact that the study was conducted in the animals’ natural habitat, and that it investigated their spontaneous behaviours. PMID:27254150

  10. Food Neophobia in Wild Rats (Rattus norvegicus) Inhabiting a Changeable Environment-A Field Study.

    Modlinska, Klaudia; Stryjek, Rafał


    Food neophobia is a reaction to novel food observed in many animal species, particularly omnivores, including Rattus norvegicus. A neophobic reaction is typically characterised by avoidance of novel food and the necessity to assess both its potential value and toxicity by the animal. It has been hypothesised that this reaction is not observed in rats inhabiting a changeable environment with a high level of variability with regard to food and food sources. This study was conducted in such changeable conditions and it aims to demonstrate the behaviour of wild rats R. norvegicus in their natural habitat. The rats were studied in a farm setting, and the experimental arena was demarcated by a specially constructed pen which was freely accessible to the rats. At regular intervals, the rats were given new flavour- and smell-altered foods, while their behaviour was video-recorded. The results obtained in the study seem to confirm the hypothesis that rats inhabiting a highly changeable environment do not exhibit food neophobia. The observed reaction to novel food may be connected with a reaction to a novel object to a larger extent than to food neophobia. The value of the results obtained lies primarily in the fact that the study was conducted in the animals' natural habitat, and that it investigated their spontaneous behaviours.

  11. Hemodynamic effects of combined focal cerebral ischemia and amyloid protein toxicity in a rat model: a functional CT study.

    Jun Yang

    Full Text Available BACKGROUND/OBJECTIVE: Clinical evidence indicates that cerebral ischemia (CI and a pathological factor of Alzheimer's disease, the β-amyloid (Aβ protein, can increase the rate of cognitive impairment in the ageing population. Using the CT Perfusion (CTP functional imaging, we sought to investigate the interaction between CI and the Aβ protein on cerebral hemodynamics. METHODS: A previously established rat model of CI and Aβ was used for the CTP study. Iodinated contrast was given intravenously, while serial CT images of sixteen axial slices were acquired. Cerebral blood flow (CBF and blood volume (CBV parametric maps were co-registered to a rat brain atlas and regions of interest were drawn on the maps. Microvascular alteration was investigated with histopathology. RESULTS: CTP results revealed that ipsilateral striatum of Aβ+CI and CI groups showed significantly lower CBF and CBV than control at the acute phase. Striatal CBF and CBV increased significantly at week 1 in the CI and Aβ+CI groups, but not in the Aβ alone or control group. Histopathology showed that average density of dilated microvessels in the ipsilateral striatum in CI and Aβ+CI groups was significantly higher than control at week 1, indicating this could be associated with hyperperfusion and hypervolemia observed from CTP results. CONCLUSION: These results demonstrate that CTP can quantitatively measure the hemodynamic disturbance on CBF and CBV functional maps in a rat model of CI interacting with Aβ.

  12. Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model.

    Wang, Di; Wang, Wei; Zhou, Yulin; Wang, Juan; Jia, Dongxu; Wong, Hei Kiu; Zhang, Zhang-Jin


    Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL.

  13. A comparative study of zirconium and titanium implants in rat: osseointegration and bone material quality.

    Hoerth, Rebecca M; Katunar, María R; Gomez Sanchez, Andrea; Orellano, Juan C; Ceré, Silvia M; Wagermaier, Wolfgang; Ballarre, Josefina


    Permanent metal implants are widely used in human medical treatments and orthopedics, for example as hip joint replacements. They are commonly made of titanium alloys and beyond the optimization of this established material, it is also essential to explore alternative implant materials in view of improved osseointegration. The aim of our study was to characterize the implant performance of zirconium in comparison to titanium implants. Zirconium implants have been characterized in a previous study concerning material properties and surface characteristics in vitro, such as oxide layer thickness and surface roughness. In the present study, we compare bone material quality around zirconium and titanium implants in terms of osseointegration and therefore characterized bone material properties in a rat model using a multi-method approach. We used light and electron microscopy, micro Raman spectroscopy, micro X-ray fluorescence and X-ray scattering techniques to investigate the osseointegration in terms of compositional and structural properties of the newly formed bone. Regarding the mineralization level, the mineral composition, and the alignment and order of the mineral particles, our results show that the maturity of the newly formed bone after 8 weeks of implantation is already very high. In conclusion, the bone material quality obtained for zirconium implants is at least as good as for titanium. It seems that the zirconium implants can be a good candidate for using as permanent metal prosthesis for orthopedic treatments.

  14. A study on 17alpha-ethinylestradiol metabolism in rat and Pleurotus ostreatus.

    Borek-Dohalska, Lucie; Valaskova, Petra; Kubickova, Bozena; Sulc, Miroslav; Kresinova, Zdena; Cajthaml, Tomas; Stiborova, Marie


    17α-Ethinylestradiol (EE2) is an endocrine disruptor that is an ingredient of oral contraceptives. Here, EE2 metabolism catalyzed by cytochromes P450 (CYP) was studied. Two model organisms, rat and ligninolytic fungus Pleurotus ostreatus, were used. To resolve the role of rat and/or fungal CYPs in EE2 oxidation, microsomes were incubated with EE2 and NADPH or cumene hydroperoxide. Using Supersomes™, we examined which of rat CYPs oxidize EE2. EE2 is effectively degraded by P. ostreatus in vivo. In vitro, EE2 is metabolized by CYPs by the NADPH-dependent and organic hydroperoxide-dependent mechanisms. Rat hepatic microsomes metabolize EE2 in the presence of NADPH to three products; two of them are hydroxylated EE2 derivatives. Using rat Supersomes™ we found that EE2 is hydroxylated by several rat CYPs, among them CYP2C6 and 2C11 are most efficient in 2-hydroxy-EE2 formation, while CYP2A and 3A catalyze EE2 hydroxylation to the second product. On the contrary, the products of the NADPH-dependent hydroxylating reactions were not detected in Pleurotus ostreatus. During the reaction of EE2 in microsomes isolated from rat and P. ostreatus in the presence of the alternate oxidant, cumene hydroperoxide, another metabolite, different from the above mentioned products, is generated. Rat CYP1A1 is the most efficient enzyme catalyzing formation of this EE2 product. The results suggest that CYPs play a role in EE2 metabolism in rat and P. ostreatus. To our knowledge this is the first finding describing ligninolythic fungal metabolism of EE2 by CYP in the presence of cumene hydroperoxide.

  15. Subchronic oral toxicity study of Vegeta in Sprague-Dawley rats

    Hedi R. Dewoto


    Full Text Available The objective of this study was to determine the safety and toxic effect of Vegeta giving orally for a period of 90 days in rats. Eighty rats of Sprague-Dawley strain were randomly devided into 4 groups. Each group consists of 20 rats, 10 male and 10 female rats. Each group received 0.25 g/ kgBW; 0.50 g / kgBW; 1.00 g / kgBW Vegeta (in aquadest solution respectively, and the control group received 5 mL /kgBW aquadest , given orally by gastric tube for 90 days. The rat’s body weight and behavior were daily evaluated. On the 90th day, the rats were decapitated and the blood samples were withdrawn for evaluation of Hemoglobin, leucocyte, SGPT, SGOT, creatinine, and ureum concentration. Visceral organs were also removed, being weighted and were examined microscopically. The results showed that Vegeta with dose of 0.25 g / kgBW; 0.50 g / kgBW, and 1.00 g / kgBW did not affect body weight, liver and renal function compared to control group. There was no significant difference for hemoglobin value compared to control group, but the number of leucocyte increased in 1.00 g / kgBW Vegeta dose group, which was possibly caused by infection. In Vegeta group, there was different spleen and brain weight in male rats, and different lung and heart weight in female rats compared to the control group. However, since it was not dose-related and there was no specific abnormality in microscopic examination compared to the control group, it was not indicated as Vegeta toxic effect. The No observed effect level (NOEL value of Vegeta for 90 day oral administration in male and female rats of Sprague-Dawley strain was 1.00 g / kgBW. (Med J Indones 2006; 15:223-8Keywords: Vegeta, subchronic toxicity, oral, rats

  16. A gene-environment study of cytoglobin in the human and rat hippocampus

    Hundahl, Christian Ansgar; Elfving, Betina; Müller, Heidi Kaastrup;


    Cygb to be up regulated by hypoxic stress. This study addresses three main questions related to Cygb expression in the hippocampus: 1) Is the rat hippocampus a valid neuroanatomical model for the human hippocampus; 2) What is the degree of co-expression of Cygb and neuronal nitric oxide synthase (n......NOS) in the rat hippocampus; 3) The effect of chronic restraint stress (CRS) on Cygb and nNOS expression....

  17. A novel silk fibroin nanofibrous membrane for guided bone regeneration: a study in rat calvarial defects

    Lu, Shijun; Wang, Peng; Zhang, Feng; Zhou, Xichao; Zuo, Baoqi; You, Xinran; Gao, Yang; Liu, Hongchen; Tang, Hailiang


    A novel membrane for guided bone regeneration (GBR), constituting silk fibroin (SF) nanofiber from native silk nanofibril solution, was prepared by electrospinning process. Another barrier membrane, a collagen-type membrane (Bio-Gide®), was used as a comparative sample. Twelve healthy male Sprague-Dawley rats were used in this study. Bilateral round defects were created in the calvarial bone. The bone regenerative efficacy was evaluated in rat calvarial defects. Animals were killed at 4 and 1...

  18. Multivariate temporal pattern analysis applied to the study of rat behavior in the elevated plus maze: methodological and conceptual highlights.

    Casarrubea, M; Magnusson, M S; Roy, V; Arabo, A; Sorbera, F; Santangelo, A; Faulisi, F; Crescimanno, G


    Aim of this article is to illustrate the application of a multivariate approach known as t-pattern analysis in the study of rat behavior in elevated plus maze. By means of this multivariate approach, significant relationships among behavioral events in the course of time can be described. Both quantitative and t-pattern analyses were utilized to analyze data obtained from fifteen male Wistar rats following a trial 1-trial 2 protocol. In trial 2, in comparison with the initial exposure, mean occurrences of behavioral elements performed in protected zones of the maze showed a significant increase counterbalanced by a significant decrease of mean occurrences of behavioral elements in unprotected zones. Multivariate t-pattern analysis, in trial 1, revealed the presence of 134 t-patterns of different composition. In trial 2, the temporal structure of behavior become more simple, being present only 32 different t-patterns. Behavioral strings and stripes (i.e. graphical representation of each t-pattern onset) of all t-patterns were presented both for trial 1 and trial 2 as well. Finally, percent distributions in the three zones of the maze show a clear-cut increase of t-patterns in closed arm and a significant reduction in the remaining zones. Results show that previous experience deeply modifies the temporal structure of rat behavior in the elevated plus maze. In addition, this article, by highlighting several conceptual, methodological and illustrative aspects on the utilization of t-pattern analysis, could represent a useful background to employ such a refined approach in the study of rat behavior in elevated plus maze. Copyright © 2014 Elsevier B.V. All rights reserved.


    C. Selva Kumar


    Full Text Available Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of Ayurvedic herbal formulation Cynodon dactylon (Bermuda grass on histopathological study and DNA fragmentation analysis in experimentally induced hypercholesteremic rats. Four groups of rats were employed namely control, hypercholesterolemia rats (4% Cholesterol+1% cholic acid, Cynodon dactylon treatment in hypercholesteremic rats and Cynodon dactylon alone treated rats. Results of DNA fragmentation was found to be greater in High cholesterol diet fed groups. Lesser fragmentation was found in high cholesterol diet + Cynodon dactylon treated group when compared to the high cholesterol diet group. Cynodon dactylon alone treated group is comparably similar to that of normal group (lesser fragmentation. Histopathological study of thoracic aorta of Cynodon dactylon treated group shows decrease in atherogenicity compared to untreated high cholesterol diet fed rats. The data demonstrated that Cynodon dactylon formulation was associated with hypolipidemic effects on the experimentally induced hypercholesteremic rats.

  20. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    Palade Philip T


    Full Text Available Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR in cardiac myocytes, with voltage clamp (VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR, and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo. Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU, in which resides the mechanistic basis of CICR. The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel. It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its

  1. Chronic toxicity study of cyclohexanone in rats and mice.

    Lijinsky, W; Kovatch, R M


    A 2-year chronic toxicity assay of cyclohexanone (CAS: 108-94-1) was conducted in F344 rats and (C57BL/6 X C3H)F1 mice by administering a solution of cyclohexanone in drinking water. Two concentrations were given to rats, 6,500 and 3,300 ppm (wt/vol). Male mice received 13,000 and 6,500 ppm, while female mice were given three concentrations, 25,000, 13,000, and 6,500 ppm. Each treatment group consisted of 50 or 52 male and 50 or 52 female rats or mice, except 47 male mice treated with the highest dose and 41 female mice treated with the highest dose, and there was a group of untreated controls of each species. Survival and weight gain were similar to those of controls at the lowest cyclohexanone dose in both sexes of both species, but weight gain was depressed at all of the higher doses. Survival was good (greater than 80% at 90 wk) in all groups except in female mice at the 2 highest doses; at 25,000 ppm of cyclohexanone, only 50% of mice lived beyond 1 year. Most of the neoplasms in the treated groups did not differ significantly in number from those in the controls. Male rats receiving 3,300 ppm cyclohexanone had a 13% incidence of adrenal cortex adenomas (7 animals) compared with an incidence of 2% in controls; the incidence of this neoplasm did not increase in the male rats receiving 6,500 ppm or in the female rats given either dose. The mice had a statistically significant increase in incidence of lymphomas-leukemias among the females given 6,500 ppm, but not among the groups given higher doses of cyclohexanone. Male mice given 6,500 ppm cyclohexanone showed an increased incidence of hepatocellular adenomas and carcinomas, 50% versus 32.5% in controls, but the incidence of these neoplasms was only 37% in the male mice given 13,000 ppm cyclohexanone. The incidence of lymphomas in male mice and of hepatocellular neoplasms in female mice given cyclohexanone did not differ from that in the controls. The evidence for carcinogenic activity of cyclohexanone is

  2. Oral subchronic immunotoxicity study of ethyl tertiary butyl ether in the rat.

    Banton, Marcy I; Peachee, Vanessa L; White, Kimber L; Padgett, Eric L


    The potential for immunotoxicological effects of ethyl tertiary butyl ether (ETBE, CAS RN 637-92-3) was studied in young adult female Crl:CD(SD) rats following subchronic oral exposures. Rats were exposed by gavage once daily for 28 consecutive days to 0, 250, 500, or 1000 mg ETBE/kg body weight (BW)/day; a concurrent positive control group received four intraperitoneal injections of at 50 mg cyclophosphamide monohydrate (CPS)/kg/day on study Days 24-27. Immunotoxicity was evaluated using a splenic antibody-forming cell (AFC) assay to assess T-cell-dependent antibody responses in rats sensitized with sheep red blood cells (SRBC). All rats survived to the scheduled necropsy. There were no effects on clinical observations, body weights, feed or water consumption, or macroscopic pathology findings in the ETBE-treated rats. No ETBE-related effects were observed on absolute or relative (to final body weight) spleen or thymus weights, spleen cellularity, or on the specific (AFC/10(6) spleen cells) or total activity (AFC/spleen) of splenic IgM AFC to the T-cell-dependent antigen SRBC. CPS produced expected effects consistent with its known immunosuppressive properties and validated the appropriateness of the AFC assay. Based on the results of this study, ETBE did not suppress the humoral component of the immune system in female rats. The no-observed-effect level for immunotoxicity was the highest dosage tested at 1000 mg/kg/day.

  3. Characterization of SV-40 Tag rats as a model to study prostate cancer

    Eltoum Isam A


    Full Text Available Abstract Background Prostate cancer is the second most frequently diagnosed cancer in men. Animal models that closely mimic clinical disease in humans are invaluable tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen (SV-40 Tag targeted probasin promoter rat model was developed. This model, however, has not been extensively characterized; hence we have investigated the ontogeny of prostate cancer and determined the role of sex steroid receptor and insulin-like growth factor-1 (IGF-1 signaling proteins in the novel SV-40 Tag rat. Methods The SV-40 Tag rat was histopathologically characterized for time to tumor development, incidence and multiplicity and in the ventral, dorsal, lateral and anterior lobes of the prostate. Immunoassay techniques were employed to measure cell proliferation, apoptosis, and sex steroid receptor and growth factor signaling-related proteins. Steroid hormone concentrations were measured via coated well enzyme linked immunosorbent assay (ELISA kits. Results Prostatic intraepithelial neoplasia (PIN and well-differentiated prostate cancer developed as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP followed by in the dorsolateral (DLP. At 8 weeks of age, testosterone and dihydrotestosterone (DHT concentrations in SV-40 Tag rats were increased when compared to non-transgenic rats. High cell proliferation and apoptotic indices were found in VP and DLP of transgenic rats. Furthermore, we observed increased protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular signal-regulated kinases in the prostates of SV-40 Tag rats. Conclusion The rapid development of PIN and prostate cancer in conjunction with the large prostate size makes the SV-40 Tag rat a useful model for studying prostate cancer. This study provides evidence of the role of sex steroid and growth factor proteins in prostate cancer development and defines appropriate windows of

  4. Pathology review of proliferative lesions of the exocrine pancreas in two chronic feeding studies in rats with ammonium perfluorooctanoate

    Jessica M. Caverly Rae


    Full Text Available Two chronic dietary studies, conducted years apart, with ammonium perfluorooctanoate (APFO in Sprague Dawley rats have been previously reported. Although both included male 300 ppm dietary dose groups, only the later study, conducted in 1990–1992 by Biegel et al., reported an increase in proliferative lesions (hyperplasia and adenoma of the acinar pancreas. An assessment of the significance of the differences between both studies requires careful consideration of: the diagnostic criteria for proliferative acinar cell lesions of the rat pancreas (for example, the diagnosis of pancreatic acinar cell hyperplasia versus adenoma is based on the two-dimensional size of the lesion rather than distinct morphological differences; the basis for those criteria in light of their relevance to biological behavior; and the potential diagnostic variability between individual pathologists for difficult-to-classify lesions. A pathology peer review of male exocrine pancreatic tissues from the earlier study, conducted in 1981–1983 by Butenhoff et al., was undertaken. This review identified an increase in acinar cell hyperplasia but not adenoma or carcinoma in the earlier study. Both studies observed a proliferative response in the acinar pancreas which was more pronounced in the study by Biegel et al. Definitive reasons for the greater incidence of proliferative lesions in the later study were not identified, but some possible explanations are presented herein. The relevance of this finding to human risk assessment, in the face of differences in the biological behavior of human and rat pancreatic proliferative lesions and the proposed mechanism of formation of these lesions, are questionable.

  5. Teratogenicity studies of alkylaryl phosphate ester plasticizers in rats.

    Robinson, E C; Hammond, B G; Johannsen, F R; Levinskas, G J; Rodwell, D E


    Santicizer 141 plasticizer (2-ethylhexyldiphenyl phosphate) and Santicizer 148 plasticizer (isodecyldiphenyl phosphate) were tested for teratogenic activity in Charles River COBS CD rats. Groups of 25 mated females were given 0, 300, 1000, or 3000 mg/kg/day by gavage on Days 6 through 15 (Santicizer 141) or 6 through 19 (Santicizer 148) of gestation. Mean maternal body weight gains were slightly and severely reduced at the mid- and high-dose levels of Santicizer 141, respectively. Body weights were not affected by treatment with Santicizer 148. Most malformations found in groups treated with either plasticizer occurred as single incidences and have been observed in historical controls. Thus, no teratogenic response was observed in rats after treatment with either of these two alkylaryl phosphates during the period of organogenesis.

  6. Dorsal and median Raphe nuclei projection to MD of Thalamus in rat: A retrograde tracer study

    Pas Bakhsh P


    Full Text Available In order to understand the function of mammalians serotonin system, we have to know the anatomical structure, because physiological changes are influenced through the anatomical changes. A number of thalamic nuclei are associated with functions known to be influenced by serotonergic input in brainstem, among them mediodorsal thalamic nucleus has relationship with limbic system and prefrontal cortex. The precise topographical projections of mesencephalic raphe nuclei to the MD nucleus of thalamus were identified in the rat using horseradish peroxidase (HRP retrograde tracing substance. Injection of HRP in MD labeled a large number of neurons in rostral to caudal part of dorsal raphe nucleus. It exhibited a strong number of neurons in ipsilateral part of DR and a few cells in its contralateral part. Numerously labeled cells were also observed ipsilateral in rostral and medial part of MnR (86% and a few cells in it's contralateral part. The present study has provided that the MD innervation by DR is more greater in density than that observed at the MnR. Upon these results and previous study, mesencephalic raphe nuclei are involved in several specific functions of thalamus as limbic system behavioral mechanism. A much more detailed knowledge is needed to show topographic relationships between mesencephalic raphe nuclei and forebrain.

  7. XAS Studies of Se Speciation in Selenite-Fed Rats

    Weekley, Claire M.; Aitken, Jade B.; Witting, Paul K.; Harris, Hugh H.


    The biological activity of selenium is dependent on its chemical form. Therefore, knowledge of Se chemistry in vivo is required for efficacious use of selenium compounds in disease prevention and treatment. Using X-ray absorption spectroscopy, Se speciation in the kidney, liver, heart, spleen, testis and red blood cells of rats fed control (~0.3 ppm Se) or selenite-supplemented (1 ppm or 5 ppm Se) diets for 3 or 6 weeks, was investigated. X-ray absorption spectroscopy revealed the presence of Se–Se and Se–C species in the kidney and liver, and Se–S species in the kidney, but not the liver. X-ray absorption near edge structure (XANES) spectra showed that there was variation in speciation in the liver and kidneys, but Se speciation was much more uniform in the remaining organs. Using principal component analysis (PCA) to interpret the Se K-edge X-ray absorption spectra, we were able to directly compare the speciation of Se in two different models of selenite metabolism – human lung cancer cells and rat tissues. The effects of Se dose, tissue type and duration of diet on selenium speciation in rat tissues were investigated, and a relationship between the duration of the diet (3 weeks versus 6 weeks) and selenium speciation was observed. PMID:25363824

  8. Acute oral toxicity and histopathological study of combination of endosulfan and cypermethrin in wistar rats.

    Raj, Jaya; Mohineesh; Ray, Ruma; Dogra, T D; Raina, Anupuma


    Endosulfan, a neurotoxic organochlorine insecticide and cypermethrin, a synthetic pyrethroid insecticide used to control pests in domestic, industrial, and agricultural situations. The present study was carried out to investigate the acute oral toxicity, behavioral and histopathological changes of combination of endosulfan and cypermethrin in albino rats. According to Miller and Tainter analysis method, at 48 h, LD50 value of combination of endosulfan and cypermethrin (ratio 1:1) in rats was found to be 691.83 mg/kg bw by oral gavage. When combination of both these pesticides was administered orally at concentration of 103.72 mg/kg bw, 172.95 mg/kg bw and 207.50 mg/kg bw, respectively, as a single dose, no significant changes in behavior of rats was observed, neither in dosed nor in control group of rats. Combination of endosulfan- and cypermethrin-treated rats showed mild histopathological changes in liver and kidney in group IV (207.50 mg/kg BW) as compared to the control. However, no significant changes were observed in brain and small intestine at either dose of combination of endosulfan and cypermethrin with respect to control. Thus, the present study, first of its kind in India, demonstrated the oral toxicity, behavioral, and histo-architectual alterations after induction of combination of endosulfan and cypermethrin at acute doses in Wistar rats.

  9. Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo


    The annual incidence of new cancer patients in China is about 2 million, 30-40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague-Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl2 solution (containing 1.4 mg Ca and 5nCi 41Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  10. Influence of corticoids on healing of the rotator cuff of rats – biomechanical study

    Leonardo Dau


    Full Text Available Objective:To compare healing strength of the infraspinatus tendon of rats with corticoid inoculation, regarding maximum tension, maximum force and rupture force, after injury and experimental repair.Methods:A total of 60 Wistar rats were subjected to tenotomy of the infraspinatus tendon, which was then sutured. Before the surgery, they were divided into a control group (C inoculated with serum and a study group (S inoculated with corticoids over the tendon. After repair, the rats were sacrificed in groups of 10 individuals in the control group and 10 in the study group at the times of one week (C1 and S1, three weeks (C3 and S3 and five weeks (C5 and S5. The rats were dissected, separating out the infraspinatus tendon with the humerus. The study specimens were subjected to a traction test, with evaluation of the maximum tension (kgf/cm2, maximum force (kgf and rupture force (kgf, comparing the study group with the respective control groups.Results:Among the rats sacrificed one week after the procedure, we observed greater maximum tension in group C1 than in group S1. The variables of maximum force (kgf and rupture force did not differ statistically between the groups investigated. In the same way, among the rats sacrificed three weeks after the procedure, group C3 only showed greater maximum tension than group S3 (p = 0.007, and the other variables did not present differences. Among the rats sacrificed five weeks after the procedure (C5 and S5, none of the parameters studied presented statistical differences.Conclusion:We concluded that corticoid diminished the resistance to maximum tension in the groups sacrificed one and three weeks after the procedure, in comparison with the respective control groups. The other parameters did not show differences between the study and control groups.

  11. Involvement of spinal somatostatin receptor SST(2A) in inflammation-induced thermal hyperalgesia: ultrastructural and behavioral studies in rats.

    Zhao, Jun; Hu, Jiang-Yuan; Zhang, Yu-Qiu; Zhao, Zhi-Qi


    Our previous results have shown that somatostatin receptor subtype SST(2A) is responsible for thermal, but not mechanical nociceptive transmission in the rat spinal cord. The present study was undertaken to further examine the ultrastructural localization of SST(2A) receptor in lamina II of the spinal dorsal horn and the role of SST(2A) receptor in thermal hyperalgesia following Complete Freund's Adjuvant (CFA)-induced inflammation. We found that SST(2A) receptors in lamina II are located primarily in postsynaptic dendrites and soma, but not in axons or synaptic terminals. CFA-induced inflammation markedly increased SST(2A) receptor-like immunoreactivity in lamina II. Paw withdrawal latency (PWL) evoked by noxious heating was obviously shortened 1 h after intraplantar injection of CFA, exhibiting thermal hyperalgesia. Pre-blocking SST(2A) activity by intrathecal pre-administration of CYN154806, a broad-spectrum antagonist of SST(2) receptor, or specific antiserum against SST(2A) receptor (anti-SST(2A)) significantly attenuated thermal hyperalgesia in a dose-dependent fashion in CFA-treated rats. But, administration of anti-SST(2A) or CYN154806 after CFA treatment had no effect upon thermal hyperalgesia. Intrathecal application of SST(2A) agonist SOM-14 at different doses prior to CFA treatment did not influence thermal hyperalgesia in inflamed rats, but at a low dose shortened PWL evoked by noxious heating in normal rats. These results suggest that spinal SST(2A) receptors play a key role in triggering the generation, but not maintenance, of thermal hyperalgesia evoked by CFA-induced inflammation. The up-regulation of SST(2A) receptors in the spinal cord may be one of the mechanisms underlying inflammation-induced thermal hyperalgesia.

  12. Induced vaginal birth after previous caesarean section

    Akylbek Tussupkaliyev; Andrey Gayday; Bibigul Karimsakova; Saule Bermagambetova; Lunara Uteniyazova; Guldana Iztleuova; Gulkhanym Kusherbayeva; Meruyert Konakbayeva; Assylzada Merekeyeva; Zamira Imangaliyeva


    Introduction The rate of operative birth by Caesarean section is constantly rising. In Kazakhstan, it reaches 27 per cent. Research data confirm that the percentage of successful vaginal births after previous Caesarean section is 50–70 per cent. How safe the induction of vaginal birth after Caesarean (VBAC) remains unclear. Methodology The studied techniques of labour induction were amniotomy of the foetal bladder with the vulsellum ramus, intravaginal administra...

  13. Dorsal lateral geniculate substructure in the Long-Evans rat: A cholera toxin B-subunit study

    Claire B. Discenza


    Full Text Available The pigmented rat is an increasingly important model in visual neuroscience research, yet the lamination of retinal projections in the dLGN has not been examined in sufficient detail. From previous studies it was known that most of the rat dLGN receives monocular input from the contralateral eye, with a small island receiving predominantly ipsilateral projections. Here we revisit the question using cholera toxin B subunit (CTB, a tracer that efficiently fills retinal terminals after intra-ocular injection. We imaged retinal termini throughout the dLGN at 0.5 um resolution and traced areas of ipsilateral and contralateral terminals to obtain a high resolution 3D reconstruction of the projection pattern. Retinal termini in the dLGN are well segregated by eye of origin, as expected. We find, however, that the ipsilateral projections form multiple discrete projection zones in three dimensions, not the single island previously described. It remains to be determined whether these subdomains represent distinct functional sublaminae, as is the case in other mammals.

  14. Columnar modelling of nucleation burst evolution in the convective boundary layer – first results from a feasibility study Part IV: A compilation of previous observations for valuation of simulation results from a columnar modelling study

    O. Hellmuth


    according to the parameterisation of the collision-controlled binary nucleation rate proposed by Weber et al. (1996, H2O vapour does not explicitly affect the particle formation. Since the H2SO4 concentration is overpredicted in the simulations presented in Paper III, the nucleation rates are too high compared to previous estimations. Therefore, the results are not directly comparable to measurements. Especially NPF events, where organics are suspected to play a key role, such as those observed at the boreal forest station in Hyytiälä (Southern Finland or at Hohenpeissenberg (mountain site in Southern Germany, can not be explained by employing simple sulphur/ammonia chemistry. However, some valuable hints regarding the role of CBL turbulence in NPF can be obtained. In the literature a number of observations on the link between turbulence and NPF can be found, whose burst patterns support a strong contribution of CBL turbulence to the NPF burst evolution simulated here. Observations, that do not correspond to the scenarios are discussed with respect to possible reasons for the differences between model and observation. The model simulations support some state-of-the-art hypotheses on the contribution of CBL turbulence to NPF. Considering the application of box models, the present study shows, that CBL turbulence, not explicitly considered in such models, can strongly affect the spatio-temporal NPF burst evolution. The columnar high-order model presented here is a helpful tool to elucidate gas-aerosol-turbulence interactions, especially the genesis of NPF bursts in the CBL. An advanced description of the cluster formation and condensation growth is required as well as a comprehensive verification/validation study using observed high-order moments. Further scenario simulations remain to be performed.

  15. C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a modelistic study.

    Francesco Di Nardo

    Full Text Available A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT was performed in seven Zucker fatty rats (ZFR, 7-to-9 week-old, and seven age-matched Zucker lean rats (ZLR. The minimal model of C-peptide (CPMM, originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM. Our results showed that the present CPMM-based interpretation of data is able to: 1 provide a suitable fit of C-Peptide data; 2 achieve a satisfactory estimation of parameters of interest 3 quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t, and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф(1, second-phase, Ф(2, and steady-state, Ф(ss, never assessed in Zucker rats before; 4 detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation.

  16. Repercussões cardíacas após infarto do miocárdio em ratas submetidas previamente a exercício físico Cardiac implications after myocardial infarction in rats previously undergoing physical exercise

    Eduardo Carvalho de Arruda Veiga


    Full Text Available FUNDAMENTO: Poucos estudos analisaram os efeitos cardíacos do exercício físico prévio à oclusão coronariana. OBJETIVO: Avaliar, em ratas submetidas a exercício físico, as repercussões do infarto do miocárdio. MÉTODOS: Ratas foram submetidas à natação ou permaneceram sedentárias por oito semanas e foram randomizadas para oclusão coronariana ou cirurgia simulada, compondo quatro grupos: Sedentário (S, Exercício (E, Sedentário infarto (SIM e Exercício infarto (EIM. Após seis semanas, foram analisados biometria, ecodopplercardiograma, hemodinâmica e mecânica miocárdica. RESULTADOS: Não foram observados cardioproteção nos animais EIM e diferença no tamanho do infarto (%VE entre EIM (38,50 ± 4,60% e SIM (36,58 ± 4,11%. Os teores de água pulmonar (% de SIM (80 ± 0,59 e EIM (80 ± 0,57 foram maiores do que em S (78 ± 0,15 e E (78 ± 0,57. A pressão sistólica (mmHg do ventrículo esquerdo (S: 130 ± 5; E: 118 ± 8; SIM: 91 ± 3; EIM: 98 ± 3 e a primeira derivada temporal (mmHg/s positiva da pressão (S: 8.216 ± 385; E: 8.437 ± 572; SIM: 4.674 ± 455; EIM: 5.080 ± 412 de S e E foram maiores do que em SIM e EIM. As frações de encurtamento da área transversa (% de SIM (27 ± 2 e EIM (25 ± 2 foram similares e menores do que E (65 ± 2 e S (69 ± 2. A relação E/A foi maior em SIM (5,14 ± 0,61 e EIM (4,73 ± 0,57 em relação a S (2,96 ± 0,24 e E (2,83 ± 0,21. Em estudos de músculos papilares isolados foi verificada depressão da capacidade contrátil semelhante em SIM e EIM, e não houve alteração da rigidez miocárdica. CONCLUSÃO: O treinamento prévio por natação não atenuou as repercussões cardíacas em virtude do infarto do miocárdio.BACKGROUND: Few studies have analyzed the cardiac effects of exercise prior to coronary occlusion. OBJECTIVE: To evaluate the effects of myocardial infarction in rats undergoing physical exercise. METHODS: Female rats underwent swimming exercise or were kept sedentary

  17. Repercussões cardíacas após infarto do miocárdio em ratas submetidas previamente a exercício físico Cardiac implications after myocardial infarction in rats previously undergoing physical exercise

    Eduardo Carvalho de Arruda Veiga


    Full Text Available FUNDAMENTO: Poucos estudos analisaram os efeitos cardíacos do exercício físico prévio à oclusão coronariana. OBJETIVO: Avaliar, em ratas submetidas a exercício físico, as repercussões do infarto do miocárdio. MÉTODOS: Ratas foram submetidas à natação ou permaneceram sedentárias por oito semanas e foram randomizadas para oclusão coronariana ou cirurgia simulada, compondo quatro grupos: Sedentário (S, Exercício (E, Sedentário infarto (SIM e Exercício infarto (EIM. Após seis semanas, foram analisados biometria, ecodopplercardiograma, hemodinâmica e mecânica miocárdica. RESULTADOS: Não foram observados cardioproteção nos animais EIM e diferença no tamanho do infarto (%VE entre EIM (38,50 ± 4,60% e SIM (36,58 ± 4,11%. Os teores de água pulmonar (% de SIM (80 ± 0,59 e EIM (80 ± 0,57 foram maiores do que em S (78 ± 0,15 e E (78 ± 0,57. A pressão sistólica (mmHg do ventrículo esquerdo (S: 130 ± 5; E: 118 ± 8; SIM: 91 ± 3; EIM: 98 ± 3 e a primeira derivada temporal (mmHg/s positiva da pressão (S: 8.216 ± 385; E: 8.437 ± 572; SIM: 4.674 ± 455; EIM: 5.080 ± 412 de S e E foram maiores do que em SIM e EIM. As frações de encurtamento da área transversa (% de SIM (27 ± 2 e EIM (25 ± 2 foram similares e menores do que E (65 ± 2 e S (69 ± 2. A relação E/A foi maior em SIM (5,14 ± 0,61 e EIM (4,73 ± 0,57 em relação a S (2,96 ± 0,24 e E (2,83 ± 0,21. Em estudos de músculos papilares isolados foi verificada depressão da capacidade contrátil semelhante em SIM e EIM, e não houve alteração da rigidez miocárdica. CONCLUSÃO: O treinamento prévio por natação não atenuou as repercussões cardíacas em virtude do infarto do miocárdio.BACKGROUND: Few studies have analyzed the cardiac effects of exercise prior to coronary occlusion. OBJECTIVE: To evaluate the effects of myocardial infarction in rats undergoing physical exercise. METHODS: Female rats underwent swimming exercise or were kept sedentary

  18. Carcinogenicity study on butylated hydroxytoluene (BHT) in Wistar rats exposed in utero

    Olsen, P.; Meyer, Otto A.; Bille, N.


    Groups of 60, 40, 40 and 60 F0 Wistar rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated and groups of 100, 80, 80 or 100 F1 rats of each sex...... were formed from 40, 29, 30 and 44 litters, respectively. After weaning, the highest dose (500 mg BHT/kg/day) was lowered to 250 mg/kg/day for the F1 rats. The numbers of litters of ten or more pups at birth decreased with increasing BHT dose. At weaning, treated F1 rats had lower body weights than...... the controls, the extent of the reduction being dose related; the effect, which persisted throughout the study, was most pronounced in the males. The survival of BHT-treated F1 rats of both sexes was significantly better than that of the controls. No significant changes attributable to BHT treatment were found...

  19. Preliminary study of therapeutic effects of panax notoginside and methylprednisolone on pulmonary fibrosis in rats

    CUI She-huai; LI Xue-jun


    Objective: To study the therapeutic effects of panax notoginside (PN) and methylprednisolone (MP) on pulmonary fibrosis in rats. Methods: Bleomycin was introduced into the bronchial tree of 75 Wistar male rats through a tracheal incision to establish a rat model of pulmonary fibrosis (PF). The rats were equally divided into 3 groups: PF group,PN treated group and MP treated group. Five rats of each group were killed 1, 3, 7, 14 and 28 d after the administration of bleomycin and the specimens of lung tissue and plasma were collected for the determination of content of collagen Ⅰ and Ⅲwith immunohistochemical method and the level of MIP-1α and MCP-1 with ELIZA. Results: The severity of PF, the content of collagen Ⅰ and Ⅲ and the level of MIP- 1 α and MCP- 1 were significantly decreased in PN and MP treated groups than in PF group ( P < 0.05). Conclusion: PN and MP are effective to control the development of PF induced with bleomycin in rats.

  20. Insulinostatic activity of cerebellin--evidence from in vivo and in vitro studies in rats.

    Strowski, Mathias Z; Kaczmarek, Przemyslaw; Mergler, Stefan; Wiedenmann, Bertram; Domin, Danuta; Szwajkowski, Przemyslaw; Wojciechowicz, Tatiana; Skrzypski, Marek; Szczepankiewicz, Dawid; Szkudelski, Tomasz; Rucinski, Marcin; Malendowicz, Ludwik K; Nowak, Krzysztof W


    Cerebellin (CER) is a neuromodulatory hexadecapeptide that originates from the precursor protein precerebellin (Cbln1). Four highly homologous isoforms of Cbln are known (Cbln1-Cbln4), which are expressed in the central nervous system (CNS) and in peripheral tissues. CER modulates synaptic structure formation in the CNS, whereas in the peripheral tissues CER regulates catecholamine secretion. Cbln is also expressed in the pancreas; however, its function in the pancreas is unknown. Here, we demonstrate the role of CER in regulating insulin secretion in vivo and in vitro. We identified Cbln1 and Cbln3 transcripts in rat pancreatic islets and detected Cbln-immunoreactivity, predominantly located in the periphery of the rat endocrine pancreas. In vivo, CER reduced plasma insulin levels in rats after 1 and 2 h. CER decreased insulin secretion from isolated rat pancreatic islets at high (11 mM), but not at low (3.33 mM) glucose concentration. CER inhibited stimulated insulin secretion from clonal rat insulinoma (INS-1) cells, reduced forskolin-induced production of cAMP and intracellular calcium concentration. Our study demonstrates for the first time that Cbln1 and Cbln3 are expressed in the rat endocrine pancreas. Furthermore, we identify CER as an insulinostatic factor, which decreases intracellular cAMP production and calcium in INS-1 cells.

  1. Quantitative MR application in depression model of rats: a preliminary study

    Wei Wang; Wenxun Li; Fang Fang; Hao Lei; Xiaoping Yin; Jianpin Qi; Baiseng Wang; Chengyuan Wang


    Objective: To investigate findings and value of quantitative MR in depression model of rats. Methods: Twenty male SD rats were divided into model group and control group randomly (10 rats in each group). The depression model of rats was erected by separation and chronic unpredictable stress. The behavior of rat was detected by open-field test and sucrose consumption. The MR images of brain tissues were produced in vivo rats with T2-and diffusion-weighted imaging. The changes of body weight and behavior score and thevalues of T2 and ADC of ROIs were compared between the two groups. Histological verification of hippocampal neuron damage was alsoperformed under ultramicrosopy. Results: Compared with the control group, T2 values in hippocampus prolonged 5.5 % ( P < 0.05),ADC values in hippocampus and in temporal lobe cortex decreased 11.7 % and 10.9% (P < 0.01)respectively in the model group. Histo-logic data confirmed severe neuronal damage in the hippocampus of the model group. Conclusion: This study capitalized on diffusion-weighted imaging as a sensitive technique for the identification of neuronal damage in depression and it provides an experimental evidence ofMRI in depression investigation and clinical application.

  2. The Characteristics of Acute Rejection after Limb Allotransplantation in Rats-An Experimental Study

    康皓; 洪光祥; 王发斌; 陈振兵; 黄启顺; 翁雨雄


    To study the characteristics of acute rejection after limb allotransplantation, 29 male Sprague-Dawley rats were randomly divided into 2 groups, with 15 rats in control group and 14 rats in experimental group. Each rat in control group underwent limb replantation. Each rat in experimental group received limb transplantation from Wistar rat. No immnosuppressive drugs were used after operation. The circulation of the transplanted limb, time and signs of rejection, histopathological changes in the tissues of the limb graft when rejected and survival time of limb grafts were evaluated. In the control group, no signs of rejection were observed, the circulation of each replanted limb was normal, it could survive for a longer time. The experimental group showed clinical signs of rejection (sub dermal edema and erythema) after a mean time of 3. 36±1.15 days, and the mean survival time of the allografts was only 7±0.78 days. Histopathological examination showed most violent rejection reaction in skin. It is concluded that with Wistar-to-SD limb transplantation without use of immunosuppression, rejection of the grafts would occur after a mean time of 3.36 ±1.15days; the earliest signs of rejection were edema and erythema of the skin, skin being the most representative component of limb graft rejection.

  3. Effects of colchicine on the intestinal transport of endogenous lipid. Ultrastructural, biochemical, and radiochemical studies in fasting rats

    Pavelka, M.; Gangl, A.


    The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, researchers have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of (/sup 14/C)linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that colchicine causes significant changes in enterocyte ultrastructure and colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte.

  4. Influence of melatonin or its antagonism on alcohol consumption in ethanol drinking rats: a behavioral and in vivo voltammetric study.

    Crespi, Francesco


    Melatonin, an indoleamine hormone synthesized in the pinealocytes, has been implicated as influencing the intake of alcohol in rats. It has been shown that this hormone is voltammetrically electroactive at the surface of pretreated carbon fiber microelectrodes in vitro and in vivo, in rat cerebral melatonergic regions such the pineal gland. The aim of this work consisted in the study of the influence of melatonin on spontaneously ethanol drinking or ethanol avoiding rats selected throughout a free choice two bottle test. It appeared that only the water preferring rats were affected by treatment with the hormone and that in vivo voltammetric related levels of melatonin were higher in the pineal gland of ethanol drinking rats versus water preferring rats. In addition, when treated with the melatonin antagonist GR128107 ethanol drinking rats significantly reduced the spontaneous consumption of alcohol.

  5. A single-arm, investigator-initiated study of the efficacy, safety, and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration previously treated with ranibizumab or bevacizumab (ASSESS study: 12-month analysis

    Singh RP


    Full Text Available Rishi P Singh, Sunil K Srivastava, Justis P Ehlers, Fabiana Q Silva, Rumneek Bedi, Andrew P Schachat, Peter K Kaiser Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA Summary statement: In subjects with active exudative age-related macular degeneration, treating with a fixed intravitreal aflibercept injection dosing regimen for 12 months demonstrated improved anatomic and vision endpoints from baseline.Purpose: Switching therapies in neovascular age-related macular degeneration (AMD may offer an advantage for some patients. This study evaluates the efficacy of intravitreal aflibercept injection (IAI in subjects previously treated with ranibizumab and/or bevacizumab.Methods: Subjects (n=26 were given monthly 2 mg of IAI for 3 months, followed by 2 mg once in every 2 months for up to 12 months. The mean absolute change from baseline in central subfield thickness (CST measured by optical coherence tomography and the mean change from baseline in best-corrected visual acuity (BCVA early treatment in diabetic retinopathy study (ETDRS letter score were obtained. Additionally, the percentage of subjects who gained or lost ≥15 letters of vision and the percentage of subjects who are 20/40 or better or 20/200 or worse were evaluated.Results: There was a mean decrease in CST of -50.3  µm (P<0.001 and a mean increase in ETDRS BCVA of +9.2 letters (P<0.001. Twenty-seven percent of subjects experienced a  ≥15-letter improvement in visual acuity, and no subject lost ≥3 lines of vision from baseline. Fifty percent of subjects were 20/40 or better, and 11.5% of subjects were 20/200 or worse at month 12.Conclusion: Fixed IAI dosing regimen for 12 months demonstrated improved anatomic and vision endpoints in subjects with active exudative AMD. Keywords: aflibercept, age-related macular degeneration, bevacizumab, ranibizumab, vascular endothelial growth factors

  6. Examining maternal influence on OLETF rats' early overweight: insights from a cross-fostering study.

    Schroeder, Mariana; Schechter, Michal; Fride, Ester; Moran, Timothy H; Weller, Aron


    Obese female Otsuka Long Evans Tokushima Fatty (OLETF) rats display increased nursing time and frequency compared to lean LETO controls, suggesting a maternal contribution to pup preobesity. In previous studies, OLETF pups presented high adiposity, showed greater suckling efficiency, initiative and weight gain from nursing than controls throughout lactation. To further elucidate maternal-infant interactions contributing to pup preobesity, we cross-fostered pups a day after birth and examined maternal behavior. Nursing frequency decreased in OLETF dams raising LETO pups (OdLp) in the third postnatal week, while LETO dams raising OLETF pups showed no significant changes. Fat % was greater in the milk of OLETF versus LETO dams. OdLp pups showed long-term body weight (BW) increase, suggesting that maternal environment can induce BW increases even in the absence of a genetic tendency. Additionally, interaction between OLETF dams and pups produces high nursing frequency, exposing the pups to abundant high-fat milk, thus strengthening their preobese phenotype.

  7. Study on the developmental toxicity of combined artesunate and mefloquine antimalarial drugs on rats.

    Boareto, Ana Cláudia; Müller, Juliane Centeno; de Araujo, Samanta Luiza; Lourenço, Ana Carolina; Lourenço, Emerson Luiz Botelho; Gomes, Caroline; Minatovicz, Bruna; Lombardi, Natália; Paumgartten, Francisco Roma; Dalsenter, Paulo Roberto


    Antimalarial drug combinations containing artemisinins (ACTs) have become first choice therapies for Plasmodium falciparum malaria. Data on safety of ACTs in pregnancy are limited and no previous study has been conducted on the developmental toxicity of artesunate-mefloquine combinations on the first trimester of gestation. To evaluate the developmental toxicity of an artesunate/mefloquine combination, pregnant rats were treated orally with artesunate (15 and 40 mg/kg bwt/day), mefloquine (30 and 80 mg/kg bwt/day) and artesunate/mefloquine (15/30 and 40/80 mg/kg bwt/day) on gestation days 9-11. Dams were C-sectioned on day 20, and their uteri and fetuses removed and examined for soft tissue and skeleton abnormalities. Artesunate increased embryolethality and the incidence of limb long bone malformations on the absence of overt maternal toxicity. Mefloquine (80 mg/kg bwt/day) was maternally toxic and enhanced fetal variations. Combination of artesunate and mefloquine did not enhance their toxicity compared to the toxicity observed after its separate administration. Embryotoxicity of artesunate was apparently attenuated when it is co-administered with mefloquine.

  8. Rat interscapular brown adipose tissue at different ages: a morphometric study.

    Sbarbati, A; Morroni, M; Zancanaro, C; Cinti, S


    Interscapular brown adipose tissue (IBAT) was studied in newborn and 1, 3, 5, 7, 13, 26, 52, 78 and 104-week-old rats maintained under standard laboratory conditions in order to define its morphological modifications and assess previous statements on an involution phase of IBAT after the first weeks of extrauterine life. Serial sections were analysed morphometrically to quantify the multilocular, the monolocular and the connective-vascular components of IBAT. Morphometry shows that the IBAT weight and volume progressively increase up to the twenty-sixth week of age, these figures remaining almost constant thereafter. The volume of the unilocular and connective components increased with age. The volume of the multilocular component increases up to the sixth month of age, and slightly reduces thereafter. The number of the multilocular adipocytes is almost constant from the third week up to the second year of life. Our results suggest that, in IBAT of adult animals, despite a slight prevalence of unilocular adipocytes, the number of multilocular cells is not reduced with respect to younger animals.

  9. Rats avoid exposure to HVdc electric fields: a dose response study.

    Creim, J A; Lovely, R H; Weigel, R J; Forsythe, W C; Anderson, L E


    Rats, given the choice, avoid exposure to alternating current (ac) 60-Hz electric fields at intensities > or = 75 kV/m. This study investigated the generality of this behavior by studying the response of rats when exposed to high voltage direct current (HVdc) electric fields. Three hundred eighty male Long Evans rats were studied in 9 experiments with 40 rats per experiment and in one experiment with 20 rats to determine 1) if rats avoid exposure to HVdc electric fields of varying field strengths, and 2) if avoidance did occur, what role, if any, the concentration of air ions would have on the avoidance behavior. In all experiments a three-compartment glass shuttlebox was used; either the left or right compartment could be exposed to a combination of HVdc electric fields and air ions while the other compartment remained sham-exposed. The third, center compartment was a transition zone between exposure and sham-exposure. In each experiment, the rats were individually assessed in 1-h sessions where half of the rats (n = 20) had the choice to locomote between the two sides being exposed or sham-exposed, while the other half of the rats (n = 20) were sham-exposed regardless of their location, except in one experiment where there was no sham-exposed group. The exposure levels for the first six experiments were 80, 55, 42.5, 30, -36, and -55 kV/m, respectively. The air ion concentration was constant at 1.4 x 10(6) ions/cc for the four positive exposure levels and -1.4 x 10(6) ions/cc for the two negative exposure levels. Rats having a choice between exposure and non-exposure relative to always sham-exposed control animals significantly reduced the amount of time spent on the exposed side at 80 kV/m (P HVdc exposure level was held constant at either -55 kV/m (for three experiments) or -55 kV/m (for 1 experiment) while the air ion concentration was varied between experiments at 2.5 x 10(5) ions/cc, 1.0 x 10(4) for two of the experiments and was below the measurement limit

  10. Ethanopharmacological study of the aqueous, chloroform, ethanol leaves extracts and latex of Calotropisprocera in diabetic rats

    Ali Ismaiel Ali-Abd Alrheam


    Full Text Available Introduction: Calotropisprocera is a member of the plant family Asclepiadaceae, a shrub about 6m high and is widely distributed in the kingdom of Saudi Arabia. This study aimed to show some medicinal potentials and biological activity of Calotropisprocera and to discover new natural, safe and effective materials available in the Saudi Arabia environment. Marerial and Methods:The leaves extracts and latex of Calotropisprocerawere investigated for its anti-hyperglycemic effect in Male Wister Albino rats. Diabetes was induced by administration of single dose of streptozotocin (STZ, 50 mg/kg, I.P. Forty two male albino rats, weighting 150-200 gm divided into seven groups, each consisted of 6 rats as follows: Group I : Normal control, Group II: Diabetic control, Group III: Diabetic rats given Glibenclamide 600 and #956;g/kg, Group IV: Diabetic rats given aqueous leaves extracts C. procera200mg/kg b. wt, Group V: Diabetic rats given chloroform leaves extracts C. procera200mg/kg b. wt, Group VI: Diabetic rats given ethanol leaves extracts C. procera200mg/kg b. wt, Group VII: Diabetic rats given latex of C. procera200mg/kg b. wt.The leaves extracts and latex of Calotropisprocera were administered as single dose per day to diabetes-induced rats for a period of 15 days.The effect of C. proceraon blood glucose level was measured in the diabetic rats. Serum lipid profile (Total cholesterol, triglycerides, low density, and high density lipoprotein also were measured. The activities were also compared to that effect produced by a standard anti-diabetic agent, glibenclamide 500 and #956;g/kg. Results and Discussion:The results showed a significant decrease in the mean level of blood glucose and serum cholesterol, Triglycrides, HDL, LDL. Calotropisprocera appears to be a rich source of phytoconstituents that activate and inhence a pharmacological response of different parts of the body and this study need further studies to shows the complete properties of the

  11. Safety assessment of meat from transgenic cattle by 90-day feeding study in rats.

    Liu, Shan; Li, Chen-Xi; Feng, Xiao-Lian; Wang, Hui-Ling; Liu, Hai-Bo; Zhi, Yuan; Geng, Gui-Ying; Zhao, Jie; Xu, Hai-Bin


    The study was carried out to evaluate the subchronic toxicity of meat derived from human lactoferrin gene-modified cattle in male and female Wistar rats. Rats were fed 5% or 10% transgenic meat diet, 5% or 10% conventional meat diet, or AIN93G diet for 90 days. During the study, body weight and food consumption were weighed weekly and clinical observations were conducted daily. At the end of the study, urinary examination, hematology and blood biochemistry examination, macroscopic and microscopic examinations were performed. There were no biologically significant differences in these factors between the rat groups fed transgenic meat diet and conventional meat diet. Therefore, the present 90-day rodent feeding study suggests that meat derived from the transgenic cattle is equivalent to meat from conventional cattle in use as dietary supplements.

  12. Effect Of Some Aflatoxins On A Lymphatic Organ (Spleen Of Male Albino Rats (Histopathological Study

    Nahed Ahmed Omar


    Full Text Available Background:The present study was planned to compare between two kinds of aflatoxins ( AFB2 and AF Mix on spleen of male albino rats. Fifty young male albino rats ,each weighing 50g, were fed on diets containing aflatoxins at concentration of 1.0 ppm either of AFB2 or AF mix. for 2, 4, 6 weeks followed by a withdrawal period of 2 weeks. Material and Methods:- Rats were randomly divided into 3 groups: the 1st group of 10 rats was fed on the standard diet. The 2nd and the 3rd groups of 20 rats each were maintained on the standard diet plus either AFB2 or AF mix. respectively. Ten animals from the latter 2 groups as withdrawal period. Pieces of spleen were subjected to histological procedures and the obtained sections (6 µm thick were stained with the haematoxylin and eosin, also, mercuric bromophenol blue stain for total protein were used in this study. Results:- Marked histopathological alterations were observed in the studied sections under the influence of AFB2 and AF mix. It was found that AFB2 induced more alterations. The most common changes were lymphocytic degeneration, fatty changes with numerous hemorrhagic areas.The two weeks withdrawal period showed a partial recovery of the developed changes. Conclusion:- This study indicated that AFB2 has a toxic effect on spleen than the equivalent level of AF mix. .Great caution must be followed to prevent the possible contamination of our food with such mycotoxins.

  13. Functional effects of the KCNQ modulators retigabine and XE991 in the rat urinary bladder

    Rode, Frederik; Svalø, Julie; Sheykhzade, Majid


    The anticonvulsant retigabine has previously been reported to inhibit bladder overactivity in rats in vivo but the mechanism and site of action are not known. In the present study we investigated the effect of retigabine in isolated rat bladder tissue. Bladders from Sprague-Dawley rats were cut t...

  14. Association between prepulse inhibition of the startle response and latent inhibition of two-way avoidance acquisition: A study with heterogeneous NIH-HS rats.

    Sánchez-González, Ana; Esnal, Aitor; Río-Álamos, Cristóbal; Oliveras, Ignasi; Cañete, Toni; Blázquez, Gloria; Tobeña, Adolf; Fernández-Teruel, Alberto


    This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms.

  15. Toxicological study on the safety of DTPA as a drug, (1). Teratological study in the rat

    Fukuda, Satoshi; Iida, Haruzo (National Inst. of Radiological Sciences, Chiba (Japan))


    In order to clarify the safety of Ca-DTPA and Zn-DTPA recommended to use as drugs in the therapeutic removal of incorporated radionuclides from the human body, the teratological study on these two agents was carried out in rats as one of a series of the toxicological tests. The teratological effects of DTPA were observed because the fetus is highly susceptible to any drug. The pregnant females of Wistar rat were injected subcutaneously daily on days 9-13 of gestation with 1, 6, 12, 24 and 36 H.D. (H.D. = human dose, 1 H.D. = body weight) of Ca-DTPA or Zn-DTPA, respectively. In the dams, no toxic effects were observed. In the fetuses, the decrease of the survival rate was observed in only the group injected daily with 36 H.D. of Ca-DTPA. Some cases of gross defects of fetuses: the exencephaly, microphthalmia, anophthalmia and fusion of ribs were observed in the groups injected daily with 12, 24 and 36 H.D. of Ca-DTPA. The results obtained show that Ca-DTPA should not be given to a pregnant woman. However, no toxic effects of either Ca-DTPA or Zn-DTPA observed in the dams or of Zn-DTPA even in the fetuses indicate that these agents can be used by a radiation worker who usually is an adult man.

  16. Microscopic Studies Of The Effect Of Some Food Additives On The Kidney Of Albino Rat

    Abd El-Tawab M. Ismail - Ashraf M.Moustafa


    Full Text Available Recently the use of synthetic food coloring additives was increased and the levels of human exposure to such agents are very broad, thus feeding over long periods may continually possess potential hazards to the human health. Also most of the food colors tested in the conventional toxicity experiments showed toxic effects at very high level of intake i.e. 1-5 % in the diet. The aim of this study was to evaluate the histological and histochemical effects of some of these substances (Sodium nitrate and sunset yellow on the liver of adult albino rats. The study included three main parts: A. Histological studies on the liver under the effect of (Sodium nitrate and sunset yellow substances. Using paraffin sections, which were stained with Hx & Eosin, Masson Trichrome B. Evaluation of histochemical activity of both alkaline phosphates enzyme and succinic dehydrogenase enzymes on the renal tissue. C. Statistical evaluation using image analyzer to detect glomerular area, area percentage of collagen fibers distribution and optical density of both alkaline phosphatase enzyme activity in glomerulus and succinic dehydrogenase enzyme activity in renal tubules. Seventy adult male albino rats were used. Nitrate and sunset yellow were given orally through a gastric tube in dose of 1 mg / kg / b.w. daily. The animals were classified into seven groups. 1. Group I (Control group 2. Group II: The animals were given sodium nitrate in a dose of 1mg/kg/bwt for one month. 3. Group III: The animals were given sun set yellow in a dose of 1mg/kg/bwt/day for one month. 4. Group IV: The animals were given sodium nitrate and sunset yellow for one month in a dose of 1mg/kg/bwt/for each drug in a separate manner. 5. Group V: The animals were given sodium nitrate similar to the previous dose as group II for one month and left 2 weeks without oral intubations. 6. Group VI: The animals were given sun set yellow No 6 in a dose and route of administrations as group III for one

  17. Histological study of the effects of oral administration of datura metel on the visual system of male wistar rats

    Ibiyeye Yetunde Rukayat


    Full Text Available This study was carried out in order to elucidate some of the effects of oral administration of Cannabis sativa on the visual system of male Wistar rats as marker of toxicity using neurohistochemical study. 12 adult male Wistar rats were used for this study. The rats were distributed into two groups (A and B. The rats in group A served as the treatment group and were administered with 300 mg/kg body weight of Cannabis sativa while the rats in group B which served as the control were administered with equal volume of phosphate buffered saline. The duration of administration was for 14d. The rats were sacrificed using cervical dislocation 24 hrs after the last administration. The brains were excised from the skulls of the animals and were completely fixed in 10% formol calcium. 72 hours after fixation, right occipital cortex, right lateral geniculate nucleus and right superior colliculus were excised separately for histological (H&E processing. Microscopic observations made from the permanent photomicrographs revealed alterations in the histoarchitecture of the visual system of the rats in the treated group compared with the rats in the treated group with preserved histological outline. Oral administration of Cannabis sativa on the visual system of male Wistar rats caused neurodegeneration of the occipital cortex, right lateral geniculate nucleus and right superior colliculus of Wistar rats.

  18. Incubation of saccharin craving and within-session changes in responding for a cue previously associated with saccharin.

    Aoyama, K; Barnes, J; Grimm, J W


    Time-dependent increases in cue-induced sucrose seeking after forced abstinence have been described in rats with a history of sucrose self-administration, suggesting sucrose craving "incubates". In the present study, we examined whether the incubation of craving generalizes to the artificial sweetener, saccharin. Thirty-one male Long-Evans rats lever pressed for 0.3% saccharin solution 1h/day for 10 days. On either Day 1 or 30 of forced abstinence, rats responded for 1h for presentation of a tone+light cue previously presented with every saccharin delivery during self-administration training. Rats responded more during this cue-reactivity test session following 30 vs. 1 day of forced abstinence ("incubation of craving"). This result is the first demonstration of the "incubation of saccharin craving" and suggests that a post-ingestive caloric consequence of self-administration is not a necessary condition for the development of incubation of sucrose craving. We also examined the time course (within-session decreases) of active-lever responding during the 1-h cue-reactivity test session. Rats in the Day 30 group responded more than rats in the Day 1 group from the beginning of the test session. In addition, within-session decreases in responding were shallower in slope in the Day 30 than the Day 1 group. These results indicate that "incubation of saccharin craving" enhances the persistence of seeking behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Studies on growth, nitrogen and energy metabolism in rats

    Thorbek, G; Chwalibog, André; Eggum, B O


    Feed intake, growth, nitrogen retention and energy metabolism were measured in 12 male Wistar rats fed ad lib. for 14 weeks with non-purified diets. The feed intake increased rapidly in 4 weeks time from 16 g/d to 25 g/d, and then it was constant in the following 10 weeks. In relation to metabolic...... live weight the energy intake decreased from about 1400 to 800 kJ GE/kg0.75. With the high intake of energy the growth curve obtained is assumed to be near maximum level. The curve can be transformed to a linear one based on log days expressed as y, LW, g = -836 + 594 X log days with CV = 7.5% and r2...... = 0.968. The nitrogen retention increased from 200 to 300 mg N/d in period III when the rats 60 days old, and then it decreased in the following 10 weeks to about 100 mg N/d. In relation to metabolic live weight nitrogen retention is assumed to be near maximum level, decreasing from 1100 to 200 mg N...

  20. A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: A comparative study of human psychophysics and rat behaviour.

    Dunham, James P; Hulse, Richard P; Donaldson, Lucy F


    Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents. We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured. Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: -11.3 °C to -11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours. Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients. Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain. Copyright © 2015. Published by Elsevier B.V.

  1. Ochratoxin A kinetics: a review of analytical methods and studies in rat model.

    Vettorazzi, A; González-Peñas, E; de Cerain, A López


    Ochratoxin A (OTA) is a thermostable mycotoxin that contaminates a great variety of foodstuffs. It is nephrotoxic in all of the mammalian species tested, the pig being the most sensitive one; among rodents, rats are the most susceptible to OTA carcinogenicity. Kinetics, by studying the absorption, distribution, metabolism and excretion of xenobiotics, is an important tool in the extrapolation of animal toxicity data for human risk assessment. The most important kinetic studies performed with OTA in rats are reviewed, together with the different methods used for OTA quantification in biological matrices. Twelve studies in Wistar, Sprague-Dawley or F344 rats, using radiolabeled OTA or TLC, HPLC-FLD or LC/MS have been summarized. Very often methods validated for food have been directly applied to tissues. Strain, sex and age differences have been detected but the interpretation is difficult due to the different experimental conditions, and the connection of the several factors that may account for these differences.

  2. Cola beverage consumption delays alveolar bone healing: a histometric study in rats

    Juliana Mazzonetto Teófilo


    Full Text Available Epidemiological studies have suggested that cola beverage consumption may affect bone metabolism and increase bone fracture risk. Experimental evidence linking cola beverage consumption to deleterious effects on bone is lacking. Herein, we investigated whether cola beverage consumption from weaning to early puberty delays the rate of reparative bone formation inside the socket of an extracted tooth in rats. Twenty male Wistar rats received cola beverage (cola group or tap water (control group ad libitum from the age of 23 days until tooth extraction at 42 days and euthanasia 2 and 3 weeks later. The neoformed bone volume inside the alveolar socket was estimated in semi-serial longitudinal sections using a quantitative differential point-counting method. Histological examination suggested a decrease in the osteogenic process within the tooth sockets of rats from both cola groups, which had thinner and sparser new bone trabeculae. Histometric data confirmed that alveolar bone healing was significantly delayed in cola-fed rats at three weeks after tooth extraction (ANOVA, p = 0.0006, followed by Tukey's test, p < 0.01. Although the results of studies in rats cannot be extrapolated directly to human clinical dentistry, the present study provides evidence that cola beverage consumption negatively affect maxillary bone formation.

  3. Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study.

    Nurulain, Syed M; Shafiullah, Mohamed; Yasin, Javed; Adem, Abdu; Kaabi, Juma Al; Tariq, Saeed; Adeghate, Ernest; Ojha, Shreesh


    Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under non-diabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD50) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBC-AChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition.

  4. Effects of aminoguanidine on infertile varicocelized rats: A functional and morphological study

    N Alizadeh


    Full Text Available "nBackgrounds and the purpose of the study:Inducible NO synthase activity has been frequently reported in varicose veins. Aminoguanidine is known to inhibit iNOS. The aim of this study was to examine the effects of aminoguanidine on varicocelized rats. "nMethods:Male Wistar rats were divided into groups A, B, C, D, E, and F (control group. Groups A, B, C, and D rats underwent left varicocele induction with a 20-gauge needle. Group E (sham rats underwent a similar procedure, but the renal vein was left intact. Ten weeks after varicocele induction, sperm parameters were evaluated in groups D, E, and F. Groups A and B received 50 mg/kg aminoguanidine or placebo, respectively, daily for 10 weeks. After 10 and 20 weeks of varicocele induction, the fertility outcomes of the experimental groups were evaluated. "nResults: The values of the sperm parameters did not differ significantly between groups B and D, but were significant when compared with groups F and E (P ≤ 0.05. The values of the sperm parameters of groups F and E showed no significant changes (P ≤ 0.05. The changes between group A and groups B and D were significant (P ≤ 0.05. Ten weeks after varicocele induction, rats of groups A, B, and C were still fertile. After 20 weeks, only half of the rats in group A were fertile. Conclusions: Aminoguanidine improved the sperm parameters and mating outcomes in vari-cocelized rats.

  5. Patient preference with respect to QoL and reduction in opioid-induced constipation (OIC) after treatment with prolonged-release (PR) oxycodone/naloxone compared with previous analgesic therapy [PREFER study].

    van Dongen, V C P C; Vanelderen, P J L; Koopmans-Klein, G; van Megen, Y J B; Van Zundert, J; Huygen, F J P M


    The aim of this study was to assess patient preference in terms of quality of life (QoL), analgesia and bowel function for patients with moderate to severe chronic non-malignant pain, when treated with oxycodone PR/naloxone PR compared with the previous WHO-step I and/or WHO-step II analgesic treatment . This was a 3-week open-label phase 3b study conducted in Belgium and the Netherlands, after 3 weeks patients could enter an extension phase. Patient preference with respect to QoL for oxycodone PR/naloxone PR treatment compared with previous WHO-step I and/or WHO-step II analgesics was assessed. A patient was considered a responder with respect to QoL if this assessment was 'better' or 'much better' compared with previous WHO-step I or II analgesics at any time point. Response rate with respect to QoL was 59.2% (95% CI: 51.7-66.8%) for the Full Analysis (FA)-population, for the Per Protocol-population response rate was 71.7% (95% CI: 63.1-80.3%). Explorative analysis showed that response rate with respect to QoL was highest in constipated patients pretreated with WHO-step II analgesics (73.8%). Mean ± SD pain score in the FA-population at start was 74.7 ± 16.6 decreasing to 53.9 ± 24.3 after a median (range) treatment period of 173.5 (31-771) days. For constipated subjects the significant reduction in constipation [improvement of the Bowel Function Index (BFI)], was -24.8 points (95% CI: -17.1 to -32.5). BFI for non-constipated subjects remained well below 28.8. Adverse events with oxycodone PR/naloxone PR treatment were well-known opioid-related adverse events. This study shows that the studied patients previously treated with WHO-step I and/or WHO-step II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to QoL. Moreover, the study shows that treatment with oxycodone PR/naloxone PR significantly reduces OIC in constipated patients and that non-constipated patients do not develop OIC during treatment with oxycodone PR/naloxone PR.

  6. Alternative kynurenic acid synthesis routes studied in the rat cerebellum

    Blanco Ayala, Tonali; Lugo Huitrón, Rafael; Carmona Aparicio, Liliana; Ramírez Ortega, Daniela; González Esquivel, Dinora; Pedraza Chaverrí, José; Pérez de la Cruz, Gonzalo; Ríos, Camilo; Schwarcz, Robert; Pérez de la Cruz, Verónica


    Kynurenic acid (KYNA), an astrocyte-derived, endogenous antagonist of α7 nicotinic acetylcholine and excitatory amino acid receptors, regulates glutamatergic, GABAergic, cholinergic and dopaminergic neurotransmission in several regions of the rodent brain. Synthesis of KYNA in the brain and elsewhere is generally attributed to the enzymatic conversion of L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). However, alternative routes, including KYNA formation from D-kynurenine (D-KYN) by D-amino acid oxidase (DAAO) and the direct transformation of kynurenine to KYNA by reactive oxygen species (ROS), have been demonstrated in the rat brain. Using the rat cerebellum, a region of low KAT activity and high DAAO activity, the present experiments were designed to examine KYNA production from L-KYN or D-KYN by KAT and DAAO, respectively, and to investigate the effect of ROS on KYNA synthesis. In chemical combinatorial systems, both L-KYN and D-KYN interacted directly with peroxynitrite (ONOO−) and hydroxyl radicals (OH•), resulting in the formation of KYNA. In tissue homogenates, the non-specific KAT inhibitor aminooxyacetic acid (AOAA; 1 mM) reduced KYNA production from L-KYN and D-KYN by 85.1 ± 1.7% and 27.1 ± 4.5%, respectively. Addition of DAAO inhibitors (benzoic acid, kojic acid or 3-methylpyrazole-5-carboxylic acid; 5 μM each) attenuated KYNA formation from L-KYN and D-KYN by ~35% and ~66%, respectively. ONOO− (25 μM) potentiated KYNA production from both L-KYN and D-KYN, and these effects were reduced by DAAO inhibition. AOAA attenuated KYNA production from L-KYN + ONOO− but not from D-KYN + ONOO−. In vivo, extracellular KYNA levels increased rapidly after perfusion of ONOO− and, more prominently, after subsequent perfusion with L-KYN or D-KYN (100 μM). Taken together, these results suggest that different mechanisms are involved in KYNA production in the rat cerebellum, and that, specifically, DAAO and ROS can function as alternative

  7. Alternative kynurenic acid synthesis routes studied in the rat cerebellum

    Tonali eBlanco Ayala


    Full Text Available Kynurenic acid (KYNA, an astrocyte-derived, endogenous antagonist of α7 nicotinic acetylcholine and excitatory amino acid receptors, regulates glutamatergic, GABAergic, cholinergic and dopaminergic neurotransmission in several regions of the rodent brain. Synthesis of KYNA in the brain and elsewhere is generally attributed to the enzymatic conversion of L-kynurenine (L-KYN by kynurenine aminotransferases (KATs. However, alternative routes, including KYNA formation from D-kynurenine (D-KYN by D-amino acid oxidase (DAAO and the direct transformation of kynurenine to KYNA by reactive oxygen species (ROS, have been demonstrated in the rat brain. Using the rat cerebellum, a region of low KAT activity and high DAAO activity, the present experiments were designed to examine KYNA production from L-KYN or D-KYN by KAT and DAAO, respectively, and to investigate the effect of ROS on KYNA synthesis. In chemical combinatorial systems, both L-KYN and D-KYN interacted directly with peroxynitrite (ONOO- and hydroxyl radicals (OH•, resulting in the formation of KYNA. In tissue homogenates, the non-specific KAT inhibitor aminooxyacetic acid (AOAA; 1 mM reduced KYNA production from L-KYN and D-KYN by 85.1 ± 1.7% and 27.1 ± 4.5%, respectively. Addition of DAAO inhibitors (benzoic acid, kojic acid or 3-methylpyrazole-5-carboxylic acid; 5 µM each attenuated KYNA formation from L-KYN and D-KYN by ~35% and ~66%, respectively. ONOO- (25 µM potentiated KYNA production from both L-KYN and D-KYN, and these effects were reduced by DAAO inhibition. AOAA attenuated KYNA production from L-KYN + ONOO- but not from D-KYN + ONOO-. In vivo, extracellular KYNA levels increased rapidly after perfusion of ONOO- and, more prominently, after subsequent perfusion with L-KYN or D-KYN (100 µM. Taken together, these results suggest that different mechanisms are involved in KYNA production in the rat cerebellum, and that, specifically, DAAO and ROS can function as alternative routes


    Wiwik Misaco Yuniarti; Ira Sari Yudaniayanti; Nusdianto Triakoso


    The aim of this study was to determine the effect of high dose calcium carbonate in rat (Rattus norvegicus) following ovaryohysterectomy. A total of twenty female rats at 13 week-old were used in this study. Following ovaryohitectomy, the animals were randomized in four treatment groups. Group P0 were :fed with standard food only P1, P2 and P2 groups treated with standard food but supplemented calcium carbonate respectively at the dose of 75 mg per animal per day, 225 mg per animal per day , ...

  9. ISPMER: Integrated system for combined PET, MRI, and electrophysiological recording in somatosensory studies in rats

    Shih, Y.-Y. [Institute of Biomedical Engineering, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, Taiwan (China); Chen, Y.-Y. [Department of Electrical and Control Engineering, National Chiao-Tung University, Hsinchu, Taiwan (China); Chen, J.-C. [Faculty of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China); Chang Chen [Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Jaw, F.-S. [Institute of Biomedical Engineering, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, Taiwan (China)], E-mail:


    The present study developed an integrated system for use in combined PET, MRI, and electrophysiological recording in somatosensory studies in rats, called ISPMER. A stereotaxic frame was designed for animal positioning that could be used in all three measurement modalities, and its dimensions complied with the gold standard of the Paxinos and Watson rat brain atlas. A graphical user interface was developed for analyzing the data using several signal processing algorithms. This integrated system provides a novel interface for the recording and processing of three-dimensional neuronal signals in three modalities.

  10. Study on the use of quantitative ultrasound evaluation of diabetic neuropathy in the rat sciatic nerve.

    Huang, Yunxia; Hu, Bing; Zhu, Jiaan


    Ultrasound is an effective tool for peripheral disease with direct imaging of morphological and echogenic changes, but it has limitations when applied to evaluation of diabetic peripheral neuropathy. The aim of this study was to assess the role of ultrasound to quantitatively evaluate diabetic peripheral neuropathy in rat sciatic nerve. In our experiments, ultrasound imaging and electrophysiological examination testing of sciatic nerves were monitored in diabetic and control rats at the period of 1st and 4th month of hyperglycemia. Cross sectional area, intraneural echo intensity, inner diameter, motor nerve conduction velocity, and histological changes were measured and compared between diabetic and control groups. Intraneural hyperechoic were observed in the diabetic rats, and the echo intensity of the sciatic nerve was increased in diabetic rats rather than control lean rats at 4th month of hyperglycemia (p diabetic peripheral neuropathy. We conclude that the echo intensity is potentially useful in detecting diabetic peripheral neuropathy, which can pave the way for more accurate and efficient diagnosis in clinical study.

  11. Chemopreventive Effects of Morindia Citrifolia Juice (noni on Experimental Breast Cancer in Rats: Preliminary Study

    Ana Milena Serrano Contreras


    Full Text Available This study determines the effect of Morindia citrifolia juice (Tahitian Noni® in the development of breast cancer induced by carcinogen agent 7.12-dimethylbenzanthracene (DMBA in rats. For this purpose, the breast cancer induction model 1.7-DMBA was used on Spraguey Dawley nulliparous rats of 35 days of age, randomly divided into three groups: group 1 control, which received no treatment, and groups 2 and 3, induced with DMBA at a dose of 55 mg/kg. The latter received a dose of noni juice of 4 ml/kg per day for 90 days. The results showed that a significant percentage (83.33% of the rats from the group induced with DMBA not treated with noni juice developed palpable breast tumors ( ≤ 2 cm of the ductal carcinoma in situ type and atypical ductal hyperplasia, compared to the other groups that did not develop any kind of tumors. In addition, it was found that rats that developed breast cancer had a lower weight gain and significantly increased water consumption (p < 0.05 compared to the other two groups. The results of the hematological and biochemical parameters showed no significant changes between groups. Histopathological changes compatible with liver toxicity were found in rats treated with noni juice. In conclusion, it was found in this preliminary study that noni juice has positive effects in modulating the development of breast cancer induced by DMBA.

  12. [Morphohistochemical study of skeletal muscles in rats after experimental flight on "Kosmos-1887"].

    Il'ina-Kakueva, E I


    Morphometric and histochemical methods were used to examine the soleus, gastrocnemius (medial portion), quadriceps femoris (central portion) and biceps brachii muscles of Wistar SPF rats two days after the 13-day flight on Cosmos-1887. It was found that significant atrophy developed only in the soleus muscle. The space flight did not change the percentage content of slow (type I) and fast (type II) fibers in fast twitch muscles. During two days at 1 g the slow soleus muscle developed substantial circulation disorders, which led to interstitial edema and necrotic changes. The gastrocnemius muscle showed small foci containing necrotic myofibers. Two days after recovery no glycogen aggregates were seen in myofibers, which were previously observed in other rats examined 4--8 hours after flight. An initial stage of muscle readaptation to 1 g occurred, when NAD.H2-dehydrogenase activity was decreased.

  13. A genome-wide SNP panel for mapping and association studies in the rat

    Nijman, Isaäc J; Kuipers, Sylvia; Verheul, Mark; Guryev, Victor; Cuppen, Edwin


    BACKGROUND: The laboratory rat (Rattus norvegicus) is an important model for human disease, and is extensively used for studying complex traits for example in the physiological and pharmacological fields. To facilitate genetic studies like QTL mapping, genetic makers that can be easily typed, like S

  14. A genome-wide SNP panel for mapping and association studies in the rat.

    Nijman, I.J.; Kuipers, S.; Verheul, M.; Guryev, V.; Cuppen, E.


    BACKGROUND: The laboratory rat (Rattus norvegicus) is an important model for human disease, and is extensively used for studying complex traits for example in the physiological and pharmacological fields. To facilitate genetic studies like QTL mapping, genetic makers that can be easily typed, like S

  15. Colon Necrosis Due to Sodium Polystyrene Sulfonate with and without Sorbitol: An Experimental Study in Rats

    Ayoub, Isabelle; Oh, Man S.; Gupta, Raavi; McFarlane, Michael; Babinska, Anna; Salifu, Moro O.


    Introduction Based on a single rat study by Lillemoe et al, the consensus has been formed to implicate sorbitol rather than sodium polystyrene sulfonate (SPS) as the culprit for colon necrosis in humans treated with SPS and sorbitol. We tested the hypothesis that colon necrosis by sorbitol in the experiment was due to the high osmolality and volume of sorbitol rather than its chemical nature. Methods 26 rats underwent 5/6 nephrectomy. They were divided into 6 groups and given enema solutions under anesthesia (normal saline, 33% sorbitol, 33% mannitol, SPS in 33% sorbitol, SPS in normal saline, and SPS in distilled water). They were sacrificed after 48 hours of enema administration or earlier if they were very sick. The gross appearance of the colon was visually inspected, and then sliced colon tissues were examined under light microscopy. Results 1 rat from the sorbitol and 1 from the mannitol group had foci of ischemic colonic changes. The rats receiving SPS enema, in sorbitol, normal saline, distilled water, had crystal deposition with colonic necrosis and mucosal erosion. All the rats not given SPS survived until sacrificed at 48 h whereas 11 of 13 rats that received SPS in sorbitol, normal saline or distilled water died or were clearly dying and sacrificed sooner. There was no difference between sorbitol and mannitol when given without SPS. Conclusions In a surgical uremic rat model, SPS enema given alone or with sorbitol or mannitol seemed to cause colon necrosis and high mortality rate, whereas 33% sorbitol without SPS did not. PMID:26413782

  16. Maternal and genetic factors in stress-resilient and -vulnerable rats: a cross-fostering study.

    Uchida, Shusaku; Hara, Kumiko; Kobayashi, Ayumi; Otsuki, Koji; Hobara, Teruyuki; Yamagata, Hirotaka; Watanabe, Yoshifumi


    Early environmental factors can modulate the development of the hypothalamic-pituitary-adrenal (HPA) axis response to stress, together with subsequent brain functions and emotional behaviors. Two rat strains, Sprague-Dawley (SD) and Fischer 344 (F344), are known to exhibit differences in HPA axis reactivity and anxiety behavior in response to restraint stress in adulthood. To investigate the contribution of maternal influences in determining HPA axis and behavioral responses to stress, a cross-fostering study was performed using stress-resilient (SD) or stress-susceptible (F344) strains. We found that SD rats adopted by either an SD (in-fostered) or an F344 (cross-fostered) dam and F344 rats adopted by an SD dam (cross-fostered) showed a suppression of the HPA axis response following 14 days of repeated restraint stress. In contrast, F344 rats adopted by an F344 dam (in-fostered) did not show such HPA axis habituation. We also found that F344 rats adopted by an F344 dam showed increased anxiety-related behaviors in social interaction and novelty-suppressed feeding tests as a result of the 14 days of restraint stress, while SD rats adopted by either an SD or an F344 dam and F344 rats adopted by an SD dam showed normal anxiety-related behaviors under the same experimental conditions. These results suggest that while genetic differences between SD and F344 strains account for some of the variations in stress vulnerability, maternal factors also contribute. (c) 2009 Elsevier B.V. All rights reserved.

  17. A 90-Day Feeding Study in Rats to Assess the Safety of Genetically Engineered Pork.

    Xiao, Gao-Jun; Jiang, Sheng-Wang; Qian, Li-Li; Cai, Chun-Bo; Wang, Qing-Qing; Ma, De-Zun; Li, Biao; Xie, Shan-Shan; Cui, Wen-Tao; Li, Kui


    Our laboratory recently produced genetically engineered (GE) Meishan pigs containing a ZFN-edited myostatin loss-of-function mutant. These GE pigs develop and grow as normal as wild type pigs but produce pork with greater lean yield and lower fat mass. To assess any potential subchronic toxicity risks of this GE pork, a 90-day feeding study was conducted in Sprague-Dawley rats. Rats were randomly divided into five groups, and fed for 90 days with basic diet and basic diets formulated with low dose and high dose pork prepared from wild type pigs and GE pigs, respectively. Animal behaviors and clinical signs were monitored twice daily, and body weight and food consumption were measured and recorded weekly. At days 45 and 90, blood tests (lipid panel, electrolytes, parameters related to liver and kidney functions, and complete blood counts) were performed. Additionally, gross pathology and histopathological analyses were performed for major organs in each group. Data analysis shows that there were no significant differences in growth rate, food consumption, and blood test parameters between rat groups fed with GE pork and wild type pork. Although differences in some liver function parameters (such as aspartate aminotransferase, total proteins, albumin, and alkaline phosphatase) and white blood cell counts (such as lymphocyte percentage and monocyte percentage) were observed between rats fed with high dose GE pork and basic diet, all test results in rats fed with GE pork are in the normal range. Additionally, there are no apparent lesions noted in all organs isolated from rats in all five feeding groups on days 45 and 90. Overall, our results clearly indicate that food consumption of GE pork produced by ZFN-edited myostatin loss-of-function mutant pigs did not have any long-term adverse effects on the health status in rats.

  18. Giant African Pouched Rats as Detectors of Tuberculosis in Human Sputum: Comparison of Two Techniques for Sputum Presentation

    Wray, Alisha M.; Mahoney, Amanda; Weetjens, Bart J.; Cox, Christophe; Jubitana, Maureen; Kazwala, Rudovic; Mfinanga, Godfrey S.; Durgin, Amy; Poling, Alan


    Previous studies have shown that pouched rats can detect the presence of "Mycobacterium tuberculosis," which causes tuberculosis, in human sputum samples obtained from clinical facilities. Although pouched rats evaluate sputum samples quickly, preparing the samples is relatively slow. The present study evaluated whether the rats can detect…

  19. Post-natal growth in the rat pineal gland: a stereological study.

    Erbagci, H; Kizilkan, N; Ozbag, D; Erkilic, S; Kervancioglu, P; Canan, S; Gumusburun, E


    The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies.

  20. The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study

    Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan


    Background Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Methods Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. Results From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9–6.6 m) and 5.4 months (95%CI 3.1–7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). Conclusions In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. Trial Registration NCT02486354 PMID:26599904

  1. Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study

    Sachin A Narvekar


    Full Text Available Background: Management of repeated implantation failure despite transfer of good-quality embryos still remains a dilemma for ART specialists. Scrapping of endometrium in the nontransfer cycle has been shown to improve the pregnancy rate in the subsequent IVF/ET cycle in recent studies. Aim: The objective of this randomized controlled trial (RCT was to determine whether endometrial injury caused by Pipelle sampling in the nontransfer cycle could improve the probability of pregnancy in the subsequent IVF cycle in patients who had previous failed IVF outcome. Setting: Tertiary assisted conception center. Design: Randomized controlled study. Materials and Methods: 100 eligible patients with previous failed IVF despite transfer of good-quality embryos were randomly allocated to the intervention group and control groups. In the intervention group, Pipelle endometrial sampling was done twice: One in the follicular phase and again in the luteal phase in the cycle preceding the embryo transfer cycle. Outcome Measure: The primary outcome measure was live birth rate. The secondary outcome measures were implantation and clinical pregnancy rates. Results: The live birth rate was significantly higher in the intervention group compared to control group (22.4% and 9.8% P = 0.04. The clinical pregnancy rate in the intervention group was 32.7%, while that in the control group was 13.7%, which was also statistically significant ( P = 0.01. The implantation rate was significantly higher in the intervention group as compared to controls (13.07% vs 7.1% P = 0.04. Conclusions: Endometrial injury in nontransfer cycle improves the live birth rate,clinical pregnancy and implantation rates in the subsequent IVF-ET cycle in patients with previous unsuccessful IVF cycles.

  2. Water permeability of rat liver mitochondria: A biophysical study.

    Calamita, Giuseppe; Gena, Patrizia; Meleleo, Daniela; Ferri, Domenico; Svelto, Maria


    The movement of water accompanying solutes between the cytoplasm and the mitochondrial spaces is central for mitochondrial volume homeostasis, an important function for mitochondrial activities and for preventing the deleterious effects of excess matrix swelling or contraction. While the discovery of aquaporin water channels in the inner mitochondrial membrane provided valuable insights into the basis of mitochondrial plasticity, questions regarding the identity of mitochondrial water permeability and its regulatory mechanism remain open. Here, we use a stopped flow light scattering approach to define the water permeability and Arrhenius activation energy of the rat liver whole intact mitochondrion and its membrane subcompartments. The water permeabilities of whole brain and testis mitochondria as well as liposome models of the lipid bilayer composing the liver inner mitochondrial membrane are also characterized. Besides finding remarkably high water permeabilities for both mitochondria and their membrane subcompartments, the existence of additional pathways of water movement other than aquaporins are suggested.

  3. Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats

    CHEN Min; ZHAO Wei-feng; LI Sa-ying; WANG Zhi; ZHANG Yun-ting; LI Guo-zhen; ZHANG Tie-mei; LUO Sen-lin; ZHOU Cheng; WU Xiao-meng; ZHOU Ni-na; CAI Kui; YANG Zhen-han; WANG Wen-chao


    Background The hypothalamus plays a central role in the regulation of metabolism by sensing metabolic demands and releasing regulatory neurotransmitters. This study investigated the response of the hypothalamus to glucose ingestion in rats by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and immunohistochemical techniques to determine the role of the hypothalamus in glycoregulation during disturbances in carbohydrate metabolism.Methods The signal intensity of the hypothalamus was monitored by fMRI for 60 minutes after oral glucose intake in 48 healthy rats (age 14 months), which included 24 normal weight rats (weighing (365±76.5) g) and 24 overweight rats (weighing (714±83.5) g). Then, 12 rats (6 normal, 6 overweight) underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for fMRI with water intake was the same as for glucose ingestion. fMRI data was processed using time cluster analysis and intensity averaging method. After fMRI,the expression of neuropeptide Y (NPY) and 5-hydroxytryptamine (5-HT) in the hypothalamus of all rats was determined by immunohistochemistry. Positive cells for NPY or 5-HT were counted.Results There was a transient, but significant, decrease in fMRI signal intensity in all rats (mean (3.12±0.78)%) in the hypothalamus within 19.5-25.5 minutes of oral glucose ingestion. In overweight rats, the decrease in signal intensity in response to the glucose ingestion was more markedly attenuated than that observed in normal weight rats ((2.2±1.5)%vs (4.2±0.7)% inhibition, t=2.12, P<0.05). There was no significant response in the hypothalamus after oral water ingestion. The percentage of NPY positive cells in obese rats were slightly lower than those in control group (21% vs 23%,t=0.71, P>0.05); but there was no significant difference between the two groups; the percentage of 5-HT positive cells in obese rats were significantly lower than

  4. Studies on absorption and metabolism of palatinose (isomaltulose) in rats.

    Tonouchi, Hidekazu; Yamaji, Taketo; Uchida, Masayuki; Koganei, Megumi; Sasayama, Akina; Kaneko, Tetsuo; Urita, Yoshihisa; Okuno, Masahiro; Suzuki, Kouji; Kashimura, Jun; Sasaki, Hajime


    We evaluated the absorption and metabolism of palatinose in rats by the carbohydrate load test and the 13C- and H2-breath tests. We compared the results of these tests with those of sucrose, since sucrose is an isomer of palatinose and generally known to be degraded and absorbed from the small intestine. In the carbohydrate load test, blood glucose and plasma insulin levels after oral administration of palatinose rose more gradually and reached a maximum that was lower than that after sucrose administration. In the 13C-breath test, rats were orally administrated [1-13C]sucrose or [1-13C]palatinose and housed in a chamber. The expired air in the chamber was collected, and the level of 13CO2 in the expired air was measured at appropriate intervals for 360 min. The value of time taken to reach the maximum concentration for expired 13CO2 from [1-13Cglucose] ([1-13Cglc]) and [1-13Cfructose] ([1-13Cfru]) palatinose was significantly longer than that from [1-13Cglc] and [1-13Cfru]sucrose, respectively. The value of area under the curve (AUC) for [1-13Cglc]palatinose was larger than that for [1-13Cglc]sucrose, but AUC for [1-13Cfru] showed no difference between palatinose and sucrose. In the H2-breath test, the concentration of H2 in the expired air was measured for 420 min. H2 was hardly detected with both palatinose and sucrose and no significant difference was observed between the two groups. These results suggest that palatinose is utilised in vivo at a rate equal to that of sucrose.

  5. Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley rats

    Madhu Katyayani Balijepalli


    Full Text Available Background: Swietenia macrophylla King. (Meliaceae seeds (SMS; commonly known as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in traditional Malay medicine for the treatment of diabetes and hypertension. The people eat only a tiny amount of raw seed, weighing not more than 5 mg. Aim: To evaluate the safety of Swietenia macrophylla seeds (SMS at a single-dose oral administration of 2 g/kg body weight (bw in sprague dawley (SD rats. Materials and Methods: Eight-week old male and female SD rats were administered a single-oral dose of 2g/kg bw. The rats′ general behavior, and toxic signs were observed throughout the 14-day study period. The food and water intake by rats and their body weight were monitored during the study period. At the end of the study period, the relative weights of the organs (lung, liver, spleen, heart, kidney, testis, stomach; the hematological and biochemical parameters were measured; the architecture and histology of the organs (liver, kidney and lungs were observed. Results: Oral administration of SMS to rats did not affect, either food or water intake; relative organ weight of vital organs; the hematological and biochemical parameters; did not show significant changes in the architecture and histology of vital organs. Overall, there were neither signs of toxicity nor deaths recorded during the study period. Conclusion: The rat dose of 2 g/kg bw is equivalent to the human dose of 325 mg/kg bw, which is well below the usual amount consumed by people, did not show any signs of toxicity in rats.

  6. Safety evaluation studies on Garden cress (Lepidium sativum L. seeds in Wistar rats

    P K Datta


    Full Text Available Summary: Garden cress (Lepidium sativum L.  leaves and seeds are used in India as  food supplement and also in traditional medicine. We have assessed the safety of Garden cress (GC seeds by conducting acute and subchronic toxicity studies in adult Wistar rats. For the acute toxicity study, 0.5 –5.0 g/kg body weight of the GC seed powder was administered through diet to rats and obvious symptoms of toxicity and mortality were monitored for 72 h . Acute doses of GC seed powder did not induce any symptoms of toxicity or mortality of  rats. In subchronic toxicity study, 1.0 – 10.0% of the GC powder was administered to rats through diet for 14 weeks. Dietary feeding of GC seed powder did not produce any mortality, no significant changes in food intake, gain in body weight, relative weight of  organs, hematological parameters, macroscopic and microscopic changes in vital organs, were observed between  experimental and control groups.  Clinical enzymes viz., LDH, SGPT were within normal levels, however, the serum ALP and SGOT were significantly increased in male rats receiving 5.0 and 10 % of GC seeds. The results showed that acute and subchronic feeding of GC seed for 14 weeks did not produce any toxic effects in male and female rats and thus can be considered non-toxic and safe.   Industrial relevance: Herbal medicines are very popular and extensively used in the developing countries. Garden cress seeds and leaves are used in food preparations.  GC seeds are given to pregnant and lactating women as natural food supplement to increase milk secretion.  GC seeds are used in herbal based medicinal preparations. The data on the acute and subchronic toxicity studies on medicinal plants are essential to assess its safety to humans, particularly for its use in pharmaceutical preparations.

  7. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika


    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  8. Cataract surgery in previously vitrectomized eyes.

    Akinci, A; Batman, C; Zilelioglu, O


    To evaluate the results of extracapsular cataract extraction (ECCE) and phacoemulsification (PHACO) performed in previously vitrectomized eyes. In this retrospective study, 56 vitrectomized eyes that had ECCE and 60 vitrectomized eyes that had PHACO were included in the study group while 65 eyes that had PHACO in the control group. The evaluated parameters were the incidence of intra-operative and postoperative complications (IPC) and visual outcomes. Chi-squared, independent samples and paired samples tests were used for comparing the results. Deep anterior chamber (AC) was significantly more common in the PHACO group of vitrectomized eyes (PGVE) and observed in eyes that had undergone extensive vitreous removal (p ECCE group and the PGVE (p > 0.05). Some of the intra-operative conditions such as posterior synechiae, primary posterior capsular opacification (PCO) and postoperative complications such as retinal detachment (RD), PCO were significantly more common in vitrectomized eyes than the controls (p ECCE group and the PGVE (p > 0.05). Deep AC is more common in eyes with extensive vitreous removal during PHACO than ECCE. Decreasing the bottle height is advised in this case. Except for this, the results of ECCE and PHACO are similar in previously vitrectomized eyes. Posterior synechiaes, primary and postoperative PCO and RD are more common in vitrectomized eyes than the controls.

  9. Study of hypoglycaemic and hypolipidemic effects of Inula viscosa L. aqueous extract in normal and diabetic rats.

    Zeggwagh, N-A; Ouahidi, M-L; Lemhadri, A; Eddouks, M


    The present study was designed to examine the hypoglycaemic and hypolipidemic activity of Inula viscsa aqueous extract on normal and diabetic rats. In normal rats, a significant reduction in blood glucose levels 2 h was observed after a single oral administration (pInula viscosa possess a hypoglycaemic but not hypolipidemic activity in normal and diabetic rats. The observed hypoglycaemic activity seems to be independent of insulin secretion.

  10. Effect of bleeding on nerve regeneration and epineural scar formation in rat sciatic nerves: an experimental study.

    Servet, Erkan; Bekler, Halil; Kılınçoğlu, Volkan; Özler, Turhan; Özkut, Afşar


    Epineural scar formation is one of the most significant negative factors affecting surgical repair after peripheral nerve injury. The scar tissue mechanically hinders axonal regeneration and causes adhesions between nerves and surrounding tissues. A hemostatic agent Ankaferd Blood Stopper (ABS; İmmun Gıda İlaç Kozmetik San. ve Tic. Ltd. Şti., Istanbul, Turkey) has not been previously used. Decreasing the postoperative bleeding and adhesions between nerve and surrounding tissues will prevent the formation of scar tissue, as well as corresponding compressive neuropathy and/or deceleration of axonal regeneration. The purpose of this experimental study was to investigate the effects of bleeding on nerve healing and scar tissue after repair of peripheral nerve injuries. The right sciatic nerve of 30 Sprague-Dawley male rats (weighing 260-330 g) was cut 1.5 cm proximal to the trifurcation and repaired primarily with 8/0 sutures using epineural technique. The rats were then divided into 3 groups. Saline was applied in Group 1 (n=10), ABS in Group 2 (n=10), and heparin in Group 3 (n=10) for 5 minutes to the repair site and surrounding tissues. In each group, electrophysiological measurements were performed with electromyography (EMG) at postoperative week 12. Magnetic resonance diffusion tensor imaging was used at week 12. Macroscopical and histopathological evaluations were conducted after sacrificing the rats at week 24 with total excision of the repaired sciatic nerves and surrounding tissues. The ABS and saline groups showed better healing than the heparin group. The ABS and saline groups were better in the histopathologic evaluations, but there was no statistically significant difference between the 2 groups. Statistically significant differences were not found between the 3 groups. Significant results may be obtained with larger studies.

  11. A method for the isolation and culture of adult rat retinal pigment epithelial (RPE cells to study retinal diseases

    Janosch Peter Heller


    Full Text Available Diseases such as age-related macular degeneration (AMD affect the retinal pigment epithelium (RPE and lead to the death of the epithelial cells and ultimately blindness. RPE transplantation is currently a major focus of eye research and clinical trials using human stem cell-derived RPE cells are ongoing. However, it remains to be established to which extent the source of RPE cells for transplantation affects their therapeutic efficacy and this needs to be explored in animal models. Autotransplantation of RPE cells has attractions as a therapy, but existing protocols to isolate adult RPE cells from rodents are technically difficult, time-consuming, have a low yield and are not optimized for long-term cell culturing. Here, we report a newly devised protocol which facilitates reliable and simple isolation and culture of RPE cells from adult rats. Incubation of a whole rat eyeball in 20 U/ml papain solution for 50 minutes yielded 4 x 104 viable RPE cells. These cells were hexagonal and pigmented upon culture. Using immunostaining, we demonstrated that the cells expressed RPE cell-specific marker proteins including cytokeratin 18 and RPE65, similar to RPE cells in vivo. Additionally, the cells were able to produce and secrete Bruch’s membrane matrix components similar to in vivo situation. Similarly, the cultured RPE cells adhered to isolated Bruch’s membrane as has previously been reported. Therefore, the protocol described in this article provides an efficient method for the rapid and easy isolation of high quantities of adult rat RPE cells. This provides a reliable platform for studying the therapeutic targets, testing the effects of drugs in a preclinical setup and to perform in vitro and in vivo transplantation experiments to study retinal diseases.

  12. Protective role of diallyl tetrasulfide on cadmium-induced testicular damage in adult rats: a biochemical and histological study.

    Ponnusamy, Murugavel; Pari, Leelavinothan


    Cadmium (Cd)-induced oxidative damage is the most serious problem that leads to reproductive system failure in both human and animals. Our previous studies indicate that diallyl tetrasulfide (DTS) from garlic has the cytoprotective and antioxidant activity against Cd-induced toxicity in vivo and in vitro. The present investigation was carried out to find the influence of DTS on peroxidative damage induced by Cd in rat testes. The Cd-exposed rat testis showed a significant (p glutathione peroxidase) and glutathione metabolizing (glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) enzymes as well as reduced levels of non-enzymic (reduced glutathione, ascorbate and total sulphydryl groups) antioxidants. In contrast, treatment with DTS (40 mg/kg body weight orally) significantly (p Testicular protection by DTS is further substantiated by remarkable reduction of Cd-induced pathological changes. Our study has revealed that DTS renders protection against Cd-induced testicular injury by reducing Cd-mediated oxidative damage.

  13. Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in the rat brain: an autoradiography study.

    Ciudad-Roberts, Andrés; Camarasa, Jorge; Pubill, David; Escubedo, Elena


    Previous studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce a heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated male Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and sacrificed them the day after to perform [(125)I]Epibatidine binding autoradiograms on serial coronal slices. MDMA induced significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory, motor, auditory and retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei. These increases ranged from 3% (retrosplenial cortex) to 30 and 34% (amygdala and substantia nigra). No increased α4 subunit immunoreactivity was found in up-regulated areas compared with saline-treated rats, suggesting a post-translational mechanism as occurs with nicotine. The heteromeric nAChR up-regulation in certain areas could account, at least in part, for the reinforcing, sensitizing and psychiatric disorders observed after long-term consumption of MDMA.

  14. Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

    Martin R.


    Full Text Available Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the cerebellum and other structures in the experimental group. This study, particularly in malnourished rats, demonstrates increased BOLD activation in the cerebellum.

  15. A three generation reproduction study with Sprague-Dawley rats consuming high-amylose transgenic rice.

    Zhou, Xing Hua; Dong, Ying; Zhao, Yan Sheng; Xiao, Xiang; Wang, Yun; He, Yuan Qing; Liu, Qiao Quan


    The transgenic rice line (TRS) enriched with amylose and resistant starch (RS) was developed by antisense RNA inhibition of starch-branching enzymes. Cereal starch with high amylose has a great benefit on human health through its resistant starch. In order to evaluate the effect of transgenic rice on rats, the rats were fed diets containing 70% TRS rice flour, its near-isogenic rice flour or the standard diet as the control through three generations. In the present study, clinical performance, reproductive capacity and pathological responses including body weight, food consumption, reproductive data, hematological parameters, serum chemistry components, organ relative weights and histopathology were examined. Some statistically significant differences were observed in rats consuming the high amylose rice diet when compared to rats fed the near-isogenic control rice diet or the conventional (non-rice) standard diet. These differences were generally of small magnitude, appeared to be random in nature, and were within normal limits for the strain of rat used, and were therefore not considered to be biologically meaningful or treatment related.

  16. Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats.

    Lin, Chien-Min; Tsai, Jo-Ting; Chang, Chen Kuei; Cheng, Juei-Tang; Lin, Jia-Wei


    Decrease of peroxisome proliferator-activated receptors-δ (PPARδ) expression has been observed after spinal cord injury (SCI). Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application. In the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage. Recovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI. The obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.

  17. Effect of single-dose amoxicillin on rat incisor odontogenesis: a morphological study.

    Kumazawa, Kaido; Sawada, Takashi; Yanagisawa, Takaaki; Shintani, Seikou


    The effect of exposure to amoxicillin on tooth development remains to be elucidated. The purpose of this study was to investigate the effect of amoxicillin on rat incisor odontogenesis. Male Wistar rats weighing approximately 100 g were given a single intraperitoneal injection of 3.0 g/kg body weight amoxicillin. One week after injection, the rats were fixed, and the lower incisors were demineralized and prepared into paraffin sections for light microscopy (LM) and immunohistochemistry. Undemineralized samples were embedded in resin and ground for processing for contact microradiography (CMR) and scanning electron microscopy (SEM). Serum calcium, phosphate, and magnesium concentrations were measured. At 1 week after amoxicillin administration, LM, CMR, and SEM revealed a clear increase in the area of interglobular dentin, representing disruption of mineralization by odontoblasts. Immunohistochemistry demonstrated moderate levels of the small integrin-binding ligand N-linked glycoprotein family dentin matrix protein 1 in large areas of interglobular dentin. On the other hand, no morphological alteration or hypomineralization was observed in the enamel. Serum calcium values showed no significant differences between the control and experimental rats during the experimental period although both serum phosphate and magnesium levels increased at day 1 after amoxicillin injection. The results suggest that a single dose of amoxicillin specifically affects normal tooth dentin mineralization, but not enamel mineralization in rat incisor odontogenesis. The present results further our understanding of the clinical association between dentin abnormality and amoxicillin exposure during tooth development.

  18. Como novos conhecimentos podem ser construídos a partir dos conhecimentos prévios: um estudo de caso How new knowledge can be constructed from previous knowledge: a case study

    Francimar Martins Teixeira


    Full Text Available O presente artigo trata sobre o estudo de caso de como uma professora utiliza os conhecimentos prévios dos estudantes durante a abordagem de um novo conceito científico. Para tanto, foram realizadas filmagens de aulas de ciências durante a execução de uma sequência didática, a fim de investigar de que maneira os conhecimentos prévios dos estudantes eram tratados em sala de aula ao longo da abordagem do tema. A partir dos resultados encontrados, percebemos nas aulas observadas como a professora lidava com os conhecimentos dos estudantes. Identificamos que houve ocasiões em que ela os considerou e outras em que os desconsiderou. Apesar de ações antagônicas, tanto o fato de considerar quanto de desconsiderar parecem ter em comum a busca de manutenção de foco sob os conceitos, entendidos pela professora, como sendo os que devem ser objeto de atenção dos alunos.This article deals with a case study about how a teacher uses previous knowledge of students to approach a new concept. To this end, sciences classes were filmed during the execution of a didactic sequence, in order to investigate how previous knowledge of the students was treated in the classroom along the approach of the theme. From these results, we saw how the teacher dealt with previous knowledge of their students. We identified that there were occasions when she considered them and others in which she disregarded them. Although they are antagonistic actions, both the facts, to consider or to dismiss, have in common the search for keeping the focus on the concepts, defined by the teacher as those that should be the object of attention for the students.

  19. Developmental toxicity studies of methyl ethyl ketoxime (MEKO) in rats and rabbits.

    Derelanko, Michael J; Rinehart, William E; Rodwell, Dean E


    The developmental toxicity of methyl ethyl ketoxime (MEKO), an industrial antioxidant used primarily as an antiskinning agent in alkyd paint, was investigated in rats and rabbits. Following preliminary dose range finding studies, groups of 25 pregnant rats or 18 pregnant rabbits were dosed by gavage with aqueous solutions of MEKO at 0, 60, 200, or 600 mg/kg (rats) or 0, 8, 14, 24, or 40 mg/kg (rabbits) on gestation days 6-15 or 6-18, respectively. In rats, dose-dependent clinical signs of maternal toxicity including reduced body weight gains were noted at 200 and 600 mg/kg. At 60 mg/kg and above enlarged spleens were observed at necropsy. The preliminary study found methemoglobin formation and reticulocytosis indicative of anemia at these dose levels. No treatment-related gestational effects, malformations or developmental variations were observed in the rats. In rabbits, 3 females aborted and 8 females were found dead at 40 mg/kg between gestation days 11 and 24. Clinical signs of maternal toxicity were present in surviving doses at this dose level. Body weight gains were reduced at 24 and 40 mg/kg. The preliminary study indicated maternal hematological effects in the rabbits similar to the rats at dose levels as low as 10 mg/kg. MEKO was not considered to have produced any treatment-related gestational effects, malformations or developmental variations in the rabbit at dose levels at or below 24 mg/kg. Because of excessive maternal mortality and abortions at the 40 mg/kg dose level, only 6 rabbits produced litters. The severe maternal toxicity and limited number of litters precluded a full assessment of developmental toxicity at 40 mg/kg. Nonetheless, MEKO did not appear to be teratogenic to the rabbit at this dose level.

  20. Immunogenicity, efficacy and safety of Nuwiq(®) (human-cl rhFVIII) in previously untreated patients with severe haemophilia A-Interim results from the NuProtect Study.

    Liesner, R J; Abashidze, M; Aleinikova, O; Altisent, C; Belletrutti, M J; Borel-Derlon, A; Carcao, M; Chambost, H; Chan, A K C; Dubey, L; Ducore, J; Fouzia, N A; Gattens, M; Gruel, Y; Guillet, B; Kavardakova, N; El Khorassani, M; Klukowska, A; Lambert, T; Lohade, S; Sigaud, M; Turea, V; Wu, J K M; Vdovin, V; Pavlova, A; Jansen, M; Belyanskaya, L; Walter, O; Knaub, S; Neufeld, E J


    Nuwiq(®) (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq(®) in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq(®) in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq(®) (inhibitor activity ≥0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory. Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24). Five patients developed low-titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor-free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as "excellent" or "good" in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was "excellent" or "good" for 8 (89%) procedures and "moderate" for 1 (11%). No tolerability concerns were evident. These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq(®) . © 2017 The Authors. Haemophilia published by John Wiley & Sons Ltd.

  1. Can previous learning alter future plasticity mechanisms?

    Crestani, Ana Paula; Quillfeldt, Jorge Alberto


    The dynamic processes related to mnemonic plasticity have been extensively researched in the last decades. More recently, studies have attracted attention because they show an unusual plasticity mechanism that is independent of the receptor most usually related to first-time learning--that is, memory acquisition-the NMDA receptor. An interesting feature of this type of learning is that a previous experience may cause modifications in the plasticity mechanism of a subsequent learning, suggesting that prior experience in a very similar task triggers a memory acquisition process that does not depend on NMDARs. The intracellular molecular cascades necessary to assist the learning process seem to depend on the activation of hippocampal CP-AMPARs. Moreover, most of these studies were performed on hippocampus-dependent tasks, even though other brain areas, such as the basolateral amygdala, also display NMDAR-independent learning.

  2. 77 FR 70176 - Previous Participation Certification


    ... URBAN DEVELOPMENT Previous Participation Certification AGENCY: Office of the Chief Information Officer... digital submission of all data and certifications is available via HUD's secure Internet systems. However...: Previous Participation Certification. OMB Approval Number: 2502-0118. Form Numbers: HUD-2530 ....

  3. Impairment of Retrograde Neuronal Transport in Cardiac Vagal Motoneurons in Streptozotocin-Induced Diabetic Rats: A Wheat Ger Agglutinin-Horseradish Peroxidase Neurohistochemical study

    A. Odekunle; Phillips, C M


    Central projections of vagal motoneurons to the heart were studied in diabetic rats using Wheat germ Agglutinin-Horseradish peroxidase (WGA-HRP). Experimental rats were rendered diabetic by intraperitoneal injection of streptozotocin in citrate buffer. The diabetic rats were maintained in a stable diabetic state by daily injection of insulin for 24 weeks. Age-matched control rats were injected intraperitoneally with citrate buffer not containing streptozotocin. Control rats were also kept ali...

  4. Sub-chronic toxicity and heavy metal toxicity study on Kappaphycus alvarezii in albino rats

    AbiramiRG; KowsalyaS


    Objective: This study aimed to evaluate the toxicity of Kappaphycus alvarezii methanolic extracts in albino rats. Methods: Sub-chronic toxicity was tested with a single dose of intraperitonal administration of the extract as per the OECD guidelines in the experimental group rats and the control group rats was fed with standard diet and water ad libitum. Mortality, behaviour changes, clinical signs and symptoms, food intake, body weight and any abnormalities of the visceral organs were observed. Results: The results revealed that the algal extract resulted in neither mortality nor any abnormalities. The Most of the serum biochemical parameters and hematological values were similar in control and experimental groups, histopathological examination of the vital organs like liver, kidney, spleen, brain and heart revealed no obvious abnormality in the control group and Kappaphycus alvarezii treated group. Conclusion: It may be concluded that Kappaphycus alvarezii rich in nutrient and nutraceutial potentials and also safety food for human consumption.

  5. Anatomical Study of the Intercostobrachial Nerve in Sprague-Dawlay Rats

    Liansheng Ning; Xin Wang; Kai Zhao; Zhenfang Yang; Hui Sun; Jie Ge


    OBJECTIVE The aim of the study was to explore the anatomy of the intercostobrachial nerve in rats.METHODS Dissections of 8 Sprague-dawley rats were performed to examine the intercostobrachial nerve. Fifteen dissections were successful.The position of the nerve, origin, termination, length and diameter were measured and recorded.RESULTS 1) 80% of the nerves originated from the second intercostal space and 20% from the first intercostal space; 2) 60% of the nerves terminated in the latissimus dorsi and 40% in the axillary skin 3) the branches of the nerves only were divided into 2 types, single and double; 4) the length of the nerves ranged from 2.4 to 3.4 cm with an average of 2.97±0.90 cm; 5) the diameter of the nerves was thicker at their origin compared to their termination.CONCLUSION The intercostobrachial nerve is simple in rats with 60%terminating in the latissimus dorsi.

  6. Experimental study of 『PERSICAE SEMEN』 on the blood injected by Endotoxin in rats



    Full Text Available This study was performed to investigate the effects of 「Persicae Semen」(PS on the blood injected by Endotoxin in rats. The blood was induced by Endotoxin injection into the caudal vein of rats and PS group taken a measurement of RBC, Hb, Hct, Platelet, WBC, ESR, CRP. The results were obtained as follows: 1. RBC, Hb, Hct, Platelet, WBC were increased with statistical significance at PS group as compared with those of the control group. 2. ESR, CRP were decreased with statistical significance at PS group as compared with those of the control group. It is concluded that PS group has significant effects on the blood injected by Endotoxin in rats. Therefore, PS group seems to be applicable to the diseases related to Endotoxin in clinics.

  7. [Biomechanical test study of rat femurs growing under different stress environment].

    Liu, Yingxi; Zhao, Wenzhi; Zhang, Jun; Li, Shouju; Li, Jingnian; Sun, Xiaojiang


    By creating two kinds of stress environment in the same animal model, we performed a three-point bending test and a compressing test on the rat femurs growing under different stress conditions to characterize the effect of stress on bone mechanical properties. The right hindlimbs were subjected to sciatic nerve resection to become cripple and were used as unloading group; the left hindlimbs bore excess load and made up the overloading group; the normal rats were used as control group. The animals were encouraged to exercise for half an hour everyday in the morning, noon and evening. The experiment observation finished in four weeks. The biomechanical parameters of femur diaphyses were measured. The experiment results showed that stress environment may change several mechanical parameters of rat femurs. This study indicated that bone tissues can adapt to its stress environment by changing its mechanical properties. The experimental model in this article is practical and reliable.

  8. Onset of mandible and tibia osteoradionecrosis – a comparative pilot study in the rat

    Damek-Poprawa, Monika; Both, Stefan; Wright, Alexander C.; Maity, Amit; Akintoye, Sunday O.


    Objectives Osteoradionecrosis (ORN) is common in the jaws following radiotherapy. We hypothesized that mandible is more susceptible to ORN than tibia based on site-disparity in hypoxic-hypocellular-hypovascular tissue breakdown. Study Design Twelve rats received 50 Gy irradiation to mandible or tibia; 4 of 12 rats further received minor surgical trauma to the irradiated sites. Structural and cellular skeletal changes were assessed with computer tomography, histology and immunostaining. Results Mandible developed ORN with 70% mean bone loss 10 weeks post-irradiation (p < 0.05) while tibia was structurally and radiological intact for 20 weeks post-irradiation. Hypocellularity, hypoxia and oxidative stress were higher in irradiated mandible (p < 0.001) than tibia (p < 0.01) but vascular damage was similar at both skeletal sites. Combined effects of radiation and minor trauma promoted mandibular alveolar bone loss and tibial fracture Conclusion ORN has a more rapid onset in mandible relative to tibia in the rat PMID:23254371

  9. Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

    Yang Cao


    Full Text Available In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

  10. Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

    Farag, Mahmoud M; Selima, Eman A; Salama, Mona A


    The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.

  11. Studies on orthocephalization. IV. Differential growth of the sphenooccipital synchondosis in the rat

    Vilmann, H; Kirkeby, S; Moss, M L


    The growth of the bone ends articulating through the sphenooccipital synchondrosis in the rat occurs differentially. Considerably more bone is during growth formed in the pharyngeal part of the anterior end of the basioccipital bone than in the cerebral part. The same conditions hold good...... to be a measure of growth rate. Sections of the sphenooccipital synchondrosis from 10 rats 10 days ago, incubated for reactions to alkaline phosphatase have formed the basis of the study. Quantitative expressions of the extension of enzymatic reaction have been collected. Statistical treatment of these data have...

  12. Pharmacodynamic study on acute hypotensive activities of Carissa carandas extract in normal rats.

    Shamim, Sumbul; Ahmad, Syed Iqbal


    This study aims to evaluate the effect of Carissa carandas extract on cardiovascular function of normal rats. Intravenous bolus injection of this extract in the doses of 5 mg kg(-1)_-45 mg kg(-1), produced dose dependent reduction in arterial blood pressure (p0.05). It was concluded that the Carissa carandas Ethanol extract possess potent acute hypotensive effect in normal rats. It stimulates the muscarinic receptors located on the endothelial cells of the vasculature. This stimulation results in the release of endothelial-derived relaxing factors (EDRFs) or nitric oxide that diffuses to vasculature smooth muscles and causes their relaxation.

  13. Nylon bands as bone cerclage - experimental study in rabbits and rats

    Claudia Valéria Seullner Brandão; Pedro Afonso Urgel Martins Costa Antunes; Caroline Abreu Estanislau; Maria Jaqueline Mamprim; Leandro Teixeira; Carlos Roberto Padovani; Paulo Vinicius Tertuliano Marinho; Bruno Watanabe Minto


    The aim of this study was to evaluate the biocampatibility of the commercial nylon band used as bone cerclage, comparing with traditional metal cerclage wires. Twenty one rabbits and fifteen rats, healthy and without orthopedics problems were used. A commercial nylon band and a surgical stainless steel wire “0” were used in right (SN) and left (SA) rabbits’s hindlimb, respectively. Otherwise, on rats SN was on the left hindlimb, and SA on the right hindlimb. Both experimental species were div...

  14. Experimental study of 『PERSICAE SEMEN』 on the blood injected by Endotoxin in rats

    Chang-Keun; Kyeong-Sun Soh; Chan-Gil Jeong


    This study was performed to investigate the effects of 「Persicae Semen」(PS) on the blood injected by Endotoxin in rats. The blood was induced by Endotoxin injection into the caudal vein of rats and PS group taken a measurement of RBC, Hb, Hct, Platelet, WBC, ESR, CRP. The results were obtained as follows: 1. RBC, Hb, Hct, Platelet, WBC were increased with statistical significance at PS group as compared with those of the control group. 2. ESR, CRP were decreased with statistical sign...

  15. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study

    Norman Ruthven Saunders


    Full Text Available The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analysed by functional groups of influx transporters, particularly solute carrier (SLC transporters. RNA-Seq was performed at embryonic day (E 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve with expression levels 2-98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15. In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g. Slc16a10, a thyroid hormone transporter gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients.

  16. Sympathetic innervation of the spleen in male Brown Norway rats: a longitudinal aging study.

    Perez, Sam D; Silva, Dorian; Millar, Ashley Brooke; Molinaro, Christine A; Carter, Jeff; Bassett, Katie; Lorton, Dianne; Garcia, Paola; Tan, Laren; Gross, Jonathon; Lubahn, Cheri; Thyagarajan, Srinivasan; Bellinger, Denise L


    Aging leads to reduced cellular immunity with consequent increased rates of infectious disease, cancer, and autoimmunity in the elderly. The sympathetic nervous system (SNS) modulates innate and adaptive immunity via innervation of lymphoid organs. In aged Fischer 344 (F344) rats, noradrenergic (NA) nerve density in secondary lymphoid organs declines, which may contribute to immunosenescence with aging. These studies suggest there is SNS involvement in age-induced immune dysregulation. The purpose of this study was to longitudinally characterize age-related change in sympathetic innervation of the spleen and sympathetic activity/tone in male Brown Norway (BN) rats, which live longer and have a strikingly different immune profile than F344 rats, the traditional animal model for aging research. Splenic sympathetic neurotransmission was evaluated between 8 and 32 months of age by assessing (1) NA nerve fiber density, (2) splenic norepinephrine (NE) concentration, and (3) circulating catecholamine levels after decapitation. We report a decline in NA nerve density in splenic white pulp (45%) at 15 months of age compared with 8-month-old (M) rats, which is followed by a much slower rate of decline between 24 and 32 months. Lower splenic NE concentrations between 15 and 32 months of age compared with 8M rats were consistent with morphometric findings. Circulating catecholamine levels after decapitation stress generally dropped with increasing age. These findings suggest there is a sympathetic-to-immune system dysregulation beginning at middle age. Given the unique T-helper-2 bias in BN rats, altered sympathetic-immune communication may be important for understanding the age-related rise in asthma and autoimmunity.

  17. Protective effects of honokiol on ischemia/reperfusion injury of rat ovary: an experimental study

    Yaman Tunc, Senem; Agacayak, Elif; Goruk, Neval Yaman; Icen, Mehmet Sait; Turgut, Abdulkadir; Alabalik, Ulas; Togrul, Cihan; Ekinci, Cenap; Ekinci, Aysun; Gul, Talip


    Aim The purpose of this study was to investigate the protective effect of honokiol on experimental ischemia/reperfusion injury of rat ovary. Materials and methods A total of 40 female Wistar albino rats were used in this study. The rats were divided into five groups as follows: sham (Group I), torsion (Group II), torsion + detorsion (Group III), torsion + detorsion + saline (Group IV), and torsion + detorsion + honokiol (Group V). Bilateral adnexa in all the rats except for those in the sham group were exposed to torsion for 3 hours. The rats in Group IV were administered saline, whereas the rats in Group V were administered honokiol by intraperitoneal route 30 minutes before detorsion. Tissue and plasma concentrations of malondialdehyde and nitric oxide were determined. Ovarian tissue was histologically evaluated. Data analyses were performed by means of Kruskal–Wallis test and Mann–Whitney U-test (Bonferroni correction) in SPSS 15.0 (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL, USA). Results The torsion and detorsion groups had higher scores in vascular congestion, hemorrhage, and inflammatory cell infiltration compared with the sham group (P<0.005). In addition, total histopathological scores were significantly higher in the torsion and detorsion groups compared with the sham group (P<0.005). A significant reduction was observed in hemorrhage, inflammatory cell infiltration, and cellular degeneration scores, of all histopathological scores, in the honokiol group (P<0.005). Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and honokiol groups (P<0.005). Ovarian tissue concentrations of nitric oxide, on the other hand, were significantly higher in the torsion group compared with the sham, saline, and honokiol groups (P<0.005). Conclusion Honokiol has a beneficial effect on ovarian torsion-related ischemia/reperfusion injury. PMID:27022246

  18. Use of a 12 months' self-referral reminder to facilitate uptake of bowel scope (flexible sigmoidoscopy) screening in previous non-responders: a London-based feasibility study

    Kerrison, Robert S; McGregor, Lesley M; Marshall, Sarah; Isitt, John; Counsell, Nicholas; Wardle, Jane; von Wagner, Christian


    Background: In March 2013, NHS England extended its national Bowel Cancer Screening Programme to include ‘one-off' Flexible Sigmoidoscopy screening (NHS Bowel Scope Screening, BSS) for men and women aged 55. With less than one in two people currently taking up the screening test offer, there is a strong public health mandate to develop system-friendly interventions to increase uptake while the programme is rolling out. This study aimed to assess the feasibility of sending a reminder to previous BSS non-responders, 12 months after the initial invitation, with consideration for its potential impact on uptake. Method: This study was conducted in the ethnically diverse London Boroughs of Brent and Harrow, where uptake is below the national average. Between September and November 2014, 160 previous non-responders were randomly selected to receive a reminder of the opportunity to self-refer 12 months after their initial invitation. The reminder included instructions on how to book an appointment, and provided options for the time and day of the appointment and the gender of the endoscopist performing the test. To address barriers to screening, the reminder was sent with a brief locally tailored information leaflet designed specifically for this study. Participants not responding within 4 weeks were sent a follow-up reminder, after which there was no further intervention. Self-referral rates were measured 8 weeks after the delivery of the follow-up reminder and accepted as final. Results: Of the 155 participants who received the 12 months' reminder (returned to sender, n=5), 30 (19.4%) self-referred for an appointment, of which 24 (15.5%) attended and were successfully screened. Attendance rates differed by gender, with significantly more women attending an appointment than men (20.7% vs 8.8%, respectively; OR=2.73, 95% CI=1.02–7.35, P=0.05), but not by area (Brent vs Harrow) or area-level deprivation. Of the 30 people who self-referred for an appointment, 27 (90

  19. Bone tissue engineering for spine fusion : An experimental study on ectopic and orthotopic implants in rats

    van Gaalen, SM; Dhert, WJA; van den Muysenberg, A; Oner, FC; van Blitterswijk, C; Verbout, AJ; de Bruijn, J.D.


    Alternatives to the use of autologous bone as a bone graft in spine surgery are needed. The purpose of this study was to examine tissue-engineered bone constructs in comparison with control scaffolds without cells in a posterior spinal implantation model in rats. Syngeneic bone marrow cells were cul




    A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fi

  1. [Histopathological studies of the rat pancreas after prolonged treatment with imuran. Preliminary findings].

    Mansi, C; Savarino, V; Picciotto, A; Testa, R; Dabove, L; Gismondi, C; Celle, G


    The AA. have studied the pathological effects on the pancreas of rats after chronic administration of azathioprine (AZA) in different doses. The most significant lesions are flattening of duct epitelium and the presence of protein plugs in the ducts. These pancreatic lesions are significantly more frequent in rate treated with higher doses than in controls and so are dose-dependent.



    In order to establish the number, the viability and the developmental potential of GABAergic neurons present in dopaminergic ventral mesencephalic (VM) grafts from embryonic rat, we have studied the survival and development of these neurons in culture. The GABAergic fraction demonstrated a highly

  3. An improved model for studies on transdermal drug absorption invivo in rats

    VOLLMER, U; MULLER, BW; WILFFERT, B; Peters, Thies


    In rats, transdermal drug absorption can be studied under physiological conditions by cannulating the peripheral skin vein, draining the area of the skin which is used for drug application, and collecting the blood. This method leads to decreased blood volume, which causes a reduction in skin blood

  4. An improved model for studies on transdermal drug absorption in-vivo in rats

    Vollmer, U.; Muller, B.W.; Wilffert, B.; Peters, Thies


    In rats, transdermal drug absorption can be studied under physiological conditions cannulating the peripheral skin vein, draining the area of the skin which is used for drug application, and collecting the blood. This method leads to decreased blood volume, which causes a reduction in skin blood flo

  5. Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats

    Jonker, D.; Kuper, C.F.; Fraile, N.; Estrella, A.; Rodríguez Otero, C.


    Lycopene, as a suspension in sunflower oil (20% w/w), was tested for subchronic toxicity by administration at dietary concentrations of 0, 0.25, 0.50, and 1.0% to groups of 20 male and 20 female Wistar rats for a period of 90 days. The lycopene examined in this study was derived from a fungal biomas

  6. One-generation reproductive toxicity study of DHA-rich oil in rats

    Blum, R.; Kiy, T.; Waalkens-Berendsen, I.; Wong, A.W.; Roberts, A.


    Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the marine protist, Ulkenia sp. The reproductive toxicity of DHA-algal oil was assessed in a one-generation study. Rats were provided diets

  7. RAT Selection and Resource Allocation in Heterogeneous Networks - OPNET Modeler in Optimization Studies

    Zakrzewska, Anna; Ruepp, Sarah Renée; Berger, Michael Stübert


    The paper addresses the problem of optimal selection of Radio Access Technology (RAT) and assignment of resources in a multistandard wireless network scenario. It is shown how OPNET Modeler can be used to perform optimization studies using Integer Linear Programming (ILP) solvers. In this way...

  8. One-generation reproductive toxicity study of DHA-rich oil in rats

    Blum, R.; Kiy, T.; Waalkens-Berendsen, I.; Wong, A.W.; Roberts, A.


    Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the marine protist, Ulkenia sp. The reproductive toxicity of DHA-algal oil was assessed in a one-generation study. Rats were provided diets cont

  9. Glutathione depletion in rat hepatocytes : a mixture toxicity study with alpha,ß-unsaturated esters

    Freidig, A.; Hofhuis, M.; Holstijn, I. van; Hermens, J.


    Glutathione (GSH) depletion is often reported as an early cytotoxic effect, caused by many reactive organic chemicals. In the present study, GSH depletion in primary rat hepatocytes was used as an in vitro effect-equivalent to measure the toxic potency of α,β-unsaturated esters (acrylates and methac




    In order to establish the number, the viability and the developmental potential of GABAergic neurons present in dopaminergic ventral mesencephalic (VM) grafts from embryonic rat, we have studied the survival and development of these neurons in culture. The GABAergic fraction demonstrated a highly di

  11. Radiological study of gastrointestinal motor activity after acute cisplatin in the rat. Temporal relationship with pica.

    Cabezos, Pablo Antonio; Vera, Gema; Castillo, Mónica; Fernández-Pujol, Ramón; Martín, María Isabel; Abalo, Raquel


    Nausea and vomiting are amongst the most severe dose-limiting side effects of chemotherapy. Emetogenic activity in rats can only be evaluated by indirect markers, such as pica (kaolin intake), or delay in gastric emptying. The aim of this work was to study, by radiological methods, the alterations in gastrointestinal motility induced by acute cisplatin in the rat, and to compare them with the development of pica. Rats received cisplatin (0-6 mg kg(-1)) at day 0. In the pica study, individual food ingestion and kaolin intake were measured each day (from day -3 to day 3). In the radiological study, conscious rats received an intragastric dose of medium contrast 0, 24 or 48 h after cisplatin injection, and serial X-rays were taken 0-24 h after contrast. Cisplatin dose-dependently induced both gastric stasis and stomach distension, showing a strict temporal relationship with the induction of both acute and delayed pica. Radiological methods, which are non-invasive and preserve animals' welfare, are useful to study the effect of emetogenic drugs in the different gastrointestinal regions and might speed up the search for new anti-emetics.

  12. Biodegradation of differently cross-linked collagen membranes: an experimental study in the rat.

    Rothamel, D.; Schwarz, F.; Sager, M.; Herten, M. van; Sculean, A.; Becker, J.M.


    The aim of the present study was to compare the biodegradation of differently cross-linked collagen membranes in rats. Five commercially available and three experimental membranes (VN) were included: (1) BioGide (BG) (non-cross-linked porcine type I and III collagens), (2) BioMend (BM), (3) BioMendE

  13. The effect of azathioprine on anastomotic healing: an experimental study in rats

    Stolzenburg, Tilo; Ljungmann, Ken; Christensen, Henrik


    healing was tested. METHODS: In an experimental study, rats were randomly given one oral dose of azathioprine (5 mg or 20 mg/kg body weight per day) or placebo. After 28 days of treatment, a left colonic anastomosis was performed. After three days of healing, the breaking strengths of the anastomoses were...

  14. Rebaudioside A: two-generation reproductive toxicity study in rats.

    Curry, Leslie L; Roberts, Ashley; Brown, Nigel


    Rebaudioside A was administered via the diet to male and female Han Wistar rats at 0, 7500, 12,500, and 25,000ppm for two generations. Rebaudioside A treatment was not associated with any signs of clinical toxicity or adverse effects on body weight, body weight gain, or food consumption. No treatment-related effects of rebaudioside A were observed in either the F0 or F1 generations on reproductive performance parameters including mating performance, fertility, gestation lengths, oestrous cycles, or sperm motility, concentration, or morphology. The survival and general condition of the F1 and F2 offspring, their pre-weaning reflex development, overall body weight gains, and the timing of sexual maturation, were not adversely affected by rebaudioside A treatment. The NOAEL for reproductive effects was 25,000ppm and the NOAEL for the survival, development, and general condition of the offspring also was considered to be 25,000ppm or 2048-2273mg/kg body weight/day.

  15. Method for functional study of mitochondria in rat hypothalamus.

    Benani, Alexandre; Barquissau, Valentin; Carneiro, Lionel; Salin, Bénédicte; Colombani, Anne-Laure; Leloup, Corinne; Casteilla, Louis; Rigoulet, Michel; Pénicaud, Luc


    Different roles of mitochondria in brain function according to brain area are now clearly emerging. Unfortunately, no technique is yet described to investigate mitochondria function in specific brain area. In this article, we provide a complete description of a procedure to analyze the mitochondrial function in rat brain biopsies. Our two-step method consists in a saponin permeabilization of fresh brain tissues in combination with high-resolution respirometry to acquire the integrated respiratory rate of the biopsy. In the first part, we carefully checked the mitochondria integrity after permeabilization, defined experimental conditions to determine the respiratory control ratio (RCR), and tested the reproducibility of this technique. In the second part, we applied our method to test its sensitivity. As a result, this method was sensitive enough to reveal region specificity of mitochondrial respiration within the brain. Moreover, we detected physiopathological modulation of the mitochondrial function in the hypothalamus. Thus this new technique that takes all cell types into account, and does not discard or select any mitochondria sub-population is very suitable to analyze the integrated mitochondrial respiration of brain biopsies.

  16. Comparative study of Rhodiola preparations on behavioral despair of rats.

    Panossian, A; Nikoyan, N; Ohanyan, N; Hovhannisyan, A; Abrahamyan, H; Gabrielyan, E; Wikman, G


    The antidepressant-like activity of an extract of the roots of Rhodiola rosea (RR), its combination with piperine containing extract (RPE), pure substances isolated from Rhodiola, such as rhodioloside, rosavin, rosin, rosarin, tyrosol, cinnamic alcohol, cinnamaldehyde and cinnamic acid has been assessed in laboratory animals through application of the Porsolt behavioural despair assay. RR increased the swimming time of rats in a dose dependent manner (ED50=7 mg/kg) and, when administered at 20mg/kg, exhibited a stronger anti-depressant type effect than either imipramine (at 30 mg/kg) or an extract of Hypericum perforatum (at 20mg/kg). Rhodioloside, and tyrosol were identified as active principles of the extract, whereas rosavin, rosarin, rosin, cinnamic alcohol, cinnamaldehyde, cinnamic acid were inactive. A fixed combination of rhodioloside, rosavin, rosarin and rosin was more active than any of the individual components alone, indicating a synergistic effect of the ingredients in RR extract. Piperine in combination with Rhodiola (RPE) distorts pharmacological effect of Rhodiola most probably due to changes of pharmacokinetic profile of rhodioloside and rosavin. RPE cannot provide predictable therapeutic effect due to herb-herb interaction. Moreover, concomitant treatment of RPE with other drugs should also be excluded due to drug-piperine interaction.

  17. Study on the Application of Previously Fermented Juice in the Forage Silage%绿汁发酵液在饲草青贮中的应用研究



    绿汁发酵液作为一种天然、无毒的青贮添加剂加工简单,经济环保。本文根据近几年的研究,对绿汁发酵液的制作方法、作用机理以及应用进展等进行了综述。%This paper is about the previously fermented juice(PFJ) which has many advantages such as uncomplicated handing, economy and environmental protection as a natural and poisonless additive. Accord-ing to recent studies, this paper summarized the manufacturing methods, mechanism and application progress of PFJ.

  18. iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study

    Peter D. Westenskow


    Full Text Available Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD, a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes.

  19. Expression and localization of pChAT as a novel method to study cholinergic innervation of rat adrenal gland.

    Elnasharty, Mohamed A; Sayed-Ahmed, Ahmed


    Cholinergic innervation of the rat adrenal gland has been analyzed previously using cholinergic markers including acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT). In the present study, we demonstrate putative cholinergic neurons in the rat adrenal gland using an antibody to pChAT, which is the product of a splice variant of ChAT mRNA that is preferentially localized in peripheral cholinergic nerves. Most of the ganglionic neurons as well as small single sporadic neurons in the adrenal gland were stained intensely for pChAT. The density of pChAT-immunoreactive (IR) fibers was distinct in the adrenal cortex and medulla. AChE-, cChAT- and VAChT-immunoreactivities were also observed in some cells and fibers of the adrenal medulla, while the cortex had few positive nerve fibers. These results indicate that ganglionic neurons of the adrenal medulla and nerve fibers heterogeneously express cholinergic markers, especially pChAT. Furthermore, the innervation of the adrenal gland, cortex and medulla, by some cholinergic fibers provides additional morphological evidence for a significant role of cholinergic mechanisms in adrenal gland functions.

  20. Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

    Bakeine, G.J. [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste (Italy)], E-mail:; Di Salvo, M. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bertolotti, A.; Nano, R. [Department of Animal Biology University of Pavia, Piazza Botta, Pavia (Italy); Clerici, A.; Ferrari, C.; Zonta, C. [Department of Surgery University of Pavia, Piazza Botta, Pavia (Italy); Marchetti, A. [Scientific Research Office, Fondazione San Matteo University Policlinic, Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy)


    In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

  1. XAS and XFM studies of selenium and copper speciation and distribution in the kidneys of selenite-supplemented rats.

    Weekley, Claire M; Shanu, Anu; Aitken, Jade B; Vogt, Stefan; Witting, Paul K; Harris, Hugh H


    Dietary selenium has been implicated in the prevention of cancer and other diseases, but its safety and efficacy is dependent on the supplemented form and its metabolites. In this study, X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM) have been used to investigate the speciation and distribution of Se and Cu in vivo. In kidneys isolated from rats fed a diet containing 5 ppm Se as selenite for 3 weeks, Se levels increased 5-fold. XFM revealed a strong correlation between the distribution of Se and the distribution of Cu in the kidney, a phenomenon that has previously been observed in cell culture (Weekley et al., JBIC, J. Biol. Inorg. Chem., 2014, DOI: 10.1007/s00775-014-1113-x). However, X-ray absorption spectra suggest that most of the Se in the kidney is found as Se-Se species, rather than Cu-bound, and that most of the Cu is bound to S and N, presumably to amino acid residues in proteins. Furthermore, SOD1 expression did not change in response to the high Se diet. We cannot rule out the possibility of some Cu-Se bonding in the tissues, but our results suggest mechanisms other than the formation of Cu-Se species and SOD1 upregulation are responsible for the highly correlated distributions of Se and Cu in the kidneys of rats fed high selenite diets.

  2. The effect of aging on the specialized conducting system: a telemetry ECG study in rats over a 6 month period.

    Rossi, Stefano; Fortunati, Ilaria; Carnevali, Luca; Baruffi, Silvana; Mastorci, Francesca; Trombini, Mimosa; Sgoifo, Andrea; Corradi, Domenico; Callegari, Sergio; Miragoli, Michele; Macchi, Emilio


    Advanced age alone appears to be a risk factor for increased susceptibility to cardiac arrhythmias. We previously observed in the aged rat heart that sinus rhythm ventricular activation is delayed and characterized by abnormal epicardial patterns although conduction velocity is normal. While these findings relate to an advanced stage of aging, it is not yet known when and how ventricular electrical impairment originates and which is the underlying substrate. To address these points, we performed continuous telemetry ECG recordings in freely moving rats over a six-month period to monitor ECG waveform changes, heart rate variability and the incidence of cardiac arrhythmias. At the end of the study, we performed in-vivo multiple lead epicardial recordings and histopathology of cardiac tissue. We found that the duration of ECG waves and intervals gradually increased and heart rate variability gradually decreased with age. Moreover, the incidence of cardiac arrhythmias gradually increased, with atrial arrhythmias exceeding ventricular arrhythmias. Epicardial multiple lead recordings confirmed abnormalities in ventricular activation patterns, likely attributable to distal conducting system dysfunctions. Microscopic analysis of aged heart specimens revealed multifocal connective tissue deposition and perinuclear myocytolysis in the atria. Our results demonstrate that aging gradually modifies the terminal part of the specialized cardiac conducting system, creating a substrate for increased arrhythmogenesis. These findings may open new therapeutic options in the management of cardiac arrhythmias in the elderly population.

  3. The effect of aging on the specialized conducting system: a telemetry ECG study in rats over a 6 month period.

    Stefano Rossi

    Full Text Available Advanced age alone appears to be a risk factor for increased susceptibility to cardiac arrhythmias. We previously observed in the aged rat heart that sinus rhythm ventricular activation is delayed and characterized by abnormal epicardial patterns although conduction velocity is normal. While these findings relate to an advanced stage of aging, it is not yet known when and how ventricular electrical impairment originates and which is the underlying substrate. To address these points, we performed continuous telemetry ECG recordings in freely moving rats over a six-month period to monitor ECG waveform changes, heart rate variability and the incidence of cardiac arrhythmias. At the end of the study, we performed in-vivo multiple lead epicardial recordings and histopathology of cardiac tissue. We found that the duration of ECG waves and intervals gradually increased and heart rate variability gradually decreased with age. Moreover, the incidence of cardiac arrhythmias gradually increased, with atrial arrhythmias exceeding ventricular arrhythmias. Epicardial multiple lead recordings confirmed abnormalities in ventricular activation patterns, likely attributable to distal conducting system dysfunctions. Microscopic analysis of aged heart specimens revealed multifocal connective tissue deposition and perinuclear myocytolysis in the atria. Our results demonstrate that aging gradually modifies the terminal part of the specialized cardiac conducting system, creating a substrate for increased arrhythmogenesis. These findings may open new therapeutic options in the management of cardiac arrhythmias in the elderly population.

  4. “Jello® Shots” and Cocktails as Ethanol Vehicles: Parametric Studies with High- and Low-Saccharin-Consuming Rats

    Nancy K. Dess


    Full Text Available Naïve humans and rats voluntarily consume little ethanol at concentrations above ~6% due to its aversive flavor. Developing procedures that boost intake of ethanol or ethanol-paired flavors facilitates research on neural mechanisms of ethanol-associated behaviors and helps identify variables that modulate ethanol intake outside of the lab. The present study explored the impact on consumption of ethanol and ethanol-paired flavors of nutritionally significant parametric variations: ethanol vehicle (gelatin or solution, with or without polycose; ethanol concentration (4% or 10%; and feeding status (chow deprived or ad lib. during flavor conditioning and flavor preference testing. Individual differences were modeled by testing rats of lines selectively bred for high (HiS or low (LoS saccharin intake. A previously reported preference for ethanol-paired flavors was replicated when ethanol had been drunk during conditioning. However, indifference or aversion to ethanol-paired flavors generally obtained when ethanol had been eaten in gelatin during conditioning, regardless of ethanol concentration, feeding status, or caloric value of the vehicle. Modest sex and line variations occurred. Engaging different behavioral systems when eating gelatin, rather than drinking solution, may account for these findings. Implications for parameter selection in future neurobiological research and for understanding conditions that influence ethanol intake outside of the lab are discussed.

  5. Histological study on side effects and tumor targeting of a block copolymer micelle on rats.

    Kawaguchi, Takanori; Honda, Takashi; Nishihara, Masamichi; Yamamoto, Tatsuhiro; Yokoyama, Masayuki


    Histological examinations were performed with polymeric micelle-injected rats for evaluations of possible toxicities of polymeric micelle carriers. Weight of major organs as well as body weight of rats was measured after multiple intravenous injections of polymeric micelles forming from poly(ethylene glycol)-b-poly(aspartate) block copolymer. No pathological toxic side effects were observed at two different doses, followed only by activation of the mononuclear phagocyte system (MPS) in the spleen, liver, lung, bone marrow, and lymph node. This finding confirms the absence of--or the very low level of--in vivo toxicity of the polymeric micelle carriers that were reported in previous animal experiments and clinical results. Then, immunohistochemical analyses with a biotinylated polymeric micelle confirmed specific accumulation of the micelle in the MPS. The immunohistochemical analyses also revealed, first, very rapid and specific accumulation of the micelle in the vasculatures of tumor capsule of rat ascites hepatoma AH109A, and second, the micelle's scanty infiltration into tumor parenchyma. This finding suggests a unique tumor-accumulation mechanism that is very different from simple EPR effect-based tumor targeting.

  6. Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study

    Rinat Abramovitch


    Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

  7. Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

    Saibo Huang


    Full Text Available The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE, longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone.

  8. Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

    Huang, Saibo; Lin, Huimin; Deng, Shang-gui


    The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH) were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH) were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE), longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone. PMID:26633476

  9. Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates.

    Huang, Saibo; Lin, Huimin; Deng, Shang-Gui


    The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH) were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH) were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl₂ treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE), longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone.

  10. A morphometric study of the intestinal mucosa of rats submitted to omentoenteropexy

    Pedro Muñoz Fernandez


    Full Text Available CONTEXT: The omentoenteropexy technique was developed as an alternative method for intestinal neovascularization, due to the angiogenic properties of factors from the omentum. OBJECTIVES: This study investigated changes in intestinal villi heights and crypts depths due to surgical techniques: seromiotomy with and without omentoenteropexy. METHOD: Thirty rats were operated on, after being divided into three groups, namely GI, GII and GIII with 10 rats each. In the GI rats were submitted to omentoenteropexy; rats in GII were submitted only to a seromiotomy, and in the GIII only laparotomy. Sixty days after the first surgery, the animals were sacrificed and a segment of intestine was removed for histology using Masson's trichrome technique and morphometric study of intestinal mucosa. RESULTS: The histological findings showed that seromiotomy with or without omentoenteropexy increased the length of intestinal villi when compared with GIII (only laparotomy (analysis of variance: P = 0.0068; GI 38.88 ± 4.17; GII 39.41± 6.33; GIII 31.85 ± 5.56; GI = GII P>0.05; GII>GIII PGIII P<0.001. CONCLUSION: No differences were demonstrated in relation to crypt depths between the groups (P = 0.60. Ongoing studies are being set forth by our group to add more data on the role of omentopexy as a tool to promote neovascularization and intestinal mucosal growth.

  11. An experimental study of retrograde axonal plasmatic flow in the peripheral nerves of rats.

    Sanguinetti, C; Tranquilli Leali, P; Grispigni, C


    Retrograde axonal flow (R.A.F.) in the sciatic nerve of Sprague Dowley rats was studied by injecting horseradish peroxidase (H.R.P.) peripherally and identifying its appearance in the related segment of the spinal cord. This called for a precise identification of the vertebro-medullary topography, the afferant root levels of the sciatic nerve, and the transport velocity of the H.R.P. Our study revealed a clear difference of neuromuscular end plate permeability as between new-born and adult animals. The vertebral column of the rat consists of 8 cervical metameres, 13 dorsal, 6 lumbar, 4 sacral, and 3 coccygeal. The sciatic nerve is derived principally from the roots L4, L5, L6 and in part from L3 and S1. The injection of H.R.P. in the sural triceps of the new-born rat produced granules in the anterior horn cells as early as 12 hours later. In similar experiments with adult rats H.R.P. in the motorneurons was never detected. In our experimental model the transport velocity of H.R.P. from the point of injection to the anterior horn cells was approximately 68 mm per day. These findings provide a foundation on which to base future studies of retrograde flows in conditions of induced pathology.

  12. A preparation for studying electrical stimulation of the retina in vivo in rat.

    Baig-Silva, M S; Hathcock, C D; Hetling, J R


    A remaining challenge to the development of electronic prostheses for vision is improving the effectiveness of retinal stimulation. Electrode design and stimulus parameters need to be optimized such that the neural output from the retina conveys information to the mind's eye that aids the patient in interpreting his or her environment. This optimization will require a detailed understanding of the response of the retina to electrical stimulation. The identity and response characteristics of the cellular targets of stimulation need to be defined and evaluated. Described here is an in vivo preparation for studying electrical stimulation of the retina in rat at the cellular level. The use of rat makes available a number of well-described models of retinal disease that motivate prosthesis development. Artificial stimulation can be investigated by adapting techniques traditionally employed to study the response of the retina to photic stimuli, such as recording at the cornea, single-cell recording, and pharmacological dissection of the response. Pilot studies include amplitude-intensity response data for subretinal and transretinal stimulation paradigms recorded in wild-type rats and a transgenic rat model of autosomal dominant retinitis pigmentosa. The ability to record single-unit ganglion cell activity in vivo is also demonstrated.

  13. 中原地区某村既往有偿献血人群艾滋病发病和死亡规律%Study on AIDS incidence and death in previous paid blood-donated population, central China

    朱新义; 崔兆麟; 黄祚军; 朱伯健; 汪宁


    Objective To study incidence and death among previous paid blood-donated AIDS sufferers.Methods A retrospective cohort study was adopted to study incidence and death of 373 previous paid blood-donated HIV sufferers and its effect factors.Results Previous paid blood-donated HIV infection was serious and the infection rate in blood-donated crowd was 35.87%(373/1040);the mean incubation period of AIDS was 8.87 years(95%CI:8.76-8.99,Kaplan-Meier method):the cumulative incidence of AIDS(10 years)was 92.23%(344/373),and the incidence of total sufferers was 11.64/100 person-year;the cumulative probability of survival of one-year,three-year,five-year AIDS sufferers was separately 94.48% (325/344),85.76%(295/344)and 83.14%(286/344),median survival time was over 5 years;the anti-virotic treatment days(960.29±486.38),infection age(33.39±9.08)disease age(41.98±8.88)had significant effects on AIDS sufferers' survival time/survival rate(x2=61.355,P=0.000;x2=6.555,P=0.010;x2=3.969,P=0.046).Conclusion The survival time of previous paid blood-donated HIV cases was longer,and their survival rate was hisher,remarkably higher than the UNAIDS'research findings.%目的 研究既往有偿献血人群获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)发病和死亡规律.方法 采用回顾性队列研究方法,对373例既往有偿献血感染人类免疫缺陷病毒(human immunodeficiency virus,HIV)者的发病、死亡规律及其影响因素进行研究.结果 既往有偿献血人群HIV感染率为35.87%(373/1040),AIDS平均潜伏期为8.87年(95%CI:8.76~8.99,Kaplan-Meier法);感染后10年累计发病率为92.23%(344/373),总人时发病率为11.64/100人年;艾滋病患者1年、3年、5年累计生存率分别为94.48%(325/344)、85.76%(295/344)和83.14%(286/344),中位生存时间超过5年;抗病毒治疗天数[(960.29±486.38)d]、感染年龄[(33.39±9.08)岁]和发病年龄[(41.98±8.88)岁]对艾滋病患者生存时间

  14. Synchrotron FTIR micro-spectroscopy study of the rat hippocampal formation after pilocarpine-evoked seizures.

    Chwiej, J; Dulinska, J; Janeczko, K; Dumas, P; Eichert, D; Dudala, J; Setkowicz, Z


    In the present work, synchrotron radiation Fourier transform infrared (SRFTIR) micro-spectroscopy and imaging were used for topographic and semi-quantitative biochemical analysis of rat brain tissue in cases of pilocarpine-induced epilepsy. The tissue samples were analyzed with a beam defined by small apertures and spatial resolution steps of 10 microm which allowed us to probe the selected cellular layers of hippocampal formation. Raster scanning of the samples has generated 2D chemical cartographies revealing the distribution of proteins, lipids and nucleic acids. Spectral analysis has shown changes in the saturation level of phospholipids and relative secondary structure of proteins. Special interest was put in the analysis of two areas of the hippocampal formation (sector 3 of the Ammon's horn, CA3 and dentate gyrus, DG) in which elemental abnormalities were observed during our previous studies. Statistically significant increase in the saturation level of phospholipids (increased ratio of the absorption intensities at around 2921 and 2958 cm(-1)) as well as conformational changes of proteins (beta-type structure discrepancies as shown by the increased ratio of the absorbance intensities at around 1631 and 1657 cm(-1) as well as the ratio of the absorbance at 1548 and 1657 cm(-1)) were detected in pyramidal cells of CA3 area as well as in the multiform and molecular layers of DG. The findings presented here suggest that abnormalities in the protein secondary structure and increases in the level of phospholipid saturation could be involved in mechanisms of neurodegenerative changes following the oxidative stress evoked in brain areas affected by pilocarpine-induced seizures.

  15. Neonatal DSP-4 treatment impairs 5-HT(1B) receptor reactivity in adult rats. Behavioral and biochemical studies.

    Ferdyn-Drosik, Marzena; Nowak, Przemysław; Bojanek, Kamila; Bałasz, Michał; Kasperski, Jacek; Skaba, Dariusz; Muchacki, Rafał; Kostrzewa, Richard M


    To examine the effect of a central noradrenergic lesion on the reactivity of the 5-HT(1B) receptor we compared intact male rats with rats in which noradrenergic nerve terminals were largely destroyed with the neurotoxin DSP-4 (50 mg/kg x 2, on the 1st and 3rd days of postnatal life). When rats attained 10 weeks of age, control and DSP-4 rats were divided into two subgroups receiving either saline or the serotonin (5-HT) synthesis inhibitor (p-chlorophenylalanine; p-CPA; 100 mg/kg). Employing an elevated plus maze test, we demonstrated that CP 94,253 (5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine hydrochloride) (4.0 mg/kg; 5-HT(1B) agonist) induced an anxiogenic-like action in control rats; however, it failed to elicit this effect in the DSP-4 group. Surprisingly, in p-CPA pretreated rats anxiogenic-like activity was observed both in control and DSP-4 treated rats. CP 94,253 significantly attenuated 5-HT synthesis in the medial prefrontal cortex (mPFC) of control rats, and SB 216641 (N-{3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl}-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-carboxamide hydrochloride) (4.0 mg/kg; 5-HT(1B) antagonist) was able to antagonize this effect. Conversely, CP 94,253 failed to significantly inhibit the 5-HT synthesis rate in DSP-4-treated rats. In the microdialysis study CP 94,253 induced long-lasting attenuation of 5-HT release in the mPFC of control rats but had no effect in DSP-4 rats. These data lead to the proposal that presynaptic 5-HT(1B) autoreceptors underwent desensitization in DSP-4 treated rats.

  16. Development of cardioplegic solution without potassium: experimental study in rat.

    Reichert, Karla; Carmo, Helison Rafael Pereira do; Lima, Fany; Torina, Anali Galluce; Vilarinho, Karlos Alexandre de Souza; Oliveira, Pedro Paulo Martins de; Silveira Filho, Lindemberg Mota; Severino, Elaine Soraya Barbosa de Oliveira; Petrucci, Orlando


    Myocardial preservation during open heart surgeries and harvesting for transplant are of great importance. The heart at the end of procedure has to resume its functions as soon as possible. All cardioplegic solutions are based on potassium for induction of cardioplegic arrest. To assess a cardioplegic solution with no potassium addition to the formula with two other commercially available cardioplegic solutions. The comparative assessment was based on cytotoxicity, adenosine triphosphate myocardial preservation, and caspase 3 activity. The tested solution (LIRM) uses low doses of sodium channel blocker (lidocaine), potassium channel opener (cromakalin), and actin/myosin cross bridge inhibitor (2,3-butanedione monoxime). Wistar rats underwent thoracotomy under mechanical ventilation and three different solutions were used for "in situ" perfusion for cardioplegic arrest induction: Custodiol (HTK), Braile (G/A), and LIRM solutions. After cardiac arrest, the hearts were excised and kept in cold storage for 4 hours. After this period, the hearts were assessed with optical light microscopy, myocardial ATP content and caspase 3 activity. All three solutions were evaluated for direct cytotoxicity with L929 and WEHI-164 cells. The ATP content was higher in the Custodiol group compared to two other solutions (P<0.05). The caspase activity was lower in the HTK group compared to LIRM and G/A solutions (P<0.01). The LIRM solution showed lower caspase activity compared to Braile solution (P<0.01). All solutions showed no cytotoxicity effect after 24 hours of cells exposure to cardioplegic solutions. Cardioplegia solutions without potassium are promised and aminoacid addition might be an interesting strategy. More evaluation is necessary for an optimal cardioplegic solution development.

  17. Development of cardioplegic solution without potassium: experimental study in rat

    Karla Reichert


    Full Text Available INTRODUCTION: Myocardial preservation during open heart surgeries and harvesting for transplant are of great importance. The heart at the end of procedure has to resume its functions as soon as possible. All cardioplegic solutions are based on potassium for induction of cardioplegic arrest. OBJECTIVE: To assess a cardioplegic solution with no potassium addition to the formula with two other commercially available cardioplegic solutions. The comparative assessment was based on cytotoxicity, adenosine triphosphate myocardial preservation, and caspase 3 activity. The tested solution (LIRM uses low doses of sodium channel blocker (lidocaine, potassium channel opener (cromakalin, and actin/myosin cross bridge inhibitor (2,3-butanedione monoxime. METHODS: Wistar rats underwent thoracotomy under mechanical ventilation and three different solutions were used for "in situ" perfusion for cardioplegic arrest induction: Custodiol (HTK, Braile (G/A, and LIRM solutions. After cardiac arrest, the hearts were excised and kept in cold storage for 4 hours. After this period, the hearts were assessed with optical light microscopy, myocardial ATP content and caspase 3 activity. All three solutions were evaluated for direct cytotoxicity with L929 and WEHI-164 cells. RESULTS: The ATP content was higher in the Custodiol group compared to two other solutions (P<0.05. The caspase activity was lower in the HTK group compared to LIRM and G/A solutions (P<0.01. The LIRM solution showed lower caspase activity compared to Braile solution (P<0.01. All solutions showed no cytotoxicity effect after 24 hours of cells exposure to cardioplegic solutions. CONCLUSION: Cardioplegia solutions without potassium are promised and aminoacid addition might be an interesting strategy. More evaluation is necessary for an optimal cardioplegic solution development.

  18. Incidence of heart failure in infarcted rats that die spontaneously

    R.L.G. Flumignan


    Full Text Available The present study reports for the first time the incidence of congestive heart failure (CHF in previously infarcted rats that died spontaneously. Previously, pulmonary (PWC and hepatic (HWC water contents were determined in normal rats: 14 control animals were evaluated immediately after sacrifice, 8 placed in a refrigerator for 24 h, and 10 left at room temperature for 24 h. In the infarcted group, 9 rats died before (acute and 28 died 48 h after (chronic myocardial infarction. Thirteen chronic animals were submitted only to autopsy (N = 13, whereas PWC and HWC were also determined in the others (N = 15. Seven rats survived 48 h and died during anesthesia. Notably, PWC differed in normal rats: ambient (75.7 ± 1.3% < control (77.5 ± 0.7% < refrigerator (79.1 ± 1.4% and there were no differences with respect to HWC. No clinical signs of CHF (dyspnea, lethargy or foot edema were observed in infarcted rats before death. PWC was elevated in all chronic and anesthetized rats. HWC was increased in 48% of chronic and in all anesthetized rats. Our data showed that PWC needs to be evaluated before 24 h post mortem and that CHF is the rule in chronic infarcted rats suffering natural death. The congestive syndrome cannot be diagnosed correctly in rats by clinical signs alone, as previously proposed.

  19. Dietary exposure to shiitake mushroom confers reductions in serum glucose, lipids, leptin and antioxidant capacity in rats

    Previously, we showed that dietary intake of shiitake mushroom (Lentinus edodes) decreased serum levels of polar lipids in rats. This study evaluated the effects of lifelong consumption of shiitake on body composition and serum cholesterol-related- and anti-oxidant indices in rats. Rat dams and th...

  20. Adriamycin activity's durational governance of different cell death types and zonality in rat liver acinus. Immunohistochemical studies

    Pedrycz Agnieszka


    Full Text Available The aim of this study was to develop and examine a model of apoptosis and necrosis of hepatocytes induced by a damaging factor - adriamycin, correlating time after its administration with cell death type, and to investigate the localisation within the liver acinus of hepatocytes dying in these two ways. The results obtained in the present and previous studies were compared in order to make a map of cell death localisation in the liver acinus, showing the effect of time in action and dose of adriamycin. The experiment was performed on 32 female Wistar rats, divided into four groups: I and II - experimental, and III and IV - control. Adriamycin (3 mg/kg b.w. was administered intraperitoneally to rats in groups I and II, and the rats were decapitated after four (group I and eight (group II weeks. Animals in control groups III and IV were given 0.5 mL of 0.9% NaCl solution, and decapitated after four and eight weeks respectively. Sections of the liver were examined with a three-stage immunohistochemical method. This method allowed to examine hepatocytes qualitatively and quantitatively for the presence of proteins involved in three types of apoptosis: induced by the mitochondrial pathway (caspase 3, 9, the intrinsic pathway related to endoplasmic reticulum stress (caspase 3, 12, and the extrinsic pathway (caspase 3, 8. One of the inflammatory markers, caspase 1, was also examined. The zonal localisation of all three types of apoptosis was assessed in the liver tissue. More oxidated hepatocytes indicated only signs of the internal mitochondrial pathway, whereas less oxidated hepatocytes induced the internal reticular pathway and the external apoptotic pathway. The period between adriamycin administration and hepatic cell investigation was a main factor of the process. A longer period post insult resulted in a more pronounced effect of the activation of apoptosis. Sections explored eight weeks after treatment with different doses of the drug (3 and 5

  1. Bioavailability study of calcium sandoz-250 by atomic absorption spectroscopy in albino rats

    Patel, Bimalkumar N.; Krishnaveni, N.; Jivani, Nurrrudin P.; Khodakiya, Akruti S.; Khodakiya, Moorti S.; Parida, Saswat K.


    Background: Calcium sandoz-250 is an Ayurvedic calcium supplement, containing Khatika Churna. Bioavailability study of the formulation is essential for estimation of peak plasma concentration (C max), time to C max and rate of absorption. Aim: To evaluate the absorption parameters of calcium sandoz-250 in albino rats by atomic absorption spectroscopic (AAS) method. Materials and Methods: Study was carried out as a single dose, open-label, randomized study. Estimation of calcium was carried ou...

  2. A combined phytohemagglutinin and a-ketoglutarate pharmacology study of gut morphology and growth in older adult rats

    Filip, R.; Harrison, Adrian Paul; Pierzynowski, S.G.


    This study has evaluated the effect of phytohaemagglutinin (PHA) in combination with alpha-ketoglutaric acid (AKG), on GI-tract morphology and N balance in adult rats. Rats, aged approx. 15 months, were assigned to one of four experimental groups, (1) Control group, (2) AKG group, (3) AKG+PHA 100...

  3. A novel ex vivo rat infection model to study protective immunity against Fasciola hepatica at the gut level

    Milligen, van F.J.; Cornelissen, J.B.W.J.; Gaasenbeek, C.P.H.; Bokhout, B.A.


    We describe an ex vivo rat infection model to study protective immunity against Fasciola hepatica at the gut level. An exact number of newly excysted juveniles (NEJs) was injected into a gut segment with an intact blood supply and which was still attached to a live anaesthetized rat. NEJs that penet

  4. Phase I/II study of docetaxel combined with resminostat, an oral hydroxamic acid HDAC inhibitor, for advanced non-small cell lung cancer in patients previously treated with platinum-based chemotherapy.

    Tambo, Yuichi; Hosomi, Yukio; Sakai, Hiroshi; Nogami, Naoyuki; Atagi, Shinji; Sasaki, Yasutsuna; Kato, Terufumi; Takahashi, Toshiaki; Seto, Takashi; Maemondo, Makoto; Nokihara, Hiroshi; Koyama, Ryo; Nakagawa, Kazuhiko; Kawaguchi, Tomoya; Okamura, Yuta; Nakamura, Osamu; Nishio, Makoto; Tamura, Tomohide


    Objectives To determine the recommended dose and efficacy/safety of docetaxel combined with resminostat (DR) in non-small cell lung cancer (NSCLC) patients with previous platinum-based chemotherapy. Materials and Methods A multicenter, open-label, phase I/II study was performed in Japanese patients with stage IIIB/IV or recurrent NSCLC and prior platinum-based chemotherapy. The recommended phase II dose was determined using a standard 3 + 3 dose design in phase I part. Resminostat was escalated from 400 to 600 mg/day and docetaxel fixed at 75 mg/m(2). In phase II part, the patients were randomly assigned to docetaxel alone (75 mg/m(2)) or DR therapy. Docetaxel was administered on day 1 and resminostat on days 1-5 in the DR group. Treatment was repeated every 21 days until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Results A total of 117 patients (phase I part, 9; phase II part, 108) were enrolled. There was no dose-limiting toxicity in phase I part; the recommended dose for resminostat was 600 mg/day with 75 mg/m(2) of docetaxel. In phase II part, median PFS (95% confidence interval [CI]) was 4.2 (2.8-5.7) months with docetaxel group and 4.1 (1.5-5.4) months with DR group (hazard ratio [HR]: 1.354, 95% CI: 0.835-2.195; p = 0.209). Grade ≥ 3 adverse events significantly more common with DR group than docetaxel group were leukopenia, febrile neutropenia, thrombocytopenia, and anorexia. Conclusion In Japanese NSCLC patients previously treated with platinum-based chemotherapy, DR therapy did not improve PFS compared with docetaxel alone and increased toxicity.

  5. Initial studies using the RatCAP conscious animal PET tomograph

    Woody, C. [Brookhaven National Laboratory, Upton, NY (United States)]. E-mail:; Vaska, P. [Brookhaven National Laboratory, Upton, NY (United States); Schlyer, D. [Brookhaven National Laboratory, Upton, NY (United States); Pratte, J.-F. [Brookhaven National Laboratory, Upton, NY (United States); Junnarkar, S. [Brookhaven National Laboratory, Upton, NY (United States); Park, S.-J. [Brookhaven National Laboratory, Upton, NY (United States); Stoll, S. [Brookhaven National Laboratory, Upton, NY (United States); Purschke, M. [Brookhaven National Laboratory, Upton, NY (United States); Southekal, S. [Stony Brook University, Stony Brook, NY (United States); Kriplani, A. [Stony Brook University, Stony Brook, NY (United States); Krishnamoorthy, S. [Stony Brook University, Stony Brook, NY (United States); Maramraju, S. [Stony Brook University, Stony Brook, NY (United States); Lee, D. [Brookhaven National Laboratory, Upton, NY (United States); Schiffer, W. [Brookhaven National Laboratory, Upton, NY (United States); Dewey, S. [Brookhaven National Laboratory, Upton, NY (United States); Neill, J. [Long Island University, Brookville, NY (United States); Kandasamy, A. [Brookhaven National Laboratory, Upton, NY (United States); O' Connor, P. [Brookhaven National Laboratory, Upton, NY (United States); Radeka, V. [Brookhaven National Laboratory, Upton, NY (United States); Fontaine, R. [Sherbrooke University, Sherbrooke, Que. (Canada); Lecomte, R. [Sherbrooke University, Sherbrooke, Que. (Canada)


    The RatCAP is a small, head-mounted PET tomograph designed to image the brain of a conscious rat without the use of anesthesia. The detector is a complete, high-performance 3D tomograph consisting of a 3.8 cm inside-diameter ring containing 12 block detectors, each of which is comprised of a 4x8 array of 2.2x2.2x5 mm{sup 3} LSO crystals readout with a matching APD array and custom ASIC, and has a 1.8 cm axial field of view. Construction of the first working prototype detector has been completed and its performance characteristics have been measured. The results show an intrinsic spatial resolution of 2.1 mm, a time resolution of {approx}14 ns FWHM, and a sensitivity of 0.7% at an energy threshold of 150 keV. First preliminary images have been obtained using {sup 18}F-FDG and {sup 11}C-methamphetamine, which show comparable image quality to those obtained from a commercial MicroPET R4 scanner. Initial studies have also been carried out to study stress levels in rats wearing the RatCAP.

  6. Study of the effect of extract of Thymus vulgaris on anxiety in male rats.

    Komaki, Alireza; Hoseini, Faeghe; Shahidi, Siamak; Baharlouei, Negar


    There is some evidence in traditional medicine for the effectiveness of Thymus vulgaris ( bǎi lǐ xiāng) in the treatment of anxiety in humans. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of extract of T. vulgaris on rat behavior in the EPM. In the present study, the data were obtained from male Wistar rats. Animals were divided into four groups: saline group and T. vulgaris groups (50 mg/kg, 100 mg/kg, and 200 mg/kg infusion for 7 days by feeding). During the test period, the total distance covered by animals, the number of open- and closed-arm entries, and the time spent in open and closed arms of the EPM were recorded. T. vulgaris increased open-arm exploration and open-arm entry in the EPM, whereas extract of this plant has no effects on the total distance covered by animals and the number of closed-arm entries. The results of the present experiment indicate that T. vulgaris may have an anxiolytic profile in rat behavior in the EPM test, which is not influenced by the locomotor activity. Further research is required to determine the mechanisms by which T. vulgaris extract exerts an anxiolytic effect in rats.

  7. Histopathological Comparison of Mosquito Net with Polypropylene Mesh for Hernia Repair: An Experimental Study in Rats.

    Sharma, Mukesh; Sharma, Deepti Bala; Chandrakar, Shiv Kumar; Sharma, Dhananjaya


    Use of mosquito net, in place of polypropylene mesh, had been reported for tension-free hernia repair, as a better cost-effective option. This experimental histopathological study was performed in rats to find out the tissue response and the foreign body reaction and its comparison between commercial polypropylene mesh and the sterilized mosquito net. This experimental study was conducted in the Department of Surgery, Government NSCB, Medical College, Jabalpur (Madhya Pradesh), India. It was carried out in 40 albino rats. A 1.5 × 0.5-cm hernial defect was created by excising full-thickness abdominal wall muscle. All rats underwent on-lay mesh repair of hernial defect (polypropylene mesh, n = 20; mosquito net, n = 20). Half of rats in each group were sacrificed on day 14, and the other half, on day 90. Sections of containing mesh were examined histopathologically for inflammatory infiltrate, giant cells, and collagen deposition. Mosquito net group showed significantly greater number of giant cells and inflammatory cells at 14 and 90 days (p  0.05 and p > 0.05, respectively). Results of mosquito net are comparable to conventional polypropylene mesh. In a setup, where cost-effectiveness is of primary importance, use of mosquito net for tension-free hernia repair can be an acceptable alternative as proven histologically, to commercially available polypropylene mesh.

  8. Study on development and localization of CTGF-immunoreactive cells in central nervous system of rats

    SU Bing-yin; CAI Wen-qin; ZHANNG Cheng-gang; B.Perbal


    Objective: To study the development of connective tissue growth factor(CTGF) immunoreactive cells in the central nervous system (CNS) of E8-P300 rats. Methods: Immunocytochemistry was employed in our study. Results: No CTGF-immunoreactive cells were detected in the CNS of rats during prenatal stages. A few of CTGF-positive cells were detected in the early postnatal stage. However, the positive cells increased gradually in later stages. CTGF-immunoreactive cells widely distributed in the CNS of rats in the first 30 to 60 days postnatally, and the density of immunoreactive products was the highest in these days. The number and staining intensity of CTGF-positive cells decreased and their area of distribution diminished gradually with age. The positive cells included neurons mainly located in the cingulate cortex,striatum, hippocampus, hypothalamus and cerebellum, and astrocytes in white matter of the spinal cord and ependymal cells of the brain. Most of CTGF-immunoreactive cells were quite big in size with a long process. Conclusion: CTGF-immunoreactive cells were found in the CNS of rats, and their numbers and positive signal decreased with the age.

  9. Wound healing properties of Indian propolis studied on excision wound-induced rats.

    Iyyam Pillai, S; Palsamy, P; Subramanian, S; Kandaswamy, M


    In traditional medicine propolis is widely used for the treatment of various ailments including ulcer and wound healing. The phytochemical screening of Indian propolis indicates the presence of biologically active ingredients in appreciable amounts. In the absence of systematic evaluation of wound healing properties of Indian propolis in the literature, the present study was undertaken. The aim of this study was to evaluate the wound healing potential of Indian propolis on excision wounds induced in experimental rats. Excision wounds were created in male Wistar rats and were treated with Indian propolis ointment (nitrofurazone was used as a reference drug - widely used for wound healing) for a period of 14 days. Control rats were treated with petroleum jelly. The parameters analyzed include wound contraction, hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA. Topical application of propolis ointment for 14 days significantly improved the wound contraction when compared to the control group of rats. The determination of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the wound matrix revealed the pro-healing effects of propolis. The results obtained were comparable with nitrofurazone. It appears that the ethanol extract of Indian propolis possesses significant pro-healing activity by accelerating the healing process at various phases of tissue repair. The presence of biologically active ingredients such as flavonoids, phenolic acids, terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may readily account for the observed prophylactic action of propolis in wound healing.

  10. Histological Study of Toxic Effects of Cisplatin Single Dose Injection on Rat Kidney



    Full Text Available Background Cisplatin, as an antineoplastic drug widely used for treatment of solid tumors, induces renal toxicity by free radical formation. Objectives The aim of the present study was to identify the histological changes of renal parenchyma after a single dose injection of cisplatin in rat, as an experimental model. Patients and Methods Twenty adult male Sprague Dawley rats, weighting about 210 ± 30 g, were randomly divided into experimental (10 and control (10 groups. The experimental group received a single dose injection of cisplatin intraperitoneally (5 mg/kg. One week after the injection, rats of both groups received deep anesthesia and were scarified. The tissue samples were removed and the prepared sections were stained by H&E and periodic acid–Schiff (PAS methods. The slides were used for both histopathological and morphometric studies. The collected data were analyzed by SPSS. Results Statistical analysis by Mann-Whitney test showed that there was a significant difference in the height of epithelium between the proximal convoluted tubule (PCT and the distal convoluted tubule (DCT of the experimental and control groups (P < 0.001. There was no significant difference in the urinary space diameter between the experimental and control groups. Focal tubular necrosis and vacuolar and eosinophilic degenerations were more prominent in the experimental group. Conclusions It seems that cisplatin can induce many quantitative and qualitative changes in proximal and distal convoluted tubules of nephron in rats.

  11. Neural correlates of sensorimotor gating: A metabolic positron emission tomography study in awake rats

    Cathrin eRohleder


    Full Text Available Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications. However, its relevance for healthy untreated animals and the functional interplay between startle- and PPI-related areas during a PPI session is so far unknown. Therefore, we studied awake rats in a PPI paradigm, startle control and background noise control, combined with behavioral [18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET. Subtractive analyses between conditions were used to identify brain regions involved in startle and PPI processing in well-hearing Black hooded rats. For correlative analysis with regard to the amount of PPI we also included hearing-impaired Lister hooded rats that startled more often, because their hearing threshold was just below the lowest prepulses. Metabolic imaging showed that the brain areas proposed for startle and PPI mediation are active during PPI paradigms in healthy untreated rats. More importantly, we show for the first time that the whole PPI modulation network is active during passive PPI sessions, where no selective attention to prepulse or startle stimulus is required. We conclude that this reflects ongoing monitoring of stimulus significance and constant adjustment of sensorimotor gating.

  12. The post-natal fate of supernumerary ribs in rat teratogenicity studies.

    Wickramaratne, G A


    A common occurrence in rat teratology studies, supernumerary ribs, have been considered to be indicative of teratogenicity by some authors but not to be so indicative by others. As a teratogenic event is, by definition a permanent change, a study to follow the fate of supernumerary ribs in the development of adulthood of the rat was undertaken. An established teratogen in the rat, aspirin, was used to increase the frequency of supernumerary ribs. Even though aspirin treatment of the dams doubled the initial frequency of supernumerary ribs the results show that over the first 60 days post-partum their frequency in both control and treated groups decline to essentially zero. This decline in frequency of supernumerary ribs is complemented by an increase in the proportion of foetuses with a fully developed transverse process on the first lumbar vertebra. The proposal that supernumerary ribs in the rat are a result of developmental delays in a labile region of the axial skeleton and not a manifestation of a teratogenic event is presented.

  13. Grape Seed Proanthocyanidin Rescues Rats from Steatosis: A Comparative and Combination Study with Metformin

    Baskaran Yogalakshmi


    Full Text Available Nonalcoholic fatty liver disease (NAFLD, a premorbid condition, lacks proper management owing to multitude of abnormalities. In this study, we compared the effects of a potent antioxidant, grape seed proanthocyanidins (GSP, and an insulin sensitizer, metformin (MET, in high-fat-fructose-diet- (HFFD- induced albino Wistar rat model of NAFLD. Either GSP (100 mg/Kg b.w or MET (50 mg/Kg b.w or both were administered as therapeutic options. HFFD-fed rats showed abnormal plasma lipid profile, inflammation, and steatosis of the liver when examined by biochemical and histology techniques. Increased lipid storage, lipogenesis, and reduced lipolysis were evident from mRNA expression studies of hepatic lipid droplets (LD proteins, sterol regulatory element binding 1c (SREBP 1c, and peroxisome proliferator activated receptor-α (PPAR-α. GSP administration to HFFD-fed rats caused 69% reduction in hepatic TG levels, whereas MET caused only 23%. The combination treatment reduced TG levels by 63%. GSP reduced the mRNA expression of SREBP1c and LD proteins and increased that of PPAR-α more effectively compared to MET in HFFD-induced hyperlipidemic rats. Combination of MET and GSP improved the metabolism of lipids effectively, but the effect was not additive in restoring lipid levels.

  14. The role of alkaloids in Ipomoea carnea toxicosis: a study in rats.

    Hueza, Isis M; Guerra, José L; Haraguchi, Mitsue; Naoki, Asano; Górniak, Silvana L


    Ipomoea carnea promotes in livestock a toxicosis histologically characterized by vacuolated cells in different organs. The toxic principles of I. carnea are the alkaloids swainsonine and calystegines B1, B2, B3 and Cl. However, it has not been determined whether the effects observed in rats treated with this plant are only due to swainsonine or if the calystegines have some additive toxic effect. Thus, the aim of the present study was to evaluate in rats the toxic effects of the L carnea aqueous fraction (AF) and of its different alkaloids when administered individually at the same concentration as in this fraction, for 14 days. No anorexic effect and/or alteration in body weight was observed in any group. The histopathologic study showed that while calystegines did not produce any toxic effects, swainsonine and I carnea AF promoted vacuolation in different organs, being more severe in the animals from the I. carnea AF group and extensible to other organs evaluated. No alterations were detected in the central nervous system of rats of any group assayed. The results obtained here suggest that calystegines may act as coadjuvants of swainsonine in I carnea toxicosis; however, little can be proposed about the neurotoxic effect of I. carnea since rats did not prove to be a good model for the reproduction of neuronal storage disease.

  15. Prenatal developmental toxicity study of ethyl tertiary-butyl ether in rats.

    Aso, Sunao; Miyata, Katsumi; Takakura, Saori; Hoshuyama, Satsuki; Muroi, Takako; Kusune, Yuji; Ajimi, Shozo; Furukawa, Kotaro


    Ethyl tertiary-butyl ether (ETBE) is commonly used as an oxygenated gasoline additive. In this study, we evaluated its developmental toxicity in rats. ETBE was administered by gavage to 21 or 22 pregnant female Sprague-Dawley rats per group at dose levels of 0, 100, 300 and 1000 mg/kg/day from days 5 through 19 postcoitum to assess its effects on pregnant animals and their embryos and fetuses applied to the OECD testing guideline (no. 414) correspondingly. There were no toxicological effects attributable to ETBE regarding clinical signs, body weight, food intake, necropsy or examination at caesarean section in pregnant animals. There were also no toxicological effects on external, visceral and skeletal examinations of embryos and fetuses. These results indicate that, under the conditions of this study, ETBE had no toxicological effects on pregnant rats or their embryos and fetuses and that the no observed adverse effect level was 1000 mg/kg/day both for pregnant rats and their embryos and fetuses.

  16. Induced vaginal birth after previous caesarean section

    Akylbek Tussupkaliyev


    Full Text Available Introduction The rate of operative birth by Caesarean section is constantly rising. In Kazakhstan, it reaches 27 per cent. Research data confirm that the percentage of successful vaginal births after previous Caesarean section is 50–70 per cent. How safe the induction of vaginal birth after Caesarean (VBAC remains unclear. Methodology The studied techniques of labour induction were amniotomy of the foetal bladder with the vulsellum ramus, intravaginal administration of E1 prostaglandin (Misoprostol, and intravenous infusion of Oxytocin-Richter. The assessment of rediness of parturient canals was conducted by Bishop’s score; the labour course was assessed by a partogram. The effectiveness of labour induction techniques was assessed by the number of administered doses, the time of onset of regular labour, the course of labour and the postpartum period and the presence of complications, and the course of the early neonatal period, which implied the assessment of the child’s condition, described in the newborn development record. The foetus was assessed by medical ultrasound and antenatal and intranatal cardiotocography (CTG. Obtained results were analysed with SAS statistical processing software. Results The overall percentage of successful births with intravaginal administration of Misoprostol was 93 per cent (83 of cases. This percentage was higher than in the amniotomy group (relative risk (RR 11.7 and was similar to the oxytocin group (RR 0.83. Amniotomy was effective in 54 per cent (39 of cases, when it induced regular labour. Intravenous oxytocin infusion was effective in 94 per cent (89 of cases. This percentage was higher than that with amniotomy (RR 12.5. Conclusions The success of vaginal delivery after previous Caesarean section can be achieved in almost 70 per cent of cases. At that, labour induction does not decrease this indicator and remains within population boundaries.

  17. TGF-mediated oscillations in the proximal intratubular pressure: differences between spontaneously hypertensive rats and Wistar-Kyoto rats

    Holstein-Rathlou, N H; Leyssac, P P


    A highly sensitive oscillatory tubulo-glomerular feedback (TGF) response has previously been demonstrated in normotensive Sprague-Dawley rats. The purpose of the present study was to examine whether such as oscillating TGF-response could be elicited in Wistar-Kyoto rats (WKY) and genetically...... hypertensive rats (SHR) and furthermore if any differences in the TGF-response characteristics between SHR and WKY rats could be detected. The closed loop function of the TGF-system was studied. In 12-18-week-old WKY rats regular oscillations in the intratubular pressure occurred spontaneously. The median...... fluid (ATF). When furosemide was added to the ATF in a concentration of 0.1 mM, the oscillations were abolished in both strains of rats. It is concluded that, in both strains of rats the oscillatory phenomena depend upon TGF activity. It is suggested that the irregular pattern of the oscillations...

  18. Usefulness of indirect alcohol biomarkers for predicting recidivism of drunk-driving among previously convicted drunk-driving offenders: results from the recidivism of alcohol-impaired driving (ROAD) study.

    Maenhout, Thomas M; Poll, Anneleen; Vermassen, Tijl; De Buyzere, Marc L; Delanghe, Joris R


    In several European countries, drivers under the influence (DUI), suspected of chronic alcohol abuse are referred for medical and psychological examination. This study (the ROAD study, or Recidivism Of Alcohol-impaired Driving) investigated the usefulness of indirect alcohol biomarkers for predicting drunk-driving recidivism in previously convicted drunk-driving offenders. The ROAD study is a prospective study (2009-13) that was performed on 517 randomly selected drivers in Belgium. They were convicted for drunk-driving for which their licence was confiscated. The initial post-arrest blood samples were collected and analysed for percentage carbohydrate-deficient transferrin (%CDT), transaminsase activities [alanine amino transferase (ALT), aspartate amino transferase (AST)], gamma-glutamyltransferase (γGT) and red cell mean corpuscular volume (MCV). The observation time for each driver was 3 years and dynamic. A logistic regression analysis revealed that ln(%CDT) (P drunk-driving. The ROAD index (which includes ln(%CDT), ln(γGT), -ln(ALT) and the sex of the driver) was calculated and had a significantly higher area under the receiver operator characteristic curve (0.71) than the individual biomarkers for drunk-driving recidivism. Drivers with a high risk of recidivating (ROAD index ≥ 25%; third tertile) could be distinguished from drivers with an intermediate risk (16% ≤ ROAD index drunk-driving. The association with gamma-glutamyltransferase, alanine amino transferase and the sex of the driver could have additional value for identifying drunk-drivers at intermediate risk of recidivism. Non-specific indirect alcohol markers, such as alanine amino transferase, gamma-glutamyltransferase, aspartate amino transferase and red cell mean corpuscular volume have minimal added value to % carbohydrate-deficient transferrin for distinguishing drunk drivers with a low or high risk of recidivism. © 2013 Society for the Study of Addiction.

  19. Quantitative study of neurofilament-positive fiber length in rat spinal cord lesions using isotropic virtual planes

    von Euler, Mia; Larsen, Jytte Overgaard; Janson, A M


    Spontaneous reocurrence of neurofilament (NF)-positive fibers has been described after spinal cord lesions in rats. However, previously introduced methods to evaluate the lesion and the regenerative fiber outgrowth suffer from several biases, why a new concept of quantitative, morphological analy...

  20. Maintenance of bladder innervation in diabetes: a stereological study of streptozotocin-treated female rats.

    Langdale, C L; Thor, K B; Marson, L; Burgard, E C


    Neuropathy and cystopathy are two common conditions in patients with chronic diabetes. Despite obvious bladder sensory and motor nerve dysfunction in diabetes, no studies have selectively explored whether sensory or motor innervation is affected in the bladder. In the present study, we tested the hypothesis that loss of bladder sensory and motor fibers is responsible for bladder sensory and motor dysfunction. Parasympathetic and sensory innervation of the bladder dome and neck were examined using immunohistochemistry (IHC) and stereology in adult female rats 12weeks after induction of diabetes by streptozotocin. Naïve and age matched rats were evaluated as controls. Diabetic rats had mean blood glucose level of >400mg/dl, and bladder weights and thicknesses that were more than doubled compared to naïve rats. In naïve rats, parasympathetic vesicular acetylcholine transporter (VAT) and sensory calcitonin gene-related peptide (CGRP) immunopositive nerve fibers were located in bladder smooth muscle and were more densely distributed in the neck compared to the dome. Within the urothelial region, CGRP nerve fibers were densely distributed while VAT nerve fibers were sparsely distributed in the bladder neck and both were virtually absent in the bladder dome. Streptozotocin induced diabetes did not change the total nerve fiber length of either VAT or CGRP stained fibers in either the neck or dome. These studies indicate that hyperglycemia, induced by streptozotocin treatment, does not result in a loss of parasympathetic VAT or CGRP sensory nerve fibers, per se, but the doubling of bladder weight and mass does indicate a decrease in innervation density.

  1. Reproductive toxicity study with a novel deoxyguanosine analogue (Metacavir) in pregnant SD rats.

    Luo, Qihui; Chen, Zhengli; Cheng, Anchun; Wang, Mingshu; Fang, Jing; Peng, Xi; Tang, Li


    Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir (200, 100, 50, 0 mg/kg body weight) during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different (P changes were observed. The present research indicated that at a dose of 200 mg/(kg·d) (i.e., 40 times the effective dose in rats), Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/(kg·d) there is no teratogenic side effects.

  2. Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes

    Richard G. Peterson


    Full Text Available Metabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes with an intact leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was crossed with a polygenetically obese Crl:CD (SD rat. Offspring were selectively inbred for obesity and diabetes for >30 generations. In the current study, ZDSD rats were followed for 6 months; routine clinical metabolic endpoints were included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD rats exhibited obesity with increased body fat, hyperglycemia, insulin resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels, abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body weight, increased insulin resistance with decreasing insulin levels, and dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD rats will provide a novel, translational animal model for the study of human metabolic diseases and for the development of new therapies.

  3. Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment.

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao


    Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (-45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (-51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.

  4. An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats

    Sekiguchi Miho


    Full Text Available Abstract Background Calcitonin is used as a treatment to reduce the blood calcium concentration in hypercalcemia and to improve bone mass in osteoporosis. An analgesic effect of calcitonin has been observed and reported in clinical situations. Ovariectomaized (OVX rats exhibit the same hormonal changes as observed in humans with osteoporosis and are an animal model of postmenopousal osteoporosis. The aim of this study to investigate antinociceptive effect of calcitonin in OVX rats using the immunohistochemical study. Methods We assessed the antinociceptive effects of calcitonin in an ovariectomized (OVX rat model, which exhibit osteoporosis and hyperalgesia, using the immunohistochemical method. Fifteen rats were ovariectomized bilaterally, and ten rats were received the same surgery expected for ovariectomy as a sham model. We used five groups: the OVX-CT (n = 5, the sham-CT (n = 5, and the OVX-CT-pcpa (n = 5 groups recieve