Sample records for asthmatic rats treated

  1. Histophatologic changes of lung in asthmatic male rats treated with hydro-alcoholic extract of Plantago major and theophylline

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    Farah Farokhi


    Full Text Available Objective: Plantago major (P. major is one of the medicinal crops in the world which has therapeutic properties for treatment of respiratory and gastrointestinal diseases. Theophylline is commonly used for the treatment of respiratory diseases. In this study, we investigated the protective effects of hydro-alcoholic extract of P. major on lung in asthmatic male rats. Materials and Methods: 32 male adult rats were randomly divided into 4 groups: The control group (C received normal saline; Asthma (A group received a normal diet; Asthma group treated with Theophylline (200 mg/kg b.w. (T; Asthma group which received p.major (100 mg/kg b.w. (P. Asthma was induced by citric acid, 0.1 mg in form of spraying. The injection of P.major extract and theophylline was administered intraperitoneally for four weeks. At the end of the treatment, all of the rats were sacrificed and lungs were taken out, fixed, and stained with H&E, toluidine blue, and PAS, then histological studies were followed with light microscope. Results: Results showed that, in asthmatic group, the mean number of mast cells was significantly increased (p<0.05. Thickness of alveolar epithelium and accumulation of glycoprotein in airways was increased. Moreover, in some of alveolar sac hemorrhaging was observed. Administration of p.major extract in asthmatic rats restored these changes towards normal group.Conclusion: The present study revealed that P. major compared with theophylline, has a protective effect on lung in asthmatic rats.

  2. Histophatologic changes of lung in asthmatic male rats treated with hydro-alcoholic extract of plantago major and theophylline

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    Farah Farokhi


    Full Text Available Objective: Plantago major (P. major is one of the medicinal crops in the world which has therapeutic properties for treatment of respiratory and gastrointestinal diseases. Theophylline is commonly used for the treatment of respiratory diseases. In this study, we investigated the protective effects of hydro-alcoholic extract of P. majoron lung in asthmatic male rats. Materials and Methods: 32 male adult rats were randomly divided into 4 groups: The control group (C received normal saline; Asthma (A group received a normal diet; Asthma group treated with Theophylline (200 mg/kg b.w. (T; Asthma group which received p.major (100 mg/kg b.w. (P. Asthma was induced by citric acid, 0.1 mg in form of spraying. The injection of P.major extract and theophylline was administered intraperitoneally for four weeks. At the end of the treatment, all of the rats were sacrificed and lungs were taken out, fixed, and stained with H&E, toluidine blue, and PAS, then histological studies were followed with light microscope. Results: Results showed that, in asthmatic group, the mean number of mast cells was significantly increased (p

  3. Neural plasticity occurs in the adrenal medulla of asthmatic rats

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    FENG Jun-tao; LI Xiao-zhao; HU Cheng-ping; WANG Jun; NIE Hua-ping


    Background Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor (NGF) in the organism.The aim of this study was to monitor the neuroendocrine alteration in the adrenal medulla of asthmatic rats.Methods Sixteen rats were randomly divided into two groups (n=8), control group and asthma group, and the asthmatic rats were sensitized and challenged with ovalbumin (OVA).The levels of NGF, epinephrine and norepinephrine in serum were detected by enzyme linked immunosorbent assay (ELISA), the NGF expression in adrenal medulla was detected by immunohistochemistry, and the changes in the ultrastructure of the adrenal medulla was observed by electron microscopy.Results The NGF expression was increased in asthmatic rats compared with control rats.Compared with control rats,the results indicated that the epinephrine level was decreased in asthmatic rats, but no significant difference was found in norepinephrine levels.We found more ganglion cells in the adrenal medulla of asthmatic rats than in control rats, with NGF immunostaining mainly located in these ganglion cells.Electron microscopic images showed the density of chromaffin granula decreased and there was shrunken nucleolemma in the adrenal medullary cells of asthmatic rats.Conclusion The innervation of the adrenal medulla is changed in asthmatic rats, and it may contribute to the epinephrine decrease in asthma.

  4. Molecular mechanism of icariin on rat asthmatic model

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    XU Chang-qing; LE Jing-jing; DUAN Xiao-hong; DU Wei-jing; LIU Bao-jun; WU Jing-feng; CAO Yu-xue; DONG Jing-cheng


    Background Effects of icariin on airway inflammation in asthmatic rats and the intervention of LPS induced inflammation are interfered with the machanism of icariin. Our study aimed to observe the effect of icariin on ovalbumin-induced imbalance of Th1/Th2 cytokine expression and its mechanism.Methods Sixty male SD rats were randomly divided into control group (PBS), asthma group (ovalbumin (OVA)-induced),dexamethasone group, and OVA+icariin low, medium and high dose groups (5, 10, 20 mg/kg, respectively). Each group had ten rats. The model of OVA sensitization was a rat asthma model. Enzyme-linked immunosorbent assay (ELISA)method was used to observe the effects of icariin on interleukin-4 (IL-4) and inerferon Y (IFN-Y) in rats' lung tissue.Immunohistochemical staining was applied to detect the intervention effects of icariin on T cells (T-bet) and gatabinding protein 3 (GATA-3) in rat pulmonary tissue. Realtime RT-PCR was used to observe the intervention effects of icariin on T-bet and GATA-3 mRNA expression in rat pulmonary tissue and spleen lymphocytes. Western blotting was used to observe the icariin intervention effects on T-bet, GATA-3 and nuclear factor-Kappa B (NF-κB) p65 protein expressions in rat pulmonary tissue.Results The ELISA results from pulmonary tissue showed that IL-4 expression was significantly reduced (P <0.05),while the IFN-y expression increased but not significantly when we compared OVA+icariin medium and high dose groups with the asthma group. Immunohistochemical staining of pulmonary tissue showed that the GATA-3 decreased significantly while the T-bet staining did not change in the OVA+icariin high dose group. In pulmonary tissue and spleen lymphocytes T-bet and GATA-3 mRNA expressions were significantly reduced (P <0.05) in icariin treatment groups compared with the asthma model group. GATA-3 and T-bet mRNA in rat spleen lymphocytes in the asthma group were higher than in the control group. GATA-3 mRNA expression in pulmonary

  5. Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats

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    Feng Jun-Tao


    Full Text Available Abstract Background Studies have shown that epinephrine release is impaired in patients with asthma. The pregnancy of female rats (dams with asthma promotes in their pups the differentiation of adrenal medulla chromaffin cells (AMCCs into sympathetic neurons, mediated by nerve growth factor, which leads to a reduction in epinephrine secretion. However, the relatedness between the alteration of AMCCs and increased asthma susceptibility in such offspring has not been established. Methods In this study, we observed the effects of allergization via ovalbumin on rat pups born of asthmatic dams. Results Compared to the offspring of untreated controls, bronchial hyperreactivity and airway inflammation were more severe in the pups from sensitized (asthmatic dams. In pups exposed to nerve growth factor (NGF in utero these effects were aggravated further, but the effects were blocked in pups whose dams had been treated with anti-NGF. Furthermore, alterations in AMCC phenotype corresponded to the degree of bronchial hyperreactivity and lung lesions of the different treatment groups. Such AMCC alterations included degranulation of chromaffin granules, reduction of epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and peripherin levels. Conclusions Our results present evidence that asthma during the pregnancy of rat dams promotes asthma susceptibility in their offspring, and that the transformation of AMCCs to neurons induced by NGF plays an important role in this process.

  6. Adrenal function in asthmatic children treated with inhaled budesonide

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    Bisgaard, H; Pedersen, S; Damkjaer Nielsen, M;


    The effect of the inhaled topical steroid budesonide on adrenal function was evaluated in 33 children (aged 7-15 years) with moderate bronchial asthma. The trial was designed as a prospective single-blind study of the effect of budesonide in daily doses of 200 microgram through 400 microgram to 800...... significantly during treatment with 800 microgram budesonide as compared to treatment with 200 microgram budesonide (95% confidence interval: 74%-112%). It is concluded, that budesonide is a topical steroid with a favourable ratio between topical and systemic effects in asthmatic children....

  7. Increased Expression of PI-3K in Asthmatic Rat T Lymphocytes

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    LIU Jin; ZHOU Shixin; XIONG Shengdao; XU Yongjian; ZHANG Zhenxiang; XIONG Weining


    In order to explore the expression of PI-3K in T lymphocytes of asthmatic rats and the relationship between PI-3K and activation of T lymphocytes, 24 Wistar rats were randomly divided into 4 groups: normal control group, asthmatic one-week group, asthmatic two-week group and asthmatic four-week group. T cells were purified from blood of each rat and the expression of PI-3K was observed by immunocytochemical fluorescence staining, the semiquantitative fluorescence intensity was measured by HPIAS-2000 analytic software, and the expression of IL-4 in supernatants was detected by ELISA. The results showed that the fluorescence intensity of T lymphocytes in asthmatic groups was significantly higher than that in normal control (P<0.001), indicating that the expression of PI-3K in T lymphocytes of asthmatic rats was significantly higher than that in those of normal controls, and the difference between acute and chronic stage asthmatic groups was significant (P<0.05). The expression levels of IL-4 protein in supernatants of asthmatic T lymphocytes were significantly higher than those in the normal controls (P<0.05). There was a significant positive correlation between the expression of PI-3K in T lymphocytes and the IL-4 protein expression in supernatants (r=0.583, P<0.01). It was suggested that PI-3K signal pathway may participate in the processes of activation and other cytological effects of asthmatic T lymphocytes, thus may play an important roles in the pathogenesis of asthma.

  8. Effect of Nuclear Factor-κB on Airway Remodeling in Asthmatic Rats

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    许淑云; 徐永健; 张珍祥; 倪望; 陈士新


    Summary: In order to investigate the effect of nuclear factor-κB (NF-κB) on airway remodeling in asthmatic rats, 18 Wistar rats were divided into three groups: asthmatic group; pyrrolidine dithiocarbamate (PDTC) group, in which rats were injected intraperitoneally with NF-κB specific inhibitor PDTC (100 mg/kg) before ovalbumin (OVA) challenge; control group. The NF-κB activity and the expression of inhibitory protein κBa (I-κBα) in airway were detected by electrophoretic mobility shift assay (EMSA), Western blot and immunohistochemistry respectively. The infiltration of inflammatory cells, the number of Goblet cells, the area of collagen and smooth muscle in airway were measured by means of image analysis system. The results showed that with the up-regulation of airway NF-κB activity in asthmatic group, the number of goblet cells (3.08 ±0.86/100μm basement membrane (BM)), the area of collagen (24.71 ± 4. 24 μm2/μm BM) and smooth muscle (13.81 ± 2.11 μm2/μm BM) in airway were significantly increased (P<0.05) as compared with control group (0.14±0. 05/100μm BM, 14.31 ±3.16 μm2/μm BM and 7.67±2.35 μm2/μm BM respectively) and PDTC group (0. 33±0. 14/100 μm BM, 18. 16±2.85 μm2/μm BM and 8.95±2.16 μm2/μm BM respectively). However, there was no significant difference between PDTC group and control group (P>0.05). It was concluded that the activity of NF-κB is increased in airway of asthmatic rats. Inhibition of NF-κB activation can attenuate constructional changes in asthma airway, suggesting NF-κB may contribute to asthmatic airway remodeling.

  9. Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

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    Jing-wen LONG; Xu-dong YANG; Lei CAO; She-min LU; Yong-xiao CAO


    Aim:Airway hyperresponsiveness is a constant feature of asthma.The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.Methods:Asthmatic E3 rats were prepared by intraperitoneal injection with OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA-PBS two weeks later.The myograph method was used to measure the responses of constriction and dilatation in the trachea,main bronchi and lobar bronchi.Results:In asthmatic E3 rata,β2 adrenoceptor-mediated relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited,and there were no obvious difference in relaxation compared with normal E3 rats.Contraction of lobar bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea or main bronchi.Airway contractions mediated by the endothelin (ET)A receptor,ETB receptor and M3 muscarinic receptor were augmented,and the augmented contraction was most obvious in lobar bronchi.The order of efficacy of contraction for lobar bronchi induced by agonists was ET-1,sarafotoxin 6c>ACh>5-HT.OX8 (an antibody against CD8+ T cells) strongly shifted and 0X35 (an antibody against CD4+ T cells) modestly shifted isoprenaline-induced concentration-relaxation curves in a nonparallel fashion to the left with an increased Rmax in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased Emax.Conclusion:The inhibition of airway relaxation and the augmentation of contraction mediated by receptors contribute to airway hyperresponsiveness and involve CD8+ and CD4+ T cells.

  10. Role of extracellular signal-regulated kinase in regulating expression of interleukin 13 in lymphocytes from an asthmatic rat model

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    LI Yuan-yuan; LIU Xian-sheng; LIU Chang; XU Yong-jian; XIONG Wei-xing


    Background The extracellular signal-regulated kinase (ERK) is widely expressed in mammal cells and involved in airway proliferation and remodeling in asthma. In this study, we intend to explore the role of ERK in the expression of the Th2 cytokine, interleukin 13 (IL-13) in lymphocytes in asthma.Methods Forty Sprague-Dawley rats were randomly divided into two groups: normal control and asthmatic groups. Peripheral blood lymphocytes were isolated and purified from the blood of each rat and divided into five groups: control, asthmatic lymphocytes, asthmatic cells stimulated with ERK activator epidermal growth factor (EGF), or with ERK inhibitor PD98059, or with EGF and PD98059 together. The expression of phosphorylated-ERK (p-ERK) was observed by immunocvtochemical staining, the expression of ERK mRNA was determined by reverse transcriptase-PCR, IL-13 protein in supernatants was measured by ELISA.Results (1) The ERK mRNA level and the percentage of cells with p-ERK in lymphocytes from asthmatic rats were significantly higher than those in normal controls, and were significantly increased by EGF administration. This effect of EGF was significantly inhibited by PD98059 pretreatment. (2) IL-13 protein in supematants of asthmatic lymphocytes was higher than that produced by normal control lymphocytes, and was significantly increased by EGF treatment. This EGF effect was partly blocked by PD98059 pretreatment. (3) There was a significant positive correlation between the percentage of cells with p-ERK in peripheral blood lymphocytes and IL-13 protein in supematants of lymphocytes from asthmatic rats.Conclusions In asthma the ERK expression and activation levels were increased, as was the protein level of IL-13. The ERK signaling pathway may be involved in the increased expression of the Th2 cytokine IL-13 in asthma.

  11. Expression of Leukemia Inhibitory Factor in Airway Epithelial Tissue of Asthmatic Rats

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    XIONG Weining; ZENG Daxiong; XU Yongjian; XIONG Shengdao; FANG Huijuan; CAO Yong; SONG Qingfeng; CAO Chao


    In order to investigate the expression of leukemia inhibitory factor (LIF) in airway epithelial tissues of normal and asthmatic rats, the influence of dexamethasone and the role of LIF in pathogenesis of asthma, 30 Sprague-Dawley (SD) rats were randomly divided into 3 groups (10 for each group): normal group, asthma model group, and dexamethasone-interfered group. In asthmamodel group and dexamethasone-interfered group, asthma rat models were established by intraperitoneal (i.p.) injection of 10% ovalbumin (OVA) and challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were pretreated with dexamethasone (2 mg/kg, i.p) 30 min before each challenge. The expression of LIF protein in lung was detected by immunohistochemistry. The results showed that LIF protein was mainly expressed in cytoplasm of bronchial epithelial cells. The expression of LIF protein in the airway epithelial tissue of asthma model group was significantly higher than that in normal group and dexamethasone-interfered group (P<0.01), but there was no significant difference between normal group and dexamethasone-interfered group (P>0.05). It was concluded that the expression of LIF was increased significantly in the airway epithelial tissue of the asthma rats, and dexamethasone could down-regulate the expression of LIF. It was suggested that LIF might play an important role in the pathogenesis of asthma as an inflammation regulator.

  12. Effect of All-trans Retinoic Acid on Airway Inflammation in Asthmatic Rats and Its Mechanism

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    方红; 金红芳; 王宏伟


    Summary: The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group,dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-κB inhibitor (IκBa), NF-κB,intercellular adhering molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between, them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IκBa was increased, while the expression of NF-κB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IκBa content and suppression of NF-cB activation and expression.

  13. The effectiveness of fish oil supplementation in asthmatic rats is limited by an inefficient action on ASM function. (United States)

    Miranda, D T S Z; Zanatta, A L; Dias, B C L; Fogaça, R T H; Maurer, J B B; Donatti, L; Calder, P C; Nishiyama, A


    Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1β in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.

  14. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

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    Xu Yu-Dong


    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

  15. Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

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    Ratzan Susan


    Full Text Available Adrenal suppression secondary to prolonged inhaled corticosteroid use is usually limited to biochemical abnormalities, with no obvious clinical effects. Acute adrenal crisis is much rarer event but has been reported with increasing frequency. We report a case of a 7-year-old asthmatic child who presented with an acute history of lethargy after a respiratory infection. He was maintained on 220 g/day of fluticasone propionate for several years. Initial evaluation revealed severe adrenal suppression, with undetectable cortisol levels and minimal response after stimulation with ACTH. After fluticasone was discontinued, a gradual recovery of the adrenal axis was seen. This case shows that acute adrenal crisis may be a consequence even at the usual prescribed doses, stressing the importance of using the lowest dose of inhaled steroids needed to control symptoms and having an increased awareness of this complication.

  16. Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

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    Angela H. Santiago


    Full Text Available Adrenal suppression secondary to prolonged inhaled corticosteroid use is usually limited to biochemical abnormalities, with no obvious clinical effects. Acute adrenal crisis is much rarer event but has been reported with increasing frequency. We report a case of a 7-year-old asthmatic child who presented with an acute history of lethargy after a respiratory infection. He was maintained on 220 μg/day of fluticasone propionate for several years. Initial evaluation revealed severe adrenal suppression, with undetectable cortisol levels and minimal response after stimulation with ACTH. After fluticasone was discontinued, a gradual recovery of the adrenal axis was seen. This case shows that acute adrenal crisis may be a consequence even at the usual prescribed doses, stressing the importance of using the lowest dose of inhaled steroids needed to control symptoms and having an increased awareness of this complication.

  17. Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

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    CAI Cui; CAO Yu-xue; ZHANG Hong-ying; LE Jing-jing; DONG Jing-cheng; CUI Yan; XU Chang-qing; LIU Bao-jun; WU Jin-feng; DUAN Xiao-hong


    Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.

  18. Increase in markers of airway inflammation after ozone exposure can be observed also in stable treated asthmatics with minimal functional response to ozone

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    Dente Federico L


    Full Text Available Abstract Background The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. Methods Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients underwent two sequential randomised exposures to either filtered air or ozone (0.3 ppm for 2 hours in a challenge chamber. Pulmonary function (PF was monitored, and patients with FEV1 decrease greater than 10% from pre-challenge value were considered as responders. Immediately after each exposure, exhaled breath condensate (EBC was collected to measure malondialdehyde (MDA. Six hours after each exposure, PF and EBC collection were repeated, and sputum was induced to measure inflammatory cell counts and soluble mediators (IL-8 and neutrophil elastase. The response to ozone was also evaluated according to the presence of polymorphism in oxidative stress related NQO1 and GSTM1 genes. Results After ozone exposure, sputum neutrophils significantly increased in responders (n = 8, but not in nonresponders (n = 15. Other markers of neutrophil activation in sputum supernatant and MDA in EBC significantly increased in all patients, but only in nonresponders the increase was significant. In nonresponders, sputum eosinophils also significantly increased after ozone. There was a positive correlation between ozone-induced FEV1 fall and increase in sputum neutrophils. No difference in functional or inflammatory response to ozone was observed between subjects with or without the combination of NQO1wt- GSTM1null genotypes. Conclusions Markers of neutrophilic inflammation and oxidative stress increase also in asthmatic subjects not responding to ozone. A greater functional response to ozone is associated with greater neutrophil airway recruitment in asthmatic subjects.

  19. Expression and significance of myeloid differentiation factor 88 in marrow dendritic cells in asthmatic rats with cigarette smoke exposure

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    LI Yi; DU Yong-cheng; XU Jian-ying; HU Xiao-yun


    Background Smoking causes frequent asthma attacks,leading to a rapid decline in lung function in patients with asthma,and it can also reduce the therapeutic effect of glucocorticeids in patients with asthma.Therefore,the present study aimed to investigate the effect of cigarette smoke on the expression of myeloid differentiation factor 88 (MyD88) in marrow dendritic cells (DCs) in asthmatic rats,and to explore the molecular mechanism of cigarette smoke exposure on asthma by DCs.Methods Forty Wistar rats were randomly divided into the following groups:control,smoke exposure,asthma,and asthma combined with smoke exposure.The animal model was established,and then rat bone marrow-derived DCs were collected.Additionally,rat spleen lymphocytes and bone marrow-derived DCs were cultured together for mixed lymphocyte responses.Interferon (IFN)-gamma and interleukin (IL)-4,IL-10,and IL-12 expressions were determined by enzyme-linked immunosorbent assay (ELISA).MyD88 expression was determined by Western blotting.The proliferation of lymphocytes was examined with methyl thiazolyl tetrazolium (MTT) colorimetric assay.Results MyD88 expression was decreased in the asthma combined with smoke exposure group compared to the asthma group (P<0.01),and IL-10 and IL-12 expressions were decreased in the asthma combined with smoke exposure group compared to control group (P<0.01).In addition,DCs stimulating activity on allogeneic lymphocytes were significantly decreased in the smoke exposure combined with asthma group compared to the control and asthma groups (P<0.01).After allogeneic mixed lymphocyte responses,IL-4 expression was increased and IFN-gamma was decreased in the asthma group and the asthma combined with smoke exposure group compared to control group (P<0.01).IL-4expression was increased and IFN-gamma was decreased in the asthma combined with smoke exposure group compared to the asthma group (P<0.01).The study also showed that MyD88 expression was positively

  20. Preventive effects of hydroalcoholic extract of saffron on hematological parameters of experimental asthmatic rats

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    Somayyeh Vosooghi


    Full Text Available Objective: Asthma is a chronic inflammatory disease of the respiratory airways distinguished by edema and infiltration of inflammatory immune cells. To test our hypothesis about the anti-inflammatory effect of saffron, we examined effects of Crocus sativus (C. sativus extract as a prophylactic anti-inflammatory agent in sensitized rats. Materials and Methods: To induce experimental asthma, rats were sensitized with injection and inhalation of ovalbumin (OA. Forty male Wistar rats were divided into 5 groups (n=8 for each: control, sensitized (asthma, and sensitized and pretreated with three different concentrations of extract, 50, 100, and 200 mg/kg, 2 times a week (group asthma+50EX, group asthma+100EX, and group asthma+200EX. After 32 days, total white blood cells (WBC counts, red blood cells (RBC, and platelet counts in blood were examined. Results: Total WBC number and eosinophil and neutrophil percentage in blood were increased, but lymphocyte decreased in sensitized animals compared with those of control group (pConclusion: Our findings indicated that the extract of C. sativus could be useful to prevent asthma as an anti-inflammatory treatment.

  1. Intracerebroventricular injection of leukotriene B4 attenuates antigen-induced asthmatic response via BLT1 receptor stimulating HPA-axis in sensitized rats

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    Jiang Jun-Xia


    Full Text Available Abstract Background Basic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA axis is the neuroendocrine-immnue pathway that functionally regulates the chronic inflammatory disease including asthma. Our previous studies showed corresponding changes of cytokines and leukotriene B4 (LTB4 between brain and lung tissues in antigen-challenged asthmatic rats. Here, we investigated how the increased LTB4 level in brain interacts with HPA axis in regulating antigen-induced asthmatic response in sensitized rats. Methods Ovalbumin-sensitized rats were challenged by inhalation of antigen. Rats received vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor was given via intracerebroventricular injection (i.c.v 30 min before challenge. Lung resistance (RL and dynamic lung compliance (Cdyn were measured before and after antigen challenge. Inflammatory response in lung tissue was assessed 24 h after challenge. Expression of CRH mRNA and protein in hypothalamus were evaluated by RT-PCR and Western Blot, and plasma levels of adrenocorticotropic hormone (ACTH and corticosterone (CORT were measured using the ELISA kits. Results Antigen challenge decreased pulmonary function and induced airway inflammation, evoked HPA axis response in sensitized rats. Administration of LTB4 via i.c.v markedly attenuated airway contraction and inflammation. Meanwhile, LTB4 via i.c.v markedly increased CORT and ACTH level in plasma before antigen challenge, and followed by further increases in CORT and ACTH levels in plasma after antigen challenge in sensitized rats. Expression of CRH mRNA and protein in hypothalamus were also significantly increased by LTB4 via i.c.v in sensitized rats after antigen challenge. These effect were completely blocked by pre-treatment with BLT1 receptor antagonist U75302 (10 ng, but not by BLT2 antagonist LY255283. Conclusions LTB4 administered via i.c.v down-regulates the airway contraction response and inflammation through

  2. [Recombination and identification of sense and antisence CyclinD1 eukaryotic expression vectors and the effects of the vectors on the proliferation of airway smooth muscle cell in asthmatic rats]. (United States)

    Qiao, Li-Fen; Xu, Yong-Jian; Liu, Xian-Sheng; Xie, Jun-Gang; Du, Chun-Ling; Zhang, Jian; Ni, Wang; Chen, Shi-Xin


    This study is to investigate the expression of CyclinD1 in asthmatic rats and construct expression plasmids of sense and antisense CyclinD1 gene and transfect them to asthmatic airway smooth muscle cell to study the effects of CyclinD1 on the proliferation of airway smooth muscle cells in asthmatic rats. CyclinD1 cDNA was obtained by RT-PCR of total RNA extracted from the airway smooth muscle in asthmatic rats. The sequence was inserted into eukaryotic expression vector pcDNA3.1 (+) to recombinate the sense and antisense pcDNA3.1-CyclinD1 eukaryotic expression vector. The two recombinations and vector were then separately transfected into airway smooth muscle cell in asthmatic rats by using liposome. The expression level of CyclinD1 was certificated by Western blotting analysis. The proliferations of ASMCs isolated from asthmatic rats were examined with cell cycle analysis, MTT colorimetric assay and proliferating cell nuclear antigen (PCNA) immunocytochemical staining. Results showed (1) Compared with control group, the content of CyclinD1 was significantly increased; (2) It was comformed by restriction endonucleasa digestion and DNA sequence analysis that the expression plasmid of sense and antisense CyclinD1 were successfully recombinated. There was significant change of CyclinD1 expression between vector and sense CyclinD1 transfected cells, and the expression level of CyclinD1 in ASMC transfected with antisense CyclinD1 was lower than that in vector transfected cells (P <0.01); (3) In the asthmatic groups, compared with the vecter group, the percentage of S + G2M phase, absorbance A value of MTT and the expression rate of PCNA protein in ASMC transfected with pcDNA3. 1-CyclinD1 vector significantly increased. The values decreased remarkably in the pcDNA3,1-as CyclinD1 group. Statistical analysis revealed that there were significant differences in these indicators of cell proliferation in three groups (P <0.01). In the normal groups, statistical analysis

  3. [Cycloferon in treating duodenal ulcers in rats]. (United States)

    Bul'on, V V; Khnychenko, L K; Sapronov, N S; Kuznetsova, N N; Anikin, V B; arinenko, R Iu; Kovalenko, A L; Alekseeva, L E


    The possibility of using cycloferon (interferon inductor) for a complex treatment (in combination with the main drug solcoseryl possessing pronounced therapeutic properties) of duodenum ulcers was experimentally studied in male rats. The experiments showed a considerable difference in the interferon status of animals with model duodenum ulcers treated with cycloferon, solcoseryl, their combination, and placebo (control). The healing effect of solcoseryl administered in combination with cycloferon exceeded that of each component administered separately.

  4. 哮喘气道重塑与氧化应激的实验研究%Airway Remodeling and Oxidative Stress in Rat Asthmatic Model

    Institute of Scientific and Technical Information of China (English)

    王尧; 杨青; 郭锋; 况九龙; 李里香


    目的 探讨大鼠支气管哮喘模型的慢性气道炎症、气道重塑特征以及与氧化应激的关系.方法 以卵蛋白为过敏原致敏,反复多次激发以模拟临床反复发作过程,建立大鼠慢性哮喘模型.64只SD大鼠随机分为正常对照组和哮喘组,每组再进一步划分4、8、12、16 周4个时间段.观察指标:①肺泡灌洗液(bronchoalveolar lavage fluid,BALF)细胞计数与分类;②肺组织病理观察:进行支气管周围炎性细胞浸润及杯状细胞增殖评分,测定支气管壁的平滑肌面积、胶原沉积面积,及肺组织TGF-β1的积分光密度值(IOD值);③测定12周大鼠肺组织匀浆MDA含量、SOD活性及肺组织TGF-β1蛋白含量.结果 ①各时间段哮喘组的BALF细胞计数与正常对照组相比,差异均有统计学意义(均P<0.01).其中中性粒细胞百分比、黏液指数随时间推移呈增加趋势.②4周哮喘组即有气道管壁增厚、平滑肌增生、胶原沉积增多、管腔变小、TGF-β1的表达增多等气道重塑的特征,与对照组比较差异均有统计学意义(均P<0.01),并随时间推移呈增加趋势,以16周哮喘组最明显.③与对照组比较,哮喘组的MDA含量、TGF-β1含量均明显升高(均P<0.01),SOD活性明显降低(P<0.01).结论 通过延长卵蛋白激发时间可以成功制备SD大鼠慢性哮喘气道重塑模型;哮喘气道重塑在早期即出现,中性粒细胞及氧化应激可能参与哮喘的气道重塑.%Objective To approach the effect of prolonged allergen on airway remodeling and to understand the correlation between the chronic airway inflammation, airway remodeling and oxidative stress in rat asthmatic model. Methods Sixty-four female SD rats were randomly divided into 2 groups : control group and asthmatic group. The rats were sensitized with ovalbumin,and repeatedly exposed to aerosolized ovalbumin for 4 , 8 , 12,16 weeks. Inflammation cell count and classification in bronchoalveolar lavage

  5. Clinical observation of Montelukast combined with Procaterol in treating pediatric asthmat-ic bronchitis%孟鲁司特联合丙卡特罗佐治小儿喘息性支气管炎的临床观察

    Institute of Scientific and Technical Information of China (English)

    严淑颜; 戴汝均


    AIM:To evaluate the efficacy of Montelukast com-bined with Procaterol in treating pediatric asthmatic bronchitis. METHODS:60 cases with asthmatic bronchitis were divided into treatment group (30 cases)and control group (30 cases)ran-domly.The control group received routine treatment,while the treatment group received oral Montelukast and Procaterol on the basic of routine therapy.RESULTS:The disappeared time of symptoms and signs in treatment group was significantly better than that in control group.CONCLUSION:Oral Montelukast combined with Procaterol has significantly curative effect in the treatment of pediatric asthmatic bronchitis.%目的:观察孟鲁司特联合丙卡特罗治疗小儿喘息性支气管炎的疗效。方法:选择喘息性支气管炎患儿60例,随机分为治疗组(30例)和对照组(30例)。对照组接受常规治疗,治疗组在常规治疗的同时口服孟鲁司特与丙卡特罗治疗。结果:治疗组症状、体征消失时间等方面均明显优于对照组。结论:口服孟鲁司特联合丙卡特罗治疗小儿喘息性支气管炎疗效显著。

  6. Effect of pregnancy on cadmium-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Takizama, Y. (Akita Univ. School of Medicine, Japan); Nakamura, I.; Kurayama, R.; Hirasawa, F.; Kawai, K.


    It is well known that itai-itai disease with the osteopathy is broken out among multiparas, 40 years of age and up Japanese residents. In this paper we described an experimental study of effect of pregnancy on cadmium treated rats. Female mature rats were administered drinking water containing 50 and 200 ppm cadmium as CdCl/sub 2/. During 180 days of the experiment, three times of pregnancy were succesful, though slight depression of body weight gain was noticed in the 200 ppm group. The cadmium was accumulated in the kidneys, liver and bone proportionally to the amount of cadmium administered. No significant change was recognized in serum calcium, phosphorus and alkaline phosphatase levels after 180 days. Though cadmium 200 ppm treated rats showed slight histological lesions in the proximal convoluted tubules of the kidney, there appeared to be no osteomalacia including excess formation of osteoid tissue.

  7. Treating 32 Senile Patients with Asthmatic Bronchitis by Adjunctive Therapy of Infrared Cough Stickers%红外止咳贴辅助治疗老年患者喘息性支气管炎32例

    Institute of Scientific and Technical Information of China (English)



    Objective:To investigate clinical effects of infrared cough sticker in the treatment for senile pa-tients with asthmatic bronchitis. Methods:Sixty-four patients were randomized into the treatment group and the con-trol group, the control group were given with routine treatment of western medicine and the treatment group with in-frared cough sticker on the base of the treatment the control group received, both groups were treated for ten days and clinical effects of both groups were compared by the end of the treatment. Results:Total effective rate of the treatment group was 93.54%, higher than 90.63%of the control group, the difference had no statistical meaning be-tween both groups (P>0.05), the treatment group was shorter than the control group obviously in disappearing time of clinical symptom and hospitalization time (P<0.05). Conclusion:Infrared cough sticker is effective in the treat-ment for senile patients with asthmatic bronchitis.%目的:观察红外止咳贴辅助治疗老年患者喘息性支气管炎的临床疗效。方法:将64例患者随机分为治疗组和对照组各32例,对照组给予常规西医治疗,治疗组在对照组治疗的基础上加用红外止咳贴,2组均连续治疗10天,治疗结束后比较2组临床疗效。结果:总有效率治疗组为93.54%,对照组为90.63%,2组比较无统计学意义(P>0.05),临床症状消失时间和住院时间治疗组明显短于对照组(P<0.05)。结论:红外止咳贴辅助治疗老年喘息性支气管炎临床疗效显著。

  8. Catalytically and noncatalytically treated automobile exhaust: biological effects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, G.P. (Univ. of Cincinnati); Lewkowski, J.P.; Hastings, L.; Malanchuk, M.


    Chronic exposure to catalytically treated or noncatalytically treated automobile exhaust significantly depressed the spontaneous locomotor activity (SLA) of rats. Exposure to H/sub 2/SO/sub 4/ alone or CO at comparable levels did not alter the SLA. Exposure to noncatalytically treated exhaust resulted in significant reductions in growth rate and food and water intake. However, these effects were not evident in the exposure to catalytically treated exhaust or in the control H/sub 2/SO/sub 4/ and CO exposures. Blood acid-base analyses indicated that exposure to either catalytically treated exhaust or H/sub 2/SO/sub 4/ elicits a metabolic alkalosis, while exposure to CO alone results in a metabolic acidosis. All acid-base parameters were within the normal range several weeks after the termination of exposure.

  9. Buccal health in asthmatic patients.

    Directory of Open Access Journals (Sweden)

    Nora Sexto Delgado


    Full Text Available Background: Buccal health as integral and determinant part of general health makes us find different ways and methods to elevate life quality in the population. Objective: To establish the risk of suffering from dental cavities in asthmatic patients. Methods: A non match case and control study constituted by 100 children selected at simple random from the universe of asthmatic patients belonging to the General Comprehensive doctor offices number 7,9,10, 11, 43, and 44 from Area II in Cienfuegos municipality. The controlled group was selected in the same offices but from the universe of non asthmatic children. The age in both groups was from 6 to 15 years old. Visits to the children´s home were carried out for the record of the information through health oral dental and buccal health knowledge surveys. Results: The index of cavities, lost, and obturated permanent teeth was higher (3, 28 than in the control group (0, 44. The buccal hygiene indexes and the level of knowledge in both groups did not show significant differences. The most used drugs in asthma therapy were salbutamol and ketotifeno which change the buccal milieu. The odds ratio technique between asthmatic and non asthmatic patients showed 4, 9 times more at risk of suffering from dental cavities in the first group. Finally, it can be stated that the asthmatic patients are more at risk of suffering from cavities than the non asthmatic ones, so a program for buccal health in these patients should be performed.

  10. Anticarcinogenic effects of curry leaves in dimethylhydrazine-treated rats. (United States)

    Khanum, F; Anilakumar, K R; Sudarshana Krishna, K R; Viswanathan, K R; Santhanam, K


    Curry leaves are one of the spices used in Indian dishes for aroma and preservation. There are no reports on the antioxidant properties of curry leaves. In this study, the antioxidant potential of curry leaves in rats treated with a known chemical carcinogen, dimethylhydrazine hydrochloride (DMH) was investigated. Food intake was reduced in the rats fed curry leaf-supplemented diet but the body and the organ weights were not affected. Vitamin A content in the liver was significantly increased whereas glutathione (GSH) content was not altered. A 50% reduction was seen in the micronuclei induced by DMH and a 30% reduction in the activity of gamma-glutamyl transpeptidase when the rats were fed a curry leaf-supplemented diet. These results indicate that curry leaves have high potential as reducer of the toxicity of DMH.

  11. Frankincense improves memory retrieval in rats treated with Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Beheshti Siamak


    Full Text Available Introduction: Frankincense has been shown to possess anti-inf lammatory activity. In this studythe effect of pretreatment with the hydro-alcoholic extract of frankincense on memory retrievalwas assessed in lipopolysaccharide (LPS treated rats.Methods: Forty-two adult male Wistar rats were distributed into 7 groups of 6 each. One groupreceived LPS (1 mg/kg; i.p pre-test. The control group received saline (1 ml/kg; i.p. 2 groups ofanimals received frankincense (50 mg/kg; P.O or DMSO 5% (1 ml/kg; P.O and 30 minutes laterLPS (1 mg/kg; i.p. Two other groups of animals received frankincense (50 mg/kg; P.O or DMSO5% (1 ml/kg; P.O and 30 minutes later saline (1 ml/kg; i.p. Another group of rats received LPS(1 mg/kg; i.p and 30 minutes later Ibuprofen (100 mg/kg; P.O. In all the experimental groups,memory retrieval was assessed 4 hours following the last injection, using a passive avoidancetask (PAT. Hippocampal TNF-α levels were measured by ELISA as an index of LPS-inducedneuroinf lammation.Results: LPS impaired memory retrieval by decreasing step-through latency (STL, significantly.LPS also increased levels of TNF-α in the hippocampus as compared to the control group.Administration of frankincense (50 mg/kg; P.O before LPS (1 mg/kg; i.p improved memoryretrieval as compared to the control group. Frankincense reduced hippocampal TNF-α level in theLPS treated rats, significantly, compared to the control group.Conclusion: The results indicate that the hydro-alcoholic extract of frankincense has the potentialto improve memory retrieval in LPS treated rats, possibly via an anti-neuroinf lammatory activity.

  12. Norepinephrine-induced diuresis in chronically ethanol-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Pohorecky, L.A. (Rutgers Univ., Piscataway, NJ (USA))


    Previous research from this laboratory indicated that noradrenergic mechanisms might mediate ethanol diuresis. Experiments described here examined changes in sensitivity of noradrenergic mechanisms in animals chronically treated with ethanol. Norepinephrine hydrochloride (0-12 ug intracerebroventricularly) produced dose-dependent diuresis in control and ethanol treated rats on the first day of treatment. Tolerance to ethanol diuresis was present after 10 day of ethanol treatment. Lack of responsiveness to norepinephrine-induced diuresis was evident only on the 20th day of treatment in both the ethanol and dextrin-maltose groups of rats. These results indicate a temporal dissociation between the tolerance to ethanol-induced and norepinephrine-induced diuresis and suggest that norepinephrine may not play a primary role in the development of tolerance to the diuretic action of ethanol.

  13. Reproductive performance of dibromochloropropane-treated female rats. (United States)

    Shaked, I; Sod-Moriah, U A; Kaplanski, J; Potashnik, G; Buchman, O


    Dibromochloropropane (DBCP) is an effective nematocide which has been shown to suppress spermatogenesis and cause infertility in both men and male rats. There are no similar reports concerning the effects of DBCP on female reproduction. The purpose of the present study was to attempt to interfere with the various phases of oogenesis. Proestral or pregnant rats were injected subcutaneously once with 40 mg/kg DBCP on one of each days of L12-L20 of gestation; a double dose (80 mg/kg) was injected in eight consecutive days (L11-L18). In addition, L13 fetuses were injected--directly into the amniotic sac--with 0.1 mg DBCP. Pooled data from the various days of gestation revealed that postimplantation losses were three times as high in the DBCP-treated animals as in DMSO-treated controls. Perinatal deaths were 58% higher and mean pup weights were 30% lower in the DBCP-treated rats than in controls. The reproductive performance of females exposed to DBCP while in utero was affected only to a limited degree (reduced number of ovulations and implantations) as compared with their DMSO counterparts. Doubling the dose (80 mg/kg) seriously reduced the birth weight of pups (50% of controls), all of which died within several hours post-partum. Direct injection of DBCP into embryos or to proestral rats did not have any adverse effects on their future reproductive performance. In contrast to the effect on spermatogenesis, it appears that oogenesis and ova are unaffected by DBCP.

  14. Exhaled carbon monoxide in asthmatics: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Huang Mao


    Full Text Available Abstract Background The non-invasive assessment of airway inflammation is potentially advantageous in asthma management. Exhaled carbon monoxide (eCO measurement is cheap and has been proposed to reflect airway inflammation and oxidative stress but current data are conflicting. The purpose of this meta-analysis is to determine whether eCO is elevated in asthmatics, is regulated by steroid treatment and reflects disease severity and control. Methods A systematic search for English language articles published between 1997 and 2009 was performed using Medline, Embase and Cochrane databases. Observational studies comparing eCO in non-smoking asthmatics and healthy subjects or asthmatics before and after steroid treatment were included. Data were independently extracted by two investigators and analyzed to generate weighted mean differences using either a fixed or random effects meta-analysis depending upon the degree of heterogeneity. Results 18 studies were included in the meta-analysis. The eCO level was significantly higher in asthmatics as compared to healthy subjects and in intermittent asthma as compared to persistent asthma. However, eCO could not distinguish between steroid-treated asthmatics and steroid-free patients nor separate controlled and partly-controlled asthma from uncontrolled asthma in cross-sectional studies. In contrast, eCO was significantly reduced following a course of corticosteroid treatment. Conclusions eCO is elevated in asthmatics but levels only partially reflect disease severity and control. eCO might be a potentially useful non-invasive biomarker of airway inflammation and oxidative stress in nonsmoking asthmatics.

  15. Effect of caffeine on rat offspring from treated dams. (United States)

    Aeschbacher, H U; Milon, H; Poot, A; Würzner, H P


    Pregnant Sprague-Dawley rats were given caffeine at 1.0, 0.5 and 0.25 g/kg diet during gestation and lactation. At birth, half of the pups from control and treated rats at each dose level were exchanged and cross fostered. Two litters were produced by each animal from each of the experimental groups. Caffeine at dietary concentrations of 0.5 and 0.25 g/kg throughout gestation and lactation had no significant effect on birth weight, litter size or development. There was also no effect at these doses following treatment during either gestation alone, or lactation alone. At 1.0 g/kg there was a slight reduction of birth weight, as well as a trend towards lower weight gain in litters from dams fed the test diet throughout gestation and lactation.

  16. 淫羊藿女贞子合用地塞米松抗哮喘大鼠的研究%Experimental study on effect of combination of Epimedii Folium/Ligustri Lucidi Fructus and dexamethasone on asthmatic rats

    Institute of Scientific and Technical Information of China (English)

    刘仁慧; 许利平; 王秀娟; 杨婧; 王培; 潘凉


    目的:研究地塞米松合用淫羊藿女贞子治疗哮喘的协同抗炎作用及对激素不良反应的改善作用.方法:给予哮喘大鼠模型腹腔注射地塞米松2周,同时配合灌胃淫羊藿女贞子,观察支气管肺泡灌洗液(BALF) IL-4,INF-γ,IL-5含量;血清COR,血浆ACTH,下丘脑CRH含量;BALF中GCR蛋白表达.结果:淫羊藿女贞子合用地塞米松能显著下调哮喘模型大鼠BALF中IL-5,IL-4含量,上调IFN-γ表达,调节Thl/Th2失衡;降低血浆ACTH,CRH含量;上调BALF中GCR的蛋白含量及结合力.结论:淫羊藿合用地塞米松可以增强激素的抗炎作用,并对内源性糖皮质激素作用途径起到保护作用.%Objective: To study the anti-inflammatory effect of the combination of Epimedii Folium, Ligustri Lucidi Fructus and dexamelhasone on asthma and its effect in inhibiting adverse reaction against hormone. Method: Dexamethasone had been injected intraperitoneally into asthmatic model rats for 2 weeks, together with the oral administration of Epimedii Folium and Ligustri Lucidi Fructus. The contents of IL-4, INF-γ, IL-5 and GCR in BALF, serum COR, plasma ACTH and hypolhalamic CRH were observed. Result: The combination of Epimedii Folium, Ligustri Lucidi Fructus and dexamethasone can significantly decrease the contents of IL-5 and IL4 in BALF and ACTH and CRH content in plasma, increase the content of IFN-γ and GCR in BALF and balance Th1/Th2. Conclusion: The combination of Epimedii Folium, Ligustri Lucidi Fructus and dexamethasone has a better anti-inflammatory effect on asthmatic model rats, and play a protective role in the pathway of endogenous dexamethasone.

  17. Cotinine Levels in Asthmatic Children

    Directory of Open Access Journals (Sweden)

    A Delpisheh


    Full Text Available Introduction: Asthmatic children are more at risk to environmental tobacco smoke exposure (ETS due to impaired lower airway function. Objective: To investigate the association of low socio-economic status and ETS exposure in asthmatic children. Design: A cross-sectional study on 425 primary school children (aged 5-11years in Merseyside, using a parent completed questionnaire and childrens’ saliva samples. Results: 25.9 % of children had doctor diagnosed asthma and 12 % had a history of hospital admission for respiratory illnesses. The symptom triad of cough, wheeze and breathlessness were reported for 8.5% of children. Mean cotinine level was 2.1 ng/ml (±0.6 SD. 45.6% of children were ETS exposed (cotinine levels >1.0 ng/ml. Asthmatic children and those from disadvantaged households were more likely to be ETS exposed, compared to non-asthmatic and those from advantaged households [OR=1.7 (95%CI=1.1-2.4] and [OR=2.1(1.8-3.2 respectively]. A synergic effect of parental asthma, deprivation and high cotinine levels on childhood asthma was observed in multivariate analysis. Conclusions: A high cotinine level was significantly associated with an increased risk of asthma in children particularly amongst disadvantaged households. Interventions aimed at limiting ETS exposure particularly among disadvantaged groups with asthmatic children are needed.

  18. Pregnancy Outcomes in Asthmatic Women

    Directory of Open Access Journals (Sweden)

    Mehran Karimi


    Full Text Available Asthma is considered to be the most common respiratory disorder complicating pregnancy. Seventy-six asthmatic and 152 non-asthmatic pregnant women were studied. Maternal asthma was significantly associated with adverse infant outcomes, including prematurity, low birth weight and the need for Cesarean delivery. The results of this study could indicate that pregnant women with asthma were at substantially increased risk for adverse infant outcomes and suggest the need for extra attention to mothers with asthma before and during pregnancy.

  19. Follicular atresia and infertility in rats treated with a gonadotropin-releasing hormone antagonist. (United States)

    Sharpe, K L; Bertero, M C; Lyon, B P; Muse, K N; Vernon, M W


    Adverse effects of the GnRH antagonist Antide on folliculogenesis and fertility were noted when we were evaluating the therapeutic value of Antide on endometriosis in a rat model. Cyclic rats with (n = 56) and without (n = 18) surgically induced endometriosis received Antide (2 mg/kg) or vehicle at noon on days 0 (proestrus), 3, 6, and 9. Rats were killed at noon on days 0, 6, 12, 18, 24, 30, 42, and 165. The number of antral follicles and the number of atretic antral follicles evaluated did not differ (P greater than 0.05) between endometriosis and control rats. Antide-treated rats had more (P less than 0.05 ) atretic antral follicles (64.7%) than vehicle-treated rats (15.3%). Antide-treated rat ovaries contained fewer corpora lutea than those of vehicle-treated rats on days 6, 12, and 18. No corpora lutea were found in Antide-treated rat ovaries after day 18. The abnormal ovarian morphology of the Antide-treated rats persisted for the duration of the project (165 days). Fertility (rats without endometriosis) was assessed by mating vehicle-and Antide-treated rats at spontaneous proestrus (n = 8) for eight posttreatment cycles as well as after follicular stimulation (n = 2). All vehicle-treated and no Antide-treated rats became pregnant. No oocytes were found in the oviducts of Antide-treated rats after eight cycles, indicating that ovulation had not occurred. The serum FSH and estradiol concentrations in the rats treated with Antide were lower (P less than 0.05) on days 6, 12, and 18, but rose to values equal to (days 24 and 30) or greater than (day 42) those in vehicle-treated rats. Serum progesterone levels in rats treated with Antide were lower (P less than 0.05) than those in vehicle-treated rats on all days tested. In conclusion, at a dosage sufficient to suppress reproductive cyclicity (and elicit the regression of endometriosis), Antide also caused long term follicular atresia and infertility.

  20. 哮喘大鼠大脑和肺组织c-fos蛋白表达与神经免疫调节%Cerebral and lung c-fos protein expression and neuroimmunomodulation in asthmatic rats

    Institute of Scientific and Technical Information of China (English)

    樊卫文; 杨志军; 罗荣城; 魏玲; 邓火金


    经免疫调节密切相关.%BACKGROUND: Increasing evidence identifies the immune system not as an isolated system with automodulations, but one that interacts with the central nervous system.OBJECTIVE: To investigate the distribution of c-fos expression in the lung and brain tissues of asthmatic rats and explore is significance.DESIGN: Randomized controlled study.SETTING: Department of Oncology, Southern Hospital, and Department of Neurosurgery, Zhujiang Hospital, Southern Medical University.MATERIALS: The experiment was conducted Department of Oncology,Southern Hospital, and Department of Neurosurgery, Zhujiang Hospital,Southern Medical University, between January and August 2004. Fourteen healthy male rats were randomized into experimental group (n=10) and control group (n=4).METHODS: On the first day of experiment, the rats in experimental group received intraperitoneal injection of 2 mL of the suspension containing 10 mg albumen, 200 mg aluminum hydroxide powder and inactivated pertussis vaccine (5×109), and subjected to inhalation of ultrasonically atomized 10 g/L albumen from on the 15th day, 2 times per hour for totally 3 days, to induce asthma in the rats. The rats in the control group received intraperitoneal injection of 2 mL normal saline on the 1st day and inhalation of ultrasonically normal saline on the 15th day, 30 mL a day for totally 3 days. The lung and brain tissues of all the anesthetized rats were fixed by perfusion, and immunohistochemical method with ovin-biotin-peroxidase complex and imaging analysis system were used to observe the distribution of Fos protein in the lung and brain.MAIN OUTCOME MEASURES: Distribution of c-Fos protein in lung and cerebrum.c-Fos in the lung and brain tissues was obviously higher in asthmatic group than in the control group (P < 0.05), located mainly in the parietal-fontal cortex, limbic forebrain (cingulum cortex, pyriform cortex and central amygdaloid nucleus and so on), thalamus paraventricular nucleus, hypothalamus paraventricular nucleus

  1. Surperoxide-mediated glomerulopathy in the endotoxin-treated pregnant rat

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Valkhof, N; Baller, JWF; Bakker, WW


    In the present study the role of superoxide in the glomerular damage in the low-dose endotoxin-infused pregnant rats was investigated. On day 14 of pregnancy, 12 rats were infused for 1 h with 1.0 mu g/kg bw endotoxin via a permanent jugular vein cannula. Of these rats, 6 were treated with SOD both

  2. Serum melatonin and hippocampus MT1 overexpression in asthmatic rat models%哮喘大鼠血清褪黑素及海马褪黑素受体1的变化

    Institute of Scientific and Technical Information of China (English)

    陈雯; 费广鹤


    Aim ToinvestigatetheexpressionofMT1 in the hippocampus and serum melatonin in the asth-matic rats, and explore the mechanism in the develop-mentofasthma.Methods SixtyadultSDratswere randomly divided into two groups: control group ( n=20 ) and asthma group ( n=40 ) . Asthma rat model was established by sensitization and stimulation with ovalbumin ( OVA ) . Immunohistochemistry, Western blot, and reverse transcription PCR ( RT-PCR ) were used to evaluate the expression of MT1 in hippocam-pus. Enzyme linked immunosorbent assay ( ELISA ) was used to detect serum melatonin level. Results TheexpressionofMT1inhippocampusatgeneand protein levels were significantly elevated in asthmatic group ( P 0.05).Conclusions MelatoninandMT1maybe involved in the pathogenesis of asthma. The up-regula-tion of MT1 in hippocampus with time-dependent pat-tern may be a compensatory response to decreased pe-ripheral melatonin levels for augmenting melatoninˊs neuroprotective and neuroimmunomodulatory effects a-gainst inflammatory reaction and stress in asthma.%目的:检测哮喘大鼠海马组织褪黑素受体1(melatonin receptor 1,MT1)的表达及血清褪黑素的水平,并探讨其在哮喘发生、发展过程中的作用机制。方法60只健康SD大鼠按随机原则分为对照组(20只)、哮喘组(40只)。通过卵清蛋白( OVA)致敏、激发建立哮喘大鼠模型,采用免疫组织化学、逆转录PCR及蛋白免疫印迹技术,检测不同时期哮喘组及对照组大鼠海马组织MT1的表达,并通过ELISA方法检测血清褪黑素水平的变化。结果与对照组比较,哮喘组大鼠海马组织MT1基因和蛋白表达水平均增加(P0.05)。结论褪黑素及MT1可能参与哮喘的发病机制。在哮喘的发生、发展中,大鼠海马组织MT1的表达上调呈时间依赖性,可能是机体应对血清褪黑素水平降低的一种适应性代偿,在哮喘炎症反应和免疫应激过程中发挥神经保护和神经免疫调节作用。

  3. Plasma diamine oxidase activity in asthmatic children

    Directory of Open Access Journals (Sweden)

    Kyoichiro Toyoshima


    Full Text Available Histamine plays an important role in the development of asthmatic symptoms. Diamine oxidase (DAO histaminase, which inactivates histamine, is located in the intestine and kidney and is released into plasma. Plasma DAO activity in asthmatic children was measured by a recently developed high performance liquid chromatographic method using histamine as the DAO substrate. Diamine oxidase activity was higher in severely asthmatic children than in those with mild asthma. A time course study during the acute exacerbation phase revealed that DAO activity rose during acute asthmatic attacks and then decreased gradually over several days. Although the mechanisms of plasma DAO activity increase during acute asthmatic attacks could not be explained, data showed that plasma DAO activity is an important index of histamine metabolism in asthmatics and may relate to some mechanisms of acute exacerbation of airway inflammation. Consequently, fluctuations in plasma DAO can be used as one of various indices of instability in management of asthma.

  4. 柠檬醛亚微乳对哮喘大鼠的免疫调节作用%Immunomodulatory Effects of Citral Submicron Emulsion on Asthmatic Rats

    Institute of Scientific and Technical Information of China (English)

    张艳; 袁菁菁; 丁兴红; 钱俊华


    [Objective] To investigate effects and mechanisms of citral submicron emulsion on asthma in Wistar rats. [Methods] Sixty Wistar rats were divided into six groups randomly, which were blank group, model group, positive control group, low, middle, high dose citral submicron emulsion groups. Rats were sensitized with antigen(ovalbumin, OVA). After two weeks, the sensitized rats were chal enged with OVA(10 g·L-1), and before the rats chal enged 2 hours were pretreated with citral submicron emulsion, once per day, every time 30 min, for four weeks. After 24 hours last atomization attack, white blood celldifferential amount, eosinophil amount, the content of IL-4 and IFN-gamma in bronchoalveolar lavage fluid(BALF) were detected. Histological changes of lung tissue were determined. [Results] Compared with blank group, EOS and IL-4 were significantly increased( P<0.01), while IFN-gamma was significantly decreased in model group( P<0.01). Compared with model group, the levels of EOS and IL-4 were significantly reduced( P<0.01), the level of IFN-gamma was increased in positive group( P<0.01). EOS and IL-4 were decreased significantly in high dose group( P<0.01), while the content of IFN-gamma was obviously increased(P<0.05). [Conclusion] EOS, IL-4 and IFN gamma play an important role in the development of asthma. Citral submicron emulsion relieved the airway inflammation in rats by reducing EOS, IL-4 level, and increasing IFN-γlevel possibly.%[目的]探讨柠檬醛亚微乳对哮喘大鼠的免疫调节作用及其作用机制。[方法]将60只Wistar大鼠随机分为空白组、模型组、阳性对照组、柠檬醛亚微乳低、中、高剂量组。以卵白蛋白(OVA)致敏大鼠,2周后给予1%OVA雾化激发,在雾化激发前2h用柠檬醛亚微乳剂雾化给药,连续4周。末次雾化攻击24h后,计数肺泡灌洗液(BALF)中白细胞总数和嗜酸性粒细胞(Eosinophil,EOS)数量,测定BALF中IL-4和IFN-γ的含量,并检测肺组

  5. Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

    Directory of Open Access Journals (Sweden)

    Shin Minkyu


    Full Text Available Abstract Background The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. Results We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine. a selective serotonin reuptake inhibitor (fluoxetine, a monoamine oxidase inhibitor (phenelzine and psychoactive herbal extracts of Nelumbinis Semen (NS. To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced. Conclusions These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.


    Directory of Open Access Journals (Sweden)

    M.H Karimi


    Full Text Available Introduction. For future health planning of our country, the type and amount of drugs used for treatment of chronic diseases should be known. Therefore, in the present study the treatment regimen of asthmatic children in the city of Mashhad was studied. Methods. To study the different types of drugs in the treatment regimen of asthmatic children in the city of Mashhad, we evaluated the treatment regimen of 366 primary school children with asthma disease. Starting, maximum and duration of action of three different bronchodilators (salbutamol inhaler, salbutamol syrup, and theophylline syrup were compared. Findings. The results of the first part of this study showed that only 31.6 percent of asthmatic children had history of treatment and only 10.6 percent had current medication. In addition, most of the treated children (38.8 percent had only bronchodilator (salbutamol syrup in their treatment regimen. The effect of salbutamol inhaler on lung function tests starts in 5 min, salbutamol syrup in 15 min and theophylline syrup at 30 min after administration. The maximum response to salbutamol inhaler, salbutamol syrup, and theophylline syrup occurred 15 min, 4 hr and 3 hr after administration, respectively. The reduction of response to salbutamol inhaler occurs after 3 hr, but there was no any reduction in response to salbutamol and theophylline syrup during study period. Conclusion. The prevalence of asthma among children in the city of Mashhad is relatively high, but most of asthmatic children are not treated. Although the oral bronchodilator in mild asthma is effective, salbutamol inhaler is needed for emergency use.

  7. Anti-asthmatic and anti-oxidative effect of Quince seed dichloromethane extract on a rat model of allergic asthma%维药榅桲籽提取物对哮喘大鼠抗炎、抗氧化功能的影响

    Institute of Scientific and Technical Information of China (English)

    麦丽帕提·木合巴提; 伊力亚斯·艾萨; 塔衣尔·吐尔逊; 哈木拉提·吾甫尔; 努尔买买提·艾买提


    目的:探讨榅桲籽提取物对实验性哮喘大鼠抗炎、抗氧化功能的影响。方法将健康雄性 SD大鼠72只随机分为正常对照组、哮喘模型组、地塞米松阳性对照组、榅桲籽低剂量组、榅桲籽中剂量组、榅桲籽高剂量组,每组12只。除了正常对照组外,其余各组以卵清蛋白致敏及激发的方法建立哮喘大鼠模型,正常对照组用PBS进行致敏和刺激。分别给予药物干预,末次给药后处死动物,采集标本,并检测 BALF和组织中炎性细胞数量、炎性细胞因子、活性氧及抗氧化酶含量,观察支气管肺组织形态学的改变。结果哮喘模型组 BALF中白细胞和 EOS增加,与正常对照组比较差异有显著统计学意义(P <0.01);榅桲籽各剂量组和阳性对照组 BALF中,白细胞和 EOS总数较哮喘模型组显著降低,差异有显著统计学意义(P <0.01)。喘模型组大鼠肺组织中 IL-4、IL-5含量均明显升高,与正常对照组比较差异有统计学意义(P <0.01);榅桲籽各剂量组大鼠肺组织中IL-4、IL-5含量较哮喘模型组明显降低,差异有统计学意义(P <0.01)。哮喘模型组MDA含量较正常对照组升高,差异有统计学意义(P <0.05);榅桲籽各治疗组MDA含量较哮喘模型组升高下降,差异有统计学意义(P <0.05)。哮喘模型组SOD、GSH活力降低,与正常对照组比较差异有显著统计学意义(P<0.01);榅桲籽治疗组SOD、GSH活力较哮喘模型组显著增加,差异有统计学意义(P <0.01)。结论维药榅桲籽可减轻气道炎症,抑制气道高反应性,改善气道氧化环境,发挥抗炎、平喘作用。%Objective To study the anti-asthmatic,anti-oxidative effect of Quince seed dichloromethane ex-tract to asthmatic rat on airway inflammation.Methods The extract was obtained from the Quince seed in dichloromethane.Rats were sensitized

  8. Embryo development alteration in rats treated with lapachol

    Directory of Open Access Journals (Sweden)

    Juliana Maganha


    Full Text Available Lapachol, a naphthoquinone extracted from plants of the genus Tabebuia (family Bignoneaceae, showed multiple therapeutic activities. Pregnant Wistar rats were treated with Lapachol from the 1st to the 4th (pre-implantation period and from 5th to 7th (implantation period post insemination day (PID. Mothers were sacrificed on the 5th or on the15th PID. Number of corpora lutea, preimplantation embryo, blastocysts, live and dead fetuses and resorptions were counted. There were no signs of maternal toxicity. The number and the morphology of embryos, during oviduct development (pre-implantation period, did not seem to be affected by this drug, but during the implantation period, lapachol was toxic causing the death of embryos and intrauterine growth retardation.O Lapachol é uma naftoquinona, extraída de plantas do gênero Tabebuia (família Bignoneaceae, que apresenta múltiplas atividades terapêuticas. Estudos prévios sobre o efeito do lapachol no início do desenvolvimento embrionário de ratas são controversos. No presente trabalho ratas Wistar prenhes foram tratadas com lapachol do 1º ao 4º dias pós-inseminação (período de pré-implantação e do 5º ao 7º dias (período de implantação do blastocisto. As mães foram sacrificadas no 5º o e no 15º dia pós-inseminação. Contaram-se corpos lúteos, embriões em fase de pré-implantação, blastocistos, fetos vivos e mortos e reabsorções.Fetos e placentas foram pesados. Não ocorreram indícios de toxicidade materna.O número e a morfologia dos embriões durante o desenvolvimento tubário não foi afetado pela droga, mas durante o período de implantação o lapachol foi tóxico, causando morte de embriões e retardo de crescimento intra-uterino.

  9. Inhibitory Effects of Moldavica Total Flavone on Airway Inflammation and Hyperresponsiveness in Ovalbumin-induced Asthmatic Rats%香青兰总黄酮对哮喘大鼠气道炎症及高反应性的改善作用

    Institute of Scientific and Technical Information of China (English)

    康小龙; 何承辉; 邢建国; 闫丽丽


    OBJECTIVE To investigate the effects of moldavica total flavone on airway inflammation and hyperrespon-siveness in ovalbumin-induced asthmatic rats. METHODS The cough model in rats and asthma model in cavies were made by using ammonia water and histamine-acetylcholine chloride to observe the antitussive and antiasthmatic actions. The inhibitory effect on airway inflammation and hyperresponsiveness in ovalbumin-induced asthmatic rats were observed. RESLUTS The moldavica total flavone in middle and high dose group could extend the cough latent period in rats(.P<0.05 or 0.01) and gasp latent period in cavies (P<0.01), decreased the levels of serum ovalbumin specific IgE (P<0.01) and eosinophil counts in bronchoalveolar lavage fluid (P<0.01), attenuate the contraction of tracheal smooth muscle in ovalbumin-induced asthmatic rats (P<0.05 or 0.01). CONCLUSION Moldavica total flavone has antitussive and antiasthmatic actions and may inhibit ariway inflammation and hyperresponsiveness in asthma.%目的研究香青兰总黄酮对哮喘大鼠气道炎症及高反应性的影响.方法采用氨水引咳实验和磷酸组胺-氯化乙酰胆碱引喘实验观察香青兰总黄酮的镇咳、平喘作用;同时观察香青兰总黄酮对哮喘大鼠支气管肺泡灌洗液(BALF)中白细胞分类计数和离体气管螺旋条张力的影响.结果香青兰总黄酮中、高剂量能延长小鼠咳嗽潜伏期,减少小鼠2 min内咳嗽次数(P<0.05或P<0.01),延长豚鼠引喘潜伏期(P<0.01);降低哮喘大鼠血清卵白蛋白特异性IgE水平(P<0.01),减少BALF中嗜酸性粒细胞数量(P<0.01)及减小离体气管螺旋条张力(P<0.05或P<0.01).结论 香青兰总黄酮具有一定镇咳、平喘作用;可改善哮喘气道炎症及高反应性.

  10. Mechanism of hypothalamic paraventricular nucleus in regulating asthmatic attack

    Institute of Scientific and Technical Information of China (English)

    Jia Liu; Rong Dong; Jian Xiao; Nina Liu


    BACKGROUD: It has been confirmed that c-fos expession increased markedly in hypothalamic paraventricular nucleus(PVN)during asthmatic attack in rats,and PVN has extensive physiological functions,involving in the regulation of respiratory system,etc.OBJECTIVE: To observe the alteration of electroencephalogram(EEG)and power spectra in PVN during the asthmatic attack,and the alteraiton of lung function and diaphragmatic muscle discharge after bilateral PVN lesion in asthmatic rats.DESIGN:A randomized control study.SETTING: Laboratory of Physiology and Pharmacology,School of Basic Medical Sciences,Southeast University.MATERIALS: Forty-eight male adult SD rats of 260-300g were used.The rats were randomly divided into 6 groups(n=8):control group,asthma group,electrolytic lesion of PVN group,KA-induced lesion of PVN group,sham electrolytic lesion of PVN group and sham kainic acid(KA)-induced lesion of PVN group.KA,chicken ovalbumin and aluminum hydroxide were purchased from American Sigma Company.Bordetella pertrssis vaccine (Institute of Biological Products of Shanghai);stereotaxic apparartus (Jianwan Ⅱ,China);Iesion-producing device (YC-2 programmable stimulato,Chengdu Iustrument Company);MD2000 signal processing system(Nanjing Medical School); data acquisition system (RM6240B,Chengdu Instrument Company).METHODS:The experiments were carried out in the Laboratory of Physiology and Pharmacology,School of Basic Medical Sciences,Southeast University from January to August in 2006.①Rats except for control group were sensitized with an intraperitoneal injection of 100 mg chicken ovalbumin and 100 mg aluminum hydroxide and Bordetella pertussis vaccine containing 5×109 heat-killed in 1 mL of sterile saline.From the fifteenth to seventeenth days rats received three times aerosolized ovalbumin challenge. In rats of the control group and asthma group three steel electrodes were placed into the left PVN(AP-1.8 mm,LR 0.4 mm,OH-7.9 mm).parietal cortex and subcutaneous tissue in

  11. Normal spatial and contextual learning for ketamine-treated rats in the pilocarpine epilepsy model. (United States)

    McKay, B E; Persinger, M A


    Cognitive impairments frequently accompany epileptic disorders. Here, we examine two neuroprotective agents, the noncompetitive NMDA antagonist ketamine and the dopaminergic antagonist acepromazine, for their efficacy in attenuating cognitive impairments in the lithium-pilocarpine (LI-PILO) model of rat limbic epilepsy. Declarative-like cognitive behaviors were assessed in a Morris water maze task that consisted successively of spatial and nonspatial (cued platform) training. Whereas the ketamine-treated (Ket) LI-PILO rats performed equally in all respects to nonseized control rats for the spatial and nonspatial components of the water maze task, the acepromazine-treated (Ace) LI-PILO rats failed to demonstrate learning in either the hidden or cued platform variants of the task and did not demonstrate any place learning in the platform-removed probe trials. We further assessed nondeclarative (associative) cognitive behaviors with a standard contextual fear-conditioning protocol. LI-PILO rats treated with acepromazine failed to learn the Pavlovian relationship; Ket LI-PILO rats performed equivalently to nonseized controls. Cumulatively, these data suggest robust cognitive sparing for LI-PILO rats with pharmacological NMDA receptor antagonism following induction of status epilepticus (SE). This cognitive sparing occurs despite earlier findings that the mean amount of total brain damage with LI-PILO is equivalent for Ket and Ace rats.

  12. Unsweetened natural cocoa has anti-asthmatic potential. (United States)

    Awortwe, C; Asiedu-Gyekye, I J; Nkansah, E; Adjei, S


    Unsweetened natural cocoa powder is enriched with nutraceutical abundance of anti-asthmatic compounds theobromine and theophylline. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9% theobromine and 0.21% caffeine. Anecdotal reports indicate that regular consumption of unsweetened natural cocoa powder (UNCP), a common practice in Ghana, West Africa, has the potential to reduce the tendency of asthmatic episodes. In the present paper we studied the effect of regular ingestion of aqueous extract of UNCP on hematological and histopathological changes that occur in ovalbumin (OVA)-sensitized guinea pigs. OVA-sensitized guinea pigs were challenged with aerosolized OVA 1 hour after ingestion of 300 mg/kg (low dose) or 600 mg/kg (high dose) of UNCP for 35 consecutive days. Histopathological and haematological changes in the OVA-sensitized guinea pigs were evaluated. Both negative and positive controls with distilled water and prednisolone, respectively, were used. OVA-sensitized guinea pigs demonstrated concentration-independent reduction in immune response to aerosolized OVA. There were no histo-architectural changes in the bronchiolar smooth muscles of the treated groups. Unsweetened natural cocoa powder has potential anti-asthmatic properties when administered orally at the doses tested.

  13. Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis (United States)

    Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta


    In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (pbone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (pbone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

  14. Effect of doxycycline on airway inflammation and remodeling in asthmatic rats%多西环素对哮喘大鼠气道炎症及气道重塑的影响

    Institute of Scientific and Technical Information of China (English)

    李静; 王亮; 杨红申; 李亚妹; 侯宏伟; 李香兰; 张聪瑶; 李玉静


    目的:探讨多西环素对哮喘大鼠气道炎症及重塑的预防作用及可能机制。方法将实验 SD 大鼠分为正常对照组、哮喘组、多西环素干预组。计数大鼠肺泡灌洗液中的细胞数并进行分类;检测血清中的白细胞介素5(IL-5)、白细胞介素13(IL-13)、肿瘤坏死因子α(TNF-α)的水平;检测肺组织中基质金属蛋白酶9(MMP-9)、肌动蛋白α(α-SMA)的表达;测定支气管基底膜周径(Pbm)、总管壁面积(WAt)、平滑肌面积(WAm)等反映气道壁厚度的指标,分析多西环素的影响。结果哮喘组与多西环素干预组的肺泡灌洗液细胞总数、嗜酸性粒细胞计数、支气管壁厚度、平滑肌厚度、血清 IL-5、IL-13及 TNF-α水平、肺组织 MMP-9、α-SMA 平均光度值均明显高于正常对照组,其中多西环素干预组均明显低于哮喘组(P <0.05)。结论多西环素可以影响炎症介质的生成及通过抑制 MMP-9的活性从而减轻哮喘的气道炎症及气道重塑。%ABSTRACT:Objective To investigate the effect of doxycycline on airway inflammation and remodeling in asthmatic rats.Methods Thirty-three male Sprague Dawley rats were randomly divided into three groups:control group,asthma group and doxycycline intervention group.Total cell number and different cell number in BALF were counted.The concentrations of serum IL-5,IL-13 were assayed by ELISA,and the concentration of serum TNF-αwas determined by radioimmunoassay.The expression of MMP-9 and α-SMA in lung tissues were observed by immunohistochemistry.Lung tissues were sliced and stained with HE.These parameters such as bronchial basement membrane perimeter (Pbm),total bronchial wall area (WAt)and smooth muscle area (WAm),which reflected the thickness of airway wall,were measured by image analysis system.Results The count of total cells and eosinophils significantly increased in asthma group and doxycycline intervention group than in control group(P <0.05),and the

  15. Zinc content in epididymal spermatozoa of metoclopramide-treated rats. (United States)

    Kaminska, B; Rozewicka, L; Dominiak, B; Mielnicka, M; Mikulska, D


    Zinc content was determined separately in spermatozoa taken from epididymal caput and cauda in rats. It was revealed that spermatozoa transported from the epididymal caput to the cauda reduce about 54% of zinc. This reduction is significantly inhibited in spermatozoa of rats receiving metoclopramide. That is also accompanied by a fall of testosterone level in blood serum and of delta 5, 3 beta-HSD activity in Leydig cells. It was found out that the reduction of zinc in spermatozoa at the time of their passage through the epididymis is the process that depends on androgens.

  16. Zinc content of maturing spermatozoa in oestrogen treated rats. (United States)

    Srivastava, A; Chowdhury, A R; Setty, B S


    Zinc content of spermatozoa collected from the caput and cauda portions of the rat epididymis was determined by atomic absorption spectroscopy. The results showed about 60% reduction in the spermatozoal zinc content by the time they reach the cauda epididymis. This reduction was inhibited in rats receiving micro dose oestrogen which induced 'functional' sterility. It appears that the fall in zinc content of spermatozoa during their transport in the epididymis is related to sperm maturation and that oestrogen treatment interferes with this reduction in sperm zinc content.

  17. The effect of eurycoma longifolia jack on spermatogenesis in estrogen-treated rats

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    Norhazlina Abdul Wahab


    Full Text Available INTRODUCTION: There is little data concerning the ability of Eurycoma longifolia Jack (EL to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. The aim of the present study was to determine the effect of EL on testicular histology and sperm count in estrogen-treated male rats. METHODS: Adult male Sprague-Dawley rats weighing 200-250 g were divided into four groups of six rats each. Group A (control was given solvent in the same manner as the treated groups were given EL. Group B was treated with EL (8 mg/kg body weight orally. Group C was treated with estradiol (E2 (intramuscular dose of 500 μg/kg body weight, and group D received a combined treatment of oral EL and intramuscular E2. After fourteen consecutive days of treatment, rats from all groups were sacrificed and subjected to spermatogenic and epididymal sperm cell counts. RESULTS: The spermatogenic cell count in the E2-treated group was significantly decreased as compared to the control (p < 0.05 and EL+E2-treated groups (p < 0.05. A similar finding was found for the epididymal sperm count; the E2-treated group had a significant decrease in the count compared to the control (p < 0.05 and EL+E2-treated groups (p < 0.05. Rats that were treated with EL alone exhibited significantly higher sperm counts and sperm motility when compared to the control group (p < 0.05. CONCLUSIONS: EL extract acts as a potential agent for reversing the effects of estrogen by increasing spermatogenesis and sperm counts in rats after fourteen consecutive days of treatment.

  18. The Power of Classic Music to Reduce Anxiety in Rats Treated with Simvastatin

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    José Geraldo Pereira da Cruz


    Full Text Available Introduction: This study was designed to investigate the effects of music in Wistar rats after sub-chronic treatment of simvastatin. The rats were orally administered with either simvastatin or saline (controls. After 4 weeks of drug treatment, the rats were selected for behavioral studies. The rats were exposed to music 24 hours before behavioral tests (Mozart’s piano sonata, KV361, Largo. Results: The experiments suggest that exposure to chronic treatment with simvastatin (1 or 10 mg/kg/day reduced anxiety levels in rats when associated with Mozart music in an elevated plus-maze. Discussion: These results indicate that music can serve as an effective adjuvant in rats treated with simvastatin, and that this species could potentially be used in other preclinical models utilizing musical interventions.

  19. Renal Glycosuria without Hyperglycemia in Cyclosporine-Treated Rats

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    Chang Hwa Lee


    Conclusion: Glycosuria may occur without hyperglycemia in cyclosporine administration. We suggest that cyclosporine may decrease tubular reabsorption of glucose in renal tubular epithelial cells, and then glycosuria could be induced by the altered glucose transporter expressions. We will analyze the glucose transporters in proximal tubule of rat kidney.

  20. Cessation of dexamethasone exacerbates airway responses to methacholine in asthmatic mice. (United States)

    Stengel, Peter W; Nickell, Laura E; Wolos, Jeffrey A; Snyder, David W


    In asthmatic mice, dexamethasone (30.0 mg/kg) was administered orally once daily on Days 24-27. One hour after dexamethasone on Day 25-27, the mice were exposed to ovalbumin aerosols. Twenty-eight days after the initial ovalbumin immunization, we found that dexamethasone reduced methacholine-induced pulmonary gas trapping and inhibited bronchoalveolar lavage eosinophils and neutrophils. However, five days after the last dose of dexamethasone and last ovalbumin aerosol exposure in other asthmatic mice, the airway obstructive response to methacholine was exacerbated in dexamethasone-treated mice compared to vehicle-treated mice on Day 32. Further, eosinophils, but not neutrophils, were still inhibited after cessation of dexamethasone. Thus, discontinuing dexamethasone worsened methacholine-induced pulmonary gas trapping of asthmatic mice in the absence of eosinophilic airway inflammation.

  1. The cytoskeleton of digitonin-treated rat hepatocytes.


    Fiskum, G.; Craig, S W; Decker, G L; Lehninger, A L


    Treatment of isolated rat hepatocptes with low concentrations of digitonin increases the permeability of the plsma membrane to cytosolic proteins without causing release of organelles such as mitochondria into the surrounding medium. Electron microscopy showed that treatment of the cells with increasing concentations of digitonin results in a progressive loss in the continuity of the plasma membrane, while most other aspects of cellular morphology remain normal. Depletion of background staini...

  2. Antiamnesic effect of stevioside in scopolamine-treated rats

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    Sharma Deepika


    Full Text Available The present study was undertaken to explore the potential of stevioside in memory dysfunction of rats. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p. in animals. Morris water maze (MWM test was employed to assess learning and memory. Brain acetylcholinestrase enzyme (AChE activity was measured to assess the central cholinergic activity. The levels of brain thiobarbituric acid-reactive species (TBARS and reduced glutathione (GSH were estimated to assess the degree of oxidative stress. Scopolamine administration induced significant impairment of learning and memory in rats, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH levels. Pretreatment of stevioside (250 mg/kg dose orally significantly reversed scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that stevioside exerts a memory-preservative effect in cognitive deficits of rats possibly through its multiple actions.

  3. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats. (United States)

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M


    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

  4. Expired nitric oxide levels in adult asthmatics

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    Chiharu Okada


    Full Text Available The expired nitric oxide (NO concentration is known to be higher in asthmatic subjects than in normal subjects. To elucidate the role of NO in asthma, we examined the expired NO concentrations in relation to the type (atopic, mixed, non- atopic, and severity (mild, moderate, severe of asthmatics, as well as the influence of steroid treatment. Twenty-seven normal subjects, 48 asthmatics, 8 subjects with allergic rhinitis, and 13 subjects with pulmonary emphysema participated in the study. The expired NO concentration was significantly higher in asthmatics and patients with allergic rhinitis than in normal subjects (P<0.01. No significant difference was observed between the expired NO concentration in patients with pulmonary emphysema and that of normal subjects. The expired NO concentrations were significantly lower in non- atopic asthma than in atopic asthma. Nitric oxide levels were significantly lower in severe asthma than in mild asthma. High doses of steroid treatment are often used in severe asthma. The dose of inhaled beclomethasone and expired NO concentrations showed a negative correlation (r= −0.51587, P<0.004. Drip infusion of hydrocortisone tended to increase the exhaled NO concentration just after drip infusion, however, it decreased after 24 h. These results suggest that steroid treatment decreases the expired NO concentrations in asthmatics, although it cannot be concluded that NO increases the severity of asthma. The measurement of expired NO concentrations is an easy, non-invasive test, which may be a useful tool for monitoring the condition of asthmatics.

  5. Effects of Zhichuan decoction on MMP-9,TIMP-1 during airway remodeling in asthmatic rats%止喘汤对哮喘大鼠模型气道重构中MMP-9、TIMP-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    霍博雅; 张占锋


    Objective:To investigate the effects of Traditional Chinese Medicine(TCM) on airway remodeling and the expression of MM P-9 and TIMP-1 in asthmatic rats. Methods: Fifty Sprague-Dawley rats were randomly divided into five groups equally:normal control group,asthmatic group,budesonide aerosol group,scutellaria baicalensis group and Zhichuan decoction group. The model of asthma was established by OVA ( ovalbumin ) sensitizing and challenging; some lung tissues were sliced and stained with HE and morphological indicators of airway were measured by image analysis, the other lung tissues were sliced and stained with Immunohistochemistry and the expression of MMP-9 、TIMP-1 and collagen type IV was observed. Results: Compared with normal controls, the thickness of airway wall in asthmatic models was significantly increased,and the expression of MMP-9 and TIMP-1 was also increased significantly ( P < 0. 01). After intervention with TCM and budesonide aerosol, compared with asthmatic models, the thickness of airway became thinner significantly, meanwhile,the expression of MMP-9 and TIMP-1 was significantly decreased(P < 0. 01 ) ; then compared the two TCM, pulmonary fibrosis of intervention with compound medical herbs was lighter than intervention with the single ( P < 0. 05 ). Airway wall thickness and collagen type IV were associated with MMP-1、 TIMP-1 and MMP-9/TIMP-1. Conclusions: The TCM could decrease the deposition of collagen type IV and reduce the airway thickness by regulating MMP-9 and TIMP-1 levels and influencing the balance between MMP-9 and TIMP-1, the compound based on asthmatic basic pathogenesis of TCM is superior to single herbs.%目的:现察中药止喘汤对哮喘大鼠气道重构的干预,并探讨其对基质金属蛋白酶-9(MMP-9)及金属蛋白酶抑制剂-1(TIMP-1)表达的影响.方法:50只Sprague-Dawley(SD)大鼠随机分为正常组、哮喘组、布地奈德(BUD)组、黄芩组及止喘汤组5组.采用卵清白蛋白(OVA)致敏加激

  6. Plasma branched chain amino acid abnormalities in sake-treated rats.

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    Full Text Available Plasma amino acid abnormalities in rats treated with large doses of sake and whisky for 3 days were investigated under adequate nutritional conditions. A significant decrease in plasma branched-chain amino acid (BCAA levels was observed in sake- but not whisky-treated rats. However, known factors affecting BCAA levels, such as serum insulin and plasma glucagon levels ahd BCAA-metabolizing enzyme (BCAA transaminase and branched chain alpha-ketoacid dehydrogenase activities in the liver and skeletal muscle, were not significantly altered in the sake group. Furthermore, ethanol-metabolizing enzyme (alcohol and aldehyde dehydrogenases and the microsomal ethanol-oxidizing system activities in the liver were not altered in the sake group. Other mechanisms need to be considered for explaining the diminished levels of plasma BCAA in sake-treated rats.

  7. 茶多酚对哮喘大鼠气道炎症和气道重塑的干预研究%The Effects of Tea Polyphenols on Airway Inflammation and Airway Remodeling in Asthmatic Rats

    Institute of Scientific and Technical Information of China (English)

    杨青; 王尧; 李里香; 况九龙


    目的:研究茶多酚(TP)对支气管哮喘大鼠早期和晚期气道氧化应激水平及气道炎症、气道重塑的影响.方法:48只大鼠随机分对照组、哮喘组、早布地奈德(BUD)组、晚BUD组、早TP组和晚TP组,每组8只.早BUD组、早TP组在造模前2周药物干预,晚BUD组、晚TP组在造模5周后药物干预.造模12周时观察各项指标.测定支气管壁的平滑肌面积、胶原沉积面积,以及肺组织转化生长因子-β1 (TGF-β1)的表达.测定肺组织TGF-β1含量、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活力.结果:早TP组、晚TP组、早BUD组干预后支气管壁平滑肌面积、胶原沉积面积和TGF-β1含量较哮喘组均有改善(P<0.05或P<0.01).晚BUD组较哮喘组无明显改善(P>0.05).哮喘组肺组织中MDA含量明显上升,SOD活性显著下降,与对照组比较差异有统计学意义(P<0.01);各药物干预后SOD活性均上升,MDA含量均下降,以早TP组最明显(P<0.01).SOD活性与MDA含量呈负相关,TGF-β1含量与MDA含量呈正相关.结论:茶多酚可能通过清除氧自由基,减少气道炎症及氧化应激,从而改善或延缓气道重塑的发生.%Objective: To observe the effects of tea polyphenols (TP) on oxidative stress level, airway inflammation and airway remodeling of early stage and late stage in asthmatic rats. Methods: Forty-eight rats were randomly divided into 6 groups, normal saline group, asthma group, early budesonide (early BUD) group, late BUD group, early TP group and late TP group. Drugs were administrated 2 weeks before sensitizing in early BUD group and early TP group, and administrated 5 weeks after sensitizing in late BUD group and late TP group. The lung tissues were harvested from rats 12 weeks after sensitizing. The smooth muscle area, collagen deposition area and the expression of transforming growth factor-β1 (TGF-βl) were assessed in bronchi and lung tissues. The contents of TGF-β1, malondialdehyde (MDA) and

  8. Improved sexual behavior in male rats treated with a Chinese herbal extract: hormonal and neuronal implications

    Institute of Scientific and Technical Information of China (English)

    Paola Zanoli; Augusta Benelli; Manuela Zavatti; Marianna Rivasi; Claudia Baraldi; Mario Baraldi


    Aim: To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior of adult male rats. Methods: The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavage, acutely (one time, 45 rain before mating test) or subchronically (daily for 10 days) in sexually potent and sexually sluggish/impo-tent rats. Sexual behavior, serum levels of luteinizing hormone (LH) and testosterone (T) were evaluated in treated rats and compared with controls receiving vehicle. The effect of the extract on central dopaminergic neurotransmis-sion was assessed in the nucleus accumbens using a microdialysis technique. Results: In sexually potent rats, both acute and subchronic treatment with the extract dosed at 30 and 60 mg/kg reduced mount latency and intromission latency. In sluggish/impotent rats, the acutely administered extract at the dose of 60 mg/kg shortened ejaculation latency, whereas subchronically administered at the doses of 30 and 60 mg/kg, reduced mount, intromission and ejaculation latencies, increasing also the percentage of mounting and ejaculating rats. The extract dosed at 60 mg/kg significantly increased LH and T following acute and subchronic administration and increased 3,4-dihydroxyphenylacetic acid levels in the nucleus accumbens, 30 rain after the acute administration. Conclusion: The improvement in both appetitive and consummatory components of sexual behavior observed in male rats treated with the extract could be scribed to increased serum T level in parallel with the activation of the central dopaminergic system.

  9. 补脾益气方药对哮喘大鼠嗜酸性粒细胞趋化因子表达的影响%Effect of traditional Chinese medicine prescription for Reinfocing Pi Qi on the expression of eotaxin in asthmatic rat model

    Institute of Scientific and Technical Information of China (English)

    许珂玉; 王艳杰; 赵丹玉; 柳春


    Objective To observe the intervention influence of traditional Chinese medicine (TCM) prescription for Reinfocing Pi Qi on the expression of eotaxin in asthmatic rat, and to explore its possible mechanism. Methods SPF male SD rats were randomly divided into normal control group (A group) . Asthmatic group (B group), normal saline group (C group) , therapeutic group of Dexamethasone (D group), therapaeutic group of TCM prescription for Reinforcing Pi Oi (E group). The asthmatic models were established by the classic way of OVA sensilization and excitation. Dexamethasone and normal saline were used as positive and negative control medicine. TCM prescription for Reinforcing Pi Qi were taken once a day in 1 mL/100 g for 14 days after seting up model in the rats of E group. The number of total cells, percentages of eo-sinophil (EOS), lymphocyte, neutrophil in bronchoaleolar lavage ( BALF) fluid were calculated. Pathological change of lung tissue were observed. The expression of eotaxin on level of mRNA and protein in lung tissue were detected by RT-PCR and Western blot assay. Results EOS number of BALF and expression of eotaxin in B group and C group were higher than those in A group (P 0.05). Conclusion TCM prescription for Reinforcing Pi Qi can decrease the level of eotaxin in asthmatic rats, and alleviate inflammatory cells infiltration in lung, then inhibit airway inflamation.%目的 观察补脾益气方药对哮喘大鼠肺组织嗜酸性粒细胞趋化因子(eotaxin)表达的干预作用.方法 SPF级雄性SD大鼠随机分为对照组(A组)、哮喘组(B组)、生理盐水治疗组(C组)、地塞米松组(D组)和补脾益气方药治疗组(E组).哮喘组通过卵蛋白(OVA)致敏、激发建立大鼠哮喘模型,以生理盐水和地塞米松分别做对照治疗.E组大鼠在复制哮喘模型后,按照1 mL/100 g体质量给予补脾方药1次/d,共14 d.计数肺泡灌洗液细胞总数、嗜酸性粒细胞(EOS)、巨噬细胞、淋巴细胞和中性粒细

  10. Effects of Cupping Therapy on the Pulmonary Functions in Asthmatic Children

    Institute of Scientific and Technical Information of China (English)


    @@ Barely using the cupping therapy, we treated 75asthmatic children at the stage of attack in outpatient department of our hospital from February 2001 toOctober 2002 to observe the changes of theirpulmonary functions before and after treatment. Areport follows.

  11. The cytoskeleton of digitonin-treated rat hepatocytes. (United States)

    Fiskum, G; Craig, S W; Decker, G L; Lehninger, A L


    Treatment of isolated rat hepatocptes with low concentrations of digitonin increases the permeability of the plsma membrane to cytosolic proteins without causing release of organelles such as mitochondria into the surrounding medium. Electron microscopy showed that treatment of the cells with increasing concentations of digitonin results in a progressive loss in the continuity of the plasma membrane, while most other aspects of cellular morphology remain normal. Depletion of background staining material from the cytosol by digitonin treatment of the cells greatly enhances the visualization of the cytoskeleton. The use of this technique, together with immunofluorescent light microscopy, has verified the presence of an actin-containing filamentous network at the hepatocyte cortex as well as intermediate filaments distributed throughout the cell. Digitonin is thus useful both for selectively permeabilizing the plasma membrane and for intensifying the appearance of intracellular structures such as microfilaments that are normally difficult to observe in cells such as hepatocytes.

  12. Complete blood count and acetylcholinesterase activity of lymphocytes of demyelinated and ovariectomized rats treated with resveratrol. (United States)

    Martins, Danieli B; Mazzanti, Cinthia M; Costa, Márcio M; França, Raqueli; Pagnoncelli, Marcielen; Maciel, Roberto M; Schmatz, Roberta; Oliveira, Lizielle; Morsch, Vera; Facco, Grasiela; Visentini, Diandra; Mann, Thais; Mazzanti, Alexandre; Lopes, Sonia T A


    Resveratrol is a phytoestrogen that has many beneficial actions. This study aimed to evaluate the effect of resveratrol on the complete blood count (CBC) and the acetylcholinesterase (AChE) activity of lymphocytes of ovariectomized rats experimentally demyelinated by ethidium bromide (EB). Forty adult female Wistar rats (60 days, 200-220 g) were divided randomly into five groups (n = 4) to evaluate the demyelination phase and five groups (n = 4) to evaluate the remyelination phase. In each phase, the groups consisted of sham rats-G1; ovariectomized rats, not demyelinated, treated only with vehicle (ethanol 25%)-G2; demyelinated ovariectomized rats treated only with vehicle-G3; ovariectomized rats, not demyelinated, treated with resveratrol-G4; and demyelinated ovariectomized rats treated with resveratrol-G5. Only during the remyelination phase, CBC showed a significant difference (p < 0.05) in the number of monocytes between G2 and G5 groups. In the demyelination phase, there was a significant decrease (p < 0.05) in the AChE activity in the G4 group, while the G5 group was statistically similar to the G1, G2 and G4 groups. In the remyelination phase, there were no significant differences in the AChE activity among the groups. The treatment for 7 days with resveratrol with or without the experimental demyelization with EB appears to influence the AChE activity of lymphocytes, without changing the number of these cells in the circulation. However, in the remyelination phase, there seems to be stabilization in its effect on the lymphocyte AChE activity.

  13. A quantitative in-vivo MR imaging study of brain dehydration in diabetic rats and rats treated with peptide hormones. (United States)

    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.

  14. Nicotine ameliorates impairment of working memory in methamphetamine-treated rats. (United States)

    Mizoguchi, Hiroyuki; Ibi, Daisuke; Takase, Fumiaki; Nagai, Taku; Kamei, Hiroyuki; Toth, Erika; Sato, Jun; Takuma, Kazuhiro; Yamada, Kiyofumi


    Nicotine is hypothesized to have therapeutic effects on attentional and cognitive abnormalities in psychosis. In this study, we investigated the effect of nicotine on impaired spatial working memory in repeated methamphetamine (METH)-treated rats. Rats were administered METH (4 mg/kg, s.c.) once a day for 7 days, and their working memory was assessed with a delayed spatial win-shift task in a radial arm maze. The task consisted of two phases, a training phase and a test phase, separated by a delay. Control animals showed impaired performance in the test phase when the delay time was increased to 120 min or longer, while METH-treated rats showed impaired performance with a shorter delay time of 90 min. Memory impairment in METH-treated rats persisted for at least 14 days after drug withdrawal. METH-induced impairment of working memory was reversed by nicotine (0.3mg/kg, p.o., for 7 days), but the effect was diminished 7 days after the withdrawal. In control rats, nicotine decreased the number of working memory errors in the test with delay time of 120 min when administered before the training phase. Neither post-training nor pre-test administration of nicotine had any effect on working memory. These findings suggest that nicotine may have some protective effect against the impairment of working memory.

  15. Reduced bone growth in rats treated with anticonvulsant drugs: a type II pseudohypoparathyroidism? (United States)

    Robinson, P B; Harris, M; Harvey, W; Papadogeorgakis, N


    The effect of anticonvulsant drugs on bone growth and calcium metabolism was studied in Wistar strain rats. Animals were treated for 40-48 days with diphenylhydantoin (DPH) or sodium valproate (SV), or were thyroparathyroidectomized (TPTX) and maintained with thyroxine supplements. Bone growth, measured radiographically as increase in bone length, was reduced by up to 12% in the drug-treated and TPTX groups. Plasma iPTH concentrations were raised twofold- to threefold by DPH and SV. Total plasma calcium was not significantly altered in the DPH-treated rats but was elevated by SV treatment. Similarly, elevated iPTH and normal calcium values were also found in carbamazepine-treated and diazepam-treated rats in a separate experiment. Plasma alkaline phosphatase was reduced by high doses of the drugs. These results imply that anticonvulsant drugs induce end-organ resistance to PTH (a feature of pseudohypoparathyroidism), which may be responsible for some of the skeletal and dental abnormalities found in patients treated with anticonvulsants.

  16. [Studies on the metabolic fate of gomisin A (TJN-101). II. Absorption and excretion in CCl4 treated rats]. (United States)

    Matsuzaki, Y; Matsuzaki, T; Ono, H; Koguchi, S; Takeda, S; Takeda, S; Funo, S; Aburada, M; Hosoya, E; Oyama, T


    The absorption and excretion of gomisin A (TJN-101) in rats whose livers were injured by carbon tetrachloride (CCl4) were investigated. After intravenous administration of TJN-101 at a dose of 5 mg/kg, the terminal elimination half-life was 1.5 h in the CCl4-treated rats, which was two times that in normal rats. The mean area under the blood concentration-time curve (AUC) value of TJN-101 in the CCl4-treated rats was twice that in normal rats, and this difference was significant (p less than 0.05). Therefore, the total body clearance of TJN-101 in the CCl4-treated rats decreased less than half of that in normal rats. Similar results were observed when it was administered orally. In the CCl4-treated rats, the serum concentration of Met. B, which was identified as a demethylenated substance and one of major metabolites, tended to decrease more than that in normal rats. On the other hand, the cumulative biliary excretion ratio of TJN-101 in 24 h after dosing in the CCl4-treated rats was 2.5 times that in normal rats. The excretion rate of Met. B in the bile in the CCl4-treated rats tended to be delayed. However, the quantitative variance of biliary excretion of Met. B was not found in both groups. The urinary excretion of TJN-101 or Met. B in 72 h after dosing in the CCl4-treated rats was lower than that in normal rats. Similar results were also observed in excretion in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. 二黄汤对哮喘模型大鼠肺组织中TGF-β1及体内IL-33的影响%The Effect of Erhuang Decoction on Transforming Growth Factor-β1 of Lung Tissues and the Expression of Leukotriene-33 in Asthmatic Rats

    Institute of Scientific and Technical Information of China (English)

    聂艳辉; 霍博雅; 孙会珍


    Objective To investigate the effect of Erhuang decoction on TGF-β1 expression of lung tiusses and the concentrations of IL-33 in asthmatic rats. Methods Fifty Sprague-Dawley rats were randomly divided into five groups equally:Control group, Asthmatic group, Budesonide aerosol group, High-dose Erhuang decoction group ( 68 g/kg)and Low-dose Erhuang decoction group(17 g/kg). The model of asthma was established by ovalbumin (OVA) sensitizing and challeng-ing. Then Erhuang decoction and budesonide aerosol was used respectively for intervention therapy. Histologic HE staining were used to observe the general pathologic alteration and to analyze the total bronchial wall area (Wat) and the muscle wall area(Wam). The protein expressions of TGF-β1 in the lung tissues were detected by immunohistochemistry. The concentra-tions serum IL-33 and BALF were tested by sandwich ELISA. Results There was significant reduction in the infiltrated inflammatory cells in all drug intervention groups compared with asthma group;The Wat and Wam in asthmatic group was significantly higher in than those in Budesonide aerosol group,High-dose Erhuang decoction group and Low-dose Erhuang decoction group ( Watμm2/μm:54.99±8.82, 52.28±7.61, 58.53±7.63 vs 79.50±5.64, P<0.05;Wamμm2/μm:22.74±2.73, 20.63±1.72, 21.20±4.50 vs 30.16±1.68, P<0.05);Compared with control group, BALF and serum IL-33 concentration were significantly higher in asthmatic group. Compared with asthmatic group, all the indicators were significantly decrease in the treatment groups after drug intervention (P<0.05). Andthere was no significant difference between the treatment groups in all the indicators. TGF-β1 expression in lung tissues in asthmatic group were significantly higher than that in control group (12.60 ± 2.25 vs 1.67 ± 0.17). Compared with asthmatic group, there was significantly reduction of TGF-β1 expression in the Budesonide aerosol group (5.51±2.48), High-dose Erhuang decoction group (5.22±2

  18. Betanin attenuates oxidative stress and inflammatory reaction in kidney of paraquat-treated rat. (United States)

    Tan, Dehong; Wang, Yiheng; Bai, Bing; Yang, Xuelian; Han, Junyan


    The effects of natural pigment betanin on oxidative stress and inflammation in kidney of paraquat-treated rat were investigated. Paraquat was injected intraperitoneally into rats to induce renal damage. The rats were randomly divided into four groups: a control group, a paraquat group, and two paraquat groups that were treated with betanin at 25 and 100 mg/kg/d three days before and two days after paraquat administration. Treatment with betanin alleviated the paraquat-incurred acute kidney injury, evidenced by histological improvement, reduced serum and urine markers for kidney injury. Betanin antagonized the paraquat-induced inflammation, indicated by reduced expression of inducible nitric oxide synthase and cyclooxygenase, blunted activation of nuclear factor kappa B, and diminished lysosomal protease activities. Betanin also decreased oxidative stress elicited by paraquat. In conclusion, betanin may have a protective effect against paraquat-induced acute kidney damage. The mechanisms of the protection appear to be the inhibition of oxidative stress and inflammation.


    NARCIS (Netherlands)



    Subfractions of the hepatic macrophage population, differing in cell size, were isolated from normal rats and rats treated with liposomal muramyl dipeptide (lipMDP) and analyzed histochemically and by ultrastructural peroxidase cytochemistry. The majority of cells in all subfractions of control rats

  20. Pixe analysis of trace elements in tissues of rats treated with anticonvulsants (United States)

    Hurd, R. W.; Van Rinsvelt, H. A.; Kinyua, A. M.; O'Neill, M. P.; Wilder, B. J.; Houdayer, A.; Hinrichsen, P. F.


    Several lines of evidence implicate metals in epilepsy. Anticonvulsant drugs are noted to alter levels of metals in humans and animals. PIXE analysis was used to investigate effects of three anticonvulsant drugs on tissue and brain cortex trace elements. The content of zinc and copper was increased in liver and spleen of rats treated with anticonvulsants while selenium was decreased in cortex.

  1. Evaluation of postpartum behaviour in rats treated with Hypericum perforatum during gestation

    Directory of Open Access Journals (Sweden)

    Vinícius A. Vieira


    Full Text Available Gestational depression is detrimental to the health of the mother and the offspring and contributes to the appearance of depressive and anxiety symptoms during the postnatal period. Traditional antidepressants have undesirable side effects when utilised during gestation, but Hypericum perforatum has been characterised as an efficient and safe antidepressant that prevents the recurrence of symptoms. This study verified the effects of Hypericum perforatumon the behaviour of Wistar rats that were treated during gestation and evaluated 10 and 60 days post-treatment. Pregnant Wistar rats were divided into four groups of ten animals each: one control group that received distilled water and three treatment groups that were treated orally with 36, 72 or 144 mg/kg Hypericum perforatumextract. At 10 and 60 days after parturition and post-treatment, the rats were submitted to the holeboard, the tail suspension, and the forced swim tests. The animals treated with 144 mg/kg Hypericum perforatumexhibited greater head-dipping activity in the hole-board test and reduced immobility in the tail suspension and forced swim tests, suggesting less anxiety and depression 10 and 60 days post-treatment.The results indicated that treating rats with Hypericum perforatumduring the gestational period decreased depressive behaviour and anxiety 10 and 60 days post-treatment.

  2. Cellular fibronectin and von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole

    NARCIS (Netherlands)

    Schultze, A.E.; Emeis, J.J.; Roth, R.A.


    The monocrotaline pyrrole (MCTP)-treated rat is a useful model for the study of certain chronic pulmonary vascular diseases. A single, i.v. administration of a low dose of MCTP causes pneumotoxicity, pulmonary vascular remodeling, sustained increases in pulmonary arterial pressure, and right ventric

  3. Disordered microbial communities in asthmatic airways.

    Directory of Open Access Journals (Sweden)

    Markus Hilty

    Full Text Available BACKGROUND: A rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. We compared the airway microbiota at three levels in adult patients with asthma, the related condition of COPD, and controls. We also studied bronchial lavage from asthmatic children and controls. PRINCIPAL FINDINGS: We identified 5,054 16S rRNA bacterial sequences from 43 subjects, detecting >70% of species present. The bronchial tree was not sterile, and contained a mean of 2,000 bacterial genomes per cm(2 surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were much more frequent in bronchi of adult asthmatics or patients with COPD than controls. We found similar highly significant increases in Proteobacteria in asthmatic children. Conversely, Bacteroidetes, particularly Prevotella spp., were more frequent in controls than adult or child asthmatics or COPD patients. SIGNIFICANCE: The results show the bronchial tree to contain a characteristic microbiota, and suggest that this microbiota is disturbed in asthmatic airways.

  4. Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine. (United States)

    Iranloye, B O; Oludare, G O


    Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat.

  5. Increased DNA damage in blood cells of rat treated with lead as assessed by comet assay

    Directory of Open Access Journals (Sweden)

    Mohammad Arif


    Full Text Available A growing body of evidence suggests that oxidative stress is the key player in the pathogenesis of lead-induced toxicity. The present study investigated lead induced oxidative DNA damage, if any in rat blood cells by alkaline comet assay. Lead was administered intraperitoneally to rats at doses of 25, 50 and 100 mg/kg body weight for 5 days consecutively. Blood collected on day six from sacrificed lead-treated rats was used to assess the extent of DNA damage by comet assay which entailed measurement of comet length, olive tail moment, tail DNA (% and tail length. The results showed that treatment with lead significantly increased DNA damage in a dose-dependent manner. Therefore, our data suggests that lead treatment is associated with oxidative stress-induced DNA damage in rat blood cells which could be used as an early bio-marker of lead-toxicity.

  6. Further evidence of benzene carcinogenicity. Results on Wistar rats and Swiss mice treated by ingestion. (United States)

    Maltoni, C; Conti, B; Perino, G; Di Maio, V


    Wistar rats and Swiss mice were treated by ingestion (stomach tube) with benzene in olive oil at a dose of 500 and 0 mg/kg b.w. once daily, 4-5 days weekly, for 104 weeks (rats) or for 78 weeks (mice). In Wistar rats, benzene caused Zymbal gland carcinomas, carcinomas of the oral cavity, and carcinomas of the nasal cavities, and an increase in the incidence of total malignant tumors. In Swiss mice, benzene produced Zymbal gland carcinomas and dysplasias and an increase in the incidence of mammary carcinomas (in females), lung tumors, and total malignant tumors. These experiments further confirm that benzene is a multipotential carcinogen as was shown before by long-term bioassays performed on Sprague-Dawley rats in the same Experimental Unit.

  7. Zebularine induces long-term survival of pancreatic islet allotransplants in streptozotocin treated diabetic rats.

    Directory of Open Access Journals (Sweden)

    Henrietta Nittby

    Full Text Available BACKGROUND: Coping with the immune rejection of allotransplants or autologous cells in patients with an active sensitization towards their autoantigens and autoimmunity presently necessitates life-long immune suppressive therapy acting on the immune system as a whole, which makes the patients vulnerable to infections and increases their risk of developing cancer. New technologies to induce antigen selective long-lasting immunosuppression or immune tolerance are therefore much needed. METHODOLOGY/PRINCIPAL FINDINGS: The DNA demethylating agent Zebularine, previously demonstrated to induce expression of the genes for the immunosuppressive enzymes indolamine-2,3-deoxygenase-1 (IDO1 and kynureninase of the kynurenine pathway, is tested for capacity to suppress rejection of allotransplants. Allogeneic pancreatic islets from Lewis rats were transplanted under the kidney capsule of Fischer rats previously made diabetic by a streptozotocin injection (40 mg/kg. One group was treated with Zebularine (225 mg/kg daily for 14 days from day 6 or 8 after transplantation, and a control group received no further treatment. Survival of the transplants was monitored by blood sugar measurements. Rats, normoglycemic for 90 days after allografting, were subjected to transplant removal by nephrectomy to confirm whether normoglycemia was indeed due to a surviving insulin producing transplant, or alternatively was a result of recovery of pancreatic insulin production in some toxin-treated rats. Of 9 Zebularine treated rats, 4 were still normoglycemic after 90 days and became hyperglycemic after nephrectomy. The mean length of normoglycemia in the Zebularine group was 67±8 days as compared to 14±3 days in 9 controls. Seven rats (2 controls and 5 Zebularine treated were normoglycemic at 90 days due to pancreatic recovery as demonstrated by failure of nephrectomy to induce hyperglycemia. CONCLUSIONS/SIGNIFICANCE: Zebularine treatment in vivo induces a long

  8. Hydrophilic interaction chromatography-mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats

    NARCIS (Netherlands)

    Kok, Miranda G M; Swann, Jonathan R; Wilson, Ian D; Somsen, Govert W; de Jong, Gerhardus J


    Hydrophilic interaction chromatography-mass spectrometry (HILIC-MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial-host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared t

  9. Transplantation of primary cultured embryonic mesencephalic neural precursor cells for treating Parkinsonian rats

    Institute of Scientific and Technical Information of China (English)

    Li Fei; Chengchuan Jiang; Linyin Feng; Yaodong Ji; Zhongliang Ding


    BACKGROUND: Choosing proper donor cells is one of keys in experimental and clinical studies on cell replacement therapy (CRT) for treating Parkinson disease (PD). Embryonic mesencephalic precursor cells (MPCs) can stably differentiate into dopaminergic neuron after in vitro proliferated culture. As compared with embryonic stem cell and neural stem cell strains, cell composition of embryonic MPCs after primary culture is also the most close to that of embryonic mesencephalic ventral cell suspension without proliferated culture. Successful experience accumulated in the latter suggests that primary cultured embryonic MPCs might be the most potential donor cells in clinical application with CRT for treating PD so far.OBJECTIVE: To investigate the feasibility of primary cultured embryonic precursor cells cultured primarily as donor cells in CRT for treating PD in rats.DESIGN: A randomized and controlled trial taking SD rats as experimental animals.SETTING: Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University.MATERIALS: This experiment was carried out at the Institute of Neuroscience, Shanghai Institute for Biological Science, Chinese Academy of Sciences from July 2003 to June 2004. Totally 26 female SD rats,with body mass of 200 to 220 g, were provided by Shanghai Experimental Animal Center of Chinese Academy of Sciences.METHODS: Stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle were perfored to develop PD model rat. Among 26 SD rats, 20 rats achieved a more than 5 turns/min in apomorphine induced rotation test, reaching the standard of PD model rats. Immunohistochemical detection was performed on 1out of 20 model rats after execution, and the other 19 rats were randomly divided into control group (n=5),sham transplantation group (n=5)and cell grafted group (n=9). Primary cultured E12 MPC cell suspension (1.2×1011 L-1)were used as donor cells. 4 μL primary cultured E12 MPC cell suspension prepared freshly was injected

  10. [Physical activities and sports in asthmatic patients]. (United States)

    Todaro, A


    Asthma patients are too often advised to refrain from sport. Enforced sedentariness, especially in children, leads to muscle hypotonia, reduced mechanical efficiency, paramorphisms, and adverse psychological consequences. Not all asthmatics develop airway spasm as a result of exercise. On the other hand, there are subjects whose bronchial hyper-reactivity is stimulated solely by muscular effort. The pathogenesis of exercise-induced bronchospasm is not fully understood. In any event, numerous studies have demonstrated the beneficial and even therapeutic effect of physical exercise and sport in cases of asthma. Provided they are practised with judgment and in accordance with a suitable programme, swimming, activities of an alternating aerobic and anaerobic type, cross-country skiing, gymnastics, and fencing are primarily indicated. Some asthmatics have also won Olympic medals. In the light of the studies carried out so far, it is strongly suggested that asthmatics be encouraged to take up sport suitable to their psychophysical characteristics, and not kept wrapped up in cotton wool.

  11. Pharmacokinetics of nebulized and oral procaterol in asthmatic and non-asthmatic subjects in relation to doping analysis

    DEFF Research Database (Denmark)

    Krogh, Nanna; Backer, Vibeke; Rzeppa, Sebastian


    The purpose of the present study was to investigate pharmacokinetics of procaterol in asthmatics and non-asthmatics after nebulized and oral administration in relation to doping. Ten asthmatic and ten non-asthmatic subjects underwent two pharmacokinetic trials. At first trial, 4 μg procaterol...... after nebulized administration. For doping control purposes, our observations indicate that it is possible to differentiate therapeutic nebulized administration of procaterol from proh ib ited use of oral procaterol....

  12. Role of Low Dosage Arsenic Trioxide on Pulmonary Dendritic Cells in Asthmatic Mice

    Institute of Scientific and Technical Information of China (English)

    周林福; 殷凯生; 周智敏


    Objective: To investigate the distribution and recruitment of pulmonary dendritic cells (DCs) and the influence of low dosage arsenic trioxide (As2O3) on them in the airway of asthmatic mice. Methods: Thirty BALB/c mice were randomly divided into 3 groups: the control group, the asthmatic group and the As2O3 treated group. The mice asthmatic model was induced via sensitizing with peritoneal injection of ovalbumin (OVA) for two times and then provocated with aerosol inhalation of OVA for a week. The treated group was peritoneally injected with 0.2 ml solution of As2O3 (4mg/kg) 0.5h after each provocation. The immunohistochemistry and computerised image analysis were applied to detect quantitatively the DCs in the lung and airway of mice. Results: All intraepithelial nonlymphoid dendritic cells-145 (NLDC-145) throughout the respiratory tree in the mice of the control group formed a network with the density of DCs varying from (575±54) cells/mm2 epithelial surface in the large airway, to (68±12) cells/mm2 epithelial surface in the small airway. The distribution of airway NLDC-145+ in the asthmatic group was similar to that in the control group, but its density was significantly upregulated (P<0.01). The distribution of airway NLDC-145 in the treated group was similar to that in the asthmatic group, only its density was significantly downregulated (P<0.01). Conclusion: There is an integral network of NLDC-145+ throughout the respiratory tree. To downregulate the density but not change the distribution of pulmonary DCs could be an important therapeutic mechanism of low dosage As2O3 in treating asthma.

  13. Structural Modulation of Gut Microbiota in Rats with Allergic Bronchial Asthma Treated with Recuperating Lung Decoction

    Institute of Scientific and Technical Information of China (English)

    KONG YanHua; SHI Qi; HAN Na; ZHANG Ling; ZHANG YuanYuan; GAO TongXin; CHENChen; LIYouLin


    ObjectiveTo investigate whether recuperating lung decoction (RLD) can modulate the composition of gut microbiota in rats during asthma treatment. MethodsFifteen Sprague-Dawley rats were divided randomly and equally into control group, model group, dexamethasone (DEX) group, RLD medium-dose group, and RLD high-dose group. The asthma model was established in all groups, except for the control group. The rats in the DEX and RLD groups were treated orally with DEX and RLD, respectively. The rats in the control and model groups were treated orally with 0.9% saline. The intestinal bacterial communities were compared among groups using 16S rRNA gene amplification and 454 pyrosequencing. ResultsThe microbial flora differed between the control and model groups, but the flora in the RLD groups was similar to that in the control group. No significant differences were observed between the RLD high-dose and medium-dose groups. RLD treatment resulted in an increase in the level beneficial bacteria in the gut, such asLactobacillusandBifidobacteriumspp. ConclusionOral administration of RLD increased the number of intestinal lactic acid-producing bacteria, such as Lactobacillus andBifidobacterium, in asthma model rats.

  14. Reduced sympathetic neurite outgrowth on uterine tissue sections from rats treated with estrogen. (United States)

    Richeri, Analía; Bianchimano, Paola; Crutcher, Keith A; Brauer, M Mónica


    In order to evaluate the contribution of substrate-bound factors to the extent and patterning of the sympathetic innervation of rat uterus following estrogen treatment, superior cervical ganglion explants from neonatal and adult ovariectomized rats were cultured on tissue sections of fresh frozen uterus from adult ovariectomized rats treated with estrogen or a vehicle. The main findings were: (1) neurite growth was greatly influenced by histological features of the underlying section; (2) on myometrial sections, neurites followed the orientation of the main axis of the longitudinally sectioned muscle cells; (3) neurites showed limited growth on transversally sectioned smooth muscle; (4) neuritic patterning was unaffected by a reduction in migrating ganglionic non-neuronal cells; (5) neurite outgrowth, but not non-neural cell migration, was markedly reduced on myometrial sections from rats treated with estrogen. These results suggest that adult myometrium continues to provide signals allowing the organotypic patterning and growth of sympathetic axons, that estrogen treatment modifies myometrial substrate properties so that it is less supportive for sympathetic neurite growth, and that adult sympathetic neurons retain their ability to recognize substrate-bound cues present in the myometrium. On endometrial sections, neurites formed radially symmetric halos, which were reduced in size on estrogen-treated endometrial substrates. Thus, changes in the neuritogenic capacity of the uterus underlie plasticity in uterine sympathetic nerves, and alterations in substrate-bound factors contribute to the diminished receptivity of the estrogenized uterus to its sympathetic innervation.

  15. Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats

    Directory of Open Access Journals (Sweden)

    Santiago Marfà


    Full Text Available At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1 were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis.


    Directory of Open Access Journals (Sweden)

    Bhatt Swati


    Full Text Available Objective: To evaluate the Acute toxicity study and Anti-asthmatic activity of Zeal Herbal Granules. Materials & Methods: In the present study, acute toxicity study was carried out as per OECD guideline 423. Anti-asthmatic activity of Zeal Herbal Granules was investigated against compound 48/80-induced mast cell degranulation. Percentage mast cell degranulation was calculated at different concentration level i.e.1, 10, 100 and 1000μg/mL. Results: Zeal Herbal Granules showed significant protection of rat mesenteric mast cells from disruption caused by compound 48/80. Significant dose dependent effect was observed in percentage mast cell degranulation at different dose level of Zeal Herbal Granules in comparison to negative control. 26.83% mast cell degranulation was observed at 100μg/mL dose level of Zeal Herbal Granules. Conclusion: The present study revealed that Zeal Herbal Granules has significant anti-asthmatic activity against compound 48/80-induced mast cell degranulation comparable to that produced by Ketotifen fumarate. There was no lethal and toxic reactions found among the tested animals. Zeal Herbal Granules can be a safe and effective drug for patient with asthmatic complaints.

  17. Prostanoid production in the presence of platelet activation in hypoxic cocaine-treated rats. (United States)

    Togna, G; Graziani, M; Sorrentino, C; Caprino, L


    To extend our previous in vitro data, we investigated the effects of cocaine on thromboxane A2 (TXA2) and prostacyclin (PGI2) production in vivo in the rat. To obtain the slight platelet activation that our in vitro experiments showed useful to highlight the effect of cocaine, we infused cocaine in rats in the presence of platelet-activating factors (circulation of blood through a perspex vascular device or by infusion of sodium arachidonate) and in various respiratory conditions. Experiments were conducted in rats breathing atmospheric air (normoxic conditions) and in rats breathing an oxygen-poor mixture (hypoxic conditions). In rats under hypoxic conditions cocaine invariably increased TXA2 plasma levels, whereas in normoxic conditions it increased TXA2 only in the presence of platelet-activating factors. Cocaine significantly increased PGI2 plasma levels in arachidonate-treated rats in hypoxic respiratory conditions; in normoxic conditions cocaine left PGI2 levels unchanged. These results support the hypothesis that in cocaine users who have concomitant pathological conditions able to activate platelets, such as atherosclerosis, coronary vasospasm or ischaemia, or both, cocaine may contribute to the onset of thrombotic phenomena by interfering with the prostaglandin system.

  18. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

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    Gustavo Nino

    Full Text Available BACKGROUND: Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. METHODS: Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. RESULTS: Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. CONCLUSIONS: There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  19. The stereological ratio of stromal/parenchymal components in postnatal prostate tissue of rats prenatally treated with diclofenac sodium


    Kara, Mikail; RAĞBETLİ, Cennet; Koyun, Necat; ÇÖLÇİMEN, Neşe; RAĞBETLİ, Murat


    Since diclofenac sodium extends the pregnancy and affects the fetus, our study aimed to stereologically investigate the components of the rat prostate with prenatally treated with diclofenac sodium. The rats were left overnight to mate. Pregnant animals were kept in a room tempreture with normal light and dark cycles and fed with normal diet. After injections to sham and treated groups for 15 days, 18 male offsprings were housed in three groups (6 placebo; 6 control; 6 treated). The 20 weeks-...

  20. Effects of Combination of Herba Epimedii,Fructus Ligustrilucidi and Dexamethasone on the Balance of ET/NO in the Asthmatic Rats%淫羊藿、女贞子配伍激素对哮喘大鼠ET/NO平衡的影响作用

    Institute of Scientific and Technical Information of China (English)

    高健翔; 张伟华; 刘仁慧


    目的 研究淫羊藿、女贞子配伍糖皮质激素对哮喘大鼠ET/NO平衡的影响作用.方法 在建立普通大鼠哮喘模型的基础上,给予腹腔注射地塞米松2周治疗,同时配合灌胃淫羊藿女贞子煎液,检测肺组织匀浆中ET-1、NO、NOS(分型)含量,并计算ET-1/NO、ET-1/NOS比值.结果 哮喘模型组较正常对照组肺组织ET-1、NO、tNOS、iNOS含量均显著上升,但cNOS含量显著降低,ET/NO无显著改变,ET/cNOS显著升高.与哮喘模型组比较,激素干预组,淫羊藿女贞子组,淫羊藿女贞子合激素组ET-1、iNOS含量、ET/cNOS均显著降低;淫羊藿女贞子合激素组NO含量显著降低;淫羊藿女贞子合激素组、淫羊藿女贞子组的cNOS含量显著上升.结论 淫羊藿女贞子配伍激素防治哮喘的作用与调节ET/NO(NOS)平衡作用有关.%Objective: To investigate the effects of ET/NO adjustment of the combination of Herba Epimedii, Fructus Ligustrilucidi and dexamethasone on asthmatic model in rats. Methods: Asthmatic model was duplicated by OVA(ovalbumin) through sensitizing and challenging in rats. The injection of dexamethasone had been injected into asthmatic model in rats for 2 weeks, compared with the same model in rats added oral administration of Epimedium and Ligustum lucidum. Levels of ET-1 ,NO,tNOS,NOS were investigated.And the ratio of ET-1/NO and ET-1/NOS was calculated. Results: Compared with the normal group,ET-1,NO,tNOS and iNOS content and the ratio of of ET to cNOS in model group were significantly higher,but cNOS content lower. Compared with the model group,the ratio of ET/cNOS and the content of ET-1 ,iNOS,in GC group,YN group and YN+GC group decreased significantly.the content of NO in YN +GC group decreased significantly. The content of cNOS in YN group and YN+GC group increased significantly. Conclusion: The effects of combination of Herba Epimedii, Fructus Ligustrilucici on asthma relates to adjusting the balance of ET/NO (NOS).

  1. Changes in antioxidant defense status in hypercholesterolemic rats treated with Ajuga iva. (United States)

    Bouderbala, S; Lamri-Senhadji, M; Prost, J; Lacaille-Dubois, M A; Bouchenak, M


    The aim of the study was to investigate the effect of aqueous extract of Ajuga iva (Ai) on serum and tissues lipid peroxidation as well as antioxidant enzymes activities in red blood cells (RBC) and tissues, in high hypercholesterolemic rats (HC). Male Wistar rats (n=12) were fed on 1% cholesterol-enriched diet for 15d. After this adaptation phase, hypercholesterolemic rats (total cholesterol=6.5+/-0.6mol/l) were divided into two groups fed the same diet and treated or not with Ai for 15d. Thiobarbituric acid reactive substances (TBARS) concentrations in serum, LDL-HDL(1), HDL(2) and HDL(3) were respectively, 5-, 7.8-, 2.3- and 5-fold lower in Ai treated than untreated hypercholesterolemic groups. TBARS concentrations were 1.4-fold lower in heart and 2.8-fold higher in kidney in Ai-HC treated than untreated HC group. Superoxide dismutase activity was respectively, 1.2- and 1.4-fold higher in RBC and muscle in Ai treated than untreated group. In RBC, Ajuga iva treatment enhanced glutathione peroxidase (GSH-Px) (+9%) and glutathione reductase (GSSH-Red) (+12%) in Ai-HC treated than untreated HC group. GSSH-Red activity was 1.4- and 1.5-fold higher in adipose tissue and heart, respectively and 3.7-fold lower in kidney in Ai treated than untreated group. Liver catalase activity was 1.6-fold higher in Ai treated than untreated group. Adipose tissue and muscle total glutathione content represented in Ai treated group 35% and 36% of the value noted in untreated group. Nitric oxide values of liver, adipose tissue and heart were 3.3-, 2.5- and 3.4-fold higher in Ai-HC than HC group. Ajuga iva treatment enhanced alpha-tocopherol contents (+25%) in Ai treated than untreated group. In conclusion, Ajuga iva treatment is more effective to improve the antioxidant capacity of RBC than that of tissues. Indeed, Ai is able to reduce the oxidative stress in hypercholesterolemic rats by increasing the antioxidant enzymes activity.

  2. Dysregulation of the stress response in asthmatic children. (United States)

    Priftis, K N; Papadimitriou, A; Nicolaidou, P; Chrousos, G P


    The stress system co-ordinates the adaptive responses of the organism to stressors of any kind. Inappropriate responsiveness may account for increased susceptibility to a variety of disorders, including asthma. Accumulated evidence from animal models suggests that exogenously applied stress enhances airway reactivity and increases allergen-induced airway inflammation. This is in agreement with the clinical observation that stressful life events increase the risk of a new asthma attack. Activation of the hypothalamic-pituitary-adrenal (HPA) axis by specific cytokines increases the release of cortisol, which in turn feeds back and suppresses the immune reaction. Data from animal models suggest that inability to increase glucocorticoid production in response to stress is associated with increased airway inflammation with mechanical dysfunction of the lungs. Recently, a growing body of evidence shows that asthmatic subjects who are not treated with inhaled corticosteroids (ICS) are likely to have an attenuated activity and/or responsiveness of their HPA axis. In line with this concept, most asthmatic children demonstrate improved HPA axis responsiveness on conventional doses of ICS, as their airway inflammation subsides. Few patients may experience further deterioration of adrenal function, a phenomenon which may be genetically determined.

  3. Bronchial hyperresponsiveness and anti-asthmatic therapy

    NARCIS (Netherlands)

    Kraan, Jan


    Many asthmatic patients experience shortness of breath or wheezing, when exposed to cold air, or irritants like baking fumes, exhaust gases or cigarette smoke. This clinical phenomenon has been called bronchial hypemsponsiveness (BHR), which is defined as an exaggerated broncho-obstructive response

  4. A novel combination of Chinese medicines to treat advanced cancers and lymphomas in rats

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    Waterhouse Dawn N


    Full Text Available Abstract Background Chinese medicine often targets more than one system and as such comprises several compounds, often in non-purified form, with treatments therefore consisting of whole extracts of herbs rather than isolated compounds. The additive and synergistic effects of the phytochemicals in OMN54, a novel mixture of extracts from three commonly used Chinese medicine components; Ganoderma lucidum, Salvia miltiorrhiza and Scutellaria barbata, were previously demonstrated to have potent anti-cancer activity. This study aims to test whether this heterogeneous, multifunctional and multitargeted agent has an acceptable toxicity profile. Methods We conducted preliminary and formal preclinical tolerability determination of OMN54 in Sprague-Dawley rats. In the preliminary study rats were given OMN54 by oral feeding daily for 14 days at doses of 1000 mg/kg, 1750 mg/kg, 2500 mg/kg or 3000 mg/kg per day. A subsequent daily dosing (x 28, 60, 120 or 180 formal toxicology study was conducted in male and female Sprague-Dawley rats at a dose of single dose of 2000 mg/kg/day. Results Significant body weight loss was noted in one of the rats treated at 3000 mg/kg/day, with decline beginning study day 11. This animal experienced mild GI toxicity in the form of diarrhoea. Gross observation indicated kidney damage (pale kidneys in both this group and in one rat treated at 2500 mg/kg/day. For the later studies, no body weight loss was noted over the course of the study. Blood counts and chemistry were not substantially altered following administration of OMN54, nor were there any findings on histological assessment of organs. Conclusion OMN54 was found to be well tolerated in rat models. OMN54 did not cause any microscopic, anatomic or pathologic changes in exposed animals at the concentrations and under the conditions employed in this study.

  5. Free serum testosterone level in male rats treated with tribulus alatus extracts

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    Walid H. El-Tantawy


    Full Text Available OBJECTIVE: The present study was undertaken to investigate the effect of Tribulus alatus extracts on free serum testosterone in male rats. MATERIALS AND METHODS: Free serum testosterone level was measured in male rats treated with alcoholic extracts of the aerial part without fruits, fruits of Tribulus alatus and their fractions. RESULTS: All tested extracts showed significant increase in the level of free serum testosterone when compared to that of corresponding control, p < 0.05. Statistical comparison of all groups revealed that the maximum level was found in groups treated with chloroformic and ethanolic fractions of fruits extract. CONCLUSION: Tribulus alatus extract appears to possess aphrodisiac activity due to its androgen increasing property.

  6. Histological changes in testes of rats treated with testosterone, nandrolone, and stanozolol (United States)

    Mohd Mutalip, Siti Syairah; Surindar Singh, Gurmeet Kaur; Mohd Shah, Aishah; Mohamad, Mashani; Mani, Vasudevan; Hussin, Siti Nooraishah


    Background: Anabolic androgenic steroids (AAS) is being used in medical treatments, but AAS also was identified to have the risks of adverse effects towards patients and consumers health. Objective: Present study was conducted to observe the effects of testosterone, nandrolone, and stanozolol (forms of AAS) intake during onset of puberty on the rat testicular histology. Materials and Methods: Juvenile male Sprague-Dawley (SD) rats (n=42) were divided into seven groups and were injected subcutaneously with medium dose of polyethylene glycol-200 (PEG-200) (control), testosterone, nandrolone, and stanozolol for six weeks (PND 41-87). The animals were weighed daily and sacrificed on PND 88. Testes were removed, weighed, and prepared for histological assessment and finally specimens were observed under microscope. Results: The results showed an insignificant increase in mean daily body weight with highest and lowest body weight gained was of 177.6±1.69 gr and 140.0±12.26 gr respectively. There was significant decrease in the testes absolute weight (p≤0.01) in all experimental groups except in the nandrolone 2.5 mg/kg/week treated group. Testicular histology of rats treated with AAS also showed slight changes in the uniformity of arrangements of seminiferous tubules. Conclusion: Data from present study suggests that AAS have been initiating the adverse effects on testicular normal functions in rats during onset of puberty. PMID:24639803

  7. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

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    Michal Sarna

    Full Text Available During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.

  8. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts. (United States)

    Sarna, Michal; Wojcik, Katarzyna A; Hermanowicz, Pawel; Wnuk, Dawid; Burda, Kvetoslava; Sanak, Marek; Czyż, Jarosław; Michalik, Marta


    During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.

  9. The antioxidant and antigenotoxic effects of pycnogenol(®) on rats treated with cisplatin. (United States)

    Aydin, Birsen; Unsal, Meftun; Sekeroglu, Zulal A; Gülbahar, Yavuz


    Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin-induced toxicity. Pycnogenol® is known for its strong antioxidant and anti-inflammatory effects. In this study, the possible protective effects of pycnogenol on kidney, bone marrow, and red blood cells in rats treated with cisplatin were investigated. The rats were divided into four groups. Group 1 was the control and groups 2, 3, and 4 were orally treated with pycnogenol (200 mg/kg bw, o.p) for 5 days, treated with cisplatin (7 mg/kg bw, i.p.) on the fifth day and treated with cisplatin plus pycnogenol, respectively. Antioxidative parameters in kidney and red blood cells were measured. Chromosome anomalies in bone marrow and renal histopathology were also investigated. Activities of pro-oxidant enzymes (myeloperoxidase and xanthine oxidase), malondialdehyde, and nitric oxide levels significantly increased but antioxidant enzymes activities decreased in the kidneys and red blood cells after cisplatin treatment. Pycnogenol treatment prior to the administration of cisplatin significantly decreased cisplatin-induced injury, as evidenced by its normalizing these parameters. Chromosomal aberrations decreased and mitotic index frequencies increased in bone marrow treated with cisplatin plus pycnogenol. These findings suggest that pycnogenol may be a useful protective agent against the toxicity associated with cisplatin therapy.

  10. Metabolomic analysis reveals metabolic disturbance in the cortex and hippocampus of subchronic MK-801 treated rats.

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    Liya Sun

    Full Text Available BACKGROUND: Although a number of proteins and genes relevant to schizophrenia have been identified in recent years, few are known about the exact metabolic pathway involved in this disease. Our previous proteomic study has revealed the energy metabolism abnormality in subchronic MK-801 treated rat, a well-established animal model for schizophrenia. This prompted us to further investigate metabolite levels in the same rat model to better delineate the metabolism dysfunctions and provide insights into the pathology of schizophrenia. METHODS: Metabolomics, a high-throughput investigatory strategy developed in recent years, can offer comprehensive metabolite-level insights that complement protein and genetic findings. In this study, we employed a nondestructive metabolomic approach (1H-MAS-NMR to investigate the metabolic traits in cortex and hippocampus of MK-801 treated rats. Multivariate statistics and ingenuity pathways analyses (IPA were applied in data processing. The result was further integrated with our previous proteomic findings by IPA analysis to obtain a systematic view on our observations. RESULTS: Clear distinctions between the MK-801 treated group and the control group in both cortex and hippocampus were found by OPLS-DA models (with R(2X = 0.441, Q(2Y = 0.413 and R(2X = 0.698, Q(2Y = 0.677, respectively. The change of a series of metabolites accounted for the separation, such as glutamate, glutamine, citrate and succinate. Most of these metabolites fell in a pathway characterized by down-regulated glutamate synthesis and disturbed Krebs cycle. IPA analysis further confirmed the involvement of energy metabolism abnormality induced by MK-801 treatment. CONCLUSIONS: Our metabolomics findings reveal systematic changes in pathways of glutamate metabolism and Krebs cycle in the MK-801 treated rats' cortex and hippocampus, which confirmed and improved our previous proteomic observation and served as a valuable reference to

  11. Memory and hippocampal architecture following short-term midazolam in western diet-treated rats. (United States)

    Rosenberger, Dorothea S; Falangola, Maria F; Ledreux, Aurélie; Nie, Xingju; Suhre, Wendy M; Boger, Heather A; Granholm, Ann-Charlotte


    The impact of short-term benzodiazepine exposure on cognition in middle-aged or older patients is a highly debated topic among anesthesiologists, critical care physicians and public media. "Western diet" (WD) consumption is linked to impaired cognition as well. The combination of benzodiazepines with substantial exposure to WD might set the stage for increased hippocampal vulnerability for benzodiazepines leading to exaggerated cognitive impairment in the postoperative period. In this study, Fischer 344 rats were fed either WD or standard rodent diet from 5 to 10.5 months of age. Rats were exposed to midazolam or placebo two days prior to an MRI scan using Diffusional Kurtosis Imaging (DKI) to assess brain microstructural integrity, followed by behavioral testing using a water radial arm maze. Hippocampal tissue was collected to assess alterations in protein biochemistry in brain regions associated with learning and memory. Our results showed that rats exposed to the combination of midazolam and WD had significantly delayed time of learning and exhibited spatial memory impairment. Further, we observed an overall increase of kurtosis metrics in the hippocampus and increased expression of the mitochondrial protein VDAC2 in midazolam-treated rats. Our data suggest that both the short-acting benzodiazepine midazolam and WD contribute to negatively affect the brain in middle-aged rats. This study is the first application of DKI on the effects of midazolam and WD exposure, and the findings demonstrate that diffusion metrics are sensitive indicators of changes in the complexity of neurite architecture.

  12. Reproductive performance of rats treated with defatted jojoba meal or simmondsin before or during gestation. (United States)

    Cokelaere, M; Daenens, P; Decuypere, E; Flo, G; Kühn, E; Van Boven, M; Vermaut, S


    The effects on food intake, growth and reproductive performance parameters of defatted jojoba meal and pure simmondsin, an extract from jojoba meal, were compared in female Wistar rats. Rats fed 0.15% simmondsin or 3% defatted jojoba meal (equivalent to 0.15% simmondsin) for 8 weeks before conception showed a similar reduction in food intake (about 20%) and a similar growth retardation compared with controls. Both treatments induced a reduction in the number of corpora lutea on gestation day 16: this effect could be ascribed to the lower food intake before conception because it was also observed in rats pair-fed to the treated ones. Rats given feed containing 0.15% simmondsin or 3% defatted jojoba meal during days 1-16 of gestation showed a similar reduction in food intake relative to controls. Foetal and placental weights were reduced, relative to controls, to a similar extent in both groups, and the reductions were slightly greater than in the corresponding pair-fed groups. We conclude that the effects on food intake, growth and reproductive performance that were seen after feeding rats defatted jojoba meal were due to the simmondsin content of the meal. The simmondsin induced reduction in food intake and probably also a relative protein shortage.

  13. Alterations in gonado somatic index, seminogram and testosterone profiles in rats treated with hexaconazole

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    P. Ravi Kumar,


    Full Text Available Hexaconazole, a triazole fungicide is widely used in crop protection. The ability of the triazoles to inhibit cytochromes P450 dependent enzymes that play an important role in steroid hormone synthesis has been reported earlier. Hence, the possible effect of hexaconazole on male accessory sex organs, seminogram and serum testosterone level was studied in male rats. A total of eighty wistar rats aged 10-12 weeks, were randomly assigned to four groups, each with twenty rats. Group I served as control and received corn oil per os @ 1ml/kg body weight. Groups II, III and IV were given hexaconazole suspension in corn oil daily @ 22.5 55.0 and 110.0mg/kg, per os , orally. Ten rats in each group were sacrificed on 30th day, while the remaining ten rats were sacrificed on 60th day. Weights of testis, prostate gland and seminal vesicles were recorded in all the rats and epididymal sperm reserve was analyzed for seminogram. Testosterone levels were also studied in the serum of treated rats. Results indicated that hexaconazole significantly decreased the weights of testis, prostate and seminal glands, indicating a decrease in gonado somatic index. The seminogram was found adversely affected in terms of decreased total epididymal sperm count and motility and increased dead sperm percent and abnormal sperm percent. Serum testosterone levels were found significantly lowered by hexaconazole both after 30 days and 60 days treatments. Decreased gonado somatic index was attributed to decreased circulating testosterone levels. Adverse affects on seminogram might have occurred from lowered testosterone levels as well as alterations in epididymal milieu due to possible presence of hexaconazole and/or its metabolites.

  14. Erlotinib preserves renal function and prevents salt retention in doxorubicin treated nephrotic rats.

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    Raed N Bou Matar

    Full Text Available Nephrotic syndrome is associated with up-regulation of the heparin-binding epidermal growth factor (HB-EGF. Erlotinib blocks the activation of the epidermal growth factor receptor (EGFR in response to HB-EGF. This study investigates the effect of Erlotinib on the progression of proteinuria, renal dysfunction, and salt retention in doxorubicin treated nephrotic rats. Male rats were divided into 3 pair-fed groups (n = 13/group as follows: Control rats (Ctrl; rats receiving intravenous doxorubicin (Dox; and rats receiving intravenous doxorubicin followed by daily oral Erlotinib (Dox + Erl. Upon establishment of high grade proteinuria, urine sodium and creatinine clearance were measured. Kidney tissue was dissected and analyzed for γ-epithelial sodium channel (γENaC, sodium-potassium -chloride co-transporter 2 (NKCC2, sodium chloride co-transporter (NCC, aquaporin 2 (AQP2, and EGFR abundances using western blot. Creatinine clearance was preserved in the Dox + Erl rats as compared to the Dox group (in ml/min: Ctrl: 5.2±.5, Dox: 1.9±0.3, Dox + Erl: 3.6±0.5. Despite a minimal effect on the degree of proteinuria, Erlotinib prevented salt retention (Urinary Na in mEq/d: Ctrl: 2.2±0.2, Dox: 1.8±0.3, Dox + Erl: 2.2±0.2. The cleaved/uncleaved γENaC ratio was increased by 41±16% in the Dox group but unchanged in the Dox + Erl group when compared to Ctrl. The phosphorylated EGFR/total EGFR ratio was reduced by 74±7% in the Dox group and by 77±4% in the Dox + Erl group. In conclusion, Erlotinib preserved renal function and prevented salt retention in nephrotic rats. The observed effects do not appear to be mediated by direct blockade of EGFR.

  15. Accumbal FosB/DeltaFosB immunoreactivity and conditioned place preference in alcohol-preferring AA rats and alcohol-avoiding ANA rats treated repeatedly with cocaine. (United States)

    Marttila, Kristiina; Petteri Piepponen, T; Kiianmaa, Kalervo; Ahtee, Liisa


    Transcription factor DeltaFosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of DeltaFosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/DeltaFosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/DeltaFosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats.

  16. Differential expression of parvalbumin in neonatal phencyclidine-treated rats and socially isolated rats. (United States)

    Kaalund, Sanne S; Riise, Jesper; Broberg, Brian V; Fabricius, Katrine; Karlsen, Anna S; Secher, Thomas; Plath, Niels; Pakkenberg, Bente


    Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration of parvalbumin-positive interneurons (PV(+) interneurons). In this study, we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia: the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical fractionator, we counted neurons, PV(+) interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV(+) interneurons (p = 0.021) and glial cells (p = 0.024) in the mPFC of neonatal phencyclidine rats, but not in SI rats. We observed no alterations in the total number of neurons, hippocampal PV(+) interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV(+) interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment is not limited to neuronal populations.

  17. Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes. (United States)

    Olver, T Dylan; McDonald, Matthew W; Grisé, Kenneth N; Dey, Adwitia; Allen, Matti D; Medeiros, Philip J; Lacefield, James C; Jackson, Dwayne N; Rice, Charles L; Melling, C W James; Noble, Earl G; Shoemaker, J Kevin


    Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

  18. Effect of acrolein exposure on the percentage of CD4 + CD25 + regulatory T cells and expression of transcription factor Foxp3 in asthmatic rats%丙烯醛暴露对哮喘大鼠CD4+CD25+调节性T细胞及转录因子Foxp3表达的影响

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    魏明; 涂玲; 梁颖红; 刘佳; 张俊华; 龚艳杰


    Objective This work was intended to investigate the effect of acrolein fog exposure on the ratio of CD4 + CD25 + regulatory T cells(Treg) and expression of transcription factor Foxp3 in asthmatic rats.Methods Sixty 6 - 8 weeks male Wistar rats were randomly divided into 4 groups according to random number table ( 15 rats for each group ) which were control group (animnals were treated with saline ),aerosolized ovalbumin( OVA )exposure group,acrolein exposure group and combined OVA and aerolein fog exposure group,respectively.The rats were exposed to air or/and to saline or OVA aerosol for 6 - 8 weeks respectively.24 h after the last challenge,4 ml of peripheral blood and lung tissue were collected from each rat.The percentage of CD4 + CD25 + T cells was determined by flow cytometry analysis.The concentration of interleukin-4(IL-4) and γ-interferon (IFN-γ)in peripheral blood and lung homogenates were measured by ELISA.The protein expression of Foxp3 in the lung was detected by Western blotting.Results The percentage of CD4 + CD25+ T cells in aerosolized OVA group( (6.23 ± 1.1 1 )% )was significantly lower than that in the normal saline group( ( 9.97 ± 1.23 )% ) ( P < 0.01 ).The percentage of CD4 + CD25 + T cells ((3.26 ±0.84)% )in OVA combined acrolein fog exposure group was remarkably lower than that in the aerosolized OVA exposure group and in the normal saline group( P < 0.01 ).11-4 in both plasma and lung ( (22.57 ±4.34),(0.86 ±0.12) ng/L) was significantly increased in the OVA exposed rats compared with the normal saline group( ( 11.57 ±2.86),(0.31 ±0.10) ng/L) ( P <0.01 ).Further remarkable increase in IL-4 of both plasma and lung tissue was observed in the group exposed to both OVA and acrolein ( ( 34.32 ± 6.21 ),( 1.45 ±0.32)ng/L) compared with the aerosolized OVA exposure group and the normal saline group( P < 0.05 ).γ-IFN of plasma and lung tissue in OVA exposed group ( ( 59.67 ± 20.12 ),( 0.56 ±0.17)ng/L) was significantly

  19. Using bosentan to treat paraquat poisoning-induced acute lung injury in rats.

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    Zhongchen Zhang

    Full Text Available BACKGROUND: Paraquat poisoning is well known for causing multiple organ function failure (MODS and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning. OBJECTIVE: To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat. METHOD: A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning; the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day; and a control group (rats were administered intragastric physiological saline. On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1, endothelin-1 (ET-1, and hydroxyproline (HYP in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes. RESULT: The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered. CONCLUSION: Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

  20. Ultra structural study of the rat cheek epithelium treated with Neem extract. (United States)

    Azmi, Muhammad Arshad; Khatoon, Nasira; Ghaffar, Rizwana Abdul


    The purpose of this study was to investigate the effects of neem extract (Azadirachta indica A. Juss) on the ultrastructure of the rat oral epithelium, because neem extract has been added in the tooth paste as an anti-plaque-forming substance in Asian countries. The non-toxic dose of 2000 mg/kg body weight of Neem extract (NBE) was applied daily to the surface of buccal epithelium for four weeks and controls did not receive Neem extract. After four weeks cheek epithelial tissues were excised and processed for light microscopy, scanning and transmission electron microscopy. Light microscopy did not show significant differences between NBE-treated and control epithelium. Difference between control and treated rats weight was non-significant. Moreover, time period was also non-significant. Irregular cell surfaces were noticed when compared to control specimens when examined by scanning electron microscopy. Under transmission electron microscopy, wider intercellular spaces were observed in the treated epithelial spinous cellular layers when compared to control. Further, more keratohyalin granules were present in experimental granular cells. It was concluded that present study showed differences between Neem-treated and control in epithelial tissues but these structural differences may not be related to adverse side effects of the Neem extract.

  1. Role of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol-treated rats. (United States)

    Zhong, Z; Connor, H D; Mason, R P; Qu, W; Gao, W; Lemasters, J J; Thurman, R G


    Reperfusion injury was studied in blood-free perfused livers from fat-loaded, ethanol-treated rats. Rats were pair-fed a modified Lieber-DeCarli liquid diet containing 36% calories as ethanol or isocaloric maltose-dextrin for 4 to 5 weeks. Reperfusion injury to the liver, which occurs in previously hypoxic regions upon reintroduction of oxygen, was studied in a low-flow, reflow perfusion model. Lactate dehydrogenase in effluent perfusate increased from basal levels of < 1 to 17 IU/g/h in livers from controls, whereas prior alcohol treatment elevated values to 37 IU/g/h. Pretreatment of rats with gadolinium chloride (GdCl3, 20 mg/kg i.v.), a selective Kupffer cell toxicant, minimized lactate dehydrogenase release during reperfusion to 7 to 8 IU/g/h in livers from both groups. Rates of malondialdehyde production were 144 and 166 nmol/g/h during reperfusion in control and alcohol-treated rats, respectively, but values reached only 54 and 79 nmol/g/h after GdCl3 treatment. Interestingly, a typical PBN/carbon-centered free radical adduct signal was detected in bile of livers from ethanol-treated rats, but not in controls or ethanol-treated rats given GdCl3. Portal pressure increased during the reperfusion period in livers from alcohol-treated rats, although not in controls, and GdCl3 reduced it significantly. Taken together, these data indicate that reperfusion injury is greater in fatty livers from alcohol-treated rats in a blood-free model. Inactivation of Kupffer cells minimized reperfusion injury in both control and alcohol-treated rats, most likely by diminishing lipid peroxidation thereby improving hepatic microcirculation.

  2. Study on effect of Baisha Green tea extract on blood pressure in treating spontaneous hypertension rats

    Institute of Scientific and Technical Information of China (English)

    Dao-rui Yu; Li-ping Ji; Yi-hong He; Jing Zhou; Chang-yan Wu; Qi-bing Liu


    Objective:To explore the effect and Mechanisms of Baisha Greentea extract on blood pressure in treating spontaneous hypertension rats.Methods:The 60 primary hypertensive rats (SHR) were randomly divided into hypertension of control group, amlodipine besylate group and the high, medium and low dose group of green tea extract of five groups, with twelve rats in each group. All treatments were given through oral, and the control group with distilled water. Each measurement of rat blood pressure was detected in the morning every week. After 7 weeks treatment, blood was collected from the rat abdominal aorta for determination of serum nitric oxide (NO) and superoxide dismutase (SOD) activity and level of plasma angiotensin II. At the same time, heart tissue was embedded in 10% neutral buffered formaldehyde fixation, paraffin and sectioned, And then observe the changes of histopathological after HE staining. Results: Compared with the SHR control group, Systolic and diastolic blood pressure of essential hypertension in high dose group and middle dose group and Amlodipine group had significantly reduced. At the same time, the NO and SOD contents of Baisha Greentea extract in high dose group (200 mg•kg-1•d-1) and middle dose group (100 mg•kg-1•d-1) and Amlodipine group (0.5 mg•kg-1•d-1) had significantly increased.Conclusion:Long-term ingestion of Baisha Greentea extract could significantly elevated serum NO and SOD levels of SHR, reduce the level of plasma angiotensinⅡ to common level, while reversed the hypertensive rat myocardial remodeling effectively.

  3. Immunohistochemical profile of some neurotransmitters and neurotrophins in the seminiferous tubules of rats treated by lonidamine

    Directory of Open Access Journals (Sweden)

    M Artico


    Full Text Available Lonidamine (LND or [1-(2,4-dichlorobenzyl-1H-indazole-3- carboxylic acid] is an anticancer and antispermatogenic drug that exerts a large number of effects on tumor cells and germ cells. Sexually mature male Sprague-Dawley rats were housed at 22°C on a 12-h light/12-h dark cycle 1 week before the experiments, with free access to food and water. LND was suspended in 0.5% methylcellulose at a concentration of 10 mg/mL and administered orally at the dose of 10 mL/kg (b.w. as a single dose. Control rats received an equal amount of vehicle. Testes were removed, fixed for 24 h in 2% glutaraldehyde and 2% paraformaldehyde in 0.1 M sodium phosphate (pH 7.2 at 22°C, rinsed with the same buffer, and stored at room temperature. From each sample, a block of tissue was removed by sectioning through the organ. After dehydration in ethanol at increasing concentrations (70-100%, each block was embedded in paraffin and serial 5 mm thick sections were cut using a rotatory microtome. The immunoreactivity for NTs has been observed in spermatogonia of untreated rats, while the rats treated with LND showed an immunohistochemical localization in all the stages of germinal cells. The generally well-expressed immunoreactivity for the neurotrophins receptors in treated rats observed in our study is presumably attributable to alterations of the receptors’ structure and/or expression leading to changes of the activity, affinity, localization or protein interactions that may depend on sensitization of ion channels (induced by LND. Neurotrophins (NTs appear to be interesting proteins for the modulation of sperm maturation and motility with a prominent role for the nerve growth factor (NGF, that may exert an autocrine or paracrine role.We therefore investigated the location and distribution of immunoreactivity for some neurotransmitters (SP, VIP, CGRP, nNOS, Chat, neurotrophins (NGF, BDNF, NT-3 and their own receptors (TrKA, TrKB, TrKC, p75 in the seminiferous tubules of

  4. Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

    Directory of Open Access Journals (Sweden)

    Andrés Quesada

    Full Text Available This study analyzes the fluorimetric determination of alanyl- (Ala, glutamyl- (Glu, leucyl-cystinyl- (Cys and aspartyl-aminopeptidase (AspAp urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG, albumin, and neutrophil gelatinase-associated lipocalin (NGAL. Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259 with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

  5. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats. (United States)

    Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin


    Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

  6. Efficacy of curcumin to reduce hepatic damage induced by alcohol and thermally treated oil in rats. (United States)

    El-Deen, Nasr A M N; Eid, Mohamed


    The authors investigated the effect of curcumin on markers of oxidative stress and liver damage in rats that chronically ingested alcohol and heated oil. Nine groups of ten Wistar male rats received combinations of curcumin 100 mg/kg body weight daily, ethanol 5 mg/kg, 15% dietary sunflower oil and 15% heated sunflower oil for 12 weeks. Serum and liver tissue were collected. Groups 4-6, which had received compounds causing oxidative stress, showed increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein and reduced high density lipoprotein, protein and albumin, compared with the controls. Reductions were observed in glutathione peroxidase and reductase gene expression, superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione concentration and catalase enzyme activity. Groups 7, 8 and 9 which received curcumin with heated oil, ethanol or both, showed lower elevations in serum and oxidative damage markers compared with the corresponding non-curcumin treated groups. It can be concluded that curcumin reduces markers of liver damage in rats treated with heated sunflower oil or ethanol.

  7. Adrenal steroidogenesis disruption caused by HDL/cholesterol suppression in diethylstilbestrol-treated adult male rat. (United States)

    Haeno, Satoko; Maeda, Naoyuki; Yamaguchi, Kousuke; Sato, Michiko; Uto, Aika; Yokota, Hiroshi


    The synthetic estrogen diethylstilbestrol is used to prevent miscarriages and as a therapeutic treatment for prostate cancer, but it has been reported to have adverse effects on endocrine homeostasis. However, the toxicity mechanism is poorly understood. Recently, we reported that diethylstilbestrol impairs adrenal steroidogenesis via cholesterol insufficiency in adult male rats. In the present study, we found that the adrenal cholesterol level was significantly reduced without of the decrease in other precursors in the adrenal steroidogenesis 24 h after a single dose of diethylstilbestrol (0.33 μg/g body mass). The serum HDL/cholesterol level was also reduced only 12 h after the diethylstilbestrol exposure. The level of Apo E, which is indispensable for HDL/cholesterol maturation, was decreased in both the HDL and VLDL/LDL fractions, whereas the level of Apo A1, which is an essential constituent of HDL, was not altered in the HDL fraction. Because the liver is a major source of Apo E and Apo A1, the secretion rates of these proteins were examined using a liver perfusion experiment. The secretion rate of Apo A1 from the liver was consistent between DES-treated and control rats, but that of Apo E was comparatively suppressed in the DES-treated rats. The disruption of adrenal steroidogenesis by diethylstilbestrol was caused by a decrease in serum HDL/cholesterol, which is the main source of adrenal steroidogenesis, due to the inhibition of Apo E secretion from the liver.

  8. Functional changes in piriform cortex pyramidal neurons in the chronic methamphetamine-treated rat. (United States)

    Hori, Nobuaki; Kadota, Tomoko; Akaike, Norio


    Chronic treatment of rats with methamphetamine (MAP) causes a range of functional changes to the central nervous system (CNS), including a toxicity that is widespread throughout the brain (Frost and Cadet 2000; Fasihpour et al. 2013). In this report, we examined the effect of chronic MAP treatment on pyramidal neurons of the rat piriform cortex, an area involved in sensory processing, associative learning and a model system for studies on synaptic plasticity. MAP treatment significantly depolarized the membrane potential and decreased neuronal input resistance. Furthermore, the voltage-dependence of both AMPA and NMDA responses was disturbed by chronic MAP treatment, and the extent of long-term potentiation (LTP) was decreased. Morphological changes of MAP-treated rat pyramidal neurons were observed as blebbing of the dendrite trees. The changes we observed represent detrimental effects on the function of piriform cortical neurons further illustrating deficits in synaptic plasticity extend beyond the hippocampus. These changes may contribute to behavioural deficits in chronic MAP-treated animals.

  9. Efficacy of curcumin to reduce hepatic damage induced by alcohol and thermally treated oil in rats

    Directory of Open Access Journals (Sweden)

    Nasr A.M.N. El-Deen


    Full Text Available The authors investigated the effect of curcumin on markers of oxidative stress and liver damage in rats that chronically ingested alcohol and heated oil. Nine groups of ten Wistar male rats received combinations of curcumin 100 mg/kg body weight daily, ethanol 5 mg/kg, 15% dietary sunflower oil and 15% heated sunflower oil for 12 weeks. Serum and liver tissue were collected. Groups 4-6, which had received compounds causing oxidative stress, showed increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein and reduced high density lipoprotein, protein and albumin, compared with the controls. Reductions were observed in glutathione peroxidase and reductase gene expression, superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione concentration and catalase enzyme activity. Groups 7, 8 and 9 which received curcumin with heated oil, ethanol or both, showed lower elevations in serum and oxidative damage markers compared with the corresponding non-curcumin treated groups.It can be concluded that curcumin reduces markers of liver damage in rats treated with heated sunflower oil or ethanol.

  10. Identification of differentially expressed genes in aflatoxin B1-treated cultured primary rat hepatocytes and Fischer 344 rats. (United States)

    Harris, A J; Shaddock, J G; Manjanatha, M G; Lisenbey, J A; Casciano, D A


    Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR-based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1-responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.

  11. Differential expression of parvalbumin interneurons in neonatal phencyclidine treated rats and socially isolated rats

    DEFF Research Database (Denmark)

    Kaalund, Sanne Simone; Riise, Jesper; Broberg, Brian;


    Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration...... of parvalbumin-positive interneurons (PV(+) interneurons). In this study we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia, the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical...... phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV(+) interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment...

  12. Change of bronchial hyperresponsiveness in asthmatic children

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    Stojković-Anđelković Anđelka


    Full Text Available Introduction. Bronchial hyperresponsiveness (BHR is a factor in predicting bronchial asthma independently of inflammation markers. Objective. The aims were to determine the frequency and important predictive facts of BHR and the effect of prophylaxis by Global Initiative for Asthma (GINA and National Asthma Education and Prevention Program (NAEPP on BHR in asthmatic children. Methods. BHR in 106 children was evaluated by the bronchoprovocation test with methacholine. Results. The prevalence rate of symptomatic BHR is 18% for crucial point of PC20=4.1±3.03 mg/ml and PD20=3.22±2.59 μmol methacholine. On average asthmatic children express moderate BHR, which persists even two years after administering prophylaxis. After two years bronchial reactivity is significantly smaller, the change of FEV1 is significantly smaller, the velocity of change of slope dose response curve (sDRC is faster and the provocative concentration of methacholine that causes wheezing is 2-3 times lower. A mild sDRC shows milder bronchoconstriction after two years. The fast change of bronchial reactivity in 41% of asthmatic children is contributed to aero-pollution with sulfur dioxide and/ or, possible insufficient and/or inadequate treatment during two years of administering prophylaxis. A simultaneous effect of allergens from home environment and grass and tree pollens and of excessive aero-pollution on children’s airways is important in the onset of symptomatic BHR. After two years of treatment by GINA and NAEPP children do not show asthma symptoms or show mild asthma symptoms, however bronchial sensitivity remains unchanged. Conclusion. Optimal duration of anti-inflammatory treatment in asthmatic children who show moderate bronchial hyperresponsiveness should be longer than two years.

  13. The transcription factor PU.1 promotes alternative macrophage polarization and asthmatic airway inflammation. (United States)

    Qian, Feng; Deng, Jing; Lee, Yong Gyu; Zhu, Jimmy; Karpurapu, Manjula; Chung, Sangwoon; Zheng, Jun-Nian; Xiao, Lei; Park, Gye Young; Christman, John W


    The transcription factor PU.1 is involved in regulation of macrophage differentiation and maturation. However, the role of PU.1 in alternatively activated macrophage (AAM) and asthmatic inflammation has yet been investigated. Here we report that PU.1 serves as a critical regulator of AAM polarization and promotes the pathological progress of asthmatic airway inflammation. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, conditional PU.1-deficient (PU/ER(T)(+/-)) mice displayed attenuated allergic airway inflammation, including decreased alveolar eosinophil infiltration and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. The reduced asthmatic inflammation in PU/ER(T)(+/-) mice was restored by adoptive transfer of IL-4-induced wild-type (WT) macrophages. Moreover, after treating PU/ER(T)(+/-) mice with tamoxifen to rescue PU.1 function, the allergic asthmatic inflammation was significantly restored. In vitro studies demonstrate that treatment of PU.1-deficient macrophages with IL-4 attenuated the expression of chitinase 3-like 3 (Ym-1) and resistin-like molecule alpha 1 (Fizz-1), two specific markers of AAM polarization. In addition, PU.1 expression in macrophages was inducible in response to IL-4 challenge, which was associated with phosphorylation of signal transducer and activator of transcription 6 (STAT6). Furthermore, DRA challenge in sensitized mice almost abrogated gene expression of Ym-1 and Fizz-1 in lung tissues of PU/ER(T)(+/-) mice compared with WT mice. These data, all together, indicate that PU.1 plays a critical role in AAM polarization and asthmatic inflammation.

  14. Inhaled different Concentrations of Budesonide in Early Phase Interfere in Airway Inflammation and Remodeling in Asthmatic Rats%早期吸入不同浓度布地奈德对哮喘大鼠气道炎症和重构的干预

    Institute of Scientific and Technical Information of China (English)

    梁蕊; 金寿德; 邵玉霞; 张新; 刘立杰; 荣海芳


    Objective: To investigate the effect of inhaled different concentrations of budesonide in early phase on the airway inflammation and remodeling in asthmatic rats. Methods: Thirty-two rats were randomly divided into 4 groups: group A (n=8,control with saline), groupB (n=8,asthma with OVA),group C (n=8, asthma with OVA treated with low concentrations of budesonide in early phase), group D (n=8, asthma with OVA treated with high concentrations of budesonide in early phase). The bronchoalveolar lavage fluids (BALF) were classification in BALF studied in each group . The pathologic alteration of the bronchi and lung tissue was observed by HE staining. Expression of NGF and TGF-β1 were detected by immunohistochemistry, collagen deposition by Masson staining. The Morphological parameters including the number of inflammatory cell per unit airway area, bronchial basement membrane perimeter (Pbm), smooth muscle area( Wam), inner airway area( Wai), collagen area( Wcol) by computer image analysis software. Results: The total cell counts and the percentage of EOS in BALF the level of TNF-α , ET-1 increased compared with group A (P<0.01), group C and D reduced significantly compared with group B (P<0.01). The expression of NGF and TGF-β1, inflammatory cell counts around bronchus, airway smooth muscle hypertrophy ,the collagen deposition of reticular basement, airway inner wall area were significant higher than those groupA( P<0.01), the data in group C and D were significant lower than those in group B(P<0.01), there were apparent difference between group C and group D compared with group A (P<0.05,P<0.01). The difference between group C and group D.(P<0.05,P<0.01) Conclusion: Inhaled different concentrations of budesonide in early phase could apparently inhibit airway inflammation and remodeling, high concentrations of budesonide than low concentrations.%目的:研究早期吸入不同浓度布地奈德对哮喘大鼠气道炎症和气道重构的干预情况.方法:32

  15. [Determination of serum immunoglobulins in asthmatic patients]. (United States)

    Cabrera Jiménez, M; Valdés Sánchez, A F; Argüelles Sobrino, D; Gómez Echevarría, A H; Lastra Alfonso, G


    One hundred eighty one asthmatic patients were evaluated at the Allergy Consultation in Hermanos Ameijeiras Clinical Surgical Hospital. A case history was made for each of the patients, where the family background and personal history of allergy was collected; possible precipitating factors (such as inhalable, food, infectious, irritant, as well as climate factors) and physical and respiratory examinations. Serum immunoglobulin tests (by means of the ultramicroanalitic system (SUMA) and the rest of Igs: IgA, IgG, IgM by means of Mancini's simple radial immunodifusion method were made. Total eosinophil count was made to all of the patients in the study as well as serial studies of the faces. An increase in the IgE and IgM figures was found in asthmatic patients related to individual controls, and in relation to the normal figures for the adult population in our country. IgA and IgG determinations were normal both in the asthmatic and control groups, related to the standard figures.

  16. Comparison of hemihypoglossal- and accessory-facial neurorrhaphy for treating facial paralysis in rats. (United States)

    Li, Dezhi; Wan, Hong; Feng, Jie; Wang, Shiwei; Su, Diya; Hao, Shuyu; Schumacher, Michael; Liu, Song


    The aim of this study was to determine the effectiveness of hypoglossal-facial nerve "side"-to-end (HemiHN-FN) and accessory-facial nerve end-to-end (AN-FN) neurorrhaphy using a predegenerated nerve graft (PNG) for reanimating facial paralysis in a rat FN injury model. A total of 25 rats with complete unilateral facial paralysis resulting from section of the right FN were divided into 5 groups (n=5 each) that were submitted to immediate, delayed (3 months after FN injury) or no (control) FN reconstruction procedures involving HemiHN-FN or AN-FN neurorrhaphy. Approximately 3 months after FN reconstruction, cholera toxin subunit B conjugate Alexa 555 (CTB-Alexa 555) was injected into the ipsilateral whisker pad muscle and CTB-Alexa 555-labeled neurons were observed in the hypoglossal or accessory nuclei of all the FN reconstruction rats, but none of these neurons were found in the controls. There were numerous myelinated and nonmyelinated axons in both PNG and repaired FN of the FN reconstruction rats. No differences were found for these numbers between the two neurorrhaphy methods for each of the treatment time points, indicating the equal effectiveness of axon regeneration. However, a significantly higher number of CTB-Alexa 555-labeled neurons was observed in the hypoglossal nucleus of the immediate HemiHN-FN neurorrhaphy-treated rats when compared to that in the accessory nucleus of the immediate AN-FN neurorrhaphy-treated rats, consistent with the surface values of the recorded MAPs at the whisker pad muscle while electro-stimulating the FN. These results suggest that HemiHN-FN neurorrhaphy produces more efficient innervation of the paralyzed facial muscles than AN-FN neurorrhaphy without sacrificing ipsilateral hypoglossal function. Taking into consideration the clinical relevance of these findings for postoperative complications and functional reanimation in relation to the central plasticity, we suggest that HemiHN-FN neurorrhaphy may be the preferable facial

  17. Histological changes in kidneys of adult rats treated with Monosodium glutamate: A light microscopic study

    Directory of Open Access Journals (Sweden)

    Singh BR, Ujwal Gajbe, Anil Kumar Reddy, Vandana Kumbhare


    Full Text Available Introduction: Monosodium Glutamate (MSG, which is chemically known as AJI-NO-MOTO also familiar as MSG in routine life. MSG is always considered to be a controversial food additive used in the world. It is a natural excitatory neurotransmitter, helps in transmitting the fast synaptic signals in one third of CNS. Liver and kidney play a crucial role in metabolism as well as elimination of MSG from the body. Present study is to detect structural changes in adult rat kidney tissue treated with MSG; observations are done with a light microscope. Materials & Methods: The study was conducted in the department of Anatomy, J.N.M.C, Sawangi (M Wardha. Thirty (30 adult Wistar rats (2-3 months old weighing about (200 ± 20g were used in the current study, animals were divided into three groups (Group – A, B, C. Group A: Control, Group B: 3 mg /gm body weight, Group C: 6 mg /gm body weight, MSG were administered orally daily for 45 days along with the regular diet. Observations & Results: The Mean values of animals weight at the end of experiment (46th day respectively were 251.2 ± 13, 244.4 ± 19.9 and 320 ± 31.1. Early degenerative changes like, Glomerular shrinkage (GSr, loss of brush border in proximal convoluted tubules and Cloudy degeneration was observed in sections of kidney treated with 3 mg/gm body weight of MSG. Animals treated with 6 mg/gm body weight of MSG showed rare changes like interstitial chronic inflammatory infiltrate with vacuolation in some of the glomeruli, and much glomerular shrinkage invaginated by fatty lobules. Conclusion: The effects of MSG on kidney tissues of adult rats revealed that the revelatory changes are directly proportional to the doses of MSG.

  18. [Progression of the mechanism study on experimental migraine treated with acupuncture in rat model]. (United States)

    Liu, Lu; Pei, Pei; Wang, Linpeng


    In the paper, by taking acupuncture and migraine as the key words to retrieve CNKI and PubMed database, the literature analysis was done on the mechanism study on experimental migraine treated with acupuncture in rat model. The results showed that acupuncture mechanism study focused on the regulation and control of the relevant neurotransmitters/neuromodulators of migraine, such as calcitonin gene-related peptide (CGRP), serotonin (5-HT), nitric oxide (NO), etc. Moreover, in the paper, the review had been done on the neurotransmitters/neuromodulators involved in the study.

  19. Evaluation of Bcl-2 Family Gene Expression in Hippocampus of 3, 4-methylenedioxymethamphetamine Treated Rats

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    Hamed Hashemi-Nasl


    Full Text Available Objective: 3,4-methylenedioxymethamphetamine (MDMA is an illicit, recreational drugthat causes cellular death and neurotoxicity. This study evaluates the effects of differentdoses of MDMA on the expression of apoptosis–related proteins and genes in the hippocampusof adult rats.Materials and Methods: In this expremental study,a total of 20 male Sprague Dawley rats(200-250 g were treated with MDMA (0, 5, 10, 20 mg/kg i.p. twice daily for 7 days. Sevendays after the last administration of MDMA, the rats were killed. Bax and Bcl-2 genesin addition to protein expressions were detected by western blot and reverse transcriptionpolymerasechain reaction (RT-PCR.Results were analyzed using one-way ANOVA andp≤0.05 was considered statistically significant.Results: Our results showed that MDMA caused dose dependent up-regulation of Baxand down-regulation of Bcl-2 in the hippocampus. There was a significant alteration inbcl-2 and bax genes density.Conclusion: Changes in apoptosis-related proteins and respective genes relating to Baxand Bcl-2 might be involved in the molecular mechanism of MDMA-induced apoptosis.

  20. Study of Diabetic cutaneous wound healing in rats treated with Lactobacillus Casei and its Exopolysaccharide

    Directory of Open Access Journals (Sweden)

    Saeed Ahmadi Majid


    Full Text Available Probiotics are live microorganisms (in most cases, bacteria that are similar to beneficial microorganisms found in the human gut. They are also called "friendly bacteria" or "good bacteria". Lactobacillus derived from products, including culture supernatants have been used for their wound healing and antiviral properties as they are believed to boost energy and to be effective remedies for allergies, common cold, lactose intolerance, and have also been shown to reduce cholesterol levels and the risk of colon cancer. Therefore, the purpose of this experiment is to study the effect of Lactobacillus casei on Diabetic wound healing. This study was designed to investigate the amount of exopolysaccharide (EPS production by L. Casei, L. Brevis, L. Bulgaricus and L. Plant arum from the genus Lactobacillus applying the phenol-sulfuric acid method and the antagonistic effects of these bacteria on some pathogenic bacteria. L. casei was selected for its high exopolysaccharide and fucoid colonise production. The animals were injected by streptozotocin at the dose of 55 mg/kg of the body weight intraperitoneal streptozotocin induced diabetes within 3 days by destroying the beta cells. Wistar male rats divided into 4 groups; 2 experimental groups, a control and a negative control (n =6; and a full-thickness wound (1× 1cm was made on the back of each rat. The current study showed a significant reduction in inflammation and a significant acceleration in wound healing on the rats treated by Lactobacillus casei as compared to control and negative control groups.

  1. Study on acute ulcerous pain in rats treated with aqueous root extract of Lonchocarpus cyanescens

    Institute of Scientific and Technical Information of China (English)

    Adegbolagun Temitope Adeoye; Adeolu Alex Adedapo; Matthew Oluwole Abatan


    Objective: To evaluate the antiulcer and analgesic effects of the aqueous root extract of Lonchocarpus cyanescens (L. cyanescens) since the plant is said to have medicinal properties. Methods: The filtrate of the aqueous root extract of the plant (100 mg/mL) was used to evaluate for antiulcer activity in 20 rats divided into five groups of four rats each, which were Groups A, B, and C that received 100, 200 and 300 mg/kg doses respectively, while Group D was served as negative control and animals of Group E received 20 mg/kg dose of ranitidine. Indomethacin at a dose of 15 mg/kg was used to induce ulcer on the day of sacrifice. For acetic writhing test (antinociception), same design was used except that Group E received 100 mg/kg dose of acetyl salicylic acid as standard drug. Abdominal contractions were induced in the animals by intraperitoneal administration of 10 mL/kg of 0.6%of acetic acid. Results: The aqueous root extract of L. cyanescens at all doses (100, 200 and 300 mg/kg) showed significant (P < 0.05) decrease in ulcer parameters compared with the negative control. The extract also produced a significant (P < 0.05) decrease in the number of writhing reflexes in treated rats compared with negative control. Conclusions: The aqueous root extract of L. cyanescens exhibited both antiulcer and analgesic effects justifying folklore claim for the health benefits of this plant.

  2. Effects of rapamycin on airway remodeling, IL-8 and IL-10 in asthmatic rats%雷帕霉素对哮喘大鼠气道重塑和白细胞介素-8白细胞介素-10的影响

    Institute of Scientific and Technical Information of China (English)

    余可斐; 熊紫君; 穆敬平; 周立志; 陈雄


    Objective To investigate the effects of rapamycin on airway remodeling and lung tissue IL-8 and IL-10 in asthmatic rats, and to explore the mechanism by which rapamycin intervene in airway inflammation and re-modeling in bronchial asthma, so as to provide experimental basis for clinical research. Methods The asthmatic rat model of airway remodeling was established. Then, 30 SD rats were randomly divided into 3 groups: normal control group, asthma group, and rapamycin intervention group, with 10 rats in each group. Airway remodeling was observed in lung tissue sections with hematoxylin-eosin staining. The IL-8 and IL-10 expressions in lung tissues of each group were measured by immunohistochemistry and image analysis technique. Results The rats in asthma group showed characteristic changes of airway remodeling, such as thickened airway walls, hyperplasia of smooth muscle, and mucus hypersecretion. Immunohistochemical staining showed increased IL-8 expression in structural cells and inflammatory cells in airway layers. The IL-10 level was significantly reduced. Compared with the asthma group, the rapamycin treatment group showed mild inflammatory reaction, less smooth muscle hyperplasia and mucus secretion. Immunohis-tochemical staining showed the lowered IL-8 expression and increased IL-10 expression in all cells, with statistical differences when compared with the control group (P<0.05). Conclusion In asthmatic rats, rapamycin can relieve air-way inflammation and remodeling, reduce IL-8 expression, increase IL-10 expression, modulate the imbalance of pro-inflammatory to anti-inflammatory cytokines proportion, and play a role in the anti-inflammation and immune regula-tion in bronchial asthma.%目的:观察雷帕霉素对哮喘大鼠模型气道重塑和肺组织白细胞介素(IL)-8、IL-10的影响,探讨其在干预支气管哮喘气道炎症和气道重塑中的作用机制,为临床研究提供实验依据。方法建立哮

  3. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats. (United States)

    Puebla, L; Rodríguez-Martín, E; Arilla, E


    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 micrograms) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity was markedly increased in hippocampal membranes from rats treated with 10 micrograms of histamine (23% +/- 1% vs. 17% +/- 1% and 37% +/- 2% vs. 23% +/- 1%, respectively). In contrast, neither the basal nor the FK-stimulated enzyme activities were affected by histamine administration. The functional activity of the hippocampal guanine-nucleotide binding inhibitory protein (Gi protein), as assessed by the capacity of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity, was not modified by histamine administration. These data suggest that the increased response of the enzyme to SS was not related to an increased functional activity of Gi proteins. In fact, the increased AC response to SS in hippocampal membranes from histamine (10 micrograms)-treated rats was associated with quantitative changes in the SS receptors. Equilibrium binding data obtained with [125I]Tyr11-SS indicate an increase in the number with specific SS receptors (541 +/- 24 vs. 365 +/- 16 fmol/mg protein, P histamine (10 micrograms)-treated rats as compared to control animals. With the aim of determining if these changes were related to histamine binding to its specific receptor sites, the histaminergic H1 and H2 receptor antagonists mepyramine and cimetidine, respectively, were administered 1 h before histamine injection. The pretreatment with mepyramine or cimetidine induced an increase in the

  4. Effects of gomisin A on liver functions in hepatotoxic chemicals-treated rats. (United States)

    Maeda, S; Takeda, S; Miyamoto, Y; Aburada, M; Harada, M


    The effects of gomisin A, which is a lignan component of schizandra fruits, on liver functions in various experimental liver injuries and on bile secretion in CCl4-induced liver injury were studied. Gomisin A weakly accelerated the disappearance of plasma ICG by itself at a high dose (100 mg/kg, i.p.). All of the hepatotoxic chemicals used in this study inhibited the excretion of ICG from plasma. Gomisin A showed a tendency to prevent the delays of the disappearance of plasma ICG induced by CCl4, d-galactosamine and orotic acid, but not that by ANIT. Bile flow and biliary outputs of total bile acids and electrolytes (Na+, K+, Cl- and HCO3-) were decreased in CCl4-treated rats. Gomisin A maintained bile flow and biliary output of each electrolyte nearly to the level of the vehicle-treated group, but did not affect biliary output of total bile acids. These findings suggest that gomisin A possesses a liver function-facilitating property in normal and liver injured rats and that its preventive action on CCl4-induced cholestasis is due to maintaining the function of the bile acids-independent fraction.

  5. Metal and Microelement Biomarkers of Neurodegeneration in Early Life Permethrin-Treated Rats

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    Cinzia Nasuti


    Full Text Available Hair is a non-invasive biological material useful in the biomonitoring of trace elements because it is a vehicle for substance excretion from the body, and it permits evaluating long-term metal exposure. Here, hair from an animal model of neurodegeneration, induced by early life permethrin treatment from the sixth to 21th day of life, has been analyzed with the aim to assess if metal and microelement content could be used as biomarkers. A hair trace element assay was performed by the ICP-MS technique in six- and 12-month-old rats. A significant increase of As, Mg, S and Zn was measured in the permethrin-treated group at 12 months compared to six months, while Si and Cu/Zn were decreased. K, Cu/Zn and S were increased in the treated group compared to age-matched controls at six and 12 months, respectively. Cr significantly decreased in the treated group at 12 months. PCA analysis showed both a best difference between treated and age-matched control groups at six months. The present findings support the evidence that the Cu/Zn ratio and K, measured at six months, are the best biomarkers for neurodegeneration. This study supports the use of hair analysis to identify biomarkers of neurodegeneration induced by early life permethrin pesticide exposure.

  6. Estimation of lipid profile and glucose level in alloxan-induced diabetic rats treated with Cymbopogon citratus (lemongrass

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    Chinwe O. Ewenighi


    Full Text Available Objective: Cymbopogon citratus extract has been reported to have hypoglycemic properties but not much is known about its hypolipidemic effects. In this study it was aimed to demonstrate the hypolipidemic and hypoglycemic potentials of Cymbopogon citratus extract on alloxan-induced diabetic rats. Methods: Eighteen male albino rats of weights between 106-118 g were used for the study and divided into three groups of six rats each. The rats of the non-diabetic control group were given 1 ml of distilled water daily. Two other groups induced with diabetes using alloxan by a single dose administration of 120 mg/kg body weight (BW; one of these diabetic rat groups were treated with Cymbopogon citratus extract daily at 1.5 ml/100 g BW for 4 weeks while the other group was left untreated. Blood samples were collected and total cholesterol (TC, triglyceride (TG, high-density lipoprotein (HDL, low-density lipoprotein (LDL and glucose levels were assayed. Results: After four weeks of treatment, data indicated significant reductions in BW, blood glucose, TG, TC and LDL levels of diabetic rats treated with Cymbopogon citratus extract compared to the non-treated group. The treated diabetic rats also indicated significantly higher HDL levels compared to the non-treated group. Conclusion: Treatment of diabetic rats with the Cymbopogon citratus extract lowered blood glucose, TG, TC and LDL levels and increased the HDL level. This shows that the extract has both hypoglycemic and hypolipidemic effects. [J Exp Integr Med 2013; 3(3.000: 249-253

  7. Tissue dyslipidemia in salmonella-infected rats treated with amoxillin and pefloxacin

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    Rotimi Solomon O


    Full Text Available Abstract Background This study investigated the effects of salmonella infection and its chemotherapy on lipid metabolism in tissues of rats infected orally with Salmonella typhimurium and treated intraperitoneally with pefloxacin and amoxillin. Methods Animals were infected with Salmonella enterica serovar Typhimurium strain TA 98. After salmonellosis was confirmed, they were divided into 7 groups of 5 animals each. While one group served as infected control group, three groups were treated with amoxillin (7.14 mg/kg body weight, 8 hourly and the remaining three groups with pefloxacin (5.71mg/kg body weight, 12 hourly for 5 and 10 days respectively. Uninfected control animals received 0.1ml of vehicle. Rats were sacrificed 24h after 5 and 10 days of antibiotic treatment and 5 days after discontinuation of antibiotic treatment. Their corresponding controls were also sacrificed at the same time point. Blood and tissue lipids were then evaluated. Results Salmonella infection resulted in dyslipidemia characterised by increased concentrations of free fatty acids (FFA in plasma and erythrocyte, as well as enhanced cholesterogenesis, hypertriglyceridemia and phospholipidosis in plasma, low density lipoprotein-very low density lipoprotein (LDL-VLDL, erythrocytes, erythrocyte ghost and the organs. The antibiotics reversed the dyslipidemia but not totally. A significant correlation was observed between fecal bacterial load and plasma cholesterol (r=0.456, p Conclusion The findings of this study suggest that salmonella infection in rats and its therapy with pefloxacin and amoxillin perturb lipid metabolism and this perturbation is characterised by cholesterogenesis.

  8. Contribution of calpains to photoreceptor cell death in N-methyl-N-nitrosourea-treated rats. (United States)

    Oka, Takayuki; Nakajima, Takeshi; Tamada, Yoshiyuki; Shearer, Thomas R; Azuma, Mitsuyoshi


    The purpose of the present study was to determine if proteolysis by the calcium-dependent enzyme calpains (EC contributed to retinal cell death in a rat model of photoreceptor degeneration induced by intraperitoneal injection of N-methyl-N-nitrosourea (MNU). Retinal degeneration was evaluated by H&E staining, and cell death was determined by TUNEL assay. Total calcium in retina was measured by atomic absorption spectrophotometry. Activation of calpains was determined by casein zymography and immunoblotting. Proteolysis of alpha-spectrin and p35 (regulator of Cdk5) were evaluated by immunoblotting. Calpain inhibitor SNJ-1945 was orally administrated to MNU-treated rats to test drug efficacy. MNU decreased the thickness of photoreceptor cell layer, composed of the outer nuclear layer (ONL) and outer segment (OS). Numerous cells in the ONL showed positive TUNEL staining. Total calcium was increased in retina after MNU. Activation of calpains and calpain-specific proteolysis of alpha-spectrin were observed after MNU injection. Oral administration of SNJ-1945 to MNU-treated rats showed a significant protective effect against photoreceptor cell loss, confirming involvement of calpains in photoreceptor degeneration. Conversion of p35 to p25 was well correlated with calpain activation, suggesting prolonged activation of Cdk5/p25 as a possible downstream mechanism for MNU-induced photoreceptor cell death. SNJ-1945 reduced photoreceptor cells death, even though MNU is one of the most severe models of photoreceptor cell degeneration. Oral calpain inhibitor SNJ-1945 may be a candidate for testing as a medication against retinal degeneration in retinitis pigmentosa.

  9. Estrogen administration modulates hippocampal GABAergic subpopulations in the hippocampus of trimethyltin-treated rats

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    Valentina eCorvino


    Full Text Available Given the well-documented involvement of estrogens in the modulation of hippocampal functions in both physiological and pathological conditions, the present study investigates the effects of 17-beta estradiol (E2 administration in the rat model of hippocampal neurodegeneration induced by trimethyltin (TMT administration (8mg/kg, characterized by loss of pyramidal neurons in CA1, CA3/hilus hippocampal subfields associated with astroglial and microglial activation, seizures and cognitive impairment. After TMT/saline treatment, ovariectomized animals received two doses of E2 (0.2 mg/kg i.p. or vehicle, and were sacrificed 48h or 7 days after TMT-treatment. Our results indicate that in TMT-treated animals E2 administration induces the early (48h upregulation of genes involved in neuroprotection and synaptogenesis, namely Bcl2, trkB, Cadherin and cyclin-dependent-kinase-5. Increased expression levels of glutamic acid decarboxylase (gad 67, neuropeptide Y (Npy, parvalbumin , Pgc-1α and Sirtuin 1genes, the latter involved in parvalbumin (PV synthesis, were also evident. Unbiased stereology performed on rats sacrificed 7 days after TMT treatment showed that although E2 does not significantly influence the extent of TMT-induced neuronal death, significantly enhances the TMT-induced modulation of GABAergic interneuron population size in selected hippocampal subfields. In particular, E2 administration causes, in TMT treated rats, a significant increase in the number of GAD67-expressing interneurons in CA1 stratum oriens, CA3 pyramidal layer, hilus and dentate gyrus, accompanied by a parallel increase in NPY-expressing cells, essentially in the same regions, and of PV-positive cells in CA1 pyramidal layer. The present results add information concerning the role of in vivo E2 administration on mechanisms involved in cellular plasticity in the adult brain.

  10. Discriminant analysis of pulmonary function parameters. Healthy adults versus mild asthmatics and moderate asthmatics.

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    Full Text Available Volume-time (V-T and flow-volume (F-V curves were measured in all the subjects of nonsmoking young males (mean value 26.3 yrs. of age, healthy and asthmatics. Eleven parameters of pulmonary function tests composed of two V-T, six F-V, and three mean time constant (MTC parameters, were calculated from the curves. These parameters were used in the two analyses through the all possible selection procedure (APSP discriminating between healthy adults and mild asthmatics and also between healthy and moderate. Flow rate at 75% of FVC (V75 proved to be the most useful parameter and V50 the next best in both analyses. The probability of misclassification using all eleven parameters was 19.64% in the analysis of healthy adults and mild asthmatics, and 4.29% in the analysis of healthy adults and moderate asthmatics. There was a little difference in the parameters selected at every step. The discriminant analysis proved that the flow-volume patterns were different according to the severity of bronchial asthma. Thus flow-volume recognition was considered to be important in analyzing the severity of bronchial asthma.

  11. DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

    Institute of Scientific and Technical Information of China (English)

    Yuka; Kobayashi; Sofya; P; Kulikova; Junko; Shibato; Randeep; Rakwal; Hiroyuki; Satoh; Didier; Pinault; Yoshinori; Masuo


    AIM:To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS:Rats were treated with an intraperitoneal injection of MK-801 [0.08(low-dose) and 0.16(highdose) mg/kg] or NaC l(vehicle control). In a first series of experiment,the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments,the whole brain of each animal was rapidly removed at 40 min post-injection,and different regions were separated:amygdala,cerebral cortex,hippocampus,hypothalamus,midbrain and ventral striatum on ice followed by DNA microarray(4 × 44 K whole rat genome chip) analysis.RESULTS:Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency(30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number(up- and down- regulations) of gene expressions in the cerebral cortex(378),midbrain(376),hippocampus(375),ventral striatum(353),amygdala(301),and hypothalamus(201) under low-dose(0.08 mg/kg) of MK-801. Under high-dose(0.16 mg/kg),ventral striatum(811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region.CONCLUSION:Acute MK-801 treatment increases synchrony of baseline gamma oscillations,and causes very early changes in gene expressions in six individual rat brain regions,a first report.

  12. Does swimming exercise affect experimental chronic kidney disease in rats treated with gum acacia?

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    Badreldin H Ali

    Full Text Available Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD. Similar benefits have also been ascribed to the dietary supplement gum acacia (GA. Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE on adenine-induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w to induce CKD, GA in the drinking water (15% w/v, or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments, during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation.

  13. Short-term growth in asthmatic children using fluticasone propionate

    NARCIS (Netherlands)

    Visser, MJ; van Aalderen, WMC; Elliott, BM; Odink, RJ; Brand, PLP


    Background: Inhaled corticosteroids may reduce short-term growth velocity in asthmatic children and knemometry is the most sensitive tool to detect this short-term growth suppression. Study objective: To compare lower leg growth velocity, as measured by knemometry, in asthmatic children during and a

  14. Blood and urinary concentrations of salbutamol in asthmatic subjects

    DEFF Research Database (Denmark)

    Elers, Jimmi; Pedersen, Lars; Henninge, John;


    Data on blood and urinary concentrations of salbutamol after inhalation and oral administration in healthy subjects are scarce. Accordingly, we examined the pharmacokinetics of inhaled and oral salbutamol in asthmatic subjects.......Data on blood and urinary concentrations of salbutamol after inhalation and oral administration in healthy subjects are scarce. Accordingly, we examined the pharmacokinetics of inhaled and oral salbutamol in asthmatic subjects....

  15. Imipramine-induced c-Fos expression in the medial prefrontal cortex is decreased in the ACTH-treated rats. (United States)

    Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Gomita, Yutaka; Araki, Hiroaki; Cui, Ranji


    Previous studies have shown that the antidepressive-like effect of tricyclic antidepressants is blocked by repeated treatments with adrenocorticotropic hormone (ACTH). However, little is known about the neuroanatomy underlying the mechanism of the imipramine treatment-resistant depression model. In the present study, first experimental evidence showed no significant difference of the serum imipramine concentrations between the saline and ACTH-treated rats. In further study, imipramine produced significant increases in the c-Fos expression in the medial prefrontal cortex (mPFC), the dentate gyrus of the hippocampus (DGH), and the central nucleus of the amygdala (CeA), in rats repeatedly treated with saline. The imipramine-increased c-Fos immunoreactivity was suppressed in the mPFC of rats repeatedly treated with ACTH. However, there was no significant difference in c-Fos expression in the DGH and CeA between ACTH- and saline-treated rats. These results suggest that the mPFC is maybe involved in effects of the imipramine in the ACTH-treated rats.

  16. Effects of alpha-adrenoceptor agonists in chronic morphine administered DSP4-treated rats: evidence for functional cross-sensitization. (United States)

    Archer, T; Fredriksson, A


    Five experiments were performed to study the effects of the Alpha-adrenoceptor agonists, clonidine and guanfacine, upon spontaneous motor activity in chronically morphine administered DSP4-treated and control rats. DSP4 (2 x 50 mg/kg, with a 10-day interval between injections) and vehicle (distilled water) were injected i.p., on each occasion 30 min after zimeldine (20 mg/kg). Morphine dosages were raised incrementally from 5 mg/kg (Days 1-3), through 10 mg/kg (Days 4-7) and 20 mg/kg (Days 8-14), to 30 mg/kg (Days 15-20). Motor activity testing occurred on Day 21, Day 22 as well as in Experiments II-V, (from 1st morphine injection). DSP4 pretreatment and chronic morphine injections each reduced motor activity during the first 30 min of testing; combined DSP4 and morphine treatment potentiated the hypoactivity. Habituation quotients indicated deficits in habituation to the novel test environment by the Vehicle-morphine (Quoteint2 only) and DSP4-morphine groups. Acute clonidine treatment (0.04 mg/kg s.c.) reduced motor activity during the first 30 min of testing but attenuated or blocked the morphine-induced hypoactivity in DSP4-treated and control rats. During the 60-90 min test period, clonidine, but not guanfacine (0.08 mg/kg), potentiated morphine-induced hyperactivity in control rats; acute clonidine enhanced this effect, whereas acute guanfacine reduced it, in the DSP4-treated rats. The enhanced hyperactivity of morphine-clonidine suggest a cross-sensitivity effect. Naloxone (0.1 mg/kg s.c.), injected after the 1st 30-min of testing, potentiated markely the clonidine-induced elevations of motor activity in morphine-administered control rats; in the DSP4-treated rats, these effects were dramatically potentiated, underlining the cross-sensitivity effect. Acute guanfacine treatment reduced motor activity during the first 30 min of testing but did not attenuate reliably morphine-induced hypoactivity in control or DSP4 rats. Naloxone did not potentiate the


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    Full Text Available : This study was done to observe the serum/plasma oxidant-antioxidant status among asthmatic patients. Plasma MDA (Malon-di-aldehyde, an oxidant and Serum SOD (superoxide dismutase, an antioxidant, were assayed among asthmatic patients and their mean values were compared with healthy volunteer controls. Values were also observed in different age groups. The difference in mean pMDA level was found statistically significantly among cases and control, higher among asthmatic patients. Likewise, s-SOD level was significantly reduced among asthmatic patients. Clearly, there was an imbalance between oxidants and antioxidants levels among asthmatic patients and this consideration may be helpful in proper planning of basket of anti-asthma interventions. Future studies are recommended.

  18. Increased nuclear ploidy, not cell proliferation, is sustained in the peroxisome proliferator-treated rat liver. (United States)

    Lalwani, N D; Dethloff, L A; Haskins, J R; Robertson, D G; de la Iglesia, F A


    Peroxisome proliferators are believed to induce liver tumors in rodents due to sustained increase in cell proliferation and oxidative stress resulting from the induction of peroxisomal enzymes. The objective of this study was to conduct a sequential analysis of the early changes in cell-cycle kinetics and the dynamics of rat liver DNA synthesis after treatment with a peroxisome proliferator. Immunofluorescent detection of proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation into DNA during S phase we used to assess rat hepatocyte proliferation in vivo during dietary administration of Wy-14,643, a known peroxisome proliferator and hepatocarcinogen in rodents. Rats were placed on diet containing 0.1% WY-14,643 and implanted subcutaneously with 5-bromo-2'deoxyuridine containing osmotic pumps 4 days prior to being sacrificed on days 4, 11, and 25 of treatment. Isolated liver nuclei labeled with fluorscein isothiocyanate (FITC)-anti-BrdU/PI and FITC-anti-PCNA/PI were analyzed for S-phase kinetics using flow cytometry. Morphometric analysis was performed to evaluate nuclear and cell size and enumeration of BrdU labeled cells, binucleated hepatocytes, and mitotic index. The BrdU labeling index increased 2-fold in livers of Wy-14,643-treated rats at day 4, but distribution of cells in G1, S phase, and G2-M did not differ significantly from controls. PCNA-positive cells decreased from 36% on day 4 to 17% on day 25, whereas the percentage of PCNA-positive cells in controls increased 2-fold from day 4 to day 11 and remained unchanged up to day 25. The differences in the number of PCNA-positive nuclei between control and Wy-14,643-treated groups were statistically significant only on day 4. Binucleated hepatocytes, determined by morphometric analysis, increased slightly on day 25 in treated rats parallel to an increase in the percentage of cells in G2-M phase. Significant shifts were noted in nuclear diameter and nuclear area after 11 and 25

  19. CD4(+), CD25(+), FOXP3 (+) T Regulatory Cell Levels in Obese, Asthmatic, Asthmatic Obese, and Healthy Children. (United States)

    Donma, Metin; Karasu, Erkut; Ozdilek, Burcu; Turgut, Burhan; Topcu, Birol; Nalbantoglu, Burcin; Donma, Orkide


    The aim of this prospective case control study is to determine CD4(+), CD25(+), and FoxP3(+) T regulatory cells (Tregs) and T helper cells (Ths) in obese, asthmatic, asthmatic obese, and healthy children. Obese (n = 40), asthmatic (n = 40), asthmatic obese (n = 40), and healthy children (n = 40) were included in this study. Blood samples collected from children were marked with CD4, CD25, ve Foxp3 in order to detect Tregs and Ths by flow cytometric method. Statistical analyses were performed. p ≤ 0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0.16 %; p ≤ 0.001), asthmatic (0.25 %; p ≤ 0.01), and asthmatic obese (0.29 %; p ≤ 0.05) groups than control group (0.38 %). Ths were counted higher in asthma group than control (p ≤ 0.01) and obese (p ≤ 0.001) groups. T cell immunity plays important roles in chronic inflammatory diseases such as obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic, and asthmatic obese children might represent a challenge of these cells.

  20. Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

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    M.F. Ribeiro


    Full Text Available The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradiol-treated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 µg rat-1 week-1 for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat-1 day-1 was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 µg estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 µg estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05. Therefore, the increase in serum prolactin levels observed in rats treated with 50 µg estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 µg estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats

  1. Reproductive efficiency of rats whose mothers treated with lead acetate during lactation: role of vitamin E

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    W. H. Yousif


    Full Text Available Reproductive efficiency of young male and female rats yielded from mothers treated with lead acetate (10 mg/kg B.W and vitamin E as an antioxidant (500 mg/kg during lactation period was studied. 27 pregnant albino rats aged 4-5 months divided into 3 groups, the first group given 0.2 ml distilled water through oral intubations (control. The second group given lead acetate (10 mg/kg B.W, while the 3rd group given lead acetate (10 mg/kg B.W with vitamin E (500 mg/kg B.Wt. Lead acetate treatment did not cause significant difference (P>0.05 in young male rats body, testes, epididymal (head, tail, prostate gland, seminal vesicle weights, number of epidiymal sperms count, percentage of live/dead sperms and sperms abnormalities accompanied with a significant increase (P0.05 in ovary and uterus weights. Lead acetate with vit. E cause significant decrease (P<0.05 in body, testes, epididymal (head, body weights, number of epididymal sperm count, percentage of live/dead and sperm abnormalities. Concerning young female rats treated with lead acetate and vit E showed a significant decrease (P<0.05 in body, uterus weights with a significant increase (P<0.05 in the duration of vaginal opening. Histopathological study revealed changes in the testes such as desquemination in some epithelial lining of seminiferous tubules and sertoli cells. Undevelopment of localized area of some seminiferous tubules with blood vessels congestion in both testes and ovaries with hyperemia in ovarian stroma, increase in follicular cells, decrease in corpus luteum formation, degeneration of ovarian follicles and increase in ovarian adipose tissue. This study concluded that lead acetate can be transmitted through mother milk to their pups. The dose of lead acetate (10 mg/kg B.W was enough to make bad effects on both male and female reproductive systems. Vitamin E (as an antioxidant found to have no improving effect in treatment of lead acetate disturbances on reproductive systems of

  2. Antimicrobial effect of chlorine dioxide on Actinobacillus actinomycetemcomitans in diabetes mellitus rats treated with insulin

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    Tantin Ermawati


    Full Text Available Background: Periodontitis is a chronic inflammatory disease of periodontal tissues. Etiology of periodontal disease includes Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans which is the most predominant disease-causing bacteria found in the gingival sulcus. Periodontitis can be exacerbated by the systemic disease, such as diabetes mellitus considered as a metabolic disease characterized by hyperglycemia due to insulin deficiency. Treatment of periodontitis is then required in patients with type I diabetes to avoid radical reaction that can not only cause bleeding, but can also prevent infection, as a result, topical antimicrobial therapy and blood glucose control are required. Topical antimicrobial chlorine dioxide is a disinfectant that is effective in killing A. actinomycetemcomitans. Purpose: This study is aimed to determine the effects of topical antimicrobial chlorine dioxide gel or rinse on the number of A. actinomycetemcomitans in DM rats treated with insulin. Methods: 20 three month old male Wistar rats with weight of 170–200 grams were divided into four groups. First, periodontitis and DM were manipulated into all groups through aloksan injection with dose of 170 mg/kg. Those rats in group I were treated with insulin and chlorine dioxide gel, those in group II were treated with insulin and chlorine dioxide rinse, those in group III were treated with insulin only, and those in group IV were without treatment. In the third and seventh weeks, the number of A. actinomycetemcomitans was measured. The data was tested by using One-Way ANOVA test followed by LSD test. Results: The study showed that chlorine dioxide gel has a greater ability in reducing the number of A. actinomycetemcomitans than chlorine dioxide rinse although both are antimicrobials. Conclusion: It can be concluded that the use of chlorine dioxide gel can more effective to decrease the number of A. actinomycetemcomitans than chlorine dioxide rinse in DM rats

  3. Glutamate co-transmission from developing medial nucleus of the trapezoid body - Lateral superior olive synapses is cochlear dependent in kanamycin-treated rats

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    Lee, Jae Ho [Institute of Tissue Regeneration Engineering (ITREN), Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Pradhan, Jonu [Department of Nanobio Medical Science, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Maskey, Dhiraj; Park, Ki Sup [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Hong, Sung Hwa [Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Suh, Myung-Whan [Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Kim, Myeung Ju, E-mail: [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Ahn, Seung Cheol, E-mail: [Department of Physiology, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of)


    Research highlights: {yields} Glutamate co-transmission is enhanced in kanamycin-treated rats. {yields} VGLUT3 expression is increased in kanamycin-treated rats. {yields} GlyR expression is decreased in kanamycin-treated rats. {yields} GlyR, VGLUT3 expression patterns are asymmetric in unilaterally cochlear ablated rat. -- Abstract: Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltage clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.

  4. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats. (United States)

    Kitagawa, Kouhei; Kitamura, Yoshihisa; Miyazaki, Toshiaki; Miyaoka, Junya; Kawasaki, Hiromu; Asanuma, Masato; Sendo, Toshiaki; Gomita, Yutaka


    The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.

  5. Acute Chlamydia pneumoniae infections in asthmatic and non-asthmatic military conscripts during a non-epidemic period. (United States)

    Juvonen, R; Bloigu, A; Paldanius, M; Peitso, A; Silvennoinen-Kassinen, S; Harju, T; Leinonen, M; Saikku, P


    Chlamydia pneumoniae respiratory tract infections were studied in 512 male military conscripts (123 asthmatic and 389 non-asthmatic) taking part in 180-day service between July 2004 and July 2005 in Kajaani, Finland. Respiratory tract infections requiring a medical consultation were analysed prospectively. At baseline, at end of service, and during each episode of respiratory infection, blood samples were obtained for measurement of C. pneumoniae antibodies. Data concerning the clinical features of each infection episode were collected. Serological evidence of acute C. pneumoniae infection was found in 34 of the 512 conscripts with antibody data available, including 9.8% of the asthmatic subjects and 5.7% of the non-asthmatic subjects (p 0.111). A serological diagnosis could be made for 25 clinical episodes in 24 conscripts. The spectrum of respiratory tract infections included 13 episodes of mild upper respiratory tract infection and seven episodes of sinusitis, with five episodes involving asthma exacerbation. Two of three pneumonias were primary infections. Primary infections were diagnosed in five subjects, and re-infection/reactivation in 19 subjects, with the latter comprising 12 non-asthmatic subjects and seven asthmatic subjects (p 0.180). Prolonged infections were present in six asthmatic subjects and one non-asthmatic subject (p 0.001). A wide variety of respiratory tract infections, ranging from common cold to pneumonia, were associated with serologically confirmed C. pneumoniae infections. Infections were often mild, with common cold and sinusitis being the most common manifestations. Acute, rapidly resolved C. pneumoniae infections were equally common among asthmatic subjects and non-asthmatic subjects, whereas prolonged infections were more common among subjects with asthma.

  6. [Multiple hepatic cysts in rat rendered diabetic by streptozotocin and treated by islets of Langerhans grafts: the role of streptozotocin]. (United States)

    Viatettes, B; Barrat, E; Lassmann, V; Guidon, J; Altomare, E; Simon, C; Vague, P


    This study is based on the investigation by light and electron microscopy of hepatic biopsies from 14 rats rendered diabetic by streptozotocin and treated by portal embolization of islets of Langerhans. Macroscopically, voluminous projecting cysts were observed, sometimes occupying a whole lobe. By light microscopy, the cysts were lined with canalicular-type epithelium. Ultrastructural studies confirmed the canalicular nature of these cells and cilia were frequently observed. The presence of identical cysts in rats rendered diabetic by streptozotocin but not treated by embolization proves that this product is the agent responsible for the induction of this adenomatosis.

  7. Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media. (United States)

    Rouse, Rodney L; Stewart, Sharron R; Thompson, Karol L; Zhang, Jun


    Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), α-glutathione S-transferase (α-Gst), µ-glutathione S-transferase (µ-Gst), and beta-2 microglobulin (β2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. β2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury.

  8. Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A Metabolomics Investigation

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    Xiaxia Cai


    Full Text Available Background: Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Methods: Five groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water, alcohol control group (basal diet, 50% alcohol (v/v, dextrose control group (basal diet, isocaloric amount of dextrose, and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg−1 respectively, 50% alcohol (v/v. The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS was applied to identify liver metabolite profiles. Results: Nucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid, as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, l-leucine, alanyl-leucine and l-phenylalanine. Conclusion: These data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury.

  9. Cofactor metals and antioxidant enzymes in cisplatin-treated rats: effect of antioxidant intervention. (United States)

    Sabuncuoglu, Suna; Eken, Ayse; Aydin, Ahmet; Ozgunes, Hilal; Orhan, Hilmi


    We explored the association between the activities of antioxidant enzymes and their metallic cofactors in rats treated with cisplatin. The antioxidant effects of aminoguanidine, and a combination of vitamins E and C were investigated. Plasma platin was significantly lower than liver and kidney. Cisplatin treatment caused significant increase in plasma Se-glutathione peroxidase activity. Activities of Se-glutathione peroxidase, glutathione S-transferase, catalase and Cu,Zn-superoxide dismutase have been found to be significantly decreased in liver and kidney compared to controls. Zn levels in these organs were diminished upon cisplatin treatment, while levels of Cu were unaffected. Interestingly, levels of iron, the cofactor of catalase, were found to be significantly increased in liver and kidney. Intervention with aminoguanidine or vitamins was generally prevented cisplatin-caused changes in the activity of enzymes and in the tissue levels of cofactor metals. These observations suggest that relation between activities of enzymes and levels of cofactor metals is multifactorial.

  10. Role of Euphorbia thymifolia L. ethanolic root extract in treating female reproductive dysfunction in rats

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    Siva Prasad Gudipudi


    Full Text Available Euphorbia thymifolia root is having the protective effect against female reproductive dysfunctions. This study is to evaluate the antioxidant activity of ethanolic extract of Euphorbia thymifolia root in treating stress induced female reproductive dysfunctions. Forced swimming stress (15min/day for 28 days and restraint stress (3h/day for 28 days were the methods employed to induce female reproductive dysfunction in rats. Ethanolic extract of Euphorbia thymifolia root was given to rats in two doses, 100 mg/kg and 200 mg/kg for 28 days along with induction of stress and its effectiveness was assessed by observing changes in SOD, catalase and lipid peroxidation of uterus and ovary. The results were analyzed by using one-way ANOVA followed by Dunnett’s test. Euphorbia thymifolia root extract showed a significant antioxidant activity which is evident by increase in the levels of SOD and catalase, decrease in the levels of lipid peroxidation confirming the antioxidant effect which was found to be dose dependent. The antioxidant activity may be due to the presence of various phytochemical constituents like alkaloids, flavonoids and other constituents present in the Euphorbia thymifolia root.

  11. Lipid peroxidation and antioxidant system in rats acutely treated with acetone. (United States)

    Mathias, M G; Almeida, B B de; Bueno, J E; Portari, G V; Jordao, A A


    Cascades of metabolic changes leading to acetone production are induced in states of energy catabolism such as starvation or the use of a ketogenic diet. The reduced capacity for cell detoxification or the increased generation of free radicals is responsible for the toxic effect of acetone. The objective of the present study was to determine the effects of acute treatment (AT) with acetone on the oxidative and metabolic status of rats. The AT group (n=16) was treated by gavage with a single administration of 7.0 g acetone/kg body weight at a concentration of 25% (m/v). Eight rats were euthanized 6 h later (AT6) and eight 24 h later (AT24). Acetone levels were determined in blood and urine and oxidative parameters were analyzed by determining thiobarbituric acid reactive species (TBARS, indicators of lipid peroxidation) and reduced glutathione (GSH) and vitamin E as antioxidant parameters. Serum glucose, blood cholesterol and triglycerieds and hepatic fat were also determined. The results indicated a significant difference in the hepatic oxidative parameters, serum glucose and in plasma triglycerides between the groups. Thus, we conclude that the administration of acute acetone doses can promote changes in some biochemical parameters and in the hepatic oxidative profile.

  12. Antioxidant profile changes in reproductive tissues of rats treated with nicotine

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    I P Oyeyipo


    Full Text Available Objectives: Nicotine intake has been associated with reduced fertility, although the mechanisms responsible are still unclear. However, oxidative stress has been repeatedly implicated as the leading cause of male infertility. This study was therefore designed to investigate the effects of nicotine administration on testicular oxidant and antioxidant system in male albino rats. Materials and Methods: Forty male rats weighing between 150 and 180 g were divided into five groups and treated orally for 30 days. Group I, which served as the control received 0.2 ml/kg normal saline, Groups II and III received 0.5 mg/kg and 1.0 mg/kg body weight (BW of nicotine respectively. The fourth and fifth groups were administered with 0.5 mg/kg and 1.0 mg/kg BW of nicotine, but were left untreated for another 30 days. Homogenate of testis and epididymis were assayed for lipid peroxidation and anti-oxidant enzyme. Results: The results show a significant decrease (P < 0.05 in testicular glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase while a significant increase (P < 0.05 was observed in testicular lipid peroxidation and nitric oxide level in both groups when compared with the control. Conclusion: This experiment established that nicotine administration is associated with decreased testicular antioxidant and increase testicular lipid peroxidation, which might be a mechanism by which nicotine induce infertility.

  13. Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM2.5-treated Rats

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats.Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter.Treated samples were endotracheally instilled into rats.Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method.DNA migration length (μm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days.In peripheral blood,the concentration of MDA decreased,but the activity of GSH-Px increased 7 and 14 days after experiments.The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood.The DNA migration length (μm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5.The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood.The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5.The DNA migration length (μm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood.The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

  14. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

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    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan


    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  15. The Difficult-to-Control Asthmatic: A Systematic Approach

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    Le Annie V


    Full Text Available Abstract With the judicious use of inhaled corticosteroids, β2 agonists, and leukotriene modifiers, most patients with asthma are easily controlled and managed. However, approximately 5% of asthmatics do not respond to standard therapy and are classified as "difficult to control." 1 Typically, these are patients who complain of symptoms interfering with daily living despite long-term treatment with inhaled corticosteroids in doses up to 2,000 μg daily. Many factors can contribute to poor response to conventional therapy, and especially for these patients, a systematic approach is needed to identify the underlying causes. First, the diagnosis of asthma and adherence to the medication regimen should be confirmed. Next, potential persisting exacerbating triggers need to be identified and addressed. Concomitant disorders should be discovered and treated. Lastly, the impact and implications of socioeconomic and psychological factors on disease control can be significant and should be acknowledged and discussed with the individual patient. Less conventional and novel strategies for treating corticosteroid-resistant asthma do exist. However, their use is based on small studies that do not meet evidence-based criteria; therefore, it is essential to sort through and address the above issues before reverting to other therapy.

  16. Histomorphological and morphometric studies of the pancreatic islet cells of diabetic rats treated with extracts of Annona muricata. (United States)

    Adeyemi, D O; Komolafe, O A; Adewole, O S; Obuotor, E M; Abiodun, A A; Adenowo, T K


    Microanatomical changes in the pancreatic islet cells of streptozotocin induced diabetic Wistar rats were studied after treatment with methanolic extracts of Annona muricata leaves. Thirty adult Wistar rats were randomly assigned into three groups (control, untreated diabetic group, and A. muricata-treated diabetic group) of ten rats each. Diabetes mellitus was experimentally induced in groups B and C by a single intra-peritoneal injection of 80 mg/kg streptozotocin dissolved in 0.1 M citrate buffer. The control rats were intraperitoneally injected with an equivalent volume of citrate buffer. Daily intra peritoneal injections of 100 mg/kg A. muricata were administered to group C rats for two weeks. Post sacrifice the pancreases of the rats were excised and fixed in Bouin's fluid. The tissues were processed for paraffin embedding and sections of 5 mum thickness were produced and stained with H & E, Gomori aldehyde fuchsin, and chrome alum haematoxylin-phloxine for demonstration of the beta-cells of islets of pancreatic islets. Histomorphological and morphometric examination of the stained pancreatic sections showed a significant increase in the number, diameter, and volume of the beta-cells of pancreatic islets of the A. muricata-treated group (5.67 +/- 0.184 N/1000 mum(2), 5.38 +/- 0.093 mum and 85.12 +/- 4.24 mum(3), respectively) when compared to that of the untreated diabetic group of rats (2.85 +/- 0.361 N/1000 mum(2), 2.85 +/- 0.362 mum and 69.56 +/- 5.216 mum(3), respectively). The results revealed regeneration of the beta-cells of islets of pancreatic islet of rats treated with extract of A. muricata.


    Institute of Scientific and Technical Information of China (English)

    孙秀珍; 刘云; 周玎


    Objective To study the variety of airborne allergenic insects and its sensibility in asthmatic patients. Methods 300 asthmatic patients and 100 normal controls underwent skin prick test (SPT) with 13 kinds of superior airborne insect vaccine, and sera sIgE of those whose SPT results were positive were tested by BSA-ELISA. Results The total positive rate of SPT with 13 kinds of insect vaccine in asthmatic patients was 58%, and it was significantly higher than that of normal control (P<0.01). The results of SPT with Stayridae, Heliothis armigera, Psilgramma menephorn and other 7 kinds of insects were more than 30% in asthmatic patients which meant these 10 kinds of insects were main allergenic insects to asthmatic patients. The positive rate of sIgE in asthmatic patients was more than 85%, while the normal control was only 6.0%. There was significant difference between two groups (P<0.01). Conclusion Stayridae, Heliothis armigera, Psilgramma menephorn and other 7 kinds of insects were main allergenic insects to asthmatic patients and perhaps they were the main allergens to the onset of asthma at the end summer or the early autumn.

  18. A proton pump inhibitor, lansoprazole, ameliorates asthma symptoms in asthmatic patients with gastroesophageal reflux disease. (United States)

    Shimizu, Yasuo; Dobashi, Kunio; Kobayashi, Setsuo; Ohki, Ichiro; Tokushima, Masahiko; Kusano, Motoyasu; Kawamura, Osamu; Shimoyama, Yasuyuki; Utsugi, Mitsuyoshi; Sunaga, Noriaki; Ishizuka, Tamotsu; Mori, Masatomo


    Aspiration of acid to the airway causes airway inflammation, and acid stress to the airway caused by gastroesophageal reflux disease (GERD) has been known as a potential mechanism of deteriorated asthma symptoms. However, the efficacy of the acid suppressive drugs, H(2)-receptor blockers (H(2) blocker) and proton pump inhibitors, on asthma symptoms and pulmonary functions remains controversial. We therefore designed the randomized prospective study to determine the efficacy of an H(2) blocker (roxatidine, 150 mg/day) and a proton pump inhibitor (lansoprazole, 30 mg/day) on asthma symptoms of 30 asthmatic patients with GERD. These patients were divided in the two groups (15 patients for each group) and treated with either roxatidine or lansoprazole. The diagnosis of GERD was established by the method of Los Angeles classification including mucosal minimum change of Grade M and questionnaire for the diagnosis of reflux disease (QUEST) score. The efficacy of acid suppressive drugs was evaluated by peak expiratory flow (PEF), asthma control questionnaire (ACQ) that evaluates the improvement of asthma symptoms, and forced expiratory volume in 1 second (FEV(1.0)). Lansoprazole, but not roxatidine, significantly improved PEF and ACQ scores (p < 0.05) with the improved QUEST scores. However, these acid suppressive drugs did not change the pulmonary function of FEV(1.0) in asthmatic patients. In conclusion, treatment with a proton pump inhibitor, lansoprazole, appears to be useful in improvement of asthma symptoms in asthmatic patients with GERD.

  19. Evaluation of hyperdiploidy in the bladder epithelial cells of male F344 rats treated with ortho-phenylphenol. (United States)

    Balakrishnan, S; Eastmond, D A


    Ortho-phenylphenol (OPP) is a broad-spectrum fungicide and anti-bacterial agent that has been shown to cause bladder cancer in male F344 rats. An earlier study to investigate the potential role of aneuploidy in OPP-induced bladder carcinogenicity, failed to detect increases in frequencies of hyperdiploidy/polyploidy in treated animals, presumably due to the presence of polyploid cells in the bladder. To overcome this problem, we utilized a novel approach to determine increases in numerical alterations in the slowly dividing replicating cells of the rat bladder following treatment with OPP. Collagenase digestion of the bladder was used to enrich for actively-dividing cells and FISH in conjunction with BrdU was employed to detect hyperdiploidy in the replicating interphase cells. Initial studies were performed using FISH with a chromosome 4 probe. Follow-up studies were conducted with OPP and a positive control, vinblastine sulfate using probes for chromosomes 4 and 19. No significant increases in hyperdiploidy/polyploidy were seen in the replicating bladder cells of the OPP-treated rats using FISH with either the chromosome 4 or 19 probes. As expected, no significant increases in hyperdiploidy were seen in the non-replicating cells. In contrast, highly significant increases in hyperdiploidy/polyploidy, as detected using FISH with probes for either chromosome 4 or 19, were seen in the replicating cells from rats treated with a combination of OPP and vinblastine. The inability to detect increases in hyperdiploidy/polyploidy in the bladder of OPP-treated rats indicates that chromosome gain is unlikely to play a major role in the early genotoxic effects of OPP. However, the increase in hyperdiploidy/polyploidy induced by vinblastine sulfate in OPP-treated rats, clearly demonstrates that this approach using FISH in combination with BrdU is capable of detecting changes in chromosome number even in slowly-dividing tissues, such as the urinary bladder.

  20. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons

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    Anand Praveen


    Full Text Available Abstract Background Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P Conclusions Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin.

  1. Profiling of hepatic gene expression in rats treated with fibric acid analogs

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    Cornwell, Paul D.; Souza, Angus T. de; Ulrich, Roger G


    Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors whose ligands include fatty acids, eicosanoids and the fibrate class of drugs. In humans, fibrates are used to treat dyslipidemias. In rodents, fibrates cause peroxisome proliferation, a change that might explain the observed hepatomegaly. In this study, rats were treated with multiple dose levels of six fibric acid analogs (including fenofibrate) for up to two weeks. Pathological analysis identified hepatocellular hypertrophy as the only sign of hepatotoxicity, and only one compound at the highest dose caused any significant increase in serum ALT or AST activity. RNA profiling revealed that the expression of 1288 genes was related to dose or length of treatment and correlated with hepatocellular hypertrophy. This gene list included expression changes that were consistent with increased mitochondrial and peroxisomal {beta}-oxidation, increased fatty acid transport, increased hepatic uptake of LDL-cholesterol, decreased hepatic uptake of glucose, decreased gluconeogenesis and decreased glycolysis. These changes are likely linked to many of the clinical benefits of fibrate drugs, including decreased serum triglycerides, decreased serum LDL-cholesterol and increased serum HDL-cholesterol. In light of the fact that all six compounds stimulated similar or identical changes in the expression of this set of 1288 genes, these results indicate that hepatomegaly is due to PPAR{alpha} activation, although signaling through other receptors (e.g. PPAR{gamma}, RXR) or through non-receptor pathways cannot be excluded.

  2. Antimutagenic Effect of Hibiscus sabdariffa L. Aqueous Extract on Rats Treated with Monosodium Glutamate (United States)

    Kerkhoff, Jacqueline; Vieira Júnior, Gerardo Magela; de Campos, Kleber Eduardo; Sugui, Marina Mariko


    Hibiscus sabdariffa L. is a plant of the Malvaceae family, commonly known as roselle. H. sabdariffa is known to contain antioxidant, cholesterol-lowering, antiobesity, insulin resistance reduction, antihypertensive, and skin cancer chemopreventive properties. This study evaluated the effects of H. sabdariffa aqueous extract against cyclophosphamide (CPA, 25 mg/Kg) induced damage to DNA in male Wistar rats by micronucleus test. Samples of H. sabdariffa calyx were obtained in the municipality of Barra do Garças, Mato Grosso, Brazil. The aqueous extract was prepared by infusion and each animal received a daily dose of 400 mg/Kg by gavage for 15 consecutive days of treatment. The presence of anthocyanins was confirmed by ferric chloride test and phenolic compounds using high-performance liquid chromatography, with emphasis on the identification of rutin. The animals were sacrificed by deepening of anaesthesia to obtain bone marrow and determination of the frequency of micronucleated polychromatic erythrocytes. The group treated with the aqueous extract of H. sabdariffa revealed a 91% reduction in micronucleus frequency when compared with the positive control group. Under the conditions tested, H. sabdariffa L. presented a protective effect to CPA-induced damage to DNA of the treated animals, and it is a potential candidate as a chemopreventive agent against carcinogenesis. PMID:28197528

  3. Potential fat-lowering and prebiotic effects of enzymatically treated okara in high-cholesterol-fed Wistar rats. (United States)

    Villanueva-Suárez, María-José; Pérez-Cózar, María-Luisa; Mateos-Aparicio, Inmaculada; Redondo-Cuenca, Araceli


    This study evaluates the effect of the lipid profile on serum, liver and faeces, and the potential prebiotic effect of diets supplemented with enzymatically treated okara (okara(ET)) in high-cholesterol fed Wistar rats. Triglyceride levels were significantly reduced in the serum (p < 0.01) and liver (p < 0.01) of okara(ET) treated rats. Total lipids, triglycerides and bile acids were significantly higher (p < 0.001) in the faeces of rats fed the okara(ET) diet. The pH of faecal contents from treated okara(ET) rats was lower (p < 0.001), probably due to the significantly higher (p < 0.001) production of short-chain fatty acids (SCFA). Okara(ET), therefore, reduced triglycerides in serum and liver, and increased the excretion of total lipids, triglycerides and bile acids, improving the lipid profile in rats fed with high-cholesterol diets. Okara(ET) fibre can improve intestinal transit by increasing faecal bulk. The decreased pH and increased SCFA production indicated that okara(ET) fibre fermentation occurred, suggesting a potential prebiotic effect.

  4. Quercetin Improves Neurobehavioral Performance Through Restoration of Brain Antioxidant Status and Acetylcholinesterase Activity in Manganese-Treated Rats. (United States)

    Adedara, Isaac A; Ego, Valerie C; Subair, Temitayo I; Oyediran, Oluwasetemi; Farombi, Ebenezer O


    The present study investigated the neuroprotective mechanism of quercetin by assessing the biochemical and behavioral characteristics in rats sub-chronically treated with manganese alone at 15 mg/kg body weight or orally co-treated with quercetin at 10 and 20 mg/kg body weight for 45 consecutive days. Locomotor behavior was monitored using video-tracking software during a 10-min trial in a novel environment whereas the brain regions namely the hypothalamus, cerebrum and cerebellum of the rats were processed for biochemical analyses. Results indicated that co-treatment with quercetin significantly (p < 0.05) prevented manganese-induced locomotor and motor deficits specifically the decrease in total distance travelled, total body rotation, maximum speed, absolute turn angle as well as the increase in time of immobility and grooming. The improvement in the neurobehavioral performance of manganese-treated rats following quercetin co-treatment was confirmed by track and occupancy plot analyses. Moreover, quercetin assuaged manganese-induced decrease in antioxidant enzymes activities and the increase in acetylcholinesterase activity, hydrogen peroxide generation and lipid peroxidation levels in the hypothalamus, cerebrum and cerebellum of the rats. Taken together, quercetin mechanisms of ameliorating manganese-induced neurotoxicity is associated with restoration of acetylcholinesterase activity, augmentation of redox status and inhibition of lipid peroxidation in brain of rats.

  5. Antioxidant Effect of Vitamin C on Lipid Profile Parameters in Paraquat treated Male Rats (Rattus Norvegicus

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    Benjamin N. Okolonkwo


    Full Text Available BACKGROUND AND AIMThe continual use of paraquat (PQ, an herbicide, in the recreational, agricultural and industrial fa- cilities for the control of weeds has severally been linked with medical emergency poisoning cases associated with cardiovascular diseases. To buttress these views in this present study, we carried out an analysis on cardiac lipid markers [Total cholesterol (TC, Triglyceride (TG, High density lipoprotein (HDL and Low density lipoprotein (LDL] of male rats under PQ insult, with and without vitamin C given to the rats as an antioxidant. We hoped to discover if truly PQ affects lipids, and if so, in what way and could it be arrested by the subsequent use of a potent antioxidant (vitamin C.METHODSMale rats in subgroups (A1, A2, B1, B2, C1, C2, D1 and D2 were intraperitoneally (ip injected with dif- ferent sub-lethal increasing doses {0, 0.02, 0.04, and 0.06 g/kg body weight (BW} of PQ respectively on monthly basis. The subgroups (A2, B2, C2 and D2 were subsequently given 200mg/L vitamin C, while the subgroups (A1, B1, C1 and D1 received only water. At the end of every month 2mls of blood samples were taken from 4 animals per subgroup under anesthetics and following interna- tionally approved standard protocol on Animal care.RESULTSThere was a dose and time of exposure dependent reduction in TC values of both the vitamin c treat- ed and the non-vitamin c treated subgroups. The increased TC values observed in the control were significantly lower (P ≤ 0.05 in the results of the subgroup on vitamin C (A2 when compared to the subgroup without vitamin C (A1 even as the time of exposure increased. The test subgroups (B1, B2, C1, C2, D1 and D2 gave a dose and exposure time dependent reduction in its TC values when com- pared to that of the control subgroups (A1 and A2 at P ≤ 0.05. The vitamin C treated test subgroups (B2, C2 and D2 were not statistically different from that of the non-vitamin C treated test subgroups (B1, C1 and D1

  6. Observation of the hepatoprotective and antioxidant activities of Trianthema decandra Linn. (Vallai sharunnai roots on carbon tetrachloride-treated rats

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    G. Balamurugan


    Full Text Available The present study was carried out to observe the hepatoprotective effect and antioxidant activity of the ethanol extract of the roots of Trianthema decandra Linn. (200 and 400 mg/kg in rats treated with carbon tetrachloride for 8 weeks. Extract at the tested doses restored the levels of all serum (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and total protein and liver homogenate enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase significantly. Histology demonstrated profound steatosis degeneration and nodule formation were observed in the hepatic architecture of carbon tetrachloride treated rats which were found to acquire near-normalcy in extract plus carbon tetrachloride administrated rats, and supported the biochemical observations. This study suggests that ethanol extract of T. decandra has a liver protective effect against carbon tetrachloride- induced hepatotoxicity and possess antioxidant activities.

  7. Requirements of glycerol and fatty acid for triglyceride synthesis and ketogenesis by hepatocytes from normal and triiodothyronine-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Olubadewo, J.O.; Heimberg, M.


    Hepatocytes from T3-treated rats synthesized less triglyceride and more ketone bodies from (1-/sup 14/C)oleate at all concentrations from 0-2 mM, than did hepatocytes from euthyroid animals; addition of 1.0 mM glycerol increased triglyceride synthesis and reduced ketogenesis in hepatocytes from T3-treated rats to the rates observed in euthyroid hepatocytes in the absence of added glycerol. Glycerol did not alter triglyceride synthesis, but reduced ketogenesis genesis by euthyroid hepatocytes. It is probable from these and other data that, in the hyperthyroid rat, glycero-3-P, and not fatty acid, is rate limiting for synthesis of triglyceride, and, secondarily for reducing rates of ketogenesis in the hepatocyte.

  8. Unscheduled DNA synthesis in rat pleural mesothelial cells treated with mineral fibres. (United States)

    Renier, A; Lévy, F; Pillière, F; Jaurand, M C


    Unscheduled DNA synthesis (UDS) was studied in confluent rat pleural mesothelial cells (RPMCs) arrested in G0/G1 with hydroxyurea (HU) and treated with various fibre types, i.e., chrysotile, crocidolite or attapulgite. In addition, the effects of UV light and of benzo[a]pyrene were determined as references. Using autoradiography after [3H]thymidine incorporation ([3H]dThd), RPMCs treated with 4 micrograms/cm2 of chrysotile fibres exhibited a low but significant enhancement of net grains compared to untreated cells. Treatment with higher doses of chrysotile was not possible because of the impairment of microscopic observation due to the presence of the fibres. Using liquid scintillation counting, RPMCs treated with chrysotile or crocidolite showed a significant dose-dependent increase in [3H]dThd incorporation compared to untreated cells. In contrast, attapulgite did not enhance [3H]dThd incorporation compared to untreated cells. Treatment of RPMCs with 1, 2 or 4 micrograms/ml of benzo[a]pyrene resulted in a significant increase in [3H]dThd incorporation. In order to discount a possible role of S cells in the augmentation of [3H]dThd incorporation, despite the presence of 5 mM HU, S cells were counted by autoradiography. Results indicated that the percentage of S cells was similar in asbestos-treated and untreated cultures. Stimulation of the S phase also seems unlikely because treatment of RPMCs with asbestos fibres in the absence of HU resulted in a reduction of [3H]dThd incorporation attributed to an impairment of the S phase by the fibres. 1-4 micrograms/ml benzo[a]pyrene or 10-50 J/m2 UV light resulted in an approximate doubling of [3H]dThd incorporation. The effects of inhibitors of DNA repair were determined in chrysotile-treated RPMCs. [3H]dThd incorporation was inhibited by cytosine arabinoside and nalidixic acid. These results show that asbestos produces UDS in RPMCs.

  9. DNA breaks induced by micromolar concentrations of dimethylnitrosamine in liver primary cell cultures from untreated and phenobarbital treated rats. (United States)

    Mendoza-Figueroa, T; López-Revilla, R; Villa-Treviño, S


    Direct genotoxic effects of the alkylating agent dimethylnitrosamine (DMN) have been difficult to detect in several short-term tests. We simplified our method to detect DNA breaks induced by DMN in rat liver primary cell cultures, and increased its sensitivity about 150 times by changing the conditions of ultracentrifugation and exposure to DMN. Additionally we increased 4 times the sensitivity of the improved assay by isolating hepatocytes from rats treated with phenobarbital (PB). Treatment for 24 h with 60 microM and 13.5 microM DMN of hepatocytes isolated from untreated and PB-treated rats, respectively, decreased the molecular weight of DNA by 50%. After 24 h exposure to 13.5 microM [14C]DMN, hepatocytes from PB-treated rats incorporated 3 times more radioactivity into trichloroacetic acid precipitable material than hepatocytes from untreated rats. Also PB-treatment increased remarkably cytotoxic effects of DMN while it did not modify the cytotoxicity nor the genotoxicity of the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. These results show that DMN is more genotoxic for hepatocytes from PB-treated rats, and suggest that the enhanced genotoxicity is probably due to an augmented metabolism of DMN by these cultures. Our improved assay of DNA breaks as an indicator of DMN genotoxicity is now as sensitive but faster to perform than hepatocyte-mediated mutagenesis. It could be used to explore genotoxic effects of other alkylating agents and the action of microsomal enzyme modifiers on genotoxicity.

  10. Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke. (United States)

    Li, Y; Mao, W W; Zhang, C G; Wan, L; Jing, C H; Hua, X M; Li, S T; Cheng, J


    Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.

  11. Achilles tendon of wistar rats treated with laser therapy and eccentric exercise

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    Maria Verônica de Souza


    Full Text Available ABSTRACTIntroduction:Both laser therapy and eccentric exercises are used in tendon injuries. However, the association of these physiotherapeutic modalities is yet little investigated.Objective:To evaluate the effect of low-level laser therapy associated to eccentric exercise (downhill walking on Achilles tendinopathy of Wistar rats.Method:Eighteen Achilles tendon from 15 adult male Wistar rats were used. Tendons were distributed in six groups (laser, eccentric exercise, laser and eccentric exercise, rest, contralateral tendon, and healthy tendon. Unilateral tendinopathy was surgically induced by transversal compression followed by scarification of tendon fibers. The treatments laser therapy (904 nm, 3J/cm² and/or eccentric exercise (downhill walking; 12 m/min; 50 min/day; 15o inclination treadmill began 24 hours after surgery and remained for 20 days. Clinical and biomechanical analyzes were conducted. Achilles tendon was macroscopically evaluated and the transversal diameter measured. Euthanasia was performed 21 days after lesion induction. Tendons of both limbs were collected and frozen at -20°C until biomechanical analysis, on which the characteristic of maximum load (N, stress at ultimate (MPa and maximum extension (mm were analyzed.Results:Swelling was observed within 72 hours postoperative. No fibrous adhesions were observed nor increase in transversal diameter of tendons. Animals with the exercised tendons, but not treated with laser therapy, presented lower (p=0.0000 locomotor capacity. No difference occurred be-tween groups for the biomechanical characteristics maximum load (p=0.4379, stress at ultimate (p=0.4605 and maximum extension (p=0.3820 evaluated, even considering healthy and contralateral tendons.Conclusion:The concomitant use of low-level laser and the eccentric exercise of downhill walking, starting 24 hours after surgically induced tendinopathy, do not result in a tendon with the same biomechanical resistance or elasticity

  12. Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons

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    Pham Serena


    Full Text Available Abstract Background Oxidative stress plays an important role in neuronal dysfunction and neuron loss in Alzheimer's brain. Previous studies have reported downregulation of CREB-mediated transcription by oxidative stress and Aβ. The promoter for CREB itself contains cyclic AMP response elements. Therefore, we examined the expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem brain and in cultured rat hippocampal neurons exposed to Aβ aggregates. Results Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse brain revealed decreases in the mRNA levels of CREB and its target, BDNF. Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB levels in hippocampus and cortex. Markers of oxidative stress were detected in transgenic mouse brain and decreased CREB staining was observed in regions showing abundance of astrocytes. There was also an inverse correlation between SDS-extracted Aβ and CREB protein levels in Alzheimer's post-mortem hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase inhibitor, decreased and the active cleaved form of caspase-9, a marker for the intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat primary hippocampal neurons to Aβ fibrils decreased CREB promoter activity. Decrease in CREB mRNA levels in Aβ-treated neurons was reversed by the antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction led to significant protection against Aβ-induced neuronal apoptosis. Conclusions Our findings suggest that chronic downregulation of CREB-mediated transcription results in decrease of CREB content in the hippocampal neurons of AD brain which may contribute to exacerbation of disease progression.

  13. Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats. (United States)

    Funatsu, Toshiyuki; Chono, Koji; Hirata, Takuya; Keto, Yoshihiro; Kimoto, Aishi; Sasamata, Masao


    The mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) suppress gastric mucosal blood flow is not fully understood, although the depletion of mucosal prostaglandin E2 has been proposed as one possible explanation. We investigated the role of gastric acid on gastric mucosal blood flow in NSAID-treated rats. A rat stomach was mounted in an ex vivo chamber, and gastric mucosal blood flow was measured sequentially in a 5-mm2 area of the gastric corpus using a scanning laser Doppler perfusion image system. Results showed that diclofenac (5 mg/kg s.c.) and indomethacin (10 mg/kg s.c.) did not affect gastric mucosal blood flow, although both strongly decreased mucosal prostaglandin E2 when saline was instilled into the gastric chamber. On replacement of the saline in the chamber with 100 mM hydrochloric acid, these drugs caused a decrease in gastric mucosal blood flow levels within 30 min. The specific cyclooxygenase (COX)-2 inhibitors celecoxib (50 mg/kg s.c.) and rofecoxib (25 mg/kg s.c.) did not affect mucosal prostaglandin E2 level, nor did they decrease gastric mucosal blood flow, even when hydrochloric acid was added to the chamber. Furthermore, measurement of vasoconstrictive factors present in the mucosa showed that endothelin-1 levels increased after administration of diclofenac s.c. in the presence of intragastric hydrochloric acid. This indicates that the presence of mucosal hydrochloric acid plays an important role in the NSAID-induced decrease in gastric mucosal blood flow, while the COX-1-derived basal prostaglandin E2, which is unlikely to control gastric mucosal blood flow itself, protects microcirculatory systems from mucosal hydrochloric acid.

  14. Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

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    Campos-Martorell M


    Full Text Available Mireia Campos-Martorell,1 Mary Cano-Sarabia,2 Alba Simats,1 Mar Hernández-Guillamon,1 Anna Rosell,1 Daniel Maspoch,2,3 Joan Montaner1,4 1Neurovascular Research Laboratory, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, 2Catalan Institute of Nanoscience and Nanotechnology (ICN2, CSIC and The Barcelona Institute of Science and Technology, Universitat Autònoma de Barcelona, Barcelona, 3Institució Catalana de Recerca i Estudis Avançats (ICREA, 4Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain Background and aims: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt surgery and treated (intravenous [IV] with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results: Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes

  15. Exercise-Induced Asthma in Asthmatic Children of Southern Iran


    Fayezi, Abbas; Amin, Reza; Kashef, Sara; Yasin, Soheila Al; Bahadoram, Mohammad


    Background: Asthma is a common illness, especially among children. Exercise-induced asthma is an important consideration, both as a factor, limiting physical activity of patients, and also as an indicator of poor long term control. We investigated pre-Valence of exercise-induced asthma in a group of asthmatic children living in southern Iran. Methods: We conducted treadmill exercise challenge test in 40 young asthmatic patients aged 6 to 18. After 8 minutes exercise to achieve 80% of maximum ...

  16. Hepatoprotective effects of Quercus infectoria gall extract against carbon tetrachloride treated liver injury in rats

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    Gaurav Lodhi


    Full Text Available Summary. In the present study, galls of Quercus infectoria possessing potent antioxidant and antiinflammatory properties were evaluated for their hepatoprotective effect against carbon tetrachloride (CCl4 induced hepatotoxicity in rats. Subcutaneous injection of CCl4, administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase (AST, alanine transaminase (ALT and tumor necrosis factor alpha (TNF-α. Histological analysis of the liver of these rats revealed marked necro-inflammatory changes that were associated with increase in the levels of TBARS, PGE2 and catalase and decrease in the levels of glutathione (GSH, superoxide dismutase (SOD and glutathione peroxidase (GPx. Daily oral administration of aqueous ethanolic extract of Quercus infectoria galls at 200, 400 and 600 mg/kg doses produced a dose dependent reduction in the serum levels of liver enzymes and inflammatory mediators and attenuated the necroinflammatory changes in the liver. The QIE treatment also normalized various biochemical parameters of oxidative stress. Our study shows that the hepatoprotective effects of QIE and silymarin were comparable and suggests that QIE could be used as a hepatoprotective agent. Industrial relevance. Research in traditional medicine has lead to the development of many modern medicines. In recent times, focus on plants research has increased all over the world and a large body of evidence has been collected to show immense potential of medicinal plants used in various traditional systems. It is very interesting to note that there is no drug available in the modern system of medicine for treating hepatic disorders; only certain herbal preparations are available to treat this quite vulnerable disease. The situation/background thus explained above warrants for developing a safe, effective and scientifically validated hepatoprotective agent taking lead from traditional medicine, which is affordable for the rural poor

  17. Experimental erythrocyte autoantibodies. V. Induction and suppression of red blood cell autoantibodies in mice injected with rat bromelain-treated red blood cells. (United States)

    Cox, K O; McAuliffe, A


    Mice injected with rat red blood cells (RBC), or rat bromelain-treated (brom) RBC, produce RBC autoantibodies and suppressor cells that specifically inhibit the autoimmune response without inhibiting the net production of antibodies against rat RBC. It has been investigated whether suppressor cells induced by injections of rat RBC are effective in preventing autoantibody production induced by rat brom RBC and vice versa. Autoantibodies were induced in C3H mice by weekly ip injections, each 0.2 ml, of a 6% suspension of rat RBC or rat brom RBC. Autoantibody production was assayed using Coombs' test. Suppressor cells were present in the spleens of mice positive in Coombs' tests and were shown by intravenous injections of 40 X 10(6) viable cells per mouse into untreated syngeneic mice 18 hr before the first injection of rat RBC or rat brom RBC. Autoantibodies eluted from mice positive in Coombs' tests after injections of rat RBC or brom RBC were absorbed by either type of rat RBC but not by RBC from sheep. This suggests that rat RBC and rat brom RBC display antigens that are similar, if not identical, to autoantigens on the mouse RBC. Spleen cells from mice injected with rat RBC suppressed autoantibodies induced by both rat RBC and rat brom RBC. In contrast, spleen cells from mice injected with rat brom RBC suppressed autoantibodies induced by rat brom RBC but not those induced by unmodified rat RBC. This differential suppression may be due to the removal from rat RBC, by bromelain, of a suppressor site and/or autoantigens of some specificities. Thus rat brom RBC may not induce the total range of specificities of autoantibodies, and of suppressor cells, induced by rat RBC.

  18. Haematological and lipid profile assays in Nigerian asthmatics

    Institute of Scientific and Technical Information of China (English)

    Caroline E Omotil; Egbagbe Eruke Elizabeth


    Objective: To assess the haematological and lipid profile assays in asthmatics. Methods: Eighty asthmatic subjects were prospectively studied in a major referral centre serving the Niger Delta region of Nigeria for 12 months (2006-2007). Clinico-haematological and serum lipid total cholesterol (TC), triglyceride (TG), and lipoproteins concentration were analyzed after adjusting for age, cigarette smoking, alcohol ingestion, hypertension and diabetes mellitus. Results: Eighty patients (34 males and 46 females) were seen with female predominating in the various age groups (M∶ F ratio, 0.7∶ 1). Total cholesterol and low density lipoproteins-cholesterol for the asthmatics was significantly higher than the controls (P2.3mmol/L) and a significant hypercholesterolemia (HC, >5.2mmol/L) according to the Adult Treatment Panel III definition in asthmatics thereby putting them at increased risk for the development of cardiovascular disease as well as other disorders related to excess lipids. There was a significant thrombocytopenia (P<0.000 1) which may accompany allergen exposure and this persists for 24 h; that asthmatics of African descent showed a significantly increased total leucocyte count (P=0.001) similar to other studies in the Western countries. Conclusion: Hyperlipidaemia is a prevalent medical problem among asthmatics; hence screening for fasting serum lipid levels to identify those who need early intervention is recommended.

  19. Physiological Changes at Altitude in Nonasthmatic and Asthmatic Subjects

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    Dianna Louie


    Full Text Available Exercised-induced asthma is not due to exercise itself per se, but rather is due to cooling and/or drying of the airway because of the increased ventilation that accompanies exercise. Travel to high altitudes is accompanied by increased ventilation of cool, often dry, air, irrespective of the level of exertion, and by itself, this could represent an 'exercise' challenge for asthmatic subjects. Exercise-induced bronchoconstriction was measured at sea level and at various altitudes during a two-week trek through the Himalayas in a group of nonasthmatic and asthmatic subjects. The results of this study showed that in mild asthmatics, there was a significant reduction in peak expiratory flow at very high altitudes. Contrary to the authors' hypothesis, there was not a significant additional decrease in peak expiratory flow after exercise in the asthmatic subjects at high altitude. However, there was a significant fall in arterial oxygen saturation postexercise in the asthmatic subjects, a change that was not seen in the nonasthmatic subjects. These data suggest that asthmatic subjects develop bronchoconstriction when they go to very high altitudes, possibly via the same mechanism that causes exercise-induced asthma.

  20. Role of Mas receptor in renal blood flow response to angiotensin-(1-7 in ovariectomized estradiol treated rats

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    Shadan Saberi


    Full Text Available The angiotensin 1-7 (Ang 1-7, is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV female rats. OV female Wistar-rats received estradiol (500 μg/kg/week or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF, and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (P dose <0.001 and A779-treated (P dose<0.01 animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05. When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

  1. The ECM deposited by basal asthmatic and non-asthmatic ASM cells is different in composition but not biological function

    NARCIS (Netherlands)

    Harkness, L.; Ashton, A.; Burgess, J.


    Aim: The remodelled asthmatic airway has increased airway smooth muscle cell (ASMC) growth, expanded vasculature, and altered extracellular matrix (ECM). The ECM is the external cellular microenvironment which regulates cell behaviour. Under proliferative, inflammatory, or fibrotic conditions, the a

  2. Comparison of the metabolism of dodecanedioic acid in vivo in control, riboflavin-deficient and clofibrate-treated rats. (United States)

    Draye, J P; Veitch, K; Vamecq, J; Van Hoof, F


    Intravenous administration of dodecanedioate (or hexadecanedioate) to anaesthetized rats resulted in the urinary excretion of medium-chain dicarboxylic acids (adipic, suberic and sebacic acids). In control animals, the recovery of infused dodecanedioate in the form of urinary medium-chain dicarboxylic acids corresponded to 30% of the infused dose (22 mumol/100 g body mass). This excretion was markedly increased in riboflavin-deficient rats (75% of the infused dose) while it was severely decreased in clofibrate-treated animals (less than 5%). The initial velocity of this process was similar in both control and riboflavin-deficient rats. In control animals, halving the infused dose of dodecanedioate to 11 mumol/100 g body mass resulted in a halving of the initial rate of the urinary appearance of medium-chain dicarboxylates, while doubling the amount of dicarboxylate administered to 44 mumol/100 g body mass did not further modify this velocity, but rather prolonged the duration of the excretion of the resulting products. In riboflavin-deficient and clofibrate-treated rats, the hepatic peroxisomal dicarboxylyl-CoA beta-oxidation activity measured as dicarboxylyl-CoA H2O2-generating oxidase and cyanide-insensitive dicarboxylyl-CoA-dependent NAD+ reduction was increased about threefold and tenfold, respectively. Dicarboxylyl-CoA synthetase activity was normal in the clofibrate-treated rat livers but was increased more than tenfold in the livers from the riboflavin-deficient animals. This work provides evidence that in the rat both mitochondria and peroxisomes are involved in the catabolism of dicarboxylates.

  3. Hormones of thyroid gland in sera of rats treated with different dose of concentrated potassium iodine solutions

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    Marković Ljiljana


    Full Text Available Introduction Potassium iodine (KI is used as a drug therapy for treating numerous diseases such as small-vessel vasculitis, erythema nodosum, vasculitis nodularis, Sweet's syndrome, tuberculosis and granulomatosis, and for iodized salt. At the same time, KI can be harmful. Iodine intake may increase the frequency of thyroiditis in humans, and may induce the occurrence of experimental thyroiditis (ET in animals. Investigations on an experimental model for the examination of thyroiditis in Wistar rats have clearly showed morphological changes in the rat thyroid evoked by KI administration. Objective The purpose of this study was to compare the effects of low and high doses of KI on the thyroid gland of Wistar rats and determine the effect on hormone status (T4, T3 and TSH in this rat strain. Methods Two groups of rats from the Wistar strain were treated with a low iodine dose (225 μg/g BW and with a high iodine dose (675 μg/g BW of KI solutions. Untreated nonimmunized animals served as controls. The solution was administrated daily intraperitoneally during the period of 26 consecutive days. Results Monitoring hormone status (TSH, T3 and T4 and morphological changes it was found that therapeutic doses of KI applied in treatment induced the occurrence of experimental thyroiditis (chronic destructive Hashimoto's thyroiditis in humans and cell necrosis in animals not carrying a genetic susceptibility. Significant inflammatory changes were observed in rats treated with a high iodine dose. Conclusion The early iodine induced cell necrosis and inflammation in the nonimmunized animals without genetic susceptibility is a new experimental model of thyroiditis. .

  4. Diet-dependent modulation of hippocampal expression of endocannabinoid signaling-related proteins in cannabinoid antagonist-treated obese rats. (United States)

    Rivera, Patricia; Luque-Rojas, María Jesús; Pastor, Antoni; Blanco, Eduardo; Pavón, Francisco J; Serrano, Antonia; Crespillo, Ana; Vida, Margarita; Grondona, Jesús M; Cifuentes, Manuel; Bermúdez-Silva, Francisco J; de la Torre, Rafael; de Fonseca, Fernando Rodríguez; Suárez, Juan


    Diet-induced obesity produces changes in endocannabinoid signaling (ECS), influencing the regulation of energy homeostasis. Recently, we demonstrated that, in high-fat-diet-fed rats, blockade of CB1 receptor by AM251 not only reduced body weight but also increased adult neurogenesis in the hippocampus, suggesting an influence of diet on hippocampal cannabinoid function. To further explore the role of hippocampal ECS in high-fat-diet-induced obesity, we investigated whether the immunohistochemical expression of the enzymes that produce (diacylglycerol lipase alpha and N-acyl phosphatidylethanolamine phospholipase D) and degrade (monoacylglycerol lipase and fatty acid amino hydrolase) endocannabinoids may be altered in the hippocampus of AM251 (3 mg/kg)-treated rats fed three different diets: standard diet (normal chow), high-carbohydrate diet (70% carbohydrate) and high-fat diet (60% fat). Results indicated that AM251 reduced caloric intake and body weight gain, and induced a modulation of the expression of ECS-related proteins in the hippocampus of animals exposed to hypercaloric diets. These effects were differentially restricted to either the 2-arachinodoyl glycerol or anandamide signaling pathways, in a diet-dependent manner. AM251-treated rats fed the high-carbohydrate diet showed a reduction of the diacylglycerol lipase alpha : monoacylglycerol lipase ratio, whereas AM251-treated rats fed the high-fat diet showed a decrease of the N-acyl phosphatidylethanolamine phospholipase D : fatty acid amino hydrolase ratio. These results are consistent with the reduced levels of hippocampal endocannabinoids found after food restriction. Regarding the CB1 expression, AM251 induced specific changes focused in the CA1 stratum pyramidale of high-fat-diet-fed rats. These findings indicated that the cannabinoid antagonist AM251 modulates ECS-related proteins in the rat hippocampus in a diet-specific manner. Overall, these results suggest that the hippocampal ECS participates

  5. Royal Jelly Modulates Oxidative Stress and Apoptosis in Liver and Kidneys of Rats Treated with Cisplatin

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    Ali Karadeniz


    Full Text Available Cisplatin (CDDP is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg-1 body weight i.p., single dose; group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day; group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA and glutathione (GSH levels, glutathione S-transferase (GST, glutathione peroxidase (GSH-Px, and superoxide dismutase (SOD activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA, elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.

  6. Royal jelly modulates oxidative stress and apoptosis in liver and kidneys of rats treated with cisplatin. (United States)

    Karadeniz, Ali; Simsek, Nejdet; Karakus, Emre; Yildirim, Serap; Kara, Adem; Can, Ismail; Kisa, Fikrullah; Emre, Habib; Turkeli, Mehmet


    Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ) against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg(-1) body weight i.p., single dose); group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day); group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA), elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.

  7. Calcitriol promotes augmented dopamine release in the lesioned striatum of 6-hydroxydopamine treated rats (United States)

    Cass, Wayne A.; Peters, Laura E.; Fletcher, Anita M.; Yurek, David M.


    Current therapies for Parkinson's disease (PD) offer symptomatic relief but do not provide a cure or slow the disease process. Treatments that could halt progression of the disease or help restore function to damaged neurons would be of substantial benefit. Calcitriol, the active metabolite of vitamin D, has been shown to have significant effects on the brain. These effects include upregulating trophic factor levels, and reducing the severity of some central nervous system lesions. While previous studies have shown that calcitriol can be neuroprotective in 6-hydroxydopamine (6-OHDA) rodent models of PD, the present experiments were designed to examine the ability of calcitriol to promote restoration of extracellular DA levels and tissue content of DA in animals previously lesioned with 6-OHDA. Male Fischer-344 rats were given a single injection of 12 µg 6-OHDA into the right striatum. Four weeks later the animals were administered vehicle or calcitriol (0.3 or 1.0 µg/kg, s.c.) once a day for eight consecutive days. Three weeks after the calcitriol treatments in vivo microdialysis experiments were conducted to measure potassium and amphetamine evoked overflow of DA from both the left and right striata. In control animals treated with 6-OHDA and vehicle there were significant reductions in both potassium and amphetamine evoked overflow of DA on the lesioned side of the brain compared to the contralateral side. In animals treated with 6-OHDA followed by calcitriol there was significantly greater potassium and amphetamine evoked overflow of DA from the lesioned striatum compared to that from the control animals. The calcitriol treatments also led to increases in postmortem tissue levels of DA in the striatum and substantia nigra. These results suggest that calcitriol may help promote recovery of dopaminergic functioning in injured nigrostriatal neurons. PMID:24858239

  8. Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with levetiracetam: a preliminary study. (United States)

    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.

  9. Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in ethanol-treated Wistar rats. (United States)

    Saravanan, R; Prakasam, A; Ramesh, B; Pugalendi, K V


    Piper betle L. is a commonly used masticatory in Asia. This study was carried out to investigate the hepatoprotective and antioxidant properties of P. betle, using ethanol intoxication as a model of hepatotoxic and oxidative damage. Ethanol-treated rats exhibited elevation of hepatic marker enzymes and disturbances in antioxidant defense when compared with normal rats. Oral administration of P. betle extract (100, 200, or 300 mg/kg body weight) for 30 days significantly (P betle extract (300 mg/kg body weight) was most effective. The results were comparable with the known hepatoprotective drug, silymarin. These results indicate that P. betle could afford a significant hepatoprotective and antioxidant effect.

  10. Oxidative damages in isolated rat hepatocytes treated with the organochlorine fungicides captan, dichlofluanid and chlorothalonil. (United States)

    Suzuki, Toshihide; Nojiri, Hisao; Isono, Hideo; Ochi, Takafumi


    The cytotoxicity and lipid peroxidative potency of the organochlorine fungicides captan (N-(trichloromethylthio)-4-cyclohexene-1,2-dicarboximide), dichlofluanid (N-dichlorofluoromethylthio-N'N'-dimethyl-N-phenylsulfamide) and chlorothalonil (2,4,5,6-tetrachloro-isophthalonitrile) were studied in isolated rat hepatocytes. These fungicides induced cytotoxicity and lipid peroxidation in a dose- and time-dependent manner. Considerable cytotoxicity and lipid peroxidation occurred after cells were treated with 25 microM and more of fungicide. The phosphatidylcholine hydroperoxide (PCOOH) content increased more than 300 times by captan (250-1000 microM), 400 times by dichlofluanid (250-1000 microM) and 20 times by chlorothalonil (25-1000 microM) after 1h of incubation, as compared with untreated control. Significant cytotoxicity occurred after 20 min (captan), 30 min (dichlofluanid) and 60 min (chlorothalonil) of incubation and lipid peroxidation was induced prior to cytotoxicity. The antioxidant alpha-tocopherol and cytochrome P450 inhibitor SKF-525A effectively prevented cytotoxicity and lipid peroxidation. Our results suggest that metabolites of these fungicides produced by the microsomal cytochrome P450 system, induced membrane phospholipid peroxidation that caused cytotoxicity.

  11. The effect of thyroxin on hepatic redox equilibrium and lipid metabolism in rats treated with doxorubicin

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    Czuba Bartosz


    Full Text Available The main side effects of the administration of doxorubicin, a widely used anticancer drug, is the generation of a reactive oxygen species (ROS in normal cells. As a result, redox disorders and secondary oxidative stress are developed. Doxorubicin ROS generation is attributed to enzymes that are produced abundantly in hepatocytes. Oxidative stress has been a well-known risk factor of doxorubicin-related toxicity. However, in addition, according to the data collected in the last decade, changes in thyroxin status can propagate ROS generation, and, thus, initiate the doxorubicin hepatic effect. Moreover, both compounds have an impact on the cell metabolism. The aim of the study was to verify the thesis that thyroxin can modulate the effect of doxorubicin with regard to redox status and lipid metabolism disorders. In our work, we determined the ratio of NADP+/ NADPH and NAD+/NADH in liver homogenates, blood ketone bodies and triglycerides in the liver and blood in rats treated with doxorubicin and thyroxin. Our results indicate that thyroxin has an insignificant effect on NAD+/NADH, NADP+/NADPH ratios and on hepatic and blood triglycerides. Moreover, thyroxin administration normalized the level of blood ketone bodies that was disturbed by doxorubicin.

  12. Histomorphometric analysis of the Achilles tendon of Wistar rats treated with laser therapy and eccentric exercise

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    Maria V. de Souza


    Full Text Available Abstract: Low-level laser therapy is recommended for the treatment of tendinopathies despite the contradictory results related to the ideal dose of energy, wavelength and time of application. This study aimed to assess the effects of laser therapy and eccentric exercise on tendinopathy of the Achilles tendon of Wistar rats. Forty-eight adult male rats were randomly distributed into four groups (L= laser; E= eccentric exercise; LE = laser and eccentric exercise; and R= rest. Laser therapy (904nm/3J/cm2 and/or eccentric exercise (downhill walking; 15o incline treadmill; 12m/min; 50min/day was started 24h after induction of unilateral tendinopathy and remained for 20 days. At 3, 7, 14 and 21 days after lesion induction, three rats from each group were euthanized and the tendons were collected for histological and morphometric analyses. There was no difference among groups or among times for the characteristics hemorrhage (p=0.4154, fibrinous adhesion formation (p=0.0712, and organization of collagen fibers (p=0.2583 and of the connective tissue (p=0.1046. For these groups, regardless of the time, eccentric exercise led to epitenon thickening (p=0.0204, which was lower in the group treated with laser therapy. Histological analysis revealed differences (p=0.0032 in the number of inflammatory cells over time. They were more numerous in the group that only exercised. This result was confirmed by morphometric analysis, which showed a significant interaction (groups x time for this characteristic. Eccentric exercise increased (p=0.0014 the inflammatory infiltrate over time (3 and 21 days. However, association with laser therapy reduced inflammatory reaction. On the other hand, the combination of the treatments increased angiogenesis in morphometric (p=0.0000 and histological (p=0.0006 analyses compared with the other groups, while the isolated application of low-level laser reduced this characteristic over time. Animals maintained at rest presented the

  13. Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazide in vitro in healthy and diabetic rats treated with probiotics. (United States)

    Al-Salami, H; Butt, G; Tucker, I; Mikov, M


    The aim of this study was to investigate the influence of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats treated with probiotics. Male Wistar rats (2-3 months, 350 +/- 50 g) were randomly allocated into four groups (n = 32); Groups 1 and 2 were healthy controls and Groups 3 and 4 were diabetic rats (alloxan 30 mg/kg was administered i.v.), which were administered probiotics for three days after the rats became diabetics. The rats were sacrificed and tissues were mounted on Ussing chambers. Then, gliclazide (200 microg/ml) was added to all the groups, while MKC (50 microg/ml) was given to Groups 2 and 4, for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. In the tissues of healthy rats treated with probiotics, MKC stimulated the net absorption of gliclazide by stimulating the absorptive and reducing the secretory unidirectional fluxes, while in tissues from diabetic rats treated with probiotics, MKC had no effect. In healthy rats treated with probiotics, the degradation of MKC by bacterial polypeptides produced divalent bile salts that inhibited Mrp2, which resulted in reducing secretion and stimulating the absorption of gliclazide. In contrast, in diabetic rats treated with probiotics, MKC had no effect possibly due to a difference in the metabolic profile and resulting in no net flux.

  14. Detection of micronuclei, cell proliferation and hyperdiploidy in bladder epithelial cells of rats treated with o-phenylphenol. (United States)

    Balakrishnan, S; Uppala, P T; Rupa, D S; Hasegawa, L; Eastmond, D A


    o-Phenylphenol (OPP), a widely used fungicide and antibacterial agent, has been considered to be among the top 10 home and garden pesticides used in the USA. Earlier studies have consistently shown that the sodium salt of OPP (SOPP) causes bladder cancer in male Fischer 344 (F344) rats, whereas OPP has produced variable results. This difference has been attributed to the presence of the sodium salt. To determine cellular and genetic alterations in the rat bladder and the influence of the sodium salt, F344 rats were administered 2% OPP, 2% NaCl and 2% NaCl + 2% OPP in their diet for 14 days. Twenty-four hours before being killed the animals were administered 5-bromo-2'-deoxyuridine (BrdU) by i.p. injection. Bladder cells were isolated, stained with DAPI and scored for the presence of micronuclei and incorporation of BrdU into replicating cells. To determine changes in chromosome number, we used fluorescence in situ hybridization (FISH) with a DNA probe for rat chromosome 4. Significant increases in the frequency of micronuclei and BrdU incorporation were seen in bladder cells of rats from all treatment groups. In contrast, the frequency of hyperdiploidy/polyploidy in treated animals was not increased over that seen in controls. A high control frequency of cells with three or more hybridization signals was seen, probably due to the presence of polyploid cells in the bladder. The presence of polyploid cells combined with cytotoxicity and compensatory cell proliferation makes it difficult to determine whether OPP is capable of inducing aneuploidy in the rat urothelium. In summary, these studies show that OPP can cause cellular and chromosomal alterations in rat bladder cells in the absence of the sodium salt. These results also indicate that at high concentrations the sodium salt can enhance chromosomal damage in the rat urothelium.

  15. Ectopic pregnancy-derived human trophoblastic stem cells regenerate dopaminergic nigrostriatal pathway to treat parkinsonian rats.

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    Tony Tung-Yin Lee

    Full Text Available BACKGROUND: Stem cell therapy is a potential strategy to treat patients with Parkinson's disease (PD; however, several practical limitations remain. As such, finding the appropriate stem cell remains the primary issue in regenerative medicine today. We isolated a pre-placental pluripotent stem cell from the chorionic villi of women with early tubal ectopic pregnancies. Our objectives in this study were (i to identify the characteristics of hTS cells as a potential cell source for therapy; and (ii to test if hTS cells can be used as a potential therapeutic strategy for PD. METHODS AND FINDINGS: hTS cells expressed gene markers of both the trophectoderm (TE and the inner cell mass (ICM. hTS cells exhibited genetic and biological characteristics similar to that of hES cells, yet genetically distinct from placenta-derived mesenchymal stem cells. All-trans retinoic acid (RA efficiently induced hTS cells into trophoblast neural stem cells (tNSCs in 1-day. Overexpression of transcription factor Nanog was possibly achieved through a RA-induced non-genomic c-Src/Stat3/Nanog signaling pathway mediated by the subcellular c-Src mRNA localization for the maintenance of pluripotency in tNSCs. tNSC transplantation into the lesioned striatum of acute and chronic PD rats not only improved behavioral deficits but also regenerated dopaminergic neurons in the nigrostriatal pathway, evidenced by immunofluorescent and immunohistological analyses at 18-weeks. Furthermore, tNSCs showed immunological advantages for the application in regenerative medicine. CONCLUSIONS: We successfully isolated and characterized the unique ectopic pregnancy-derived hTS cells. hTS cells are pluripotent stem cells that can be efficiently induced to tNSCs with positive results in PD rat models. Our data suggest that the hTS cell is a dynamic stem cell platform that is potentially suitable for use in disease models, drug discovery, and cell therapy such as PD.

  16. Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin. (United States)

    Meziri, Fayçal; Binda, Delphine; Touati, Sabeur; Pellegrin, Maxime; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal


    Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.

  17. Effects of 1,25-( OH)2D3 on eotaxin and IL-8 in BALF of asthmatic rat%1,25-二羟维生素D3对哮喘大鼠BALF中Eotaxin及IL-8表达的影响

    Institute of Scientific and Technical Information of China (English)

    田维敏; 尚云晓; 蔡栩栩; 魏秀清


    目的 观察1,25-(OH)2D3对哮喘大鼠BALF中Eotaxin及IL-8表达的影响.方法 50只Wistar大鼠随机分为正常对照组(N)、哮喘组(A)、1,25-(OH)2D3组(VD)、布地奈德组(B)及1,25-( OH)2D3+布地奈德联合治疗组(L),每组10只.用ELISA法检测BALF中Eotaxin及IL-8的表达水平.结果 各组Eotaxin和IL-8表达比较:A组较其他各组明显增高(P<0.01、P<0.05);VD组较A组明显降低(P<0.05),但仍高于N组、B组及L组(P<0.01);L组较A组、VD组及B组明显减低(P<0.05、P<0.01).结论 哮喘急性发作时,BALF中Eotaxin及IL-8的表达水平显著增高,1,25-(OH)2D3有效抑制了哮喘时的Eotaxin和IL-8的表达水平,与布地奈德联合治疗作用更为明显.%Objective To observe the effects of 1,25-(OH)2D3 on the levels of eotaxin and IL-8 in BALF of asthmatic rats. Methods SO Wistar rats were randomly divided into five groups:Normal control group(N) .asthma group(A) ,1,25-(OH)2D3 group(VD) ,budesonide group(B) ,and therapeutic alliance group of 1,25-(OH)2D3 and budesonide ( L) ,10 rats for each group. The expressive levels of eotaxin and IL-8 in BALF were detected by ELISA. Results The levels of eotaxin and IL-8 increased more significantly in group A than those of other groups( P <0. 01, P < 0. 05 ) ; the levels in group VD decreased markedly compared with group A ( P < 0. 05 ) , but remarkably higher than group N, group B and group L(P<0. 01); the levels of group L decreased more markedly than those of group A, group B and group VD( P < 0. 05 ,P < 0. 01). Conclusion The levels of eotaxin and IL-8 in BALF of acute episodes of asthma significantly increased. 1,25-(OH)2D3 can efficiently inhibit the levels of eotaxin and IL-8 in asthma,and the combination of 1,25-( OH)2D3 and budesonide has a more significant effect.

  18. Susceptibility of asthmatic children to respiratory infection

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    Pereira Júlio C. R.


    Full Text Available OBJECTIVE: A case-control study of patients with pneumonia was conducted to investigate whether wheezing diseases could be a risk factor. METHODS: A random sample was taken from a general university hospital in S. Paulo City between March and August 1994 comprising 51 cases of pneumonia paired by age and sex to 51 non-respiratory controls and 51 healthy controls. Data collection was carried out by two senior paediatricians. Diagnoses of pneumonia and presence of wheezing disease were independently established by each paediatrician for both cases and controls. Pneumonia was radiologically confirmed and repeatability of information on wheezing diseases was measured. Logistic regression analysis was used to identify risk factors. RESULTS: Wheezing diseases, interpreted as proxies of asthma, were found to be an important risk factor for pneumonia with an odds ratio of 7.07 (95%CI= 2.34-21.36, when the effects of bedroom crowding (odds ratio = 1.49 per person, 95%CI= 0.95-2.32 and of low family income (odds ratio = 5.59 against high family income, 95%CI= 1.38-22.63 were controlled. The risk of pneumonia attributable to wheezing diseases is tentatively calculated at 51.42%. CONCLUSION: It is concluded that at practice level asthmatics should deserve proper surveillance for infection and that at public health level pneumonia incidence could be reduced if current World Health Organisation's guidelines were reviewed as to include comprehensive care for this illness.

  19. Molecular sieve of the rat glomerular basement membrane: a transmission electron microscopic study of enzyme-treated specimens.

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    Full Text Available Isolated rat glomerular basement membrane was treated with elastase and observed by transmission electron microscopy. The treatment with elastase revealed the fundamental structure of the glomerular basement membrane quite clearly, and enabled the observation of a sieve structure within the glomerular basement membrane. This sieve structure may play a major role in the filtration of blood as well as in the production of urine. Treatment with antibody showed that the sieve was mainly constituted of type IV collagen.

  20. Effect of intracerebroventricularly injected insulin on urinary sodium excretion by cerebroventricular streptozotocin-treated rats

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    R.F. Macedo


    Full Text Available Recent evidence suggests that insulin may influence many brain functions. It is known that intracerebroventricular (icv injection of nondiabetogenic doses of streptozotocin (STZ can damage insulin receptor signal transduction. In the present study, we examined the functional damage to the brain insulin receptors on central mechanisms regulating glomerular filtration rate and urinary sodium excretion, over four periods of 30 min, in response to 3 µl insulin or 0.15 NaCl (vehicle injected icv in STZ-treated freely moving Wistar-Hannover rats (250-300 g. The icv cannula site was visually confirmed by 2% Evans blue infusion. Centrally administered insulin (42.0 ng/µl increased the urinary output of sodium (from 855.6 ± 85.1 to 2055 ± 310.6 delta%/min; N = 11 and potassium (from 460.4 ± 100 to 669 ± 60.8 delta%/min; N = 11. The urinary sodium excretion response to icv insulin microinjection was markedly attenuated by previous central STZ (100 µg/3 µl administration (from 628 ± 45.8 to 617 ± 87.6 delta%/min; N = 5 or by icv injection of a dopamine antagonist, haloperidol (4 µg/3 µl (from 498 ± 39.4 to 517 ± 73.2 delta%/min; N = 5. Additionally, insulin-induced natriuresis occurred by increased post-proximal tubule sodium rejection, despite an unchanged glomerular filtration rate. Excluding the possibility of a direct action of STZ on central insulin receptor-carrying neurons, the current data suggest that the insulin-sensitive response may be processed through dopaminergic D1 receptors containing neuronal pathways.

  1. Involvement of oxidative stress in the regulation of NPY/CART-mediated appetite control in amphetamine-treated rats. (United States)

    Hsieh, Yih-Shou; Chen, Pei-Ni; Yu, Ching-Han; Chen, Chia-Hui; Tsai, Tsung-Ta; Kuo, Dong-Yih


    Amphetamine (AMPH) treatment can suppress appetite and increase oxidative stress in the brain. AMPH-induced appetite suppression is associated with the regulation of neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus. The present study explored whether antioxidants, including glutathione S-transferase (GST) and glutathione peroxidase (GP), were involved in this NPY/CART-mediated appetite control. Rats were treated daily with AMPH for four days. Changes in food intake and expression levels of hypothalamic NPY, CART, GST, and GP were examined and compared. Results showed that, in AMPH-treated rats, (1) food intake and NPY expression decreased, while CART, GST, and GP expression increased; (2) NPY knockdown in the brain enhanced the decrease in NPY and the increases in CART, GST, and GP expression; and (3) central inhibition of reactive oxygen species production decreased GST and GP and modulated AMPH anorexia and the expression levels of NPY and CART. The present results suggest that oxidative stress in the brain participates in regulating NPY/CART-mediated appetite control in AMPH-treated rats. These results may advance the knowledge regarding the molecular mechanism of AMPH-evoked or NPY/CART-mediated appetite suppression.

  2. Pectinase-treated Panax ginseng extract (GINST) rescues testicular dysfunction in aged rats via redox-modulating proteins. (United States)

    Won, Yu-Jin; Kim, Bo-Kyung; Shin, Yong-Kyu; Jung, Seung-Hyo; Yoo, Sung-Kwang; Hwang, Seock-Yeon; Sung, Jong-Hwan; Kim, Si-Kwan


    The root of Panax ginseng improves testicular function both in humans and animals. However, the molecular mechanism by which ginseng exerts this effect has not been elucidated. Changes in protein expression in the rat testis in response to a pectinase-treated P. ginseng extract (GINST) were identified using 2-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF MS. Number of sperm, Sertoli cells and germ cells, and the Sertoli Cell Index decrease in the testis of aged rats (AR) relative to young control rats (YCR). However, those parameters were completely restored in GINST-treated AR (GINST-AR). A proteomic analysis identified 14 proteins that were differentially expressed between vehicle-treated AR (V-AR) and GINST-AR. Out of these, the expression of glutathione-S-transferase (GST) mu5 and phospholipid hydroperoxide (PH) glutathione peroxidase (GPx) was significantly up-regulated in GINST-AR compared to V-AR. The activity of GPx and GST, as well as the expression of glutathione, in the testis of GINST-AR was higher than that in V-AR. The levels of lipid peroxidation (LPO) increased in AR compared with YCR, but this change was reversed by GINST-AR. These results suggest that the administration of GINST enhances testicular function by elevating GPx and GST activity, thus resulting in increased glutathione, which prevents LPO in the testis.

  3. Noninvasive positive pressure ventilation in acute asthmatic attack

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    A. Soroksky


    Full Text Available Asthma is characterised by reversible airway obstruction. In most patients, control of disease activity is easily achieved. However, in a small minority, asthma may be fatal. Between the two extremes lie patients with severe asthmatic attacks, refractory to standard treatment. These patients are at an increased risk of recurrent severe attacks, with respiratory failure, and mechanical ventilation. Invasive mechanical ventilation of the asthmatic patient is associated with a higher risk of complications and, therefore, is a measure of last resort. Noninvasive positive pressure ventilation (NPPV is another treatment modality that may be beneficial in patients with severe asthmatic attack who are at an increased risk of developing respiratory failure. These patients have the potential to benefit from early respiratory support in the form of NPPV. However, reports of NPPV in asthmatic patients are scarce, and its usage in asthmatic attacks is, therefore, still controversial. Only a few reports of NPPV in asthma have been published over the last decade. These studies mostly involve small numbers of patients and those who have problematic methodology. In this article we review the available evidence for NPPV in asthma and try to formulate our recommendations for NPPV application in asthma based on the available evidence and reports.

  4. Gene expression in asthmatic airway smooth muscle: a mixed bag. (United States)

    Pascoe, Christopher D; Swyngedouw, Nicholas E; Seow, Chun Y; Paré, Peter D


    It has long been known that airway smooth muscle (ASM) contraction contributes significantly to the reversible airflow obstruction that defines asthma. It has also been postulated that phenotypic changes in ASM contribute to the airway hyper-responsiveness (AHR) that is a characteristic feature of asthma. Although there is agreement that the mass of ASM surrounding the airways is significantly increased in asthmatic compared with non-asthmatic airways, it is still uncertain whether there are quantitative or qualitative changes in the level of expression of the genes and proteins involved in the canonical contractile pathway in ASM that could account for AHR. This review will summarize past attempts at quantifying gene expression changes in the ASM of asthmatic lungs as well as non-asthmatic ASM cells stimulated with various inflammatory cytokines. The lack of consistent findings in asthmatic samples coupled with the relative concordance of results from stimulated ASM cells suggests that changes to the contractility of ASM tissues in asthma may be dependent on the presence of an inflammatory environment surrounding the ASM layer. Removal of the ASM from this environment could explain why hypercontractility is rarely seen ex vivo.

  5. Characterization of the immune inflammatory profile in obese asthmatic children. (United States)

    Magrone, Thea; Simone, Maria; Altamura, Maria; Munno, Irene


    Asthma and obesity are two common disorders often associated in children and characterized by an inflammatory status. Growing evidences support a connection between obesity and asthma since weight reduction can improve asthmatic symptoms. In this study, we have enrolled eighty children: 17 non asthmatics and non obese, 19 obese, 28 asthmatics-obese and, 16 asthmatics non-obese, respectively. In all participants, respiratory functional tests and body mass index (BMI) were calculated. Moreover, systemic inflammation of biomarkers such as T helper (h)1-type, Th2-type and T regulatory-type serum cytokines along with major adipokines was determined. Data will show that the association between asthma and obesity leads to a predominant Th1-type response with an increase in pro-inflammatory cytokines. This inflammatory profile in asthmatics-obese children is sustained by elevated serum levels of leptin and visfatin, while adiponectin concentration is rather diminished. Finally, levels of systemic inflammatory biomarkers positively correlate with the increase in BMI values in all population subgroups.

  6. Airways obstruction in asthmatics induced by body cooling. (United States)

    Chen, W Y; Horton, D J


    Pulmonary and thermoregulatory reactions to body cooling were studied in eight asthmatic and five normal subjects. The cooling was achieved by a cold shower at water temperature (T) of 15 degrees C for 1 min, followed by exposing the wet body to a high wind generated by a fan for another minute. The skin T, oral T and pulmonary functions were measured before and after cooling. After the cooling, skin T fell a mean of 7 degrees in all subjects and the oral T fell 0.5 degrees in the normals and 0.7 degrees in the asthmatics. In asthmatics, the post-cooling forced expiratory volume in 1 s (FEV1) and maximal mid-expiratory flow (MMEF) fell significantly (P less than .05) to a mean of 79% and 72%of baseline, respectively, and thoracic gas volume (TGV) and airway resistance (Raw) increased significantly to 133% and 198% of baseline, respectively. In normal subjects a small but significant increase in Raw was found. No obstruction developed in the asthmatics after a warm shower at 37 degrees or after breathing the cold shower mist. It is suggested that it is body cooling which leads first to vasoconstriction and then cooling of respiratory mucosa that initiates bronchoconstriction in asthmatics.

  7. Paraoxonase 1 phenotype and paraoxonase activity in asthmatic patients.

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    Nurhan Sarioglu


    Full Text Available Oxidative stress is involved in the pathogenesis of asthma. Paraoxonase 1 (PON1 and arylesterase are esterase enzymes displaying antioxidant characteristics. PON1 activity varies widely among individuals and ethnic groups, partly related to polymorphisms. The aim of this study was to determine the activities of PON1 and arylesterase including the phenotype distribution of PON1 in asthmatic patients and healthy subjects. Forty-nine asthmatic patients and 41 healthy people were included in this study. Serum PON1 and arylesterase activities were determined by spectrophotometric assays, as well as the lipid profiles. The PON1 ratio (salt stimulated paraoxonase/arylesterase was trimodally distributed and this ratio was used to determine the individual phenotypes of all subjects. The PON1 activity in the asthmatic patients was significantly lower (p=0.024 when compared to the healthy control group, however no significant difference in the activity of arylesterase was observed between the two groups. The prevalence of the PON1 phenotypes in the asthmatic population were 26.5%, 16.3% and 57.2 % for QQ, QR and RR, respectively. PON1 activity was significantly lower in asthmatic patients; in addition, the results of this investigation indicated that PON1 RR phenotype may be an important risk factor in asthma disease.

  8. Leukotriene B4, administered via intracerebroventricular injection, attenuates the antigen-induced asthmatic response in sensitized guinea pigs

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    Jiang Jun-Xia


    Full Text Available Abstract Background Despite intensive studies focused on the pathophysiology of asthmatic inflammation, little is known about how cross-talk between neuroendocrine and immune systems regulates the inflammatory response during an asthmatic attack. We recently showed corresponding changes of cytokines and leukotriene B4 (LTB4 in brain and lung tissues of antigen-challenged asthmatic rats. Here, we investigated how LTB4 interacts with the neuroendocrine-immune system in regulating antigen-induced asthmatic responses in sensitized guinea pigs. Methods Ovalbumin-sensitized guinea pigs were challenged by inhalation of antigen. Vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor was given via intracerebroventricular injection (i.c.v. 30 min before challenge. Airway contraction response was evaluated using Penh values before and after antigen challenge. The inflammatory response in lung tissue was evaluated 24 h after challenge. The LTB4 content of lung and brain homogenate preparations was detected by reversed phase high-performance liquid chromatography (RP-HPLC. Plasma levels of adrenocorticotropic hormone (ACTH and corticosterone (CORT were measured using ELISA kits. Results Antigen challenge impaired pulmonary function and increased inflammatory cell infiltration in lung tissue. These responses could be significantly suppressed by LTB4, 30 ng i.c.v., in ovalbumin-sensitized guinea pigs. LTB4 content of lung and brain homogenates from antigen-challenged guinea pigs was significantly increased. In addition, administration of LTB4 via i.c.v. markedly increased CORT and ACTH level in plasma before antigen challenge, and there were further increases in CORT and ACTH levels in plasma after antigen challenge. U75302, 100 ng i.c.v., completely blocked the effects of LTB4. In addition, U75302, 100 ng via i.c.v. injection, markedly decreased LTB4 content in lung homogenates, but not in brain homogenates. Conclusions Increased LTB4 levels in

  9. Corticosterone treatment of pregnant low dose endotoxin-treated rats : Inhibition of the inflammatory response

    NARCIS (Netherlands)

    Faas, MM; Slot, K; Koiter, TR; Schuiling, GA


    PROBLEM: Can the endotoxin-induced inflammatory response, underlying experimental pre-eclampsia, in pregnant rats be inhibited by corticosterone? METHOD OF STUDY: On day 10 of pregnancy, rats were implanted with pellets containing 25% corticosterone and 75% cholesterol (n = 10) or with 100% choleste

  10. Accumulating evidence for increased velocity of airway smooth muscle shortening in asthmatic airway hyperresponsiveness. (United States)

    Ijpma, Gijs; Matusovsky, Oleg; Lauzon, Anne-Marie


    It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma.

  11. Bone mineral density in asthmatic patients on inhaled corticosteroids in a developing country

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    Yeh Chunn Kuan


    Conclusion: The risk factors for osteoporosis and osteopenia among asthmatic patients were older age and lower BMI, but not the cumulative dose of ICS. Asthmatic patients on ICS have no added risk of osteoporosis or osteopenia as compared with non-asthmatic subjects.

  12. Fertility, developmental toxicity and teratogenicity in albino rats treated with methanol sub-fraction of Carica papaya seeds

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    S Shrivastava


    Full Text Available Objective: To evaluate the status of fertility, developmental stages during gestation and teratological changes, if any, following oral administration of methanol sub-fraction (MSF of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats. Materials and Methods: The MSF was administered at the doses of 50 mg contraceptive dose (CD, 100 mg (2x CD, 250 mg (5x CD and 500 mg (10x CD/kg body wt/day along with vehicle-treated control using 10 male and 20 female Wistar rats in each group. Necropsies were performed one day before the expected parturition. Status of gravid/non-gravid uterus, the number of corpora lutea in the ovary, implantation status, fetal wellbeing, fetal resorption, fetal body weight, external, visceral and skeletal malformations were recorded. Results: Pregnancies were recorded in vehicle-treated control animals and in the animals treated with 50 mg/kg body wt/day. The animals treated with 2x CD, 5x CD and 10x CD did not get pregnant. The fetuses and the status of the ovary, uterus and implantation, fetal body weight, soft tissues and skeletal structures were recorded normal. Data were comparable to those of control. Conclusion: The results suggest that the test substance had no developmental toxicity and teratogenicity which could affect pregnancy, implantation and gestation.

  13. Hydrophilic interaction chromatography-mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats. (United States)

    Kok, Miranda G M; Swann, Jonathan R; Wilson, Ian D; Somsen, Govert W; de Jong, Gerhardus J


    Hydrophilic interaction chromatography-mass spectrometry (HILIC-MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial-host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared to a control group. Urine samples were collected at day zero, four and eight, and analyzed by HILIC-MS. Multivariate data analysis was applied to the urinary metabolic profiles to identify biochemical variation between the treatment groups. Principal component analysis found a clear distinction between those animals receiving antibiotics and the control animals, with twenty-nine discriminatory compounds of which twenty were down-regulated and nine up-regulated upon treatment. In the treatment group receiving antibiotics for four days, a recovery effect was observed for seven compounds after cessation of antibiotic administration. Thirteen discriminatory compounds could be putatively identified based on their accurate mass, including aconitic acid, benzenediol sulfate, ferulic acid sulfate, hippuric acid, indoxyl sulfate, penicillin G, phenol and vanillin 4-sulfate. The rat urine samples had previously been analyzed by capillary electrophoresis (CE) with MS detection and proton nuclear magnetic resonance ((1)H NMR) spectroscopy. Using CE-MS and (1)H NMR spectroscopy seventeen and twenty-five discriminatory compounds were found, respectively. Both hippuric acid and indoxyl sulfate were detected across all three platforms. Additionally, eight compounds were observed with both HILIC-MS and CE-MS. Overall, HILIC-MS appears to be highly complementary to CE-MS and (1)H NMR spectroscopy, identifying additional compounds that discriminate the urine samples from antibiotic-treated and control rats.

  14. The application of lesion sterilization and tissue repair 3Mix-MP for treating rat's dental pulp tissue

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    Raditya Nugroho


    Full Text Available Background: Lesion sterilization and tissue repair (LSTR 3Mix-MP are three broad-spectrum antibiotics, including metronidazole, ciprofloxacin and minocycline are mixed with propylene glycol or macrogol. There is the possibility ofthe healing process that marked proliferation ofnew blood vessels and proliferation offibroblasts in the treatment ofirreversible pulpitis by pulp capping LSTR 3MixMP because of  the principle of the method LSTR 3Mix-MP is to kill bacteria. Purpose: The purpose of this study to prove the effect of LSTR 3Mix-MP on chronic inflammation and the healing process in rat dental pulp tissue in vivo. Methods: Rattus norvegicus anaesthetized by using ketamine and xylazine dissolved in sterile isotonic saline solution (0.2 ml/50gr mm on the upper right thigh. Cavity preparation class I to perforation by using a low speed tapered diamond round bur. In the treatment group, rats were treated 3Mix-MP at a dose of10 mg and then covered with glass ionomer cement for 7 days on the pulp that has been opened for 3 days. The control group treated with saline irrigation on the pulp that has been opened for 3 days. Rats were killed after seven days, and then made preparations pulp tissue to count the number oflymphocytes, macrophages, plasma cells, blood vessels, and fibroblasts Results: There is an increase in the average number ofmacrophage cells, plasma, and fibroblasts; and decreased lymphocytes and blood vessels in the treated group exposure LSTR 3Mix-MP. Conclusion:LSTR 3Mix-MP can reduce chronic inflammation process and enhance the healing process in rat dental pulp tissue.

  15. Steroid Phobia among Parents of Asthmatic Children: Myths and Truth

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    Magdy M Zedan


    Full Text Available Asthma is one of the most common chronic diseases of childhood. Inhaled corticosteroids (ICS are the recommended controller drug for asthma treatment. The aim of our study was to determine concerns and fears of parents of children with asthma towards the use of ICS. One hundred parents of asthmatic children were interviewed using structural questionnaire. Airway inflammation was reported by only 6% of interviewed parents, whereas airway narrowing was addressed by 34%. Interesting data, 71% of parents were concerned with the role of steroids in asthma treatment, but more than half (53% of them addressed fears from side effects. Apparent gaps were found in knowledge of parents of asthmatic children about ICS as controller asthma medication. So, physician and health providers should explain to asthmatic parents that airway inflammation is the core for asthma management. This may remove fears about ICS and thus improve adherence to treatment.

  16. Effect of omega-3 fatty acids on haemostatic functions in urocortin-treated obese rats. (United States)

    El-Gendy, Ahmed A; Abbas, Amr M


    Urocortin 1 (UCN1) decreases food intake. We investigated the effects of UCN1 and omega-3 fatty acids (FA) on metabolic and coagulation parameters in high fat diet (HFD)-fed rats. Fifty male Sprague Dawley rats were divided into five groups; control, HFD, HFD with omega-3 FA, HFD with UCN1, and HFD with UCN1 and omega-3 FA. Food intake, body weight (BW), body mass index (BMI), Lee index, glucose, insulin, HOMA-IR, triglycerides, cholesterol, low (LDL) and high (HDL) density lipoproteins, fibrinogen, plasminogen activator inhibitor 1 (PAI-1), fibrin degradation product (FDP), clotting time, bleeding time, prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet aggregation were measured. Food intake, BW, BMI, Lee index, glucose, insulin, HOMA-IR, triglycerides, cholesterol, LDL, fibrinogen, platelet aggregation, PAI-1, and FDP increased while bleeding and clotting times, PT, and aPTT decreased in HFD rats. UCN1 decreased food intake, BW, BMI, Lee index, bleeding and clotting times, PT, and aPTT and increased fibrinogen, PAI-1, FDP, and platelet aggregation in HFD rats. Omega-3 FA decreased food intake, BW, BMI, Lee index, platelet aggregation, glucose, insulin, HOMA-IR, triglycerides, and increased HDL and bleeding time in HFD rats. We concluded that UCN1 worsens the hypercoagulable state in HFD rats while omega-3 FA improve the insulin resistance and decrease the platelet aggregation in those rats.

  17. Effect and significance of cigarette smoke exposure on the expression of CD80, CD86 by marrow-derived dendritic cells from asthmatics rat%香烟烟雾暴露对哮喘大鼠树突状细胞共刺激分子CD80、CD86表达的影响及意义

    Institute of Scientific and Technical Information of China (English)

    李毅; 杜永成; 许建英; 胡晓芸; 张彩苹


    Objective To study the effect of cigarette smoke exposure on the expression of CD80,CD86 and relationship with the activity and immune balance of Iymphocytes by marrow-derived dendritic cells (DCs) from asthmatics rat.Methods Forty Wistar rats were randomly divided into control group,smoke exposure group,asthma group,asthma combined smoke exposure group. Established animal models,then rat bone marrow denved DCs and spleen lymphocytes were cultivated, and mixed lymphocyte responses (MLR) was done.Collected cell and cell supernatant.The expression of CD80 and CD85 was determined by flow cytometric analysis,and the proliferations of lymphocytes was examined with MTT colorimetric assay.The expression of IFN-γ and IL-4 was determined by using the enzyme linked immunosorbent assay (ELISA).Results ① Compared with asthma group,the expression levels of CD86 and CD86 decreased significantly in asthma combined smoke exposure group (P < 0.01,respectively ).Compared with control group,the expression levels of CD80 decreased in asthma combined smoke exposure group significantly ( P <0.01).②Compared with control group,the stimulating activity of DCs on allogeneic lymphocytes increased significantly in both asthma group and asthma combined smoke exposure group ( P < 0.01,respectively).Compared with asthma group,the stimulating activity of DCs on allogeneic lymphocytes decreased in asthma combined smoke exposure group significantly ( P <0.01).③ Compared with the control group,the expression of IFN-γ decreased and the expression of IL-4 increased remarkably in both the cigarette smoke exposure combined asthma group and the asthma group ( P <0.01,respectively).Compared with the asthma group,the expression of IFN-γ decreased and the expression of IL-4 increased remarkably in the cigarette smoke exposure combined asthma group ( P <0.01,respectively).④ The expresion levels of CD80 was positively correlated with IFN-γ and the activity of lymphocytes,and negatively

  18. Phytochemistry, anti-asthmatic and antioxidant activities of Anchomanes difformis(Blume) Engl. leaf extract

    Institute of Scientific and Technical Information of China (English)

    Ovuakporie-Uvo Oghale; Mac Donald Idu


    Objective: To study the phytochemistry, anti-asthmatic and antioxidant activities of the aqueous leaf extract of Anchomanes difformis(Blume) Engl.(A. difformis) and to verify claims of use in folk medicine.Methods: For anti-asthmatic activity, male and female guinea pigs with average body weight of(451.4 ± 118.1) g were divided into six groups of six animals each. Group 1served as control(distilled water); Group 2 was administered with salbutamol(reference drug) only; Group 3 served as ovalbumin sensitized group, Group 4, 5 and 6 were treated with A. difformis extract at doses of 100, 200 and 400 mg/kg, respectively. Described methods were used to test fluid viscosity, fluid volume and quantitative phytochemistry analysis. Absorbance was read using a UV–Vis spectrophotometer and results computed in percentage. Total antioxidant assays [2, 2-diphenyl-1-picrylhydrazyl(DPPH) and lipid peroxidation assay], were carried out using reported procedures.Results: The anti-asthmatic evaluation showed that protection from asthma of the animals in Group 6(400 mg/kg, 32.7%) were similar to that in Group 2(salbutamol, 33.0%).Excised trachea was free of mucus secretion in Group 5(200 mg/kg) as was observed in the control group. Fluid volume increase in Groups 3 and 6 indicated mucus secretion.DPPH radical scavenging activity of extract was effective as ascorbic acid which served as standard at 20 mg/m L. But, the extract elicited low lipid peroxidation activity compared with the reference(tocopherol) at concentrations tested.Conclusions: A. difformis aqueous leaf extract is safe and possesses positive antiasthmatic and antioxidant activities as claimed by traditional herbal practitioners in Delta State.

  19. Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice (United States)

    Huang, Wen-Chung; Fang, Li-Wen; Liou, Chian-Jiun


    Phloretin (PT), isolated from the apple tree, was previously demonstrated to have antioxidative and anti-inflammatory effects in macrophages and anti-adiposity effects in adipocytes. Inflammatory immune cells generate high levels of reactive oxygen species (ROS) for stimulated severe airway hyperresponsiveness (AHR) and airway inflammation. In this study, we investigated whether PT could reduce oxidative stress, airway inflammation, and eosinophil infiltration in asthmatic mice, and ameliorate oxidative and inflammatory responses in tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin (OVA) to induce asthma symptoms. Mice were randomly assigned to the five experimental groups: normal controls; OVA-induced asthmatic mice; and OVA-induced mice injected intraperitoneally with one of the three PT doses (5, 10, or 20 mg/kg). In addition, we treated inflammatory human tracheal epithelial cells (BEAS-2B cells) with PT to assess oxidative responses and the levels of proinflammatory cytokines and chemokines. We found that PT significantly reduced goblet cell hyperplasia and eosinophil infiltration, which decreased AHR, inflammation, and oxidative responses in the lungs of OVA-sensitized mice. PT also decreased malondialdehyde levels in the lung and reduced Th2 cytokine production in bronchoalveolar lavage fluids. Furthermore, PT reduced ROS, proinflammatory cytokines, and eotaxin production in BEAS-2B cells. PT also suppressed monocyte cell adherence to inflammatory BEAS-2B cells. These findings suggested that PT alleviated pathological changes, inflammation, and oxidative stress by inhibiting Th2 cytokine production in asthmatic mice. PT showed therapeutic potential for ameliorating asthma symptoms in the future. PMID:28243240

  20. Iron bioavailability and utilization in rats are lower from lime-treated corn flour than from wheat flour when they are fortified with different sources of iron. (United States)

    Hernández, Miguel; Sousa, Virginia; Moreno, Ambar; Villapando, Salvador; López-Alarcón, Mardya


    Although iron bioavailability from wheat flour fortified with iron has been widely studied, the bioavailability of lime-treated corn flour has not been evaluated sufficiently. We compared iron bioavailability and utilization of lime-treated corn flour and wheat flour supplemented with various iron sources. Bioavailability and utilization were determined in Sprague-Dawley rats using the iron balance and hemoglobin depletion-repletion methods. Rats were iron depleted by feeding them a low iron, casein diet for 10 d. During the repletion period, the rats were fed diets based on lime-treated corn flour or wheat flour, both supplemented with ferrous fumarate, ferrous sulfate, ferric citrate and reduced iron for 14 d. Hemoglobin was determined at the end of depletion and repletion periods. The phytate concentration was lower in wheat flour (114 mg/100g) than in lime-treated corn flour (501 mg/100g). Iron bioavailability and utilization by rats were higher from fortified and unfortified wheat flour than from the lime-treated corn flour counterparts. Iron utilization was greater in rats fed wheat flour supplemented with ferrous sulfate, followed by fumarate and citrate than in rats fed reduced iron. In lime-treated corn flour, iron utilization by rats fed unfortified flour and flour fortified with reduced iron did not differ, but utilization was higher in rats fed corn flour fortified with iron sulfate, fumarate and citrate than with reduced iron. We conclude that fortification of lime-treated corn flour with reduced iron has no effect on iron bioavailability or utilization, probably due to the high phytate content. Other iron compounds must be selected to fortify lime-treated corn flour when intended for public nutrition programs.

  1. Angiopoietin-1 mRNA expression in estradiol-treated ovariectomized rats with focal cerebral ischemia after reperfusion

    Institute of Scientific and Technical Information of China (English)

    Ling Tang; Jun Zuo; Yonghong Wang; Yuanda Zhou; Haixia He


    RNA expression levels of Angpt1, Angpt2, Tie2, vascular endothelial growth factor (Vegf), VegfR1, and VegfR2.RESULTS: In WT ovariectomized rats treated with estradiol, the change in cerebral blood flow following cerebral ischemi',dreperfusion, capillary density in the basal nuclei and parietal lobe cortex and Angpt1 mRNA level were significantly higher than in the control group (P < 0.01). We did not identify any such changes in ERKO rats treated with estradiol. In addition, the plasma estradiol levels in WT and ERKO ovariectomized rats treated with estradiol were remarkably higher than in their corresponding control groups (P < 0.01).CONCLUSION: Angpt1 is a critical factor in many processes during the repair of cerebral ischemia/reperfusion injury. For example, it confers estrogen-mediated protection, restoration of cerebral blood flow and increases in brain capillary density. It is emerging as an important molecule for estradiol-mediated neuroprotection.

  2. Use of DES-treated rats as an animal model for assessment of pituitary adenoma imaging agents

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    Otto, C.A.; Marshall, J.C.; Lloyd, R.V.; Sherman, P.S.; Fisher, S.J.; Valoppi, V.L.; Rogers, W.L.; Wieland, D.M.


    Prolactin (PRL) secreting pituitary adenomas are the most common type of pituitary tumors. An imaging agent which specifically localized in prolactinomas would be of considerable clinical value. Tritiated spiroperidol (/sup 3/HSp) was selected for initial evaluation as a possible imaging agent based on: (1) demonstrated localization in the pituitary and (2) demonstrated binding to human PRL-secreting tumor tissue. DES was implanted in Fischer F344 rats which induced prolactinoma formation. /sup 3/HSp concentrations in pituitary and other tissues of DES-treated rats were assessed in female rats and correlation studies showed that a 5-fold increase in serum PRL was associated with a 6-fold increase in both pituitary weight and % dose/organ accumulation of /sup 3/HSp. The number of pituitary D/sub 2/ receptors per mg of protein in tissue homogenates was similar in both normal and DES-treated females. A blocking study with (+)-butaclamol demonstrated a D/sub 2/ receptor-mediated component to /sup 3/HSp localization. In summary, an animal model for prolactinoma was characterized. An assessment of /sup 3/HSp accumulation indicates that radiolabelled spiroperidol shows excellent potential for detecting PRL-secreting tumors of the pituitary.

  3. Decreased expression of alpha-2-HS glycoprotein in the sera of rats treated with Eurycoma longifolia extract

    Directory of Open Access Journals (Sweden)

    Yeng eChen


    Full Text Available Eurycoma longifolia is a Malaysian native herb that has been widely used as an aphrodisiac and a remedy for andropause. Although the physiological effects of the plant extract were predicted as a result of the alterations in protein expression, the key protein(s involved in these alterations are still unclear. In the present study, we have investigated the effect of standardized Eurycoma longifolia extract on serum protein expression up to 28 days following oral administration in rats. Serum protein profiles were analyzed by 2-dimensional electrophoresis, and altered proteins were identified via mass spectrometry. We observed that alpha-2-HS glycoprotein (AHS was significantly decreased in the serum of experimentally treated rats compared to controls. Moreover, reduction in AHS was confirmed using competitive enzyme-linked immunosorbent assay. AHS expression is known to be associated with insulin resistance and diabetes. Our data indicated that serum AHS was reduced in rats treated with standardized E. longifolia extract, and therefore form a prelude for further investigation into the effects of this natural extract in animal models involving infertility and diabetes.

  4. Gene expression profiles of hepatocytes treated with La(NO3)3 of rare earth in rats

    Institute of Scientific and Technical Information of China (English)

    Hui Zhao; Wei-Dong Hao; Hou-En Xu; Lan-Qin Shang; You-Yong Lu


    AIM: To compare the gene expression between La(NO3)3-exposed and control rats in vivo.METHODS: Rats were fed La(NO3)3 once daily at a dose of 20 mg/kg for one month by gavage. Gene expression of hepatocytes was detected using mRNA differential display (DD) technique and cDNA microarray and compared between treated and control groups.RESULTS: Six differentially expressed sequence tags were cloned by DD, of which five were up regulated and one was down regulated in treated rats. Two sequences were determined. One band was novel. The other shared 100%sequence homology with AU080263 Sugano mouse brain mncb Mus musculus cDNA clone MNCb-5435 5′. With DNA microarray, 136 differentially expressed genes were identified including 131 over-expressed genes and 5 under-expressed genes. Most of these differentially expressed genes were cell signal and transmission genes, genes associated with metabolism, protein translation and synthesis.CONCLUSION: La(NO3)3 could change the expression levels of some kinds of genes. Further analysis of the differentially expressed genes would be helpful for understanding the wide biological effect spectrum of rare earth elements.

  5. Latent inhibition in rats neonatally treated chronically with MK-801: differential effects on conditioned taste aversion and conditioned emotional response. (United States)

    Niikura, Ryo; Nozawa, Takashi; Yamada, Kazuo; Kato, Katsunori; Ichitani, Yukio


    Chronic neonatal blockade of N-methyl-d-aspartate (NMDA) receptors produces various abnormal behaviors in adulthood animals. This study investigated the effects of neonatal treatment chronically with MK-801 in rats on the preexposure-induced retardation of CS-US association, i.e. latent inhibition (LI), of two aversive classical conditioning tasks in adulthood. In conditioned taste aversion (CTA) using sucrose taste and LiCl, neonatal chronic MK-801 (0.4 mg/kg twice/day) treatment attenuated the inhibitory effect of sucrose preexposure on the aversive conditioning, although the treatment did not affect CTA conditioning itself. On the other hand, in conditioned emotional response (CER) using tone and electrical foot shock, rats neonatally treated with MK-801 showed the same degree of inhibitory effect of tone preexposure on the aversive conditioning compared with neonatally vehicle-treated rats, and also showed the same level of CER conditioning itself. Thus, the effect of chronic neonatal blockade of NMDA receptors on the LI of classical conditioning in adulthood was differentiated by the task employed. Results suggest that LI of CTA paradigm compared with that of CER is more sensitive to abnormal development after chronic neonatal blockade of NMDA receptors as an index of cognitive/attentional deficits caused by the treatment.


    Institute of Scientific and Technical Information of China (English)

    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

  7. Sepsis progression to multiple organ dysfunction in carotid chemo/baro-denervated rats treated with lipopolysaccharide. (United States)

    Nardocci, Gino; Martin, Aldo; Abarzúa, Sebastián; Rodríguez, Jorge; Simon, Felipe; Reyes, Edison P; Acuña-Castillo, Claudio; Navarro, Cristina; Cortes, Paula P; Fernández, Ricardo


    Sepsis progresses to multiple organ dysfunction (MOD) due to the uncontrolled release of inflammatory mediators. Carotid chemo/baro-receptors could play a protective role during sepsis. In anesthetized male rats, we measured cardiorespiratory variables and plasma TNF-α, glucocorticoids, epinephrine, and MOD marker levels 90min after lipopolysaccharide (LPS) administration in control (SHAM surgery) and bilateral carotid chemo/baro-denervated (BCN) rats. BCN prior to LPS blunted the tachypneic response and enhanced tachycardia and hypotension. BCN-LPS rats also showed blunted plasma glucocorticoid responses, boosted epinephrine and TNF-α responses, and earlier MOD onset with a lower survival time compared with SHAM-LPS rats. Consequently, the complete absence of carotid chemo/baro-sensory function modified the neural, endocrine and inflammatory responses to sepsis. Thus, carotid chemo/baro-receptors play a protective role in sepsis.

  8. Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats

    NARCIS (Netherlands)

    M. Verburg (Melissa); I.B. Renes (Ingrid); H.P. Meijer; J.A. Taminiau; H.A. Büller (Hans); A.W.C. Einerhand (Sandra); J. Dekker (Jan)


    textabstractProliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths

  9. Tissue injuries of wistar rats treated with hydroalcoholic extract of Sonchus oleraceus L.

    Directory of Open Access Journals (Sweden)

    Franciele Carla Prichoa


    Full Text Available The use of plant species is emerging as an important alternative in the treatment of injuries. Therefore, the extract of Sonchus oleraceus 10% was employed in the repair of skin lesions. A total of 36 male Wistar rats were subjected to a punch injury and divided into three groups: a negative control, receiving no treatment, a positive control, treated with Dersani, and the experimental group treated with the extract. The injury was assessed macroscopically and microscopically. Morphometric data was collected at the 3rd, 5th and 7th postoperative day, and the experimental group showed greater changes in shrinkage of the lesion compared to control groups. On the 3rd postoperative day, the injury in the experimental group showed less necrotic tissue, lower slough and more granulation tissue in relation to the positive control group. On the 7th and 10th postoperative day, the injury in the experimental group showed lower slough compared to the positive control group. Microscopic analysis of lesions on the 5th postoperative day revealed increased fibroplasia in the experimental group compared to control groups, while on the 14th postoperative day less neovascularization was evident in the experimental group and increased formation of hair follicles in the negative control group. The extract of S. oleraceus provided tissue repair in accordance with normal physiological patterns thus confirming empirical evidence for its use.O emprego de espécies vegetais vem surgindo como alternativa no tratamento de lesões. Dessa forma, foi utilizado o extrato hidroalcoólico de Sonchus oleraceus a 10% na reparação de lesões cutâneas. Trinta e seis ratos machos Wistar, foram submetidos a uma lesão com "punch" e distribuídos em três grupos: controle negativo, não recebeu tratamento; controle positivo, tratado com Dersani; e o experimental, tratado com extrato. A lesão foi avaliada macroscopicamente e microscopicamente. Os dados morfométricos mostraram que

  10. Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration. (United States)

    Choi, Jonghye; Kim, Heyjin; Kim, Pilje; Jo, Eunhye; Kim, Hyun-Mi; Lee, Moo-Yeol; Jin, Seon Mi; Park, Kwangsik


    Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage.

  11. Alteration in the fatty acid composition of liver, kidney and plasma from diethylhexyl phthalate-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Okita, J.R.; Okita, R.T. (Medical Coll. of Wisconsin, Milwaukee (United States))


    Cytochromes P-450 are induced in rat liver microsomes by a number of compounds which cause peroxisome proliferation. One such compound, diethylhexyl phthalate (DEHP), induces P-450 IVA1 which catalyzes {omega}- and ({omega}-1)-hydroxylation of fatty acids. In liver of rats fed DEHP, there is a 10-fold induction of {omega}-hydroxylation of laurate and ({omega}-1)-hydroxylation of palmitate, as compared to control rat liver. There is a 3-fold induction of other hydroxylations, such as W-hydroxylation of palmitate and {omega}- ({omega}-1)-hydroxylation of syristate. Despite these increases in hydroxylase activity, the authors have not been able to demonstrate increases in hydroxy fatty acids or dicarboxylic acids in liver or plasma of rats fed DEHP. However, alterations in the fatty acid composition of lipids in liver, kidney cortex and plasma were observed. They consistently observed increases in oleate (expressed as mol% of total fatty acid) in liver (11% in control increased to 24% in DEHP-treated), kidney cortex (12% to 16%) and plasma (13% to 24%). This increase in oleate was quite striking when expressed as ug/gm tissue or ug/al plasma. DEHP treatment resulted in increased oleate in mitochondrial, microsomal and cytosolic fractions of liver.

  12. A metabonomic analysis of serum from rats treated with ricinine using ultra performance liquid chromatography coupled with mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Jing Peng

    Full Text Available A metabonomic approach based on ultra performance liquid chromatography coupled with mass spectrometry (UPLC/MS was used to study the hepatotoxicity of ricinine in rats. Potential biomarkers of ricinine toxicity and toxicological mechanism were analyzed by serum metabonomic method. The significant differences in the metabolic profiling of the control and treated rats were clear by using the principal components analysis (PCA of the chromatographic data. Significant changes of metabolite biomarkers like phenylalanine, tryptophan, cholic acid, LPC and PC were detected in the serum. These biochemical changes were related to the metabolic disorders in amino acids and phospholipids. This research indicates that UPLC/MS-based metabonomic analysis of serum samples can be used to predict the hepatotoxicity and further understand the toxicological mechanism induced by ricinine. This work shows that metabonomics method is a valuable tool in drug mechanism study.

  13. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug. (United States)

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig


    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

  14. Oxidative stress is reduced in Wistar rats exposed to smoke from tobacco and treated with specific broad-band pulse electromagnetic fields

    Directory of Open Access Journals (Sweden)

    Bajić V.


    Full Text Available There have been a number of attempts to reduce the oxidative radical burden of tobacco. A recently patented technology, pulse electromagnetic technology, has been shown to induce differential action of treated tobacco products versus untreated products on the production of reactive oxygen species (ROS in vivo. In a 90-day respiratory toxicity study, Wistar rats were exposed to cigarette smoke from processed and unprocessed tobacco and biomarkers of oxidative stress were compared with pathohistological analysis of rat lungs. Superoxide dismutase (SOD activity was decreased in a dose-dependent manner to 81% in rats exposed to smoke from normal cigarettes compared to rats exposed to treated smoke or the control group. These results correspond to pathohistological analysis of rat lungs, in which those rats exposed to untreated smoke developed initial signs of emphysema, while rats exposed to treated smoke showed no pathology, as in the control group. The promise of inducing an improved health status in humans exposed to smoke from treated cigarettes merits further investigation.

  15. Aged garlic extract ameliorates immunotoxicity, hematotoxicity and impaired burn-healing in malathion- and carbaryl-treated male albino rats. (United States)

    Ramadan, Gamal; El-Beih, Nadia M; Ahmed, Rehab S A


    Malathion and carbaryl are the most widely used organophosphate and carbamate insecticides, respectively, especially in developing countries; they pose a potential health hazard for both humans and animals. Here, we evaluated the protective effects of an odorless (free from allicin) Kyolic aged garlic extract (AGE, containing 0.1% S-allylcysteine; 200 mg/kg body weight) on the toxicity induced by 0.1 LD50 of malathion (89.5 mg/kg body weight) and/or carbaryl (33.9 mg/kg body weight) in male Wistar rats. Doses were orally administered to animals for four consecutive weeks. The present study showed that AGE completely modulated most adverse effects induced by malathion and/or carbaryl in rats including the normocytic normochromic anemia, immunosuppression, and the delay in the skin-burning healing process through normalizing the count of blood cells (erythrocytes, leucocytes and platelets), hemoglobin content, hematocrit value, blood glucose-6-phosphodehydrogenase activity, weights and cellularity of lymphoid organs, serum γ-globulin concentration, and the delayed type of hypersensitivity response to the control values, and accelerating the inflammatory and proliferative phases of burn-healing. In addition, AGE completely modulated the decrease in serum reduced glutathione (GSH) concentration and the increase in clotting time in malathion alone and carbaryl alone treated rats. Moreover, AGE induced a significant increase (P < 0.001) in serum GSH concentration (above the normal value) and accelerating burn-healing process in healthy rats. In conclusion, AGE was effective in modulating most adverse effects induced in rats by malathion and carbaryl, and hence may be useful as a dietary adjunct for alleviating the toxicity in highly vulnerable people to insecticides intoxication. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 789-798, 2017.


    Directory of Open Access Journals (Sweden)

    R. Amin


    Full Text Available Theophylline, (1,3-dimethylxanthine is widely used as a smooth muscle relaxant, myocardial stimulant and a diuretic agent. The most frequent use of theophylline is in treatment of acute and chronic asthma as a bronchodilator.To determine the effect of Theophylline on serum electrolyte and uric acid, 21 asthmatic children (age range 1,5-7 years with severe acute asthma and 25 patients with chronic asthma (5-15 years who were being treated with slow-release theophylline were enrolled in this study. Fifty age and sex matched normal children took part as control. Blood samples (5ml were withdrawn before, during and after completion of the course of intravenous theophylline treatment (0.05-0.70 mg/kg/ hr. Sera obtained were used for analysis of K+, Na+, phosphorus, calcium and uric acid by RA-1000 automated analyzer and the following results were obtained:(1 After treatment, total serum calcium in acute asthmatic patients decreased significantly compared with controls (PWe conclude that the serum levels of phosphate, potassium, calcium and uric acid should be monitored in patient receiving theophylline especially during prolonged use and critical emergency cases.

  17. Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats

    Directory of Open Access Journals (Sweden)



    Full Text Available We examined the influence of chronic adrenocorticotropic hormone (ACTH treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.

  18. Clinical effectiveness of conventional influenza vaccination in asthmatic children

    NARCIS (Netherlands)

    Smits, A J; Hak, E; Stalman, W A B; van Essen, G A; Hoes, A W; Verheij, Th J M


    Influenza immunization rates among young asthmatics remain unsatisfactory due to persistent concern about the impact of influenza and the benefits of the vaccine. We assessed the effectiveness of the conventional inactivated trivalent sub-unit influenza vaccine in reducing acute respiratory disease

  19. Increasing ventilation as an intervention in homes of asthmatic children

    DEFF Research Database (Denmark)

    Hogaard, Nina Viskum; Rubak, Sune Leisgaard Mørck; Halken, Susanne


    in children. We conducted a double-blind, placebo-controlled intervention study with 46 asthmatic, house dust mite allergic children. The aim was to investigate the association between indoor air quality in homes and severity of asthma, in particular the effect of increased ventilation rate and expected lower...

  20. Atopic asthmatic subjects but not atopic subjects without ... (United States)

    BACKGROUND: Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined. OBJECTIVE: We sought to determine whether atopic status modulates ozone response phenotypes in human subjects. METHODS: Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations. RESULTS: All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significa

  1. Functional phenotype of airway myocytes from asthmatic airways

    NARCIS (Netherlands)

    Wright, David B.; Trian, Thomas; Siddiqui, Sana; Pascoe, Chris D.; Ojo, Oluwaseun O.; Johnson, Jill R.; Dekkers, Bart G. J.; Dakshinamurti, Shyamala; Bagchi, Rushita; Burgess, Janette K.; Kanabar, Varsha


    In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still remai

  2. Pollution effects on asthmatic children in Europe: the PEACE study.

    NARCIS (Netherlands)

    Roemer, W.


    This thesis is based upon the 'Pollution Effects on Asthmatic Children in Europe (PEACE)' study. The PEACE study is a multi-centre study of the acute effects of particles with a 50% cut-off aerodynamic diameter of 10 µm (PM 10 ), Black Smoke (BS), SO 2 and NO 2 on re

  3. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

    DEFF Research Database (Denmark)

    Bisgaard, H; Nielsen, K G


    We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...

  4. Exercise-induced asthma and the asthmatic athlete. (United States)

    Enright, T


    Almost all asthmatics involved in moderate to heavy exercise will experience exercise-induced asthma (EIA). Up to 14% of athletes exhibit EIA, symptoms of which include dyspnea, coughing, chest tightness and wheezing. Education, warm-up exercises and pre-treatment with the appropriate medications can enable an athlete to excel and even win a gold medal in the 1996 Olympic games.

  5. Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats. (United States)

    Miyake, Ayaka; Kitamura, Yoshihisa; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki


    In the present study, we examined the effect of ACTH on the immobilization of rats in the forced swim test and hippocampal cell proliferation after administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg, s.c.) significantly decreased the duration of immobility in saline- and ACTH-treated rats. Chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized cell proliferation in ACTH-treated rats. We then investigated the effects of (+)-8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and cyclin D1 (elements of cyclic adenosine monophosphate response element-binding protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did not change in either saline- or ACTH-treated rats. These findings suggest that the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be attributed to an enhancement of hippocampal cell proliferation, at least in part due to an enhancement of cyclin D1 expression.

  6. Protective effect of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide. (United States)

    Aghaei, S; Nikzad, H; Taghizadeh, M; Tameh, A A; Taherian, A; Moravveji, A


    Cancer treatment with cyclophosphamide (CP) may result in reproductive toxicity as one of its side effects. The pumpkin seed is a rich natural source of antioxidant. We have assessed the possible protective efficacy of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology of CP-treated rats. Male adult Wistar rats were categorised into four groups. Group 1 served as control and received intraperitoneal (IP) injection of isotonic saline solution. Group 2 rats were treated with CP by IP injection in a single dose of 100 mg/kg body weight, only once. Group 3 and 4 received CP plus 300 and 600 mg/kg pumpkin seed extract respectively. Six weeks after treatment, sperm characteristics, biochemical parameters and histopathological changes were examined. Results showed that, sperm characteristics in CP-treated rats were significantly decreased. Biochemical analysis results showed that the co-administration of 300 mg pumpkin seed extract could increase the total antioxidant capacity (TAC) level significantly. In CP-treated rats, histopathological changes such as vacuolisation, disorganisation and separation of epididymal epithelium were observed as well. Interestingly, pumpkin seed extract could improve the above-mentioned parameters remarkably in CP-treated rats. Our findings indicated that pumpkin seed extract might be used as protective agent against CP-induced reproductive toxicity.

  7. Changes of Cerebral β-Endorphin in Rats Treated with Combination therapy of Melatonin and Electroacupuncture

    Institute of Scientific and Technical Information of China (English)

    周敏明; 俞昌喜; 王妙珍; 曹小定; 吴根诚


    Objective: To explore the strengthening of acupuncture analgesic mechanism on the level of β-endorphin and proopimelanocortin mRNA expression in the arcuate nucleus of hypothalamus in rats following electroacupuncture(EA) combined with melatonin (MEL). Methods: Integrated optical density (IOD) was measured by ABC immuno-histochemical and in situ hybridization technique with computerized image processing. The rat's brain was coronally sectioned after combination of EA and MEL. Results: IOD of β-endorphin-like immunopositive substance in rat's brain was lowered significantly, which was measured after MEL (60 mg/kg) was injected intraperitoneally and followed by EA 30 min later for 30 min, and the IOD of cerebral POMC mRNA positive substance increased significantly 10 hrs later. Conclusion:The mechanism of MEL in enhancing EA analgesic effect might be related with the release and synthesis of β-endorphin

  8. Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract. (United States)

    Mediani, Ahmed; Abas, Faridah; Maulidiani, M; Khatib, Alfi; Tan, Chin Ping; Ismail, Intan Safinar; Shaari, Khozirah; Ismail, Amin; Lajis, N H


    Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.

  9. Effect of combination therapy consisting of enalapril, α-lipoic acid, and menhaden oil on diabetic neuropathy in a high fat/low dose streptozotocin treated rat. (United States)

    Davidson, Eric P; Holmes, Amey; Coppey, Lawrence J; Yorek, Mark A


    We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or menhaden oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and menhaden oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and menhaden oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.

  10. Heavy metals in the spinal cord of normal rats and of animals treated with chelating agents

    DEFF Research Database (Denmark)

    Schrøder, H D; Fjerdingstad, E; Danscher, G


    The amounts of zinc, copper, and lead in the rat spinal cord were determined by means of flameless atomic absorption spectrophotometry. Zinc was present in a concentration about 100 p.p.m. (dry weight), copper in a concentration about 5 p.p.m., and lead in slightly more than 1 p.p.m. Analysis...... of various levels along the cranio-caudal axis of the rat spinal cord revealed differences in the heavy metal content. The Timm sulfide silver staining method has demonstrated that metals in the spinal cord have a distinct regional distribution. To obtain a differentiation between the stainable metals...

  11. Adverse renal effects of hydrochlorothiazide in rats with myocardial infarction treated with an ACE inhibitor

    NARCIS (Netherlands)

    Westendorp, Bart; Hamming, Inge; Szymanski, Mariusz K.; Navis, Gerjan; van Goor, Harry; Buikema, Hendrik; van Gilst, Wiek H.; Schoemaker, Regien G.


    Diuretics, when added to angiotensin-converting enzyme inhibitors (ACE inhibitors) treatment, can augment the response to ACE inhibitors, but may have adverse effects on renal function, which negatively affect prognosis. While in heart failure rats combined therapy initially improved cardiac functio

  12. Upregulation of voltage-activated potassium channels in hippocampus of Aβ25.35-treated rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-liangWANG; Ya-pingPAN


    AIM: Potassium channels dysfunction has been indicated in Alzheimer disease. In the present study, the mRNA and protein expression alterations and the functional changes ot VOltage- activated potassium channels were studied in rat hippocampus after a single intracerebro- ventricular injection of β-amyloid peptide 25-35 (Aβ25.35). METHODS: The expressions of mRNA

  13. Uptake of /sup 67/Ga in the heart of rats treated with isoproterenol

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, T.; Kojima, S.; Kubodera, A.


    Gallium-67 citrate (/sup 67/Ga) accumulation and various enzyme activities during the repair of rat heart with infarct-like lesions induced by isoproterenol (ISP) treatment were measured for 10 days after treatment. Serum creatine phosphokinase (CPK) and glutamic oxalacetic transaminase (GOT) activities were increased immediately after ISP treatment, reaching maximum levels of activity of 545+-64 U/ml and 542+-94 KU/ml, respectively, within 12 h. Uptake of /sup 67/Ga in the rat heart was elevated 12 h after ISP treatment, reaching a maximum on day 1 (0.267+-0.020% dose/g heart). This pattern was essentially similar to the pattern of uronic acid content in the 1.2 M NaCl fraction, which contained mainly heparan sulfate (HS). The activity of glucose-6-phosphate dehydrogenase (G-6-PDH), a marker enzyme for fibrogenesis of damaged tissues, was also elevated 12 h after the ISP treatment, reaching a maximum of approximately 2.47 times that of the control heart on day 1. On the other hand, there were no significant changes in the /sup 67/Ga uptake and uronic acid content in any of the fractions of the liver and kidneys. These findings suggested that HS might be an acceptor for /sup 67/Ga accumulation during the repair of rat heart with infarct-like lesions, in accord with our previous results on CCl/sub 4/-damaged rat liver.

  14. Messenger RNA patterns in rat liver nuclei before and after treat-ment with growth hormone. (United States)

    Drews, J; Brawerman, G


    Like cortisol, growth hormone enhances RNA synthesis in rat liver nuclei. However, DNA-RNA hybridization experiments show that the application of growth hormone does not stimulate the formation of new species of messenger RNA. The latter phenomenon was observed after treatment with cortisol.

  15. A study of airway smooth muscle in asthmatic and non-asthmatic airways using PS-OCT (Conference Presentation) (United States)

    Adams, David C.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.


    Present understanding of the pathophysiological mechanisms of asthma has been severely limited by the lack of an imaging modality capable of assessing airway conditions of asthma patients in vivo. Of particular interest is the role that airway smooth muscle (ASM) plays in the development of asthma and asthma related symptoms. With standard Optical Coherence Tomography (OCT), imaging ASM is often not possible due to poor structural contrast between the muscle and surrounding tissues. A potential solution to this problem is to utilize additional optical contrast factors intrinsic to the tissue, such as birefringence. Due to its highly ordered structure, ASM is strongly birefringent. Previously, we demonstrated that Polarization Sensitive OCT(PS-OCT) has the potential to be used to visualize ASM as well as easily segment it from the surrounding (weakly) birefringent tissue by exploiting a property which allows it to discriminate the orientation of birefringent fibers. We have already validated our technology with a substantial set of histological comparisons made against data obtained ex vivo. In this work we present a comprehensive comparison of ASM distributions in asthmatic and non-asthmatic human volunteers. By isolating the ASM we parameterize its distribution in terms of both thickness and band width, calculated volumetrically over centimeters of airway. Using this data we perform analyses of the asthmatic and non-asthmatic airways using a broad number and variety and subjects.

  16. Maintenance of bladder innervation in diabetes: a stereological study of streptozotocin-treated female rats. (United States)

    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.

  17. Hepatoprotective, antioxidant, and ameliorative effects of ginger (Zingiber officinale Roscoe) and vitamin E in acetaminophen treated rats. (United States)

    Abdel-Azeem, Amal S; Hegazy, Amany M; Ibrahim, Khadiga S; Farrag, Abdel-Razik H; El-Sayed, Eman M


    Ginger is a remedy known to possess a number of pharmacological properties. This study investigated efficacy of ginger pretreatment in alleviating acetaminophen-induced acute hepatotoxicity in rats. Rats were divided into six groups; negative control, acetaminophen (APAP) (600 mg/kg single intraperitoneal injection); vitamin E (75 mg/kg), ginger (100 mg/kg), vitamin E + APAP, and ginger + APAP. Administration of APAP elicited significant liver injury that was manifested by remarkable increase in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), arginase activities, and total bilirubin concentration. Meanwhile, APAP significantly decreased plasma total proteins and albumin levels. APAP administration resulted in substantial increase in each of plasma triacylglycerols (TAGs), malondialdhyde (MDA) levels, and total antioxidant capacity (TAC). However, ginger or vitamin E treatment prior to APAP showed significant hepatoprotective effect by lowering the hepatic marker enzymes (AST, ALT, ALP, and arginase) and total bilirubin in plasma. In addition, they remarkably ameliorated the APAP-induced oxidative stress by inhibiting lipid peroxidation (MDA). Pretreatment by ginger or vitamin E significantly restored TAGs, and total protein levels. Histopathological examination of APAP treated rats showed alterations in normal hepatic histoarchitecture, with necrosis and vacuolization of cells. These alterations were substantially decreased by ginger or vitamin E. Our results demonstrated that ginger can prevent hepatic injuries, alleviating oxidative stress in a manner comparable to that of vitamin E. Combination therapy of ginger and APAP is recommended especially in cases with hepatic disorders or when high doses of APAP are required.

  18. Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with lamotrigine. (United States)

    Zalewska-Kaszubska, Jadwiga; Bajer, Bartosz; Gorska, Dorota; Andrzejczak, Dariusz; Dyr, Wanda; Bieńkowski, Przemysław


    Several recent studies have indicated that lamotrigine, similarly to other antiepileptic drugs, may be useful in the therapy of alcohol dependence. The rationale for using lamotrigine in the treatment of alcohol addiction is based on its multiple mechanisms of action which include inhibition of voltage-sensitive sodium channels, modulation voltage-gated calcium currents and transient potassium outward current. However, the known mechanism of lamotrigine does not fully explain its efficacy in alcohol addiction therapy. For this reason we have decided to examine the effect of lamotrigine on the opioid system. Our previous studies showed that topiramate and levetiracetam (antiepileptic drugs) as well as the most effective drugs in alcohol addiction therapy i.e. naltrexone and acamprosate, when given repeatedly, all increased plasma beta endorphin (an endogenous opioid peptide) level, despite operating through different pharmacological mechanisms. It is known that low beta-endorphin level is often associated with alcohol addiction and also that alcohol consumption elevates the level of this peptide. This study aims to assess the effect of repeated treatment with lamotrigine on voluntary alcohol intake and beta-endorphin plasma level in alcohol preferring rats (Warsaw high preferring (WHP) rats). We observed a decrease in alcohol consumption in rats treated with lamotrigine. However we didn't observe significant changes in beta-endorphin level during withdrawal of alcohol, which may indicate that the drug does not affect the opioid system. We suppose that lamotrigine may be useful in alcohol dependence therapy and presents a potential area for further study.

  19. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  20. Distribution profile of gadolinium in gadolinium chelate-treated renally-impaired rats: role of pharmaceutical formulation. (United States)

    Fretellier, Nathalie; Salhi, Mariem; Schroeder, Josef; Siegmund, Heiko; Chevalier, Thibaut; Bruneval, Patrick; Jestin-Mayer, Gaëlle; Delaloge, Francette; Factor, Cécile; Mayer, Jean-François; Fabicki, Jean-Michel; Robic, Caroline; Bonnemain, Bruno; Idée, Jean-Marc; Corot, Claire


    While not acutely toxic, chronic hepatic effect of certain gadolinium chelates (GC), used as contrast agent for magnetic resonance imaging, might represent a risk in renally-impaired patients due to free gadolinium accumulation in the liver. To answer this question, this study investigated the consequences of the presence of small amounts of either a soluble gadolinium salt ("free" Gd) or low-stability chelating impurity in the pharmaceutical solution of gadoteric acid, a macrocyclic GC with high thermodynamic and kinetic stabilities, were investigated in renally-impaired rats. Renal failure was induced by adding 0.75% adenine in the diet for three weeks. The pharmaceutical and commercial solution of gadoteric acid was administered (5 daily intravenous injections of 2.5 mmol Gd/kg) either alone or after being spiked with either "free" gadolinium (i.e., 0.04% w/v) or low-stability impurity (i.e., 0.06 w/v). Another GC, gadodiamide (low thermodynamic and kinetic stabilities) was given as its commercial solution at a similar dose. Non-chelated gadolinium was tested at two doses (0.005 and 0.01 mmol Gd/kg) as acetate salt. Gadodiamide induced systemic toxicity (mortality, severe epidermal and dermal lesions) and substantial tissue Gd retention. The addition of very low amounts of "free", non-chelated gadolinium or low thermodynamic stability impurity to the pharmaceutical solution of the thermodynamically stable GC gadoteric acid resulted in substantial capture of metal by the liver, similar to what was observed in "free" gadolinium salt-treated rats. Relaxometry studies strongly suggested the presence of free and soluble gadolinium in the liver. Electron microscopy examinations revealed the presence of free and insoluble gadolinium deposits in hepatocytes and Kupffer cells of rats treated with gadoteric acid solution spiked with low-stability impurity, free gadolinium and gadodiamide, but not in rats treated with the pharmaceutical solution of gadoteric acid. The

  1. Change in pharmacokinetic behavior of intravenously administered midazolam due to increased CYP3A2 expression in rats treated with menthol. (United States)

    Nagai, Katsuhito; Suzuki, Sho; Yamamura, Ayumi; Konishi, Hiroki


    Menthol is used widely as a constituent of functional foods and chemical drugs. The present study investigated changes in the pharmacokinetic behavior of intravenously administered midazolam (MDZ), a probe for CYP3A, when rats were treated with menthol. The study also examined which isoforms of CYP3A1 and 3A2 were menthol-inducible and contributed to the altered disposition of midazolam. Menthol was administered intraperitoneally to rats once daily for 3 days at a dose of 10 mg/kg, while the control rats received vehicle alone. The pharmacokinetic examination of i.v. administered midazolam revealed that serum midazolam concentrations at each sampling point were lower in the menthol-treated rats than in the control rats. Regarding the pharmacokinetic parameters of the menthol-treated group, the area under the curve (AUC) was decreased significantly and, correspondingly, the elimination rate constant at terminal phase (ke) was increased significantly without significant changes in the volume of distribution at steady state (Vdss). The metabolic production of the 1'-hydroxylated and 4'-hydroxylated forms of MDZ by hepatic microsomes was significantly greater in the menthol-treated rats than in the control rats. The expression levels of mRNA and protein for hepatic CYP3A2 were more than 2.5-fold higher than the control levels when the rats were treated with menthol, whereas no changes were observed in the expression levels of CYP3A1. These results indicate that menthol enhanced the elimination clearance of midazolam by inducing hepatic CYP3A2 and that careful attention should be paid when menthol is ingested in combination with drugs that act as substrates for CYP3A.

  2. The effect of arbutin on lipid peroxidation and antioxidant capacity in the serum of cyclosporine-treated rats (United States)

    Khadir, Fatemeh; Pouramir, Mahdi; Joorsaraee, Seyyed Gholamali; Feizi, Farideh; Sorkhi, Hadi; Yousefi, Fatemeh


    Background: Cyclosporine A (CsA) is a potent immunosuppressant drug with therapeutic and toxic actions. The use of CsA is limited by its toxicity. Several researchers had proposed that oxidative stress could play an important role in CsA-induced toxicity. Arbutin has recently been shown to possess antioxidative and free radical scavenging abilities. The present study was designed to investigate the in vivo effects of arbutin on lipid peroxidation and antioxidant capacity in the serum of cyclosporine treated rats. Methods: Adult male Wistar rats were divided into six groups (n=8/group): (I) control (no CsA and arbutin administration), (II and III) were treated subcutaneously (Sc) with arbutin (50,100 mg/kg/bw), respectively, (IV) administered CsA (25 mg/kg/bw) intraperitoneally (IP), (V and VI) received the combination of CsA (25 mg/kg/bw) i.p and arbutin (50,100 mg/kg/bw) Sc daily, respectively. At the end of the treatment (after3 weeks), serum lipid peroxidation was measured by thiobarbituric acid-reacting substances (TBARS) and serum total antioxidant capacity (ferric reducing ability of plasma [FRAP]) was assayed based on spectrophotometric method. Results: TBARS had been significantly increased by CsA administration compared with control rats. Arbutin (50mg/kg/bw) completely prevented this effect, but arbutin (100 mg/kg/bw) alone or in combination with CsA significantly increased lipid peroxidation compared with controls. Conclusion: Our data indicate that arbutin (50mg/kg/bw) had protective effect in the CsA-induced toxicity but high concentration of arbutin (100mg/kg/bw) showed meaningful oxidative and lipoperoxidative effects. PMID:26644892

  3. Altered regulation of luteinizing hormone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

    Energy Technology Data Exchange (ETDEWEB)

    Bookstaff, R.C.


    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) severely decreases plasma androgen concentrations, yet plasma luteinizing hormone (LH) concentrations remain unchanged. The mechanism by which TCDD prevents the expected compensatory increase in plasma LH was investigated. No effect on the plasma disappearance rate of LH or on pituitary capacity to synthesize or secrete LH was detected. Rather, TCDD altered the regulation of LH secretion by substantially increasing the potency of both androgens and estrogens as feedback inhibitors of LH secretion. The mechanism by which TCDD alters androgen-regulated LH secretion was further investigated. Seven days after dosing, TCDD decreased plasma testosterone concentrations but prevented the expected compensatory increases in pituitary gonadotropin-releasing hormone (GnRH) receptor number, pituitary responsiveness to GnRH, and plasma LH concentrations as seen in similarly hypoandrogenic vehicle dosed rats. Furthermore, the TCDD dose-response relationships for preventing the compensatory increases in pituitary GnRH receptor number and plasma LH concentration were similar. However, in the absence of gonadal steroids (7 days after castration) TCDD did not affect the compensatory increases in pituitary GnRH receptor number, pituitary responsiveness to GnRH, or plasma LH concentration. All of these parameters increased substantially relative to intact TCDD treated rats, and to levels virtually identical to those seen in castrated control rats. Treatment of castrated rats with testosterone restored the ability of TCDD to prevent these compensatory increases. Taken together, these results demonstrate that the presence of androgens is required for TCDD to alter the regulation of pituitary GnRH receptors.

  4. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    Directory of Open Access Journals (Sweden)

    King Nicholas JC


    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  5. Effects of leptin on airway inflammation and the expression of Th1/Th2 cytokines in asthmatic rats%瘦素对支气管哮喘大鼠气道炎症及Th1/Th2细胞因子表达作用的影响

    Institute of Scientific and Technical Information of China (English)

    曹娟; 陈建辉; 朱述阳


    Objective To investigate the effects of hptin on airway inflammation and the expression of Th1/Th2 cytokines. Methods The obesity and acute asthma models were established in 40 female SD rats, which were randomly divided into a normal weight control group (group A), a normal weight asthmatic group (group B), a normal weight intervention group (group C), an obese control group (group D) and an obese asthmatic group (group E). The airway resistance and airway responsiveness were calculated by transpulmonary pressure and gas flow rate. The numbers of leukocytes, eosinophils (EOS) and neutrephils (N) in brenchoalveolar lavage fluid (BALF) were counted. The concentrations of interleukin-4 (IL-4), interferon-γ(IFN-γ) and leptin in serum and BALF were determined by ELISA. The protein and Mrna expression of leptin was measured by Western blot and RT-PCR respectively. Results The airway resistance in group C and E [(0.890±0.106)cm H2O·ml-1·s-1 (1.024±0.096)cm H2O·ml-1·s-1(1.129±0.107) cm H2O·ml-1·s-1, (0.946±0.104) cm H2O·ml-1·s-1, (1.124±0.095)cm H2O·ml-1·s-1, (1.135±0.105) cm H2O·ml-1·s-1,respectively.] was increased significantly compared to group B [(0.638±0.128) cm H2O·ml-1·s-1, (0.745±0.073) cm H2O·ml-1·s-1,(0.773±0.090) cm H2O·ml-1·s-1] (q=7.128, 8.712, 8.318, 11.300, 11.258, 11.447, all P<0.05). The numbers of leukocyte and neutrophils in group C and E [(91±9)×104/ml, (108±21)×104/ml, (12.4±4.0)×104/ml, (14.2±5.9)×104/ml, respectively.] were increased significantly compared to group B [(79±7)×104/ml, (2.4±1.1)×104/ml] (q= 2.923, 7.063, 8.629, 10.182,all P<0.05). The concentrations of IFN-γ were [(42.3±3.5) ng/L, (45.1±4.8) ng/L, (19.2±1.8) ng/L, (20.3±1.5)ng/L] in group C and E respectively, which were significantly higher than those of group B[(16.5±1.4) ng/L,(9.3±1.0) ng/L] (q= 21.607, 23.952, 16.919, 18.799, all P<0.05). The protein and Mrna expression of leptin in lung tissue in group C and E[(0.40±0.07)ng/L,(0

  6. Cruciferous vegetables reduce morphological markers of colon cancer risk in dimethylhydrazine-treated rats. (United States)

    Arikawa, Andrea Y; Gallaher, Daniel D


    Consumption of cruciferous vegetables has been associated with reduced colon cancer risk in human populations. However, little experimental evidence exists to support this association. Here, we report the effects of diets containing cruciferous vegetables on colon cancer risk. In Expt. 1, rats were fed a vegetable-free (basal) diet or diets containing different lyophilized cruciferous vegetables in concentrations between 4 and 10%. In Expt. 2, rats were fed the basal diet or diets containing 10-22.6% fresh cruciferous vegetables. Diets were fed for 2 wk (Expt. 1) or 3 wk (Expt. 2) before and 7 wk (Expt. 1) or 12 wk (Expt. 2) after administration of the colon carcinogen 1,2-dimethylhydrazine. Rats fed fresh vegetables were also injected with a low dose of carcinogen 18-24 h prior to termination. Groups fed lyophilized vegetables did not differ in aberrant crypt foci (ACF), sialomucin-producing foci, or mucin-depleted foci (MDF) numbers. However, all fresh vegetable diets significantly decreased ACF (approximately 40%) and MDF numbers. Activities of the hepatic phase I enzyme CYP2E1 did not differ among groups in either experiment. Hepatic glutathione S-transferase (GST) and quinone reductase activities did not differ among groups fed fresh vegetables, whereas the lyophilized cabbage diets decreased GST activity compared with the basal diet. Groups did not differ in apoptosis and cell proliferation labeling indices in colonic mucosa. This study indicates that fresh but not lyophilized cruciferous vegetables reduce colon cancer risk in rats. These results do not support changes in hepatic carcinogen metabolism or colonic crypt cytokinetics as a mechanism.

  7. Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc. (United States)

    Medici, Valentina; Santon, Alessandro; Sturniolo, Giacomo Carlo; D'Incà, Renata; Giannetto, Sabrina; Albergoni, Vincenzo; Irato, Paola


    The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh(8)dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.

  8. Ultrastructural observation on pulmonary fibrosis in E9 rats treated with compoundCarapax trionycis formula

    Institute of Scientific and Technical Information of China (English)

    Jin Ren; Li-Xuan Wang; Xue-Cheng Ji; Jia-Ying Zhou; Man-Ying Zhang


    Objective:To investigate ultrastructural changes in pulmonary tissue of a rat model of pulmonary fibrosis following treatment with compoundCarapax trionycis(C. trionycis;Biejia inChinese) formula.Methods:Sixty maleSprague-Dawley rats were randomly divided into four groups(n=15): compoundC. trionycis formula high-, middle-, and low-dose groups as well as model group. Pulmonary fibrosis was induced by bleomycin.Five rats from each group weresacrificed on day 7,14 and28 of the drug treatment, respectively.The pulmonary tissue was harvested followed by hematoxylin-eosin staining and subsequent transmission electron microscopy.TheSzapiel’s method was used to assess the degree of alveolitis and pulmonary fibrosis.Results:Compared with the model group, the compoundC. trionycis formula groups had slighter pulmonary alveolitis after the7-day treatment and also had alleviated alveolar inflammation and pulmonary fibrosis after the14-day treatment.After the28-day treatment, the compoundC. trionycis formula groups showed deposition of a small amount of fibrous tissue and lesions occupying less than21% of the whole lung area, while the model group showed focal or diffuse fibrous deposition, narrow alveolar cavity, disordered lung structure, and lesions in larger than51% of the whole lung area. Conclusions:The compoundC. trionycis formula can inhibit the proliferation of collagen fibers and resist pulmonary fibrosis.

  9. Morphological Analysis of the Enamel Organ in Rats Treated with Fluoxetine (United States)

    Silva, Igor Henrique Morais; Leão, Jair Carneiro; Evêncio, Liriane Baratella; Porter, Stephen Ross; de Castro, Raul Manhães


    PURPOSE: Previous studies have evaluated the presence of serotonin in the dental epithelia and mesenchyme during odontogenesis, suggesting its participation in tooth development. MATERIALS AND METHODS: Here, we used fluoxetine, a selective serotonin re-uptake inhibitor, at a dose of 10 mg/kg, administered for 20 days during pregnancy in 12 Wistar rats to examine the influence of this drug on the development of the enamel organ of the upper first molars of rat fetuses at 17 days of intra-uterine life (i.u.l.), and at one, five and ten days postpartum. The pregnant rats were anesthetized with xylazine at 10 mg/kg and ketamine at 25 mg/kg. The fetuses were removed and beheaded; their jaws were removed, and the upper jaws were exposed. The tissues were fixed in Bouin’s fixative, decalcified in 5% nitric acid for 4 – 12 h, conventionally processed for microscopy, and embedded in paraffin. Serial sections of approximately 5 μm were obtained and stained with hematoxylin and eosin, as well as periodic acid-Schiff. RESULTS AND CONCLUSION: Morphological analysis showed no structural changes in the experimental group compared to the controls, suggesting that, at the dose used, fluoxetine does not interfere with serotonin-mediated development of the enamel organ or the process of amelogenesis. PMID:20126347

  10. Morphological analysis of the enamel organ in rats treated with fluoxetine

    Directory of Open Access Journals (Sweden)

    Henrique Morais Silva


    Full Text Available PURPOSE: Previous studies have evaluated the presence of serotonin in the dental epithelia and mesenchyme during odontogenesis, suggesting its participation in tooth development. MATERIALS AND METHODS: Here, we used fluoxetine, a selective serotonin re-uptake inhibitor, at a dose of 10 mg/kg, administered for 20 days during pregnancy in 12 Wistar rats to examine the influence of this drug on the development of the enamel organ of the upper first molars of rat fetuses at 17 days of intra-uterine life (i.u.l., and at one, five and ten days postpartum. The pregnant rats were anesthetized with xylazine at 10 mg/kg and ketamine at 25 mg/kg. The fetuses were removed and beheaded; their jaws were removed, and the upper jaws were exposed. The tissues were fixed in Bouin's fixative, decalcified in 5% nitric acid for 4 - 12 h, conventionally processed for microscopy, and embedded in paraffin. Serial sections of approximately 5 mm were obtained and stained with hematoxylin and eosin, as well as periodic acid-Schiff. RESULTS AND CONCLUSION: Morphological analysis showed no structural changes in the experimental group compared to the controls, suggesting that, at the dose used, fluoxetine does not interfere with serotonin-mediated development of the enamel organ or the process of amelogenesis.

  11. Lipid peroxidation in the liver of rats treated with V and/or Mg in drinking water. (United States)

    Scibior, Agnieszka; Zaporowska, Halina; Niedźwiecka, Irmina


    The effect of V(5+) and Mg treatment on spontaneous and stimulated lipid peroxidation (LPO) was studied in liver supernatants obtained from outbred 5-month-old, albino male Wistar rats. The 2-month-old animals daily received deionized water to drink (control, group I); group II - water solution of NaVO(3) (SMV) at a concentration of 0.125 mg V ml(-1); group III - water solution of MgSO(4) (MS) at a concentration of 0.06 mg Mg ml(-1), group IV - water solution of SMV-MS at the same concentrations as in groups II and III for V and Mg, respectively, over a 12-week period. Three metal salts were selected as agents that may modify the LPO process (FeSO(4), NaVO(3) and MgSO(4)). V-intoxicated rats and those treated with V and Mg in combination had higher liver spontaneous malondialdehyde (MDA) formation, compared with the control and Mg-supplemented animals. In the same groups of animals the total antioxidant status (TAS) was also significantly lowered, in comparison with the control. In the supernatants obtained from the above-mentioned groups of rats a significant increase in MDA concentration was found in the presence of exogenous 30 microm FeSO(4) as well as 30, 100, 200 and 400 microm NaVO(3), compared with groups I and III. Significantly elevated MDA production was also observed in the supernatants obtained from the rats exposed to V and Mg in combination in the presence of exogenous 100 and 200 microm MgSO(4) in comparison with the control and group III as well as in the presence of exogenous 400 and 600 microm MgSO(4) compared only with group III. In vitro treatment with 1000 microm MgSO(4 )of control liver supernatants and those obtained from group III significantly enhanced MDA level, compared with spontaneous MDA formation. The two-way ANOVA indicated that the changes in the basal MDA level and in TAS in the rats at combined V and Mg application, were not due to V-Mg interaction, but resulted from independent action of V. In addition, the three-way ANOVA

  12. Postmortem Attraction of Sarcosaprophagous Diptera to Tramadol-Treated Rats and Morphometric Aspects of the Developed Larvae. (United States)

    AbouZied, E M


    The presence of some specific drugs in animal tissues may affect the time of minimal postmortem intervals estimated during forensic entomological investigations. To test the effects of a specific drug on decomposition, a field study was conducted at Fayoum University campus, Egypt, from March to May 2013, using tramadol, a synthetic analgesic opioid used to treat moderate to severe pain in humans. Albino rats were used as the animal model during this study. The duration of the fresh stage of tramadol treated rat (Ttr) carcasses was significantly shorter (2.4 ± 0.27 days) compared to tramadol free rat (Tfr) carcasses (6.4 ± 0.49 days). The dry carcass stage of Ttr lasted longer (10.3 ± 0.99 days) as compared to (7.4 ± 0.18 days) the Tfr carcass. The decomposition process of the (Ttr) carcass was not significantly faster (24.9 ± 1.58 days) as compared to (Tfr) carcasses (29.5 ± 1.69). Lucilia cuprina (Wiedemann), Chrysomya albiceps (Wiedemann), and Musca domestica L. were less attracted to Ttr carcass-baited traps than traps with Tfr carcasses. However, females of Sarcophaga spp. showed a greater attraction to Ttr carcasses. Females of another sarcophagid fly, Wohlfahrtia spp. exhibited similar attraction tendencies to both types of trap baits. Larvae of S. argyrostoma (Robineau-Desvoidy) collected from Ttr carcasses developed to a significantly longer total body length (10.4 ± 0.04 mm) as compared to the average length of the larvae collected from Tfr carcasses (8.9 ± 0.34 mm). During days 9-13 after rat death, the relative lengths of larvae from Ttr carcasses were not significantly different from Tfr carcasses. Larvae fed on Ttr carcasses pupated 2 days later than the control larvae.

  13. Expression of metallothionein gene at different time in testicular interstitial cells and liver of rats treated with cadmium

    Institute of Scientific and Technical Information of China (English)

    Xu-Yi Ren; Yong Zhou; Jian-Peng Zhang; Wei-Hua Feng; Bing-Hua Jiao


    AIM: Rodent testes are generally more susceptible to cadmium (Cd)-induced toxicity than liver. To clarify the molecular mechanism of Cd-induced toxicity in testes, we compared metallothionein (MT) gene expression, MT protein accumulation, and Cd retention at different time in freshly isolated testicular interstitial cells and liver of rats treated with Cd.METHODS: Adult male Sprague-Dawley rats weighing 250-280 g received a s.c injection of 4.0 μmol Cd/kg and were euthanized by CO2 asphyxiation 1h, 3 h, 6 h, or 24 h later.Tissue was sampled and testicular interstitial cells were isolated. There were three replicates per treatment and 3animals per replicate for RNA analyses, others, three replicates per treatment and one animal per replicate. MT1 and MT2 mRNA levels were determined by semi-quantitative RT-PCR analysis followed by densitometry scanning, and MT was estimated by the enzyme-linked immunosorbent assay (ELISA) method. Cadmium content was determined by atomic absorption spectrophotometry. The same parametersd were also analyzed in the liver, since this tissue unquestionably accumulate MT.RESULTS: The rat testis expressed MT1 and MT2, the major isoforms. We also found that untreated animals contained relatively high basal levels of both isoform mRNA, which were increased after Cd treatment in liver and peaked at 3 h, followed by a decline. In contrast, the mRNA levels in interstitial cells peaked at 6 h. Interestingly, the induction of MT1 mRNA was lower than MT2 mRNA in liver of rat treated with Cd, but it was opposite to interstitial cells. Cd exposure substantially increased hepatic MT (3.9-fold increase), but did not increase MT translation in interstitial cells. CONCLUSION: Cd-induced expression of MT isoforms is not only tissue dependent but also time-dependent. The inability to induce the metal-detoxicating MT-protein in response to Cd, may account for a higher susceptibility of testes to Cd toxicity and carcinogenesis compared to liver.

  14. Hyaline droplet accumulation in kidney of rats treated with hexachloro-1:3-butadiene: influence of age, dose and time-course. (United States)

    Cristofori, Patrizia; Defazio, Rossella; Chiusolo, Arianna; Mongillo, Michele; Bartolucci, Giovanni Battista; Chiara, Federica; Trevisan, Andrea


    The present research investigates the occurrence of hyaline droplet (HD) accumulation related to age, dose and time after treatment in male Wistar rats given a single i.p. injection of hexachloro-1:3-butadiene (HCBD). In the study on age, rats from 1 to 12 months of age were treated with 100 mg kg(-1) body weight (b.w.) HCBD dose. Rats treated at 2 months of age showed a greater accumulation of HD than the other age groups; HD accumulation was not observed in 1-month-old rats. In the dose-response study, the treatment with 25, 50 and 100 mg kg(-1) b.w. at 2 months of age caused HD accumulation in the proximal convoluted tubule at all doses, with the 100 mg kg(-1) b.w. group slightly more affected. Finally, in the time-course study, rats treated with a 100 mg kg(-1) b.w. dose at 2 months of age and sacrificed at 6, 12, 24, 48, 72 and 96 h post-dosing showed a time-related HD accumulation in terms of incidence and severity, after 6 h, with a peak at 24 and 48 h and decreasing at 72 and 96 h. The present results show that HD accumulation is an early finding, and is unrelated to dose level and particularly evident in rats of 2 month of age. These findings in male rats treated with HCBD emphasize the importance of considering the age of rats at the start of a study. The more sensitive model was used in the detection of nephrotoxic effects of chemicals.

  15. Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats. (United States)

    Min, Jung-Ah; Lee, Hye-Ryeon; Kim, Jae-Ick; Ju, Anes; Kim, Dai-Jin; Kaang, Bong-Kiun


    Type 2 diabetes and chronic heavy alcohol consumption each have been known to be associated with the impairment of hippocampus-dependent cognitive functions. Although both conditions often coexist clinically and there is accumulated evidence of a relationship between the two, the combined effect on hippocampal long-term potentiation (LTP) has not yet been investigated. We compared the effect of type 2 diabetes itself with that of type 2 diabetes with chronic heavy alcohol consumption on the hippocampal LTP using Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, which resembles the characteristics of human type 2 diabetes. Ten of 16-week-old male OLETF rats were randomized into two treatment groups according to weight: the OLETF-Alcohol (O-A, n=5) and the OLETF-Control (O-C, n=5). The rats in the O-A group were fed Lieber-DeCarli Regular EtOH over a 10-week period and the amount of alcohol consumption was 8.42±2.52g/kg/day. To ensure the effect of poor glycemic control on LTP, intraperitoneal glucose tolerance test was performed after a 10-week treatment. The hippocampal LTP was measured by extracellular field excitatory post-synaptic potentials at Shaffer collateral (SC) synapses in the CA1 region. Although the O-A group showed significantly lower fasting and postprandial glucose (Palcohol consumption could potentiate the impairment of hippocampal LTP in individuals with impaired glucose tolerance or early type 2 diabetes, even though it did not aggravate, but did improve glycemic control. Clinical attention to chronic heavy drinking will be required in preventing cognitive impairment in individuals with type 2 diabetes.

  16. Hypokalemia: a potent risk for QTc prolongation in clarithromycin treated rats. (United States)

    Karmakar, Sanmoy; Padman, Aswathi; Swamy Mane, Naga; Sen, Tuhinadri


    Clarithromycin belongs to macrolide group of antibiotics commonly known for their proarrhythmic potency. Besides agents interfering with CYP 3A, electrolyte imbalance might influence repolarization problems of clarithromycin. The proarrhythmic tendency of clarithromycin particularly in association with hypokalemia manifested a change in QT interval in rat electrocardiogram (ECG). Varying degree of hypokalemia was induced by intraperitoneal injection of furosemide (50, 30, and 10 mg/kg, for seven days). The serum electrolyte levels confirmed that hypokalemia was established in the groups receiving furosemide. Simultaneously, clarithromycin was orally administered in the doses of 100 and 80 mg/kg for seven days. ECG was measured for 5 min in anaesthetised rat before and after 2 h of treatment. The QT interval was corrected for heart rate and reported as corrected QT (QTc). Distinct QTc interval prolongation was observed in groups receiving furosemide (50 and 30 mg/kg) alone and in all the groups receiving clarithromycin alongside furosemide. Neither, clarithromycin (80 mg/kg) nor furosemide (10 mg/kg) exhibited any significant change in the QTc interval but in combination these drugs led to a significant increase in the QTc interval. Most interestingly, potassium supplementation was found to reduce QTc interval in the group presenting with maximum QTc prolongation. These results suggest that hypokalemic condition potentiates the clarithromycin induced QTc prolongation, thereby indicating the importance of monitoring serum electrolyte during clarithromycin therapy. Although, selection of rat for examination of proarrhythmic liability is controversial, this report may be considered as an evidence of hypokalemia potentiating clarithromycin induced QTc prolongation.

  17. Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats.

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    Rita Cascão

    Full Text Available Rheumatoid arthritis (RA is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA.Celastrol was administered to AIA rats both in the early (4 days after disease induction and late (11 days after disease induction phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.Our results validate celastrol as a promising compound for the treatment of arthritis.

  18. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats


    Puebla Jiménez, Lilian; Rodríguez Martín, Eulalia; Arilla Ferreiro, Eduardo


    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 ¿g) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal ...

  19. Increased astrocytic expression of metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan; Moos, Torben


    The cerebral distribution of metallothioneins I and II (MT-I + II) was studied in adult rats subjected to i.p. injection with the gliotoxin 6-aminonicotinamide (6-AN). Grey matter regions of the brainstem heralded numerous OX-42-positive macrophages and microglia, indicating that 6-AN primarily...... caused damage to this part of the brain. In the grey matter regions infiltrated with OX-42-positive cells, astrocytes identified by anti-GFAP and MT-I + II antibodies were almost absent. By contrast, in the peripheral zone of the lesioned regions numerous reactive GFAP- and MT-I + II-positive astrocytes...

  20. The neurochemical profile of the hippocampus in isoflurane-treated and unanesthetized rat pups

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    Menshanov Petr N.


    Full Text Available In vivo study of cerebral metabolism in neonatal animals by high-resolution magnetic resonance spectroscopy (MRS is an important tool for deciphering the developmental origins of adult diseases. Up to date, all in vivo spectrum acquisition procedures have been performed in neonatal rodents under anesthesia. However, it is still unknown if the inhaled anesthetic isoflurane, which is commonly used in magnetic resonance imaging studies, could affect metabolite levels in the brain of neonatal rats. Moreover, the unanesthetized MRS preparation that uses neonatal rodent pups is still lacking.

  1. Transplacental and mammary passage of radioactivity in rats treated vaginally and orally with (/sup 14/C)propranolol

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    Buttar, H.S.; Moffatt, J.H.; Bura, C.


    Single doses (10 mg/kg) of an aqueous solution of (14C)propranolol were administered either orally (po) or intravaginally (ivg) on gestational d 15, or on postpartum d 7-10. Upon ivg administration, (14C)propranolol was quickly transferred to systemic circulation and the mean blood (14C) concentrations were significantly greater during the first 0.25-2 h than in po dosed counterparts. About 98% of the ivg applied dose was absorbed after 6 h in gravid rats, and the combined 6-h excretions of radioactivity in the urine (ivg = 24.6%; po = 22.9%) and feces (ivg = 16.8%; po = 14.6%) were equivalent in both groups. At the end of 6 h, the levels of (14C) in the urinary bladder, adrenal, uterus, ovary, spleen, skeletal muscle, brain, heart, lung and fat were significantly higher in ivg treated rats than po dosed animals. Compared with the maternal plasma (ivg = 0.76; po = 0.88 microgram/ml), the mean concentrations of (14C) in the placentas were similar in both groups, while the amounts of (14C) were three to five times lower in the amniotic fluids and the fetuses of both po and ivg treated dams. In lactating rats, over 99% of the administered radioactivity was absorbed from the vagina within 6 h. The blood concentrations of (14C) were significantly elevated at 0.5 and 1 h in the per vaginam treated animals, and afterward the disappearance rate of (14C) followed a similar course in both groups. Following ivg application, the milk radioactivity peaked at 0.5 h and declined rapidly. However, the appearance of (14C) in milk was rather slow after oral dosing: the milk (14C) peaked between 2 and 3 h posttreatment and remained steady thereafter. The milk to blood (M/B) (14C) concentration ratios were markedly greater during 0.5 to 1 h in the ivg group than in their po dosed counterparts.

  2. Biospeciation of tungsten in the serum of diabetic and healthy rats treated with the antidiabetic agent sodium tungstate. (United States)

    Gómez-Gómez, M Milagros; Rodríguez-Fariñas, Nuria; Cañas-Montalvo, Benito; Domínguez, Jorge; Guinovart, Joan; Cámara-Rica, Carmen


    It is known that oral administration of sodium tungstate preserves the pancreatic beta cell function in diabetic rats. Healthy and streptozotocin-induced diabetic rats were treated with sodium tungstate for one, three or six weeks, after which the species of W in serum, were analysed. An increase in serum W with treatment time was observed. After six weeks, the serum W concentration in diabetic rats (70 mg L(-1)) was about 4.6 times higher than in healthy specimens. This different behaviour was also observed for Cu accumulation, while the Zn pattern follows the contrary. The patterns observed in the retention of Cu and Zn may be attributable to a normalization of glycaemia. The speciation analysis of W was performed using 2D separations, including an immunoaffinity packing and a SEC (Size Exclusion Chromatography) column coupled to an ICP-MS (Inductively Coupled Plasma Mass Spectrometry) for elemental detection. Ultrafiltration data together with SEC-ICP-MS results proved that around 80% of serum W was bound to proteins, the diabetic rats registering a higher W content than their healthy counterparts. Most of the protein-bound W was due to a complex with albumin. An unknown protein with a molecular weight higher than 100 kDa was also found to bind a small amount of W (about 2%). MALDI-TOF (Matrix-Assisted Laser Desorption Ionization Time-of-Flight) analysis of the desalted and concentrated chromatographic fractions confirmed albumin as the main protein bound to tungstate in rat serum, while no binding to transferrin (Tf) was detected. The interaction between glutathione and W was also evaluated using standard solutions; however, the formation of complexes was not observed. The stability of the complexes between W and proteins when subjected to more stringent procedures, like those used in proteomic methodologies (denaturing with urea or SDS, boiling, sonication, acid media, reduction with β-mercaptoethanol (BME) or DTT (dithiotreitol) and alkylation with

  3. Determinants of lung function and airway hyperresponsiveness in asthmatic children

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Anhøj, J;


    Genetic Study (SAGA). RESULTS: The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV(1) percent predicted (FEV(1)% pred) was 0......BACKGROUND: Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying...... effect of steroid treatment. METHODS: We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma...

  4. Relationship between airway pathophysiology and airway inflammation in older asthmatics

    DEFF Research Database (Denmark)

    Porsbjerg, Celeste M; Gibson, Peter G; Pretto, Jeffrey J;


    BACKGROUND AND OBJECTIVE: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma......: Mean patient age was 67 years (confidence interval: 63-71) with a mean FEV1 of 78 % predicted (confidence interval: 70-85%). AHR correlated with sputum eosinophils (r = 0.68, P = 0.005) and eNO (r = 0.71, P ... or eNO. CONCLUSIONS: In older patients with asthma, airway inflammatory cells are linked to abnormal airway physiology. Eosinophilic airway inflammation is associated with AHR while neutrophilic inflammation may be an important determinant of airflow limitation at rest and airway closure during...

  5. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction. (United States)

    Perez, Thierry; Chanez, Pascal; Dusser, Daniel; Devillier, Philippe


    Asthma is a disease characterized by inflammation which affects both proximal and distal airways. We evaluated the prevalence of small airway obstruction (SAO) in a group of clinically stable asthmatics with both normal forced expiratory volume in the first second (FEV1) and normal FEV1/forced vital capacity (FVC) and treated with an association of inhaled corticosteroids (ICSs) and long acting β2-agonists (LABAs). Clinical evaluation included the measurement of dyspnea, asthma control test and drug compliance. The prevalence of SAO was estimated by spirometry and plethysmography and defined by the presence of one or more of the following criteria: functional residual capacity (FRC) > 120% predicted (pred), residual volume (RV) > pred + 1.64 residual standard deviation (RSD), RV/total lung capacity (TLC) > pred + 1.64 RSD, forced expiratory flow (FEF)25-75% slow vital capacity (SVC) - FVC > 10%. Among the 441 patients who were included, 222 had normal FEV1 and FEV1/FVC. At least one criteria of SAO was found in 115 (52%) mainly lung hyperinflation (39% based on high FRC, RV or RV/TLC) and more rarely distal airflow limitation (15% based on FEF25-75% or FEF50%) or expiratory trapping (10% based on increased SVC - FVC). In the patients with only SAO (no PAO), there was no relationship between SAO, asthma history and the scores of dyspnea, asthma control or drug compliance. These results suggest that in asthmatics with normal FEV1 and FEV1/FVC, treated with ICSs and LABAs, SAO is found in more than half of the patients indicating that the routinely used lung function tests can underestimate dysfunctions occurring in the small airways.

  6. Role of thirst and visual barriers in the differential behavior displayed by streptozotocin-treated rats in the elevated plus-maze and the open field test. (United States)

    Rebolledo-Solleiro, Daniela; Crespo-Ramírez, Minerva; Roldán-Roldán, Gabriel; Hiriart, Marcia; Pérez de la Mora, Miguel


    Conflicting results have been obtained by several groups when studying the effects of streptozotocin (STZ)-treated rats in the elevated plus-maze (EPM). Since thirst is a prominent feature in STZ-induced diabetic-like condition, we studied whether the walls of the closed arms of the EPM, by limiting the search for water in the environment, may contribute to the observed differential behavioral outcomes. The aim of this study was to ascertain whether visual barriers within the EPM have an influence on the behavior of STZ-treated rats in this test of anxiety. A striking similarity between STZ-treated (50 mg/kg, i.p., in two consecutive days) and water deprived rats (72 h) was found in exploratory behavior in the EPM, showing an anxiolytic-like profile. However the anxiolytic response of STZ-treated rats exposed to the EPM shifts into an anxiogenic profile when they are subsequently tested in the open-field test, which unlike the EPM is devoid of visual barriers. Likewise, water deprived rats (72 h) also showed an anxiogenic profile when they were exposed to the open-field test. Our results indicate that experimental outcomes based on EPM observations can be misleading when studying physiological or pathological conditions, e.g. diabetes, in which thirst may increase exploratory behavior.


    Białek, Agnieszka; Tokarz, Andrzej; Zagrodzki, Paweł


    The aim of this study was to investigate how supplementation of diet of female Sprague-Dawley rats with different doses of conjugated linoleic acids and for a varied period of time influences breast cancer risk, fatty acids profile and lipids peroxidation in chemically induced mammary tumors. Animals were divided into nine groups with different modifications of diet (vegetable oil, 1.0 or 2.0% of CLA) and period of supplementation, which lasted after (A), before (B) and before and after (BA) carcinogenic agent--7,12-dimethylbenz[a]anthracene administration at 50th day of life. Mammary adenocarcinomas occurred in all groups, but CLA supplementation decreased the cancer morbidity. Two percent CLA seems to be excessive because of the coexisting cachexia. Two CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) were detected in tumors but content of rumenic acid was higher. Dietary supplementation significantly influenced some unsaturated fatty acids content (C18:2 n-6 trans, C20:1, C20:5 n-3, C22:2), but the anti- or prooxidant properties of CLA were not confirmed. CLA can inhibit chemically induced mammary tumors development in female rats, but their cytotoxic action seems not to be connected with lipids peroxidation. CLA isomers differ with their incorporation into cancerous tissues and they influence the content of some other fatty acids.


    Directory of Open Access Journals (Sweden)

    Nilam Nigam


    Full Text Available NSAIDs are frequently used for relief of inflammati on and Antihistaminics are indicated for simultaneous administration for aller gic manifestations. Opioids analgesics have been reported to interact with Antihistaminics. To e xplore the interacting potentiality, in the present study the effects of combined treatment with NSAIDs and antihistaminics were examined in rats. Anti-inflammatory effect was eval uated by Carrageenan induced hind paw oedema in rats. NSAIDs like aspirin, ibuprofen and pir oxicam were selected for study on per se and on concurrent administration with Antihistamini cs such as Promethazine, Cetrizine and Astemizole. All NSAIDs protected animals show anti-i nflammatory activity. Aspirin shows highly significant potentiation of anti-inflammatory effect at all dose level, however ibuprofen and piroxicam show highly significant anti-inflammatory effect at higher doses only and on concurrent administration of antihistaminics, aspiri n, piroxicam and ibuprofen with all antihistaminics produced highly significant potentiat ion except ibuprofen with Cetrizine produced significant potentiation of anti-inflammator y response at higher doses only.

  9. Nourishing Yin and Promoting Blood Circulation of TCM to Treat Hemorheologic Disorder Induced by Diabetes Mellitus in Rats

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    Rong Xia


    Full Text Available Diabetes mellitus, DM, is commonly accompanied with various stages of hemorheologic disturbances that are the main causes of the development of chronic DM. In this study, simple Chinese material medica [yang-yin jiang-tang preparation (YYJT] was given to alloxan-induced DM rats and analyzed to compare the changes of fasting blood glucose (FBG, fasting insulin (FINS, hemorheologic parameters and insulin-like growth factor II (IGF-II before and after administration. The results suggested that YYJT can significantly downregulate FBG (P < 0.005, improve insulin resistance and beta-cell secretion (P < 0.05, decrease whole blood viscosity at low and high shear rates, gathering of blood index test (GIT and fibrinogen (FIB (P < 0.05, and enlarge the function of IGF-II (P < 0.05. We concluded that YYJT could prevent and treat hemorheologic disorder in DM rats by means of reducing glucose, improving insulin resistance and elevating IGF-II.

  10. Nociceptive and Neuronal Evaluation of the Sciatic Nerve of Wistar Rats Subjected to Compression Injury and Treated with Resistive Exercise

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    Juliana Sobral Antunes


    Full Text Available Background. To investigate the climb stairs resistance exercise on nociception and axonal regeneration in the sciatic nerve of rats. Methods. 24 Wistar rats were divided: control group (CG—no injury, exercise group (EG—no injury with physical exercise, lesion group (LG—injury, but without exercise, and treated group (LEG—injury and physical exercise. LG and LEG were subjected to sciatic nerve compression with hemostat. From the 3rd day after injury began treatment with exercise, and after 22 days occurs the removal of a nerve fragment for morphological analysis. Results. Regarding allodynia, CG obtained values less than EG (p=0.012 and larger than LG and LEG (p<0.001. Histological results showed that CG and EG had normal appearance, as LG and LEG showed up with large amounts of inflammatory infiltration, degeneration and disruption of nerve fibers, and reduction of the myelin sheath; however LEG presented some regenerated fibers. From the morphometric data there were significant differences, for nerve fiber diameter, comparing CG with LG and LEG and comparing axon diameter and the thickness of the myelin of the CG to others. Conclusion. Climb stairs resistance exercise was not effective to speed up the regenerative process of axons.

  11. Expression of metallothioneins I and II related to oxidative stress in the liver of aluminium-treated rats. (United States)

    Ghorbel, Imen; Chaabane, Mariem; Elwej, Awatef; Boudawara, Ons; Abdelhedi, Sameh; Jamoussi, Kamel; Boudawara, Tahya; Zeghal, Najiba


    Hepatotoxicity, induced by aluminium chloride (AlCl3), has been well studied but there are no reports about liver metallothionein (MT) genes induction. Therefore, it is of interest to establish the mechanism involving the relation between MT gene expression levels and the oxidative stress status in hepatic cells of aluminium-treated rats. Aluminium (Al) was administered to rats in their drinking water at a dose of 50 mg/kg body weight for three weeks. AlCl3 provoked hepatotoxicity objectified by an increase in malondialdehyde (MDA), hydrogen peroxide (H2O2), advanced oxidation protein products (AOPP), protein carbonyls (PCO) and a decrease in reduced glutathione (GSH), non-protein thiols (NPSH) and vitamin C. CAT and Glutathione peroxidase (GPx) activities were decreased while Mn-SOD gene expression, total Metallothionein content and MT I and MT II genes induction were increased. There are changes in plasma of some trace elements, albumin levels, transaminases, LDH and ALP activities. All these changes were supported by histopathological observations.

  12. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests. (United States)

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro


    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement.

  13. High prevalence of gastroesophageal reflux disease with minimal mucosal change in asthmatic patients. (United States)

    Shimizu, Yasuo; Dobashi, Kunio; Kobayashi, Setsuo; Ohki, Ichiro; Tokushima, Masahiko; Kusano, Motoyasu; Kawamura, Osamu; Shimoyama, Yasuyuki; Utsugi, Mitsuyoshi; Mori, Masatomo


    It is known that the prevalence of gastroesophageal reflux disease (GERD) in asthmatic patients is high. Although an endoscopic diagnosis of GERD based on the established Los Angeles (LA) classification requires the detection of erosive mucosal breaks, there are patients with GERD who have prominent erythema of the esophageal membrane without erosive mucosal breaks. Non-erosive mucosal change denotes the minimal change of the discoloring type of reflux esophagitis. This study was undertaken to determine the prevalence of GERD in asthmatic patients using the LA classification with the inclusion of minimal change, compared to the prevalence determined using the established LA classification without minimal change. The presence of GERD in asthmatic patients (n = 78), non-asthmatic disease control patients (n = 56), and healthy subjects (n = 150) was evaluated by endoscopic examination. The frequency of GERD in asthmatic patients based on the LA classification with minimal change was higher (54/78, 69.2%) than in asthmatic patients based on the LA classification without minimal change (37/78, 47.4%) (p disease control patients (17/56, 30.4%) and healthy subjects (27/150, 18.0%) based on the LA classification with minimum change. These data indicate that asthmatic patients have a high frequency of GERD. In addition, without the inclusion of minimum change to the diagnosis of GERD, the prevalence of GERD appears to be underestimated in asthmatic patients. Therefore, physicians should carefully observe asthmatic patients with minimal change on endoscopy.

  14. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

    Directory of Open Access Journals (Sweden)

    B Alex Merrick

    Full Text Available Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1, a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL. Paired-end reads were mapped to the rat genome (Rn4 with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005 compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c

  15. CNTF-Treated Astrocyte Conditioned Medium Enhances Large-Conductance Calcium-Activated Potassium Channel Activity in Rat Cortical Neurons. (United States)

    Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing


    Seizure activity is linked to astrocyte activation as well as dysfunctional cortical neuron excitability produced from changes in calcium-activated potassium (KCa) channel function. Ciliary neurotrophic factor-treated astrocyte conditioned medium (CNTF-ACM) can be used to investigate the peripheral effects of activated astrocytes upon cortical neurons. However, CNTF-ACM's effect upon KCa channel activity in cultured cortical neurons has not yet been investigated. Whole-cell patch clamp recordings were performed in rat cortical neurons to evaluate CNTF-ACM's effects upon charybdotoxin-sensitive large-conductance KCa (BK) channel currents and apamin-sensitive small-conductance KCa (SK) channel current. Biotinylation and RT-PCR were applied to assess CNTF-ACM's effects upon the protein and mRNA expression, respectively, of the SK channel subunits SK2 and SK3 and the BK channel subunits BKα1 and BKβ3. An anti-fibroblast growth factor-2 (FGF-2) monoclonal neutralizing antibody was used to assess the effects of the FGF-2 component of CNTF-ACM. CNTF-ACM significantly increased KCa channel current density, which was predominantly attributable to gains in BK channel activity (p ACM produced a significant increase in BKα1 and BKβ3 expression (p  0.05). Blocking FGF-2 produced significant reductions in KCa channel current density (p > 0.05) as well as BKα1 and BKβ3 expression in CNTF-ACM-treated neurons (p > 0.05). CNTF-ACM significantly enhances BK channel activity in rat cortical neurons and that FGF-2 is partially responsible for these effects. CNTF-induced astrocyte activation results in secretion of neuroactive factors which may affect neuronal excitability and resultant seizure activity in mammalian cortical neurons.

  16. Cannabinoid CB2 receptors in the enteric nervous system modulate gastrointestinal contractility in lipopolysaccharide-treated rats. (United States)

    Duncan, Marnie; Mouihate, Abdeslam; Mackie, Ken; Keenan, Catherine M; Buckley, Nancy E; Davison, Joseph S; Patel, Kamala D; Pittman, Quentin J; Sharkey, Keith A


    Enhanced intestinal transit due to lipopolysaccharide (LPS) is reversed by cannabinoid (CB)2 receptor agonists in vivo, but the site and mechanism of action are unknown. We have tested the hypothesis that CB2 receptors are expressed in the enteric nervous system and are activated in pathophysiological conditions. Tissues from either saline- or LPS-treated (2 h; 65 microg/kg ip) rats were processed for RT-PCR, Western blotting, and immunohistochemistry or were mounted in organ baths where electrical field stimulation was applied in the presence or absence of CB receptor agonists. Whereas the CB2 receptor agonist JWH133 did not affect the electrically evoked twitch response of the ileum under basal conditions, in the LPS-treated tissues JWH133 was able to reduce the enhanced contractile response in a concentration-dependent manner. Rat ileum expressed CB2 receptor mRNA and protein under physiological conditions, and this expression was not affected by LPS treatment. In the myenteric plexus, CB2 receptors were expressed on the majority of neurons, although not on those expressing nitric oxide synthase. LPS did not alter the distribution of CB2 receptor expression in the myenteric plexus. In vivo LPS treatment significantly increased Fos expression in both enteric glia and neurons. This enhanced expression was significantly attenuated by JWH133, whose action was reversed by the CB2 receptor antagonist AM630. Taking these facts together, we conclude that activation of CB2 receptors in the enteric nervous system of the gastrointestinal tract dampens endotoxin-induced enhanced intestinal contractility.

  17. Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1 (United States)

    Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.


    The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

  18. Preventing and Treating Actions of Compound Lian Zhu Capsule on Micrangium Lesions in Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    Duan Wenzhuo; Gong Haimin; Wang Jiafu; Ding Yi; Liu Tongmei; Wang Jianying; Li Yueqing


    Tissue culture, biochemical techniques and radioimmunoassay were used to study the effects of Compound sugar, glycosylated hemoglobin (GHb), urinary protein and malondialdehyde (MDA) contents, aldose reductase (AR) activity and 3H-TdR incorporation rate in the vascular smooth muscle cell (VSMC) were significantly higher, and plasma NO content in the diabetes mellitus (DM) group were significantly lower than those in the normal control group (both P<0.05). The above indexes in the Chinese medicine (TCM)treatment group were improved significantly as compared with the DM group, with no significantly differences, except urine volume and urinary protein, as compared with the normal control group. It is suggested that Compound Lian Zhu Capsules can significantly alleviate the complicated lesions of the micrangium in diabetic rats.

  19. Tyrosine hydroxylase expression in the midbrain of Parkinson's disease model rats treated with Xifeng Dingchan decoction

    Institute of Scientific and Technical Information of China (English)

    Enli Luo


    This study showed that abnormal behavioral changes were greatly improved in rats displaying Parkinson's disease-like symptoms after intragastric administration of Xifeng Dingchan decoction at 15, 7.5, 3.75 g/kg per day. In addition, tyrosine hydroxylase mRNA expression in the substantia nigra of the midbrain was up-regulated, and tyrosine hydroxylase content in the midbrain ventral tegmentum and substantia nigra pars compacta was also increased. The effect of administration of Xifeng Dingchan decoction at 7.5 g/kg per day was similar to that of Madopar at 67.5 mg/kg per day. These results indicate that the therapeutic effect of Xifeng Dingchan decoction on Parkinson's disease is associated with the up-regulated protein and mRNA expression of tyrosine hydroxylase in the midbrain.

  20. Increased contraction frequency in rat uterine strips treated in vitro with o,p prime -DDT

    Energy Technology Data Exchange (ETDEWEB)

    Juberg, D.R.; Loch-Caruso, R. (Univ. of Michigan, Ann Arbor (United States))


    Elevated levels of DDT and other organochlorine pesticides have been associated with spontaneous abortion and preterm birth in several species, including humans. Despite the prevalence of organochlorine pesticides in the environment, a mechanistic basis for this association has not been explored. Furthermore, while DDT has been associated with inhibition of calcium ATPases, altered gap junctional communication and electrophysiological changes, all of which could affect the excitation-contraction process characteristic of smooth muscle, direct effects of DDT on uterine smooth muscle have not been reported. This study was initiated to assess the direct effects of o,p{prime}-DDT (an estrogenic isomer present in the technical grade preparation) on pregnant rat uterine tissue.

  1. Biocompatibility of supercritical CO2-treated titanium implants in a rat model. (United States)

    Hill, C M; Kang, Q K; Wahl, C; Jimenez, A; Laberge, M; Drews, M; Matthews, M A; An, Y H


    Supercritical phase CO2 is a promising method for sterilizing implantable devices and tissue grafts. The goal of this study is to evaluate the biocompatibility of titanium implants sterilized by supercritical phase CO2 in a rat subcutaneous implantation model. At 5 weeks post implantation titanium implants sterilized by supercritical phase CO2 produce a soft tissue reaction that is comparable to other methods of sterilization (steam autoclave, ultraviolet light radiation, ethylene oxide gas, and radio-frequency glow-discharge), as indicated by the thickness and density of the foreign body capsule, although there were some differences on the capillary density. Overall the soft tissue response to the implants was similar among all methods of sterilization, indicating supercritical phase CO2 treatment did not compromise the biocompatibility of the titanium implant.

  2. Prostacyclin effects on the blood pressure responses to norepinephrine in rats treated with aspirin or indomethacin. (United States)

    Carmignani, M; Marchetti, P; Caprino, L


    The atherosclerotic condition is associated with a reduction of PGI2 synthesis; moreover, in the presence of elevated serum cholesterol levels, pressor responses to norepinephrine are potentiated. In order to verify if a complete inhibition of PGI2 production affects the vascular reactivity, it was assayed two cycloxygenase inhibitors (lysine acetylsalicylate and indomethacin) in rats. The two drugs significantly potentiated the blood pressure responses to norepinephrine, and completely inhibited PGI2-like substances production by arterial rings. The prostacyclin infusion (15 ng/kg/min, i.v.) completely reversed such potentiation, without any major modification in the basal blood pressure values. These results show that PGI2 production is responsible for vascular tone modulation and may partially explain the altered vascular reactivity in the atherosclerotic condition.

  3. Investigation of liver tissue and biochemical parameters of adult wistar rats treated with Arctium lappa L.

    Directory of Open Access Journals (Sweden)

    Fabrícia Souza Predes


    Full Text Available This study was carried out to evaluate the effects of Arctium lappa L. (burdock on the liver of adult male Wistar rats as measured by light microscopy and biochemical parameters. The rats received the extract in water bottles at doses of 10 or 20 g/L daily for 40 days. There were no significant changes in the plasma levels of albumin, aspartate transaminase (AST, alanine transaminase (ALT, gamma glutamyl transferase (GGT, total protein, total cholesterol, urea, uric acid, triacylglycerol, calcium, phosphorus, chlorine and direct bilirubin. The morphological analysis did not reveal histopathological alterations in liver tissue. Both biochemical and morphological data did not indicate A. lappa toxicity.A bardana (Arctium lappa L é uma planta trazida do Japão e aclimatada no Brasil, e é extensamente utilizada na medicina popular em todo mundo. Este estudo foi realizado para avaliar os possíveis efeitos da A. lappa no fígado e nos parâmetros bioquímicos plasmáticos em ratos Wistar adultos. Estes receberam a infusão de bardana nas doses de 10 ou 20 g de folhas secas /L de água, por 40 dias. Não houve alteração significativa nos níveis plasmáticos de albumina, aspartato transaminase (AST, alanina transaminase (ALT, gamma glutamil transferase (GGT, proteínas totais, colesterol total, uréia, ácido úrico, triglicérides, cálcio, fósforo, bilirrubina direta e cloro. A análise morfológica não revelou alterações histopatológicas no fígado. Os dados bioquímicos e morfológicos não indicaram a toxicidade da bardana.

  4. Structural changes of gut microbiota in a rat non-alcoholic fatty liver disease model treated with a Chinese herbal formula. (United States)

    Yin, Xiaochen; Peng, Jinghua; Zhao, Liping; Yu, Yunpeng; Zhang, Xu; Liu, Ping; Feng, Qin; Hu, Yiyang; Pang, Xiaoyan


    Accumulating evidence indicates that disruption of the gut microbiota by a high-fat diet (HFD) may play a pivotal role in the progression of metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). In this study, the structural changes of gut microbiota were analyzed in an HFD-induced NAFLD rat model during treatment with an ancient Chinese herbal formula (CHF) used in clinical practice -Qushi Huayu Fang. CHF treatment significantly reduced body weight, alleviated hepatic steatosis, and decreased the content of triglycerides and free fatty acids in the livers of the rats. Gut microbiota of treated and control rats were profiled with polymerase chain reaction-denaturing gradient gel electrophoresis and bar-coded pyrosequencing of the V3 region of 16S rRNA genes. Both analyses indicated that the CHF-treated group harbored significantly different gut microbiota from that of model rats. Partial least squares discriminant analysis and taxonomy-based analysis were further employed to identify key phylotypes responding to HFD and CHF treatment. Most notably, the genera Escherichia/Shigella, containing opportunistic pathogens, were significantly enriched in HFD-fed rats compared to controls fed normal chow (P<0.05) but they decreased to control levels after CHF treatment. Collinsella, a genus with short chain fatty acid producers, was significantly elevated in CHF-treated rats compared to HFD-fed rats (P<0.05). The results revealed that the bacterial profiles of HFD-induced rats could be modulated by the CHF. Elucidation of these differences in microbiota composition provided a basis for further understanding the pharmacological mechanism of the CHF.

  5. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available Glucocorticoid (GC induced osteoporosis (GIO is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1 In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2 In vitro study: In concentration from 10(-6 mol/L to 10(-7 mol/L, Sal B stimulated bone marrow stromal cell (MSC differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin m

  6. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis (United States)

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie


    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  7. Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin

    Directory of Open Access Journals (Sweden)

    Schaan B.D.


    Full Text Available Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP variability in rats (164.5 ± 1.7 g 7, 14, 30 and 120 days after streptozotocin (STZ injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN and root mean square of successive difference of RR intervals (RMSSD. MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1 - (MAPn] x density. The indices represent the maximum concentration of points (P1, the longitudinal axis (P2, and the transversal axis (P3 and MN represents P1 x P2 x P3 x 10-3. STZ induced increased urinary glucose in diabetic (D rats compared to controls (C. Seven days after STZ, diabetes reduced resting HR from 380.6 ± 12.9 to 319.2 ± 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 ± 1.67 to 19.87 ± 2.60 ms, did not change MAP, and reduced P1 from 61.0 ± 5.3 to 51.5 ± 1.8 arbitrary units (AU, P2 from 41.3 ± 0.3 to 29.0 ± 1.8 AU, and MN from 171.1 ± 30.2 to 77.2 ± 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r = -0.76, P = 0.03 as well as with the MN index (r = -0.83, P = 0.01. We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The

  8. Chiral metabolism of propafenone in rat hepatic microsomes treated with two inducers

    Institute of Scientific and Technical Information of China (English)

    Quan Zhou; Tong-Wei Yao; Su Zeng


    AIM: To study the influence of inducers of drug metabolism enzyme, β-naphthoflavone (BNF) and dexamethasone (DEX), on the stereoselective metabolism of propafenone in the rat hepatic microsomes. METHODS: Phase I metabolism of propafenone was studied using the microsomes induced by BNF and DEX and the non-induced microsome was used as the control. The enzymatic kinetics parameters of propafenone enantiomers were calculated by regress analysis of Eadie-Hofstee Plots.Propafenone enantiomer concentrations were assayed by a chiral HPLC. RESULTS: The metabolite of propafenone, N-desalkylpropafenone, was found after incubstion of propafenone with the rat hepatic microsomes induced by BNF and DEX. In these two groups, the stereoselectivity favoring R ( - ) isomer was observed in metabolism st Iow substrate concentrations of racemic propafenone, but lost the stereoselectivity st high substrate concentrations.However; in control group, no stereeselectivity was observed. The enzyme kinetic parameters were: ① Km.Control group: R( - ) 83 ± 6, S( + ) 94 ± 7; BNF group: R (-)105 ± 6, S( + )128 ± 14; DEX group: R( - ) 86± 11, S( + ) 118 ± 16; ② vmax. Control group: R( - ) 0.75 ± 0.16, S( + ) 0.72±0.07; BNF group: R( - )1.04± 0.15, S( + )1.07±14; DEX group: R( - ) 0.93 ± 0.06, S( + ) 1.04 ± 0.09; (③)Clint. Control group: R( - ) 8.9± 1.1, S( + ) 7.6±0.7; BNFgroup: R( - )9.9±0.9, S( + )8.3±0.7; DEX group: R( - )10.9± 0.8, S( + ) 8.9 ± 0.9. The enantiomeric differences in Km and Clint were both significant, but not in Vmax, in BNF and DEX group. Whereas enantiomeric differences in three parameters were all insignificant in control group.Furthermore, Km and Umax were both significantly less than those in BNF or DEX group. In the rat liver microsorne induced by DEX, nimodipine (NDP) decreased the stereoselectivity in propafenone metabolism at Iow substrate concentration. The inhibition of NDP on the metabolism of propafenone was stereo.selective with R

  9. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats

    Institute of Scientific and Technical Information of China (English)

    Mehmet Kanter; Omer Coskun; Mustafa Budancamanak


    AIM: To investigate the effects of Nigella sativa L (NS)and Urtica dioica L (UD) on lipid peroxidation, antioxidant enzyme systems and liver enzymes in CCl4-treated rats.METHODS: Fifty-six healthy male Wistar albino rats were used in this study. The rats were randomly allotted into one of the four experimental groups: A (CCl4-only treated), B (CCl4+UD treated), C (CCl4+NS treated) and D (CCl4+UD+NS treated), each containing 14 animals.All groups received CCl4 (0.8 mL/kg of body weight, sc,twice a week for 60 d). Tn addition, B, C and D groups also received daily J.p. injections of 0.2 mL/kg NS or/and 2 mL/kg UD oils for 60 d. Group A, on the other hand,received only 2 mL/kg normal saline solution for 60 d.Blood samples for the biochemical analysis were taken by cardiac puncture from randomly chosen-seven rats in each treatment group at beginning and on the 60th d of the experiment.RESULTS: The CCl4 treatment for 60 d increased thelipid peroxidation and liver enzymes,and also decreasedthe antioxidant enzyme levels. NS or UD treatment (aloneor combination) for 60 d decreased the elevated lipidperoxidation and liver enzyme levels and also increasedthe reduced antioxidant enzyme levels.The weight ofrats decreased in group A,and increased in groups B, Cand D.CONCLUSION: NS and UD decrease the lipid peroxidation and liver enzymes, and increase the antioxidant defense system activity in the CCl4-treated rats.

  10. Increased strontium uptake in trabecular bone of ovariectomized calcium-deficient rats treated with strontium ranelate or strontium chloride. (United States)

    Pemmer, Bernhard; Hofstaetter, Jochen G; Meirer, Florian; Smolek, Stephan; Wobrauschek, Peter; Simon, Rolf; Fuchs, Robyn K; Allen, Matthew R; Condon, Keith W; Reinwald, Susan; Phipps, Roger J; Burr, David B; Paschalis, Eleftherios P; Klaushofer, Klaus; Streli, Christina; Roschger, Paul


    Based on clinical trials showing the efficacy to reduce vertebral and non-vertebral fractures, strontium ranelate (SrR) has been approved in several countries for the treatment of postmenopausal osteoporosis. Hence, it is of special clinical interest to elucidate how the Sr uptake is influenced by dietary Ca deficiency as well as by the formula of Sr administration, SrR versus strontium chloride (SrCl(2)). Three-month-old ovariectomized rats were treated for 90 days with doses of 25 mg kg(-1) d(-1) and 150 mg kg(-1) d(-1) of SrR or SrCl(2) at low (0.1% Ca) or normal (1.19% Ca) Ca diet. Vertebral bone tissue was analysed by confocal synchrotron-radiation-induced micro X-ray fluorescence and by backscattered electron imaging. Principal component analysis and k-means clustering of the acquired elemental maps of Ca and Sr revealed that the newly formed bone exhibited the highest Sr fractions and that low Ca diet increased the Sr uptake by a factor of three to four. Furthermore, Sr uptake in bone of the SrCl(2)-treated animals was generally lower compared with SrR. The study clearly shows that inadequate nutritional calcium intake significantly increases uptake of Sr in serum as well as in trabecular bone matrix. This indicates that nutritional calcium intake as well as serum Ca levels are important regulators of any Sr treatment.

  11. Kinetics of radioiodine in the rats treated repeatedly with mercuric chloride

    Energy Technology Data Exchange (ETDEWEB)

    Grosicki, A.; Kossakowski, S. [National Veterinary Research Institute, Pulawy (Poland)


    Repeated administration of HgCl{sub 2} at doses of 0.5 and 1.0 mg/kg b.w. for 28 days decreased I-125 concentrations in the thyroid gland in a dose-related manner. In contrast, the carcass retention of I-125 increased, especially in the group treated with a smaller dose of mercury. Both doses of mercury markedly changed the distribution pattern of I-125 in the organs. However, the changes were transitory. (author). 15 refs, 2 figs, 1 tab.

  12. Effects of bupropion on the forced swim test and release of dopamine in the nucleus accumbens in ACTH-treated rats. (United States)

    Kitamura, Yoshihisa; Yagi, Takahiko; Kitagawa, Kouhei; Shinomiya, Kazuaki; Kawasaki, Hiromu; Asanuma, Masato; Gomita, Yutaka


    The dopamine reuptake inhibitor bupropion has clinically been proven to improve depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which bupropion acts in this model was explored specifically in relation to the site of action through the use of microinjections into the medial prefrontal cortex and nucleus accumbens. Bupropion significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by D2 and D3 receptor antagonists in normal rats. Furthermore, infusions of bupropion into the nucleus accumbens, but not medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Bupropion treatment plus repeated ACTH treatment significantly increased the extracellular dopamine concentration. These findings suggest the antidepressant-like effect of bupropion to be related to levels of dopamine in the rat nucleus accumbens.

  13. Aging and Oxidative Stress Decrease Pineal Elongation Factor 2: In Vivo Protective Effect of Melatonin in Young Rats Treated With Cumene Hydroperoxide. (United States)

    Muñoz, Mario F; Argüelles, Sandro; Cano, Mercedes; Marotta, Francesco; Ayala, Antonio


    We studied the alterations of Elongation Factor 2 (eEF2) in the pineal gland of aged rats as well as the possible protective role of exogenous melatonin on these changes in young rats treated with cumene hydroperoxide (CH), a compound that promotes lipid peroxidation and inhibits protein synthesis. The study was performed using male Wistar rats of 3 (control), 12, and 24 months and 3-month-old rats treated with CH, melatonin, and CH plus melatonin. We found that pineal eEF-2 is affected by aging and CH, these changes being prevented by exogenous melatonin in the case of CH-treated rats. The proteomic studies show that many other proteins are affected by aging and oxidative stress in the pineal gland. The results suggest that one of the possible mechanisms underlying pineal gland dysfunction during aging is the effect of lipid peroxidation on eEF-2, which is a key component of protein synthesis machinery. J. Cell. Biochem. 118: 182-190, 2017. © 2016 Wiley Periodicals, Inc.

  14. Training improves physical fitness and decreases CRP also in asthmatic conscripts. (United States)

    Juvonen, Raija; Bloigu, Aini; Peitso, Ari; Silvennoinen-Kassinen, Sylvi; Saikku, Pekka; Leinonen, Maija; Hassi, Juhani; Harju, Terttu


    To study the respiratory and physical health of young men, 224 asthmatic and 668 non-asthmatic military conscripts were recruited from the intake groups of July 2004 and January 2005 in Kajaani, Finland. Factors affecting respiratory health were elicited by a questionnaire at the beginning of the service, and results of high sensitive C-reactive protein (hsCRP) determination, peak expiratory flow (PEF), and 12-minute running test were collected at the beginning and the end of the service. Respiratory infections were diagnosed by a study physician. Upon entering military service, asthmatics had frequent exercise- and cold-related asthma symptoms (69.6% and 76.3%), and 48% of them had no medication for asthma. At the beginning, 25.8% of asthmatics and 19.1% of non-asthmatics had a poor result of less than 2,200 m (p = 0.05) in the 12-minute running test, and after 180 to 362 days of service, the corresponding percentages were 11.7% and 9.7% (p = 0.434). The levels of hsCRP, a marker of low-grade systemic inflammation, decreased significantly among both asthmatics, 1.5 (p = 0.001), and non-asthmatics, 1.6 mg/L (p < 0.001). Asthmatic men had 0.2 and non-asthmatics 0.1 respiratory infections per month (p < 0.001). In summary, asthmatic conscripts can enhance their physical fitness by training similarly to non-asthmatic ones. Their levels of hsCRP also decrease.

  15. Endothelial, renal and hepatic variables in wistar rats treated with Vancomycin

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    Full Text Available Vancomycin (VCM is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.

  16. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet

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    Alessandra Ferramosca


    Full Text Available In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group, a diet with 35% fat (HF group, or a high-fat diet supplemented with 2.5% krill oil (HF+KO group. The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism.

  17. [Mutagenicity of the urine of rats treated with benzidine dyes (author's transl)]. (United States)

    Tanaka, K


    Today industrial use of benzidine is restricted in many countries. However, little attention is paid to those substances which may decompose themselves in the body and release benzidine or benzidine-like substances. I investigated the mutagenicity of urinary ingredients of rats to which benzidine and three kinds of azo dyes were separately administered through the alimentary tract. The azo dyes were Direct Black EX(EX), Direct Green BK(BK), and Direct Bordeaux BK(BK), all having 4,4'-diazobiphenyl group in each structure. The mutagenicity of the urine extract with ether was tested on Salmonella typhimurium TA 98 and TA 100. Urinary metabolites of benzidine showed stronger mutagenicity than benzidine itself on both TA 98 and TA 100 in the presence of S9 mix. EX itself showed mutagenicity only on TA 98, whereas B and BK were nonmutagens. Nevertheless, the urine extract of each azo dye showed strong mutagenicity of the same pattern as benzidine. As a result it is suggested that benzidine might be released in the intestine of experimental animals after the administration of each azo dye. Mutagenic activity of urine sample is important and full of suggestions from the viewpoint of carcinogenicity of aromatic amines.

  18. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet. (United States)

    Ferramosca, Alessandra; Conte, Annalea; Zara, Vincenzo


    In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5% krill oil (HF+KO group). The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism.

  19. Behavioral changes and cholinesterase activity of rats acutely treated with propoxur. (United States)

    Thiesen, F V; Barros, H M; Tannhauser, M; Tannhauser, S L


    Early assessment of neurological and behavioral effects is extremely valuable for early identification of intoxications because preventive measures can be taken against more severe or chronic toxic consequences. The time course of the effects of an oral dose of the anticholinesterase agent propoxur (8.3 mg/kg) was determined on behaviors displayed in the open-field and during an active avoidance task by rats and on blood and brain cholinesterase activity. Maximum inhibition of blood cholinesterase was observed within 30 min after administration of propoxur. The half-life of enzyme-activity recovery was estimated to be 208.6 min. Peak brain cholinesterase inhibition was also detected between 5 and 30 min of the pesticide administration, but the half-life for enzyme activity recovery was much shorter, in the range of 85 min. Within this same time interval of the enzyme effects, diminished motor and exploratory activities and decreased performance of animals in the active avoidance task were observed. Likewise, behavioral normalization after propoxur followed a time frame similar to that of brain cholinesterase. These data indicate that behavioral changes that occur during intoxication with low oral doses of propoxur may be dissociated from signs characteristic of cholinergic over-stimulation but accompany brain cholinesterase activity inhibition.

  20. Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients

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    Chun-Hua Chi


    Conclusions: The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.

  1. The in vivo antioxidant effect of vitamin C on hemogram in Paraquat treated male rats (rattus norvegicus

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    Benjamin Nnamdi Okolonkwo


    Full Text Available Paraquat (PQ is one of the most used herbicide globally; applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on hemograms [hemoglobin (Hb, packed cell volume (PCV and total white blood cells count] of rats under these toxic insults. The animals grouped (A-D, comprising subgroups without vitamin C (A1, B1, C1, D1 and subgroups on vitamin C (A2, B2, C2, D2, received different sub-lethal doses of PQ administered intraperitoneally monthly to the animals over a period of three months. The Hb values obtained were significantly reduced (P≤0.05 at month 1 and (P≤0.001 at months 2 and 3. These changes became more pronounced with increased dose and time. Vitamin C treated subgroups (B2, C2 and D2 had better Hb values than those without it (B1, C1 and D1 but the values were still significantly low when compared to the control subgroups (A1 and A2. This same trend was observed in the PCV results obtained. The Control subgroups showed that vitamin C treated subgroup (A2 had a more improved hemogram values than subgroup on water only (A1, but they were all higher than that of the test subgroups. These PQ induced anaemia were ameliorated by the subsequent administration of vitamin C, and continuous treatment with vitamin C restored the health status of the animals so treated.

  2. Thioacetamide-induced acute liver toxicity in rats treated with Balanites roxburghii extracts

    Institute of Scientific and Technical Information of China (English)

    Mallikarjuna Rao Talluri; Rajananda Swamy Tadi; Ganga Rao Battu


    Objective: To evaluate the antioxidant and thioacetamide induced liver toxicity using extracts of aerial parts of Balanites roxburghii (B. roxburghii). Methods: The in-vitro antioxidant activity was estimated for different extracts on super-oxide, hydroxyl and 1,1-diphenyl-2-picrylhydrazyl free radicals and the hepatoprotective activity of the selected plant extracts was evaluated by using thioacetamide-induced liver intoxication in rats model. Results: There were no visible signs of toxicity, mortality and no behavioral changes were observed for the selected plant extracts (hydroalcoholic, ethyl acetate and hexane) at 2 000 mg/kg body weight. The plant extracts showed dose-dependent effectiveness in the inhibition of free radicals generation and hepatoprotective nature. The hydroalcoholic extract showed more scavenging activity as compared to other extracts with IC50 values of (332.50 ± 1.30) mg, (302.00 ± 1.50) mg and (230.40 ± 1.10) mg on superoxide, hy-droxyl and 1,1-diphenyl-2-picrylhydrazyl free radicals. Aerial parts of B. roxburghii at three dose levels such as 125 mg/kg, 250 mg/kg and 500 mg/kg showed dose dependent percentage protection as standard drugs and on enhancement activities of serum biomarker enzymes (aspartate aminotransferase, alanine transaminase, alkaline phos-phatase, total bilirubin and total protein) observed in thioacetamide-induced hepatotox-icity. The hydroalcoholic extract showed significant results at 500 mg/kg body weight as compared to other extracts (P Conclusions: It was observed that the B. roxburghii plant extracts are non-toxic and have capacity to restore the physiological changes caused by the hepatotoxic compounds.

  3. Hyperdopaminergic tone in HIV-1 protein treated rats and cocaine sensitization (United States)

    Ferris, Mark J.; Frederick-Duus, Danielle; Fadel, Jim; Mactutus, Charles F; Booze, Rosemarie M.


    In the United States, one-third of infected individuals contracted Human Immunodeficiency Virus-1 (HIV-1) via injecting drugs with contaminated needles or through risky behaviors associated with drug use. Research demonstrates concomitant administration of psychostimulants and HIV-1-proteins damage neurons to a greater extent than viral proteins or the drug alone. To model the onset of HIV-1-infection in relation to a history of drug use, the current research compared behavior and extracellular dopamine and metabolite levels following Tat1–86 infusions in animals with and without a history of cocaine (Coc) experience (10 mg/kg; i.p.; 1 injection/day × 9 days). Animals receiving a behaviorally sensitizing regimen of Coc demonstrated a decrease in extracellular dopamine concentration in the nucleus accumbens, consistent with evidence describing up-regulation of dopamine transporter uptake. Contrary to this effect, Tat1–86 microinfusion into the nucleus accumbens following the sensitizing regimen of Coc caused a significant increase in extracellular dopamine levels (nM) within 48 h with no difference in percent of baseline response to Coc. After 72 h, Tat + Coc treated animals demonstrated a blunted effect on potassium-stimulated extracellular dopamine release (percent of baseline) with a corresponding decrease in expression of behavioral sensitization to Coc challenge. A persistent decrease in extracellular dopamine metabolite levels was found across all time-points in Tat-treated animals, regardless of experience with Coc. The current study provides evidence for divergent neurochemical and behavioral outcomes following Tat-treatment; contingent upon experience with Coc. PMID:20796175

  4. Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats

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    Ellouz Meriem


    Full Text Available Abstract Background Olive oil's beneficial effects are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. In this study, we assess the effects of virgin olive oil and its fractions on 2,4-D- induced oxidative damage in the liver of rats. Methods Male Wistar rats were randomly divided into eight groups of ten each: (C a control group, (D group that received 2,4-D (5 mg/kg b.w., (D/EVOO group treated with 2,4-D plus extra virgin olive oil, (D/OOHF group that received 2,4-D plus hydrophilic fraction, (D/OOLF group treated with 2,4-D plus lipophilic fraction, (EVOO group that received only extra virgin olive oil, (OOHF group given hydrophilic fraction and (OOLF group treated with lipophilic fraction. These components were daily administered by gavage for 4 weeks. Results A significant liver damage was observed in rats treated with 2,4-D via increased serum levels of transaminases and alkaline phosphatase, hepatic lipid peroxidation and decreased hepatic antioxidant enzyme activities, namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The liver's fatty acid composition was also significantly modified with 2,4-D exposure. However, extra virgin olive oil and hydrophilic fraction intake during 2,4-D treatment induced a significant increase in the antioxidant enzyme activities and a decrease in the conjugated dienes (CD and thiobarbituric acid-reactive substances (TBARs levels in the liver. The lipophilic fraction supplemented to 2,4-D- treated rats did not show any improvement in the liver oxidative status while a marked improvement was detected in the hepatic fatty acid composition of rats supplemented with olive oil and the two fractions. Conclusion We concluded that the protective effect of olive oil against oxidative damage induced by 2,4-D is mainly related to the antioxidant potential of its hydrophilic fraction.

  5. Ethnic and migrant differences in the use of anti-asthmatic medication for children

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    Cantarero-Arévalo, Lourdes; Ersbøll, Annette Kjaer; Holstein, Bjørn E;


    Ethnic differences in the use of anti-asthmatic medication have been reported, with ethnic minorities being at a higher risk of suboptimal asthma control. As contextual socioeconomic characteristics may play a role, we analysed whether ethnic differences in the use of anti-asthmatic medication...... among children residing in the Capital Region of Denmark varied by place of residence....

  6. Molecular Mechanism of the Additive Effects of Leukotriene Modifier in Asthmatic Patients Receiving Steroid Therapy

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    Kazuto Matsunaga


    Conclusions: LM caused a greater improvement in pulmonary function and airway inflammation in asthmatics with AR. The RANTES-mediated pathway may be involved in the improvement of the airflow limitation and airway lability by LM additive therapy in asthmatics receiving steroid therapy.

  7. Correlation between signs of temporomandibular (TMD) and cervical spine (CSD) disorders in asthmatic children. (United States)

    Chaves, Thaís Cristina; Grossi, Débora Bevilaqua; de Oliveira, Anamaria Siriani; Bertolli, Fabiana; Holtz, Amanda; Costa, Dirceu


    Neck accessory respiratory muscles and mouth breathing suggest a direct relationship among asthma, Temporomandibular (TMD) and Cervical Spine (CSD) Disorders. This study was performed to evaluate and correlate TMD, CSD in asthmatic and non-asthmatic. Thirty asthmatic children (7.1 +/- 2.6 years old), 30 non-asthmatic predominantly mouth breathing children (Mouth Breathing Group - MBG) (8.80 +/- 1.61 years) and 30 non-asthmatic predominantly nasal breathing children (Nasal breathing Group - NBG) (9.00 +/- 1.64 years) participated in this study and they were submitted to clinical index to evaluate stomatognathic and cervical systems. Spearman correlation test and Chi-square were used. The level of significance was set at p temporomandibular joint (TMJ), TMJ sounds, pain during cervical extension and rotation, palpatory tenderness of sternocleidomastoids and paravertabrae muscles and a severe reduction in cervical range of motion were observed in AG. Both AG and MBG groups demonstrated palpatory tenderness of posterior TMJ, medial and lateral pterygoid, and trapezius muscles when compared to NBG. Results showed a positive correlation between the severity of TMD and CSD signs in asthmatic children (r = 0.48). No child was considered normal to CSD and cervical mobility. The possible shortening of neck accessory muscles of respiration and mouth breathing could explain the relationship observed between TMD, CSD signs in asthmatic children and emphasize the importance of the assessment of temporomandibular and cervical spine regions in asthmatic children.

  8. Inner and outer portions of colonic circular muscle: ultrastructural and immunohistochemical changes in rat chronically treated with otilonium bromide.

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    Chiara Traini

    Full Text Available Rat colonic circular muscle, main target of otilonium bromide (OB spasmolytic activity, is subdivided in an inner and outer portion. Since the inner one is particularly rich in organelles involved in calcium availability (caveolae, smooth endoplasmic reticulum, mitochondria, the expression of specific markers (Caveolin-1, eNOS, calreticulin, calsequestrin in comparison with the outer portion was investigated. The possible changes of these organelles and related markers, and of muscarinic receptors (Mr2 were then studied after OB chronic exposition. Rats were treated with 2-20 mg/kg/OB for 10 or 30 days. Proximal colon was processed by electron microscopy, immunohistochemistry, and western blot. In colon strips the stimulated contractility response to muscarinic agonist was investigated. The inner portion showed a higher expression of Caveolin-1 and Mr2, but not of eNOS, calreticulin and calsequestrin, compared to the outer portion. Chronic OB treatment caused similar ultrastructural and immunohistochemical changes in both portions. Organelles and some related markers were increased at 10 days; Mr2 expression and muscle contractility induced by methacholine was increased at 30 days. The present findings: 1 provide new information on the immunohistochemical properties of the inner portion of the circular layer that are in favour of a role it might play in colonic motility distinct from that of the outer portion; 2 demonstrate that chronically administered OB interferes with cell structures and molecules responsible for calcium handling and storage, and modifies cholinergic transmission. In conclusion, chronic OB administration in the colonic circular muscle layer directly interacts with the organelles and molecules calcium-related and with the Mr2.

  9. FT-Raman spectroscopic study of skin wound healing in diabetic rats treated with Cenostigma macrophyllum Tul

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    Coelho, Nayana Pinheiro Machado de Freitas; Martins, Marcelino, E-mail: [Faculdade Diferencial Integral (FACID), Teresina, PI (Brazil); Costa, Charlytton Luis Sena da; Maia Filho, Antonio Luis [Universidade Estadual do Piaui (UESPI), Teresina, PI (Brazil); Raniero, Leandro; Martin, Airton Abrahao; Arisawa, Emilia Angela Loschiavo [Universidade do Vale do Paraiba (UNIVAP), Sao Jose dos Campos, SP (Brazil). Instituto de Pesquisa e Desenvolvimento


    Introduction: patients with diabetes mellitus exhibit a delay in the lesion repair process. The active components of Cenostigma macrophyllum may represent a viable alternative to facilitate the recovery of these lesions. The aim of this study was to evaluate the effects of emulsion oil-water Cenostigma macrophyllum in the repair process of lesions in rats with induced diabetes. Methods: 63 male rats (Wistar, 200-250 g body weight, 30-40 days old) were distributed into the following groups: control (C), diabetic (D) and diabetic treated with Cenostigma macrophyllum (P), subdivided based on the experimental times, days 7, 14 and 28, with 21 animals per main group. Diabetes mellitus (DM) was induced by administration of streptozotocin (50 mg/kg via penile vein and 12-h fasting) and confirmed at day 21 (glycemic index > 240 mg/dL). In the animals of group P, 0.5 ml of the oil-water emulsion obtained from the plant seed was used. The samples were removed and hemisectioned, and one portion was used for the quantitative histological analysis of collagen using Masson's trichrome staining, while another portion was analyzed by FT-Raman spectroscopy. Results: A higher percentage area of the volume of collagen fibers was observed for the experimental time Day 14 in group P compared with group D (p < 0.001). Regarding the ratio of areas of the amides I (1700-1600 cm{sup -1}) and III (1245-1345 cm{sup -1}), the groups D and P show the opposite behavior. Conclusion: Cenostigma macrophyllum accelerated the repair process in skin of diabetic ratsfor14 days. (author)

  10. The Protective Effects of Carrot Seed Extract on Spermatogenesis and Cauda Epididymal Sperm Reserves in Gentamicin Treated Rats

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    Mohammad Nouri


    Full Text Available Objective: Carrot (Daucus carota L. is known to possess antifertility properties in female.However, according to Iranian traditional medicine, it can increase the potency in men. Theaim of this study was to investigate the influence of carrot seed extract (CSE on spermatogenesis,number and motility of sperms in cauda epididyme in male rats.Materials and Methods: Forty adult male rats were randomly divided into 5 groups: controlgroup, groups receiving low- and high doses of CSE, animals that received high-dose of CSEwith gentamicin, and a gentamicin only group. After 4 weeks treatment, fasting serum sampleswere obtained for the sex hormone analysis. Under anesthesia, testis, cauda epididymidesand sperm ducts were dissected and sperm count, motility and cauda epididymis spermreserves (CESR were determined. Histopathological changes of testis were also studied toassess spermatogenesis. Data analysis was performed using one-way ANOVA followed byTukey HSD tests.Results: Administration of CSE caused a significant increase in CESR compared with thecontrol (28.2 ± 1.8 vs. 45.1 ± 2.0, ×106. The extract could also protect testis from the gentamicin-induced necrosis. The CSE administration caused about 3.5-times increase in theLH levels even in spite of receiving 5 mg/kg/day gentamicin with no significant effect on FSHlevels. The testosterone concentrations in the group received 400 mg/kg CSE were 30% and83% higher than its levels in the control and the gentamicin treated group, respectively.Conclusion: CSE can overcome reproductive toxicity of gentamicin and induces spermatogenesisprobably mainly through the elevation of testosterone levels.

  11. Association of School Social Networks' Influence and Mass Media Factors with Cigarette Smoking among Asthmatic Students (United States)

    Kanamori, Mariano; Beck, Kenneth H.; Carter-Pokras, Olivia


    Background: Around 10% of adolescent students under 18 years have current asthma. Asthmatic adolescents smoke as much or more than non-asthmatic adolescents. We explored the association between exposure to mass media and social networks' influence with asthmatic student smoking, and variations of these exposures by sex. Methods: This study…

  12. Educating Asthmatic Children in European Ambulatory Pediatrics: Facts and Insights. (United States)

    Robberecht, Marie Noëlle; Beghin, Laurent; Deschildre, Antoine; Hue, Valérie; Reali, Laura; Plevnik-Vodušek, Vesna; Moretto, Marilena; Agustsson, Sigurlaug; Tockert, Emile; Jäger-Roman, Elke; Deplanque, Dominique; Najaf-Zadeh, Abolfazl; Martinot, Alain


    The aim of this study was to assess the role of European ambulatory pediatricians in caring for asthmatic children, especially in terms of their therapeutic education. We developed a survey that was observational, declarative, retrospective and anonymous in nature. 436 ambulatory pediatricians in Belgium, France, Germany, Italy, Luxembourg and Slovenia were asked to participate in the survey providing information on three children over 6 years old suffering from persistent asthma, who had been followed for at least 6 months. We considered the pediatricians' profile, and their role in the therapeutic education of children. 277 pediatricians (64%) responded: 81% were primary care pediatricians; 46% participated in networks; 4% had specific training in Therapeutic Patient Education; 69% followed more than 5 asthmatic children per month, and over long periods (7 ± 4 years). The profiles of 684 children were assessed. Answers diverged concerning the provision of a Personalized Action Plan (60-88%), training the child to measure and interpret his Peak Expiratory Flow (31-99%), and the prescription of pulmonary function tests during the follow-up programme of consultations (62-97%). Answers converged on pediatricians' perception of their role in teaching children about their condition and its treatment (99%), about inhalation techniques (96%), and in improving the children's ability to take preventive measures when faced with risk situations (97%). This study highlights the role of European pediatricians in caring for asthmatic children, and their lack of training in Therapeutic Patient Education. Programmes and tools are required in order to train ambulatory pediatricians in Therapeutic Patient Education, and such resources should be integrated into primary health care, and harmonized at the European level.

  13. Attenuated response to repeated daily ozone exposures in asthmatic subjects

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    Gong, H. Jr.; Linn, W.S. [Rancho Low Amigos Medical Center, Downey, CA (United States); McManus, M.S. [Univ. of California, Los Angeles, CA (United States)


    The development of attenuated response ({open_quotes}tolerance{close_quotes}) to daily ozone (O{sub 3}) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures in unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O{sub 3} in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O{sub 3} exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 {degrees}C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O{sub 3} exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O{sub 3} day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O{sub 3} exposure and remained somewhat elevated after all subsequent O{sub 3} exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O{sub 3} predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O{sub 3} exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics. 27 refs., 3 figs., 4 tabs.

  14. Opposing effects of low molecular weight heparins on the release of inflammatory cytokines from peripheral blood mononuclear cells of asthmatics.

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    Madhur D Shastri

    Full Text Available T-cell-mediated inflammatory cytokines, such as interleukin (IL-4, IL-5, IL-13 and tumor necrosis factor-alpha (TNF-α, play an important role in the initiation and progression of inflammatory airways diseases. Low-molecular-weight heparins (LMWHs, widely used anticoagulants, possess anti-inflammatory properties making them potential treatment options for inflammatory diseases, including asthma. In the current study, we investigated the modulating effects of two LMWHs (enoxaparin and dalteparin on the release of cytokines from stimulated peripheral blood mononuclear cells (PBMCs of asthmatic subjects to identify the specific components responsible for the effects.PBMCs from asthmatic subjects (consist of ~75% of T-cells were isolated from blood taken from ten asthmatic subjects. The PBMCs were pre-treated in the presence or absence of different concentrations of LMWHs, and were then stimulated by phytohaemagglutinin for the release of IL-4, IL-5, IL-13 and TNF-α. LMWHs were completely or selectively desulfated and their anticoagulant effect, as well as the ability to modulate cytokine release, was determined. LMWHs were chromatographically fractionated and each fraction was tested for molecular weight determination along with an assessment of anticoagulant potency and effect on cytokine release.Enoxaparin inhibited cytokine release by more than 48%, whereas dalteparin increased their release by more than 25%. The observed anti-inflammatory effects of enoxaparin were independent of their anticoagulant activities. Smaller fractions, in particular dp4 (four saccharide units, were responsible for the inhibitory effect of enoxaparin. Whereas, the larger fractions, in particular dp22 (twenty two saccharide units, were associated with the stimulatory effect of dalteparin.Enoxaparin and dalteparin demonstrated opposing effects on inflammatory markers. These observed effects could be due to the presence of structurally different components in the two

  15. Lymphocytes sensitivity to Fas stimulation in healthy and asthmatic children.

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    Katarzyna Gomułka


    Full Text Available The T cell hypothesis of asthma is based on the concept that the disease is driven and maintained by the persistence of a specialized subset of chronically activated T memory cells sensitized against an array of allergenic, occupational or viral antigens. Overreaction of CD4+ T cells in the peripheral blood and airway tissues is an invariant feature of asthma; therefore a potent mechanism for augmenting the number of activated T cells in this disease would be the resistance to the normally programmed pathway for cell death. The aim of the study was to evaluate the presence of apoptotic markers on peripheral blood lymphocytes from healthy and asthmatic children before and after stimulation with antiCD95 antibodies. The blood was collected from 21 children with atopic asthma suffering from allergic rhinitis because of house dust mite and/or grass pollen allergens and 8 healthy children matched for their age and sex. Blood was mixed with purified monoclonal antibody antiCD95 (Beckman Coulter, incubated for 24 hours and than stained with Annexin V andPI (Becton Dickinson. Prepared suspensions were analyzed with Cytomics FC 500 (Beckman Coulter flow cytometer. Annexin V(+/PI(- cells were characterized as early apoptotic, Annexin V(+/PI(+ as late apoptotic and Annexin V(-/PI(+ as dead. In unstimulated sample from asthmatic children 21.09+/-11.20% cells were characterized as Annexin V positive/PI negative. After stimulation with antiCD95 Annexin V positive/PI negative cells constituted 18.72+/-9.42% of cells, p=0.1. In unstimulated sample from healthy children 11.69+/-6.70% cells were characterized as Annexin V positive/PI negative. In the sample stimulated with antiCD95 16.54+/-2.98% of cells were Annexin V positive/PI negative, p=0.02. There were no differences between results of late apoptotic and necrotic lymphocytes from healthy and asthmatic children. Performed research indicates that lymphocytes from asthmatic children are resistant to Fas

  16. Diabetes mellitus and insulin in an aspirin sensitive asthmatic. (United States)

    Caplin, I


    The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms

  17. Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30. (United States)

    Sofic, E; Salkovic-Petrisic, M; Tahirovic, I; Sapcanin, A; Mandel, S; Youdim, M; Riederer, P


    Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.

  18. Changes in Iron Metabolism and Oxidative Status in STZ-Induced Diabetic Rats Treated with Bis(maltolato Oxovanadium (IV as an Antidiabetic Agent

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    Cristina Sánchez-González


    Full Text Available The role of vanadium as a micronutrient and hypoglycaemic agent has yet to be fully clarified. The present study was undertaken to investigate changes in the metabolism of iron and in antioxidant defences of diabetic STZ rats following treatment with vanadium. Four groups were examined: control; diabetic; diabetic treated with 1 mgV/day; and Diabetic treated with 3 mgV/day. The vanadium was supplied in drinking water as bis(maltolato oxovanadium (IV (BMOV. The experiment had a duration of five weeks. Iron was measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, and femur. Superoxide dismutase, catalase, NAD(PH: quinone-oxidoreductase-1 (NQO1 activity, and protein carbonyl group levels in the liver were determined. In the diabetic rats, higher levels of Fe absorbed, Fe content in kidney, muscle, and femur, and NQO1 activity were recorded, together with decreased catalase activity, in comparison with the control rats. In the rats treated with 3 mgV/day, there was a significant decrease in fasting glycaemia, Fe content in the liver, spleen, and heart, catalase activity, and levels of protein carbonyl groups in comparison with the diabetic group. In conclusion BMOV was a dose-dependent hypoglycaemic agent. Treatment with 3 mgV/day provoked increased Fe deposits in the tissues, which promoted a protein oxidative damage in the liver.

  19. Coenzyme Q10 remarkably improves the bio-energetic function of rat liver mitochondria treated with statins. (United States)

    Mohammadi-Bardbori, Afshin; Najibi, Asma; Amirzadegan, Najmeh; Gharibi, Raziyeh; Dashti, Ayat; Omidi, Mahmoud; Saeedi, Arastoo; Ghafarian-Bahreman, Ali; Niknahad, Hossein


    CoQ10 shares a biosynthetic pathway with cholesterol therefore it can be a potential target of the widely available lipid-lowering agents such as statins. Statins are the most widely prescribed cholesterol-lowering drugs with the ability to inhibit HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase. Preclinical and clinical safety data have shown that statins do not cause serious adverse effects in humans. However, their long-term administration is associated with a variety of myopatic complaints. The aim of this study was to investigate whether CoQ10 supplementation of animals under high fat diet (HFD) treated with statins is able to bypass the mitochondrial metabolic defects or not? Animals were divided into 7 groups and fed with either regular (RD) or HFD during experiments. The first group considered as regular control and fed with a RD. Groups 2-7 including HFD control, CoQ10 (10mg/kg), simvastatin (30mg/kg), atorvastatin (30mg/kg), simvastatin+CoQ10 or atorvastatin+CoQ10 treated orally for 30 days and fed with HFD. At the end of treatments, the animals were killed and blood samples were collected for biochemical examinations. The rat liver mitochondria were isolated and several mitochondrial indices including succinate dehydrogenase activity (SDA), ATP levels, mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPP) were determined. We found that triglyceride (Tg), cholesterol (Chol) and low-density lipoprotein (LDL) were augmented with HFD compared to RD and treatment with statins remarkably lowered the Tg, Chol and LDL levels. Mitochondrial parameters including, SDA, ATP levels, MMP and MPP were reduced with statin treatment and improved by co-administration with CoQ10.

  20. Rats

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    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.

  1. Influence of doxycycline on serum IgE,protein expression of phosphorylated p38 mitogen-activated protein kinase and MMP-9 in lung tissue of asthmatic rats%多西环素对哮喘大鼠血清 IgE、肺组织磷酸化 p38及基质金属蛋白酶9的影响

    Institute of Scientific and Technical Information of China (English)

    王亮; 李亚妹; 杨红申; 孟静; 杨超; 侯宏伟; 李香兰


    Objective To observe the influence of doxycycline on airway inflammation and remodeling in asthmatic rats.Methods Thirty-three SD male rats were randomly divided into three groups (1 1 rats in each group):normal control group,asthma group and doxycycline intervention group.After inhalation of doxycycline,the change of matrix metalloproteinase 9(MMP-9),phosphorylation of p38 of lung tissue and serum IgE were investigated.Results MMP-9 in lung tissue was significantly higher in asthma group and intervention group than in control group.The level of serum IgE was significantly higher in asthma group than in intervention group.The expression of phosphorylated p38 in asthma group was significantly higher than that of intervention group.Conclusion Doxycycline can alleviate inflammation of airway through reducing inflammatory cells and improve airway remodeling through downregulating the expression of MMP-9.In addition,doxycycline can ameliorate airway inflammation,airway remodeling and airway hyper-responsiveness by influencing serum IgE and the protein expression of phosphorylated p38 mitogen-activated protein kinase in lung tissue.%目的:建立大鼠哮喘模型,探讨多西环素对哮喘大鼠气道炎症和气道重塑的影响。方法取健康雄性大鼠33只,随机分为3组:正常对照组、哮喘模型组、多西环素干预组。应用给予哮喘大鼠雾化吸入多西环素,观察干预后大鼠肺组织中基质金属蛋白酶9(MMP-9)及磷酸化的 p38、血清中 IgE 水平的变化。结果与正常对照组相比,哮喘模型组、多西环素干预组 MMP-9的水平显著升高(P <0.05)。哮喘模型组血清 IgE、肺组织磷酸化的 p38磷酸化的 p38/β-actin 水平明显高于多西环素干预组(P <0.01)。结论多西环素可减少肺泡灌洗液中炎性细胞的数量,从而减轻气道炎症;多西环素可下调 MMP-9的水平,从而减缓气道重塑。通过对血清 IgE 和肺组织磷酸化的 p38的影响,

  2. ETB receptor activation as a mechanism of modulation of inflammatory pain and neurogenic inflammation in the temporomandibular joint of capsaicin-treated rats

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    Thiago E. V. Lemos


    Full Text Available Background: Endothelin (ET, a peptide best known for its vascular effects, also evokes pain and hyperalgesia, independently of its vascular actions. Data suggest that ET can have nociceptive effects, acting directly on receptors expressed in sensory neurons. As such, the aim this study was to investigate the direct effect of ET on hyperalgesia and edema, induced by carrageenan, on the temporomandibular joint (TMJ of capsaicin-treated rats. Methods: Capsaicin was administered by subcutaneous injection to newborn, male Wistar rats. Inflammation was induced 60 days later by a single intra-articular injection of carrageenan into the left TMJ (control group received sterile saline. Inflammatory parameters, such as plasma extravasation, leukocyte influx and mechanical allodynia (measured as the head-withdrawal force threshold were evaluated 4 h after edematogenic stimulus. ET-1 and ET-3, and the ET-B receptor (ETBR antagonist were administered 3 min before edematogenic stimulus. ET and transient receptor potential vanilloid (TRPV1 mRNA expression was assessed by reverse-transcription polymerase chain reaction (RT-PCR. Edema formation was evaluated by measurement of the extravascular accumulation of injected 125I-human serum albumin into the TMJ soft tissues of anesthetized rats. Results: Capsaicin neonatal treatment significantly reduced edema formation, leukocyte influx and mechanical allodynia in TMJ, when compared to the control group, while the ETBR antagonist increased plasma extravasation and hyperalgesia in the capsaicin-treated group. ET-1 treatment reduced both plasma extravasation and myeloperoxidase activity. Capsular mRNA for ET-1 was significantly augmented in the TMJ of capsaicin-treated rats, when compared to controls. Conclusions: Our results suggest, for the first time, that ET-1, via ETBR activation, reduces plasma extravasation, leukocyte influx and inflammatory pain in the temporomandibular joint of capsaicin-treated rats. [J Exp

  3. Proteomic Analysis Reveals the Deregulation of Inflammation-Related Proteins in Acupuncture-Treated Rats with Asthma Onset

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    Yu-Dong Xu


    Full Text Available Although the beneficial effects of acupuncture in asthma treatment have been well documented, little is known regarding the biological basis of this treatment. Changes in the lung proteome of acupuncture-treated rats with asthma onset were comparatively analyzed using a two-dimensional gel electrophoresis (2DE and mass-spectrometry- (MS- based proteomic approach. Acupuncture on specific acupuncture points appeared to improve respiratory function and reduce the total number of leukocytes and eosinophils in bronchoalveolar lavage fluid in OVA-induced asthma onset. Image analysis of 2DE gels revealed 32 differentially expressed acupuncture-specific protein spots in asthma onset; 30 of which were successfully identified as 28 unique proteins using LC-MS/MS. Bioinformatic analyses indicated that these altered proteins are most likely involved in inflammation-related biological functions, and the functional associations of these proteins result in an inflammation signaling pathway. Acupuncture regulates the pathway at different levels by regulating several key nodal proteins, including downregulating of proinflammatory proteins (e.g., S100A8, RAGE, and S100A11 and upregulating of anti-inflammatory proteins (e.g., CC10, ANXA5, and sRAGE. These deregulated inflammation-related proteins may mediate, at least in part, the antiasthmatic effect of acupuncture. Further functional investigation of these acupuncture-specific effector proteins could identify new drug candidates for the prophylaxis and treatment of asthma.

  4. Bypassing hazard of housekeeping genes: Their evaluation in rat granule neurons treated with cerebrospinal fluid of Multiple Sclerosis subjects

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    Deepali eMathur


    Full Text Available Gene expression studies employing real-time PCR has become an intrinsic part of biomedical research. Appropriate normalization of target gene transcript(s based on stably expressed housekeeping genes is crucial in individual experimental conditions to obtain accurate results. In multiple sclerosis (MS, several gene expression studies have been undertaken, however, the suitability of housekeeping genes to express stably in this disease is not yet explored. Recent research suggests that their expression level may vary under different experimental conditions. Hence it is indispensible to evaluate their expression stability to accurately normalize target gene transcripts. The present study aims to evaluate the expression stability of seven housekeeping genes in rat granule neurons treated with cerebrospinal fluid of MS patients. The selected reference genes were quantified by real time PCR and their expression stability was assessed using GeNorm and NormFinder algorithms. Both methods reported transferrin receptor (Tfrc and microglobulin beta-2 (B2m the most stable genes whereas beta-actin (ActB and glyceraldehyde-3-phosphate-dehydrogenase (Gapdh the most fluctuated ones. Altogether our data demonstrate the significance of pre-validation of housekeeping genes for accurate normalization and indicates Tfrc and B2m as best endogenous controls in MS. ActB and Gapdh are not recommended in gene expression studies related to the current one.

  5. Smith-Lemli-Opitz syndrome produced in rats with AY 9944 treated by intravenous injection of lipoprotein cholesterol. (United States)

    Chambers, C M; McLean, M P; Ness, G C


    A limitation to treating Smith-Lemli-Opitz infants by giving dietary cholesterol is their impaired ability to absorb cholesterol due to a deficiency of bile acids. Since intravenously administered lipoprotein cholesterol should not require bile acids for uptake into tissues, we tested the effects of this form of cholesterol on tissue cholesterol and 7-dehydrocholesterol levels in an animal model of SLO, created by feeding rats 0.02% AY 9944. Intravenous administration of 15 mg of bovine cholesterol supertrate twice daily increased serum cholesterol levels from 11 to over 250 mg/dl. This treatment increased liver cholesterol levels from 309 to over 900 micrograms/g and lowered hepatic 7-dehydrocholesterol levels from 1546 to 909 micrograms/g. A combination of iv cholesterol and 2% dietary cholesterol was most effective as it raised hepatic cholesterol levels to 1950 micrograms/g, which is 50% above normal. 7-Dehydrocholesterol levels were decreased to 760 micrograms/g. Similar responses were seen for heart, lung, kidney, and testes. Brain sterol levels were not significantly affected. AY 9944 caused a modest increase in hepatic HMG-CoA reductase activity. Administration of dietary cholesterol together with iv cholesterol lowered hepatic HMG-CoA reductase activity to barely detectable levels. The data indicate that the combination of iv and dietary cholesterol was most effective in raising cholesterol levels, lowering 7-dehydrocholesterol levels, and inhibiting de novo cholesterol biosynthesis.

  6. Use of Propolis Hydroalcoholic Extract to Treat Colitis Experimentally Induced in Rats by 2,4,6-Trinitrobenzenesulfonic Acid

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    Cely Cristina Martins Gonçalves


    Full Text Available This study focused on the therapeutic effect of a propolis SLNC 106PI extract on experimental colitis. Wistar adult rats received 0.8 mL rectal dose of one of the following solutions: saline (group S, 20 mg TNBS in 50% ethanol (group TNBS, 20 mg TNBS in 50% ethanol and propolis extract in saline (group TNBS-P, propolis extract in saline (group SP, and 20 mg TNBS in 50% ethanol and 50 mg/kg mesalazine (group TNBS-M. The animals were euthanized 7 or 14 days after the colitis induction. Samples of the distal colon were harvested for the analysis of myeloperoxidase (MPO enzyme activity and for morphometric analysis in paraffin-embedded histological sections with hematoxylin-eosin or histochemical staining. The animals treated with TNBS exhibited the typical clinical signs of colitis. Increased MPO activity confirmed the presence of inflammation. TNBS induced the development of megacolon, ulceration, transmural inflammatory infiltrate, and thickened bowel walls. Treatment with propolis moderately reduced the inflammatory response, decreased the number of cysts and abscesses, inhibited epithelial proliferation, and increased the number of goblet cells. The anti-inflammatory activity of the propolis SLNC 106 extract was confirmed by the reductions in both the inflammatory infiltrate and the number of cysts and abscesses in the colon mucosa.

  7. Elevation of serum pancreatic amylase and distortion of pancreatic cyto-architecture in type 1 diabetes mellitus rats treated with Ocimum gratissimum

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    Okon Uduak Akpan


    Full Text Available Background: Diabetes mellitus has been shown to cause severe impairment in exocrine pancreatic function and cyto-architecture. Ocimum grattissimum has been reported to lower blood glucose levels in experimental diabetic animals. This study, therefore, aims to investigate if treatment with O. grattissimum can alleviate these pancreatic complications of diabetes mellitus. The phytoconstituents and median lethal dose of the plant extract were determined. Materials and Methods: Eighteen rats were divided into three groups of six rats each. Diabetes mellitus was induced by single intraperitoneal injection of 65 mg/kg streptozotocin. Group 1 was the control and were given normal feed only; Group 2 was of diabetic untreated rats, while Group 3 was O. grattissimum-treated diabetic rats at a dose of 1,500 mg/kg. After 28 days, blood was collected by cardiac puncture of the anaesthetised animals and the serum was obtained for analysis of serum pancreatic amylase. Permanent preparations using routine biopsy method were employed for histological preparations. Results: Results showed that the level of pancreatic serum amylase in the test groups (diabetic and diabetic-treated were significantly higher (P < 0.05 than the control group, while the diabetic-treated group was significantly lower than the diabetic group. Atrophic acinar tissue without β-cells was noted in the diabetic and diabetic-treated groups. Patchy areas of necrosis, oedematous interstitium, haemorrhagic and necrotic acinar cells were present in diabetic-treated groups. Conclusion: Direct association exists between the hyperglycaemic state caused by diabetes mellitus and the elevation of the serum pancreatic amylase and distortion of pancreatic cyto-achitecture. O. grattissimum-treatment reduced serum pancreatic amylase level to near normal and limit the extent of structural damage.

  8. Gene transfer of a β2-adrenergic receptor kinase inhibitor up-regulates the level of β2-adrenergic receptor and cAMP in the asthmatic murine lung

    Institute of Scientific and Technical Information of China (English)

    Mao Huang; Yan Wu; Xin Yao; Wuangjian Cha; Kaisheng Yin


    Objective: To investigate the effects of gene transfer of a β-adrenergic receptor(β-AR) kinase inhibitor(β ARKct)on pulmonary β2-adrenergic receptor and cAMP following β2-AR agonist treatment in asthmatic mice, and to analyze the relationship between the routes of gene delivery and the changes of β2AR and cAMP. Methods: BALB/c mice were sensitized and challenged by ovalbumin to establish the asthmatic model treated with βAR agonist ( salbutamol injected intramuscularly). The plasmid with the expression of βARKct was constructed and βARKct gene transfer was performed through intravenous injection or intratracheal instillation in asthmatic mice.The gene expression was measured with Western blot analysis, and the changes of pulmonary β-AR and cAMP evaluated by Radioimmunoassay. Results: The expression of tranfered βARKct gene was detectable in lungs and it was expressed more in the lungs of the mice receiving intratracheally plasmid than those receiving intravenously. The levels of βAR and cAMP were upregulated after using plasmid-βARKct to the asthmatic mice treated with β AR agonist. Conclusion: Our results indicated that there were down-regulation of βAR and cAMP in asthmatic mice treated with βAR agonist. Gene transfer of βARKct could inhibit the extent of the down-regulation of βAR and cAMP. The route of gene delivery could also affect the degree of up-regulation of βAR and cAMP. Gene transfer βARKct may provide a novel approach to the therapeutic strategy for asthma.

  9. Identification of anti-asthmatic compounds in Pericarpium citri reticulatae and evaluation of their synergistic effects

    Institute of Scientific and Technical Information of China (English)

    Qian SHI; Ze LIU; Yang YANG; Peng GENG; Yuan-yuan ZHU; Qi ZHANG; Fang BAI; Gang BAI


    Aim: To investigate the anti-asthmatic mechanisms of the traditional Chinese medicine Pericarpium citri reticulatae (PCR).Methods: The alkaloid section (AS) of PCR was extracted using an ion exchange resin, separated, and purified into different fractions by semi-preparative HPLC. These fractions were screened for beta2-adrenergic receptor (β2AR) agonistic activity using rat β2AR-transfected CHO-CRE-EGFP cells. AS and its isolated components were characterized by ultra-performance liquid chromatography/quadrupole time-of-flight MS (UPLC/Q-Tof MS) and were evaluated for their spasmolytic and antitussive activities both in vitro and in vivo in a guinea pig model.Results: We demonstrated that the AS component responsible for activating β2AR signaling was synephrine. Both AS and synephrine showed significant spasmolytic effects on acetylcholine chloride (ACh)-induced contractions in isolated guinea pig trachea, and they protected against histamine-induced experimental asthma by prolonging the latent period. We further identified stachydrine as the antitussive component that could significantly reduce citric acid-induced coughing. The combination of these two bioactive compounds had a more potent spasmolytic activity in comparison with the single use of synephrine or stachydrine.Conclusion: We conclude that synephrine and stachydrine are the key components of AS that mediate asthma relief due to their synergism when used in combination.

  10. Lung function and short-term outcome in young asthmatic children

    DEFF Research Database (Denmark)

    Klug, B; Bisgaard, H


    technique. Rint, sRaw, Xrs,5 and Rrs,5 were suggestive of impaired lung function in 44%, 14%, 11% and 7.5% of the children, respectively, with a predominance of children aged 2-3 yrs. Sixty-five per cent were treated with inhaled steroids, and 35% were treated only with beta2-agonists as needed; lung......The aims of this study were to investigate lung function in 2-5-yr-old stable asthmatic children consecutively referred from general practitioners and to analyse the outcome on the basis of their requirement for antiasthmatic treatment and symptoms after 1.6-4.5 yrs. Lung function was measured...... in 110 children with a mean+/-SD age of 3.8+/-1.0 yrs using the interruptor technique (resistance assessed using the interruptor technique (Rint)), whole body plethysmography (specific airway resistance (sRaw) and respiratory resistance (Rrs,5)and reactance at 5 Hz (Xrs,5) using the impulse oscillation...

  11. Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

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    S.G. Suke


    Full Text Available The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg, an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05 and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05, catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05 and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05 showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05, and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05 and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05 response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05 suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05 suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

  12. Gas chromatography-mass spectrometry profile of urinary organic acids of Wistar rats orally treated with ozonized unsaturated triglycerides and ozonized sunflower oil. (United States)

    Jardines, Daniel; Correa, Teresa; Ledea, Oscar; Zamora, Zullyt; Rosado, Aristides; Molerio, Jesús


    The main products in the ozonolysis of unsaturated triglycerides or vegetable oils are peroxides, aldehydes, Criegee ozonides and carboxylic acids. Some of these compounds are present in different concentrations in the biological fluids. The aim of this work is to study, using gas chromatography-mass spectrometry (GC-MS), the organic acid excretion in urine of rats orally treated with ozonized sunflower oil (OSO), ozonized triolein or ozonized trilinolein. Oral administration of OSO to Wistar rats has produced changes in the urinary content of dicarboxylic organic acids. Among others heptanedioic (pimelic acid) and nonanedioic acids (azelaic acid) were the major increased dicarboxylic acids found. The urinary dicarboxylic acid profiles of rats which received ozonized triolein only showed an increase in heptanedioic and nonanedioic acids. However, when ozonized trilinolein is applied, the profile is similar to that obtained when OSO is administered. A biochemical mechanism is proposed to explain the formation of dicarboxylic acids from ozonated unsaturated triglycerides.

  13. Hepatotoxicity or hepatoprotection? Pattern recognition for the paradoxical effect of the Chinese herb Rheum palmatum L. in treating rat liver injury.

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    Jia-bo Wang

    Full Text Available The hepatotoxicity of some Chinese herbs has been a cause for concern in recent years. However, some herbs, such as rhubarb, have been documented as having both therapeutic and toxic effects on the liver, leading to the complex problem of distinguishing the benefits from the risks of using this herb. To comparatively analyze the dose-response relationship between rhubarb and hepatic health, we administrated total rhubarb extract (RE to normal and carbon tetrachloride (CCl(4-treated rats for 12 weeks at 4 dosage levels (2.00, 5.40, 14.69 and 40.00 g·kg(-1, measured as the quantity of crude material, followed by biochemical and histopathological tests of the rats' livers. A composite pattern was extracted by factor analysis, using all the biochemical indices as variables, into a visual representation of two mathematically obtained factors, which could be interpreted as the fibrosis factor and the cellular injury factor, according to the values of the variable loadings. The curative effect of administering the two lowest dosages of RE to CCl(4-treated rats was mainly expressed as a decrease in the extent of cellular injury. The hepatoprotective mechanism of RE might be related to its antioxidant effect, the antagonism of the free radical damage to hepatocytes caused by CCl(4. By contrast, the RE-induced liver damage was mainly expressed as a significant increase in the amount of fibrosis in both normal rats at all dosage levels and CCl(4-treated rats at the two highest dosage levels. Therefore, the hepatotoxic potential of RE could be attributable to the liver cell fibrosis induced by high doses of the herb. This study illustrates the bidirectional potential of rhubarb and demonstrates the feasibility of using factor analysis to study the dose-response relationships between herbal medicines and hepatotoxicity or the healing effects of these herbs by extracting the underlying interrelationships among a number of functional bio-indices in a holistic

  14. The Anatomic Pathology Evaluation of Liver with Diethylinitrosamine Treated via Intraperitoneal Injection Singly and Peros for 90 Days Carcinogenicity Study in F344 Rats

    Institute of Scientific and Technical Information of China (English)

    LI Shan-shan; KANEKO Toyozo; XING Rui-chang; WANG Xiu-wen; LI Bo; ZHANG Lin; LI Bao-wen; LANG Shu-hui; YANG Yan-wei; ZHANG Di; ZHANG Yang; NARAMA Isao; KAWAYI Zeshow


    Objective:To establish the integrity experiment method of short(medium)-term carcinogenicity test pursuant to GLP, make into relative SOP and improve the safeguard in the center.Methods:Diethylinitrosamine(DEN) is known as carcinogenic agent,whose target organ is liver. Using the two-stage carcinogenesis test method, DEN was treated to F344 rats via intraperitoneal injection singly(200 mg/kg), and peros administrated for 90 days(10 ppm). The liver in any group rat will be examined by light microscopy.Results:In pathologic examination, no liver cell tumor was shown in the livers of the rats that were singly treated with a carcinogenic chemical-DEN.Foci of cellular alteration were observed in the livers of these rats. The proliferation lesions of liver from slight to seveity(foci of cellular alteration-hepatocelluar adenoma-hepatocellular carcinoma)were observed in the livers of the rats which exposed peros to a low dose of DEN for 90 days after initiation by a single intraperitoneal injection. The incidence of hepatocelluar tumor was 35% in male animal,which was not shown in the liver of female rat.Conclusion:For current results, it may be possible that low-dose DEN acts as a promotor of hepatocelluar tumor if it was exposed in a population for a long time. It is considered that male hormone has a synergistic effect on hepatocelluar tumor development of DEN. This two-stage carcinogenesis test might be a new model for the study of drug induced and promoted carcinogenesis,which could be used to evaluate the carcinogenesis of chemical compound fast.

  15. Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children

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    Barnes Peter J


    Full Text Available Abstract Background The role of leukotriene (LT B4, a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB4 in exhaled breath condensate (EBC has hampered its quantitative assessment in this biological fluid. We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO was measured as an independent marker of airway inflammation. Methods Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB4 concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB4 values were expressed as the total amount (in pg of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups. Results Compared with healthy children [87.5 (82.5–102.5 pg, median and interquartile range], exhaled LTB4 was increased in steroid-naïve atopic asthmatic [255.1 (175.0–314.7 pg, p 4 than steroid-naïve asthmatics [125.0 (25.0–245.0 pg vs 255.1 (175.0–314.7 pg, p Conclusion In contrast to exhaled NO concentrations, exhaled LTB4 values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB4 in asthmatic children. LC/MS/MS analysis of exhaled LTB4 might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children.

  16. Effect of Nifedipine and S-Adenosylmethionine in the liver of rats treated with CCl[sub 4] and ethanol for one month

    Energy Technology Data Exchange (ETDEWEB)

    Cutrin, C.; Menino, J.M.; Otero, X.; Miguez, J.; Perez-becerra, E.; Barrio, E. (Univ. of Santiago de Compostela, Galicia (Spain))


    An experimental model of toxic liver injury in rats was employed to assay the effect of Nifedipine (a calcium antagonist blocker) and S-Adenosylmethionine. An important decrease in both perivenular fibrosis and cirrhosis was found. Furthermore, a significant decrease in lactic acid levels was found in the group of animals treated with pharmacologic therapy, although no correlation was seen between lactic acid levels and the different degrees of perivenular fibrosis. No significant variations in ALT and AST enzymes were observed between both groups, as opposed to a significant decrease in LDH enzyme in the Nifedipine+S-Adenosylmethionine group. The results indicate an improvement in the histologic picture of the liver in rats treated by means of pharmacological association, without any change in inflammatory infiltrate and with a slight decrease in necrosis, indicating an action mechanism via creeping fibrosis.

  17. Changes in blood sugar levels of rats experimentally infected withTrypanosoma brucei and treated with imidocarb dipropionate and diminazene aceturate

    Institute of Scientific and Technical Information of China (English)

    Nwoha Rosemary Ijeoma Ogechi; Omamegbe Joseph Omalathebu


    Objective:To determine the effect ofTrypanosoma brucei (T. brucei) on blood sugar level of infected rats. Methods: The experiment was done with 42 albino rats grouped into 3 groups of 14 members each. Group A was uninfected (control group), Group B was infected withT. brucei and treated with diminazene aceturate, and Group C was infected withT. brucei and treated with imidocarb dipropionate. Blood samples were collected from the media canthus of the experimental rats on Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 for the assessment of change in blood sugar levels. The blood sugar levels were determined with a glucometer (Accu-chek active serialNo.GN:10023338). Results: By 4 to 5 days post infection, there was a significant increase (P 0.05) was observed in the groups when compared with the control group till Day 12 of the experiment. Conclusions:T. brucei caused a significant increase in blood sugar of infected rats.

  18. Effect of bicuculline and angiotensin II fragment 3-7 on learning and memory processes in rats chronically treated with ethanol. (United States)

    Kuziemka-Leska, M; Car, H; Wiśniewski, K


    The aim of this study was to determine the possible influence of bicuculline, the antagonist of GABA-A receptor on behavioral activity (recall, acquisition of conditioned reflexes) of angiotension II fragment 3-7 (A II 3-7) in rats chronically treated with ethanol. Long term (9 weeks) ethanol intoxication profoundly impaired learning and memory processes in all testes used. The GABA-A receptor antagonist bicuculline (0.5 mg/kg ip) did not influence exploratory and motor activity in the control rats, but we observed tendency (without significance) to decrease the locomotor activity, in the alcohol-intoxicated groups of animals, when the drug was injected together with A II 3-7 (2 microgram icv). Bicuculline did not influence retrieval process in passive avoidance recall in both investigated groups, and when the drug was given together with AII 3-7 significantly enhanced its action in the control group and in rats chronically treated with ethanol. Bicuculline significantly improved acquisition in the active avoidance test in the control and alcohol-intoxicated groups. Bicuculline injected together with A II 3-7 significantly decreased its action in the control group. Coadministration of bicuculline with A II 3-7 did not significantly change the activity of A II 3-7 in the acquisition of active avoidance test in the alcohol-intoxicated groups of rats.

  19. Percutaneous Absorption of Salicylic Acid after Administration of Trolamine Salicylate Cream in Rats with Transcutol® and Eucalyptus Oil Pre-Treated Skin

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    Paniz Sajjadi


    Full Text Available Purpose: This study was conducted to assess the effect of skin pre-treatment with Transcutol® and eucalyptus oil on systemic absorption of topical trolamine salicylate in rat. Methods: Pharmacokinetic parameters of salicylic acid following administration of trolamine salicylate on rat skin pre-treated with either Transcutol® or eucalyptus oil were determined using both non-compartmental and non-linear mixed effect modeling approaches and compared with those of control group. Results: Median (% of interquartile range/median of salicylic acid AUC0-8hr (ng/mL/hr values in Transcutol® or eucalyptus oil treated rats were 2522(139% and 58976(141%, respectively as compared to the 3023(327% of the control group. Skin pre-treatment with eucalyptus oil could significantly decrease extravascular volume of distribution (V/F and elimination rate constant (k of salicylic acid. Conclusion: Unlike Transcutol®, eucalyptus oil lead to enhanced transdermal absorption of trolamine salicylate through rat skin.

  20. A Novel Cyclic PTH(1-17) analog with bone anabolic activity and efficacy sufficient to treat established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Morko, Jukka; Peng, ZhiQi; Vääräniemi, Jukka;

    osteopenia was confirmed by peripheral quantitative computed tomography (pQCT). Treatment was started at 7 weeks after the operations and continued for 6 weeks. The osteopenic rats were treated subcutaneously, once a day with ZP2307 at doses of 2.0, 6.0, 20.0, 60.0 and 200.0 µg/kg/d, and with PTH(1-34) used...

  1. Microbubble-mediated ultrasound promotes accumulation of bone marrow mesenchymal stem cell to the prostate for treating chronic bacterial prostatitis in rats



    Chronic bacterial prostatitis (CBP) is an intractable disease. Although bone marrow mesenchymal stem cells (BMMSCs) are able to regulate inflammation in CBP, the effect of microbubble-mediated ultrasound- induced accumulation of BMMSCs on CBP remains unclear. To address this gap, a model of CBP was established in SD rats, which were then treated with BMMSCs alone (BMMSC group), BMMSCs with ultrasound (ultrasound group), BMMSCs with microbubble-mediated ultrasound (MMUS group) and compared wit...

  2. Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese. (United States)

    Andrade, Vanda; Mateus, M Luísa; Batoréu, M Camila; Aschner, Michael; dos Santos, A P Marreilha


    Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60mg/L), Mn (10mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p<0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p<0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p<0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture.

  3. Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur. (United States)

    Padilla, S; Marshall, R S; Hunter, D L; Lowit, A


    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.

  4. HRCT findings of asthmatic children under maintenance therapy

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    Hong, Hyun Sook; Park, Jai Soung; Goo, Dong Erk; Lee, Hae Kyung; Kwon, Kui Hyang; Choi, Deuk Lin; Pyun, Bok Yang [Soonchunhyang University Hospital, Seoul (Korea, Republic of)


    The purpose of this study was to evaluate the HRCT findings of bronchial asthma during maintenance bronchodilator therapy and to determine whether there were irreversible bronchial changes occurred in pediatric patients with this condition. HRCT findings of the lung in 21 asthmatic children (14 boys and 7 girls aged between 3.5 and 13.8 (mean: 7.7) years) who were receiving maintenance bronchodilator therapy were retrospectively studied. At the time of CT examination, 16 were receiving nonsteroid bronchodilator therapy only, and five were receiving both bronchodilator and steroid therapy. Thirteen patients were defined as allergic and eight were nonallergic. The clinical severity of chronic asthma was graded as severe in seven cases, and moderate in 14. The duration of the disease ranged from 4 months to 6 years (mean 3.2 years). HRCT was performed in 19 cases for evaluation of the atelectasis, hyperinflation, and prominent bronchovascular bundles seen on plain radiographs, and in two cases for evaluation following acute exacerbation. A CT W-2000 scanner (Hitachi Medical Co. Tokyo, Japan) was used during the end inspiratory phase, and in addition, ten patients were scanned during the expiratory phase. Scans were reviewed for evidence of bronchial thickening, bronchiectasis, emphysema, abnormal density, mucus plugs, and other morphological abnormalities. The presence of bronchial wall thickening or air trapping was evaluated according to the duration, severity and type of asthma. Among the 21 patients, 7 (33.3%) had normal HRCT findings, while in 14 (66.7%), bronchial wall thickening was demonstrated. Eleven of the 14 patients with bronchial wall thickening(78.6%) also had air trapping. No patient was suffering from bronchiectasis or emphysema. There were no statistically significant correlations between the presence of bronchial wall thickening or air trapping and the duration of the disease, its severity, or type of asthma. There was, however, a statistically

  5. Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats

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    Casalotti Stefano O


    Full Text Available Abstract Background Pseudoephedrine is a drug commonly prescribed as a nasal decongestant and bronchodilator and is also freely available in cold remedies and medications. The structural and pharmacological similarity of pseudoephedrine to amphetamine has led to evaluation of its psychomotor stimulant properties within the central nervous system. Previous investigations have shown that the acute responses to pseudoephedrine were similar to those of amphetamine and other psychostimulants. Results This study examined the effect of chronic administration of pseudoephedrine in rat nucleus accumbens and striatum and identified three further similarities to amphetamine. (i Chronic exposure to pseudoephedrine reduced the c-Fos response to acute pseudoephedrine treatment suggesting that pseudoephedrine induced tolerance in the animals. (ii In animals chronically treated with amphetamine or pseudoephedrine the acute c-Fos response to pseudoephedrine and amphetamine was reduced respectively as compared to naïve animals indicating cross-tolerance for the two drugs. (iiiThe known involvement of the dopamine system in the response to amphetamine and pseudoephedrine was further confirmed in this study by demonstrating that pseudoephedrine similarly to amphetamine, but with lower potency, inhibited [3H]dopamine uptake in synaptosomal preparations. Conclusion This work has demonstrated further similarities of the effect of pseudoephedrine to those of amphetamine in brain areas known to be associated with drug addiction. The most significant result presented here is the cross tolerance effect of amphetamine and psudoephedrine. This suggests that both drugs induce similar mechanisms of action in the brain. Further studies are required to establish whether despite its considerable lower potency, pseudoephedrine could pose health and addiction risks in humans similar to that of known psychostimulants.

  6. Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats

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    Ton So


    Full Text Available Abstract Background The metabolic syndrome (MetS is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR. With the onset of IR, the expression of lipoprotein lipase (LPL, a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA, the bioactive constituent of licorice roots (Glycyrrhiza glabra inhibits 11β-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS. Results In this study, daily oral administration of 50 mg/kg of GA for one week led to significant increase in LPL expression in the quadriceps femoris (p p > 0.05 of the GA-treated rats compared to the control. Decrease in adipocyte size (p > 0.05 in both the visceral and subcutaneous adipose tissue depots accompanies such selective induction of LPL expression. Consistent improvement in serum lipid parameters was also observed, with decrease in serum free fatty acid, triacylglycerol, total cholesterol and LDL-cholesterol but elevated HDL-cholesterol (p > 0.05. Histological analysis using tissue lipid staining with Oil Red O showed significant decrease in lipid deposition in the abdominal muscle and quadriceps femoris (p p > 0.05. Conclusion Results from this study may imply that GA could counteract the development of visceral obesity and improve dyslipidaemia via selective induction of tissue LPL expression and a positive shift in serum lipid parameters respectively, and retard the development of IR associated with tissue steatosis.

  7. Effect of tocopherol on biochemical blood parameters in pleuritis-induced rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. (United States)

    Całkosiński, Ireneusz; Rosińczuk-Tonderys, Joanna; Bronowicka-Szydełko, Agnieszka; Dzierzba, Katarzyna; Bazan, Justyna; Dobrzyński, Maciej; Majda, Jacek; Gamian, Andrzej


    The aim of this study was to evaluate the effect of tocopherol on pleuritis-induced rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were treated with a single TCDD dose of 5 μg/kg body weight (b.w.) and then for 3 weeks they were daily supplemented with tocopherol at a dose of 30 mg/kg b.w. The inflammation was initiated by intrapleural injection of a single dose of 1% carrageenin solution in a volume of 0.15 ml. Changes in biochemical blood parameters were measured three times at the 24th, 72nd and 120th hour of pleuritis and the blood was collected from 20 animals of each group of rats (group with the control inflammation; group treated with TCDD and with control inflammation; group treated with TCDD, supplemented with tocopherol and with the inflammation). The following biochemical parameters were measured: tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, IL-4, IL-6, procollagen, telopeptide, fibrinogen, cholesterol, urea, creatinine, aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT). Daily supplementation of tocopherol caused significant changes in the level of TNF, IL-1, IL-4, IL-6, urea, creatinine, AspAT and AlAT. According to the results of these studies, we suggest that tocopherol supplementation in high doses could act as a protective treatment to improve liver metabolism.

  8. Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ

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    Shu-Wu Xie


    Full Text Available Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three β-defensins (Defb2, Defb18 and Defb39, which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy.

  9. Neuroprotective Effect of Gui Zhi (Ramulus Cinnamomi on Ma Huang- (Herb Ephedra- Induced Toxicity in Rats Treated with a Ma Huang-Gui Zhi Herb Pair

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    Fang-hao Zheng


    Full Text Available Herb Ephedra (Ma Huang in Chinese and Ramulus Cinnamomi (Gui Zhi in Chinese are traditional Chinese herbs, often used together to treat asthma, nose and lung congestion, and fever with anhidrosis. Due to the adverse effects of ephedrine, clinical use of Ma Huang is restricted. However, Gui Zhi extract has been reported to decrease spontaneous activity in rats and exert anti-inflammatory and neuroprotective effects. The present study explored the possible inhibitory effect of Gui Zhi on Ma Huang-induced neurotoxicity in rats when the two herbs were used in combination. All Ma Huang and Ma Huang-Gui Zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (n=6 rats/group were administered Ma Huang or the Ma Huang-Gui Zhi herb pair extracts for 7 days (ephedrine = 48 mg/kg, and locomotor activity was measured. After 7 days, oxidative damage in the prefrontal cortex was measured. Gui Zhi decreased hyperactivity and sensitization produced by repeated Ma Huang administration and attenuated oxidative stress induced by Ma Huang. The results of this study demonstrate the neuroprotective potential of Gui Zhi in Ma Huang-induced hyperactivity and oxidative damage in the prefrontal cortex of rats when used in combination.

  10. Neuroprotective effect of gui zhi (ramulus cinnamomi) on ma huang- (herb ephedra-) induced toxicity in rats treated with a ma huang-gui zhi herb pair. (United States)

    Zheng, Fang-Hao; Wei, Ping; Huo, Hui-Ling; Xing, Xue-Feng; Chen, Fei-Long; Tan, Xiao-Mei; Luo, Jia-Bo


    Herb Ephedra (Ma Huang in Chinese) and Ramulus Cinnamomi (Gui Zhi in Chinese) are traditional Chinese herbs, often used together to treat asthma, nose and lung congestion, and fever with anhidrosis. Due to the adverse effects of ephedrine, clinical use of Ma Huang is restricted. However, Gui Zhi extract has been reported to decrease spontaneous activity in rats and exert anti-inflammatory and neuroprotective effects. The present study explored the possible inhibitory effect of Gui Zhi on Ma Huang-induced neurotoxicity in rats when the two herbs were used in combination. All Ma Huang and Ma Huang-Gui Zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (n = 6 rats/group) were administered Ma Huang or the Ma Huang-Gui Zhi herb pair extracts for 7 days (ephedrine = 48 mg/kg), and locomotor activity was measured. After 7 days, oxidative damage in the prefrontal cortex was measured. Gui Zhi decreased hyperactivity and sensitization produced by repeated Ma Huang administration and attenuated oxidative stress induced by Ma Huang. The results of this study demonstrate the neuroprotective potential of Gui Zhi in Ma Huang-induced hyperactivity and oxidative damage in the prefrontal cortex of rats when used in combination.

  11. Curcumin as a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats.

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    Guo-Xin Hu

    Full Text Available BACKGROUND: 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1 activates glucocorticoid locally in liver and fat tissues to aggravate metabolic syndrome. 11β-HSD1 selective inhibitor can be used to treat metabolic syndrome. Curcumin and its derivatives as selective inhibitors of 11β-HSD1 have not been reported. METHODOLOGY: Curcumin and its 12 derivatives were tested for their potencies of inhibitory effects on human and rat 11β-HSD1 with selectivity against 11β-HSD2. 200 mg/kg curcumin was gavaged to adult male Sprague-Dawley rats with high-fat-diet-induced metabolic syndrome for 2 months. RESULTS AND CONCLUSIONS: Curcumin exhibited inhibitory potency against human and rat 11β-HSD1 in intact cells with IC50 values of 2.29 and 5.79 µM, respectively, with selectivity against 11β-HSD2 (IC50, 14.56 and 11.92 µM. Curcumin was a competitive inhibitor of human and rat 11β-HSD1. Curcumin reduced serum glucose, cholesterol, triglyceride, low density lipoprotein levels in high-fat-diet-induced obese rats. Four curcumin derivatives had much higher potencies for Inhibition of 11β-HSD1. One of them is (1E,4E-1,5-bis(thiophen-2-yl penta-1,4-dien-3-one (compound 6, which had IC50 values of 93 and 184 nM for human and rat 11β-HSD1, respectively. Compound 6 did not inhibit human and rat kidney 11β-HSD2 at 100 µM. In conclusion, curcumin is effective for the treatment of metabolic syndrome and four novel curcumin derivatives had high potencies for inhibition of human 11β-HSD1 with selectivity against 11β-HSD2.

  12. Enhancement of protein kinase C activity and chemiluminescence intensity in mitochondria isolated from the kidney cortex of rats treated with cephaloridine. (United States)

    Kohda, Yuka; Gemba, Munekazu


    The development of nephrotoxicity induced by cephaloridine (CER) has been reported to be due to reactive oxygen species (ROS). Protein kinase C (PKC) has been suggested to modulate the generation of ROS. We investigated the possible participation of ROS generation assessed by chemiluminescence (CL) and PKC activity in rat kidney cortical mitochondria in the development of CER-induced nephrotoxicity. We first evaluated the magnitude of the nephrotoxic damage caused by CER in rats. The plasma parameters and ultrastructural morphology changes were increased markedly 24hr after the treatment of rats with CER. We demonstrated that the treatment of rats with CER clearly evoked not only enhancement of Cypridina luciferin analog (CLA)-dependent CL intensity, but also the activation of PKC in mitochondria isolated from the kidney cortex of rats 1.5 and 3.5 hr after injection of the drug. These changes were detected in advance of those observed in plasma and by electron microscopy. The increase in CLA-dependent CL intensity detected in the kidney cortical mitochondria 1.5 and 3.5 hr after injection of CER was inhibited completely by the addition of superoxide dismutase, suggesting the generation of superoxide anion in these mitochondria during the early stages of CER-induced nephrotoxicity. These results suggest that the activation of PKC and the enhancement of superoxide anion generation in kidney cortical mitochondria precede the increases in plasma parameters and the electron micrographic changes indicative of renal dysfunction in rats treated with CER. Additionally, they suggest a possible relationship between PKC activation in mitochondria and free radical-induced CER nephrotoxicity in rats.

  13. Inhaled beclomethasone in pregnant asthmatic women--a systematic review. (United States)

    de Aguiar, M M; da Silva, H J; Rizzo, J Â; Leite, D F B; Silva Lima, M E P L; Sarinho, E S C


    The aim of this study was to systematically review the safety and efficacy of inhaled beclomethasone for asthma treatment in pregnant women. We performed a systematic review in Medline, LILACS and SciELO electronic databases in December 2012. A total of 3433 articles were found by using the keywords asthma, pregnancy and beclomethasone. Among these, 1666 were from Medline, via PubMed, and 1767 were from LILACS and SciELO. Nine of these articles were selected. Only one paper suggested an increased foetal risk for congenital malformations, and one other for offspring endocrine and metabolic disturbances. Data are mostly reassuring, supporting the use of glucocorticoid inhalants during pregnancy, and we found no evidence of inferiority in relation to efficacy and safety of beclomethasone compared to other drugs used in pregnant asthmatic women.

  14. Kounis syndrome secondary to amoxicillin use in an asthmatic patient. (United States)

    Viana-Tejedor, Ana; Espinosa, M Ángeles; Cuesta, J; Núñez, A; Bueno, H; Fernández-Avilés, F


    A sixty-four year old man with a past history of hypercholesterolemia, asthma, food allergy, epilepsy and myocardial infarction was admitted to the emergency department because of a generalized erythema, nausea, vomiting, and chest pain after taking an oral dose of amoxicillin. Electrocardiography showed ST segment elevation in anterior leads. After coronary angiography, type 2 variant of Kounis syndrome was diagnosed. We present the first case of oral amoxicillin induced Kounis syndrome in an asthmatic patient with severe anaphylactic shock. The present report also shows that atopic people expressing an amplified mast cell degranulation may have more serious hemodynamic decompensation during hypersensitivity reactions. Case selective mast cell surface membrane stabilization should be considered a potential therapeutic strategy for people with food induced allergy, for atopic patients and for patients who have already experienced a first Kounis syndrome.

  15. Bronchodilatory effect of Portulaca oleracea in airways of asthmatic patients. (United States)

    Malek, F; Boskabady, M H; Borushaki, M T; Tohidi, M


    Therapeutic effects of Portulaca oleracea for respiratory diseases are indicated in ancient Iranian medical books. The relaxant effect of this plant have also been observed on smooth muscle tissue in previous studies. Therefore, in the present study, the bronchodilatory effect of the boiled extract of Portulaca oleracea in the airway of asthmatic patients was examined. The relaxant effect of the orally administered 0.25 ml/kg of 5% boiled extract in comparison with 3 mg/kg oral theophylline and 200 microg inhaled salbutamol was studied by measuring forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MEF(25-75)), and specific airway conductance (sGaw). The FEV1, PEF, MEF(25-75), and sGaw were measured before, administration and repeated 15, 30, 60, 90, and 120 min after administration of the oral extract and theopylline. For inhaled salbutamol measurements were performed 5, 15, 30, and 60 min post-inhalation. Results showed that the boiled extract of Portulaca oleracea caused significant increases in all measured pulmonary function tests (PFTs), (P < 0.05 to P < 0.01). There was no significant difference between the maximum increase in measured PFTs due to the boiled extract and theophylline. However, maximum increase in PEF and MEF(25-75) due to the boiled extract were significantly lower than those of salbutamol (P < 0.05 for both cases). The onset of brochodilatory effect of extract was similar to that of theophylline beginning 60 min, but the effect of extract decline after 120 min after administration. In conclusion, the results of the present study showed that Portulaca oleracea has a relatively potent but transient bronchodilatory effect on asthmatic airways.

  16. Comparison of morning and afternoon exercise training for asthmatic children

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    C.S. Silva


    Full Text Available Fitness improvement was used to compare morning with afternoon exercise periods for asthmatic children. Children with persistent moderate asthma (according to GINA criteria, 8 to 11 years old, were divided into 3 groups: morning training group (N = 23, afternoon training group (N = 23, and non-training group (N = 23. The program was based on twice a week 90-min sessions for 4 months. We measured the 9-min running distance, resting heart rate and abdominal muscle strength (sit-up number before and after the training. All children took budesonide, 400 µg/day, and an on demand inhaled ß-agonist. The distance covered in 9 min increased (mean ± SEM from 1344 ± 30 m by 248 ± 30 m for the morning group, from 1327 ± 30 m by 162 ± 20 m for the afternoon group, and from 1310 ± 20 m by 2 ± 20 m for the control group (P 0.05 for morning with afternoon comparison. The reduction of resting heart rate from 83 ± 1, 85 ± 2 and 86 ± 1 bpm was 5.1 ± 0.8 bpm in the morning group, 4.4 ± 0.8 bpm in the afternoon group, and -0.2 ± 0.7 bpm in the control group (P > 0.05 for morning with afternoon comparison and P 0.05 for morning with afternoon comparison and P < 0.05 versus control. No statistically significant differences were detected between the morning and afternoon groups in terms of physical training of asthmatic children.

  17. iTRAQ-Based Proteomics Analysis of Serum Proteins in Wistar Rats Treated with Sodium Fluoride: Insight into the Potential Mechanism and Candidate Biomarkers of Fluorosis (United States)

    Wei, Yan; Zeng, Beibei; Zhang, Hua; Chen, Cheng; Wu, Yanli; Wang, Nanlan; Wu, Yanqiu; Shen, Liming


    Fluorosis induced by exposure to high level fluoride is quite widespread in the world. The manifestations of fluorosis include dental mottling, bone damage, and impaired malfunction of soft tissues. However, the molecular mechanism of fluorosis has not been clarified until now. To explore the underlying mechanisms of fluorosis and screen out serum biomarkers, we carried out a quantitative proteomics study to identify differentially expressed serum proteins in Wistar rats treated with sodium fluoride (NaF) by using a proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ). We fed Wistar rats drinking water that had 50, 150, and 250 mg/L of dissolved NaF for 24 weeks. For the experimental duration, each rat was given an examination of the lower incisors to check for the condition of dental fluorosis (DF). By the end of the treatment, fluoride ion concentration in serum and lower incisors were detected. The results showed that NaF treatment can induce rat fluorosis. By iTRAQ analysis, a total of 37 differentially expressed serum proteins were identified between NaF-treated and control rats. These proteins were further analyzed by bioinformatics, out of which two proteins were validated by enzyme-linked immunoadsorbent assays (ELISA). The major proteins were involved in complement and coagulation cascade, inflammatory response, complement activation, defense response, and wound response, suggesting that inflammation and immune reactions may play a key role in fluorosis pathogenesis. These proteins may contribute to the understanding of the mechanism of fluoride toxicity, and may serve as potential biomarkers for fluorosis. PMID:27690006

  18. Effects of Gum acacia aqueous extract on the histology of the intestine and enzymes of both the intestine and the pancreas of albino rats treated with Meloxicam

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    Ahmed M.A Abd El-Mawla


    Full Text Available Background: Non-steroidal anti-inflammatory drugs (NSAIDs cause gastrointestinal damage both in the upper and lower gastrointestinal tract, in addition to their undesirable side effects on the pancreas. Meloxicam like all NSAIDs has damaging effects on the gastrointestinal tract including perforations, ulcers and bleeding. Objective: The present work describes the effects of Gum acacia aqueous extract on the histology of intestine and enzymes of both intestine and Pancreas of albino rats treated with Meloxicam. Materials and Methods: This study was performed on four groups of equally weighed male rats, each group included ten animals; the first group was received a diet containing 0.2 mg/kg bw meloxicam per day; the second was given 1gm Gum acacia per day in its diet; the third was given meloxicam followed by gum in the same doses per day; while the fourth group (control rats was placed on a normal diet and water. All rats were received their diet for a period of 21 days. Results: A considerable protective effect of Gum acacia aqueous extract on the histology of intestine of albino rats treated with meloxicam was recorded. In addition, the study displayed a significant increase (P < 0.001 in the intestinal enzymes; lipase, amylase, alkaline phosphatase (ALP and lactate dehydrogenase (LDH in the 1 st and 3 rd groups animals while these enzymes were significantly decreased (P < 0.001 in the 2 nd group when compared with the 4 th control group. Conclusion: This study concluded that Gum acacia provides a protection and defense against the harmful effects of meloxicam therapy used as one of the novel anti-Cox-1 and Cox-2 NSAIDs.

  19. IFN-γ regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes. (United States)

    Singh, Deepali; Kumar, Vinod; Singh, Chetna


    Maneb (MB) and paraquat (PQ) provoke oxidative stress-mediated cell damage. Role of xanthine oxidase (XO) in oxidative stress and its association with nitric oxide (NO)/NO synthase (NOS) have been widely reported. While inducible NOS (iNOS) is implicated in MB+PQ-induced toxicity in rat polymorphonuclear leukocytes (PMNs), role of XO and its alliance with iNOS have not yet been established. The study investigated the role of XO in MB+PQ-induced oxidative stress in rat PMNs and its regulation by iNOS and inflammatory cytokines. MB+PQ-augmented reactive oxygen species (ROS), superoxide, nitro-tyrosine, lipid peroxidation (LPO), and nitrite levels along with the catalytic activity of iNOS, superoxide dismutase (SOD), and XO. XO inhibitor, allopurinol (AP), alleviated MB+PQ-induced changes except nitrite content and iNOS activity. Conversely, an iNOS inhibitor, aminoguanidine, mitigated MB+PQ-induced LPO, nitrite, iNOS, and nitro-tyrosine levels; however, no change was observed in ROS, SOD, and XO. Nuclear factor-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), tumor necrosis factor-alpha (TNF-α) inhibitor, pentoxyfylline, and an anti-inflammatory agent, dexamethasone, attenuated MB+PQ-induced increase in XO, superoxide, and ROS with parallel reduction in the expression of interferon-gamma (IFN-γ), TNF-α, and interleukin-1β (IL-1β) in rat PMNs. Exogenous IFN-γ, TNF-α, and IL-1β enhanced superoxide, ROS, and XO in the PMNs of control and MB+PQ-treated rats; however, IFN- γ was found to be the most potent inducer. Moreover, AP ameliorated cytokine-induced free radical generation and restored XO activity towards normalcy. The results thus demonstrate that XO mediates oxidative stress in MB+PQ-treated rat PMNs via iNOS-independent but cytokine (predominantly IFN-γ)-dependent mechanism.

  20. Alkaline comet assay in liver and stomach, and micronucleus assay in bone marrow, from rats treated with 2-acetylaminofluorene, azidothymidine, cisplatin, or isobutyraldehyde. (United States)

    Kraynak, A R; Barnum, J E; Cunningham, C L; Ng, A; Ykoruk, B A; Bennet, B; Stoffregen, D; Merschman, M; Freeland, E; Galloway, S M


    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM) initiative international validation study of the in vivo rat alkaline comet assay (comet assay), we examined the ability of the assay to determine the genotoxicity of 2-acetylaminofluorene (AAF), azidothymidine (AZT), cisplatin (CPN), and isobutyraldehyde (IBA) in liver and glandular stomach of male Sprague-Dawley rats. Rats were given oral doses of test compound or control once daily for three days. High dose levels were approximately maximum tolerated doses and were based on preliminary range-finding studies. Tissues were harvested 3h after the final dose (48h after the initial dose). A bone marrow micronucleus assay (MN) was also conducted on the rats treated with AZT, CPN, and IBA. Acute toxic effects of treatment were determined primarily through histomorphologic analysis of liver and stomach but also by body weight and serum liver enzyme changes. The comet assay was conducted on fresh tissue preparations but frozen samples from two studies were also assayed. Statistically significant dose-related differences in comet % DNA in tail were found in liver and stomach for the genotoxin AZT and in liver for the genotoxin CPN, but not in liver or stomach for the non-genotoxin IBA. Statistically significant differences in % DNA in tail were measured in liver for the low and mid dose of the genotoxin AAF, but not the high dose. The comet assays of frozen liver suspensions from CPN- and AAF-treated rats yielded comparable results to the assays of fresh preparations. There were no indications of significant toxicity induced by any treatment. The micronucleus assay was positive for CPN and AZT and negative for IBA. In conclusion, the in vivo comet assay is capable of detecting genotoxic effects of a variety of chemicals and may fill an important role in the genotoxicity test battery.

  1. iTRAQ-Based Proteomics Analysis of Serum Proteins in Wistar Rats Treated with Sodium Fluoride: Insight into the Potential Mechanism and Candidate Biomarkers of Fluorosis

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    Yan Wei


    Full Text Available Fluorosis induced by exposure to high level fluoride is quite widespread in the world. The manifestations of fluorosis include dental mottling, bone damage, and impaired malfunction of soft tissues. However, the molecular mechanism of fluorosis has not been clarified until now. To explore the underlying mechanisms of fluorosis and screen out serum biomarkers, we carried out a quantitative proteomics study to identify differentially expressed serum proteins in Wistar rats treated with sodium fluoride (NaF by using a proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ. We fed Wistar rats drinking water that had 50, 150, and 250 mg/L of dissolved NaF for 24 weeks. For the experimental duration, each rat was given an examination of the lower incisors to check for the condition of dental fluorosis (DF. By the end of the treatment, fluoride ion concentration in serum and lower incisors were detected. The results showed that NaF treatment can induce rat fluorosis. By iTRAQ analysis, a total of 37 differentially expressed serum proteins were identified between NaF-treated and control rats. These proteins were further analyzed by bioinformatics, out of which two proteins were validated by enzyme-linked immunoadsorbent assays (ELISA. The major proteins were involved in complement and coagulation cascade, inflammatory response, complement activation, defense response, and wound response, suggesting that inflammation and immune reactions may play a key role in fluorosis pathogenesis. These proteins may contribute to the understanding of the mechanism of fluoride toxicity, and may serve as potential biomarkers for fluorosis.

  2. Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition. (United States)

    Allen, Jodi C; Seidel, Petra; Schlosser, Tobias; Ramsay, Emma E; Ge, Qi; Ammit, Alaina J


    Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

  3. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis (United States)

    Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study com...

  4. Do dental procedures affect lung function and arterial oxygen saturation in asthmatic patients?

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    Magdy Mahmoud Emara


    Conclusion: Asthmatic patients may be at a higher risk of developing oxygen desaturation after dental procedures regardless of their type with and without local anesthesia and a decrease in PEF after dental procedures with local anesthesia.

  5. Cardiorespiratory fitness of asthmatic children and validation of predicted aerobic capacity

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    Lochte, Lene; Angermann, Marie; Larsson, Benny


    INTRODUCTION: Predicted aerobic capacity (PAC) was estimated by submaximal exercise test and compared with monitored aerobic capacity (MAC) measured by laboratory conditions [maximal oxygen uptake (VO(2peak))] in 18 children and adolescents, 10 asthmatics and 8 matched controls. Objectives...


    Introduction: The elderly and those with cardiovascular disease are susceptible to particulate matter (PM) exposures. Asthmatics are thought to be primarily affected by PM via airway inflammation. We investigated whether factors in blood hemostasis change in response to fluctuat...

  7. Evaluation of Right Ventricular Function by Tissue Doppler Echocardiography in Asthmatic Children

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    Mehdi Ghaderian


    Full Text Available BackgroundAsthma is the most chronic inflammatory disorder of the airways in children and asthmatic patients can experience cardiac dysfunction, pulmonary hypertension and finally cor pulmonale later in life. We aimed to investigate Right Ventricular (RV functions in asthmatic children by conventional and tissue Doppler echocardiography (TDE.Materials and Methods Pulmonary function tests, conventional and TDE examinations were performed on 42 asthmatic and 42 age- and gender matched healthy controls subjects (n=42.Results Compared with healthy children the RV wall was statistically thicker among asthmatic patients (P= 0.01. Conventional echocardiography had not significant difference between cases and controls, but TDE had significant difference between these two groups. Peak E’ velocity, A’ velocity, E’/A’ ratio and S’ in lateral and medial sites of tricuspid annulus valve, were significantly differ from control group in our patients (P

  8. Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide. (United States)

    Aghaie, Somaieh; Nikzad, Hossein; Mahabadi, Javad Amini; Taghizadeh, Mohsen; Azami-Tameh, Abolfazl; Taherian, Aliakbar; Sajjadian, Seyyed Mohammad Sajjad; Kamani, Mehran


    Reproductive toxicity is one of the side effects of cyclophosphamide (CP) in cancer treatment. Pumpkin seeds and Zingiber officinale are natural sources of antioxidants. We investigated the possible protective effect of combined pumpkin seed and Zingiber officinale extracts on sperm characteristics, epididymal histology and biochemical parameters of CP-treated rats. Male adult Wistar rats were divided randomly into six groups. Group 1, as a control, received an isotonic saline solution injection intraperitoneally (IP). Group 2 were injected IP with a single dose of CP (100 mg/kg) once. Groups 3 and 4 received CP plus 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract (50:50). Groups 5 and 6 received only 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract. Six weeks after treatment, sperm characteristics, histopathological changes and biochemical parameters were assessed. In CP-treated rats, motile spermatozoa were decreased, and abnormal or dead spermatozoa increased significantly (P < 0.001) but administration of the mixed extract improved sperm parameters. Epididymal epithelium and fibromascular thickness were also improved in extract-treated rats compared to control or CP groups. Biochemical analysis showed that the administration of combined extracts could increase the total antioxidant capacity (TAC) level significantly in groups 3, 4, 5 and 6. Interestingly, the mixed extract could decrease most of the side effects of CP such as vacuolization and separation of epididymal tissue. Our findings indicated that the combined extracts might be used as a protective agent against CP-induced reproductive toxicity.


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    Ajayi Sunday A


    Full Text Available This research work accessed the effects of kolaviron (a methanolic extract of Garcinia kola seeds on microanatomy of kidneys and biochemical parameters with a view to determining its relationship to renal functions treated with clomiphene citrate. A total of thirty adult female Wistar rats were used for this experiment. The animals were randomly divided into six (6 groups: A, B, C, D, E and F with five (5 animals in each group. Group A, were the control group that were given distilled water orally once daily for 14 days; Group B were given kolaviron orally at concentration of 200 mg/kg body weight once daily for 14 days; Group C were given kolaviron orally at concentration of 100 mg/kg twice daily for 14 days; Group D were given clomiphene citrate orally at concentration of 0.50 mg/kg body weight for 5 days; Group E were given kolaviron orally at concentration of 200 mg/kg body weight once daily for 14 days after which clomiphene citrate were administered at concentration of 0.50 mg/kg body weight for 5 days; Group F were given kolaviron orally at concentration of 100 mg/kg body weight twice daily for 14 days after which clomiphene citrate were administered at concentration of 0.50 mg/kg body weight for 5 days. Five milliliters (5 ml of blood were collected by occular puncture with the aid of capillary tubes from the animals for biochemical analysis. At the end of the experimental period, the animals were anaesthesized by chloroform inhalation. The kidneys were removed and fixed in 10% formol saline for Haematoxylin and Eosin staining. The results showed that Relative kidney weight (f=1.595, df=5, P<0.05 was not increased significantly across the groups. Potassium (f=0.754, df=5, chloride (f=0.529, df=5, interstitial calcium (f=0.835, df=5, total calcium (f=0.840, df=5, silver ions (f=0.517, df=5, and pH (f=0.785, df=5 were not reduced significantly (p< 0.05 when group A was compared with all the groups but sodium ions reduced significantly (f=1

  10. House-plant placement for indoor air purification and health benefits on asthmatics



    Objectives Some plants were placed in indoor locations frequented by asthmatics in order to evaluate the quality of indoor air and examine the health benefits to asthmatics. Methods The present study classified the participants into two groups: households of continuation and households of withdrawal by a quasi-experimental design. The households of continuation spent the two observation terms with indoor plants, whereas the households of withdrawal passed the former observation terms with ind...

  11. The role of visfatin on the regulation of inflammation and apoptosis in the spleen of LPS-treated rats. (United States)

    Xiao, Ke; Zou, Wei-Hua; Yang, Zhi; Zia ur Rehman; Ansari, Abdur Rahman; Yuan, Huai-Rui; Zhou, Ying; Cui, Lu; Peng, Ke-Mei; Song, Hui


    The purpose of the present study is to determine if visfatin is involved in inflammation or apoptosis induced by LPS in rat. Forty Wistar rats were divided into four groups: saline group, LPS group, visfatin group and Visfatin + LPS co-stimulated group. Spleen samples from each group of rats were collected for study. The spleen structure was examined by histological imaging. Apoptosis was evaluated with TUNEL reaction. Caspase-3 was detected with immunohistochemistry and western blot. The apoptosis-related genes were detected by qPCR and inflammatory cytokines were tested by ELISA. Our main findings were as follows. (1) Macrophages were markedly increased in the visfatin group compared with the saline group. This finding was confirmed when spleen samples were examined with western blot using CD68 antibody. (2) Visfatin promoted the expression of CD68 and caspase-3 in rat spleen, whereas visfatin could inhibit the expression of CD68 and activated caspase-3 in spleen of LPS-induced acute inflammation. (3) Visfatin had a pro-apoptotic effect on normal rat spleen, whereas it exerted an anti-apoptotic effect during LPS-induced lymphocytes apoptosis in rat spleen. Moreover, the effect of visfatin on cell apoptosis was mediated by the mitochondrial pathway. (4) Visfatin could modulate both the anti-inflammatory cytokines and pro-inflammatory cytokines in rat spleen, such as IL-10, IL-4, IL-6, TNF-α and IL-1β. Taken together, we demonstrate that visfatin could participate in the inflammatory process in rat spleen by modulating the macrophages and inflammatory cytokines. Also, visfatin plays a dual role in the apoptosis in rat spleen, which is mediated by the mitochondrial pathway.

  12. Modulation of Insulin Receptor Substrate-1 and Some Inflammatory Variables in Hyperinsulinemic Rats Treated with Cinnamon Extract

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    Mohamed H. Mahfouz


    Full Text Available Cinnamon Extract (CE has shown to be generally safe when ingested and to have many pharmacological properties. Problem statement: Study the effects of daily intake of CE on the modulation of hepatic, cardiac Insulin Receptor Substrate-1 (IRS-1 and their relations to some inflammatory variables in hyperinsulinemic rats. Approach: The influence of CE administered orally was studied in hyperinsulinemic rats. Eighteen male Wistar rats were divided into 3 groups of 6 rats each. Group 1; control animals received starch as control diet, while Groups 2; rats were fed a "high-fructose diet"(60%. Group 3; fructose-fed rats received orally CE (0.5 mL/rat/day from the 16th day of fructose feeding in experimental period. The animals were maintained in their respective groups for 30 days. At the end of the experimental period, Serum levels of glucose, insulin, lipid profile, Total Antioxidant Capacity (TAC, Malondialdehyde (MDA, sialic acid and soluble Fas (sFas were assayed. Hepatic and cardiac IRS-1 levels were also evaluated. Results: Fed high fructose diet to rats induced significant elevations in serum levels of glucose, insulin, triacylglycerol, HDL-c, sialic acid, sFas and MDA, while the level of serum TAC was significantly reduced as compared to controls. Also significant reduction in the levels of hepatic and cardiac IRS-1 were recorded as compared to controls. Oral administration of cinnamon extract to fructose-fed rats alleviated the effects of fructose and these rats showed a normal level of the parameters studied. The percentage changes of IRS-1 level in fructose-fed rats before and after treatment with CE were 38.51 for liver and 31.92% for cardiac muscle. This increase in IRS-1 level after treatment is still lowered than control level with the percentage change -11.82 and -9.93% for liver and cardiac muscle respectively. There was a significant positive correlation between IRS-1 and TAC level whereas there was negative correlation between IRS-1

  13. A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice. (United States)

    Shinagawa, Kazuhiko; Ploplis, Victoria A; Castellino, Francis J


    Eosinophil counts in the bronchoalveolar lavage fluid of wild-type (WT) mice increased after ovalbumin (OVA) challenge, a response that was diminished in comparably challenged low-expressing coagulation factor VII (FVII(tTA/tTA)) mice. Levels of T helper type 2 (Th2) cytokines, IL-4, IL-5, and IL-13, and eosinophil-attracting chemokines, eotaxin and RANTES, were also lower in the OVA-challenged FVII(tTA/tTA) mice. Eosinophils purified from low-FVII mice underwent apoptosis at a faster rate compared with WT eosinophils, and eosinophil migration in response to eotaxin was reduced in eosinophils obtained from FVII(tTA/tTA) mice. Airway hyperresponsiveness and mucous layer thickness were reduced in OVA-treated FVII(tTA/tTA) mice, and addition of exogenous coagulation factor X (FX) enhanced mucin production in human epithelial NCI-H292 cells. Correspondingly, incubation of FX with NCI-H292 cells resulted in activated (a) FX production, suggesting that the components required for FX activation were present on NCI-H292 cells. These results demonstrate that FVIIa functions in the asthmatic response to an allergen by stimulating lung eosinophilia, airway hyperresponsiveness, and mucin production, this latter effect through its ability to activate FX in conjunction with tissue factor.

  14. Pancreatic alpha-cell dysfunction contributes to the disruption of glucose homeostasis and compensatory insulin hypersecretion in glucocorticoid-treated rats.

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    Alex Rafacho

    Full Text Available Glucocorticoid (GC-based therapies can cause insulin resistance (IR, glucose intolerance, hyperglycemia and, occasionally, overt diabetes. Understanding the mechanisms behind these metabolic disorders could improve the management of glucose homeostasis in patients undergoing GC treatment. For this purpose, adult rats were treated with a daily injection of dexamethasone (1 mg/kg b.w., i.p. (DEX or saline as a control for 5 consecutive days. The DEX rats developed IR, augmented glycemia, hyperinsulinemia and hyperglucagonemia. Treatment of the DEX rats with a glucagon receptor antagonist normalized their blood glucose level. The characteristic inhibitory effect of glucose on glucagon secretion was impaired in the islets of the DEX rats, while no direct effects were found on α-cells in islets that were incubated with DEX in vitro. A higher proportion of docked secretory granules was found in the DEX α-cells as well as a trend towards increased α-cell mass. Additionally, insulin secretion in the presence of glucagon was augmented in the islets of the DEX rats, which was most likely due to their higher glucagon receptor content. We also found that the enzyme 11βHSD-1, which participates in GC metabolism, contributed to the insulin hypersecretion in the DEX rats under basal glucose conditions. Altogether, we showed that GC treatment induces hyperglucagonemia, which contributes to an imbalance in glucose homeostasis and compensatory β-cell hypersecretion. This hyperglucagonemia may result from altered α-cell function and, likely, α-cell mass. Additionally, blockage of the glucagon receptor seems to be effective in preventing the elevation in blood glucose levels induced by GC administration.

  15. Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats. (United States)

    Adewole, Stephen O; Ojewole, John A O


    Extracts from various morphological parts of Annona muricata Linn. (Annonaceae) are widely used medicinally in many parts of the world for the management, control and/or treatment of a plethora of human ailments, including diabetes mellitus (DM). The present study was undertaken to investigate the possible protective effects of A. muricata leaf aqueous extract (AME) in rat experimental paradigms of DM. The animals used were broadly divided into four (A, B, C and D) experimental groups. Group A rats served as 'control' animals and received distilled water in quantities equivalent to the administered volumes of AME and reference drugs' solutions intraperitoneally. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of streptozotocin (STZ, 70 mg kg(-1)). Group C rats were additionally treated with AME (100 mg kg(-1) day(-1), p.o.) as from day 3 post STZ injection, for four consecutive weeks. Group D rats received AME (100 mg kg(-1) day(-1) p.o.) only for four weeks. Post-euthanization, hepatic tissues were excised and processed biochemically for antioxidant enzymes and lipid profiles, such as catalase (CAT), reactive oxygen species (ROS), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), respectively. Treatment of Groups B and C rats with STZ (70 mg kg(-1) i. p.) resulted in hyperglycaemia, hypoinsulinaemia, and increased TBARS, ROS, TC, TG and LDL levels. STZ treatment also significantly decreased (pmuricata extract has a protective, beneficial effect on hepatic tissues subjected to STZ-induced oxidative stress, possibly by decreasing lipid peroxidation and indirectly enhancing production of insulin and endogenous antioxidants.

  16. Effect of Nd:YAG laser light on post-extractive socket healing in rats treated with zoledronic acid and dexamethasone (United States)

    Mergoni, Giovanni; Merigo, Elisabetta; Passerini, Pietro; Corradi, Domenico; Maestri, Roberta; Bussolati, Ovidio; Bianchi, Massimiliano; Sala, Roberto; Govoni, Paolo; Namour, Samir; Vescovi, Paolo


    Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Material and Methods Thirty male Sprague-Dawley rats were divided in 4 groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10) and treatment plus laser group (T+L, n = 10). Rats of group T and T+L received zoledronate 0,1 mg/Kg and dexamethasone 1 mg/Kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks the first maxillary molars were extracted in all rats. Rats of groups L and T+L received laser therapy (Nd:YAG, 1064 nm, 1.25W, 15Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4 and 6 after surgery. At 8 days from extraction, the sockets were clinically assessed with a grading score and the wound area was measured with a dedicate software. Histomorphometric evaluation and western blot analysis of osteopontin and osteocalcin expression were performed. Results Group T+L showed a trend toward a better clinical grading score compared to group T (grade I 22% Vs 28 % - grade II 56% Vs 28% - grade III 22% Vs 44%, respectively). The average wound area was similar among the groups. Inhibition of osteoclastic alveolar bone resorption was found in groups T and T+L (Plaser irradiation. Conclusion Our findings suggest that laser irradiation after tooth extraction can promote osteoblast differentiation, as demonstrated by the higher expression of osteocalcin. Thus, laser irradiation could be considered a way to improve socket healing in conditions at risk for MRONJ development.

  17. Intratracheal dosing with disodium cromoglycate inhibits late asthmatic response by attenuating eicosanoid production in guinea pigs. (United States)

    Nabe, Takeshi; Yamamoto, Maki; Suga, Mikiko; Kohno, Shigekatsu


    Disodium cromoglycate is an anti-asthmatic drug that has mast cell-stabilizing effects and other anti-inflammatory effects. However, the mechanisms of its anti-inflammatory effects are unclear. In this study, we evaluated effects of disodium cromoglycate on eosinophilia, early and late asthmatic responses, and production of arachidonic acid metabolites in guinea pig lungs. Guinea pigs were alternately sensitized and challenged by exposure to mists of ovalbumin+Al(OH)(3) and ovalbumin, respectively. Disodium cromoglycate (0.5-2 mg/0.1 ml/animal) administered intratracheally before the fifth challenge dose-dependently inhibited asthmatic response, but early asthmatic response was not affected. Disodium cromoglycate at 2 mg/animal potently suppressed increases in cysteinyl leukotrienes (CysLTs) and thromboxane A(2) in the lung during late asthmatic response. Eosinophilia was slightly reduced by disodium cromoglycate. The inhibitory effect of disodium cromoglycate on late asthmatic response is apparently due to inhibition of the release of arachidonic acid metabolites, some of which may be derived from eosinophils that infiltrate the lung.

  18. The neurogenic effects of exogenous neuropeptide Y: early molecular events and long-lasting effects in the hippocampus of trimethyltin-treated rats.

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    Valentina Corvino

    Full Text Available Modulation of endogenous neurogenesis is regarded as a promising challenge in neuroprotection. In the rat model of hippocampal neurodegeneration obtained by Trimethyltin (TMT administration (8 mg/kg, characterised by selective pyramidal cell loss, enhanced neurogenesis, seizures and cognitive impairment, we previously demonstrated a proliferative role of exogenous neuropeptide Y (NPY, on dentate progenitors in the early phases of neurodegeneration. To investigate the functional integration of newly-born neurons, here we studied in adult rats the long-term effects of intracerebroventricular administration of NPY (2 µg/2 µl, 4 days after TMT-treatment, which plays an adjuvant role in neurodegeneration and epilepsy. Our results indicate that 30 days after NPY administration the number of new neurons was still higher in TMT+NPY-treated rats than in control+saline group. As a functional correlate of the integration of new neurons into the hippocampal network, long-term potentiation recorded in Dentate Gyrus (DG in the absence of GABAA receptor blockade was higher in the TMT+NPY-treated group than in all other groups. Furthermore, qPCR analysis of Kruppel-like factor 9, a transcription factor essential for late-phase maturation of neurons in the DG, and of the cyclin-dependent kinase 5, critically involved in the maturation and dendrite extension of newly-born neurons, revealed a significant up-regulation of both genes in TMT+NPY-treated rats compared with all other groups. To explore the early molecular events activated by NPY administration, the Sonic Hedgehog (Shh signalling pathway, which participates in the maintenance of the neurogenic hippocampal niche, was evaluated by qPCR 1, 3 and 5 days after NPY-treatment. An early significant up-regulation of Shh expression was detected in TMT+NPY-treated rats compared with all other groups, associated with a modulation of downstream genes. Our data indicate that the neurogenic effect of NPY

  19. Novel receptor-derived cyclopeptides to treat heart failure caused by anti-β1-adrenoceptor antibodies in a human-analogous rat model.

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    Valérie Boivin

    Full Text Available Despite recent therapeutic advances the prognosis of heart failure remains poor. Recent research suggests that heart failure is a heterogeneous syndrome and that many patients have stimulating auto-antibodies directed against the second extracellular loop of the β1 adrenergic receptor (β1EC2. In a human-analogous rat model such antibodies cause myocyte damage and heart failure. Here we used this model to test a novel antibody-directed strategy aiming to prevent and/or treat antibody-induced cardiomyopathy. To generate heart failure, we immunised n = 76/114 rats with a fusion protein containing the human β1EC2 (amino-acids 195-225 every 4 weeks; n = 38/114 rats were control-injected with 0.9% NaCl. Intravenous application of a novel cyclic peptide mimicking β1EC2 (β1EC2-CP, 1.0 mg/kg every 4 weeks or administration of the β1-blocker bisoprolol (15 mg/kg/day orally was initiated either 6 weeks (cardiac function still normal, prevention-study, n = 24 (16 treated vs. 8 untreated or 8.5 months after the 1st immunisation (onset of cardiomyopathy, therapy-study, n = 52 (40 treated vs. 12 untreated; n = 8/52 rats from the therapy-study received β1EC2-CP/bisoprolol co-treatment. We found that β1EC2-CP prevented and (alone or as add-on drug treated antibody-induced cardiac damage in the rat, and that its efficacy was superior to mono-treatment with bisoprolol, a standard drug in heart failure. While bisoprolol mono-therapy was able to stop disease-progression, β1EC2-CP mono-therapy -or as an add-on to bisoprolol- almost fully reversed antibody-induced cardiac damage. The cyclo¬peptide acted both by scavenging free anti-β1EC2-antibodies and by targeting β1EC2-specific memory B-cells involved in antibody-production. Our model provides the basis for the clinical translation of a novel double-acting therapeutic strategy that scavenges harmful anti-β1EC2-antibodies and also selectively depletes memory B-cells involved in the production of such

  20. Effects of fructose-1,6-diphosphate on concentration of calcium and activities of sarcoplosnic Ca2+-ATPase in cardiomyocytes of Adriamycin-treated rats

    Institute of Scientific and Technical Information of China (English)

    CAI Wei; CHEN Jun-zhu; RUAN Li-ming; WANG Yi-na


    Objective: To observe the effects of fructose-1,6-diphosphate (FDP) on serum levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB), as well as the concentration of calcium in cardiomyocytes (Myo[Ca2+]) and activity of sarcoplosnic Ca2+-ATPase (SRCa2+-ATPase) in Adriamycin (ADR)-treated rats. Methods: Rats were intraperitoneally injected with ADR (2.5mg/kg every other day for 6 times) and then with different dosages of FDP (every other day for twenty-one times). Bi-antibodies sandwich Enzyme linked immune absorption assay (ELISA) was performed to detect serum level of cTnI. CK-MB was detected by monoclonal antibody, Myo[Ca2+] was detected by fluorescent spectrophotometry and the activity of SRCa2+-ATPase was detected by inorganic phosphate method. Results: FDP (300, 600, 1200 mg/kg) significantly reduced the serum levels of cTnI and CK-MB, while at the same time decreased calcium concentration and increased SRCa2+-ATPase activity in cardiomyocytes of ADR-treated rats (P<0.01). Conclusions: FDP might alleviate the cardiotoxic effects induced by ADR through decreasing calcium level as well as increasing SRCa2+-ATPase activity in cardiomyocytes.

  1. Bladder response to acute sacral neuromodulation while treating rats in different phases of complete spinal cord injury: a preliminary study

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    Ping Shi


    Full Text Available Background: Compared to conventional therapies, sacral neuromodulation (SNM may offer an alternative, non-destructive treatment for SCI patients with bladder dysfunction. Understanding bladder response to SNM treatment for SCI in different phases may yield new insights for innovative use of this promising technique. Materials and Methods: Female Sprague-Dawley rats were used in this study to examine the effects of acute SNM on bladder reflex in complete SCI rats. All rats were anesthetized and set up for continuous saline infusion. Acute SNM treatment was implemented for about 6 hours for each rat. Cystometric parameters, including time between contractions, contraction duration, bladder peak pressure, and number of uninhibited contractions, were analyzed and compared within rats before and after SNM treatment. Results: For the spinally transected rats during early phase (less than two weeks post spinalization, the time between contractions and contraction duration both increased after SNM treatments, yet the increased amplitude was about or less than 20%. For the spinally transected rats with a longer days survival (about two to four weeks post spinalization, the time between contractions and contraction duration substantially increased after SNM treatment and the changes for their average values were more than 90%. For the spinally transected rats with a much longer days survival (more than five weeks post spinalization, the time between contractions and contraction duration increased after SNM treatments, yet the magnitude of changes were less than 30%. Conclusion: The present study suggested that the significant effectiveness of SNM for complete SCI played its role after the spinal shock phase and prior to the development of detrusor overactivity. It indicated that the time point of SNM treatment is necessary to be paid attention.

  2. Inhibition of lipopolysaccharide-induced liver injury in rats treated with a hepatic drug-metabolizing enzyme inducer p,p'-DDT. (United States)

    Shimada, Yuko; Tomita, Mariko; Yoshida, Toshinori; Fukuyama, Tomoki; Katoh, Yoshitaka; Ohnuma-Koyama, Aya; Takahashi, Naofumi; Soma, Katsumi; Kojima, Sayuri; Ohtsuka, Ryoichi; Takeda, Makio; Kuwahara, Maki; Harada, Takanori


    Hepatocellular hypertrophy in association with drug-metabolizing enzyme induction is considered to be an adaptive change associated with drug metabolism. To improve our understanding of liver hypertrophy, we determined the effect of a single ip injection of either lipopolysaccharide (LPS) or vehicle in male F344 rats with hepatocellular hypertrophy induced by oral delivery of p,p'-DDT for 2 weeks. The rats were sacrificed 3h or 24h after LPS or vehicle injection. LPS induced a focal hepatocellular necrosis in rats fed the control diet. When rats pre-treated with p,p'-DDT were injected with LPS, necrotic foci surrounded by ballooned hepatocytes were observed in the liver. The change was consistent with reduced LPS-mediated increases in plasma hepatic biomarkers, neutrophil influx, and apoptosis, and also associated with hepatic mRNA levels of TNF-α, CYPs, and NOS2. By contrast, when combined with p,p'-DDT and LPS, faint hepatocellular fatty change was extended, together with a synergistic increase in total blood cholesterol. These results suggest that hepatocytes exposed to p,p'-DDT are protected from the cell-lethal toxic effects of an exogenous stimulus, resulting in cell ballooning rather than necrosis in association with reduced inflammation and apoptosis, but compromised by an adverse effect on lipid metabolism.

  3. Histological and Histomorphometric studies of ethanol-injured pylorus and duodenum of Wistar rats pre-treated with Moringa oliefera extract

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    Olayemi Kafilat Olaibi


    Full Text Available Background: This study investigated the effects of pre-treatment with Moringa oleifera extract on the histomorphology and histomorphometry of the pylorus and duodenum of rats following ethanol-induced gastrointestinal injury. Methods: Following extract and ethanol treatment, pylorus and duodenum of the rats were processed for histological procedures, and tissue quantification of total antioxidant capacity, to access the protective abilities of the extract. Results: We showed that Moringa oleifera extract significantly reduces (p<0.05 total lesion area of the secretory portion of stomach following ethanol induced damage. Also the extract, to a great extent preserved the histological integrity of the pylorus and duodenum, and also significantly improved (p<0.05 the % of glandular mucosa of the pylorus that was intact and the ratio of villi height to crypt depth following ethanol damage. There was significant difference in pyloric and duodenal concentration of total antioxidant capacity between ethanol injured rats compared to control and extract treated groups. Conclusion: The present study confirms the antiulcer properties of Moringa oleifera extract, and demonstrates that the extract preserves the histological integrity and dimensions of the various layers of pylorus and duodenum of Wistar rats, thereby preventing a decrease gastrointestinal surface area following ethanol induced injury.

  4. Post-natal development of rats` offspring treated with the ethanol extract of Neem leaves (Azadirachta indica A. Juss during pregnancy and lactation

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    Vanessa Carla Lima da Silva


    Full Text Available Teratogenicity and developmental abnormalities in the offspring of female rats that ingested ethanol extract of Neem plants during pregnancy and lactation period were assessed. Twenty-four female Wistar rats were randomly distributed in control group and in three experimental groups and treated during the 4th, 5th, and 6th day of pregnancy. After birth, the lactating females received, by gavage, 65, 135 and 200 mg kg-1 of Neem ethanol extract, during 15 days. Results show, there was no significant difference in body mass index of neonatal rats in the 4 groups evaluated, whereas mean rate of offspring survival was 79.4%. Hair growth, incisor teeth eruption, ear detachment, eyelid opening, and spontaneous ambulation were similar for all groups. Likewise, physical development and development of motor activity, ambulation, and postural reflexes were similar for all groups. The administration of Neem ethanol extract did not cause any reproductive or systemic toxicity in animals. Results show that, Neem ethanol extract safe at doses 65, 135 and 200 mg kg-1 in pregnant or lactating rats.

  5. Activation of K{sup +} channels and Na{sup +}/K{sup +} ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats

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    Fiorim, Jonaina, E-mail: [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Ribeiro Júnior, Rogério Faustino, E-mail: [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Azevedo, Bruna Fernades, E-mail: [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Simões, Maylla Ronacher, E-mail: [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Padilha, Alessandra Simão, E-mail: [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Stefanon, Ivanita, E-mail: [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Alonso, Maria Jesus, E-mail: [Departamento de Ciencias de la Salud III, Universidad Rey Juan Carlos, Alcorcón (Spain); Salaices, Mercedes, E-mail: [Departamento de Farmacología, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPaz) (Spain); Vassallo, Dalton Valentim, E-mail: [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil)


    Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K{sup +} channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K{sup +} channels and Na{sup +}/K{sup +}-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent doses 0.05 μg/100 g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilator response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O{sub 2}{sup −} production, and apocynin (0.3 μM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K{sup +}-induced relaxation curves. Ouabain (100 μM) plus L-NAME (100 μM), aminoguanidine (50 μM) or tetraethylammonium (TEA, 2 mM) reduced the K{sup +}-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 μM) or charybdotoxin (0.1 μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K{sup +} channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress. -- Highlights: ► Increased free radicals production ► Increased Na{sup +}/K{sup +} ATPase activity ► Promotes activation of the K{sup +} channels and reduced vascular reactivity ► These effects preserve endothelial function against oxidative

  6. Acid and alkaline phosphatase activities in a novel phosphorothionate (RPR-11) treated male and female rats. Evidence of dose and time-dependent response. (United States)

    Rahman, M F; Siddiqui, M K; Jamil, K


    The effect of a novel phosphorothionate, the methyl ester of 2-butenoic acid-3-diethoxy phosphinothioyl (RPR-II) was studied on membrane bound target enzymes Acid (AcP) and Alkaline (AkP) Phosphatases in different tissues of male and female albino Wistar rats. Three sub-chronic doses 0.014 (low), 0.028 (medium) and 0.042 (high)mg/kg-1 were administered to the rats daily for a period of 90 days. The long term and repeated administration of RPR-II caused significant increase of AcP and AkP in serum and kidney (AcP), whereas these enzymes simultaneously decreased significantly in liver, kidney (female rat AkP) and lung tissues in both male and female rats after 45 and 90 days of treatment. However, the kidney AcP increased significantly in both the sexes which is suggestive of an increase in synthesis of this enzyme which may be an adaptive mechanism to the toxicant stress. The changes in serum, liver, kidney and lung of both male and female rats by this compound were statistically significant when compared with two way Anova showing that they are dose and time dependent. The alterations in male rats were statistically insignificant when compared with female rats showing no sexual dimorphism by this compound. Recovery was observed after 28 days of post treatment (withdrawal study) indicating reversal of the toxic symptoms once the toxicant is removed. High degree negative correlation was observed for serum versus liver and lung and in other cases substantial correlation was observed. The changes observed in these enzymes showed that liver was most susceptible followed by lung and kidney. There are marker enzymes and their increase in different tissues might be due to the increased permeability of plasma membrane or cellular necrosis, showing the stress condition of the treated rats. This investigation elucidates the effect of these biomarker enzymes which increased in blood, might be due to the necrosis of liver, kidney and lung tissues by this compound.

  7. Effects of vitamin E on the proliferation and collagen synthesis of rat hepatic stellate cells treated with IL-2 or TNF-α

    Institute of Scientific and Technical Information of China (English)

    展玉涛; 王宇; 魏来; 陈红松


    Objective To study the effects of vitamin E on the proliferation and collagen synthesis of rat hepatic stellate cells treated with interleukin-2 (IL-2 ) or tumor necrosis factor-α (TNF-α).Methods Hepatic stellate cells were isolated from male Sprague-Dawley rats by using modified Friedman's method. Using the isolated cells cultured and treated with IL-2 or TNF-α, we studied the effects of vitamin E on their proliferation and collagen synthesis through an 3 H-thymidine and 3 H-proline incorporation assay, as well as through observation of these cells under a contrary phase microscope. Results Adding IL-2 increased the both proliferation and collagen synthesis of hepatic stellate cells. Their proliferation was also increased by the addition of TNF-α, although it decreased collagen synthesis. Vitamin E had marked inhibitory effects on the ability of cells treated with IL-2 or TNF-α to reproduce or synthesize collagen.Conclusion Vitamin E can inhibit the proliferation and collagen synthesis of hepatic stellate cells. It is possible that vitamin E affects liver fibrosis through these activities.

  8. Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)

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    Hagland, Hanne R.; Nilsson, Linn I.H. [Department of Biomedicine, University of Bergen (Norway); Burri, Lena [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Nikolaisen, Julie [Department of Biomedicine, University of Bergen (Norway); Berge, Rolf K. [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Department of Heart Disease, Haukeland University Hospital (Norway); Tronstad, Karl J., E-mail: [Department of Biomedicine, University of Bergen (Norway)


    Highlights: Black-Right-Pointing-Pointer We investigated mechanisms of mitochondrial regulation in rat hepatocytes. Black-Right-Pointing-Pointer Tetradecylthioacetic acid (TTA) was employed to activate mitochondrial oxidation. Black-Right-Pointing-Pointer Mitochondrial biogenesis and respiration were induced. Black-Right-Pointing-Pointer It was confirmed that PPAR target genes were induced. Black-Right-Pointing-Pointer The mechanism involved activation mTOR. -- Abstract: The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR{alpha}-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.


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    E. F. Kulbekov


    Full Text Available Hepatic decompensation problems make it timely to search for the methods of its treatment. Stem cells usage in attempt to restore structures of organs and tissues is a promising direction of researches. However the problem of possible blast-cell transformation slows down studies in this direction. Attempt of thymalinum use as an antitumoral immune system's modulator may be successful and may widen the possibilities of stem cells use in hepatology. On the basis of toxical affection of rats' lever by tetrachloromethane and paracetamol we have studied hepatoprotective activity of thymalinum and suspension of rats' red bone marrow (RBM and a thymalinum + suspension of RBM complex. Hepatoprotective action was estimated by the volume of discharged bile of control group rats which received paracetamol comparing with intact animals. This confirms the absence of reliable hepatotoxical action of paracetamol following the methodology applied. Significant reduction of discharged bile volume of control group rats which received tetrachloromethane comparing with intact animals confirms the successfulness of the formation method of hepatitis model in animals which received tetrachloromethane. The animals which were given tetrachloromethane and thymalinum + suspension of RBM combination had bigger volume of bile discharged than control group animals. Hepatoprotective action tendency of thymalinum + suspension of RBM combination shown before on mice is also true for rats

  10. Tolerance to repeated stress in rats with lesions of the serotoninergic neurons of the Median Raphe Nucleus and chronically treated with imipramine. (United States)

    Silva, K; Carvalho, M C; Padovan, C M


    Repeated exposure to aversive events leads to the development of tolerance to stress, which involves the serotonergic pathway originated in the Median Raphe Nucleus (MnRN) to the Dorsal Hippocampus (DH). However, it is not clear whether these lesion-induced deficits can be attenuated by treatment with antidepressants. Therefore, the aim of this work was to investigate the effects of chronic treatment with Imipramine (IMI) in rats with lesions in the MnRN and exposed to restraint stress. Male Wistar rats with or without neurochemical lesions of the MnRN serotonergic neurons with the neurotoxin 5,7-DHT were submitted to acute (2h) or chronic restraint (2h/day/seven consecutive days) and treated with saline (1 ml/kg) or imipramine (15 mg/kg) via intraperitoneal twice a day during the same period. In acutely restrained rats, stress occurred on the last day of treatment. Test in the elevated plus maze (EPM) was performed 24h later. After EPM test, animals were sacrificed and had their brains removed. Dorsal hippocampus and striatum were dissected and the levels of 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) measured by HPLC analysis. Our results showed that in control rats exposure to acute restraint stress decreased exploration of the open and enclose arms of the EPM, an effect that was attenuated by imipramine. In rats with 5,7-DHT lesions, acute restraint did not change the exploration of the EPM, independently of the treatment. On the other hand, when chronically restrained, saline treated rat with 5,7-DHT lesion showed a reduced exploration of the open arms of the EPM. This effect was attenuated by simultaneous treatment with imipramine. HPLC analysis showed significantly decreases on 5-HT and 5-HIAA levels in the hippocampus, but not in the striatum. These later results confirm that 5,7-DHT lesions of the MnRN had significant impact on the serotonergic projections to the dorsal hippocampus which seems to be essential for the development of tolerance to repeated

  11. Effect of combination of extracts of ginseng and ginkgo biloba on acetylcholine in amyloid beta-protein-treated rats determined by an improved HPLC

    Institute of Scientific and Technical Information of China (English)

    Jian-xun LIU; Wei-hong CONG; Li XU; Jian-nong WANG


    AIM: To determine the concentration of acetylcholine (ACh) in amyloid beta-protein (Aβ) treated rats and offer a method determining ACh as well. METHODS: A 1-month combination of extrats of ginseng and ginkgo biloba(Naoweikang) ig administration to rats was performed daily after bilateral injection of Aβ1-40 (4 g/L, 1 μL for each side) into hippocampus. After decollation, homogenizing, and centrifuging and extracting, a high pressure liquid chromatographic (HPLC) method using electrochemical detection (ECD) combined with two immobilized enzyme reactors was used to determine ACh in rat whole brain. RESULTS: With a mobile phase consisting of disodium hydrogen orthophosphate, tetramethylammonium chloride (TMAC1), octanesulfonic acid sodium salt (OSA) and"Reagent MB" at a final pH of 8.0, ACh was determined while removing the interfering choline in less than 10 min at a flow rate of 0.35 mL/min on a platinum (Pt) working electrode at a potential of +300 mV vs a solid-state palladium (Pd) reference electrode. Linear regression analysis of peak area vs concentration demonstrated linearity in the 28.01 to 1400.06 μg/L injection range. The r-value was 0.9978. The limit of detection (LOD) is 0.28 ng on column. ACh in whole brain decreased by 20.34 % (from 162.1±32.7 to 134.7±14.0 μg/L, P<0.05) after bilateral injection of Aβ into rat hippocampus. After Naoweikang administration (31 and 15.5 mg/kg, respectively), ACh increased by 19.97 % (from 134.7+14.0 to 161.6+26.2 μg/L, P<0.05) and 18.56 % (from 134.7+14.0 to 159.7+22.9 μg/L, P<0.05), respectively. CONCLUSION: Naoweikang significantly increased the level of ACh in whole brain of Aβ treated rats. And a sensitive, selective and reliable method for routinely determining ACh in rat whole brain was established in this study.

  12. Effect of melatonin on the production of microsomal hydrogen peroxide and cytochrome P-450 content in rat treated with aflatoxin B(1). (United States)

    Awney, Hala A; Attih, Ahmed M; Habib, Sami L; Mostafa, Mostafa H


    Aflatoxin B(1) (AFB(1)) is a food contaminant fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this study we went on to show the effect of melatonin as a free radical scavenger on the production of microsomal hydrogen peroxide (H(2)O(2)) during the metabolic activation AFB(1). The production of microsomal H(2)O(2) in vitro during the metabolic activation of different chemical carcinogens has been reported previously. We also studied the effect of melatonin on the cytochrome P-450 content as a major microsomal monooxygenase isoenzymes system in rat liver responsible for the metabolic activation of AFB(1). The amounts of H(2)O(2) and cytochrome P-450 contents in rat treated with melatonin (0.2 mg/kg BW) and/or AFB(1) (0.2 mg/kg BW) at various time intervals has been measured. Animals treated with melatonin exhibited markedly inhibition in the amounts of H(2)O(2) after 1, 3, and 6 h. The highest level of inhibition (3.0 nmol H(2)O(2)/mg protein) was detected after 6 h. However, cytochrome P-450 contents were also decreased after the same period of time. The highest level of inhibition (2.1 nmol/mg protein) was detected after 3 h of injection. A pronounced augmentation of H(2)O(2) production was observed in rat treated with AFB(1) only. The highest level of H(2)O(2) (100 nmol/mg protein) was measured after 1 h. Cytochrome P-450 contents were also decreased in response to AFB(1) injection over the same time intervals. Contrary data was detected in animals received both AFB(1) and melatonin. The generation of H(2)O(2) was inhibited by melatonin after 1, 3 and 6 h. The highest level of inhibition (44.2 nmol/mg protein) was observed after 6 h. Finally, these data suggested that melatonin as a free radical scavenger inhibited the microsomal production of H(2)O(2) in rat treated with AFB(1).

  13. Barrier disrupting effects of alternaria alternata extract on bronchial epithelium from asthmatic donors.

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    Marina S Leino

    Full Text Available Sensitization and exposure to the allergenic fungus Alternaria alternata has been associated with increased risk of asthma and asthma exacerbations. The first cells to encounter inhaled allergens are epithelial cells at the airway mucosal surface. Epithelial barrier function has previously been reported to be defective in asthma. This study investigated the contribution of proteases from Alternaria alternata on epithelial barrier function and inflammatory responses and compared responses of in vitro cultures of differentiated bronchial epithelial cells derived from severely asthmatic donors with those from non-asthmatic controls. Polarised 16HBE cells or air-liquid interface (ALI bronchial epithelial cultures from non-asthmatic or severe asthmatic donors were challenged apically with extracts of Alternaria and changes in inflammatory cytokine release and transepithelial electrical resistance (TER were measured. Protease activity in Alternaria extracts was characterised and the effect of selectively inhibiting protease activity on epithelial responses was examined using protease inhibitors and heat-treatment. In 16HBE cells, Alternaria extracts stimulated release of IL-8 and TNFα, with concomitant reduction in TER; these effects were prevented by heat-treatment of the extracts. Examination of the effects of protease inhibitors suggested that serine proteases were the predominant class of proteases mediating these effects. ALI cultures from asthmatic donors exhibited a reduced IL-8 response to Alternaria relative to those from healthy controls, while neither responded with increased thymic stromal lymphopoietin (TSLP release. Only cultures from asthmatic donors were susceptible to the barrier-weakening effects of Alternaria. Therefore, the bronchial epithelium of severely asthmatic individuals may be more susceptible to the deleterious effects of Alternaria.

  14. Anti-Inflammatory Effects of Ginsenoside Rg3 via NF-κB Pathway in A549 Cells and Human Asthmatic Lung Tissue

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    In-Seung Lee


    Full Text Available Objective. There is limited information of the anti-inflammatory effects of Rg3 on inflamed lung cells and tissues. Therefore, we confirmed the anti-inflammatory mechanism of ginsenoside Rg3 in inflamed human airway epithelial cells (A549 and tissues whether Rg3 regulates nuclear factor kappa B (NF-κB activity. Methods. To induce the inflammation, IL-1β (10 ng/ml was treated to A549 cells for 4 h. The effects of Rg3 on NF-κB activity and COX-2 expression were evaluated by western blotting analysis in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. Using multiplex cytokines assay, the secretion levels of NF-κB-mediated cytokines/chemokines were measured. Result. Rg3 showed the significant inhibition of NF-κB activity thereby reduced COX-2 expression was determined in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. In addition, among NF-κB-mediated cytokines, the secretion levels of IL-4, TNF-α, and eotaxin were significantly decreased by Rg3 in asthma tissues. Even though there was no significant difference, IL-6, IL-9, and IL-13 secretion showed a lower tendency compared to saline-treated human asthmatic airway epithelial tissues. Conclusion. The results from this study demonstrate the potential of Rg3 as an anti-inflammatory agent through regulating NF-κB activity and reducing the secretion of NF-κB-mediated cytokines/chemokines.

  15. Righting elicited by novel or familiar auditory or vestibular stimulation in the haloperidol-treated rat: rat posturography as a model to study anticipatory motor control. (United States)

    Clark, Callie A M; Sacrey, Lori-Ann R; Whishaw, Ian Q


    External cues, including familiar music, can release Parkinson's disease patients from catalepsy but the neural basis of the effect is not well understood. In the present study, posturography, the study of posture and its allied reflexes, was used to develop an animal model that could be used to investigate the underlying neural mechanisms of this sound-induced behavioral activation. In the rat, akinetic catalepsy induced by a dopamine D2 receptor antagonist (haloperidol 5mg/kg) can model human catalepsy. Using this model, two experiments examined whether novel versus familiar sound stimuli could interrupt haloperidol-induced catalepsy in the rat. Rats were placed on a variably inclined grid and novel or familiar auditory cues (single key jingle or multiple key jingles) were presented. The dependent variable was movement by the rats to regain equilibrium as assessed with a movement notation score. The sound cues enhanced movements used to regain postural stability and familiar sound stimuli were more effective than unfamiliar sound stimuli. The results are discussed in relation to the idea that nonlemniscal and lemniscal auditory pathways differentially contribute to behavioral activation versus tonotopic processing of sound.

  16. Función adrenal y metabolismo lipídico en niños asmáticos tratados con budesonida Adrenal function and lipid metabolism in asthmatic children with budesonide treatment

    Directory of Open Access Journals (Sweden)

    Mariela Paoli-de Valeri


    Full Text Available Objetivo. Evaluar el efecto de bajas dosis de budesonida inhalado sobre la función adrenal y el metabolismo lipídico en niños asmáticos. Material y métodos. Se estudiaron: 10 niños asmáticos (edad promedio, 8.6 años tratados con budesonida inhalado (200-300 µg/día por un lapso mayor a tres meses (grupo A; 15 niños asmáticos (edad promedio, 7.8 años sin tratamiento esteroideo (grupo B, y 10 niños no asmáticos (grupo C. Se determinaron los niveles de cortisol basal y postestímulo con ACTH, andrógenos adrenales, lípidos y cortisol urinario. Resultados. Entre los grupos A y B no hubo diferencias significativas en las variables estudiadas. En los niños asmáticos (grupo A-B el cortisol urinario fue significativamente mayor en relación con el grupo C. Los niveles de triglicéridos, colesterol total, colesterol de la lipoproteína de baja densidad e índices aterogénicos fueron mayores en el grupo de niños asmáticos, con y sin budesonida, comparados con el grupo C. Conclusiones. El tratamiento con dosis bajas de budesonida inhalado en niños asmáticos no modificó la función del eje adrenal ni el metabolismo lipídico. Los pacientes asmáticos presentaron un perfil lipídico aterogénico que podría incrementar el riesgo de enfermedad cardiovascular.Objective. To assess the effect of low doses of inhaled budesonide on the adrenal function and lipid metabolism of asthmatic children. Material and methods. The study included 10 asthmatic children (mean age, 8.8 years treated with inhaled budesonide (200-300 µg/day for a period longer than 3 months (group A; 15 asthmatic children (mean age, 7.8 years without steroid treatment (group B and 10 non-asthmatic children (group C. Basal cortisol levels, as well as postACTH, adrenal androgens, lipids and urinary cortisol were determined. Results. No significant differences were detected between groups A and B in the studied variables. In asthmatic children, urinary cortisol was

  17. Effects of dermatophagoides pteronyssinus allergen-specific immunotherapy on the serum interleukin-13 and pulmonary functions in asthmatic children

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhuang-gui; LI Ming; CHEN Yan-feng; JI Jing-zhi; LI Ya-ting; CHEN Wei; CHEN Fen-hua; CHEN Hong


    Background Airway remodeling is the specific pathological characteristics of asthma, which is related to the clinical symptoms, pulmonary function, and airway hyperreactivity. This study aimed at exploring the effects of dermatophagoides pteronyssinus allergen-specific immunotherapy (SIT) on the serum interleukin (IL)-13 and pulmonary functions in asthmatic children.Methods Fifty-eight pediatric asthma patients allergic to dust mite participated in this study. Thirty-five children received SIT with a standardized dermatophagoides pteronyssinus extract for one year (SIT group), and the other 23 children treated with inhaled corticosteroids (ICS group) according to the Global Initiative for Asthma (GINA) for one year. Serum levels of IL-13, IL-4 and interferon (IFN)-y were examined and the pulmonary functions were checked before and after the treatment.Results After the treatment, the number of emergency visiting for asthma attack in SIT group was significantly less than that in ICS group. The serum levels of IL-4 and IL-13 were clearly reduced, IFN-γ and the ratio of IFN-γ/IL-4 were significantly increased, the pulmonary functions (forced vital capacity (FVC), forced expiratory volume in one second percentage (FEV1%) and peak expiratory flow percentage (PEF%) were significantly improved in the SIT group.Meanwhile, IFN-y and the ratio of IFN-γ/IL-4 were greatly increased, but serum levels of IL-4 and IL-13 had less changes,the pulmonary functions (FVC, FEV1% and PEF%) were poorly improved in ICS group. The basic pulmonary functions in both groups were at the same level, which had made more improvement in SIT group than in ICS group one year later.Conclusions One year of dermatophagoides pteronyssinus SIT can significantly reduce the frequencies of emergency visiting for asthma attack and improve the pulmonary functions of children with allergic asthma, and that is attributed to SIT, which can reduce the levels of IL-4 and IL-13 and regulate the imbalance of the

  18. IL-25 promotes Th2 immunity responses in airway inflammation of asthmatic mice via activation of dendritic cells. (United States)

    Hongjia, Li; Caiqing, Zhang; Degan, Lu; Fen, Liu; Chao, Wang; Jinxiang, Wu; Liang, Dong


    Allergic asthma occurs as a consequence of inappropriate immunologic inflammation to allergens and characterized by Th2 adaptive immune response. Recent studies indicated that interleukin (IL)-25, a member of the IL-17 cytokine family, had been implicated in inducing Th2 cell-dependent inflammation in airway epithelium and IL-25-deficient mice exhibit impaired Th2 immunity responses; however, how these cytokines influence innate immune responses remains poorly understood. In this study, we used ovalbumin (OVA) sensitization and challenge to induce the murine asthmatic model and confirmed by histological analysis of lung tissues and serum levels of total and OVA-specific immunoglobulin (Ig)-E. The expression of IL-25 was detected by quantitative real-time PCR and immunohistochemistry, respectively, and the dendritic cells (DCs) activation was detected by levels of CD80 and CD86 in bronchoalveolar lavage fluid (BALF) by flow cytometry. The mice sensitized and challenged with OVA showed high expression of IL-25 in both mRNA and protein levels in lungs. We detected the expression of CD80 and CD86 in BALF was also increased. A tight correlation between IL-25 mRNA and other Th2 cells producing cytokines such as IL-4, IL-5, and IL-13 in BALF was identified. Furthermore, when the asthmatic mice were treated with inhaled corticosteroids, the inflammatory cells infiltration and the inflammatory cytokines secretion were significantly decreased. In this study, we show that IL-25 promoted the accumulation of co-stimulatory molecules of CD80 and CD86 on DCs and then induced the differentiation of prime naive CD4(+) T cells to become proinflammatory Th2 cells and promoted Th2 cytokine responses in OVA-induced airway inflammation. The ability of IL-25 to promote the activation and differentiation of DCs population was identified as a link between the IL-17 cytokine family and the innate immune response and suggested a previously unrecognized innate immune pathway that promotes Th2

  19. Risk factors in pediatric asthmatic patients. Cases and control studies.

    Directory of Open Access Journals (Sweden)

    Rafael Alejandro Gómez Baute


    Full Text Available Background: Asthma constitutes the first disease among chronic diseases in children. The morbid-mortality promoted to continue being elevated in spite of the new therapies. For this reason it is a disease with high priority for investigation in pediatric ages. Method: A control and case group study was carried out. The samples was composed by 72 asthmatic children from three General Comprehensive doctor offices from Palmira health area located in Cienfuegos Province, Cuba; and a control group of 72 children apparently healthy from the same population. A questionnaire with the different risk variables was elaborated. Odds ratio technique was used to estimate the risk. Results: low weight at birth, family history of asthma, brochiolitis antecedent and the excessive usage of antibiotics in children under 1 year old were the main risks found. Conclusions: It is conclusive that the exposure to home allergen plus a genetic favorable factor, the prematurity, and brochiolitis constituted the most outstanding elements to suffer from asthma in the population studied.

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