WorldWideScience

Sample records for swine induce altered

  1. Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs.

    Science.gov (United States)

    Thomas, Milton; Wang, Zhao; Sreenivasan, Chithra C; Hause, Ben M; Gourapura J Renukaradhya; Li, Feng; Francis, David H; Kaushik, Radhey S; Khatri, Mahesh

    2015-01-15

    Swine influenza is widely prevalent in swine herds in North America and Europe causing enormous economic losses and a public health threat. Pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. Current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. In this study, we evaluated the protective efficacy of an intranasal Poly I:C adjuvanted UV inactivated bivalent swine influenza vaccine consisting of Swine/OH/24366/07 H1N1 and Swine/CO/99 H3N2, referred as PAV, in maternal antibody positive pigs against an antigenic variant and a heterologous swine influenza virus challenge. Groups of three-week-old commercial-grade pigs were immunized intranasally with PAV or a commercial vaccine (CV) twice at 2 weeks intervals. Three weeks after the second immunization, pigs were challenged with the antigenic variant Swine/MN/08 H1N1 (MN08) and the heterologous Swine/NC/10 H1N2 (NC10) influenza virus. Antibodies in serum and respiratory tract, lung lesions, virus shedding in nasal secretions and virus load in lungs were assessed. Intranasal administration of PAV induced challenge viruses specific-hemagglutination inhibition- and IgG antibodies in the serum and IgA and IgG antibodies in the respiratory tract. Importantly, intranasal administration of PAV provided protection against the antigenic variant MN08 and the heterologous NC10 swine influenza viruses as evidenced by significant reductions in lung virus load, gross lung lesions and significantly reduced shedding of challenge viruses in nasal secretions. These results indicate that Poly I:C or its homologues may be effective as vaccine adjuvants capable of generating cross-protective immunity against antigenic variants/heterologous swine influenza viruses in pigs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine.

    Science.gov (United States)

    Clark, Bradley A; Alloosh, Mouhamad; Wenzel, James W; Sturek, Michael; Kostrominova, Tatiana Y

    2011-05-01

    Ossabaw swine fed excess kilocalorie diet develop metabolic syndrome (MS) characterized by obesity, hypertension, insulin resistance, and glucose intolerance with/without dyslipidemia. The purpose of this study was to test the hypothesis that MS would have a detrimental effect on skeletal muscle structure and cause changes in the expression of myosin heavy chains (MHCs). Adult male Ossabaw swine were fed for 24 wk high-fructose or high-fat/cholesterol/fructose diets to induce normolipidemic MS (MetS) or dyslipidemic MS (DMetS), respectively, and were compared with the lean swine on control diet. MetS swine showed mild MS, lacking increases in total and low density lipoprotein (LDL) cholesterol, both of which were highly upregulated in DMetS swine. There was an ∼1.2-fold increase in the cross-sectional areas of muscle fibers in MetS and DMetS groups compared with control for biceps femoris and plantaris muscles. In plantaris muscles, DMetS diet caused an ∼2-fold decrease in slow MHC mRNA and protein expression and an ∼1.2- to 1.8-fold increase in the number of intramyocellular lipid (IMCL) droplets without large changes in the size of the droplets. There was a trend to the decrease in slow MHC expression in muscles of swine on MetS diet. The number of IMCL droplets in muscle fibers of the MetS group was comparable to controls. These data correlate well with the data on total plasma cholesterol (control = 60, MetS = 70, and DMetS = 298 mg/dl) and LDL (control = 29, MetS = 30, and DMetS = 232 mg/dl). We conclude that structural changes observed in skeletal muscle of obese Ossabaw swine correlate with those previously reported for obese humans.

  3. Histopathological Evaluation of Horse Serum-induced Immune Complex Vasculitis in Swine: Implication to Coronary Artery Lesions in Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Saji Philip

    2014-08-01

    Conclusion: HS can induce IC vasculitis in swine. The rashes and 2D echocardiographic and histopathological studies of the acute to healing phases showed close similarities with KD, and it is concluded that swine may serve as a unique experimental model for IC vasculitis and for various therapeutic trials.

  4. The in-feed antibiotic carbadox induces phage gene transcription in the swine gut microbiome

    Science.gov (United States)

    Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40 percent of young pigs in the U.S. and has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo effects of carbadox on swin...

  5. Actinobacillus pleuropneumoniae challenge in swine: diagnostic of lung alterations by infrared thermography.

    Science.gov (United States)

    Menzel, Anne; Beyerbach, Martin; Siewert, Carsten; Gundlach, Melanie; Hoeltig, Doris; Graage, Robert; Seifert, Hermann; Waldmann, Karl-Heinz; Verspohl, Jutta; Hennig-Pauka, Isabel

    2014-09-16

    Actinobacillus pleuropneumoniae (A.pp.) is the causative agent of porcine pleuropneumonia leading to high economic losses in the pig industry. Infrared thermography (IRT) of the thorax might offer a new method to select swine with lung alterations for further diagnostics. In this study 50 german landrace pigs were infected with A.pp. in an established model for respiratory tract disease, while 10 healthy pigs served as control animals. To avoid drift errors during IR measurements absolute skin temperatures and temperature differences between a thoracal and an abdominal region were assessed for its diagnostic validity. IRT findings during the course of experimental A.pp.-infection were verified by computed tomography (CT) before and on days 4 and 21 after infection. Significant correlations were found between clinical scores, CT score and lung lesion score. Ambient temperature, body temperature and abdominal surface temperature were factors influencing the skin surface temperature of the thorax. On day 4 but not on day 21 after infection the right thoracal temperature was significantly higher and the difference between a thoracal region in the height of the left 10th vertebra and an abdominal region was significantly lower in infected pigs than in control pigs. At a cut off of 28°C of right thoracal temperature the specificity of the method was 100% (CI 95%: 69-100%) and the sensitivity 66% (CI 95%: 51-79%). At a cut off of 2°C temperature difference between thoracal and abdominal region on the left body site the specificity of the method was 100% (CI 95%: 69-100%) and the sensitivity 32% (CI 95%: 19-47%) with all control pigs detected negative. Orientation for lung biopsy by IRT resulted in 100% specificity and sensitivity (CI 95%: 69-100%) of bacteriological examination of tissue samples during the acute stage of infection. IRT might be a valuable tool for the detection of inflammatory lung alterations in pigs, especially during the acute stage of infection and

  6. ALTERATIONS INDUCED BY LOW LEVELS OF DEOXYNIVALENOL IN WEANED PIGLETS

    Directory of Open Access Journals (Sweden)

    DANIELA ELIZA MARIN

    2007-05-01

    Full Text Available Deoxynivalenol (DON is a mycotoxin produced by different species of Fusarium genus that may contaminate feed and food. In the present study we investigated the effect of low levels of DON on the modulation of performance, hemodynamic parameters, cellular and humoral immune response in weaned pigs. Histological alterations in different organ tissues were also analyzed. Our results showed that a short in vivo exposure (14 days of weanling piglets to 0; 0.5; 1.5 mg/day of DON significantly induced a dose dependent increase of cellular immune response (lymphocytes proliferation and leucocytes numbers. The 0.5 and 1.5 mg/day of DON modulated also the humoral immune response by increasing the immunoglobulin A synthesis with 7.32 % and 37.98 % and by decreasing that of immunoglubulin G with 11.15 % and 36.87 %, respectively when compared with the control. DON produced also alterations in the hemodynamic parameters of intoxicated piglets; the activity of lactate dehydrogenase significantly increased while the activity of L-glutamate, alkaline phosphatase, urea and creatinine significantly decreased. Both doses of the toxin induced microscopic alterations of the internal organ structure. By contrast, ingestion of the contaminated material had no effect on the performance (weight gain, feed consumption, and feed efficiency, organ weights, and total serum concentration of cholesterol, calcium, sodium and potassium. Taken together these results suggest that even when present at low level DON can affect blood parameters, humoral and cellular immune response in weaned piglets with a significant importance for the swine health.

  7. The Role of Mitochondrial Oxidation in Endotoxin-Induced Liver-Dependent Swine Pulmonary Edema

    Science.gov (United States)

    Siore, Amsel M.; Parker, Richard E.; Cuppels, Chris; Thorn, Natalie; Hansen, Jason M.; Stecenko, Arlene A.; Brigham, Kenneth L.

    2012-01-01

    We reported previously studies in an in situ perfused swine preparation demonstrating that endotoxemia induced lung injury required the presence of the liver and that the response was accompanied by oxidative stress. To determine whether lung and liver mitochondrial oxidative stress was important to the response, we compared the effects of equimolar amounts of two antioxidants, n-acetylcysteine, which does not replenish mitochondrial glutathione, and procysteine which does, on endotoxemia induced lung injury in the swine preparation. In a swine perfused liver-lung preparation, we measured physiologic, biochemical and cellular responses of liver and lung to endotoxemia with and without the drugs. Endotoxemia caused oxidation of the mitochondria-specific protein, thioredoxin-2, in both the lungs and the liver. Procysteine reduced thioredoxin-2 oxidation, attenuated hemodynamic, gas exchange, hepatocellular dysfunction, and cytokine responses and prevented lung edema. n-acetylcysteine had more modest effects and did not prevent lung edema. Conclusions: We conclude that mitochondrial oxidation may be critical to the pathogenesis of endotoxemia-induced liver-dependent lung injury and that choices of antioxidant therapy for such conditions must consider the desired subcellular target in order to be optimally effective. PMID:22925572

  8. A Pro23His mutation alters prenatal rod photoreceptor morphology in a transgenic swine model of retinitis pigmentosa.

    Science.gov (United States)

    Scott, Patrick A; Fernandez de Castro, Juan P; Kaplan, Henry J; McCall, Maureen A

    2014-04-28

    Functional studies have detected deficits in retinal signaling in asymptomatic children from families with inherited autosomal dominant retinitis pigmentosa (RP). Whether retinal abnormalities are present earlier during gestation or shortly after birth in a subset of children with autosomal dominant RP is unknown and no appropriate animal RP model possessing visual function at birth has been available to examine this possibility. In a recently developed transgenic P23H (TgP23H) rhodopsin swine model of RP, we tracked changes in pre- and early postnatal retinal morphology, as well as early postnatal retinal function. Domestic swine inseminated with semen from a TgP23H miniswine founder produced TgP23H hybrid and wild type (Wt) littermates. Outer retinal morphology was assessed at light and electron microscopic levels between embryonic (E) and postnatal (P) day E85 to P3. Retinal function was evaluated using the full field electroretinogram at P3. Embryonic TgP23H rod photoreceptors are malformed and their rhodopsin expression pattern is abnormal. Consistent with morphological abnormalities, rod-driven function is absent at P3. In contrast, TgP23H and Wt cone photoreceptor morphology (E85-P3) and cone-driven retinal function (P3) are similar. Prenatal expression of mutant rhodopsin alters the normal morphological and functional development of rod photoreceptors in TgP23H swine embryos. Despite this significant change, cone photoreceptors are unaffected. Human infants with similarly aggressive RP might never have rod vision, although cone vision would be unaffected. Such aggressive forms of RP in preverbal children would require early intervention to delay or prevent functional blindness.

  9. Iodoacetic acid, but not sodium iodate, creates an inducible swine model of photoreceptor damage.

    Science.gov (United States)

    Noel, Jennifer M; Fernandez de Castro, Juan P; Demarco, Paul J; Franco, Luisa M; Wang, Wei; Vukmanic, Eric V; Peng, Xiaoyan; Sandell, Julie H; Scott, Patrick A; Kaplan, Henry J; McCall, Maureen A

    2012-04-01

    Our purpose was to find a method to create a large animal model of inducible photoreceptor damage. To this end, we tested in domestic swine the efficacy of two chemical toxins, known to create photoreceptor damage in other species: Iodoacetic Acid (IAA) and Sodium Iodate (NaIO(3)). Intravenous (IV) administration of NaIO(3) up to 90 mg/kg had no effect on retinal function and 110 mg/kg was lethal. IV administration of IAA (5-20 mg/kg) produced concentration-dependent changes in visual function as measured by full-field and multi-focal electroretinograms (ffERG and mfERG), and 30 mg/kg IAA was lethal. The IAA-induced effects measured at two weeks were stable through eight weeks post-injection, the last time point investigated. IAA at 7.5, 10, and 12 mg/kg produce a concentration-dependent reduction in both ffERG b-wave and mfERG N1-P1 amplitudes compared to baseline at all post-injection times. Comparisons of dark- and light-adapted ffERG b-wave amplitudes show a more significant loss of rod relative to cone function. The fundus of swine treated with ≥10 mg/kg IAA was abnormal with thinner retinal vessels and pale optic discs, and we found no evidence of bone spicule formation. Histological evaluations show concentration-dependent outer retinal damage that correlates with functional changes. We conclude that NaIO(3,) is not an effective toxin in swine. In contrast, IAA can be used to create a rapidly inducible, selective, stable and concentration-dependent model of photoreceptor damage in swine retina. Because of these attributes this large animal model of controlled photoreceptor damage should be useful in the investigation of treatments to replace damaged photoreceptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells.

    Science.gov (United States)

    Conley, Sabena M; Zhu, Xiang-Yang; Eirin, Alfonso; Tang, Hui; Lerman, Amir; van Wijnen, Andre J; Lerman, Lilach O

    2018-02-20

    Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Domestic pigs consumed a lean or obese diet (n=6 each) for 16weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change>1.4, pinsulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS. Copyright © 2017. Published by Elsevier B.V.

  11. A Swine Model of Percutaneous Intracoronary Ethanol Induced Acute Myocardial Infarction and Ischemic Mitral Regurgitation.

    Science.gov (United States)

    Shi, Weiwei; McIver, Bryant V; Kalra, Kanika; Sarin, Eric L; Schmarkey, Susan; Duggan, Michael; Thourani, Vinod H; Guyton, Robert A; Padala, Muralidhar

    2017-08-01

    Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

  12. Host specific differences alter the requirement for certain Salmonella genes during swine colonization.

    Science.gov (United States)

    Bearson, Bradley L; Bearson, Shawn M D

    2011-06-02

    The pathogenic potential of Salmonella is determined during the complex interaction between pathogen and host, requiring optimal regulation of multiple bacterial genetic systems within variable in vivo environments. The mouse model of systemic disease has been an extremely productive model to investigate the pathogenesis of Salmonella enterica serovar Typhimurium (S. Typhimurium). Although the mouse model is a widely used paradigm for studying the pathogenesis of systemic disease caused by Salmonella, investigations concerning food safety interventions should employ natural hosts to examine gastrointestinal colonization by Salmonella. Recent research has demonstrated specific differences in the attenuation of certain S. Typhimurium mutants in mice compared to swine. This variation in pathogenesis between the mouse model and pigs for the S. Typhimurium mutants is presumably dependent upon either the requirements for specific gene products during systemic disease (mouse) versus gastrointestinal colonization (pig) or host specific differences. In addition, host specific diversity in Salmonella colonization of swine has also been described in comparison to other food-producing animals, including cattle and chickens. Differences in Salmonella colonization and pathogenesis across diverse animal species highlight the importance of species-specific studies of gastrointestinal colonization for the development of Salmonella interventions to enhance pork safety. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Multiple exposures to swine barn air induce lung inflammation and airway hyper-responsiveness

    Directory of Open Access Journals (Sweden)

    Willson Philip

    2005-06-01

    Full Text Available Abstract Background Swine farmers repeatedly exposed to the barn air suffer from respiratory diseases. However the mechanisms of lung dysfunction following repeated exposures to the barn air are still largely unknown. Therefore, we tested a hypothesis in a rat model that multiple interrupted exposures to the barn air will cause chronic lung inflammation and decline in lung function. Methods Rats were exposed either to swine barn (8 hours/day for either one or five or 20 days or ambient air. After the exposure periods, airway hyper-responsiveness (AHR to methacholine (Mch was measured and rats were euthanized to collect bronchoalveolar lavage fluid (BALF, blood and lung tissues. Barn air was sampled to determine endotoxin levels and microbial load. Results The air in the barn used in this study had a very high concentration of endotoxin (15361.75 ± 7712.16 EU/m3. Rats exposed to barn air for one and five days showed increase in AHR compared to the 20-day exposed and controls. Lungs from the exposed groups were inflamed as indicated by recruitment of neutrophils in all three exposed groups and eosinophils and an increase in numbers of airway epithelial goblet cells in 5- and 20-day exposure groups. Rats exposed to the barn air for one day or 20 days had more total leukocytes in the BALF and 20-day exposed rats had more airway epithelial goblet cells compared to the controls and those subjected to 1 and 5 exposures (P Conclusion We conclude that multiple exposures to endotoxin-containing swine barn air induce AHR, increase in mucus-containing airway epithelial cells and lung inflammation. The data also show that prolonged multiple exposures may also induce adaptation in AHR response in the exposed subjects.

  14. The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Timothy A. Johnson

    2017-08-01

    Full Text Available Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome and phage population dynamics (fecal dsDNA viromes. Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66 related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1, suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ≤0.07, suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration.

  15. The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome

    Science.gov (United States)

    Johnson, Timothy A.; Severin, Andrew J.; Bayles, Darrell O.; Nasko, Daniel J.; Wommack, K. Eric; Howe, Adina

    2017-01-01

    ABSTRACT Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66) related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1), suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ≤0.07), suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration. PMID:28790203

  16. Genetic alterations during radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Kodama, Seiji

    1995-01-01

    This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

  17. Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury.

    Science.gov (United States)

    Xu, Tong; Wang, Cunlian; Zhang, Ruihua; Xu, Mingju; Liu, Baojian; Wei, Dong; Wang, Guohua; Tian, Shufei

    2015-10-01

    Oxidative stress injury is an important pathogenesis of influenza virus in critically ill patients. The present study investigated the efficacy of carnosine, an antioxidant and free radical scavenger, on a model of acute lung injury (ALI) induced by H9N2 swine influenza virus. Female specific-pathogen-free BALB/c mice were randomized into four groups and treated as follows: (1) H9N2 group, (2) mock control group, (3) H9N2+carnosine group and (4) carnosine control group. The H9N2 group mice were inoculated intranasally with A/Swine/Hebei/012/2008/ (H9N2) virus (100 μl) in allantoic fluid (AF), whilst mock-infected animals were intranasally inoculated with non-infectious AF. Carnosine [10 mg (kg body mass)- 1] was administered orally (100 μl) for 7 days consecutively. The survival rate, lung water content, TNF-α and IL-1β levels, lung histopathology, myeloperoxidase (MPO) activity, and Toll-like receptor (TLR)-4 levels were determined at 2, 4, 6, 8 and 14 days after inoculation. Carnosine treatment effectively decreased the mortality (43 versus 75 %, P lungs and decreased the lung wet/dry mass ratio (P lungs of infected mice (P < 0.05), which supported the use of carnosine for managing severe influenza cases.

  18. Early changes in microbial colonization selectively modulate intestinal enzymes, but not inducible heat shock proteins in young adult Swine.

    Directory of Open Access Journals (Sweden)

    Marie-Edith Arnal

    Full Text Available Metabolic diseases and obesity are developing worldwide in a context of plethoric intake of high energy diets. The intestine may play a pivotal role due to diet-induced alterations in microbiota composition and increased permeability to bacterial lipopolysaccharide inducing metabolic inflammation. Early programming of metabolic disorders appearing in later life is also suspected, but data on the intestine are lacking. Therefore, we hypothesized that early disturbances in microbial colonization have short- and long-lasting consequences on selected intestinal components including key digestive enzymes and protective inducible heat shock proteins (HSP. The hypothesis was tested in swine offspring born to control mothers (n = 12 or mothers treated with the antibiotic amoxicillin around parturition (n = 11, and slaughtered serially at 14, 28 and 42 days of age to assess short-term effects. To evaluate long-term consequences, young adult offspring from the same litters were offered a normal or a fat-enriched diet for 4 weeks between 140 and 169 days of age and were then slaughtered. Amoxicillin treatment transiently modified both mother and offspring microbiota. This was associated with early but transient reduction in ileal alkaline phosphatase, HSP70 (but not HSP27 and crypt depth, suggesting a milder or delayed intestinal response to bacteria in offspring born to antibiotic-treated mothers. More importantly, we disclosed long-term consequences of this treatment on jejunal alkaline phosphatase (reduced and jejunal and ileal dipeptidylpeptidase IV (increased and decreased, respectively of offspring born to antibiotic-treated dams. Significant interactions between early antibiotic treatment and later diet were observed for jejunal alkaline phosphatase and sucrase. By contrast, inducible HSPs were not affected. In conclusion, our data suggest that early changes in bacterial colonization not only modulate intestinal architecture and function transiently

  19. Determination of the postmortem interval by Laser Induced Breakdown Spectroscopy using swine skeletal muscles

    Science.gov (United States)

    Marín-Roldan, A.; Manzoor, S.; Moncayo, S.; Navarro-Villoslada, F.; Izquierdo-Hornillos, R. C.; Caceres, J. O.

    2013-10-01

    Skin and muscle samples are useful to discriminate individuals as well as their postmortem interval (PMI) in crime scenes and natural or caused disasters. In this study, a simple and fast method based on Laser Induced Breakdown Spectroscopy (LIBS) has been developed to estimate PMI using swine skeletal muscle samples. Environmental conditions (moisture, temperature, fauna, etc.) having strong influence on the PMI determination were considered. Time-dependent changes in the emission intensity ratio for Mg, Na, Hα and K were observed, as a result of the variations in their concentration due to chemical reactions in tissues and were correlated with PMI. This relationship, which has not been reported previously in the forensic literature, offers a simple and potentially valuable means of estimating the PMI.

  20. Characterization and therapeutic alteration of the biliary excretion and enterohepatic cycling of zearalenone in sexually immature swine

    Energy Technology Data Exchange (ETDEWEB)

    Biehl, M.L.

    1989-01-01

    The purposes of these studies were to characterize the biliary excretion and enterohepatic cycling (EHC) of zearlenone (ZEN) in young pigs and to therapeutically mimic the effect of bile removal in enhancing body clearance of ZEN. ({sup 3}H)ZEN was administered intravenously (IV), orally, and intravenous with bile removal (IVB) to female, 10- to 14-week old pigs. The biological half of total plasma radioactivity in IV and orally dosed pigs (86.6h) was much greater than that of IVB pigs (3.34h). Secondary peaks in plasma metabolite concentrations were seen during the terminal elimination phase in IV and oral animals and metabolites were still detectable at 48h postdosing. In IVB pigs, these peaks were absent, relative metabolite profiles were altered and ZEN and metabolites were no longer detectable after 16 hrs. Biliary recovery of radioactivity, principally as glucuronide conjugates was extensive (45.61 {plus minus} 4.73%) and significantly greater than that of fecal recovery in IV (6.56 {plus minus} 0.78%) or oral (21.74 {plus minus} 1.56%) pigs. Absorption of ZEN from the intestinal tract was estimated to be 80-85%. Intraduodenal administration of bile containing ({sup 3}H)ZEN and glucuronide metabolites resulted in recovery of 64.5 {plus minus} 4.89% of the dose in bile, 20.78 {plus minus} 3.94% in urine, and the presence of glucuronide conjugates of ZEN and {alpha}-zearalenol (ZEL) in portal and jugular plasma. Evidence for metabolism of ZEN by the intestinal mucosa was present. A pharmacokinetic compartmental model for the disposition of intravenously administered ZEN and metabolites in swine is proposed. The mean terminal elimination rate and corresponding biological half life for ZEN in IV pigs was 0.03h{sup {minus}1} and 28.97h, respectively, and for IVB pigs 0.24h {sup {minus}1} and 2.94h.

  1. Acute respiratory distress syndrome induced by a swine 2009 H1N1 variant in mice.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available Acute respiratory distress syndrome (ARDS induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus.Mice were inoculated with A/swine/Shandong/731/2009 (SD/09, which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8-10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines.These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus.

  2. N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury.

    Science.gov (United States)

    Zhang, Rui-Hua; Li, Chun-Hong; Wang, Cun-Lian; Xu, Ming-Ju; Xu, Tong; Wei, Dong; Liu, Bao-Jian; Wang, Guo-Hua; Tian, Shu-Fei

    2014-09-01

    The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on H9N2 swine influenza virus-induced acute lung injury (ALI) were investigated in mice. BALB/c mice were inoculated intranasally with 10(7) 50% tissue culture infective doses (TCID(50)) of A/swine/HeBei/012/2008/(H9N2) viruses with or without NAC treatments to induce ALI model. The result showed that pulmonary inflammation, pulmonary edema, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6, IL-1β and CXCL-10 in BALF were attenuated by NAC. Moreover, our data showed that NAC significantly inhibited the levels of TLR4 protein and TLR4 mRNA in the lungs. Pharmacological inhibitors of TLR4 (E5564) exerted similar effects like those determined for NAC in H9N2 swine influenza virus-infected mice. These results suggest that antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Swine mycoplasmoses

    DEFF Research Database (Denmark)

    Kobisch, M.; Friis, N.F.

    1996-01-01

    /tonsillar samples and can induce antibodies in blood and joint fluid. Predisposing factors play an important role. M. flocculare is widely distributed in swine, in normal and pneumonic lungs and in nasal cavities, but no pathogenic capability has been described. There is great interest in this mycoplasma because......Mycoplasma hyopneumoniae is the primary agent of enzootic pneumonia in pigs. The lung lesions, generally observed in young pigs, are characterised by a hyperplasia of the epithelial cells and an increased perivascular and peribronchiolar accumulation of mononuclear cells. Following M. hyopneumoniae...

  4. Pseudorabies Virus Induces Viability Changes and Oxidative Stress in Swine Testis Cell-Line

    Directory of Open Access Journals (Sweden)

    Xiao-Zhan Zhang§1, Ye Chen§1, Hong-Liang Huang§2, Dong-Lei Xu1, Chang-Bao Ren2, Bi-Tao Liu1, Shuo Su1 and Zhao-Xin Tang1, 2*

    2013-11-01

    Full Text Available In this study, we evaluated the association between pseudorabies (PRV virus-induced viability changes and oxidative stress in vitro cultivated swine testis (ST cells. The kinetic of 2, 12, 24, 36 and 48 h during the cell culture with PRV by using a multiplicity of infection (MOI of 1 TCID50 per cell were adopted. The results suggested a complex relation between cell viability and oxidative stress during PRV infection. In the early stages of PRV infection, the cell viability was higher than the control group, and the state of cellular oxidative stress remained relatively stable. After 24 h, the cell viability began to decrease, and the amount of the cellular malondialdehyde in ST cells increased significantly, and the activities of superoxide dismutase and catalase decreased significantly (P<0.05. Meanwhile, the rising concentrations of cellular hydrogen peroxide were detected prior to the changes in cell viability and oxidative stress. In conclusion, the PRV infection of ST cells leads to oxidative stress, and this stress could play a crucial role on the cell viability as the PRV infection time progresses.

  5. Determination of the postmortem interval by Laser Induced Breakdown Spectroscopy using swine skeletal muscles

    International Nuclear Information System (INIS)

    Marín-Roldan, A.; Manzoor, S.; Moncayo, S.; Navarro-Villoslada, F.; Izquierdo-Hornillos, R.C.; Caceres, J.O.

    2013-01-01

    Skin and muscle samples are useful to discriminate individuals as well as their postmortem interval (PMI) in crime scenes and natural or caused disasters. In this study, a simple and fast method based on Laser Induced Breakdown Spectroscopy (LIBS) has been developed to estimate PMI using swine skeletal muscle samples. Environmental conditions (moisture, temperature, fauna, etc.) having strong influence on the PMI determination were considered. Time-dependent changes in the emission intensity ratio for Mg, Na, Hα and K were observed, as a result of the variations in their concentration due to chemical reactions in tissues and were correlated with PMI. This relationship, which has not been reported previously in the forensic literature, offers a simple and potentially valuable means of estimating the PMI. - Highlights: • LIBS has been applied for Postmortem Interval estimation. • Environmental and sample storage conditions have been considered. • Significant correlation of elemental emission intensity with PMI has been observed. • Pig skeletal muscle samples have been used

  6. Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression.

    Science.gov (United States)

    Dlugolenski, Daniel; Jones, Les; Howerth, Elizabeth; Wentworth, David; Tompkins, S Mark; Tripp, Ralph A

    2015-05-01

    Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment

  7. Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

    Science.gov (United States)

    Dlugolenski, Daniel; Jones, Les; Howerth, Elizabeth; Wentworth, David; Tompkins, S. Mark

    2015-01-01

    ABSTRACT Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. IMPORTANCE Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza

  8. Vodka and wine consumption in a swine model of metabolic syndrome alters insulin signaling pathways in the liver and skeletal muscle.

    Science.gov (United States)

    Elmadhun, Nassrene Y; Lassaletta, Antonio D; Chu, Louis M; Bianchi, Cesario; Sellke, Frank W

    2012-09-01

    The purpose of this study was to examine the effects of alcohol in the context of metabolic syndrome on insulin signaling pathways in the liver and skeletal muscle. Twenty-six Yorkshire swine were fed a hypercaloric, high-fat diet for 4 weeks then split into 3 groups: hypercholesterolemic diet alone (HCC, n = 9), hypercholesterolemic diet with vodka (HCVOD, n = 9), and hypercholesterolemic diet with wine (HCW, n = 8) for 7 weeks. Animals underwent intravenous dextrose challenge before euthanasia and tissue collection. HCC, HCVOD, and HCW groups had similar blood fasting glucose levels, liver function test, and body mass index. Thirty and 60 minutes after dextrose infusion, HCVOD and HCW groups had significantly increased blood glucose levels compared with the HCC group. The HCW group had significantly increased levels of insulin compared with the HCC group. Immunoblotting in skeletal muscle demonstrated that alcohol up-regulates p-IRS1, IRS2, AKT, AMPKα, PPARα, Fox01, and GLUT4. In the liver, HCW had up-regulation of AKT, AMPKα, and GLUT4 compared with HCC. Skeletal muscle immunohistochemistry demonstrated increased sarcolemmal expression of GLUT4 in both alcohol groups compared with HCC. Moderate alcohol consumption in a swine model of metabolic syndrome worsens glucose metabolism by altering activation of the insulin signaling pathway in the liver and skeletal muscle. Copyright © 2012 Mosby, Inc. All rights reserved.

  9. Occupational Hazards of Fyling Pigs: A Swine model of Hypobaric Induced Neuronal Injury

    Science.gov (United States)

    2017-04-22

    59 MDW/SGVU SUBJECT: Profess ional Presentation Approval 18 APR 20 17 1. Your paper, entitled Occupational Hazards of Flving Pigs : A Swine Model of...RANK1’GRAOE, ’TITlE OF RE \\llEW’ER 45. REVIEWER 31GNAT’IJRE so_ o,o.TE FR-C"\\/.OUS EDlnCNB ARE Ol>SCLETE OCCU PATIONAL HAZARDS OF FLYING PIGS : A SWINE...necessitates intubation or anesthetization of exposure subjects, miniature pigs (Sus scrofa domestica) were repetiti vely exposed to non-hypoxic

  10. Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.

    Science.gov (United States)

    Sommer, Wiebke; Buechler, Gwen; Jansson, Katharina; Avsar, Murat; Knöfel, Ann-Kathrin; Salman, Jawad; Hoeffler, Klaus; Siemeni, Thierry; Gottlieb, Jens; Karstens, Johann H; Jonigk, Danny; Reising, Ansgar; Haverich, Axel; Strüber, Martin; Warnecke, Gregor

    2017-04-01

    Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism. © 2017 Steunstichting ESOT.

  11. Endometriosis induces gut microbiota alterations in mice.

    Science.gov (United States)

    Yuan, Ming; Li, Dong; Zhang, Zhe; Sun, Huihui; An, Min; Wang, Guoyun

    2018-02-15

    What happens to the gut microbiota during development of murine endometriosis? Mice with the persistence of endometrial lesions for 42 days develop a distinct composition of gut microbiota. Disorders in the immune system play fundamental roles in changing the intestinal microbiota. No study has used high-throughput DNA sequencing to show how endometriosis changes the gut microbiota, although endometriosis is accompanied by abnormal cytokine expression and immune cell dysfunction. This study includes a prospective and randomized experiment on an animal endometriosis model induced via the intraperitoneal injection of endometrial tissues. The mice were divided into endometriosis and mock groups and were sacrificed at four different time points for model confirmation and fecal sample collection. To detect gut microbiota, 16S ribosomal-RNA gene sequencing was performed. Alpha diversity was used to analyze the complexity and species diversity of the samples through six indices. Beta diversity analysis was utilized to evaluate the differences in species complexity. Principal coordinate analysis and unweighted pair-group method with arithmetic means clustering were performed to determine the clustering features. The microbial features differentiating the fecal microbiota were characterized by linear discriminant analysis effect size method. The endometriosis and mock mice shared similar diversity and richness of gut microbiota. However, different compositions of gut microbiota were detected 42 days after the modeling. Among the discriminative concrete features, the Firmicutes/Bacteroidetes ratio was elevated in mice with endometriosis, indicating that endometriosis may induce dysbiosis. Bifidobacterium, which is known as a commonly used probiotic, was also increased in mice with endometriosis. N/A. More control groups should be further studied to clarify the specificity of the dysbiosis induced by endometriosis. This study was performed only on mice. Thus, additional data

  12. Swine Influenza (Swine Flu) in Pigs

    Science.gov (United States)

    ... Avian Swine Variant Pandemic Other Key Facts about Swine Influenza (Swine Flu) in Pigs Language: English (US) Español Recommend on Facebook Tweet ... visit the CDC seasonal flu website . What is Swine Influenza? Swine Influenza (swine flu) is a respiratory ...

  13. Evidence for retrovirus in miniature swine with radiation-induced leukemia or metaplasia

    International Nuclear Information System (INIS)

    Frazier, M.E.

    1985-01-01

    Biochemical and morphological evidence indicates that a type-C retrovirus is present in the blood of swine (both leukemic and nonleukemic) exposed to strontium-90 radiation. Nonexposed swine that were leukemic also had virus present. The virus was shown to contain and RNase-sensitive DNA polymerase activity with cation, detergent and template requirements similar to those of known viral reverse transcriptases. The buoyant density of the virus was 1.14 to 1.16 g/ml, whih can be converted, by treatment with ether, to a virion core having a density of 1.2 to 1.23 g/ml. Linear regression analysis indicated a correlation between virus-associated DNA polymerase activity and the number of blast cells in the peripheral blood. (Author)

  14. Pollutant Induced Altered Behaviours in Fish: A Review of Selected ...

    African Journals Online (AJOL)

    Pollutant Induced Altered Behaviours in Fish: A Review of Selected Literature. UU Gabriel, B Uedeme-Naa, OA Akinrotimi. Abstract. The issue of environmental pollution has become a global phenomenon in recent years, of importance is the aquatic environment, which acts as a sink for these contaminants which pose ...

  15. Extracellular ATP does not induce P2X7 receptor-dependent responses in cultured renal- and liver-derived swine macrophages

    Directory of Open Access Journals (Sweden)

    Takato Takenouchi

    2014-01-01

    Full Text Available The P2X7 receptor (P2X7R is an ATP-gated cation channel that is abundantly expressed in monocytes/macrophages. P2X7R activation by ATP results in various cellular responses including Ca2+ influx, membrane pore formation, and cytokine secretion. Since P2X7R has low affinity for ATP, high concentrations of ATP (in the mM range are generally required to activate this receptor in vitro. Functional expression of P2X7R has been detected in monocytes/macrophages obtained from different animal species including humans, rodents, dogs, and bovines, but so far it has not been detected in swine (Sus scrofa. In this study, we investigated the expression and functions of P2X7R in swine macrophages, which were isolated from mixed primary cultures of swine kidney or liver tissue. The P2X7R mRNA and protein expression observed in the swine macrophages was comparable to that seen in a c-myc-immortalized mouse kidney-derived clonal macrophage cell line (KM-1. However, extracellular ATP did not induce P2X7R-dependent sustained Ca2+ influx, membrane pore formation, or the secretion of the bioactive cytokine interleukin-1β in the swine macrophages, whereas these responses were clearly observed in the mouse KM-1 cells after stimulation with millimolar concentrations of ATP as a positive control. These findings suggest that the ATP/P2X7R pathway is impaired in swine macrophages at least in the culture conditions used in the present study.

  16. An avirulent chimeric Pestivirus with altered cell tropism protects pigs against lethal infection with classical swine fever virus

    International Nuclear Information System (INIS)

    Reimann, Ilona; Depner, Klaus; Trapp, Sascha; Beer, Martin

    2004-01-01

    A chimeric Pestivirus was constructed using an infectious cDNA clone of bovine viral diarrhea virus (BVDV) [J. Virol. 70 (1996) 8606]. After deletion of the envelope protein E2-encoding region, the respective sequence of classical swine fever virus (CSFV) strain Alfort 187 was inserted in-frame resulting in plasmid pA/CP7 E 2alf. After transfection of in vitro-transcribed CP7 E 2alf RNA, autonomous replication of chimeric RNA in bovine and porcine cell cultures was observed. Efficient growth of chimeric CP7 E 2alf virus, however, could only be demonstrated on porcine cells, and in contrast to the parental BVDV strain CP7, CP7 E 2alf only inefficiently infected and propagated in bovine cells. The virulence, immunogenicity, and 'marker vaccine' properties of the generated chimeric CP7 E 2alf virus were determined in an animal experiment using 27 pigs. After intramuscular inoculation of 1 x 10 7 TCID 50 , CP7 E 2alf proved to be completely avirulent, and neither viremia nor virus transmission to contact animals was observed; however, CSFV-specific neutralizing antibodies were detected from day 11 after inoculation. In addition, sera from all animals reacted positive in an E2-specific CSFV-antibody ELISA, but were negative for CSFV-E RNS -specific antibodies as determined with a CSFV marker ELISA. After challenge infection with highly virulent CSFV strain Eystrup, pigs immunized with CP7 E 2alf were fully protected against clinical signs of CSFV infection, viremia, and shedding of challenge virus, and almost all animals scored positive in a CSFV marker ELISA. From our results, we conclude that chimeric CP7 E 2alf may not only serve as a tool for a better understanding of Pestivirus attachment, entry, and assembly, but also represents an innocuous and efficacious modified live CSFV 'marker vaccine'

  17. Prevention of swine dysentery with a combination of lincomycin and spectinomycin and resistance of swine dysentery to tylosin and sodium arsanilate.

    Science.gov (United States)

    Olson, L D; Rodabaugh, D E

    1976-07-01

    The addition of a combination of lincomycin and spectinomycin to feed at the total concentrations of 44 and 77 mg/kg, beginning at the time of exposure and continuing for 8 weeks, prevented experimentally induced swine dysentery in swine. The disease did not develop after the medication was withdrawn. In contrast, swine dysentery, similar to that seen in the nonmedicated swine, did develop in simultaneously exposed swine treated with feed containing either 44 mg of tylosin or 99 mg sodium arsanilate/kg. The swine fed sodium arsanilate and which developed hemorrhagic diarrhea had a more severe form of this type of diarrhea than did the nonmedicated swine. After reexposure to inefective inoculum of swine dysentery 86 days after initial exposure, all remaining swine previously medicated with either tylosin or sodium arsanilate and all nonmedicated swine were immune; whereas 17 of the 24 swine fed the combination of lincomycin and spectinomycin were susceptible to swine dysentery and developed diarrhea.

  18. Early Changes in Microbial Colonization Selectively Modulate Intestinal Enzymes, but Not Inducible Heat Shock Proteins in Young Adult Swine

    NARCIS (Netherlands)

    Arnal, M.E.; Zhang, J.; Messori, S.; Bosi, P.; Smidt, H.; Lallès, J.P.

    2014-01-01

    Metabolic diseases and obesity are developing worldwide in a context of plethoric intake of high energy diets. The intestine may play a pivotal role due to diet-induced alterations in microbiota composition and increased permeability to bacterial lipopolysaccharide inducing metabolic inflammation.

  19. Avian influenza A virus PB2 promotes interferon type I inducing properties of a swine strain in porcine dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Ocana-Macchi, Manuela; Ricklin, Meret E.; Python, Sylvie; Monika, Gsell-Albert [Institute of Virology and Immunoprophylaxis, Mittelhaeusern (Switzerland); Stech, Juergen; Stech, Olga [Friedrich-Loeffler Institut, Greifswald-Insel Riems (Germany); Summerfield, Artur, E-mail: artur.summerfield@ivi.admin.ch [Institute of Virology and Immunoprophylaxis, Mittelhaeusern (Switzerland)

    2012-05-25

    The 2009 influenza A virus (IAV) pandemic resulted from reassortment of avian, human and swine strains probably in pigs. To elucidate the role of viral genes in host adaptation regarding innate immune responses, we focussed on the effect of genes from an avian H5N1 and a porcine H1N1 IAV on infectivity and activation of porcine GM-CSF-induced dendritic cells (DC). The highest interferon type I responses were achieved by the porcine virus reassortant containing the avian polymerase gene PB2. This finding was not due to differential tropism since all viruses infected DC equally. All viruses equally induced MHC class II, but porcine H1N1 expressing the avian viral PB2 induced more prominent nuclear NF-{kappa}B translocation compared to its parent IAV. The enhanced activation of DC may be detrimental or beneficial. An over-stimulation of innate responses could result in either pronounced tissue damage or increased resistance against IAV reassortants carrying avian PB2.

  20. Avian influenza A virus PB2 promotes interferon type I inducing properties of a swine strain in porcine dendritic cells

    International Nuclear Information System (INIS)

    Ocaña-Macchi, Manuela; Ricklin, Meret E.; Python, Sylvie; Monika, Gsell-Albert; Stech, Jürgen; Stech, Olga; Summerfield, Artur

    2012-01-01

    The 2009 influenza A virus (IAV) pandemic resulted from reassortment of avian, human and swine strains probably in pigs. To elucidate the role of viral genes in host adaptation regarding innate immune responses, we focussed on the effect of genes from an avian H5N1 and a porcine H1N1 IAV on infectivity and activation of porcine GM-CSF-induced dendritic cells (DC). The highest interferon type I responses were achieved by the porcine virus reassortant containing the avian polymerase gene PB2. This finding was not due to differential tropism since all viruses infected DC equally. All viruses equally induced MHC class II, but porcine H1N1 expressing the avian viral PB2 induced more prominent nuclear NF-κB translocation compared to its parent IAV. The enhanced activation of DC may be detrimental or beneficial. An over-stimulation of innate responses could result in either pronounced tissue damage or increased resistance against IAV reassortants carrying avian PB2.

  1. Modified live virus vaccine induces a distinct immune response profile compared to inactivated influenza A virus vaccines in swine

    Science.gov (United States)

    Genetic and antigenic diversity within H1 influenza A virus (IAV) subtypes circulating in swine is increasing. The need for cross-protective influenza vaccines in swine is necessary as the virus becomes more diverse. This study compared the humoral and cell-mediated immune response of modified live ...

  2. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically de...

  3. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    Science.gov (United States)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  4. Maternal antibiotic-induced early changes in microbial colonization selectively modulate colonic permeability and inducible heat shock proteins, and digesta concentrations of alkaline phosphatase and TLR-stimulants in swine offspring.

    Directory of Open Access Journals (Sweden)

    Marie-Edith Arnal

    Full Text Available Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12 or mothers treated with the antibiotic (ATB amoxicillin around parturition (n = 11. Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic

  5. Membrane alterations induced by nonstructural proteins of human norovirus.

    Directory of Open Access Journals (Sweden)

    Sylvie Y Doerflinger

    2017-10-01

    Full Text Available Human noroviruses (huNoV are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4 variants. The viral nonstructural (NS proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV. Characteristic membrane alterations induced by ORF1 expression resembled those found in MNV infected cells, consisting of vesicle accumulations likely built from the endoplasmic reticulum (ER which included single membrane vesicles (SMVs, double membrane vesicles (DMVs and multi membrane vesicles (MMVs. In-depth analysis using electron tomography suggested that MMVs originate through the enwrapping of SMVs with tubular structures similar to mechanisms reported for picornaviruses. Expression of GII.4 NS1-2, NS3 and NS4 fused to GFP revealed distinct membrane alterations when analyzed by correlative light and electron microscopy. Expression of NS1-2 induced proliferation of smooth ER membranes forming long tubular structures that were affected by mutations in the active center of the putative NS1-2 hydrolase domain. NS3 was associated with ER membranes around lipid droplets (LDs and induced the formation of convoluted membranes, which were even more pronounced in case of NS4. Interestingly, NS4 was the only GII.4 protein capable of inducing SMV and DMV formation when expressed individually. Our work provides the first ultrastructural analysis of norovirus GII.4 induced vesicle clusters and suggests that their morphology and biogenesis is most similar to picornaviruses. We further identified NS4 as a key factor in the formation of membrane alterations of huNoV and

  6. Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

    Science.gov (United States)

    Suez, Jotham; Korem, Tal; Zeevi, David; Zilberman-Schapira, Gili; Thaiss, Christoph A; Maza, Ori; Israeli, David; Zmora, Niv; Gilad, Shlomit; Weinberger, Adina; Kuperman, Yael; Harmelin, Alon; Kolodkin-Gal, Ilana; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran

    2014-10-09

    Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.

  7. Aging induced ER stress alters sleep and sleep homeostasis

    Science.gov (United States)

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2014-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

  8. Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.

    Science.gov (United States)

    Brown, Marishka K; Chan, May T; Zimmerman, John E; Pack, Allan I; Jackson, Nicholas E; Naidoo, Nirinjini

    2014-06-01

    Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Investigation of cadmium-induced alterations in renal glomerular function

    International Nuclear Information System (INIS)

    Long, T.J.

    1982-01-01

    This research was designed to test the hypothesis that certain aspects of cadmium-induced renal dysfunction are the result of glomerular, rather than classic tubular, injury. To determine whether cadmium-induced proteinuria was due to altered glomerular function, cadmium was administered chronically at a concentration of 185 ppm in the drinking water. This protocol resulted in the production of proteinuria which when analyzed by high pressure liquid chromatography and radioimmunoassay was indistinguishable from that occurring in control rats. Glomerular filtration rate, renal blood flow, and filtration fraction were all significantly depressed after 20-30 weeks of exposure. In order to further investigate these alterations in glomerular function, an acute exposure model was developed. It was found that a single i.p. injection of cadmium in mercaptoethanol resulted in the onset of acute renal failure. The clinical picture was characterized by a reduction in glomerular filtrate rate of 50-90% within 24 hours, with partial to total recovery occurring by day 7 post-exposure. Histological evidence indicated that to a large extent the reduction in GFR was due to tubular blockade and/or backleak of filtrate across damaged tubules

  10. Myeloid leukemias and virally induced lymphomas in miniature inbred swine; development of a large animal tumor model

    Directory of Open Access Journals (Sweden)

    RAIMON eDURAN-STRUUCK

    2015-11-01

    Full Text Available The lack of a large animal transplantable tumor model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable tumor model a close reality. Here, we discuss our experience with myeloid and lymphoid tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable tumor model.

  11. Determination of fluoroquinolone antibiotics via ionic-liquid-based, salt-induced, dual microextraction in swine feed.

    Science.gov (United States)

    Wang, Huili; Gao, Ming; Gao, Jiajia; Yu, Nana; Huang, Hong; Yu, Qing; Wang, Xuedong

    2016-09-01

    In conventional microextraction procedures, the disperser (organic solvent or ionic liquid) is left in the aqueous phase and discarded after finishing the microextraction process. Because the disperser is water-soluble, it results in low extraction recovery for polar compounds. In this investigation, an ionic-liquid-based microextraction (ILBME) was integrated with salting-out assisted liquid-liquid microextraction (SALLME) to build an ionic-liquid-based, salt-induced, dual microextraction (ILSDME) for isolation of five fluoroquinolone antibiotics (FQs) with high polarity (log P, -1.0 to 1.0). The proposed ILSDME method incorporates a dual microextraction by converting the disperser in the ILBME to the extractor in the SALLME. Optimization of key factors was conducted by integrating single-factor experiments and central composite design. The optimized experimental parameters were 80 μL [C8MIM][PF6] as extractor, 505 μL acetone as disperser, pH = 2.0, 4.1 min extraction time, and 4.2 g of Na2SO4. Under optimized conditions, high ERs (90.6-103.2 %) and low LODs (0.07-0.61 μg kg(-1)) were determined for five FQs in swine feed. Experimental precision based on RSDs was 1.4-5.2 % for intra-day and 2.4-6.9 % for inter-day analyses. The combination of ILBME with SALLME increased FQ recoveries by 15-20 % as compared with SALLME, demonstrating that the ILSDME method can enhance extraction efficiency for polar compounds compared to single-step microextraction. Therefore, the ILSDME method developed in this study has wide application for pretreatment of moderately to highly polar pollutants in complex matrices. Graphical Abstract A dual microextraction was developed by integrating ionic-liquid-based microextraction with salting-out assisted liquid-liquid microextraction for isolation of five fluoroquinolone antibiotics (FQs) with high polarity (log P = -1.0 to 1.0). The principle of dual microextraction is based on converting the remaining disperser from

  12. Tooth alterations in areas of bisphosphonate-induced osteonecrosis.

    Science.gov (United States)

    de Camargo Moraes, Paulo; Silva, Carolina Amália Barcellos; Soares, Andresa Borges; Passador-Santos, Fabrício; Corrêa, Maria Elvira Pizzigatti; de Araújo, Ney Soares; de Araújo, Vera Cavalcanti

    2015-03-01

    Osteonecrosis of the jaw is a potential side effect when using bisphosphonates. Most studies on the effects of bisphosphonates on teeth have been conducted in vitro or in animal models of tooth development. Therefore, the aim of this study was to describe alterations found in human teeth extracted from areas of bisphosphonate-induced osteonecrosis. Using a retrospective study design, 16 teeth from 13 patients were extracted from areas of bisphosphonate-induced osteonecrosis during surgical debridement. The specimens were decalcified and embedded in paraffin. A series of 5-μm sections were prepared, stained with hematoxylin and eosin (H&E) and observed under a light microscope. The majority of the patients were female (53.85 %), with a mean age of 60.23 ± 13.18 years. Zoledronate (IV) was the most common bisphosphonate used (92.3 %), over a mean period of 2 years. The commonest alteration observed was hypercementosis (87.5 %), followed by pulpar necrosis (81.25 %), pulp stones attached to the dentine and loose pulp stones in the pulp chamber and root canals in addition to linear calcifications (68.75 %), dentinoid/osteoid material formation (18.75 %), and dental ankylosis (6.25 %). Patients undergoing bisphosphonate therapy present diverse tooth alterations, which should be closely monitored by clinicians to prevent complications. It is paramount that the teeth involved in oral lesions are always examined. Attention should be drawn to the need to establish preventive measures, in terms of dental treatment, for patients prior to starting bisphosphonate therapy.

  13. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

    Directory of Open Access Journals (Sweden)

    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  14. Virus Innexins induce alterations in insect cell and tissue function.

    Science.gov (United States)

    Hasegawa, Daniel K; Erickson, Stephanie L; Hersh, Bradley M; Turnbull, Matthew W

    2017-04-01

    Polydnaviruses are dsDNA viruses that induce immune and developmental alterations in their caterpillar hosts. Characterization of polydnavirus gene families and family members is necessary to understand mechanisms of pathology and evolution of these viruses, and may aid to elucidate the role of host homologues if present. For example, the polydnavirus vinnexin gene family encodes homologues of insect gap junction genes (innexins) that are expressed in host immune cells (hemocytes). While the roles of Innexin proteins and gap junctions in insect immunity are largely unclear, we previously demonstrated that Vinnexins form functional gap junctions and alter the junctional characteristics of a host Innexin when co-expressed in paired Xenopus oocytes. Here, we test the effect of ectopic vinnexin expression on host cell physiology using both a lepidopteran cell culture model and a dipteran whole organism model. Vinnexin expression in the cell culture system resulted in gene-specific alterations in cell morphology and a slight, but non-statistically significant, reduction in gap junction activity as measured by dye transfer, while ectopic expression of a lepidopteran innexin2 gene led to morphological alterations and increase in gap junction activity. Global ectopic expression in the model dipteran, Drosophila melanogaster, of one vinnexin (vinnexinG) or D. melanogaster innexin2 (Dm-inx2) resulted in embryonic lethality, while expression of the other vinnexin genes had no effect. Furthermore, ectopic expression of vinnexinG, but not other vinnexin genes or Dm-inx2, in D. melanogaster larval gut resulted in developmental arrest in the pupal stage. These data indicate the vinnexins likely have gene-specific roles in host manipulation. They also support the use of Drosophila in further analysis of the role of Vinnexins and other polydnavirus genes in modifying host physiological processes. Finally, our findings suggest the vinnexin genes may be useful to perturb and

  15. Microcirculation alterations in experimentally induced gingivitis in dogs.

    Science.gov (United States)

    Matsuo, Masato; Okudera, Toshimitsu; Takahashi, Shun-Suke; Wada-Takahashi, Satoko; Maeda, Shingo; Iimura, Akira

    2017-01-01

    The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.

  16. Treadmill Exercise Induces Hippocampal Astroglial Alterations in Rats

    Directory of Open Access Journals (Sweden)

    Caren Bernardi

    2013-01-01

    Full Text Available Physical exercise effects on brain health and cognitive performance have been described. Synaptic remodeling in hippocampus induced by physical exercise has been described in animal models, but the underlying mechanisms remain poorly understood. Changes in astrocytes, the glial cells involved in synaptic remodeling, need more characterization. We investigated the effect of moderate treadmill exercise (20 min/day for 4 weeks on some parameters of astrocytic activity in rat hippocampal slices, namely, glial fibrillary acidic protein (GFAP, glutamate uptake and glutamine synthetase (GS activities, glutathione content, and S100B protein content and secretion, as well as brain-derived neurotrophic factor (BDNF levels and glucose uptake activity in this tissue. Results show that moderate treadmill exercise was able to induce a decrease in GFAP content (evaluated by ELISA and immunohistochemistry and an increase in GS activity. These changes could be mediated by corticosterone, whose levels were elevated in serum. BDNF, another putative mediator, was not altered in hippocampal tissue. Moreover, treadmill exercise caused a decrease in NO content. Our data indicate specific changes in astrocyte markers induced by physical exercise, the importance of studying astrocytes for understanding brain plasticity, as well as reinforce the relevance of physical exercise as a neuroprotective strategy.

  17. Comparison of immune responses against foot-and-mouth disease virus induced by fusion proteins using the swine IgG heavy chain constant region or β-galactosidase as a carrier of immunogenic epitopes

    International Nuclear Information System (INIS)

    Li Guangjin; Chen Weizao; Yan Weiyao; Zhao Kai; Liu Mingqiu; Zhang Jun; Fei Liang; Xu Quanxing; Sheng Zutian; Lu Yonggan; Zheng Zhaoxin

    2004-01-01

    Previously, we demonstrated that a fusion protein (Gal-FMDV) consisting of β-galactosidase and an immunogenic peptide, amino acids (141-160)-(21-40)-(141-160), of foot-and-mouth disease virus (FMDV) VP1 protein induced protective immune responses in guinea pigs and swine. We now designed a new potential recombinant protein vaccine against FMDV in swine. The immunogenic peptide, amino acids (141-160)-(21-40)-(141-160) from the VP1 protein of serotype O FMDV, was fused to the carboxy terminus of a swine immunoglobulin G single heavy chain constant region and expressed in Escherichia coli. The expressed fusion protein (IgG-FMDV) was purified and emulsified with oil adjuvant. Vaccination twice at an interval of 3 weeks with the emulsified IgG-FMDV fusion protein induced an FMDV-specific spleen proliferative T-cell response in guinea pigs and elicited high levels of neutralizing antibody in guinea pigs and swine. All of the immunized animals were efficiently protected against FMDV challenge. There was no significant difference between IgG-FMDV and Gal-FMDV in eliciting immunity after vaccination twice in swine. However, when evaluating the efficacy of a single inoculation of the fusion proteins, we found that IgG-FMDV could elicit a protective immune response in swine, while Gal-FMDV only elicited a weak neutralizing activity and could not protect the swine against FMDV challenge. Our results suggest that the IgG-FMDV fusion protein is a promising vaccine candidate for FMD in swine

  18. Multiple linear B-cell epitopes of classical swine fever virus glycoprotein E2 expressed in E.coli as multiple epitope vaccine induces a protective immune response

    Directory of Open Access Journals (Sweden)

    Wei Jian-Chao

    2011-07-01

    Full Text Available Abstract Classical swine fever is a highly contagious disease of swine caused by classical swine fever virus, an OIE list A pathogen. Epitope-based vaccines is one of the current focuses in the development of new vaccines against classical swine fever virus (CSFV. Two B-cell linear epitopes rE2-ba from the E2 glycoprotein of CSFV, rE2-a (CFRREKPFPHRMDCVTTTVENED, aa844-865 and rE2-b (CKEDYRYAISSTNEIGLLGAGGLT, aa693-716, were constructed and heterologously expressed in Escherichia coli as multiple epitope vaccine. Fifteen 6-week-old specified-pathogen-free (SPF piglets were intramuscularly immunized with epitopes twice at 2-week intervals. All epitope-vaccinated pigs could mount an anamnestic response after booster vaccination with neutralizing antibody titers ranging from 1:16 to 1:256. At this time, the pigs were subjected to challenge infection with a dose of 1 × 106 TCID50 virulent CSFV strain. After challenge infection, all of the rE2-ba-immunized pigs were alive and without symptoms or signs of CSF. In contrast, the control pigs continuously exhibited signs of CSF and had to be euthanized because of severe clinical symptoms at 5 days post challenge infection. The data from in vivo experiments shown that the multiple epitope rE2-ba shown a greater protection (similar to that of HCLV vaccine than that of mono-epitope peptide(rE2-a or rE2-b. Therefore, The results demonstrated that this multiple epitope peptide expressed in a prokaryotic system can be used as a potential DIVA (differentiating infected from vaccinated animals vaccine. The E.coli-expressed E2 multiple B-cell linear epitopes retains correct immunogenicity and is able to induce a protective immune response against CSFV infection.

  19. Compartmentalization and ultrastructural alterations induced by chromium in aquatic macrophytes.

    Science.gov (United States)

    Mangabeira, Pedro A; Ferreira, Aluane S; de Almeida, Alex-Alan F; Fernandes, Valéria F; Lucena, Emerson; Souza, Vânia L; dos Santos Júnior, Alberto J; Oliveira, Arno H; Grenier-Loustalot, Marie F; Barbier, Fréderique; Silva, Delmira C

    2011-12-01

    The aim of the present study was to identify the sites of accumulation of Cr in the species of macrophytes that are abundant in the Cachoeira river, namely, Alternanthera philoxeroides, Borreria scabiosoides, Polygonum ferrugineum and Eichhornia crassipes. Plants were grown in nutritive solution supplemented with 0.25 and 50 mg l(-1) of CrCl(3)·6H(2)O. Samples of plant tissues were digested with HNO(3)/HCl in a closed-vessel microwave system and the concentrations of Cr determined using inductively-coupled plasma mass spectrometry (ICP-MS). The ultrastructure of root, stem and leaf tissue was examined using transmission electron microscopy (TEM) and secondary ion mass spectrometry (SIMS) in order to determine the sites of accumulation of Cr and to detect possible alterations in cell organelles induced by the presence of the metal. Chromium accumulated principally in the roots of the four macrophytes (8.6-30 mg kg(-1) dw), with much lower concentrations present in the stems and leaves (3.8-8.6 and 0.01-9.0 mg kg(-1) dw, respectively). Within root tissue, Cr was present mainly in the vacuoles of parenchyma cells and cell walls of xylem and parenchyma. Alterations in the shape of the chloroplasts and nuclei were detected in A. philoxeroides and B. scabiosoides, suggesting a possible application of these aquatic plants as biomarkers from Cr contamination.

  20. Phytic acid decreases deoxynivalenol and fumonisin B1-induced changes on swine jejunal explants

    Directory of Open Access Journals (Sweden)

    Elisângela Olegário da Silva

    2014-01-01

    Full Text Available The purpose of the present study was to investigate the effects of phytic acid (IP6 on morphological and immunohistochemical parameters on intestinal explants exposed to deoxynivalenol (DON and fumonisin B1 (FB1. The jejunal explants were exposed for 4 h to different treatments: control, DON (10 μM, DON plus 2.5 mM or 5 mM IP6, FB1 (70 μM, and FB1 plus 2.5 mM or 5 mM IP6. Both mycotoxins induced significant intestinal lesions and decreased villi height. The presence of 2.5 mM and 5 mM IP6 significantly inhibited the morphological changes caused by the mycotoxins. DON induced a significant increase in caspase-3 (83% and cyclooxygenase-2 (71.3% expression compared with the control. The presence of 5 mM IP6 induced a significant decrease in caspase-3 (43.7% and Cox-2 (48% expression compared with the DON group. FB1 induced a significant increase in caspase-3 expression (47% compared to the control, whereas IP6 induced no significant change in this expression. A significant decrease in cell proliferation was observed when explants were exposed to 5 mM of IP6 in comparison with the DON and FB1 groups. The present data provide evidence that phytic acid modulates the toxic effects induced by DON and FB1 on intestinal tissue.

  1. Evaluation of a modified live-virus vaccine for the prevention of porcine parvovirus-induced reproductive disease in swine.

    Science.gov (United States)

    Paul, P S; Mengeling, W L

    1980-12-01

    Each of 5 gilts was vaccinated IM with modified live-virus (MLV) vaccine for porcine parvovirus (PPV), and 5 gilts were used as nonvaccinated controls. Vaccinated gilts developed hemagglutination-inhibiting (HI) antibodies to PPV (titer of 320 to 1,280) by 2 weeks after vaccination. All gilts wee bred, and at about 40 days of gestation their immunity was challenged by intranasal and oral administration of a virulent strain of PPV. Gilts were killed at about 84 days of gestation and their litters were examined. Litters from vaccinated gilts comprised 59 live and 2 dead fetuses. Neither the virus nor antibodies to the virus were detected in any of the fetuses. In contrast, litters from nonvaccinated gilts comprised 25 live and 29 dead fetuses, and PPV was isolated from all dead and 9 live fetuses. Viral antigen was detected by direct immunofluorescence in the lungs of all PPV-infected fetuses, and 7 of the live infected fetuses had HI antibodies. Modified live virus did not cause transplacental fetal infection in 3 seronegative gilts inoculated at about 40 days of gestation. All 3 gilts had antibodies to PPV (80 to 640) when killed at about 84 days of gestation, and neither HI antibodies nor PPV were detected in any of the 20 live and 1 dead fetuses from these gilts. Modified live virus replicated in the tissues of fetuses of 2 gilts inoculated in utero. Seven of 8 fetuses inoculated with MLV died and were infected. These results demonstrated the efficacy of MLV vaccine for the prevention of PPV-induced reproductive disease in swine. Although MLV did not cross the placental barrier in pregnant animals, its pathogenicity for porcine fetuses after direct in utero inoculation indicates that its use should be limited to nonpregnant animals.

  2. PB1-F2 Protein Does Not Impact the Virulence of Triple-Reassortant H3N2 Swine Influenza Virus in Pigs but Alters Pathogenicity and Transmission in Turkeys

    Science.gov (United States)

    Deventhiran, Jagadeeswaran; Kumar, Sandeep R. P.; Raghunath, Shobana; Elankumaran, Subbiah

    2015-01-01

    considered an important virulence marker of IAV pathogenicity. Our study demonstrated that the expression of PB1-F2 does not impact the pathogenicity of TR H3N2 SIV in pigs. On the other hand, deletion of PB1-F2 caused TR H3N2 SIV to induce clinical disease early and resulted in effective transmission among the turkey poults. Our study emphasizes the continuing need to better understand the virulence determinants for IAV in intermediate hosts, such as swine and turkeys, and highlights the host-specific role of PB1-F2 protein. PMID:26468540

  3. PB1-F2 Protein Does Not Impact the Virulence of Triple-Reassortant H3N2 Swine Influenza Virus in Pigs but Alters Pathogenicity and Transmission in Turkeys.

    Science.gov (United States)

    Deventhiran, Jagadeeswaran; Kumar, Sandeep R P; Raghunath, Shobana; Leroith, Tanya; Elankumaran, Subbiah

    2016-01-01

    virulence marker of IAV pathogenicity. Our study demonstrated that the expression of PB1-F2 does not impact the pathogenicity of TR H3N2 SIV in pigs. On the other hand, deletion of PB1-F2 caused TR H3N2 SIV to induce clinical disease early and resulted in effective transmission among the turkey poults. Our study emphasizes the continuing need to better understand the virulence determinants for IAV in intermediate hosts, such as swine and turkeys, and highlights the host-specific role of PB1-F2 protein. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Intraosseous Hydroxocobalamin in the Treatment of Acute, Severe Cyanide Induced Cardiotoxicity in a Swine (Sus Scrofa) Model - An Alternate Administration Route for Chemical Mass Casualties

    Science.gov (United States)

    2012-04-05

    Ut:IVI:I... I 11:111VI:> Hydroxocobalamin, hypotension, cyanide , poisoning , intraosseous, Vitamin B 12a, Vitamin B 12 I 1:). :>CI...U I111 T L.L~:>:>II...Il l Ll:. ~IIIU :>Utili I Ll: :>a. I...UIIIII1~1... I IIIVIVItll:l1 lntraosseous hydroxocobalamin in the treatment of acute, severe cyanide induced...between 2 groups of swine in acute cyanide toxicity and treated with IV HOC or 10 HOC. We also compared blood cyanide , lactate, pH, nitrotyrosine levels

  5. Hyperthermia-induced Neural Alterations Impair Proprioception and Balance.

    Science.gov (United States)

    Mtibaa, Khouloud; Thomson, Athol; Nichols, David; Hautier, Christophe; Racinais, Sebastien

    2018-01-01

    Hyperthermia has been shown to affect both central and peripheral nervous systems. However, the consequences of these alterations on the proprioceptive mechanisms underlying human movement control remain unclear. The aim of this study was to investigate the effect of passive hyperthermia on various measures of proprioception and balance, two key components of injury prevention and movement efficiency. After a familiarization session, 14 volunteers (8 males, 6 females) completed two experimental sessions in temperate (CON, 24°C) and hot (HOT, 44°C-50°C) conditions, in a counterbalanced order. Participants were tested for neural function (electrically evoked M-wave and Hoffman reflex, Soleus), active movement discrimination (five positions, 50 trials, dorsiflexion), dynamic balance (Star Excursion Balance Test, three directions), and static balance (single-leg stance). Both rectal (39.0°C ± 0.3°C vs 36.9°C ± 0.6°C) and mean skin (37.9°C ± 1.0°C vs 32.0°C ± 2.7°C) temperatures were significantly higher in HOT than CON (P 0.05) amplitudes, increased the mean error for active movement discrimination (0.58°± 0.13° vs 0.50° ± 0.11°, +17%, P proprioception and balance parameters measured. These observations might be due to heat-induced alterations in efferent and afferent signals to and from the muscle.

  6. MYOELECTRIC ALTERATIONS AFTER VOLUNTARY INDUCED HIGH - AND LOW - FREQUENCY FATIGUE

    Directory of Open Access Journals (Sweden)

    Vojko Strojnik

    2008-06-01

    Full Text Available The aim of the study was to find whether voluntary induced high- and low-frequency peripheral fatigue exhibit specific alteration in surface EMG signal (SEMG during evoked and maximum voluntary contractions. Ten male students of physical education performed 60 s long stretch-shortening cycle (SSC exercise with maximal intensity and 30 s long concentric (CON exercise with maximal intensity. To verify voluntary induced peripheral fatigue, knee torques during low- (T20 and high-frequency electrical stimulation (T100 of relaxed vastus lateralis muscle (VL were obtained. Contractile properties of the VL were measured with passive twitch and maximal voluntary knee extension test (MVC. Changes in M-waves and SEMG during MVC test were used to evaluate the differences in myoelectrical signals. T100/T20 ratio decreased by 10.9 ± 8.4 % (p < 0.01 after the SSC exercise and increased by 35.9 ± 17.5 % (p < 0.001 after the CON exercise. Significant SEMG changes were observed only after the CON exercise where peak to peak time of the M-waves increased by 9.2 ± 13.3 % (p < 0.06, SEMG amplitude during MVC increased by 32.9 ± 21.6 % (p < 0.001 and SEMG power spectrum median frequency decreased by 11.0 ± 10.5 % (p < 0.05. It is concluded that high frequency fatigue wasn't reflected in SEMG, however the SEMG changes after the CON seemed to reflect metabolic changes due to acidosis

  7. New insights into uremia-induced alterations in metabolic pathways.

    Science.gov (United States)

    Rhee, Eugene P; Thadhani, Ravi

    2011-11-01

    This article summarizes recent studies on uremia-induced alterations in metabolism, with particular emphasis on the application of emerging metabolomics technologies. The plasma metabolome is estimated to include more than 4000 distinct metabolites. Because these metabolites can vary dramatically in size and polarity and are distributed across several orders of magnitude in relative abundance, no single analytical method is capable of comprehensive metabolomic profiling. Instead, a variety of analytical techniques, including targeted and nontargeted liquid chromatography-mass spectrometry, have been employed for metabolomic analysis of human plasma. Recent efforts to apply this technology to study uremia have reinforced the common view that end-stage renal disease is a state of generalized small molecule excess. However, the identification of precursor depletion and downstream metabolite excess - for example, with tryptophan and downstream kynurenine metabolites, with low molecular weight triglycerides and dicarboxylic acids, and with phosphatidylcholines, choline, and trimethylamine-N-oxide - suggest that uremia may directly modulate these metabolic pathways. Metabolomic studies have also begun to expand some of these findings to individuals with chronic kidney disease and in model systems. Uremia is associated with diverse, but incompletely understood metabolic disturbances. Metabolomic approaches permit higher resolution phenotyping of these disturbances, but significant efforts will be required to understand the functional significance of select findings.

  8. A novel swine model of ricin-induced acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Shahaf Katalan

    2017-02-01

    Full Text Available Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS.

  9. Immunization of African Indigenous Pigs with Attenuated Genotype I African Swine Fever Virus OURT88/3 Induces Protection Against Challenge with Virulent Strains of Genotype I.

    Science.gov (United States)

    Mulumba-Mfumu, L K; Goatley, L C; Saegerman, C; Takamatsu, H-H; Dixon, L K

    2016-10-01

    The attenuated African swine fever virus genotype I strain OURT88/3 has previously been shown to induce protection of European breeds of domestic pigs against challenge with virulent isolates. To determine whether protective immune responses could also be induced in indigenous breeds of pigs from the Kinshassa region in Democratic Republic of Congo, we immunized a group of eight pigs with OURT88/3 strain and challenged the pigs 3 weeks later with virulent genotype I strain OURT88/1. Four of the pigs were protected against challenge. Three of the eight pigs died from African swine fever virus and a fourth from an unknown cause. The remaining four pigs all survived challenge with a recent virulent genotype I strain from the Democratic Republic of Congo, DRC 085/10. Control groups of non-immune pigs challenged with OURT88/1 or DRC 085/10 developed signs of acute ASFV as expected and had high levels of virus genome in blood. © 2015 Blackwell Verlag GmbH.

  10. Vitamin D deficiency induces cardiac hypertrophy and inflammation in epicardial adipose tissue in hypercholesterolemic swine.

    Science.gov (United States)

    Gupta, Gaurav K; Agrawal, Tanupriya; DelCore, Michael G; Mohiuddin, Syed M; Agrawal, Devendra K

    2012-08-01

    Vitamin D is a sectosteroid that functions through Vitamin D receptor (VDR), a transcription factor, which controls the transcription of many targets genes. Vitamin D deficiency has been linked with cardiovascular diseases, including heart failure and coronary artery disease. Suppressor of cytokine signaling (SOCS)3 regulates different biological processes such as inflammation and cellular differentiation and is an endogenous negative regulator of cardiac hypertrophy. The purpose of this study was to test the hypothesis that vitamin D deficiency causes cardiomyocyte hypertrophy and increased proinflammatory profile in epicardial adipose tissue (EAT), and this correlates with decreased expression of SOCS3 in cardiomyocytes and EAT. Eight female Yucatan miniswine were fed vitamin D-sufficient (900 IU/d) or vitamin D-deficient hypercholesterolemic diet. Lipid profile, metabolic panel, and serum 25(OH)D levels were regularly measured. After 12 months animals were euthanized and histological, immunohistochemical and qPCR studies were performed on myocardium and epicardial fat. Histological studies showed cardiac hypertrophy, as judged by cardiac myocyte cross sectional area, in the vitamin D-deficient group. Immunohistochemical and qPCR analyses showed significantly decreased mRNA and protein expression of VDR and SOCS3 in cardiomyocytes of vitamin D-deficient animals. EAT from vitamin D-deficient group had significantly higher expression of TNF-α, IL-6, MCP-1, and decreased adiponectin in association with increased inflammatory cellular infiltrate. Interestingly, EAT from vitamin D-deficient group had significantly decreased expression of SOCS3. These data suggest that vitamin D deficiency induces hypertrophy in cardiomyocytes which is associated with decreased expression of VDR and SOCS3. Vitamin D deficiency is also associated with increased inflammatory markers in EAT. Activity of VDR in the body is controlled through regulation of vitamin D metabolites. Therefore

  11. Commercial bacterins did not induce detectable levels of antibodies in mice against Mycoplasma hyopneumoniae antigens strongly recognized by swine immune system

    Directory of Open Access Journals (Sweden)

    Andressa Fisch

    2016-01-01

    Full Text Available Enzootic Pneumonia (EP caused by Mycoplasma hyopneumoniae results in major economic losses to the swine industry. Hence, the identification of factors that provide protection against EP could help to develop effective vaccines. One such factor that provides partial protection are bacterins. Therefore, the aim of this study was to verify the induction of antibodies against fifteen M. hyopneumoniae antigens, strongly recognized by the swine immune system during natural infection, in mice vaccinated with six commercial bacterins. Each group of mice was inoculated with one bacterin, and seroconversion was assessed by indirect ELISA using recombinant antigens and M. hyopneumoniae 7448 whole cell extract. Sera from one inoculated group recognized antigen MHP_0067, and sera from four inoculated groups recognized antigens MHP_0513 and MHP_0580. None of the bacterins was able to induce seroconversion against the twelve remaining antigens. This absence of a serological response could be attributed to the lack of antigen expression in M. hyopneumoniae strains used in bacterin production. Additionally the partial protection provided by these vaccines could be due to low expression or misfolding of antigens during vaccine preparation. Therefore, the supplementation of bacterins with these recombinant antigens could be a potential alternative in the development of more effective vaccines.

  12. The cholesterol system of the swine

    International Nuclear Information System (INIS)

    Aigueperse, Jocelyne

    1979-01-01

    The purpose of this work was to characterize the dynamic system of adult female Large White swine. The content of this system and its relationships with both the external environment and between the different parts of the system were explained. The analysis of these results in terms of compared physiology showed that the structure of the cholesterol system was the same in man and in the swine. Consequently, the swine constitutes a good biological tool to study human cholesterol indirectly and to foresee the changes that might be induced in various physio-pathological cases. (author) [fr

  13. Chromium, Nickel and Zinc Induced Histopathological Alterations in ...

    African Journals Online (AJOL)

    Degenerative histopathalogical alterations were seen in liver due to chronic exposure of the fish, Labeo rohita to chlorides of chromium, nickel and zinc for 30 days. However, more severe degenerative changes were observed in case of zinc chloride exposed fish than nickel chloride and chromium chloride treated fishes, ...

  14. Chromium, Nickel and Zinc Induced Histopathological Alterations in ...

    African Journals Online (AJOL)

    Michael Horsfall

    ABSTRACT: Degenerative histopathalogical alterations were seen in liver due to chronic exposure of the fish, Labeo rohita to chlorides of chromium, nickel and zinc for 30 days. However, more severe degenerative changes were observed in case of zinc chloride exposed fish than nickel chloride and chromium chloride ...

  15. Histological and histochemical alterations in the kidney induced by lead

    International Nuclear Information System (INIS)

    Jarrar, Bashir M.

    2003-01-01

    Although lead intoxication is one of the most common forms of metal intoxication,the histochemichal alterations in renal tissues due to chronic lead exposure is limited and has not yet been well identified. A total of 60 male Wistar albino rats were exposed to lead acetate trihydrate( 0.0, 0.25, 0.5, 1.0 and 2% for 1 to 12 months) in drinking water to investigate the histological and histochemical alterations in renal tissues due to lead. Chronic exposure to the subtoxic doses of lead produced distinct progressive tubular, glomerular and interstitial damages. Tubular changes occured earlier than the glomerular and interstitial ones,and included anisokaryosis, nuclear pyknosis,karyomeglay, development of intranuclear cytoplasmic inclusions together with tubular dilation, necrosis,vacuolization, tubular hyperplasia and solid tubular adenoma. The glomrular alterations were mainly mesangial hypercellularity, segmental glomerulosclerosis, glomerular hyalinization and glomerular tuft alterations. The findings indicate that lead produces significant histological and histochemical changes in the kidney that lead to severe complications. (author)

  16. Induced-hypercholesterolemia as a probable cause of alterations in ...

    African Journals Online (AJOL)

    Methods: The telemetry technique was used to investigate the cardiovascular dysfunctions in induced hypercholesterolemia in Wistar Kyoto (WKY) rats. Methods for this investigation include: inducing hypercholesterolemic condition in Wistar Kyoto rats through diet; measuring the blood cholesterol levels of the experimental ...

  17. Altered Neutrophil Function in Localized Juvenile Periodontitis: Intrinsic or Induced?

    Science.gov (United States)

    Agarwal, Sudha; Huang, Jian Ping; Piesco, Nicholas P; Suzuki, Jon B; Riccelli, Angelina E; Johns, Lee P

    1996-03-01

    Localized juvenile periodontitis (LJP) is an aggressive periodontal disease of familial nature. Neutrophils from a majority of patients with this disease exhibit decreased Chemotaxis with increased adherence, oxidative burst, and degranulation in response to opsonized bacteria. It is proposed that the biological basis for these altered neutrophil functions in LJP may be due either to intrinsic cell abnormalities or to the effect of factors present in the sera of LJP patients, which can modulate neutrophil functions. LJP neutrophils exhibit a lower number of receptors for chemoattractants and GP-110 molecules which are known to facilitate Chemotaxis. Furthermore, these cells exhibit lower signal transduction in response to a biological stimulus. These observations suggest that intrinsic cellular defects may be responsible for altered neutrophil functions in LJP. However, healthy neutrophils, when treated with very low concentrations of proinflammatory cytokines, also exhibit the characteristics of altered or "defective" LJP neutrophils. Additionally, healthy neutrophils, when treated with LJP serum, also exhibit many of the characteristics associated with LJP neutrophils. Attempts to identify these factors have shown that cytokines like TNF-α and/or IL1 β in LJP sera may be at least partially responsible for modulating neutrophil functions in LJP. These cytokines are primarily produced by activated macrophages, indicating a role for these cells in the etiology of LJP. The hyper-responsiveness of these cells to an immunologic challenge can result in local increases in cytokines leading to excessive bone loss and tissue damage at the site of infection, while systemic elevations in cytokines would lead to decreased neutrophil Chemotaxis, both of which are observed in LJP. Present evidence indicates that neutrophil functions are indeed altered in the majority of LJP patients. However, the biological basis for the alteration may not be due to the neutrophils themselves

  18. 9 CFR 85.10 - Interstate movement of swine semen and swine embryos for insemination of or implantation into swine.

    Science.gov (United States)

    2010-01-01

    ... swine embryos for insemination of or implantation into swine. 85.10 Section 85.10 Animals and Animal... and swine embryos for insemination of or implantation into swine. Swine semen and swine embryos moved interstate for insemination of swine or implantation into swine shall be accompanied by a document issued by...

  19. Localization of pellicle-induced open contacts using Charge-Induced Voltage Alteration

    Energy Technology Data Exchange (ETDEWEB)

    Cole, E.I. Jr.; Soden, J.M.

    1993-08-01

    The recently developed Charge-Induced Voltage Alteration (CIVA) technique for localizing open metal conductors was used successfully to identify transistors with electrically open metal-1 contacts to silicon. The transistors were in the I/O port circuitry of a failing microcontroller and were completely covered by a metal-2 power bus. The root cause of the open contacts was a subtle scratch in the pellicle over the contact reticle. The scratch prevented full exposure of the photoresist, resulting in incomplete removal of the interlevel oxide in several contact windows. In addition to this powerful new application of CIVA, a number of failure analysis techniques utilizing both the electrical and physical properties of the failing microcontrollers were employed to identify and confirm the open contacts. These techniques are reviewed and recommendations are given for improved pellicle/reticle inspection.

  20. Uranium-induced sensory alterations in the zebrafish Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Faucher, K., E-mail: kfaucher@hotmail.fr [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France); Floriani, M.; Gilbin, R.; Adam-Guillermin, C. [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France)

    2012-11-15

    The effect of chronic exposure to uranium ions (UO{sub 2}{sup 2+}) on sensory tissues including the olfactory and lateral line systems was investigated in zebrafish (Danio rerio) using scanning electron microscopy. The aim of this study was to determine whether exposure to uranium damaged sensory tissues in fish. The fish were exposed to uranium at the concentration of 250 {mu}g l{sup -1} for 10 days followed by a depuration period of 23 days. Measurements of uranium uptake in different fish organs: olfactory rosettes and bulbs, brain, skin, and muscles, were also determined by ICP-AES and ICP-MS during the entire experimental period. The results showed that uranium displayed a strong affinity for sensory structures in direct contact with the surrounding medium, such as the olfactory and lateral line systems distributed on the skin. A decreasing gradient of uranium concentration was found: olfactory rosettes > olfactory bulbs > skin > muscles > brain. At the end of the experiment, uranium was present in non-negligible quantities in sensory tissues. In parallel, fish exposed to uranium showed severe sensory tissue alterations at the level of the olfactory and lateral line systems. In both sensory systems, the gross morphology was altered and the sensory hair cells were significantly damaged very early after the initiation of exposure (from the 3rd day). At the end of the experiment, after 23 days of depuration, the lateral line system still displayed slight tissue alterations, but approximately 80% of the neuromasts in this system had regenerated. In contrast, the olfactory system took more time to recover, as more than half of the olfactory rosettes observed remained destroyed at the end of the experiment. This study showed, for the first time, that uranium is able to damage fish sensory tissues to such an extent that tissue regeneration is delayed.

  1. ALTERATIONS INDUCED BY LOW LEVELS OF DEOXYNIVALENOL IN WEANED PIGLETS

    OpenAIRE

    DANIELA ELIZA MARIN; IONELIA TARANU; CRISTINA TABUC; G. STEFAN; ANCA DINISCHIOTU; GINA MANDA; GABRIELA DUMITRESCU

    2007-01-01

    Deoxynivalenol (DON) is a mycotoxin produced by different species of Fusarium genus that may contaminate feed and food. In the present study we investigated the effect of low levels of DON on the modulation of performance, hemodynamic parameters, cellular and humoral immune response in weaned pigs. Histological alterations in different organ tissues were also analyzed. Our results showed that a short in vivo exposure (14 days) of weanling piglets to 0; 0.5; 1.5 mg/day of DON significantly ind...

  2. Sodium phenylbutyrate abrogates African swine fever virus replication by disrupting the virus-induced hypoacetylation status of histone H3K9/K14.

    Science.gov (United States)

    Frouco, Gonçalo; Freitas, Ferdinando B; Martins, Carlos; Ferreira, Fernando

    2017-10-15

    African swine fever virus (ASFV) causes a highly lethal disease in swine for which neither a vaccine nor treatment are available. Recently, a new class of drugs that inhibit histone deacetylases enzymes (HDACs) has received an increasing interest as antiviral agents. Considering studies by others showing that valproic acid, an HDAC inhibitor (HDACi), blocks the replication of enveloped viruses and that ASFV regulates the epigenetic status of the host cell by promoting heterochromatinization and recruitment of class I HDACs to viral cytoplasmic factories, the antiviral activity of four HDACi against ASFV was evaluated in this study. Results showed that the sodium phenylbutyrate fully abrogates the ASFV replication, whereas the valproic acid leads to a significant reduction of viral progeny at 48h post-infection (-73.9%, p=0.046), as the two pan-HDAC inhibitors tested (Trichostatin A: -82.2%, p=0.043; Vorinostat: 73.9%, p=0.043). Further evaluation showed that protective effects of NaPB are dose-dependent, interfering with the expression of late viral genes and reversing the ASFV-induced histone H3 lysine 9 and 14 (H3K9K14) hypoacetylation status, compatible to an open chromatin state and possibly enabling the expression of host genes non-beneficial to infection progression. Additionally, a synergic antiviral effect was detected when NaPB is combined with an ASFV-topoisomerase II poison (Enrofloxacin). Altogether, our results strongly suggest that cellular HDACs are involved in the establishment of ASFV infection and emphasize that further in vivo studies are needed to better understand the antiviral activity of HDAC inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Alterations in oral microbial flora induced by waterpipe tobacco smoking.

    Science.gov (United States)

    Shakhatreh, Muhamad Ali K; Khabour, Omar F; Alzoubi, Karem H; Masadeh, Majed M; Hussein, Emad I; Bshara, George N

    2018-01-01

    Waterpipe smoking is a global health problem and a serious public concern. Little is known about the effects of waterpipe smoking on oral health. In the current study, we examined the alterations of oral microbial flora by waterpipe smoking. One hundred adult healthy subjects (59 waterpipe smokers and 41 non-smokers) were recruited into the study. Swabs were taken from the oral cavity and subgingival regions. Standard culturing techniques were used to identify types, frequency, and mean number of microorganisms in cultures obtained from the subjects. It was notable that waterpipe smokers were significantly associated with a history of oral infections. In subgingiva, Acinetobacter and Moraxella species were present only in waterpipe smokers. In addition, the frequency of Candida albicans was higher in the subgingiva of waterpipe smokers ( p = 0.023) while the frequency of Fusobacterium nucleatum was significantly lower in the subgingiva of waterpipe smokers ( p = 0.036). However, no change was observed in other tested bacteria, such as Campylobacter species; Viridans group streptococci, Enterobacteriaceae , and Staphylococcus aureus . In oral cavity and when colony-forming units were considered, the only bacterial species that showed significant difference were the black-pigmented bacteria ( p < 0.001). This study provides evidence indicating that some of the oral microflora is significantly altered by waterpipe smoking.

  4. Alcohol induced alterations to the human fecal VOC metabolome.

    Directory of Open Access Journals (Sweden)

    Robin D Couch

    Full Text Available Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis. However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1 an elevation in the oxidative stress biomarker tetradecane; (2 a decrease in five fatty alcohols with anti-oxidant property; (3 a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4 a decrease in alcohol consumption natural suppressant caryophyllene; (5 a decrease in natural product and hepatic steatosis attenuator camphene; and (6 decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies.

  5. Radiation-induced motility alterations in medulloblastoma cells

    International Nuclear Information System (INIS)

    Rieken, Stefan; Rieber, Juliane; Brons, Stephan

    2015-01-01

    Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α 5 . The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α 5 , which lead to increased cell adherence to extracellular matrix proteins. (author)

  6. Haemoatopoietic alterations induced by carbaryl in Clarias batrachus

    African Journals Online (AJOL)

    The aim of the study was to assess the effect induced by Sevin a carbamate pesticide on hematological indices of Clarias batrachus. The effect was studied based on the results of acute toxicity tests and comparison of control with experimental group. The fish was exposed to varying levels of the toxicant and sub lethal ...

  7. Specitic gene alterations in radiation-induced tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Joo Mee; Kang, Chang Mo; Lee, Seung Sook; Cho, Chul Koo; Bae, Sang Woo; Lee, Su Jae; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    To identify a set of genes involved in the development of radiation-induced tumorigenesis, we used DNA microarrays consisting of 1,176 mouse genes and compared expression profiles of radioresistant cells, designated NIH3T3-R1 and -R4. These cells were tumorigenic in a nude mouse grafting system, as compared to the parental NIH3T3 cells. Expressions of MDM2, CDK6 and CDC25B were found to increase more than 3-fold. Entactin protein levels were downregulated in NIH3T3-R1 and -R4 cells. Changes in expression genes were confirmed by reverse transcription-PCR or western blotting. When these genes were transfected to NIH3T3 cells, the CDC25B and MDM2 overexpressing NIH3T3 cells showed radioresistance, while 2 CDK6 overexpressing cells did not. In the case of entactin overexpressing NIH3T3-R1 or R-4 cells were still radioresistant. Furthermore, the CDC25B and MDM2 overexpressing cells grafted to nude mice, were tumorigenic. NIH3T3-R1 and R4 cells showed increased radiation-induced apoptosis, accompanied by faster growth rate, rather than and earlier radiation-induced G2/M phase arrest, suggesting that the radioresistance of NIH3T3-R1 and R4 cells was due to faster growth rate, rather than induction of apoptosis. In the case of MDM2 and CDC25B overexpressing cells, similar phenomena, such as increased apoptosis and faster growth rate, were shown. The above results, therefore, demonstrate involvement of CDC25B and MDM2 overexpression in radiation-induced tumorigenesis and provide novel targets for detection of radiation-induced carcinogenesis.

  8. Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model.

    Science.gov (United States)

    Rojas, Mauricio; Parker, Richard E; Thorn, Natalie; Corredor, Claudia; Iyer, Smita S; Bueno, Marta; Mroz, Lyle; Cardenes, Nayra; Mora, Ana L; Stecenko, Arlene A; Brigham, Kenneth L

    2013-03-04

    The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice. A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury. We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating

  9. Alterations induced in Escherichia Coli cells by gamma radiation

    International Nuclear Information System (INIS)

    Kappke, J.; Schelin, H.R.; Paschuk, S.A.; Denyak, V.; Silva, E.R. da; Jesus, E.F.O. de; Lopes, R.T.; Carlin, N.; Toledo, E.S.

    2007-01-01

    Modifications occurred in Escherichia coli cells exposed to gamma radiation ( 60 Co source) were investigated. The irradiations were done at the LIN-COPPE laboratory of the UFRJ and the analysis at the Biology Department of the UTFPR. The E. coli cells were irradiated with 30, 60, 90, 120, 150, 180, 210, 240, 300, 480, 600 e 750 Gy doses. The samples were analyzed with Gram-stain, biochemical tests in EPM, MIO and Lysine Broth, Simmons Cytrate Medium and Rhamnose Broth, antibiogram and isolation of auxotrophic mutants. It was observed that for the received doses the E. coli did not show morphological alterations in the tests. Some E. Coli cells showed to be able to deaminade the L-tryptophan or they changed their sensibility for amoxillin and cephaloonine after the irradiation. The existence of aauxotrophic mutants after irradiation was also verified. (author)

  10. Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

    Directory of Open Access Journals (Sweden)

    Raffaele Nardone

    2013-01-01

    Full Text Available Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS. Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.

  11. Thiamine deficiency induced neurochemical, neuroanatomical, and neuropsychological alterations: a reappraisal.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Storti, Monica; Christova, Monica; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2013-01-01

    Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.

  12. Hepatoepigenetic Alterations in Viral and Nonviral-Induced Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Mankgopo M. Kgatle

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a major public health concern and one of the leading causes of tumour-related deaths worldwide. Extensive evidence endorses that HCC is a multifactorial disease characterised by hepatic cirrhosis mostly associated with chronic inflammation and hepatitis B/C viral infections. Interaction of viral products with the host cell machinery may lead to increased frequency of genetic and epigenetic aberrations that cause harmful alterations in gene transcription. This may provide a progressive selective advantage for neoplastic transformation of hepatocytes associated with phenotypic heterogeneity of intratumour HCC cells, thus posing even more challenges in HCC treatment development. Epigenetic aberrations involving DNA methylation, histone modifications, and noncoding miRNA dysregulation have been shown to be intimately linked with and play a critical role in tumour initiation, progression, and metastases. The current review focuses on the aberrant hepatoepigenetics events that play important roles in hepatocarcinogenesis and their utilities in the development of HCC therapy.

  13. Alterations in offspring behavior induced by chronic prenatal cocaine dosing.

    Science.gov (United States)

    Smith, R F; Mattran, K M; Kurkjian, M F; Kurtz, S L

    1989-01-01

    Sperm-positive female Long-Evans hooded rats were dosed subcutaneously with 10 mg/kg/day cocaine or an equal volume of vehicle (0.9% sterile saline) from gestation day 4 (GD4) through GD18. Offspring were assessed for development of negative geotaxis, righting reflex, spontaneous alternation, and open field activity, and for adult behaviors including DRL-20 acquisition, water maze, visual discrimination, barbiturate sleep time, shuttlebox avoidance, footshock sensitivity, and tail flick latency. Cocaine dosing produced no significant effects on dam weight gain, any measure of litter size and weight, or early postnatal behavioral tests, but there were significant drug effects on development of spontaneous alternation, development of open field activity, DRL-20 acquisition, water maze performance, tail flick, and footshock sensitivity. These data suggest that chronic administration of a modest dose of cocaine during gestation in the rat alters a number of behaviors in the offspring.

  14. Tityus fasciolatus envenomation induced cardio-respiratory alterations in rats.

    Science.gov (United States)

    Pinto, M C L; Borboleta, L R; Melo, M B; Labarrére, C R; Melo, M M

    2010-06-01

    The present study characterized envenomation in young rats by Tityus fasciolatus, an endemic scorpion to Central Brazilian and state of Minas Gerais. Electrocardiographic examinations were performed prior to treatment and every 5 min during the first 30 min after envenomation. The cardiac blood profile [creatine kinase, CK isoenzyme MB, lactate dehydrogenase, aspartate aminotransferase and troponina] together with macroscopic and microscopic alterations in the lungs and heart were evaluated. Envenomated animals showed ECG changes suggesting electrolytic imbalance, myocarditis and venom interference on the conduction tissue. Biochemical analyses indicated myocardial damage with high levels of CK, CK-MB and LDH. Macroscopic and microscopic findings included detection of pulmonary haemorrhages. In conclusion, T. fasciolatus venom leads to acute cardio-respiratory changes in young rats. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Alterations in oral microbial flora induced by waterpipe tobacco smoking

    Directory of Open Access Journals (Sweden)

    Shakhatreh MAK

    2018-02-01

    Full Text Available Muhamad Ali K Shakhatreh,1 Omar F Khabour,1 Karem H Alzoubi,2 Majed M Masadeh,3 Emad I Hussein,4 George N Bshara1 1Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Irbid, Jordan; 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Biological Sciences, Yarmouk University, Irbid, Jordan Background: Waterpipe smoking is a global health problem and a serious public concern. Little is known about the effects of waterpipe smoking on oral health. In the current study, we examined the alterations of oral microbial flora by waterpipe smoking. Methods: One hundred adult healthy subjects (59 waterpipe smokers and 41 non-smokers were recruited into the study. Swabs were taken from the oral cavity and subgingival regions. Standard culturing techniques were used to identify types, frequency, and mean number of microorganisms in cultures obtained from the subjects. Results: It was notable that waterpipe smokers were significantly associated with a history of oral infections. In subgingiva, Acinetobacter and Moraxella species were present only in waterpipe smokers. In addition, the frequency of Candida albicans was higher in the subgingiva of waterpipe smokers (p = 0.023 while the frequency of Fusobacterium nucleatum was significantly lower in the subgingiva of waterpipe smokers (p = 0.036. However, no change was observed in other tested bacteria, such as Campylobacter species; Viridans group streptococci, Enterobacteriaceae, and Staphylococcus aureus. In oral cavity and when colony-forming units were considered, the only bacterial species that showed significant difference were the black-pigmented bacteria (p < 0.001. Conclusion: This study provides evidence indicating that some of the oral microflora is significantly altered by

  16. Proteomic analysis of swine serum following highly virulent classical swine fever virus infection

    Directory of Open Access Journals (Sweden)

    Guo Huan-cheng

    2011-03-01

    Full Text Available Abstract Background Classical swine fever virus (CSFV belongs to the genus Pestivirus within the family Flaviviridae. Virulent strains of classical swine fever virus (CSFV cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide. Methods To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C. The samples were treated to remove serum albumin and immunoglobulin (IgG, and then subjected to two-dimension differential gel electrophoresis. Results Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis. Conclusion These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.

  17. PEDF-induced alteration of metabolism leading to insulin resistance.

    Science.gov (United States)

    Carnagarin, Revathy; Dharmarajan, Arunasalam M; Dass, Crispin R

    2015-02-05

    Pigment epithelium-derived factor (PEDF) is an anti-angiogenic, immunomodulatory, and neurotrophic serine protease inhibitor protein. PEDF is evolving as a novel metabolic regulatory protein that plays a causal role in insulin resistance. Insulin resistance is the central pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, polycystic ovarian disease, and metabolic syndrome, and PEDF is associated with them. The current evidence suggests that PEDF administration to animals induces insulin resistance, whereas neutralisation improves insulin sensitivity. Inflammation, lipolytic free fatty acid mobilisation, and mitochondrial dysfunction are the proposed mechanism of PEDF-mediated insulin resistance. This review summarises the probable mechanisms adopted by PEDF to induce insulin resistance, and identifies PEDF as a potential therapeutic target in ameliorating insulin resistance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Ecstasy-Induced Caspase Expression Alters Following Ginger Treatment

    Directory of Open Access Journals (Sweden)

    Sara Soleimani Asl

    2013-11-01

    Full Text Available Introduction: Exposure to 3-4, methylenedioxymethamphetamine (MDMA leads to cell death. Herein, we studied the protective effects of ginger on MDMA- induced apoptosis. Methods: 15 Sprague dawley male rats were administrated with 0, 10 mg/kg MDMA, or MDMA along with 100mg/kg ginger, IP for 7 days. Brains were removed to study the caspase 3, 8, and 9 expressions in the hippocampus by RT-PCR. Data was analyzed by SPSS 16 software using the one-way ANOVA test. Results: MDMA treatment resulted in a significant increase in caspase 3, 8, and 9 as compared to the sham group (p<0.001. Ginger administration however, appeared to significantly decrease the same (p<0.001. Discussion: Our findings suggest that ginger consumption may lead to the improvement of MDMA-induced neurotoxicity.

  19. Heat-induced alterations in the cell nucleus

    International Nuclear Information System (INIS)

    Kampinga, H.H.

    1989-01-01

    Hyperthermia may kill eukaryotic cells and may also enhance the radiosensitivity of those cells that survive the heat treatment. Clinically, the possible use of hyperthermia as an adjuvant in the radiotherapeutic treatment of cancer needs the understanding of mechanisms that underlay heat-induced cell death and radiosensitization. By in vitro heating of established human (HeLaS3) and rodent (Ehrlich Ascites Tumor and LM fibroblast) cell lines, both killing and radiosensitization were investigated. (author). 1067 refs.; 76 figs.; 19 tabs

  20. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  1. Alterations in glucose kinetics induced by pentobarbital anesthesia

    International Nuclear Information System (INIS)

    Lang, C.H.; Bagby, G.J.; Hargrove, D.M.; Hyde, P.M.; Spitzer, J.J.

    1987-01-01

    Because pentobarbital is often used in investigations related to carbohydrate metabolism, the in vivo effect of this drug on glucose homeostasis was studied. Glucose kinetics assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, were determined in three groups of catheterized fasted rats: conscious, anesthetized and body temperature maintained, and anesthetized but body temperature not maintained. After induction of anesthesia, marked hypothermia developed in rats not provided with external heat. Anesthetized rats that developed hypothermia showed a decrease in mean arterial blood pressure (25%) and heart rate (40%). Likewise, the plasma lactate concentration and the rates of glucose appearance, recycling, and metabolic clearance were reduced by 30-50% in the hypothermic anesthetized rats. Changes in whole-body carbohydrate metabolism were prevented when body temperature was maintained. Because plasma pentobarbital levels were similar between the euthermic and hypothermic rats during the first 2 h of the experiment, the rapid reduction in glucose metabolism in this latter group appears related to the decrease in body temperature. The continuous infusion of epinephrine produced alterations in glucose kinetics that were not different between conscious animals and anesthetized rats with body temperature maintained. Thus pentobarbital-anesthetized rats became hypothermic when kept at room temperature and exhibited marked decreases in glucose metabolism. Such changes were absent when body temperature was maintained during anesthesia

  2. Sertraline Induces Toxicity and Behavioral Alterations in Planarians

    Directory of Open Access Journals (Sweden)

    Isabela Salvador Thumé

    2017-01-01

    Full Text Available Toxicity attributed to sertraline has been demonstrated recently in different cell types and also in some organisms. We investigated the effect of sertraline on planarians, which are considered suitable for investigations in neurotoxicology and currently are widely used as an animal model in neuropharmacological studies. Planarians treated with 10 µM sertraline showed a rapid reduction in their spontaneous movement until they became completely motionless and then showed a series of asynchronous paroxysms (seizures followed by progressive tissue damage, beginning 48 h after the sertraline treatment, and died approximately 72 h later. Our data showed that sertraline does not cause planarian death within the range of therapeutic concentrations; however, behavioral alterations were observed with concentrations that can be considered compatible with therapeutic ones, such as a significant reduction in planarian locomotory activity at 0.4 µM. Treatment with 4 µM sertraline had a significant effect, reducing planarian locomotory activity and increasing the number of asynchronous paroxysms; both effects were significantly maintained even 24 h after the sertraline was withdrawn. These behavioral changes observed at low micromolar concentrations suggest that sertraline might have residual biological consequences for planarians, even after it is withdrawn.

  3. Sertraline Induces Toxicity and Behavioral Alterations in Planarians.

    Science.gov (United States)

    Thumé, Isabela Salvador; Frizzo, Marcos Emílio

    2017-01-01

    Toxicity attributed to sertraline has been demonstrated recently in different cell types and also in some organisms. We investigated the effect of sertraline on planarians, which are considered suitable for investigations in neurotoxicology and currently are widely used as an animal model in neuropharmacological studies. Planarians treated with 10  µ M sertraline showed a rapid reduction in their spontaneous movement until they became completely motionless and then showed a series of asynchronous paroxysms (seizures) followed by progressive tissue damage, beginning 48 h after the sertraline treatment, and died approximately 72 h later. Our data showed that sertraline does not cause planarian death within the range of therapeutic concentrations; however, behavioral alterations were observed with concentrations that can be considered compatible with therapeutic ones, such as a significant reduction in planarian locomotory activity at 0.4  µ M. Treatment with 4  µ M sertraline had a significant effect, reducing planarian locomotory activity and increasing the number of asynchronous paroxysms; both effects were significantly maintained even 24 h after the sertraline was withdrawn. These behavioral changes observed at low micromolar concentrations suggest that sertraline might have residual biological consequences for planarians, even after it is withdrawn.

  4. Tartrazine induced neurobiochemical alterations in rat brain sub-regions.

    Science.gov (United States)

    Bhatt, Diksha; Vyas, Krati; Singh, Shakuntala; John, P J; Soni, Inderpal

    2018-03-01

    Tartrazine is a synthetic lemon yellow azo dye primarily used as a food coloring. The present study aimed to screen the neurobiochemical effects of Tartrazine in Wistar rats after administering the Acceptable Daily Intake (ADI) level. Tartrazine (7.5 mg/kg b.w.) was administered to 21 day old weanling rats through oral gavage once daily for 40 consecutive days. On 41st day, the animals were sacrificed and brain sub regions namely, frontal cortex, corpus striatum, hippocampus and cerebellum were used to determine activities of anti-oxidant enzymes viz. Superoxide Dismutase (SOD), Catalase (CAT), Glutathione-Stransferase (GST), Glutathione Reductase (GR) and Glutathione Peroxidase (GPx) and levels of lipid peroxides using Thio-barbituric Acid Reactive Substance (TBARS) assay. Our investigation showed a significant decrease in SOD and CAT activity, whereas there occurred a decline in GST and GR activity with an increase in GPx activity to counteract the oxidative damage caused by significantly increased levels of lipid peroxides. The possible mechanism of this oxidative damage might be attributed to the production of sulphanilc acid as a metabolite in azofission of tartrazine. It may be concluded that the ADI levels of food azo dyes adversely affect and alter biochemical markers of brain tissue and cause oxidative damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Methoxychlor induces atresia by altering Bcl2 factors and inducing caspase activity in mouse ovarian antral follicles in vitro

    Science.gov (United States)

    Basavarajappa, Mallikarjuna S.; Karman, Bethany N.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2012-01-01

    Methoxychlor (MXC) is an organochlorine pesticide widely used in many countries against various species of insects that attack crops and domestic animals. MXC reduces fertility by increasing atresia (death) of antral follicles in vivo. MXC also induces atresia of antral follicles after 96 h in vitro. The current work tested the hypothesis that MXC induces morphological atresia at early time points (24 and 48 h) by altering pro-apoptotic (Bax, Bok, Casp3, and caspase activity) and anti-apoptotic (Bcl2 and Bcl-xL) factors in the follicles. The results indicate that at 24 h, MXC increased Bcl-xL and Bax mRNA levels and increased the ratio of Bax/Bcl2. At 48–96 h, MXC induced morphological atresia. At 24–96 h, MXC increased caspase activities. These data suggest that MXC may induce atresia by altering Bcl2 factors and inducing caspase activities in antral follicles. PMID:23000595

  6. Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-09-03

    Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntington’s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  7. Characteristics of Yorkshire swine natural killer cells

    International Nuclear Information System (INIS)

    Ferguson, F.G.; Botticelli, G.; Confer, F.L.; Pinto, A.J.

    1986-01-01

    Since natural killer (NK) cells have a role in immune surveillance, they are important to consider in disease pathogenesis and resistance. We examined cell aspects responsible for NK cell mediated cytotoxicity in Yorkshire swine. Using cell separation procedures, peripheral blood lymphocytes were examined for reactivity to a panel of tumor targets, kinetics of lysis, morphology, surface receptor characteristics and response to immunoregulators. YAC-1 lymphoma and K-562 myeloid leukemia cells were sensitive to swine NK cells; whereas, several other tumor lines were not. In kinetic studies, swine NK cells were slower in initiation of the lytic process than cells responsible for NK activity in other species; small agranular lymphocytes are responsible for this activity in swine. These cells were examined for the presence of a surface marker, asialo GM1, which is common to NK cells in several other species. Swine NK cells respond to an interferon inducer, poly I:C, with enhanced NK activity. Cells in Yorkshire swine have characteristics which are unique but also have characteristics common to NK cells in other species

  8. Mesenchymal Stem Cells Induce Expression of CD73 in Human Monocytes In Vitro and in a Swine Model of Myocardial Infarction In Vivo

    Directory of Open Access Journals (Sweden)

    Marta Monguió-Tortajada

    2017-11-01

    Full Text Available The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP/ADP to AMP and to adenosine (Ado, respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tissue-derived MSCs (cATMSCs and umbilical cord MSCs similarly polarize monocytes toward a regulatory M2 phenotype, which maintained the expression of CD39 and induced expression of CD73 in a cell contact dependent fashion, correlating with increased functional activity. In addition, the local treatment with porcine cATMSCs using an engineered bioactive graft promoted the in vivo CD73 expression on host monocytes in a swine model of myocardial infarction. Our results suggest the upregulation of ectonucleotidases on MSC-conditioned monocytes as an effective mechanism to amplify the long-lasting immunomodulatory and healing effects of MSCs delivery.

  9. Blood concentrations of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma during experimentally induced swine dysentery

    Directory of Open Access Journals (Sweden)

    Jensen-Waern Marianne

    2008-08-01

    Full Text Available Abstract Background Knowledge of the cytokine response at infection with Brachyspira hyodysenteriae can help understanding disease mechanisme involved during swine dysentery. Since this knowledge is still limited the aim of the present study was to induce dysentery experimentally in pigs and to monitor the development of important immunoregulatory cytokines in blood collected at various stages of the disease. Methods Ten conventional pigs (~23 kg were orally inoculated with Brachyspira hyodysenteriae B204T. Eight animals developed muco-haemorrhagic diarrhoea with impaired general body condition. Blood was sampled before inoculation and repeatedly during acute dysentery and recovery periods and cytokine levels of IL-1β, IL-6, Il-10, TNF-α and IFN-γ were measured by ELISA. Results IL-1β was increased at the beginning of the dysentery period and coincided with the appearance of Serum amyloid A and clinical signs of disease. TNF-α increased in all animals after inoculation, with a peak during dysentery, and IL-6 was found in 3 animals during dysentery and in the 2 animals that did not develop clinical signs of disease. IL-10 was found in all sick animals during the recovery period. IFN-γ was not detected on any occasion. Conclusion B. hyodysenteriae inoculation induced production of systemic levels of IL-1β during the dysentery period and increased levels of IL-10 coincided with recovery from dysentery.

  10. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    Science.gov (United States)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in

  11. Common swine models of cardiovascular disease for research and training.

    Science.gov (United States)

    Crisóstomo, Verónica; Sun, Fei; Maynar, Manuel; Báez-Díaz, Claudia; Blanco, Virginia; Garcia-Lindo, Monica; Usón-Gargallo, Jesús; Sánchez-Margallo, Francisco Miguel

    2016-02-01

    Cardiovascular diseases are a major health concern and therefore an important topic in biomedical research. Large animal models allow researchers to assess the safety and efficacy of new cardiovascular procedures in systems that resemble human anatomy; additionally, they can be used to emulate scenarios for training purposes. Among the many biomedical models that are described in published literature, it is important that researchers understand and select those that are best suited to achieve the aims of their research, that facilitate the humane care and management of their research animals and that best promote the high ethical standards required of animal research. In this resource the authors describe some common swine models that can be easily incorporated into regular practices of research and training at biomedical institutions. These models use both native and altered vascular anatomy of swine to carry out research protocols, such as testing biological reactions to implanted materials, surgically creating aneurysms using autologous tissue and inducing myocardial infarction through closed-chest procedures. Such models can also be used for training, where native and altered vascular anatomy allow medical professionals to learn and practice challenging techniques in anatomy that closely simulates human systems.

  12. Systematic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis

    International Nuclear Information System (INIS)

    Fisher, M.S.; Kripke, M.L.

    1977-01-01

    Chronic irradiation of mice with ultraviolet (uv) light produces a systemic alteration of an immunologic nature. This alteration is detectable in mice long before primary skin cancers induced by uv light begin to appear. The alteration results in the failure of uv-irradiated mice to reject highly antigenic, transplanted uv-induced tumors that are rejected by unirradiated syngeneic recipients. The immunologic aspect of this systemic alteration was demonstrated by transferring lymphoid cells from uv-irradiated mice to lethally x-irradiated recipients. These recipients were unable to resist a later challenge with a syngeneic uv-induced tumor, whereas those given lymphoid cells from normal donors were resistant to tumor growth. Parabiosis of normal mice with uv-irradiated mice, followed by tumor challenge of both parabionts with a uv-induced tumor, resulted in the growth of the challenge tumors in both uv-irradiated and unirradiated mice. Splenic lymphocytes from tumor-implanted uv-treated mice were not cytotoxic in vitro against uv-induced tumors, whereas under identical conditions cells from tumor-implanted, unirradiated mice were highly cytotoxic. Our findings suggest that repeated uv irradiation can circumvent an immunologic mechanism that might otherwise destroy nascent uv-induced primary tumors that are strongly antigenic

  13. Grinding-induced metallurgical alterations in the binder phase of WC-Co cemented carbides

    OpenAIRE

    Yang, Jing; Roa Rovira, Joan Josep; Schwind, Martin; Odén, M.; Johansonn Joesaar, M. P.; Llanes Pitarch, Luis Miguel

    2017-01-01

    The metallic binder phase dictates the toughening behavior of WC-Co cemented carbides (hardmetals), even though it occupies a relative small fraction of the composite. Studies on deformation and phase transformation of the binder constituent are scarce. Grinding represents a key manufacturing step in machining of hardmetal tools, and is well-recognized to induce surface integrity alterations. In this work, metallurgical alterations of the binder phase in ground WC-Co cemented carbides have be...

  14. Alteration of radiation-induced hematotoxicity by amifostine

    International Nuclear Information System (INIS)

    Momm, Felix; Bechtold, Christine; Rudat, Volker; Strnad, Vratislav; Tsekos, Alexander; Fischer, Karin; Henke, Michael

    2001-01-01

    Purpose: To investigate whether amifostine can reduce radiation hematotoxicity. Patients and Methods: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5x2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m 2 amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n=501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. Results: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10 3 /mm 3 to 5.8x10 3 /mm 3 (difference: 2.3x10 3 /mm 3 ). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. Conclusion: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study

  15. Activation of PI3-kinase/Akt induced small bowel cell apoptosis during laparoscopic ischaemia-reperfusion of swine jejunum.

    Science.gov (United States)

    Puglisi, F; Lacitigniola, L; Loverre, A; Capuano, P; Martines, G; Staffieri, F; Rossi, G; Crovace, A

    2009-01-01

    This study aimed to detect small bowel cell apoptosis by evaluating the nuclear activation of transcription factors, nuclear factor-kappaB (NF-kappaB) and Akt pathways as well as detecting apoptotic cells by TUNEL assay, during ischaemia-reperfusion (I/R) injury by Arterio-Venous Occlusion (AVO) of ajejunal loop in swine, using a laparoscopic procedure. A jejunal loop was isolated and a biopsy sample (T0) obtained. Biopsies were obtained at 30 minutes (T30I) and 60 minutes (T60I) after clamping and again during reperfusion (R), T30R and T60R. Standard H&E stains and immunohistochemical study for infiltrating polymorphonuclear leukocytes and TUNEL assays were performed. The activation of Akt and NF-kappaB in the animal model was evaluated by indirect immunofluorescence and confocal microscopy. Our results confirmed that I/R injury of the jejunum did not only cause epithelial damage, but also activated the molecular pathways triggering an apoptotic reaction (by pro-inflammatory cytokines) and an anti-apoptotic mechanism that can lead to the regeneration of injured tissue.

  16. Pneumonia induced by swine-origin influenza A (H1N1) infection. Chest computed tomography findings in children

    International Nuclear Information System (INIS)

    Yamada, Kentaro; Shinmoto, Hiroshi; Hamamoto, Manabu; Yoshida, Yusuke; Kawauchi, Toshio; Kaji, Tatsumi; Kosuda, Shigeru

    2011-01-01

    The purpose of this study was to determine the features of chest computed tomography (CT) in children with swine-origin influenza A (H1N1) virus (S-OIV). The study population consisted of 16 children with laboratory-confirmed S-OIV infection (12 boys, 4 girls), with an age range of 5-10 years (mean 6.3 years). Pneumonia was suspected in these patients based on clinical features or confirmed by radiography. All subjects underwent CT for close evaluation of pneumonia, including characteristics, distribution, extent, and other findings such as pleural effusion, pneumothorax, and pneumomediastinum. The predominant CT finding was consolidation plus ground-grass opacity (GGO) (11/16, 69%). The consolidation-dominant pattern was found in 10 of 16 (66%) patients, and 1 (6%) was GGO-dominant. One (6%) had only GGO. In all, 7 of the 16 patients had segmental or lobar consolidation. Abnormal opacities were primarily distributed in the central lung zone (8/16, 50%) and were multifocal (15/16, 94%). Four showed atelectasis (4/16, 25%). Pneumomediastinum was observed in 4 of 16 (25%). One patient had negative radiographic findings but was positive on CT. Multifocal consolidation with central distribution is a common CT finding in children with S-OIV, but there are few GGO-dominant cases. Widespread consolidation (segmental or lobar) is also common. (author)

  17. Cypermethrin induced alterations in nitrogen metabolism in freshwater fishes.

    Science.gov (United States)

    Kumar, Amit; Sharma, Bechan; Pandey, Ravi S

    2011-04-01

    In the present study, two fresh water fishes namely, Channa punctatus and Clarias batrachus, were exposed to three sub-acute concentrations of synthetic pyrethroid, cypermethrin, for 96 h to evaluate the role of amino acids in fulfilling the immediate energy needs of fishes under pyrethroid induced stress as well as to find out the mechanism of ammonia detoxification. The experiments were designed to estimate the levels of free amino acid, urea, ammonia and the activities of aspartate aminotransferase (AAT), alanine aminotransferase (AlAT), glutamate dehydrogenase (GDH), glutamine synthetase (GS) and arginase in some of the vital organs like brain, gills, liver, kidney and muscle of both fish species. The significant decrease in the levels of amino acids concomitant with remarkable increase in the activities of AAT, AlAT and GDH in these vital tissues of fish species elucidated the amino acid catabolism as one of the main mechanism of meeting out the immediate energy demand of the fishes in condition of cypermethrin exposure. The levels of ammonia were significantly increased at 10% of 96 h LC(50) of cypermethrin in the different organs such as brain, gills, liver, kidney and muscle of both fish species while 15% and 20% concentrations of 96 h LC(50) of cypermehrin registered remarkable decline in both fish species. The differential increment in the activities of GDH, GS and arginase and in the level of urea established three different alternative mechanisms of ammonia detoxification. The results indicated that in C. punctatus, the prevalent mode of nitrogen excretion is in the form of conversion of ammonia into glutamine and glutamate while in C. batrachus, the excessive nitrogen is excreted in the form of urea synthesized from ammonia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. ENDOCRINE ALTERATIONS IN REPRODUCTIVE SWINES OF HIGH PERFORMANCE ALTERAÇÕES ENDÓCRINAS EM REPRODUTORES SUÍNOS DE ALTO DESEMPENHO

    Directory of Open Access Journals (Sweden)

    Ana Luisa Neves Alvarenga

    2010-04-01

    Full Text Available

    The aim of this work was to describe the sexual and reproductive behavior of male swines of high performance, submitted to a training protocol for semen collection so that they were incorporated in breeding of reproducers of the Swine Production Sector of the Animal Science Department of the Federal University of Lavras. Animals had been submitted to measurements of testicular biometry and weighing for evaluations of testicular development and of daily gain weight (DGW. After the training period, blood samples  were collected for accomplishment of hormonal analyses of serum testosterone, oestradiol, FSH, and LH. Differences were observed in testosterone and oestradiol levels, average number of daily dummy jumps, and average ejaculation time. Animal A presented a volume of 369.68 mL and 412.67 mL, to the right and left testicle, respectively, on average eight daily dummy jumps during the period of training and the average ejaculation time was of 261 seconds. The Animal B did not carry through jump during the training and presented testicular volume of 359.76 mL right and left of 315.10 mL. Hormonal levels for animal A had been of 0.0153 ng/mL and 0.7015 ng/mL for testosterone and oestradiol, respectively. On the other hand, Animal B presented plasmatic concentration of testosterone of 0.0011 ng/mL and 0.0241 ng/mL of oestradiol. The concentrations of FSH and LH had been similar between the animals being 0.10 mU/mL and 0.10 U/L, respectively. These differences observed possibly explain both males’s sexual behavior during the period of training and semen collected.

    KEY WORDS: Boar, libido, hormones, sexual behavior.

    Objetivando descrever o comportamento sexual e reprodutivo de machos suínos de alto desempenho, submeteram-se os animais a um protocolo de treinamento para colheita de sêmen, a fim de que fossem incorporados ao plantel de reprodutores do Setor de Suinocultura do Departamento de Zootecnia da UFLA. Submeteram

  19. Swine mycoplasmoses

    DEFF Research Database (Denmark)

    Kobisch, M.; Friis, N.F.

    1996-01-01

    infection, immune reactions are observed and resistance is induced in pigs. Laboratory diagnosis is generally performed by an immunofluorescent test and by enzyme-linked immunosorbent assay. Antibiotics are useful but the development of resistance has been described. Vaccination seems to be an effective...... method of controlling the disease. M. hyorhinis, generally transmitted by sows to piglets through nasal secretions, exists in a high percentage in the respiratory tract of healthy pigs. But some strains can induce serofibrinous to fibrinopurulent polyserositis and arthritis. M. hyorhinis is isolated from...

  20. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

    Science.gov (United States)

    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

  1. Pollutant-induced alterations of granulocyte morphology in the earthworm Eisenia foetida.

    Science.gov (United States)

    Calisi, Antonio; Lionetto, Maria Giulia; Schettino, Trifone

    2009-07-01

    Earthworms are considered convenient indicators of land use and soil fertility. Recently the use of biomarkers in earthworms has been increasingly investigated. The aim of this work was to study possible pollutant-induced morphometric alterations in Eisenia foetida granulocytes in view of future applications as a sensitive, simple, and quick biomarker for soil monitoring and assessment applications. Results showed consistent enlargement of earthworm granulocytes induced by exposure to either copper sulfate or methiocarb. The increase of cellular size was time-dependent and was about 100% after 14 days of exposure for both treatments. In order to verify the applicability of morphometric granulocyte alteration, a battery of standardized biomarkers such as lysosomal membrane stability, metallothionein induction, or acetylcholinesterase (AChE) inhibition were also determined. We recommend the use of morphometric alterations of granulocytes as a suitable biomarker of pollutant effect to be included in a multibiomarker strategy including responses at different levels of biological organization.

  2. Cold-induced alteration in the global structure of the male sex ...

    Indian Academy of Sciences (India)

    In Drosophila melanogaster, dosage compensation occurs through hypertranscription of sex-linked genes in males. ... [Kulkarni-Shukla S., Barge A. P., Vartak R. S. and Kar A. 2008 Cold-induced alteration in the global structure of the male sex chromosome ..... forms acetylated at specific lysine residues define individual.

  3. Effect of Admixed Micelles on the Microstructure Alterations of Reinforced Mortar Subjected to Chloride Induced Corrosion

    NARCIS (Netherlands)

    Hu, J.; Koleva, D.A.; Van Breugel, K.

    2011-01-01

    This paper reports the main results from the influence of the initially admixed nano-aggregates (0.5 g/l PEO113-b-PS70 micelles previously dissolved in demi-water) on microstructural alterations of the reinforced mortar subjected to chloride induced corrosion. The morphology of hydration/corrosion

  4. Effects of Ascorbic Acid on Garlic-induced Alterations in Semen ...

    African Journals Online (AJOL)

    Effects of Ascorbic Acid on Garlic-induced Alterations in Semen Parameters Of Wistar Rats. GO Omotoso, IO Onanuga, AAG Jimoh. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/tjhc.v18i2.69616 · AJOL African Journals ...

  5. Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.

    Science.gov (United States)

    Fernandez, Diego C; Pasquini, Laura A; Dorfman, Damián; Aldana Marcos, Hernán J; Rosenstein, Ruth E

    2012-01-01

    Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.

  6. Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.

    Directory of Open Access Journals (Sweden)

    Diego C Fernandez

    Full Text Available Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.

  7. Roles of p38 MAPK in the regulation of the inflammatory response to swine influenza virus-induced acute lung injury in mice.

    Science.gov (United States)

    Wei, D; Huang, Z H; Zhang, R H; Wang, C L; Xu, M J; Liu, B J; Wang, G H; Xu, T

    2014-01-01

    Swine influenza virus (SIV), one of the most important zoonotic agents, is associated with major public health concerns. The current study was conducted to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in the regulation of the inflammatory response to acute lung injury (ALI) induced by SIV of H9N2 subtype (H9N2-SIV) in mice. For this purpose, BALB/c mice were intranasally infected with 20 LD(50) of H9N2-SIV (infected group), while non-infected mice served as control (control group). To assess the effect of p38 MAPK, its specific inhibitor SB203580 was employed followed by SIV infection (SB group). At various times after infection, mouse lungs were subjected to pathological and histological observations and detection of inflammatory cytokines tumor necrosis factor α (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 and phosphorylated p38 MAPK. The obtained results showed obvious inflammatory responses, injury and raised levels of inflammatory cytokines and phosphorylated p38 MAPK in the lungs of virus-infected mice. In the mice inoculated with the virus alone, the level of phosphorylated p38 MAPK increased from day 2 and peaked at day 6 post infection (p.i.). However, SB203580 caused lower increases in inflammatory cytokines and phosphorylated p38 MAPK and a milder lung injury. These findings indicate that the activation of p38 MAPK upregulated the inflammatory responses to H9N2-SIV-induced ALI, increased its severity and promoted the production of inflammatory cytokines.

  8. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic.

    Science.gov (United States)

    Ortega-Domínguez, Bibiana; Aparicio-Trejo, Omar Emiliano; García-Arroyo, Fernando E; León-Contreras, Juan Carlos; Tapia, Edilia; Molina-Jijón, Eduardo; Hernández-Pando, Rogelio; Sánchez-Lozada, Laura Gabriela; Barrera-Oviedo, Diana; Pedraza-Chaverri, José

    2017-09-01

    Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD + -dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Altered magnesium transport in slices of kidney cortex from chemically-induced diabetic rats

    International Nuclear Information System (INIS)

    Hoskins, B.

    1981-01-01

    The uptake of magnesium-28 was measured in slices of kidney cortex from rats with alloxan-diabetes and from rats with streptozotocin-diabetes of increasing durations. In both forms of chemically-induced diabetes, magnesium-28 uptake by kidney cortex slices was significantly increased over uptake measured in kidney cortex slices from control rats. Immediate institution of daily insulin therapy to the diabetic rats prevented the diabetes-induced elevated uptake of magnesium without controlling blood glucose levels. Late institution of daily insulin therapy was ineffective in restoring the magnesium uptake to control values. These alterations in magnesium uptake occurred prior to any evidence of nephropathy (via the classic indices of proteinuria and increased BUN levels). The implications of these findings, together with our earlier demonstrations of altered calcium transport by kidney cortex slices from chemically-induced diabetic rats, are discussed in terms of disordered divalent cation transport being at least part of the basic pathogenesis underlying diabetic nephropathy

  10. Replicon particle vaccine protects swine against influenza.

    Science.gov (United States)

    Bosworth, B; Erdman, M M; Stine, D L; Harris, I; Irwin, C; Jens, M; Loynachan, A; Kamrud, K; Harris, D L

    2010-12-01

    An alphavirus derived replicon particle (RP) vaccine expressing the cluster IV H3N2 swine influenza virus (SIV) hemagglutinin (HA) gene induced protective immunity against homologous influenza virus challenge. However, pigs with maternal antibody had no protective immunity against challenge after vaccination with RP vaccines expressing HA gene alone or in combination with nucleoprotein gene. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Transcription analysis on response of swine lung to H1N1 swine influenza virus.

    Science.gov (United States)

    Li, Yongtao; Zhou, Hongbo; Wen, Zhibin; Wu, Shujuan; Huang, Canhui; Jia, Guangmin; Chen, Huanchun; Jin, Meilin

    2011-08-08

    As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs. At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p swine influenza virus infection in pigs. The observed gene expression profile could help to screen the potential host agents for reducing the prevalence of swine influenza virus and further understand the molecular pathogenesis associated with H1N1 infection in pigs.

  12. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  13. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

    Directory of Open Access Journals (Sweden)

    Shinya Akatsuka

    Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

  14. Histological and Physiological Alterations Induced by Thermal Neutron Fluxes in Male Swiss Albino Mice

    International Nuclear Information System (INIS)

    Alzergy, A.A.; Emara, N.M.; Abd El-Latif, A.A.; El-Saady, S.M.M.; Emara, N.M.; Abd El-Latif, A.A.

    2010-01-01

    This work was performed to investigate the biological effects of different thermal neutron fluxes (0.27x10 8 , 0.52X10 8 , 1.089X10 8 , 2.16X10 8 and 4.32X10 8 ) on liver and kidney of male mice using neutron irradiation cell with Ra-Be(α,n) 3 mCi neutron source Leybold (55930). Exposed to various fluxes of thermal neutron induced a dramatic alterations in hepatic and renal functions as indicated by biochemical estimation of several parameters (bilirubin, SGT, and alkaline phosphate .Urea , total protein, and albumin) and confirmed by histological examinations Thermal neutron exposure induces marked increase in the serum activities of total bilirubin, alanine amino transaminase (ALT or GPT), and alkaline phosphate, whereas, urea, total protein and albumin showed marked decline as compared to control group. The physiological changes induced in thermal neutron fluxes dependent manner. Histopathological results revealed mild to severe type of necrosis, and degenerative changes in liver and kidney of male mice exposed to thermal neutron fluxes. Also it was found that the histopathological alterations induced in thermal neutron fluxes dependent manner. It was found that exposed to thermal neutron fluxes irradiation plays prominent role in the development of the physiological alterations in male Swiss albino mice. The Former up normalities as a result of the sequence events followed interaction of radiation with the former biological mater (liver and kidney) of male Swiss albino mice, which are, physical, physicochemical, chemical, and biological stages.

  15. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  16. Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism

    Directory of Open Access Journals (Sweden)

    Mario Negrette-Guzmán

    2015-01-01

    Full Text Available It has been shown that curcumin (CUR, a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM- induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2-related factor 2 (Nrf2 nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

  17. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    International Nuclear Information System (INIS)

    Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

    2014-01-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced

  18. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced

  19. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Park

    2015-01-01

    Full Text Available It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH mRNA and activating serotonin transporter (SERT in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study.

  20. Recent advances in the understanding of sepsis-induced alterations in the neuroendocrine system.

    Science.gov (United States)

    Wahab, Fazal; Atika, Bibi; Oliveira-Pelegrin, Gabriela Ravanelli; Rocha, Maria José Alves

    2013-12-01

    Sepsis is a fatal systemic inflammatory disease. It is caused by an immune system inflammatory response to the entry of microorganisms or their products into the blood circulatory system. The pathophysiological mechanisms of sepsis are still poorly understood. The presence of microorganisms in the systemic circulation causes activation of the immune system, which in turn leads to a robust release of inflammatory cytokines. These inflammatory cytokines result in alterations across all important physiological systems, including the neuroendocrine system. Neuroendocrine responses differ between the acute and the late phase of sepsis. In the acute phase there are robust alterations in the secretion of neuroendocrine hormones in response to body demand. In the late phase, the plasma concentrations of some hormones remain low, despite heavy systemic demand, whereas several others increase despite of diminished needs. In this review, we give a brief overview on sepsis-induced major alterations in neuroendocrine secretions, and summarize current knowledge about mechanisms and targets for their treatment.

  1. DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Mankgopo Magdeline Kgatle

    2017-01-01

    Full Text Available Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV, hepatitis B virus (HBV, and Epstein-Barr virus (EBV. Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

  2. Antivenom reversal of biochemical alterations induced by black scorpion Heterometrus fastigiousus Couzijn venom in mice

    Directory of Open Access Journals (Sweden)

    MK Chaubey

    2009-01-01

    Full Text Available In the present study, Heterometrus fastigiousus venom (HFV was employed as antigen to produce species-specific scorpion antivenom (SAV in albino mice (NIH strain. To determine SAV efficacy, it was pre-incubated with 10 LD50 of HFV and then injected subcutaneously into mice. Subsequently, mortality was observed after 24 hours. Minimum effective dose (MED was 12.5 LD50 of HFV/mL of SAV. SAV effectiveness to reverse HFV-induced biochemical alterations in mice was analyzed by challenge method. Simultaneously, mice received subcutaneously 40% of 24-hour-LD50 of HFV and intravenously SAV. After four hours, changes in serum glucose, free amino acids, uric acids, pyruvic acid, cholesterol, total protein, alkaline phosphatase, acid phosphatase, lactic dehydrogenase and glutamate-pyruvate transaminase enzyme level were determined. Treatment with species-specific SAV resulted in the reversal of HFV-induced biochemical alterations.

  3. Transforming growth factor-β2 induces morphological alteration of human corneal endothelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2014-10-01

    Full Text Available AIM:To investigate the morphological altering effect of transforming growth factor-β2 (TGF-β2 on untransfected human corneal endothelial cells (HCECs in vitro.METHODS: After untransfected HCECs were treated with TGF-β2 at different concentrations, the morphology, cytoskeleton distribution, and type IV collagen expression of the cells were examined with inverted contrast light microscopy, fluorescence microscopy, immunofluorescence or Western Blot.RESULTS:TGF-β2 at the concentration of 3-15 μg/L had obviously alterative effects on HCECs morphology in dose and time-dependent manner, and 9 μg/L was the peak concentration. TGF-β2 (9 μg/L altered HCE cell morphology after treatment for 36h, increased the mean optical density (P<0.01 and the length of F-actin, reduced the mean optical density (P<0.01 of the collagen type IV in extracellular matrix (ECM and induced the rearrangement of F-actin, microtubule in cytoplasm and collagen type IV in ECM after treatment for 72h. CONCLUTION:TGF-β2 has obviously alterative effect on the morphology of HCECs from polygonal phenotype to enlarged spindle-shaped phenotype, in dose and time-dependence manner by inducing more, elongation and alignment of F-actin, rearrangement of microtubule and larger spread area of collagen type IV.

  4. Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

    International Nuclear Information System (INIS)

    Tong, Ying; Smith, M.A.; Tucker, S.B.

    1997-01-01

    Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

  5. Radiation-induced epigenetic alterations after low and high LET irradiations

    International Nuclear Information System (INIS)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-01-01

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise in the

  6. Radiation-induced epigenetic alterations after low and high LET irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut, E-mail: uaypa001@umaryland.edu [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Baulch, Janet E. [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2011-02-10

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NF{kappa}B), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise

  7. Swine brucellosis: current perspectives

    Directory of Open Access Journals (Sweden)

    Olsen SC

    2016-12-01

    Full Text Available SC Olsen, FM Tatum Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA Abstract: Brucella suis is a significant zoonotic species that is present in domestic livestock and wildlife in many countries worldwide. Transmission from animal reservoirs is the source of human infection as human-to-human transmission is very rare. Although swine brucellosis causes economic losses in domestic livestock, preventing human infection is the primary reason for its emphasis in disease control programs. Although disease prevalence varies worldwide, in areas outside of Europe, swine brucellosis is predominantly caused by B. suis biovars 1 and 3. In Europe, swine are predominantly infected with biovar 2 which is much less pathogenic in humans. In many areas worldwide, feral or wild populations of swine are important reservoir hosts. Like other Brucella spp. in their natural host, B. suis has developed mechanisms to survive in an intracellular environment and evade immune detection. Limitations in sensitivity and specificity of current diagnostics require use at a herd level, rather for individual animals. There is currently no commercial vaccine approved for preventing brucellosis in swine. Although not feasible in all situations, whole-herd depopulation is the most effective regulatory mechanism to control swine brucellosis. Keywords: livestock, transmission, pathogenicity, vaccine, host, infection

  8. Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle.

    Science.gov (United States)

    Sirvent, Pascal; Mercier, Jacques; Vassort, Guy; Lacampagne, Alain

    2005-04-15

    Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, and fatigability) occur frequently. We hypothesized that the iatrogenic effects of statins could result from alterations in Ca(2+) homeostasis. Acute applications of simvastatin on human skeletal muscle fibers triggered a Ca(2+) wave of intra-cellular Ca(2+) that mostly originates from sarcoplasmic reticulum (SR) Ca(2+)-release. In addition, simvastatin increased mitochondrial NADH content and induced mitochondrial membrane depolarization (EC(50)=1.96 microM) suggesting an altered mitochondrial function. Consequently on simvastatin application, a weak mitochondrial Ca(2+) efflux (EC(50)=7.8 microM) through permeability transient pore and Na(+)/Ca(2+) exchanger was triggered, preceding the large SR-Ca(2+) release. Increased SR Ca(2+) content after acute application of statin is also suggested by the increased Ca(2+) spark amplitude and by the effect of cyclopiazonic acid. We thus conclude that simvastatin induced alterations in mitochondrial function which lead to an increase in cytoplasmic Ca(2+), SR-Ca(2+) overload, and Ca(2+) waves. Taken together, these statin-induced muscle dysregulations may contribute to myotoxicity.

  9. RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

    International Nuclear Information System (INIS)

    Rousseau, Matthieu; Gaugler, Marie-Hélène; Rodallec, Audrey; Bonnaud, Stéphanie; Paris, François; Corre, Isabelle

    2011-01-01

    Highlights: ► We explore the role of RhoA in endothelial cell response to ionizing radiation. ► RhoA is rapidly activated by single high-dose of radiation. ► Radiation leads to RhoA/ROCK-dependent actin cytoskeleton remodeling. ► Radiation-induced apoptosis does not require the RhoA/ROCK pathway. ► Radiation-induced alteration of endothelial adhesion and migration requires RhoA/ROCK. -- Abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.

  10. Influence of mycotoxin zearalenone on the swine reproductive failure

    Directory of Open Access Journals (Sweden)

    Prodanov-Radulović Jasna Z.

    2013-01-01

    Full Text Available Reproductive failure in swine is often a difficult diagnostic problem. If diagnoses of infectious disease or management related problems are not obtained, feed quality and safety may be questioned. Mycotoxins are often present in swine feed in the amount that can have detrimental impact on production and reproduction. Problems are expressed only as alterations of the reproductive cycle, reduced feed intake, slow growth or impaired feed efficiency. In Serbia, generally speaking, high concentrations of mycotoxins were noticed, especially mycotoxin zearalenone. High presence of zearalenone in swine feed is probably due to climatic influence and should be monitored constantly. This paper includes field observations regarding the influence of moldy feed containing mycotoxin zearalenone on the occurrence of the reproductive failure in swine breeding categories (sows, gilts and boars. The material for this research was obtained from four swine farms where certain reproductive disorders and health problems in breeding animals were detected. Depending on the specificity of each evaluated case and available material, the applied research methods included: anamnestic and clinical evaluation, pathomorphological examination, standard laboratory testing for detection of aerobic and anaerobic bacteria, and microbiological feed testing, in order to examine the presence of fungi and mycotoxins by applying the method of thin layer chromatography. On the basis of the obtained results, it could be concluded that mycotoxin zearalenone was detected in all examined feed samples. The presence of mycotoxin in feed was directly related to the reproductive failures in the examined swine categories (vulvovaginitis, endometritis, rebreeding, infertility. Swine reproduction represents the base for intensive swine production. The presence of mycotoxins in swine feed have influence on the reproduction and health status of pigs and under certain conditions may significantly

  11. Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood.

    Science.gov (United States)

    Golubeva, Anna V; Crampton, Sean; Desbonnet, Lieve; Edge, Deirdre; O'Sullivan, Orla; Lomasney, Kevin W; Zhdanov, Alexander V; Crispie, Fiona; Moloney, Rachel D; Borre, Yuliya E; Cotter, Paul D; Hyland, Niall P; O'Halloran, Ken D; Dinan, Timothy G; O'Keeffe, Gerard W; Cryan, John F

    2015-10-01

    Early-life adverse experiences, including prenatal stress (PNS), are associated with a higher prevalence of neurodevelopmental, cardiovascular and metabolic disorders in affected offspring. Here, in a rat model of chronic PNS, we investigate the impact of late gestational stress on physiological outcomes in adulthood. Sprague-Dawley pregnant dams were subjected to repeated restraint stress from embryonic day 14 to day 20, and their male offspring were assessed at 4 months of age. PNS induced an exaggeration of the hypothalamic-pituitary-adrenal (HPA) axis response to stress, as well as an elevation of blood pressure and impairment of cognitive function. Altered respiratory control was also observed, as demonstrated by increased variability in basal respiratory frequency and abnormal frequency responses to both hypoxic and hypercapnic challenges. PNS also affected gastrointestinal neurodevelopment and function, as measured by a decrease in the innervation density of distal colon and an increase in the colonic secretory response to catecholaminergic stimulation. Finally, PNS induced long lasting alterations in the intestinal microbiota composition. 16S rRNA gene 454 pyrosequencing revealed a strong trend towards decreased numbers of bacteria in the Lactobacillus genus, accompanied by elevated abundance of the Oscillibacter, Anaerotruncus and Peptococcus genera in PNS animals. Strikingly, relative abundance of distinct bacteria genera significantly correlated with certain respiratory parameters and the responsiveness of the HPA axis to stress. Together, these findings provide novel evidence that PNS induces long-term maladaptive alterations in the gastrointestinal and respiratory systems, accompanied by hyper-responsiveness to stress and alterations in the gut microbiota. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Induced defences alter the strength and direction of natural selection on reproductive traits in common milkweed.

    Science.gov (United States)

    Thompson, K A; Cory, K A; Johnson, M T J

    2017-06-01

    Evolutionary biologists have long sought to understand the ecological processes that generate plant reproductive diversity. Recent evidence indicates that constitutive antiherbivore defences can alter natural selection on reproductive traits, but it is unclear whether induced defences will have the same effect and whether reduced foliar damage in defended plants is the cause of this pattern. In a factorial field experiment using common milkweed, Asclepias syriaca L., we induced plant defences using jasmonic acid (JA) and imposed foliar damage using scissors. We found that JA-induced plants experienced selection for more inflorescences that were smaller in size (fewer flowers), whereas control plants only experienced a trend towards selection for larger inflorescences (more flowers); all effects were independent of foliar damage. Our results demonstrate that induced defences can alter both the strength and direction of selection on reproductive traits, and suggest that antiherbivore defences may promote the evolution of plant reproductive diversity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  13. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, J.G.P. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Universidade Iguaçu, Campos V, Itaperuna, RJ (Brazil); Faculdade de Minas, Muriaé, MG (Brazil); Vasques, E.R. [Departamento de Gastroenterologia, LIM 37, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Arida, R.M. [Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cavalheiro, E.A. [Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cabral, F.R.; Torres, L.B. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Godoy, C.M.G. [Departamento de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, SP (Brazil); Gomes da Silva, S. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Núcleo de Pesquisas Tecnológicas, Programa Integrado em Engenharia Biomédica, Universidade de Mogi das Cruzes, Mogi das Cruzes, SP (Brazil)

    2015-01-13

    The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

  14. Sepsis induced by cecal ligation and perforation (CLP) alters nucleotidase activities in platelets of rats.

    Science.gov (United States)

    Pereira, Renata S; Bertoncheli, Claudia M; Adefegha, Stephen A; Castilhos, Lívia G; Silveira, Karine L; Rezer, João Felipe P; Doleski, Pedro H; Abdalla, Fátima H; Santos, Karen F; Leal, Claudio A M; Santos, Roberto C V; Casali, Emerson A; Moritz, Cesar E J; Stainki, Daniel R; Leal, Daniela B R

    2017-10-01

    Sepsis is a potentially lethal condition, and it is associated with platelet alterations. The present study sought to investigate the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), E-5'-nucleotidase, and ecto-adenosine deaminase (E-ADA) in the platelets of rats that were induced with sepsis. Male Wistar rats were divided into three groups of ten animals each: a negative control group (normal; NC); a group that underwent surgical procedures (sham); and a group that underwent cecal ligation and perforation (CLP). The induction of sepsis was confirmed by bacteremia, and the causative pathogen identified was Escherichia coli. Hematological parameters showed leukocytosis and thrombocytopenia in animals in the septic group. The results also revealed that there were significant (p CLP group compared to the sham and control groups. Conversely, ADP hydrolysis was significantly decreased (p CLP group compared to the sham and control groups. Purine levels were analyzed by high-performance liquid chromatography (HPLC) in serum samples from control, sham, and CLP groups. Increased concentrations of ATP, adenosine, and inosine were found in the CLP group compared to the sham and control groups. Conversely, the concentrations of ADP and AMP in the CPL group were not significantly altered. We suggest that alterations in hematological parameters, nucleotide hydrolysis in platelets, and nucleotide concentrations in serum samples of rats with induced sepsis may be related to thromboembolic events. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. In-situ pyrogenic production of biodiesel from swine fat.

    Science.gov (United States)

    Lee, Jechan; Tsang, Yiu Fai; Jung, Jong-Min; Oh, Jeong-Ik; Kim, Hyung-Wook; Kwon, Eilhann E

    2016-11-01

    In-situ production of fatty acid methyl esters from swine fat via thermally induced pseudo-catalytic transesterification on silica was investigated in this study. Instead of methanol, dimethyl carbonate (DMC) was used as acyl acceptor to achieve environmental benefits and economic viability. Thermo-gravimetric analysis of swine fat reveals that swine fat contains 19.57wt.% of water and impurities. Moreover, the fatty acid profiles obtained under various conditions (extracted swine oil+methanol+NaOH, extracted swine oil+DMC+pseudo-catalytic, and swine fat+DMC+pseudo-catalytic) were compared. These profiles were identical, showing that the introduced in-situ transesterification is technically feasible. This also suggests that in-situ pseudo-catalytic transesterification has a high tolerance against impurities. This study also shows that FAME yield via in-situ pseudo-catalytic transesterification of swine fat reached up to 97.2% at 380°C. Therefore, in-situ pseudo-catalytic transesterification can be applicable to biodiesel production of other oil-bearing biomass feedstocks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Radiation-induced alterations in murine lymphocyte homing patterns. I. Radiolabeling studies

    International Nuclear Information System (INIS)

    Crouse, D.A.; Feldbush, T.L.; Evans, T.C.

    1976-01-01

    In vitro x-irradiation of 51 Cr-labeled spleen, lymph node, bone marrow, or thymus cells was found to alter their subsequent in vivo distribution significantly in syngeneic BDF 1 mice. Irradiated cells demonstrated an increased distribution to the liver and a significantly lower retention in the lungs. Cells going to the lymph nodes or Peyer's patches showed a significant exposure-dependent decrease in homing following irradiation. Irradiated lymph node cells homed in greater numbers to the spleen and bone marrow, while irradiated cells from other sources showed no preferential distribution to the same tissues. Sampling host tissues at various times after irradiation and injection did not demonstrate any return to normal patterns of distribution. The alterations in lymphocyte homing observed after in vitro irradiation appear to be due to the elimination of a selective population of lymphocytes or membrane alterations of viable cells, and the detection of these homing changes is in turn dependent upon the relative numbers of various lymphoid subpopulations which are obtained from different cell sources. Radiation-induced alterations in the normal homing patterns of lymphoid cells may thus be of considerable importance in the evaluation of subsequent functional assays in recipient animals

  17. Analysis of unstable chromosome alterations frequency induced by neutron-gamma mixed field radiation

    International Nuclear Information System (INIS)

    Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Vale, Carlos H.F.P.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F.; Calixto, Merilane S.; Santos, Neide

    2009-01-01

    Nowadays monitoring chromosome alterations in peripheral blood lymphocytes have been used to access the radiation absorbed dose in individuals exposed accidental or occupationally to gamma radiation. However there are not many studies based on the effects of mixed field neutron-gamma. The radiobiology of neutrons has great importance because in nuclear factories worldwide there are several hundred thousand individuals monitored as potentially receiving doses of neutron. In this paper it was observed the frequencies of unstable chromosome alterations induced by a gamma-neutron mixed field. Blood was obtained from one healthy donor and exposed to mixed field neutron-gamma sources 241 AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphases were analyzed for the presence of chromosome alterations by two experienced scorers. The results suggest that there is the possibility of a directly proportional relationship between absorbed dose of neutron-gamma mixed field radiation and the frequency of unstable chromosome alterations analyzed in this paper. (author)

  18. Experimental pathophysiology of systemic alterations induced by Bothrops asper snake venom.

    Science.gov (United States)

    Gutiérrez, José María; Escalante, Teresa; Rucavado, Alexandra

    2009-12-01

    Moderate and severe envenomations by the snake Bothrops asper provoke systemic alterations, such as systemic bleeding, coagulopathy, hypovolemia, hemodynamic instability and shock, and acute renal failure. Systemic hemorrhage is a typical finding of these envenomations, and is primarily caused by the action of P-III snake venom metalloproteinases (SVMPs). This venom also contains a thrombin-like serine proteinase and a prothrombin-activating P-III SVMP, both of which cause defibrin(ogen)ation. Thrombocytopenia, predominantly induced by a C-type lectin-like protein, and platelet hypoaggregation, caused by the two defibrin(ogen)ating enzymes, also contribute to hemostatic disturbances, which potentiate the systemic bleeding induced by hemorrhagic SVMPs. Cardiovascular disturbances leading to shock are due to the combined effects of hemorrhagic toxins, other venom components that increase vascular permeability, the action of hypotensive agents in the venom and of endogenous mediators, and the potential cardiotoxic effect of some toxins. Renal alterations are likely to be caused by direct cytotoxicity of venom components in the kidney, and by renal ischemia resultant from hypovolemia and hypoperfusion. Lethality induced by B. asper venom is the consequence of several combined effects among which the action of P-III SVMPs is especially relevant.

  19. Dietary Fatty Acids Alter Lipid Profiles and Induce Myocardial Dysfunction without Causing Metabolic Disorders in Mice.

    Science.gov (United States)

    Chen, Bainian; Huang, Yifan; Zheng, Dong; Ni, Rui; Bernards, Mark A

    2018-01-19

    Oversupply of bulk saturated fatty acids (SFA) induces metabolic disorders and myocardial dysfunction. We investigated whether, without causing metabolic disorders, the uptake of individual dietary SFA species alters lipid profiles and induces myocardial dysfunction. C57BL/6 mice were fed various customized long-chain SFA diets (40% caloric intake from SFA), including a beef tallow (HBD), cocoa butter (HCD), milk fat (HMD) and palm oil diet (HPD), for 6 months. An isocaloric fat diet, containing medium-chain triglycerides, served as a control (CHD). Long-term intake of dietary long-chain SFA differentially affected the fatty acid composition in cardiac phospholipids. All long-chain SFA diets increased the levels of arachidonic acid and total SFA in cardiac phospholipids. The preferential incorporation of individual SFA into the cardiac phospholipid fraction was dependent on the dietary SFA species. Cardiac ceramide content was elevated in all mice fed long-chain SFA diets, while cardiac hypertrophy was only presented in mice fed HMD or HPD. We have demonstrated that the intake of long-chain SFA species differentially alters cardiac lipid profiles and induces cardiac dysfunction, without causing remarkable metabolic disorders.

  20. Stress/aggressiveness-induced immune changes are altered in adult rats submitted to neonatal malnutrition.

    Science.gov (United States)

    Barreto-Medeiros, Jairza; Queiros-Santos, Adenilda; Cabral-Filho, José Eulálio; Ferreira E Silva, Wylla Tatiana; Leandro, Carol Góis; Deiró, Tereza Cristina; Manhaes-de-Castro, Raul; Machado Barbosa de-Castro, Célia Maria

    2007-01-01

    Neonatal malnutrition induces metabolic and endocrine changes that have beneficial effects on the neonatal in the short term but, in the longer term, these alterations lead to maladaptations. We investigated the effect of neonatal malnutrition on immune responses in adult rats submitted or not to an aggressiveness test. Male Wistar rats were distributed to one of two groups according to their mothers' diet during lactation: the well-nourished group (group C, n = 42, receiving 23% of protein) and the malnourished group (group MN, n = 42, receiving 8% of protein). After weaning, all rats received normoproteic diet. Ninety days after birth, each group was subdivided into three subgroups: control rats (n = 14, respectively), aggressive rats (n = 14, respectively) and rats receiving foot shock (FS; n = 14, respectively). Plasma corticosterone concentration was measured after FS sessions. Leukocyte counts and humoral immunity were evaluated. In neonatal malnourished animals, FS-induced stress reduced plasma corticosterone concentration. Intraspecific aggressiveness induced alterations in leukocyte counts and antibody titers 7 and 15 days after immunization. Neonatal malnourished animals showed no changes in the immune parameters evaluated. Expression of intraspecific aggressiveness activates the immune system. Neonatal malnutrition seems to have a long-lasting effect on components of both neuroendocrine and immune functions.

  1. Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

    Science.gov (United States)

    Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

    2018-01-01

    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

  2. Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes.

    Directory of Open Access Journals (Sweden)

    Natalia Igosheva

    Full Text Available The negative impact of obesity on reproductive success is well documented but the stages at which development of the conceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recent findings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed the consequences of maternal obesity on mitochondria in early embryogenesis.Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women.

  3. Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat.

    Science.gov (United States)

    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Chávez-Saldaña, Margarita; Rojas, Patricia; Gutiérrez-Pérez, Oscar; Rojas, Carolina; Arteaga-Silva, Marcela

    2016-02-01

    Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)- and glial fibrillary acidic protein (GFAP)-immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using 'open-field' test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP- and VIP-immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP-immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  4. Cytosine methylation alteration in natural populations of Leymus chinensis induced by multiple abiotic stresses.

    Directory of Open Access Journals (Sweden)

    Yingjie Yu

    Full Text Available BACKGROUND: Human activity has a profound effect on the global environment and caused frequent occurrence of climatic fluctuations. To survive, plants need to adapt to the changing environmental conditions through altering their morphological and physiological traits. One known mechanism for phenotypic innovation to be achieved is environment-induced rapid yet inheritable epigenetic changes. Therefore, the use of molecular techniques to address the epigenetic mechanisms underpinning stress adaptation in plants is an important and challenging topic in biological research. In this study, we investigated the impact of warming, nitrogen (N addition, and warming+nitrogen (N addition stresses on the cytosine methylation status of Leymus chinensis Tzvel. at the population level by using the amplified fragment length polymorphism (AFLP, methylation-sensitive amplified polymorphism (MSAP and retrotransposon based sequence-specific amplification polymorphism (SSAP techniques. METHODOLOGY/PRINCIPAL FINDINGS: Our results showed that, although the percentages of cytosine methylation changes in SSAP are significantly higher than those in MSAP, all the treatment groups showed similar alteration patterns of hypermethylation and hypomethylation. It meant that the abiotic stresses have induced the alterations in cytosine methylation patterns, and the levels of cytosine methylation changes around the transposable element are higher than the other genomic regions. In addition, the identification and analysis of differentially methylated loci (DML indicated that the abiotic stresses have also caused targeted methylation changes at specific loci and these DML might have contributed to the capability of plants in adaptation to the abiotic stresses. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that abiotic stresses related to global warming and nitrogen deposition readily evoke alterations of cytosine methylation, and which may provide a molecular basis for rapid

  5. Stress-induced alterations in estradiol sensitivity increase risk for obesity in women.

    Science.gov (United States)

    Michopoulos, Vasiliki

    2016-11-01

    The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

  6. Corticosteroid treatment ameliorates acute lung injury induced by 2009 swine origin influenza A (H1N1 virus in mice.

    Directory of Open Access Journals (Sweden)

    Chenggang Li

    Full Text Available BACKGROUND: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection. METHODOLOGY/PRINCIPAL FINDINGS: We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection. CONCLUSIONS/SIGNIFICANCE: Using the established, very susceptible 2009 Pandemic Influenza A (H1N1 mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1 pandemics.

  7. Modification of mercury-induced biochemical alterations in blood of Swiss albino mice by Spirulina fusiformis.

    Science.gov (United States)

    Sharma, Mukesh Kumar; Patni, Reena; Kumar, Madhu; Kumar, Ashok

    2005-09-01

    The present investigation has been undertaken to evaluate the role of Spirulina fusiformis in modifying the mercury-induced biochemical alterations in Swiss albino mice. Animals were divided into four groups: (i) control group - only vehicle (0.9% NaCl/olive oil) was given; (ii) HgCl(2) treated group - 5.0mg/kg b.w. HgCl(2) administered as i.p.; (iii) Spirulina treated group - 800mg/kg b.w. Spirulina extract was administered orally; (iv) combination group -S. fusiformis was administered 10 days before mercuric chloride administration and continued up to 30 days after mercuric chloride administration (5.0mg/kg b.w.). The animals were sacrificed on 1, 3, 7, 15 and 30 days and the activity of serum alkaline and acid phosphatase, serum iron level, serum calcium level, blood lipid peroxidation content and blood glutathione (GSH) level were measured. In the present investigation, mercury intoxication causes significant increase (Pcalcium level, acid phosphatase and lipid peroxidation content and significant decrease in iron level, alkaline phosphatase and glutathione level. Spirulina pre- and post-treatment with mercury prevented or reduces mercury-induced alterations in terms of calcium level, iron level, acid and alkaline phosphatase activity in serum, and lipid peroxidation and GSH level in blood. Thus from the present investigation, it can be concluded that Spirulina pre- and post-treatment with HgCl(2) significantly modulate or modify mercury-induced biochemical alteration in blood of Swiss albino mice.

  8. Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?

    Science.gov (United States)

    Holman, Natalie S; Mosedale, Merrie; Wolf, Kristina K; LeCluyse, Edward L; Watkins, Paul B

    2016-06-01

    Drug-induced liver injury (DILI) is a significant clinical and economic problem in the United States, yet the mechanisms that underlie DILI remain poorly understood. Recent evidence suggests that signaling molecules released by stressed hepatocytes can trigger immune responses that may be common across DILI mechanisms. Extracellular vesicles released by hepatocytes, principally hepatocyte-derived exosomes (HDEs), may constitute one such signal. To examine HDE alterations as a function of drug-induced stress, this work utilized prototypical hepatotoxicant acetaminophen (APAP) in male Sprague-Dawley (SD) rats, SD rat hepatocytes, and primary human hepatocytes. HDE were isolated using ExoQuick precipitation reagent and analyzed by quantification of the liver-specific RNAs albumin and microRNA-122 (miR-122). In vivo, significant elevations in circulating exosomal albumin mRNA were observed at subtoxic APAP exposures. Significant increases in exosomal albumin mRNA were also observed in primary rat hepatocytes at subtoxic APAP concentrations. In primary human hepatocytes, APAP elicited increases in both exosomal albumin mRNA and exosomal miR-122 without overt cytotoxicity. However, the number of HDE produced in vitro in response to APAP did not increase with exosomal RNA quantity. We conclude that significant drug-induced alterations in the liver-specific RNA content of HDE occur at subtoxic APAP exposures in vivo and in vitro, and that these changes appear to reflect selective packaging rather than changes in exosome number. The current findings demonstrate that translationally relevant HDE alterations occur in the absence of overt hepatocellular toxicity, and support the hypothesis that HDE released by stressed hepatocytes may mediate early immune responses in DILI. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

    Science.gov (United States)

    Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

    2018-02-20

    The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

  10. Correlation between oxidative stress and alteration of intracellular calcium handling in isoproterenol-induced myocardial infarction.

    Science.gov (United States)

    Díaz-Muñoz, Mauricio; Alvarez-Pérez, Marco Antonio; Yáñez, Lucía; Vidrio, Susana; Martínez, Lidia; Rosas, Gisele; Yáñez, Mario; Ramírez, Sotero; de Sánchez, Victoria Chagoya

    2006-09-01

    Myocardial Ca(2+) overload and oxidative stress are well documented effects associated to isoproterenol (ISO)-induced myocardial necrosis, but information correlating these two issues is scarce. Using an ISO-induced myocardial infarction model, 3 stages of myocardial damage were defined: pre-infarction (0-12 h), infarction (12-24 h) and post-infarction (24-96 h). Alterations in Ca(2+) homeostasis and oxidative stress were studied in mitochondria, sarcoplasmic reticulum and plasmalemma by measuring the Ca(2+) content, the activity of Ca(2+) handling proteins, and by quantifying TBARs, nitric oxide (NO) and oxidative protein damage (changes in carbonyl and thiol groups). Free radicals generated system, antioxidant enzymes and oxidative stress (GSH/GSSG ratio) were also monitored at different times of ISO-induced cardiotoxicity. The Ca(2+) overload induced by ISO was counterbalanced by a diminution in the ryanodine receptor activity and the Na(+)-Ca(+2) exchanger as well as by the increase in both calcium ATPases activities (vanadate- and thapsigargine-sensitive) and mitochondrial Ca(2+) uptake during pre-infarction and infarction stages. Pro-oxidative reactions and antioxidant defences during the 3 stages of cardiotoxicity were observed, with maximal oxidative stress during the infarction. Significant correlations were found among pro-oxidative reactions with plasmalemma and sarcoplasmic reticulum Ca(2+) ATPases, and ryanodine receptor activities at the onset and development of ISO-induced infarction. These findings could be helpful in the design of antioxidant therapies in this pathology.

  11. Alteration of human serum albumin binding properties induced by modifications: A review

    Science.gov (United States)

    Maciążek-Jurczyk, Małgorzata; Szkudlarek, Agnieszka; Chudzik, Mariola; Pożycka, Jadwiga; Sułkowska, Anna

    2018-01-01

    Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers.

  12. Sex-related differences in cadmium-induced alteration of drug action in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schnell, R.C.; Pence, D.H.; Prosser, T.D.; Miya, T.S.

    1976-01-01

    Three days after pretreatment of rats of both sexes with cadmium (2 mg/kg, i.p.), the duration of hypnosis induced by hexobarbital (75 mg/kg, i.p.) was potentiated in males but not females. Likewise, similar treatment with cadmium leads to significant inhibition of the metabolism of hexobarbital by hepatic microsomal enzymes obtained from male but not female animals. These data suggest that there is a sex-related difference in the ability of cadmium to alter drug action in rats.

  13. Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

    Science.gov (United States)

    Zhang, Ming; Wang, Yanrang; Wang, Qian; Yang, Deyi; Zhang, Jingshu; Wang, Fengshan; Gu, Qing

    2013-09-01

    To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P workers (P hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

  14. In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

    International Nuclear Information System (INIS)

    Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

    1988-01-01

    Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

  15. Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice.

    Science.gov (United States)

    Aswad, Hala; Forterre, Alexis; Wiklander, Oscar P B; Vial, Guillaume; Danty-Berger, Emmanuelle; Jalabert, Audrey; Lamazière, Antonin; Meugnier, Emmanuelle; Pesenti, Sandra; Ott, Catherine; Chikh, Karim; El-Andaloussi, Samir; Vidal, Hubert; Lefai, Etienne; Rieusset, Jennifer; Rome, Sophie

    2014-10-01

    Exosomes released from cells can transfer both functional proteins and RNAs between cells. In this study we tested the hypothesis that muscle cells might transmit specific signals during lipid-induced insulin resistance through the exosomal route. Exosomes were collected from quadriceps muscles of C57Bl/6 mice fed for 16 weeks with either a standard chow diet (SD) or an SD enriched with 20% palm oil (HP) and from C2C12 cells exposed to 0.5 mmol/l palmitate (EXO-Post Palm), oleate (EXO-Post Oleate) or BSA (EXO-Post BSA). HP-fed mice were obese and insulin resistant and had altered insulin-induced Akt phosphorylation in skeletal muscle (SkM). They also had reduced expression of Myod1 and Myog and increased levels of Ccnd1 mRNA, indicating that palm oil had a deep impact on SkM homeostasis in addition to insulin resistance. HP-fed mouse SkM secreted more exosomes than SD-fed mouse SkM. This was reproduced in-vitro using C2C12 cells pre-treated with palmitate, the most abundant saturated fatty acid of palm oil. Exosomes from HP-fed mice, EXO-Post Palm and EXO-Post Oleate induced myoblast proliferation and modified the expressions of genes involved in the cell cycle and muscle differentiation but did not alter insulin-induced Akt phosphorylation. Lipidomic analyses showed that exosomes from palmitate-treated cells were enriched in palmitate, indicating that exosomes likely transfer the deleterious effect of palm oil between muscle cells by transferring lipids. Muscle exosomes were incorporated into various tissues in vivo, including the pancreas and liver, suggesting that SkM could transfer specific signals through the exosomal route to key metabolic tissues. Exosomes act as 'paracrine-like' signals and modify muscle homeostasis during high-fat diets.

  16. Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia-Induced Vascular Alterations.

    Science.gov (United States)

    Arnaud, Claire; Bouyon, Sophie; Recoquillon, Sylvain; Brasseur, Sandrine; Lemarié, Emeline; Briançon-Marjollet, Anne; Gonthier, Brigitte; Toral, Marta; Faury, Gilles; Martinez, M Carmen; Andriantsitohaina, Ramaroson; Pepin, Jean-Louis

    2018-01-25

    Obstructive sleep apnea is characterized by repetitive pharyngeal collapses during sleep, leading to intermittent hypoxia (IH), the main contributor of obstructive sleep apnea-related cardiovascular morbidity. In patients and rodents with obstructive sleep apnea exposed to IH, vascular inflammation and remodeling, endothelial dysfunction, and circulating inflammatory markers are linked with IH severity. The nonmuscle myosin light chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative stress in different cardiovascular and inflammatory diseases. Thus, in the present study, we hypothesized that nmMLCK plays a key role in the IH-induced vascular dysfunctions and inflammatory remodeling. Twelve-week-old nmMLCK +/+ or nmMLCK -/- mice were exposed to 14-day IH or normoxia. IH was associated with functional alterations characterized by an elevation of arterial blood pressure and stiffness and perturbations of NO signaling. IH caused endothelial barrier dysfunction (ie, reduced transendothelial resistance in vitro) and induced vascular oxidative stress associated with an inflammatory remodeling, characterized by an increased intima-media thickness and an increased expression and activity of inflammatory markers, such as interferon-γ and nuclear factor-κB, in the vascular wall. Interestingly, nmMLCK deletion prevented all IH-induced functional and structural alterations, including the restoration of NO signaling, correction of endothelial barrier integrity, and reduction of both oxidative stress and associated inflammatory response. nmMLCK is a key mechanism in IH-induced vascular oxidative stress and inflammation and both functional and structural remodeling. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  17. Radiation-induced alterations of osteogenic and chondrogenic differentiation of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Séverine Cruet-Hennequart

    Full Text Available While human mesenchymal stem cells (hMSCs, either in the bone marrow or in tumour microenvironment could be targeted by radiotherapy, their response is poorly understood. The oxic effects on radiosensitivity, cell cycle progression are largely unknown, and the radiation effects on hMSCs differentiation capacities remained unexplored. Here we analysed hMSCs viability and cell cycle progression in 21% O2 and 3% O2 conditions after medical X-rays irradiation. Differentiation towards osteogenesis and chondrogenesis after irradiation was evaluated through an analysis of differentiation specific genes. Finally, a 3D culture model in hypoxia was used to evaluate chondrogenesis in conditions mimicking the natural hMSCs microenvironment. The hMSCs radiosensitivity was not affected by O2 tension. A decreased number of cells in S phase and an increase in G2/M were observed in both O2 tensions after 16 hours but hMSCs released from the G2/M arrest and proliferated at day 7. Osteogenesis was increased after irradiation with an enhancement of mRNA expression of specific osteogenic genes (alkaline phosphatase, osteopontin. Osteoblastic differentiation was altered since matrix deposition was impaired with a decreased expression of collagen I, probably through an increase of its degradation by MMP-3. After induction in monolayers, chondrogenesis was altered after irradiation with an increase in COL1A1 and a decrease in both SOX9 and ACAN mRNA expression. After induction in a 3D culture in hypoxia, chondrogenesis was altered after irradiation with a decrease in COL2A1, ACAN and SOX9 mRNA amounts associated with a RUNX2 increase. Together with collagens I and II proteins decrease, associated to a MMP-13 expression increase, these data show a radiation-induced impairment of chondrogenesis. Finally, a radiation-induced impairment of both osteogenesis and chondrogenesis was characterised by a matrix composition alteration, through inhibition of synthesis and

  18. Molecular alterations in tumorigenic human bronchial and breast epithelial cells induced by high let radiation

    Science.gov (United States)

    Hei, T. K.; Zhao, Y. L.; Roy, D.; Piao, C. Q.; Calaf, G.; Hall, E. J.

    Carcinogenesis is a multi-stage process with sequence of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer. In the present study, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells were irradiated with graded doses of either 150 keV/μm alpha particles or 1 GeV/nucleon 56Fe ions. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Cell fusion studies indicated that radiation-induced tumorigenic phenotype in BEP2D cells could be completely suppressed by fusion with non-tumorigenic BEP2D cells. The differential expressions of known genes between tumorigenic bronchial and breast cells induced by alpha particles and their respective control cultures were compared using cDNA expression array. Among the 11 genes identified to be differentially expressed in BEP2D cells, three ( DCC, DNA-PK and p21 CIPI) were shown to be consistently down-regulated by 2 to 4 fold in all the 5 tumor cell lines examined. In contrast, their expressions in the fusion cell lines were comparable to control BEP2D cells. Similarly, expression levels of a series of genes were found to be altered in a step-wise manner among tumorigenic MCF-10F cells. The results are highly suggestive that functional alterations of these genes may be causally related to the carcinogenic process.

  19. Prenatal tactile stimulation attenuates drug-induced behavioral sensitization, modifies behavior, and alters brain architecture.

    Science.gov (United States)

    Muhammad, Arif; Kolb, Bryan

    2011-07-11

    Based on the findings of postnatal tactile stimulation (TS), a favorable experience in rats, the present study examined the influence of prenatal TS on juvenile behavior, adult amphetamine (AMPH) sensitization, and structural alteration in the prefrontal cortex (PFC) and the striatum. Female rats received TS through a baby hair brush throughout pregnancy, and the pups born were tested for open field locomotion, elevated plus maze (EPM), novel object recognition (NOR), and play fighting behaviors. Development and persistence of drug-induced behavioral sensitization in adults were tested by repeated AMPH administration and a challenge, respectively. Structural plasticity in the brain was assessed from the prefrontal cortical thickness and striatum size from serial coronal sections. The results indicate that TS females showed enhanced exploration in the open field. TS decreased the frequency of playful attacks whereas the response to face or evade an attack was not affected. Anxiety-like behavior and cognitive performance were not influenced by TS. AMPH administration resulted in gradual increase in locomotor activity (i.e., behavioral sensitization) that persisted at least for 2 weeks. However, both male and female TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Furthermore, the drug-associated alteration in the prefrontal cortical thickness and striatum size observed in controls were prevented by TS experience. In summary, TS during prenatal development modified juvenile behavior, attenuated drug-induced behavioral sensitization in adulthood, and reorganized brain regions implicated in drug addiction. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Glycophenotypic alterations induced by Pteridium aquilinum in mice gastric mucosa: synergistic effect with Helicobacter pylori infection.

    Directory of Open Access Journals (Sweden)

    Joana Gomes

    Full Text Available The bracken fern Pteridium aquilinum is a plant known to be carcinogenic to animals. Epidemiological studies have shown an association between bracken fern exposure and gastric cancer development in humans. The biological effects of exposure to this plant within the gastric carcinogenesis process are not fully understood. In the present work, effects in the gastric mucosa of mice treated with Pteridium aquilinum were evaluated, as well as molecular mechanisms underlying the synergistic role with Helicobacter pylori infection. Our results showed that exposure to Pteridium aquilinum induces histomorphological modifications including increased expression of acidic glycoconjugates in the gastric mucosa. The transcriptome analysis of gastric mucosa showed that upon exposure to Pteridium aquilinum several glycosyltransferase genes were differently expressed, including Galntl4, C1galt1 and St3gal2, that are mainly involved in the biosynthesis of simple mucin-type carbohydrate antigens. Concomitant treatment with Pteridium aquilinum and infection with Helicobacter pylori also resulted in differently expressed glycosyltransferase genes underlying the biosynthesis of terminal sialylated Lewis antigens, including Sialyl-Lewis(x. These results disclose the molecular basis for the altered pattern of glycan structures observed in the mice gastric mucosa. The gene transcription alterations and the induced glycophenotypic changes observed in the gastric mucosa contribute for the understanding of the molecular mechanisms underlying the role of Pteridium aquilinum in the gastric carcinogenesis process.

  1. Glycophenotypic alterations induced by Pteridium aquilinum in mice gastric mucosa: synergistic effect with Helicobacter pylori infection.

    Science.gov (United States)

    Gomes, Joana; Magalhães, Ana; Carvalho, Ana S; Hernandez, Gilberto E; Papp, Suzanne L; Head, Steven R; Michel, Valérie; David, Leonor; Gärtner, Fátima; Touati, Eliette; Reis, Celso A

    2012-01-01

    The bracken fern Pteridium aquilinum is a plant known to be carcinogenic to animals. Epidemiological studies have shown an association between bracken fern exposure and gastric cancer development in humans. The biological effects of exposure to this plant within the gastric carcinogenesis process are not fully understood. In the present work, effects in the gastric mucosa of mice treated with Pteridium aquilinum were evaluated, as well as molecular mechanisms underlying the synergistic role with Helicobacter pylori infection. Our results showed that exposure to Pteridium aquilinum induces histomorphological modifications including increased expression of acidic glycoconjugates in the gastric mucosa. The transcriptome analysis of gastric mucosa showed that upon exposure to Pteridium aquilinum several glycosyltransferase genes were differently expressed, including Galntl4, C1galt1 and St3gal2, that are mainly involved in the biosynthesis of simple mucin-type carbohydrate antigens. Concomitant treatment with Pteridium aquilinum and infection with Helicobacter pylori also resulted in differently expressed glycosyltransferase genes underlying the biosynthesis of terminal sialylated Lewis antigens, including Sialyl-Lewis(x). These results disclose the molecular basis for the altered pattern of glycan structures observed in the mice gastric mucosa. The gene transcription alterations and the induced glycophenotypic changes observed in the gastric mucosa contribute for the understanding of the molecular mechanisms underlying the role of Pteridium aquilinum in the gastric carcinogenesis process.

  2. Proteomic Alterations in Response to Hypoxia Inducible Factor 2α in Normoxic Neuroblastoma Cells.

    Science.gov (United States)

    Cimmino, Flora; Pezone, Lucia; Avitabile, Marianna; Persano, Luca; Vitale, Monica; Sassi, Mauro; Bresolin, Silvia; Serafin, Valentina; Zambrano, Nicola; Scaloni, Andrea; Basso, Giuseppe; Iolascon, Achille; Capasso, Mario

    2016-10-07

    Hypoxia inducible factor (HIF)-2α protein expression in solid tumors promotes stem-like phenotype in cancer stem cells and increases tumorigenic potential in nonstem cancer cells. Recently, we have shown that HIF-1/2α gene expression is correlated to neuroblastoma (NB) poor survival and to undifferentiated tumor state; HIF-2α protein was demonstrated to enhance aggressive features of the disease. In this study, we used proteomic experiments on NB cells to investigate HIF-2α downstream-regulated proteins or pathways with the aim of providing novel therapeutic targets or bad prognosis markers. We verified that pathways mostly altered by HIF-2α perturbation are involved in tumor progression. In particular, HIF-2α induces alteration of central metabolism and splicing control pathways. Simultaneously, WNT, RAS/MAPK, and PI3K/AKT activity or expression are affected and may impact the sensitivity and the intensity of HIF-2α-regulated pathways. Furthermore, genes coding the identified HIF-2α-related markers built a signature able to stratify NB patients with unfavorable outcome. Taken together, our findings underline the relevance of dissecting the downstream effects of a poor survival marker in developing targeted therapy and improving patient stratification. Future prospective studies are needed to translate the use of these data into the clinical practice.

  3. Role of rosemary leaves extract against radiation-induced hematological and biochemical alterations in mice

    International Nuclear Information System (INIS)

    Acharya, G. S.; Goyal, P. K.

    2008-01-01

    The present paper is a study of the modulatory effect of Rosmarinus officinalis leaves extract on radiation-induced hematological and biochemical changes in Swiss albino mice.The dose reduction factor for the Rosemary extract against gamma rays was calculated 1.53 from LD 50/30 values. The Rosemary extract was administered orally for 5 consecutive days prior to radiation exposure. The hematological and biochemical parameters were assessed from day 1 to 30 post-irradiation intervals. The total erythrocyte count, total leucocytes count, hemoglobin, and hematocrit values in the experimental group were found to be elevated as compared to the control group of mice. Furthermore, the Rosemary extract treatment enhanced reduced glutathione content in the liver and blood against radiation-induced depletion. Treatment with the plant extract brought a significant fall in the lipid peroxidation level, suggesting rosemary's role in protection against radiation-induced membrane and cellular damage. The results from the present study suggest a radio-protective effect of the Rosemary extract against radiation-induced hematological and biochemical alterations in mice. (author)

  4. Kalpaamruthaa ameliorates mitochondrial and metabolic alterations in diabetes mellitus induced cardiovascular damage.

    Science.gov (United States)

    Latha, Raja; Shanthi, Palanivelu; Sachdanandam, Panchanadham

    2014-12-01

    Efficacy of Kalpaamruthaa on the activities of lipid and carbohydrate metabolic enzymes, electron transport chain complexes and mitochondrial ATPases were studied in heart and liver of experimental rats. Cardiovascular damage (CVD) was developed in 8 weeks after type 2 diabetes mellitus induction with high fat diet (2 weeks) and low dose of streptozotocin (2 × 35 mg/kg b.w. i.p. in 24 hr interval). In CVD-induced rats, the activities of total lipase, cholesterol ester hydrolase and cholesterol ester synthetase were increased, while lipoprotein lipase and lecithin-cholesterol acyltransferase activities were decreased. The activities of lipid-metabolizing enzymes were altered by Kalpaamruthaa in CVD-induced rats towards normal. Kalpaamruthaa modulated the activities of glycolytic enzymes (hexokinase, phosphogluco-isomerase, aldolase and glucose-6-phosphate dehydrogenase), gluconeogenic enzymes (glucose-6-phosphatase and fructose-1, 6-bisphosphatase) and glycogenolytic enzyme (glycogen phosphorylase) along with increased glycogen content in the liver of CVD-induced rats. The activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, α-ketoglutarate dehydrogenase, Complexes and ATPases (Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) were decreased in CVD-induced rats, which were ameliorated by the treatment with Kalpaamruthaa. This study ascertained the efficacy of Kalpaamruthaa for the treatment of CVD in diabetes through the modulation of metabolizing enzymes and mitochondrial dysfunction.

  5. Oilseed cultivars developed from induced mutations and mutations altering fatty acid composition

    International Nuclear Information System (INIS)

    Bhatia, C.R.; Nichterlein, K.; Maluszynski, M.

    1999-01-01

    One hundred and sixty-three cultivars of annual oilseed crops, developed using induced mutations, have been officially approved and released for cultivation in 26 countries. The maximum number of cultivars have been released in soybean (58), followed by groundnut (44), sesame (16), linseed (15), rapeseed (14), Indian mustard (8), castorbean (4), white mustard (3) and sunflower (1). The majority (118 of 163) of the cultivars have been developed as direct mutants and 45 of 163 by using the induced mutants in a crossing programme. While in soybean 53 out of 58 cultivars were selected as direct mutants, in groundnut 22 from 44 were developed after hybridization. Eighty-three cultivars were developed directly by exposing seeds to gamma or X-rays. Attempts have been made to infer the successful dose range, defined as the range which led to the development, registration and release of the maximum number of mutant cultivars for gamma and X-rays. The successful dose ranges in Gy for the main oilseed crops are: soybean 100-200, groundnut 150-250, rapeseed 600-800, Indian mustard 700 and sesame 100-200. The main characteristics of the new cultivars, besides higher yield, are altered plant type, early flowering and maturity and oil content. Mutants altering fatty acid composition have been isolated in soybean, rapeseed, sunflower, linseed and minor oil crops. New cultivars having altered fatty acid composition have been released in rapeseed, sunflower and linseed. The latter, previously grown for non-edible oil, has been converted to a new edible oil crop. (author)

  6. Environmental particulate matter induces murine intestinal inflammatory responses and alters the gut microbiome.

    Directory of Open Access Journals (Sweden)

    Lisa Kish

    Full Text Available Particulate matter (PM is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions.Wild-type 129/SvEv mice were gavaged with Ottawa urban PM10 (EHC-93 for 7-14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM10 for measurement of proliferation. Long-term effects of exposure (35 days on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10(-/- mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum.Short-term treatment of wild-type mice with PM10 altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10(-/- mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10(-/- mice had increased disease as evidenced by enhanced histological damage.Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine.

  7. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

    Science.gov (United States)

    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

    2010-12-01

    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  8. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  10. Atrophic Rhinitis of Swine

    Science.gov (United States)

    This book chapter for the 8th edition of the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals describes the current state of knowledge regarding progressive atrophic rhinitis of swine. Topics covered include clinical signs and lesions, characteristics and methods of detection for...

  11. Swine Brucellosis: Current Perspectives

    Science.gov (United States)

    Brucella suis is a significant zoonosis that is present in domestic livestock and wildlife in many countries worldwide. Transmission from animal reservoirs is the source of human infection as human to human transmission is very rare. Although swine brucellosis causes economic losses in domestic liv...

  12. A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs.

    Science.gov (United States)

    Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling; Chen, Hualan

    2017-11-01

    Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by

  13. Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

    Directory of Open Access Journals (Sweden)

    William P Lafuse

    Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

  14. Moderate Hyperbilirubinemia Alters Neonatal Cardiorespiratory Control and Induces Inflammation in the Nucleus Tractus Solitarius

    Directory of Open Access Journals (Sweden)

    Marie-Laure Specq

    2016-09-01

    Full Text Available Hyperbilirubinemia (HB occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term, namely control (n = 6 and HB (n = 5, were studied. At day 5 of life, moderate HB (150-250 µmol/L was induced during 17h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia. Recordings were repeated 72 hours after HB induction, just before euthanasia. In addition, neuropathological studies were performed to investigate for cerebral bilirubin deposition as well as for signs of glial reactivity in brainstem structures involved in cardiorespiratory control. Results revealed that sustained and moderate HB: i decreased baseline respiratory rate and increased the time spent in apnea; ii blunted the cardiorespiratory inhibition normally observed during both laryngeal and pulmonary chemoreflexes and iii increased heart rate in response to acute hypoxia. These acute physiological changes were concurrent with an activation of Alzheimer type II astrocytes throughout the brain, including the brainstem. Concomitantly, bilirubin deposits were observed in the leptomeninges, but not in brain parenchyma. While most cardiorespiratory alterations returned to normal 72 hours after HB normalization, the expression of glial fibrillary acid protein (GFAP and Ionized calcium binding adaptor molecule 1 (Iba1 was still increased within the nucleus tractus solitarius. In conclusion, moderate and sustained HB in preterm lambs induced cardiorespiratory alterations, the latter of which were associated with neurohistopathological changes. These changes are indicative of an inflammatory response in the

  15. Methimazole-Induced Hypothyroidism Enhances HSV-1 Infectivity without Altering Circulating Leukocytes in the Rat

    Directory of Open Access Journals (Sweden)

    Hadi Feizi

    2015-04-01

    Full Text Available Backgrounds & objectives: In addition to their genomic actions, thyroid hormones (THs can modulate the immune responses through cell surface receptors. One of these is the antiviral effect of THs. Methimazole, as an anti-thyroid compound, is widely used to treat hyperthyroid patients. It also reduces blood leukocytes, granulocytes in particular, and thereby may affect the immune response. Recently, we reported that methimazole-induced hypothyroidism intensifies herpes simplex virus-1(HSV-1 infectivity. To determine whether the effect is mediated through alterations in circulating leukocytes, we assessed the HSV-1 infectivity and circulating leukocytes in methimazole-induced hypothyroid rat.   Methods: Male Sprague Dawley rats received methimazole (200 μg/ml in their drinking water for 2 weeks. Rats were then inoculated with a non-lethal single dose of HSV-1, and sacrificed 3 days later to harvest their spleen. Spleen extract was prepared, and virus yield was determined by evaluation of cytopathic effects (CPE induced by the extract in a Vero cell culture system. For quantitative analysis, standard method of Reed-Muench was employed. The routine Wright’s staining protocol was used for blood leukocytes differential count.   Results: The CPE development was significantly increased in the cell cultures exposed to the spleen extract of methimazole-treated animals (P < 0.05, indicating a higher virus yield and intensified virus infectivity. However, the effect of methimazole on blood leukocytes was minimal.   Conclusion: Our data suggest that methimazole increases the susceptibility to HSV-1 infection, at least in part, by blocking THs synthesis but not alterations in circulating leukocytes.

  16. Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.

  17. A comprehensive proteomic analysis of totarol induced alterations in Bacillus subtilis by multipronged quantitative proteomics.

    Science.gov (United States)

    Reddy, Panga Jaipal; Ray, Sandipan; Sathe, Gajanan J; Gajbhiye, Akshada; Prasad, T S Keshava; Rapole, Srikanth; Panda, Dulal; Srivastava, Sanjeeva

    2015-01-30

    The rapid emergence of microbial drug resistance indicates the urgent need for development of new antimicrobial agents. Bacterial cell division machinery is considered as a promising antimicrobial target. Totarol is a naturally existing diterpenoid, which has the ability to restrain bacterial growth by perturbing the cell division. The present study was conducted to investigate the proteomic alterations in Bacillus subtilis as a consequence of totarol treatment to decipher its mechanism of action and possible molecular targets. Cellular proteome of the totarol treated B. subtilis AH75 strain was analyzed by using multiple complementary proteomic approaches. After the drug treatment, 12, 38 and 139 differentially expressed (1.5 fold change) proteins were identified using 2-DE, DIGE and iTRAQ analyses, respectively. In silico functional analysis of the identified differentially expressed proteins indicated a possible effect of totarol on the central metabolism for energy production, heme biosynthesis and chemotaxis. Interestingly, the primary dehydrogenases, which play a vital role in generating the reducing equivalent, were found to be repressed after totarol treatment indicating an apparent metabolic shutdown. Consequently, multiple cellular assays including resazurin assay and FACS analysis of 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) staining confirmed the effect of totarol on respiratory activity and cellular metabolism. The exact mechanism of action of totarol is still unclear and further investigations are essential to identify the molecular/cellular targets of this potential antimicrobial agent. The present study demonstrates the application of differential proteome to decipher the mechanism of action and molecular targets of totarol in B. subtilis. Our quantitative proteome analysis revealed that totarol induced alterations in the expression levels of 139 proteins (1.5 fold change and ≥2 peptides) in B. subtilis. Findings obtained from this study

  18. JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets

    International Nuclear Information System (INIS)

    Verma, Saguna; Ziegler, Katja; Ananthula, Praveen; Co, Juliene K.G.; Frisque, Richard J.; Yanagihara, Richard; Nerurkar, Vivek R.

    2006-01-01

    Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus-host interactions influencing persistence and pathogenicity are not well understood, although significant regulation of JCV activity is thought to occur at the level of transcription. Regulation of the JCV early and late promoters during the lytic cycle is a complex event that requires participation of both viral and cellular factors. We have used cDNA microarray technology to analyze global alterations in gene expression in JCV-permissive primary human fetal glial cells (PHFG). Expression of more than 400 cellular genes was altered, including many that influence cell proliferation, cell communication and interferon (IFN)-mediated host defense responses. Genes in the latter category included signal transducer and activator of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS), and cig5. The expression of these genes was further confirmed in JCV-infected PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity of JCV in inducing this strong antiviral response. Results obtained by real-time RT-PCR and Western blot analyses supported the microarray data and provide temporal information related to virus-induced changes in the IFN response pathway. Our data indicate that the induction of an antiviral response may be one of the cellular factors regulating/controlling JCV replication in immunocompetent hosts and therefore constraining the development of PML

  19. Aluminum Toxicity-Induced Alterations of Leaf Proteome in Two Citrus Species Differing in Aluminum Tolerance

    Directory of Open Access Journals (Sweden)

    Huan Li

    2016-07-01

    Full Text Available Seedlings of aluminum-tolerant ‘Xuegan’ (Citrus sinensis and Al-intolerant ‘sour pummelo’ (Citrus grandis were fertigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl3·6H2O. Al toxicity-induced inhibition of photosynthesis and the decrease of total soluble protein only occurred in C. grandis leaves, demonstrating that C. sinensis had higher Al tolerance than C. grandis. Using isobaric tags for relative and absolute quantification (iTRAQ, we obtained more Al toxicity-responsive proteins from C. sinensis than from C. grandis leaves, which might be responsible for the higher Al tolerance of C. sinensis. The following aspects might contribute to the Al tolerance of C. sinensis: (a better maintenance of photosynthesis and energy balance via inducing photosynthesis and energy-related proteins; (b less increased requirement for the detoxification of reactive oxygen species and other toxic compounds, such as aldehydes, and great improvement of the total ability of detoxification; and (c upregulation of low-phosphorus-responsive proteins. Al toxicity-responsive proteins related to RNA regulation, protein metabolism, cellular transport and signal transduction might also play key roles in the higher Al tolerance of C. sinensis. We present the global picture of Al toxicity-induced alterations of protein profiles in citrus leaves, and identify some new Al toxicity-responsive proteins related to various biological processes. Our results provide some novel clues about plant Al tolerance.

  20. Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats

    International Nuclear Information System (INIS)

    Pari, Leelavinothan; Murugavel, Ponnusamy

    2007-01-01

    Cadmium (Cd) is a neurotoxic metal, which induces oxidative stress and membrane disturbances in nerve system. The garlic compound diallyl tetrasulfide (DTS) has the cytoprotective and antioxidant activity against Cd induced toxicity. The present study was carried out to investigate the efficacy of DTS in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), membrane bound enzymes, lipid peroxidation (LPO) and antioxidant status in the brain of rats. In rats exposed to Cd (3 mg/kg/day subcutaneously) for 3 weeks, a significant (P + K + -ATPase, Mg 2+ -ATPase and Ca 2+ -ATPase) were observed in brain tissue. Oral administration of DTS (40 mg/kg/day) with Cd significantly (P < 0.05) diminished the levels of LPO and protein carbonyls and significantly (P < 0.05) increased the activities of ATPases, antioxidant enzymes, GSH and TSH in brain. These results indicate that DTS attenuate the LPO and alteration of antioxidant and membrane bound enzymes in Cd exposed rats, which suggest that DTS protects the brain function from toxic effects of Cd

  1. Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy.

    Science.gov (United States)

    Pascua, P; Camello-Almaraz, C; Pozo, M J; Martin-Cano, F E; Vara, E; Fernández-Tresguerres, J A; Camello, P J

    2012-06-01

    Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.

  2. High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity

    Science.gov (United States)

    2017-01-01

    The contribution of high fructose corn syrup (HFCS) to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO) and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6) received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets. PMID:29287121

  3. Ageratum enation virus Infection Induces Programmed Cell Death and Alters Metabolite Biosynthesis in Papaver somniferum

    Directory of Open Access Journals (Sweden)

    Ashish Srivastava

    2017-07-01

    Full Text Available A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L. plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV and Ageratum leaf curl betasatellite (ALCB, respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch’s postulates. Comprehensive microscopic analysis of infiltrated plants reveals severe structural anomalies in leaf and stem tissues represented by unorganized cell architecture and vascular bundles. Moreover, the characteristic blebs and membranous vesicles formed due to the virus-induced disintegration of the plasma membrane and intracellular organelles were also present. An accelerated nuclear DNA fragmentation was observed by Comet assay and confirmed by TUNEL and Hoechst dye staining assays suggesting virus-induced programmed cell death. Virus-infection altered the biosynthesis of several important metabolites. The biosynthesis potential of morphine, thebaine, codeine, and papaverine alkaloids reduced significantly in infected plants except for noscapine whose biosynthesis was comparatively enhanced. The expression analysis of corresponding alkaloid pathway genes by real time-PCR corroborated well with the results of HPLC analysis for alkaloid perturbations. The changes in the metabolite and alkaloid contents affect the commercial value of the poppy plants.

  4. PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.

    Science.gov (United States)

    Orth, P; Cucchiarini, M; Wagenpfeil, S; Menger, M D; Madry, H

    2014-06-01

    To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  5. Protective effect of thymoquinone against lead-induced antioxidant defense system alteration in rat liver.

    Science.gov (United States)

    Mabrouk, Aymen

    2017-09-01

    Alteration of the antioxidant system may be related to lead (Pb) hepatotoxicity. This study was carried out to investigate the possible beneficial effect of thymoquinone (TQ), the major active ingredient of volatile oil of Nigella sativa seeds, against Pb-induced liver antioxidant defense system impairment. Adult male rats were randomized into four groups: control group received no treatment, Pb group was exposed to 2000 ppm of Pb acetate in drinking water, Pb-TQ group was cotreated with Pb plus TQ (5 mg/kg/day, per os) and TQ group receiving only TQ. All treatments were applied for five weeks. TQ alone did not induce any significant changes in the enzymatic and non-enzymatic antioxidant status. By contrast, Pb exposure significantly decreased not only reduced glutathione level, but also superoxide dismutase, glutathione peroxidase, catalase and glutathione reductase activities in the liver tissue. Interestingly, when coadministrated with Pb, TQ significantly improved the affected antioxidant parameters. In conclusion, our results indicate a protective effect of TQ against Pb-induced liver antioxidant capacity impairment and suggest that this component might be a clinically promising alternative in Pb hepatotoxicity.

  6. Aluminum Toxicity-Induced Alterations of Leaf Proteome in Two Citrus Species Differing in Aluminum Tolerance.

    Science.gov (United States)

    Li, Huan; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Lu, Yi-Bin; Chen, Li-Song

    2016-07-21

    Seedlings of aluminum-tolerant 'Xuegan' (Citrus sinensis) and Al-intolerant 'sour pummelo' (Citrus grandis) were fertigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl₃·6H₂O. Al toxicity-induced inhibition of photosynthesis and the decrease of total soluble protein only occurred in C. grandis leaves, demonstrating that C. sinensis had higher Al tolerance than C. grandis. Using isobaric tags for relative and absolute quantification (iTRAQ), we obtained more Al toxicity-responsive proteins from C. sinensis than from C. grandis leaves, which might be responsible for the higher Al tolerance of C. sinensis. The following aspects might contribute to the Al tolerance of C. sinensis: (a) better maintenance of photosynthesis and energy balance via inducing photosynthesis and energy-related proteins; (b) less increased requirement for the detoxification of reactive oxygen species and other toxic compounds, such as aldehydes, and great improvement of the total ability of detoxification; and (c) upregulation of low-phosphorus-responsive proteins. Al toxicity-responsive proteins related to RNA regulation, protein metabolism, cellular transport and signal transduction might also play key roles in the higher Al tolerance of C. sinensis. We present the global picture of Al toxicity-induced alterations of protein profiles in citrus leaves, and identify some new Al toxicity-responsive proteins related to various biological processes. Our results provide some novel clues about plant Al tolerance.

  7. Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

    Science.gov (United States)

    Světlák, M; Bob, P; Roman, R; Ježek, S; Damborská, A; Chládek, J; Shaw, D J; Kukleta, M

    2013-01-01

    In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description.

  8. Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats

    International Nuclear Information System (INIS)

    Picard, C.

    2000-12-01

    Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT 3 receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

  9. TGF-β signaling alters the pattern of liver tumorigenesis induced by Pten inactivation

    Science.gov (United States)

    Morris, Shelli M.; Carter, Kelly T.; Baek, Ji Yeon; Koszarek, Amanda; Yeh, Matthew M.; Knoblaugh, Sue E.; Grady, William M.

    2014-01-01

    Hepatocarcinogenesis results from the accumulation of genetic and epigenetic changes in liver cells. A common mechanism through which these alterations induce liver cancer is by deregulating signaling pathways. A number of signaling pathways, including the PI3K/PTEN/AKT and transforming growth factor β (TGF-β) pathways have been implicated in normal liver development as well as in cancer formation. In this study, we assessed the effect of the TGF-β signaling pathway on liver tumors induced by Pten (phosphatase and tensin homologue) loss. Inactivation of only the TGF-β receptor type II, Tgfbr2, in the mouse liver (Tgfbr2LKO) had no overt phenotype, while inactivation of Pten alone (PtenLKO), resulted in the formation of both hepatocellular carcinomas (HCC) and cholangiocarcinomas (CC). Interestingly, deletion of both Pten and Tgfbr2 (PtenLKO;Tgfbr2LKO) in the mouse liver resulted in a dramatic shift in tumor type to predominantly CC. Assessment of the PI3K/PTEN/AKT pathway revealed increased phosphorylation of AKT and GSK-3β in both the PtenLKO and PtenLKO;Tgfbr2LKO mice, suggesting that this pathway is constitutively active regardless of the status of the TGF-β signaling pathway. However, phosphorylation of p70 S6 kinase was observed in the liver of all three phenotypes (Tgfbr2LKO, PtenLKO, PtenLKO;Tgfbr2LKO) indicating that the loss of Tgfbr2 and/or Pten leads to an increase in this signaling pathway. Analysis of markers of liver progenitor/stem cells revealed that the loss of TGF-β signaling resulted in increased expression of c-Kit and CD133. Furthermore, in addition to increased c-Kit and CD133, Scf and EpCam expression were also increased in the double knock-out mice. These results suggest that the alteration in tumor types between the PtenLKO mice and PtenLKO;Tgfbr2LKO mice is secondary to the altered regulation of stem cell features induced by the loss of TGF-β signaling. PMID:25132272

  10. Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.

    Science.gov (United States)

    Areal, Lorena Bianchine; Herlinger, Alice Laschuk; Pelição, Fabrício Souza; Martins-Silva, Cristina; Pires, Rita Gomes Wanderley

    2017-08-01

    Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Alterations and abnormal mitosis of wheat chromosomes induced by wheat-rye monosomic addition lines.

    Directory of Open Access Journals (Sweden)

    Shulan Fu

    Full Text Available BACKGROUND: Wheat-rye addition lines are an old topic. However, the alterations and abnormal mitotic behaviours of wheat chromosomes caused by wheat-rye monosomic addition lines are seldom reported. METHODOLOGY/PRINCIPAL FINDINGS: Octoploid triticale was derived from common wheat T. aestivum L. 'Mianyang11'×rye S. cereale L. 'Kustro' and some progeny were obtained by the controlled backcrossing of triticale with 'Mianyang11' followed by self-fertilization. Genomic in situ hybridization (GISH using rye genomic DNA and fluorescence in situ hybridization (FISH using repetitive sequences pAs1 and pSc119.2 as probes were used to analyze the mitotic chromosomes of these progeny. Strong pSc119.2 FISH signals could be observed at the telomeric regions of 3DS arms in 'Mianyang11'. However, the pSc119.2 FISH signals were disappeared from the selfed progeny of 4R monosomic addition line and the changed 3D chromosomes could be transmitted to next generation stably. In one of the selfed progeny of 7R monosomic addition line, one 2D chromosome was broken and three 4A chromosomes were observed. In the selfed progeny of 6R monosomic addition line, structural variation and abnormal mitotic behaviour of 3D chromosome were detected. Additionally, 1A and 4B chromosomes were eliminated from some of the progeny of 6R monosomic addition line. CONCLUSIONS/SIGNIFICANCE: These results indicated that single rye chromosome added to wheat might cause alterations and abnormal mitotic behaviours of wheat chromosomes and it is possible that the stress caused by single alien chromosome might be one of the factors that induced karyotype alteration of wheat.

  12. Integrated circuit failure analysis by low-energy charge-induced voltage alteration

    Science.gov (United States)

    Cole, Jr., Edward I.

    1996-01-01

    A scanning electron microscope apparatus and method are described for detecting and imaging open-circuit defects in an integrated circuit (IC). The invention uses a low-energy high-current focused electron beam that is scanned over a device surface of the IC to generate a charge-induced voltage alteration (CIVA) signal at the location of any open-circuit defects. The low-energy CIVA signal may be used to generate an image of the IC showing the location of any open-circuit defects. A low electron beam energy is used to prevent electrical breakdown in any passivation layers in the IC and to minimize radiation damage to the IC. The invention has uses for IC failure analysis, for production-line inspection of ICs, and for qualification of ICs.

  13. The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome.

    Directory of Open Access Journals (Sweden)

    Scott T Kelley

    Full Text Available Women with polycystic ovary syndrome (PCOS have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet.

  14. Haemato-biochemical alterations induced by lead acetate toxicity in wistar rats

    Directory of Open Access Journals (Sweden)

    S. G. Suradkar

    Full Text Available An experiment was conducted to study the haemato-biochemical alterations induced by lead acetate toxicity in 48 Wistar rats of either sex, divided uniformly into four different groups. The rats of group I received only deionised water as control while, group II, III and IV were given lead acetate @ 1 PPM, 100 PPM and 1000 PPM, in drinking deionised water respectively for 28 days. In group III and IV dose dependant significant (P<0.05 reductions in TEC, Hb, PCV and TLC were observed. No significant change was observed in neutrophil, eosinophil, basophil and monocyte count in any treatment groups, whereas the lymphocyte count decreased significantly (P<0.05 in group III and IV. A dose dependant significant (P<0.05 increase in AST, ALP, AKP, GGT, BUN and creatinine was experiential while TP and albumin levels were decreased in group III and IV. [Vet World 2009; 2(11.000: 429-431

  15. Structural and functional alterations of catalase induced by acriflavine, a compound causing apoptosis and necrosis.

    Science.gov (United States)

    Attar, Farnoosh; Khavari-Nejad, Sarah; Keyhani, Jacqueline; Keyhani, Ezzatollah

    2009-08-01

    Acriflavine is an antiseptic agent causing both apoptosis and necrosis in yeast. In this work, its effect on the structure and function of catalase, a vital enzyme actively involved in protection against oxidative stress, was investigated. In vitro kinetic studies showed that acriflavine inhibited the enzymatic activity in a competitive manner. The residual activity detectable after preincubation of catalase (1.5 nmol/L) with various concentrations of acriflavine went from 50% to 20% of the control value as the acriflavine concentration increased from 30 to 90 micromol/L. Correlatively with the decrease in activity, alterations in the enzyme's conformation were observed as indicated by fluorescence spectroscopy, circular dichroism spectroscopy, and electronic absorption spectroscopy. The enzyme's intrinsic fluorescence obtained upon excitation at either 297 nm (tryptophan residues) or 280 nm (tyrosine and tryptophan residues) decreased as a function of acriflavine concentration. Circular dichroism studies showed alterations of the protein structure by acriflavine with up to 13% decrease in alpha helix, 16% increase in beta-sheet content, 17% increase in random coil, and 4% increase in beta turns. Spectrophotometric studies showed a blueshift and modifications in the chromicity of catalase at 405 nm, corresponding to an absorbance band due to the enzyme's prosthetic group. Thus, acriflavine induced in vitro a profound change in the structure of catalase so that the enzyme could no longer function. Our results showed that acriflavine, a compound producing apoptosis and necrosis, can have a direct effect on vital functions in cells by disabling key enzymes.

  16. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    Science.gov (United States)

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Gestational protein restriction induces alterations in placental morphology and mitochondrial function in rats during late pregnancy.

    Science.gov (United States)

    Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Moraes, Camila; Amaral, Maria Esmeria Corezola; Catisti, Rosana

    2013-12-01

    The placenta acts a regulator of nutrient composition and supply from mother to fetus and is the source of hormonal signals that affect maternal and fetal metabolism. Thus, appropriate development of the placenta is crucial for normal fetal development. We investigated the effect of gestational protein restriction (GPR) on placental morphology and mitochondrial function on day 19 of gestation. Pregnant dams were divided into two groups: normal (NP 17 % casein) or low-protein diet (LP 6 % casein). The placentas were processed for biochemical, histomorphometric and ultrastructural analysis. The integrity of rat placental mitochondria (RPM) isolated by conventional differential centrifugation was measured by oxygen uptake (Clark-type electrode). LP animals presented an increase in adipose tissue and triacylglycerol and a decrease in serum insulin levels. No alterations were observed in body, liver, fetus, or placenta weight. There was also no change in serum glucose, total protein, or lipid content. Gestational protein restriction had tissue-specific respiratory effects, with the observation of a small change in liver respiration (~13 %) and considerable respiratory inhibition in placenta samples (~37 %). The higher oxygen uptake by RPM in the LP groups suggests uncoupling between respiration and oxidative phosphorylation. In addition, ultrastructural analysis of junctional zone giant cells from LP placenta showed a disorganized cytoplasm, with loss of integrity of most organelles and intense vacuolization. The present results led us to hypothesize that GPR alters placental structure and morphology, induces sensitivity to insulin, mitochondrial abnormalities and suggests premature aging of the placenta. Further studies are needed to test this hypothesis.

  18. Kinetics of radiation-induced structural alterations in electron-irradiated polymer-based composites

    International Nuclear Information System (INIS)

    Zaikin, Yu.A.; Potanin, A.S.; Koztaeva, U.P.

    2002-01-01

    Complete text of publication follows. In our previous studies measurements of internal friction temperature dependence were used for characterization of thermally activated and radiation-induced structural evolution in different types of polymer-based composites. This paper supplements these measurements with kinetic studies of internal friction (IF) parameters and EPR signals in a glass-cloth epoxy-filled laminate ST-ETF after electron irradiation up to doses of 1-10 MGy. Experiment have shown that the lifetime of free radicals in this composite considerably exceeds the characteristic time of molecular structural rearrangement due to scission and cross-linking after irradiation, as determined from IF measurements. This result is explained by slow proceeding of sterically hindered disproportionation reactions that stabilize the end groups of the macro-chain disrupt during irradiation and finally fix the act of scission. A mathematical model is formulated for description of structural evolution and alterations of IF parameters in polymer-based composites during and after electron irradiation. The description is based on the track model of radiation damage in polymers and phenomenological theory of radiation-induced structural transformations. General description does not give details of radiation-chemical conversion in different structural components of composites but indicates the direction of their structural evolution. In the model considered a composite material was divided into three parts (binder, filler, and a boundary layer). It was supposed that after primary distribution of radiation energy radiation-chemical conversion proceeds independently in each of these regions. It was also suggested that all the radical reactions were of the second order. On the example of glass-cloth laminate ST-ETF it is shown that this model allows to describe alterations in composite structural characteristics during irradiation and in the course of their self-organization after

  19. Profiling of altered metabolomic states in Nicotiana tabacum cells induced by priming agents.

    Directory of Open Access Journals (Sweden)

    Msizi Innocent Mhlongo

    2016-10-01

    Full Text Available Metabolomics has developed into a valuable tool for advancing our understanding of plant metabolism. Plant innate immune defenses can be activated and enhanced so that, subsequent to being pre-sensitized, plants are able to launch a stronger and faster defense response upon exposure to pathogenic microorganisms, a phenomenon known as priming. Here, three contrasting chemical activators, namely acibenzolar-S-methyl, azelaic acid and riboflavin, were used to induce a primed state in Nicotiana tabacum cells. Identified biomarkers were then compared to responses induced by three phytohormones - abscisic acid, methyljasmonate and salicylic acid. Altered metabolomes were studied using a metabolite fingerprinting approach based on liquid chromatography and mass spectrometry. Multivariate data models indicated that these inducers cause time-dependent metabolic perturbations in the cultured cells and revealed biomarkers of which the levels are affected by these agents. A total of 34 metabolites were annotated from the mass spectral data and online databases. Venn diagrams were used to identify common biomarkers as well as those unique to a specific agent. Results implicate 20 cinnamic acid derivatives conjugated to (i quinic acid (chlorogenic acids, (ii tyramine, (iii polyamines or (iv glucose as discriminatory biomarkers of priming in tobacco cells. Functional roles for most of these metabolites in plant defense responses could thus be proposed. Metabolites induced by the activators belong to the early phenylpropanoid pathway, which indicates that different stimuli can activate similar pathways but with different metabolite fingerprints. Possible linkages to phytohormone-dependent pathways at a metabolomic level were indicated in the case of cells treated with salicylic acid and methyljasmonate. The results contribute to a better understanding of the priming phenomenon and advance our knowledge of cinnamic acid derivatives as versatile defense

  20. Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

    Science.gov (United States)

    Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

    2013-05-05

    Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

  1. Alterations in keratins and associated proteins during 4- Nitroquinoline-1-oxide induced rat oral carcinogenesis

    Directory of Open Access Journals (Sweden)

    Deepak Kanojia

    2012-01-01

    Full Text Available Background: Oral squamous cell carcinoma (OSCC is the sixth largest group of malignancies globally and the single largest group of malignancies in the Indian subcontinent. Despite the advances in treatment and therapeutic modalities the five year survival rate of OSCC has not changed in the last few decades, and remains less than 40%. Several studies have focused on defining molecular markers that can either detect cancer at an early stage or can predict patient′s outcome. However, such markers are still undefined. Keratins (K are epithelia predominant intermediate filament proteins which are expressed in a differentiation dependent and site specific manner. Keratins are being used as biomarkers in different epithelial disorders including cancer. They are associated with desmoplakin and α6β4 integrin which are components of desmosomes and hemidesmosomes respectively. Materials and Methods: 4-Nitroquinoline 1-Oxide (4NQO was used as a carcinogen for the development of various stages of oral carcinogenesis in rat lingual mucosa. Two-Dimentional gel electrophoresis was performed for the separation of Keratins followed by western blotting for their specific identification. Western blotting and RT PCR was carried out for desmoplakin and α6β4 integrin respectively to understand their levels. Immunohistochemical analysis was carried out to further study the localization of desmoplakin and α6 integrin. Results: In this study we have analysed the alterations in Keratins and associated proteins during sequential stages of 4NQO induced rat oral carcinogenesis. Our results showed that the alterations primarily begin after the dysplastic changes in the lingual epithelium like the elevation of Keratins 5/6a, ectopic expression of Keratin 8, increase in suprabasal expression of α6 integrin and increase in desmoplakin levels. Most of these alterations persisted till the development of SCC except desmoplakin, the levels of which were downregulated in

  2. Genotoxicity of swine effluents.

    Science.gov (United States)

    Techio, V H; Stolberg, J; Kunz, A; Zanin, E; Perdomo, C C

    2011-01-01

    This study aimed at the investigation of genotoxic effects of swine effluents from different stages of a treatment system for swine wastes through bioassay of stamen hairs and micronuclei in Tradescantia (clone BNL 4430). No significant differences (p≥0.05) regarding the genic mutations were found in the bioassay of stamen hairs, independently of the effluent analysed. For the genotoxicity test with micronuclei, the plants exposed to raw wastes, to sludge, and to effluent of the biodigester have presented higher rates of chromosomal damages (micronuclei), with significant differences in relation to the control group and other effluent of the waste treatment system (p≤0.05). The association between the chemical parameters and the genotoxicity data have shown that the variables COD and TKN have presented significant correlation (p≤0.05) with the number of mutagenic events in the tetrads.

  3. The Relation between Fructose-Induced Metabolic Syndrome and Altered Renal Haemodynamic and Excretory Function in the Rat

    Directory of Open Access Journals (Sweden)

    Mohammed H. Abdulla

    2011-01-01

    Full Text Available This paper explores the possible relationships between dietary fructose and altered neurohumoral regulation of renal haemodynamic and excretory function in this model of metabolic syndrome. Fructose consumption induces hyperinsulinemia, hypertriglyceridaemia, insulin resistance, and hypertension. The pathogenesis of fructose-induced hypertension is dubious and involves numerous pathways acting both singly and together. In addition, hyperinsulinemia and hypertension contribute significantly to progressive renal disease in fructose-fed rats. Moreover, increased activity of the renin-angiotensin and sympathetic nervous systems leading to downregulation of receptors may be responsible for the blunted vascular sensitivity to angiotensin II and catecholamines, respectively. Various approaches have been suggested to prevent the development of fructose-induced hypertension and/or metabolic alteration. In this paper, we address the role played by the renin-angiotensin and sympathetic nervous systems in the haemodynamic alterations that occur due to prolonged consumption of fructose.

  4. Emersion induces nitrogen release and alteration of nitrogen metabolism in the intertidal genus Porphyra.

    Science.gov (United States)

    Kim, Jang K; Kraemer, George P; Yarish, Charles

    2013-01-01

    We investigated emersion-induced nitrogen (N) release from Porphyra umbilicalis Kütz. Thallus N concentration decreased during 4 h of emersion. Tissue N and soluble protein contents of P. umbilicalis were positively correlated and decreased during emersion. Growth of P. umbilicalis did not simply dilute the pre-emersion tissue N concentration. Rather, N was lost from tissues during emersion. We hypothesize that emersion-induced N release occurs when proteins are catabolized. While the δ(15)N value of tissues exposed to emersion was higher than that of continuously submerged tissues, further discrimination of stable N isotopes did not occur during the 4 h emersion. We conclude that N release from Porphyra during emersion did not result from bacterial denitrification, but possibly as a consequence of photorespiration. The release of N by P. umbilicalis into the environment during emersion suggests a novel role of intertidal seaweeds in the global N cycle. Emersion also altered the physiological function (nitrate uptake, nitrate reductase and glutamine synthetase activity, growth rate) of P. umbilicalis and the co-occurring upper intertidal species P. linearis Grev., though in a seasonally influenced manner. Individuals of the year round perennial species P. umbilicalis were more tolerant of emersion than ephemeral, cold temperate P. linearis in early winter. However, the mid-winter populations of both P. linearis and P. umbilicalis, had similar temporal physiological patterns during emersion.

  5. Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats

    Directory of Open Access Journals (Sweden)

    Abdulrahman K. Al-Asmari

    2014-01-01

    Full Text Available The potential effect of camel milk (CM against gentamicin (GM induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p., and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA and myeloperoxidase (MPO activity while the antioxidant enzymes like superoxide dismutase (SOD and glutathione s-transferase (GST activity decreased significantly (P≤0.05. Administration of CM significantly (P≤0.05 inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent.

  6. Aspirin-mediated acetylation induces structural alteration and aggregation of bovine pancreatic insulin.

    Science.gov (United States)

    Yousefi, Reza; Taheri, Behnaz; Alavi, Parnian; Shahsavani, Mohammad Bagher; Asadi, Zahra; Ghahramani, Maryam; Niazi, Ali; Alavianmehr, Mohammad Mehdi; Moosavi-Movahedi, Ali Akbar

    2016-01-01

    The simple aggregation of insulin under various chemical and physical stresses is still an important challenge for both pharmaceutical production and clinical formulation. In the storage form, this protein is subjected to various chemical modifications which alter its physicochemical and aggregation properties. Aspirin (acetylsalicylic acid) which is the most widely used medicine worldwide has been indicated to acetylate a large number of proteins both in vitro and in vivo. In this study, as insulin treated with aspirin at 37°C, a significant level of acetylation was observed by flourescamine and o-phthalaldehyde assay. Also, different spectroscopic techniques, gel electrophoresis, and microscopic assessment were applied to compare the structural variation and aggregation/fibrillation propensity among acetylated and non-acetylated insulin samples. The results of spectroscopic assessments elucidate that acetylation induces insulin unfolding which is accompanied with the exposure of protein hydrophobic patches, a transition from alpha-helix to beta-sheet and increased propensity of the protein for aggregation. The kinetic studies propose that acetylation increases aggregation rate of insulin under both thermal and chemical stresses. Also, gel electrophoresis and dynamic light scattering experiments suggest that acetylation induces insulin oligomerization. Additionally, the results of Thioflavin T fluorescence study, Congo red absorption assessment, and microscopic analysis suggest that acetylation with aspirin enhances the process of insulin fibrillation. Overall, the increased susceptibility of acetylated insulin for aggregation may reflect the fact that this type of modification has significant structural destabilizing effect which finally makes the protein more vulnerable for pathogenic aggregation/fibrillation.

  7. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions.

    Science.gov (United States)

    Bian, Xiaoming; Tu, Pengcheng; Chi, Liang; Gao, Bei; Ru, Hongyu; Lu, Kun

    2017-09-01

    Maintaining the balance of the gut microbiota and its metabolic functions is vital for human health, however, this balance can be disrupted by various external factors including food additives. A range of food and beverages are sweetened by saccharin, which is generally considered to be safe despite controversial debates. However, recent studies indicated that saccharin perturbed the gut microbiota. Inflammation is frequently associated with disruptions of the gut microbiota. The aim of this study is to investigate the relationship between host inflammation and perturbed gut microbiome by saccharin. C57BL/6J male mice were treated with saccharin in drinking water for six months. Q-PCR was used to detect inflammatory markers in mouse liver, while 16S rRNA gene sequencing and metabolomics were used to reveal changes of the gut microbiota and its metabolomic profiles. Elevated expression of pro-inflammatory iNOS and TNF-α in liver indicated that saccharin induced inflammation in mice. The altered gut bacterial genera, enriched orthologs of pathogen-associated molecular patterns, such as LPS and bacterial toxins, in concert with increased pro-inflammatory metabolites suggested that the saccharin-induced liver inflammation could be associated with the perturbation of the gut microbiota and its metabolic functions. Copyright © 2017. Published by Elsevier Ltd.

  8. Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

    Science.gov (United States)

    Kammouni, W; Figarella, C; Baeza, N; Marchand, S; Merten, M D

    1997-12-18

    Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

  9. Emersion induces nitrogen release and alteration of nitrogen metabolism in the intertidal genus Porphyra.

    Directory of Open Access Journals (Sweden)

    Jang K Kim

    Full Text Available We investigated emersion-induced nitrogen (N release from Porphyra umbilicalis Kütz. Thallus N concentration decreased during 4 h of emersion. Tissue N and soluble protein contents of P. umbilicalis were positively correlated and decreased during emersion. Growth of P. umbilicalis did not simply dilute the pre-emersion tissue N concentration. Rather, N was lost from tissues during emersion. We hypothesize that emersion-induced N release occurs when proteins are catabolized. While the δ(15N value of tissues exposed to emersion was higher than that of continuously submerged tissues, further discrimination of stable N isotopes did not occur during the 4 h emersion. We conclude that N release from Porphyra during emersion did not result from bacterial denitrification, but possibly as a consequence of photorespiration. The release of N by P. umbilicalis into the environment during emersion suggests a novel role of intertidal seaweeds in the global N cycle. Emersion also altered the physiological function (nitrate uptake, nitrate reductase and glutamine synthetase activity, growth rate of P. umbilicalis and the co-occurring upper intertidal species P. linearis Grev., though in a seasonally influenced manner. Individuals of the year round perennial species P. umbilicalis were more tolerant of emersion than ephemeral, cold temperate P. linearis in early winter. However, the mid-winter populations of both P. linearis and P. umbilicalis, had similar temporal physiological patterns during emersion.

  10. Trophic cascade induced by molluscivore predator alters pore-water biogeochemistry via competitive release of prey.

    Science.gov (United States)

    van Gils, Jan A; van der Geest, Matthijs; Jansen, Erik J; Govers, Laura L; de Fouw, Jimmy; Piersma, Theunis

    2012-05-01

    Effects of predation may cascade down the food web. By alleviating interspecific competition among prey, predators may promote biodiversity, but the precise mechanisms of how predators alter competition have remained elusive. Here we report on a predator-exclosure experiment carried out in a tropical intertidal ecosystem, providing evidence for a three-level trophic cascade induced by predation by molluscivore Red Knots (Calidris canutus) that affects pore water biogeochemistry. In the exclosures the knots' favorite prey (Dosinia isocardia) became dominant and reduced the individual growth rate in an alternative prey (Loripes lucinalis). Dosinia, a suspension feeder, consumes suspended particulate organic matter (POM), whereas Loripes is a facultative mixotroph, partly living on metabolites produced by sulfur-oxidizing chemoautotrophic bacteria, but also consuming suspended POM. Reduced sulfide concentrations in the exclosures suggest that, without predation on Dosinia, stronger competition for suspended POM forces Loripes to rely on energy produced by endosymbiotic bacteria, thus leading to an enhanced uptake of sulfide from the surrounding pore water. As sulfide is toxic to most organisms, this competition-induced diet shift by Loripes may detoxify the environment, which in turn may facilitate other species. The inference that predators affect the toxicity of their environment via a multi-level trophic cascade is novel, but we believe it may be a general phenomenon in detritus-based ecosystems.

  11. Gene alterations in radiation-induced F344 rat lung tumors

    International Nuclear Information System (INIS)

    Kelly, G.; Hahn, F.F.

    1994-01-01

    The p53 tumor suppressor gene is frequently altered in all major histopathologic types of human lung tumors. Reported p53 mutations include base substitutions, allelic loss, rearrangements, and deletions. Point mutations resulting in base substitutions are clustered within a highly conserved region of the gene encoding exons 508, and mutations in this region substantially extend the half-life of the p53 protein. In addition to its prominent importance in lung carcinogenesis, the p53 gene plays a critical role in the cellular response to genetic damage caused by radiation. Specifically, the protein product of p53 induces a pause or block at the G 1 to S boundary of the cell cycle following radiation-caused DNA damage. This G 1 block may allow the cell time to repair the damaged DNA prior to replication. Cells lacking a functional p53 protein fail to pause for repair and consequently accumulate mutations in the genome at an accelerated rate. p53 has also been implicated as a controlling factor in apoptosis or in programmed cell death induced by DNA-damaging agents, such as ionizing radiation. The p53 gene is mutated in approximately 50% of squamous cell carcinomas from uranium miners who inhaled high doses of radon daughters. The purpose of the present study was to determine if a similar percentage of squamous cell carcinomas with p53 mutations developed in the lungs of rats exposed to aerosols of 239 PuO 2

  12. The ultrastructural alterations in rat corneas with experimentally-induced diabetes mellitus

    International Nuclear Information System (INIS)

    Take, G.; Karabay, G.; Erdogan, D.; Duyar, I.

    2006-01-01

    To examine the ultrastructural changes of rat corneas in streptozotocin (STZ) induced diabetes mellitus and the and the follow-up insulin treatment. Sprague-Dawley type rats were used for experimental procedures during the period from January to April 2003 at Baskent University, Ankara, Turkey. Rats were studied in four groups: group 1: controls, group 2 sham controls (single dose IV sodium citrate); group 3 STZ-induced diabetes mellitus (Single dose 45mg/kg STZ intravenously), group 4: diabetes mellitus + insulin treatment (8U/day). We observed degenerative changes in the epithelial layer, stromal keratocytes and endothelial cells in diabetic group. In contrast, the corneal layers have revealed positive alterations in the insulin-treated group. The statistical analysis, showed significant narrowing in the epithelial layer in the diabetic group (p0.02), whereas thickening was observed in the epithelial basement membrane and Descemet's membrane (p=0.002). It was determined that that diabetes mellitus causes degenerative changes in cornea, which are positively influenced by short-term insulin treatment. (author)

  13. Spaceflight induces both transient and heritable alterations in DNA methylation and gene expression in rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Ou Xiufang; Long Likun; Zhang Yunhong; Xue Yiqun; Liu Jingchun; Lin Xiuyun; Liu Bao

    2009-01-01

    Spaceflight represents a complex environmental condition in which several interacting factors such as cosmic radiation, microgravity and space magnetic fields are involved, which may provoke stress responses and jeopardize genome integrity. Given the inherent property of epigenetic modifications to respond to intrinsic as well as external perturbations, it is conceivable that epigenetic markers like DNA methylation may undergo alterations in response to spaceflight. We report here that extensive alteration in both DNA methylation and gene expression occurred in rice plants subjected to a spaceflight, as revealed by a set of characterized sequences including 6 transposable elements (TEs) and 11 cellular genes. We found that several features characterize the alterations: (1) All detected alterations are hypermethylation events; (2) whereas alteration in both CG and CNG methylation occurred in the TEs, only alteration in CNG methylation occurred in the cellular genes; (3) alteration in expression includes both up- and down-regulations, which did not show a general correlation with alteration in methylation; (4) altered methylation patterns in both TEs and cellular genes are heritable to progenies at variable frequencies; however, stochastic reversion to wild-type patterns and further de novo changes in progenies are also apparent; and (5) the altered expression states in both TEs and cellular genes are also heritable to selfed progenies but with markedly lower transmission frequencies than altered DNA methylation states. Furthermore, we found that a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, the SWI/SNF chromatin remodeller (DDM1) and siRNA-related proteins are extremely sensitive to perturbation by spaceflight, which might be an underlying cause for the altered methylation patterns in the space-flown plants. We discuss implications of spaceflight-induced epigenetic variations with regard to health safety

  14. Magnetic field is the dominant factor to induce the response of Streptomyces avermitilis in altered gravity simulated by diamagnetic levitation.

    Science.gov (United States)

    Liu, Mei; Gao, Hong; Shang, Peng; Zhou, Xianlong; Ashforth, Elizabeth; Zhuo, Ying; Chen, Difei; Ren, Biao; Liu, Zhiheng; Zhang, Lixin

    2011-01-01

    Diamagnetic levitation is a technique that uses a strong, spatially varying magnetic field to simulate an altered gravity environment, as in space. In this study, using Streptomyces avermitilis as the test organism, we investigate whether changes in magnetic field and altered gravity induce changes in morphology and secondary metabolism. We find that a strong magnetic field (12T) inhibit the morphological development of S. avermitilis in solid culture, and increase the production of secondary metabolites. S. avermitilis on solid medium was levitated at 0 g*, 1 g* and 2 g* in an altered gravity environment simulated by diamagnetic levitation and under a strong magnetic field, denoted by the asterix. The morphology was obtained by electromicroscopy. The production of the secondary metabolite, avermectin, was determined by OD(245 nm). The results showed that diamagnetic levitation could induce a physiological response in S. avermitilis. The difference between 1 g* and the control group grown without the strong magnetic field (1 g), showed that the magnetic field was a more dominant factor influencing changes in morphology and secondary metabolite production, than altered gravity. We have discovered that magnetic field, rather than altered gravity, is the dominant factor in altered gravity simulated by diamagnetic levitation, therefore care should to be taken in the interpretation of results when using diamagnetic levitation as a technique to simulate altered gravity. Hence, these results are significant, and timely to researchers considering the use of diamagnetic levitation to explore effects of weightlessness on living organisms and on physical phenomena.

  15. Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms.

    Directory of Open Access Journals (Sweden)

    Rebecca E Haddock

    Full Text Available BACKGROUND: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH mechanism; which predominates in smaller resistance vessels and is characterized in this study. METHODOLOGY/PRINCIPAL FINDINGS: Membrane potential, vessel diameter and luminal pressure were recorded in 4(th order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (∼30 kJ, fat over 16-20 weeks. Age and sexed matched controls received standard chow (∼12 kJ, fat. Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SK(Ca/IK(Ca inhibition; with such activity being impaired in obesity. SK(Ca-IK(Ca activation with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine (CyPPA and 1-ethyl-2-benzimidazolinone (1-EBIO, respectively, hyperpolarized and relaxed vessels from control and obese rats. IK(Ca-mediated EDH contribution was increased in obesity, and associated with altered IK(Ca distribution and elevated expression. In contrast, the SK(Ca-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (K(ir and Na(+/K(+-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential K

  16. Brief rewarming blunts hypothermia-induced alterations in sensation, motor drive and cognition

    Directory of Open Access Journals (Sweden)

    Marius Brazaitis

    2016-12-01

    hypothermia-induced alterations in neural drive transmission (4.3±0.5 versus 3.4±0.8 mV H-reflex and 4.9±0.2 versus 4.4±0.4 mV V-wave, P<0.05, which increased central fatigue during a 2-min maximum load (P<0.05. Furthermore, only in brief warm water rewarming cerebral alterations were restored to the control level and it was indicated by shortened reaction times (P<0.05.Conclusions: Brief rewarming in warm water rather than the same duration rewarming in thermoneutral environment blunted the hypothermia-induced alterations for thermoregulation, sensation, motor drive and cognition, despite the fact that rectal and deep muscle temperature remained lowered.

  17. Ultrastructure and lipid alterations induced by cadmium in tomato (Lycopersicon esculentum) chloroplast membranes.

    Science.gov (United States)

    Djebali, W; Zarrouk, M; Brouquisse, R; El Kahoui, S; Limam, F; Ghorbel, M H; Chaïbi, W

    2005-07-01

    The effects of cadmium (Cd) uptake on ultrastructure and lipid composition of chloroplasts were investigated in 28-day-old tomato plants (Lycopersicon esculentum var. Ibiza F1) grown for 10 days in the presence of various concentrations of CdCl2. Different growth parameters, lipid and fatty acid composition, lipid peroxidation, and lipoxygenase activity were measured in the leaves in order to assess the involvement of this metal in the generation of oxidative stress. We first observed that the accumulation of Cd increased with external metal concentration, and was considerably higher in roots than in leaves. Cadmium induced a significant inhibition of growth in both plant organs, as well as a reduction in the chlorophyll and carotenoid contents in the leaves. Ultrastructural investigations revealed that cadmium induced disorganization in leaf structure, essentially marked by a lowered mesophyll cell size, reduced intercellular spaces, as well as severe alterations in chloroplast fine structure, which exhibits disturbed shape and dilation of thylakoid membranes. High cadmium concentrations also affect the main lipid classes, leading to strong changes in their composition and fatty acid content. Thus, the exposure of tomato plants to cadmium caused a concentration-related decrease in the fatty acid content and a shift in the composition of fatty acids, resulting in a lower degree of fatty acid unsaturation in chloroplast membranes. The level of lipid peroxides and the activity of lipoxygenase were also significantly enhanced at high Cd concentrations. These biochemical and ultrastructural changes suggest that cadmium, through its effects on membrane structure and composition, induces premature senescence of leaves.

  18. Alteration of contractile and regulatory proteins in estrogen-induced hypertrophy of female rabbit bladder.

    Science.gov (United States)

    Lin, Alpha Dian-Yu; Levin, Robert M; Kogan, Barry A; Whitbeck, Catherine; Leggett, Robert E; Kearns, Christine; Mannikarottu, Anita

    2006-11-01

    Estrogen is essential to mediate physiologic functions in female bladders. Deficiency of estrogen has been speculated to be an etiologic factor for bladder dysfunction in postmenopausal women. Our previous studies have demonstrated that estrogen supplementation in female rabbits induces a "functional hypertrophy" of the urinary bladder smooth muscle. The present study investigated the alterations in the contractile and regulatory proteins in this model. Twenty New Zealand white female rabbits were separated into five groups of 4 rabbits each. Group 1 served as the control, groups 2 to 6 underwent ovariectomy (Ovx), and group 2 served as the Ovx without estradiol treatment group. Two weeks after Ovx, groups 3 to 5 were given 17-beta estradiol (1 mg/kg/day) by subcutaneous implant for 1, 3, and 7 days, respectively. The expression of the contractile and regulatory proteins, such as myosin light chain kinase, rho-kinase, and caldesmon, was analyzed by Western blotting. The expression of myosin light chain kinase was enhanced by estradiol supplementation. The expression of rho-kinase-alpha was increased significantly (20-fold) after Ovx, which was downregulated after estrogen supplementation. No significant change was seen in rho-kinase-beta after Ovx or estradiol supplementation. The expression of caldesmon isoforms was enhanced by 1-day estradiol supplementation but decreased to lower levels than those of the control group by 3 and 7 days of estrogen treatment. The results of the present study have provided more understanding about the role of the contractile and regulatory proteins in detrusor muscle, in both dysfunctional atrophy induced by Ovx and functional hypertrophy induced by estrogen supplementation.

  19. Protective effect of flax seed oil against radiation induced hematological alterations in mammals

    International Nuclear Information System (INIS)

    Sharma, Jyoti; Singh, Ritu; Goyal, P.K.; Singh, Seema

    2014-01-01

    Human beings are exposed to ionizing and non ionizing radiation from natural as well as manmade sources. Ionizing radiations are one of the predominant exogenous factors that have deleterious consequences to human life. Exposure to ionizing radiations damages the hematopoietic, gastrointestinal or central nervous systems, depending on radiation dose. Hence, there is an urgent need to prevent such deleterious effects caused due to ionizing radiations. Chemical protection involves the use of synthetic and natural products against planned radiation exposure. Medicinal plants are rich in antioxidants and their chemical constituents may be the potential source for radioprotective agents. Linum usitatissimum plant (family: Linaceae), source of flaxseed oil (FSO), is well known for its anticarcinogenic, antidiabetic, cardioprotector, antiulcer properties owing to the presence of various phytochemicals. The present study has been focused to find out the preventive action of flaxseed oil against radiation induced hematological and biochemical lesions in mammals. For this purpose, FSO (50μL/animal/day) was orally administered to Swiss albino mice for five days, prior to 6 Gy gamma radiation exposure. The animals were sacrificed on 1 st , 3 rd , 7 th , 15 th and 30 th day after irradiation. Radiation treated control group exhibited significant reduction in erythrocytes count, hemoglobin content, hematocrit value and total WBC count in peripheral blood. In contrast, pretreatment with FSO significantly increased all these blood constituents. Further, the antioxidant parameters such as reduced glutathione, catalase, and superoxide dismutase showed a significant elevation in FSO pretreated group which were reduced in irradiated control group. Similarly, radiation induced increase lipid peroxidation in blood was significantly inhibited after FSO treatment. The present results indicate that the flaxseed oil has the ability to debilitate the radiation induced adverse alterations in

  20. Deletion of the African Swine Fever Virus Gene DP148R Does Not Reduce Virus Replication in Culture but Reduces Virus Virulence in Pigs and Induces High Levels of Protection against Challenge.

    Science.gov (United States)

    Reis, Ana L; Goatley, Lynnette C; Jabbar, Tamara; Sanchez-Cordon, Pedro J; Netherton, Christopher L; Chapman, David A G; Dixon, Linda K

    2017-12-15

    Many of the approximately 165 proteins encoded by the African swine fever virus (ASFV) genome do not have significant similarity to known proteins and have not been studied experimentally. One such protein is DP148R. We showed that the DP148R gene is transcribed at early times postinfection. Deletion of this gene did not reduce virus replication in macrophages, showing that it is not essential for replication in these cells. However, deletion of this gene from a virulent isolate, Benin 97/1, producing the BeninΔDP148R virus, dramatically reduced the virulence of the virus in vivo All pigs infected with the BeninΔDP148R virus survived infection, showing only transient mild clinical signs soon after immunization. Following challenge with the parental virulent virus, all pigs immunized by the intramuscular route (11/11) and all except one immunized by the intranasal route (5/6) survived. Mild or no clinical signs were observed after challenge. As expected, control nonimmune pigs developed signs of acute African swine fever (ASF). The virus genome and infectious virus were observed soon after immunization, coincident with the onset of clinical signs (∼10 6 genome copies or 50% tissue culture infective doses/ml). The levels of the virus genome declined over an extended period up to 60 days postimmunization. In contrast, infectious virus was no longer detectable by days 30 to 35. Gamma interferon (IFN-γ) was detected in serum between days 4 and 7 postimmunization, and IFN-γ-producing cells were detected in all pigs analyzed following stimulation of immune lymphocytes with whole virus. ASFV-specific antibodies were first detected from day 10 postimmunization. IMPORTANCE African swine fever (ASF) is endemic in Africa, parts of the Trans Caucasus, the Russian Federation, and several European countries. The lack of a vaccine hinders control. Many of the ASF virus genes lack similarity to known genes and have not been characterized. We have shown that one of these, DP

  1. Circoviral infections in swine

    Directory of Open Access Journals (Sweden)

    Ivetić Vojin

    2002-01-01

    Full Text Available Circoviral infections in swine have appeared only recently and they today attract the attention of large numbers of researchers all over the world. They represent a great mystery, an unknown in veterinary medicine, both in our country and in the world. The causes of these infections are circoviruses, called after the DNA which is shaped like a circle. A large number of authors today believe the PCV-2 causes two pathological entities in weaned piglets which are known as porcine multisystemic wasting syndrome (PMWS and porcine dermatitis nephropathy syndrome (PDNS. Current investigations indicate that there is a causal connection between these two syndromes. These two new diseases, which have recently spread all over the world, cause serious losses, great concern and confusion, especially when they occur simultaneously or in a sequence in the same herd, or in parallel with other pathogenes, primarily with the porcine reproductive and respiratory syndrome virus (PRRSV and the porcine parvovirus (PPV. PMWS was first described in Canada in 1991. It most often affect pigs aged 5-12 weeks. The main clinical expression, depending on the stage of progression is diarrhea, delayed development or depressed growth, stuntedness, dyspnea ictherus, eyelid swelling, and lymphadenopathy. More rarely, there are neurological symptoms. Prominent suppression of the immune system is the main characteristic of PMWS, and a wave of secondary bacterial infection is also observed. PDNS is a new disease of economic importance, which mostly affects older swine, from 5 weeks to 5 months of age. The most prominent clinical symptoms in seriously ill piglets is extensive dermatitis, mostly on the chest, abdomen, haunches and forelegs, with the appearance of purple-red swellings of different shape and size. The swine are depressive febrile, anorectic, all of which leads to stunted growth. They are inactive. Mortality is often about 15%. PDNS is a differentially diagnostically

  2. Surface and elemental alterations of dental alloys induced by electro discharge machining (EDM).

    Science.gov (United States)

    Zinelis, Spiros

    2007-05-01

    To evaluate the surface and elemental alterations induced by electro discharge machining (EDM) on the surface of dental cast alloys used for the fabrication of implant retained meso- and super-structures. A completed cast model of an arch that received dental implants was used for the preparation of six wax patterns which were divided into three groups (Au, Co and Ti). The wax patterns of the Au and Co groups were invested with conventional phosphate-bonded silica-based investment material and the Ti group with magnesia-based investment material. The investment rings of the Au and Co groups were cast with an Au-Ag alloy (Stabilor G) and a Co-Cr base alloy (Okta C), respectively, while the investment rings of group Ti were cast with cp Ti (Biotan). One casting of each group was subjected to electro discharge machining (EDM); the other was conventionally ground and polished. The surface morphology and the elemental compositions of conventionally and EDM-finished surfaces were studied by SEM/X-ray EDS analysis. Six spectra were collected from each surface employing the area scan mode and the mean value of each element between conventionally and EDM-finished surfaces was statistically analyzed by t-test (a=0.05). Then the specimens of each group were cut perpendicular to their longitudinal axis and after metallographic grinding and polishing the cross-sections studied under the SEM. The EDM surfaces showed a significant increase in C due to the decomposition of the dielectric fluid during spark erosion. Moreover, a significant Cu uptake was noted on these surfaces from the decomposition of the Cu electrodes used for EDM. Cross-sectional analysis showed that all alloys developed a superficial zone (recast layer) varying from 2 microm for Au-Ag to 10 microm for Co-Cr alloy. The elemental composition of dental alloy surfaces is significantly altered after EDM treatment.

  3. Alterations in regulatory T cells induced by specific oligosaccharides improve vaccine responsiveness in mice.

    Directory of Open Access Journals (Sweden)

    Marcel A Schijf

    Full Text Available Prophylactic vaccinations are generally performed to protect naïve individuals with or without suppressed immune responsiveness. In a mouse model for Influenza vaccinations the specific alterations of CD4(+CD25(+Foxp3(+ regulatory T-cells (Tregs in the immune modulation induced by orally supplied oligosaccharides containing scGOS/lcFOS/pAOS was assessed. This dietary intervention increased vaccine specific DTH responses. In addition, a significant increased percentage of T-bet(+ (Th1 activated CD69(+CD4(+ T cells (p<0.001 and reduced percentage of Gata-3(+ (Th2 activated CD69(+CD4(+T cells (p<0.001 was detected in the mesenteric lymph nodes (MLN of mice receiving scGOS/lcFOS/pAOS compared to control mice. Although no difference in the number or percentage of Tregs (CD4(+Foxp3(+ could be determined after scGOS/lcFOS/pAOS intervention, the percentage of CXCR3 (+ /T-bet(+ (Th1-Tregs was significantly reduced (p<0.05 in mice receiving scGOS/lcFOS/pAOS as compared to mice receiving placebo diets. Moreover, although no absolute difference in suppressive capacity could be detected, an alteration in cytokine profile suggests a regulatory T cell shift towards a reducing Th1 suppression profile, supporting an improved vaccination response.These data are indicative for improved vaccine responsiveness due to reduced Th1 suppressive capacity in the Treg population of mice fed the oligosaccharide specific diet, showing compartmentalization within the Treg population. The modulation of Tregs to control immune responses provides an additional arm of intervention using alternative strategies possibly leading to the development of improved vaccines.

  4. Ceftriaxone reverses ketamine-induced lasting EEG and astrocyte alterations in juvenile mice.

    Science.gov (United States)

    Dodman, K; Featherstone, R E; Bang, J; Liang, Y; Siegel, S J

    2015-11-01

    Ketamine, an N-methyl-d-aspartate receptor antagonist, is used as a pediatric anesthetic because of its favorable safety profile. It is also being investigated as an antidepressant. Unfortunately, ketamine causes adverse reactions including hallucinations and is associated with a high prevalence of abuse among adolescents. Although chronic ketamine use has been shown to produce cognitive impairments even years following cessation, little is known about its long-term consequences on adolescents. The beta-lactam ceftriaxone has been shown to attenuate alcohol withdrawal, and alleviate early brain injury and memory impairments following subarachnoid hemorrhage. However, its ability to reverse the effects of adolescent ketamine exposure is not known. Previous data indicate that ketamine causes a reduction in the number of Excitatory Amino Acid Transporter Type 2 (EAAT2)-containing astrocytes. Additionally, the beta lactam antibiotic ceftriaxone increased expression of EAAT2. As EAAT2 is a principal mechanism of glutamate clearance from the synapse, the current study tests the hypothesis that ceftriaxone may reverse functional consequences of ketamine exposure. We examined the effects of chronic ketamine in juvenile mice as well as reversal by ceftriaxone using electroencephalography (EEG). Subsequently, we assessed the effects of these treatments on markers of astrocyte proliferation, using Glial Fibrillary Acidic Protein (GFAP), and function, as evidenced by EAAT2. Juvenile mice exposed to chronic ketamine showed lasting alterations in EEG measurements as well as markers of astrocyte number and function. These alterations were reversed by ceftriaxone. Data suggest that ceftriaxone may be able to ameliorate ketamine-induced long-term disturbances in adolescent brains. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Toxicity of drinking water disinfection byproducts: cell cycle alterations induced by the monohaloacetonitriles.

    Science.gov (United States)

    Komaki, Yukako; Mariñas, Benito J; Plewa, Michael J

    2014-10-07

    Haloacetonitriles (HANs) are a chemical class of drinking water disinfection byproducts (DBPs) that form from reactions between disinfectants and nitrogen-containing precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. HANs, previously demonstrated to be genotoxic, were investigated for their effects on the mammalian cell cycle. Treating Chinese hamster ovary (CHO) cells with monoHANs followed by the release from the chemical treatment resulted in the accumulation of abnormally high DNA content in cells over time (hyperploid). The potency for the cell cycle alteration followed the order: iodoacetonitrile (IAN) > bromoacetonitrile (BAN) ≫ chloroacetonitrile (CAN). Exposure to 6 μM IAN, 12 μM BAN and 900 μM CAN after 26 h post-treatment incubation resulted in DNA repair; however, subsequent cell cycle alteration effects were observed. Cell proliferation of HAN-treated cells was suppressed for as long as 43 to 52 h. Enlarged cell size was observed after 52 h post-treatment incubation without the induction of cytotoxicity. The HAN-mediated cell cycle alteration was mitosis- and proliferation-dependent, which suggests that HAN treatment induced mitosis override, and that HAN-treated cells proceeded into S phase and directly into the next cell cycle. Cells with multiples genomes would result in aneuploidy (state of abnormal chromosome number and DNA content) at the next mitosis since extra centrosomes could compromise the assembly of bipolar spindles. There is accumulating evidence of a transient tetraploid state proceeding to aneuploidy in cancer progression. Biological self-defense systems to ensure genomic stability and to eliminate tetraploid cells exist in eukaryotic cells. A key tumor suppressor gene, p53, is oftentimes mutated in various types of human cancer. It is possible that HAN disruption of the normal cell cycle and the generation of aberrant cells with an abnormal number of

  6. OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature.

    Science.gov (United States)

    Domnik, N J; Seaborn, G; Vincent, S G; Akl, S G; Redfearn, D P; Fisher, J T

    2012-01-01

    Altered autonomic (ANS) tone in chronic respiratory disease is implicated as a factor in cardiovascular co-morbidities, yet no studies address its impact on cardiovascular function in the presence of murine allergic airway (AW) hyperresponsiveness (AHR). Since antigen (Ag)-induced AHR is used to model allergic asthma (in which ANS alterations have been reported), we performed a pilot study to assess measurement feasibility of, as well as the impact of allergic sensitization to ovalbumin (OVA) on, heart rate variability (HRV) in a murine model. Heart rate (HR), body temperature (T(B)), and time- and frequency-domain HRV analyses, a reflection of ANS control, were obtained in chronically instrumented mice (telemetry) before, during and for 22 h after OVA or saline aerosolization in sensitized (OVA) or Alum adjuvant control exposed animals. OVA mice diverged significantly from Alum mice with respect to change in HR during aerosol challenge (P < 0.001, Two-Way ANOVA; HR max change Ctrl = +80 ± 10 bpm vs. OVA = +1 ± 23 bpm, mean ± SEM), and displayed elevated HR during the subsequent dark cycle (P = 0.006). Sensitization decreased the T(B) during aerosol challenge (P < 0.001). Sensitized mice had decreased HRV prior to challenge (SDNN: P = 0.038; Low frequency (LF) power: P = 0.021; Low/high Frequency (HF) power: P = 0.042), and increased HRV during Ag challenge (RMSSD: P = 0.047; pNN6: P = 0.039). Sensitized mice displayed decreased HRV subsequent to OVA challenge, primarily in the dark cycle (RMSSD: P = 0.018; pNN6: P ≤ 0.001; LF: P ≤ 0.001; HF: P = 0.040; LF/HF: P ≤ 0.001). We conclude that implanted telemetry technology is an effective method to assess the ANS impact of allergic sensitization. Preliminary results show mild sensitization is associated with reduced HRV and a suppression of the acute T(B)-response to OVA challenge. This approach to assess altered ANS control in the acute OVA model may also be beneficial in chronic AHR models.

  7. Molecular mechanisms of cis-urocanic acid and permethrin-induced alterations in cutaneous immunity.

    Science.gov (United States)

    Prater, M R; Blaylock, B L; Holladay, S D

    2003-12-01

    Cutaneous cis-urocanic acid (cUCA) or ultraviolet B exposure has been shown to cause diminished cutaneous contact hypersensitivity (CH) and to induce systemic tolerance (increased regulatory T lymphocytes) in mice. Permethrin is also a known CH inhibitor, but the molecular mechanisms are currently poorly understood. In this study, CH was evaluated in four strains of mice: an immunosensitive strain (C57BL/6N), an immunoresistant strain (SvImJ), a strain developed from C57BL/6N mice but genetically altered at both the tumor necrosis factor-alpha receptors (TNFalphap55R and p75R), and a strain developed from C57BL/6N but genetically deleted at the interferon-gamma (IFNgamma) locus. CH was evaluated in each group via oxazolone challenge following a 5-day exposure to intradermal (ID) cUCA or a single exposure to topical permethrin, or co-exposure to both chemicals in 5-week-old female C57BL/6N, SvImJ, and C57BL/6N mice genetically altered at the TNFalpha or IFNgamma locus. A 5-day exposure to ID cUCA or a single exposure to topical permethrin resulted in diminished CH response in C57BL/6N mice, and this effect was exacerbated with concurrent exposure to both chemicals. CH in SvImJ was both cUCA- and permethrin-resistant relative to C57BL/6N mice, as 5-day cUCA or a single exposure to permethrin did not diminish CH, nor did concurrent exposure to cUCA and permethrin. Mice deleted at both TNFalphaR loci displayed similar but somewhat blunted diminished CH responses to cUCA or permethrin. This trend became significant with combined chemical exposure. IFNgamma knockout mice displayed similar diminished CH responses to cUCA or permethrin alone. Unlike C57BL/6N mice, the IFNgamma knockout mice did not show a further reduction in CH with combined chemical exposure. These results suggest the following: (1)Mouse strains show variable susceptibility to permethrin- and cUCA-induced immunomodulation. (2)TNFalpha may be involved in the immunomodulatory effects of cUCA and permethrin

  8. Swine influenza H1N1 virus induces acute inflammatory immune responses in pig lungs: a potential animal model for human H1N1 influenza virus.

    Science.gov (United States)

    Khatri, Mahesh; Dwivedi, Varun; Krakowka, Steven; Manickam, Cordelia; Ali, Ahmed; Wang, Leyi; Qin, Zhuoming; Renukaradhya, Gourapura J; Lee, Chang-Won

    2010-11-01

    Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

  9. Ractopamine hydrochloride induces behavioral alterations and oxidative status imbalance in zebrafish.

    Science.gov (United States)

    Sachett, Adrieli; Bevilaqua, Fernanda; Chitolina, Rafael; Garbinato, Cristiane; Gasparetto, Henrique; Dal Magro, Jacir; Conterato, Greicy M; Siebel, Anna M

    2018-01-01

    The occurrence of ractopamine (RAC) hydrochloride in water bodies is of significant concern due to its ecological impacts and toxicity to humans. RAC hydrochloride is a β-adrenergic agonist drug used as a feed additive to (1) improve feed efficiency, (2) rate of weight gain, and (3) increase carcass leanness in animals raised for their meat. This drug is excreted by animals in urine and introduced into the environment affecting nontarget organisms including fish. In wastewater released from farms, RAC concentrations were detected from 0.124 µg/L to 30.1 µg/L, and in levels ranging from 1.3 × 10 -5 to 5.4 × 10 -4 μg/L in watersheds. The aim of this study was to examine the effects of exposure to RAC at 0.1, 0.2, 0.85, 8.5, or 85 µg/L dissolved in water on behavior and oxidative status in adult zebrafish. At 0.85 µg/L, RAC treatment increased exploratory behavior of zebrafish; while at 8.5 µg/L, decreased locomotor and exploratory activities were noted. With respect to oxidative stress biomarkers, results showed that RAC at 0.2 µg/L induced lipid peroxidation and elevated total thiol content in zebrafish brain. All drug tested concentrations produced a fall in nonprotein thiol content. Finally, RAC at 0.85, 8.5, or 85 µg/L increased catalase enzyme activity. Our results demonstrated that the exposure to RAC induced behavioral alterations and oxidative stress in zebrafish.

  10. Islet-cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance?

    Science.gov (United States)

    van Raalte, Daniël H; Kwa, Kelly A A; van Genugten, Renate E; Tushuizen, Maarten E; Holst, Jens J; Deacon, Carolyn F; Karemaker, John M; Heine, Robert J; Mari, Andrea; Diamant, Michaela

    2013-04-01

    Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system. A randomized, placebo-controlled, double-blind, dose-response intervention study was conducted in 32 healthy males (age: 21±2years; BMI: 21.9±1.7kg/m(2)). Participants were allocated to prednisolone 7.5mg once daily (n=12), prednisolone 30mg once daily (n=12), or placebo (n=8) for two weeks. Beta-cell function was measured by hyperglycemic clamp with arginine stimulation, glucagon levels were measured following a standardized meal test. We found that prednisolone treatment dose-dependently reduced C-peptide secretion following arginine stimulation on top of hyperglycemia (ASI-iAUCCP): -2.8 (-5.2;0.2) and -3.1 (-8.8; -1.0) nmolL(-1)min(-1) for prednisolone 7.5mg and prednisolone 30mg, respectively (P=0.035 vs. placebo). Fasting glucagon levels increased dose-dependently (vs. placebo; P=0.001), whereas postprandial glucagon levels were only increased by prednisolone 30mg. Changes in parasympathetic activity related with changes in fasting glucose levels (r=-0.407; P=0.03) and showed a trend towards correlation with fasting glucagon concentrations (r=-0.337; P=0.07). The change in sympathovagal balance was inversely related to ASI-iAUCCP (r=-0.365; P=0.05). We conclude that in addition to inducing insulin resistance, prednisolone treatment dose-dependently impaired islet-cell function. Altered sympathovagal balance may be related to these effects. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. PEX11β induces peroxisomal gene expression and alters peroxisome number during early Xenopus laevis development

    Directory of Open Access Journals (Sweden)

    Damjanovski Sashko

    2011-04-01

    Full Text Available Abstract Background Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that de novo peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although de novo biogenesis and divisions are likely important mechanisms, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as frogs where large embryonic yolk and fatty acid stores must be quickly metabolized, and resulting reactive oxygen species eliminated. Here we elucidate the role of Pex11β in regulating peroxisomal gene expression and number in Xenopus laevis embryogenesis. Results Microinjecting haemagglutinin (HA tagged Pex11β in early embryos resulted in increased RNA levels for peroxisome related genes PMP70 and catalase at developmental stages 10 and 20, versus uninjected embryos. Catalase and PMP70 proteins were found in punctate structures at stage 20 in control embryos, whereas the injection of ectopic HA-Pex11β induced their earlier localization in punctate structures at stage 10. Furthermore, the peroxisomal marker GFP-SKL, which was found localized as peroxisome-like structures at stage 20, was similarly found at stage 10 when co-microinjected with HA-Pex11β. Conclusions Overexpressed Pex11β altered peroxisomal gene levels and induced the early formation of peroxisomes-like structures during development, both of which demonstrate that Pex11β may be a key regulator of peroxisome number in early Xenopus embryos.

  12. Alteration of the renin-angiotensin system in caerulein induced acute pancreatitis in the mouse.

    Science.gov (United States)

    Gaddam, Ravinder Reddy; Ang, Abel Damien; Badiei, Alireza; Chambers, Stephen T; Bhatia, Madhav

    2015-01-01

    The objective of this study was to determine if RAS bioactive enzymes and peptides are perturbed in acute pancreatitis and associated lung injury. The intervention group of mice were treated with ten hourly intraperitoneal (i.p.) injections of caerulein (50 μg/kg) to induce acute pancreatitis. Animals were euthanized, samples of pancreas, lung and blood were collected, and plasma was prepared and stored for subsequent analysis. ACE and ACE2 activities were determined by spectrofluorometric assay. ACE, ACE2, Ang II and Ang-(1-7) levels were quantified by ELISA. There was a significant decrease in ACE2 enzymatic activity in pancreatic and lung tissues of mice with acute pancreatitis. In contrast, there were no significant changes in measured levels of ACE and ACE2 in the pancreas, and lung or activity of ACE in pancreatic and lung tissue following acute pancreatitis. There were no significant differences in the activities and levels of circulating ACE and ACE2 following acute pancreatitis. The ACE to ACE2 activity ratio was markedly increased in pancreatic and lung tissues of mice with acute pancreatitis. No significant changes were observed in the levels of Ang II except for a decrease in lung tissue. No changes were observed in Ang-(1-7) levels in pancreas, lung and plasma between the groups. The Ang II to Ang-(1-7) ratio was increased in the pancreas but was decreased in the lung following caerulein treatment. These data suggest dysregulation of RAS in acute pancreatitis as evidenced by altered Ang II/Ang-(1-7) levels induced by the imbalance of ACE/ACE2 activity. Copyright © 2015. Published by Elsevier India Pvt Ltd.

  13. Chronic stress-induced alterations in mouse colonic 5-HT and defecation responses are strain dependent.

    Science.gov (United States)

    Julio-Pieper, Marcela; O'Mahony, Cliona M; Clarke, Gerard; Bravo, Javier A; Dinan, Timothy G; Cryan, John F

    2012-03-01

    Mood disorders and chronic stress are frequently associated with gastrointestinal (GI) symptoms including diarrhoea or constipation. Locally produced serotonin [5-hydroxytryptamine (5-HT)] regulates GI motility and is a key factor in the pathophysiology of stress-associated GI disorders. We aimed to establish whether chronic stress can differentially affect faecal output and colon 5-HT concentration in two inbred mouse strains: BALB/c and C57BL/6 which differ in their ability to cope with stress. Adult male BALB/c and C57BL/6 mice were restrained for 2 h daily for 10 days. Defecation was monitored during each stress session. Twenty-four hours after the last session of stress, plasma corticosterone concentration was higher than control in both strains, indicative of a physiological effect of chronic stress; however, stress-induced diarrhoea was more persistent in C57BL/6 mice. Basal concentration of colon 5-HT was higher in C57BL/6 mice, and stress elicited an increase in colon 5-HT only in this strain. Finally, naïve BALB/c mice had a higher sensitivity (incidence of diarrhoea) to 5-HT (0.33 mg/kg, i.p.) than C57BL/6 mice. Our results suggest that differential defecation responses to stress may be associated with colon 5-HT concentration, which may in turn reflect the individual sensitivity to 5-HT. In addition, C57BL/6 mice emerge as a relevant model for studying GI alterations induced by chronic stress.

  14. Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats

    NARCIS (Netherlands)

    Ouwens, D.M.; de Boer, C.; Fodor, M.; Galan, P.; Heine, R.J.; Maassen, J.A.; Diamant, M.

    2005-01-01

    Aims/hypothesis: Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic

  15. Structural Chromosomal Alterations Induced by Dietary Bioflavonoids in Fanconi Anemia Lymphocytes

    Directory of Open Access Journals (Sweden)

    Gonzalo Guevara

    2007-06-01

    Full Text Available IntroductionFanconi anemia is an autosomal recessive diseasecharacterized by a variety of congenital abnormalities,progressive bone marrow failure,increased chromosomal instability and higherrisk to acute myeloid leukemia, solid tumors. Thisentity can be considered an appropriate biologicalmodel to analyze natural substances with possiblegenotoxic effect. The aims of this study wereto describe and quantify structural chromosomalaberrations induced by 5 flavones, 2 isoflavonesand a topoisomerase II chemotherapeutic inhibitorin Fanconi anemia lymphocytes in order todetermine chromosomal numbers changes and/or type of chromosomal damage.Materials and methodsChromosomes stimulated by phytohaemagglutininM, from Fanconi anemia lymphocytes,were analysed by conventional cytogenetic culture.For each chemical substance and controls,one hundred metaphases were evaluated. Chromosomalalterations were documented by photographyand imaging analyzer. To statisticalanalysis was used chi square test to identify significantdifferences between frequencies of chromosomaldamage of basal and exposed cellcultured a P value less than 0.05.ResultsThere were 431 chromosomal alterations in1000 metaphases analysed; genistein was themore genotoxic bioflavonoid, followed in descendentorder by genistin, fisetin, kaempferol,quercetin, baicalein and miricetin. Chromosomalaberrations observed were: chromatidbreaks, chromosomal breaks, cromatid andchromosomal gaps, quadriratials exchanges,dicentrics chromosome and complex rearrangements.ConclusionBioflavonoids as genistein, genistin and fisetin,which are commonly present in the human diet,showed statistical significance in the number ofchromosomal aberrations in Fanconi anemialymphocytes, regarding the basal damage.

  16. Environmental estrogen(s) induced swimming behavioural alterations in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Goundadkar, Basavaraj B; Katti, Pancharatna

    2017-09-01

    The present study is an attempt to investigate the effects of long-term (75days) exposure to environmental estrogens (EE) on the swimming behaviour of zebrafish (Danio rerio). Adult zebrafish were exposed semi-statically to media containing commonly detected estrogenic water contaminants (EE2, DES and BPA) at a concentration (5ng/L) much lower than environmentally recorded levels. Time spent in swimming, surface preference, patterns and path of swimming were recorded (6mins) for each fish using two video cameras on day 15, 30 60 and 75. Video clips were analysed using a software program. Results indicate that chronic exposure to EE leads to increased body weight and size of females, reduced (Pswimming time, delay in latency, increased (P<0.05) immobility, erratic movements and freezing episodes. We conclude that estrogenic contamination of natural aquatic systems induces alterations in locomotor behaviour and associated physiological disturbances in inhabitant fish fauna. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 3'-Azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta

    International Nuclear Information System (INIS)

    Collier, Abby C.; Helliwell, Rachel J.A.; Keelan, Jeffrey A.; Paxton, James W.; Mitchell, Murray D.; Tingle, Malcolm D.

    2003-01-01

    The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas. Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays. Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK. The effect of AZT on the activities of glutathione-S-transferase, β-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting. AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro. In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, β-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased. We conclude that AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells. These findings have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier

  18. Severe riboflavin deficiency induces alterations in the hepatic proteome of starter Pekin ducks.

    Science.gov (United States)

    Tang, Jing; Hegeman, Maria A; Hu, Jian; Xie, Ming; Shi, Wenbiao; Jiang, Yong; de Boer, Vincent; Guo, Yuming; Hou, Shuisheng; Keijer, Jaap

    2017-11-01

    Suboptimal vitamin B2 status is encountered globally. Riboflavin deficiency depresses growth and results in a fatty liver. The underlying mechanisms remain to be established and an overview of molecular alterations is lacking. We investigated hepatic proteome changes induced by riboflavin deficiency to explain its effects on growth and hepatic lipid metabolism. In all, 360 1-d-old Pekin ducks were divided into three groups of 120 birds each, with twelve replicates and ten birds per replicate. For 21 d, the ducks were fed ad libitum a control diet (CAL), a riboflavin-deficient diet (RD) or were pair-fed with the control diet to the mean daily intake of the RD group (CPF). When comparing RD with CAL and CPF, growth depression, liver enlargement, liver lipid accumulation and enhanced liver SFA (C6 : 0, C12 : 0, C16 : 0, C18 : 0) were observed. In RD, thirty-two proteins were enhanced and thirty-one diminished (>1·5-fold) compared with CAL and CPF. Selected proteins were confirmed by Western blotting. The diminished proteins are mainly involved in fatty acid β-oxidation and the mitochondrial electron transport chain (ETC), whereas the enhanced proteins are mainly involved in TAG and cholesterol biosynthesis. RD causes liver lipid accumulation and growth depression probably by impairing fatty acid β-oxidation and ETC. These findings contribute to our understanding of the mechanisms of liver lipid metabolic disorders due to RD.

  19. Acrylamide alters neurotransmitter induced calcium responses in murine ESC-derived and primary neurons.

    Science.gov (United States)

    Sisnaiske, Julia; Hausherr, Vanessa; Krug, Anne K; Zimmer, Bastian; Hengstler, Jan G; Leist, Marcel; van Thriel, Christoph

    2014-07-01

    Stem cell-derived specialized cell types are of interest as an alternative cell system to identify and research neurotoxic effects and modes of action. Developmental toxicity may be studied during differentiation, while organ-specific toxicity may be assessed in fully functional cells, such as neurons. In this study we tested if fully differentiated neurons derived from murine embryonic stem cells (ESCN) could be used to investigate the effects of the well characterized neurotoxic model compound acrylamide (ACR) and if ESCN behave similar to murine primary cortical neurons (pCN) from 16 days old embryos. We characterized the differentiation process of cryopreserved ESC-derived neural precursor cells (NPC) differentiating to ESCN. During the differentiation process (days 11-20) a strong increase in calcium responses to glutamate, acetylcholine and GABA were observed. Moreover, neuron specific marker proteins, β-III-tubulin, MAP2, Tau, Rbfox3 and synaptophysin showed similar patterns to pCN. In ESCN and pCN the neuronal structure, e.g. neurites, was not affected by low concentrations of ACR [0.5-1.6mM]. However, 24h incubation periods with 0.5-1.6mM ACR led to a reduction of acetylcholine and glutamate induced calcium responses. In conclusion, we show that non-cytotoxic concentrations of ACR alter neurotransmission in ESCN as well as pCN. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task.

    Science.gov (United States)

    Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

    2015-01-01

    It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. © 2015 S. Karger GmbH, Freiburg.

  1. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

    Directory of Open Access Journals (Sweden)

    Carl-Johan Boraxbekk

    2015-07-01

    Full Text Available Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010 after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA. Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

  2. PTH [1-34]-induced alterations predispose the mandibular condylar cartilage to mineralization.

    Science.gov (United States)

    Dutra, E H; O'Brien, M H; Gutierrez, T; Lima, A; Nanda, R; Yadav, S

    2017-06-01

    To study the effects of intermittent parathyroid hormone (PTH [1-34]) on the mandibular condylar cartilage (MCC) and subchondral bone in adult female mice. Twenty-two, 20-week-old female mice were used for in vivo experiments. The experimental mice (n=11) received daily intraperitoneal injections of PTH [1-34] for 3 weeks, while control mice (n=11) received intraperitoneal injections of 0.9% saline solution. Mice were euthanized and then micro-computed tomography (micro-CT); histology and immunostaining were carried out to assess the response. Intermittent PTH [1-34] led to early MCC breakdown and surface irregularities. Micro-CT analyses indicated that PTH [1-34] treatment led to increased bone volume fraction, tissue density and trabecular thickness, while decreasing the trabecular spacing. Histological analyses showed decreased proteoglycan secretion, increased bone turnover (TRAP staining) and increased mineralization. Furthermore, PTH [1-34] treatment showed increased apoptosis of the cells. Our immunohistochemistry showed increased expression of pSMAD158 in the MCC and subchondral bone with PTH administration, whereas sclerostin (SOST) expression was decreased. Intermittent PTH [1-34] results in early mineralization of the MCC, which may result in cartilage degeneration. Our results identified a novel mechanism by which PTH [1-34] induces alteration in the microarchitecture of the MCC and the subchondral bone. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

    Science.gov (United States)

    Lambertenghi-Deliliers, G; Zanon, P L; Pozzoli, E F; Bellini, O; Praga, C

    1978-02-28

    The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

  4. Environmental enrichment reduces behavioural alterations induced by chronic stress in Japanese quail.

    Science.gov (United States)

    Laurence, A; Houdelier, C; Calandreau, L; Arnould, C; Favreau-Peigné, A; Leterrier, C; Boissy, A; Lumineau, S

    2015-02-01

    Animals perceiving repeated aversive events can become chronically stressed. Chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis can have deleterious consequences on physiological parameters (e.g. BW, blood chemistry) and behaviour (e.g. emotional reactivity, stereotypies, cognition). Environmental enrichment (EE) can be a mean to reduce animal stress and to improve welfare. The aim of this study was first, to assess the effects of EE in battery cages on the behaviour of young Japanese quail and second, to evaluate the impact of EE on quail exposed to chronic stress. The experiment involved quail housed in EE cages and submitted or not to a chronic stress procedure (CSP) (EE cages, control quail: n=16, CSP quail: n=14) and quail housed in standard cages and exposed or not to the CSP (standard non-EE cages, control quail: n=12, CSP quail: n=16). Our procedure consisted of repeated aversive events (e.g. ventilators, delaying access to food, physical restraint, noise) presented two to five times per 24 h, randomly, for 15 days. During CSP, EE improved quail's welfare as their stereotypic pacing decreased and they rested more. CSP decreased exploration in all quail. After the end of CSP, quail presented increased emotional reactivity in emergence test. However, the effect of EE varied with test. Finally, chronic stress effects on comfort behaviours in the emergence test were alleviated by EE. These results indicate that EE can alleviate some aspects of behavioural alterations induced by CSP.

  5. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

    Directory of Open Access Journals (Sweden)

    Amal Abdussalam Ali A. Hmaid

    2018-03-01

    Full Text Available Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C or cold (4 ± 1 °C and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis. Keywords: Cardiomyocyte, Cardiac hypertrophy, l-Arginine, l-NAME, Myocardium

  6. A comparison of Selective Aortic Arch Perfusion and Resuscitative Endovascular Balloon Occlusion of the Aorta for the management of hemorrhage-induced traumatic cardiac arrest: A translational model in large swine.

    Directory of Open Access Journals (Sweden)

    Ed B G Barnard

    2017-07-01

    Full Text Available Survival rates remain low after hemorrhage-induced traumatic cardiac arrest (TCA. Noncompressible torso hemorrhage (NCTH is a major cause of potentially survivable trauma death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA at the thoracic aorta (Zone 1 can limit subdiaphragmatic blood loss and allow for IV fluid resuscitation when intrinsic cardiac activity is still present. Selective Aortic Arch Perfusion (SAAP combines thoracic aortic balloon hemorrhage control with intra-aortic oxygenated perfusion to achieve return of spontaneous circulation (ROSC when cardiac arrest has occurred.Male Yorkshire Landrace cross swine (80.0 ± 6.0 kg underwent anesthesia, instrumentation for monitoring, and splenectomy. TCA was induced by laparoscopic liver lobe resection combined with arterial catheter blood withdrawal to achieve a sustained systolic blood pressure <10 mmHg, cardiac arrest. After 3 min of arrest, swine were allocated to one of three interventions: (1 REBOA plus 4 units of IV fresh whole blood (FWB, (2 SAAP with oxygenated lactated Ringer's (LR, 1,600 mL/2 min, or (3 SAAP with oxygenated FWB 1,600 mL/2 min. Primary endpoint was survival to the end of 60 min of resuscitation, a simulated prehospital phase. Thirty animals were allocated to 3 groups (10 per group-5 protocol exclusions resulted in a total of 35 animals being used. Baseline measurements and time to cardiac arrest were not different amongst groups. ROSC was achieved in 0/10 (0%, 95% CI 0.00-30.9 REBOA, 6/10 (60%, 95% CI 26.2-87.8 SAAP-LR and 10/10 (100%, 95% CI 69.2-100.0 SAAP-FWB animals, p < 0.001. Survival to end of simulated 60-minute prehospital resuscitation was 0/10 (0%, 95% CI 0.00-30.9 for REBOA, 1/10 (10%, 95% CI 0.25-44.5 for SAAP-LR and 9/10 (90%, 95% CI 55.5-99.7 for SAAP-FWB, p < 0.001. Total FWB infusion volume was similar for REBOA (2,452 ± 0 mL and SAAP-FWB (2,250 ± 594 mL. This study was undertaken in laboratory conditions, and as such may have

  7. Influence of Monosodium Glutamate on Radiation-Induced Biochemical Alterations in Male Albino Rats

    International Nuclear Information System (INIS)

    Saada, H. N.; Said, U. Z.; Shedid, S.M.; Mahdy, E. M. E.; Elmezayen, H. E.

    2014-01-01

    no effect on insulin resistance and their co-administration produces an additive effect compared to each single treatment. Regarding lipid profile, MSG as well as RAD-exposure induced hyperlipidaemia more noticeable in case of irradiation. Their co-administration had potentiated hyperlipidaemia compared to each single treatment. It is concluded that exposure to MSG together with RAD increased oxidative stress and neurotransmitter alteration in the brain and the risk of metabolic syndrome. It is thus recommended to limit the intake of MSG when human are at risk of overexposure to ionizing radiation.

  8. CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina.

    Science.gov (United States)

    Zeiss, Caroline J; Allore, Heather G; Towle, Virginia; Tao, Weng

    2006-03-01

    Ciliary neurotrophic factor (CNTF) provides morphologic preservation of rods in several animal models of retinitis pigmentosa (RP). However, CNTF may alter photoreceptor morphology and rod photoreceptor differentiation in vitro, as well as affecting normal retinal electrophysiology. In addition, the capacity of CNTF to support other cell types affected secondarily in RP (cones and ganglion cells) is unclear. The purposes of this study were to examine the effects of CNTF upon a canine model of RP, the rod-cone degeneration (rcd-1) dog. Archival tissue from a previous study assessing the capacity of CNTF to rescue photoreceptors in rcd-1 dogs was used. One eye was treated for 7 weeks before being explanted. The contralateral eye was untreated. A total of 23 rcd-1 dogs and seven control dogs (four untreated and three CNTF-treated) were used. Morphometric data describing outer and inner nuclear layer thickness, inner retinal thickness, cones and ganglion cells were collected at nine evenly spaced points along each retina and analysed using a mixed effects model. Immunohistochemistry was performed on a subset of 11 dogs for expression of rhodopsin, human cone arrestin (hCAR) and recoverin. CNTF protected the outer nuclear layer and increased inner retinal thickness in a dose-dependent manner (both were maximal at CNTF doses of 1-6 ng day-1). Significant cone loss or reduction of inner nuclear layer width in rcd-1 did not occur in this model, therefore we were unable to assess the protective effect of CNTF upon these parameters. CNTF did not afford significant ganglion cell protection. CNTF induced morphologic changes in rods and ganglion cells, as well as reducing expression of hCAR and rhodopsin, but not recoverin. The dose of CNTF which provided optimal outer nuclear layer protection also resulted in several other effects, including altered ganglion cell morphology, increased thickness of the entire retina, and reduced expression of some phototransduction proteins

  9. Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus

    International Nuclear Information System (INIS)

    Banerjee, Chaitali; Goswami, Ramansu; Datta, Soma; Rajagopal, R.; Mazumder, Shibnath

    2011-01-01

    We had earlier shown that exposure to arsenic (0.50 μM) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca 2+ ) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca 2+ homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca 2+ levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: → Altered Ca 2+ homeostasis leads to arsenic-induced HKM apoptosis. → Calpain-2 plays a critical role in the process. → ERK is pro-apoptotic in arsenic-induced HKM apoptosis. → Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

  10. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

    Directory of Open Access Journals (Sweden)

    Chatterjee Ajay K

    2003-02-01

    Full Text Available Abstract Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders.

  11. Stressor-induced proteome alterations in zebrafish: A meta-analysis of response patterns

    Energy Technology Data Exchange (ETDEWEB)

    Groh, Ksenia J., E-mail: ksenia.groh@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf (Switzerland); ETH Zürich, Swiss Federal Institute of Technology, Department of Chemistry and Applied Biosciences, 8093 Zürich (Switzerland); Suter, Marc J.-F. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf (Switzerland); ETH Zürich, Swiss Federal Institute of Technology, Department of Environmental Systems Science, 8092 Zürich (Switzerland)

    2015-02-15

    Highlights: • We compared reported proteome changes induced by various stressors in zebrafish. • Several proteins groups frequently responding to diverse stressors were identified. • These included energy metabolism enzymes, heat shock and cytoskeletal proteins. • Insufficient proteome coverage impedes identification of more specific responses. • Further research needs for proteomics in ecotoxicology are discussed. - Abstract: Proteomics approaches are being increasingly applied in ecotoxicology on the premise that the identification of specific protein expression changes in response to a particular chemical would allow elucidation of the underlying molecular pathways leading to an adverse effect. This in turn is expected to promote the development of focused testing strategies for specific groups of toxicants. Although both gel-based and gel-free global characterization techniques provide limited proteome coverage, the conclusions regarding the cellular processes affected are still being drawn based on the few changes detected. To investigate how specific the detected responses are, we analyzed a set of studies that characterized proteome alterations induced by various physiological, chemical and biological stressors in zebrafish, a popular model organism. Our analysis highlights several proteins and protein groups, including heat shock and oxidative stress defense proteins, energy metabolism enzymes and cytoskeletal proteins, to be most frequently identified as responding to diverse stressors. In contrast, other potentially more specifically responding protein groups are detected much less frequently. Thus, zebrafish proteome responses to stress reported by different studies appear to depend mostly on the level of stress rather than on the specific stressor itself. This suggests that the most broadly used current proteomics technologies do not provide sufficient proteome coverage to allow in-depth investigation of specific mechanisms of toxicant action

  12. Radio-induced alteration in cordierite - Implications for petrology, gemmology and materials science

    Science.gov (United States)

    Krickl, R.; Nasdala, L.; Grambole, D.; Kaindl, R.

    2009-04-01

    Cordierite is a common metamorphic and magmatic mineral, which is used as petrologic tool for reconstructing the history of its host rock. Further applications include cordierite gemstones and the use of synthetic analogs in ceramics. Cordierite is stable over a wide temperature and pressure range and relatively resistant to chemical alteration; however, its properties can be significantly changed upon the impact of external irradiation. In the course of a comprehensive study, natural radiohaloes in cordierite (a widespread feature caused by the impact of alpha-particles originating from radioactive inclusions) as well as artificial analogs produced by implantation of 8.8 MeV He2+ ions were investigated using modern micro-techniques. Additional irradiation experiments were performed using O6+ ions, electrons and gamma-rays. Ion irradiation causes yellow colouration that is strongly pleochroic, and fades at higher doses. The possibility of radiation-treatment for enhancing the quality of gem-cordierite is discussed. While samples remain crystalline up to doses of 1016 He2+/cm2, the same material is fully amorphised when irradiated with the same dose of 30 MeV O6+ ions. These different observations may help to estimate the performance assessment of cordierite-ceramics in radiated environments. A very important result concerning the petrological use of cordierite is the radio-induced transformation of channel constituents: Inside the irradiated areas the vibrational bands of CO2 decrease in intensity, whereas two new bands appear at 2135 cm-1 (both IR- and Raman-active; cf. Nasdala et al., 2006) and 1550 cm-1 (only Raman-activ). They are assigned to stretching vibrations of carbon monoxide and molecular oxygen, respectively, thus indicating a radio-chemical transformation 2CO2 → 2CO + O2 in alpha-irradiated cordierite. This study yields the first spectroscopic evidence for the irradiation-induced formation of molecular oxygen in cordierite. Polarised vibrational

  13. Stressor-induced proteome alterations in zebrafish: A meta-analysis of response patterns

    International Nuclear Information System (INIS)

    Groh, Ksenia J.; Suter, Marc J.-F.

    2015-01-01

    Highlights: • We compared reported proteome changes induced by various stressors in zebrafish. • Several proteins groups frequently responding to diverse stressors were identified. • These included energy metabolism enzymes, heat shock and cytoskeletal proteins. • Insufficient proteome coverage impedes identification of more specific responses. • Further research needs for proteomics in ecotoxicology are discussed. - Abstract: Proteomics approaches are being increasingly applied in ecotoxicology on the premise that the identification of specific protein expression changes in response to a particular chemical would allow elucidation of the underlying molecular pathways leading to an adverse effect. This in turn is expected to promote the development of focused testing strategies for specific groups of toxicants. Although both gel-based and gel-free global characterization techniques provide limited proteome coverage, the conclusions regarding the cellular processes affected are still being drawn based on the few changes detected. To investigate how specific the detected responses are, we analyzed a set of studies that characterized proteome alterations induced by various physiological, chemical and biological stressors in zebrafish, a popular model organism. Our analysis highlights several proteins and protein groups, including heat shock and oxidative stress defense proteins, energy metabolism enzymes and cytoskeletal proteins, to be most frequently identified as responding to diverse stressors. In contrast, other potentially more specifically responding protein groups are detected much less frequently. Thus, zebrafish proteome responses to stress reported by different studies appear to depend mostly on the level of stress rather than on the specific stressor itself. This suggests that the most broadly used current proteomics technologies do not provide sufficient proteome coverage to allow in-depth investigation of specific mechanisms of toxicant action

  14. FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

    Science.gov (United States)

    Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

    2017-03-01

    FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Conformation and activity alteration of horseradish peroxidase induced by the interaction with gene carrier polyethyleneimines

    Science.gov (United States)

    Huang, Aimin; Wei, Bangzhi; Mo, Junyong; Wang, Yajing; Ma, Lin

    2018-01-01

    Polyethyleneimine (PEI) has long been considered as ;golden standard; for polymeric gene delivery carriers. However the molecular basis of the cytotoxicity of PEI is poorly understood. Little is known about the effects of PEI on the structure and functions of biomacromolecules. In this work, fluorescence, UV-vis absorption, circular dichroism spectroscopy were conducted to investigate the influence of PEI of average molecular weight 25, 10 and 1.8 kDa (denoted as PEI25k, PEI10k and PEI1.8k) on the conformation of horseradish peroxidase (HRP) and its catalytic efficiency. Zeta-potential measurement and isothermal titration calorimetry were used to reveal the mechanism of the interaction between PEIs and HRP. PEIs were found to bind onto the surface of HRP predominantly via hydrophobic interaction and hydrogen bond or van der Waals interaction. The complex formation between HRP and PEI induced a more compact conformation of the enzyme and an increased hydrophobicity of the microenvironment surrounding heme pocket. The conformational change of HRP had little impact on the affinity towards H2O2 and phenol. However, the increase in the non-planarity of porphyrin ring in the heme group led to an increase in the exposure degree of the active center and thus an enhancement of catalytic efficiency of HRP in the presence of high molecular weight PEIs (PEI25k and PEI10k). The polymer size played an important role in PEI-HRP interaction. PEI of low molecular weight (PEI1.8k) was less efficient to alter the conformation and catalytic activity of HRP in aqueous solutions.

  16. Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1.

    Science.gov (United States)

    Szewczyk, Bernadeta; Kotarska, Katarzyna; Daigle, Mireille; Misztak, Paulina; Sowa-Kucma, Magdalena; Rafalo, Anna; Curzytek, Katarzyna; Kubera, Marta; Basta-Kaim, Agnieszka; Nowak, Gabriel; Albert, Paul R

    2014-11-01

    The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two of its key transcriptional modulators, NUDR and Freud-1, was examined in the prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most widespread changes, with significant reduction in both mRNA and protein levels of NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud-1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1 and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor, Freud-1 and NUDR mRNA's but not protein were reduced. In PS rats PFC 5-HT1A receptor protein was reduced more in females than males; while in Hp Freud-1 protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5-HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced. Overall, CMS and stress during pregnancy produced the most salient changes in 5-HT1A receptor and transcription factor expression, suggesting a primary role for altered transcription factor expression in chronic regulation of 5-HT1A receptor expression. By contrast, OB (in males) and PS (in females) produced gender-specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for post-transcriptional regulation. These and previous data suggest that chronic stress might be a key regulator of NUDR/Freud-1 gene expression.

  17. REM sleep deprivation reverses neurochemical and other depressive-like alterations induced by olfactory bulbectomy.

    Science.gov (United States)

    Maturana, Maira J; Pudell, Cláudia; Targa, Adriano D S; Rodrigues, Laís S; Noseda, Ana Carolina D; Fortes, Mariana H; Dos Santos, Patrícia; Da Cunha, Cláudio; Zanata, Sílvio M; Ferraz, Anete C; Lima, Marcelo M S

    2015-02-01

    There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD.

  18. Boldenone-induced apoptotic, structural, and functional alterations in the liver of rabbits

    Directory of Open Access Journals (Sweden)

    R.F. Mayada

    2015-03-01

    Full Text Available Boldenone undecylenate (BOL is an anabolic androgenic steroid used in livestock to improve growth and food conversion. This study investigated the actions of BOL on structure and functions of rabbit liver as well as the effects of its withdrawal. Eighteen mature male New Zealand rabbits were divided into 2 groups: Control group (n=6 were injected with 0.25 mL corn oil/kg body weight (BW, while BOL group (n=12 received 3 intramuscular injections, 2 wk apart, of BOL (4.5 mg/kg BW. Animals were scarified 1 d after last injection except for 6 rabbits from BOL group that served as the BOL-withdrawal group (4 wk after the 3rd injection. Intramuscular injection of BOL increased (P<0.05 malondialdehyde (MDA level, but markedly lowered activities of superoxide dismutase (SOD and catalase (CAT and reduced glutathione (GSH concentration compared to both control and BOL-withdrawal groups. Treatment with BOL significantly (P<0.05 increased serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST compared to the control group. BOL injection caused different histopathological alterations and apoptosis in liver, but these changes were less evident in the BOL-withdrawal group. Expression of p53 and tumour necrosis factor-α (TNF-α genes was up regulated in BOL compared to control group, while the expressions of p53 and TNF-α were down regulated in BOL-withdrawal group in comparison with BOL group. In conclusion, BOL injection induced structural and functional changes in the liver of rabbits, increasing oxidative stress and mediators of apoptosis such as ROS, p53 and TNF-α. All these parameters returned to near the control values after withdrawal.

  19. PFOS induces behavioral alterations, including spontaneous hyperactivity that is corrected by dexamfetamine in zebrafish larvae.

    Directory of Open Access Journals (Sweden)

    Stefan Spulber

    Full Text Available Perfluorooctane sulfonate (PFOS is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response, and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae.

  20. Metaxin deficiency alters mitochondrial membrane permeability and leads to resistance to TNF-induced cell killing.

    Science.gov (United States)

    Ono, Koh; Wang, Xiaofei; Kim, Sung Ouk; Armstrong, Lucas C; Bornstein, Paul; Han, Jiahuai

    2010-02-01

    Metaxin, a mitochondrial outer membrane protein, is critical for TNF-induced cell death in L929 cells. Its deficiency, caused by retroviral insertion-mediated mutagenesis, renders L929 cells resistance to TNF killing. In this study, we further characterized metaxin deficiency-caused TNF resistance in parallel with Bcl-X(L) overexpression-mediated death resistance. We did not find obvious change in mitochondria membrane potential in metaxin-deficient (Met(mut)) and Bcl-X(L)-overexpressing cells, but we did find an increase in the release rate of the mitochondrial membrane potential probe rhodamine 123 (Rh123) that was preloaded into mitochondria. In addition, overexpression of a function-interfering mutant of metaxin (MetaΔTM/C) or Bcl-X(L) in MCF-7.3.28 cells also resulted in an acquired resistance to TNF killing and a faster rate of Rh123 release, indicating a close correlation between TNF resistance and higher rates of the dye release from the mitochondria. The release of Rh123 can be controlled by the mitochondrial membrane permeability transition (PT) pore, as targeting an inner membrane component of the PT pore by cyclosporin A (CsA) inhibited Rh123 release. However, metaxin deficiency and Bcl-X(L) overexpression apparently affect Rh123 release from a site(s) different from that of CsA, as CsA can overcome their effect. Though both metaxin and Bcl-X(L) appear to function on the outer mitochondrial membrane, they do not interact with each other. They may use different mechanisms to increase the permeability of Rh123, since previous studies have suggested that metaxin may influence certain outer membrane porins while Bcl-X(L) may form pores on the outer membrane. The alteration of the mitochondrial outer membrane properties by metaxin deficiency and Bcl-X(L) overexpression, as indicated by a quicker Rh123 release, may be helpful in maintaining mitochondrial integrity.

  1. Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model.

    Science.gov (United States)

    Chaudhari, Nirja K; Nampoothiri, Laxmipriya P

    2017-02-01

    Polycystic ovarian syndrome (PCOS), one of the leading causes of infertility seen in women, is characterized by anovulation and hyperandrogenism, resulting in ovarian dysfunction. In addition, associations of several metabolic complications like insulin resistance, obesity, dyslipidemia and psychological co-morbidities are well known in PCOS. One of the major factors influencing mood and the emotional state of mind is neurotransmitters. Also, these neurotransmitters are very crucial for GnRH release. Hence, the current study investigates the status of neurotransmitters in PCOS. A PCOS rat model was developed using testosterone. Twenty-one-day-old rats were subcutaneously injected with 10 mg/kg body weight of testosterone propionate (TP) for 35 days. The animals were validated for PCOS characteristics by monitoring estrus cyclicity, serum testosterone and estradiol levels and by histological examination of ovarian sections. Neurotransmitter estimation was carried out using fluorometric and spectrophotometric methods. TP-treated animals demonstrated increased serum testosterone levels with unaltered estradiol content, disturbed estrus cyclicity and many peripheral cysts in the ovary compared to control rats mimicking human PCOS. Norepinephrine (NE), dopamine, serotonin, γ-amino butyric acid (GABA) and epinephrine levels were significantly low in TP-induced PCOS rats compared to control ones, whereas the activity of acetylcholinesterase in the PCOS brain was markedly elevated. Neurotransmitter alteration could be one of the reasons for disturbed gonadotropin-releasing hormone (GnRH) release, consequently directing the ovarian dysfunction in PCOS. Also, decrease in neurotransmitters, mainly NE, serotonin and dopamine (DA) attributes to mood disorders like depression and anxiety in PCOS.

  2. Epileptic seizures induce structural and functional alterations on brain tissue membranes.

    Science.gov (United States)

    Turker, Sevgi; Severcan, Mete; Ilbay, Gul; Severcan, Feride

    2014-12-01

    Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audiogenetically susceptible epileptic seizures on structure, content and function of rat brain membrane components using Fourier transform infrared (FT-IR) spectroscopy. The findings have shown that both two types of epileptic seizures stimulate the variations in the molecular organization of membrane lipids, which have potential to influence the structures in connection with functions of membrane proteins. Moreover, less fluid lipid structure and a decline in content of lipids obtained from the ratio of CH3 asym/lipid, CH2 asym/lipid, CO/lipid, and olefinicCH/lipid and the areas of the PO2 symmetric and asymmetric modes were observed. Moreover, based on IR data the changes in the conformation of proteins were predicted by neural network (NN) analysis, and displayed as an increase in random coil despite a decrease in beta sheet. Depending on spectral parameters, we have successfully differentiated treated samples from the control by principal component analysis (PCA) and cluster analysis. In summary, FT-IR spectroscopy may offer promising attempt to identify compositional, structural and functional alterations in brain tissue membranes resulting from epileptic activities. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Acupuncture induces divergent alterations of functional connectivity within conventional frequency bands: evidence from MEG recordings.

    Directory of Open Access Journals (Sweden)

    Youbo You

    Full Text Available As an ancient Chinese healing modality which has gained increasing popularity in modern society, acupuncture involves stimulation with fine needles inserted into acupoints. Both traditional literature and clinical data indicated that modulation effects largely depend on specific designated acupoints. However, scientific representations of acupoint specificity remain controversial. In the present study, considering the new findings on the sustained effects of acupuncture and its time-varied temporal characteristics, we employed an electrophysiological imaging modality namely magnetoencephalography with a temporal resolution on the order of milliseconds. Taken into account the differential band-limited signal modulations induced by acupuncture, we sought to explore whether or not stimulation at Stomach Meridian 36 (ST36 and a nearby non-meridian point (NAP would evoke divergent functional connectivity alterations within delta, theta, alpha, beta and gamma bands. Whole-head scanning was performed on 28 healthy participants during an eyes-closed no-task condition both preceding and following acupuncture. Data analysis involved calculation of band-limited power (BLP followed by pair-wise BLP correlations. Further averaging was conducted to obtain local and remote connectivity. Statistical analyses revealed the increased connection degree of the left temporal cortex within delta (0.5-4 Hz, beta (13-30 Hz and gamma (30-48 Hz bands following verum acupuncture. Moreover, we not only validated the closer linkage of the left temporal cortex with the prefrontal and frontal cortices, but further pinpointed that such patterns were more extensively distributed in the ST36 group in the delta and beta bands compared to the restriction only to the delta band for NAP. Psychophysical results for significant pain threshold elevation further confirmed the analgesic effect of acupuncture at ST36. In conclusion, our findings may provide a new perspective to lend

  4. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.

    Science.gov (United States)

    Huang, Yanjuan; Hu, Nan; Gao, Xuejiao; Yan, Zhixiang; Li, Sai; Jing, Wanghui; Yan, Ru

    2015-05-05

    Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Benzoylecgonine exposure induced oxidative stress and altered swimming behavior and reproduction in Daphnia magna.

    Science.gov (United States)

    Parolini, Marco; De Felice, Beatrice; Ferrario, Claudia; Salgueiro-González, Noelia; Castiglioni, Sara; Finizio, Antonio; Tremolada, Paolo

    2018-01-01

    Several monitoring studies have shown that benzoylecgonine (BE) is the main illicit drug residue commonly measured in the aquatic system worldwide. Few studies have investigated the potential toxicity of this molecule towards invertebrate and vertebrate aquatic non-target organisms focusing on effects at low levels of the biological organization, but no one has assessed the consequences at higher ones. Thus, the present study was aimed at investigating the toxicity of a 48-h exposure to two concentrations of BE, similar to those found in aquatic ecosystems (0.5 μg/L and 1.0 μg/L), on the cladoceran Daphnia magna at different levels of the ecological hierarchy. We relied on a multi-level approach focusing on the effects at biochemical/biomolecular (biomarkers), individual (swimming activity) and population (reproduction) levels. We measured the amount of reactive oxygen species and of the activity of antioxidant (SOD, CAT, and GPx) and detoxifying (GST) enzymes to assess if BE exposure can alter the oxidative status of D. magna specimens, while the lipid peroxidation (TBARS) was measured as a marker of oxidative damage. Moreover, we also measured the acetylcholinesterase (AChE) activity because it is strictly related to behavioral changes in aquatic organisms. Changes in swimming behavior were investigated by a video tracking analysis, while the consequences on reproduction were assessed by a chronic toxicity test. Our results showed that BE concentrations similar to those found in aquatic ecosystems induced oxidative stress and inhibited AChE activity, affecting swimming behavior and the reproduction of Daphnia magna individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Holmskov, U.; Aalbæk, B.

    2005-01-01

    pyogenes and Streptococcus suis serotype 2, respectively. By comparing normal and diseased lung tissue from the same lungs, increased diffuse pSP-D immunoreactivity was seen in the surfactant in both acute and chronic bronchopneumonias, while such increased expression of pSP-D was generally not present...

  7. Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting

    Science.gov (United States)

    Schrage, William G.; Woodman, Christopher R.; Laughlin, M. Harold

    2002-01-01

    The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (approximately 300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 microM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 300 microM) reduced flow-induced dilation by 65-70% in Con and HLU 1As. In contrast, L-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with L-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of L-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10(-9)-10(-4) M) in soleus 2As. L-NNA reduced ACh-induced dilation by approximately 40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment with L-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.

  8. Antibody repertoire development in swine

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Sun, J.; Wertz, N.; Šinkora, Marek

    2006-01-01

    Roč. 30, - (2006), s. 199-221 ISSN 0145-305X Institutional research plan: CEZ:AV0Z50200510 Keywords : swine * b cells * immunoglobulins Subject RIV: EE - Microbiology, Virology Impact factor: 3.399, year: 2006

  9. Swine Flu: Prevention to Pandemic

    Directory of Open Access Journals (Sweden)

    Preeti Padda

    2015-03-01

    Full Text Available Swine flu, also known as swine influenza, pig influenza, hog flu and pig flu, is a respiratory disease caused by viruses (influenza viruses that infect the respiratory tract of pigs, resulting in nasal secretions, a barking cough, decreased appetite, and listless behaviour. Swine flu produces most of the same symptoms in pigs as human flu produces in people. Mostly people who are closely associated with pigs (for example, pork processors and farmers acquire the infection and similarly pigs get infected occasionally human flu infection. The cross-species infections (swine virus to man; human flu virus to pigs have always been confined to local areas and have not spread across borders in either pigs or humans. Unfortunately, this cross-species situation with influenza viruses has had the potential to change and cause epidemics and pandemics. Most recent pandemic has been reported in 2009,  where "swine flu" strain, first seen in Mexico, was termed as H1N1 as it was mainly infecting people and exhibited two main surface antigens, H1 (hemagglutinin type 1 and N1 (neuraminidase type1. This unique eight RNA strands from novel H1N1 flu have one strand derived from human flu strains, two from avian (bird strains, and five from swine strains. Since then it has been infecting people here and there. 

  10. Sulpiride-Induced Hyperprolactinemia in Mature Female Rats: Evidence for Alterations in The Reproductive System, Pituitary and Ovarian Hormones

    OpenAIRE

    Sara Mostafapour; Samad Zare; Rajab Ali Sadrkhanlou; Abbas Ahmadi; Mazdak Razi

    2014-01-01

    Background: The prevalence of hyperprolactinemia following administration of conventional antipsychotic drugs requires further investigation. The current study is designed to evaluate the effect of sulpiride (SPD)-induced hyperprolactinemia on alterations to ovarian follicular growth, gonadotropins, and ovarian hormones and to analyze the extent of potential problems in mammary glands. Materials and Methods: A total of 40 albino Wistar rats were divided into four groups: con...

  11. Are there structural alterations in the enamel organ of offspring of rats with alloxan-induced diabetes mellitus?

    OpenAIRE

    Silva-Sousa,Yara Teresinha Corrêa; Peres,Luiz Cesar; Foss,Milton César

    2003-01-01

    Enamel hypoplasia is the most common developmental defect of human teeth that may be seen in deciduous teeth of babies born to diabetic women. In the present experimental study, we analyzed the enamel organ of the mandibular incisors of the offspring of rats with alloxan-induced diabetes. By light microscopy, no alterations could be found in the enamel organ of rats born to diabetic mothers compared to normal ones, except in one case. In contrast, significant differences were detected with co...

  12. 9 CFR 94.10 - Swine from regions where classical swine fever exists.

    Science.gov (United States)

    2010-01-01

    ... swine fever exists. 94.10 Section 94.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND RESTRICTED...

  13. Investigation of Chitosan for Prevention of Diabetic Progression Through Gut Microbiota Alteration in Sugar Rich Diet Induced Diabetic Rats.

    Science.gov (United States)

    Prajapati, Bhumika; Rajput, Parth; Jena, Prasant Kumar; Seshadri, Sriram

    2015-01-01

    Sugar rich diet induces inflammation and insulin resistance mainly through gut microbiota alteration. Gut microflora dysbiosis increases plasma lipopolysaccharide and reduces short chain fatty acids to impair the insulin signaling cascades by different molecular pathways to progress into diabetes. Chitosan based formulations have major significance in insulin delivery system due to their ability to protect the insulin from enzymatic degradation and its efficient inter-epithelial transport. This study was designed to investigate the effect of chitosan administration on gut microflora mediated signaling pathways to prevent the diet induced diabetes. Male wistar rats were divided into non-diabetic group with a normal diet (CD), diabetic group with high sucrose diet (HSD) and treatment group with HSD and chitosan (60 mg/kg). After 8 weeks of the study, significant alterations in two major gut dominant microbial phyla i.e Firmicutes and Bacteroides and four dominant microbial species i.e. Lactobacilli, Bifidobacteria, Escherichia and Clostridia were observed in HSD group compared to CD. This microbial dysbiosis in dominant phyla was significantly prevented in chitosan administrated HSD group. Chitosan administration had also reduced the HSD induced activation of Toll like receptors and Nod like receptors signaling pathways compared to HSD control group to reduce the inflammation. These suggest that chitosan can prevent the progression of Type 2 Diabetes through gut microbiota alteration, reducing endotoxin and microbes mediated inflammation.

  14. Binding characteristics of swine erythrocyte insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dieberg, G.; Bryan, G.S.; Sartin, J.L.; Williams, J.C.; Prince, T.J.; Kemppainen, R.J.

    1985-09-01

    Crossbred gilts had 8.8 +/- 1.1% maximum binding of ( SVI)insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows had a significant increase in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet and a low-fiber diet did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine.

  15. Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian 'avian-like' H1N1 swine viruses in mice.

    Science.gov (United States)

    Castrucci, Maria R; Facchini, Marzia; Di Mario, Giuseppina; Garulli, Bruno; Sciaraffia, Ester; Meola, Monica; Fabiani, Concetta; De Marco, Maria A; Cordioli, Paolo; Siccardi, Antonio; Kawaoka, Yoshihiro; Donatelli, Isabella

    2014-05-01

    To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian "avian-like" (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs. Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice. Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study. Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses. Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge. Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans. © 2013 The Authors Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  16. Variant (Swine Origin) Influenza Viruses in Humans

    Science.gov (United States)

    ... Types Seasonal Avian Swine Variant Other Variant Influenza Viruses: Background and CDC Risk Assessment and Reporting Language: ... Background CDC Assessment Reporting Background On Variant Influenza Viruses Swine flu viruses do not normally infect humans. ...

  17. β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Darimont Christian

    2004-08-01

    Full Text Available Abstract Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG and diacylglycerol (DAG accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

  18. Tissue culture-induced alteration in cytosine methylation in new rice ...

    African Journals Online (AJOL)

    Zizania DNA introgression could induce a large number of genetic and epigenetic changes of the new rice recombinant inbred lines genome. In this present study, we employed inter-simple sequence repeat (ISSR) to further study the genetic and epigenetic changes that are induced by tissue culture. Changes induced by ...

  19. Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane.

    Science.gov (United States)

    Hernández-Rabaza, Vicente; Cabrera-Pastor, Andrea; Taoro-González, Lucas; Malaguarnera, Michele; Agustí, Ana; Llansola, Marta; Felipo, Vicente

    2016-02-16

    Patients with liver cirrhosis and minimal hepatic encephalopathy (MHE) show mild cognitive impairment and spatial learning dysfunction. Hyperammonemia acts synergistically with inflammation to induce cognitive impairment in MHE. Hyperammonemia-induced neuroinflammation in hippocampus could contribute to spatial learning impairment in MHE. Two main aims of this work were: (1) to assess whether chronic hyperammonemia increases inflammatory factors in the hippocampus and if this is associated with microglia and/or astrocytes activation and (2) to assess whether hyperammonemia-induced neuroinflammation in the hippocampus is associated with altered membrane expression of glutamate and GABA receptors and spatial learning impairment. There are no specific treatments for cognitive alterations in patients with MHE. A third aim was to assess whether treatment with sulforaphane enhances endogenous the anti-inflammatory system, reduces neuroinflammation in the hippocampus of hyperammonemic rats, and restores spatial learning and if normalization of receptor membrane expression is associated with learning improvement. We analyzed the following in control and hyperammonemic rats, treated or not with sulforaphane: (1) microglia and astrocytes activation by immunohistochemistry, (2) markers of pro-inflammatory (M1) (IL-1β, IL-6) and anti-inflammatory (M2) microglia (Arg1, YM-1) by Western blot, (3) membrane expression of GABA, AMPA, and NMDA receptors using the BS3 cross-linker, and (4) spatial learning using the radial maze. The results reported show that hyperammonemia induces astrocytes and microglia activation in the hippocampus, increasing pro-inflammatory cytokines IL-1β and IL-6. This is associated with altered membrane expression of AMPA, NMDA, and GABA receptors which would be responsible for altered neurotransmission and impairment of spatial learning in the radial maze. Treatment with sulforaphane promotes microglia differentiation from pro-inflammatory M1 to anti

  20. Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine.

    Science.gov (United States)

    Henningson, Jamie N; Rajao, Daniela S; Kitikoon, Pravina; Lorusso, Alessio; Culhane, Marie R; Lewis, Nicola S; Anderson, Tavis K; Vincent, Amy L

    2015-03-23

    In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared lung pathology, viral replication and shedding and the antigenic relationships of four wild-type H1N1pdm09 viruses in pigs: one human (CA/09) and three isolated in swine after the pandemic (IL/09, IL/10, and MN/10). The swine strains were selected based upon unique amino acid substitutions in the HA protein. All selected viruses resulted in mild disease and viral shedding through nasal and oral fluids, however, viral replication and the degree of pathology varied between the isolates. A/Swine/IL/5265/2010 (IL/10), with substitutions I120M, S146G, S186P, V252M, had lower viral titers in the lungs and nasal secretions and fewer lung lesions. The other two swine viruses caused respiratory pathology and replicated to titers similar to the human CA/09, although MN/10 (with mutations D45Y, K304E, A425S) had lower nasal shedding. Swine-adapted H1N1pdm09 have zoonotic potential, and have reassorted with other co-circulating swine viruses, influencing the evolution of IAV in swine globally. Further, our results suggest that amino acid changes in the HA gene have the potential to alter the virulence of H1N1pdm09 in swine. Importantly, the limited clinical signs in pigs could result in continued circulation of these viruses with other endemic swine IAVs providing opportunities for reassortment. Published by Elsevier B.V.

  1. Re-examine tumor-induced alterations in hemodynamic responses of BOLD fMRI. Implications in presurgical brain mapping

    International Nuclear Information System (INIS)

    Wang, Liya; Ali, Shazia; Fa, Tianning; Mao, Hui; Dandan, Chen; Olson, Jeffrey

    2012-01-01

    Background: Blood oxygenation level dependent (BOLD) fMRI is used for presurgical functional mapping of brain tumor patients. Abnormal tumor blood supply may affect hemodynamic responses and BOLD fMRI signals. Purpose: To perform a multivariate and quantitative investigation of the effect of brain tumors on the hemodynamic responses and its impact on BOLD MRI signal time course, data analysis in order to better understand tumor-induced alterations in hemodynamic responses, and accurately mapping cortical regions in brain tumor patients. Material and Methods: BOLD fMRI data from 42 glioma patients who underwent presurgical mapping of the primary motor cortex (PMC) with a block designed finger tapping paradigm were analyzed, retrospectively. Cases were divided into high grade (n = 24) and low grade (n = 18) groups based on pathology. The tumor volume and distance to the activated PMCs were measured. BOLD signal time courses from selected regions of interest (ROIs) in the PMCs of tumor affected and contralateral unaffected hemispheres were obtained from each patient. Tumor-induced changes of BOLD signal intensity and time to peak (TTP) of BOLD signal time courses were analyzed statistically. Results: The BOLD signal intensity and TTP in the tumor-affected PMCs are altered when compared to that of the unaffected hemisphere. The average BOLD signal level is statistically significant lower in the affected PMCs. The average TTP in the affected PMCs is shorter in the high grade group, but longer in the low grade tumor group compared to the contralateral unaffected hemisphere. Degrees of alterations in BOLD signal time courses are related to both the distance to activated foci and tumor volume with the stronger effect in tumor distance to activated PMC. Conclusion: Alterations in BOLD signal time courses are strongly related to the tumor grade, the tumor volume, and the distance to the activated foci. Such alterations may impair accurate mapping of tumor-affected functional

  2. Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration

    Directory of Open Access Journals (Sweden)

    Abdelhalim Mohamed

    2012-01-01

    Full Text Available Abstract Background Nanoparticles (NPs can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods To investigate particle-size effect of GNPs on the hepatic tissue, a total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltrate by chronic inflammatory cells and congestive dilated central veins. Conclusions The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS generation which in turn may induce stress in the hepatocytes to

  3. Vitamin E Prevents Cold Wrap Restraint Stress-Induced Intestinal Fluid Transport Alterations in Rats

    Directory of Open Access Journals (Sweden)

    Scott Burdick

    1994-01-01

    Full Text Available Psychological stress may alter gastrointestinal absorptive function by increasing the quantity of intestinal free radicals or by lowering endogenous intestinal free radical scavenging capacity. Vitamin E has been shown to be a potent endogenous antioxidant and free radical scavenger under both physiological and pathological conditions. The purpose of this study was to determine whether cold wrap restraint stress altered in vivo intestinal fluid absorption in rats, and whether vitamin E administration prior to the induction of cold wrap restraint stress could prevent such changes in intestinal secretion. Jejunal, ileal and colonic fluid and electrolyte transport rates were measured in vivo using an isolated loop technique. Cold wrap restraint stress reduced in vivo fluid absorption in the ileum and colon, but not in the jejunum. Administration of vitamin E prior to the cold wrap restraint stress procedure completely prevented this alteration of ileal and colonic fluid absorption.

  4. Deletion of African swine fever virus interferon inhibitors from the genome of a virulent isolate reduces virulence in domestic pigs and induces a protective response.

    Science.gov (United States)

    Reis, Ana Luisa; Abrams, Charles C; Goatley, Lynnette C; Netherton, Chris; Chapman, Dave G; Sanchez-Cordon, Pedro; Dixon, Linda K

    2016-09-07

    African swine fever virus (ASFV) encodes multiple copies of MGF360 and MGF530/505 gene families. These genes have been implicated in the modulation of the type I interferon (IFN) response. We investigated the effect of modulating the IFN response on virus attenuation and induction of protective immunity by deleting genes MGF360 (MGF360-10L, 11L, 12L, 13L, 14L) and MGF530/505 (MGF530/505-1R, 2R and 3R) and interrupting genes (MGF360-9L and MGF530/505-4R) in the genome of the virulent ASFV isolate Benin 97/1. Replication of this deletion mutant, BeninΔMGF, in porcine macrophages in vitro was similar to that of the parental virulent virus Benin 97/1 and the natural attenuated isolate OURT88/3, which has a similar deletion of MGF360 and 530/505 genes. Levels of IFN-β mRNA in macrophages infected with virulent Benin 97/1 isolate were barely detectable but high levels were detected in macrophages infected with OURT88/3 and intermediate levels in macrophages infected with BeninΔMGF. The data confirms that these MGF360 and MGF530/505 genes have roles in suppressing induction of type I IFN. Immunisation and boost of pigs with BeninΔMGF showed that the virus was attenuated and all pigs (5/5) were protected against challenge with a lethal dose of virulent Benin 97/1. A short transient fever was observed at day 5 or 6 post-immunisation but no other clinical signs. Following immunisation and boost with the OURT88/3 isolate 3 of 4 pigs were protected against challenge. Differences were observed in the cellular and antibody responses in pigs immunised with BeninΔMGF compared to OURT88/3. Deletion of IFN modulators is a promising route for construction of rationally attenuated ASFV candidate vaccine strains. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Effectiveness of Sunscreen at Preventing Solar UV-Induced Alterations of Human Stratum Corneum

    Science.gov (United States)

    Martinez, O.; Dauskardt, R.; Biniek, K.; Novoa, F.

    2012-12-01

    The outermost layer of the epidermis, the stratum corneum, protects the body from harmful environmental conditions by serving as a selective barrier. Solar ultraviolet (UV) radiation is one of the most common conditions the body encounters and is responsible for many negative skin responses, including compromised barrier function. UV exposure has dramatic effects on stratum corneum cell cohesion and mechanical integrity that are related to its effects on the stratum corneum's intercellular lipids. Hypothesis Sunscreen contains chemicals that absorb UV radiation to prevent the radiation from penetrating the skin. Thus, it is expected that the application of sunscreen on human stratum corneum will reduce UV-induced alterations of human stratum corneum. Procedures/Equipment Human tissue was processed in order to isolate the stratum corneum, the top layer of the epidermis. Double cantilever beam (DCB) testing was used to study the effect of UV radiation on human stratum corneum. Two different types of DCB samples were created: control DCB samples with the application of carrier and UV light to the stratum corneum and DCB samples with the application of sunscreen and UV light to the stratum corneum. For the control sample, one side of the stratum corneum was glued to a polycarbonate beam and carrier was applied. Then, the sample was placed 10 cm away from the UV lamp inside of the environmental chamber and were exposed to UV dosages of about 800 J/cm2. Once this step was complete, a second polycarbonate beam was glued to the other side of the stratum corneum. The steps were similar for the DCB sample that had sunscreen applied and that was exposed to UV light. After gluing one side of the stratum corneum to a polycarbonate beam, Octinoxate sunscreen was applied. The next steps were similar to those of the control sample. All DCB samples were then let out to dry for two hours in a dry box in order for the moisture from the lab to be extracted. Each DCB sample was tested

  6. Chronic Sleep Disruption Alters Gut Microbiota, Induces Systemic and Adipose Tissue Inflammation and Insulin Resistance in Mice.

    Science.gov (United States)

    Poroyko, Valeriy A; Carreras, Alba; Khalyfa, Abdelnaby; Khalyfa, Ahamed A; Leone, Vanessa; Peris, Eduard; Almendros, Isaac; Gileles-Hillel, Alex; Qiao, Zhuanhong; Hubert, Nathaniel; Farré, Ramon; Chang, Eugene B; Gozal, David

    2016-10-14

    Chronic sleep fragmentation (SF) commonly occurs in human populations, and although it does not involve circadian shifts or sleep deprivation, it markedly alters feeding behaviors ultimately promoting obesity and insulin resistance. These symptoms are known to be related to the host gut microbiota. Mice were exposed to SF for 4 weeks and then allowed to recover for 2 weeks. Taxonomic profiles of fecal microbiota were obtained prospectively, and conventionalization experiments were performed in germ-free mice. Adipose tissue insulin sensitivity and inflammation, as well as circulating measures of inflammation, were assayed. Effect of fecal water on colonic epithelial permeability was also examined. Chronic SF-induced increased food intake and reversible gut microbiota changes characterized by the preferential growth of highly fermentative members of Lachnospiraceae and Ruminococcaceae and a decrease of Lactobacillaceae families. These lead to systemic and visceral white adipose tissue inflammation in addition to altered insulin sensitivity in mice, most likely via enhanced colonic epithelium barrier disruption. Conventionalization of germ-free mice with SF-derived microbiota confirmed these findings. Thus, SF-induced metabolic alterations may be mediated, in part, by concurrent changes in gut microbiota, thereby opening the way for gut microbiome-targeted therapeutics aimed at reducing the major end-organ morbidities of chronic SF.

  7. Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats.

    Science.gov (United States)

    Ola-Mudathir, F K; Suru, S M

    2015-11-01

    Cadmium (Cd) has been implicated in increased prostate gland malignancy risk in both wildlife and humans. This study examines the chemoprotective roles of onion and garlic extracts on Cd-induced biochemical alterations in the prostate glands of rats. Adult male Wistar rats were randomly divided into nine groups: control group received double distilled water; Cd group received Cd alone (1.5 mg/100 g bwt per day); extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g bwt per day) for 1 week and then co-treated with Cd (1.5 mg/100 g bwt per day) for additional 3 weeks. Oxidant/antioxidant status and acid phosphatase (ACPtotal and ACPprostatic ) activity were examined in prostate glands. Cd intoxication caused a marked (P garlic extract significantly minimised these alterations. The onion extract offered a dose-dependent protection. Our findings suggest a chemoprotective capability for onion and garlic extracts against Cd-induced biochemical alteration in the prostate glands. © 2014 Blackwell Verlag GmbH.

  8. Exposure to the insecticide endosulfan induces liver morphology alterations and oxidative stress in fruit-eating bats (Artibeus lituratus).

    Science.gov (United States)

    Oliveira, Jerusa Maria; Brinati, Alessandro; Miranda, Liany Divina Lima; Morais, Danielle Barbosa; Zanuncio, José Cola; Gonçalves, Reggiani Vilela; Peluzio, Maria do Carmo Gouveia; Freitas, Mariella Bontempo

    2017-02-01

    Exposure to pesticides may increase the generation of reactive oxygen species (ROS), leading to oxidation of cell membrane lipids and proteins. Although fruit bats are potentially exposed to pesticides during their entire lifespan, the impacts of this exposure are still poorly investigated. We examined the effects of low, commercially recommended concentrations (0, 1.05 and 2.1 g/l) of an organochlorine insecticide endosulfan (EDS) formulation on oxidative responses in the liver and kidneys of Neotropical fruit bats (Artibeus lituratus), as well as possible liver morphological alterations following a 35-day oral exposure. Superoxide dismutase activity was significantly decreased upon exposure to 1.05 g/l of EDS in the liver and kidneys, catalase was decreased in the liver of 2.1 g/l EDS-exposed bats, while glutathione S-transferase was increased in the liver of 2.1 g/l EDS-exposed bats. Protein carbonyls increased following the exposure to the highest EDS dose tested. Endosulfan-induced morphological alterations in the liver included cell degeneration and cell death, with apparent cytoplasm lipid accumulation (steatosis) and pyknotic nuclei, karyolysis and deposit of collagen fibres. Our findings suggest that exposure to low concentrations of EDS induced a certain extent of oxidative damage in fruit bats, which may have led to liver morphological alterations. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  9. Swine Flu -A Comprehensive View

    Science.gov (United States)

    Singh, Vandana; Sood, Meenakshi

    2012-07-01

    The present article is aimed on comprehensive view of Swine flu. It was first isolated from pigs in 1930 in USA. Pandemic caused by H1N1 in 2009 brought it in limelight. Itís a viral respiratory disease caused by viruses that infects pigs, resulting in nasal secretions, barking cough, decreased appetite, and listless behavior. Swine virus consist of eight RNA strands, one strand derived from human flu strains, two from avian (bird) strains, and five from swine strains. Swine flu spreads from infected person to healthy person by inhalation or ingestion of droplets contaminated with virus while sneezing or coughing. Two antiviral agents have been reported to help prevent or reduce the effects of swine flu, flu shot and nasal spray. WHO recommended for pandemic period to prevent its future outbreaks through vaccines or non-vaccines means. Antiviral drugs effective against this virus are Tamiflu and Relenza. Rapid antigen testing (RIDT), DFA testing, viral culture, and molecular testing (RT-PCR) are used for its diagnosis in laboratory

  10. Pre-Existing Differences and Diet-Induced Alterations in Striatal Dopamine Systems of Obesity-Prone Rats

    Science.gov (United States)

    Vollbrecht, Peter J.; Mabrouk, Omar S.; Nelson, Andrew D.; Kennedy, Robert T.; Ferrario, Carrie R.

    2016-01-01

    Objective Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2/D3 dopamine receptor-mediated transmission prior to and after consumption of “junk-foods” in obesity-prone and obesity-resistant rats. Methods Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2/D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Results Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. Conclusions These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. PMID:26847484

  11. Mechano-growth factor induces migration of rat mesenchymal stem cells by altering its mechanical properties and activating ERK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jiamin; Wu, Kewen; Lin, Feng; Luo, Qing; Yang, Li; Shi, Yisong [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Sung, Kuo-Li Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412 (United States)

    2013-11-08

    Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study, MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.

  12. Mechano-growth factor induces migration of rat mesenchymal stem cells by altering its mechanical properties and activating ERK pathway

    International Nuclear Information System (INIS)

    Wu, Jiamin; Wu, Kewen; Lin, Feng; Luo, Qing; Yang, Li; Shi, Yisong; Song, Guanbin; Sung, Kuo-Li Paul

    2013-01-01

    Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study, MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics

  13. Heat-induced alterations in cashew allergen solubility and IgE binding

    Directory of Open Access Journals (Sweden)

    Christopher P. Mattison

    Full Text Available Cashew nuts are an increasingly common cause of food allergy. We compare the soluble protein profile of cashew nuts following heating. SDS-PAGE indicate that heating can alter the solubility of cashew nut proteins. The 11S legumin, Ana o 2, dominates the soluble protein content in ready to eat and mildly heated cashew nuts. However, we found that in dark-roasted cashew nuts, the soluble protein profile shifts and the 2S albumin Ana o 3 composes up to 40% of the soluble protein. Analysis of trypsin-treated extracts by LC/MS/MS indicate changes in the relative number and intensity of peptides. The relative cumulative intensity of the 5 most commonly observed Ana o 1 and 2 peptides are altered by heating, while those of the 5 most commonly observed Ana o 3 peptides remaine relatively constant. ELISA experiments indicate that there is a decrease in rabbit IgG and human serum IgE binding to soluble cashew proteins following heating. Our findings indicate that heating can alter the solubility of cashew allergens, resulting in altered IgE binding. Our results support the use of both Ana o 2 and Ana o 3 as potential cashew allergen diagnostic targets. Keywords: Cashew nut, Food allergy, Immunoglobulin E, Mass-spectrometry, Peptide, Solubility

  14. Mercury induced haemocyte alterations in the terrestrial snail Cantareus apertus as novel biomarker.

    Science.gov (United States)

    Leomanni, Alessandro; Schettino, Trifone; Calisi, Antonio; Lionetto, Maria Giulia

    2016-01-01

    The aim of the present work was to study the response of a suite of cellular and biochemical markers in the terrestrial snail Cantareus apertus exposed to mercury in view of future use as sensitive tool suitable for mercury polluted soil monitoring and assessment. Besides standardized biomarkers (metallothionein, acetylcholinesterase, and lysosomal membrane stability) novel cellular biomarkers on haemolymph cells were analyzed, including changes in the spread cells/round cells ratio and haemocyte morphometric alterations. The animals were exposed for 14 days to Lactuca sativa soaked for 1h in HgCl2 solutions (0.5 e 1 μM). The temporal dynamics of the responses were assessed by measurements at 3, 7 and 14 days. Following exposure to HgCl2 a significant alteration in the relative frequencies of round cells and spread cells was evident, with a time and dose-dependent increase of the frequencies of round cells with respect to spread cells. These changes were accompanied by cellular morphometric alterations. Concomitantly, a high correspondence between these cellular responses and metallothionein tissutal concentration, lysosomal membrane stability and inhibition of AChE was evident. The study highlights the usefulness of the terrestrial snail C. apertus as bioindicator organism for mercury pollution biomonitoring and, in particular, the use of haemocyte alterations as a suitable biomarker of pollutant effect to be included in a multibiomarker strategy. Copyright © 2016. Published by Elsevier Inc.

  15. Trophic cascade induced by molluscivore predator alters pore-water biogeochemistry via competitive release of prey

    NARCIS (Netherlands)

    van Gils, Jan A.; van der Geest, Matthijs; Jansen, Erik J.; Govers, Laura L.; de Fouw, Jimmy; Piersma, Theunis

    Effects of predation may cascade down the food web. By alleviating interspecific competition among prey, predators may promote biodiversity, but the precise mechanisms of how predators alter competition have remained elusive. Here we report on a predator-exclosure experiment carried out in a

  16. Trophic cascade induced by molluscivore predator alters pore-water biogeochemistry via competitive release of prey

    NARCIS (Netherlands)

    van Gils, J.A.; van der Geest, M.; Jansen, E.J.; Govers, L.L.; de Fouw, J.; Piersma, T.

    2012-01-01

    Effects of predation may cascade down the food web. By alleviating interspecific competition among prey, predators may promote biodiversity, but the precise mechanisms of how predators alter competition have remained elusive. Here we report on a predator-exclosure experiment carried out in a

  17. Polychlorinated biphenyl-induced alterations of thyroid hormone homeostasis and brain development in the rat

    NARCIS (Netherlands)

    Morse, D.C.

    1995-01-01

    Introduction

    The work described in this thesis was undertaken to gain insight in the processes involved in the developmental neurotoxicity of polychlorinated biphenyls. It has been previously hypothesized that the alteration of thyroid hormone status by PCBs may

  18. Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function

    DEFF Research Database (Denmark)

    Yang, Jason H.; Bhargava, Prerna; McCloskey, Douglas

    2017-01-01

    Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect eithe...... the immunomodulatory potential of antibiotics and reveal the local metabolic microenvironment to be an important determinant of infection resolution....

  19. Alterations in biochemical and physiological characters in radiation-induced mutants of grain legumes

    International Nuclear Information System (INIS)

    Mueller, H.P.

    1984-01-01

    Selected examples from different grain legumes are studied. The biochemically and physiologically detectable alterations in distintc characters as caused by the action of mutant genes are presented comparatively. The interactions between different mutant genes in order to evaluated the influence of the genotypic constitution on the expression of mutated genes are emphasized. (M.A.C.) [pt

  20. Western diet-induced anxiolytic effects in mice are associated with alterations in tryptophan metabolism.

    Science.gov (United States)

    Ohland, Christina L; Pankiv, Evelina; Baker, Glen; Madsen, Karen L

    2016-10-01

    Western-style diets high in saturated fat and refined carbohydrate have been shown to alter gut microbiota as well as being associated with altered behaviour and learning ability. The objective of this study was to determine the effects of short-term intake of a Western-style diet on intestinal cytokine expression, tryptophan metabolism, and levels of neurotransmitters in the brain. At 7 weeks of age, 129S1/SvImJ mice were placed on a standard chow or Western-style diet (fat 33%, refined carbohydrates 49%) for 3 weeks. Anxiety-like behaviour was assessed by the latency to step-down test and exploration assessed in a Barnes maze. Neurotransmitter levels in forebrains were analysed by high-pressure liquid chromatography. Liver metabolism was examined by 1 H nuclear magnetic resonance (NMR). Cytokine expression in the intestine was measured using MesoScale discovery platform. mRNA levels of tryptophan hydroxylase (Tph) and indoleamine 2,3-dioxygenase (IDO) in the brain and intestine were measured using qPCR. Results showed that mice fed the Western diet displayed reduced exploratory and anxiety-like behaviour. Anxiolytic effects correlated with increased hippocampal brain-derived neurotrophic factor (BDNF) and tryptophan levels. Brain serotonin was not altered. These changes were associated with reduced expression of small intestinal indoleamine 2,3-dioxygenase, a tryptophan-processing enzyme. Western diet-fed mice exhibited low-grade systemic and intestinal inflammation along with altered liver metabolic profiles. In conclusion, diets high in fat and refined sugar are associated with increased levels of brain BDNF and tryptophan and decreased exploratory and anxiety-like behaviour. These behavioural changes correlated with altered intestinal tryptophan metabolism and liver metabolic profiles.

  1. Alterations in hyperpolarization-activated cyclic nucleotidegated cation channel (HCN expression in the hippocampus following pilocarpine-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Yun-Jung Oh, Jongju Na, Ji-Heon Jeong, Dae-Kyoon Park, Kyung-Ho Park, Jeong-Sik Ko & Duk-Soo Kim*

    2012-11-01

    Full Text Available To understand the effects of HCN as potential mediators in thepathogenesis of epilepsy that evoke long-term impairedexcitability; the present study was designed to elucidate whetherthe alterations of HCN expression induced by status epilepticus(SE is responsible for epileptogenesis. Although HCN1 immunoreactivitywas observed in the hippocampus, its immunoreactivitieswere enhanced at 12 hrs following SE. Although, HCN1immunoreactivities were reduced in all the hippocampi at 2weeks, a re-increase in the expression at 2-3 months followingSE was observed. In contrast to HCN1, HCN 4 expressions wereun-changed, although HCN2 immunoreactive neurons exhibitedsome changes following SE. Taken together, our findings suggestthat altered expressions of HCN1 following SE may be mainlyinvolved in the imbalances of neurotransmissions to hippocampalcircuits; thus, it is proposed that HCN1 may play animportant role in the epileptogenic period as a compensatoryresponse.

  2. Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Khan, Haseena Banu Hedayathullah; Shanmugavalli, R; Rajendran, Deepa; Bai, Mookambikai Ramya; Sorimuthu, Subramanian

    2013-12-01

    Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.

  3. Forced oscillation technique in the detection of smoking-induced respiratory alterations: diagnostic accuracy and comparison with spirometry

    Directory of Open Access Journals (Sweden)

    Alvaro Camilo Dias Faria

    2010-01-01

    Full Text Available INTRODUCTION: Detection of smoking effects is of utmost importance in the prevention of cigarette-induced chronic airway obstruction. The forced oscillation technique offers a simple and detailed approach to investigate the mechanical properties of the respiratory system. However, there have been no data concerning the use of the forced oscillation technique to evaluate respiratory mechanics in groups with different degrees of tobacco consumption. OBJECTIVES: (1 to evaluate the ability of the forced oscillation technique to detect smoking-induced respiratory alterations, with special emphasis on early alterations; and (2 to compare the diagnostic accuracy of the forced oscillation technique and spirometric parameters. METHODS: One hundred and seventy subjects were divided into five groups according to the number of pack-years smoked: four groups of smokers classified as 60 pack-years and a control group. The four groups of smokers were compared with the control group using receiver operating characteristic (ROC curves. RESULTS: The early adverse effects of smoking in the group with 60 pack-years, the diagnostic performance of the forced oscillation technique was similar to that observed with spirometry. CONCLUSIONS: This study revealed that forced oscillation technique parameters were able to detect early smoking-induced respiratory involvement when pathologic changes are still potentially reversible. These findings support the use of the forced oscillation technique as a versatile clinical diagnostic tool in helping with chronic obstructive lung disease prevention, diagnosis, and treatment.

  4. Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism.

    Science.gov (United States)

    Afzal, Muhammad; Kazmi, Imran; Khan, Ruqaiyah; Rana, Poonam; Kumar, Vikas; Al-Abbasi, Fahad A; Zamzami, Mazin A; Anwar, Firoz

    2017-06-01

    Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1β (IL-1β) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Preliminary study about frequencies of unstable chromosome alterations induced by gamma beam and neutron-gamma mixed field

    International Nuclear Information System (INIS)

    Mendes, Mariana E.; Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F.; Calixto, Merilane S.; Santos, Neide

    2011-01-01

    The estimate on approximate dose in exposed individual can be made through conventional cytogenetic analysis of dicentric, this technique has been used to support physical dosimetry. It is important to estimate the absorbed dose in case of accidents with the aim of developing an appropriate treatment and biological dosimetry can be very useful in case where the dosimetry is unavailable. Exposure to gamma and neutron radiation leads to the same biological effects such as chromosomal alterations and cancer. However, neutrons cause more genetic damage, such as mutation or more structural damage, such as chromosome alterations. The aim of research is to compare frequencies of unstable chromosome alterations induced by a gamma beam with those from neutron-gamma mixed field. Two blood samples were obtained from one healthy donor and irradiated at different sources. The first sample was exposed to mixed field neutron-gamma sources 241 AmBe at the Neutron Calibration Laboratory (NCL - CRCN/NE - PE - Brazil) and the second one was exposed to 137 Cs gamma rays at 137 Cs Laboratory (CRCN/NE - PE - Brazil), both exposures resulting in an absorbed dose of 0.66Gy. Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. These preliminary results showed a similarity in associated dicentrics frequency per cell (0.041 and 0.048) after 137 Cs and 241 AmBe sources irradiations, respectively. However, it was not observed centric rings frequency per cell (0.0 and 0.027). This study will be continue to verify the frequencies of unstable chromosome alterations induced by only gamma beam and neutron-gamma mixed field. (author)

  6. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.

    Directory of Open Access Journals (Sweden)

    Lara Bull-Otterson

    Full Text Available Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD. Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3-V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.

  7. Preliminary study about frequencies of unstable chromosome alterations induced by gamma beam and neutron-gamma mixed field

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Mariana E.; Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F. [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Calixto, Merilane S.; Santos, Neide [Universidade Federal de Pernanmbuco (CCB/UFPE), Recife, PE (Brazil). Centro de Ciencias Biologicas. Dept. de Genetica

    2011-07-01

    The estimate on approximate dose in exposed individual can be made through conventional cytogenetic analysis of dicentric, this technique has been used to support physical dosimetry. It is important to estimate the absorbed dose in case of accidents with the aim of developing an appropriate treatment and biological dosimetry can be very useful in case where the dosimetry is unavailable. Exposure to gamma and neutron radiation leads to the same biological effects such as chromosomal alterations and cancer. However, neutrons cause more genetic damage, such as mutation or more structural damage, such as chromosome alterations. The aim of research is to compare frequencies of unstable chromosome alterations induced by a gamma beam with those from neutron-gamma mixed field. Two blood samples were obtained from one healthy donor and irradiated at different sources. The first sample was exposed to mixed field neutron-gamma sources {sup 241}AmBe at the Neutron Calibration Laboratory (NCL - CRCN/NE - PE - Brazil) and the second one was exposed to {sup 137}Cs gamma rays at {sup 137}Cs Laboratory (CRCN/NE - PE - Brazil), both exposures resulting in an absorbed dose of 0.66Gy. Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. These preliminary results showed a similarity in associated dicentrics frequency per cell (0.041 and 0.048) after {sup 137}Cs and {sup 241}AmBe sources irradiations, respectively. However, it was not observed centric rings frequency per cell (0.0 and 0.027). This study will be continue to verify the frequencies of unstable chromosome alterations induced by only gamma beam and neutron-gamma mixed field. (author)

  8. Engineered Swine Models of Cancer

    Directory of Open Access Journals (Sweden)

    Adrienne L. Watson

    2016-05-01

    Full Text Available Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs in cancer modeling are immense. In this review, we discuss how pigs have been and can be used as a biomedical models for cancer research, with an emphasis on current technologies. We have focused on applications of precision genetics that can provide models that mimic human cancer predisposition syndromes. In particular, we describe the advantages of targeted gene-editing using custom endonucleases, specifically TALENs and CRISPRs, and transposon systems, to make novel pig models of cancer with broad preclinical applications.

  9. Influenza A virus infections in swine: pathogenesis and diagnosis.

    Science.gov (United States)

    Janke, B H

    2014-03-01

    Influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "Spanish flu" human pandemic. All influenza viruses of significance in swine are type A, subtype H1N1, H1N2, or H3N2 viruses. Influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. Cell death is due to direct virus infection and to insult directed by leukocytes and cytokines of the innate immune system. The most virulent viruses consistently express the following characteristics of infection: (1) higher or more prolonged virus replication, (2) excessive cytokine induction, and (3) replication in the lower respiratory tract. Nearly all the viral proteins contribute to virulence. Pigs are susceptible to infection with both human and avian viruses, which often results in gene reassortment between these viruses and endemic swine viruses. The receptors on the epithelial cells lining the respiratory tract are major determinants of infection by influenza viruses from other hosts. The polymerases, especially PB2, also influence cross-species infection. Methods of diagnosis and characterization of influenza viruses that infect swine have improved over the years, driven both by the availability of new technologies and by the necessity of keeping up with changes in the virus. Testing of oral fluids from pigs for virus and antibody is a recent development that allows efficient sampling of large numbers of animals.

  10. Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats

    International Nuclear Information System (INIS)

    Femia, Angelo Pietro; Luceri, Cristina; Toti, Simona; Giannini, Augusto; Dolara, Piero; Caderni, Giovanna

    2010-01-01

    Azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats. For gene expression analysis, 9 tumours (TUM) and their paired normal mucosa (NM) were hybridized on 4 × 44K Whole rat arrays (Agilent) and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH) was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent) and the results were analyzed by CGH Analytics (Agilent). Microarray gene expression analysis showed that Defcr4, Igfbp5, Mmp7, Nos2, S100A8 and S100A9 were among the most up-regulated genes in tumours (Fold Change (FC) compared with NM: 183, 48, 39, 38, 36 and 32, respectively), while Slc26a3, Mptx, Retlna and Muc2 were strongly down-regulated (FC: -500; -376, -167, -79, respectively). Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFα/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated. a-CGH analysis showed that four TUM out of ten had one or two chromosomal aberrations. Importantly, one sample showed a deletion on chromosome 18 including Apc. The results showed complex gene expression alterations in adenocarcinomas encompassing many altered pathways. While a-CGH analysis showed a low degree of genomic imbalance, it is interesting to

  11. Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT1receptor activation.

    Science.gov (United States)

    Occhieppo, Victoria Belén; Marchese, Natalia Andrea; Rodríguez, Iara Diamela; Basmadjian, Osvaldo Martin; Baiardi, Gustavo; Bregonzio, Claudia

    2017-06-01

    The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT 1 -receptors (AT 1 -R), modulates neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Our aim for the present work was to evaluate the role of AT 1 -R in long-term alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analysed at the somatosensory cortex. Thermal nociception was evaluated as a physiological outcome of this brain area. Male Wistar rats (250-320 g) were administered with AT 1 -R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1-5) and Amph/saline (2.5 mg/kg i.p., days 6-10). The four experimental groups were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On day 17, the animals were sacrificed and their brains were processed for Nissl staining and immunohistochemistry against glial fibrillary acidic protein (GFAP) and von Willebrand factor. In another group of animals, thermal nociception was evaluated using hot plate test, in the four experimental groups, on day 17. Data were analysed with two-way anova followed by Bonferroni test. Our results indicate that Amph exposure induces an increase in: neuronal apoptosis, astrocyte reactivity and microvascular network, evaluated as an augmented occupied area by vessels, branching points and their tortuosity. Moreover, Amph exposure decreased the thermal nociception threshold. Pretreatment with the AT 1 -R blocker prevented the described alterations induced by this psychostimulant. The decreased thermal nociception and the structural changes in somatosensory cortex could be considered as extended neuroadaptative responses to Amph, involving AT 1 -R activation. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption.

    Science.gov (United States)

    Moyano, Paula; de Frias, Mariano; Lobo, Margarita; Anadon, María José; Sola, Emma; Pelayo, Adela; Díaz, María Jesús; Frejo, María Teresa; Del Pino, Javier

    2018-02-01

    Cadmium, an environmental neurotoxic compound, produces cognitive disorders, although the mechanism remains unknown. Previously, we described that cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF). This effect, partially mediated by M1 receptor blockade, triggering it through AChE splices variants alteration, may explain cadmium effects on learning and memory processes. Cadmium has been also reported to induce oxidative stress generation leading to M2 and M4 muscarinic receptors alteration, in hippocampus and frontal cortex, which are necessary to maintain cell viability and cognitive regulation, so their alteration in BF could also mediate this effect. Moreover, it has been reported that antioxidant treatment could reverse cognitive disorders, muscarinic receptor and AChE variants alterations induced by cadmium. Thus, we hypothesized that cadmium induced cell death of BF cholinergic neurons is mediated by oxidative stress generation and this mechanism could produce this effect, in part, through AChE variants altered by muscarinic receptors disruption. To prove this, we evaluated in BF SN56 cholinergic neurons, whether cadmium induces oxidative stress and alters muscarinic receptors, and their involvement in the induction of cell death through alteration of AChE variants. Our results show that cadmium induces oxidative stress, which mediates partially the alteration of AChE variants and M2 to M4 muscarinic receptors expression and blockage of M1 receptor. In addition, cadmium induced oxidative stress generation by M1 and M3 receptors alteration through AChE variants disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Swine in biomedical research. Vol. 3

    Energy Technology Data Exchange (ETDEWEB)

    Tumbleson, M.E.

    1986-01-01

    This volume presents information on the following topics: hemodynamic characteristics of the conscious resting pig; cardiovascular and metabolic responses to acute and chronic exercise in swine (ILLEGIBLE) a large animal model for studies (ILLEGIBLE) effects of heparin-protamine interaction in swine - intravenous vs. intraarterial; swine as animal models in cardiovascular research; studies of coronary thrombosis in swine with von Willebrand's disease; role of plasma intermediate and low density lipoproteins in early atherogenesis in hyperlipidemic swine; swine as a model in renal physiology and nephrology; the pig as a model for studying kidney disease in man; hypertension of renal origin and the effects of Captopril in miniature pigs; porcine natural killer/killer cell system; the behavior of pig lymphocyte populations in vivo; a review of spontaneous and experimental porcine eperythrozoonosis; and Sinclair swine melanoma.

  14. Methionine reduces the valproic acid-induced spina bifida rate in mice without altering valproic acid kinetics.

    Science.gov (United States)

    Ehlers, K; Elmazar, M M; Nau, H

    1996-01-01

    The antiepileptic drug valproic acid (VPA) is an established human teratogen causing spin bifida aperta. We recently developed a mouse model in which spina bifida aperta and occulta are induced with VPA. In a search for protection against neural tube defects, we investigated the effect of methionine on the incidence of VPA-induced spina bifida in the mouse. To induce spina bifida, we injected VPA (350 mg VPA-Na/kg body weight) subcutaneously three times on d 9 of gestation at 0, 6 and 12 h. In some mice, L-methionine (3 x 70 mg/kg body weight) was injected intraperitoneally 30 min before each VPA administration. When fetuses were examined on d 18, methionine treatment slightly reduced the VPA-induced spina bifida aperta rate from 5 to 1% (P > 0.05, no significant difference). The incidence of VPA-induced spina bifida occulta (90%) was significantly lower (28%) when methionine was also administered (P bifida in mice without altering VPA kinetics.

  15. Molecular alterations underlying the spontaneous and γ-ray-induced point mutations at the white locus of Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Aleksandrova, M.V.; Lapidus, I.L.; Aleksandrov, I.D.; Karpovskij, A.L.

    1996-01-01

    The white locus in D.Melanogaster was selected as a target gene for the study of the mutational spectra of spontaneously arising and radiation-induced gene mutations in a whole organism. Analysis of 6 spontaneous and 73 γ-ray-induced white mutations by a combination of cytological, genetic and molecular techniques revealed that on the chromosomal and genetic levels all spontaneous mutations showed themselves to be point mutants. The share of such mutants among all heritable radiation-induced gene mutations is about 40%, whereas the rest ones are due to exchange breaks (8%) as well as multilocus, single-locus or partial-locus (intragenic) deletions (52%). The DNAs from 4 spontaneous and 17 γ-ray-induced point mutants were analysed by Southern blot-hybridization. The three spontaneous and 7 radiation mutants showed an altered DNA sequence at the left (distal) half of the white gene due to insertion or DNA rearrangement. The rest (58%) of the radiation-induced point mutations did not indicate any alternations in this part of the gene as detected by this technique and probes employed. 15 refs., 3 figs., 1 tab

  16. Altered lipid accumulation in Nannochloropsis salina CCAP849/3 following EMS and UV induced mutagenesis

    Directory of Open Access Journals (Sweden)

    T.A. Beacham

    2015-09-01

    Full Text Available Microalgae have potential as a chemical feed stock in a range of industrial applications. Nannochloropsis salina was subject to EMS mutagenesis and the highest lipid containing cells selected using fluorescence-activated cell sorting. Assessment of growth, lipid content and fatty acid composition identified mutant strains displaying a range of altered traits including changes in the PUFA content and a total FAME increase of up to 156% that of the wild type strain. Combined with a reduction in growth this demonstrated a productivity increase of up to 76%. Following UV mutagenesis, lipid accumulation of the mutant cultures was elevated to more than 3 fold that of the wild type strain, however reduced growth rates resulted in a reduction in overall productivity. Changes observed are indicative of alterations to the regulation of the omega 6 Kennedy pathway. The importance of these variations in physiology for industrial applications such as biofuel production is discussed.

  17. Altered lipid accumulation in Nannochloropsis salina CCAP849/3 following EMS and UV induced mutagenesis.

    Science.gov (United States)

    Beacham, T A; Macia, V Mora; Rooks, P; White, D A; Ali, S T

    2015-09-01

    Microalgae have potential as a chemical feed stock in a range of industrial applications. Nannochloropsis salina was subject to EMS mutagenesis and the highest lipid containing cells selected using fluorescence-activated cell sorting. Assessment of growth, lipid content and fatty acid composition identified mutant strains displaying a range of altered traits including changes in the PUFA content and a total FAME increase of up to 156% that of the wild type strain. Combined with a reduction in growth this demonstrated a productivity increase of up to 76%. Following UV mutagenesis, lipid accumulation of the mutant cultures was elevated to more than 3 fold that of the wild type strain, however reduced growth rates resulted in a reduction in overall productivity. Changes observed are indicative of alterations to the regulation of the omega 6 Kennedy pathway. The importance of these variations in physiology for industrial applications such as biofuel production is discussed.

  18. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

    OpenAIRE

    Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

    2015-01-01

    Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 mon...

  19. Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues

    OpenAIRE

    Dilek Akşit; Alper Yazıcı; Hasan Akşit; Esin S. Sarı; Arzu Yay; Onur Yıldız; Adil Kılıç; Sıtkı S. Ermiş; Kamil Seyrek

    2016-01-01

    Background: Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. Aims: The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. Study Design: Animal experiment. Methods: Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was ...

  20. Altered pulmonary defense system in lung injury induced by didecyldimethylammonium chloride in mice.

    Science.gov (United States)

    Ohnuma, Aya; Yoshida, Toshinori; Horiuchi, Haruka; Fukumori, Junko; Tomita, Mariko; Kojima, Sayuri; Takahashi, Naofumi; Fukuyama, Tomoki; Hayashi, Koichi; Yamaguchi, Satoru; Ohtsuka, Ryoichi; Kashimoto, Yukiko; Kuwahara, Maki; Takeda, Makio; Kosaka, Tadashi; Nakashima, Nobuaki; Harada, Takanori

    2011-07-01

    Didecyldimethylammonium chloride (DDAC), a representative dialkyl-quaternary ammonium compound (QAC), could contaminate working atmospheres when used in disinfectant operation and adversely affect human health. Furthermore, the development of bacteria resistant to DDAC might become public health concern. We postulated that DDAC instillation in the lungs alters pulmonary antioxidant and antimicrobial responses and increases susceptibility to systemic administration of a bacterial component lipopolysaccharide (LPS). Mice were intratracheally instilled with DDAC and sacrificed 1, 3, or 7 days after treatment. Pulmonary cytotoxicity in recovered bronchoalveolar lavage was evident on Days 1 and 7, and inflammatory cell influx and interleukin-6 expression peaked on Day 7, in association with altered antioxidant and antimicrobial responses, as demonstrated by measuring heme oxygenase-1, glutathione peroxidase 2, lactoferrin, and mouse β-defensin-2 and -3 mRNA in the lung samples. The impaired defense system tended to enhance the inflammatory reaction caused by a systemic administration of LPS; the effect was in association with increased expression of toll-like receptor-4 mRNA. The results suggest that DDAC alters pulmonary defense system, which may contribute to susceptibility to an exogenous infectious agent.

  1. Silver nanoparticles do not alter human osteoclastogenesis but induce cellular uptake

    Directory of Open Access Journals (Sweden)

    Linda Pauksch

    2014-01-01

    In conclusion, our results indicate nanosilver-induced cell stress at higher concentrations. For this reason antibacterial benefits and possible health risks should be weighed in more detail in further studies.

  2. Aterogênese em artéria ilíaca comum de suínos submetidos à homocisteinemia induzida pela ingestão de metionina Atherogenesis in swine iliac artery with homocystinemia induced by methionine ingestion

    Directory of Open Access Journals (Sweden)

    Luís Henrique Gil França

    2006-03-01

    Full Text Available OBJETIVO: Avaliar os efeitos da homocisteinemia induzida na artéria ilíaca de suínos. MATERIAL E MÉTODO: Realizou-se estudo experimental comparativo em dois grupos homogêneos de sete suínos da raça Macau, com peso entre 20 e 30 kg durante 30 dias. Os animais foram divididos em dois grupos, sendo um deles alimentado com metionina adicionada à dieta por um período de 4 semanas. Foram colhidas amostras de sangue para a dosagem de colesterol, triglicerídeos, HDL e homocisteína. Os animais foram submetidos à arteriografia para avaliação da perviedade das artérias ilíacas e, posteriormente, sacrificados. As artérias ilíacas foram enviadas para análise histológica. RESULTADOS: Os animais sobreviveram ao experimento, e não houve alterações significativas nos níveis de colesterol total, triglicerídeos e HDL nos dois grupos. O exame microscópico do grupo-controle não apresentou alterações patológicas e foi semelhante em todas as preparações examinadas. No grupo da dieta com metionina, as placas eram formadas por macrófagos espumosos, mas não foram observadas células musculares lisas, cristais de colesterol ou células inflamatórias. A túnica média apresentava-se com lâmina elástica interna íntegra. No grupo-controle, não houve alteração nos níveis de homocisteína durante o experimento. No grupo-metionina, houve aumento dos níveis séricos da homocisteína, com valor médio de 59,80 µmol/l após 30 dias de dieta rica em metionina. CONCLUSÃO: A homocisteinemia induzida pela metionina causa aterogênese nas artérias ilíacas de suínos.OBJECTIVE: To assess the effects of induced homocystinemia in the swine iliac artery. MATERIAL AND METHOD: A comparative experimental study with two homogeneous groups of seven pigs from the Macao specimen, weighed between 20 and 30 kg, which were assessed during 30 days. The pigs were divided into two groups. One of them was fed with a methionine-rich diet for a 4-week period

  3. Alterations in the Helicoverpa armigera midgut digestive physiology after ingestion of pigeon pea inducible leucine aminopeptidase.

    Directory of Open Access Journals (Sweden)

    Purushottam R Lomate

    Full Text Available Jasmonate inducible plant leucine aminopeptidase (LAP is proposed to serve as direct defense in the insect midgut. However, exact functions of inducible plant LAPs in the insect midgut remain to be estimated. In the present investigation, we report the direct defensive role of pigeon pea inducible LAP in the midgut of Helicoverpa armigera (Lepidoptera: Noctuidae and responses of midgut soluble aminopeptidases and serine proteinases upon LAP ingestion. Larval growth and survival was significantly reduced on the diets supplemented with pigeon pea LAP. Aminopeptidase activities in larvae remain unaltered in presence or absence of inducible LAP in the diet. On the contrary, serine proteinase activities were significantly decreased in the larvae reared on pigeon pea LAP containing diet as compared to larvae fed on diet without LAP. Our data suggest that pigeon pea inducible LAP is responsible for the degradation of midgut serine proteinases upon ingestion. Reduction in the aminopeptidase activity with LpNA in the H. armigera larvae was compensated with an induction of aminopeptidase activity with ApNA. Our findings could be helpful to further dissect the roles of plant inducible LAPs in the direct plant defense against herbivory.

  4. Overview of Classical Swine Fever (Hog Cholera, Classical Swine fever)

    Science.gov (United States)

    Classical swine fever is a contagious often fatal disease of pigs clinically characterized by high body temperature, lethargy, yellowish diarrhea, vomits and purple skin discoloration of ears, lower abdomen and legs. It was first described in the early 19th century in the USA. Later, a condition i...

  5. Control of African swine fever epidemics in industrialized swine populations

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Bøtner, Anette; Mortensen, Sten

    2016-01-01

    resulted in marginal improvements to the control of the epidemics. However, adding testing of dead animals in the protection and surveillance zones was predicted to be the optimal control scenario for an ASF epidemic in industrialized swine populations without contact to wild boar. This optimal scenario...

  6. Effect of Ocimum basilicum extract on cadmium-induced testicular histomorphometric and immunohistochemical alterations in albino rats

    Science.gov (United States)

    Nooh, Hanna Z.

    2013-01-01

    The present study examined the efficacy of Ocimum basilicum (basil) extract, a natural herb, with antioxidant properties, against testicular toxicity induced by cadmium (Cd), which is one of the most important toxic heavy metals. The intoxicated rats showed significant alterations in the testicular tissue including decreased seminiferous epithelium height and changes in the arrangement of spermatogenic layers. Hypospermatogensis with cytoplasmic vacuolization and pyknotic nuclei were observed. Intertubular hemorrahage and absence of spermatozoa were noted. Decreased cell proliferation was reflected by a decrease in Ki-67 expression, whereas the increase in apoptotic rate was associated with a decrease in the Bcl/Bax ratio. Concomitant treatment with aqueous basil extract led to an improvement in histological, morphometrical and immunohistochemical changes induced by Cd. The beneficial effects of basil extract could be attributed to its antioxidant properties. PMID:23869259

  7. Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons.

    Science.gov (United States)

    Lam, D K; Sessle, B J; Hu, J W

    2008-10-15

    Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central

  8. Altered dopamine levels induced by the parasite Profilicollis antarcticus on its intermediate host, the crab Hemigrapsus crenulatus

    Directory of Open Access Journals (Sweden)

    JOSÉ MIGUEL ROJAS

    2005-01-01

    Full Text Available A serotonergic pathway is apparently involved in parasite-host interactions. Previous studies conducted in our laboratory showed increased rates in oxygen consumption and alterations in body posture in the crab Hemigrapsus crenulatus parasitized by the acanthocephalan, Profilicollis antarcticus. Such changes may be related to the functions described for biogenic amines in crustaceans. During the infective stage the acanthocephalans live freely in the hemocelomic cavity, suggesting that the possible alteration induced by biogenic amines may be related to their neurohormonal function in crustaceans. To test whether the presence of P. antarcticus produced neurohormonal changes in its intermediate host, H. crenulatus, we analyzed serotonin and dopamine levels in the host using HPLC with electrochemical detection. Two groups of 11 female crabs were studied; one group was artificially inoculated with two cystacanths while the other was used as the control. Our results show a dramatic increase in hemolymph dopamine, but not serotonin in H. crenulatus parasitized by the acanthocephalan P. antarcticus. Our results, along with those reported by Maynard (1996, suggest a parasite-specific strategy involved in the behavior alteration caused by the acanthocephalans on their intermediate host. The use of a biogenic amine as a mechanism of interaction by the parasites gives them an endless number of alternative potential actions on their intermediate hosts

  9. Subcortical grey matter alterations in cocaine dependent individuals with substance-induced psychosis compared to non-psychotic cocaine users.

    Science.gov (United States)

    Willi, Taylor S; Lang, Donna J; Honer, William G; Smith, Geoff N; Thornton, Allen E; Panenka, William J; Procyshyn, Ric M; Vila-Rodriguez, Fidel; Su, Wayne; Vertinsky, A Talia; Leonova, Olga; Rauscher, Alexander; MacEwan, G William; Barr, Alasdair M

    2016-10-01

    After prolonged psychostimulant abuse, transient psychotic symptoms referred to as "substance-induced psychosis" (SIP) can develop - closely resembling symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and schizophrenias suggests that similar underlying neural deficits may contribute to the expression of psychosis across these disorders. To date, neuroanatomical characterization of grey matter structural alterations in SIP has been limited to methamphetamine associated psychosis, with no studies controlling for potential neurotoxic effects of the psychostimulant that precipitates psychosis. To investigate grey matter subcortical alterations in SIP, a voxel-based analysis of magnetic resonance images (MRI) was performed between a group of 74 cocaine dependent nonpsychotic individuals and a group of 29 individuals with cocaine-associated psychosis. The cocaine-associated psychosis group had significantly smaller volumes of the thalamus and left hippocampus, controlling for age, total brain volume, current methamphetamine dependence, and current marijuana dependence. No differences were present in bilateral caudate structures. The findings of reduced thalamic and hippocampal volumes agree with previous reports in the schizophrenia literature, suggesting alterations of these structures are not specific to schizophrenia, but may be common to multiple forms of psychosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Temporal Dynamics of the Default Mode Network Characterize Meditation-Induced Alterations in Consciousness

    Science.gov (United States)

    Panda, Rajanikant; Bharath, Rose D.; Upadhyay, Neeraj; Mangalore, Sandhya; Chennu, Srivas; Rao, Shobini L.

    2016-01-01

    Current research suggests that human consciousness is associated with complex, synchronous interactions between multiple cortical networks. In particular, the default mode network (DMN) of the resting brain is thought to be altered by changes in consciousness, including the meditative state. However, it remains unclear how meditation alters the fast and ever-changing dynamics of brain activity within this network. Here we addressed this question using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to compare the spatial extents and temporal dynamics of the DMN during rest and meditation. Using fMRI, we identified key reductions in the posterior cingulate hub of the DMN, along with increases in right frontal and left temporal areas, in experienced meditators during rest and during meditation, in comparison to healthy controls (HCs). We employed the simultaneously recorded EEG data to identify the topographical microstate corresponding to activation of the DMN. Analysis of the temporal dynamics of this microstate revealed that the average duration and frequency of occurrence of DMN microstate was higher in meditators compared to HCs. Both these temporal parameters increased during meditation, reflecting the state effect of meditation. In particular, we found that the alteration in the duration of the DMN microstate when meditators entered the meditative state correlated negatively with their years of meditation experience. This reflected a trait effect of meditation, highlighting its role in producing durable changes in temporal dynamics of the DMN. Taken together, these findings shed new light on short and long-term consequences of meditation practice on this key brain network. PMID:27499738

  11. Induced Sporicidal Activity of Chlorhexidine against Clostridium difficile Spores under Altered Physical and Chemical Conditions

    Science.gov (United States)

    Nerandzic, Michelle M.; Donskey, Curtis J.

    2015-01-01

    Background Chlorhexidine is a broad-spectrum antimicrobial commonly used to disinfect the skin of patients to reduce the risk of healthcare-associated infections. Because chlorhexidine is not sporicidal, it is not anticipated that it would have an impact on skin contamination with Clostridium difficile, the most important cause of healthcare-associated diarrhea. However, although chlorhexidine is not sporicidal as it is used in healthcare settings, it has been reported to kill spores of Bacillus species under altered physical and chemical conditions that disrupt the spore’s protective barriers (e.g., heat, ultrasonication, alcohol, or elevated pH). Here, we tested the hypothesis that similarly altered physical and chemical conditions result in enhanced sporicidal activity of chlorhexidine against C. difficile spores. Principal Findings C. difficile spores became susceptible to heat killing at 80°C within 15 minutes in the presence of chlorhexidine, as opposed to spores suspended in water which remained viable. The extent to which the spores were reduced was directly proportional to the concentration of chlorhexidine in solution, with no viable spores recovered after 15 minutes of incubation in 0.04%–0.0004% w/v chlorhexidine solutions at 80°C. Reduction of spores exposed to 4% w/v chlorhexidine solutions at moderate temperatures (37°C and 55°C) was enhanced by the presence of 70% ethanol. However, complete elimination of spores was not achieved until 3 hours of incubation at 55°C. Elevating the pH to ≥9.5 significantly enhanced the killing of spores in either aqueous or alcoholic chlorhexidine solutions. Conclusions Physical and chemical conditions that alter the protective barriers of C. difficile spores convey sporicidal activity to chlorhexidine. Further studies are necessary to identify additional agents that may allow chlorhexidine to reach its target within the spore. PMID:25861057

  12. Temporal dynamics of the default mode network characterise meditation induced alterations in consciousness

    Directory of Open Access Journals (Sweden)

    Rajanikant Panda

    2016-07-01

    Full Text Available Current research suggests that human consciousness is associated with complex, synchronous interactions between multiple cortical networks. In particular, the default mode network (DMN of the resting brain is thought to be altered by changes in consciousness, including the meditative state. However, it remains unclear how meditation alters the fast and ever-changing dynamics of brain activity within this network. Here, we addressed this question using simultaneous electroencephalography (EEG and functional imaging (fMRI to compare the spatial extents and temporal dynamics of the DMN during rest and meditation. Using fMRI, we identified key reductions in the posterior cingulate hub of the DMN, along with increases in right frontal and left temporal areas, in experienced meditators during rest and during meditation, in comparison to healthy controls. We employed the simultaneously recorded EEG data to identify the topographical microstate corresponding to the DMN. Analysis of the temporal dynamics of this microstate revealed that the average duration and frequency of occurrence of DMN microstate was higher in meditators compared to healthy controls. Both these temporal parameters increased during meditation, reflecting the state effect of meditation. In particular, we found that the alteration in the duration of the DMN microstate when meditators entered the meditative state correlated negatively with their years of meditation experience. This reflected a trait effect of meditation, highlighting its role in producing durable changes in temporal dynamics of the DMN. Taken together, these findings shed new light on short and long-term consequences of meditation practice on this key brain network.

  13. Blonanserin-induced Mood Alteration in Schizophrenia and Schizoaffective Disorder: Two Cases.

    Science.gov (United States)

    Min, Aran; Kim, Daeho

    2013-12-01

    We report two outpatients, one with schizophrenia and one with schizoaffective disorder, who developed manic or hypomanic episodes following the initiation of blonanserin during the course of treatment. Blonanserin is a novel antipsychotic that acts as a 5-HT and D2 receptor antagonist. Both patients developed hypomanic episodes within 2 weeks of receiving a small dose (6-8 mg) of blonanserin, and one patient later developed full-blown mania; both episodes ended within 1 month of discontinuing blonanserin. The mood alteration observed in these cases suggests a possible antidepressant effect of blonanserin; thus, clinicians should monitor mood changes when administering this antipsychotic.

  14. Montelukast prevents microparticle-induced inflammatory and functional alterations in human bronchial smooth muscle cells.

    Science.gov (United States)

    Fogli, Stefano; Stefanelli, Fabio; Neri, Tommaso; Bardelli, Claudio; Amoruso, Angela; Brunelleschi, Sandra; Celi, Alessandro; Breschi, Maria Cristina

    2013-10-01

    Microparticles (MPs) are membrane fragments that may play a role in the pathogenesis of chronic respiratory diseases. We aimed to investigate whether human monocytes/macrophage-derived MPs could induce a pro-inflammatory phenotype in human bronchial smooth muscle cells (BSMC) and the effect of montelukast in this setting. Experimental methods included isolation of human monocytes/macrophages and generation of monocyte-derived MPs, RT-PCR analysis of gene expression, immunoenzymatic determination of pro-inflammatory factor release, bioluminescent assay of intracellular cAMP levels and electromobility shift assay analysis of NF-κB nuclear translocation. Stimulation of human BSMC with monocyte-derived MPs induced a pro-inflammatory switch in human BSMC by inducing gene expression (COX-2 and IL-8), protein release in the supernatant (PGE2 and IL-8), and heterologous β2-adrenoceptor desensitization. The latter effect was most likely related to autocrine PGE2 since pre-treatment with COX inhibitors restored the ability of salbutamol to induce cAMP synthesis in desensitized cells. Challenge with MPs induced nuclear translocation of NF-κB and selective NF-κB inhibition decreased MP-induced cytokine release in the supernatant. Montelukast treatment prevented IL-8 release and heterologous β2-adrenoceptor desensitization in human BSMC exposed to monocyte-derived MPs by blocking NF-κB nuclear translocation. These findings provide evidence on the role of human monocyte-derived MPs in the airway smooth muscle phenotype switch as a novel potential mechanism in the progression of chronic respiratory diseases and on the protective effects by montelukast in this setting. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Bio-molecular alterations induced by a chemical or radiating stress in isolated human cells

    International Nuclear Information System (INIS)

    Gault, N.

    2004-01-01

    After having recalled some aspects of radiobiology (effects of ionizing radiations, molecular targets of radiations, cellular responses with respect to the radiation), the author discusses various aspects of radio-sensitivity: intrinsic radio-sensitivity of tumoral and normal cells, DNA injuries and in vitro radio-sensitivity, genes of susceptibility to ionizing radiations, clustered injuries. Then she reports investigations performed by infrared micro-spectroscopy: characterization of pathological lines, of biological processes, of oxidative injuries induced by xenobiotics, of injuries induced by ionizing radiations

  16. Toll-Like Receptor-4 Mediated Inflammation Is Involved in the Cardiometabolic Alterations Induced by Intermittent Hypoxia

    Directory of Open Access Journals (Sweden)

    Laureline Poulain

    2015-01-01

    Full Text Available Objective. Intermittent hypoxia (IH is a major component of sleep apnea syndrome as its cardiometabolic complications have been mainly attributed to IH. The pathophysiology is still poorly understood but there are some similarities with the obesity-associated cardiometabolic complications. As the latter results from inflammation involving toll-like receptor-4 (TLR4 signaling, we assessed this pathway in the cardiometabolic consequences of IH. Methods. Lean adult male TLR4-deficient (TLR4−/− mice and their controls (C57BL/6 mice were exposed to either IH (FiO2 21-5%, 1 min cycle, 8 h/day or air (normoxic mice for 4 weeks. Animals were assessed at 1-week exposure for insulin tolerance test and after 4-week exposure for morphological and inflammatory changes of the epididymal fat and thoracic aorta. Results. IH induced insulin resistance, morphological and inflammatory changes of the epididymal fat (smaller pads and adipocytes, higher release of TNF-α and IL-6 and aorta (larger intima-media thickness and higher NFκB-p50 activity. All these alterations were prevented by TLR4 deletion. Conclusion. IH induces metabolic and vascular alterations that involve TLR4 mediated inflammation. These results confirm the important role of inflammation in the cardiometabolic consequences of IH and suggest that targeting TLR4/NFκB pathway could represent a further therapeutic option for sleep apnea patients.

  17. NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian cancer cells to cisplatin.

    Directory of Open Access Journals (Sweden)

    Chao Lin

    Full Text Available Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy.

  18. Naringenin ameliorates kainic acid-induced morphological alterations in the dentate gyrus in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Park, Jungha; Jeong, Kyoung Hoon; Shin, Won-Ho; Bae, Young-Seuk; Jung, Un Ju; Kim, Sang Ryong

    2016-10-19

    Granule cell dispersion (GCD) in the dentate gyrus (DG) of the hippocampus is a morphological alteration characteristic of temporal lobe epilepsy. Recently, we reported that treatment with naringin, a flavonoid found in grapefruit and citrus fruits, reduced spontaneous recurrent seizures by inhibiting kainic acid (KA)-induced GCD and neuronal cell death in mouse hippocampus, suggesting that naringin might have beneficial effects for preventing epileptic events in the adult brain. However, it is still unclear whether the beneficial effects of naringin treatment are mediated by the metabolism of naringin into naringenin in the KA-treated hippocampus. To investigate this possibility, we evaluated whether intraperitoneal injections of naringenin could mimic naringin-induced effects against GCD caused by intrahippocampal KA injections in mice. Our results showed that treatment with naringenin delayed the onset of KA-induced seizures and attenuated KA-induced GCD by inhibiting activation of the mammalian target of rapamycin complex 1 in both neurons and reactive astrocytes in the DG. In addition, its administration attenuated the production of proinflammatory cytokines such as tumor necrosis tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) from microglial activation in the DG following KA treatment. These results suggest that naringenin may be an active metabolite of naringin and help prevent the progression of epileptic insults in the hippocampus in vivo; therefore, naringenin may be a beneficial metabolite of naringin for the treatment of epilepsy.

  19. NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

    Science.gov (United States)

    Lin, Chao; Zhao, Xin-yu; Li, Lei; Liu, Huan-yi; Cao, Kang; Wan, Yang; Liu, Xin-yu; Nie, Chun-lai; Liu, Lei; Tong, Ai-ping; Deng, Hong-xin; Li, Jiong; Yuan, Zhu; Wei, Yu-quan

    2012-01-01

    Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy. PMID:22590594

  20. Microbiome overview in swine lungs.

    Science.gov (United States)

    Siqueira, Franciele Maboni; Pérez-Wohlfeil, Esteban; Carvalho, Fabíola Marques; Trelles, Oswaldo; Schrank, Irene Silveira; Vasconcelos, Ana Tereza Ribeiro; Zaha, Arnaldo

    2017-01-01

    Mycoplasma hyopneumoniae is the etiologic agent of swine enzootic pneumonia. However other mycoplasma species and secondary bacteria are found as inhabitants of the swine respiratory tract, which can be also related to disease. In the present study we have performed a total DNA metagenomic analysis from the lungs of pigs kept in a field condition, with suggestive signals of enzootic pneumonia and without any infection signals to evaluate the bacteria variability of the lungs microbiota. Libraries from metagenomic DNA were prepared and sequenced using total DNA shotgun metagenomic pyrosequencing. The metagenomic distribution showed a great abundance of bacteria. The most common microbial families identified from pneumonic swine's lungs were Mycoplasmataceae, Flavobacteriaceae and Pasteurellaceae, whereas in the carrier swine's lungs the most common families were Mycoplasmataceae, Bradyrhizobiaceae and Flavobacteriaceae. Analysis of community composition in both samples confirmed the high prevalence of M. hyopneumoniae. Moreover, the carrier lungs had more diverse family population, which should be related to the lungs normal flora. In summary, we provide a wide view of the bacterial population from lungs with signals of enzootic pneumonia and lungs without signals of enzootic pneumonia in a field situation. These bacteria patterns provide information that may be important for the establishment of disease control measures and to give insights for further studies.

  1. Microbiome overview in swine lungs.

    Directory of Open Access Journals (Sweden)

    Franciele Maboni Siqueira

    Full Text Available Mycoplasma hyopneumoniae is the etiologic agent of swine enzootic pneumonia. However other mycoplasma species and secondary bacteria are found as inhabitants of the swine respiratory tract, which can be also related to disease. In the present study we have performed a total DNA metagenomic analysis from the lungs of pigs kept in a field condition, with suggestive signals of enzootic pneumonia and without any infection signals to evaluate the bacteria variability of the lungs microbiota. Libraries from metagenomic DNA were prepared and sequenced using total DNA shotgun metagenomic pyrosequencing. The metagenomic distribution showed a great abundance of bacteria. The most common microbial families identified from pneumonic swine's lungs were Mycoplasmataceae, Flavobacteriaceae and Pasteurellaceae, whereas in the carrier swine's lungs the most common families were Mycoplasmataceae, Bradyrhizobiaceae and Flavobacteriaceae. Analysis of community composition in both samples confirmed the high prevalence of M. hyopneumoniae. Moreover, the carrier lungs had more diverse family population, which should be related to the lungs normal flora. In summary, we provide a wide view of the bacterial population from lungs with signals of enzootic pneumonia and lungs without signals of enzootic pneumonia in a field situation. These bacteria patterns provide information that may be important for the establishment of disease control measures and to give insights for further studies.

  2. Heavy-ion radiation induces both activation of multiple endogenous transposable elements and alterations in DNA methylation in rice

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Li, Xishan; Xiaolin, Cui; Li, Xiang

    2012-07-01

    Space radiation represents a complex environmental condition in which several interacting factors such as electron, neutron, proton, heavy-ion are involved, which may provoke stress responses and jeopardize genome integrity. Given the inherent property of epigenetic modifications to respond to intrinsic aswell as external perturbations, it is conceivable that epigenetic markers like DNA methylation and transposition may undergo alterations in response to space radiation. Cytosine DNA methylation plays important roles in maintaining genome stability and controlling gene expression. A predominant means for Transposable elements (TEs) to cause genetic instability is via their transpositional activation. To find the detailed molecular characterization of the nature of genomic changes induced by space radiation, the seeds of rice were exposed to 0.02, 0.2, 1, 2 and 20 Gy dose of ^{12}C heavy-ion radiation, respectively. We found that extensive alteration in both DNA methylation and gene expression occurred in rice plants after different dose of heavy-ion radiation. Here we shown that heavy-ion radiation has induced transposition of mPing and Tos17 in rice, which belong to distinct classes including the miniature inverted terminal repeat TEs (MITEs) and long-terminal repeat (LTR) retrotransposons, respectively. mPing and Tos17 mobility were found to correlate with cytosine methylation alteration detected by MSAP and genetic variation detected by AFLP. The result showed that at least in some cases transposition of TEs was associated with cytosine demethylation within the elements. Our results implicate that the heavy-ion radiation represents a potent mutagenic agent that can cause genomic instabilities by eliciting transposition of endogenous TEs in rice. Keywords: Heavy-ion radiation, DNA methylation, Transposable elements, mPing, Tos17

  3. Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.

    Science.gov (United States)

    Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert

    2016-09-01

    Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.

  4. Thiamethoxam Actara® induced alterations in kidney liver cerebellum and hippocampus of male rats

    Directory of Open Access Journals (Sweden)

    Hassina Khaldoun-Oularbi

    2017-12-01

    Full Text Available Thiamethoxam (TMX, a second-generation neonicotinoid insecticide, is one of the most widely used insecticides in Algeria. The present study assessed the effects of repeated subchronic exposure to the commercial formulation of thiamethoxam (Actara®, 25% WG in albino male rats. The toxic effects of thiamethoxam (TMX were studied biochemically and histopathologically. Twenty-eight male albino rats weighing between 226 and 243 g were randomly assigned to four groups. One group served as control, and the other three were served as experimental groups administered a neonicotinoid thiamethoxam (TMX; 26, 39 and 78 mg/kg/day for 6 weeks. The effects of the insecticide on various biochemical parameters were evaluated at 2, 4 and 6 weeks. Histopathological studies were carried out in the liver, kidney, cerebellum and hippocampus at the end of the experiment. Changes in biochemical parameters glucose, ALT (alanine aminotransferase, AST (aspartate aminotransferase, γGT (gamma-glutamyltransferase ALP (alkaline phosphatase urea and creatinine were observed in treated-groups in a dose dependent manner when compared to the control. Histopathological alterations were more intense in male rats from the TMX high dose group than those from group 2 and 3. Based on these results, subchronic oral administration of thiamethoxam altered the biochemical parameters, which correlated with histopathological changes in the liver kidney and brain.

  5. Eugenol Induces Phenotypic Alterations and Increases the Oxidative Burst in Cryptococcus

    Directory of Open Access Journals (Sweden)

    Júnia C. O. Alves

    2017-12-01

    Full Text Available Eugenol is a phenolic compound and the main constituent of the essential oil of clove India. Although there are reports of some pharmacological effects of eugenol, this study is the first that proposes to evaluate the antifungal effects of this phenol against both Cryptococcus gattii and C. neoformans cells. The effect of eugenol against yeast cells was analyzed for drug susceptibility, alterations in cell diameter, capsule properties, amounts of ergosterol, oxidative burst, and thermodynamics data. Data demonstrated that there is no interaction between eugenol and fluconazole and amphotericin B. Eugenol reduced the cell diameter and the capsule size, increased cell surface/volume, changed positively the cell surface charge of cryptococcal cells. We also verified increased levels of reactive oxygen species without activation of antioxidant enzymes, leading to increased lipid peroxidation, mitochondrial membrane depolarization and reduction of lysosomal integrity in cryptococcal cells. Additionally, the results showed that there is no significant molecular interaction between eugenol and C. neoformans. Morphological alterations, changes of cellular superficial charges and oxidative stress play an important role in antifungal activity of eugenol against C. gattii and C. neoformans that could be used as an auxiliary treatment to cutaneous cryptococcosis.

  6. Imidacloprid induced alterations in enzyme activities and energy reserves of the land snail, Helix aspersa.

    Science.gov (United States)

    Radwan, M A; Mohamed, M S

    2013-09-01

    The in vivo sublethal toxic effects (0.2 and 0.6 LD50) of topically applied imidacloprid on biochemical biomarkers in the land snail, Helix aspersa was examined. Biochemical perturbations were assessed by measuring the three enzymatic (Acetylcholinesterase, AChE; catalase, CAT and glutathione-S-transferase, GST) activities and three energy reserves (protein, glycogen and lipids) in the snails. Snail samples were taken from each sublethal dose and control groups at 1, 3 and 7 days after treatment. The results revealed that there were overall decrease in AChE activity as well as depletion of lipids and glycogen contents in the imidacloprid-treated snails compared to control groups. The CAT and GST activities of treated snails with the sublethal doses of imidacloprid were significantly higher than those of untreated controls along the three times of exposure. Moreover, an increase in the level of total proteins was observed in animals treated with 0.6 LD50 imidacloprid compared to control groups. The alterations in all tested biochemical perturbations were most pronounced with the 0.6 LD50 than 0.2 LD50. This study suggests that alterations of the enzyme activities and energy reserves in this species that could be useful as biomarkers of imidacloprid exposure in the evaluation of terrestrial impacts of this insecticide. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Gravity Vector Changes Induce Alterations in Nervous and Testicular Cells in Cultures and in Testis Slices

    Science.gov (United States)

    Uva, B.; Strollo, F.; Ricci, F.; Masini, M. A.

    Cultured astrocytes, neurons and testicular cells (myoid, germ, Sertoli, Leydig cells) as well as rat testes and testes'slices, were subjected to modeled microgravity using a three dimensional Random Positioning Machine (10-6G) for 5min, 30min, 1h, 24h and 32h. Parallel cell cultures and tissues were submitted to hypergravity using an hyperfuge (2.5G) for the same period of time. At the end of the rotations the cultures and tissues were fixed, the tissue was sectioned (5 micron). All the specimens were processed for immunohistochemical identification of microtubules, mitochondria, 3 hydroxysteroid dehydrogenase, 17 hydroxysteroid dehydrogenase, caspase 7, heat shock proteins and identification of DNA fragmentation. At 5min at modeled microgravity and hypergravity, the histology of the cells in culture and the tissues was altered, microtubules and mitochondria were disorganized. Numerous cells underwent apoptosis. Immunostaining for enzymes involved in ion transmembrane transport, as Na+/K+ATPase and cotransporter proteins, and in steroidogenesis diminished or was abolished. At 1h in modeled microgravity or hypergravity, HSPs were expressed and ion transport enzymes as well as steroidogenic enzymes were again immunostainable. These data show that microgravity and hypergravity cause only transient alterations, and tissues and cells in cultures are able to adapt to different gravity conditions.

  8. Altitude training induced alterations in erythrocyte rheological properties: a controlled comparison study in rats.

    Science.gov (United States)

    Bor-Kucukatay, Melek; Colak, Ridvan; Erken, Gülten; Kilic-Toprak, Emine; Kucukatay, Vural

    2014-01-01

    Altitude training is frequently used by athletes to improve sea-level performance. However, the objective benefits of altitude training are controversial. This study aimed to investigate the possible alterations in hemorheological parameters in response to altitude training. Sprague Dawley rats, were divided into 6 groups: live low-train low (LLTL), live high-train high (LHTH), live high-train low (LHTL) and their controls live high and low (LHALC), live high (LHC), live low (LLC). LHC and LHTH groups were exposed to hypoxia (15% O2, altitudes of 3000 m), 4 weeks. LHALC and LHTL were exposed to 12 hours hypoxia/normoxia per day, 4 weeks. Hypoxia was maintained by a hypoxic tent. The training protocol corresponded to 60-70% of maximal exercise capacity. Rats of training groups ran on treadmill for 20-30 min/day, 4 days/week, 4 weeks. Erythrocyte deformability of LHC group was increased compared to LHALC and LLC. Deformability of LHTH group was higher than LHALC and LLTL groups. No statistically significant alteration in erythrocyte aggregation parameters was observed. There were no significant relationships between RBC deformability and exercise performance. The results of this study show that, living (LHC) and training at altitude (LHTH) seems more advantageous in hemorheological point of view.

  9. POTENTIAL MECHANISMS RESPONSIBLE FOR CHLOROTRIAZINE-INDUCED ALTERATIONS IN CATECHOLAMINES IN PHEOCHROMOCYTOMA (PC12) CELLS

    Science.gov (United States)

    ABSTRACTPotential Mechanisms Responsible for Chlorotriazine-induced Changes in Catecholamine Metabolism in Pheochromocytoma (PC12) Cells*PARIKSHIT C. DAS1, WILLIAM K. McELROY2 , AND RALPH L. COOPER2+ 1Curriculum in Toxicology, University of North Carolina, Chape...

  10. In vivo cross-sectional characterization of cerebral alterations induced by intracerebroventricular administration of streptozotocin.

    Directory of Open Access Journals (Sweden)

    Audrey Kraska

    Full Text Available Cerebral aging is often associated with the occurrence of neurodegenerative diseases leading to dementia. Animal models are critical to elucidate mechanisms associated to dementia and to evaluate neuroprotective drugs. Rats that received intracerebroventricular injection of streptozotocin (icv-STZ have been reported as a model of dementia. In these animals, this drug induces oxidative stress and brain glucose metabolism impairments associated to insulin signal transduction failure. These mechanisms are reported to be involved in the pathogenesis of Alzheimer's disease and other dementia. Icv-STZ rats also display memory impairments. However, little is known about the precise location of the lesions induced by STZ administration. In this context, the present study characterized the cerebral lesions induced by two-doses of icv-STZ by using high-field magnetic resonance imaging to easily and longitudinally detect cerebral abnormalities and by using immunohistochemistry to evaluate neuronal loss and neuroinflammation (astrocytosis and microgliosis. We showed that, at high doses, icv-STZ induces severe and acute neurodegenerative lesions in the septum and corpus callosum. The lesions are associated with an inflammation process. They are less severe and more progressive at low doses. The relevance of high and low doses of icv-STZ to mimic dementia and evaluate new drugs is discussed in the final part of this article.

  11. Alteration of complex negative emotions induced by music in euthymic patients with bipolar disorder.

    Science.gov (United States)

    Choppin, Sabine; Trost, Wiebke; Dondaine, Thibaut; Millet, Bruno; Drapier, Dominique; Vérin, Marc; Robert, Gabriel; Grandjean, Didier

    2016-02-01

    Research has shown bipolar disorder to be characterized by dysregulation of emotion processing, including biases in facial expression recognition that is most prevalent during depressive and manic states. Very few studies have examined induced emotions when patients are in a euthymic phase, and there has been no research on complex emotions. We therefore set out to test emotional hyperreactivity in response to musical excerpts inducing complex emotions in bipolar disorder during euthymia. We recruited 21 patients with bipolar disorder (BD) in a euthymic phase and 21 matched healthy controls. Participants first rated their emotional reactivity on two validated self-report scales (ERS and MAThyS). They then rated their music-induced emotions on nine continuous scales. The targeted emotions were wonder, power, melancholy and tension. We used a specific generalized linear mixed model to analyze the behavioral data. We found that participants in the euthymic bipolar group experienced more intense complex negative emotions than controls when the musical excerpts induced wonder. Moreover, patients exhibited greater emotional reactivity in daily life (ERS). Finally, a greater experience of tension while listening to positive music seemed to be mediated by greater emotional reactivity and a deficit in executive functions. The heterogeneity of the BD group in terms of clinical characteristics may have influenced the results. Euthymic patients with bipolar disorder exhibit more complex negative emotions than controls in response to positive music. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion

    Science.gov (United States)

    Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter

    2015-01-01

    ABSTRACT The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions—T492S, N722D, R752K, and S1132F—were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. IMPORTANCE Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in

  13. Mesenchymal Stem Cells Induce Expression of CD73 in Human Monocytes In Vitro and in a Swine Model of Myocardial Infarction In Vivo

    OpenAIRE

    Marta Monguió-Tortajada; Marta Monguió-Tortajada; Santiago Roura; Santiago Roura; Santiago Roura; Carolina Gálvez-Montón; Carolina Gálvez-Montón; Marcella Franquesa; Marcella Franquesa; Antoni Bayes-Genis; Antoni Bayes-Genis; Antoni Bayes-Genis; Antoni Bayes-Genis; Francesc E. Borràs; Francesc E. Borràs

    2017-01-01

    The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP)/ADP to AMP and to adenosine (Ado), respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs) have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tiss...

  14. Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations-Protective Effects of the Oxygen Radical Scavenger Edaravone

    DEFF Research Database (Denmark)

    Hara, Naomi; Chijiiwa, Miyuki; Yara, Miki

    2015-01-01

    at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups-CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE...

  15. PAH-induced sublethal narcosis alters the bioenergetics and bioaccumulation of Fundulus heteroclitus

    Energy Technology Data Exchange (ETDEWEB)

    Merten, A. [NOAA Office of Response and Restoration, Hazardous Materials and Response, Seattle (United States); Beard, E.; Baker, B. [Univ. of Maryland, Solomons (United States)

    2004-09-15

    Accumulation of non-polar narcotic chemicals in organisms alters their metabolic rates and, therefore their energetic demands. Since exposure of these hydrophobic chemicals is primarily through the diet, we hypothesize that decreasing metabolic rates caused by accumulation of narcotics reduces feeding which, in turn, decreases further exposure to the narcotic. Thus, dietary exposure to and accumulation of narcotics may cause a negative feedback, reducing net bioaccumulation. The purpose of this short paper is to discuss the results of a long-term fish contaminant exposure study and to describe a fish bioenergetics model coupled to a PCBbioaccumulation model. The laboratory component consisted of exposing the estuarine fish Fundulus heteroclitus to environmentally-relevant levels of hydrophobic organic contaminants (HOCs) through their diet. We developed the model to further examine and understand the consequences of sublethal narcosis at both the individual and population levels of Fundulus heteroclitus.

  16. DNA methylation alterations induced by transient exposure of MCF-7 cells to maghemite nanoparticles.

    Science.gov (United States)

    Bonadio, Raphael S; Arcanjo, Ana Carolina; Lima, Emilia Cd; Vasconcelos, Alline T; Silva, Renata C; Horst, Frederico H; Azevedo, Ricardo B; Poças-Fonseca, Marcio José; F Longo, João Paulo

    2017-12-01

    To evaluate the DNA methylation profile of MCF-7 cells during and after the treatment with maghemite nanoparticles (MNP-CIT). Noncytotoxic MNP-CIT concentrations and cell morphology were evaluated by standard methods. DNA methylation was assessed by whole genome bisulfite sequencing. DNA methyltransferase (DNMT) genes expression was analyzed by qRT-PCR. A total of 30 and 60 µgFeml -1 MNP-CIT accumulated in cytoplasm but did not present cytotoxic effects. The overall percentage of DNA methylation was not affected, but 58 gene-associated regions underwent DNA methylation reprogramming, including genes related to cancer onset. DNMT transcript levels were also modulated. Transient exposure to MNP-CIT promoted epigenomic changes and altered the DNMT genes regulation in MCF-7 cells. These events should be considered for biomedical applications.

  17. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells

    Science.gov (United States)

    Mimeault, Murielle; Batra, Surinder K

    2013-01-01

    Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse. PMID:23301832

  18. Forced oscillation technique in the detection of smoking-induced respiratory alterations: diagnostic accuracy and comparison with spirometry.

    Science.gov (United States)

    Faria, Alvaro Camilo Dias; Costa, Alessandra Alves da; Lopes, Agnaldo Jose; Jansen, Jose Manoel; Melo, Pedro Lopes de

    2010-01-01

    Detection of smoking effects is of utmost importance in the prevention of cigarette-induced chronic airway obstruction. The forced oscillation technique offers a simple and detailed approach to investigate the mechanical properties of the respiratory system. However, there have been no data concerning the use of the forced oscillation technique to evaluate respiratory mechanics in groups with different degrees of tobacco consumption. (1) to evaluate the ability of the forced oscillation technique to detect smoking-induced respiratory alterations, with special emphasis on early alterations; and (2) to compare the diagnostic accuracy of the forced oscillation technique and spirometric parameters. One hundred and seventy subjects were divided into five groups according to the number of pack-years smoked: four groups of smokers classified as 60 pack-years and a control group. The four groups of smokers were compared with the control group using receiver operating characteristic (ROC) curves. The early adverse effects of smoking in the group with technique parameters. In this group, the comparisons of the ROC curves showed significantly better diagnostic accuracy (p technique parameters. On the other hand, in groups of 20-39, 40-59, and > 60 pack-years, the diagnostic performance of the forced oscillation technique was similar to that observed with spirometry. This study revealed that forced oscillation technique parameters were able to detect early smoking-induced respiratory involvement when pathologic changes are still potentially reversible. These findings support the use of the forced oscillation technique as a versatile clinical diagnostic tool in helping with chronic obstructive lung disease prevention, diagnosis, and treatment.

  19. Neonicotinoid insecticides alter induced defenses and increase susceptibility to spider mites in distantly related crop plants.

    Directory of Open Access Journals (Sweden)

    Adrianna Szczepaniec

    Full Text Available Chemical suppression of arthropod herbivores is the most common approach to plant protection. Insecticides, however, can cause unintended, adverse consequences for non-target organisms. Previous studies focused on the effects of pesticides on target and non-target pests, predatory arthropods, and concomitant ecological disruptions. Little research, however, has focused on the direct effects of insecticides on plants. Here we demonstrate that applications of neonicotinoid insecticides, one of the most important insecticide classes worldwide, suppress expression of important plant defense genes, alter levels of phytohormones involved in plant defense, and decrease plant resistance to unsusceptible herbivores, spider mites Tetranychus urticae (Acari: Tetranychidae, in multiple, distantly related crop plants.Using cotton (Gossypium hirsutum, corn (Zea mays and tomato (Solanum lycopersicum plants, we show that transcription of phenylalanine ammonia lyase, coenzyme A ligase, trypsin protease inhibitor and chitinase are suppressed and concentrations of the phytohormone OPDA and salicylic acid were altered by neonicotinoid insecticides. Consequently, the population growth of spider mites increased from 30% to over 100% on neonicotinoid-treated plants in the greenhouse and by nearly 200% in the field experiment.Our findings are important because applications of neonicotinoid insecticides have been associated with outbreaks of spider mites in several unrelated plant species. More importantly, this is the first study to document insecticide-mediated disruption of plant defenses and link it to increased population growth of a non-target herbivore. This study adds to growing evidence that bioactive agrochemicals can have unanticipated ecological effects and suggests that the direct effects of insecticides on plant defenses should be considered when the ecological costs of insecticides are evaluated.

  20. Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Llorens, Franc; Thüne, Katrin; Sikorska, Beata; Schmitz, Matthias; Tahir, Waqas; Fernández-Borges, Natalia; Cramm, Maria; Gotzmann, Nadine; Carmona, Margarita; Streichenberger, Nathalie; Michel, Uwe; Zafar, Saima; Schuetz, Anna-Lena; Rajput, Ashish; Andréoletti, Olivier; Bonn, Stefan; Fischer, Andre; Liberski, Pawel P; Torres, Juan Maria; Ferrer, Isidre; Zerr, Inga

    2017-04-27

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP Sc ). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca 2+ ) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca 2+ responsive genes in sCJD brain tissue, accompanied by two Ca 2+ -dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrP Sc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca 2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention.

  1. Vimentin and laminin are altered on cheek pouch microvessels of streptozotocin-induced diabetic hamsters

    Directory of Open Access Journals (Sweden)

    Jemima Fuentes R Silva

    2011-01-01

    Full Text Available OBJECTIVE: Normal endothelial cells respond to shear stress by elongating and aligning in the direction of fluid flow. Hyperglycemia impairs this response and contributes to microvascular complications, which result in deleterious effects to the endothelium. This work aimed to evaluate cheek pouch microvessel morphological characteristics, reactivity, permeability, and expression of cytoskeleton and extracellular matrix components in hamsters after the induction of diabetes with streptozotocin. METHODS: Syrian golden hamsters (90-130 g were injected with streptozotocin (50 mg/kg, i.p. or vehicle either 6 (the diabetes mellitus 6 group or 15 (the diabetes mellitus 15 group days before the experiment. Vascular dimensions and density per area of vessels were determined by morphometric and stereological measurements. Changes in blood flow were measured in response to acetylcholine, and plasma extravasation was measured by the number of leakage sites. Actin, talin, α-smooth muscle actin, vimentin, type IV collagen, and laminin were detected by immunohistochemistry and assessed through a semiquantitative scoring system. RESULTS: There were no major alterations in the lumen, wall diameters, or densities of the examined vessels. Likewise, vascular reactivity and permeability were not altered by diabetes. The arterioles demonstrated increased immunoreactivity to vimentin and laminin in the diabetes mellitus 6 and diabetes mellitus 15 groups. DISCUSSION: Antibodies against laminin and vimentin inhibit branching morphogenesis in vitro. Therefore, laminin and vimentin participating in the structure of the focal adhesion may play a role in angiogenesis. CONCLUSIONS: Our results indicated the existence of changes related to cell-matrix interactions, which may contribute to the pathological remodeling that was already underway one week after induction of experimental diabetes.

  2. Mapping transient hyperventilation induced alterations with estimates of the multi-scale dynamics of BOLD signal.

    Directory of Open Access Journals (Sweden)

    Vesa J Kiviniemi

    2009-07-01

    Full Text Available Temporal blood oxygen level dependent (BOLD contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD trends of the form 1/f α. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow.

  3. MafB antagonizes phenotypic alteration induced by GM-CSF in microglia

    Energy Technology Data Exchange (ETDEWEB)

    Koshida, Ryusuke, E-mail: rkoshida-myz@umin.ac.jp; Oishi, Hisashi, E-mail: hoishi@md.tsukuba.ac.jp; Hamada, Michito; Takahashi, Satoru

    2015-07-17

    Microglia are tissue-resident macrophages which are distributed throughout the central nervous system (CNS). Recent studies suggest that microglia are a unique myeloid population distinct from peripheral macrophages in terms of origin and gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine regulating myeloid development, has been shown to stimulate proliferation and alter phenotype of microglia in vitro. However, how its signaling is modulated in microglia is poorly characterized. MafB, a bZip transcriptional factor, is highly expressed in monocyte-macrophage lineage cells including microglia, although its role in microglia is largely unknown. We investigated the crosstalk between GM-CSF signaling and MafB by analyzing primary microglia. We found that Mafb-deficient microglia grew more rapidly than wild-type microglia in response to GM-CSF. Moreover, the expression of genes associated with microglial differentiation was more downregulated in Mafb-deficient microglia cultured with GM-CSF. Notably, such differences between the genotypes were not observed in the presence of M-CSF. In addition, we found that Mafb-deficient microglia cultured with GM-CSF barely extended their membrane protrusions, probably due to abnormal activation of RhoA, a key regulator of cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative regulator of GM-CSF signaling in microglia. These findings could provide new insight into the modulation of cytokine signaling by transcription factors in microglia. - Highlights: • GM-CSF alters the phenotype of microglia in vitro more potently than M-CSF. • Transcription factor MafB antagonizes the effect of GM-CSF on microglia in vitro. • MafB deficiency leads to RhoA activation in microglia in response to GM-CSF. • We show for the first time the function of MafB in microglia.

  4. Exposure and Figure Out of Climate Induced Alterations in the Wetlands of Banglades

    Science.gov (United States)

    Siddiquee, S. A.; Rahman, M. Z.

    2015-12-01

    Unique geographic location and geo-morphological conditions of Bangladesh have made the wetlands of this country one of the most vulnerable to climate change. Wetland plays a crucial role in maintaining the ecological balance of ecosystems and cultural figures and which occupy around 50% of the area. Drought, excessive temperature, mountain snowfields and glaciers melting, riverbank erosion, salinity intrusion, flashflood, storm surges, higher water temperatures, precipitation anomalies, coastal cyclones, seasonal anomalies and extremes are main threats to the wetland ecosystem. Enhanced UV-B radiation and increased summer precipitation will significantly increase dissolved organic carbon concentrations altering major biogeochemical cycles and also will result into the expansion of range for many invasive aquatic weeds. Generally, rising temperature will lower water quality through a fall in oxygen concentrations, release of phosphorus from sediments, increased thermal stability, and altered mixing patterns. As a result biodiversity is getting degraded, many species of flora and fauna are getting threatened, and wetland-based ecosystem is getting degenerated. At the same time, the living conditions of local people are deteriorating as livelihoods, socioeconomic institutions, and extensive cultural values as well. For conserving and managing wetlands technology, legislation, educational knowledge, action plan strategy and restoration practices are required. In order to address the human needs in the changing climate community-based adaptation approaches and wetland restoration, practices had been taken in almost every type of wetlands in Bangladesh. Therefore, Bangladesh now needs a comprehensive strategy and integrated system combining political, economic, social, technological approaches and institutional supports to address sustainable wetland restoration, conservation and the newly added crisis, climate change.

  5. Consistent and heritable alterations of DNA methylation are induced by tissue culture in maize.

    Science.gov (United States)

    Stelpflug, Scott C; Eichten, Steven R; Hermanson, Peter J; Springer, Nathan M; Kaeppler, Shawn M

    2014-09-01

    Plants regenerated from tissue culture and their progenies are expected to be identical clones, but often display heritable molecular and phenotypic variation. We characterized DNA methylation patterns in callus, primary regenerants, and regenerant-derived progenies of maize using immunoprecipitation of methylated DNA (meDIP) to assess the genome-wide frequency, pattern, and heritability of DNA methylation changes. Although genome-wide DNA methylation levels remained similar following tissue culture, numerous regions exhibited altered DNA methylation levels. Hypomethylation events were observed more frequently than hypermethylation following tissue culture. Many of the hypomethylation events occur at the same genomic sites across independent regenerants and cell lines. The DNA methylation changes were often heritable in progenies produced from self-pollination of primary regenerants. Methylation changes were enriched in regions upstream of genes and loss of DNA methylation at promoters was associated with altered expression at a subset of loci. Differentially methylated regions (DMRs) found in tissue culture regenerants overlap with the position of naturally occurring DMRs more often than expected by chance with 8% of tissue culture hypomethylated DMRs overlapping with DMRs identified by profiling natural variation, consistent with the hypotheses that genomic stresses similar to those causing somaclonal variation may also occur in nature, and that certain loci are particularly susceptible to epigenetic change in response to these stresses. The consistency of methylation changes across regenerants from independent cultures suggests a mechanistic response to the culture environment as opposed to an overall loss of fidelity in the maintenance of epigenetic states. Copyright © 2014 by the Genetics Society of America.

  6. Neonicotinoid Insecticides Alter Induced Defenses and Increase Susceptibility to Spider Mites in Distantly Related Crop Plants

    Science.gov (United States)

    Szczepaniec, Adrianna; Raupp, Michael J.; Parker, Roy D.; Kerns, David; Eubanks, Micky D.

    2013-01-01

    Background Chemical suppression of arthropod herbivores is the most common approach to plant protection. Insecticides, however, can cause unintended, adverse consequences for non-target organisms. Previous studies focused on the effects of pesticides on target and non-target pests, predatory arthropods, and concomitant ecological disruptions. Little research, however, has focused on the direct effects of insecticides on plants. Here we demonstrate that applications of neonicotinoid insecticides, one of the most important insecticide classes worldwide, suppress expression of important plant defense genes, alter levels of phytohormones involved in plant defense, and decrease plant resistance to unsusceptible herbivores, spider mites Tetranychus urticae (Acari: Tetranychidae), in multiple, distantly related crop plants. Methodology/Principal Findings Using cotton (Gossypium hirsutum), corn (Zea mays) and tomato (Solanum lycopersicum) plants, we show that transcription of phenylalanine amonia lyase, coenzyme A ligase, trypsin protease inhibitor and chitinase are suppressed and concentrations of the phytohormone OPDA and salicylic acid were altered by neonicotinoid insecticides. Consequently, the population growth of spider mites increased from 30% to over 100% on neonicotinoid-treated plants in the greenhouse and by nearly 200% in the field experiment. Conclusions/Significance Our findings are important because applications of neonicotinoid insecticides have been associated with outbreaks of spider mites in several unrelated plant species. More importantly, this is the first study to document insecticide-mediated disruption of plant defenses and link it to increased population growth of a non-target herbivore. This study adds to growing evidence that bioactive agrochemicals can have unanticipated ecological effects and suggests that the direct effects of insecticides on plant defenses should be considered when the ecological costs of insecticides are evaluated. PMID

  7. Geomorphic Change Induced by 100 years of Flow Alteration on the Diamond Fork River, Central Utah

    Science.gov (United States)

    Jones, J.; Belmont, P.; Wilcock, P. R.

    2017-12-01

    Changes in hydrology and sediment supply affect the form of rivers. The rate of change of fluvial form is controlled by a variety of factors, including valley confinement, sediment size, and antecedent condition. The Diamond Fork River in central Utah has been altered by trans-basin flows delivered from the Colorado River system for over a century. Beginning in 1915, water used for irrigation was delivered through a tributary, Sixth Water Creek, with daily summer flows regularly exceeding the 50 - 100 year flood. Elevated flows caused drastic geomorphic change - resulting in incision and widening of the channel, and the destruction of riparian vegetation. Beginning in 1997, the outlet for the trans-basin diversion was moved downstream on Sixth Water, bypassing a large landslide, and flows were drastically reduced in 2004 through management actions. We delineated eight distinct process domains for the Sixth Water-Diamond Fork system and examined the response of each process domain to the altered flow and sediment regimes through the analysis of aerial photographs and repeat cross-sections. We measured a variety of channel metrics, including channel width, areal extent of bars and islands, and sinuosity in ArcGIS. Results indicate that unconfined reaches that were wide and braided during the period of elevated flows have narrowed to become single threaded and meandering in response to the reduced flows. Confined reaches have experienced minor changes since the reduction in flows, suggesting that confinement is a primary control on the degree of channel response. These findings and complimentary studies will provide managers of Sixth Water and Diamond Fork with a greater understanding of the physical response of the streams, and the resulting effects on ecological communities.

  8. Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice.

    Science.gov (United States)

    Li, Jibiao; Matye, David J; Wang, Yifeng; Li, Tiangang

    2017-04-01

    Sortilin 1 (Sort1) is a trafficking receptor that has been implicated in the regulation of plasma cholesterol in humans and mice. Here, we use metabolomics and hyperinsulinemic-euglycemic clamp approaches to obtain further understanding of the in vivo effects of Sort1 deletion on diet-induced obesity as well as on adipose lipid and glucose metabolism. Results show that Sort1 knockout (KO) does not affect Western diet-induced obesity nor adipose fatty acid and ceramide concentrations. Under the basal fasting state, chow-fed Sort1 KO mice have decreased adipose glycolytic metabolites, but Sort1 deletion does not affect insulin-stimulated tissue glucose uptake during the insulin clamp. These results suggest that Sort1 loss-of-function in vivo does not affect obesity development, but differentially modulates adipose glucose metabolism under fasting and insulin-stimulated states. © 2017 Federation of European Biochemical Societies.

  9. Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

    DEFF Research Database (Denmark)

    Genster, Ninette; Østrup, Olga; Schjalm, Camilla

    2017-01-01

    Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested....... Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation....

  10. Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis.

    Directory of Open Access Journals (Sweden)

    Takeshi Okinami

    Full Text Available Lower urinary tract symptoms (LUTS include storage, voiding and post-micturition symptoms, featuring many urological diseases. Storage symptoms are the most frequent among these and associated with overactive bladder and non-bacterial bladder inflammation such as interstitial cystitis/bladder pain syndrome (IC/BPS. Gap junction, a key regulator of hyperactive conditions in the bladder, has been reported to be involved in pathological bladder inflammation. Here we report involvement of gap junction in the etiology of storage symptoms in bladder inflammation. In this study, cyclophosphamide-induced cystitis was adapted as a model of bladder inflammation. Cyclophosphamide-treated mice showed typical storage symptoms including increased urinary frequency and reduced bladder capacity, with concurrent up-regulation of connexin 43 (GJA1, one of the major gap junction proteins in the bladder. In isometric tension study, bladder smooth muscle strips taken from the treated mice showed more pronounced spontaneous contraction than controls, which was attenuated by carbenoxolone, a gap junction inhibitor. In voiding behavior studies, the storage symptoms in the treated mice characterized by frequent voiding were alleviated by 18α-glycyrrhetinic acid, another gap junction inhibitor. These results demonstrate that cyclophosphamide-induced mouse model of cystitis shows clinical storage symptoms related with bladder inflammation and that gap junction in the bladder may be a key molecule of these storage symptoms. Therefore, gap junction in the bladder might be an alternative therapeutic target for storage symptoms in bladder inflammation.

  11. Alteration of complex negative emotions induced by music in euthymic patients with bipolar disorder

    OpenAIRE

    Choppin , Sabine; Trost , Wiebke; Dondaine , Thibaut; Millet , Bruno; Drapier , Dominique; Vérin , Marc; Robert , Gabriel; Grandjean , Didier

    2016-01-01

    Inversion erronée des noms des 2 premiers auteurs dans la version postprint publiée par la revue. Wiebke Trost est 1er auteur, affiliée au Swiss Center for Affective Sciences ; Sabine Choppin est 2e auteur.; International audience; Background Research has shown bipolar disorder to be characterized by dysregulation of emotion processing, including biases in facial expression recognition that is most prevalent during depressive and manic states. Very few studies have examined induced emotions w...

  12. Altered Expression of Signaling Genes in Jurkat Cells upon FTY720 Induced Apoptosis

    Directory of Open Access Journals (Sweden)

    Shaoheng He

    2010-09-01

    Full Text Available FTY720, a novel immunosuppressant, has a marked activity in decreasing peripheral blood T lymphocytes upon oral administration. Recent investigations suggest that the action of FTY720 on lymphocytes may result from its ability to induce cell apoptosis. However, the cell signaling mechanism involved in the FTY720-induced cell apoptosis remains unclear. Here we examined the apoptotic signal pathways mediated by FTY720 in Jurkat cells using microarray analysis. The results showed that FTY720 can induce Jurkat cell apoptosis in a dose and time dependent manner as assessed by cell viability, Hoechst 33258 staining, Annexin V binding and DNA fragmentation tests. cDNA microarray analysis showed that 10 µM of FTY720 up-regulated 54 and down-regulated 10 genes in Jurkat cells among the 458 apoptotic genes examined following the 6 h incubation period. At least five-fold increased expression of modulator of apoptosis-1 (MOAP-1, vascular endothelial growth factor (VEGF, tumor necrosis factor receptor-associated factors (TRAF 6, Caspase 2 (CASP 2, E2F transcription factor 1 (E2F 1 and Casapse 5 (CASP 5 genes was observed in microarray analyses; these results were confirmed with reverse transcription polymerase chain reaction (RT-PCR examination. Our findings suggest that the mitochondria related signaling pathways are the key pathways involved in the FTY720-induced apoptosis in Jurkat cells. And our results provide a new insight into the mechanism of FTY720, which allows us to draw the first simple diagram showing the potential pathways mediated by FTY720.

  13. Altered expression of signaling genes in Jurkat cells upon FTY720 induced apoptosis.

    Science.gov (United States)

    Wang, Fang; Tan, Wenfeng; Guo, Dunming; Zhu, Xiaomin; Qian, Keqing; He, Shaoheng

    2010-09-02

    FTY720, a novel immunosuppressant, has a marked activity in decreasing peripheral blood T lymphocytes upon oral administration. Recent investigations suggest that the action of FTY720 on lymphocytes may result from its ability to induce cell apoptosis. However, the cell signaling mechanism involved in the FTY720-induced cell apoptosis remains unclear. Here we examined the apoptotic signal pathways mediated by FTY720 in Jurkat cells using microarray analysis. The results showed that FTY720 can induce Jurkat cell apoptosis in a dose and time dependent manner as assessed by cell viability, Hoechst 33258 staining, Annexin V binding and DNA fragmentation tests. cDNA microarray analysis showed that 10 μM of FTY720 up-regulated 54 and down-regulated 10 genes in Jurkat cells among the 458 apoptotic genes examined following the 6 h incubation period. At least five-fold increased expression of modulator of apoptosis-1 (MOAP-1), vascular endothelial growth factor (VEGF), tumor necrosis factor receptor-associated factors (TRAF 6), Caspase 2 (CASP 2), E2F transcription factor 1 (E2F 1) and Casapse 5 (CASP 5) genes was observed in microarray analyses; these results were confirmed with reverse transcription polymerase chain reaction (RT-PCR) examination. Our findings suggest that the mitochondria related signaling pathways are the key pathways involved in the FTY720-induced apoptosis in Jurkat cells. And our results provide a new insight into the mechanism of FTY720, which allows us to draw the first simple diagram showing the potential pathways mediated by FTY720.

  14. Neuropathic Pain-like Alterations in Muscle Nociceptor Function Associated with Vibration-induced Muscle Pain

    OpenAIRE

    Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

    2010-01-01

    We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense and long-lasting barrage of actio...

  15. Induced polyploidy dramatically increases the size and alters the shape of fruit in Actinidia chinensis

    Science.gov (United States)

    Wu, Jin-Hu; Ferguson, A. Ross; Murray, Brian G.; Jia, Yilin; Datson, Paul M.; Zhang, Jingli

    2012-01-01

    Background and Aims Some otherwise promising selections of Actinidia chinensis (kiwifruit) have fruit that are too small for successful commercialization. We have therefore made the first detailed study in diploid kiwifruit of the effects of chromosome doubling induced by colchicine on fruit size, shape and crop loading. Methods Flow cytometric analysis of young leaves and chromosome analysis of flower buds and root tips was used to confirm the stability of induced autotetraploids. Fruit weight, size and crop load were measured in the third year after planting in the field and for three consecutive years. DNA fingerprinting was used to confirm the origin of the material. Key Results There was a very significant increase in fruit size in induced autotetraploids of different genotypes of A. chinensis. With the commercially important diploid cultivar ‘Hort16A’, most regenerants, Type A plants, had fruit which were much the same shape as fruit of the diploid but, at the same fruit load, were much larger and heavier. Some regenerants, Type B plants, produced fruit similar to ‘fasciated’ fruit. Fruit of the autotetraploids induced from three female red-fleshed A. chinensis selections were also 50–60 % larger than fruit of their diploid progenitors. The main increase in fruit dimensions was in their diameters. These improved fruit characteristics were stable over several seasons. Conclusions Chromosome doubling has been shown to increase significantly fruit size in autotetraploid A. chinensis, highlighting the considerable potential of this technique to produce new cultivars with fruit of adequate size. Other variants with differently shaped fruit were also produced but the genetic basis of this variation remains to be elucidated. Autoploids of other Actinidia species with commercial potential may also show improved fruit characteristics, opening up many new possibilities for commercial development. PMID:21980192

  16. Chloroquine attenuates paraquat-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis.

    Science.gov (United States)

    Shen, Haitao; Wu, Na; Wang, Yu; Zhao, Hongyu; Zhang, Lichun; Li, Tiegang; Zhao, Min

    2017-05-01

    Paraquat is one of the most extensively used herbicides and has high toxicity for humans and animals. However, there is no effective treatment for paraquat poisoning. The aim of the present study was to evaluate the effects of chloroquine on paraquat-induced lung injury in mice. Mice received a single intraperitoneal injection of paraquat and a daily intraperitoneal injection of the indicated dosages of chloroquine or dexamethasone. The histological changes, inflammation and oxidative stress in the lungs were examined at day 3, and the degree of pulmonary fibrosis was examined at day 28. H&E staining showed that chloroquine markedly attenuated lung injury induced by paraquat. In addition, the inflammatory responses induced by paraquat were inhibited after treatment with chloroquine, as indicated by the decreased number of leukocytes, the reduced levels of TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid, the reduced NO content, and downregulation of iNOS expression in lung tissues. No different effect was found between high-dose chloroquine and dexamethasone. Additionally, the treatment with chloroquine increased the activity of SOD and decreased the level of MDA in the lung tissues. The expressions of the anti-oxidative proteins, Nrf2, HO-1 and NQO1, were also upregulated by chloroquine treatment. The high-dose chloroquine was more effective than dexamethasone in its anti-oxidation ability. Finally, the results of Masson's staining illustrated that chloroquine markedly attenuated fibrosis in the paraquat-exposed lungs. Immunohistochemistry staining showed that the expressions of the pro-fibrotic proteins TGF-β and α-SMA were downregulated after treatment with chloroquine. In conclusion, chloroquine effectively attenuated paraquat-induced lung injury in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells.

    Science.gov (United States)

    Pan, Shi; Sharma, Pawan; Shah, Sushrut D; Deshpande, Deepak A

    2017-07-01

    Airway remodeling, including increased airway smooth muscle (ASM) mass, is a hallmark feature of asthma and COPD. We previously identified the expression of bitter taste receptors (TAS2Rs) on human ASM cells and demonstrated that known TAS2R agonists could promote ASM relaxation and bronchodilation and inhibit mitogen-induced ASM growth. In this study, we explored cellular mechanisms mediating the antimitogenic effect of TAS2R agonists on human ASM cells. Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in inhibition of cell survival, which was largely reversed by bafilomycin A1, an autophagy inhibitor. Transmission electron microscope studies demonstrated the presence of double-membrane autophagosomes and deformed mitochondria. In ASM cells, TAS2R agonists decreased mitochondrial membrane potential and increased mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like protein 1 (DLP1) reversed TAS2R agonist-induced mitochondrial membrane potential change and attenuated mitochondrial fragmentation and cell death. Furthermore, the expression of mitochondrial protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) and mitochondrial localization of DLP1 were significantly upregulated by TAS2R agonists. More importantly, inhibiting Bnip3 mitochondrial localization by dominant-negative Bnip3 significantly attenuated cell death induced by TAS2R agonist. Collectively the TAS2R agonists chloroquine and quinine modulate mitochondrial structure and function, resulting in ASM cell death. Furthermore, Bnip3 plays a central role in TAS2R agonist-induced ASM functional changes via a mitochondrial pathway. These findings further establish the cellular mechanisms of antimitogenic effects of TAS2R agonists and identify a novel class of receptors and pathways that can be targeted to mitigate airway remodeling as well as bronchoconstriction in obstructive airway diseases. Copyright © 2017 the American Physiological

  18. Neuropathic pain-like alterations in muscle nociceptor function associated with vibration-induced muscle pain.

    Science.gov (United States)

    Chen, Xiaojie; Green, Paul G; Levine, Jon D

    2010-11-01

    We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ∼15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ∼44Hz during a 1min suprathreshold stimulus) much greater than that has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration-exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  19. Dopamine and paraquat enhance α-synuclein-induced alterations in membrane conductance

    Science.gov (United States)

    Feng, Li Rebekah; Maguire-Zeiss, Kathleen A.

    2011-01-01

    We have previously demonstrated that α-synuclein overexpression increases the membrane conductance of dopaminergic-like cells. Although α-synuclein is thought to play a central role in the pathogenesis of several neurodegenerative diseases including Parkinson’s disease, multiple system atrophy and diffuse Lewy body disease the mechanism of action is not completely understood. In this study we sought to determine whether multiple factors act together with α-synuclein to engender cell vulnerability through an augmentation of membrane conductance. Here we employed a cell model that mimics dopaminergic neurons coupled with α-synuclein overexpression and oxidative stressors. We demonstrate an enhancement of α-synuclein-induced toxicity in the presence of combined treatment with dopamine and paraquat, two molecules known to incite oxidative stress. In addition we show that combined dopamine and paraquat treatment increases the expression of heme oxygenase-1, an antioxidant response protein. Finally, we demonstrate for the first time that combined treatment of dopaminergic cells with paraquat and dopamine enhances α-synuclein-induced leak channel properties resulting in increased membrane conductance. Importantly, these increases are most robust when both paraquat and dopamine are present suggesting the need for multiple oxidative insults to augment α-synuclein-induced disruption of membrane integrity. PMID:21735318

  20. Arsenite induces apoptosis in human mesenchymal stem cells by altering Bcl-2 family proteins and by activating intrinsic pathway

    International Nuclear Information System (INIS)

    Yadav, Santosh; Shi Yongli; Wang Feng; Wang He

    2010-01-01

    Purpose: Environmental exposure to arsenic is an important public health issue. The effects of arsenic on different tissues and organs have been intensively studied. However, the effects of arsenic on bone marrow mesenchymal stem cells (MSCs) have not been reported. This study is designed to investigate the cell death process caused by arsenite and its related underlying mechanisms on MSCs. The rationale is that absorbed arsenic in the blood circulation can reach to the bone marrow and may affect the cell survival of MSCs. Methods: MSCs of passage 1 were purchased from Tulane University, grown till 70% confluency level and plated according to the experimental requirements followed by treatment with arsenite at various concentrations and time points. Arsenite (iAs III ) induced cytotoxic effects were confirmed by cell viability and cell cycle analysis. For the presence of canonic apoptosis markers; DNA damage, exposure of intramembrane phosphotidylserine, protein and m-RNA expression levels were analyzed. Results: iAs III induced growth inhibition, G2-M arrest and apoptotic cell death in MSCs, the apoptosis induced by iAs III in the cultured MSCs was, via altering Bcl-2 family proteins and by involving intrinsic pathway. Conclusion: iAs III can induce apoptosis in bone marrow-derived MSCs via Bcl-2 family proteins, regulating intrinsic apoptotic pathway. Due to the multipotency of MSC, acting as progenitor cells for a variety of connective tissues including bone, adipose, cartilage and muscle, these effects of arsenic may be important in assessing the health risk of the arsenic compounds and understanding the mechanisms of arsenic-induced harmful effects.

  1. Microbiota in fermented feed and swine gut.

    Science.gov (United States)

    Wang, Cheng; Shi, Changyou; Zhang, Yu; Song, Deguang; Lu, Zeqing; Wang, Yizhen

    2018-04-01

    Development of alternatives to antibiotic growth promoters (AGP) used in swine production requires a better understanding of their impacts on the gut microbiota. Supplementing fermented feed (FF) in swine diets as a novel nutritional strategy to reduce the use of AGP and feed price, can positively affect the porcine gut microbiota, thereby improving pig productivities. Previous studies have noted the potential effects of FF on the shift in benefit of the swine microbiota in different regions of the gastrointestinal tract (GIT). The positive influences of FF on swine gut microbiota may be due to the beneficial effects of both pre- and probiotics. Necessarily, some methods should be adopted to properly ferment and evaluate the feed and avoid undesired problems. In this mini-review, we mainly discuss the microbiota in both fermented feed and swine gut and how FF influences swine gut microbiota.

  2. Effect of St. John's Wort (Hypericum perforatum treatment on restraint stress-induced behavioral and biochemical alteration in mice

    Directory of Open Access Journals (Sweden)

    Prakash Atish K

    2010-05-01

    Full Text Available Abstract Background A stressful stimulus is a crucial determinant of health and disease. Antidepressants are used to manage stress and their related effects. The present study was designed to investigate the effect of St. John's Wort (Hypericum perforatum in restraint stress-induced behavioral and biochemical alterations in mice. Methods Animals were immobilized for a period of 6 hr. St. John's Wort (50 and 100 mg/kg was administered 30 minutes before the animals were subjecting to acute immobilized stress. Various behavioral tests parameters for anxiety, locomotor activity and nociceptive threshold were assessed followed by biochemical assessments (malondialdehyde level, glutathione, catalase, nitrite and protein subsequently. Results 6-hr acute restraint stress caused severe anxiety like behavior, antinociception and impaired locomotor activity as compared to unstressed animals. Biochemical analyses revealed an increase in malondialdehyde, nitrites concentration, depletion of reduced glutathione and catalase activity as compared to unstressed animal brain. Five days St. John's Wort treatment in a dose of 50 mg/kg and 100 mg/kg significantly attenuated restraint stress-induced behavioral (improved locomotor activity, reduced tail flick latency and antianxiety like effect and oxidative damage as compared to control (restraint stress. Conclusion Present study highlights the modest activity of St. John's Wort against acute restraint stress induced modification.

  3. Obesity Induces Artery-Specific Alterations: Evaluation of Vascular Function and Inflammatory and Smooth Muscle Phenotypic Markers

    Directory of Open Access Journals (Sweden)

    Antonio Garcia Soares

    2017-01-01

    Full Text Available Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA and thoracic aorta (TA. Endothelium-dependent relaxation in SMA and TA was not modified by obesity. In contrast, contraction induced by depolarization and contractile agonists was reduced in SMA, whereas only contraction induced by adrenergic agonist was reduced in TA of obese mice. Obesity increased the mRNA expression of pro- and anti-inflammatory cytokines in SMA and TA. The expression of genes necessary for maintaining contractile ability was increased by obesity, but the increase was more pronounced in TA. Collagen deposition was increased in SMA, but not in TA, of obese mice. Although the endothelial function was still preserved, the SM of the two artery types was impaired by obesity, but the impairment was higher in SMA, which could be associated with SM phenotypic changes.

  4. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

    Directory of Open Access Journals (Sweden)

    Alessandro Ieraci

    2016-01-01

    Full Text Available Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

  5. Role of macrophages in the altered epithelial function during a type 2 immune response induced by enteric nematode infection.

    Directory of Open Access Journals (Sweden)

    Luigi Notari

    Full Text Available Parasitic enteric nematodes induce a type 2 immune response characterized by increased production of Th2 cytokines, IL-4 and IL-13, and recruitment of alternatively activated macrophages (M2 to the site of infection. Nematode infection is associated with changes in epithelial permeability and inhibition of sodium-linked glucose absorption, but the role of M2 in these effects is unknown. Clodronate-containing liposomes were administered prior to and during nematode infection to deplete macrophages and prevent the development of M2 in response to infection with Nippostrongylus brasiliensis. The inhibition of epithelial glucose absorption that is associated with nematode infection involved a macrophage-dependent reduction in SGLT1 activity, with no change in receptor expression, and a macrophage-independent down-regulation of GLUT2 expression. The reduced transport of glucose into the enterocyte is compensated partially by an up-regulation of the constitutive GLUT1 transporter consistent with stress-induced activation of HIF-1α. Thus, nematode infection results in a "lean" epithelial phenotype that features decreased SGLT1 activity, decreased expression of GLUT2 and an emergent dependence on GLUT1 for glucose uptake into the enterocyte. Macrophages do not play a role in enteric nematode infection-induced changes in epithelial barrier function. There is a greater contribution, however, of paracellular absorption of glucose to supply the energy demands of host resistance. These data provide further evidence of the ability of macrophages to alter glucose metabolism of neighboring cells.

  6. A modelling framework to evaluate human-induced alterations of network sediment connectivity and quantify their unplanned adverse impact

    Science.gov (United States)

    Bizzi, S.; Schmitt, R. J. P.; Giuliani, M.; Castelletti, A.

    2016-12-01

    World-wide human-induced alterations of sediment transport, e.g. due to dams, sand and gravel mining along rivers and channel maintenance, translated into geomorphic changes, which have had major effects on ecosystem integrity, human livelihoods, ultimately negatively impacting also on the expected benefit from building water infrastructures. Despite considerable recent advances in modelling basin-scale hydrological and geomorphological processes, our ability to quantitatively simulate network sediment transport, foresee effects of alternative scenarios of human development on fluvial morpho-dynamics, and design anticipatory planning adaptation measures is still limited. In this work, we demonstrate the potential of a novel modelling framework called CASCADE (CAtchment SEdiment Connectivity And Delivery (Schmitt et al., 2016)) to characterize sediment connectivity at the whole river network scale, predict the disturbing effect of dams on the sediment transport, and quantify the associated loss with respect to the level of benefits that provided the economic justification for their development. CASCADE allows tracking the fate of a sediment from its source to its multiple sinks across the network. We present the results from two major, transboundary river systems (3S and Red River) in South-East Asia. We first discuss the ability of CASCADE to properly represent sediment connectivity at the network scale using available remote sensing data and information from monitoring networks. Secondly, we assess the impacts on sediment connectivity induced by existing and planned dams in the 3S and Red River basins and compare these alterations with revenues in terms of hydropower production. CASCADE outputs support a broader understanding of sediment connectivity tailored for water management issues not yet available, and it is suitable to enrich assessments of food-energy-water nexus. The model framework can be embedded into the design of optimal siting and sizing of water

  7. Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue.

    Science.gov (United States)

    Klotz, J L; Brown, K R; Xue, Y; Matthews, J C; Boling, J A; Burris, W R; Bush, L P; Strickland, J R

    2012-02-01

    As part of a 2-yr study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and serotonin receptors. Experiment 1 examined vasoconstrictive activities of 5-hydroxytryptamine (5HT), α-methylserotonin (ME5HT; a 5HT(2) receptor agonist), d-lysergic acid (LSA), and ergovaline (ERV) on lateral saphenous veins collected from steers immediately removed from a high-endophyte-infected tall fescue pasture (HE) or a low-endophyte-infected mixed-grass (LE) pasture. Using the same pastures, Exp. 2 evaluated effects of grazing 2 levels of toxic endophyte-infected tall fescue on vasoconstrictive activities of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), BW 723C86 (BW7), CGS-12066A (CGS), and 5-carboxamidotryptamine hemiethanolate maleate (5CT), agonists for 5HT(2A),( 2B), 5HT(1B), and 5HT(7) receptors, respectively. One-half of the steers in Exp. 2 were slaughtered immediately after removal from pasture, and the other one-half were fed finishing diets for >91 d before slaughter. For Exp. 1, maximal contractile intensities were greater (P grazing LE pastures than HE pastures for 5HT (73.3 vs. 48.9 ± 2.1%), ME5HT (52.7 vs. 24.9 ± 1.5%), and ERV (65.7 vs. 49.1 ± 2.6%). Onset of contractile response did not differ for 5HT (P = 0.26) and ERV (P = 0.93), but onset of ME5HT contraction was not initiated (P grazing steers. For Exp. 2, maximal contractile intensities achieved with DOI were 35% less (P grazing HE pastures. Contractile response to CGS did not differ between pasture groups, and there was an absence of contractile response to BW7 in both groups. There were no differences between endophyte content in contractile responses after animals were finished for >91 d. Experiment 1 demonstrated that grazing of HE pastures for 89 to 105 d induces

  8. Neuroplastic alteration of TTX-resistant sodium channel with visceral pain and morphine-induced hyperalgesia

    Directory of Open Access Journals (Sweden)

    Chen J

    2012-11-01

    Full Text Available Jinghong Chen,1,2,4 Ze-hui Gong,4 Hao Yan,2 Zhijun Qiao,3 Bo-yi Qin41Department of Internal Medicine, Neuroscience Program, The University of Texas Medical Branch, Galveston, TX, USA; 2The Divisions of Pharmacy, Pharmacology core lab, MD Anderson Cancer Center, Houston, TX, USA; 3University of Texas-Pan American, Edinburg, TX, USA; 4Beijing Institute of Pharmacology and Toxicology, Beijing, China Abstract: The discovery of the tetrodotoxin-resistant (TTX-R Na+ channel in nociceptive neurons has provided a special target for analgesic intervention. In a previous study we found that both morphine tolerance and persistent visceral inflammation resulted in visceral hyperalgesia. It has also been suggested that hyperexcitability of sensory neurons due to altered TTX-R Na+ channel properties and expression contributes to hyperalgesia; however, we do not know if some TTX-R Na+ channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. To evaluate the effects of morphine tolerance and visceral inflammation on the channel, we investigated the dorsal root ganglia (DRG neuronal change following these chronic treatments. Using whole-cell patch clamp recording, we recorded TTX-R Na+ currents in isolated adult rat lumbar and sacral (L6-S2 DRG neurons from normal and pathologic rats with colon inflammatory pain or chronic morphine treatment. We found that the amplitudes of TTX-R Na+ currents were signiflcantly increased in small-diameter DRG neurons with either morphine tolerance or visceral inflammatory pain. Meanwhile, the result also showed that those treatments altered the kinetics properties of the electrical current (ie, the activating and inactivating speed of the channel was accelerated. Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage

  9. Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism.

    Science.gov (United States)

    Wada, Hiromi

    2017-03-01

    Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development. Copyright © 2016 Elsevier

  10. Diet-induced alterations of hGH secretion in man.

    Science.gov (United States)

    Merimee, T J; Pulkkinen, A J; Burton, C E

    1976-05-01

    Studies were designed to determine whether variations in diet composition could modify the secretion of human growth hormone. Eight men and seven women ingested experimental diets for 10-12 days. Each experimental diet was preceded by a control diet for five days. Experimental diets studied in men were a) 2300 calorie, 80% carbohydrate (8 men); b) 2300 calorie, 75% high-fat (7 men); c) 2300 calorie, 70% high-protein (5 men); d) 3600 calorie, "control" (40% carbohydrate, 40% fat, 20% protein) (5 men); and e) 3600 calorie, 80% high-carbohydrate (5 men). A control diet and a high-carbohydrate (5 men). A control diet and a high-carbohydrate diet at the 2300 calorie level were studied in women. Each diet study was terminated by a 72 hour fast. Serum samples were collected hourly for 24 hours after each control period, on the eigth, ninth, or tenth day of each study, and during the final day of each fast. High-carbohydrate diets at the 2300 calorie level caused a significant decrease of growth hormone values in serum in each of eight men (sign test of significance, P less than .01). The mean figures were likewise significantly decreased. Isocaloric diets of high fat and high protein did not alter growth hormone concentrations in serum. A high-caloric diet similar to the control diet in composition was without effect on growth hormone secretion in men; however, a high-carbohydrate diet at the higher caloric level again depressed growth hormone values in plasma. On the third day of a 72 hour fast, growth hormone values in serum increased 287% in men, from a mean control serum concentration of 4.4 +/- 0.8 ng/ml to 11.9 +/- 5.0 ng/ml (P less than .01). Women, unlike men, had no significant decrease in growth hormone concentrations in serum over a 24 hour period after the high-carbohydrate diet, and the increase after starvation was significantly less than that in men, achieving significance only when evaluated by paired analysis. Growth hormone values in serum after the

  11. Deprivation of straw bedding alters PGF(2alpha)-induced nesting behaviour in female pigs.

    Science.gov (United States)

    Burne; Murfitt; Gilbert

    2000-10-01

    Sows are highly motivated to build a maternal nest on the day preceding parturition. A model for nest building has been established in pigs, in which exogenously administered prostaglandin F(2alpha) (PGF(2alpha)) may be used to elicit nesting behaviour in cyclic, pseudopregnant and pregnant pigs. The aim of this experiment was to examine the effects of deprivation of straw bedding on PGF(2alpha)-induced nest building in pseudopregnant Large White gilts. Oestradiol valerate injections (5 mg/day) were given on days 11-15 of the oestrous cycle to induce pseudopregnancy. The pigs were housed individually in a pen (2.8x1.7 m) and provided with 2-kg fresh straw each day. On the test day, on day 46 or 47 of pseudopregnancy, half of the pigs were deprived of straw (substrate effect) and they were injected intramuscularly with saline or 15 mg of PGF(2alpha) (Lutalyse, Upjohn) (treatment effect) allocated in a Latin-square design. Behaviour was recorded onto video tapes for 1 h either side of treatment for analysis using a computerised event recorder. PGF(2alpha)-treated pigs housed in bare or strawed pens showed significantly higher frequencies of pawing and rooting, and stood for longer than saline-treated controls. This treatment effect has been previously shown to be comparable to pre-partum nest building. The removal of straw significantly reduced the frequency of pawing and the duration of rooting by PGF(2alpha)-treated pigs. The results demonstrate that nesting behaviour can be initiated by exogenously administered PGF(2alpha) and is further modified by the provision of straw. This suggests that PGF(2alpha)-induced nesting behaviour is subject to environmental feedback.

  12. Alteration in Fecal Microbiota Associated with Grain-induced Subacute Ruminal Acidosis Challenge in Dairy Cows

    DEFF Research Database (Denmark)

    Danscher, Anne Mette; Derakshani, Hooman; Li, Shucong

    2014-01-01

    % concentrate) for four weeks before the trial. SARA was induced by gradual substitution of 40% of TMR with grain pellets (50:50 wheat:barley) over 3 days. Full SARA diet was fed for four days. Rumen pH was measured continuously by indwelling probes (eCow). Feces samples were taken at 9 am and 9 pm on last day......Introduction: High prevalence of subacute rumen acidosis (SARA) in dairy herds has been reported with large impact on production and welfare. The field diagnosis of SARA is currently unclear and primarily based on point measurements of rumen pH, which are inaccurate. Consequently, SARA cases...

  13. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

  14. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J.

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

  15. Choroidal neovascularization induced by immunogenic alteration of the retinal pigment epithelium in dengue Fever.

    Science.gov (United States)

    Veloso, Carlos Eduardo; Schmidt-Erfurth, Ursula; Nehemy, Márcio B

    2015-01-01

    To report the first case of choroidal neovascularization (CNV) secondary to dengue fever. A 54-year-old female was referred to our department with blurred vision and metamorphopsia in her left eye. Two weeks earlier, she had presented all of the classic symptoms of dengue fever including a positive serology. Her best-corrected visual acuity (BCVA) was 20/150 in the left eye. She underwent a fundus examination, fluorescein angiography (FA) and spectral domain optical coherence tomography. All findings were consistent with CNV secondary to dengue fever. FA revealed a classic CNV associated with focal retinal pigment epithelium (RPE) destruction and detachment. Three consecutive monthly injections of intravitreal ranibizumab resulted in functional and anatomical improvement for as long as 6 months with a BCVA of 20/25. However, CNV recurred 2 years later, again with an improvement after ranibizumab therapy, but with persistence of a fibrovascular RPE detachment, highlighting the pathomechanism of a classic CNV formation. Maculopathy in dengue fever may be followed by CNV as a result of the immunologic alteration of the RPE. Physicians should be aware of this manifestation to be able to initiate adequate treatment with excellent functional and anatomical results.

  16. Intervention strategies for cesarean section–induced alterations in the microbiota-gut-brain axis

    Science.gov (United States)

    Moya-Pérez, Angela; Luczynski, Pauline; Renes, Ingrid B.; Wang, Shugui; Borre, Yuliya; Anthony Ryan, C.; Knol, Jan; Stanton, Catherine; Dinan, Timothy G.

    2017-01-01

    Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the early-life factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations. PMID:28379454

  17. Reservoir-induced Alterations in Flood Seasonality: Patterns, Processes, and Implications

    Science.gov (United States)

    Abeshu, G. W.; Li, H. Y.; Yigzaw, W.; Hejazi, M. I.; Tang, J.; Demissie, Y.

    2017-12-01

    Reservoirs are by far the most significant human activities that are imposing hydrologic alterations, specifically related to extreme flow conditions. This study presents the effects of reservoir regulation on flood seasonality in different hydrologic and climate settings across the contiguous United States. The data employed consists of reservoir information from the National Inventory of Dams (NID) and Global Reservoir and Dam (GRanD) database along with USGS stream flow data for pre- and post-impoundment periods. A new flood seasonality index was developed with circular statistics to reveal any significant shifts in flood timing between pre- and post-impoundments periods at each USGS station. Reservoir Impact Index (RII) was developed as a function of storage capacity and mean annual streamflow to quantify the regulation effects of reservoirs on flood seasonality. Process understanding of how reservoir regulation affects flow seasonality was analyzed based on RII using simple but physically-based reservoir models with different degrees of complexity, e.g., simple linear and hedging models. Results indicate that the shift in seasonality of annual maximum flood (AMF) at downstream generally increases with increasing RII, given that reservoir has enough storage to regulate the flood. The process modeling results also imply that reservoir state prior to the occurrence of AMF, antecedent climatic patterns and catchment state affect the shift in AMF arrival at downstream. These findings will help improve the ability to examine issues connected to flood frequency characteristics including nutrient delivery, sediment load and stream temperature shifts at downstream of dams.

  18. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids.

    Science.gov (United States)

    Stenman, Lotta K; Holma, Reetta; Korpela, Riitta

    2012-03-07

    To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism. Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF). Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon. High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.

  19. Alteration of human serum albumin tertiary structure induced by glycation. Spectroscopic study.

    Science.gov (United States)

    Szkudlarek, A; Maciążek-Jurczyk, M; Chudzik, M; Równicka-Zubik, J; Sułkowska, A

    2016-01-15

    The modification of human serum albumin (HSA) structure by non-enzymatic glycation is one of the underlying factors that contribute to the development of complications of diabetes and neurodegenerative diseases. The aim of the present work was to estimate how glycation of HSA altered its tertiary structure. Changes of albumin conformation were investigated by comparison of glycated (gHSA) and non-glycated human serum albumin (HSA) absorption spectra, red edge excitation shift (REES) and synchronous spectra. Effect of glycation on human serum albumin tertiary structure was also investigated by (1)H NMR spectroscopy. Formation of gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance has been registered. Analysis of red edge excitation shift effect allowed for observation of structural changes of gHSA in the hydrophobic pocket containing the tryptophanyl residue. Moreover changes in the microenvironment of tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous fluorescence spectroscopy have been confirmed. The influence of glycation process on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p-toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence analysis showed that environment of both binding site I and II is modified by galactose glycation. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Alteration of methotrexate binding to human serum albumin induced by oxidative stress. Spectroscopic comparative study.

    Science.gov (United States)

    Maciążek-Jurczyk, M; Sułkowska, A; Równicka-Zubik, J

    2016-01-05

    Changes of oxidative modified albumin conformation by comparison of non-modified (HSA) and modified (oHSA) human serum albumin absorption spectra, Red Edge Excitation Shift (REES) effect and fluorescence synchronous spectra were investigated. Studies of absorption spectra indicated that changes in the value of absorbance associated with spectral changes in the region from 200 to 250nm involve structural alterations related to variations in peptide backbone conformation. Analysis of the REES effect allowed for the observation of changes caused by oxidation in the region of the hydrophobic pocket containing the tryptophanyl residue. Synchronous fluorescence spectroscopy confirmed changes of the position of the tryptophanyl and tyrosil residues fluorescent band. Effect of oxidative stress on binding of methotrexate (MTX) was investigated by spectrofluorescence, UV-VIS and (1)HNMR spectroscopy. MTX caused the fluorescence quenching of non-modified (HSA) and modified (oHSA) human serum albumin molecule. The values of binding constants, Hill's coefficients and a number of binding sites in the protein molecule in the high affinity binding site were calculated for the binary MTX-HSA and MTX-oHSA systems. For these systems, qualitative analysis in the low affinity binding sites was performed with the use of the (1)HNMR technique. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes

    Science.gov (United States)

    Nyalwidhe, Julius O.; Gallagher, Glen R.; Glenn, Lindsey M.; Morris, Margaret A.; Vangala, Pranitha; Jurczyk, Agata; Bortell, Rita; Harlan, David M.; Nadler, Jerry L.

    2017-01-01

    Enteroviral infections have been associated with the development of type 1 diabetes (T1D), a chronic inflammatory disease characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Cultured human islets, including the insulin-producing beta cells, can be infected with coxsackievirus B4 (CVB4) and thus are useful for understanding cellular responses to infection. We performed quantitative mass spectrometry analysis on cultured primary human islets infected with CVB4 to identify molecules and pathways altered upon infection. Corresponding uninfected controls were included in the study for comparative protein expression analyses. Proteins were significantly and differentially regulated in human islets challenged with virus compared with their uninfected counterparts. Complementary analyses of gene transcripts in CVB4-infected primary islets over a time course validated the induction of RNA transcripts for many of the proteins that were increased in the proteomics studies. Notably, infection with CVB4 results in a considerable decrease in insulin. Genes/proteins modulated during CVB4 infection also include those involved in activation of immune responses, including type I interferon pathways linked to T1D pathogenesis and with antiviral, cell repair, and inflammatory properties. Our study applies proteomics analyses to cultured human islets challenged with virus and identifies target proteins that could be useful in T1D interventions. PMID:29264452

  2. Poly (A+ transcriptome assessment of ERBB2-induced alterations in breast cell lines.

    Directory of Open Access Journals (Sweden)

    Dirce Maria Carraro

    Full Text Available We report the first quantitative and qualitative analysis of the poly (A⁺ transcriptome of two human mammary cell lines, differentially expressing (human epidermal growth factor receptor an oncogene over-expressed in approximately 25% of human breast tumors. Full-length cDNA populations from the two cell lines were digested enzymatically, individually tagged according to a customized method for library construction, and simultaneously sequenced by the use of the Titanium 454-Roche-platform. Comprehensive bioinformatics analysis followed by experimental validation confirmed novel genes, splicing variants, single nucleotide polymorphisms, and gene fusions indicated by RNA-seq data from both samples. Moreover, comparative analysis showed enrichment in alternative events, especially in the exon usage category, in ERBB2 over-expressing cells, data indicating regulation of alternative splicing mediated by the oncogene. Alterations in expression levels of genes, such as LOX, ATP5L, GALNT3, and MME revealed by large-scale sequencing were confirmed between cell lines as well as in tumor specimens with different ERBB2 backgrounds. This approach was shown to be suitable for structural, quantitative, and qualitative assessment of complex transcriptomes and revealed new events mediated by ERBB2 overexpression, in addition to potential molecular targets for breast cancer that are driven by this oncogene.

  3. Counteracting effects on free radicals and histological alterations induced by a fraction with casearins

    Directory of Open Access Journals (Sweden)

    ÉVERTON JOSÉ FERREIRA DE ARAÚJO

    2015-09-01

    Full Text Available ABSTRACTCasearia sylvestris Swartz is a medicinal plant widely distributed in Brazil. It has anti-inflammatory, antiulcer and antitumor activities and is popularly used to treat snakebites, wounds, diarrhea, flu and chest colds. Its leaves are rich in oxygenated tricyclic cis-clerodane diterpenes, particulary casearins. Herein, we evaluated the antioxidant activities of a fraction with casearins (FC isolated from C. sylvestrisand histological changes on the central nervous system and livers of Mus musculus mice. Firstly, in vitro studies (0.9, 1.8, 3.6, 5.4 and 7.2 μg/mL revealed EC50 values of 3.7, 6.4 and 0.16 µg/mL for nitrite, hydroxyl radical and TBARS levels, respectively. Secondly, FC (2.5, 5, 10 and 25 mg/kg/day was intraperitoneally administered to Swiss mice for 7 consecutive days. Nitrite levels in the hippocampus (26.2, 27.3, 30.2 and 26.6 µM and striatum (26.3, 25.4, 34.3 and 27.5 µM increased in all treated animals (P < 0.05. Lower doses dropped reduced glutathione, catalase and TBARS levels in the hippocampus and striatum. With the exception of this reduction in TBARS formation, FC displayed only in vitro antioxidant activity. Animals exhibited histological alterations suggestive of neurotoxicity and hepatotoxicity, indicating the need for precaution regarding the consumption of medicinal formulations based on Casearia sylvestris.

  4. Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity

    Science.gov (United States)

    Horn, E.; Agricola, H.; Böser, S.; Förster, S.; Kämper, G.; Riewe, P.; Sebastian, C.

    "Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (μg). The contrary physiological and behavioral results indicate a facilitation of 1g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of μg- or 3g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

  5. Proprioceptive neuromuscular facilitation training induced alterations in muscle fibre type and cross sectional area.

    Science.gov (United States)

    Kofotolis, N; Vrabas, I S; Vamvakoudis, E; Papanikolaou, A; Mandroukas, K

    2005-03-01

    To compare the effects of proprioceptive neuromuscular facilitation (PNF) and isokinetic training on fibre type distribution and cross sectional area of the vastus lateralis muscle. Twenty four male university students were divided into two equal groups: PNF training and isokinetic training (ISO). The training regimen for the PNF group consisted of three sets of 30 repetitions against maximal resistance, alternating two patterns of sequential movements of the right lower extremity: (a) toe flexion and ankle plantar flexion and eversion; (b) knee extension and hip extension, abduction, and internal rotation. The ISO group performed three sets of 30 repetitions alternating knee extension and flexion of the right leg at angular velocities of 180 and 90 degrees /s in an isokinetic dynamometer (Cybex). Both groups trained three times a week for a total of eight weeks. Muscle biopsy specimens were obtained from the right vastus lateralis muscle before and after training. The mean percentage area of type IIB fibre was significantly decreased (p<0.01) after eight weeks of PNF training, whereas that of type IIA fibre was significantly (p<0.05) increased. The mean percentage area of ISO trained type IIAB fibres exhibited an augmentative pattern (p<0.01) with a parallel reduction (p<0.05) in type IIA. Percentage fibre type distribution exhibited a similar pattern. Both PNF and ISO training alter fibre type distribution and mean cross sectional area. These changes occur in the type II fibre subgroup.

  6. Chronic radiation-induced leukemogenesis: alterations of hematopoietic progenitor repair functions during preclinical phases

    International Nuclear Information System (INIS)

    Seed, T.M.; Kaspar, L.V.; Grdina, D.J.; Frazier, M.E.

    1987-01-01

    Chronic exposure to low daily doses of whole-body gamma irradiation elicits a high incidence of myeloid leukemia (ML) and related myeloproliferative diseases (MPD) in beagles. Previously, the authors identified and partially characterized a four-phase sequence of evolving MPD as a consequence of chronic radiation exposure. With a focus on preclinical alterations in granulocyte/monocyte-committed stem cells, they have identified two critical events in the process: (i) an early event, involving the coupling of acquired radioresistance of the stem cell with renewed proliferative capacity; and (ii) a late event, involving acquired autocrine functions and associated change in stem cell clonality. In terms of the early event, repair-associated parameters are currently being examined on the cellular level by both split-dose and low dose-rate-type assays with survival enhancement used as the measured end point. On the molecular level, these parameters are examined by microfluorometric alkaline elution assays with DNA damage and repair used as end points

  7. CHOP THERAPY INDUCED MITOCHONDRIAL REDOX STATE ALTERATION IN NON-HODGKIN'S LYMPHOMA XENOGRAFTS

    Directory of Open Access Journals (Sweden)

    H. N. XU

    2013-04-01

    Full Text Available We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and survival. The redox state can be imaged by the redox scanner that collects the fluorescence signals from both the oxidized-flavoproteins (Fp and the reduced form of nicotinamide adenine dinucleotide (NADH in snap-frozen tissues and has been previously employed to study tumor aggressiveness and treatment responses. Here, with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large B-cell lymphoma cell line (DLCL2. The mice were treated with CHOP therapy, i.e., cyclophosphamide (C + hydroxydoxorubicin (H + Oncovin (O + prednisone (P with CHO administration on day 1 and prednisone administration on days 1–5. The Fp content of the treated group was significantly decreased (p = 0.033 on day 5, and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group (p = 0.048. The decrease of the Fp heterogeneity (measured by the mean standard deviation had a border-line statistical significance (p = 0.071. The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOP therapy.

  8. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Gazdzinski, Lisa M.; Cormier, Kyle; Lu, Fred G.; Lerch, Jason P.; Wong, C. Shun; Nieman, Brian J.

    2012-01-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  9. Developmental exposure to Passiflora incarnata induces behavioural alterations in the male progeny.

    Science.gov (United States)

    Bacchi, André D; Ponte, Bianca; Vieira, Milene L; de Paula, Jaqueline C C; Mesquita, Suzana F P; Gerardin, Daniela C C; Moreira, Estefânia G

    2013-01-01

    Passiflora incarnata is marketed in many countries as a phytomedicine and is prescribed mainly as a sedative and anxiolytic. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. To evaluate the reproductive and developmental toxicity of P. incarnata, Wistar female rats were gavaged with 30 or 300 mg kg(-1) of this herb from gestational Day (GD) 0 to postnatal Day (PND) 21. P. incarnata treatment did not influence dams' bodyweight or food intake or their reproductive performance (post-implantation loss, litter size, litter weight). There was also no influence on the physical development of pups (bodyweight gain, day of vaginal opening or preputial separation) or their behaviour in the open-field at PND 22, 35 and 75. Sexual behaviour was disrupted in adult male pups exposed to 300 mg kg(-1) of P. incarnata; in this group, only 3 out of 11 pups were sexually competent. This behavioural disruption was not accompanied by alterations in plasma testosterone levels, reproductive-related organs and glands weights or sperm count. It is hypothesised that aromatase inhibition may be involved in the observed effect.

  10. Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats.

    Science.gov (United States)

    Rai, Devendra K; Rai, Prashant Kumar; Gupta, Aradhna; Watal, Geeta; Sharma, Bechan

    2009-04-01

    Wistar rats of 6-8 weeks in age weighing between 120-150 g were exposed to the fixed doses of each of the carbamate pesticides such as cartap (50% LD(50)) and carbofuran (50% LD(50)) as well as a combination of these two with 25% LD(50) of each for one week. The effect of treatments was studied in terms of serum lipid parameters such as high-density lipoprotein, total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein. Treatment with individual doses of carbofuran (50% LD(50)) and cartap (50 % LD(50)) caused significant alterations in the levels of serum lipid parameters. The pesticides treatment resulted in marked decrease in the level of serum high-density lipoprotein where as that of other lipids got significantly elevated. Further, the rats exhibited relatively higher impact of pesticides when treated with the compounds in combination (25 % LD(50) of each). The results indicated that these compounds when used together may exert enhanced effect on the levels of serum lipids in rat.

  11. Does exposure to very high levels of natural radiation induce hematological alterations in humans?

    International Nuclear Information System (INIS)

    Ghiassi-Nejad, M.

    2003-01-01

    Full text: It has long been known that total body exposure to moderate doses decrease the number of circulating erythrocytes, platelets, granulocytes, and lymphocytes. However, data on hematopoietic effects of exposure to very low doses of ionizing radiation in humans are scarce. Recently it has been reported that hematological parameters have significant positive associations with the radiation dose received by residents lived near a nuclear power plant. Ramsar, a city in northern Iran, has some inhabited areas with the highest levels of natural radiation studied so far. A population of about 2000 is exposed to average annual radiation levels of 10.2 mGy y -1 and the highest recorded external gamma dose rates are about 130 mGy y -1 . In this study, hematological parameters such as counts of leukocytes, lymphocytes, monocytes, granulocytes, red blood cells, hemoglobin, hematocrit, MCV, MCH, MCHC, RDW, PLT, and MPV were measured in the inhabitants. The results of this study indicated that there was no any statistically significant alteration in hematological parameters of the inhabitants of very high background radiation areas of Ramsar compared to those of a neighboring control area

  12. Supplementary Material for: Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-01-01

    Abstract Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntingtonâ s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  13. TPP and TCEP induce oxidative stress and alter steroidogenesis in TM3 Leydig cells.

    Science.gov (United States)

    Chen, Guanliang; Zhang, Songbin; Jin, Yuanxiang; Wu, Yan; Liu, Ling; Qian, Haifeng; Fu, Zhengwei

    2015-11-01

    Effects of triphenyl phosphate (TPP) and tris-(2-chloroethyl) phosphate (TCEP) exposure on induction of oxidative stress and endocrine disruption were investigated in TM3 cells. After 24h exposure, cell growth declined and morphology changed in TPP and TCEP treated groups with high dosages. Significant increases in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST) activities and their respective gene expressions in a dose-dependent and/or time-dependent manner in TPP or TCEP groups. Moreover, the expression of main genes related to testosterone (T) synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α), 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) were dramatically reduced by TPP and TCEP treatments, especially with the high dosage for 24h. TPP and TCEP treatments for 24h caused significant decreases in T levels in the medium. Furthermore, co-treatments of hCG with TPP or TCEP could inhibit hCG-induced changes in the expression of P450scc, P450-17α and 17β-HSD and T levels. Taken together, TPP and TCEP could induce oxidative stress and endocrine disruption in TM3 cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Burn-induced alterations in toll-like receptor-mediated responses by bronchoalveolar lavage cells.

    Science.gov (United States)

    Oppeltz, Richard F; Rani, Meenakshi; Zhang, Qiong; Schwacha, Martin G

    2011-09-01

    Burn is associated with profound inflammation and activation of the innate immune system in multiple organ beds, including the lung. Similarly, toll-like receptors (TLR) are associated with innate immune activation. Nonetheless, it is unclear what impact burn has on TLR-induced inflammatory responses in the lung. Male C57BL/6 mice were subjected to burn (3rd degree, 25% TBSA) or sham procedure and 1, 3 or 7 days thereafter, bronchoalveolar lavage (BAL) fluid was collected and cells were isolated and cultured in vitro with specific TLR agonists as follows: Zymosan (TLR-2), LPS (TLR-4) and CpG-ODN (TLR-9). Supernatants were collected 48 h later and assayed for inflammatory cytokine levels (IL-1β, IL-6, IL-10, IL-17, TNF-α, KC, MCP-1, MIP-1α, MIP-1β and RANTES) by Bioplex. BAL fluid from sham and burn mice did not contain detectable cytokine levels. BAL cells, irrespective of injury, were responsive to TLR-2 and TLR-4 activation. Seven days after burn, TLR-2 and TLR-4 mediated responses by BAL cells were enhanced as evidenced by increased production of IL-6, IL-17, TNF-α, MCP-1, MIP-1β and RANTES. Burn-induced changes in TLR-2 and TLR-4 reactivity may contribute to the development of post-burn complications, such as acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

    Science.gov (United States)

    Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

    2013-01-01

    Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

  16. Structural and functional alterations of two multidomain oxidoreductases induced by guanidine hydrochloride.

    Science.gov (United States)

    Jiao, Ming; Zhou, Yu-Ling; Li, Hong-Tao; Zhang, De-Ling; Chen, Jie; Liang, Yi

    2010-01-01

    The unfolding and refolding of two multidomain oxidoreductases, bovine liver catalase and flavoprotein bovine milk xanthine oxidase (XO), have been analyzed by fluorescence spectroscopy, circular dichroism, and activity measurements. Two intermediates, a partially folded active dimer disassembled from the native tetramer and a partially folded inactivated monomer, are found to exist in the conformational changes of catalase induced by guanidine hydrochloride (GdnHCl). Similarly, two intermediates, an active, compacted intermediate bound by flavin adenine dinucleotide (FAD) partially and an inactive flexible intermediate with FAD completely dissociated, exist in the conformational changes of XO induced by GdnHCl. The activity regains completely and an enhancement in activity compared with the native catalase or native XO is observed by dilution of catalase or XO incubated with GdnHCl at concentrations not >0.5 or 1.8 M into the refolding buffer, but the yield of reactivation for catalase or XO is zero when the concentration of GdnHCl is >1.5 or 3.0 M. The addition of FAD provides a remarkable protection against the inactivation of XO by GdnHCl under mild denaturing conditions, and the conformational change of XO is irreversible after FAD has been removed in the presence of a strong denaturing agent. These findings provide impetus for exploring the influences of cofactors such as FAD on the structure-function relationship of xanthine oxidoreductases.

  17. Plant cell death and cellular alterations induced by ozone: Key studies in Mediterranean conditions

    International Nuclear Information System (INIS)

    Faoro, Franco; Iriti, Marcello

    2009-01-01

    An account of histo-cytological and ultrastructural studies on ozone effect on crop and forest species in Italy is given, with emphasis on induced cell death and the underlying mechanisms. Cell death phenomena possibly due to ambient O 3 were recorded in crop and forest species. In contrast, visible O 3 effects on Mediterranean vegetation are often unclear. Microscopy is thus suggested as an effective tool to validate and evaluate O 3 injury to Mediterranean vegetation. A DAB-Evans blue staining was proposed to validate O 3 symptoms at the microscopic level and for a pre-visual diagnosis of O 3 injury. The method has been positively tested in some of the most important crop species, such as wheat, tomato, bean and onion and, with some restriction, in forest species, and it also allows one to gain some very useful insights into the mechanisms at the base of O 3 sensitivity or tolerance. - Ozone-induced cell death is a frequent phenomenon in Mediterranean conditions, not only in the most sensitive crops but also in forest species.

  18. Histone peptide AKRHRK enhances H2O2-induced DNA damage and alters its site specificity

    International Nuclear Information System (INIS)

    Midorikawa, Kaoru; Murata, Mariko; Kawanishi, Shosuke

    2005-01-01

    Histone proteins are involved in compaction of DNA and the protection of cells from oxygen toxicity. However, several studies have demonstrated that the metal-binding histone reacts with H 2 O 2 , leading to oxidative damage to a nucleobase. We investigated whether histone can accelerate oxidative DNA damage, using a minimal model for the N-terminal tail of histone H4, CH 3 CO-AKRHRK-CONH 2 , which has a metal-binding site. This histone peptide enhanced DNA damage induced by H 2 O 2 and Cu(II), especially at cytosine residues, and induced additional DNA cleavage at the 5'-guanine of GGG sequences. The peptide also enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and ESR spin-trapping signal from H 2 O 2 and Cu(II). Cyclic redox reactions involving histone-bound Cu(II) and H 2 O 2 , may give rise to multiple production of radicals leading to multiple hits in DNA. It is noteworthy that the histone H4 peptide with specific sequence AKRHRK can cause DNA damage rather than protection under metal-overloaded condition

  19. [Alteration of renal hemodynamic in adriamycin-induced nephrosis rats administrated with Wulingsan].

    Science.gov (United States)

    He, Lan; Cai, Yu; Chen, Zhao-Hui; Jiang, Jian-Min; Wang, Ning-Sheng

    2006-08-01

    To investigate the effect of traditional classical compound Wulingsan on renal hemodynamic in rats with adriamycin (ADR)-induced nephrosis. After establishing a model of rats with adriamycin-induced nephrosis, we administrated wulin-san to the ADR rats via oral gavage for four weeks and measured mean arterial blood preasure (MABP) with manometer. Renal clearance of paraaminohippuric acid (PAH) and inulin were detected, then renal plasma flow (RPF) and glomerular filtration rate (GFR) were calculated. Renal vascular resistance (RVR) was calculated as the division of MABP by RPF. Renal endothelin (ET) and angiotensin II (Ang II) were detected with radioimmunity assay kits, and nitrous oxide (NO) was detected with biochemical kits. There was no significant change of GFR in ARD rats, but RPF and NO were decreased, which accompanied by enhanced RVR, ET and Ang II. RPF was increased in the administrated rats, in company with RVR, ET and Ang II decreased, whereas NO was not influenced after the administration. Wulingsan can improve the renal hemodynamic in ADR rats, at least in part by modulating the levels of vasoactive factor.

  20. Deltamethrin-induced nuclear erythrocyte alteration and damage to the gills and liver of Colossoma macropomum.

    Science.gov (United States)

    Cunha, Fernanda Dos Santos; Sousa, Natalino da Costa; Santos, Rudã Fernandes Brandão; Meneses, Juliana Oliveira; do Couto, Márcia Valéria Silva; de Almeida, Fabrício Tavares Cunha; de Sena Filho, José Guedes; Carneiro, Paulo César Falanghe; Maria, Alexandre Nizio; Fujimoto, Rodrigo Yudi

    2018-03-20

    Deltamethrin is one of the most commonly used pyrethroids in the world, and it has a high toxic potential, mainly on aquatic organism. Thus, the purpose of this study was to evaluate LC 50 values of deltamethrin on tambaqui (Colossoma macropomum) fingerlings and to investigate genotoxic effects and histopathological responses. Fish were exposed to different concentrations of deltamethrin (0, 6.16 × 10 -3 ; 6.44 × 10 -2 ; 1.34 × 10 -1 , and 1.93 × 10 -1  mg L -1 ) for 96 h. In addition, a genotoxicity analysis was carried out on peripheral blood erythrocytes and histopathological changes were classified by the severity degree of damage and organ functioning. The 96 h LC 50 value for tambaqui was estimated at 5.56 × 10 -2  mg L -1 using a static test system. Nuclear abnormalities in exposed fish included micronuclei, blebbed, notched, 8-shaped, and binucleated nuclei forms. Deltamethrin significantly induced a notched nucleus compared to other abnormalities. A histopathological examination showed hepatic lesions and gill damage. Deltamethrin was found to be highly toxic; it induced genotoxicity and caused liver and gill inflammation in tambaqui.

  1. Swine in biomedical research. V. 1

    Energy Technology Data Exchange (ETDEWEB)

    Tumbleson, M.E.

    1986-01-01

    This volume presents information on the following topics: the history of pigs; conceptual and operational history of the development of miniature swine; breeding program and population standards of the Gottingen miniature swine; moral, social and scientific aspects of the use of swine in research; fertility in gilts inseminated with frozen boar semen stored at -196 C for eight years; ultrastructure of piglet liver; porcine models in surgical research; anesthesia in swine; pulse monitoring, intravascular and instramuscular injection sites in pigs; collagen biosynthesis and collagen content as a measure of dermal healing in experimental wounds in domestic swine; methods for hair removal; swine as a cardiac surgical model; bone marrow transplantation in miniature swine; technical aspects of small intestinal transplantation in young pigs; models; the pig in studies of diarrhea pathophysiology; use of swine to validate airflow perturbation device for airways resistance measurements in humans; swine as a model for human diabetes; and the weanling Yorkshire pig as an animal model for measuring percutaneous penetration.

  2. H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

    Directory of Open Access Journals (Sweden)

    Marion Russier

    2017-03-01

    Full Text Available A pandemic-capable influenza virus requires a hemagglutinin (HA surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5 and human and ferret (pH ≤5.5 species. Using an early 2009 pandemic H1N1 (pH1N1 virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5, HA1-Y17H (pH 6.0, and HA2-R106K (pH 5.3. All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0 acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses.

  3. Cardiac energy metabolic alterations in pressure overload–induced left and right heart failure (2013 Grover Conference Series)

    Science.gov (United States)

    Lopaschuk, Gary D.

    2015-01-01

    Abstract Pressure overload of the heart, such as seen with pulmonary hypertension and/or systemic hypertension, can result in cardiac hypertrophy and the eventual development of heart failure. The development of hypertrophy and heart failure is accompanied by numerous molecular changes in the heart, including alterations in cardiac energy metabolism. Under normal conditions, the high energy (adenosine triphosphate [ATP]) demands of the heart are primarily provided by the mitochondrial oxidation of fatty acids, carbohydrates (glucose and lactate), and ketones. In contrast, the hypertrophied failing heart is energy deficient because of its inability to produce adequate amounts of ATP. This can be attributed to a reduction in mitochondrial oxidative metabolism, with the heart becoming more reliant on glycolysis as a source of ATP production. If glycolysis is uncoupled from glucose oxidation, a decrease in cardiac efficiency can occur, which can contribute to the severity of heart failure due to pressure-overload hypertrophy. These metabolic changes are accompanied by alterations in the enzymes that are involved in the regulation of fatty acid and carbohydrate metabolism. It is now becoming clear that optimizing both energy production and the source of energy production are potential targets for pharmacological intervention aimed at improving cardiac function in the hypertrophied failing heart. In this review, we will focus on what alterations in energy metabolism occur in pressure overload induced left and right heart failure. We will also discuss potential targets and pharmacological approaches that can be used to treat heart failure occurring secondary to pulmonary hypertension and/or systemic hypertension. PMID:25992268

  4. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

    Science.gov (United States)

    Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

    2017-07-01

    Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

  5. Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics

    Directory of Open Access Journals (Sweden)

    Isak Demirel

    2017-06-01

    Full Text Available It is known that an ineffective antibiotic treatment can induce morphological shifts in uropathogenic Escherichia coli (UPEC but the virulence properties during these shifts remain to be studied. The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL-producing UPEC (ESBL019 during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. Microarray results showed that the different morphological states of ESBL019 had significant transcriptional alterations of a large number of genes (Transition; 7%, Filamentation; 32%, and Reverted 19% of the entities on the array. All three morphological states of ESBL019 were associated with a decreased energy metabolism, altered iron acquisition systems and altered adhesion expression. In addition, genes associated with LPS synthesis and bacterial motility was also altered in all the morphological states. Furthermore, the transition state induced a significantly higher release of TNF-α from bladder epithelial cells compared to all other morphologies, while the reverted state was unable to induce TNF-α release. Our findings show that the morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.

  6. KIT(D816V) Induces SRC-Mediated Tyrosine Phosphorylation of MITF and Altered Transcription Program in Melanoma

    DEFF Research Database (Denmark)

    Phung, Bengt; Kazi, Julhash U; Lundby, Alicia

    2017-01-01

    The oncogenic D816V mutation of the KIT receptor is well characterized in systemic mastocytosis and acute myeloid leukemia. Although KIT(D816V) has been found in melanoma, its function and involvement in this malignancy is not understood. Here we show that KIT(D816V) induces tyrosine phosphorylat.......Implications: This study demonstrates that an oncogenic tyrosine kinase mutant, KIT(D816V), can alter the transcriptional program of the transcription factor MITF in melanoma Mol Cancer Res; 15(9); 1265-74. ©2017 AACR....... complex formation, thus preventing MITF phosphorylation, the cells became hypersensitive to SRC inhibitors. We have therefore delineated a mechanism behind the oncogenic effects of KIT(D816V) in melanoma and provided a rationale for the heightened SRC inhibitor sensitivity in KIT(D816V) transformed cells...

  7. Effect of milk hydrolysates on inflammation markers and drug-induced transcriptional alterations in cell-based models

    DEFF Research Database (Denmark)

    Nielsen, Ditte Søvsø Gundelund; Theil, Peter Kappel; Larsen, Lotte Bach

    2012-01-01

    . The underlying mechanisms that support inflammation and wound healing are not completely understood, but transcriptional alterations may be used as markers for inflammation and wound healing. The bioactivity of 3 CH prepared by treatment of commercial casein with pepsin (60 min) followed by corolase (0, 10......B (NFκB) by real-time PCR. Furthermore, the effect of CH on lipopolysaccharide-induced inflammation was evaluated in macrophages by measuring PG E2 levels. Casein hydrolysates treated with corolase for 10 or 60 min after pepsin treatment downregulated transcription of TGF-β1 and NFκB (P ..., the hydrolysate prepared by pepsin treatment only (0 min corolase) had a pro-inflammatory effect on macrophages via PG E2 stimulation (P

  8. DNA damage-induced alterations in chromatin contribute to genomic integrity and age-related changes in gene expression

    Science.gov (United States)

    Oberdoerffer, Philipp; Michan, Shaday; McVay, Michael; Mostoslavsky, Raul; Vann, James; Park, Sang-Kyu; Hartlerode, Andrea; Stegmuller, Judith; Hafner, Angela; Loerch, Patrick; Wright, Sarah M.; Mills, Kevin D.; Bonni, Azad; Yankner, Bruce A.; Scully, Ralph; Prolla, Tomas A.; Alt, Frederick W.; Sinclair, David A.

    2008-01-01

    Genomic instability and alterations in gene expression are hallmarks of eukaryotic aging. The yeast histone deacetylase Sir2 silences transcription and stabilizes repetitive DNA, but during aging or in response to a DNA break, the Sir complex relocalizes to sites of genomic instability, resulting in the desilencing of genes that cause sterility, a characteristic of yeast aging. Using embryonic stem cells, we show that mammalian Sir2, SIRT1, represses repetitive DNA and a functionally diverse set of genes across the mouse genome. In response to DNA damage, SIRT1 dissociates from these loci and relocalizes to DNA breaks to promote repair, resulting in transcriptional changes that parallel those in the aging mouse brain. Increased SIRT1 expression promotes survival in a mouse model of genomic instability and suppresses age-dependent transcriptional changes. Thus, DNA damage-induced redistribution of SIRT1 and other chromatin modifying proteins may be a conserved mechanism of aging in eukaryotes. PMID:19041753

  9. Biospectroscopy of Nanodiamond-Induced Alterations in Conformation of Intra- and Extracellular Proteins: A Nanoscale IR Study.

    Science.gov (United States)

    Khanal, Dipesh; Kondyurin, Alexey; Hau, Herman; Knowles, Jonathan C; Levinson, Olga; Ramzan, Iqbal; Fu, Dong; Marcott, Curtis; Chrzanowski, Wojciech

    2016-08-02

    The toxicity of nanomaterials raises major concerns because of the impact that nanomaterials may have on health, which remains poorly understood. We need to explore the fate of individual nanoparticles in cells at nano and molecular levels to establish their safety. Conformational changes in secondary protein structures are one of the main indicators of impaired biological function, and hence, the ability to identify these changes at a nanoscale level offers unique insights into the nanotoxicity of materials. Here, we used nanoscale infrared spectroscopy and demonstrated for the first time that nanodiamond-induced alterations in both extra- and intracellular secondary protein structures lead to the formation of antiparallel β-sheet, β-turns, intermolecular β-sheet, and aggregation of proteins. These conformational changes of the protein structure may result in the loss of functionality of proteins and in turn lead to adverse effects.

  10. Methyl Jasmonate-Induced Lipidomic and Biochemical Alterations in the Intertidal Macroalga Gracilaria dura (Gracilariaceae, Rhodophyta).

    Science.gov (United States)

    Kumari, Puja; Reddy, C R K; Jha, Bhavanath

    2015-10-01

    The role of exogenously added methyl jasmonate (MeJA), a lipid-derived signaling compound, in inducing oxidative stress in the marine red macroalga Gracilaria dura was investigated. MeJA at a concentration of 1-100 µM was a strong stimulant of reactive oxygen species (H(2)O(2), HO· and O(2) (·-)) (P < 0.05) causing considerable oxidative stress in G. dura. This further led to lipid peroxidation and degradation of the pigments Chl a and phycocyanin, with a concomitant increase in phycoerythrin. The MeJA-induced oxidative burst also led to the induction of a fatty acid oxidation cascade, resulting in the synthesis of hydroxy-oxylipins and the up-regulation of the 13-lipoxygenase pathway. Electrospray ionization-mass spectrometry-based shotgun lipidomic analysis revealed that monogalactosyldiacylglycerol (a chloroplastic glycerolipid) and phosphatidylcholine (extrachloroplastidic phopholipid) were the most affected lipid classes. The degradation of 18:3-fatty acid-containing monogalactosyldiacylglycerol inferred that it provided fatty acyl chains for the biosynthesis of 13-hydroperoxylinolenic acid, which was further directed towards either the jasmonate pathway or other alternative pathways of the fatty acid oxidation cascade, analogous to higher plants. Also, G. dura modulated the lipid acyl chains in such a way that no significant change was observed in the fatty acid profile of the treated thalli as compared with those of the control, except for C16:0, C16:1 (n-9), C20:3 (n-6) and C20:4 (n-6) (P < 0.05). Furthermore, MeJA caused the accumulation of phenolic compounds and the up-regulation of enzymes involved in secondary metabolism such as polyphenol oxidase, shikimate dehydrogenase and phenylalanine ammonia-lyase, indicating a shift towards secondary metabolism as a defense strategy to combat the induced oxidative stress. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For

  11. Root exudate-induced alterations in Bacillus cereus cell wall contribute to root colonization and plant growth promotion.

    Directory of Open Access Journals (Sweden)

    Swar