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Sample records for detects alterations induced

  1. Detection of radioiodine-induced cytogenetic alterations in circulating lymphocytes of thyroid patients

    Energy Technology Data Exchange (ETDEWEB)

    Kasuba, V [Inst. for Medical Recearch and Occupational Health, Zagreb (Croatia). Laboratory for Mutagenesis; Konrady, A; Koeteles, G J [Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Budapest (Hungary); Kusic, Z [Clinical Hospital Sestre Milosrdnice, Zagreb (Croatia). Dept. of Oncology and Nuclear Medicine

    1994-10-01

    Radioiodines are often used for experimental purposes and for diagnosis and therapy in clinical practice. Human population might also be exposed to radioiodines in nuclear accidents. The ionizing energy of radioiodine affects not only the thyroid where it concentrates but also other tissues, especially the lymphocytes during their circulation through and around the gland containing the radioisotopes. Therefore, it seemed to be of interest to carry out investigations concerning the cytogenetic alterations in blood lymphocytes of patients treated with iodine-131. The method of choice was the relatively easily performable micronucleus assay in cytokinesis-blocked cultures of human peripheral lymphocytes. The test was performed on blood samples of 30 patients before the radioisotope treatment and one, two and four days after, one as well as 6 and - in a few cases - 12 weeks later. The amounts of iodine-131 injected were dependent on the clinical practices to reach the therapeutic radiation doses for hyperthyroidism and adenomas and were in the range of 220 and 5180 MBq. it was observed that the micronucleus frequency increased in the treated hyperthyroid patients while in patients with toxic adenomas the radioiodine did not result in an increase or even as compared to the pretreatment values in a few cases decreased values were seen. The results suggest individual differences in radiosensitivity as well as that the frequency of cytogenetic alterations depend on the physiological or pathological conditions of the thyroid. The significance of this observation will be discussed for dose assessments by cytogenetic techniques due to internal radioiodine. (author).

  2. A kernel version of multivariate alteration detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack

    2013-01-01

    Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations.......Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations....

  3. Multislice quantitative computed tomography allows early detection of bone mineral density alterations induced by atherogenic diet in a growing rat experimental model

    International Nuclear Information System (INIS)

    Gubert, M.J.; Monforte, F.; Calo, C.; Lylyk, P.; Friedman, M.F.; Gamba, C.A.

    2012-01-01

    Purpose. To demonstrate the utility of Multislice Quantitative Computed Tomography (MS-QCT) in the early detection of mandibular bone mineral density (BMD) alterations induced by an atherogenic diet in a growing rat experimental model. Materials and Methods. Male weanling Wistar rats (n =16) were divided by body weight (Wt) into 2 groups: control (C) and experimental (E), with no significant differences in the mean initial Wt (p>0.05). C was fed rodent stock diet ad libitum, and E an atherogenic diet for 3 weeks (3w). Zoometry (body weight and length) and diet intake (g/100g rat/day) were monitored. At 3 w in serum (mg/dL) lipidlipoprotein profile was studied: total cholesterol (t-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C) and MSQCT (Philips 64 CT, quantified with the eFilm Workstation 2.1) in seven mandibular areas (MA): n. 1 to 4: from chin to mandibular foramen, n. 5: coronoid process, n. 6: condylar process, n. 7: angular process. Statistics: Pearson's correlation between BMD in each MA and serum t-C. p 0.05). Correlation coefficients (r) and their significance levels (p) were relevant in 5/7 MA. MA1:-0.580 (p=0.019), MA2:-0.709 (p=0.002), MA3:-0.635 (p=0.008), MA5:-0.674 (p=0.004), MA6:-0.564 (p=0.023). Conclusions. These results suggest that MS-QCT is an imaging diagnostic method that allows the early detection of mandible bone architecture alterations induced by an atherogenic diet. Inverse correlation between BMD and t-C would indicate an association between an atherogenic diet intake and potential temporomandibular disorders. (authors)

  4. Exploring the potential of acquisition curves of the anhysteretic remanent magnetization as a tool to detect subtle magnetic alteration induced by heating

    Science.gov (United States)

    de Groot, Lennart V.; Dekkers, Mark J.; Mullender, Tom A. T.

    2012-03-01

    Recently, many new methods and improved protocols to determine the absolute paleointensity of lavas reliably have been proposed. Here we study eight recent flows from three different volcanic edifices (Mt. Etna, La Palma and Hawaii) with the so-called multispecimen parallel differential pTRM (MSP) method including the recently proposed domain-state correction (MSP-DSC) (Fabian and Leonhardt, 2010). Surprisingly, apart from approximately correct paleointensity values, we observe major underestimates of the paleofield. These deviations are possibly related to alteration that is not revealed by rock-magnetic analysis. We explore the potential of high-resolution acquisition curves of the anhysteretic remanent magnetization (ARM) to detect subtle alteration in the samples. It appears that assessing changes in the ARM acquisition properties before and after heating to the desired MSP temperature discriminates between underestimates and approximately correct estimations of the paleofield in the outcomes of the MSP-DSC protocol. By combining observations from the domain-state corrected MSP protocol and ARM acquisition experiments before and after heating, an extended MSP protocol is suggested which makes it possible to assess the best set temperature for the MSP-DSC protocol and to label MSP results as being approximately correct, or an underestimate of the paleofield.

  5. Aqueous alteration detection in Tikhonravov crater, Mars

    Science.gov (United States)

    Mancarella, F.; Fonti, S.; Alemanno, G.; Orofino, V.; Blanco, A.

    2018-03-01

    The existence of a wet period lasting long enough to allow the development of elementary forms of life on Mars has always been a very interesting issue. Given this perspective, the research for geological markers of such occurrences has been continually pursued. Once a favorable site is detected, effort should be spent to get as much information as possible aimed at a precise assessment of the genesis and evolution of the areas showing the selected markers. In this work, we discuss the recent finding of possible deposits pointing to the past existence of liquid water in Tikhonravov crater located in Arabia Terra. Comparison of CRISM spectra and those of laboratory minerals formed by aqueous alteration has led us to the conclusion that the studied areas within the impact crater host phyllosilicates deposits. In addition, analysis of the CRISM spectra has resulted in the tentative identification of carbonates mixed with phyllosilicates.

  6. Hypergravity-induced altered behavior in Drosophila

    Science.gov (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  7. 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.)

  8. Detection of metal induced cytopathological alterations and DNA damage in the gills and hepatopancreas of green mussel Perna viridis from Ennore Estuary, Chennai, India

    International Nuclear Information System (INIS)

    Vasanthi, Lourduraj A.; Revathi, Peranandam; Babu Rajendran, Ramaswamy; Munuswamy, Natesan

    2017-01-01

    This study report the impact of heavy metals on cytopathology and DNA damage in the gills and hepatopancreas of Perna viridis collected from Ennore estuary and the Kovalam coastal waters. Principal Component Analysis (PCA) showed significant differences among all variables at the scale of plots. The ultrastructural alterations such as lack of microvilli, distorted mitochondria, electron dense particles and the presence of large mucous droplets were common in the gill and hepatopancreatic cells of mussels from Ennore estuary. However, the gill and hepatopancreatic cells of P. viridis from Kovalam revealed normal compartmentalization of cells. The percentage of tail DNA in the mussels from Ennore estuary was recorded as 12.44 and 10.14% in the gills and hepatopancreas respectively. Overall, it has been demonstrated that the Comet and cytopathological assays are useful biomarkers to assess the level of pollution and it provide reliable information on ecotoxicology and genotoxicology of coastal waters. - Highlights: • Bioaccumulation of heavy metals was studied in P. viridis from Ennore estuary. • Heavy metal accumulation leads to severe cellular and DNA damage. • Comet assay and cytopathology proved to be a biomarker in ecotoxicology. • The data justifies the need of remedial measures along Ennore Estuary.

  9. Diabetes induces metabolic alterations in dental pulp.

    Science.gov (United States)

    Leite, Mariana Ferreira; Ganzerla, Emily; Marques, Márcia Martins; Nicolau, José

    2008-10-01

    Diabetes can interfere in tissue nutrition and can impair dental pulp metabolism. This disease causes oxidative stress in cells and tissues. However, little is known about the antioxidant system in the dental pulp of diabetics. Thus, it would be of importance to study this system in this tissue in order to verify possible alterations indicative of oxidative stress. The aim of this study was to evaluate some parameters of antioxidant system of the dental pulp of healthy (n = 8) and diabetic rats (n = 8). Diabetes was induced by streptozotocin in rats. Six weeks after diabetes induction, a pool of the dental pulp of the 4 incisors of each rat (healthy and diabetic) was used for the determination of total protein and sialic acid concentrations and catalase and peroxidase activities. Data were compared by a Student t test (p pulps from both groups presented similar total protein concentrations and peroxidase activity. Dental pulps of diabetic rats exhibited significantly lower free, conjugated, and total sialic acid concentrations than those of control tissues. Catalase activity in diabetic dental pulps was significantly enhanced in comparison with that of control pulps. The result of the present study is indicative of oxidative stress in the dental pulp caused by diabetes. The increase of catalase activity and the reduction of sialic acid could be resultant of reactive oxygen species production.

  10. Relationship of histochemically detectable altered hepatocyte foci to hepatic tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Peraino, C.; Staffeldt, E.F.; Carnes, B.A.; Ludeman, V.A.; Blomquist, J.A.; Vesselinovitch, S.D.

    1984-01-01

    A new experimental system was used to examine the stages of chemically induced hepatic neoplasia in the rat. The treatment protocol involved the intraperitoneal injection of a single non-necrogenic dose of carcinogen (N-nitrosodiethylamine (NDEA) or benzo(a)pyrene (BP)) into male and female rats within one day after birth, followed by dietary exposure to promoter (0.05% phenobarbital) from weaning. Rats were killed at intervals, and their livers were examined for tumors and for histochemically detectable foci of altered hepatocytes. The data showed that (1) the new treatment protocol was highly efficient in foci and tumor production; (2) growth rates and incidence levels of foci were directly related to hepatocarcinogenic effectiveness (NDEA > BP), whereas both carcinogens had similar effects on foci phenotypic properties; (3) after their formation, foci at a given level of phenotypic complexity did not become progressively more complex; (4) incidence levels of foci were sex-dependent (females > males), but growth rates of foci were the same for both sexes; (5) growth rates and growth capacities (ranges of possible growth rates) of foci were directly related to phenotypic complexity levels of foci; (6) frequencies and phenotypic complexities of foci were inversely related; the reverse was true for tumors, although 10% of the tumors were relatively simple (three markers or fewer); (7) marker frequency distribution patterns were completely different in foci and in tumors.

  11. Detection Of Alterations In Audio Files Using Spectrograph Analysis

    Directory of Open Access Journals (Sweden)

    Anandha Krishnan G

    2015-08-01

    Full Text Available The corresponding study was carried out to detect changes in audio file using spectrograph. An audio file format is a file format for storing digital audio data on a computer system. A sound spectrograph is a laboratory instrument that displays a graphical representation of the strengths of the various component frequencies of a sound as time passes. The objectives of the study were to find the changes in spectrograph of audio after altering them to compare altering changes with spectrograph of original files and to check for similarity and difference in mp3 and wav. Five different alterations were carried out on each audio file to analyze the differences between the original and the altered file. For altering the audio file MP3 or WAV by cutcopy the file was opened in Audacity. A different audio was then pasted to the audio file. This new file was analyzed to view the differences. By adjusting the necessary parameters the noise was reduced. The differences between the new file and the original file were analyzed. By adjusting the parameters from the dialog box the necessary changes were made. The edited audio file was opened in the software named spek where after analyzing a graph is obtained of that particular file which is saved for further analysis. The original audio graph received was combined with the edited audio file graph to see the alterations.

  12. Induced mutation altering flower colour in Chrysanthemum

    Energy Technology Data Exchange (ETDEWEB)

    Datta, S K [National Botanical Research Institute, Lucknow (India)

    1989-01-01

    Full text: 'Flirt' is a double Korean type, small flowered Chrysanthemum of red colour. Rooted cuttings were treated with 1.5-2.5 krad gamma rays. A chimeral flower colour mutant was detected after 1.5 krad treatment. After purification through repeated cuttings a mutant clone was developed and released as commercial cultivar 'Man Bhawan'. It produces bi-coloured flower-heads: yellow and red at full bloom stage becoming completely yellow later on. By chromatography, 6 pigment spots could be identified in the variety 'Flirt' but only 5 in the mutant, violet (hRf 69.83) being absent. Spectrophotometric analysis of petal extracts showed presence of three peaks in both 'Flirt' and 'Man Bhawan' at full bloom stage but only two in 'Man Bhawan' at fading stage. (author)

  13. Aging induced ER stress alters sleep and sleep homeostasis

    OpenAIRE

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

    2013-01-01

    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 ...

  14. Texture alteration detection in bitemporal images of lesions with psoriasis

    DEFF Research Database (Denmark)

    Maletti, Gabriela Mariel; Ersbøll, Bjarne Kjær

    2003-01-01

    The objective of this work is to explore the feasibility of quantifying textural change between pairs of segmented patterns without registering them. The Multi-variate Alteration Detection (M.A.D.) Transform is applied to a texture model constructed with the data of segmented psoriasis lesions im...... images. The texture model is Haralick's co-occurrence matrix, which is computed and normalized for each single band with the equalized data of a given lesion. The contribution of each single color band to the textural change is analyzed....

  15. Hypoxia‐induced alterations of G2 checkpoint regulators

    OpenAIRE

    Hasvold, Grete; Lund-Andersen, Christin; Lando, Malin; Patzke, Sebastian; Hauge, Sissel; Suo, ZhenHe; Lyng, Heidi; Syljuåsen, Randi G.

    2016-01-01

    Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, genome stability is also surveilled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can influence the DNA damage‐induced cell cycle checkpoints. Here, we show that hypoxia (24 h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting o...

  16. Congenital heart malformations induced by hemodynamic altering surgical interventions

    Directory of Open Access Journals (Sweden)

    Madeline eMidgett

    2014-08-01

    Full Text Available Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load.

  17. Genomic alterations detected by comparative genomic hybridization in ovarian endometriomas

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    L.C. Veiga-Castelli

    2010-08-01

    Full Text Available Endometriosis is a complex and multifactorial disease. Chromosomal imbalance screening in endometriotic tissue can be used to detect hot-spot regions in the search for a possible genetic marker for endometriosis. The objective of the present study was to detect chromosomal imbalances by comparative genomic hybridization (CGH in ectopic tissue samples from ovarian endometriomas and eutopic tissue from the same patients. We evaluated 10 ovarian endometriotic tissues and 10 eutopic endometrial tissues by metaphase CGH. CGH was prepared with normal and test DNA enzymatically digested, ligated to adaptors and amplified by PCR. A second PCR was performed for DNA labeling. Equal amounts of both normal and test-labeled DNA were hybridized in human normal metaphases. The Isis FISH Imaging System V 5.0 software was used for chromosome analysis. In both eutopic and ectopic groups, 4/10 samples presented chromosomal alterations, mainly chromosomal gains. CGH identified 11q12.3-q13.1, 17p11.1-p12, 17q25.3-qter, and 19p as critical regions. Genomic imbalances in 11q, 17p, 17q, and 19p were detected in normal eutopic and/or ectopic endometrium from women with ovarian endometriosis. These regions contain genes such as POLR2G, MXRA7 and UBA52 involved in biological processes that may lead to the establishment and maintenance of endometriotic implants. This genomic imbalance may affect genes in which dysregulation impacts both eutopic and ectopic endometrium.

  18. 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.

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

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    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

  20. Hyperthermia-induced alteration of yeast susceptibility to mutation

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Morrison, D.P.

    1985-01-01

    Diploid yeast (s. cerevisiae) were examined for alterations in susceptibility to induced mutation following hyperthermia treatment. In cells grown at 23 0 C, a non-lethal heat exposure (38 0 C, 30 min) markedly suppressed mutation induced by a subsequent non-killing dose of MNNG of MNU. Mutation by ENU, 8-MOP + UVA, or γ-rays was not affected. An intermediate level of mutation suppression was observed for mutation by 254nm UV or MMS. Mutation by MNNG was not suppressed by the same heat treatment delivered after the mutagen exposure. In a split dose experiment (two MNNG treatments separated by a heat exposure) no suppression of mutation was observed. Treatment with cycloheximide mimicked the effect of heat treatment. These data suggest that mutation induction by MNNG or MNU is protein synthesis dependent, i.e. an error-prone repair system is induced by exposure to MNNG or MNU but not by ENU, 8-MOP+UVA or γ-irradiation. We propose that hyperthermia treatment, by inducing stress protein synthesis at the expense of normal protein synthesis, precludes induction of this error-prone system. Therefore, in heat treated cells, DNA lesions produced by MNNG or MNU exposure must be resolved by an essentially constitutive system which is less error-prone than the inducible one

  1. The alteration of chromatin domains during damage repair induced by ionizing radiation

    International Nuclear Information System (INIS)

    Cress, A.E.; Olson, K.M.; Olson, G.B.

    1995-01-01

    Several groups previously have reported the ability of chromatin structure to influence the production of damage induced by ionizing radiation. The authors' interest has been to determine whether chromatin structural alterations exist after ionizing radiation during a repair interval. The earlier work investigated this question using biochemical techniques. The crosslinking of nuclear structural proteins to DNA after ionizing radiation was observed. In addition, they found that the chromatin structure in vitro as measured by sucrose density gradient sedimentation, was altered after ionizing radiation. These observations added to earlier studies in which digital imaging techniques showed an alteration in feulgen-positive DNA after irradiation prompted the present study. The object of this study was to detect whether the higher order structure of DNA into chromatin domains within interphase human cells was altered in interphase cells in response to a radiation induced damage. The present study takes advantage of the advances in the detection of chromatin domains in situ using DNA specific dyes and digital image processing of established human T and B cell lines

  2. Prevention of shockwave induced functional and morphological alterations: an overview.

    Science.gov (United States)

    Sarica, Kemal; Yencilek, Faruk

    2008-03-01

    Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

  3. 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

  4. 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.

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

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    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

  6. 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.

  7. 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.

  8. Herbicide injury induces DNA methylome alterations in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Gunjune Kim

    2017-07-01

    Full Text Available The emergence of herbicide-resistant weeds is a major threat facing modern agriculture. Over 470 weedy-plant populations have developed resistance to herbicides. Traditional evolutionary mechanisms are not always sufficient to explain the rapidity with which certain weed populations adapt in response to herbicide exposure. Stress-induced epigenetic changes, such as alterations in DNA methylation, are potential additional adaptive mechanisms for herbicide resistance. We performed methylC sequencing of Arabidopsis thaliana leaves that developed after either mock treatment or two different sub-lethal doses of the herbicide glyphosate, the most-used herbicide in the history of agriculture. The herbicide injury resulted in 9,205 differentially methylated regions (DMRs across the genome. In total, 5,914 of these DMRs were induced in a dose-dependent manner, wherein the methylation levels were positively correlated to the severity of the herbicide injury, suggesting that plants can modulate the magnitude of methylation changes based on the severity of the stress. Of the 3,680 genes associated with glyphosate-induced DMRs, only 7% were also implicated in methylation changes following biotic or salinity stress. These results demonstrate that plants respond to herbicide stress through changes in methylation patterns that are, in general, dose-sensitive and, at least partially, stress-specific.

  9. Thermally-induced voltage alteration for integrated circuit analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cole, E.I. Jr.

    2000-06-20

    A thermally-induced voltage alteration (TIVA) apparatus and method are disclosed for analyzing an integrated circuit (IC) either from a device side of the IC or through the IC substrate to locate any open-circuit or short-circuit defects therein. The TIVA apparatus uses constant-current biasing of the IC while scanning a focused laser beam over electrical conductors (i.e. a patterned metallization) in the IC to produce localized heating of the conductors. This localized heating produces a thermoelectric potential due to the Seebeck effect in any conductors with open-circuit defects and a resistance change in any conductors with short-circuit defects, both of which alter the power demand by the IC and thereby change the voltage of a source or power supply providing the constant-current biasing. By measuring the change in the supply voltage and the position of the focused and scanned laser beam over time, any open-circuit or short-circuit defects in the IC can be located and imaged. The TIVA apparatus can be formed in part from a scanning optical microscope, and has applications for qualification testing or failure analysis of ICs.

  10. 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

  11. 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.

  12. Induced videokeratography alterations in patients with excessive meibomian secretions.

    Science.gov (United States)

    Markomanolakis, Marinos M; Kymionis, George D; Aslanides, Ioannis M; Astyrakakis, Nikolaos; Pallikaris, Ioannis G

    2005-01-01

    To describe lipid-induced specific videokeratographic (VKG) corneal changes and subsequent resolution after eyelid washing. VKG was performed with C-Scan corneal topography. In all patients an excessive meibomian gland lipid secretion was found with or without coexistent chronic posterior blepharitis. After the initial VKG, a meticulous cleaning of the lids with a mild alkali shampoo (10% Johnson's baby shampoo in sterile water) was done, first by gently scrubbing the closed eyelid fissure with the solution to mobilize and emulsify any Meibomian gland secretions followed by cleaning of the upper and lower margins individually, using Q-tip applicators soaked in the detergent. Three patients with tear film lipid layer excess (TFLE), which correlated with the presence of a superior or central corneal steepening in VKG, were studied. In two of the subjects, careful lid washing reversed either completely or partially this VKG effect, whereas in the last patient the VKG changes after artificially increasing the tear film lipid content is described. Meibomian gland lipid secretions may induce mainly superior and occasionally central VKG corneal steepening that is not correlated with any slit-lamp pathologic findings. Computerized corneal topography can help detect such corneal abnormalities, and their reversibility may distinguish them from other pathologic conditions (such as contact lens-induced warpage, eccentric ablations, irregular astigmatism, superior keratoconus).

  13. 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.

  14. 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

  15. 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

  16. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ou Xiufang [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Long Likun [Inspection and Quarantine Technology Centre of Zhongshan Entry-Exit Inspection and Quarantine Bureau, Zhongshan 528400, Guangdong Province (China); Zhang Yunhong; Xue Yiqun; Liu Jingchun; Lin Xiuyun [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Liu Bao [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China)], E-mail: baoliu6677@yahoo.com.cn

    2009-03-09

    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

  18. 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

  19. Transcriptomic biomarkers of altered erythropoiesis to detect autologous blood transfusion.

    Science.gov (United States)

    Salamin, Olivier; Mignot, Jonathan; Kuuranne, Tiia; Saugy, Martial; Leuenberger, Nicolas

    2018-03-01

    Autologous blood transfusion is a powerful means of improving performance and remains one of the most challenging methods to detect. Recent investigations have identified 3 candidate reticulocytes genes whose expression was significantly influenced by blood transfusion. Using quantitative reverse transcription polymerase chain reaction as an alternative quantitative method, the present study supports that delta-aminolevulinate synthase 2 (ALAS2), carbonic anhydrase (CA1), and solute carrier family 4 member 1 (SLC4A1) genes are down-regulated post-transfusion. The expression of these genes exhibited stronger correlation with immature reticulocyte fraction than with reticulocytes percentage. Moreover, the repression of reticulocytes' gene expression was more pronounced than the diminution of immature reticulocyte fraction and reticulocyte percentage following blood transfusion. It suggests that the 3 candidate genes are reliable predictors of bone marrow's response to blood transfusion and that they represent potential biomarkers for the detection of this method prohibited in sports. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Chronophin activation is necessary in Doxorubicin-induced actin cytoskeleton alteration.

    Science.gov (United States)

    Lee, Su Jin; Park, Jeen Woo; Kang, Beom Sik; Lee, Dong-Seok; Lee, Hyun-Shik; Choi, Sooyoung; Kwon, Oh-Shin

    2017-06-01

    Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and 14-3-3ζ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to 14-3-3ζ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling. [BMB Reports 2017; 50(6): 335-340].

  1. Radiation induced alterations in the endotoxin of S. typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Nerkar, D P; Govekar, L G; Kumta, U S; Sreenivasan, A [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

    1977-09-01

    The lipopolysaccharide (LPS) of S. typhimurium has been shown to be significantly detoxified after in vivo irradiation at 500 krad. Radiation is thus a useful method for converting endotoxin into toxoid. The structural alterations in the detoxified LPS were shown to be mainly in the lipid A molecule, resulting in the loss of ..beta..-hydroxymyristic acid.

  2. 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)

  3. 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 ...

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

    Indian Academy of Sciences (India)

    Cold-induced alteration in the global structure of the male sex ... dar et al. 1978). Chromosome preparated from a single pair of salivary glands show extremely puffy and diffuse ..... Akhtar A. 2003 Dosage compensation: an intertwined world of.

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

    CSIR Research Space (South Africa)

    Mhlongo, MI

    2016-10-01

    Full Text Available 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...

  6. Coarctation induces alterations in basement membranes in the cardiovascular system

    DEFF Research Database (Denmark)

    Lipke, D W; McCarthy, K J; Elton, T S

    1993-01-01

    ventricular hypertrophy was maximal within 5 days. In immunohistochemical studies, fibronectin and laminin were increased and the basement membrane chondroitin sulfate proteoglycan decreased in both the subendothelial space and smooth muscle cell basement membranes of the aorta above the clip compared...... membrane components in the heart and vasculature peaked before maximal cardiac hypertrophy (5 days). These studies indicate that alterations in basement membrane component deposition in the hypertrophied vasculature occur at both transcriptional and translational levels and suggest that the cell attachment...

  7. Altered functional brain connectivity in patients with visually induced dizziness

    Directory of Open Access Journals (Sweden)

    Angelique Van Ombergen

    2017-01-01

    Conclusions: We found alterations in the visual and vestibular cortical network in VID patients that could underlie the typical VID symptoms such as a worsening of their vestibular symptoms when being exposed to challenging visual stimuli. These preliminary findings provide the first insights into the underlying functional brain connectivity in VID patients. Future studies should extend these findings by employing larger sample sizes, by investigating specific task-based paradigms in these patients and by exploring the implications for treatment.

  8. Saccharomyces cerevisiae mutants with enhanced induced mutation and altered mitotic gene conversion.

    Science.gov (United States)

    Ivanov, E L; Kovaltzova, S V; Korolev, V G

    1989-08-01

    We have developed a method to isolate yeast (Saccharomyces cerevisiae) mutants with enhanced induced mutagenesis based on nitrous acid-induced reversion of the ade2-42 allele. Six mutants have been isolated and designated him (high induced mutagenesis), and 4 of them were studied in more detail. The him mutants displayed enhanced reversion of the ade2-42 allele, either spontaneous or induced by nitrous acid, UV light, and the base analog 6-N-hydroxylaminopurine, but not by gamma-irradiation. It is worth noting that the him mutants turned out not to be sensitive to the lethal effects of the mutagens used. The enhancement in mutation induced by nitrous acid, UV light, and 6-N-hydroxylaminopurine has been confirmed in a forward-mutation assay (induction of mutations in the ADE1, ADE2 genes). The latter agent revealed the most apparent differences between the him mutants and the wild-type strain and was, therefore, chosen for the genetic analysis of mutants, him mutations analyzed behaved as a single Mendelian trait; complementation tests indicated 3 complementation groups (HIM1, HIM2, and HIM3), each containing 1 mutant allele. Uracil-DNA glycosylase activity was determined in crude cell extracts, and no significant differences between the wild-type and him strains were detected. Spontaneous mitotic gene conversion at the ADE2 locus is altered in him1 strains, either increased or decreased, depending on the particular heteroallelic combination. Genetic evidence strongly suggests him mutations to be involved in a process of mismatch correction of molecular heteroduplexes.

  9. 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.

  10. 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.

  11. 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.

  12. Alterations in glucose kinetics induced by pentobarbital anesthesia

    International Nuclear Information System (INIS)

    Lang, C.H.; Bagby, G.J.; Spitzer, J.J.

    1986-01-01

    Pentobarbital is a common anesthetic agent used in animal research that is known to alter sympathetic function and may also affect carbohydrate metabolism. The in vivo effects of iv pentobarbital on glucose homeostasis were studied in chronically catheterized fasted rats. Whole body glucose kinetics, assessed by the constant iv infusion of [6- 3 H]- and [U- 14 C]-glucose, were determined in all rats in the conscious state. Thereafter, glucose metabolism was followed over the next 4 hr in 3 subgroups of rats; conscious, anesthetized with body temperature maintained, and anesthetized with body temperature not maintained. Hypothermia (a 5 0 C decrease) developed spontaneously in anesthetized rats kept at ambient temperature (22 0 C). No differences were seen in MABP and heart rate between conscious and normothermic anesthetized rats; however, hypothermic anesthetized rats showed a decrease in MABP (20%) and heart rate (35%). Likewise, plasma glucose and lactate concentrations, the rate of glucose appearance (Ra), recycling and metabolic clearance (MCR) did not differ between conscious and normothermic anesthetized animals. In contrast, hypothermic anesthetized rats showed a 50% reduction in plasma lactate, a 40% drop in glucose Ra, and a 30-40% decrease in glucose recycling and MCR. Thus, pentobarbital does not appear to alter in vivo glucose kinetics, compared to unanesthetized controls, provided that body temperature is maintained

  13. 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)

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

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    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.

  15. Alterations and Abnormal Mitosis of Wheat Chromosomes Induced by Wheat-Rye Monosomic Addition Lines

    Science.gov (United States)

    Fu, Shulan; Yang, Manyu; Fei, Yunyan; Tan, Feiquan; Ren, Zhenglong; Yan, Benju; Zhang, Huaiyu; Tang, Zongxiang

    2013-01-01

    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. PMID:23936213

  16. 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)

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

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    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.

  18. 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.

  19. Altered brain network modules induce helplessness in major depressive disorder.

    Science.gov (United States)

    Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Fang, Yiru; Shen, Dinggang

    2014-10-01

    The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. 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

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

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    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.

  2. Infrequent alterations of the P53 gene in rat skin cancers induced by ionising-radiation

    International Nuclear Information System (INIS)

    Jin, Y.; Burns, F.J.; Garte, S.J.; Hosselet, S.; New York Univ., NY

    1996-01-01

    Radiation carcinogenesis almost certainly involves multiple genetic alterations. Identification of such genetic alterations would provide information to help understand better the molecular mechanism or radiation carcinogenesis. The energy released by ionizing radiation has the potential to produce DNA strand breaks, major gene deletions or rearrangements, and other base damages. Alterations of the p53 gene, a common tumour suppressor gene altered in human cancers, were examined in radiation-induced rat skin cancers. Genomic DNA from a total of 33rat skin cancers induced by ionizing radiation was examined by Southern blot hybridization for abnormal restriction fragment patterns in the p53 gene. A abnormal p53 restriction pattern was found in one of 16 cancers induced by electron radiation and in one of nine cancers induced by neon ions. The genomic DNA from representative cancers, including the two with an abnormal restriction pattern was further examined by polymerase chain reaction amplification and direct sequencing in exons 5-8 of the p53 gene. The results showed that one restriction fragment length polymorphism (RFLP)-positive cancer induced by electron radiation had a partial gene deletion which was defined approximately between exons 2-8, while none of the other cancers showed sequence changes. Our results indicate that the alterations in the critical binding region of the p53 gene are infrequent in rat skin cancers induced by either electron or neon ion radiation. (Author)

  3. 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.

  4. Ecstasy-Induced Caspase Expression Alters Following Ginger Treatment

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    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.

  5. 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

  6. Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction.

    Science.gov (United States)

    Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V; Will, Nathan E; Irmady, Krithi; Lee, Francis S; Hempstead, Barbara L; Bracken, Clay

    2013-01-01

    A common single-nucleotide polymorphism (SNP) in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This SNP is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism, we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75(NTR) and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand, which modulates neuronal morphology.

  7. 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

  8. 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.

  9. 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.

  10. Parvovirus induced alterations in nuclear architecture and dynamics.

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    Teemu O Ihalainen

    2009-06-01

    Full Text Available The nucleus of interphase eukaryotic cell is a highly compartmentalized structure containing the three-dimensional network of chromatin and numerous proteinaceous subcompartments. DNA viruses induce profound changes in the intranuclear structures of their host cells. We are applying a combination of confocal imaging including photobleaching microscopy and computational methods to analyze the modifications of nuclear architecture and dynamics in parvovirus infected cells. Upon canine parvovirus infection, expansion of the viral replication compartment is accompanied by chromatin marginalization to the vicinity of the nuclear membrane. Dextran microinjection and fluorescence recovery after photobleaching (FRAP studies revealed the homogeneity of this compartment. Markedly, in spite of increase in viral DNA content of the nucleus, a significant increase in the protein mobility was observed in infected compared to non-infected cells. Moreover, analysis of the dynamics of photoactivable capsid protein demonstrated rapid intranuclear dynamics of viral capsids. Finally, quantitative FRAP and cellular modelling were used to determine the duration of viral genome replication. Altogether, our findings indicate that parvoviruses modify the nuclear structure and dynamics extensively. Intranuclear crowding of viral components leads to enlargement of the interchromosomal domain and to chromatin marginalization via depletion attraction. In conclusion, parvoviruses provide a useful model system for understanding the mechanisms of virus-induced intranuclear modifications.

  11. Detection of random alterations to time-varying musical instrument spectra.

    Science.gov (United States)

    Horner, Andrew; Beauchamp, James; So, Richard

    2004-09-01

    The time-varying spectra of eight musical instrument sounds were randomly altered by a time-invariant process to determine how detection of spectral alteration varies with degree of alteration, instrument, musical experience, and spectral variation. Sounds were resynthesized with centroids equalized to the original sounds, with frequencies harmonically flattened, and with average spectral error levels of 8%, 16%, 24%, 32%, and 48%. Listeners were asked to discriminate the randomly altered sounds from reference sounds resynthesized from the original data. For all eight instruments, discrimination was very good for the 32% and 48% error levels, moderate for the 16% and 24% error levels, and poor for the 8% error levels. When the error levels were 16%, 24%, and 32%, the scores of musically experienced listeners were found to be significantly better than the scores of listeners with no musical experience. Also, in this same error level range, discrimination was significantly affected by the instrument tested. For error levels of 16% and 24%, discrimination scores were significantly, but negatively correlated with measures of spectral incoherence and normalized centroid deviation on unaltered instrument spectra, suggesting that the presence of dynamic spectral variations tends to increase the difficulty of detecting spectral alterations. Correlation between discrimination and a measure of spectral irregularity was comparatively low.

  12. MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.

    Science.gov (United States)

    Di Pasqua, Laura G; Berardo, Clarissa; Rizzo, Vittoria; Richelmi, Plinio; Croce, Anna Cleta; Vairetti, Mariapia; Ferrigno, Andrea

    2016-08-01

    Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8-week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8 weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8 weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH.

  13. 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

  14. Genistein-induced alterations of radiation-responsive gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Grace, M.B. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: grace@afrri.usuhs.mil; Blakely, W.F.; Landauer, M.R. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    In order to clarify the molecular mechanism of radioprotection and understand biological dosimetry in the presence of medical countermeasure-radioprotectants, their effects on ionizing radiation (IR)-responsive molecular biomarkers must be examined. We used genistein in a radiation model system and measured gene expression by multiplex QRT-PCR assay in drug-treated healthy human blood cultures. Genistein has been demonstrated to be a radiosensitizer of malignant cells and a radioprotector against IR-induced lethality in a mouse model. Whole-blood cultures were supplemented with 50, 100, and 200{mu}M concentrations of genistein, 16 h prior to receiving a 2-Gy ({sup 60}Co-{gamma} rays, 10 cGy/min) dose of IR. Total RNA was isolated from whole blood 24 h postirradiation for assessments. Combination treatments of genistein and IR resulted in no significant genistein effects on ddb2 and bax downstream transcripts to p53, or proliferating cell-nuclear antigen, pcna, necessary for DNA synthesis and cell-cycle progression. Use of these radiation-responsive targets would be recommended for dose-assessment applications. We also observed decreased expression of pro-survival transcript, bcl-2. Genistein and IR-increased expression of cdkn1a and gadd45a, showing that genistein also stimulates p53 transcriptional activity. These results confirm published molecular signatures for genistein in numerous in vitro models. Evaluation of gene biomarkers may be further exploited for devising novel radiation countermeasure and/or therapeutic strategies.

  15. Dissolved oxygen detection by galvanic displacement-induced

    Indian Academy of Sciences (India)

    Dissolved oxygen detection by galvanic displacement-induced graphene/silver nanocomposite ... dissolved oxygen (DO) detection based on a galvanic displacement synthesized reduced graphene oxide–silver nanoparticles ... Current Issue

  16. Analysis of radiation-induced genome alterations in Vigna unguiculata

    Directory of Open Access Journals (Sweden)

    van der Vyver C

    2011-09-01

    Full Text Available Christell van der Vyver1, B Juan Vorster2, Karl J Kunert3, Christopher A Cullis41Institute for Plant Biotechnology, Department of Genetics, University of Stellenbosch, Stellenbosch, South Africa; 2Department of Plant Production and Soil Science, and 3Department of Plant Science, Forestry and Agricultural Biotechnology Institute, University of Pretoria, Pretoria, South Africa; 4Case Western Reserve University, Department of Biology, Cleveland, OH, USAAbstract: Seeds from an inbred Vigna unguiculata (cowpea cultivar were gamma-irradiated with a dose of 180 Gy in order to identify and characterize possible mutations. Three techniques, ie, random amplified polymorphic DNA, microsatellites, and representational difference analysis, were used to characterize possible DNA variation among the mutants and nonirradiated control plants both immediately after irradiation and in subsequent generations. A large portion of putative radiation-induced genome changes had significant similarities to chloroplast sequences. The frequency of mutation at three of these isolated polymorphic regions with chloroplast similarity was further determined by polymerase chain reaction screening using a large number of individual parental, M1, and M2 plants. Analysis of these sequences indicated that the rate at which various regions of the genome is mutated in irradiation experiments differs significantly and also that mutations have variable “repair” rates. Furthermore, regions of the nuclear DNA derived from the chloroplast genome are highly susceptible to modification by radiation treatment. Overall, data have provided detailed information on the effects of gamma irradiation on the cowpea genome and about the ability of the plant to repair these genome changes in subsequent plant generations.Keywords: mutation breeding, gamma radiation, genetic mutations, cowpea, representational difference analysis

  17. Fast and sensitive detection of indels induced by precise gene targeting

    DEFF Research Database (Denmark)

    Yang, Zhang; Steentoft, Catharina; Hauge, Camilla

    2015-01-01

    The nuclease-based gene editing tools are rapidly transforming capabilities for altering the genome of cells and organisms with great precision and in high throughput studies. A major limitation in application of precise gene editing lies in lack of sensitive and fast methods to detect...... and characterize the induced DNA changes. Precise gene editing induces double-stranded DNA breaks that are repaired by error-prone non-homologous end joining leading to introduction of insertions and deletions (indels) at the target site. These indels are often small and difficult and laborious to detect...

  18. Radiation-induced alterations of histone post-translational modification levels in lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Maroschik, Belinda; Gürtler, Anne; Krämer, Anne; Rößler, Ute; Gomolka, Maria; Hornhardt, Sabine; Mörtl, Simone; Friedl, Anna A

    2014-01-01

    Radiation-induced alterations in posttranslational histone modifications (PTMs) may affect the cellular response to radiation damage in the DNA. If not reverted appropriately, altered PTM patterns may cause long-term alterations in gene expression regulation and thus lead to cancer. It is therefore important to characterize radiation-induced alterations in PTM patterns and the factors affecting them. A lymphoblastoid cell line established from a normal donor was used to screen for alterations in methylation levels at H3K4, H3K9, H3K27, and H4K20, as well as acetylation at H3K9, H3K56, H4K5, and H4K16, by quantitative Western Blot analysis at 15 min, 1 h and 24 h after irradiation with 2 Gy and 10 Gy. The variability of alterations in acetylation marks was in addition investigated in a panel of lymphoblastoid cell lines with differing radiosensitivity established from lung cancer patients. The screening procedure demonstrated consistent hypomethylation at H3K4me3 and hypoacetylation at all acetylation marks tested. In the panel of lymphoblastoid cell lines, however, a high degree of inter-individual variability became apparent. Radiosensitive cell lines showed more pronounced and longer lasting H4K16 hypoacetylation than radioresistant lines, which correlates with higher levels of residual γ-H2AX foci after 24 h. So far, the factors affecting extent and duration of radiation-induced histone alterations are poorly defined. The present work hints at a high degree of inter-individual variability and a potential correlation of DNA damage repair capacity and alterations in PTM levels

  19. Mitomycin C induced alterations in antioxidant enzyme levels in a model insect species, Spodoptera eridania.

    Science.gov (United States)

    Batcabe, J P; MacGill, R S; Zaman, K; Ahmad, S; Pardini, R S

    1994-05-01

    1. An insect species, the southern armyworm Spodoptera eridania, was used as an in vivo model to examine mitomycin C's (MMC) pro-oxidant effect reflected in alterations of antioxidant enzymes. 2. Following a 2-day exposure to 0.01 and 0.05% w/w dietary concentrations, MMC only induced superoxide dismutase activity. All other enzyme activities were not affected, indicating oxidative stress was mild. 3. Following a 5-day exposure to 0.05% w/w dietary MMC, the activities of superoxide dismutase, glutathione-S-transferase and its peroxidase activity and DT-diaphorase were induced. GR activity was not altered. The high constitutive catalase activity was also not affected. These responses of S. eridania's antioxidant enzymes are analogous to those of mammalian systems in alleviating MMC-induced oxidative stress. 4. S. eridania emerges as an appropriate non-mammalian model for initial and cost-effective screening of drug-induced oxidative stress.

  20. Alteration mineral mapping in inaccessible regions using target detection algorithms to ASTER data

    International Nuclear Information System (INIS)

    Pour, A B; Hashim, M; Park, Y

    2017-01-01

    In this study, the applications of target detection algorithms such as Constrained Energy Minimization (CEM), Orthogonal Subspace Projection (OSP) and Adaptive Coherence Estimator (ACE) to shortwave infrared bands of the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data was investigated to extract geological information for alteration mineral mapping in poorly exposed lithologies in inaccessible domains. The Oscar II coast area north-eastern Graham Land, Antarctic Peninsula (AP) was selected in this study to conduct a satellite-based remote sensing mapping technique. It is an inaccessible region due to the remoteness of many rock exposures and the necessity to travel over sever mountainous and glacier-cover terrains for geological field mapping and sample collection. Fractional abundance of alteration minerals such as muscovite, kaolinite, illite, montmorillonite, epidote, chlorite and biotite were identified in alteration zones using CEM, OSP and ACE algorithms in poorly mapped and unmapped zones at district scale for the Oscar II coast area. The results of this investigation demonstrated the applicability of ASTER shortwave infrared spectral data for lithological and alteration mineral mapping in poorly exposed lithologies and inaccessible regions, particularly using the image processing algorithms that are capable to detect sub-pixel targets in the remotely sensed images, where no prior information is available. (paper)

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Allergen-Induced Dermatitis Causes Alterations in Cutaneous Retinoid-Mediated Signaling in Mice

    Science.gov (United States)

    Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Dubrac, Sandrine; Rühl, Ralph

    2013-01-01

    Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases. PMID:23977003

  6. PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity

    Science.gov (United States)

    Madeo, G.; Schirinzi, T.; Martella, G.; Latagliata, E.C.; Puglisi, F.; Shen, J.; Valente, E.M.; Federici, M.; Mercuri, N.B.; Puglisi-Allegra, S.; Bonsi, P.; Pisani, A.

    2014-01-01

    Background Homozygous or compound heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene are causative of autosomal recessive, early onset PD. Single heterozygous mutations have been repeatedly detected in a subset of patients as well as in non-affected subjects, and their significance has long been debated. Several neurophysiological studies from non-manifesting PINK1 heterozygotes have shown the existence of neural plasticity abnormalities, indicating the presence of specific endophenotypic traits in the heterozygous state. Methods In the present study, we performed a functional analysis of corticostriatal synaptic plasticity in heterozygous PINK1 knock-out (PINK1+/−) mice by a multidisciplinary approach. Results We found that, despite a normal motor behavior, repetitive activation of cortical inputs to striatal neurons failed to induce long-term potentiation (LTP), whereas long-term depression (LTD) was normal. Although nigral dopaminergic neurons exhibited normal morphological and electrophysiological properties with normal responses to dopamine receptor activation, we measured a significantly lower dopamine release in the striatum of PINK1+/−, compared to control mice, suggesting that a decrease in stimulus-evoked dopamine overflow acts as a major determinant for the LTP deficit. Accordingly, pharmacological agents capable of increasing the availability of dopamine in the synaptic cleft restored a normal LTP in heterozygous mice. Moreover, MAO-B inhibitors rescued a physiological LTP and a normal dopamine release. Conclusions Our results provide novel evidence for striatal plasticity abnormalities even in the heterozygous disease state. These alterations might be considered an endophenotype to this monogenic form of PD, and a valid tool to characterize early disease stage and design possible disease-modifying therapies. PMID:24167038

  7. 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 ...

  8. 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

  9. 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.

  10. 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

  11. Sparse representation and Bayesian detection of genome copy number alterations from microarray data.

    Science.gov (United States)

    Pique-Regi, Roger; Monso-Varona, Jordi; Ortega, Antonio; Seeger, Robert C; Triche, Timothy J; Asgharzadeh, Shahab

    2008-02-01

    Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) that are associated with the development and behavior of tumors. Advances in microarray technology have allowed for greater resolution in detection of DNA copy number changes (amplifications or deletions) across the genome. However, the increase in number of measured signals and accompanying noise from the array probes present a challenge in accurate and fast identification of breakpoints that define CNA. This article proposes a novel detection technique that exploits the use of piece wise constant (PWC) vectors to represent genome copy number and sparse Bayesian learning (SBL) to detect CNA breakpoints. First, a compact linear algebra representation for the genome copy number is developed from normalized probe intensities. Second, SBL is applied and optimized to infer locations where copy number changes occur. Third, a backward elimination (BE) procedure is used to rank the inferred breakpoints; and a cut-off point can be efficiently adjusted in this procedure to control for the false discovery rate (FDR). The performance of our algorithm is evaluated using simulated and real genome datasets and compared to other existing techniques. Our approach achieves the highest accuracy and lowest FDR while improving computational speed by several orders of magnitude. The proposed algorithm has been developed into a free standing software application (GADA, Genome Alteration Detection Algorithm). http://biron.usc.edu/~piquereg/GADA

  12. Stability of medicines after repackaging into multicompartment compliance aids: eight criteria for detection of visual alteration.

    Science.gov (United States)

    Albert, Valerie; Lanz, Michael; Imanidis, Georgios; Hersberger, Kurt E; Arnet, Isabelle

    2017-01-01

    Multicompartment compliance aids (MCA) are widely used by patients. They support the management of medication and reduce unintentional nonadherence. MCA are filled with medicines unpacked from their original packaging. Swiss pharmacists currently provide MCA for 1-2 weeks, although little and controversial information exists on the stability of repackaged medicines. We aimed to validate the usefulness of a simple screening method capable of detecting visual stability problems with repackaged medicines. We selected eight criteria for solid formulations from The International Pharmacopoeia : (1) rough surface, (2) chipping, (3) cracking, (4) capping, (5) mottling, (6) discoloration, (7) swelling, and (8) crushing. A selection of 24 critical medicines was repackaged in three different MCA (Pharmis ® , SureMed™, and self-produced blister) and stored at room temperature for 4 weeks. Pharmis ® was additionally stored at accelerated conditions. Appearance was scored weekly. Six alterations (rough surface, cracking, mottling, discoloration, swelling, and crushing) were observed at accelerated conditions. No alteration was observed at room temperature, except for the chipping of tablets that had been stuck to cold seal glue. The eight criteria can detect alterations of the appearance of oral solid medicines repackaged in MCA. In the absence of specific guidelines, they can serve as a simple screening method in community pharmacies for identifying medicines unsuitable for repackaging.

  13. 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.

  14. 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.

  15. Intra-strain polymorphisms are detected but no genomic alteration is found in cloned mice

    International Nuclear Information System (INIS)

    Gotoh, Koshichi; Inoue, Kimiko; Ogura, Atsuo; Oishi, Michio

    2006-01-01

    In-gel competitive reassociation (IGCR) is a method for differential subtraction of polymorphic (RFLP) DNA fragments between two DNA samples of interest without probes or specific sequence information. Here, we applied the IGCR procedure to two cloned mice derived from an F1 hybrid of the C57BL/6Cr and DBA/2 strains, in order to investigate the possibility of genomic alteration in the cloned mouse genomes. Each of the five of the genomic alterations we detected between the two cloned mice corresponded to the 'intra-strain' polymorphisms in the C57BL/6Cr and DBA/2 mouse strains. Our result suggests that no severe aberration of genome sequences occurs due to somatic cell nuclear transfer

  16. 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.

  17. 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.

  18. Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

    Science.gov (United States)

    Máthé, Csaba; M-Hamvas, Márta; Vasas, Gábor

    2013-01-01

    Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs), a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN), an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs) are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS) and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization. PMID:24084787

  19. Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

    Directory of Open Access Journals (Sweden)

    Gábor Vasas

    2013-09-01

    Full Text Available Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs, a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN, an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization.

  20. 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

  1. 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

  2. Phenobarbital Induces Alterations in the Proteome of Hepatocytes and Mesenchymal Cells of Rat Livers

    Science.gov (United States)

    Klepeisz, Philip; Sagmeister, Sandra; Haudek-Prinz, Verena; Pichlbauer, Melanie; Grasl-Kraupp, Bettina; Gerner, Christopher

    2013-01-01

    Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs) have concentrated on alterations induced in hepatocytes (HCs). A potential role of non-parenchymal liver cells (NPCs) in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB) which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme. PMID:24204595

  3. Phenobarbital induces alterations in the proteome of hepatocytes and mesenchymal cells of rat livers.

    Directory of Open Access Journals (Sweden)

    Philip Klepeisz

    Full Text Available Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs have concentrated on alterations induced in hepatocytes (HCs. A potential role of non-parenchymal liver cells (NPCs in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme.

  4. 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

  5. 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.

  6. Detection of Greenhouse-Gas-Induced Climatic Change

    Energy Technology Data Exchange (ETDEWEB)

    Jones, P.D.; Wigley, T.M.L.

    1998-05-26

    The objective of this report is to assemble and analyze instrumental climate data and to develop and apply climate models as a basis for (1) detecting greenhouse-gas-induced climatic change, and (2) validation of General Circulation Models.

  7. 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.

  8. Halobenzoquinone-Induced Alteration of Gene Expression Associated with Oxidative Stress Signaling Pathways.

    Science.gov (United States)

    Li, Jinhua; Moe, Birget; Liu, Yanming; Li, Xing-Fang

    2018-06-05

    Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) that effectively induce reactive oxygen species and oxidative damage in vitro. However, the impacts of HBQs on oxidative-stress-related gene expression have not been investigated. In this study, we examined alterations in the expression of 44 genes related to oxidative-stress-induced signaling pathways in human uroepithelial cells (SV-HUC-1) upon exposure to six HBQs. The results show the structure-dependent effects of HBQs on the studied gene expression. After 2 h of exposure, the expression levels of 9 to 28 genes were altered, while after 8 h of exposure, the expression levels of 29 to 31 genes were altered. Four genes ( HMOX1, NQO1, PTGS2, and TXNRD1) were significantly upregulated by all six HBQs at both exposure time points. Ingenuity pathway analysis revealed that the Nrf2 pathway was significantly responsive to HBQ exposure. Other canonical pathways responsive to HBQ exposure included GSH redox reductions, superoxide radical degradation, and xenobiotic metabolism signaling. This study has demonstrated that HBQs significantly alter the gene expression of oxidative-stress-related signaling pathways and contributes to the understanding of HBQ-DBP-associated toxicity.

  9. 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.

  10. Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

    Science.gov (United States)

    Prodam, F; Gasco, V; Caputo, M; Zavattaro, M; Pagano, L; Marzullo, P; Belcastro, S; Busti, A; Perino, C; Grottoli, S; Ghigo, E; Aimaretti, G

    2013-08-01

    Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (phypopituitaric patients. In particular, triglycerides (phypopituitaric TBI patients. We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Salicylic acid-induced germination, biochemical and developmental alterations in rye (Secale cereale L.)

    OpenAIRE

    Yanik, Fatma; Aytürk, Özlem; Çetinbaş-Genç, Aslihan; Vardar, Filiz

    2018-01-01

    Salicylic acid (SA) is one of the endogenous plant growth regulators that modulate various metabolic and physiological events. To evaluate the exogenous SA-induced germination, biochemical and developmental alterations, different concentrations (10, 100, 500 and 1000 μM) of SA were applied to rye (Secale cereale L.) seeds in hydroponic culture conditions for 15 days. The observations revealed that seed germination and root elongation were stimulated in 10 μM SA treatment, however they were in...

  12. 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

  13. 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

  14. High salt diet induces metabolic alterations in multiple biological processes of Dahl salt-sensitive rats.

    Science.gov (United States)

    Wang, Yanjun; Liu, Xiangyang; Zhang, Chen; Wang, Zhengjun

    2018-06-01

    High salt induced renal disease is a condition resulting from the interactions of genetic and dietary factors causing multiple complications. To understand the metabolic alterations associated with renal disease, we comprehensively analyzed the metabonomic changes induced by high salt intake in Dahl salt-sensitive (SS) rats using GC-MS technology and biochemical analyses. Physiological features, serum chemistry, and histopathological data were obtained as complementary information. Our results showed that high salt (HS) intake for 16 weeks caused significant metabolic alterations in both the renal medulla and cortex involving a variety pathways involved in the metabolism of organic acids, amino acids, fatty acids, and purines. In addition, HS enhanced glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) and amino acid metabolism and suppressed the TCA (citrate synthase and aconitase) cycle. Finally, HS intake caused up-regulation of the pentose phosphate pathway (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), the ratio of NADPH/NADP + , NADPH oxidase activity and ROS production, suggesting that increased oxidative stress was associated with an altered PPP pathway. The metabolic pathways identified may serve as potential targets for the treatment of renal damage. Our findings provide comprehensive biochemical details about the metabolic responses to a high salt diet, which may contribute to the understanding of renal disease and salt-induced hypertension in SS rats. Copyright © 2018. Published by Elsevier Inc.

  15. 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

  16. Altered dopamine levels induced by the parasite Profilicollis antarcticus on its intermediate host, the crab Hemigrapsus crenulatus.

    Science.gov (United States)

    Rojas, José Miguel; Ojeda, F Patricio

    2005-01-01

    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.

  17. Biomarkers for the early detection of cancer treatment induced cardiotoxicity

    NARCIS (Netherlands)

    Bulten, Ben

    2016-01-01

    In this thesis, the role of several imaging and nonimaging markers for the detection of anthracycline-induced and trastuzumab-induced cardiotoxicity (respectively AIC and TIC) is evaluated. Especially, the pathophysiology of these processes and the interrelationship of the various markers are

  18. Chromosome alterations in the X-ray-induced transformants of cultured mouse cell line

    International Nuclear Information System (INIS)

    Kodama, Seiji; Komatsu, Kenshi; Okumura, Yutaka; Sasaki, M.S.

    1989-01-01

    Mouse m5S cells were subjected to soft X-ray irradiation. Twenty-four transformants were separated as indicators of focus formation. Two clones, cl.4103 and cl.6310, were chosen for the analysis of chromosome alterations in transformants. A parent strain, m5S/1M, served as the control. Anchorage independence (AG) was not detected in the control strain, irrespective of culture conditions and population doubling number (PDN). In the case of transformants, the frequency of AG was increased with increasing PDN for cl.4103, and was constant for cl.6310, irrespective of PDN. Karyotype of m5S/1M was 42, X, -Y, +der (6) t(6;13), t(8;8), +8, +15. In addition, -13, der(10) and -der(6)t(6;13), der(5), +mar occurred as karyotype alterations for cl.4103 and cl. 6310, respectively. The present experiment indicated that chromosome alterations secondary to primary alterations occur in a high frequency in the transforming process of X-ray irradiated cells, and that the secondary chromosome alterations result in selective proliferation of transformed clones. (Namekawa, K)

  19. 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.

  20. 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.

  1. Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.

    Science.gov (United States)

    2017-07-01

    We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up ( P  cancer-associated gene expression alterations between the two airway sites ( P  lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P  = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P  = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. These results support that the airway epithelial field of lung cancer-associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Probing Contaminant-Induced Alterations in Chlorophyll Fluorescence by AC-Dielectrophoresis-Based 2D-Algal Array

    Directory of Open Access Journals (Sweden)

    Coralie Siebman

    2018-02-01

    Full Text Available The investigation of contaminant impact on algae requires rapid and reliable cell collection and optical detection. The capability of alternative current (AC dielectrophoresis (DEP collection of whole cell arrays with combined fluorescence microscopy detection to follow the alterations of chlorophyll fluorescence during environmental contaminant exposure was explored. The application of an AC-field of 100 V cm−1, 100 Hz for 30 min to capture and immobilize the cells of green alga Chlamydomonas reinhardtii in two-dimensional (2D arrays does not induce changes in chlorophyll fluorescence. The results demonstrate that DEP-based 2D-arrays allow non-invasive detection of chlorophyll fluorescence change upon exposure to high concentrations of copper oxide nanoparticles and ionic copper. These results were in agreement with data obtained by flow cytometry used as a comparative method. The tool was also applied to follow the effect of a number of ubiquitous contaminants such as inorganic mercury, methylmercury, and diuron. However, a statistically significant short-term effect was observed only for mercury. Overall, DEP-based 2D-arrays of algal cells with fluorescence detection appear to be suitable for stain-free probing the effects on the photosynthetic microorganisms in highly polluted environment.

  3. AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination.

    Science.gov (United States)

    Kobayashi, Maki; Aida, Masatoshi; Nagaoka, Hitoshi; Begum, Nasim A; Kitawaki, Yoko; Nakata, Mikiyo; Stanlie, Andre; Doi, Tomomitsu; Kato, Lucia; Okazaki, Il-mi; Shinkura, Reiko; Muramatsu, Masamichi; Kinoshita, Kazuo; Honjo, Tasuku

    2009-12-29

    To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5' to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one strand of DNA. Curiously, Top1 reduction or AID overexpression causes the genomic instability. Here, we report that the inactivation of Top1 by its specific inhibitor camptothecin drastically blocked both the S region cleavage and CSR, indicating that Top1 is responsible for the S region cleavage in CSR. Surprisingly, AID expression suppressed Top1 mRNA translation and reduced its protein level. In addition, the decrease in the Top1 protein by RNA-mediated knockdown augmented the AID-dependent S region cleavage, as well as CSR. Furthermore, Top1 reduction altered DNA structure of the Smu region. Taken together, AID-induced Top1 reduction alters S region DNA structure probably to non-B form, on which Top1 can introduce nicks but cannot religate, resulting in S region cleavage.

  4. Orthodontic treatment-induced temporal alteration of jaw-opening reflex excitability.

    Science.gov (United States)

    Sasaki, Au; Hasegawa, Naoya; Adachi, Kazunori; Sakagami, Hiroshi; Suda, Naoto

    2017-10-01

    The impairment of orofacial motor function during orthodontic treatment needs to be addressed, because most orthodontic patients experience pain and motor excitability would be affected by pain. In the present study, the temporal alteration of the jaw-opening reflex excitability was investigated to determine if orthodontic treatment affects orofacial motor function. The excitability of jaw-opening reflex evoked by electrical stimulation on the gingiva and recorded bilaterally in the anterior digastric muscles was evaluated at 1 (D1), 3 (D3), and 7 days (D7) after orthodontic force application to the teeth of right side; morphological features (e.g., osteoclast genesis and tooth movement) were also evaluated. To clarify the underlying mechanism of orthodontic treatment-induced alteration of orofacial motor excitability, analgesics were administrated for 1 day. At D1 and D3, orthodontic treatment significantly decreased the threshold for inducing the jaw-opening reflex but significantly increased the threshold at D7. Other parameters of the jaw-opening reflex were also evaluated (e.g., latency, duration and area under the curve of anterior digastric muscles activity), and only the latency of the D1 group was significantly different from that of the other groups. Temporal alteration of the jaw-opening reflex excitability was significantly correlated with changes in morphological features. Aspirin (300 mg·kg -1 ·day -1 ) significantly increased the threshold for inducing the jaw-opening reflex, whereas a lower dose (75-150 mg·kg -1 ·day -1 ) of aspirin or acetaminophen (300 mg·kg -1 ·day -1 ) failed to alter the jaw-opening reflex excitability. These results suggest that an increase of the jaw-opening reflex excitability can be induced acutely by orthodontic treatment, possibly through the cyclooxygenase activation. NEW & NOTEWORTHY It is well known that motor function is affected by pain, but the effect of orthodontic treatment-related pain on the trigeminal

  5. Genetic and epigenetic alterations induced by different levels of rye genome integration in wheat recipient.

    Science.gov (United States)

    Zheng, X L; Zhou, J P; Zang, L L; Tang, A T; Liu, D Q; Deng, K J; Zhang, Y

    2016-06-17

    The narrow genetic variation present in common wheat (Triticum aestivum) varieties has greatly restricted the improvement of crop yield in modern breeding systems. Alien addition lines have proven to be an effective means to broaden the genetic diversity of common wheat. Wheat-rye addition lines, which are the direct bridge materials for wheat improvement, have been wildly used to produce new wheat cultivars carrying alien rye germplasm. In this study, we investigated the genetic and epigenetic alterations in two sets of wheat-rye disomic addition lines (1R-7R) and the corresponding triticales. We used expressed sequence tag-simple sequence repeat, amplified fragment length polymorphism, and methylation-sensitive amplification polymorphism analyses to analyze the effects of the introduction of alien chromosomes (either the entire genome or sub-genome) to wheat genetic background. We found obvious and diversiform variations in the genomic primary structure, as well as alterations in the extent and pattern of the genomic DNA methylation of the recipient. Meanwhile, these results also showed that introduction of different rye chromosomes could induce different genetic and epigenetic alterations in its recipient, and the genetic background of the parents is an important factor for genomic and epigenetic variation induced by alien chromosome addition.

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

    International Nuclear Information System (INIS)

    Tavares, J.G.P.; Vasques, E.R.; Arida, R.M.; Cavalheiro, E.A.; Cabral, F.R.; Torres, L.B.; Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A.; Godoy, C.M.G.; Gomes da Silva, S.

    2015-01-01

    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

  7. 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.

  8. Propiconazole induces alterations in the hepatic metabolome of mice: relevance to propiconazole-induced hepatocarcinogenesis

    Science.gov (United States)

    Propiconazole is a mouse hepatotumorigenic fungicide and has been the subject of recent mechanistic investigations on its carcinogenic mechanism of action. The goals of this study were: 1. To identify metabolomic changes induced in the liver by increasing doses of propiconazole i...

  9. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Priscilla L.G.; Brandao, Jose Odinilson de C.; Vale, Carlos H.F.P.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F. [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil)], e-mail: psouza@cnen.gov.br, e-mail: jodinilson@cnen.gov.br; Calixto, Merilane S.; Santos, Neide [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica

    2009-07-01

    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 {sup 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)

  11. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

    International Nuclear Information System (INIS)

    Patterson, Rachel; Vega, Libia; Trouba, Kevin; Bortner, Carl; Germolec, Dori

    2004-01-01

    Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

  12. Dramatyping: a generic algorithm for detecting reasonable temporal correlations between drug administration and lab value alterations

    Directory of Open Access Journals (Sweden)

    Axel Newe

    2016-03-01

    Full Text Available According to the World Health Organization, one of the criteria for the standardized assessment of case causality in adverse drug reactions is the temporal relationship between the intake of a drug and the occurrence of a reaction or a laboratory test abnormality. This article presents and describes an algorithm for the detection of a reasonable temporal correlation between the administration of a drug and the alteration of a laboratory value course. The algorithm is designed to process normalized lab values and is therefore universally applicable. It has a sensitivity of 0.932 for the detection of lab value courses that show changes in temporal correlation with the administration of a drug and it has a specificity of 0.967 for the detection of lab value courses that show no changes. Therefore, the algorithm is appropriate to screen the data of electronic health records and to support human experts in revealing adverse drug reactions. A reference implementation in Python programming language is available.

  13. Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection.

    Science.gov (United States)

    Pavel, Ana B; Campbell, Joshua D; Liu, Gang; Elashoff, David; Dubinett, Steven; Smith, Kate; Whitney, Duncan; Lenburg, Marc E; Spira, Avrum

    2017-11-01

    We have previously shown that gene expression alterations in normal-appearing bronchial epithelial cells can serve as a lung cancer detection biomarker in smokers. Given that miRNAs regulate airway gene expression responses to smoking, we evaluated whether miRNA expression is also altered in the bronchial epithelium of smokers with lung cancer. Using epithelial brushings from the mainstem bronchus of patients undergoing bronchoscopy for suspected lung cancer (as part of the AEGIS-1/2 clinical trials), we profiled miRNA expression via small-RNA sequencing from 347 current and former smokers for which gene expression data were also available. Patients were followed for one year postbronchoscopy until a final diagnosis of lung cancer ( n = 194) or benign disease ( n = 153) was made. Following removal of 6 low-quality samples, we used 138 patients (AEGIS-1) as a discovery set to identify four miRNAs (miR-146a-5p, miR-324-5p, miR-223-3p, and miR-223-5p) that were downregulated in the bronchial airway of lung cancer patients (ANOVA P cancer patients (GSEA FDR lung cancer significantly improves its performance (AUC) in the 203 samples (AEGIS-1/2) serving an independent test set (DeLong P lung cancer, and that they may regulate cancer-associated gene expression differences. Cancer Prev Res; 10(11); 651-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. ReadDepth: a parallel R package for detecting copy number alterations from short sequencing reads.

    Directory of Open Access Journals (Sweden)

    Christopher A Miller

    2011-01-01

    Full Text Available Copy number alterations are important contributors to many genetic diseases, including cancer. We present the readDepth package for R, which can detect these aberrations by measuring the depth of coverage obtained by massively parallel sequencing of the genome. In addition to achieving higher accuracy than existing packages, our tool runs much faster by utilizing multi-core architectures to parallelize the processing of these large data sets. In contrast to other published methods, readDepth does not require the sequencing of a reference sample, and uses a robust statistical model that accounts for overdispersed data. It includes a method for effectively increasing the resolution obtained from low-coverage experiments by utilizing breakpoint information from paired end sequencing to do positional refinement. We also demonstrate a method for inferring copy number using reads generated by whole-genome bisulfite sequencing, thus enabling integrative study of epigenomic and copy number alterations. Finally, we apply this tool to two genomes, showing that it performs well on genomes sequenced to both low and high coverage. The readDepth package runs on Linux and MacOSX, is released under the Apache 2.0 license, and is available at http://code.google.com/p/readdepth/.

  15. Detection of time-varying harmonic amplitude alterations due to spectral interpolations between musical instrument tones.

    Science.gov (United States)

    Horner, Andrew B; Beauchamp, James W; So, Richard H Y

    2009-01-01

    Gradated spectral interpolations between musical instrument tone pairs were used to investigate discrimination as a function of time-averaged spectral difference. All possible nonidentical pairs taken from a collection of eight musical instrument sounds consisting of bassoon, clarinet, flute, horn, oboe, saxophone, trumpet, and violin were tested. For each pair, several tones were generated with different balances between the primary and secondary instruments, where the balance was fixed across the duration of each tone. Among primary instruments it was found that changes to horn and bassoon [corrected] were most easily discriminable, while changes to saxophone and trumpet timbres were least discriminable. Among secondary instruments, the clarinet had the strongest effect on discrimination, whereas the bassoon had the least effect. For primary instruments, strong negative correlations were found between discrimination and their spectral incoherences, suggesting that the presence of dynamic spectral variations tends to increase the difficulty of detecting time-varying alterations such as spectral interpolation.

  16. Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.

    Directory of Open Access Journals (Sweden)

    Yuan Yan Sin

    Full Text Available Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1, which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2 mice. The resulting mice (Arg-Cre die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency.

  17. A large-scale perspective on stress-induced alterations in resting-state networks

    Science.gov (United States)

    Maron-Katz, Adi; Vaisvaser, Sharon; Lin, Tamar; Hendler, Talma; Shamir, Ron

    2016-02-01

    Stress is known to induce large-scale neural modulations. However, its neural effect once the stressor is removed and how it relates to subjective experience are not fully understood. Here we used a statistically sound data-driven approach to investigate alterations in large-scale resting-state functional connectivity (rsFC) induced by acute social stress. We compared rsfMRI profiles of 57 healthy male subjects before and after stress induction. Using a parcellation-based univariate statistical analysis, we identified a large-scale rsFC change, involving 490 parcel-pairs. Aiming to characterize this change, we employed statistical enrichment analysis, identifying anatomic structures that were significantly interconnected by these pairs. This analysis revealed strengthening of thalamo-cortical connectivity and weakening of cross-hemispheral parieto-temporal connectivity. These alterations were further found to be associated with change in subjective stress reports. Integrating report-based information on stress sustainment 20 minutes post induction, revealed a single significant rsFC change between the right amygdala and the precuneus, which inversely correlated with the level of subjective recovery. Our study demonstrates the value of enrichment analysis for exploring large-scale network reorganization patterns, and provides new insight on stress-induced neural modulations and their relation to subjective experience.

  18. 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.

  19. 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

  20. Cytosine Methylation Alteration in Natural Populations of Leymus chinensis Induced by Multiple Abiotic Stresses

    Science.gov (United States)

    Yu, Yingjie; Yang, Xuejiao; Wang, Huaying; Shi, Fengxue; Liu, Ying; Liu, Jushan; Li, Linfeng; Wang, Deli; Liu, Bao

    2013-01-01

    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 adaptation by

  1. Casticin induced apoptotic cell death and altered associated gene expression in human colon cancer colo 205 cells.

    Science.gov (United States)

    Shang, Hung-Sheng; Liu, Jia-You; Lu, Hsu-Feng; Chiang, Han-Sun; Lin, Chia-Hain; Chen, Ann; Lin, Yuh-Feng; Chung, Jing-Gung

    2017-08-01

    Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca 2+ productions, level of mitochondria membrane potential (ΔΨ m ) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death. Casticin induced cell morphological changes, decreased cell viability and induced G2/M phase arrest in colo 205 cells. Casticin increased ROS production but decreased the levels of ΔΨ m , and Ca 2+ , increased caspase-3, -8, and -9 activities. The cDNA microarray indicated that some of the cell cycle associated genes were down-regulated such as cyclin-dependent kinase inhibitor 1A (CDKN1A) (p21, Cip1) and p21 protein (Cdc42/Rac)-activated kinase 3 (PAK3). TNF receptor-associated protein 1 (TRAP1), CREB1 (cAMP responsive element binding protein 1) and cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27, Kip1) genes were increased but matrix metallopeptidase 2 (MMP-2), toll-like receptor 4 (TLR4), PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, bet), and CaMK4 (calcium/calmodulin-dependent protein kinase IV) genes were inhibited. Results suggest that casticin induced cell apoptosis via the activation of the caspase- and/or mitochondria-dependent signaling cascade, the accumulation of ROS and altered associated gene expressions in colo 205 human colon cancer cells. © 2016 Wiley Periodicals, Inc.

  2. The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

    Science.gov (United States)

    Khoe, Clairine V; Chung, Long H; Murray, Vincent

    2018-06-01

    The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-12-01

    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)

  11. Root exudate-induced alterations in Bacillus cereus cell wall contribute to root colonization and plant growth promotion.

    Directory of Open Access Journals (Sweden)

    Swarnalee Dutta

    Full Text Available The outcome of an interaction between plant growth promoting rhizobacteria and plants may depend on the chemical composition of root exudates (REs. We report the colonization of tobacco, and not groundnut, roots by a non-rhizospheric Bacillus cereus (MTCC 430. There was a differential alteration in the cell wall components of B. cereus in response to the REs from tobacco and groundnut. Attenuated total reflectance infrared spectroscopy revealed a split in amide I region of B. cereus cells exposed to tobacco-root exudates (TRE, compared to those exposed to groundnut-root exudates (GRE. In addition, changes in exopolysaccharides and lipid-packing were observed in B. cereus grown in TRE-amended minimal media that were not detectable in GRE-amended media. Cell-wall proteome analyses revealed upregulation of oxidative stress-related alkyl hydroperoxide reductase, and DNA-protecting protein chain (Dlp-2, in response to GRE and TRE, respectively. Metabolism-related enzymes like 2-amino-3-ketobutyrate coenzyme A ligase and 2-methylcitrate dehydratase and a 60 kDa chaperonin were up-regulated in response to TRE and GRE. In response to B. cereus, the plant roots altered their exudate-chemodiversity with respect to carbohydrates, organic acids, alkanes, and polyols. TRE-induced changes in surface components of B. cereus may contribute to successful root colonization and subsequent plant growth promotion.

  12. Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome

    Directory of Open Access Journals (Sweden)

    Imourana Alassane-Kpembi

    2018-05-01

    Full Text Available Type B trichothecene mycotoxin deoxynivalenol (DON is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae, have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE was observed after treatment by yeast only. By contrast, 3619 probes—corresponding to 2771 genes—were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes. Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

  13. Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome.

    Science.gov (United States)

    Alassane-Kpembi, Imourana; Pinton, Philippe; Hupé, Jean-François; Neves, Manon; Lippi, Yannick; Combes, Sylvie; Castex, Mathieu; Oswald, Isabelle P

    2018-05-15

    Type B trichothecene mycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae , have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE) was observed after treatment by yeast only. By contrast, 3619 probes-corresponding to 2771 genes-were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes). Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

  14. Alteration zone mapping for detecting potential mineralized areas in Kaladawan of north altyn tagh using ASTER data

    International Nuclear Information System (INIS)

    Yong-gui, Zhou; Bai-lin, Chen; Xing-tong, Chen; Zheng-le, Chen

    2014-01-01

    The Kaladawan area has been found developing intense hydrothermal altered rocks associated with mineralized area such as Kaladaban Pb-Zn deposit, A-bei Ag-Pb depositduring earlier geological investigations.Yet the sparse vegetation cover and excellent bedrock exposure make it a suitable place for the use of remote sensing methods for lithological mapping. ASTER data has been used in this study to identify alteration zones, and then to detect potential mineralized areas. Band ratio and PCA procedures were applied based on the analysis of spectral properties of typical alteration minerals. Band 4/2 and mineralogic indices proposed by Ninomiya were designed to map the distribution of Fe-oxides and alteration zones. Selected bands combinations were transformed in a PCA procedure to map the Al-OH, Mg-OH, CO 3 2− and Fe-oxides altered minerals. The analysis focused on the spatial distribution of hydrothermal altered minerals. Band ratio result images including both Fe-oxides and mineralogic indices show high-level similarity with the PCA transform procedure. They both show intense hydrothermal alteration zone in Kaladaban,west Kaladawan and A-bei area. Hence, these areas are considered to have potential for further mineralogic exploration. The results were validated by field work in the Kaladaban and west Kaladawan area,indicating that this method can be a useful tool for detecting potential mineralization area in Kaladawan and similar areas elsewhere

  15. 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.

  16. High-Altitude-Induced alterations in Gut-Immune Axis: A review.

    Science.gov (United States)

    Khanna, Kunjan; Mishra, K P; Ganju, Lilly; Kumar, Bhuvnesh; Singh, Shashi Bala

    2018-03-04

    High-altitude sojourn above 8000 ft is increasing day by day either for pilgrimage, mountaineering, holidaying or for strategic reasons. In India, soldiers are deployed to these high mountains for their duty or pilgrims visit to the holy places, which are located at very high altitude. A large population also resides permanently in high altitude regions. Every year thousands of pilgrims visit Holy cave of Shri Amarnath ji, which is above 15 000 ft. The poor acclimatization to high altitude may cause alteration in immunity. The low oxygen partial pressure may cause alterations in gut microbiota, which may cause changes in gut immunity. Effect of high altitude on gut-associated mucosal system is new area of research. Many studies have been carried out to understand the physiology and immunology behind the high-altitude-induced gut problems. Few interventions have also been discovered to circumvent the problems caused due to high-altitude conditions. In this review, we have discussed the effects of high-altitude-induced changes in gut immunity particularly peyer's patches, NK cells and inflammatory cytokines, secretary immunoglobulins and gut microbiota. The published articles from PubMed and Google scholar from year 1975 to 2017 on high-altitude hypoxia and gut immunity are cited in this review.

  17. Role of Rosemary leaves extract against radiation-induced hematological and biochemical alterations in mice

    Directory of Open Access Journals (Sweden)

    Acharya Garima S.

    2008-01-01

    Full Text Available 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 LD50/30 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.

  18. Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

    Science.gov (United States)

    Liu, Y; Cheng, H; Zhou, Y; Zhu, Y; Bian, R; Chen, Y; Li, C; Ma, Q; Zheng, Q; Zhang, Y; Jin, H; Wang, X; Chen, Q; Zhu, D

    2013-01-01

    Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells. PMID:23412387

  19. 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)

  20. 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

  1. Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits.

    Science.gov (United States)

    Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ibrahim, Muhammad

    2017-06-01

    Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (Pjuice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 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

  3. Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1.

    Science.gov (United States)

    Rodrigues, Elizabeth M; Scudder, Samantha L; Goo, Marisa S; Patrick, Gentry N

    2016-02-03

    Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ. Synaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression. Copyright © 2016 the authors 0270-6474/16/361590-06$15.00/0.

  4. 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

  5. Alterations to melanocortinergic, GABAergic and cannabinoid neurotransmission associated with olanzapine-induced weight gain.

    Directory of Open Access Journals (Sweden)

    Katrina Weston-Green

    Full Text Available BACKGROUND/AIM: Second generation antipsychotics (SGAs are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. METHODOLOGY/RESULTS: Levels of pro-opiomelanocortin (POMC, neuropeptide Y (NPY and glutamic acid decarboxylase (GAD(65, enzyme for GABA synthesis mRNA expression, and cannabinoid CB1 receptor (CB1R binding density (using [(3H]SR-141716A were examined in the arcuate nucleus (Arc and dorsal vagal complex (DVC of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days. Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD(65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. CONCLUSIONS: Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug.

  6. 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.

  7. Circular RNA alterations are involved in resistance to avian leukosis virus subgroup-J-induced tumor formation in chickens.

    Science.gov (United States)

    Zhang, Xinheng; Yan, Yiming; Lei, Xiaoya; Li, Aijun; Zhang, Huanmin; Dai, Zhenkai; Li, Xinjian; Chen, Weiguo; Lin, Wencheng; Chen, Feng; Ma, Jingyun; Xie, Qingmei

    2017-05-23

    Avian leukosis virus subgroup (ALV-J) is an oncogenic neoplasm-inducing retrovirus that causes significant economic losses in the poultry industry. Recent studies have demonstrated circular RNAs (circRNAs) are implicated in pathogenic processes; however, no research has indicated circRNAs are involved in resistance to disease. In this study, over 1800 circRNAs were detected by circRNA sequencing of liver tissues from ALV-J-resistant (n = 3) and ALV-J-susceptible chickens (n = 3). 32 differentially expressed circRNAs were selected for analyzing including 12 upregulated in ALV-J-resistant chickens and 20 upregulated in ALV-J-susceptible chickens, besides, the top five microRNAs (miRNAs) for 12 upregulated circRNAs in ALV-J-resistant chickens were analyzed. Gene ontology and KEGG pathway analyses were performed for miRNA target genes, the predicted genes were mainly involved in immune pathways. This study provides the first evidence that circRNA alterations are involved in resistance to ALV-J-induced tumor formation. We propose circRNAs may help to mediate tumor induction and development in chickens.

  8. Temporal interpolation alters motion in fMRI scans: Magnitudes and consequences for artifact detection.

    Directory of Open Access Journals (Sweden)

    Jonathan D Power

    Full Text Available Head motion can be estimated at any point of fMRI image processing. Processing steps involving temporal interpolation (e.g., slice time correction or outlier replacement often precede motion estimation in the literature. From first principles it can be anticipated that temporal interpolation will alter head motion in a scan. Here we demonstrate this effect and its consequences in five large fMRI datasets. Estimated head motion was reduced by 10-50% or more following temporal interpolation, and reductions were often visible to the naked eye. Such reductions make the data seem to be of improved quality. Such reductions also degrade the sensitivity of analyses aimed at detecting motion-related artifact and can cause a dataset with artifact to falsely appear artifact-free. These reduced motion estimates will be particularly problematic for studies needing estimates of motion in time, such as studies of dynamics. Based on these findings, it is sensible to obtain motion estimates prior to any image processing (regardless of subsequent processing steps and the actual timing of motion correction procedures, which need not be changed. We also find that outlier replacement procedures change signals almost entirely during times of motion and therefore have notable similarities to motion-targeting censoring strategies (which withhold or replace signals entirely during times of motion.

  9. 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

  10. 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

  11. 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.

  12. 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.

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

    Science.gov (United States)

    Meyers, Allison M; Mourra, Devry; Beeler, Jeff A

    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.

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

    Directory of Open Access Journals (Sweden)

    Allison M Meyers

    Full Text Available 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.

  15. 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

  16. Detection of early caries by laser-induced breakdown spectroscopy

    Science.gov (United States)

    Sasazawa, Shuhei; Kakino, Satoko; Matsuura, Yuji

    2015-07-01

    To improve sensitivity of dental caries detection by laser-induced breakdown spectroscopy (LIBS) analysis, it is proposed to utilize emission peaks in the ultraviolet. We newly focused on zinc whose emission peaks exist in ultraviolet because zinc exists at high concentration in the outer layer of enamel. It was shown that by using ratios between heights of an emission peak of Zn and that of Ca, the detection sensitivity and stability are largely improved. It was also shown that early caries are differentiated from healthy part by properly setting a threshold in the detected ratios. The proposed caries detection system can be applied to dental laser systems such as ones based on Er:YAG-lasers. When ablating early caries part by laser light, the system notices the dentist that the ablation of caries part is finished. We also show the intensity of emission peaks of zinc decreased with ablation with Er:YAG laser light.

  17. 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.

  18. Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells.

    Science.gov (United States)

    Canella, Rita; Benedusi, Mascia; Martini, Marta; Cervellati, Franco; Cavicchio, Carlotta; Valacchi, Giuseppe

    2018-08-01

    The lung tissue is one of the main targets of oxidative stress due to external sources and respiratory activity. In our previous work, we have demonstrated in that O 3 exposure alters the Cl - current-voltage relationship, with the appearance of a large outward rectifier component mainly sustained by outward rectifier chloride channels (ORCCs) in human lung epithelial cells (A549 line). In the present study, we have performed patch clamp experiments, in order to identify which one of the O 3 byproducts (4hydroxynonenal (HNE) and/or H 2 O 2 ) was responsible for chloride current change. While 4HNE exposition (up to 25 μM for 30' before electrophysiological analysis) did not reproduce O 3 effect, H 2 O 2 produced by glucose oxidase 10 mU for 24 hr before electrophysiological analysis mimicked O 3 response. This result was confirmed treating the cell with catalase (CAT) before O 3 exposure (1,000 U/ml for 2 hr): CAT was able to rescue Cl - current alteration. Since CAT is regulated by Nrf2 transcription factor, we pre-treated the cells with the Nrf2 activators, resveratrol and tBHQ. Immunochemical and immunocytochemical results showed Nrf2 activation with both substances that lead to prevent OS effect on Cl - current. These data bring new insights into the mechanisms involved in OS-induced lung tissue damage, pointing out the role of H 2 O 2 in chloride current alteration and the ability of Nfr2 activation in preventing this effect. © 2017 Wiley Periodicals, Inc.

  19. 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

  20. Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease.

    Science.gov (United States)

    Lecommandeur, Emmanuelle; Baker, David; Cox, Timothy M; Nicholls, Andrew W; Griffin, Julian L

    2017-07-01

    Drug-induced phospholipidosis (DIPL) is characterized by an increase in the phospholipid content of the cell and the accumulation of drugs and lipids inside the lysosomes of affected tissues, including in the liver. Although of uncertain pathological significance for patients, the condition remains a major impediment for the clinical development of new drugs. Human Sandhoff disease (SD) is caused by inherited defects of the β subunit of lysosomal β-hexosaminidases (Hex) A and B, leading to a large array of symptoms, including neurodegeneration and ultimately death by the age of 4 in its most common form. The substrates of Hex A and B, gangliosides GM2 and GA2, accumulate inside the lysosomes of the CNS and in peripheral organs. Given that both DIPL and SD are associated with lysosomes and lipid metabolism in general, we measured the hepatic lipid profiles in rodent models of these two conditions using untargeted LC/MS to examine potential commonalities. Both model systems shared a number of perturbed lipid pathways, notably those involving metabolism of cholesteryl esters, lysophosphatidylcholines, bis(monoacylglycero)phosphates, and ceramides. We report here profound alterations in lipid metabolism in the SD liver. In addition, DIPL induced a wide range of lipid changes not previously observed in the liver, highlighting similarities with those detected in the model of SD and raising concerns that these lipid changes may be associated with underlying pathology associated with lysosomal storage disorders. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  1. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

  2. Picrotoxin-induced behavioral tolerance and altered susceptibility to seizures: effects of naloxone.

    Science.gov (United States)

    Thomas, J; Nores, W L; Pariser, R

    1993-07-01

    The role of opiate mechanisms in the development of tolerance and altered susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with naloxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then tested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencies to different types of seizures, the duration of postseizure immobility, and the number of focal seizure episodes were scored. In the vehicle-treated group, repeated picrotoxin injections led to an increased susceptibility to myoclonic and focal seizures and to decreased duration of postseizure immobility. Naloxone pretreatment significantly decreased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related behaviors. Naloxone did not alter the development of tolerance or sensitivity, indicating that naloxone-insensitive opiate mechanisms or nonopiate mechanisms may be involved in these processes.

  3. Senescence-Induced Alterations of Laminin Chain Expression Modulate Tumorigenicity of Prostate Cancer Cells1

    Science.gov (United States)

    Sprenger, Cynthia C T; Drivdahl, Rolf H; Woodke, Lillie B; Eyman, Daniel; Reed, May J; Carter, William G; Plymate, Stephen R

    2008-01-01

    Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs) are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM α4 and β2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM α4 or β2 chain or both chains. Increased expression of either the LM α4 or β2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer. PMID:19048114

  4. Senescence-Induced Alterations of Laminin Chain Expression Modulate Tumorigenicity of Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Cynthia C.T. Sprenger

    2008-12-01

    Full Text Available Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM α4 and β2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM α4 or β2 chain or both chains. Increased expression of either the LM α4 or β2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer.

  5. Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

    Science.gov (United States)

    Bridges, Robert S.

    2015-01-01

    The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

  6. 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.

  7. Osteocyte Alterations Induce Osteoclastogenesis in an In Vitro Model of Gaucher Disease

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    Constanza Bondar

    2017-01-01

    Full Text Available Gaucher disease (GD is caused by mutations in the glucosylceramidase β (GBA 1 gene that confer a deficient level of activity of glucocerebrosidase (GCase. This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement. Bone compromise is the most disabling aspect of the Gaucher disease. However, the pathophysiological aspects of skeletal alterations are not yet fully understood. The bone tissue homeostasis is maintained by a balance between resorption of old bone by osteoclasts and new bone formation by osteoblasts. A central player in this balance is the osteocyte as it controls both processes. We studied the involvement of osteocytes in an in vitro chemical model of Gaucher disease. The osteocyte cell line MLO-Y4 was exposed to conduritol-β-epoxide (CBE, an inhibitor of GCase, for a period of 7, 14 and 21 days. Conditioned media from CBE-treated osteocytes was found to induce osteoclast differentiation. GCase inhibition caused alterations in Cx43 expression and distribution pattern and an increase in osteocyte apoptosis. Osteoclast differentiation involved osteocyte apoptotic bodies, receptor activator of nuclear factor κ-B ligand (RANKL and soluble factors. Thus, our results indicate that osteocytes may have a role to play in the bone pathophysiology of GD.

  8. Post-factum detection of radiation treatment of meat and fish by means of DNA alterations identified by gas chromatography-mass spectrometry or pulsed-field gel electrophoresis

    International Nuclear Information System (INIS)

    Mayer, M.

    1994-01-01

    The doctoral thesis explains methods and experiments for post-factum detection of radiation-induced alterations of DNA. There are various manifestations of such alterations. Ionizing radiation can directly alter the bases and/or sugar component, or can indirectly induce DNA damage by way of forming water radicals. Both mechanisms result in base derivatives, released for some part from the DNA strand, or formed by alterations of the 2-deoxyribose, inducing strand breaks ( single and double strand breaks). The first part of the thesis explains the approach applying GC-MS for detection of radiation-induced base derivatives, using herring sperm DNA as a model DNA. Some typical types of base derivatives were identified (thymine glycol, 5-hydroxycytosine).Some base derivatives were also found in DNA samples derived from poultry meat. These base derivatives are known to be indicators of food processing with ionizing radiation, but surprisingly were also found in non-irradiated controls, although in minor amounts. The second part discusses the identification of strand breaks applying the pused-field gel electrophoresis. This method is capable of producing evidence that irradiation markedly enhances the short-chain DNA molecules as compared to non-irradiated controls. DNA molecules of a size of approx. 2.2 million base pairs are almost completely broken into short-chain fragments. The method reliably detects radiation treatments down to 1500 Gy, even if applied long ago. (orig./MG) [de

  9. Early detection of chemotherapy-refractory patients by monitoring textural alterations in diffuse optical spectroscopic images

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J., E-mail: Gregory.Czarnota@sunnybrook.ca [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Vorauer, Eric [Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Chin, Lee [Department of Radiation Oncology, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Tran, William T. [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Wright, Frances C. [Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Surgery, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Gandhi, Sonal [Division of Medical Oncology, Sunnybrook Health Sciences Centre, and Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Yaffe, Martin J. [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M4N 3M5 (Canada)

    2015-11-15

    Purpose: Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean values of these functional metabolic maps. Methods: Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. Results: Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001 < p < 0.049), and mean value of water

  10. Impact of ginger aqueous extract on carbimazole induced testicular degenerative alterations and oxidative stress in albino rats

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    Saber Abdel-Rahman Sakr

    2017-04-01

    Full Text Available Objective: To evaluate the effect of ginger (Zingiber officinale aqueous extract, a natural herb, with antioxidant properties, on testicular toxicity and oxidative stress induced by the antithyroid drug carbimazole in albino rats. Methods: Four groups of male albino rats were used. Group I served as control. Group II rats were treated with ginger aqueous extract (24 mg/mL. Group III rats were given orally carbimazole (1.35 mg/kg bw. Group IV rats were given carbimazole and ginger extract. Animals were sacrificed and their testes were removed and stained with H&E for histological examination. Sperms were collected from epididymis for detection of sperm head abnormalities. Immunohistochemical expression of PCNA and Bax was detected in the testes. MDA, CAT and GSH were measured in the sera. Results: Treating rats with carbimazole revealed significant alterations in the tissue of testis including decreased seminiferous epithelium height, decreased diameter of seminiferous tubule and changes in the spermatogenic layers arrangement. Intertubular hemorrhage and congested blood vessels were noted. An increase in sperm head abnormalities was recorded. Decreased cell proliferation was reflected by a decrease in PCNA expression, while the increase in apoptotic rate was accompanied with an increase in Bax expression. Oxidative stress was demonstrated by an increase in malondialdehyde and decrease in activity of catalase and glutathione. Combined treatment of carbimazole and aqueous ginger extract led to an improvement in histological, morphometrical, immunohistochemical changes and oxidative stress induced by carbimazole. Conclusions: The ameliorative effects of ginger extract could be due to its antioxidant properties.

  11. 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

  12. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.

    Science.gov (United States)

    Malykhina, Anna P; Lei, Qi; Erickson, Chris S; Epstein, Miles L; Saban, Marcia R; Davis, Carole A; Saban, Ricardo

    2012-12-19

    This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na(+) channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and

  13. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

    Directory of Open Access Journals (Sweden)

    Malykhina Anna P

    2012-12-01

    Full Text Available Abstract Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1 and cholinergic nerves (ChAT was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a

  14. Data set of Aspergillus flavus induced alterations in tear proteome: Understanding the pathogen-induced host response to fungal infection

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    Jeyalakshmi Kandhavelu

    2016-12-01

    Full Text Available Fungal keratitis is one of the leading causes of blindness in the tropical countries affecting individuals in their most productive age. The host immune response during this infection is poorly understood. We carried out comparative tear proteome analysis of Aspergillus flavus keratitis patients and uninfected controls. Proteome was separated into glycosylated and non-glycosylated fractions using lectin column chromatography before mass spectrometry. The data revealed the major processes activated in the human host in response to fungal infection and reflected in the tear. Extended analysis of this dataset presented here complements the research article entitled “Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection [1]” (Jeyalakhsmi Kandhavelu, Naveen Luke Demonte, Venkatesh Prajna Namperumalsamy, Lalitha Prajna, Chitra Thangavel, Jeya Maheshwari Jayapal, Dharmalingam Kuppamuthu, 2016. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PRIDE:PXD003825.

  15. Cat retinal ganglion cell receptive-field alterations after 6-hydroxydopamine induced dopaminergic amacrine cell lesions

    International Nuclear Information System (INIS)

    Maguire, G.W.; Smith, E.L. III

    1985-01-01

    Optic tract single-unit recordings were used to study ganglion cell response functions of the intact cat eye after 6-hydroxydopamine (6-OHDA) lesioning of the dopaminergic amacrine cell (AC) population of the inner retina. The impairment of the dopaminergic AC was verified by high pressure-liquid chromatography with electrochemical detection of endogenous dopamine content and by [ 3 H]dopamine high-affinity uptake; the dopaminergic ACs of the treated eyes demonstrated reduced endogenous dopamine content and reduced [ 3 H]dopamine uptake compared with that of their matched controls. Normal appearing [ 3 H]GABA and [ 3 H]-glycine uptake in the treated retinas suggests the absence of any nonspecific action of the 6-OHDA on the neural retina. The impairment of the dopaminergic AC population was found to alter a number of response properties in off-center ganglion cells, but this impairment had only a modest effect on the on-center cells. An abnormally high proportion of the off-center ganglion cells in the 6-OHDA treated eyes possessed nonlinear, Y-type receptive fields. These cells also possessed shift-responses of greater than normal amplitude, altered intensity-response functions, reduced maintained activities, and more transient center responses. Of the on-center type cells, only the Y-type on-center cells were affected by 6-OHDA, possessing higher than normal maintained activities and altered intensity-response functions. The on-center X-cells were unaffected by 6-OHDA treatment. The dopaminergic AC of the photopically adapted cat retina therefore modulates a number of ganglion cell response properties and within the limits of this study is most prominent in off-center ganglion cell circuitry

  16. Alteration of the redox state with reactive oxygen species for 5-fluorouracil-induced oral mucositis in hamsters.

    Directory of Open Access Journals (Sweden)

    Fumihiko Yoshino

    Full Text Available Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis.

  17. Papain-induced changes in rabbit cartilage; alterations in the chemical structure of the cartilage matrix.

    Science.gov (United States)

    TSALTAS, T T

    1958-10-01

    Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S(35) content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S(35) in the serum and an increase of S(35) and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery.

  18. Detection of greenhouse-gas-induced climatic change

    International Nuclear Information System (INIS)

    Wigley, T.M.L.; Jones, P.D.

    1992-01-01

    The aims of the US Department of Energy's Carbon Dioxide Research Program are to improve assessments of greenhouse-gas-induced climatic change and to define and reduce uncertainties through selected research. This project will address: The regional and seasonal details of the expected climatic changes; how rapidly will these changes occur; how and when will the climatic effects of CO 2 and other greenhouse gases be first detected; and the relationships between greenhouse-gas-induced climatic change and changes caused by other external and internal factors. The present project addresses all of these questions. Many of the diverse facets of greenhouse-gas-related climate research can be grouped under three interlinked subject areas: modeling, first detection and supporting data. This project will include the analysis of climate forcing factors, the development and refinement of transient response climate models, and the use of instrumental data in validating General Circulation Models (GCMs)

  19. Methylmercury-induced alterations in astrocyte functions are attenuated by ebselen.

    Science.gov (United States)

    Yin, Zhaobao; Lee, Eunsook; Ni, Mingwei; Jiang, Haiyan; Milatovic, Dejan; Rongzhu, Lu; Farina, Marcelo; Rocha, Joao B T; Aschner, Michael

    2011-06-01

    Methylmercury (MeHg) preferentially accumulates in glia of the central nervous system (CNS), but its toxic mechanisms have yet to be fully recognized. In the present study, we tested the hypothesis that MeHg induces neurotoxicity via oxidative stress mechanisms, and that these effects are attenuated by the antioxidant, ebselen. Rat neonatal primary cortical astrocytes were pretreated with or without 10 μM ebselen for 2h followed by MeHg (0, 1, 5, and 10 μM) treatments. MeHg-induced changes in astrocytic [(3)H]-glutamine uptake were assessed along with changes in mitochondrial membrane potential (ΔΨ(m)), using the potentiometric dye tetramethylrhodamine ethyl ester (TMRE). Western blot analysis was used to detect MeHg-induced ERK (extracellular-signal related kinase) phosphorylation and caspase-3 activation. MeHg treatment significantly decreased (pEbselen fully reversed MeHg's (1 μM) effect on [(3)H]-glutamine uptake at 1 min. At higher MeHg concentrations, ebselen partially reversed the MeHg-induced astrocytic inhibition of [(3)H]-glutamine uptake [at 1 min (5 and 10 μM) (pEbselen fully reversed the effect of 1 μM MeHg treatment for 1h on astrocytic ΔΨ(m) and partially reversed the effect of 5 and 10 μM MeHg treatments for 1h on ΔΨ(m). In addition, ebselen inhibited MeHg-induced phosphorylation of ERK (pebselen reinforce the idea that organic selenocompounds represent promising strategies to counteract MeHg-induced neurotoxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

  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. 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)

  2. 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.

  3. 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.

  4. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    Science.gov (United States)

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  5. 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

  6. Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats.

    Science.gov (United States)

    Izumi, Hirohisa; Minegishi, Mario; Sato, Yohei; Shimizu, Takashi; Sekine, Kazunori; Takase, Mitsunori

    2015-10-01

    Bifidobacterium breve M-16V (M16V) is a probiotic bacterial strain with a long tradition of use in neonatal intensive care units in some countries. Previous study showed that the effects of M16V administration on gene expression were greater during the weaning period than in the neonatal period and were greater in the colon than in the small intestine and spleen, suggesting that M16V has anti-inflammatory effects. In this study, we evaluated the effects of inflammation during the weaning period and the effects of M16V on normal and inflammatory conditions. From postnatal day (PD) 21 to 34, weanling rats were administered of 2.5 × 10(9) of M16V daily, and colitis was induced by administration of 2% dextran sulfate sodium from PD28 to 35. Colitis severity, immune function, and microbiota were investigated. Colitis caused a reduction in body weight gain, colon shortening, poor nutritional status, anemia, changes in blood and spleen lymphocyte populations, spleen T-cell malfunctions, and alterations in colon microbiota. M16V administration improved some but not all of the changes induced by colitis. M16V could suppress inflammation and, therefore, can be considered a safe strain to use not only during the neonatal period but also the weaning period.

  7. Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

    Directory of Open Access Journals (Sweden)

    Rodrigo eIturriaga

    2014-12-01

    Full Text Available The carotid body (CB plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure and obstructive sleep apnea (OSA. Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH, a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation.

  8. Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

    Science.gov (United States)

    Iturriaga, Rodrigo; Andrade, David C.; Del Rio, Rodrigo

    2014-01-01

    The carotid body (CB) plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular, and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure, and obstructive sleep apnea (OSA). Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH), a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation. PMID:25520668

  9. Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity

    Directory of Open Access Journals (Sweden)

    Pauza Mary E

    2008-03-01

    Full Text Available Abstract A common complication associated with diabetes is painful or painless diabetic peripheral neuropathy (DPN. The mechanisms and determinants responsible for these peripheral neuropathies are poorly understood. Using both streptozotocin (STZ-induced and transgene-mediated murine models of type 1 diabetes (T1D, we demonstrate that Transient Receptor Potential Vanilloid 1 (TRPV1 expression varies with the neuropathic phenotype. We have found that both STZ- and transgene-mediated T1D are associated with two distinct phases of thermal pain sensitivity that parallel changes in TRPV1 as determined by paw withdrawal latency (PWL. An early phase of hyperalgesia and a late phase of hypoalgesia are evident. TRPV1-mediated whole cell currents are larger and smaller in dorsal root ganglion (DRG neurons collected from hyperalgesic and hypoalgesic mice. Resiniferatoxin (RTX binding, a measure of TRPV1 expression is increased and decreased in DRG and paw skin of hyperalgesic and hypoalgesic mice, respectively. Immunohistochemical labeling of spinal cord lamina I and II, dorsal root ganglion (DRG, and paw skin from hyperalgesic and hypoalgesic mice reveal increased and decreased TRPV1 expression, respectively. A role for TRPV1 in thermal DPN is further suggested by the failure of STZ treatment to influence thermal nociception in TRPV1 deficient mice. These findings demonstrate that altered TRPV1 expression and function contribute to diabetes-induced changes in thermal perception.

  10. Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats.

    Science.gov (United States)

    Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Adachi, Lauren Naomi Spezia; de Macedo, Isabel Cristina; Cioato, Stefania Giotti; de Freitas, Joice S; de Souza, Andressa; Quevedo, Alexandre; Caumo, Wolnei; Torres, Iraci Lucena da Silva

    2016-10-01

    Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals.

  11. 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.

  12. 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

  13. Proteome alteration induced by hTERT transfection of human fibroblast cells.

    Science.gov (United States)

    Mazzucchelli, Gabriel D; Gabelica, Valérie; Smargiasso, Nicolas; Fléron, Maximilien; Ashimwe, Wilson; Rosu, Frédéric; De Pauw-Gillet, Marie-Claire; Riou, Jean-François; De Pauw, Edwin

    2008-04-17

    Telomerase confers cellular immortality by elongating telomeres, thereby circumventing the Hayflick limit. Extended-life-span cells have been generated by transfection with the human telomerase reverse transcriptase (hTERT) gene. hTERT transfected cell lines may be of outstanding interest to monitor the effect of drugs targeting the telomerase activity. The incidence of hTERT gene transfection at the proteome level is a prerequisite to that purpose. The effect of the transfection has been studied on the proteome of human fibroblast (WI38). Cytosolic and nuclear fractions of WI38 cells, empty vector transfected WI38 (WI38-HPV) and hTERT WI38 cells were submitted to a 2D-DIGE (Two-Dimensional Differential In-Gel Electrophoresis) analysis. Only spots that had a similar abundance in WI38 and WI38-HPV, but were differentially expressed in WI38 hTERT were selected for MS identification. This method directly points to the proteins linked with the hTERT expression. Number of false positive differentially expressed proteins has been excluded by using control WI38-HPV cells. The proteome alteration induced by hTERT WI38 transfection should be taken into account in subsequent use of the cell line for anti-telomerase drugs evaluation. 2D-DIGE experiment shows that 57 spots out of 2246 are significantly differentially expressed in the cytosolic fraction due to hTERT transfection, and 38 were confidently identified. In the nuclear fraction, 44 spots out of 2172 were selected in the differential proteome analysis, and 14 were identified. The results show that, in addition to elongating telomeres, hTERT gene transfection has other physiological roles, among which an enhanced ER capacity and a potent cell protection against apoptosis. We show that the methodology reduces the complexity of the proteome analysis and highlights proteins implicated in other processes than telomere elongation. hTERT induced proteome changes suggest that telomerase expression enhances natural cell repair

  14. Proteome alteration induced by hTERT transfection of human fibroblast cells

    Directory of Open Access Journals (Sweden)

    Riou Jean-François

    2008-04-01

    Full Text Available Abstract Background Telomerase confers cellular immortality by elongating telomeres, thereby circumventing the Hayflick limit. Extended-life-span cells have been generated by transfection with the human telomerase reverse transcriptase (hTERT gene. hTERT transfected cell lines may be of outstanding interest to monitor the effect of drugs targeting the telomerase activity. The incidence of hTERT gene transfection at the proteome level is a prerequisite to that purpose. The effect of the transfection has been studied on the proteome of human fibroblast (WI38. Cytosolic and nuclear fractions of WI38 cells, empty vector transfected WI38 (WI38-HPV and hTERT WI38 cells were submitted to a 2D-DIGE (Two-Dimensional Differential In-Gel Electrophoresis analysis. Only spots that had a similar abundance in WI38 and WI38-HPV, but were differentially expressed in WI38 hTERT were selected for MS identification. This method directly points to the proteins linked with the hTERT expression. Number of false positive differentially expressed proteins has been excluded by using control WI38-HPV cells. The proteome alteration induced by hTERT WI38 transfection should be taken into account in subsequent use of the cell line for anti-telomerase drugs evaluation. Results 2D-DIGE experiment shows that 57 spots out of 2246 are significantly differentially expressed in the cytosolic fraction due to hTERT transfection, and 38 were confidently identified. In the nuclear fraction, 44 spots out of 2172 were selected in the differential proteome analysis, and 14 were identified. The results show that, in addition to elongating telomeres, hTERT gene transfection has other physiological roles, among which an enhanced ER capacity and a potent cell protection against apoptosis. Conclusion We show that the methodology reduces the complexity of the proteome analysis and highlights proteins implicated in other processes than telomere elongation. hTERT induced proteome changes suggest

  15. Effects of interleukins 2 and 12 on TBT-induced alterations of MAP kinases p38 and p44/42 in human natural killer cells.

    Science.gov (United States)

    Aluoch, Aloice O; Whalen, Margaret M

    2006-01-01

    NK cells are lymphocytes in the non-adaptive immune system that protect the body against intracellular pathogens and eliminate tumor cells. Tributyltin (TBT) is a toxic chemical that has been detected in human foods as well as in human blood. The role of TBT in immunosuppression has been described, including inhibition of the human NK-cell cytotoxic function. Previous studies indicated that exposure of NK cells to TBT for 1 h induced progressive and irreversible inhibition of cytotoxic function. However, it was found that if NK cells were incubated in TBT-free media with either IL-2 or IL-12, loss of cytotoxic function was prevented/reversed within 24 h. Molecular studies established that loss of cytotoxic function is accompanied by alteration of MAP kinases (MAPKs) p38 and p44/42 phosphorylation. This study examined whether interleukin-mediated recovery of cytotoxicity involved reversal of tributyltin-altered p38 and p44/42 phosphorylation. The results indicated that there was no substantial IL-2 prevention/reversal of the TBT-induced alteration of phosphorylation of either p38 or p44/42 after either a 24 or 48 h recovery period. Additionally, IL-12 caused no substantial prevention/reversal of the TBT-induced alteration of phosphorylation of the MAPKs seen after either 24 or 48 h. These data suggest that IL-2 and/or IL-12-mediated recovery of NK cytotoxic function is not a result of prevention/reversal of TBT-induced phosphorylation of p38 and p44/42 MAPKs at the 24 or 48 h time points. Copyright 2005 John Wiley & Sons, Ltd.

  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. Chemical Detection Based on Adsorption-Induced and Photo-Induced Stresses in MEMS Devices

    Energy Technology Data Exchange (ETDEWEB)

    Datskos, P.G.

    1999-04-05

    Recently there has been an increasing demand to perform real-time in-situ chemical detection of hazardous materials, contraband chemicals, and explosive chemicals. Currently, real-time chemical detection requires rather large analytical instrumentation that are expensive and complicated to use. The advent of inexpensive mass produced MEMS (micro-electromechanical systems) devices opened-up new possibilities for chemical detection. For example, microcantilevers were found to respond to chemical stimuli by undergoing changes in their bending and resonance frequency even when a small number of molecules adsorb on their surface. In our present studies, we extended this concept by studying changes in both the adsorption-induced stress and photo-induced stress as target chemicals adsorb on the surface of microcantilevers. For example, microcantilevers that have adsorbed molecules will undergo photo-induced bending that depends on the number of absorbed molecules on the surface. However, microcantilevers that have undergone photo-induced bending will adsorb molecules on their surfaces in a distinctly different way. Depending on the photon wavelength and microcantilever material, the microcantilever can be made to bend by expanding or contracting the irradiated surface. This is important in cases where the photo-induced stresses can be used to counter any adsorption-induced stresses and increase the dynamic range. Coating the surface of the microstructure with a different material can provide chemical specificity for the target chemicals. However, by selecting appropriate photon wavelengths we can change the chemical selectivity due to the introduction of new surface states in the MEMS device. We will present and discuss our results on the use of adsorption-induced and photo-induced bending of microcantilevers for chemical detection.

  18. Induced Temporal Signatures for Point-Source Detection

    International Nuclear Information System (INIS)

    Stephens, Daniel L.; Runkle, Robert C.; Carlson, Deborah K.; Peurrung, Anthony J.; Seifert, Allen; Wyatt, Cory R.

    2005-01-01

    Detection of radioactive point-sized sources is inherently divided into two regimes encompassing stationary and moving detectors. The two cases differ in their treatment of background radiation and its influence on detection sensitivity. In the stationary detector case the statistical fluctuation of the background determines the minimum detectable quantity. In the moving detector case the detector may be subjected to widely and irregularly varying background radiation, as a result of geographical and environmental variation. This significant systematic variation, in conjunction with the statistical variation of the background, requires a conservative threshold to be selected to yield the same false-positive rate as the stationary detection case. This results in lost detection sensitivity for real sources. This work focuses on a simple and practical modification of the detector geometry that increase point-source recognition via a distinctive temporal signature. A key part of this effort is the integrated development of both detector geometries that induce a highly distinctive signature for point sources and the development of statistical algorithms able to optimize detection of this signature amidst varying background. The identification of temporal signatures for point sources has been demonstrated and compared with the canonical method showing good results. This work demonstrates that temporal signatures are efficient at increasing point-source discrimination in a moving detector system

  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. Photodynamic therapy induces antifibrotic alterations in primary human vocal fold fibroblasts.

    Science.gov (United States)

    Zhang, Chi; Wang, Jiajia; Chou, Adriana; Gong, Ting; Devine, Erin E; Jiang, Jack J

    2018-04-18

    Photodynamic therapy (PDT) is a promising treatment modality for laryngeal dysplasia, early-stage carcinoma, and papilloma, and was reported to have the ability to preserve laryngeal function and voice quality without clinical fibrotic response. We aimed to investigate the mechanism behind the antifibrotic effects of PDT on primary human vocal fold fibroblasts (VFFs) in vitro. In vitro analysis from one human donor. Cell viability of VFFs in response to varying doses of PDT was investigated by the Cell Counting Kit-8 method. Sublethal-dose PDT (SL-PDT) was used for the following experiments. Expression of genes related to vocal fold extracellular matrix formation was analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Effects of PDT on cell migration, collagen contraction, and transforming growth factor β-1 (TGF-β1)-induced myofibroblast differentiation were also analyzed. PDT affects the viability of VFFs in a dose-dependent manner. SL-PDT significantly changed the expression profile of VFFs with antifibrotic effects. It also inhibited cell migration, reduced collagen contraction, and reversed the fibroblast-myofibroblast differentiation induced by TGF-β1. SL-PDT induces antifibrotic alterations in VFFs. This could explain the low incidence of vocal fold scar associated with PDT. Moreover, PDT may be useful in treating existing vocal fold scars. Further studies should focus on the in vivo effect of PDT on vocal fold wound healing and scar remodeling. NA Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Alteration of hepatic structure and oxidative stress induced by intravenous nanoceria

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Michael T., E-mail: mttsen01@louisville.edu [Dept of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky (United States); Lu, Xiaoqin, E-mail: x0lu0003@louisville.edu [Dept of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky (United States); Duan, Xiaoxian, E-mail: x0duan02@louisville.edu [Dept of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky (United States); Hardas, Sarita S., E-mail: sarita.hardas@uky.edu [Dept. of Chemistry, University of Kentucky, Lexington, Kentucky (United States); Sultana, Rukhsana, E-mail: rsult2@uky.edu [Dept. of Chemistry, University of Kentucky, Lexington, Kentucky (United States); Wu, Peng, E-mail: peng.wu@uky.edu [Dept of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky (United States); Unrine, Jason M., E-mail: jason.unrine@uky.edu [Dept of Plant and Soil Sciences, University of Kentucky, Lexington, Kentucky (United States); Graham, Uschi, E-mail: graham@caer.uky.edu [Center for Applied Energy Research, University of Kentucky, Lexington, Kentucky (United States); Butterfield, D. Allan, E-mail: dabcns@uky.edu [Dept. of Chemistry, University of Kentucky, Lexington, Kentucky (United States); Grulke, Eric A., E-mail: eric.grulke@uky.edu [Dept of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky (United States); Yokel, Robert A., E-mail: ryokel@email.uky.edu [Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky (United States)

    2012-04-15

    Beyond the traditional use of ceria as an abrasive, the scope of nanoceria applications now extends into fuel cell manufacturing, diesel fuel additives, and for therapeutic intervention as a putative antioxidant. However, the biological effects of nanoceria exposure have yet to be fully defined, which gave us the impetus to examine its systemic biodistribution and biological responses. An extensively characterized nanoceria (5 nm) dispersion was vascularly infused into rats, which were terminated 1 h, 20 h or 30 days later. Light and electron microscopic tissue characterization was conducted and hepatic oxidative stress parameters determined. We observed acute ceria nanoparticle sequestration by Kupffer cells with subsequent bioretention in parenchymal cells as well. The internalized ceria nanoparticles appeared as spherical agglomerates of varying dimension without specific organelle penetration. In hepatocytes, the agglomerated nanoceria frequently localized to the plasma membrane facing bile canaliculi. Hepatic stellate cells also sequestered nanoceria. Within the sinusoids, sustained nanoceria bioretention was associated with granuloma formations comprised of Kupffer cells and intermingling CD3{sup +} T cells. A statistically significant elevation of serum aspartate aminotransferase (AST) level was seen at 1 and 20 h, but subsided by 30 days after ceria administration. Further, elevated apoptosis was observed on day 30. These findings, together with increased hepatic protein carbonyl levels on day 30, indicate ceria-induced hepatic injury and oxidative stress, respectively. Such observations suggest a single vascular infusion of nanoceria can lead to persistent hepatic retention of particles with possible implications for occupational and therapeutic exposures. -- Highlights: ► Time course study on nanoceria induced hepatic alterations in rats. ► Serum AST elevation indicated acute hepatotoxicity. ► Ceria is retained for up to 30 days in Kupffer cells

  2. Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns

    Science.gov (United States)

    Ajarem, Jamaan S.; Al-Basher, Gadh; Allam, Ahmed A.

    2017-01-01

    Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns. PMID:28588748

  3. 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.

  4. Diffusion MRI and the Detection of Alterations Following Traumatic Brain Injury

    Science.gov (United States)

    2017-06-13

    vascular injury, disruption of water home- ostasis), changes in tissue composition (e.g., increased or decreased cellu- larity), and alterations in...related alterations Tissue environment Expected diffusion changes Major citations dMRI evidence Neurons cell loss necrosis and apoptosis atrophy...structure and signaling, vascular coupling, and waste removal, among others. Astrocytes are at least as numerous as neurons in the brain (Herculano-Houzel

  5. Altered expression of γ-secretase components in animal model of major depressive disorder induced by reserpine administration.

    Science.gov (United States)

    Lee, Hye-Ryun; Hwang, In-Sik; Kim, Ji-Eun; Choi, Sun-Il; Lee, Young-Ju; Goo, Jun-Seo; Lee, Eon-Pil; Choi, Hae-Wook; Kim, Hong-Sung; Lee, Jae-Ho; Jung, Young-Jin; Hwang, Dae-Youn

    2012-06-01

    Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of γ-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (Pprecursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of γ-secretase components decreased (P<0.03). Among the three components of the γ-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

  6. Perinatal exposure to lead induces morphological, ultrastructural and molecular alterations in the hippocampus

    International Nuclear Information System (INIS)

    Baranowska-Bosiacka, I.; Strużyńska, L.; Gutowska, I.; Machalińska, A.; Kolasa, A.; Kłos, P.; Czapski, G.A.; Kurzawski, M.; Prokopowicz, A.; Marchlewicz, M.

    2013-01-01

    Highlights: ► Pre- and neonatal Pb exposure decreased the number of hippocampal neurons. ► Lead caused ultrastructural alterations in CA1 region of hippocampus. ► Hippocampus is highly vulnerable to low level perinatal Pb exposure. ► Lead decreased BDNF level in the developing brain. ► Decreased Bax/Bcl2 ratio may protect hippocampus against Pb-induced apoptosis. -- Abstract: The aim of this paper is to examine if pre- and neonatal exposure to lead (Pb) may intensify or inhibit apoptosis or necroptosis in the developing rat brain. Pregnant experimental females received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring; the control group received distilled water. During the feeding of pups, mothers from the experimental group were still receiving PbAc. Pups were weaned at postnatal day 21 and the young rats of both groups then received only distilled water until postnatal day 28. This treatment protocol resulted in a concentration of Pb in rat offspring whole blood (Pb-B) below the threshold of 10 μg/dL, considered safe for humans.We studied Casp-3 activity and expression, AIF nuclear translocation, DNA fragmentation, as well as Bax, Bcl-2 mRNA and protein expression as well as BDNF concentration in selected structures of the rat brain: forebrain cortex (FC), cerebellum (C) and hippocampus (H). The microscopic examinations showed alterations in hippocampal neurons.Our data shows that pre- and neonatal exposure of rats to Pb, leading to Pb-B below 10 μg/dL, can decrease the number of hippocampus neurons, occurring concomitantly with ultrastructural alterations in this region. We observed no morphological or molecular features of severe apoptosis or necrosis (no active Casp-3 and AIF translocation to nucleus) in young brains, despite the reduced levels of BDNF. The potential protective factor against apoptosis was probably the decreased Bax/Bcl-2 ratio, which requires further investigation. Our

  7. 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

  8. 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.

  9. Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal.

    Science.gov (United States)

    Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

    2009-01-01

    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(alpha). 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 alpha, fractal dimension D(f), 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 alpha was able to differentiate also blood vessels from grey matter changes. D(f) 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.

  10. 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.

  11. Evaluation of genetic alteration induced by radon gas using the micronucleus test (Tradescantia sp. clone KU-20)

    International Nuclear Information System (INIS)

    Bruschi, Armando L.; Azevedo, Heliana de; Macacini, Jose F.; Roque, Claudio V.

    2011-01-01

    The first observations over the existence of radon gas (Rn), initially known as 'thorium emanation', were carried out between the end of 19 th and beginning of 20 th centuries. A result of uranium-238 (U 238 ) radioactive decay, radon is a tasteless, odorless and colorless gas under room temperature, with a 3.825-day half life and particle α emission in its decay, and as final product of its disintegration, the stable lead-206 isotope (Pb 206 ). Being it is the gas with the highest density known, closed and poor ventilated environments are favorable to its accumulation, with its inhalation being the highest health risk. The use of vegetal bioindicators has shown to be excellent on the monitoring of air quality and on mutagenic potential of various pollutants contained in the atmosphere. Within this context, the objective of this study was to evaluate the micronucleus test application potential utilizing the Tradescantia sp. clone KU-20, in order to evaluate genetic alterations induced by radon gas. Stems of Tradescantia sp. clone KU-20, previously immerse in Hoagland solution, were introduced in a radon detection equipment's calibration chamber (Alphaguard), containing radium salt. Afterwards, the accommodated stems were exposed to radon gas (the average radon concentration was 7.639 KBq/m3) for 24 hours. The results demonstrated an increase on micronucleus formation (39.23 + 2.143 MCN/100 tetrads) in stems exposed in relation to the negative control (18.00 + 1.396 MCN/100 tetrads). The difference between the values indicated a significant increase on micronucleus frequency in the inflorescences subjected to radon gas. The presented results demonstrated the micronucleus test application potential using Tradescantia clone KU-20 to evaluate genetic effects induced by radon gas. (author)

  12. Multivariate Alteration Detection (MAD) and MAF Postprocessing in Multispectral, Bitemporal Image Data: New Approaches to Change Detection Studies

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Conradsen, Knut; Simpson, James J.

    1998-01-01

    type analyses of simple difference images. Case studies with AHVRR and Landsat MSS data using simple linear stretching and masking of the change images show the usefulness of the new MAD and MAF/MAD change detection schemes. Ground truth observations confirm the detected changes. A simple simulation...

  13. Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.

    Directory of Open Access Journals (Sweden)

    Aslan T Turer

    Full Text Available To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS.Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006, ADP (+42%, p = 0.01, AMP (+79%, p = 0.004, GDP (+69%, p = 0.003, GMP (+58%, p = 0.01, IMP (+50%, p = 0.03, xanthine (+61%, p = 0.0006], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.

  14. Altered rectal sensory response induced by balloon distention in patients with functional abdominal pain syndrome

    Directory of Open Access Journals (Sweden)

    Kudaira Miwako

    2009-11-01

    Full Text Available Abstract Background Functional abdominal pain syndrome (FAPS has chronic unexplained abdominal pain and is similar to the psychiatric diagnosis of somatoform pain disorder. A patient with irritable bowel syndrome (IBS also has chronic unexplained abdominal pain, and rectal hypersensitivity is observed in a majority of the patients. However, no reports have evaluated the visceral sensory function of FAPS precisely. We aimed to test the hypothesis that FAPS would show altered visceral sensation compared to healthy controls or IBS. The present study determined the rectal perceptual threshold, intensity of sensation using visual analogue scale (VAS, and rectal compliance in response to rectal balloon distention by a barostat in FAPS, IBS, and healthy controls. Methods First, the ramp distention of 40 ml/min was induced and the thresholds of discomfort, pain, and maximum tolerance (mmHg were measured. Next, three phasic distentions (60-sec duration separated by 30-sec intervals of 10, 15 and 20 mmHg were randomly loaded. The subjects were asked to mark the VAS in reference to subjective intensity of sensation immediately after each distention. A pressure-volume relationship was determined by plotting corresponding pressures and volumes during ramp distention, and the compliance was calculated over the linear part of the curve by calculating from the slope of the curve using simple regression. Results Rectal thresholds were significantly reduced in IBS but not in FAPS. The VAS ratings of intensity induced by phasic distention (around the discomfort threshold of the controls were increased in IBS but significantly decreased in FAPS. Rectal compliance was reduced in IBS but not in FAPS. Conclusion An inconsistency of visceral sensitivity between lower and higher pressure distention might be a key feature for understanding the pathogenesis of FAPS.

  15. Detection of alteration associated with a porphyry copper deposit in southern Arizona

    Science.gov (United States)

    Abrams, M. J.; Siegal, B. S.

    1977-01-01

    Computer processing of Landsat MSS data was performed using contrast stretching and band-to-band ratioing. A false color ratio composite picture showed color anomalies which coincided with known areas of alteration on and about Red Mountain. A helicopter survey of the study area was undertaken using a portable field reflectance spectrometer. One hundred fifty-six spectra were obtained in the 0.4 to 2.5 micrometer wavelength region. The spectra were digitized, and contour maps for 24 wavelength intervals were produced; no spectral anomalies were evident for the known altered areas. A contour map produced from the 1.6 and 2.2 micrometer ratio generally delineated the alteration areas. The 1.3, 1.6, and 2.2 micrometer wavelength data were canonically transformed using a transformation empirically derived from discriminant function analysis of altered and unaltered materials for the Goldfield, Nevada region, and a contour map was produced for the first canonical variable. The known areas of alteration were clearly defined on the contour map.

  16. alpha-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia.

    Science.gov (United States)

    Cappon, G D; Broening, H W; Pu, C; Morford, L; Vorhees, C V

    1996-10-01

    Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.

  17. Heritable alteration of DNA methylation induced by whole-chromosome aneuploidy in wheat.

    Science.gov (United States)

    Gao, Lihong; Diarso, Moussa; Zhang, Ai; Zhang, Huakun; Dong, Yuzhu; Liu, Lixia; Lv, Zhenling; Liu, Bao

    2016-01-01

    Aneuploidy causes changes in gene expression and phenotypes in all organisms studied. A previous study in the model plant Arabidopsis thaliana showed that aneuploidy-generated phenotypic changes can be inherited to euploid progenies and implicated an epigenetic underpinning of the heritable variations. Based on an analysis by amplified fragment length polymorphism and methylation-sensitive amplified fragment length polymorphism markers, we found that although genetic changes at the nucleotide sequence level were negligible, extensive changes in cytosine DNA methylation patterns occurred in all studied homeologous group 1 whole-chromosome aneuploid lines of common wheat (Triticum aestivum), with monosomic 1A showing the greatest amount of methylation changes. The changed methylation patterns were inherited by euploid progenies derived from the aneuploid parents. The aneuploidy-induced DNA methylation alterations and their heritability were verified at selected loci by bisulfite sequencing. Our data have provided empirical evidence supporting earlier suggestions that heritability of aneuploidy-generated, but aneuploidy-independent, phenotypic variations may have an epigenetic basis. That at least one type of aneuploidy - monosomic 1A - was able to cause significant epigenetic divergence of the aneuploid plants and their euploid progenies also lends support to recent suggestions that aneuploidy may have played an important and protracted role in polyploid genome evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  18. 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

  19. 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.

  20. 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.

  1. Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

    Science.gov (United States)

    Saba, T M; Antikatzides, T G

    1979-04-01

    The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

  2. 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.

  3. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

    Science.gov (United States)

    van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

  4. Exhaustive Exercise-induced Oxidative Stress Alteration of Erythrocyte Oxygen Release Capacity.

    Science.gov (United States)

    Xiong, Yanlian; Xiong, Yanlei; Wang, Yueming; Zhao, Yajin; Li, Yaojin; Ren, Yang; Wang, Ruofeng; Zhao, Mingzi; Hao, Yitong; Liu, Haibei; Wang, Xiang

    2018-05-24

    The aim of the present study is to explore the effect of exhaustive running exercise (ERE) in the oxygen release capacity of rat erythrocytes. Rats were divided into sedentary control (C), moderate running exercise (MRE) and exhaustive running exercise groups. The thermodynamics and kinetics properties of the erythrocyte oxygen release process of different groups were tested. We also determined the degree of band-3 oxidative and phosphorylation, anion transport activity and carbonic anhydrase isoform II(CAII) activity. Biochemical studies suggested that exhaustive running significantly increased oxidative injury parameters in TBARS and methaemoglobin levels. Furthermore, exhaustive running significantly decreased anion transport activity and carbonic anhydrase isoform II(CAII) activity. Thermodynamic analysis indicated that erythrocytes oxygen release ability also significantly increased due to elevated 2,3-DPG level after exhaustive running. Kinetic analysis indicated that exhaustive running resulted in significantly decreased T50 value. We presented evidence that exhaustive running remarkably impacted thermodynamics and kinetics properties of RBCs oxygen release. In addition, changes in 2,3-DPG levels and band-3 oxidation and phosphorylation could be the driving force for exhaustive running induced alterations in erythrocytes oxygen release thermodynamics and kinetics properties.

  5. 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

  6. Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lukas, R.J.; Bennett, E.L.

    1979-01-01

    The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

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

    Science.gov (United States)

    Hmaid, Amal Abdussalam Ali A; Markelic, Milica; Otasevic, Vesna; Masovic, Sava; Jankovic, Aleksandra; Korac, Bato; Korac, Aleksandra

    2018-03-01

    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 (N ω -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.

  8. Detection of ROS Induced Proteomic Signatures by Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Brian McDonagh

    2017-07-01

    Full Text Available Reversible and irreversible post-translational modifications (PTMs induced by endogenously generated reactive oxygen species (ROS in regulatory enzymes and proteins plays an essential role in cellular signaling. Almost all cellular processes including metabolism, transcription, translation and degradation have been identified as containing redox regulated proteins. Specific redox modifications of key amino acids generated by ROS offers a dynamic and versatile means to rapidly alter the activity or functional structure of proteins in response to biochemical, environmental, genetic and pathological perturbations. How the proteome responds to these stimuli is of critical importance in oxidant physiology, as it can regulate the cell stress response by reversible and irreversible PTMs, affecting protein activity and protein-protein interactions. Due to the highly labile nature of many ROS species, applying redox proteomics can provide a signature footprint of the ROS species generated. Ideally redox proteomic approaches would allow; (1 the identification of the specific PTM, (2 identification of the amino acid residue that is modified and (3 the percentage of the protein containing the PTM. New developments in MS offer the opportunity of a more sensitive targeted proteomic approach and retrospective data analysis. Subsequent bioinformatics analysis can provide an insight into the biochemical and physiological pathways or cell signaling cascades that are affected by ROS generation. This mini-review will detail current redox proteomic approaches to identify and quantify ROS induced PTMs and the subsequent effects on cellular signaling.

  9. Real-time Microseismic Processing for Induced Seismicity Hazard Detection

    Energy Technology Data Exchange (ETDEWEB)

    Matzel, Eric M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-10-31

    Induced seismicity is inherently associated with underground fluid injections. If fluids are injected in proximity to a pre-existing fault or fracture system, the resulting elevated pressures can trigger dynamic earthquake slip, which could both damage surface structures and create new migration pathways. The goal of this research is to develop a fundamentally better approach to geological site characterization and early hazard detection. We combine innovative techniques for analyzing microseismic data with a physics-based inversion model to forecast microseismic cloud evolution. The key challenge is that faults at risk of slipping are often too small to detect during the site characterization phase. Our objective is to devise fast-running methodologies that will allow field operators to respond quickly to changing subsurface conditions.

  10. 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.

  11. 3-Bromopyruvate treatment induces alterations of metabolic and stress-related pathways in glioblastoma cells.

    Science.gov (United States)

    Chiasserini, Davide; Davidescu, Magdalena; Orvietani, Pier Luigi; Susta, Federica; Macchioni, Lara; Petricciuolo, Maya; Castigli, Emilia; Roberti, Rita; Binaglia, Luciano; Corazzi, Lanfranco

    2017-01-30

    Glioblastoma (GBM) is the most common and aggressive brain tumour of adults. The metabolic phenotype of GBM cells is highly dependent on glycolysis; therefore, therapeutic strategies aimed at interfering with glycolytic pathways are under consideration. 3-Bromopyruvate (3BP) is a potent antiglycolytic agent, with a variety of targets and possible effects on global cell metabolism. Here we analyzed the changes in protein expression on a GBM cell line (GL15 cells) caused by 3BP treatment using a global proteomic approach. Validation of differential protein expression was performed with immunoblotting and enzyme activity assays in GL15 and U251 cell lines. The results show that treatment of GL15 cells with 3BP leads to extensive changes in the expression of glycolytic enzymes and stress related proteins. Importantly, other metabolisms were also affected, including pentose phosphate pathway, aminoacid synthesis, and glucose derivatives production. 3BP elicited the activation of stress response proteins, as shown by the phosphorylation of HSPB1 at serine 82, caused by the concomitant activation of the p38 pathway. Our results show that inhibition of glycolysis in GL15 cells by 3BP influences different but interconnected pathways. Proteome analysis may help in the molecular characterization of the glioblastoma response induced by pharmacological treatment with antiglycolytic agents. Alteration of the glycolytic pathway characterizes glioblastoma (GBM), one of the most common brain tumours. Metabolic reprogramming with agents able to inhibit carbohydrate metabolism might be a viable strategy to complement the treatment of these tumours. The antiglycolytic agent 3-bromopyruvate (3BP) is able to strongly inhibit glycolysis but it may affect also other cellular pathways and its precise cellular targets are currently unknown. To understand the protein expression changes induced by 3BP, we performed a global proteomic analysis of a GBM cell line (GL15) treated with 3BP. We

  12. The Muon-Induced Neutron Indirect-Detection EXperiment. MINIDEX

    Energy Technology Data Exchange (ETDEWEB)

    Palermo, Matteo

    2016-06-06

    A new experiment to measure muon-induced neutrons is introduced. The design of the Muon-Induced Neutron Indirect Detection EXperiment, MINIDEX, is presented and its installation and commissioning in the Tuebingen Shallow Underground Laboratory are described. Results from its first data taking period, run I, are presented. Muon-induced neutrons are not only an interesting physics topic by itself, but they are also an important source of background in searches for possible new rare phenomena like neutrinoless double beta decay or directly observable interactions of dark matter. These subjects are of great importance to understand the development of the early universe. Therefore, a new generation of ton-scale experiments which require extremely low background levels is under consideration. Reliable Monte Carlo simulations are needed to design such future experiments and estimate their background levels and sensitivities. The background due to muon-induced neutrons is hard to estimate, because of inconsistencies between different experimental results and discrepancies between measurements and Monte Carlo predictions. Especially for neutron production in high-Z materials, more experimental data and related simulation studies are clearly needed. MINIDEX addresses exactly this subject. Already the first five months of data taking provided valuable data on neutron production, propagation and interaction in lead. A first round of comparisons between MINIDEX data and Monte Carlo predictions are presented. In particular, the predictions of two Monte Carlo packages, based on GEANT4, are compared to the data. The data show an overall 70-100% higher rate of muon-induced events than predicted by the Monte Carlo packages. These packages also predict a faster time evolution of the muon-induced signal than observed in the data. Nevertheless, the time until the signal from the muon-induced events is completely collected was correctly predicted by the Monte Carlos. MINIDEX is foreseen

  13. 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.

  14. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gazdzinski, Lisa M.; Cormier, Kyle [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Lu, Fred G. [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Lerch, Jason P. [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Wong, C. Shun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Nieman, Brian J., E-mail: bjnieman@phenogenomics.ca [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2012-12-01

    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.

  15. FEMALE MICE ARE RESISTANT TO Fabp1 GENE ABLATION-INDUCED ALTERATIONS IN BRAIN ENDOCANNABINOID LEVELS

    Science.gov (United States)

    Martin, Gregory G.; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K.; Dangott, Lawrence J.; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J.; Kier, Ann B.; Schroeder, Friedhelm

    2017-01-01

    Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing ECs, i.e arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: i) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; ii) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or iii) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO). PMID:27450559

  16. Metabolic system alterations in pancreatic cancer patient serum: potential for early detection

    International Nuclear Information System (INIS)

    Ritchie, Shawn A; Jin, Wei; Sajobi, Tolulope T; Jayasinghe, Dushmanthi; Chitou, Bassirou; Yamazaki, Yasuyo; White, Thayer; Goodenowe, Dayan B; Akita, Hirofumi; Takemasa, Ichiro; Eguchi, Hidetoshi; Pastural, Elodie; Nagano, Hiroaki; Monden, Morito; Doki, Yuichiro; Mori, Masaki

    2013-01-01

    The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects. A non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasims (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population. FI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p<0.000025). The metabolic systems included 36-carbon ultra long-chain fatty acids, multiple choline-related systems including phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of selected markers from each system ranged between 0.93 ±0.03 and 0.97 ±0.02. No significant correlations between any of the systems and disease-stage, gender, or treatment were observed. Biomarker PC-594 (an ultra long

  17. Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.

    Directory of Open Access Journals (Sweden)

    Carlos Guerrero-Bosagna

    Full Text Available Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell that influences the onset of a specific disease (male infertility. A gestating female rat (F0 generation was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell epigenome and transcriptome that correlates with adult onset disease (male infertility. The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.

  18. Sex influences in behavior and brain inflammatory and oxidative alterations in mice submitted to lipopolysaccharide-induced inflammatory model of depression.

    Science.gov (United States)

    Mello, Bruna Stefânia Ferreira; Chaves Filho, Adriano José Maia; Custódio, Charllyany Sabino; Cordeiro, Rafaela Carneiro; Miyajima, Fabio; de Sousa, Francisca Cléa Florenço; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Macedo, Danielle

    2018-07-15

    Peripheral inflammation induced by lipopolysaccharide (LPS) causes a behavioral syndrome with translational relevance for depression. This mental disorder is twice more frequent among women. Despite this, the majority of experimental studies investigating the neurobiological effects of inflammatory models of depression have been performed in males. Here, we sought to determine sex influences in behavioral and oxidative changes in brain regions implicated in the pathophysiology of mood disorders (hypothalamus, hippocampus and prefrontal cortex - PFC) in adult mice 24 h post LPS challenge. Myeloperoxidase (MPO) activity and interleukin (IL)-1β levels were measured as parameters of active inflammation, while reduced glutathione (GSH) and lipid peroxidation as parameters of oxidative imbalance. We observed that male mice presented behavioral despair, while females anxiety-like alterations. Both sexes were vulnerable to LPS-induced anhedonia. Both sexes presented increased MPO activity in the PFC, while male only in the hippocampus. IL-1β increased in the PFC and hypothalamus of animals of both sexes, while in the hippocampus a relative increase of this cytokine in males compared to females was detected. GSH levels were decreased in all brain areas investigated in animals of both sexes, while increased lipid peroxidation was observed in the hypothalamus of females and in the hippocampus of males after LPS exposure. Therefore, the present study gives additional evidence of sex influence in LPS-induced behavioral alterations and, for the first time, in the oxidative changes in brain areas relevant for mood regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Mei Liu

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.

  1. Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery

    Science.gov (United States)

    McClung, Joseph M.; DeRuisseau, Keith C.; Whidden, Melissa A.; Van Remmen, Holly; Richardson, Arlan; Song, Wook; Vrabas, Ioannis S.; Powers, Scott K.

    2010-01-01

    Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions. Diaphragm muscle from wild-type littermates (WT) and from CAT, SOD1 and SOD2 overexpressing mice were subjected to an in vitro contractile protocol to investigate the force–frequency characteristics, the fatigue properties and the time course of recovery from fatigue. The CAT, SOD1 and SOD2 overexpressors produced less specific force (in N cm−2) at stimulation frequencies of 20–300 Hz and produced lower maximal tetanic force than WT littermates. The relative development of muscle fatigue and recovery from fatigue were not influenced by transgenic overexpression of any antioxidant enzyme. Morphologically, the mean cross-sectional area (in μm2) of diaphragm myofibres expressing myosin heavy chain type IIA was decreased in both CAT and SOD2 transgenic animals, and the percentage of non-contractile tissue increased in diaphragms from all transgenic mice. In conclusion, our results do not support the hypothesis that overexpression of independent antioxidant enzymes protects diaphragm muscle from contraction-induced fatigue or improves recovery from fatigue. Moreover, our data are consistent with the concept that a basal level of ROS is important to optimize muscle force production, since transgenic overexpression of major cellular antioxidants is associated with

  2. 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

  3. Altered Gene Expression Profile in Mouse Bladder Cancers Induced by Hydroxybutyl(butylnitrosamine

    Directory of Open Access Journals (Sweden)

    Ruisheng Yao

    2004-09-01

    Full Text Available A variety of genetic alterations and gene expression changes are involved in the pathogenesis of bladder tumor. To explore these changes, oligonucleotide array analysis was performed on RNA obtained from carcinogen-induced mouse bladder tumors and normal mouse bladder epithelia using Affymetrix (Santa Clara, CA MGU74Av2 GeneChips. Analysis yielded 1164 known genes that were changed in the tumors. Certain of the upregulated genes included EGFR-Ras signaling genes, transcription factors, cell cycle-related genes, and intracellular signaling cascade genes. However, downregulated genes include mitogen-activated protein kinases, cell cycle checkpoint genes, Rab subfamily genes, Rho subfamily genes, and SH2 and SH3 domains-related genes. These genes are involved in a broad range of different pathways including control of cell proliferation, differentiation, cell cycle, signal transduction, and apoptosis. Using the pathway visualization tool GenMAPP, we found that several genes, including TbR-l, STAT1, Smad1, Smad2, Jun, NFκB, and so on, in the TGF-β signaling pathway and p115 RhoGEF, RhoGDl3, MEKK4A/MEKK4B, P13KA, and JNK in the G13 signaling pathway were differentially expressed in the tumors. In summary, we have determined the expression profiles of genes differentially expressed during mouse bladder tumorigenesis. Our results suggest that activation of the EGFR-Ras pathway, uncontrolled cell cycle, aberrant transcription factors, and G13 and TGF-β pathways are involved, and the cross-talk between these pathways seems to play important roles in mouse bladder tumorigenesis.

  4. 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.

  5. Diethylnitrosamine initiation does not alter clofibric acid-induced hepatocarcinogenesis in the rat.

    Science.gov (United States)

    Michel, Cecile; Desdouets, Chantal; Slaoui, Mohamed; Isaacs, Kevin Robert; Roberts, Ruth Angela; Boitier, Eric

    2007-09-01

    Clofibric acid (CLO) is a nongenotoxic hepatocarcinogen in rodents that causes altered hepatocellular foci and/or neoplasms. Initiation by DNA-damaging agents such as diethylnitrosamine (DEN) accelerates focus and tumor appearance and could therefore significantly contribute to shortening of the regulatory 2-year rodent carcinogenicity bioassays. However, it is crucial to evaluate the histological and molecular impact of initiation with DEN on hepatocarcinogenesis promoted by CLO. Male F344 rats were given a single nonnecrogenic injection of DEN (0 or 30 mg/kg) followed by Control diet or CLO (5000 ppm) in diet for up to 20 months. Histopathology and gene expression profiling were performed in liver tumors and surrounding nontumoral liver tissues. The molecular signature of DEN was characterized and its histopathological and immunohistopathological effects on focus and tumor types were also determined. Although foci and tumors appeared earlier in the DEN+CLO-treated group compared to the group treated with CLO alone, DEN had little impact on gene expression in nontumoral tissues since the gene expression profiles were highly similar between Control and DEN-treated rats, and DEN+CLO- and CLO-treated rats. Finally, tumors obtained from DEN+CLO and CLO-treated groups displayed highly correlated gene expression profiles (r>0.83, independently of the time-point). The pathways involved in tumor development revealed by Gene Ontology functional analysis are similar when driven either by spontaneous initiation or by a chemically induced initiation step. Our work described here may contribute to the design optimization of shorter preclinical tests for the evaluation of the nongenotoxic hepatocarcinogenic potential of drugs under development.

  6. 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.

  7. 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.

  8. 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.

  9. Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death.

    Science.gov (United States)

    Chou, Susan S; Clegg, Michael S; Momma, Tony Y; Niles, Brad J; Duffy, Jodie Y; Daston, George P; Keen, Carl L

    2004-10-01

    Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1-C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-alpha, whereas PKC-alpha phosphorylation was not altered. Inhibition of PKC-alpha with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-delta, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-delta fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-delta inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-delta, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-delta to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.

  10. Colloid Detection in Natural Ground Water from Ruprechtov by Laser-Induced Breakdown Detection

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, W.; Geckeis, H.; Goetz, R. [FZK - Inst. fuer Nukleare Entsorgung, Ka rlsruhe (Germany)]. e-mail: hauser@ine.fzk.de; Noseck, U. [Gesellschaft fuer Anlagen- und Reaktorsicherheit, D-38122 Braunschweig (Germany); Laciok, A. [Nuclear Research Inst. Rez plc, Waste and Environmental Management Dept., Husinec-Rez, PSC 250 68 (Czech Republic)

    2007-06-15

    A borehole ground water sampling system and a mobile laser-induced breakdown detection (LIBD) equipment for colloid detection combined with a geomonitoring unit have been applied to characterize the natural background colloid concentration in ground waters of the Ruprechtov natural analogue site (Czech Republic). Ground water has been sampled using steel cylinders. To minimize artifacts during ground water sampling the contact to atmospheric oxygen has been excluded. The ground water samples collected in this way are transported to the laboratory where they have been connected to a series of flow-through detection cells. Argon gas is used to press the ground water through these detection cells for colloid analysis (LIBD), pH, Eh, electrical conductivity and oxygen content. After the above mentioned analysis additional samples are taken for chemical analysis by ICP-AES, ICP-MS, IC- and DOC-detection. Our data obtained by in-situ- and laboratory- measurements point out that the natural colloid concentration found at the Ruprechtov site is a strong function of the ground water ionic strength. The LIBD determined natural background colloid concentrations found at Ruprechtov are compared with data of studies performed in Aespoe (Sweden) and Grimsel (Switzerland)

  11. Multivariate alteration detection (MAD) in multispectral, bi-temporal image data: A new approach to change detction studies

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Conradsen, Knut

    This paper introduces a new orthogonal transformation, the multivariate alteration detection (MAD) transformation, based on an established multivariate statistical technique canonical correlation analysis. The theory for canonical correlation analysis is sketched and a result necessary...... for the definition of the MAD transformation is proven. As opposed to traditional univariate change detection schemes our scheme transforms two sets of multivariate observations (e.g. two multispectral satellite images covering the same geographical area acquired at different points in time) into a difference...... between two linear combinations of the original variables explaining maximal change (i.e. the difference explaining maximal variance) in all variables simultaneously. The MAD transformation is invariant to linear scaling. The MAD transformation can be used iteratively. First, it can be used to detect...

  12. Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Su, Hui [Iowa State Univ., Ames, IA (United States)

    2001-01-01

    Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, we introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties of suitably designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, we demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm2 for 40-μm wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection.

  13. Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

    International Nuclear Information System (INIS)

    Hui Su

    2001-01-01

    Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, we introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties of suitably designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, we demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm(sub 2) for 40-(micro)m wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection

  14. Ebselen alters cellular oxidative status and induces endoplasmic reticulum stress in rat hippocampal astrocytes.

    Science.gov (United States)

    Santofimia-Castaño, Patricia; Izquierdo-Alvarez, Alicia; de la Casa-Resino, Irene; Martinez-Ruiz, Antonio; Perez-Lopez, Marcos; Portilla, Juan C; Salido, Gines M; Gonzalez, Antonio

    2016-05-16

    Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. Because of its properties, it may be protective against injury to the nervous tissue. However, evidence suggests that its glutathione peroxidase activity could underlie certain deleterious actions on cell physiology. In this study we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular oxidative status, cytosolic free-Ca(2+) concentration ([Ca(2+)]c), setting of endoplasmic reticulum stress and phosphorylation of glial fibrillary acidic protein and major mitogen-activated protein kinases were analyzed. Our results show that ebselen induced a concentration-dependent increase in the generation of reactive oxygen species in the mitochondria. We observed a concentration-dependent increase in global cysteine oxidation and in the level of malondialdehyde in the presence of ebselen. We also detected increases in catalase, glutathione S-transferase and glutathione reductase activity. Ebselen also evoked a concentration-dependent increase in [Ca(2+)]c. Moreover, we observed a concentration-dependent increase in the phosphorylation of the unfolded protein response markers, eukaryotic translation initiation factor 2α and X-box binding protein 1. Finally, ebselen also induced an increase in the phosphorylation of glial fibrillary acidic protein, SAPK/JNK, p38 MAPK and p44/42 MAPK. Our results provide strong evidence that implicate endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in an oxidative damage of cells in the presence of ebselen. The compound thus might exert deleterious actions on astrocyte physiology that could compromise their function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Detecting altered postural control after cerebral concussion in athletes with normal postural stability

    OpenAIRE

    Cavanaugh, J; Guskiewicz, K; Giuliani, C; Marshall, S; Mercer, V; Stergiou, N

    2005-01-01

    Objective: To determine if approximate entropy (ApEn), a regularity statistic from non-linear dynamics, could detect changes in postural control during quiet standing in athletes with normal postural stability after cerebral concussion.

  16. Simultaneous Detection of Both Single Nucleotide Variations and Copy Number Alterations by Next-Generation Sequencing in Gorlin Syndrome.

    Directory of Open Access Journals (Sweden)

    Kei-ichi Morita

    Full Text Available Gorlin syndrome (GS is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs. In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals, whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions.

  17. Simultaneous Detection of Both Single Nucleotide Variations and Copy Number Alterations by Next-Generation Sequencing in Gorlin Syndrome.

    Science.gov (United States)

    Morita, Kei-ichi; Naruto, Takuya; Tanimoto, Kousuke; Yasukawa, Chisato; Oikawa, Yu; Masuda, Kiyoshi; Imoto, Issei; Inazawa, Johji; Omura, Ken; Harada, Hiroyuki

    2015-01-01

    Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions.

  18. Global warming alters sound transmission: differential impact on the prey detection ability of echolocating bats

    Science.gov (United States)

    Luo, Jinhong; Koselj, Klemen; Zsebők, Sándor; Siemers, Björn M.; Goerlitz, Holger R.

    2014-01-01

    Climate change impacts the biogeography and phenology of plants and animals, yet the underlying mechanisms are little known. Here, we present a functional link between rising temperature and the prey detection ability of echolocating bats. The maximum distance for echo-based prey detection is physically determined by sound attenuation. Attenuation is more pronounced for high-frequency sound, such as echolocation, and is a nonlinear function of both call frequency and ambient temperature. Hence, the prey detection ability, and thus possibly the foraging efficiency, of echolocating bats and susceptible to rising temperatures through climate change. Using present-day climate data and projected temperature rises, we modelled this effect for the entire range of bat call frequencies and climate zones around the globe. We show that depending on call frequency, the prey detection volume of bats will either decrease or increase: species calling above a crossover frequency will lose and species emitting lower frequencies will gain prey detection volume, with crossover frequency and magnitude depending on the local climatic conditions. Within local species assemblages, this may cause a change in community composition. Global warming can thus directly affect the prey detection ability of individual bats and indirectly their interspecific interactions with competitors and prey. PMID:24335559

  19. Global warming alters sound transmission: differential impact on the prey detection ability of echolocating bats.

    Science.gov (United States)

    Luo, Jinhong; Koselj, Klemen; Zsebok, Sándor; Siemers, Björn M; Goerlitz, Holger R

    2014-02-06

    Climate change impacts the biogeography and phenology of plants and animals, yet the underlying mechanisms are little known. Here, we present a functional link between rising temperature and the prey detection ability of echolocating bats. The maximum distance for echo-based prey detection is physically determined by sound attenuation. Attenuation is more pronounced for high-frequency sound, such as echolocation, and is a nonlinear function of both call frequency and ambient temperature. Hence, the prey detection ability, and thus possibly the foraging efficiency, of echolocating bats and susceptible to rising temperatures through climate change. Using present-day climate data and projected temperature rises, we modelled this effect for the entire range of bat call frequencies and climate zones around the globe. We show that depending on call frequency, the prey detection volume of bats will either decrease or increase: species calling above a crossover frequency will lose and species emitting lower frequencies will gain prey detection volume, with crossover frequency and magnitude depending on the local climatic conditions. Within local species assemblages, this may cause a change in community composition. Global warming can thus directly affect the prey detection ability of individual bats and indirectly their interspecific interactions with competitors and prey.

  20. Detection of the Level of Reactive Oxygen Species Induced by Ionizing Radiation in Cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Chung, Dong Min; Kim, Jin-Hong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    By definition, the direct effect is referred to interaction between photon and DNA molecule, whereas the indirect effect is mediated by the reactive oxygen species (ROS) generated by radiolysis and subsequent reaction. It has been reported that ROS produced after exposure to IR can react with cellular materials such as DNA, proteins, carbohydrates and lipids. ROS is free radicals such as the superoxide anion, hydroxyl radicals and the non-radical hydrogen peroxide. Cells generate ROS during aerobic metabolism. Excessive production of ROS can lead to oxidative stress, genetic alteration and even cell death. It has been reported that ROS plays a critical role in radiation-induced cell injury. Thus, it is of great interest to determine the radiation-induced ROS level. Many kinds of methods to detect the level of ROS have been developed so far. There were random changes of fluorescence intensity in the treatment after irradiation. This result meant that this protocol was not appropriate for determination of radiation-induced ROS. On the other hand, the fluorescence intensity was increased in a dose-dependent manner when the cells were treated with the DCFH-DA solution before irradiation. Conclusions can be drawn from the experimental results of this study. In order to properly measure the ROS level in the cells exposed to ionizing radiation, the cells should be treated with the DCFH-DA solution before irradiation.

  1. Highly sensitivity adhesion molecules detection in hereditary haemochromatosis patients reveals altered expression.

    LENUS (Irish Health Repository)

    Norris, S

    2012-02-01

    Several abnormalities in the immune status of patients with hereditary haemochromatosis (HH) have been reported, suggesting an imbalance in their immune function. This may include persistent production of, or exposure to, altered immune signalling contributing to the pathogenesis of this disorder. Adhesion molecules L-, E- and P-Selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) are some of the major regulators of the immune processes and altered levels of these proteins have been found in pathological states including cardiovascular diseases, arthritis and liver cancer. The aim of this study was to assess L-, E- and P-Selectin, ICAM-1 and VCAM-1 expression in patients with HH and correlate these results with HFE mutation status and iron indexes. A total of 139 subjects were diagnosed with HH (C282Y homozygotes = 87, C282Y\\/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 healthy control subjects with no HFE mutation (N\\/N), 18 normal subjects heterozygous for the H63D mutation served as age-sex-matched controls. We observed a significant decrease in L-selectin (P = 0.0002) and increased E-selectin and ICAM-1 (P = 0.0006 and P = 0.0059) expression in HH patients compared with healthy controls. This study observes for the first time that an altered adhesion molecules profile occurs in patients with HH that is associated with specific HFE genetic component for iron overload, suggesting that differential expression of adhesion molecules may play a role in the pathogenesis of HH.

  2. A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples

    Directory of Open Access Journals (Sweden)

    LaFramboise William A

    2011-01-01

    Full Text Available Abstract Background Genomic instability in cancer leads to abnormal genome copy number alterations (CNA as a mechanism underlying tumorigenesis. Using microarrays and other technologies, tumor CNA are detected by comparing tumor sample CN to normal reference sample CN. While advances in microarray technology have improved detection of copy number alterations, the increase in the number of measured signals, noise from array probes, variations in signal-to-noise ratio across batches and disparity across laboratories leads to significant limitations for the accurate identification of CNA regions when comparing tumor and normal samples. Methods To address these limitations, we designed a novel "Virtual Normal" algorithm (VN, which allowed for construction of an unbiased reference signal directly from test samples within an experiment using any publicly available normal reference set as a baseline thus eliminating the need for an in-lab normal reference set. Results The algorithm was tested using an optimal, paired tumor/normal data set as well as previously uncharacterized pediatric malignant gliomas for which a normal reference set was not available. Using Affymetrix 250K Sty microarrays, we demonstrated improved signal-to-noise ratio and detected significant copy number alterations using the VN algorithm that were validated by independent PCR analysis of the target CNA regions. Conclusions We developed and validated an algorithm to provide a virtual normal reference signal directly from tumor samples and minimize noise in the derivation of the raw CN signal. The algorithm reduces the variability of assays performed across different reagent and array batches, methods of sample preservation, multiple personnel, and among different laboratories. This approach may be valuable when matched normal samples are unavailable or the paired normal specimens have been subjected to variations in methods of preservation.

  3. Effects of 4-phenyl butyric acid on high glucose-induced alterations in dorsal root ganglion neurons.

    Science.gov (United States)

    Sharma, Dilip; Singh, Jitendra Narain; Sharma, Shyam S

    2016-12-02

    Mechanisms and pathways involving in diabetic neuropathy are still not fully understood but can be unified by the process of overproduction of reactive oxygen species (ROS) such as superoxide, endoplasmic reticulum (ER) stress, downstream intracellular signaling pathways and their modulation. Susceptibility of dorsal root ganglion (DRG) to internal/external hyperglycemic environment stress contributes to the pathogenesis and progression of diabetic neuropathy. ER stress leads to abnormal ion channel function, gene expression, transcriptional regulation, metabolism and protein folding. 4-phenyl butyric acid (4-PBA) is a potent and selective chemical chaperone; which may inhibit ER stress. It may be hypothesized that 4-PBA could attenuate via channels in DRG in diabetic neuropathy. Effects of 4-PBA were determined by applying different parameters of oxidative stress, cell viability, apoptosis assays and channel expression in cultured DRG neurons. Hyperglycemia-induced apoptosis in the DRG neuron was inhibited by 4-PBA. Cell viability of DRG neurons was not altered by 4-PBA. Oxidative stress was significantly blocked by the 4-PBA. Sodium channel expression was not altered by the 4-PBA. Our data provide evidence that the hyperglycemia-induced alteration may be reduced by the 4-PBA without altering the sodium channel expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. 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

    in the field are often not detected. Thus, other and better markers of SARA are needed. The purpose of this research was to study the feces microbiome during SARA and assess the possibilities of using feces microbial markers as indicators of SARA. Methods: Six lactating, rumen cannulated, Danish Holstein cows...... were used in a blocked design study including two blocks. In the first block, two cows received control diet and two cows received SARA-challenge diet. In the second block, former control cows received SARA diet while two new cows received control diet. Cows received a total mixed ration (TMR; 24......% 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...

  5. Distillery effluent induced alterations in the haematological profile of fingerlings of Colisa fasciatus.

    Science.gov (United States)

    Shukla, Anuradha; Shukla, J P

    2013-09-01

    Present study deals with the impact of Gorakhpur distillery effluent at various concentration levels (5, 10 and 20%) on the blood profile of fingerling of, Colisa fosciotus after 30 days of exposure. Observations revealed that 5% of effluent concentration produced no significant alterations in various haematological parameters except for clotting time and immature erythrocytes. However, 10% of effluent concentration brought significant alterations in hematocrit as well as clotting time and 20% of effluent concentration produced highly significant (P<0.001) alteration in most of the haematological parameters except for hemoglobin percentage.

  6. Renal Alterations in Feline Immunodeficiency Virus (FIV-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

    Directory of Open Access Journals (Sweden)

    Mauro Pistello

    2012-08-01

    Full Text Available Human immunodeficiency virus (HIV is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  7. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    Science.gov (United States)

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  8. Alterations in body fluid content can be detected by bioelectrical impedance analysis.

    Science.gov (United States)

    Scheltinga, M R; Jacobs, D O; Kimbrough, T D; Wilmore, D W

    1991-05-01

    The electrical resistance across the whole body and its segments to the conduction of a weak alternating current was determined in human subjects under three different conditions: (1) during bed rest, (2) during infusion of 1 liter of saline, and (3) during donation of 1 unit of blood. During bed rest, extracellular and total body water were measured by dilution of bromide and heavy water, respectively. Electrical resistance obtained from electrodes placed on proximal portions of extremities ("proximal resistance") accounted for less than 50% of that determined by electrodes positioned on routinely used portions of a hand and foot ("whole body resistance"). Following saline infusion, resistance determined from the whole body and all its segments fell (P less than 0.001); the magnitude of the drop in both proximal and whole body resistance was inversely related to the volume of total body water (TBW) (r = -0.82, P less than 0.002, and r = -0.73, P less than 0.01, respectively). In contrast, blood donation was associated with significantly increased resistance at both measurement sites. TBW predicted from anthropometrics was inversely related to both proximal (r = -0.90, P less than 0.001) and whole body resistance (r = -0.75, P less than 0.001). Bioelectrical impedance analysis is a simple technique which may be useful in monitoring minimal alterations in TBW. Furthermore, altered fluid status may be predicted more accurately by changes in proximal resistance compared to changes in traditionally used whole body resistance.

  9. Ursodeoxycholic acid alleviates cholestasis-induced histophysiological alterations in the male reproductive system of bile duct-ligated rats.

    Science.gov (United States)

    Saad, Ramadan A; Mahmoud, Yomna I

    2014-12-01

    Ursodeoxycholic acid is the most widely used drug for treating cholestatic liver diseases. However, its effect on the male reproductive system alterations associated with cholestasis has never been studied. Thus, this study aimed to investigate the effect of ursodeoxycholic acid on cholestasis-induced alterations in the male reproductive system. Cholestasis was induced by bile duct ligation. Bile duct-ligated rats had higher cholestasis biomarkers and lower levels of testosterone, LH and FSH than did the Sham rats. They also had lower reproductive organs weights, and lower sperm motility, density and normal morphology than those of Sham rats. Histologically, these animals suffered from testicular tubular atrophy, interstitial edema, thickening of basement membranes, vacuolation, and depletion of germ cells. After ursodeoxycholic acid administration, cholestasis-induced structural and functional alterations were significantly ameliorated. In conclusion, ursodeoxycholic acid can ameliorate the reproductive complications of chronic cholestasis in male patients, which represents an additional benefit to this drug. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Wavelength comparison for laser induced breakdown spectroscopy caries detection

    Science.gov (United States)

    Amaral, Marcello M.; Raele, Marcus P.; Ana, Patrícia A.; Núñez, Sílvia C.; Zamataro, Claudia B.; Zezell, Denise M.

    2018-02-01

    Laser Induced Breakdown Spectroscopy (LIBS) is a technique capable to perform elemental analyses of a variety of samples, independent of matter state. Other spectroscopy techniques may require a destructive and time-consuming sample preparation. On the other hand, LIBS is a less destructive technique with no (or considerably less) sample preparation, using a relatively simple experimental setup. LIBS also provides a multielement analysis into one single spectrum acquisition, applying a Nd:YAG short-pulsed laser to ensure the stoichiometry between the sample and the generated plasma. LIBS have been applied on the study of carious lesions using a Nd:YAG into its fundamental emission at 1064 nm. It was shown that ratio of P/Ca and Zn/Ca can be used to monitor the cariogenic process. Another minor elements, e.g. C and Cu, associated with bacteria biofilm were also measured with the Nd:YAG laser. The fundamental wavelength emission (1064 nm) of Nd:YAG is coincident with a hydroxyapatite transmission window and it may affect the result. In order to address this issue a study used the second harmonic of the Nd:YAG laser at 532 nm. It was show that it is also possible perform LIBS on carious lesion using the Nd:YAG at 532 nm. However, there is not a work direct comparing the LIBS at 532 nm and 1064 nm for carious lesion detection. So, the aim of this work was to investigate the influence of laser wavelength on the LIBS performance for carious lesion detection. In both cases the carious lesion was detected with the advantage of no interference with hydroxyapatite at 532 nm.

  11. 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...

  12. Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status.

    Science.gov (United States)

    Lebda, Mohamed A; Tohamy, Hossam G; El-Sayed, Yasser S

    2017-05-01

    Dietary intake of fructose corn syrup in sweetened beverages is associated with the development of metabolic syndrome and obesity. We hypothesized that inflammatory cytokines play a role in lipid storage and induction of liver injury. Therefore, this study intended to explore the expression of adipocytokines and its link to hepatic damage. Rats were assigned to drink water, cola soft drink (free access) and aspartame (240 mg/kg body weight/day orally) for 2 months. The lipid profiles, liver antioxidants and pathology, and mRNA expression of adipogenic cytokines were evaluated. Subchronic intake of soft drink or aspartame substantially induced hyperglycemia and hypertriacylglycerolemia, as represented by increased serum glucose, triacylglycerol, low-density lipoprotein and very low-density lipoprotein cholesterol, with obvious visceral fatty deposition. These metabolic syndromes were associated with the up-regulation of leptin and down-regulation of adiponectin and peroxisome proliferator activated receptor-γ (PPAR-γ) expression. Moreover, alterations in serum transaminases accompanied by hepatic oxidative stress involving induction of malondialdehyde and reduction of superoxide dismutase, catalase, and glutathione peroxidase and glutathione levels are indicative of oxidative hepatic damage. Several cytoarchitecture alterations were detected in the liver, including degeneration, infiltration, necrosis, and fibrosis, predominantly with aspartame. These data suggest that long-term intake of soft drink or aspartame-induced hepatic damage may be mediated by the induction of hyperglycemia, lipid accumulation, and oxidative stress with the involvement of adipocytokines. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Alterations in the neural circuits from peripheral afferents to the spinal cord: possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Zhen-Zhen eKou

    2014-01-01

    Full Text Available Diabetic polyneuropathy (DPN presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies in the dorsal root ganglion (DRG and spinal cord of streptozotocin (STZ-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN.

  14. 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.

  15. 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 ...

  16. Schizophrenia alters intra-network functional connectivity in the caudate for detecting speech under informational speech masking conditions.

    Science.gov (United States)

    Zheng, Yingjun; Wu, Chao; Li, Juanhua; Li, Ruikeng; Peng, Hongjun; She, Shenglin; Ning, Yuping; Li, Liang

    2018-04-04

    Speech recognition under noisy "cocktail-party" environments involves multiple perceptual/cognitive processes, including target detection, selective attention, irrelevant signal inhibition, sensory/working memory, and speech production. Compared to health listeners, people with schizophrenia are more vulnerable to masking stimuli and perform worse in speech recognition under speech-on-speech masking conditions. Although the schizophrenia-related speech-recognition impairment under "cocktail-party" conditions is associated with deficits of various perceptual/cognitive processes, it is crucial to know whether the brain substrates critically underlying speech detection against informational speech masking are impaired in people with schizophrenia. Using functional magnetic resonance imaging (fMRI), this study investigated differences between people with schizophrenia (n = 19, mean age = 33 ± 10 years) and their matched healthy controls (n = 15, mean age = 30 ± 9 years) in intra-network functional connectivity (FC) specifically associated with target-speech detection under speech-on-speech-masking conditions. The target-speech detection performance under the speech-on-speech-masking condition in participants with schizophrenia was significantly worse than that in matched healthy participants (healthy controls). Moreover, in healthy controls, but not participants with schizophrenia, the strength of intra-network FC within the bilateral caudate was positively correlated with the speech-detection performance under the speech-masking conditions. Compared to controls, patients showed altered spatial activity pattern and decreased intra-network FC in the caudate. In people with schizophrenia, the declined speech-detection performance under speech-on-speech masking conditions is associated with reduced intra-caudate functional connectivity, which normally contributes to detecting target speech against speech masking via its functions of suppressing masking-speech signals.

  17. 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

  18. Mercury heavy-metal-induced physiochemical changes and genotoxic alterations in water hyacinths [Eichhornia crassipes (Mart.)].

    Science.gov (United States)

    Malar, Srinivasan; Sahi, Shivendra Vikram; Favas, Paulo J C; Venkatachalam, Perumal

    2015-03-01

    Mercury heavy metal pollution has become an important environmental problem worldwide. Accumulation of mercury ions by plants may disrupt many cellular functions and block normal growth and development. To assess mercury heavy metal toxicity, we performed an experiment focusing on the responses of Eichhornia crassipes to mercury-induced oxidative stress. E. crassipes seedlings were exposed to varying concentrations of mercury to investigate the level of mercury ions accumulation, changes in growth patterns, antioxidant defense mechanisms, and DNA damage under hydroponics system. Results showed that plant growth rate was significantly inhibited (52 %) at 50 mg/L treatment. Accumulation of mercury ion level were 1.99 mg/g dry weight, 1.74 mg/g dry weight, and 1.39 mg/g dry weight in root, leaf, and petiole tissues, respectively. There was a decreasing trend for chlorophyll a, b, and carotenoids with increasing the concentration of mercury ions. Both the ascorbate peroxidase and malondialdehyde contents showed increased trend in leaves and roots up to 30 mg/L mercury treatment and slightly decreased at the higher concentrations. There was a positive correlation between heavy metal dose and superoxide dismutase, catalase, and peroxidase antioxidative enzyme activities which could be used as biomarkers to monitor pollution in E. crassipes. Due to heavy metal stress, some of the normal DNA bands were disappeared and additional bands were amplified compared to the control in the random amplified polymorphic DNA (RAPD) profile. Random amplified polymorphic DNA results indicated that genomic template stability was significantly affected by mercury heavy metal treatment. We concluded that DNA changes determined by random amplified polymorphic DNA assay evolved a useful molecular marker for detection of genotoxic effects of mercury heavy metal contamination in plant species.

  19. 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

  20. Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

    Science.gov (United States)

    Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

    2018-07-04

    Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

  1. Stability of medicines after repackaging into multicompartment compliance aids: eight criteria for detection of visual alteration

    OpenAIRE

    Albert, Valerie; Lanz, Michael; Imanidis, Georgios; Hersberger, Kurt E.; Arnet, Isabelle

    2017-01-01

    Introduction Multicompartment compliance aids (MCA) are widely used by patients. They support the management of medication and reduce unintentional nonadherence. MCA are filled with medicines unpacked from their original packaging. Swiss pharmacists currently provide MCA for 1–2 weeks, although little and controversial information exists on the stability of repackaged medicines. Objective We aimed to validate the usefulness of a simple screening method capable of detecting visual stability pr...

  2. Detecting altered connectivity patterns in HIV associated neurocognitive impairment using mutual connectivity analysis

    Science.gov (United States)

    Abidin, Anas Zainul; D'Souza, Adora M.; Nagarajan, Mahesh B.; Wismüller, Axel

    2016-03-01

    The use of functional Magnetic Resonance Imaging (fMRI) has provided interesting insights into our understanding of the brain. In clinical setups these scans have been used to detect and study changes in the brain network properties in various neurological disorders. A large percentage of subjects infected with HIV present cognitive deficits, which are known as HIV associated neurocognitive disorder (HAND). In this study we propose to use our novel technique named Mutual Connectivity Analysis (MCA) to detect differences in brain networks in subjects with and without HIV infection. Resting state functional MRI scans acquired from 10 subjects (5 HIV+ and 5 HIV-) were subject to standard preprocessing routines. Subsequently, the average time-series for each brain region of the Automated Anatomic Labeling (AAL) atlas are extracted and used with the MCA framework to obtain a graph characterizing the interactions between them. The network graphs obtained for different subjects are then compared using Network-Based Statistics (NBS), which is an approach to detect differences between graphs edges while controlling for the family-wise error rate when mass univariate testing is performed. Applying this approach on the graphs obtained yields a single network encompassing 42 nodes and 65 edges, which is significantly different between the two subject groups. Specifically connections to the regions in and around the basal ganglia are significantly decreased. Also some nodes corresponding to the posterior cingulate cortex are affected. These results are inline with our current understanding of pathophysiological mechanisms of HIV associated neurocognitive disease (HAND) and other HIV based fMRI connectivity studies. Hence, we illustrate the applicability of our novel approach with network-based statistics in a clinical case-control study to detect differences connectivity patterns.

  3. Detection of rainfall-induced landslides on regional seismic networks

    Science.gov (United States)

    Manconi, Andrea; Coviello, Velio; Gariano, Stefano Luigi; Picozzi, Matteo

    2017-04-01

    Seismic techniques are increasingly adopted to detect signals induced by mass movements and to quantitatively evaluate geo-hydrological hazards at different spatial and temporal scales. By analyzing landslide-induced seismicity, it is possible obtaining significant information on the source of the mass wasting, as well as on its dynamics. However, currently only few studies have performed a systematic back analysis on comprehensive catalogues of events to evaluate the performance of proposed algorithms. In this work, we analyze a catalogue of 1058 landslides induced by rainfall in Italy. Among these phenomena, there are 234 rock falls, 55 debris flows, 54 mud flows, and 715 unspecified shallow landslides. This is a subset of a larger catalogue collected by the Italian research institute for geo-hydrological protection (CNR IRPI) during the period 2000-2014 (Brunetti et al., 2015). For each record, the following information are available: the type of landslide; the geographical location of the landslide (coordinates, site, municipality, province, and 3 classes of geographic accuracy); the temporal information on the landslide occurrence (day, month, year, time, date, and 3 classes of temporal accuracy); the rainfall conditions (rainfall duration and cumulated event rainfall) that have resulted in the landslide. We consider here only rainfall-induced landslides for which exact date and time were known from chronicle information. The analysis of coeval seismic data acquired by regional seismic networks show clear signals in at least 3 stations for 64 events (6% of the total dataset). Among them, 20 are associated to local earthquakes and 2 to teleseisms; 10 are anomalous signals characterized by irregular and impulsive waveforms in both time and frequency domains; 33 signals are likely associated to the landslide occurrence, as they have a cigar-shaped waveform characterized by emerging onsets, duration of several tens of seconds, and low frequencies (1-10 Hz). For

  4. Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection.

    Science.gov (United States)

    Mathieson, Sean R; Livingstone, Vicki; Low, Evonne; Pressler, Ronit; Rennie, Janet M; Boylan, Geraldine B

    2016-10-01

    Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. Post-phenobarbital seizures showed significantly lower amplitude (pphenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Analysis of human reticulocyte genes reveals altered erythropoiesis: potential use to detect recombinant human erythropoietin doping.

    Science.gov (United States)

    Varlet-Marie, Emmanuelle; Audran, Michel; Lejeune, Mireille; Bonafoux, Béatrice; Sicart, Marie-Therese; Marti, Jacques; Piquemal, David; Commes, Thérèse

    2004-08-01

    Enhancement of oxygen delivery to tissues is associated with improved sporting performance. One way of enhancing oxygen delivery is to take recombinant human erythropoietin (rHuEpo), which is an unethical and potentially dangerous practice. However, detection of the use of rHuEpo remains difficult in situations such as: i) several days after the end of treatment ii) when a treatment with low doses is conducted iii) if the rHuEpo effect is increased by other substances. In an attempt to detect rHuEpo abuse, we selected erythroid gene markers from a SAGE library and analyzed the effects of rHuEpo administration on expression of the HBB, FTL and OAZ genes. Ten athletes were assigned to the rHuEpo or placebo group. The rHuEpo group received subcutaneous injections of rHuEpo (50 UI/kg three times a week, 4 weeks; 20 UI/kg three times a week, 2 weeks). HBB, FTL and OAZ gene profiles were monitored by real time-polymerase chain reaction (PCR) quantification during and for 3 weeks after drug administration. The global analysis of these targeted genes detected in whole blood samples showed a characteristic profile of subjects misusing rHuEpo with a increase above the threshold levels. The individual analysis of OAZ mRNA seemed indicative of rHuEpo treatment. The performance-enhancing effect of rHuEpo treatment is greater than the duration of hematologic changes associated with rHuEpo misuse. Although direct electrophoretic methods to detect rHuEpo have been developed, recombinant isoforms of rHuEpo are not detectable some days after the last subcutaneous injection. To overcome these limitations indirect OFF models have been developed. Our data suggest that, in the near future, it will be possible to consolidate results achievable with the OFF models by analyzing selected erythroid gene markers as a supplement to indirect methods.

  6. Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells.

    Science.gov (United States)

    Liu, Qian; Sun, Shanquan; Yu, Wei; Jiang, Jin; Zhuo, Fei; Qiu, Guoping; Xu, Shiye; Jiang, Xuli

    2015-04-01

    Long non-coding RNAs (lncRNAs), a recently discovered class of non-coding genes, are transcribed throughout the genome. Emerging evidence suggests that lncRNAs may be involved in modulating various aspects of tumor biology, including regulating gene activity in response to external stimuli or DNA damage. No data are available regarding the expression of lncRNAs during genotoxic stress-induced apoptosis and/or necrosis in human glioma cells. In this study, we detected a change in the expression of specific candidate lncRNAs (neat1, GAS5, TUG1, BC200, Malat1, MEG3, MIR155HG, PAR5, and ST7OT1) during DNA damage-induced apoptosis in human glioma cell lines (U251 and U87) using doxorubicin (DOX) and resveratrol (RES). We also detected the expression pattern of these lncRNAs in human glioma cell lines under necrosis induced using an increased dose of DOX. Our results reveal that the lncRNA expression patterns are distinct between genotoxic stress-induced apoptosis and necrosis in human glioma cells. The sets of lncRNA expressed during genotoxic stress-induced apoptosis were DNA-damaging agent-specific. Generally, MEG3 and ST7OT1 are up-regulated in both cell lines under apoptosis induced using both agents. The induction of GAS5 is only clearly detected during DOX-induced apoptosis, whereas the up-regulation of neat1 and MIR155HG is only found during RES-induced apoptosis in both cell lines. However, TUG1, BC200 and MIR155HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. In conclusion, our findings suggest that the distinct regulation of lncRNAs may possibly involve in the process of cellular defense against genotoxic agents.

  7. Frequency of motor alterations detected through manometry in patients with esophageal symptoms and scleroderma.

    Science.gov (United States)

    Pérez Y López, N; Lugo-Zamudio, G; Barbosa-Cobos, R E; Wong-Lam, A; Torres-López, E

    Scleroderma can present with esophageal involvement causing important morbidity. To describe the manometric findings and clinical characteristics of patients with scleroderma and esophageal symptoms. Patients with scleroderma and esophageal symptoms were evaluated through esophageal manometry within the time frame of one year. Descriptive statistics were carried out and the continuous variables were expressed as means and standard deviation. Frequencies were expressed as percentages. The study included 24 female patients with a mean age of 53.5 years and mean disease progression of 7.84 years. The most frequent findings were short and hypotonic lower esophageal sphincter (mean length 1.58cm and mean tone 9.49mmHg) and ineffective esophageal motility (mean non-transmitted waves 92.91%, mean effective primary peristalsis 40.05%, and mean amplitude 13.11mmHg). The most frequent symptom was dysphagia. Scleroderma is associated with lower esophageal sphincter alterations and symptomatic ineffective esophageal motility. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

    Science.gov (United States)

    Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

    1995-02-06

    EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

  9. Aptamer-Assisted Detection of the Altered Expression of Estrogen Receptor Alpha in Human Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Rajesh Ahirwar

    Full Text Available An increase in the expression of estrogen receptors (ER and the expanded population of ER-positive cells are two common phenotypes of breast cancer. Detection of the aberrantly expressed ERα in breast cancer is carried out using ERα-antibodies and radiolabelled ligands to make decisions about cancer treatment and targeted therapy. Capitalizing on the beneficial advantages of aptamer over the conventional antibody or radiolabelled ligand, we have identified a DNA aptamer that selectively binds and facilitates the detection of ERα in human breast cancer tissue sections. The aptamer is identified using the high throughput sequencing assisted SELEX screening. Biophysical characterization confirms the binding and formation of a thermodynamically stable complex between the identified DNA aptamer (ERaptD4 and ERα (Ka = 1.55±0.298×108 M(-1; ΔH = 4.32×104±801.1 cal/mol; ΔS = -108 cal/mol/deg. Interestingly, the specificity measurements suggest that the ERaptD4 internalizes into ERα-positive breast cancer cells in a target-selective manner and localizes specifically in the nuclear region. To harness these characteristics of ERaptD4 for detection of ERα expression in breast cancer samples, we performed the aptamer-assisted histochemical analysis of ERα in tissue samples from breast cancer patients. The results were validated by performing the immunohistochemistry on same samples with an ERα-antibody. We found that the two methods agree strongly in assay output (kappa value = 0.930, p-value <0.05 for strong ERα positive and the ERα negative samples; kappa value = 0.823, p-value <0.05 for the weak/moderate ER+ve samples, n = 20. Further, the aptamer stain the ERα-positive cells in breast tissues without cross-reacting to ERα-deficient fibroblasts, adipocytes, or the inflammatory cells. Our results demonstrate a significant consistency in the aptamer-assisted detection of ERα in strong ERα positive, moderate ERα positive and ERα negative

  10. Oral contraceptives may alter the detection of emotions in facial expressions.

    Science.gov (United States)

    Hamstra, Danielle A; De Rover, Mischa; De Rijk, Roel H; Van der Does, Willem

    2014-11-01

    A possible effect of oral contraceptives on emotion recognition was observed in the context of a clinical trial with a corticosteroid. Users of oral contraceptives detected significantly fewer facial expressions of sadness, anger and disgust than non-users. This was true for trial participants overall as well as for those randomized to placebo. Although it is uncertain whether this is an effect of oral contraceptives or a pre-existing difference, future studies on the effect of interventions should control for the effects of oral contraceptives on emotional and cognitive outcomes. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  11. 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

  12. 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.

  13. 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

    2016-03-01

    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. 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. 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. 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. © 2016 The Obesity Society.

  14. Detection of Altered Risk Factors in Hospitalized Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Avany Fernandes Pereira

    2002-09-01

    Full Text Available OBJECTIVE: To assess biochemical, anthropometric, and dietary variables considered risk factors for coronary artery disease. METHODS: Using anthropometrics, dietary allowance, and blood biochemistry, we assessed 84 patients [54 males (mean age of 55± 8 years and 30 females (mean age of 57±7 years], who had severe ( > or = 70% coronary artery obstruction and nonsevere forms of coronary artery disease determined by cardiac catheterization. The severe form of the disease prevailed in 70% of the males and 64% of the females, and a high frequency of familial antecedents (92% ' 88% and history of acute myocardial infarction (80% ' 70% were observed. Smoking predominated among males (65% and diabetes mellitus among females (43%. RESULTS: Males and females had body mass index and body fat above the normal values. Females with nonsevere lesions had HDL > 35 mg/dL, and this constituted a discriminating intergroup indicator. Regardless of the severity of the disease, hyperglycemia and hypertriglyceridemia were found among females, and cholesterolemia > 200 mg/dL in both sexes, but only males had LDL fraction > 160 mg/dL and homocysteine > 11.7 mmol/L. The male dietary allowance was inadequate in nutrients for homocysteine metabolism and in nutrients with an antioxidant action, such as the vitamins B6, C, and folate. Individuals of both sexes had a higher lipid and cholesterol intake and an inadequate consumption of fiber. The diet was classified as high-protein, high-fat, and low-carbohydrate. CONCLUSION: The alterations found had no association with the severity of lesions, indicating the need for more effective nutritional intervention.

  15. [Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].

    Science.gov (United States)

    de Gea-García, J H; Benali, L; Galcerá-Tomás, J; Padilla-Serrano, A; Andreu-Soler, E; Melgarejo-Moreno, A; Alonso-Fernández, N

    2014-03-01

    Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  16. 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.

  17. Laser-induced fluorescence in the detection of esophageal carcinoma

    Science.gov (United States)

    Wang, Kenneth K.; Gutta, Kumar; Laukka, Mark A.; Densmore, John

    1995-01-01

    Laser induced fluorescence (LIF) is a technique which can perform an 'optical biopsy' of gastrointestinal mucosa. LIF was performed in resected specimens using a pulsed N2-laser coupled fiberoptically to a probe. Fluorescence was measured using a 0.2 meter spectroscope with an intensified photodiode array. Measurements were made on fresh (esophagus, and adenocarcinoma. Each tissue section was examined using an optical probe consisting of a central fiber for delivering the excitation energy and a 6 fiber bundle surrounding the central fiber for detection of the fluorescence. An excitation wavelength of 337 nm was used which generated 3-ns pulses while fluorescence intensities were acquired from 300-800 nm. Spectra were obtained from each section in a standardized fashion and background spectra subtracted. Fluorescence readings were taken from 54 normal esophageal sections and 32 sections of adenocarcinoma. A fluorescence index obtained from the tumor sections was 0.68+/- 0.01 compared with 0.51+/- 0.01 for the normal sections (pesophagus with good accuracy.

  18. 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

  19. 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

  20. Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

    Science.gov (United States)

    Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

    2014-01-01

    Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

  1. Endosulfan affects health variables in adult zebrafish (Danio rerio) and induces alterations in larvae development

    DEFF Research Database (Denmark)

    Velasco-Santamaria, Y. M.; Handy, R. D.; Sloman, K. A.

    2011-01-01

    to controls. Both concentrations of endosulfan caused a 4.0 fold increase in Na(+)K(+)-ATPase activity compared to controls (ANOVA, p ANOVA, p ... alterations in the progeny of fish exposed to endosulfan were observed. Heart beat frequency was significantly lower in larvae from exposed adults to 0.16 mu g/L compared to the control (ANOVA, p

  2. Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo

    International Nuclear Information System (INIS)

    Wan Ibrahim, Wan Norhamidah; Tofighi, Roshan; Onishchenko, Natalia; Rebellato, Paola; Bose, Raj; Uhlén, Per; Ceccatelli, Sandra

    2013-01-01

    Perfluorinated compounds are ubiquitous chemicals of major concern for their potential adverse effects on the human population. We have used primary rat embryonic neural stem cells (NSCs) to study the effects of perfluorooctane sulfonate (PFOS) on the process of NSC spontaneous differentiation. Upon removal of basic fibroblast growth factor, NSCs were exposed to nanomolar concentrations of PFOS for 48 h, and then allowed to differentiate for additional 5 days. Exposure to 25 or 50 nM concentration resulted in a lower number of proliferating cells and a higher number of neurite-bearing TuJ1-positive cells, indicating an increase in neuronal differentiation. Exposure to 50 nM also significantly increased the number of CNPase-positive cells, pointing to facilitation of oligodendrocytic differentiation. PPAR genes have been shown to be involved in PFOS toxicity. By q-PCR we detected an upregulation of PPARγ with no changes in PPARα or PPARδ genes. One of the downstream targets of PPARs, the mitochondrial uncoupling protein 2 (UCP2) was also upregulated. The number of TuJ1- and CNPase-positive cells increased after exposure to PPARγ agonist rosiglitazone (RGZ, 3 μM) and decreased after pre-incubation with the PPARγ antagonist GW9662 (5 μM). RGZ also upregulated the expression of PPARγ and UCP2 genes. Meanwhile GW9662 abolished the UCP2 upregulation and decreased Ca 2+ activity induced by PFOS. Interestingly, a significantly higher expression of PPARγ and UCP3 genes was also detected in mouse neonatal brain after prenatal exposure to PFOS. These data suggest that PPARγ plays a role in the alteration of spontaneous differentiation of NSCs induced by nanomolar concentrations of PFOS. - Highlights: • PFOS decreases proliferation of neural stem cells (NSCs). • PFOS induces neuronal and oligodendrocytic differentiation in NSCs. • PFOS alters expression of PPARγ and UCP2 in vitro. • PFOS alters expression of PPARγ and UCP3 in vivo. • Block of PPARγ by

  3. Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wan Ibrahim, Wan Norhamidah, E-mail: hamidah@science.upm.edu.my [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Tofighi, Roshan, E-mail: Roshan.Tofighi@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Onishchenko, Natalia, E-mail: Natalia.Onishchenko@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Rebellato, Paola, E-mail: Paola.Rebellato@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm (Sweden); Bose, Raj, E-mail: Raj.Bose@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden); Uhlén, Per, E-mail: Per.Uhlen@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm (Sweden); Ceccatelli, Sandra, E-mail: Sandra.Ceccatelli@ki.se [Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm (Sweden)

    2013-05-15

    Perfluorinated compounds are ubiquitous chemicals of major concern for their potential adverse effects on the human population. We have used primary rat embryonic neural stem cells (NSCs) to study the effects of perfluorooctane sulfonate (PFOS) on the process of NSC spontaneous differentiation. Upon removal of basic fibroblast growth factor, NSCs were exposed to nanomolar concentrations of PFOS for 48 h, and then allowed to differentiate for additional 5 days. Exposure to 25 or 50 nM concentration resulted in a lower number of proliferating cells and a higher number of neurite-bearing TuJ1-positive cells, indicating an increase in neuronal differentiation. Exposure to 50 nM also significantly increased the number of CNPase-positive cells, pointing to facilitation of oligodendrocytic differentiation. PPAR genes have been shown to be involved in PFOS toxicity. By q-PCR we detected an upregulation of PPARγ with no changes in PPARα or PPARδ genes. One of the downstream targets of PPARs, the mitochondrial uncoupling protein 2 (UCP2) was also upregulated. The number of TuJ1- and CNPase-positive cells increased after exposure to PPARγ agonist rosiglitazone (RGZ, 3 μM) and decreased after pre-incubation with the PPARγ antagonist GW9662 (5 μM). RGZ also upregulated the expression of PPARγ and UCP2 genes. Meanwhile GW9662 abolished the UCP2 upregulation and decreased Ca{sup 2+} activity induced by PFOS. Interestingly, a significantly higher expression of PPARγ and UCP3 genes was also detected in mouse neonatal brain after prenatal exposure to PFOS. These data suggest that PPARγ plays a role in the alteration of spontaneous differentiation of NSCs induced by nanomolar concentrations of PFOS. - Highlights: • PFOS decreases proliferation of neural stem cells (NSCs). • PFOS induces neuronal and oligodendrocytic differentiation in NSCs. • PFOS alters expression of PPARγ and UCP2 in vitro. • PFOS alters expression of PPARγ and UCP3 in vivo. • Block of PPAR

  4. Altered regulation of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.

    Science.gov (United States)

    Jung, Ji Yong; Lee, Jay Wook; Kim, Sejoong; Jung, Eun Sook; Jang, Hye Ryoun; Han, Jin Suk; Joo, Kwon Wook

    2009-12-01

    Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na(+)/K(+)/2Cl(-) cotransporter (NKCC2) and Na(+)/Cl(-) cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-γ increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-α and ENaC-β in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-α and ENaC-β were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.

  5. Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

    Directory of Open Access Journals (Sweden)

    RN Jadeja

    Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

  6. Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

    Science.gov (United States)

    Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

    2006-01-01

    Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

  7. Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Su, Hui [Iowa State Univ., Ames, IA (United States)

    2001-01-01

    Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, the author introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties of suitably designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, they demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm2 for 40-μm wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection. In the second part of this dissertation, the author used laser-induced native fluorescence coupled with capillary electrophoresis (LINF-CE) and microscope imaging to study the single cell degranulation. On the basis of good temporal correlation with events observed through an optical microscope, they have identified individual peaks in the fluorescence electropherograms as serotonin released from the granular core on contact with the surrounding fluid.

  8. Micronuclei: sensitivity for the detection of radiation induced damage

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Nasazzi, N.B.; Taja, M.R.

    1998-01-01

    The in vitro cytokinesis-block (CB) micronucleus (MN) assay for human peripheral blood has been used extensively for the assessment of chromosomal damage induced by ionizing radiation and chemicals and considered a suitable biological dosimeter for estimating in vivo whole body exposures, particularly in the case of large scale radiation accidents. One of the major drawbacks of the MN assay is its reduced sensitivity for the detection of damage induced by low doses of low LET radiation, due to the high variability among the spontaneous MN frequencies. It is suggested that age, smoking habit and sex are the main confounding factors that contribute to the observed variability. Previous work in our laboratory, shows a significant positive correlation of the spontaneous and radiation induced MN frequencies with age and smoking habit, the latter being the strongest confounder. These findings led to in vitro studies of the dose-response relationships for smoking and non smoking donors evaluated separately, using 60 Co γ rays. The objectives of the present work are: 1-To increase the amount of data of the dose-response relationships, using γ rays from a 60 Co source, for smoking and non smoking donors, in order to find, if applicable, a correction factor for the calibration curve that takes into account the smoking habit of the individual in the case of accidental overexposure dose assessment, particularly in the low dose range. 2-To establish general conclusions on the current state of the technique. The sample for smoking and non smoking calibration curves was enlarged in the range of 0Gy to 2Gy. The fitting of both curves, performed up to the 2Gy dose, resulted in a linear quadratic model. MN distribution among bi nucleated cells was found to be over dispersed with respect to Poisson distribution, the average ratio of variance to mean being 1.13 for non smokers and 1.17 for smokers. Each fitted calibration curve, for smoking and non smoking donors, fell within the 95

  9. 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.

  10. 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.

  11. 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)

  12. 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)

  13. 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.

  14. 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

  15. 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 91 d. Experiment 1 demonstrated that grazing of HE pastures for 89 to 105 d induces functional alterations in blood vessels, as evidenced by reduced contractile capacity and altered serotonergic receptor activity. Experiment 2 demonstrated that grazing HE pastures alters vascular responses, which may be mediated through altered serotonin receptor activities, and these alterations may be ameliorated by the removal of ergot alkaloid exposure as demonstrated by the absence of differences in finished steers.

  16. Detection of early metabolic alterations in the ocular fundus of diabetic patients by time-resolved autofluorescence of endogenous fluorophores

    Science.gov (United States)

    Schweitzer, D.; Klemm, M.; Quick, S.; Deutsch, L.; Jentsch, S.; Hammer, M.; Dawczynski, J.; Kloos, C. H.; Mueller, U. A.

    2011-07-01

    Measurements of time-resolved autofluorescence (FLIM) at the human ocular fundus of diabetic patients permit the detection of early pathologic alterations before signs of diabetic retinopathy are visible. The measurements were performed by the Jena Fluorescence Lifetime Laser Scanner Ophthalmoscope applying time-correlated single photon counting (TCSPC) in two spectral channels (K1: 490-560 nm, K2:560-700ps). The fluorescence was excited by 70 ps pulses (FWHM) at 448 nm. The decay of fluorescence intensity was triple-exponentially approximated. The frequency of amplitudes, lifetimes, and relative contributions was compared in fields of the same size and position in healthy subjects and in diabetic patients. The most sensitive parameter was the lifetime T2 in the short-wavelength channel, which corresponds to the neuronal retina. The changes in lifetime point to a loss of free NADH and an increased contribution of protein-bound NADH in the pre-stage of diabetic retinopathy.

  17. 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.

  18. Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers.

    Science.gov (United States)

    Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

    2014-01-01

    Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

  19. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

    OpenAIRE

    Almeida-Reis, Rafael; Theodoro-Junior, Osmar A.; Oliveira, Bruno T. M.; Oliva, Leandro V.; Toledo-Arruda, Alessandra C.; Bonturi, Camila R.; Brito, Marlon V.; Lopes, Fernanda D. T. Q. S.; Prado, Carla M.; Florencio, Ariana C.; Martins, Mílton A.; Owen, Caroline A.; Leick, Edna A.; Oliva, Maria L. V.; Tibério, Iolanda F. L. C.

    2017-01-01

    Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.??C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respirator...

  20. Hypoxia-induced redox alterations and their correlation with {sup 99m}Tc-MIBI and {sup 99m}Tc-HL-91 uptake in colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Abrantes, Ana Margarida [Biophysics/Biomathematics Institute, IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal)], E-mail: mabrantes@ibili.uc.pt; Silva Serra, Maria Elisa [Chemistry Department, Faculty of Sciences and Technology, University of Coimbra, 3000-535 Coimbra (Portugal); Goncalves, Ana Cristina [Biochemistry Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Rio, Joana; Oliveiros, Barbara; Laranjo, Mafalda [Biophysics/Biomathematics Institute, IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Rocha-Gonsalves, Antonio Manuel [Chemistry Department, Faculty of Sciences and Technology, University of Coimbra, 3000-535 Coimbra (Portugal); Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Sarmento-Ribeiro, Ana Bela [Biochemistry Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Filomena Botelho, Maria [Biophysics/Biomathematics Institute, IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal); Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra (Portugal)

    2010-02-15

    Colorectal cancer is one of the most common malignancies in the Western world and is an example of a solid tumour in which hypoxia is a common feature and develops because of the inability of the vascular system to supply adequate amounts of oxygen to growing tumours. Hypoxia effects on tumour cell biology can be detected and characterized using different methods. The use of imaging with {gamma}-emitting radionuclides to detect hypoxic tissue was first suggested by Chapman in 1979 [N Engl J Med 301 (1979) 1429-1432]. {sup 99m}Tc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime, also known as {sup 99m}Tc-HL-91, has been among the most studied hypoxia markers. The objective of this study was to correlate the uptake of {sup 99m}Tc-HL-91 and {sup 99m}Tc-MIBI in colon cancer cells under normoxic and hypoxic conditions and to compare this information with some parameters such as oxidative stress and mitochondrial dysfunction of the cells analyzed by flow cytometry. Our results show that the in vitro {sup 99m}Tc-HL-91 uptake is higher in hypoxic conditions, which is confirmed by the decreased uptake of {sup 99m}Tc-MIBI. Flow cytometry results demonstrate that hypoxic conditions used are not enough to induce cellular death, but are responsible for the alterations in the intracellular redox environment, namely, increase of ROS production, proteic pimonidazol-derived adduct formation and alteration in the mitochondrial membrane permeability. Therefore, these results confirm that {sup 99m}Tc-HL-91 is a radiopharmaceutical with favourable characteristics for detecting hypoxia.

  1. Hypoxia-induced redox alterations and their correlation with 99mTc-MIBI and 99mTc-HL-91 uptake in colon cancer cells

    International Nuclear Information System (INIS)

    Abrantes, Ana Margarida; Silva Serra, Maria Elisa; Goncalves, Ana Cristina; Rio, Joana; Oliveiros, Barbara; Laranjo, Mafalda; Rocha-Gonsalves, Antonio Manuel; Sarmento-Ribeiro, Ana Bela; Filomena Botelho, Maria

    2010-01-01

    Colorectal cancer is one of the most common malignancies in the Western world and is an example of a solid tumour in which hypoxia is a common feature and develops because of the inability of the vascular system to supply adequate amounts of oxygen to growing tumours. Hypoxia effects on tumour cell biology can be detected and characterized using different methods. The use of imaging with γ-emitting radionuclides to detect hypoxic tissue was first suggested by Chapman in 1979 [N Engl J Med 301 (1979) 1429-1432]. 99m Tc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime, also known as 99m Tc-HL-91, has been among the most studied hypoxia markers. The objective of this study was to correlate the uptake of 99m Tc-HL-91 and 99m Tc-MIBI in colon cancer cells under normoxic and hypoxic conditions and to compare this information with some parameters such as oxidative stress and mitochondrial dysfunction of the cells analyzed by flow cytometry. Our results show that the in vitro 99m Tc-HL-91 uptake is higher in hypoxic conditions, which is confirmed by the decreased uptake of 99m Tc-MIBI. Flow cytometry results demonstrate that hypoxic conditions used are not enough to induce cellular death, but are responsible for the alterations in the intracellular redox environment, namely, increase of ROS production, proteic pimonidazol-derived adduct formation and alteration in the mitochondrial membrane permeability. Therefore, these results confirm that 99m Tc-HL-91 is a radiopharmaceutical with favourable characteristics for detecting hypoxia.

  2. Sub-acute deltamethrin and fluoride toxicity induced hepatic oxidative stress and biochemical alterations in rats.

    Science.gov (United States)

    Dubey, Nitin; Khan, Adil Mehraj; Raina, Rajinder

    2013-09-01

    The current study investigated the effects of deltamethrin, fluoride (F(-)) and their combination on the hepatic oxidative stress and consequent alterations in blood biochemical markers of hepatic damage in rats. Significant hepatic oxidative stress and hepatic damage were observed in the toxicant exposed groups. These changes were higher in the deltamethrin-F(-) co-exposure treatment group, depicting a positive interaction between the two chemicals.

  3. Projected effects of Climate-change-induced flow alterations on stream macroinvertebrate abundances.

    Science.gov (United States)

    Kakouei, Karan; Kiesel, Jens; Domisch, Sami; Irving, Katie S; Jähnig, Sonja C; Kail, Jochem

    2018-03-01

    Global change has the potential to affect river flow conditions which are fundamental determinants of physical habitats. Predictions of the effects of flow alterations on aquatic biota have mostly been assessed based on species ecological traits (e.g., current preferences), which are difficult to link to quantitative discharge data. Alternatively, we used empirically derived predictive relationships for species' response to flow to assess the effect of flow alterations due to climate change in two contrasting central European river catchments. Predictive relationships were set up for 294 individual species based on (1) abundance data from 223 sampling sites in the Kinzig lower-mountainous catchment and 67 sites in the Treene lowland catchment, and (2) flow conditions at these sites described by five flow metrics quantifying the duration, frequency, magnitude, timing and rate of flow events using present-day gauging data. Species' abundances were predicted for three periods: (1) baseline (1998-2017), (2) horizon 2050 (2046-2065) and (3) horizon 2090 (2080-2099) based on these empirical relationships and using high-resolution modeled discharge data for the present and future climate conditions. We compared the differences in predicted abundances among periods for individual species at each site, where the percent change served as a proxy to assess the potential species responses to flow alterations. Climate change was predicted to most strongly affect the low-flow conditions, leading to decreased abundances of species up to -42%. Finally combining the response of all species over all metrics indicated increasing overall species assemblage responses in 98% of the studied river reaches in both projected horizons and were significantly larger in the lower-mountainous Kinzig compared to the lowland Treene catchment. Such quantitative analyses of freshwater taxa responses to flow alterations provide valuable tools for predicting potential climate-change impacts on species

  4. Effects of topographical and mechanical property alterations induced by oxygen plasma modification on stem cell behavior.

    Science.gov (United States)

    Yang, Yong; Kulangara, Karina; Lam, Ruby T S; Dharmawan, Rena; Leong, Kam W

    2012-10-23

    Polymeric substrates intended for cell culture and tissue engineering are often surface-modified to facilitate cell attachment of most anchorage-dependent cell types. The modification alters the surface chemistry and possibly topography. However, scant attention has been paid to other surface property alterations. In studying oxygen plasma treatment of polydimethylsiloxane (PDMS), we show that oxygen plasma treatment alters the surface chemistry and, consequently, the topography and elasticity of PDMS at the nanoscale level. The elasticity factor has the predominant effect, compared with the chemical and topographical factors, on cell adhesions of human mesenchymal stem cells (hMSCs). The enhanced focal adhesions favor cell spreading and osteogenesis of hMSCs. Given the prevalent use of PDMS in biomedical device construction and cell culture experiments, this study highlights the importance of understanding how oxygen plasma treatment would impact subsequent cell-substrate interactions. It helps explain inconsistency in the literature and guides preparation of PDMS-based biomedical devices in the future.

  5. 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.

  6. Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

    Science.gov (United States)

    Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

    2012-07-01

    The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

  7. 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......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.......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....

  8. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

    Science.gov (United States)

    Loiola, Rodrigo Azevedo; Dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-06-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation, and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit, and elevated serum triglycerides, cholesterol, and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.

  9. Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

    Directory of Open Access Journals (Sweden)

    Alya Annabi

    2015-11-01

    Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

  10. Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection.

    Science.gov (United States)

    Kandhavelu, Jeyalakshmi; Demonte, Naveen Luke; Namperumalsamy, Venkatesh Prajna; Prajna, Lalitha; Thangavel, Chitra; Jayapal, Jeya Maheshwari; Kuppamuthu, Dharmalingam

    2017-01-30

    Aspergillus flavus and Fusarium sp. are primary causative agents of keratitis that results in corneal tissue damage leading to vision loss particularly in individuals from the tropical parts of the world. Proteins in the tear film collected from control and keratitis patients was profiled and compared. A total of 1873 proteins from control and 1400 proteins from patient tear were identified by mass spectrometry. While 847 proteins were found to be glycosylated in the patient tear, only 726 were glycosylated in control tear. And, some of the tear proteins showed alterations in their glycosylation pattern after infection. Complement system proteins, proteins specific for neutrophil extracellular traps and proteins involved in would healing were found only in the patient tear. The presence of these innate immune system proteins in the tear film of patients supports the previous data indicating the involvement of neutrophil and complement pathways in antifungal defense. High levels of wound healing proteins in keratitis patient tear implied activation of tissue repair during infection. The early appearance of the host defense proteins and wound healing response indicates that tear proteins could be used as an early marker system for monitoring the progression of pathogenesis. Identification of negative regulators of the above defense pathways in keratitis tear indicates an intricate balance of pro and anti-defense mechanisms operating in fungal infection of the eye. Tear proteins from control and mycotic keratitis patients were separated into glycoproteins and non-glycosylated proteins and then identified by mass spectrometry. Tear proteins from keratitis patients showed alteration in the glycosylation pattern indicating the alteration of glycosylation machinery due to infection. Neutrophil extracellular traps specific proteins, complement pathway proteins, as well as wound healing proteins, were found only in patient tear showing the activation of antifungal defense

  11. Nutrient Availability Alters the Effect of Autophagy on Sulindac Sulfide-Induced Colon Cancer Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Shiun-Kwei Chiou

    2012-01-01

    Full Text Available Autophagy is a catabolic process by which a cell degrades its intracellular materials to replenish itself. Induction of autophagy under various cellular stress stimuli can lead to either cell survival or cell death via apoptotic and/or autophagic (nonapoptotic pathways. The NSAID sulindac sulfide induces apoptosis in colon cancer cells. Here, we show that inhibition of autophagy under serum-deprived conditions resulted in significant reductions of sulindac sulfide-induced apoptosis in HT-29 colon cancer cells. In contrast, inhibition of autophagy under conditions where serum is available significantly increased sulindac sulfide-induced apoptosis in HT-29 cells. We previously showed that the apoptosis inhibitor, survivin, plays a role in regulating NSAID-induced apoptosis and autophagic cell death. Here, we show that survivin protein half-life is increased in the presence of autophagy inhibitors under serum-deprived conditions, but not under conditions when serum is available. Thus, the increased levels of survivin may be a factor contributing to inhibition of sulindac sulfide-induced apoptosis under serum-deprived conditions. These results suggest that whether a cell lives or dies due to autophagy induction depends on the balance of factors that regulate both autophagic and apoptotic processes.

  12. Proteomic alterations induced by ionic liquids in Aspergillus nidulans and Neurospora crassa.

    Science.gov (United States)

    Martins, Isabel; Hartmann, Diego O; Alves, Paula C; Planchon, Sébastien; Renaut, Jenny; Leitão, M Cristina; Rebelo, Luís P N; Silva Pereira, Cristina

    2013-12-06

    This study constitutes the first attempt to understand at the proteomic level the fungal response to ionic liquid stress. Ascomycota are able to grow in media supplemented with high concentrations of an ionic liquid, which, in turn, lead to major alterations in the fungal metabolic footprint. Herein, we analysed the differential accumulation of mycelial proteins in Aspergillus nidulans and Neurospora crassa after their exposure to two of the most commonly used ionic liquids: 1-ethyl-3-methylimidazolium chloride or cholinium chloride. Data obtained showed that numerous stress-responsive proteins (e.g. anti-ROS defence proteins) as well as several critical biological processes and/or pathways were affected by either ionic liquid. Amongst other changes, these compounds altered developmental programmes in both fungi (e.g. promoting the development of Hülle cells or conidiation) and led to accumulation of osmolytes, some of which may play an important role in multiple stress responses. In particular, in N. crassa, both ionic liquids increased the levels of proteins which are likely involved in the biosynthesis of unusual metabolites. These data potentially open new perspectives on ionic liquid research, furthering their conscious design and their use to trigger production of targeted metabolites. The present study emphasises the importance of understanding ionic liquid's stress responses, crucial to further their safe large-scale usage. Knowledge of the alterations prompted at a cellular and biochemical level gives also fresh perspectives on how to employ these "novel" compounds to manipulate proteins or pathways of biotechnological value. The results presented here provide meaningful insights into the understanding of fungi stress and adaptation responses to anthropogenic chemicals used in industry. © 2013.

  13. Multimolecular Salivary Mucin Complex Is Altered in Saliva of Cigarette Smokers: Detection of Disulfide Bridges by Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Motoe Taniguchi

    2013-01-01

    Full Text Available Saliva contains mucins, which protect epithelial cells. We showed a smaller amount of salivary mucin, both MG1 and MG2, in the premenopausal female smokers than in their nonsmoking counterparts. Smokers' MG1, which contains almost 2% cysteine/half cystine in its amino acid residues, turned out to be chemically altered in the nonsmoker’s saliva. The smaller acidic glycoprotein bands were detectable only in smoker’s saliva in the range of 20–25 kDa and at 45 kDa, suggesting that degradation, at least in part, caused the reduction of MG1 mucin. This is in agreement with the previous finding that free radicals in cigarette smoke modify mucins in both sugar and protein moieties. Moreover, proteins such as amylase and albumin are bound to other proteins through disulfide bonds and are identifiable only after reduction with DTT. Confocal laser Raman microspectroscopy identified a disulfide stretch band of significantly stronger intensity per protein in the stimulated saliva of smokers alone. We conclude that the saliva of smokers, especially stimulated saliva, contains significantly more oxidized form of proteins with increased disulfide bridges, that reduces protection for oral epithelium. Raman microspectroscopy can be used for an easy detection of the damaged salivary proteins.

  14. Arsenic induced clinico-hemato-pathological alterations in broilers and its attenuation by vitamin e and selenium

    International Nuclear Information System (INIS)

    Mashkoor, J.; Khan, A.; Khan, M.Z.; Saleemi, M.K.; Mahmood, F.

    2012-01-01

    Present study was carried out to know the arsenic (As) induced toxico-pathological alterations in broiler chicks and their attenuation with vitamin E (Vit E) and selenium (Se). A total of 90 day-old broiler chicks were equally distributed into 5 groups. Groups 1-4 were administered As at 50 mg/kg BW daily through feed for 30 days. In addition to A , groups 2 to 4 received Vitamin E at 150 mg/kg BW, selenium at 0.25 mg/kg BW and Vitamin E plus selenium, respectively. Group 5 (Control) received normal drinking water for 30 days. Dullness, depression, open mouth breathing, increased thirst; ruffled feathers, pale comb, skin irritation and watery diarrhea were the most striking clinical signs. The body weight and feed intake was significantly decreased in treated birds. The erythrocyte counts, hemoglobin concentration and packed cell volume decreased (P<0.05) in treated broilers with As or As with Se and Vit E. Grossly pale and hemorrhagic liver and swollen kidneys were observed in As treated birds. Arsenic treated groups showed significant decrease in serum. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation. In kidneys, condensation of tubular epithelium nuclei, epithelial cell necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed. In conclusion As induced toxico-pathological alterations and vitamin E and selenium partially ameliorate the toxic effects in broilers chicks. (author)

  15. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  16. Alterations in the nuclear matrix protein mass correlate with heat-induced inhibition of DNA single-strand-break repair

    International Nuclear Information System (INIS)

    Warters, R.L.; Brizgys, L.M.; Lyons, B.W.

    1987-01-01

    The total protein mass co-isolating with the nuclear matrix or nucleoid from Chinese hamster ovary (CHO) cells was observed to increase in heated cells as a function of increasing exposure temperature between 43 0 C and 45 0 C or of exposure time at any temperature. The sedimentation distance of the CHO cell nucleoid in sucrose gradients increased with increasing exposure time at 45 0 C. Both these nuclear alterations correlated in a log-linear manner with heat-induced inhibition of DNA strand break repair. A two-fold threshold increase in nuclear matrix protein mass preceded any substantial inhibition of repair of DNA single-strand breaks. When preheated cells were incubated at 37 0 C the nuclear matrix protein mass and nucleoid sedimentation recovered with a half-time of about 5 h, while DNA single-strand-break repair recovered with a half-time of about 2 h. When preheated cells were placed at 41 0 C a further increase was observed in the nuclear matrix protein mass and the half-time of DNA strand break repair, while nucleoid sedimentation recovered toward control values. These results implicate alterations in the protein mass of the nuclear matrix in heat-induced inhibition of repair of DNA single-strand breaks. (author)

  17. Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

    Science.gov (United States)

    Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-02-01

    Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

  18. Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice.

    Science.gov (United States)

    Lima, Leandro Ceotto Freitas; Saliba, Soraya Wilke; Andrade, João Marcus Oliveira; Cunha, Maria Luisa; Cassini-Vieira, Puebla; Feltenberger, John David; Barcelos, Lucíola Silva; Guimarães, André Luiz Sena; de-Paula, Alfredo Mauricio Batista; de Oliveira, Antônio Carlos Pinheiro; Santos, Sérgio Henrique Sousa

    2017-07-01

    Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity.

    Science.gov (United States)

    Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F; Rosenblatt, Mark I

    2015-12-01

    In an effort to elucidate possible neural mechanisms underlying diminished tearing in dry eye disease, this study sought to determine if hyperosmolar tears, a ubiquitous sign of dry eye disease, produce functional changes in corneal nerve responses to drying of the cornea and if these changes correlate with alterations in corneal nerve morphology. In vivo extracellular electrophysiological recordings were performed in rat trigeminal ganglion neurons that innervated the cornea before, and up to 3 hours after, the ocular application of continuous hyperosmolar tears or artificial tears. In corollary experiments, immunohistochemical staining was performed to compare corneal nerve morphology in control and in eyes treated with hyperosmolar solutions. Our previous studies identified a population of corneal afferents, dry-sensitive neurons that are strongly excited by corneal dessication ("dry response"), a response thought to trigger the lacrimation reflex. In the present study, we found that the dry responses of corneal dry-sensitive neurons were depressed or even completely abolished by hyperosmolar tears in a time- (30 minutes to 3 hours) and dose (450- to 1000-mOsm solutions)-dependent manner. Furthermore, eyes treated with hyperosmolar tears for 3 hours contained large numbers of morphologically abnormal (granular, fragmented, or prominently beaded) subbasal nerves that appeared to be undergoing degeneration. These results demonstrate that tear hyperosmolarity, considered to be a "core" mechanism of dry eye disease, significantly decreases physiological sensitivity and morphologic integrity of the corneal nerves important in tear production. These alterations might contribute to the diminished tearing seen clinically in dry eye patients.

  4. Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Irie, Miho; Hayakawa, Eisuke; Fujimura, Yoshinori; Honda, Youhei; Setoyama, Daiki; Wariishi, Hiroyuki; Hyodo, Fuminori; Miura, Daisuke

    2018-01-29

    Clinical application of the major anticancer drug, cisplatin, is limited by severe side effects, especially acute kidney injury (AKI) caused by nephrotoxicity. The detailed metabolic mechanism is still largely unknown. Here, we used an integrated technique combining mass spectrometry imaging (MSI) and liquid chromatography-mass spectrometry (LC-MS) to visualize the diverse spatiotemporal metabolic dynamics in the mouse kidney after cisplatin dosing. Biological responses to cisplatin was more sensitively detected within 24 h as a metabolic alteration, which is much earlier than possible with the conventional clinical chemistry method of blood urea nitrogen (BUN) measurement. Region-specific changes (e.g., medulla and cortex) in metabolites related to DNA damage and energy generation were observed over the 72-h exposure period. Therefore, this metabolomics approach may become a novel strategy for elucidating early renal responses to cisplatin, prior to the detection of kidney damage evaluated by conventional method. Copyright © 2018. Published by Elsevier Inc.

  5. p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia

    International Nuclear Information System (INIS)

    Tierney, L.A.; Hahn, F.F.; Lechner, J.F.

    1996-01-01

    Inhalation of high-linear energy transfer radiation in the form of radon progeny is a suspected cause of human lung cancer. To gain insight into the types of genetic derangements caused by this type of radiation, lung tumors from beagle dogs exposed to 239 PuO 2 and those arising in animals with no known carcinogen exposure were examined for evidence of aberrations in genes known to be altered in lung tumors. Altered expression of the p53 tumor suppressor gene and proto-oncogene erbB-2 proteins (p185 erbB2 ) was evaluated by immunohistochemical analysis of 117 tumors representing different histological types in exposed (n = 80) and unexposed (n = 37) animals. Twenty-eight tumors were analyzed for K-ras proto-oncogene mutations by polymerase chain reaction amplification and direct sequencing. Fourteen percent (16/116) of all lung neoplasms showed elevated nuclear accumulation of p53 protein. Regardless of exposure history, adenosquamous and squamous cell cancers comprised 94% of all tumors with p53 abnormalities. Eighteen percent (21/117) of all tumors had evidence of erbB-2 protein overexpression. K-ras mutations were not detected in codons 12, 13 or 61 of tumors from unexposed (n = 9) or plutonium-exposed dogs (n = 19). These data indicate that p53 and K-ras gene abnormalities as a result of missense mutation are infrequent events in spontaneous and 239 PuO 2 -induced lung neoplasia in this colony of beagle dogs. Alternative mechanisms of gene alteration may be involved in canine pulmonary carcinogenesis. 45 refs., 3 figs., 2 tabs

  6. 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.

  7. Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection.

    Science.gov (United States)

    Staley, Elizabeth M; Yarbrough, Vanisha R; Schoeb, Trenton R; Daft, Joseph G; Tanner, Scott M; Steverson, Dennis; Lorenz, Robin G

    2012-09-01

    P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1α, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

  8. DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available PURPOSE: In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. METHODS AND MATERIALS: In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. RESULTS: Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. CONCLUSIONS: Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

  9. Flavopiridol induces apoptosis in glioma cell lines independent of retinoblastoma and p53 tumor suppressor pathway alterations by a caspase-independent pathway.

    Science.gov (United States)

    Alonso, Michelle; Tamasdan, Cristina; Miller, Douglas C; Newcomb, Elizabeth W

    2003-02-01

    Flavopiridol is a synthetic flavone, which inhibits growth in vitro and in vivo of several solid malignancies such as renal, prostate, and colon cancers. It is a potent cyclin-dependent kinase inhibitor presently in clinical trials. In this study, we examined the effect of flavopiridol on a panel of glioma cell lines having different genetic profiles: five of six have codeletion of p16(INK4a) and p14(ARF); three of six have p53 mutations; and one of six shows overexpression of mouse double minute-2 (MDM2) protein. Independent of retinoblastoma and p53 tumor suppressor pathway alterations, flavopiridol induced apoptosis in all cell lines but through a caspase-independent mechanism. No cleavage products for caspase 3 or its substrate poly(ADP-ribose) polymerase or caspase 8 were detected. The pan-caspase inhibitor Z-VAD-fmk did not inhibit flavopiridol-induced apoptosis. Mitochondrial damage measured by cytochrome c release and transmission electron microscopy was not observed in drug-treated glioma cells. In contrast, flavopiridol treatment induced translocation of apoptosis-inducing factor from the mitochondria to the nucleus. The proteins cyclin D(1) and MDM2 involved in the regulation of retinoblastoma and p53 activity, respectively, were down-regulated early after flavopiridol treatment. Given that MDM2 protein can confer oncogenic properties under certain circumstances, loss of MDM2 expression in tumor cells could promote increased chemosensitivity. After drug treatment, a low Bcl-2/Bax ratio was observed, a condition that may favor apoptosis. Taken together, the data indicate that flavopiridol has activity against glioma cell lines in vitro and should be considered for clinical development in the treatment of glioblastoma multiforme.

  10. Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.

    Science.gov (United States)

    Nocca, G; De Palma, F; Minucci, A; De Sole, P; Martorana, G E; Callà, C; Morlacchi, C; Gozzo, M L; Gambarini, G; Chimenti, C; Giardina, B; Lupi, A

    2007-03-01

    Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

  11. 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

  12. Selenium deficiency-induced alterations in ion profiles in chicken muscle.

    Directory of Open Access Journals (Sweden)

    Haidong Yao

    Full Text Available Ion homeostasis plays important roles in development of metabolic diseases. In the present study, we examined the contents and distributions of 25 ions in chicken muscles following treatment with selenium (Se deficiency for 25 days. The results revealed that in chicken muscles, the top ranked microelements were silicon (Si, iron (Fe, zinc (Zn, aluminum (Al, copper (Cu and boron (B, showing low contents that varied from 292.89 ppb to 100.27 ppm. After Se deficiency treatment, essential microelements [Cu, chromium (Cr, vanadium (V and manganese (Mn], and toxic microelements [cadmium (Cd and mercury (Hg] became more concentrated (P < 0.05. Elements distribution images showed generalized accumulation of barium (Ba, cobalt (Co, Cu, Fe and V, while Cr, Mn, and Zn showed pin point accumulations in muscle sections. Thus, the ion profiles were generally influenced by Se deficiency, which suggested a possible role of Se deficiency in muscle dysfunctions caused by these altered ion profiles.

  13. Altered expression and insulin-induced trafficking of Na+-K+-ATPase in rat skeletal muscle

    DEFF Research Database (Denmark)

    Galuska, Dana; Kotova, Olga; Barres, Romain

    2009-01-01

    Skeletal muscle Na(+)-K(+)-ATPase plays a central role in the clearance of K(+) from the extracellular fluid, therefore maintaining blood [K(+)]. Na(+)-K(+)-ATPase activity in peripheral tissue is impaired in insulin resistant states. We determined effects of high-fat diet (HFD) and exercise......(+)-K(+)-ATPase activity after 4 wk of HFD. Exercise training restored alpha(1)-, alpha(2)-, and beta(1)-subunit expression and Na(+)-K(+)-ATPase activity to control levels and reduced beta(2)-subunit expression 2.2-fold (P ... phospholemman. Phospholemman mRNA and protein expression were increased after HFD and restored to control levels after ET. Insulin-stimulated translocation of the alpha(2)-subunit to plasma membrane was impaired by HFD, whereas alpha(1)-subunit translocation remained unchanged. Alterations in sodium pump...

  14. Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Mody, Nimesh

    2017-11-01

    Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

  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. 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.

  17. Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases.

    Science.gov (United States)

    Zhou, Yan; Proudnikov, Dmitri; Yuferov, Vadim; Kreek, Mary Jeanne

    2010-02-16

    From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and resultant changes in hormone levels, have been documented to occur after chronic intermittent exposure to heroin, morphine, other opiates, cocaine, other stimulants, and alcohol in animal models and in human molecular genetics. The best studied of the stress-responsive systems in humans and mammalian species in general is undoubtedly the HPA axis. In addition, there are stress-responsive systems in other parts in the brain itself, and some of these include components of the HPA axis, such as CRF and CRF receptors, along with POMC gene and gene products. Several other stress-responsive systems are known to influence the HPA axis, such as the vasopressin-vasopressin receptor system. Orexin-hypocretin, acting at its receptors, may effect changes which suggest that it should be properly categorized as a stress-responsive system. However, less is known about the interactions and connectivity of some of these different neuropeptide and receptor systems, and in particular, about the possible connectivity of fast-acting (e.g., glutamate and GABA) and slow-acting (including dopamine, serotonin, and norepinephrine) neurotransmitters with each of these stress-responsive components and the resultant impact, especially in the setting of chronic exposure to drugs of abuse. Several of these stress-responsive systems and components, primarily based on our laboratory-based and human molecular genetics research of addictive diseases, will be briefly discussed in this review. Copyright 2009 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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.

  20. 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

  1. Endoplasmic reticulum stress induces different molecular structural alterations in human dilated and ischemic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Ana Ortega

    Full Text Available BACKGROUND: The endoplasmic reticulum (ER is a multifunctional organelle responsible for the synthesis and folding of proteins as well as for signalling and calcium storage, that has been linked to the contraction-relaxation process. Perturbations of its homeostasis activate a stress response in diseases such as heart failure (HF. To elucidate the alterations in ER molecular components, we analyze the levels of ER stress and structure proteins in human dilated (DCM and ischemic (ICM cardiomyopathies, and its relationship with patient's functional status. METHODS AND RESULTS: We examined 52 explanted human hearts from DCM (n = 21 and ICM (n = 21 subjects and 10 non-failing hearts as controls. Our results showed specific changes in stress (IRE1, p<0.05; p-IRE1, p<0.05 and structural (Reticulon 1, p<0.01 protein levels. The stress proteins GRP78, XBP1 and ATF6 as well as the structural proteins RRBP1, kinectin, and Nogo A and B, were upregulated in both DCM and ICM patients. Immunofluorescence results were concordant with quantified Western blot levels. Moreover, we show a novel relationship between stress and structural proteins. RRBP1, involved in procollagen synthesis and remodeling, was related with left ventricular function. CONCLUSIONS: In the present study, we report the existence of alterations in ER stress response and shaping proteins. We show a plausible effect of the ER stress on ER structure in a suitable sample of DCM and ICM subjects. Patients with higher values of RRBP1 had worse left ventricular function.

  2. 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

    . 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.......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...

  3. The Role of Oxidative Stress-Induced Epigenetic Alterations in Amyloid- ? Production in Alzheimer's Disease

    OpenAIRE

    Zuo, Li; Hemmelgarn, Benjamin T.; Chuang, Chia-Chen; Best, Thomas M.

    2015-01-01

    An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer’s disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aβ) plaques as a hallmark, the connection betwee...

  4. 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

  5. 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...

  6. Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

    OpenAIRE

    Máthé, Csaba; Mikóné Hamvas, Márta; Vasas, Gábor

    2013-01-01

    Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs), a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN), an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studi...

  7. Dietary Chlorella vulgaris Ameliorates Altered Immunomodulatory Functions in Cyclophosphamide-Induced Immunosuppressive Mice

    Science.gov (United States)

    Cheng, Dai; Wan, Zhaodong; Zhang, Xinyu; Li, Jian; Li, He; Wang, Chunling

    2017-01-01

    Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential. PMID:28684674

  8. Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring.

    Science.gov (United States)

    Kesby, James P; O'Loan, Jonathan C; Alexander, Suzanne; Deng, Chao; Huang, Xu-Feng; McGrath, John J; Eyles, Darryl W; Burne, Thomas H J

    2012-04-01

    Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.

  9. 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.

  10. Laser-induced fluorescence detection strategies for sodium atoms and compounds in high-pressure combustors

    Science.gov (United States)

    Weiland, Karen J. R.; Wise, Michael L.; Smith, Gregory P.

    1993-01-01

    A variety of laser-induced fluorescence schemes were examined experimentally in atmospheric pressure flames to determine their use for sodium atom and salt detection in high-pressure, optically thick environments. Collisional energy transfer plays a large role in fluorescence detection. Optimum sensitivity, at the parts in 10 exp 9 level for a single laser pulse, was obtained with the excitation of the 4p-3s transition at 330 nm and the detection of the 3d-3p fluorescence at 818 nm. Fluorescence loss processes, such as ionization and amplified spontaneous emission, were examined. A new laser-induced atomization/laser-induced fluorescence detection technique was demonstrated for NaOH and NaCl. A 248-nm excimer laser photodissociates the salt molecules present in the seeded flames prior to atom detection by laser-induced fluorescence.

  11. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    Science.gov (United States)

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 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.

  13. Mercury Induced Biochemical Alterations As Oxidative Stress In Mugil Cephalus In Short Term Toxicity Test

    OpenAIRE

    J.S.I Rajkumar; Samuel Tennyson

    2013-01-01

    Mugil cephalus juveniles of size 2.5 ±0.6cm were exposed to mercury in short term chronic toxicity test through static renewal bioassay to detect the possible biochemical agent as biomarkers in aquatic pollution and in estuarine contamination as specific. Lipid peroxidation levels, glutathione S -transferase, catalase, reduced glutathione and acetylcholinesterase were studied as biochemical parameters. Increased thio-barbituric acid reactive substances levels were observed under exposur...

  14. Evaluation of cell proliferation, apoptosis, and dna-repair genes as potential biomarkers for ethanol-induced cns alterations

    Directory of Open Access Journals (Sweden)

    Hicks Steven D

    2012-10-01

    Full Text Available Abstract Background Alcohol use disorders (AUDs lead to alterations in central nervous system (CNS architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1 was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5 showed a highly significant correlation with AUD-induced decreases in the volume of the left

  15. Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

    Science.gov (United States)

    Yadav, Monu; Jindal, Deepak Kumar; Dhingra, Mamta Sachdeva; Kumar, Anil; Parle, Milind; Dhingra, Sameer

    2018-04-01

    Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

  16. Morphological divergence and flow-induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats.

    Science.gov (United States)

    Franssen, Nathan R; Stewart, Laura K; Schaefer, Jacob F

    2013-11-01

    Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.

  17. 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.

  18. Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

    Directory of Open Access Journals (Sweden)

    Daina S. E. Dickins

    2015-01-01

    Full Text Available Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years underwent intermittent theta burst stimulation (iTBS whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS.

  19. Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

    Science.gov (United States)

    Dickins, Daina S. E.; Sale, Martin V.

    2015-01-01

    Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS. PMID:26064691

  20. AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization.

    Science.gov (United States)

    Mahboubi, Hicham; Koromilas, Antonis E; Stochaj, Ursula

    2016-10-01

    Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, cytoskeletal organization, and the abundance of translation initiation factors. Specifically, AMPK activation increased stress-induced eukaryotic initiation factor (eIF) 2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of histone deacetylase 6 (HDAC6) was diminished. This loss of HDAC6 was accompanied by increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  1. 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

  2. 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

  3. Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

    Science.gov (United States)

    Alattar, M H; Ravindranath, T M; Choudhry, M A; Muraskas, J K; Namak, S Y; Dallal, O; Sayeed, M M

    2001-01-01

    Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats. Copyright 2001 S. Karger AG, Basel

  4. Rauwolfia serpentina improves altered glucose and lipid homeostasis in fructose-induced type 2 diabetic mice.

    Science.gov (United States)

    Azmi, Muhammad Bilal; Qureshi, Shamim A

    2016-09-01

    Rauwolfia serpentina is well-reported in traditional medicines for the treatment of hypertensive and neurological disorders. However, its antidiabetic potential has been currently described in both alloxan-treated and normoglycemic mice. Present effort was carried out to investigate the effect of methanol root extract (MREt) of R.serpentina in fructose-induced type 2 diabetic mice. Experimental mice were grouped into normal control (distilled water 1ml/kg) and fructose-induced type 2 diabetic groups (10% fructose 1 ml/kg).The second group sub-divided into negative (0.05% DMSO 1ml/kg) control, positive (pioglitazone 15mg/kg) control and three test groups (MREt 10, 30 & 60 mg/kg). Each treatment was given orally for 14 days consecutively then mice were sacrificed in order to collect serum and liver samples to analyze physical, biochemical as well as hematological markers. MREt significantly improved percent body weight and glycemic change along with serum insulin, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), very low-density lipoprotein (VLDL-c), high-density lipoprotein-cholesterols (HDL-c), total hemoglobin, glycosylated hemoglobin, hepatic glycogen, coronary risk and fasting insulin resistance indices while suppressed down the activity of 3-hydroxy-3-methylglutaryl Coenzyme A reductase enzyme in test groups when compared with diabetic controls. The present findings conclude that MREt of R. serpentina can effectively betters the carbohydrate and lipid homeostasis by either inhibiting fructose absorption in intestine or decreasing insulin resistance in fructose-induced type 2 diabetic mice.

  5. Acute stress induces selective alterations in cost/benefit decision-making.

    Science.gov (United States)

    Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

    2012-09-01

    Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1-3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression.

  6. Age-dependent methamphetamine-induced alterations in vesicular monoamine transporter-2 function: implications for neurotoxicity.

    Science.gov (United States)

    Truong, Jannine G; Wilkins, Diana G; Baudys, Jakub; Crouch, Dennis J; Johnson-Davis, Kamisha L; Gibb, James W; Hanson, Glen R; Fleckenstein, Annette E

    2005-09-01

    Tens of thousands of adolescents and young adults have used illicit methamphetamine. This is of concern since its high-dose administration causes persistent dopaminergic deficits in adult animal models. The effects in adolescents are less studied. In adult rodents, toxic effects of methamphetamine may result partly from aberrant cytosolic dopamine accumulation and subsequent reactive oxygen species formation. The vesicular monoamine transporter-2 (VMAT-2) sequesters cytoplasmic dopamine into synaptic vesicles for storage and perhaps protection against dopamine-associated oxidative consequences. Accordingly, aberrant VMAT-2 function may contribute to the methamphetamine-induced persistent dopaminergic deficits. Hence, this study examined effects of methamphetamine on VMAT-2 in adolescent (postnatal day 40) and young adult (postnatal day 90) rats. Results revealed that high-dose methamphetamine treatment caused greater acute (within 1 h) decreases in vesicular dopamine uptake in postnatal day 90 versus 40 rats, as determined in a nonmembrane-associated subcellular fraction. Greater basal levels of VMAT-2 at postnatal day 90 versus 40 in this purified fraction seemed to contribute to the larger effect. Basal tissue dopamine content was also greater in postnatal day 90 versus 40 rats. In addition, postnatal day 90 rats were more susceptible to methamphetamine-induced persistent dopaminergic deficits as assessed by measuring VMAT-2 activity and dopamine content 7 days after treatment, even if drug doses were adjusted for age-related pharmacokinetic differences. Together, these data demonstrate dynamic changes in VMAT-2 susceptibility to methamphetamine as a function of development. Implications with regard to methamphetamine-induced dopaminergic deficits, as well as dopamine-associated neurodegenerative disorders such as Parkinson's disease, are discussed.

  7. Acute Stress Induces Selective Alterations in Cost/Benefit Decision-Making

    Science.gov (United States)

    Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

    2012-01-01

    Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1–3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression. PMID:22569506

  8. Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice

    OpenAIRE

    Hodes, Georgia E.; Hill-Smith, Tiffany E.; Lucki, Irwin

    2010-01-01

    Antidepressant induced increases in neurogenesis and neurotrophin mobilization in rodents and primates are proposed to be necessary for behavioral efficacy. The current study examines the relationship between the effects of fluoxetine treatment on behavior, cell proliferation and the neurotrophin BDNF in females. Female MRL/MpJ mice were treated acutely (5 and 10 mg/kg) or chronically (2.5, 5 and 10 mg/kg b.i.d.) with fluoxetine and tested in the tail suspension test (TST) and or novelty indu...

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

    OpenAIRE

    Meyers, Allison M.; Mourra, Devry; Beeler, Jeff A.

    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 ...

  10. Stress-induced Premature Promotes Prostate Cancer Growth and Metastasis through Alteration of Microenvironment

    Science.gov (United States)

    2012-01-01

    comprised of NF-YA, -YB and -YC proteins. NF- Y can interact with p53 to transcriptionally repress specific genes , including Cdc2 and Chk2 (Yun et al...cells already have lowered p53 (Figure 1e). NF- Y A–C proteins bind p53 and suppress transcrip- tion of target genes involved in cell cycle regulation...regulation in H(2)O(2)- induced premature senescence of human diploid fibroblasts and regulatory control exerted by the papilloma virus E6 and E7

  11. Pneumocystis carinii in bronchoalveolar lavage and induced sputum: detection with a nested polymerase chain reaction

    DEFF Research Database (Denmark)

    Skøt, J; Lerche, A G; Kolmos, H J

    1995-01-01

    To evaluate polymerase chain reaction (PCR) for detection of Pneumocystis carinii, 117 bronchoalveolar lavage (BAL) specimens, from HIV-infected patients undergoing a diagnostic bronchoscopy, were processed and a nested PCR, followed by Southern blot and hybridization with a P32-labelled probe......, but sensitivity dropped markedly with this system. A further 33 patients had both induced sputum and bronchoalveolar lavage performed and the induced sputum was analysed using PCR and routine microbiological methods. The PCR sensitivity on induced sputum was equal to that of routine methods. At present...... the evaluated PCR cannot replace routine microbiological methods for detection of Pneumocystis carinii, on either BAL fluid or induced sputum....

  12. 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.

  13. 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.

  14. X-ray induced alterations in the differentiation and mineralization potential of murine preosteoblastic cells

    Science.gov (United States)

    Hu, Yueyuan; Lau, Patrick; Baumstark-Khan, Christa; Hellweg, Christine E.; Reitz, Günther

    2012-05-01

    To evaluate the effects of ionizing radiation (IR) on murine preosteoblastic cell differentiation, we directed OCT-1 cells to the osteoblastic lineage by treatment with a combination of β-glycerophosphate (β-GP), ascorbic acid (AA), and dexamethasone (Dex). In vitro mineralization was evaluated based on histochemical staining and quantification of the hydroxyapatite content of the extracellular bone matrix. Expression of mRNA encoding Runx2, transforming growth factor β1 (TGF-β1), osteocalcin (OCN), and p21CDKN1A was analyzed. Exposure to IR reduced the growth rate and diminished cell survival of OCT-1 cells under standard conditions. Notably, calcium content analysis revealed that deposition of mineralized matrix increased significantly under osteogenic conditions after X-ray exposure in a time-dependent manner. In this study, higher radiation doses exert significant overall effects on TGF-β1, OCN, and p21CDKN1A gene expression, suggesting that gene expression following X-ray treatment is affected in a dose-dependent manner. Additionally, we verified that Runx2 was suppressed within 24 h after irradiation at 2 and 4 Gy. Although further studies are required to verify the molecular mechanism, our observations strongly suggest that treatment with IR markedly alters the differentiation and mineralization process of preosteoblastic cells.

  15. Blood banking-induced alteration of red blood cell oxygen release ability.

    Science.gov (United States)

    Li, Yaojin; Xiong, Yanlian; Wang, Ruofeng; Tang, Fuzhou; Wang, Xiang

    2016-05-01

    Current blood banking procedures may not fully preserve red blood cell (RBC) function during storage, contributing to the decrease of RBC oxygen release ability. This study was undertaken to evaluate the impact of routine cold storage on RBC oxygen release ability. RBC units were collected from healthy donors and each unit was split into two parts (whole blood and suspended RBC) to exclude possible donor variability. Oxygen dissociation measurements were performed on blood units stored at 4 °C during a 5-week period. 2,3-diphosphoglycerate levels and fluorescent micrographs of erythrocyte band 3 were also analysed. P50 and oxygen release capacity decreased rapidly during the first 3 weeks, and then did not change significantly. In contrast, the kinetic properties (PO2-t curve and T*50) of oxygen release changed slowly during the first 3 weeks of storage, but then decreased significantly in the last 2 weeks. 2,3-diphosphoglycerate decreased quickly during the first 3 weeks of storage to almost undetectable levels. Band 3 aggregated significantly during the last 2 weeks of storage. RBC oxygen release ability appears to be sensitive to routine cold storage. The thermodynamic characteristics of RBC oxygen release ability changed mainly in the first 3 weeks of storage, due to the decrease of 2,3-diphosphoglycerate, whereas the kinetic characteristics of RBC oxygen release ability decreased significantly at the end of storage, probably affected by alterations of band 3.

  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. General toxicity and peripheral nerve alterations induced by chronic vincristine treatment in the rabbit.

    Science.gov (United States)

    Norido, F; Finesso, M; Fiorito, C; Marini, P; Favaro, G; Fusco, M; Tessari, F; Prosdocimi, M

    1988-05-01

    The effects of five 0.3 mg/kg intravenous administrations of vincristine (VCR) at weekly intervals were studied in the rabbit. Body weight gain was impaired starting from the first injection, while gross signs of motor paralysis and hair loss initiated from the third week. At the end of the observation period blood analysis revealed normocytic normochromic anemia, elevated serum creatine kinase, and low serum alkaline phosphatase, whereas all the tested parameters related to liver and kidney functions where within normal limits. The decreased number of red blood cells was the consequence of a complete, although reversible, blockade of staminal hematopoietic activity. Two important indexes of peripheral nerve function were clearly altered at the end of the treatment: (i) the sciatic nerve conduction velocity in vitro was 27% reduced and (ii) the latency between sciatic nerve stimulation and extensor digitorum longus (EDL) twitch in vivo was 34% prolonged. The usefulness of the rabbit as an animal model to study side-effects of VCR treatment is discussed.

  18. 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

  19. Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Diaz-Villasenor, Andrea; Burns, Anna L.; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

    2007-01-01

    Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the impairment of the expression of genes related to type 2 diabetes by arsenic as one of the possible mechanisms by which it leads to the disease. Many factors are involved in the manner in which arsenic contributes to the occurrence of diabetes. The reviewed studies suggest that arsenic might increase the risk for type 2 diabetes via multiple mechanisms, affecting a cluster of regulated events, which in conjunction trigger the disease. Arsenic affects insulin sensitivity in peripheral tissue by modifying the expression of genes involved in insulin resistance and shifting away cells from differentiation to the proliferation pathway. In the liver arsenic disturbs glucose production, whereas in pancreatic beta-cells arsenic decreases insulin synthesis and secretion and reduces the expression of antioxidant enzymes. The consequences of these changes in gene expression include the reduction of insulin secretion, induction of oxidative stress in the pancreas, alteration of gluconeogenesis, abnormal proliferation and differentiation pattern of muscle and adipocytes as well as peripheral insulin resistance

  20. 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.

  1. 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.

  2. 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

  3. Dissolved oxygen detection by galvanic displacement-induced ...

    Indian Academy of Sciences (India)

    3Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Hong Kong ..... This work. Table 2. The responses of common interference on the RGO/Ag- modified ... Under optimized conditions, the detection.

  4. Ant colony induced decision trees for intrusion detection

    CSIR Research Space (South Africa)

    Botes, FH

    2017-06-01

    Full Text Available platform. Intrusion Detection Systems (IDS) analyse network traffic to identify suspicious patterns with the intention to compromise the system. Practitioners train classifiers to classify the data within different categories e.g. malicious or normal...

  5. 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.

  6. Does altered fractionation influence the risk of radiation-induced optic neuropathy?

    International Nuclear Information System (INIS)

    Bhandare, Niranjan; Monroe, Alan T.; Morris, Christopher G.; Bhatti, M. Tariq; Mendenhall, William M.

    2005-01-01

    Purpose: To analyze the parameters that influence the risk of radiation-induced optic neuropathy (RION) after radiotherapy for head-and-neck tumors. Methods and Materials: Between 1964 and 2000, 273 patients with tumors of the nasopharynx, paranasal sinuses, nasal cavity, and hard palate adenoid cystic carcinomas were treated with curative intent and had radiation fields that included the optic nerves and/or chiasm. Patients were followed for at least 1 year after radiotherapy. Results: Radiation-induced optic neuropathy developed in 32 eyes of 24 patients (9%). The 5-year rates of freedom from RION according to the total dose and once- vs. twice-daily fractionation were as follows: ≤63 Gy once daily, 95%; ≤63 Gy twice daily, 98%; >63 Gy once daily, 78%; and >63 Gy twice daily, 91%. Multivariate analysis revealed that the total dose affected the risk of RION (p = 0.0047), with patient age (p = 0.0909), once-daily vs. twice-daily fractionation (p = 0.0684), and overall treatment time (p = 0.0972) were marginally significant. The use of adjuvant chemotherapy did not significantly influence the likelihood of developing RION. Conclusion: The likelihood of developing RION is primarily influenced by the total dose. Hyperfractionation may reduce the risk of experiencing this complication

  7. Alteration of polyethersulphone membranes through UV-induced modification using various materials: A brief review

    Directory of Open Access Journals (Sweden)

    Law Yong Ng

    2017-05-01

    Full Text Available Polyethersulphone (PES membranes have been widely applied in various separation applications such as microfiltration, ultrafiltration and nanofiltration. This has occurred as these membranes are easy to form, have good mechanical strength and good chemical stability (resistant to acidic or alkaline conditions due to the presence of aromatic hydrocarbon groups in the structure. PES membranes are commonly fabricated through the phase inversion method due to the simplicity of the process. However, PES membranes are generally hydrophobic, which usually requires them to be modified before application. In most cases, these methods can reduce the hydrophobicity of the membrane surface and thus reduce membrane fouling during application. This review will further discuss the recently developed UV-induced modifications of PES membranes. The UV-induced grafting method is easy to apply to existing PES membranes, with or without the need for a photo-initiator. Additionally, nanoparticles entrapped in PES membranes subsequently exposed to UV-irradiation have been reported to possess photo-catalytic activity. However, UV-irradiation methods still require special care in order to produce membranes with the best performance.

  8. 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.

  9. 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

  10. 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

  11. Parietal disruption alters audiovisual binding in the sound-induced flash illusion.

    Science.gov (United States)

    Kamke, Marc R; Vieth, Harrison E; Cottrell, David; Mattingley, Jason B

    2012-09-01

    Selective attention and multisensory integration are fundamental to perception, but little is known about whether, or under what circumstances, these processes interact to shape conscious awareness. Here, we used transcranial magnetic stimulation (TMS) to investigate the causal role of attention-related brain networks in multisensory integration between visual and auditory stimuli in the sound-induced flash illusion. The flash illusion is a widely studied multisensory phenomenon in which a single flash of light is falsely perceived as multiple flashes in the presence of irrelevant sounds. We investigated the hypothesis that extrastriate regions involved in selective attention, specifically within the right parietal cortex, exert an influence on the multisensory integrative processes that cause the flash illusion. We found that disruption of the right angular gyrus, but not of the adjacent supramarginal gyrus or of a sensory control site, enhanced participants' veridical perception of the multisensory events, thereby reducing their susceptibility to the illusion. Our findings suggest that the same parietal networks that normally act to enhance perception of attended events also play a role in the binding of auditory and visual stimuli in the sound-induced flash illusion. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis

    Directory of Open Access Journals (Sweden)

    Timothy Budden

    2013-01-01

    Full Text Available UVB radiation is the most mutagenic component of the UV spectrum that reaches the earth’s surface and causes the development of DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts. UV radiation usually results in cellular death, but if left unchecked, it can affect DNA integrity, cell and tissue homeostasis and cause mutations in oncogenes and tumour-suppressor genes. These mutations, if unrepaired, can lead to abnormal cell growth, increasing the risk of cancer development. Epidemiological data strongly associates UV exposure as a major factor in melanoma development, but the exact biological mechanisms involved in this process are yet to be fully elucidated. The nucleotide excision repair (NER pathway is responsible for the repair of UV-induced lesions. Patients with the genetic disorder Xeroderma Pigmentosum have a mutation in one of eight NER genes associated with the XP complementation groups XP-A to XP-G and XP variant (XP-V. XP is characterized by diminished repair capacity, as well as a 1000-fold increase in the incidence of skin cancers, including melanoma. This has suggested a significant role for NER in melanoma development as a result of UVB exposure. This review discusses the current research surrounding UVB radiation and NER capacity and how further investigation of NER could elucidate the role of NER in avoiding UV-induced cellular death resulting in melanomagenesis.

  13. Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

    Science.gov (United States)

    Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

    2018-01-01

    Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

  14. 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.

  15. Glucocorticoid-Induced Fetal Programming Alters the Functional Complement of Angiotensin Receptors Subtypes within the Kidney

    OpenAIRE

    Gwathmey, TanYa M.; Shaltout, Hossam A.; Rose, James C.; Diz, Debra I.; Chappell, Mark C.

    2011-01-01

    We examined the impact of fetal programming on the functional responses of renal angiotensin receptors. Fetal sheep were exposed in utero to betamethasone (BMX; 0.17 mg/kg) or control (CON) at 80–81 days gestation with full term delivery. Renal nuclear and plasma membrane fractions were isolated from 1.0–1.5 year old sheep for receptor binding and fluorescence detection of reactive oxygen species (ROS) or nitric oxide (NO). Mean arterial blood pressure and blood pressure variability were sign...

  16. 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.

  17. Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

    Directory of Open Access Journals (Sweden)

    Fatemeh Sarhadi Kholari

    2016-11-01

    Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

  18. Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.

    Science.gov (United States)

    Schneider, Patrick; Petzold, Sandra; Sommer, Angela; Nitsch, Robert; Schwegler, Herbert; Vogt, Johannes; Roskoden, Thomas

    2018-01-15

    Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1 -/- ) mice and PRG-1/LPA 2 -receptor double knockout (PRG-1 -/- /LPA 2 -/- ) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test. PRG-1 -/- mice displayed significantly longer path lengths and higher running speed in both open field conditions. In addition, PRG-1 -/- mice spent significantly longer time in the larger open field and displayed rearing and self-grooming behavior. Furthermore PRG-1 -/- mice displayed stereotypical behavior resembling phenotypes of psychiatric disorders in the smaller sized open field arena. Altogether, this behavior is similar to the stereotypical behavior observed in animal models for psychiatric disease of autistic spectrum disorders which reflects a disrupted balance between glutamatergic and GABAergic synapses. These differences indicate an altered excitation/inhibition balance in neuronal circuits in PRG-1 -/- mice as recently shown in the somatosensory cortex [38]. In contrast, PRG-1 -/- /LPA 2 -/- did not show significant changes in behavior in the open field suggesting that these specific alterations were abolished when the LPA 2 -receptor was lacking. Our findings indicate that PRG-1 deficiency led to over-excitability caused by an altered LPA/LPA 2 -R signaling inducing a behavioral phenotype typically observed in animal models for psychiatric disorders. Copyright

  19. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

    DEFF Research Database (Denmark)

    Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J

    2015-01-01

    -surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery....... The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic......Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were...

  20. 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.

  1. Possible GABAergic modulation in the protective effect of zolpidem in acute hypoxic stress-induced behavior alterations and oxidative damage.

    Science.gov (United States)

    Kumar, Anil; Goyal, Richa

    2008-03-01

    Hypoxia is an environmental stressor that is known to elicit alterations in both the autonomic nervous system and endocrine functions. The free radical or oxidative stress theory holds that oxidative reactions are mainly underlying neurodegenerative disorders. In fact among complex metabolic reactions occurring during hypoxia, many could be related to the formation of oxygen derived free radicals, causing a wide spectrum of cell damage. In present study, we investigated possible involvement of GABAergic mechanism in the protective effect of zolpidem against acute hypoxia-induced behavioral modification and biochemical alterations in mice. Mice were subjected to acute hypoxic stress for a period of 2 h. Acute hypoxic stress for 2 h caused significant impairment in locomotor activity, anxiety-like behavior, and antinocioceptive effect in mice. Biochemical analysis revealed a significant increased malondialdehyde, nitrite concentrations and depleted reduced glutathione and catalase levels. Pretreatment with zolpidem (5 and 10 mg/kg, i.p.) significantly improved locomotor activity, anti-anxiety effect, reduced tail flick latency and attenuated oxidative damage (reduced malondialdehyde, nitrite concentration, and restoration of reduced glutathione and catalase levels) as compared to stressed control (hypoxia) (P zolpidem (5 mg/kg) was blocked significantly by picrotoxin (1.0 mg/kg) or flumazenil (2 mg/kg) and potentiated by muscimol (0.05 mg/kg) in hypoxic animals (P zolpidem (5 mg/kg) per se (P zolpidem against hypoxic stress.

  2. ALTERED EXPRESSION OF SURFACE RECEPTORS AT EA.HY926 ENDOTHELIAL CELL LINE INDUCED WITH PLACENTAL SECRETORY FACTORS

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2012-01-01

    Full Text Available Abstract. Placental cell populations produce a great variety of angiogenic factors and cytokines than control angiogenesis in placenta. Functional regulation of endothelial cells proceeds via modulation of endothelial cell receptors for endogenous angiogenic and apoptotic signals. Endothelial phenotype alteration during normal pregnancy and in cases of preclampsia is not well understood. The goal of this investigation was to evaluate altered expression of angiogenic and cytokine receptors at EA.hy926 endothelial cells under the influence of placental tissue supernatants. Normal placental tissue supernatants from 1st and 3rd trimesters, and pre-eclamptic placental tissue supernatants (3rd trimester stimulated angiogenic and cytokine receptors expression by the cultured endothelial cells, as compared with their background expression. Tissue supernatants from placental samples of 3rd trimester caused a decreased expression of angiogenic and cytokine receptors by endothelial cells, thus reflecting maturation of placental vascular system at these terms. Supernatants from preeclamptic placental tissue induced an increase of CD119 expression, in comparison with normal placental supernatants from the 3rd trimester. This finding suggests that IFNγ may be a factor of endothelial activation in pre-eclampsia. The study was supported by grants ГК №02.740.11.0711, НШ-3594.2010.7., and МД-150.2011.7.